[{ "paper_id": "000b7d1517ceebb34e1e3e817695b6de03e2fa78", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "00142f93c18b07350be89e96372d240372437ed9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ACKNOwLeDGMeNTS JG, GN, and SA are supported by the CARIPLO foundation, SA is supported by the European Research Council, and the INGM is supported by the \"Romeo ed Enrica Invernizzi\" foundation.", "It is largely accepted that pDC-derived IFN-\u03b1 is important to contain human viral infections. Thus, stabilized pegylated IFN-\u03b1 is a widely used therapy for HCV patients. IFN-\u03bb appears to be similar effective, but is less toxic presumably because of the more restricted expression of its receptor (164) . Interestingly, the HCV glycoprotein E2 is a ligand for BDCA-2, which is specifically expressed on pDCs ( Table 1 ) and inhibits IFN-\u03b1 production (174, 175) . In this way, HCV might inhibit IFN-\u03b1 production to establish chronic infection. Finally, pDCs are also targeted by human immunodeficiency virus (HIV), but whether they play a protective or detrimental role is still unclear (176) .", "High numbers of human DCs can be generated in vitro by culturing monocytes with cytokines (41) , and the large majority of studies on human DCs have been done with these monocytederived DCs. They are primary cells and show many behaviors of in vivo occurring DCs, including cytokine production as well as stable and potent antigen presentation upon maturation with TLR ligands (125) . However, monocyte-derived DCs are not the appropriate model to study the role of specialized DC subsets in human immune responses." ] },{ "paper_id": "0022796bb2112abd2e6423ba2d57751db06049fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nonclimatic factors include the epidemiology, ecology, and distribution of the vector, socioeconomic, and environmental factors; climatic factors include weather variability, climate change, and extreme events. These factors are discussed in detail in the following sections.", "Taiwan. Before 2009, the Taiwan Centers for Disease Control (TCDC) used only a clinical case definition for reporting dengue, which may have led to over-reporting. The TCDC's current dengue case definition, established in 2009 and in use since, requires laboratory confirmation for reported cases [189] . Dengue must be reported to TCDC within 24 hours [72] . A central command center was established to provide resources and personnel from various ministries (Education, Interior, National Defense) and agencies (department of health, environmental protection administration, government information office). The aim was to foster close cooperation with local government units and public education to reduce vector breeding. These efforts have been associated with reduced case numbers from 2010 to 2012 [70] . However, it is difficult to confirm this trend because of the short period.", "Singapore has in place community-based programs for the removal of potential breeding habitats [193] , which involve the community in mosquito control through environmental management, health education, and community ownership (\"bottom-up\" approach) (e.g., \"Do the Mozzie Wipeout\" Campaign, \"Do the 5-Step Mozzie Wipeout\") [194] . This is essential for avoiding community complacency. However, the community-based approach can be slow or demotivating and, as a consequence, unsustainable [195] . Bottom-up and top-down approaches should be combined [195] ." ] },{ "paper_id": "00326efcca0852dc6e39dc6b7786267e1bc4f194", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Organizational details of intensive care units vary considerably. The presence and utilization of PICUs, intermediate units, stepdown units, and specialty-specific units differ from country to country, state to state (18) . Composition of PICU team members has not been standardized and is often driven by the availability of resources in that institution. Most team members (physicians, nurses, respiratory therapists, pharmacists, dieticians, etc.) have completed some form of pediatric ICU-specific training.", "The need for excellence in clinical care does not end simply with the referral. In an urban population in Guinea-Bissau, 45% of children under 5 years were hospitalized, and the in-hospital mortality was 12% in 2007 (34), compared with an inpatient mortality of 0.84% in the US in 2009-2010 (35) . Challenges in presentation, triage, initial management, and admission to the hospital setting prompted guideline development and interventions for improved patient outcomes. Nolan et al. demonstrated that more than half of children were undertreated or inappropriately treated with antibiotics, fluids, or oxygen in 21 hospitals across seven countries in Asia and Africa (36) .", "With unacceptably high mortality rates in children highlighted both during times of epidemics and in times of relative steady state, the WHO and UNICEF strategies for reducing mortality in children under 5 years initially focused on outpatient management and primary care (29) . The first WHO guidelines, the Integrated Management of Childhood Illness (IMCI), are an evidence-based strategy for assessing and treating sick children in the ambulatory care setting. Even with the focus on primary care, these guidelines assume that sick children will be referred to a hospital for escalation of care if needed (29) . With appropriate IMCI use, 16-46% of children will require referral to a hospital (30) (31) (32) (33) .", "While some might see tradeoffs between interventions to stem current epidemics and investments in health systems for the future, these two notions can coexist. Indeed, building systems that provide high-quality care in crisis can be used to provide effective critical care disease management and chronic care once the epidemic has subsided. The HIV epidemic is an important example of how quality, system-based interventions in times of disease outbreak can serve a country's healthcare system as a whole.", "Recent historical examples include the severe acute respiratory syndrome (SARS) and H1N1 influenza epidemics. As of June 2015, the overall fiscal impact of the Ebola epidemic has been estimated to be upwards of $30 billion, while only $7.1 billion has been pledged thus far (7, 8) ." ] },{ "paper_id": "00352a58c8766861effed18a4b079d1683fec2ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Frontiers in Synaptic Neuroscience | www.frontiersin.org", "MH, CLD and PJ wrote the manuscript and contributed to the Figure and Table. FUNDING This work was funded in part by grants from the National Science Foundation (IOS#135862) and National Institutes of Health (NS101534) to PJ and by the Synapse Neurobiology T32 Training Grant (NS61764) from the National Institutes of Health to MH.", "Ionotropic GABA A receptors mediate the majority of fast inhibitory transmission in the brain. GABA A receptors are comprised of hetero-pentamers and ubiquitination of specific subunits can regulate receptor trafficking and degradation in an activity-dependent manner (Saliba et al., 2007; Jacob et al., 2008; Arancibia-C\u00e1rcamo et al., 2009) ." ] },{ "paper_id": "0043d044273b8eb1585d3a66061e9b4e03edc062", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Ministry of Health of the People's Republic of China (PRC) estimates that 5 million people currently have active TB with 80% of cases in rural areas, particularly in the poorest provinces in north and north-western PRCincluding Ningxia Hui Autonomous Region (NHAR) [1] ." ] },{ "paper_id": "0049ba8861864506e1e8559e7815f4de8b03dbed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human Immunodeficiency Virus type 1 (HIV-1) envelope spike is a trimeric complex consisting of three noncovalently linked heterodimers of gp120 and gp41. Gp120, an exterior glycoprotein, mediates cell attachment, receptor and co-receptor binding. Gp41, a transmembrane glycoprotein, mediates viral and cell membrane fusion, which is critical for viral core to enter target cells. Both gp120 and gp41 are derived by cleavage of a common precursor gp160.", "Drosophila Schneider 2 (S2) cells were purchased from Invitrogen Life Technologies and maintained in 75 cm flask (Corning) at the cell density between 0.2 to 2 \u00d7 10 6 cells per ml in the Express FIVE\u00ae SFM medium (Invitrogen Life Technologies) supplemented with 10% FBS, 100 U/ml penicillin, 100 U/ml streptomycin and 100 mg/L L-glutamine at 28\u00b0C without additional CO 2 ." ] },{ "paper_id": "00623bf2715e25d3acacb3f210d6888ed840e3cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following antibodies were used in this study: phospho-EGF receptor rabbit mAb (CST, USA); anti-CAT1 (Abcam, UK); caveolin-1 antibody, phospho-PKC \u03b1 antibody, and \u03b2-tubulin antibody (EnoGene Biotech, USA). The next day, membranes were washed three times with TBST and incubated with HRP-conjugated secondary antibodies for 2 h at room temperature. The membranes were then washed with TBST for 5 min four times. Protein band detection was performed using ECL reagents (Thermo Scientific, USA).", "TGEV strain SHXB (GenBank: KP202848.1) was provided by the Jiangsu Academy of Agricultural Sciences (JAAS, Jiangsu Province, China) [29] . For experimental assays, cells were infected with TGEV at a multiplicity of infection (MOI) of 3 for 1 h at 37 \u00b0C in serum-free medium and washed with phosphate-buffered saline (PBS, pH 7.2) three times to remove unbound virus. Cells were then cultured in maintenance medium (DMEM containing 2% FBS).", "Protein was obtained from IPEC-J2 cells at the indicated time points post-infection using ice-cold radioimmunoprecipitation assay (RIPA) lysis buffer containing 10 mM phenylmethylsulfonyl fluoride (PMSF). Total protein concentrations were determined using a bicinchoninic acid (BCA) protein assay kit (Thermo Scientific, USA). Cell lysates that contained equal amounts of protein were denatured, subjected to 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and transferred to polyvinylidene difluoride (PVDF) membranes (Millipore, USA). Membranes were blocked with Tris-buffered saline (TBS) containing 5% nonfat dry milk for 2 h, and incubated with the indicated primary antibodies at 4 \u00b0C overnight." ] },{ "paper_id": "0072159e1ebecc889e9bcabb58bb45c47e18a403", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Screening of proline-rich motif reading array identifies BAG3 as an EBOV VP40 PPxY interactor", "As the major filovirus matrix protein, VP40 plays a central role in directing virion assembly and egress from infected cells. Three minimal functional domains of VP40 are required for efficient VLP egress, including a membrane (M) binding region, a self-interaction (I) domain, and one or more late (L) domain motifs. The L-domain motifs hijack or recruit specific host cell proteins that facilitate or promote efficient virus-cell separation [3, 4, 6, [48] [49] [50] [51] [52] [53] . Here, we" ] },{ "paper_id": "007618ad76a3548195ab5d11c1e2459931c91cd1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: E.N. and J.K. were involved in the conception, literature review and drafting the manuscript; J.K., I.L., and E.C. critically revised the manuscript for important intellectual content; E.N., J.K., and E.C. conceptualized the review, supervised all aspects of the study, and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted. All authors read and approved the final manuscript. ", "Accumulating evidence demonstrates that despite being a suboptimal replication system, monocytes/macrophages cannot escape viral attack. Pathogens attack a variety of cells and utilize diverse bypass mechanisms to enter, change cell machinery and impact the fate of cellular decisions in favour of their replication and propagation.", "Therefore, it has to be assumed that viruses manipulate the cell biology of monocytes/macrophages in order to utilize them as a repository for dissemination, to promote long-term persistence within infected tissues and for enabling virus replication under favourable conditions." ] },{ "paper_id": "007bf75961da42a7e0cc8e2855e5c208a5ec65c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hemagglutination assay was performed in V-shaped 96-well plates (Greiner Bio-One). Two-fold serial dilutions in 50 ml PBS, 0.1% BSA of HE 0 -Fc or of purified HE 0 ectodomains (starting amounts indicated in the text) were mixed with 50 ml of a rat erythrocyte suspension (Rattus norvegicus strain Wistar; 0.5% in PBS) and incubated for 2 hours on ice.", "Diffraction data of crystals of MHV-S HE and its complex ( Table 1) were collected at ESRF station ID-14-1 and ID-14-3, respectively. Diffraction data of native and ligand-soaked HE crystals were processed using XDS [38] and scaled using SCALA from the CCP4 suite [39] . Molecular replacement was performed using PHASER with BCoV-Mebus HE as template (PDB ID: 3CL5; [23] ). Models were built manually with Coot [40] and refinement was carried out using REFMAC [41] . Water molecules were added using ARP/WARP, graphics generated with PYMOL (http://pymol.sourceforge.net).", "The crystal structures of a number of 9-O-Ac-Sia-specific nidovirus HEs have been solved [23, 24] . Unlike the receptorbinding site (RBS) of influenza C virus HEF [28] , the RBSs of the corona-and torovirus HEs seem to be exceptionally plastic as they appear to have undergone significant changes and adaptations that altered their overall architecture in a relatively short evolutionary time span. Based on these observations, we anticipated and speculated [23] that this plasticity might have allowed for even more substantial adjustments in the RBS of the murine coronavirus HE as to produce an entirely novel binding site specific for 4-O-acetylated Sias." ] },{ "paper_id": "0080d3bd9fb92e022c27715c2d1249042aa998b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Female or male 6-8 week old IFN a/b/c receptor deficient mice (AG129) were purchased from B&K Universal Limited with permission from Dr. M. Aguet (ISREC, School of Life Sciences Ecole Polytechnique F\u00e9d\u00e9rale (EPFL)). IFN a/b receptor deficient mice (IFNAR) on a C57BL/6 background were provided by Prof. Ulrich Kalinke [33] . All mice were bred and kept under specific pathogen-free conditions at the Biomedical Resource Centre, Singapore. For immunization, BHK-21 derived mutant and WT viruses were used. For challenge experiments DENV produced in C6/36 cells was used.", "Virus was isolated from mouse serum with Qiagen Viral RNA extraction Kit.", "(TIF) ", "Fifty ng of viral RNA were used to prepare cDNA libraries using the Illumina TruSeq RNA sample preparation kit according to manufacturer's protocol. The only protocol modification was the removal of the mRNA enrichment step. The cDNA libraries were sequenced as a multiplex in a single lane of an Illumina HiSeq2000 (Next Generation Sequencing Core facility, Genomic Institute of Singapore). One to 2 million 50 bp paired-end reads were generated for each virus.", "The mouse experiments were conducted according to the rules and guidelines of the Agri-Food and Veterinary Authority (AVA) and the National Advisory Committee for Laboratory Animal Research (NACLAR), Singapore. The experiments were reviewed and approved by the Institutional review board of Biological Resource Center, Singapore (IACUC protocols 90474 and 100536)." ] },{ "paper_id": "0089aa4b17549b9774f13a9e2e12a84fc827d60b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Far-UV CD spectra were recorded using a Jasco J-715 spectropolarimeter (Jasco, Gross-Umstadt, Germany) equipped with a PTC 343 Peltier element. Experiments were performed in quartz cuvettes with 0.1 cm path length at a protein concentration of 0.15 mg/ml and far-UV spectra were recorded from 190 to 260 nm in 10 mM potassium phosphate, pH 8.0 at 20 uC. 16 spectra were accumulated for each protein analyzed and subsequently baseline corrected. The composition of secondary structure elements was calculated using the CD spectra deconvolution software CDNN [23] . Thermal transition experiments were monitored at 208 nm with a heating rate of 20 uC per hour. Data were normalized by setting the signal of the native protein to 1.", "Variant Medium-Chain acyl-CoA Dehydrogenase. PLoS ONE 9(4): e93852." ] },{ "paper_id": "008c1ceaeffe7abc87b031af39fae2632fa72897", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "input to the next layer just by computing an identity function." ] },{ "paper_id": "008d980cbcc283a9b707de3d9a02573dde8528ac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dendrogram constructed using UPGMA, showed low genetic differences and high genetic similarities among three populations (Thally, Kharkoo and Astore). Shagarthang population exhibited one degree separation from the above three populations, while Basho population appeared as a separate clade (Fig. 6) . AMOVA suggested no significant variance among populations indicating no populations' differentiation among regions. Variance contributed by variability was 46% among individuals and that within individuals was 54%, while 0% was observed among populations (Fig. 7) . ", "The following information was supplied regarding data availability:", "Supplemental information for this article can be found online at http://dx.doi.org/10.7717/ peerj.7672#supplemental-information.", "Samreen Aruge performed the experiments, analyzed the data, prepared figures and/or tables. Hafsa Batool performed the experiments, prepared figures and/or tables. Fida M. Khan analyzed the data, contributed reagents/materials/analysis tools, prepared figures and/or tables, authored or reviewed drafts of the paper, approved the final draft, collected samples. Fakhar-i-Abbas conceived and designed the experiments, contributed reagents/ materials/analysis tools, prepared figures and/or tables, approved the final draft, collected samples. Safia Janjua conceived and designed the experiments, approved the final draft." ] },{ "paper_id": "009002e8a66b8c1df088cf04069629fd76b13bb9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "0093f9ae0861afc0d29fff935ae6a3af898cea00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "www.nature.com/scientificreports SCIENTIFIC REPORTS | 5 : 8850 | DOI: 10.1038/srep08850 S1). Other candidate viral genomes were not detected by metagenomic analysis.", "In addition, the gag region of proviral DNA was amplified by nested PCR using primers (Tga1, Tga2, Tga3, and Tga4) that specifically detected the gag region of the SRV/D-T (SRV-4) 12 .", "www.nature.com/scientificreports SCIENTIFIC REPORTS | 5 : 8850 | DOI: 10.1038/srep08850", "Antibody tests against viral pathogens. To determine the virus that was responsible for the disease, antibodies against Ebola, Marburg, Lassa, and Crimean-Congo hemorrhagic fever viruses, all of which induce hemorrhagic syndromes in humans, were examined at the National Institute of Infectious Diseases, Japan. Neutralizing antibodies against CDV were also tested, because CDV is known to cause a lethal disease in macaques 26 ." ] },{ "paper_id": "0094b25e2500306fadbdfb41d520f2970bb086d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author(s) declare that they have no competing interests." ] },{ "paper_id": "00951716e01c8e0cc341770389fc38d1b5455210", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This cross-sectional study, conducted during December 2010-February 2011, used both quantitative and qualitative data-collection techniques.", "Since our study area included 90 clusters, we used cluster-sampling methodology for data-collection. In total, 15 clusters were randomly selected for the KAP study. Approximately 200 households from each cluster were randomly selected from the household list prepared by the demographic surveillance maintained by the ICVB project. An adult from each household who could provide information regarding his/her family was purposively selected for interview.", "A semi structured questionnaire was used for collecting quantitative data (see Additional file 2). It comprised a series of questions developed through literature review [9, 32, 33] and revised to match with the cultural views. Multiple answers were recorded per question based on predefined categories but no probing of remaining unmentioned categories was done. The questionnaire was divided into the following three main sections:" ] },{ "paper_id": "009892e02bc1a4c9abf6f547b979e68ecbde8087", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nasopharyngeal samples were taken according to a recently described procedure using swabs (Sigma-Virocult\u00ae M40 compliant. MWE. Corsham Wiltshire, UK) after saline instillation [24] .", "Quantitative variables are reported as mean \u00b1 standard deviation. Quantitative variables were compared using a nonparametric statistical test (Wilcoxon signed rank for paired comparisons). Pearson's correlation coefficient (r) was used to assess relationships between two variables. Statistical analyses were performed using SAS v9.4 (SAS Institute, Cary, NC, USA) or GraphPad Prism V6.00 (GraphPad Software, La Jolla, CA, USA). The significance level was set at 0.05.", "For the six patients presenting a RSV infection, the clinical progression was uncomplicated (Table 3) ." ] },{ "paper_id": "00acd3fd31ed0cde8df286697caefc5298e54df1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It will be important to further characterize these NIVs and determine whether their differences confer distinctive biological behaviours, such as unique growth properties, antiviral resistance and discrete clinical outcomes among infected individuals. Strainfocussed studies could also identify how many distinct HRVs circulate in a single respiratory season, how often a given strain recurs in a population and just how many HRV strains there are." ] },{ "paper_id": "00ae0041374cbbf28df0d2cbeb08c1396a4f7878", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The reaction schemes for the two kinds of OAS activities measured in this paper are depicted in reaction 1 and reaction 2, respectively.", "For the PDE12 activity assay the following reaction scheme was used:", "The authors declare that they have no competing interests." ] },{ "paper_id": "00af80743cef9bd8c04c532d74e9c67f0c9312e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "00b88130d2a7c8489e209742494303b6731d7544", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "AcMNPV and rBV were propagated in Sf9 cells cultured in TMN-FH medium (BD Biosciences) containing 100 \u03bcg/ml kanamycin and 10% FBS. Ac/CAG-FrC-OVA and AcMNPV were purified as described previously [39, 43, 44] . The viral titers were determined by a plaque assay.", "Supplementary information accompanies this paper at https://doi.org/10. 1186/s13036-019-0207-y. " ] },{ "paper_id": "00c19aff3efc6e6430f77d81580ac927990ad5a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bronchoscopy was performed using an Olympus BF-1 T160 (Olympus, Tokyo, Japan) bronchoscope that has an outer diameter of 6.0 mm with a 2.8 mm working channel. All procedures were performed under moderate sedation using a combination of fentanyl and midazolam. BAL was obtained from the bronchopulmonary segment corresponding to CT scan findings for focal infiltrates while the right middle lobe or lingular was preferred in the cases with diffuse infiltrates. BAL samples were sent for standardized investigations consisting of cytology and microbiological analysis.", "Trial registration: ClinicalTrials.gov identifier NCT01374542. Registered June 16, 2011." ] },{ "paper_id": "00c88aab2bfcca0db253c972382e5eee245d071e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Motivated by the recent outbreaks in the Americas, two studies from Arizona State University have described the production of Zika virus glycoprotein antigens in plants. The first successfully expressed a soluble E protein which retained native antigenicity based on the binding of a panel of monoclonal antibodies and elicited both cellular and humoral responses in immunized mice. Furthermore, the levels of neutralizing antibodies in immunized animals exceeded the threshold required for protective immunity (Yang et al., 2017b) . The same group has also developed a VLP vaccine comprised of the hepatitis B core antigen presenting the Zika virus E protein domain III, to circumvent potentially inducing antibody-dependent enhancement (ADE) of infection against dengue infection (Yang et al., 2017a) .", "Molecular farming is on the cusp of being accepted as a mainstream technology for the production of heterologous pharmaceuticals, with particular appeal for resource-limited regions. Recent years have borne witness to the licensure of the first plant-made pharmaceutical for use in humans-taliglucerase alpha-with several more presently advancing through clinical trials. Plant-made pharmaceuticals have proven to be highly scalable and safe in humans, despite unfounded concerns regarding the impact of plant-specific glycosylation. Limitations of expression yields have been addressed with improved expression vectors enabling high levels of expression of many pharmaceutically relevant proteins.", "Given the extended period of divergent evolution of mammals and plants, the low expression levels reported for many viral glycoproteins may be due to incompatibility with the endogenous plant chaperone machinery. In support of this, putative homologues of key chaperones known to interact with glycoproteins exhibit low-level sequence identity to their human counterparts. We are currently exploring the co-expression of human molecular chaperones in planta (patent application: PA167643/P) to improve the production of heterologous glycoproteins, based on the hypothesis that the endogenous plant chaperones may represent a critical bottleneck for high levels of expression." ] },{ "paper_id": "00cb1a95986171a256f5ef14701bd8f571221a28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tyrosine kinase WNV West Nile virus YFV Yellow fever virus", "TLRs have also been implicated in the activation of DCs by YF-17D [27] . DCs recovered from MyD88, TLR2, TLR7 and TLR9 -deficient mice all exhibited reduced levels of cytokine production in response to YF-17D. In addition, human fibroblasts stably transfected with TLR8 and an NF-\u03baB luciferase reporter responded more robustly to YF-17D, suggesting that this TLR8 is also capable of detecting the virus [27] .", "The role of the RLR system in controlling yellow fever virus (YFV) has yet to be examined. However, both RIG-I and MDA5 expression was upregulated in peripheral blood mononuclear cells (PBMCs) recovered from individuals vaccinated with YF-17D [15] , suggesting a possible role for both of these PRRs in responding to YFV in vivo. Combined, these studies indicate that RIG-I is involved in sensing all flavivirus infections; however, MDA5's role is virus-dependent." ] },{ "paper_id": "00ccc4ef2b6c6f238836b7feb5123bd6a822cc08", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA was isolated from LCM tissues, using the miRNeasy FFPE Kit (no. 217504, Qiagen), as described in the above section.", "In 2009, the swine-origin H1N1 influenza A virus (IAV) emerged and caused outbreaks of respiratory illness in humans around the world. After the 2009 pandemic, outbreaks of that strain have continued to cause serious illness and increased mortality, particularly in young adults and children [1] . The physiopathology of pandemic H1N1 (pH1N1) infection differs between individuals. Whilst most patients develop mild upper respiratory-tract infection [2], some patients progress to develop severe lower respiratory tract complications [3] . In addition, high rates of clinically unapparent infections have been reported by seroepidemiological studies [4, 5] . This evidence suggests that the severity of influenza is, at least, partially determined by host factors.", "Viral titration from lungs samples and nasal swabs was performed on control and infected animals, and determined by plaque forming units (PFU) as described previously [23] . A portion of around 0.2 g of the right caudal lung lobe and nasal swabs were placed in 0.5 mL of Dulbecco's Modified Eagle's Medium (DMEM) (Bio-Whittaker \u00ae , Lonza, Verviers, Belgium) with 600 \u00b5g/mL penicillin and streptomycin, and frozen at \u221280 \u00b0C until further processing." ] },{ "paper_id": "00cf719db65d07c0c7bdea9defaea448fc5f5786", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Experiments were performed in accordance with federal and cantonal guidelines (Tierschutzgesetz) under the permission numbers SG07/62 and SG07/63 granted by the Veterinary Office of the Canton of St. Gallen.", "The data on target cell persistence (C(t)) display kinetics which differs for some cell types or under certain conditions from the exponential (denoted by E) behavior C(t)~C(0) : e {d0C : t . It is rather consistent with the Gompertz kinetics (denoted by G) as described by equation", "Finally, the rate equation for the density of uninfected target cells reads", "The persistence of virus and type I IFN in medium displays an exponential kinetics. The corresponding decay rate constants for MHV (d V ) and IFNa (d I ) were estimated by a linear regression procedure for the log-transformed values of the virus titer and IFN concentration using GraphPad Prism v.4 software (http://www. graphpad.com). The parameter estimates and their 95% Confidence Intervals (CIs) are presented in Table S1 ." ] },{ "paper_id": "00dce8da5fcee849b30c9d7a7e358c5855b14ca9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To summarize, the mechanisms by which herpesviruses trigger autoimmunity are variable. Both, molecular mimicry and bystander activation were reported in EBV-and HSV-induced autoimmunity. Not only that, EBV also has the ability to immortalize autoreactive infected B cells. In addition, as neurotropic viruses, herpesviruses can infect and kill CNS cells directly, leading to several AIDs.", "Bystander activation was also a suggested mechanism by which CVB4 induce or accelerate diabetes. Mouse studies have indicated that by evoking beta cells damage, CVB4 infection promotes the release of self-antigens, which are then presented by macrophages to autoreactive T cells [32] ." ] },{ "paper_id": "00f1ef126735474ccaf3a8d1cce9a4823d7f1228", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All of these results are in agreement with the participation of electrogenerated MQI in the Michael addition reaction with BS [28] [29] [30] [31] [32] [33] [34] . Fig. 1c is the cyclic voltammogram of BS which indicates that in the studied potential range, BS is not electroactive." ] },{ "paper_id": "00f7d667e3362066c08f7d6594d1d3b0cb16e08e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "00fcc6277c19f6b180232d7a6fe0b0abfafb21f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lowest leukocyte count -per mm 3 2,500 (600-11,500) 2,080 (810-13,000) 0.590", "Appendix S1. (DOC)" ] },{ "paper_id": "010ad052b58172981e089bc73b9ad16a732960f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nonetheless, our results support a significant protective function for xbp-1 within the cells targeted by Cry5B.", "All experiments were performed a minimum of three times. LC 50 values were determined by PROBIT analysis [43] . The lethal concentration assays are represented graphically using nonlinear regression performed with the software GraphPad Prism. Statistical analysis between two values was compared with a paired t-test. Statistical analysis among three or more values was compared with matched one way ANOVA using the Tukey post test. Lifespan data was analyzed with Kaplan-Meier survival curves. Statistical significance was set at p,0.05.", "Found at: doi:10.1371/journal.ppat.1000176.s001 (0.03 MB DOC)" ] },{ "paper_id": "01110a24b6ce133ae80d21a36c7994e364ba296c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Table S11 Summary of the classification type random forest algorithms performed and overall prediction error. (DOCX)", "Emerging infectious diseases (EIDs) continue to represent a significant public health threat, as illustrated by the 2009 H1N1 influenza pandemic and the 2003 severe acute respiratory syndrome (SARS) epidemic. Of particular concern are the 60%+ of EIDs of zoonotic origin [1, 2] . In addition to influenza and SARS [3] , notable examples include hantaviruses [4] , Nipah and Hendra viruses [5] and HIV [6] .", "Text S1 Includes a more detailed description of the methods used throughout, as well as Figures S1, S2 , S3, S4, S5 and Tables S1, S2, S3, S4, S5, S6, S7, S8, S9, S10, S11. (DOCX)" ] },{ "paper_id": "0113b9a8d82039e8474e887038d643853b5fdfeb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Presentations were used to introduce the participants to each module, then they would work through case studies in group discussions which included exercises on using data collection and reporting tools.", "Supporting IDSR contributes to a strengthened healthcare system", "Not applicable." ] },{ "paper_id": "0116dea9b6d4c58748d1a38b69b4fe6e06868aa4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Surface staining reagents including Mouse anti Pig CD163: RPE (MCA2311PE, Bio-Rad). After staining, cells were fixed in 1% formaldehyde and analyzed on FACScan (Becton-Dickinson, Franklin Lakes, NJ, USA) upgraded with a red laser (Cytek Development, Fremont, CA, USA). Data analysis was conducted using FlowJo software (Tree Star, Inc., Ashland, OR, USA).", "Total RNA was prepared using Trizol reagent (Takara, China) based on the instruction by manufacture. Then, cDNA was synthesized by an oligo (dT)15 primer and SuperScript\u2122 II reverse transcriptase reagents (Takara, China). Quantitative real-time PCR was performed with the iTaq\u2122 Universal SYBR GREEN Supermix using a CFX96 Optics Module instrument (Bio-Rad, Hercules, CA, USA). The forward and reverse primer sequences were summarized in Table 1 .", "Each experiment was independently replicated on three individual pigs, and all experiments were replicated at least three times. Data were presented as mean\u00b1s.e.m. when indicated. Statistical analysis was conducted by t-test with a 95% confidence limit, and two-way ANOVA for multi-group comparisons by Prism 7.0 (GraphPad Software Inc., USA). Differences were considered significant at P<0.05. All data are representatives of at least three independent experiments." ] },{ "paper_id": "011b8a7002da6c0fae7ca76c127567a6462daf5d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Immediately following a 2-h incubation period, we returned the chamber to the BSC and removed the cell culture dish. We added 500 l of TSB to each well containing droplets, which we resuspended via pipetting and then placed into separate cryovials for each well's solution. We placed the vials in a \u03ea20\u00b0C freezer for 20 min before moving them to a \u03ea80\u00b0C freezer for long-term storage. Prior to assaying these samples, we thawed them at room temperature before sampling and refreezing.", "Samples for each experimental condition included negative-control cultures containing 500 l of Phi6 stock solution. We stored these controls in polyethylene tubes and did not spot them as droplets but otherwise incubated them in the RH chamber and stored and assayed them identically to the test cultures.", "Chamber to control RH and AH. To control humidity, we used a chamber as previously described (13) . We placed two polyethylene petri dishes filled with 10 to 20 ml of a saturated salt solution into the bottom of a glass desiccator. Saturated solutions of potassium acetate, magnesium chloride, potassium carbonate, magnesium nitrate, sodium chloride, potassium chloride, and potassium sulfate provided stable RH at 23%, 33%, 43%, 61%, 75%, 85%, and 98%, respectively. We also placed a battery-powered computer fan into the chamber to promote airflow and a more rapid establishment of an RH equilibrium." ] },{ "paper_id": "01234cee305e37a78cedea8148bf6177d47fe66b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Camel peripheral blood mononuclear cells (PBMC) were obtained from na\u00efve animals from a previous experiment 22 . Human PBMC were obtained from 3 healthy blood donors (Sanquin Bloodbank, Rotterdam, The Netherlands). The use of PBMCs for scientific research was approved by the Sanquin Bloodbank after informed consent was obtained from the blood donors.", "As an additional control, nasal turbinate of a non-infected dromedary (collected during routine necropsy at the Department of Pathology, University of Veterinary Medicine Hannover, Germany) was used. Euthanasia of the animal was performed due to non-respiratory disease." ] },{ "paper_id": "01285aff189f375f52b762256d8f419ccad3077c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background. Recent detections of circulating serotype 2 vaccine-derived poliovirus in northern Nigeria (Borno and Sokoto states) and Pakistan (Balochistan Province) and serotype 1 wild poliovirus in Pakistan, Afghanistan, and Nigeria (Borno) represent public health emergencies that require aggressive response.", "Conclusions. Eradication efforts for vaccine-preventable diseases need to create performance expectations for countries to immunize all people living within their borders and maintain high coverage with appropriate interventions.", "Eradication efforts for vaccine-preventable diseases need to create performance expectations for countries to identify and reach all people living within their borders with maintained high coverage with appropriate interventions. " ] },{ "paper_id": "012debf5a240a496518af146ddfc16c958339c2b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Some reflections on our methodological approach are due here. Perhaps the major advantage of our overall strategythe use of foreign, or otherwise external social scientists to conduct open-ended interviews with in-country expertswas that it provided the opportunity for the latter to reflect on their work in a way that can offer a fresh perspective on what may often seem self-evident to them as 'insiders' [51] .", "Not applicable." ] },{ "paper_id": "0132b8c2721692d9f53bd33a738fa94618bb4e91", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Syphilis spirochete Treponema pallidum ssp. pallidum remains the enigmatic pathogen, since no virulence factors have been identified and the pathogenesis of the disease is poorly understood. Increasing rates of new syphilis cases per year have been observed recently.", "Finally, the stain solution was removed, and arrays were washed in non-stringent wash buffer followed by two 30 sec washes in 0.5 \u00d7 SSC and a 15 sec wash in 70% EtOH. Arrays were spun dry in a custom centrifuge and stored until scanning." ] },{ "paper_id": "013ff749a58f92db7e227f7acbe47d050175851c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The genome sequence reported in this study will promote a better understanding of the molecular pathogenesis and genetic diversity of PEDV.", "Accession number(s). The complete genome sequence of PEDV strain CH/GX/2015/ 750A has been deposited in GenBank under the accession no. KY793536.", "This work was supported by grants from the Science and Technology Projects of Fishery and Husbandry of Guangxi Province, China (grants 201633041, 201633044, and 201633034)." ] },{ "paper_id": "014336e4855d194c1833ba91c8ae3b302cbeafe2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The peripheral lymphocytes were separated from anticoagulant blood. The concentration was diluted to 1.0 \u00d7 10 6 cells/ml with PBS. For two-color staining, peripheral blood mononuclear cells were treated with a mixture of anti-CD3 monoclonal antibody (IgG2a) and anti-CD4 (IgG2b), CD8 (IgG2a) followed by incubation with a mixture of PE-conjugated anti-pig IgG2a (for anti-CD3) and either Alexa Flour 647 mouse anti-pig IgG2b (for anti-CD4), FITC anti-pig IgG2a (for anti-CD8), respectively [39, 40] . Then, flow cytometry analysis was performed on a BD FACSCaliburTM (BD Biosciences, USA). T cell subsets was represented as the percentages of CD3+, CD3+CD4+, CD3+CD8+ in peripheral blood.", "All methods and experimental protocols were conducted under the approved guidelines of Sichuan Agriculture University (Chengdu, China) and approved by the ethical committee of the Laboratory Animals Care (Chengdu, China).", "Diarrhea index \u00bc summary of diarrhea scores animal number in the group \u00c2 number of days of trials" ] },{ "paper_id": "014d7df59dc6c5ed456bf19b76b394e920d3a9dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The protocol for capturing and sampling of bats was approved by the Chung Yuan Christian University Animal Care and Use committee and the agriculture bureau of regional government (No. 105024).", "Results" ] },{ "paper_id": "015729be3f439e9ef2033276a4ef14df8873dda9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2.6. Statistical Analysis. The selectivity index (SI) was determined by the ratio of TC 50 to IC 50. All experiments were performed in triplicate, and three independent experiments were conducted. Data were presented as mean \u00b1 SD and ", "Herpes simplex virus type 1 (HSV-1) is an important pathogen for humans, and discovery of novel effective antiherpetic drugs without adverse effects is of great interest. The primary symptoms of herpes infection include a prodromal flu-like syndrome with fever, headache, malaise, diffuse myalgias, followed by local symptoms consisting of itching and painful papules. Gingivostomatitis and pharyngitis are the most frequent clinical manifestations of first episodes of HSV-1 infection. After establishing latency, HSV can reactivate, causing frequent recurrent infections in some patients, whereas most people experience few recurrences [1] . The clinical manifestation of the disease exhibits different severity in immunocompetent patients and in addition some patients always encounter recurrent attacks [2] . However in immunocompromised patients and neonates, herpetic infections can cause serious systemic illnesses. Recurrent herpes labialis is the most frequent clinical manifestation of reactivated HSV-1 infection.", "Grant from Iranian Ministry of Health (to A. Astani)." ] },{ "paper_id": "015a5be4701f244a51d6c244c2ba5b69ac68dd9d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Exosomes labeling and confocal imaging. Exosomes were loaded with 1X CellMask Deep Red Plasma Membrane stain for 10 minutes at 37\u00b0C. Exosomes were then washed with PBS and centrifuged at 100,000 x g for 70 minutes in TLA 100.3 rotor (Beckman Coulter) to pellet exosomes and resuspended in culture medium.", "Filovirus outbreaks occur sporadically, but with increasing frequency. With no current approved filovirus therapeutics, the 2014 Makona Ebola virus epidemic in Guinea, Sierra PLOS Pathogens |" ] },{ "paper_id": "015c335c8cb9e5eabb352e81c0f38bf6f781b202", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was conducted in a rural area of Rachuonyo South district, Nyanza Province in the western Kenyan highlands that spans about 300 km 2 .", "There is one main road that runs through the area and the landscape consists of rolling hills and several large rivers (Fig. 1) . The population mostly comprises people from the Luo ethnic group whose main occupation is subsistence agriculture. Compounds typically comprise extended families living in proximity to their fields or in multi-unit structures in the few, more urban, market centres [26] .", "The ideal geolocation approach in a rural setting will ultimately depend on the information available, the objectives, whether it be monitoring for epidemics or planning for disease control interventions, and the required spatial precision/accuracy. The geocoding approach requires that an accurate and up-to-date list of names of compound heads is available, which is unlikely to be the case outside areas of active community-based research. The geocoding approach also relies on names recorded being complete and recorded consistently; a difficult task in busy facilities. There may also be challenges in obtaining correct information from people who may want to remain anonymous. Moreover, a systematic bias is inevitable as compounds whose head has a common name or is the head of multiple compounds will never be matched unless other variables are also considered. However, in areas where a complete database is available, through land registries for example, or if overall accuracy is less important, geocoding could provide a useful geolocation approach.", "For compounds that were incorrectly located, the median distance to the correct block was 489 m (IQR 229-1036 m), 1036 m (IQR 737-1737), and 1737 m (IQR 1179-2728) for the block only, >500 m buffer, and >1000 m buffer, respectively. The median distance of compounds incorrectly located from the identified cells was 539 m (IQR 236-1095 m), 1055 m (IQR 737-1644) including a 500 m buffer, and 1588 m (IQR 1200-2180 m) including a 1000 m buffer. Moreover, the proportion of people that were correctly identified to a specific block or cell significantly varied per facility (block only, P = 0\u00b7007; >500 m, P = 0\u00b7003; >1000 m, P < 0\u00b70001).", "This study was approved by the ethics committees of the London School of Hygiene and Tropical Medicine (LSHTM 5956) and the Kenya Medical Research Institute (SSC 1589). Individual informed consent was sought from all participants of the health-facility survey by signature or thumbprint accompanied with the signature of an independent witness. As defined in the Kenya national guidelines, participants aged <18 years who were pregnant, married, or a parent were considered 'mature minors' and consented for themselves [31] ." ] },{ "paper_id": "0162b627476379a84d5a92480a881efdd3063f66", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "01669153236899edec9fff5fc4fb19a742c3dfef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our study had several limitations that could influence the results of analyses performed. False negative laboratory results may have been obtained due to the late referral of patients to clinics. Individual questionnaires were filled out during sampling and subsequent data regarding course of disease were not collected so we were unable to assess disease severity characteristics (developing pneumonia, need for ICU, etc.). For the same reason, we did not evaluate chronic conditions among non-fatal ILI/SARI cases to determine risk factors associated with any severe courses of disease.", "https://doi.org/10.1371/journal.pone.0201207.g005" ] },{ "paper_id": "0180abece22ace6548f4601591c98059808d0509", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Selective pressure analysis. The number of synonymous substitutions per synonymous site, d S , and non-synonymous substitutions per non-synonymous site, d N , in VP1 were calculated using Nei-Gojobori method (Jukes-Cantor) in MEGA5. Sites under positive selection were inferred using single-likelihood ancestor counting (SLAC) and fixed effects likelihood (FEL) methods as implemented in DataMonkey server (http://www.datamonkey.org). The overall \u03c9 (d N /d S ) value was calculated according to NJ trees under the TrN93 substitution model. Positive selection for a site was considered to be statistically significant if P-value was < 0.1. A mixed-effects model of evolution (MEME) was further used to identify positively selected sites under episodic diversifying selection in particular positions among different clades within a phylogenetic tree even when positive selection is not evident across the entire tree. The relative residue abundance within BC and DE-surface exposed loops were depicted using WebLogo.", "A bimodal age distribution was observed among the 30 patients (male: female = 19:11) with EV-D68 infections (Table 1) , which included 22 children (< 18 years), one 37-year-old adult and seven elderlies (> 60 years). Of the seven elderlies, two resided in elderly homes (patients 19 and 23). A 15-year-old adolescent (patient 6) and a 37-year-old adult (patient 13) were also institutionalized. Close contacts of three patients were noted to have recent respiratory illnesses, including siblings of patients 3 and 4, and domestic helper of patient 28. One elderly (patient 20) had recent travel history to mainland China. No epidemiological linkage was identified among the 30 patients.", "Scientific RepoRts | 6:25147 | DOI: 10.1038/srep25147" ] },{ "paper_id": "0181010a40e179c9b66d8b1f0eaac4fbf0ab6341", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "018269476cd191365d6b8bed046078aea07c8c01", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The parameters of the BHRP model were shown in Table 1 .", "Therefore, the BHRP model was simplified as RP model and is shown as follows:", "In the model, people and viruses have different dimensions. Based on our previous research [15] , we therefore used the following sets to perform the normalization:", "By the next generation matrix approach, we can get the next generation matrix and R 0 for the RP model: ", "The R 0 of the normalized RP model is shown as follows:" ] },{ "paper_id": "01880ef487dfed3681dd6d296a0a82417b8f38a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Poliovirus is found within the Human Enterovirus C species of the Picornaviridae family and can be classified into three distinct serotypes (1, 2 and 3). Most poliovirus infections cause an asymptomatic incubation period followed by a minor illness characterized by fever, headache and sore throat which mainly affects children. However, PV infections can lead to paralytic poliomyelitis which can result in death. Following the WHO 1988 polio eradication program, the number of poliomyelitis has been reduced by 99% worldwide but a small number of countries still have sporadic outbreaks of polio [22] .", "A previous study compared a DENV vaccine candidate strain, DENV-3 PGMK30FRhL3 (PGMK30), which produced acute febrile illnesses with another clinically safe DENV vaccine " ] },{ "paper_id": "0188acc1eba8c0a3adef55aeada7de552cf855be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bootscanning analyses were performed using the default settings of SimPlot software [20] . ChinaGD02 strain was used as the query sequence and was compared to those of other HCoV-NL63 subgenotype strains.", "The complete and partial genomes of human coronavirus NL63 identified in this study were deposited in GenBank under the accession numbers: MK334043-MK334047, MK342125-MK342133." ] },{ "paper_id": "018b618ea132d47ffb43b003a6c78cb9eeadc017", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell lines originally purchased from American Tissue Culture Collection (ATCC), such as human embryonic kidney (HEK 293T, ATCC CRL-3216) and baby hamster kidney (BHK21, ATCC CCL-10) cells, were adhered to recommended ethics approvals and standards.", "antibodies from macaques infected with the third closely related isolate of CHIKV.", "(PDF)" ] },{ "paper_id": "01a462bf8cf2cd973d1651b991d27c9556d2ae3c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.ppat.1006714.g004", "https://doi.org/10.1371/journal.ppat.1006714.g008", "The structures were solved by molecular replacement using the PHENIX suite of programs [79] . Rebuilding was performed with Coot [80] . Refinement involved two TLS groups (one for each molecule). Initial noncrystallographic symmetry restraints were removed in later stages of refinement.", "The symptoms occurring during compatible infections (e.g. chlorotic symptoms) represent the final outcome of complex biochemical and physiological perturbations occurring upon replication and spread of the virus, and result from both the combination of virus demands, cellular stresses and host defense reactions [55] . Despite recent progress in deciphering plant/ virus interactions using systems biology approaches [56] [57] [58] [59] , the molecular mechanisms involved in disease symptoms still remain unclear." ] },{ "paper_id": "01b5ae0cce289ca9cdcebc4079f960e833cfbd79", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Many betaretroviruses were investigated (JSRV to mIAP in Table 1 ). All of the viruses in this group rely on double frameshifting mechanism to express their pro and pol genes. ", "During the translation process, ribosomes are capable of performing some nonstandard decoding events which provided that appropriate signals are present in the mRNA being translated. These unusual events are referred to as \"recoding\" [1, 2] . Two of the major recoding mechanisms are programmed \u22121 ribosomal frameshifting (PRF) and stop codon readthrough. These mechanisms are utilized by retroviruses and some other RNA viruses to express their structural and enzymatic proteins at a defined ratio [1, [3] [4] [5] . Both \u22121 frameshifting and stop codon readthrough are site specific and occur at a defined frequency much higher than the background error rates of maintaining the reading frames.", "There are three primate (simian or human) lentiviruses: simian immunodeficiency viruses (SIV) and human immunodeficiency viruses type-1 and type-2 (HIV-1 and HIV-2) in the Recode database. The database gives only one representative sequence for each of these viruses. These are the particular sequences we investigate in this study. No potential pseudoknot was detected downstream from the gagpol frameshift site in SIV." ] },{ "paper_id": "01be6aef7ae6555eef2062bddb57f8643d1244e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To investigate the best order of EPSs' antiviral effects, three experimental procedures were used as follows:", "Statistical data processing was performed according to standard approaches for calculating statistical errors (standard deviation) using Microsoft Excel 2010. The results were expressed as mean \u00b1 S.D. for three independent experiments. The Student's t-test (unpaired, two-sided t-test) was used to evaluate the difference between the test sample and control. A p value of <0.05 was considered statistically significant.", "Therefore, the development of new antiviral drugs that would be effective against adenoviruses without adverse effects, for a wide range of patients, including long-term users, is very urgent." ] },{ "paper_id": "01bf19ea2cb2baab425377eaae3286190e9bf975", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical comparisons were performed using GraphPad Prism 5 (GraphPad Software Inc., USA). Results are presented as means \u00b1 SEM, and statistical significance was assessed at P < 0.05, 0.01, or 0.001.", "Cloning and Sequencing of the ev21 Element and ALV-J Genomes", "The full-length proviral ALV-J genomes were amplified with previously published primers ." ] },{ "paper_id": "01c25f9838ef8e005bf720c4f76e67a9f1038ff0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Three covariant matrices were constructed as:", "1 C = \u23a1 \u23a3 1 C 1,1 1 C 1,2 1 C 1,3 1 C 2,1 1 C 2,2 1 C 2,3 1 C 3,1 1 C 3,2 1 C 3,3 \u23a4 \u23a6 ", "Here, expansion of D 2 yielded three equations:" ] },{ "paper_id": "01c6c44650ad5466cdb134a28d0b14700fa3906d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The variables Z and h are unobserved, and the goal is to infer their joint posterior distribution,", "Assuming all non-synonymous mutations at a given gene have the same selection coefficient and all synonymous mutations are neutral, population genetic theory says that v should be given by [70, 90] :", "Cytokine/chemokine C-C motif: CCL1 (P = 5.2610 24 ), CCL20 (P = 7.6610 24 );", "The prior probability of a history Z i is simply a product of the prior and the relevant switching probabilities:" ] },{ "paper_id": "01c6ed4b3dee404e4d908af40ab93183b573e9ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Patient allocation will follow a concealed process using sealed, fully opaque, numbered envelopes.", "Frequency and duration of follow-up", "Not applicable." ] },{ "paper_id": "01cadfe2bb23b6989e57fce2ba744691557faa93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The reported perceptions of risk in this study are low. However, the actual risks are also likely to be low for a well-trained and experienced volunteer. Thus, we believe that the perceived risks represent the actual risks.", "We used our descriptive analysis of the data and a linear regression to study the relation between the sum score of each domain versus the age group and country where the volunteer worked. We calculated the sum scores by adding up the scores within each domain.", "Koopmans, Chantal Reusken, Aura Timen.", "Of the 251 volunteers, 162 (65%) volunteered to go to Sierra Leone, 76 (30%) went to Guinea, and 13 (5%) went to Liberia. The first 70 participants (28%) volunteered in 2014, and the remaining 180 (72%) volunteered in 2015. Most volunteers (45%) were 26 to 35 years old and 27% were 36 to 45 years old." ] },{ "paper_id": "01cff21366d475b5bc294c90da89a521b510234a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "01e22956c79df3220a67bce71cf22de95d29b723", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ELISA plates were coated with 50 ng of purified virus or 100 ng of rE in carbonate buffer at pH 9.6 for 2 hrs at room temperature and incubated with blocking buffer (0.05% TBS-T containing 3% skim milk or 3% normal goat serum) at 37 o C for 1 hr. Human immune sera or hMAbs serially diluted in blocking buffer were added for 1 hr at 37uC followed by alkaline phosphataseconjugated goat anti-human IgG (Sigma) for 1 hr at 37uC. Finally, p-nitrophenyl phosphate substrate (Sigma) was added to each well and the reaction was allowed to develop for 15 minutes before recording optical density at 405 nm on a spectrophotometer.", "DENV neutralizing antibodies was measured by a focus reduction neutralization test (FRNT) with Vero cells or using a flow cytometry-based neutralization assay with the U937 human monocytic cell line stably transfected with DC-SIGN as previously described [31] .", "Human Antibody Response to Dengue Infection www.plosntds.org or the A strand regions that have previously been described as targets of mouse MAbs [23] ( Figure 4C )." ] },{ "paper_id": "02049ffbdb20997055c4def3516af0e6e40dd427", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following source data is available for figure 3:", "The following source data is available for figure 6:", "mRNA quantification by quantitative reverse transcriptase-PCR (qRT-PCR)" ] },{ "paper_id": "021144f6c1945b9bff9ea9e4b04b24dcf53330b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PEDV belongs to the Alphacoronavirus genus and can cause an acute and highly contagious enteric disease. Its clinical symptoms include watery diarrhea, severe enteritis, vomiting, and weight loss; the mortality rate can reach 50%-90% in suckling piglets [8] [9] [10] . In 1977, Pensaert isolated a new coronavirus-like particle associated with diarrhea from Belgian swine breeding farms. This virus was different from TGEV and was designated CV777 [11] . Subsequently, the disease was reported in the United . Since 2010, massive PED outbreaks have been reported in Asia. In April 2013, there was a sudden occurrence of PED disease that rapidly spread across the United States, causing high rates of death among piglets [8] . Currently, PED is considered a pandemic disease that causes substantial economic losses to pork producers all over the world.", "Insect cells were cultured in Sf-900 II SFM (Invitrogen, Life Technologies, Carlsbad, CA, USA) at 27 \u00b0C. HEK-293T cells were grown in RPMI 1640 medium (Gibco, Waltham, MA, USA) supplemented with 10% fetal bovine serum at 37 \u00b0C with 5% CO2. CV777 is a PEDV prototype strain [11] , and CHGD-01 is a PEDV variant field isolate that was isolated in China in 2011 [21] .", "Insect cells were cultured in Sf-900 II SFM (Invitrogen, Life Technologies, Carlsbad, CA, USA) at 27\u02ddC. HEK-293T cells were grown in RPMI 1640 medium (Gibco, Waltham, MA, USA) supplemented with 10% fetal bovine serum at 37\u02ddC with 5% CO 2 . CV777 is a PEDV prototype strain [11] , and CHGD-01 is a PEDV variant field isolate that was isolated in China in 2011 [21] ." ] },{ "paper_id": "021af77daa9633d212e816cdbaf9f89240bfa3a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal experiments were approved by the Animal Care and Use Committee of the Fourth Military Medical University.", "The neuroblast cell line Neuro2a was bought from ATCC and kept in DMEM (Gibco, Grand Island, NY, USA) containing 10% fetal bovine serum (FBS, Gibco, Grand Island, NY, USA).", "All statistical analyses used GraphPad Prism version 6.01 software. Statistical differences were determined using the Student's t-test. P-values < 0.05 were considered significant ( * P < 0.05, * * P < 0.01, and * * * P < 0.001)." ] },{ "paper_id": "021fba0f252408868fa29b65686dedb3b3d6bf02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Global pesticide production should be highly effective, confer low toxicity and high safety coefficient, and exhibit satisfactory selectivity and environmental compatibility. Botanical pesticides have been widely investigated and applied because of their desirable properties [1] . New natural biological active compounds must also be discovered to promote the development of environmentally friendly pesticides [2] . As such, the use of biological active ingredients [3] or action targets [4] as guides is an important aspect in research and development of botanical pesticides." ] },{ "paper_id": "02276a07ed2aa49afe07d97e7d7286b2b6fea532", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MDA5 is also subject to several types of activation that resemble those that activate RIG-I. Indeed, PP1\u03b1/\u03b3, USP3, RNF123, and TRIM40 target RIG-I and LGP2 and viral evasion", "Over the past decade, our understanding of intracellular sensor-mediated antiviral responses has expanded, and we know much more about the molecular mechanisms by which they are regulated via host and viral factors. This knowledge not only allows us to understand viral pathogenesis but also reveals how intracellular sensors are activated and regulated. Extensive knowledge of these mechanisms will allow for research and development of novel anti-inflammatory agents, immunostimulatory agents, new vaccines, and antiviral agents that target cellular regulators or specific viral proteins. Regardless, further work is needed to identify other cytosolic sensors (such as novel sensors of nucleic acids), other positive or negative regulatory molecules and related pathways, and novel escape mechanisms utilized by new viruses or variants.", "Taken together, results to date show that viruses express specific proteins that interfere with RIG-I " ] },{ "paper_id": "022efb5d64e88419546d697b6a5a96e6bc8a9fab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LGP2 activation supports MDA5-dependent signalling while inhibiting both RIG-I and Dicer. 82, 83 TLR and RLR activation stimulates IFN-I expression, which activates JAK-STAT signalling to modulate expression of hundreds of IFN-stimulated genes, thereby placing infected cells and local tissues in an antiviral state. 8 stimulation, 84 the IFN and RNAi systems compete in a manner detrimental to the efficacy of RNAi-based therapeutics.", "Viral infection often induces cytoskeletal remodelling, resulting in cytopathic morphologies including syncytia and tumor-like aggregates. Cells treated with actin depolymerising agents such as cytochalasin D show drastic reductions in production of numerous viruses, 38 Figure 2 ). Vimentin is reported to play a key role in replication complex assembly and modulating viral protein expression levels in DenV and HCV infection, respectively. 39, 40 Withaferin D targets the soluble form of vimentin 41 (Table 2) and has anticancer properties, although the effects of vimentin-targeting drugs in the context of infection have yet to be extensively studied.", "LGP2 recognises RNA as short as 12 nt irrespective of phosphorylation or hydroxylation at the 5 0 end.", "RNA virus evolution attempts to resolve this information economy paradox by extensively employing functional genomic secondary structures and noncoding regions, genome segmentation, compression (e.g. RNA editing, overprinting and frameshift reading) and gene product pleiotropy or multifunctionality (e.g. intrinsically disordered proteins). 17, [19] [20] [21] Yet another way is to manipulate host cell factors that are themselves multi-interacting or multifunctional 'hubs' of cellular activity, 22 whereby a single viral gene product subverts a single host factor to achieve net favorable control over numerous cellular processes. This can enable the virus to extract maximum utility from its informationally limited genome at minimal informational cost. Multiplying this effect across several viral and/or host gene products may enable the virus to extract a substantial 'return on investment' in terms of replicative fitness.", "Remarkably, siRNA-LNP 'cocktails' of perfect complementarity to Ebola virus (EboV) RNA have been reported to confer 100% protection in nonhuman primates when administered as late as 3 days post-lethal challenge. 54 Nevertheless, nucleotide escape mutants and genetic variation between EboV strains in different geographic locations necessitate accurate, up-to-date sequencing data on circulating strains in order to continuously generate effective siRNA cocktails. Recently, a protocol employing the MinION portable sequencer was developed that enabled the direct sequencing of an intact RNA virus genome (IAV) for the first time. 95 Direct sequencing of field EboV strains would drastically reduce the current development time of new siRNA-LNPs. Nevertheless, further improvements in this sequencing technology will be required for accurate, cost-effective, routine sequencing of substantially lower-yielding and genetically diverse field strains.", "Nearly 20 years elapsed between the first patent filings and the realisation of an approved RNAi-based therapeutic. While challenges remain, the coming decade appears likely to mark the beginning of the growth curve for creative new approaches to RNA-based therapeutics for antiviral and immunotherapeutic applications." ] },{ "paper_id": "0234207cba8165f1e1852b92ae0fa0d9e2f870fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 7:44122 | DOI: 10.1038/srep44122" ] },{ "paper_id": "023858d3191988a37587ab951db561a3db3ae2cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples were not collected from patients with chronic respiratory ailments; non-consenting caregivers, with history of hospitalization in the preceding 14 days, not admitted in hospital and children aged > 5 years." ] },{ "paper_id": "023af2216525c16fa52a75b99cc91ebb03e93107", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "interactions with Val530 and Pro531 of RBD, while light chain residues Asn30 and Asp92 form hydrogen bonds with main chain atoms of RBD residues Val527 and Ser532, respectively (Fig. 3C ).", "Neutralization assays were performed by incubating 100TCID50 (median tissue culture infectious dose) of pseudoviruses with 16 serial 1:3 dilutions of purified antibody at 37 \u00b0C for 1 hour. Huh7 cells (about 1.5 \u00d7 10 4 per well) were then added to the antibody and virus mixture. Infectivity was quantified by the luciferase activity 48 hours after infection. IC50s were calculated using the dose-response inhibition model in GraphPad Prism (GraphPad Software Inc.).", "route of transmission to humans could result from direct or indirect contact with this reservoir or with another intermediate. The prevalence of MERS-CoV-neutralizing antibodies in camels and the recent isolation of MERS-CoV from dromedary camels suggest that camels could be one of the intermediate hosts [15] [16] [17] ." ] },{ "paper_id": "023b805a96c852619186f55af4bbbdd5f9fa8156", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fecal and intestinal samples were collected from the Animal Disease", "Supplementary Materials: The following are available online at http://www.mdpi.com/2073-4425/9/12/591/s1, Table S1 : Oligonucleotides used for this study. ", "Materials and Methods" ] },{ "paper_id": "023dff96542ca1e77e3a1d08a2f3893ca1ebc057", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "c.", "e.", "Figure S1" ] },{ "paper_id": "0241ada1b12eaacadc56a59586bc1728a580583d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are presented as the means \u00b1 standard deviation (SD). Significant differences were determined by oneway analysis of variance (ANOVA) followed by Tukey's post hoc t test (GraphPad Prism \u00a9 Software).", "Cells were resuspended in 150 \u03bcl of FACS buffer (1 \u00d7 PBS containing 2% (v/v) FBS, 0.3% (w/v) NaN 3 and 1 mM EDTA) and incubated for 60 min at 4\u00b0C with a 1:100 dilution of antibodies specific for CD81 (AbD Serotec) or SR-BI (BD BioSciences) Following three rinses with FACS buffer, bound antibodies were detected by incubation for 1 h at 4\u00b0C with an phycoerythrin (PE)conjugated anti-mouse (BD Pharmingen) antibody at a dilution of 1:200. Cells stained with an irrelevant mouse immunoglobulin G (IgG) antibody and respective PEconjugated secondary antibody served as negative controls. Cells were washed three times, fixed in FACS buffer containing 4% (w/v) PFA, and analyzed by flow cytometry using the DakoCytomation CyAn system (Dako, Carpinteria, CA) and Summit Software v4.3 (Dako)." ] },{ "paper_id": "02480623218229a12cdbc4800defc262f7cc175c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IL-6 and IL-8 concentrations in HTR-8/Vneo supernatant exposed to LPS, ssRNA, or VEH for 12 h were determined using a human IL-6/8 ELISA Development Kit (Invitrogen by Thermo Scientific, Wilmington, NC, USA) according to the manufacturer's instructions (minimum detection limit, 2 pg/mL; intra-assay variation, 4.94%).", "Explant tissues attached to Matrigel were collected by cutting the membrane from the transwell inserts, were washed once with PBS (1x), and were fixed with paraformaldehyde (4%, 1 h). The tissues were dehydrated in ascending grades of ethanol, cleared in xylene, and embedded in paraffin. Sections (5 \u00b5m) were mounted on slides for Immunohistochemistry.", "Sequence Reference " ] },{ "paper_id": "024d0bef5417a110fb52607e85ec80eb4d7d92a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Semi-thin sections of 1 \u03bcm were obtained using an ultramicrotome (Ultracut E, Leica-Reichert Jung, Wetzlar, Germany) and stained with toluidine blue for correlative light microscopy. Ultrathin sections were cut at 70 nm, collected on copper grids (200 meshes) and stained with uranyl acetate and lead citrate. Images were examined in a Hitachi H-7100 electron microscope equipped with a Gatan 832 digital camera (Gatan, Inc.)." ] },{ "paper_id": "025509677d6507aaf63c46fc8efbe60b6d63a820", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We collected blood samples (in sterile EDTA tubes with vacutainer blood-sampling system (BD)) from mothers at 53-54 and 112 gestation days (at 0 and 59 days post-fetal inoculation), on the day of parturition, and 14 and 21 days after parturition. After blood centrifugation (2,000g, 20 min, +4\u02daC) plasma was aliquoted and immediately frozen (-80\u02daC). Colostrum was collected at delivery day, centrifuged (2,000g, 20 min, +4\u02daC), and immediately frozen at -80\u02daC.", "RNA was isolated using TRIzol (Thermo Fisher Scientific) lysis and extraction, and then cleaned using Total RNA Purification Kit (Norgen Biotek). RNA was assessed on a Bioanalyzer and all samples had RNA Integrity above 8.5. Complementary DNA (cDNA) libraries for sequencing were prepared using NEBNext Ultra II Directional RNA Library Prep Kit for Illumina with rRNA depletion (New England Biolabs). Libraries were sequenced on a NovaSeq as paired-end reads using the 150 base read kit. Over the whole experiment, there was an average of 26 million paired-end reads per sample. Sequencing data were mapped and quantified using the pseudo alignment method of Kallisto [132] . A sequence database of coding and non-coding transcripts was generated from ENSEMBL Sus scrofa 11.1. The count table was assembled using tximport in R and normalized using EdgeR then converted into a normal distribution using the voom function and differential expression was calculated using linear and Bayes models as part of the R package limma. Gene set enrichment was done using human annotation of Gene Ontology using the R function camera.", "We used low-passage, contemporary, Asian-lineage Zika virus (ZIKV) strain PRVABC59 [GenBank: KU501215.1] isolated from human serum specimen (Puerto Rico, 2015) [120] . After two passages on C6/36 cells, cell culture media containing ZIKV was centrifuged (12,000g, 20 min, +4\u02daC), and the supernatant was collected. Media from virus-negative C6/36 cells was used for mock-inoculation. The absence of mycoplasma contamination in all inoculums and cell cultures was confirmed using LookOut Mycoplasma PCR Detection Kit (Sigma-Aldrich).", "The set enrichment results from camera were graphed in Cytoscape using the Enrichment-Map plugin. All networks were generated using a Jaccard + Overlap with a cutoff of 0.375 and a Combined Constant of 0.5. Sub-networks were discovered using GLay cluster and annotated using the WordCloud plugin of the top 4 words with a bonus of 8 for word co-occurrence. Gene expression data are provided in S2 Table. An accession number for RNA-seq data is PRJNA573521 in NCBI BioProject." ] },{ "paper_id": "0257dffb6a2cc8bdf6d252c400a38419ef256505", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(a) S1", "(b) S2 " ] },{ "paper_id": "0257e6797e12beb91a4a4fcd7130f90d84260718", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "authors contributed equally to this work. Citation details: Yusim,K., Yoon,H., Foley,B. et al. Integrated sequence and immunology filovirus database at Los Alamos.", "Database URL: www.hfv.lanl.gov", "This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited." ] },{ "paper_id": "0263ef539a1344a642b1f4ff11aee6bc6ca84a34", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2017, 9, 54 6 of 9", "(1) to highlight diversity and excellence of Canadian virology research;", "(2) to mobilize Canadian virus researchers across different disciplines (basic, clinical, social and epidemiological) to create a broader base of research expertise committed to tackling new challenges. " ] },{ "paper_id": "026447f6e8f25d774926c5f38f8c8ae1f62aa54d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A number of recent reports have underlined the relevance of astrovirus infections also in livestock populations. Although summarizing all available data on astrovirus detection in mammalian livestock would by far exceed the scope of this review article, we here give a short overview on the current state of knowledge regarding bovine, ovine and porcine astroviruses (BoAstV, OvAstV, PoAstV). These species are highlighted because of the recent detection of novel BoAstV and OvAstV strains causing encephalitis [43] [44] [45] [46] [47] [48] , and the sequence similarities observed when comparing PoAstV strains with other mammalian strains including human astroviruses [49, 50] . These animal species live in close contact to humans and might therefore play a role in the transmission of astroviruses that are not strictly species-specific.", "Novel astroviruses have been identified by metagenomics approaches whenever diseases of unknown etiology have occurred e.g., in humans, cattle or sheep [18, 45, 47, 48] . Metagenomics have been widely used as an unbiased system to obtain potentially causative viral sequences in case standard procedures such as PCR fail to reveal the causative agent. Furthermore, it can be utilized to obtain more sequence information or even full-length sequences. With regards to the lack of bat astrovirus isolates, metagenomics might be a suitable alternative to gain more detailed sequence information for further analyses. Nonetheless, small sample sizes and low virus titers in the samples might also impede these approaches.", "There is strong evidence that multiple astrovirus sero-and subtypes may infect pigs. However, the clinical significance of this finding is still doubtful, since various samples were collected from healthy pigs [13, 56] . However, multiple studies from South Africa [57] , Canada [13, 49] , USA [50, 58] , Colombia [59] , China [60] , Croatia [56, 61] , Czech Republic [62] , Germany [63] and Hungary [12] have described several novel astroviruses to be circulating in the pig population. Astrovirus partial and full-length sequences were detected in fecal and extraintestinal samples such as serum [12, 13, 49, [56] [57] [58] 62] . There is a remarkably high fecal prevalence of astroviruses in pigs combined with a broad genetic diversity [13, 56, 59, 61] . At least five lineages (PoAstV1-5) were identified to circulate in the investigated area of the USA with generally low sequence similarities [50] . Frequent co-infections of individual pigs with multiple astrovirus strains were found that might favor recombination events [50] . Phylogenetic links to astroviruses linked to other animal species were observed that could imply past cross-species transmission and recombination events, which might have included cattle, roe deer, mink, cats, humans and potentially other species [13, 50, 56, 59, 61] . Although the clinical significance for pigs remains to be investigated, these recent findings underline the importance of pigs as a porcine astrovirus reservoir." ] },{ "paper_id": "02652961663ca435c195fb0ed3e43642e04cfab3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "0266337807a2aab25e7dc43967cba01860fe5d86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical assessment. After screening and assent, a clinical officer or assistant medical officer then sought a detailed clinical history, followed by a physical examination. The attending officer entered all clinical data in a standardized electronic clinical case report form on the tablets using ODK Collect.", "Statistical analysis. Statistical analyses were performed using SAS version 9.3 software (SAS Inc., Cary, NC). Descriptive statistics was presented as medians, ranges, and interquartile ranges for continuous variables and as proportions for categorical variables.", "The lack of consistency in methodological approaches to AFI surveillance in low-resource areas has resulted in an Figure 2 is not to scale. This figure appears in color at www.ajtmh.org.", "Research ethics. This study obtained ethical clearance from the National Health Research Ethics Committee of the National Institute for Medical Research (NIMR/HQ/R.8a/Vol. IX/1735) in Tanzania." ] },{ "paper_id": "026c59766e222f22b416a6525ae3194a140b5faa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Identified viral fragments were used as a template for primer design (sequences available on request) to obtain the nearly complete genome sequences. Sequencing was performed employing Big Dye terminator chemistry (BigDyeH Terminator v1.1 Cycle Sequencing Kit, Applied Biosystems, Nieuwerkerk aan de IJssel, The Netherlands).", "Absolute quantification of viral DNA (copies/ml of serum or whole blood, copies/g of tissue) was achieved by real-time qPCR using plasmid-based standards and primers and probes listed in table 1 (HotstarTaq Plus Master Mix Kit, Qiagen, Hilden, Germany).", "Primer and MID (Multiplex Identifier) sequences were trimmed from every read. Sequences were then assembled with Codon-Code Aligner software version 3.5.6. Contigs and unassembled sequences were compared to known nucleotide and protein sequences contained in GenBank database using different BLAST tools (blastn, blastx and tblastx) [25] .", "No other reads with clear identity to any known viruses were detected in any of the samples." ] },{ "paper_id": "02753048c4dc699d155288935b9dc6517a79f279", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Future studies will test NIPARAB protection in an animal model susceptible to NiV, such as Syrian golden hamsters, and will also establish the minimum protective dose and capacity to reduce NiV disease severity and/or mortality. Furthermore, protection against HeV challenge will be assessed since there is wide evidence for sera cross reactivity between these two henipaviruses. [52] [53] [54] ", "npj Vaccines (2019) 4:15 ; https://doi." ] },{ "paper_id": "02766b20eeb39ff051a2f110def2e4bf8b9b010b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The combined peptide mixtures were separated by reversed phase high-performance liquid chromatography (HPLC) (Ekspert ultraLC 100, AB Sciex, USA) on a Durashell-C18 reverse phase column (4.6 mm 6 250 mm, 5 mm 100 \u00c5 , Agela). The mobile phases used were composed of 20 mM ammonium formate (pH 10) in water (labeled mobile phase A) and 20 mM ammonium formate (pH 10) in acetonitrile(ACN) (mobile phase B). The flow rate was 0.8 mL/min, and the elutant was collected into 48 centrifuge tubes at each minute after the first 5 min. Each aliquot was then dried by vacuum freezing.", "After introducing TGEV into the ST cells, we observed the induction of typical CPEs, including cell rounding, swelling, granular degeneration of the cytoplasm, cell detachment, and severely diseased cell morphology, from 40 to 64 h after inoculation ( ", "The peptides were then analyzed with a nanoflow reversedphase liquid chromatography-tandem mass spectrometry (nano-RPLC-MS/MS) system (TripleTOF 5600, AB Sciex, USA). The above 48 tubes were merged into 10 components dissolved in 2% ACN and 0.1% formic acid (FA), then centrifuged at 12,000 6 g for 10 min. The supernatant (8 ml) was used for loading at a rate of 2 ml/min, with a separation rate of 0.3 ml/min. The mobile phase A used in this analysis was composed of 2% ACN and 0.2% FA, while mobile phase B was composed of 98% ACN and 0.1% FA. The following MS parameters were utilized: source gas parameters (ion spray voltage: 2. ", "Western blot confirmation of altered expression for three of the differentially expressed proteins" ] },{ "paper_id": "02783b0989ab6a54fd4af139d787b69b9d9d009e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. Extraction of total nucleic acid; reverse transcription to convert target RNA sequences to cDNA -1 hour 2. Multiplexed amplification of targeted gene sequences by thermal cycling -2.5 hour 3. Pooling, purification and fragmentation of amplification products -0.5 hour 4. End-labeling (biotinylation) of amplification products -0.5 hour 5. Hybridization of labeled products to microarrays -4 hour to 16 hour (overnight preferred) 6. Washing and staining arrays -1.5 hour 7. Scanning arrays for data acquisition -0.15 hour", "The Naval Health Research Center (NHRC) collects, analyzes, and archives throat-swab specimens from human subjects as part of respiratory infection surveillance at US basic military training facilities. Research use of donated specimens is permitted under the local Institutional Review Board's approved protocol-compliant informed consent (see Acknowledgments). Throat swabs are suspended in stabilizing transport media and archived frozen at 280uC. Viral culture and PCR-based testing protocols are used at the NHRC diagnostic laboratory to determine the presence or absence of influenza virus, and these assays are accredited by the College of American Pathologists as compliant with the Clinical Laboratory Improvement Amendments of 1988, and the Department of Defense Clinical Laboratory Improvement Program of 1994.", "This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose." ] },{ "paper_id": "027f86c44365e0ba6a6c26e24134c4c3e98a72ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Taken together, proteomic analyses are boosting our knowledge of viral replication and disease etiology and are allowing the identification of new cellular targets that might be suitable for drug development.", "These approaches are complementary and allow the exploration of different interaction search spaces. Other methods have also been developed to be amenable to a high-throughput format. Among them, MAPPIT is a cytokine-based mammalian PPI trap assay [45] and LUMIER is a tag-precipitation assay coupled to renilla luciferase [46] . To our knowledge, none of these methods has yet been applied in a high-throughput VH PPI study.", "Antiviral small molecules that inhibit cellular functions or VH PPIs have been reported in the literature, but currently no database has been developed to reference them. Below, we review a selection of host-oriented molecules with antiviral activity in vitro or in vivo against two major viruses infecting humans, influenza and HCVs.", "Combining the evolving VH PPI dataset with the drugtarget interactions described in DrugBank has already revealed the great potential of drug repurposing for the discovery of antiviral molecules (Figure 3b ). This potential has been accelerating since the first high-throughput screenings for VH PPIs." ] },{ "paper_id": "028382edbe67a35f1e099fa0607fa9a4922a45d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/ mBio.00229-17. ", "Female C57BL/6 or P2X7 receptor knockout mice (8 to 10 weeks old) purchased from Jackson Laboratories (Bar Harbor, ME) were used for all experiments. For virus challenges, mice were anesthetized by intraperitoneal injection of a mixture of ketamine (100 mg/kg of body weight) and xylazine (5 mg/kg) before intranasal administration of a lethal dose of influenza virus PR/8 or NL/09 in a volume of 30 l. Animals were monitored daily for clinical signs of illness, and body weights were recorded daily for 14 days. Upon reaching 75% of initial body weight, animals were humanely euthanized." ] },{ "paper_id": "02843e9be924677d6541e0221a26501ce2111aaa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Histological examination. Porcine tracheae and bronchi were obtained from a local slaughterhouse and fixed in 10% paraformaldehyde (PFA), processed routinely, embedded in paraffin, sectioned at 5 \u03bc m, and stained with hematoxylin and eosin (H&E).", "Cy3-labeled antibody against \u03b2 -tubulin (Sigma). Secondary antibodies were Alexa Fluor \u00ae 488, 568 or 633 conjugated antibodies (Life Technologies). All antibodies were diluted in 1% bovine serum albumin and incubated in RT for 1 h. IFA was performed by using a Leica TCS SP5 AOBS confocal laser scanning microscope. For the processing and analyses of confocal images, LAS AF Lite software (Leica) and ImageJ/Fuji software (National Institutes of Health) were used. The image stacks with a z-or y-distance of 1.0 \u03bc m per plane were merged. The images were generated by ImageJ/Fuji software using maximum intensity projection filter. The results were repeated at least with six PBECs from three independent donors, three fields per culture were examined by confocal laser scanning microscopy.", "Data are shown as means \u00b1 SEM. All statistical analyses were done by using Prism 5 software (GraphPad Software)." ] },{ "paper_id": "0293ec2b1cf8097392297cffd06854d2f37348f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For both patient groups, traditional standard-of-care laboratory diagnostic tests for respiratory infections were performed according to the requests of physicians, including smears, cultures, and serological tests. The serological test in our study was the PNEUMOSLIDE IgM (Vircell) commercial kit based on indirect immunofluorescence.", "The prospective cohort was enrolled in Shanghai, China, between ", "Yiyi Qian https://orcid.org/0000-0002-0714-3894" ] },{ "paper_id": "02974b9466bf593193d05ada669d7ff0567bb657", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "02998402c64a65e3ea2fd0fdd8f688aeebda6192", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by the Ministry of Agriculture and Rural Development of Vietnam (726/2017/H\u00d0-KHCN-CNSH) and the Ministry of Agriculture, Forestry and Fisheries of Japan.", "Data availability. The genome sequence of the XTND/2018 strain has been deposited in DDBJ/ENA/GenBank (accession number LC493088). The raw sequence reads were deposited in the DDBJ Sequence Read Archive (DRA) under the BioProject and DRA accession numbers PRJDB8629 and DRA008757, respectively.", "Sapelovirus A (SV-A) is currently spreading as an enteric pathogen of pigs worldwide. We isolated SV-A strain XTND/2018 from the small intestine of a dead pig with severe diarrhea in the north of Vietnam and determined the genomic sequence. This is the first report of the genomic sequence of SV-A circulating in Vietnam." ] },{ "paper_id": "02a009e42054081b441d0f4b203679c4b0cae38d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The marmoset study requires a sample size of 3 for adequate power to determine if the incidence of seroconversion is significantly greater than that which would be expected in the population. This sample size will allow the experimenter to detect seroconversion in at least 2 of 3 animals (66%) versus the expected population constant of <1% at a 95% confidence level using a one-tailed binomial test for proportions.", "Hantaviruses are negative-sense RNA viruses transmitted to humans from small animal hosts. Different viral species are associated with one of two disease syndromes: hemorrhagic fever with renal syndrome (HFRS), or hantavirus pulmonary syndrome (HPS) [1] . Hantaan virus a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 (HTNV), primarily found in Asia, is among the most prevalent HFRS-causing hantaviruses with a case fatality rate of between 1-15% [2] . Puumala virus (PUUV) causes most HFRS cases in Europe, though its case fatality rate is lower at <1% [3, 4] . There are currently no FDA licensed vaccines or therapeutics for either HFRS or HPS [5] .", "Urine was expressed from anesthetized ferrets and analyzed by urinalysis regent strips (VWR, Radnor, PA)." ] },{ "paper_id": "02a29bd2f39ecdbbb5e51a003c0bc7818029f384", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza is a respiratory communicable disease caused by influenza viruses (IVs), which are classified antigenically based on the distinctions of the nucleoprotein (NP) into four genera: Influenza-A viruses (IAV), influenza-B viruses (IBV), influenza-C viruses (ICV), and influenza-D viruses (IDV) [10] . IVs have single-stranded, segmented, viral RNA genome (vRNA). Both IAV and IBV contain eight segments, while ICV and IDV contain only seven segments [11] . The genomic eight segments of IAV translate to more than 10 viral proteins [12] .", "Mice showing a weight loss more than 30% of the initial body weight were euthanized and documented as dead. Body weight was monitored daily for 2 wpi.", "The animal trial in our study was conducted in accordance with the guidelines of the Egyptian animal welfare regulations and legislation. The ethics committee of the NRC, Egypt, approved the animal trial with number (16-247) and the regulations of Animal Welfare Assurance with identification number (A5939-01). All experiments were performed in a biosafety level 2 (BSL2) containment laboratory approved for such use by the local authorities (NRC, Egypt). For MERS-CoV neutralization assays, Class III Biological Safety Cabinet SEA-III BSC (Germfree, Ormond Beach, FL, USA) was used." ] },{ "paper_id": "02a9fd5f564cb3a5b6b1fdbcd9df585b8e24a2de", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study protocol was reviewed and approved by the Ethics Committee of Huazhong University of Science and Technology (permit number S240). Written informed consent was obtained from all human participants on or before each study.", "The grave threat posed either by the highly pathogenic avian influenza virus or by another emerging virus like the 2009 pandemic H1N1 (pH1N1) requires rapid laboratory detection of the first cases or clusters of influenza infection [1] . PCR-based nucleic acid (NA) assays are the first-choice techniques for flu surveillance and diagnosis due to their rapidity, sensitivity and specificity, although virus isolation is still critical for antigenic analysis and characterization of influenza virus (flu-v) [1, 2] .", "Throat swabs. A total of 49 throat swabs were retrospectively selected for this study. These samples had been characterized by PCR as positive (strong, medium or weak) for pH1N1, seasonal flu A/H1, H3, or flu B virus.", "To ensure that all the samples could be handled safely within containment level 2 facilities, a pH1N1 isolate A/Zhongshan/ SWL02/2009(H1N1) (pH1N1SWL02) was used as a representative human/avian flu-v for investigation of sample pretreatment, mock-infected sample preparation and evaluation assays. This virus was propagated and titrated in Madin-Darby canine kidney cells to contain 10 5.7 50% tissue culture infective doses (TCID 50 ) per ml. After serial 10-fold dilution of the virus culture supernatant with viral transport medium (VTM), aliquots of the virus were stored at -70uC prior to use to avoid multiple freeze-thaw cycles." ] },{ "paper_id": "02aabb0b8eb8a3f3692e162442bbed19c5f915b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Biology (whole organism) Subject Areas: ecology/health and disease and epidemiology/molecular biology", "Data accessibility. The list of samples, the Illumina reads of the 16S bacterial sequence data and the OTU tables have been deposited in Dryad (http://dx.doi.org/10.5061/dryad.54f1jc2) [58] . Genetic sequences generated for Leptospira, herpesvirus and adenoviruses, using specific primers, are available on GenBank under accession numbers MG680317-MG608402.", "The microbiota is a fundamental and dynamic dimension of individuals, shaped by physiological, dietary and social factors [1] , and can in turn affect host development, metabolism and susceptibility to pathogens [2, 3] . Host-microbiota interactions are, thus, an important factor in vertebrate ecology and evolution [4] . However, in contrast with numerous studies on humans and laboratory animals, few studies have investigated the causes and consequences of microbiota variation in wild vertebrates, and studies based on longitudinal sampling of the same populations are especially rare [5] [6] [7] [8] ." ] },{ "paper_id": "02b20ad26d6b2f05b38712292186edbf3aa05862", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Third, as a way to understand this better, one would like to do the same study using Stochastic difference equations. It will allow one to better understand the effect of network structure.", "We have carefully edited to captions to improve their utility when interpreting our results.", "Comparing the results with results produced by an SIR based network model is good but as they stand need more work. Specifically, one needs to understand the joint interaction of network and transmission probability p." ] },{ "paper_id": "02b8dea56378d11fe92d6a60ff37a34b0d6ea63e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All values are expressed as the mean \u00b1 standard deviation. Statistical analyses were performed with Student's t test using SPSS software, and P < 0.05 was considered significant.", "The sequences of the upstream and downstream primers were respectively as follows: 5'-ATGGGGCTGGAGCACTC-CCAAG-3' and 5'-TGTGGCAGCACCAGGGCAGC-3' for MMP-2 (1,070 bp); 5'-GGTCCCCCCACTGCTGGCCCT-TCTACGGC-3' and 5'-CACCTCCACTCCTCCCTTTCC-3' for MMP-9 (750 bp); 5'-ACATCAACGAGGGGGAGACG-3' and 5'-GGCTTCAGACAGGCAGGACA-3' for CD147 (492 bp); and 5'-CTGAACGGGAAGCT CACTGG-3' and 5'-TGAGGTCCACCACCCTGTTG-3' for glyceraldehyde phosphate dehydrogenase (313 bp). PCR analysis was performed under the following conditions: denaturation at 94\u00b0C for 2 minutes and then 25-30 cycles of denaturation for 30 seconds at 94\u00b0C; renaturation for 60 seconds at 56\u00b0C for MMP-2, at 58\u00b0C for MMP-9 and at 57\u00b0C for CD147 and glyceraldehyde phosphate dehydrogenase; and extension for 90 seconds at 72\u00b0C. The amplified products were analyzed by agarose gel electrophoresis using 1% gel, followed by ethidium bromide staining.", "(page number not for citation purposes)" ] },{ "paper_id": "02bfb4c09489a5f48c23e8441e37b055bf7228ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and is proteolytically cleaved into 4 individual mature proteins by the virus-encoded nsP2 protease in a specific manner while the structural proteins are subsequently translated from a subgenomic mRNA 7 .", "next study. The current study clearly demonstrates properties that the protease domain possesses which implies that these properties may also be expressed in vivo and this is the obvious justification for all recombinant protein characterization studies.", "Stability test. Thermal stability of the nsP2 protease was determined as previously described 31 ." ] },{ "paper_id": "02c4e304d5e063e9bd66d293a8c1472a5865c173", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "02c9b77cb2898b1597278dbf32a0c61be93d1983", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vector construction, plant transformation and characterization via PCR, Southern blot, northern blot and western blot", "1862" ] },{ "paper_id": "02d808df510466b74102dd922486bf922a5ed947", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ethanol extracts and subfractions were analyzed by ultraperformance liquid chromatography-photodiode array-quadrupoletime of flight-mass spectrometry (UPLC-PDA-Q-TOF-MS).", "ARTICLE HISTORY" ] },{ "paper_id": "02da3b3b4a31f4e15f06a0f076524bea9ab0f92a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "L.Z. and D.Y. conceived and designed the research; D.Z. and M.L. performed the experimental work and wrote the manuscript; Y.C. performed the docking study; Y.Z., S.B., J.Z., F.W. and K.C.R. participated in the experimental work, analyzed the data and discussed the results. All the authors read and approved the final manuscript.", "The biological assays were performed following a previously reported procedure [23] . The Huh7.5.1 cell line and the HCV infectious virus J399EM were kindly provided by Xin-Wen Chen, Wuhan Institute of Virology, Chinese Academy of Sciences. Huh7.5.1 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) containing 10% (v/v) fetal bovine serum, 0.5 mg/mL G418, 100 IU/mL penicillin, and 100 mg/mL streptomycin.", "Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/20/04/6978/s1." ] },{ "paper_id": "02e34b2fe0968cb8a46313fe767858da7e2691b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Overlapping genes (whereby the same nucleotide sequence codes for two or more proteins in different reading frames) are particularly common in RNA viruses, where they may serve as mechanisms to optimize the coding potential of compact genomes, regulate gene expression, or circumvent the host cell's canonical -though not ubiquitous -rule of 'one functional protein per mRNA'. However, such genes can be difficult to detect using conventional gene-finding software.", "Over the past few years we have engaged in a systematic survey of viral genomes for previously undetected overlapping genes. While many of these merit detailed analysis and experimental follow-up (either because they are in important and well-studied viruses or because they involve novel non-canonical translation mechanisms), there remain a miscellany of promising candidate new overlapping genes that we are not currently in a position to follow up experimentally but, nonetheless, may be of interest to the community. The purpose of this article is to communicate five of these candidates.", "Bat coronaviruses 1A, 1B, HKU8" ] },{ "paper_id": "02fdaf97dd0af539eada2af2f1563e0d77a28f92", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ebolaviruses, members of the family Filoviridae, cause severe hemorrhagic fever in humans and nonhuman primates, with human case fatality rates of up to 90% 1,2 . As proven by the latest epidemic of Ebola virus disease (EVD) in West Africa, ebolaviruses pose a significant public health concern. However, no effective prophylaxis or treatment for EVD is as yet commercially available. Five distinct species are known in the genus Ebolavirus, Zaire ebolavirus, Sudan ebolavirus, Ta\u00ef forest ebolavirus, Bundibugyo ebolavirus, and Reston ebolavirus, represented by Ebola virus (EBOV), Sudan virus (SUDV), Ta\u00ef forest virus (TAFV), Bundibugyo virus (BDBV), and Reston virus (RESTV), respectively 3 . Of these, EBOV, SUDV, and BDBV have caused EVD outbreaks with increased frequency in Central and West Africa in the last decade 1,2,4 .", "Ebolaviruses express a single transmembrane glycoprotein (GP) that is responsible for both receptor binding and membrane fusion, and thus the only known target of neutralizing antibodies. GP undergoes proteolytic cleavage by host proteases such as furin, resulting in the two subunits, GP1 and GP2, which are linked by a disulfide bond 5,6 . The GP1 subunit (amino acids 33-501) contains the core of the glycoprotein, receptor binding domain (RBD), a glycan cap, and a large mucin-like domain which extends around the RBD 7 . The GP2 (amino acids 502-676) subunit contains the internal fusion loop (IFL), heptad repeats 1 and 2 (HR1 and HR2), the transmembrane region (TM), and the cytoplasmic tail (CT) 8 . During the transport of ebolavirus particles to late endosomes, low pH leads to proteolytic processing of GPs by host cysteine proteases such as cathepsins 9 , and the exposed receptor binding site of the proteolytically digested GP is thought to interact with a host receptor, Niemann Pick C1, followed by membrane fusion 8, 10, 11 .", "Scientific RepoRts | 6:20514 | DOI: 10 .1038/srep20514 BDBV) has not been demonstrated due to antigenic differences among the species 21 . Since SUDV and BDBV have also shown their potential to cause public health emergencies during several outbreaks in Central Africa, it is difficult to determine the priority for development of countermeasure against those ebolaviruses." ] },{ "paper_id": "02fe68e2ba45e7f0c6f746d4b3db36f8f99ae4f5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "0304ed96b29c38014a17bacefcc294a02c04d0a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Expression was performed in E. coli BL 21 codonplus using a pET-22b vector system with a pelB-leader sequence for export to the periplasm of E.coli. After transformation cells were cultivated at 180 rpm and 30\u00b0C in shaking flasks in 400 mL LB-medium. After the OD600 had ", "Expression and purification of para-nitrobenzyl-esterase 13 (pNB-Est 13)", "We tested each hydrolase in combination with each ester to determine which hydrolases are the most active ones and which substrates have the highest accessibility (Fig 4) ." ] },{ "paper_id": "03148d1ba3c986ec7306ab2a90bcd6082c512f49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Between Table S1 .", "Lihong Yuan and Jinping Chen conceived and designed the experiments. Lihong Yuan, Min Li, Linmiao Li and Xiaolin Mei carried out the lab work. Lihong Yuan and Min Li participated in data analysis. Lihong Yuan, Jinping Chen, Corina Monagin, Aleksei Chmura, Bradley S. Schneider, Jonathan H. Epstein, Zhengli Shi and Peter Daszak wrote the paper." ] },{ "paper_id": "031fd47b33af0e00eeb5e76c0d010df92df6bef6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Anecdotally, these authors are aware of a resident who developed an anterior cruciate ligament tear following a fall while running to a code. As mentioned above, one author developed acute neck pain following multiple rounds of vigorous CPR during an overnight code. He ultimately developed neurological symptoms with tingling in his fingers and was found to have a cervical epidural hematoma that was managed conservatively with improvement in symptoms. There is also a news media story of a paramedic developing a myocardial infarction (MI) while performing CPR on a patient experiencing an MI [42] .", "Jackson and Sturrock describe a case of \"resuscitation shoulder\" or the partial tear of a rotator cuff experienced by a resident physician after performing repetitive and prolonged chest compressions on several patients over three consecutive nights while on call [41] . Similar injuries have been described following repetitive athletic pursuits.", "The effect of rescuer fatigue during prolonged codes has also been discussed with decreased compression depth achieved [43] . It can be hypothesized that as resuscitators develop fatigue, they may develop altered posture and increase the risk of musculoskeletal strain or sprain.", "Background \"Code blue\" events are cardiopulmonary resuscitation efforts that occur in hospital settings. A dedicated multidisciplinary resuscitation team rapidly convenes at the bedside, initiates cardiopulmonary resuscitation (CPR), and performs an assessment of the situation. Cardiac defibrillation, establishment of intravenous (IV) access, placement of an advanced airway, blood draws, and medication administration, among other tasks, are integrated into these code situations. Multiple hospital staff are frequently present including physicians at all training levels, medical students, nurses, critical care staff, laboratory technicians, social workers, and clergy; increasingly, patient family members are also at the bedside.", "Given the perceived increased risk of parenteral exposure, measures beyond universal precautions are essential, including the use of safer syringes using newer engineered controls. These devices have a mechanism that retracts or covers the exposed needle to prevent accidental exposure following patient intervention [5, 6] ." ] },{ "paper_id": "03203ab50eb64271a9e825f94a1b1a6c46ea14b3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Production of viral particles and co-inoculation. To generate the parental virus particles, plasmids pCa37 and pMark-S were mechanically inoculated into individual plants as previously described [33] . All plants were turnips (B. rapa cv, ''Just Right'') grown under glasshouse conditions at 23 8C with a 16/8 (light/dark) photoperiod.", "Interestingly, this recombination rate does not vary throughout the genome (Kruskal-Wallis test, p = 0.16).", "Thirty days post-inoculation, all symptomatic leaves were harvested and viral particles were purified as described earlier [45] ." ] },{ "paper_id": "0326bf875d2a22d7c4a4328dcd34c2d801fd110e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "N Global health priorities are many and varied; however, unlike high profile diseases such as HIV/AIDS, malaria, and H5N1 avian influenza, the neglected tropical diseases have historically been ''forgotten'' in terms of funding and collective action for control.", "N Five of the eight neglected zoonotic diseases-cysticercosis, rabies, echinococcus, human African trypanosomiasis, and leishmaniasis-are included in the list of NTDs identified by Resolution WHA66.12. However, anthrax, bovine tuberculosis, and brucellosis are still lacking the high-level advocacy required to mobilise political support for their control in endemic countries. ", "Control of zoonotic disease requires integrated action from both human and animal health sectors alongside support and consultation from other sectors or industries. The rapid response to recent zoonoses outbreaks, such as those of West Nile virus and monkeypox in the United States, Hendra virus in Australia, Nipah virus in Malaysia and Singapore, severe acute respiratory syndrome (SARS) in China and Canada, and highly pathogenic avian influenza (HPAI), demonstrates how the mobilisation of considerable political and financial support for the control of emerging diseases is possible on a regional-if not global-scale. These emerging and reemerging zoonoses would appear to be far from ''neglected;'' the Food and Agriculture Organisation of the United Nations (FAO)'s ''Global Programme for Avian Influenza Control and Eradication'' received a projected budget of US$882 million in 2006 [1] . HPAI in particular continues to attract a substantial amount of support [2] , largely driven by ''fearful'' policy narratives concerning global health securitisation and pandemic preparedness [3] ." ] },{ "paper_id": "0330ede445d96dd0a27f474f945d6ce2e7085f15", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/JVI .01751-17.", "SUPPLEMENTAL FILE 1, XLSX file, 0.1 MB.", "CRISPR Cas9 knockdown of GBF1. Three different targets for human GBF1 were selected and cloned into pSpCas9(BB)-2A-GFP (PX458) (Addgene number 48138) using the protocol established by F. Zhang (66) . The primer sequences were as follows: TBE 434F, CRISPR Cas9 GBF1.1 (CACCGATGGATTAC GTCAATCCCCG); TBE 435R, CRISPR Cas9 GBF1.1 (AAACCGGGGATTGACGTAATCCATC); TBE 436F, CRISPR Cas9 GBF1.2 (CACCGACACGACCGCCATAACTCAG); TBE 437R, CRISPR Cas9 GBF1.2 (AAACCTGAGTTATGG CGGTCGTGTC); TBE 438F, CRISPR Cas9 GBF1.3 (CACCGACAGTGATTGACAGCACCG); and TBE 439R, CRISPR Cas9 GBF1.3 (AAACCGGTGCTGTCAATCACTGTC). All three target plasmids were cotransfected at a ratio of 1:1:1; at 48 h posttransfection, the cells were reseeded and used for experiments." ] },{ "paper_id": "033321dcd825a79a8ba380ba3d52d4ea71f45c81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was supported by the Leibniz graduate school Emerging Infectious Diseases (EIDIS) and the DEWIN program of Hannover Medical School. Sebastian Bolduan and Michael Schindler were supported by the Else Kr\u00f6ner-Fresenius Stiftung. Michael Schindler and Stefan P\u00f6hlmann were supported by DFG (SCHI1073/4-1, PO 716/8-1). ", "(C) Transduction of target cells by wt and mutant GPs was determined as described for Figure 1B . The average \u00b1 standard error of the mean (SEM) of at least three separate experiments is shown. Signals measured for wt GPs were set as 100%." ] },{ "paper_id": "033460fbe61491f8505732ee22a5cb3387f3e4a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The positive rate (%) www.nature.com/scientificreports www.nature.com/scientificreports/ with all known VP1 genes of GIII.2 strains (including the strains of this study), and 75.9-76.5% nt identity (81.1-82.2% aa identity) with the VP1 gene of the single possible GIII.3 strain.", "BnoV detection and co-infections. 20 .4% (43/211) of the diarrheic samples were detected as BNoVpositive by RT-PCR, and 14 of the 25 farms sampled in five provinces were positive for BNoV (Fig. 1) . Of the 43 BNoV-positive diarrheic samples, 38 were co-infected with bovine rotavirus (BRV), Bovine coronavirus (BCoV), and/or Bovine viral diarrhea virus (BVDV) ( Table 1 ). The co-infected of distinct BNoV genotype in each region was shown in Supplementary Table 3 .", "Recombination events were predicted with SimPlot and Recombination Detection Program (RDP) 4.0 with RDP, GeneConv, Chimaera, MaxChi, SiScan, and BootScan (recombinant score: 0.548). A recombination breakpoint was predicted at nt 5034 in the genome. The putative major parental strain was Bo/Adam/2006/No (GenBank accession number JX145650), but the minor parental strain was not found. However, using SimPlot, recombination breakpoint was predicted at 5055 bp in genome (Fig. 5) . Although the recombination breakpoints predicted by RDP 4.0 and SimPlot differ, both programs showed that the recombination breakpoint was located at the ORF1-ORF2 overlap. A phylogenetic tree based on the sequences upstream and downstream from the predicted recombination breakpoint supported a recombination event (data not shown)." ] },{ "paper_id": "033b167546d99b583a32a437dc71c73bdad6e83d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "(PDF)", "As a measure of genetic differentiation we estimated F ST between all the virus lineages based on the heterozygosity (H) of the SNPs we called [62] :" ] },{ "paper_id": "034cab326c750ea98f621e9c65371b8f139fbfb4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This review focuses on the numerous influenza A virus (IAV) omics-related studies of host responses that have been published over the last two decades. While vaccination strategies exist to combat the seasonal spread of IAV, these viruses can mutate and undergo genetic reassortment that can evade vaccines and other therapeutics. Of particular concern is that not just humans, but wild and domesticated birds can spread IAV, including recent highly pathogenic bird flu isolates of H7 and H5 designation that cause high mortality rates in infected humans. Additionally, IAV is also endemic in pigs, with the 2009 H1N1 global pandemic caused from a swine-to-human spillover event.", "Swine influenza viruses (SIV) have the zoonotic potential to cause global pandemics in humans, such as the 2009 H1N1 pandemic (pH1N1) that spread across the globe [6] . Swine are considered a mixing vessel for novel influenza reassortment, as pigs have the capacity to support influenza strains of human, swine, and avian origin. While swine influenza is a public health concern, compared to humans, we have a limited understanding as to swine host responses to influenza infection at the -omics level [7, 8] .", "Influenza A viruses (IAV) continually evolve and have the capacity to cause global pandemics. Because IAV represents an ongoing threat, identifying novel therapies and host innate immune factors that contribute to IAV pathogenesis is of considerable interest. This review summarizes the relevant literature as it relates to global host responses to influenza infection at both the proteome and transcriptome level. The various-omics infection systems that include but are not limited to ferrets, mice, pigs, and even the controlled infection of humans are reviewed. Discussion focuses on recent advances, remaining challenges, and knowledge gaps as it relates to influenza-omics infection outcomes. . As IAV strains evolve and sequence information from the IAV cannot currently determine pathogenicity, -omics platforms can be a powerful tool to compare emergent IAV strain data with previously circulating strains for the purpose of threat characterization.", "Monitoring multiple reservoirs of IAV for zoonotic spillover events into humans therefore requires the characterization of IAV isolates on a continual basis and to define host responses-including -omics approaches-in multiple species. As IAV strains evolve and sequence information from the IAV cannot currently determine pathogenicity, -omics platforms can be a powerful tool to compare emergent IAV strain data with previously circulating strains for the purpose of threat characterization.", "As prior virus systems biology reviews have noted [64] [65] [66] , -omics approaches often seek to define virus-host immune responses to better design therapeutics such as antivirals and better vaccine strategies. The field of virus -omics is an evolving discipline that has increased in complexity and popularity over the last decade. Comprehensive proteomics and transcriptomics influenza studies not only require laboratory competency under biosafety level-3 (BSL-3) conditions, but competency in computational modeling to handle the sheer amount of data generated. Collaboration between research groups is paramount to ensure adequate resource sharing and data availability to others in the virology community. Lastly, while the field of virus -omics can be costly, the high-throughput molecular techniques and computational tools used in these studies should continue to advance so as to allow more research to contribute to the field of systems virology." ] },{ "paper_id": "035dfb6e2398c95bbf6b65db97b443908a43e093", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RIEMS and all necessary applications are installed locally on a server equipped with four Intel Xeon E7450 processors (each 6 cores with a frequency of 2400 MHz) and 64 GB PC2-5300 (DDR2-667 MHz) ECC RAM. The server is linked with 2 \u00d7 4 Gbit/s ports to the storage area network. The operating system is CentOS release 5.10 with Linux kernel release 2.6.18-371.1.2.e15." ] },{ "paper_id": "035f1d6b6c461d045fd19d69e4e9c1de221f4a0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Steps to predict drug targets in silico", "Are these targets really druggable?", "Using DNA sequences, couples of non synonymous (A-A) and couples of synonymous mutations (S-S) were determined. A D' coefficient were then computed from these data as explained in [13, 14] . " ] },{ "paper_id": "036bbd8c099c5721274abb4067872f2a68b6193a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "S ince its first appearance in 2012, Middle East respiratory syndrome (MERS) has affected more than 25 countries in 4 continents, with more than 2,400 cases and an extremely high fatality rate of more than 30%. The total number of mortalities due to MERS is already greater than that due to severe acute respiratory syndrome. MERS coronavirus (MERS-CoV), a betacoronavirus from subgenus Merbecovirus, has been confirmed to be the etiological agent (1) . Human dipeptidyl peptidase 4 was found to be the cellular receptor for MERS-CoV (2) . Subsequent detection of MERS-CoV and its antibodies in dromedary, or one-humped, camels (Camelus dromedarius) in various countries in the Middle East and North Africa have suggested that these animals are probably the reservoir for MERS-CoV (3) (4) (5) . Other betacoronaviruses in bats from the subgenus Merbecovirus (e.g., Tylonycteris bat CoV HKU4, Pipistrellus bat CoV HKU5, Hypsugo bat CoV HKU25), and hedgehogs were found to be closely related to MERS-CoV (6) (7) (8) (9) .", "A total of 29 and 11 serum samples, respectively, were collected from 29 Bactrian camels and 11 hybrid camels from a private collection in Dubai (April to May 2019) ( Table 1) , and 92 serum samples were collected from Bactrian camels on a camel farm in Xinjiang (November 2012) (16) . Antibodies against the S protein of MERS-CoV were tested using microplates precoated with purified (His) 6 -tagged recombinant receptorbinding domain of S (RBD-S) of MERS-CoV and detected with 1:8,000 diluted horseradish peroxidase-conjugated goat anti-llama IgG (Life Technologies, Carlsbad, CA, USA) conjugate (S-ELISA) (17) . The cutoff of the ELISA was defined as three standard deviations above the mean absorbance value of 10 dromedary serum samples that tested negative with the neutralization antibody test. The neutralization antibody test was performed by incubating serially diluted camel sera with 100 50% tissue culture infective dose (TCID 50 ) MERS-CoV for 2 hours before infecting the Vero cells for 1 hour. The cytopathic effect (CPE) was observed for 5 days, and the sera were regarded as positive for neutralizing antibody if no CPE was observed in the infected cells (18) . All tests were performed in triplicate.", "In addition to the dromedaries, there are two additional surviving Old World camels, the Bactrian, or two-humped, camels (Camelus bactrianus) and the wild Bactrian camels (Camelus ferus), both inhabitants of Central Asia. Moreover, a dromedary and a Bactrian camel can mate and result in a hybrid camel offspring. Previous published serological studies showed that sera of Bactrian camels were all negative for MERS-CoV antibodies, suggesting that Bactrian camels may not be a reservoir of MERS-CoV ( Fig. 1 ) (10) (11) (12) (13) (14) . However, a recent study revealed that direct inoculation of Bactrian camels intranasally with MERS-CoV can lead to infection with abundant virus shedding and seroconversion (15) . Therefore, we hypothesize that those Bactrian camels, and even the hybrid camels, that reside in countries where there are dromedaries can be infected with MERS-CoV. To test this hypothesis, we examined the presence of MERS-CoV antibodies in Bactrian and hybrid camels in Dubai, the United Arab Emirates (where dromedaries are also present), and Bactrian camels in Xinjiang, China (where dromedaries are absent), using a MERS-CoV spike (S) protein-based enzyme-linked immunosorbent assay (ELISA) and neutralization antibody test." ] },{ "paper_id": "03774b269b5de5338590b1960b6468881604a3dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "03797126b6e6689cc02878e641e5271d3b9a5d3b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ticks such as Haemaphysalis longicornis and Rhipicephalus microplus are implicated as the prominent vectors for transmitting SFTSV [7] . With regards to SFTSV hosts, various vertebrate species are considered to have been infected, as evidenced by high SFTSV seroprevalence in domestic animals in SFTS endemic regions [8, 9] . Additionally, reported cases of human-tohuman transmission through contact with blood or body fluid, including infections in healthcare workers from patients, pose a further threat to the public [10, 11] . Furthermore, the discovery of H. longicornis tick in the United States indicates the possibility that SFTSV could spread to other continents, highlighting the need to prevent disease transmission [12] .", "In order to produce histidine tagged SFTSV Gn glycoprotein, a ligand for surface plasmon resonance analysis, a Gn-C\u03ba with six carboxy-terminal poly-histidine residues was designed and produced as described above.", "In the delayed treatment model, the antibody treatment started from 1, 3, 4, or 5 d.p.i. and continued for 4 consecutive days (Fig 3A) . At a 2 PFU viral dose, all mice survived when treatments with Ab10 were delayed until 3 d.p.i., and 80% survived when the treatments were delayed until 4 or 5 d.p.i. (Fig 3B and 3C ). Mice not treated until 4 d.p.i. had significant weight loss. At a 20 PFU viral dose, delaying Ab10 antibody treatment until 1 or 3 d.p.i. protected all or 80% of mice, respectively. Mice with treatment delayed until 1 d.p.i. did not lose weight, whereas mice with treatment delayed until 3 d.p.i. lost 8% of their body weight. When treatment was delayed until 4 d.p.i. or later, all the mice died.", "Antibodies play a pivotal role in preventing viral entry into cells and can induce lysis of infected cells through antibody-dependent cellular cytotoxicity or complement-dependent cytotoxicity [33] [34] [35] . Polysera from recovered patients or from vaccinated donors have been used as prophylactic agents for various viral diseases, including hepatitis B and rabies [36] . As an alternative approach, virus-directed monoclonal antibodies have also been developed and tested as therapies or as prophylaxis for viral diseases. Palivizumab (Synagis) was marketapproved for the prophylaxis of RSV in 1998. In addition, antibodies against HIV [37] [38] [39] , RSV [40] , Ebola virus [41] and influenza virus [42, 43] demonstrated potent efficacy in animal models. Antibodies targeting emerging or re-emerging viruses including MERS-CoV [44] [45] [46] and Zika virus [47] [48] [49] were also developed and are being tested in clinical trials. In the past several decades, antibodies have become one of the major therapeutic agents for cancer and autoimmune disease with indications that have rapidly broadened in recent years. Recent technical improvements in the discovery and manufacturing steps of therapeutic antibody production have also allowed rapid and successful antibody development to combat emerging infectious diseases [50] ." ] },{ "paper_id": "0391c13dbb9949494913c209424ed61d3a652753", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary information accompanies this paper at https ://doi. org/10.1186/s1295 1-019-0569-9." ] },{ "paper_id": "0396bc111213d601eeb67ae191530309bdbb6220", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical significance was determined using the Student's t-test or one-way analysis of variance. Results were regarded as significant if two-tailed p values were <0.05. All data are expressed as mean \u00b1 standard error of the mean. ", "Exploiting host signal pathway(s) is an effective virulence strategy employed by a number of viral hemorrhagic fever pathogens. Cyclic adenosine monophosphate (cAMP) is a common secondary ubiquitous messenger involved in several cellular processes; cAMP translates environmental signals into downstream effects at multiple cellular levels [25] [26] [27] . Many pathogens have developed strategies to modulate cAMP levels within host cells, including the vascular endothelium [28] , by hijacking the host cell machinery for their own benefit during various stages of their life cycle, including entry, internalization, fusion, replication, and release [28] [29] [30] [31] [32] . However, it is not known if filoviruses employ similar strategies.", "The mouse experiments performed for this study were carried out in accordance with National Institutes of Health, United States Dept. of Agriculture, and UAMS Division of Laboratory Animal Medicine and Institutional Animal Care and Use Committee (IACUC) guidelines. The protocol supporting this study was approved by the UTMB IACUC (1506030).", "Filoviruses seem to target both the immune system [15] [16] [17] and vascular endothelia [18] [19] [20] [21] , causing the most severe form of viral hemorrhagic fever (VHF). Filoviral infection initiates diffuse vascular endothelium dysfunction marked by bleeding, fluid distribution disorders, and disseminated intravascular coagulation (DIC), leading to organ failure in the latter stages of disease [17, 19, [22] [23] [24] . The vascular endothelium is a monolayer of cells lining blood vessels. Under physiological conditions, the endothelium plays a pivotal role in providing the proper hemostatic balance. Dysregulation of the barrier formed by the endothelium can increase vascular permeability and cause hypotensive shock syndrome; it is seen in many fatal diseases, including VHF cases [18, 19] . However, the mechanism(s) triggering endothelium disruption during EBOV infection is still not fully understood." ] },{ "paper_id": "039ca136c69c998e9a2677259d9de2941a13304a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "U p until now (6/11/2013) , H7N9 IAVs infected 133 and killed 39 people in China, although only few cases have been reported since the beginning of May 2013. The new human H7N9 virus is a reassortant virus that acquired its hemagglutinin (HA) subtype 7 (H7) and neuraminidase (NA) subtype 9 (N9) gene segments as well as the other gene segments from (different) avian IAVs [1] [2] [3] . Analysis of the gene sequences indicates that the novel H7N9 viruses may be better adapted to infect humans than other avian influenza A viruses. H7N9 viruses isolated from human possess for instance the E627K substitution in the PB2 RNA polymerase subunit, which has been shown to facilitate RNA replication in mammalian cells [4] [5] [6] and transmission between ferrets 7 .", "Introduction of the Q226L mutation in the teal H7 protein resulted in decreased binding to a2-3 sialosides and increased binding to a2-6/a2-8 sialosides, resembling, apart from some quantitative differences, the patterns observed for the human H7 protein.", "NA activity assays. Activity of the NA proteins expressed in HEK293T cells was analyzed using a previously described fetuin-based assay 25 . In brief, fetuin-coated 96well plates, were incubated with limiting dilutions of recombinant soluble NA protein for 2 hour at 37uC. After washing, the plates were incubated with biotinylated peanut agglutinin (PNA, 2.5 mg/ml; Galab Technologies). Binding of PNA correlates with the amount of SIA released from galactose. The specificity of the NA proteins was determined by measuring the binding of biotinylated SNA or MAL I (both from Galab Technologies) after incubation of fetuin with NA. The binding of PNA, SNA and MAL-I was detected using horseradish peroxidase-labeled streptavidin. NA activity assays were performed at least twice in triplicate. The mean values of at least two independent experiments are shown. The amount of NA protein required for half maximum PNA binding (EC50) was determined using the GraphPad Prism software.", "HA binding assays. Receptor-binding of HA was analyzed using a fetuin solid-phase binding and hemagglutination assays 20, 21 and by performing HA histochemistry on formalin-fixed, paraffin-embedded human tissues similarly as described previously 24 . Glycan array analysis of the HA proteins was performed by the Core H of the Consortium for Functional Glycomics as described previously 20, 21 . The fetuinbinding assays were performed at least twice in triplicate. The mean values of at least two independent experiments are shown. HA proteins were expressed in HEK293S GnT1(2) cells, except for the HA histochemistry, for which HA proteins expressed in HEK293T cells were used." ] },{ "paper_id": "039ca723ee32358eb70a084eaee19e1b6adc3033", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "03a158fb5fcbfccd841b4a9638e840a0302b9459", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:39730 | DOI: 10.1038/srep39730 structural relationship. These data imply that in the absence of available L1 crystal structures, homology models have utility as surrogate structures for the prediction of structural differences between L1 proteins.", "Oncogenic human papillomavirus (HPV) genotypes are the causative infectious agents of approximately 5% of all human cancers worldwide 1 . Infection with an oncogenic HPV genotype plays a fundamental role in the development of cervical carcinoma, one of the leading causes of cancer death in women and it is also an identified risk factor associated with the development of other anogenital cancers and head and neck cancers 2 . The oncogenic genotypes HPV16 and HPV18 account for ca. 70% of cervical cancer cases worldwide 3 and the majority of the oncogenic HPV genotypes are closely related to either HPV16 or HPV18 within the Alpha-9 or Alpha-7 species groups, respectively.", "Scientific RepoRts | 6:39730 | DOI: 10.1038/srep39730" ] },{ "paper_id": "03ae4b61aa2d9641f38287806612fc16f58d4299", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "03b35e72b8abfe6c88da27e72b5ecc8e77211dd2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analysis of the sequencing results was conducted using Mothur software (v1.35) [52] . Paired-end reads were aligned ", "Lastly, it is unknown whether the organisms identified using next generation sequencing methods are functionally or metabolically active. Future computational studies are needed to specifically examine the metabolomics of the bacteria identified." ] },{ "paper_id": "03b9acce84a4799d4be1152a36abfaf52fb3b523", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Respondents were well distributed over all geographic regions and across different urbanization levels (about 13.6% rural and 86.4% urban) that matched the distributions of the total population. The household size averaged 4.5. For those over 18 years old (adults), 56.4% were married, and 37.6% received at least college education. About 37.9% of adults were service-sector workers, and 23.8% were manual workers; others were either students (5.5%) or not working (32.8%).", "After two-and-a-half months of fieldwork, we completed 1,954 successful interviews. The respondents (or their parents or guardians) provided 1,943 contact diaries that recorded every person with whom they had contacted during the past 24 hours (up to a maximum of 40 persons, a cutoff set to limit time and space). The ''crude'' (or ''minimum'') response rate was about 46.4% (or 51.3% after excluding ineligible cases such as wrong addresses, etc.)(The response rates are calculated by international standards, cf. [21] [22] .", "The most active age group of all is schoolchildren (ages 5-14), who average around 16-18 contacts. These super spreaders of influenza viruses make 2-3 times as many contacts as the least active age groups [3, 8, 12] . Furthermore, about half of these children's contacts involve a touch or other kind of physical contact.", "Many policy implementations for disease control rely on modeling how infectious diseases spread. To increase the effectiveness of such modeling, one of the most comprehensive efforts seeks to collect empirical data by means of large-scale probability surveys and infers the findings to the population upon which a policy is to be implemented. Such a task becomes more urgent for densely populated societies that may be more susceptible to a pandemic outbreak.", "Under the influence of the Chinese culture that overly stresses guanxi (or relationship) [16] [17] , Taiwan's residents tend to make contact with others often in their everyday lives. Asking questions about interpersonal contacts thus turns out to be significant not only for research on disease infections but also for more general social issues [18] . Under such circumstances, Taiwan offers an opportunity for exploring how rigorous diary-approach surveys may further facilitate researchers' and policy makers' understanding of how infectious diseases spread." ] },{ "paper_id": "03bb746ba6fb4c250b5f8f9ff0e5013b2c49b8f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hepatitis B virus (HBV) infection continues to be a serious clinical challenge, which induces the development of liver cirrhosis and hepatocellular carcinoma, even leading to mortality, in many areas of the world [1, 2] . Currently, the utility of first-line antiviral agents or immune system modulators recommended by the World Health Organization can only help to reduce and control the viral load and minimize liver damage, but cannot effectively clear the infection and seldom achieve a cure [3, 4] . Thus, these current therapies remain far from satisfactory. In particular, the wide spread of multidrug-resistant HBV strains is increasingly threatening the efficacy of currently available antiviral drugs [5, 6] . Therefore, there is an urgent need to actively develop and test promising novel therapies to target HBV." ] },{ "paper_id": "03ca47766e6f3e8d5d71fa25d86803f82d690b38", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Targets Predicted by Discovery Studio 4.5", "G-bS, J-xY, and X-bS conducted the study. MW designed the detailed experiments, performed the study, and collected and analyzed data. Y-yD, YT, PL, and X-sL took part in the cell experiments in this study. All Authors commented the study and approved the final manuscript. ", "The results are expressed as the means \u00b1 standard deviation. Comparisons were performed using Student's t-test or one-way ANOVA followed by Tukey's multiple comparison test using Prism 5.00 software. Statistical significance was set at p < 0.05. All data are the result of at least three independent experiments." ] },{ "paper_id": "03d32bf9da6495150f5016a0bf2d4b7647620c7d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "03d40dcd5d29728439528bd955afcba42bc0c2b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to spread among poultry and have frequently broken the species barrier and transmitted to humans. As of February 2012, there were 583 confirmed human H5N1 infections from 15 countries, with a fatality rate of .59% (344), alarming that the consequences of a H5N1 pandemic could be catastrophic. Therefore, many efforts have focused on the development of effective therapeutics and vaccines in preparedness. Of them the neutralizing antibody-based strategies have been particularly explored.", "To determine the effect of disulfide bond reduction on the binding of anti-HA mAbs, an ELISA plate was coated with recombinant HK06-HA at a concentration of 1 mg/ml and then treated with dithiothreitol (DTT) at a concentration of 10 mM for 1 h at 37uC, followed by washes. The plate wells were then treated with 50 mM iodoacetamide for 1 h at 37uC. After washes, a standard ELISA was performed as described above.", "Therefore, three discontinuous sites, designated site I (I116, I117, P118), site II (W122, S123), and site III (Y164, T167) are likely involved in the AVFluIgG01 epitope. In the 3D structure, the epitope residues are adjacent to each other at the tip of the membrane-distal globular domain of HA monomer, in close proximity to the receptor-binding domain (Fig. 4) . Importantly, these amino acids are highly conserved among diverse H5N1 clades and subclades [12] [13] 17] , underlying the broad-spectrum H5N1-neutralizing activity by AVFluIgG01." ] },{ "paper_id": "03d7c96afa37141562c3ac9297882dbe59d2e0e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "03dce266594748330a10d2d11dbe611bf42aa42d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Contributed directly to the writing and drafting, editing, and final approval of the article before submission CS, JN, and MM.", "Development of a vaccine for rhinovirus remains a universal hope of the public health and scientific communities. For over a half century, the prospect of developing an HRV vaccine has remained bleak. There remain many technical, logistical, and fundamental biological challenges to developing a successful vaccine for HRV. Mice and cottons rats are important models for testing of efficacy of vaccines to elicit neutralizing antibodies, however, they are not fully permissive to infection and can only resemble some aspects of HRV pathogenesis in humans (Bartlett et al., 2008; Blanco et al., 2014a) . Recent advances in producing mice that are transgenic for human ICAM-1 have made them an improved model for study of HRV infection (Bartlett et al., 2008 ). Yet, any vaccine preparation would likely have to be studied directly in humans.", "This work was supported by funding from a Holcomb Awards Committee (HAC) Faculty Research Grant (CS), the Butler University Department of Biological Sciences, and faculty startup funding (CS) from Butler University." ] },{ "paper_id": "03e779f9defa0b9cb6a9943947e41b9c1532e3d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "03e9a22249dd6e201e347bb87cf96a931120f5c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "293 T (human kidney epithelial) and Vero (African green monkey kidney) cells were grown in Dulbecco's modified Eagle's medium (DMEM; Mediatech-Cellgro) supplemented with 10% fetal bovine serum and antibiotics at 37uC in 5% CO 2 .", "The genes encoding influenza HA 1918, Nipah G and F were commercially synthesized and then cloned into pCAGGS vector. Junin and Lujo GPC in pCAGGS from Dr. Thomas Briese.", "We envisage this pseudotyped MCR assay as a platform technology that will enable the preparation and storage of a specific sets of assay reagents for a wide range of viral pathogens, at low cost, in advance of any actual outbreak of the corresponding viral disease. This could form the basis for an efficacious and timely outbreak response, immediately following the identification of dangerous new viruses." ] },{ "paper_id": "03f315449023c980e42af7eb150d0cd9cab57f5a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analyses were performed using SPSS version 16 for windows. The association between MERS-CoV prevalence in camels and the study variables (sampling site, origin, age, and sex) were analyzed by Pearson Chi-square test of independence. Statistical significance was considered at p-value less than 0.05.", "Serum micro-neutralization assay was conducted as described by Perera et al. (2013) [13] , using Vero-E6 cell monolayers. Briefly, serial two-fold dilutions of 200 \u00b5L heat-inactivated sera (56 \u2022 C Viruses 2019, 11, 717 4 of 16 for 30 min) were made, starting with a dilution of 1:10. The serum dilutions were mixed with equal volumes of 200 tissue culture infectious dose (TCID 50 ) of dromedary MERS-CoV Egypt NRCE-HKU270. After 1h of incubation at 37 \u2022 C, 35 \u00b5L of the virus-serum mixture was added in quadruplicate to Vero-E6 cell monolayers in 96-well microtiter plates. After 1 h of adsorption, an additional 150 \u00b5L of culture medium was added to each well. The plates were then incubated for three more days at 37 \u2022 C in 5% CO 2 in a humidified incubator. A virus back-titration was performed without immune serum to assess input virus dose. Cytopathic effect (CPE) was read at three days post infection. The highest serum dilution that completely protected the cells from CPE in at least half of the wells was considered as the neutralizing antibody titer and was estimated using the Reed-Muench method. Positive cut off points were set at values greater or equal to 1:20 serum dilution points.", "This study was carried out in accordance with the principles of the Animal Welfare Act of the United States of America. The protocol was approved by the Institutional Animal Care and Use Committee at St. Jude Children's Research Hospital. Also, the ethics committee of the National Research Centre, Egypt, approved the animal sampling protocol (Approval code: 17-070)." ] },{ "paper_id": "03fa4232b3fbc44b6029d52c3120f4e82fdc49c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Homology modelling of the OC43 3CL pro", "Assessing the binding conformation and free energy of binding of 16R", "During coronavirus replication the large open reading frame (ORF) 1a/1ab genes, located at the 5' end of the genome, are responsible for expressing two large replicase polyproteins (pp). These are co-or post-translationally cleaved by the virally encoded 3CL pro and Papain-like protease to yield 16 non-structural proteins responsible for viral replication [9] . The 3CL pro is also termed the main protease as it cleaves a total of 11 cleavage sites within pp1a and pp1ab [10] , in comparison to only three cleavage sites predicted for the papain-like protease [11] .", "Human coronaviruses have a worldwide distribution and are frequently associated with self-limiting upper respiratory tract disease or \"the common cold\". They can, however, also present with high morbidity outcomes of the lower respiratory tract including bronchiolitis, pneumonia, [1] [2] [3] , asthmatic exacerbations [4] and acute exacerbations of chronic obstructive pulmonary disease (COPD) [5] , where human coronavirus OC43 has been shown to be the prevalent strain in several regions [6] . Given the high burden of coronaviruses to human health, and their potential for genetic recombination to give rise to the emergence of completely novel strains, the presence of antiviral strategies is paramount. However, there is currently no commercially available molecular entity which is capable of inhibiting infection with human coronaviruses [7] . The 3CL pro has been validated as an effective drug target in several studies and has even been termed \"the Achilles' heel of coronaviruses\" [8] making it an ideal target for the identification of novel lead compounds." ] },{ "paper_id": "03fd3a4ec79ffea2a049338b2818457e98496df6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To determine the statistically significant difference between the VN titers generated after inoculation with the three FCoVs, the unpaired two-tailed Student T test with equal variances was applied. The p value under 0.05 was considered as a statistically significant difference.", "High copy number (.10 3 ) genomic qRT-PCR results were confirmed with subgenomic qRT-PCR assay not only from organs but all fecal and blood samples (data not shown).", "One of the two aa substitutions affecting nsp3 was found in papain-like protease 2 responsible for proteolytic processing of nsp1 and nsp2 [26] , proteins with functions of host gene expression inhibition [27] and cellular signaling disruption [28] .", "Serum samples were taken using VacuetteH tube (Greiner Bio-One, Germany) at days 0, 7, 14, 21, 28, 35 and 42 p.i. For antibody ELISA tests, the FCoV EIA Kit, (BV European Veterinary Laboratory, The Netherlands) was used according to the recommendations of the manufacturer." ] },{ "paper_id": "0401a5bebe76fc07dde0f103a248118ce30facda", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rift Valley Fever (RVF) is a mosquito-borne viral zoonosis, which periodically causes disease outbreaks in humans and livestock. Infection by RVF virus (RVFV) causes abortion or resorption of the fetus in pregnant domestic ruminants, with newborn mortality approaching 100%. Transmission of RVFV to humans, either through contact with bodily fluids of infected animals or through mosquito bites, may result in mild to moderate influenza-like symptoms and severe retinitis, encephalitis and hemorrhagic fever [1, 2] .", "RVFV was first described in Kenya in 1931 [3] . Major outbreaks of RVF have been reported in Egypt in 1977 , Kenya in 1997 -1998 , Saudi Arabia in 2000 -2001 , Yemen in 2000 -2001 , and South Africa in 1951 ,1974 -1976 [1, [4] [5] [6] [7] [8] . The recent outbreak of RVF in Kenya in November 2006 through March 2007, where several hundred human cases were confirmed in 6 of 8 provinces had a devastatingly high case-fatality rate for hospitalized patients while there were up to 180,000 infected mildly ill or asymptomatic people within the highly affected areas [9] [10] [11] . Sero-surveys suggested an attack rate up to 13% of residents in heavily affected areas; livestock deaths and abortions were also noted during the outbreak [9, 11] .", "RVFV belongs to the order of Bunyavirales, family Phenuiviridae, genus Phlebovirus. The members of this family carry a tri-segmented single stranded RNA genome. The M (medium) and L (large) segments are of negative orientation, whereas the S (small) segment has an ambisense polarity. The L segment encodes the RNA-dependent RNA-polymerase while the M segment encodes the two glycoproteins Gn and Gc and also the non-structural protein NSm. The small segment encodes the nucleocapsid (N) protein and a non-structural protein NSs using an ambisense coding strategy [1, 2] . The N protein is highly conserved and it is one of the most immunodominant viral proteins among members of the Phenuiviridae family [12] [13] [14] ." ] },{ "paper_id": "04034022f265da392051b3e3fcef2e580247d6c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the neutralization assay, two-fold serial dilutions ranging from 1:10 to 1:5120 were prepared in quadruplicate.", "Background: Marburg virus (MARV) causes severe haemorrhagic fever in humans and nonhuman primates and has a high mortality rate. However, effective drugs or licensed vaccines are not currently available to control the outbreak and spread of this disease." ] },{ "paper_id": "040c9714be80e4a337f6737d17e94171c25cc076", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ebola and marburgviruses are enveloped, negative single-strand RNA viruses of the Filoviridae family [1] . Since the discovery of Marburg virus (MARV) in 1967 [2] and Ebola virus (EBOV) in 1976 [3] , the US Centre of Disease Control has reported several epidemic outbreaks in humans and nonhuman primates [4, 5] . Despite intense world-wide research efforts, no antiviral treatments or vaccines have yet been licensed. In addition to primates, filoviruses infect pigs, dogs, duikers, and fruit bats in nature, and rodents and ferrets can be infected experimentally [6] [7] [8] [9] [10] [11] [12] .", "Luciferase-based GP-driven entry was measured as previously described [48] . ", "Remnant cells were scraped from the wells into 1% SDS/PBS for immunoblot analysis. 3% lysates were run through an SDS/PAGE gel and transferred onto a nitrocellulose membrane. NP or tubulin protein detection was carried out by the same goat EBOV and MARV antisera as used for IF and a tubulin specific mab, respectively, followed by antigoat IRDye680-conjugated secondary ab incubation. Immuno-labelled proteins were detected with and odyssey infrared-imaging system (LI-COR).", "Surrogate HIV-based pseudovirion packaging plasmid HIV Gag-pol, transfer plasmids CSLucW2 (Firefly luciferase expression) or CSGW (hrGFP), and envelope plasmid for VSV-G protein and its backbone plasmid pcDNA3.1 have been described previously [43] . The pWPI-mCherry-BSD bicistronic expression vector was generated by introduction of the mCherry DNA sequence into a pWPI-BSD empty vector [44] . Both plasmids were digested with restriction enzymes BamHI and SpeI. The mCherry encoding fragment was gel isolated, purified and ligated into the new lentivirus expressing vector. mCherry expression was confirmed by pseudovirion generation and fluorescence-activated cell sorting (FACS) analysis. Lenti-X TM Tet-On \u00ae inducible expression system plasmids pLVX-Tet3G and pLVX-TRE3G-ZsGreen1 were purchased from Takara Bio. (Mountain View, CA, USA)." ] },{ "paper_id": "0414c8763c6ec295be60d86698ec3a76e981e54f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since these approaches use available sugar (e.g. from sugar cane or corn), they do not depend on expensive technology to obtain sugar from lignocellulose or for direct light conversion (e.g. photobioreactors). At the same time, they allow to synthesize drop-in fuels (see above).", "Several pathway engineering approaches aim to synthesize biofuels from lignocellulosic polysaccharides (cellulose, hemicellulose), making available non-edible plant parts. For example, a pathway to produce isobutanol was constructed in a native cellulose-degrading bacterium using various genes from different organisms [78] . Similarly, genes to make use of cellulose or hemicellulose were transferred into different microorganisms, some of them containing one or several exogenous genes, in order to synthesize butanol, biodiesel or hydrocarbons [77, 79, 80] .", "The author(s) confirm that this article content has no conflicts of interest.", "More recently the function to seek and degrade a pollutant was generated by coupling in E. coli a synthetic aptamer riboswitch that recognizes the herbizide atrazine to the translation of the mRNA for the protein (CheZ) controlling E. coli motility. Additionally, these cells were equipped with an atrazine chlorohydrolase gene (atzA) for atrazine degradation, derived from Pseudomonas sp. soil bacteria [53] ( Fig. 2B) ." ] },{ "paper_id": "04299cd1ecb45c984de64da12daf3ccc1fe2abe2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(3) mediators released by the gut immune response.", "The intestinal microbiota is a collection of microorganisms that live within the gastrointestinal tract, with concentrations of up to 10 11 -10 12 cells/g luminal contents.", "SCFAs: short-chain fatty acids; IBS-C: constipation predominant-irritable bowel syndrome; MMC: migrating myoelectric complex; 5-HT: 5-hydroxytryptamine; SUS: starch utilization system; SIBO: small intestinal bacterial overgrowth; TGF-\u03b2: transforming growth factor-\u03b2; TNF-\u03b1: tumor necrosis factor \u03b1; FMT: fecal microbiota transplantation; STC: slow transit constipation." ] },{ "paper_id": "042a57ce54d353b67f9faff39f7829c45dc7b101", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Objetivo: Relatar o caso de um lactente que necessitou de intuba\u00e7\u00e3o traqueal no setor de emerg\u00eancia pedi\u00e1trica por conta de laringite aguda grave e que, ap\u00f3s a extuba\u00e7\u00e3o traqueal programada, fez uso, com sucesso, da c\u00e2nula nasal de alto fluxo, a qual, possivelmente, evitou a falha da extuba\u00e7\u00e3o traqueal. " ] },{ "paper_id": "042c9d15e000e5ea7b91612b4c10175e88112278", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Spike protein sequences, easily obtained by Sanger sequencing, are widely used to speculate about vaccine protection (7), but as the immunity for IBV is not based only on the humoral response to this protein (8, 9) , the availability of full genomes for vaccine strains is core to accurately predicting protection markers.", "The D274 genome is 27,599 nucleotides (nt) long [poly(A) tail included] and annotated in the order 5= UTR and leader RNA (nt 1 to 528), ORF1a (nt 529 to 12327), and ORF1ab (nt 529 to 20360) with a ribosomal frameshift, followed by the spike S (nt 20311 to 23802), 3a (nt 23802 to 23975), 3b (nt 23975 to 24169), envelope E (nt 24150 to 24473), membrane M (nt 24442 to 25122), 5a (nt 25481 to 25678), 5b (nt 25675 to 25923), and nucleocapsid N (nt 25866 to 27095) genes and a 3= UTR (nt 27096 to 27599).", "This work was funded by CNPq (Brazilian National Board for Scientific and Technological Development) grant numbers 307291/2017-0 and 400604/2016-7.", "IBV occurs as 6 genotypes with a total of 34 lineages based on the spike S gene and is involved in multisystemic, highly contagious infections of chickens (1, 2) . The IBV positive-sense, single-stranded 5= capped RNA genome with circa 27 kb codes for the replicase complex (open reading frame 1 [ORF1]); the four structural proteins spike S, envelope protein E, membrane protein M, and nucleocapsid protein N; and accessory proteins 3a, 3b, 5a, and 5b, with an untranslated region (UTR) at both the 5= and 3= ends of the genome (3, 4) .", "A plethora of types of avian infectious bronchitis virus (IBV) (Nidovirales: Coronaviridae: Coronavirinae: Gammacoronavirus: Avian coronavirus [AvCoV]) strains are used in live and inactivated vaccine formulations worldwide to prevent infection with or lessen the symptoms caused by the diverse number of field strains of the virus in chickens (1) ." ] },{ "paper_id": "0435b8c5081db34e2c6c62b8f7b998927fa28776", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Breast Enhanced proliferation and migration", "Nrf2 upregulates Notch1 and HES-1(proliferation) via G6PD/HIF-1 and regulates EMT (migration) [44] Increased glucose uptake and NADPH production Histone deacetylase inhibitor reprograms metabolism by upregulating G6PD", "[32]" ] },{ "paper_id": "044b6504465e3d1b00fcc328c6731bcd034b1691", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Aliquots of sample lysates were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), followed by transferring proteins to polyvinylidene difluoride (PVDF) membrane. The membrane was blocked with 5% (w/v) skim milk in Tris-buffered saline (TBS), containing 0.05% Tween-20 (TBST), at 37 \u2022 C for 2 h, followed by washing three times with TBST. Then the membrane was incubated overnight at 4 \u2022 C with mouse polyclonal antibody against \u03b2-actin (ABclonal, Wuhan, China), rabbit polyclonal antibodies against HSP90B1, ANXN4, APN (ABclonal), or MX1, (Protein-Tech, Wuhan, China). After washing three times with PBST, the membrane was incubated with Horseradish peroxidase (HRP)-conjugated goat anti-mouse/rabbit IgG (ABclonal) at 37 \u2022 C for 2 h. Finally, the protein bands were visualized using the Clarity\u2122 Western ECL Blotting Substrate (Bio-Rad, Hercules, CA, USA).", "A total of 100 mg of jejunum homogenates were suspended in 500 \u00b5L PBS, freeze-thawed three times at \u221280 \u2022 C, and centrifuged at 12,000\u00d7 g, for 10 min, at 4 \u2022 C. Next, 200 \u00b5L of clarified supernatant was transferred into a separate sterile tube for total RNA extraction by using Tripure Isolation Reagent (Roche, Indianapolis, USA) according to the manufacturer's instructions. The cDNA was obtained by RT-PCR using the PrimescriptTM RT Master Mix (TakaRa, Tokyo, Japan). The real-time RT-PCR assay used the following primer and probe sequences: PEDV forward primer: 5 -CGTACAGGTAAGTCAATTAC-3 , PEDV reverse primer: 5 -GATGAAGCATTGACTGAA-3 , and PEDV Taq-Man \u00ae probe: FAM-TTCGTCACAGTCGCCAAGG-TAMRA. The PCR was performed using the following parameters: 50 \u2022 C for 2 min, 95 \u2022 C for 10 min, 40 cycles with 95 \u2022 C for 15 s, 56 \u2022 C for 30 s and 72 \u2022 C for 31 s.", "These iTRAQ labeled peptide samples were then redissolved in 200 \u00b5L buffer A solution (20 mM HCOONH4, 2 M NaOH, pH 10). The dissolved sample (100 \u00b5L) was passed through high-performance liquid chromatography (HPLC) on Phenomenex columns (Gemini-NX 3u C18 110 A; 150*2.00 mm). Before HPLC, Phenomenex columns were balanced with 95% buffer A and 5% buffer B (20 mM HCOONH4, 2 M NaOH, 80% acrylonitrile [CAN], pH 10), for 30 min. Peptides were separated by a linear gradient formed from buffer A and buffer B, from 5% to 50% of buffer B at a flow rate of 0.2 mL/min. The ultraviolet (UV) detector was set at 214 nm and a total of 24 fractions were collected. and mobile phase B (0.1% FA, 95% ACN), from 5% to 40% of mobile phase B for 70 min, at a flow rate of 300 nL/min. For MS analysis, a TripleTOF 5600 system (AB SCIEX, Foster City, CA, USA) was used in Information Dependent Mode. MS spectra were acquired across the range of 400-1250 m/z in high resolution mode (>30,000), using 250 ms accumulation time per spectrum. A maximum of 20 precursors per cycle were chosen for fragmentation from each MS spectrum with 100 ms minimum accumulation time for each precursor and dynamic exclusion for 20 s. Tandem mass spectra were recorded in high sensitivity mode (resolution > 15,000), with turned on rolling collision and iTRAQ reagent collision energy adjustment." ] },{ "paper_id": "0450e1d435d63e69e1867c2eba65c0c08af70038", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "L-\u03b1-phosphatidyl-L-serine was obtained as a 10 mg/ml solution in chloroform:methanol (95:5) (Sigma, St Louis, MO). To generate liposomes, phospholipid was dried in a glass tube under nitrogen, and resuspended in PBS to a final concentration of 5 mM. This solution was sonicated on ice 3 times for 5 min each, using a W-385 sonicator with a microtip on output level 3 (Heat Systems Ultrasonics). The liposomes were filtered through a 0.2 \u00b5m pore-size syringe filter and were used immediately unless otherwise described." ] },{ "paper_id": "04510f144938a17bf2c2a9683ce3479ff0246b94", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analyses were performed using the SPSS 13.0 computer software program (SPSS, Inc., Chicago, IL). Survival was analyzed using the log-rank (Mantel-Cox) method. The significance of variability among the experimental groups was determined by the Mann-Whitney U test. All differences were considered statistically significant at p < 0.05.", "Abbreviations CVB3: coxsackievirus group B type3; miRNA: microRNA; MAPK: mitogen-activated protein kinase; HSP27: heat shock protein; MOI: multiplicity of infection; siRNA: small interference RNA; UTR : untranslated regions; VP1: viral protein 1." ] },{ "paper_id": "045b111f0f2584890e9271399aa93c917a496662", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "x Excluded a priori because of assumed collinearity with urea." ] },{ "paper_id": "04603867552ffafcaeff68fe8bf7f190ebb08a78", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "which translates mathematically into" ] },{ "paper_id": "0469d052ac583aa5b739be7fedecec5307548d49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The higher reported concerns for cancers, unemployment and meningitis, reported also by other French studies [7] may be due to their higher prevalence and strong mediatisation in France." ] },{ "paper_id": "046a56d635edc933ed8f30ccf1ae9fd488dfe645", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The above-mentioned data was statistically analyzed by the SPSS software (version 21.0, SPSS, USA, http:// spss.en.softonic.com/) in groups compare using Student's ttest with significant differences defined at p < 0.05, while p < 0.01 represents a highly significant difference.", "Protein concentration was measured using the BCA protein assay reagent (Thermo Fisher Scientific Inc., USA) and equal mass (~35 \u03bcg) samples were fractionated by electrophoresis through 15% polyacrylamide gels. The gels were stained by Coomassie brilliant blue R-250 (Bio-Rad Laboratories, Inc., USA) and de-stained with a de-staining solution (10% acetic acid + 30% ethanol + 60% ddH 2 O). The images were gathered by Lane 1D image shooting software (Beijing SAGE Creation Science Co., Ltd, China).", "The bacterial strains BL21 (E. coli B Fdcm ompT hsdS (r B m B -) gal \u03bb) (DE3), the plasmids pET22b(+)-hLSECtin-CRD and pGEX-6P-hLSECtin-CRD were prepared in our laboratory. The plasmids pET28b and pET28b-Tat were provided by Dr. Chenggang Zhang from our institute. The plasmid pCDNA3.1amyc-his-hLSECtin was provided by Dr. Li Tang from our institute." ] },{ "paper_id": "04799a6c57e1d3f9488b24a4fc2580bbb3818665", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Using the anti-VP6 antibody, we established a differentiating ELISA for PRV. These experiments provided basis for determination of PRV.", "The obtained VP6 sequence was deposited in GenBank database and compared with reference PRV VP6 sequences using DNASTAR software. The name, GenBank accession number and virus isolation location of these genes are shown in Table 1 . At the same time, a phylogenetic tree was constructed by neighbor-joining method base on these VP6 amino acid sequences using the DNASTAR program [25] [26] [27] . The bootstrap probabilities of each node were calculated using 1,000 replicates.", "Generation of polyclonal antiserum to Pro-VP6 was processed according to references with modifications [17] [18] [19] 28] . A New Zealand rabbit was immunized with 2 mL of gel-purified Pro-VP6 (1 mg/mL) emulsified with equal amounts of Freund's complete adjuvant via subcutaneous injection. After ten days, 2 mL of the same antigen mixed with Freund's incomplete adjuvant were injected into the rabbit weekly at two intervals. Antiserum was collected from the peripheral blood of the rabbit." ] },{ "paper_id": "047a76d5e047a00728847bcdd162cb925486d0ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each biomedical image technique is appropriate for certain diagnostics. For example, MRI enables the spatial localisation required for cross-sectional imaging whereas ultrasound images allow physicians the visualisation of soft tissues and have revolutionised obstetric care [7] . However, digital radiology is still the backbone of diagnostic bioimaging, mainly due to three reasons: (1) its capability to detect unsuspected pathologies; (2) being not invasive; and (3) having a low radiation dose and low cost [8] .", "In particular, the Bhattacharyya distance [42] is used to provide a measure of the similarity of two histograms. Considering two histograms 1 and 2 , this distance is defined by", "\u2212 min \u2208pathologic ( ( ) , ( )) ," ] },{ "paper_id": "0480084eefee6333df832a821af8945ea7ab379a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "professional visits were less likely in summer compared to spring and autumn.", "Additional file 1: The contact log (in English) is available in as an additional file.", "Data was entered and stored in Microsoft Office Access 2007 (Microsoft Co., Redmond, Washington, USA), and analysed using Stata Statistical Software: Release 11.2 (StataCorp. 2009, College Station, Texas, USA)." ] },{ "paper_id": "048b240dcabbd623a6cda8c4236ea50d7961315c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusion/Significance: While there has been an increase in imports of amphibian and reptiles into Thailand, erratic patterns in proportions of captive-bred specimens and volumes suggests either capricious markets or errors in reporting. Large discrepancies with respect to origin point to misreporting or possible violations of the rules and intentions of CITES.", "The import of live reptiles into Thailand via Macao is restricted to the year 2006 when 102 individuals of 9 species were reexported from Macao. While Macao reported the re-export of these animals, for 78 individuals (76%) of 7 species there are no corresponding records of the animals ever being imported into Macao (Table 2) ." ] },{ "paper_id": "0491da5ae5c2fa38824350bde5462ed82ebc24e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The blot was probed with polyclonal gp120 antibody.", "Subtype C (96ZM651 strain)", "Nabs: Neutralizing antibodies CHO: Chinese hamster ovary" ] },{ "paper_id": "049294a884d39102b06a634ba0f4bd3185fcc478", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The klassevirus 1 contig had a genomic organization similar to other picornaviruses ( Figure 1A -C). Conserved Pfam [26] motifs characteristic of picornaviruses were present including two picornavirus capsid proteins, RNA helicase, 3C cysteine protease, and RNA dependent RNA polymerase.", "5'-GGAAACCCAACCACGCTGTA-3') and", "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "049d68aa5279d807e4125c33a3d563f6df987cb4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical Analysis. For analysis of two unpaired samples, the nonparametric Mann-Whitney U test was used. A significant difference was defined as P < .05. All values were represented as the means \u00b1 SEM.", "Morphometric Evaluation. The percentages of the distribution area of the cells immunoreactive for thrombomodulin among those immunoreactive for CD34 were estimated from 30 randomly selected color images at a magnification of 400 in each case using a digital image analysis system (Lumina Vision, Mitani Corporation, Fukui, Japan).", "High mobility group protein B1 (HMGB1) was originally identified as a nuclear nonhistone protein with DNA-binding domains and implicated as an important endogenous danger signaling molecule [3] as well as a late mediator of systemic inflammation in septic shock [4, 5] , thus having a putative role in the pathogenesis of acute lung injury [6, 7] ." ] },{ "paper_id": "04a02b2f24ba9cf14a860a98b25f65ef2afd73fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hern\u00e1 n Makse", "The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. ", "s\u00f0fx t;prior g n ; fo t;prior g n \u00de s 2 t;prior \u00f0o i t;post \u00c0 o i t;prior \u00de:", "z L as the MLE of the parameter vector." ] },{ "paper_id": "04a0ec4b6cb5eeb0d2cbf2c8ea8829b5c476b1b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Week after installation " ] },{ "paper_id": "04a253fd34bd82b3cf7868fca967469c66e392ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "poly I:C was purchased from invivogen. RO 90-7501, chloroquin, SB202190 and U0126 were purchased from Sigma. LY294002 and SP600125 were from Cell Signaling. IKK-2 inhibitor IV was purchased from Santa Cruz Technology.", "RO 90-7501 enhances the antiviral response induced by poly I:C", "RO 90-7501 enhances poly I:C-induced activation of IFNb promoter, but does not change the activation kinetics" ] },{ "paper_id": "04abbb8d91bd1a15a6c70ce3c0bd339f92468265", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "04b5f15cca91a7b810216682780f8ea6e1ab3046", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Camels have been associated with human civilization for thousands of years as a form of transportation of people and goods, a source of meat, milk and wool, and a player in recreational a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "The data generated in this study is available online. Illumina ", "To minimize the issue of contamination, we have run sample processing, pre-amplification, library preparation, and sequencing in a contained hood in separate rooms. Each RNA sample was reverse-transcribed and amplified with a modified random amplification (Round AB) protocol as described previously [32] . PCR amplicons obtained from the pre-amplification were purified with Agencourt AmPure XP (Beckman Coulter) and subsequently fragmented by sonication using a Covaris LE220 focused-ultrasonicator (Covaris) in order to achieve efficient library generation. Library construction for Illumina sequencing was carried out for each sample individually using NEB Ultra II DNA Library Prep Kit (New England Biolabs) with dual index barcoding according to the manufacturer's instructions. Library construction was done either manually or on an automated NGS workstation, Zephyr G3 NGS Workstation (Perki-nElmer). Quality of the libraries generated was evaluated using a 2200 TapeStation Nucleic Acid System (Agilent Technologies) and library DNA concentrations were measured using Qubit 2.0 fluorometer (Thermo Fisher Scientific). The libraries were then normalized, pooled, and sequenced on an Illumina HiSeq 2500 (2x125) or MiSeq (2x300) instrument, aiming for 5-10 million pair-end reads per sample following the company's standard protocols." ] },{ "paper_id": "04b9001d61d666e065f28a9e628991f4d76d71bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The nature of this general Internet-based survey amongst healthy volunteers from the general population does not require formal medical ethical approval according to the Dutch law [29] .", "Timing of the three surveys related to the course of the Influenza A (H1N1) outbreak", "Demographic characteristics of respondents are listed in Table 1 . Overall, there were no significant differences between surveys. Focusing on survey 3, mean age was 51 years (range 19-89 years) and most respondents (92%) were of Dutch origin. Thirty-eight percent had a lower education (i.e. primary education, lower general or lower vocational education or less), 36% an intermediate (i.e. secondary general or vocational education), and 26% a higher education (i.e. higher professional education or university). The majority of respondents were employed. About three quarters were married or cohabitating and in 27% of the households there were one or more children under 18 years. Compared to the general Dutch population (Table 1) , the respondents were older, more often of Dutch origin, and more often unemployed/ retired." ] },{ "paper_id": "04bc03c90437934a75fc6fdc228817234ef84c3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "animals BALB/c and C57BL/6 male mice (6-8 weeks old, male) were obtained from Guangdong Medical laboratory Animal Center (Guangdong, China) while Rag1 \u2212/\u2212 mice (B6 background) were purchased from Jackson Laboratory (Bar Harbor, ME, USA). All mice were housed under a specific pathogen-free condition. ", "immunohistochemistry Allografts were fixed with 4% paraformaldehyde for 24 h and then embedded in paraffin. Tissues were cut into 3-\u03bcm thick sections and placed on slides. The sections were then used for H&E and immunohistochemistry staining. For immunohistochemistry, slides with sections were incubated with primary anti-CD3 antibody (1:100, Abcam) at 4\u00b0C overnight, then secondary antibody HRP-anti-Rabbit IgG (Maxim), followed by diaminobenzidine color development. For quantitative analyses, slides were imaged at a magnification of 200\u00d7. The area of inflammation/infiltration and integrated optical density (IOD) of CD3 were measured using ImagePro plus 6 software.", "Comparisons of the means were performed using Student's t-test and one-way ANOVA. Data were presented as the mean \u00b1 SD and analyzed through GraphPad Prism 6 (GraphPad Software, La Jolla, CA, USA). The analysis of graft survival was conducted using Kaplan-Meier method (log-rank test). A value of P < 0.05 was considered statistically significant.", "This study was carried out in accordance with the recommendations of the \"Chinese national guidelines for the Care and Use of Laboratory Animals\" and the protocol was approved by \"the Institutional Animal Care and Use Committee of Guangdong Provincial Academy of Chinese Medical Sciences. \" aUThOr cOnTriBUTiOns FQ designed and performed experiments; HL and C-LL conducted partial experiments; GN provided idea and edited the manuscript; and ZD designed experiments and wrote the paper. " ] },{ "paper_id": "04be45dba1c24d640d5da8298c5f01e3165d84c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Between 1980 and 2008, the number of people with type 2 diabetes (T2D) worldwide increased from approximately 150 million to 350 million 1 . According to the World Health Organization, the global economic burden of T2D is tremendous, consuming 2.5-15% of countries' primary healthcare budgets 2 . Till now, the use of oral antidiabetic drugs (OADs) remains the preferred pharmacological therapy due to many patients' fear of insulin administration and its adverse effects, such as hypoglycemia and weight gain 3,4 .", "Several classes of OAD are available on the market, including biguanide (metformin), sulfonylureas, alpha-glucosidase inhibitors, meglitinides, thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP-4) inhibitors, and newer sodium-glucose cotransporter 2 (SGLT2) inhibitors. In addition to mediating", "Statistical analysis. The baseline demographic characteristics of the cohort were analyzed using descriptive statistics. We conducted conditional logistic regression with adjustment for potential confounding factors, including OAD use, insulin use, and all other predefined comorbidities associated with the risk of sepsis (Table 1) . ORs were computed to compare OAD exposure of cases and controls. The Microsoft SQL Server 2012 (Microsoft Corp., Redmond, Washington, USA) was used for data linkage, processing, and sampling. All analyses were performed using STATA statistical software (version 13.0; StataCorp., College Station, Texas, USA). Statistical significance was defined as P < 0.05." ] },{ "paper_id": "04c1c40f4464bc035e57d0ecf2f8a033e4e7f466", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations LRTI: Lower Respiratory Tract Infection; RSV: Respiratory Syncytial Virus.", "Non-identifiable administrative data was utilized for the purposes of this analysis and therefore ethics approval was not required.", "Competing interests YS has no competing interests or conflicts of interest to disclose." ] },{ "paper_id": "04c221e49d8355ce52360d5e37dc583f6502cc92", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine mycoplasmas medium, Middlebrook 7H9 broth base medium, Mycoplasma gallisepticum medium and Yeast Peptone Dextrose (YPD) medium were purchased from Qingdao Hope Bio-Technology Co., Ltd (Qingdao, Shandong, China). 1640 medium and horse serum were bought from Gibco (GrandIsland, NY, USA). DMEM (Hyclone, Beijing, China) supplemented with 10 % or 2 % heat-inactivated fetal calf serum (FCS; Hyclone, USA), 100 IU/ml penicillin G and 100 \u03bcg/mL streptomycin was used for cell growth or maintenance medium. A 0.25 % trypsin (Hyclone, Beijing, China) was prepared in pH 7.2 phosphate buffer saline (PBS). A 0.5 % 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide (Biosharp, Hefei, Anhui, China) was prepared in PBS. These solutions were sterilized through a 0.22 \u03bcm Millipore membrane filter. Dimethyl sulfoxide (DMSO) was purchased from Sigma (St Louis, MO, USA).", "Extraction Kit were the products of TIANGEN biotech Co., Ltd (Beijing, China). Trizol Regent was purchased from Ambion (Shanghai, China). All other chemicals and reagents commercially available were of the highest analytical grade.", "pMD18-T vector, M-MLV Rtase, Rnasin, Trans1-T1 competent cell, SYBR Premix Ex TaqTM II (Tli RNaseH Plus) were purchased from TaKaRa (Dalian, Liaoning, China).", "To determine the reproducibility of the real-time PCR, the standard plasmid was diluted to 3.74 \u00d7 10 4 , 3.74 \u00d7 10 5 and 3.74 \u00d7 10 6 copies/\u03bcL respectively in DEPC treated water. To evaluate intra-assay variability, each dilution was analyzed in triplicate. To measure inter-assay variability, each dilution was analyzed in three different runs performed by two different operators on different days. Coefficients of variation for cycle threshold (Ct) values within each block and among blocks (using the mean values from each block) were determined." ] },{ "paper_id": "04c80346278c76be38e11fba9ee1a0fccc13c57f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data are expressed as mean \u00b1 standard error. Differences between the two groups were analyzed using the Mann-Whitney U test, Wilcoxon's test, and the Fisher's exact test. Differences were judged significant for p <0.05 (two-tailed). Adjusted odds ratios were calculated using logistic regression analysis. All statistical analyses were conducted using JMP Version 6 (SAS Institute, Cary, NC, USA). The level of statistical significance was defined as 0.05." ] },{ "paper_id": "04cf308cfa2f72131ecbb07bacb894bab15aa66e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rift Valley fever (RVF) is a disease of major public health and economic concern, affecting humans and livestock throughout Africa [1] [2] [3] [4] [5] [6] and the Arabian Peninsula [7] . The etiological agent of this zoonosis, Rift Valley fever virus (RVFV), is an arbovirus belonging to the Phlebovirus genus in the family Bunyaviridae. RVFV infection is severe in animals, especially sheep, cattle, and goats, resulting in high mortality rates in newborns and near 100% abortion rates in pregnant animals. In humans, infection is usually self-limiting, but a small percent of cases (1-2%) can progress to severe hepatitis with hemorrhagic manifestations. In addition, retinal inflammation can lead to permanent vision loss in about 1-10% of infected patients [6] .", "Design of membrane-interacting peptides RVFV Gc amino acid sequence was analyzed to identify regions of the predicted protein having a positive Wimley-White interfacial hydrophobicity score (WWIHS), indicating a potential to interact with lipid bilayers [25] . Five non-transmembrane domain regions within RVFV Gc were found with significant WWIHS values, and peptides analogous to these five regions were synthesized (RVFV-1, -2, -3, -4, -5; Table 1 ).", "To rule out the possibility that the decreased virus infectivity was due to peptide toxicity on the Vero E6 cells, we performed a MTT toxicity assay as described in Materials and Methods. Neither RVFV-6 nor RVFV-6sc reduced Vero E6 cell viability at peptide concentrations up to 50 mM ( Figure 2D )." ] },{ "paper_id": "04d02a37dcbb17916d2a5c03288cb9b59000ebba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "04d638b3c1d8b8fcd771e569e439b364d4ac2c1a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(0) Comments agreements between both methods [mean (range): 0.91 (0.83-1.00)] were found for 10/15 viral agents.", "No competing interests were disclosed." ] },{ "paper_id": "04d774680876efd10e478ed5f2ef7a7a2e860acf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An Observational, Analytical, Cross-Sectional Study Was Performed.", "Genotype determination was performed on 55 samples (64%). Sequenced viruses in RSV-A clustered with reference viruses in genotypes GA2 (n = 6) and ON (n = 17) (Supplementary Figure S1 ). All RSV-B viruses clustered with reference viruses in genotype BA (n = 32), as shown in Supplementary Figure S2 . We found no difference in disease severity between GA2, ON, and BA genotype ( Figure 1C ", "This FONCECYT study N \u2022 11121536 was approved by the Local Ethics Committee of the North Metropolitan Health Service (25 October 2012) and the Faculty of Medicine, Universidad de Chile (28 June 2012). Informed consent was signed by the parents of all study participants." ] },{ "paper_id": "04d9df812fd77e1231263d42ab45e570cd94d956", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A protocol for the systematic review was written a priori.", "Grey literature (literature that is not commercially published) was identified by searching the websites of health technology assessment and related agencies, professional associations, and other specialized databases. Google and other Internet search engines were used to search for additional information. These searches were supplemented by hand searching the bibliographies and abstracts of key papers, and through contacts with appropriate experts and agencies.", "The search included all languages and was limited to articles published between Jan 1, 1990 and Oct 22, 2010. Conference abstracts were excluded from the search results. Regular alerts were established on EMBASE, MEDLINE, CINAHL and PubMed, and information retrieved via alerts was current to Jan 15, 2011." ] },{ "paper_id": "04dc7b970967766934f12292c0a007ebabe22652", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the local ethics committee and carried out in accordance with the Declaration of Helsinki. The parents provided written informed consent to publish the report and the picture appearing in Figure 1 .", "KG first drafted the manuscript. CS and UF contributed to WES analysis. AB, FB, FS, GK, and RM cared for the child. JD-D and DW performed cytogenetic analysis. AB cared for the child and critically revised the manuscript for important intellectual content. MK cared for the child, designed, and supervised the project and critically reviewed and revised the manuscript for important intellectual content. All authors approved the final manuscript as submitted.", "The authors thank their patients and their family." ] },{ "paper_id": "04e314a46a06814267d29c2e6dfc00bf4121cc94", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. ", "Another group of investigators proposed a mechanistic model for this pathway [56] . Receptor interacting protein kinase-3 (RIP3), which is an essential kinase for necroptotic cell death signaling, was identified by high-throughput siRNA screening as a positive regulator of CVB3 replication [56] . Depletion of RIP3 diminishes CVB3 propagation by inhibiting autophagosome formation before it is fused to the lysosome. Interestingly, in the later stage of infection, the viral protease 3Cpro targets RIP3 and abrogates RIP3-mediated necrotic signaling [56] . These results suggest that autophagy induction, which could be beneficial for viruses, is a temporal event and that this system is targeted by viral proteases during the later stage of infection in order to prevent cell death.", "Recently, reticulon (RTN) family proteins were identified as host factors that interact with NS4B of HCV and negatively regulate HCV genome replication [34] . Reticulons are a highly conserved eukaryotic family of proteins that contain two short hairpin transmembrane domains (TMDs) that predominantly occupy the membrane bilayer outer leaflet [35] . Since the short hairpin TMDs of reticulon are able to expand the area of the cytoplasmic outer leaflet relative to the luminal inner leaflet of the bilayer, they generate positive membrane curvature, which is an architectural feature seen in ER tubules [35] . In mammalian cells, the reticulon family of proteins consists of four members, RTN1-RTN4, but the functional differences among the four members are currently poorly understood." ] },{ "paper_id": "04ed44ad0aed30771e1ba0f38e4aa00101d1b8c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. Primary data that support the findings of this study are available from the corresponding author on request.", "Here, we show that polyvalent inactivated HRV vaccines generate broad nAb responses in a BALB/c mouse model (up to 25-valent) as well as a rhesus macaque (RM) model (up to 50-valent). Immunogenicity of polyvalent inactivated HRV vaccines is not affected by increasing valency, and it relates to antigen dose. A highly polyvalent strategy may facilitate practical HRV vaccine development.", "In this study, we demonstrate that polyvalent inactivated HRV vaccine expanded to a 50-valent composition, with alum adjuvant, is immunogenic against approximately one-third of circulating HRV types. Although fifty HRV types is a minority, these data provide proof of principle for a highly polyvalent vaccine approach. Forty years ago, the prospects for a polyvalent HRV vaccine were dour for good reasons 17 . However, progress in technology 34 and advancement of more complex vaccines renders impediments to a polyvalent HRV vaccine manageable. Scale-up of HRV vaccines may be facilitated by related vaccine production processes and new cost-saving manufacturing technologies [35] [36] [37] . Inactivated HRV has a positive history of clinical efficacy 6, 8, 9 .", "Vaccination. Before immunization, all HRV types were inactivated by addition of 0.025% formalin followed by incubation with stirring for 72 h at 37\u00b0C, as previously described for HRV vaccine 33 . Complete inactivation of infectivity was confirmed by end point TCID 50 titration in H1-HeLa cells. Formalin inactivation by this method resulted in greater immunogenicity in mice than alternative inactivation by b-propiolactone, suggesting formalin inactivation preserved antigenic determinants. Mice were vaccinated i.m. with inactivated HRV strains mixed with 100 mg of Alhydrogel adjuvant 2% (aluminium hydroxide wet gel suspension, alum; Sigma catalog A8222 or Invivogen catalog vac-alu) according to instructions of the manufacturers. The total volume per mouse was 100 ml, administered in 50 ml per thigh. Mice were given a second identical vaccination (boost) at the time indicated in figure legends. RMs were vaccinated i.m. with inactivated HRV strains mixed with 500 mg of Alhydrogel adjuvant 2%. The total volume per RM was 1 ml, administered in one leg. RMs were boosted with an identical vaccination at four weeks." ] },{ "paper_id": "04f4cff6c1a32e0edb50bdb8daf00f82708a5142", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Despite the important reduction in reported malaria incidence during the last decade in a number of countries worldwide, malaria infection still represents one of the major global public health threats. The World Health Organization (WHO) estimated an annual global burden of 207 million malaria cases and 627,000 deaths in 2012 [1] .", "Spectra of peptides were recorded on a JASCO J-810 spectrometer (JASCO corporation, Tokyo, Japan) equipped with a temperature controller and a 0.1 cm path length cuvette. The measurements were made in water at pH 7.3 and 22uC and at a peptide concentration of 0.15 mg/mL.", "Circular dichroism (CD) studies of 16 randomly selected peptides indicate that they assume a total or partial a-helical conformation in water. Peptides 40-43, 55, 60 and 65 exhibit a CD pattern characteristic of a high a-helical content as indicate for PvPep40 ( Figure 1A " ] },{ "paper_id": "04fa24d6f02d6b2fd44a0cb7aa2a7e7149e6cacc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Based on the fact that SA is HA receptor, SA-based inhibitors can be exploited as potential anti-HA agents. Because one influenza virion usually contains about 350-400 HA trimers on its surface [9] , monovalent SA analogs ( Figure 3 ) would be unable to compete with the highly multivalent interactions between viruses and their host cells. Therefore, inhibitors of the bivalent, tetravalent and even polyvalent sialosides afford an enhanced inhibitory activity over monovalent ligands [20] . The polyvalent sialosides show high potency in vitro [20] . It is currently acknowledged that recognition of \u03b1-2,6 SAs is indispensable for the influenza viruses to gain their efficient transmissibility in human.", "Russia approved an anti-influenza drug, Arbidol, in 1993, which acted by increasing influenza virus HA stability and preventing low pH-induced HA transition to its fusogenic state [53] . However, this potent broad-spectrum antiviral drug is only well-known in Russia and China. A recent study exploiting the characteristics of arbidol-resistant mutants of influenza virus has confirmed its inhibitory mechanism [54] .", "Most of the founded small molecules are more potent in inhibiting group 1 IAV than group 2 IAVs. Vanderlinden et al. reported a new series of N-(1-thia-4-azaspiro [4.5] decan-4-yl)carboxamide inhibitors which show marked antiviral activity against group 2 influenza A/H3N2 viruses [68] . The lead compound 4c has an IC50 of 9.6 \u03bcM and a selectivity index of 10. This compound has specific activity against the H3 subtype, but not the H1, H5 and H7 subtypes.", "Two neuraminidase inhibitors, oseltamivir and zanamivir, were both approved in 1999 for treatment and prevention for acute uncomplicated flu caused by influenza A and B. Neuraminidase inhibitors interfere with the enzymatic activity of the NA protein, which is critical for the efficient release of newly synthesized viruses from infected cells. However, resistant virus strains are constantly emerging, especially to oseltamivir [3] . Different from the oral administration oseltamivir, zanamivir can only be inhaled due to its low bioavailability, which makes the limited use of this drug. In 2009, a new NA inhibitor, peramivir, was authorized for the emergent treatment of certain hospitalized patients with known or suspected 2009 H1N1 influenza." ] },{ "paper_id": "050e73f86cfa4ab3f3fc84b0cb55ac779fb9abc2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "proteins in overlapping reading frames: the nucleoprotein (N) and a non-structural protein (NS S ) which suppresses type 1 interferon (IFN) in the mammal host. The M segment encodes a single polyprotein (M polyprotein) that is post-translationally processed into two glycoproteins (G N and G C ), and a non-structural protein (NS M ) [3] . G N and G C are the major proteins to which neutralizing antibodies are directed [4, 5] . The L segment encodes a single open reading frame for the RNA-dependent RNA polymerase (L) [6] .", "C6/36 cells (Aedes albopictus mosquito larvae) were maintained in Earle's MEM supplemented with 10% fetal bovine serum (HyClone), 2 mM L-glutamine (Invitrogen), and 1 mM non-essential amino acids. Vero cells (African green monkey kidney) were maintained in Opti-PRO\u2122SFM medium (Invitrogen) supplemented with 4 mM L-glutamine (Invitrogen).", "Histopathological changes were not observed in respiratory nasal epithelium or muscles of the upper rear limb." ] },{ "paper_id": "0511ed1c3e91902ab662c81f8fc20c83a840e8d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Written informed consent was obtained from the study participants. This study was reviewed and approved by the Singapore military's Joint Medical Committee for Research, and the National University of Singapore's ethics review committee. ", "Abbreviations FRI: Febrile respiratory illness; AOR: Adjusted odds ratio; CI: Confidence interval; SAF: Singapore Armed Forces; MVI: Mono-viral infection.", "Smoking has been shown to increase risk of upper respiratory infection among recruits [36] , Hajj medical mission personnel [59] , infants and children exposed to parental smoking [60] . Hence, it is not surprising to observe smoking as a risk factor of FRI in our study. There are some studies that had shown that cigarette smoking impairs oral and respiratory tract immunity [61] [62] [63] . This may have predispose smokers to a higher chance of viral infection resulting in FRI. However, further study is warranted to investigate mechanism behind this observation." ] },{ "paper_id": "05186884eb6aed574507e7f0f9316375ffbc6494", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "05192151667b1bb4e3405de11f6e4ae2f844e7c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Genus ", "Length of nucleotides 29,727 30,119", "Antigenic components inducing the immune system without introducing viral particles, whole or otherwise." ] },{ "paper_id": "051cf89045450e5eff3fc9ba4fdc518fe1d623b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "05252b1035b0647c566b72ef0ef269f3fc385c90", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "05257a2230897ea006b3f68dbf0d71e1e7216f55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each year about 200-250 autologous and 100-120 allogeneic transplantations are performed. The majority of allogeneic transplant patients receive peripheral blood stem cells after a reduced conditioning regimen.", "The Heidelberg University Hospital is a tertiary referral center. The department of hematology comprises four inpatient wards for adult patients-two wards for normal and high-dose chemotherapy, one intermediate care unit and one transplant unit-as well as several outpatient clinics and a day hospital where chemotherapy on an outpatient basis is administered. Most of the patients treated suffer from malignant lymphoma, multiple myeloma, and acute leukemia.", "We used Stata version 11 (Stata Corp., College Station, TX, USA) for all statistical analyses. Fisher's exact test was applied for univariate analyses, logistic regression models were used for multivariate analyses." ] },{ "paper_id": "0529ed2074b15413b032e82de1fcce37efde51a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Dunnett's test was conducted by using GraphPad Prism v4.0. Data are presented as means \u00b1 S.D, and P < 0.05 were calculated by using Student's t-test and considered as significant differences as described .", "Electronic supplementary material The online version of this article (" ] },{ "paper_id": "052a16d442ede77ed4bdeaa05037270f251dedc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An analysis of variance and Student's t-test were used to evaluate potential differences among the different groups with regard to the humoral immune responses, viral burdens, and body weights. Differences between groups were considered significant at P < 0.05.", "Six-week-old BALB/c female mice were purchased from Southern Medicine University, Guangzhou, China, and were housed, fed in microisolator units according to the Veterinary guidelines of South China Agricultural University and all animal experiments were approved by the South China Agricultural University Institutional Animal Care and Use Committee.", "The hemagglutination inhibition (HI) assay and virus neutralization (VN) assay were performed as described previously [23] .", "Purified virus particles were absorbed onto carboncoated copper grids and incubated with a monoclonal antibody (mAb) against HA of H9N2 (prepared in our lab) for 1 h. The grids were incubated with goat antimouse IgG labeled with 5-nm gold particles (Sigma) for 30 min. After 3 additional PBS washes, the grids were stained with 2% phosphotungstic acid (Sigma, St. Louis, MO, USA) and examined under transmission electron microscopy (H-7500; Hitachi, Tokyo, Japan)." ] },{ "paper_id": "0537823ee7ac420f3f6e1a1261afa425dd4cd1a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine deltacoronavirus (PDCoV) strain CHN-GD16-03 and swine acute diarrhea syndrome coronavirus (SADS-CoV) were provided by Professor Jing-Yun Ma, who works at the College of Animal Science, South China Agricultural University, Guangzhou, China. Porcine reproductive respiratory syndrome virus (PRRSV) strain JXA1 was purchased from China Animal Disease Control Center, Beijing, China. Pseudorabies virus (PRV) strain HB-98, classical swine fever virus (CSFV) strain C attenuate vaccine, porcine circovirus type 2 (PCV2) killed vaccine, transmissible gastroenteritis virus of swine (TGEV) attenuate vaccine, porcine epidemic diarrhea virus (PEDV) CV777 attenuate vaccine, porcine rotavirus (RV) NX attenuate vaccine, porcine parvovirus (PPV) CP-99 killed vaccine, and pig foot-and-mouth disease virus (FMDV) killed vaccine were purchased from commercial vaccine companies. Swine influenza virus (SIV) was isolated and preserved in our laboratory.", "The data used to support the findings of this study are available from the corresponding author upon request.", "Coronaviruses (CoVs) belong to the family Coronaviridae; they can infect a variety of hosts and cause various illnesses, including respiratory infections and enteric diseases [1] [2] [3] [4] [5] . Based on phylogenetic analysis, we can classify CoVs into four major genera: alpha-CoV, beta-CoV, gamma-CoV, and delta-CoV [5, 6] . Porcine deltacoronavirus, which belongs to delta-CoV, was first reported in an epidemiology investigation in Hong Kong [5] . Thereafter, PDCoV was detected and isolated across the world [7] [8] [9] [10] [11] [12] [13] . The PDCoV genome is approximately 25-kb long, containing a 5 \u8020 untranslated coding region (UTR), replication-associated genes (1a, 1b), a spike (s) gene, an envelope (e) gene, a matrix (m) gene, a nucleocapsid (n) gene, two nonstructural genes (ns6, ns7), and a 3 \u8020 UTR gene.", "It is important to note that PDCoV is a newly discovered coronavirus, which is circulating across the world [2, 9, 13, 14, 21] . Low feed remuneration is observed in pigs infected with PDCoV pathogens; the impact of PDCoV was more severe in infected newborn piglets, which ultimately succumbed to the virus and died. Currently, there are no effective treatments and vaccines against PDCoV infection." ] },{ "paper_id": "0539cdf9c5215f7d1f53d1cb7af556ba1f799937", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The special phi29 DNA polymerase and polymerase chain reaction (PCR) reagents were obtained from TakaRa Company. T4 DNA ligase was purchased from New England Biolabs. 3`-Amino-modified fluorescence probes and other oligonucleotides used in this study were synthesized by Shanghai Invitrogen Inc. (China). 3-Aminopropyltriethoxysilane (APTES, 99% ) was purchased from Aldrich. Microscope slides (DAKO, Catalog no.S3003) were used as PCR reaction containers. The instruments used in this experiment were: PCR thermocycler (PTC-200, MJ Research), real-time PCR (Peltier thermal cycler, Eastwin), microarray scanner (LS-300, Tecan), and microarray spotter (PRXSYS 5500, Cartesian)", "Molecules 2010, 15 620" ] },{ "paper_id": "053aa0c7280e2bb41a033cb0ae7c0d6bd07afc40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The source and genotypes of yeast strains used in this study are listed in Table 1 . E. coli strain used was DH5\u03b1 (Bethesda Research Laboratories). Yeast transformation (38) , media and genetic procedures have been described previously (39) .", "For the overexpression of the Lys-tRNA encoded by the tK(UUU)L gene, we first introduced SphI and NheI restriction sites to plasmids pMB38-9mer (FF and WT) carrying the 'CUU-AAA-C' sequence by PCR oligonucleotide directed mutagenesis. Oligonucleotides used were 5 -GGTGTCGGGGCGCATGCATGACCCAGTCAC-3 and 5 -AGAGTGCACCATATGCGGTGTGAGCT AGCGCACAGATGCG-3 . The tK(UUU)L gene was amplified from strain UMY2067 by using oligonucleotides 5 AAAAGCATGCCGGTAGAGTCTCTT-CTTGGTC-3 and 5 AAAAGCTAGCCGGTA-AGAGAGAAACCTCCA-3 and cloned between SphI and NheI sites of these plasmids.", "Supplementary Data are available at NAR Online." ] },{ "paper_id": "0542a6ae26f57a5ffa35dcfebdec5004ff45688c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Of note, Ortiz and colleagues raised the concern that there is a lack of clinical studies in the setting of a public health emergency [such as the A(H1N1)pdm09 pandemic] to inform clinical care, particularly in low-resource settings [44] .", "By utilizing an already existing clinical study infrastructure through the INSIGHT network, we were able to rapidly develop a system for studying the emergence of a novel influenza A virus and clinical outcomes of infection in an international setting. We have maintained this system to continue observational cohort studies to assess clinical outcomes of seasonal influenza across diverse geographic areas and patient populations, and to serve as a platform for treatment studies. Further, the INSIGHT FLU network is currently being adapted to include other emerging respiratory viruses of global public health importance [e.g. MERS-CoV, avian influenza A(H7N9) virus]." ] },{ "paper_id": "05445d95af0648219e8eb051ab3015b2a4615027", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "P-values and 95% CIs were constructed using 2-tailed tests. Pvalues ,0.05 were considered statistically significant. Statistical analyses were performed using R, version 3.0.2 [34] ." ] },{ "paper_id": "054e3e247ad11de2be71be7215e30a44222271ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nonetheless, such an oligomerization behavior may be relevant to RNP packaging.", "The solution structure (PDB ID: 2JW8) and crystal structure (PDB ID: 2CJB) of the CTD spanning residues 248-365 were obtained from the Protein Data Bank (www.rcsb.org). All structure images were prepared with PyMOL (www.pymol.org).", "Disulfide trapping samples were boiled for 2 min at 94uC in the presence and absence of b-mercaptoethanol. The boiling time was kept short (2 min) to avoid protein aggregation. The samples were then loaded on a NuPage 4-12% Bis-Tris gel (Invitrogen, CA) and run at room temperature according to manufacturer's instructions. The gel was digitized on a UVP BioDoc-It equipped with a fluorescent plate (UVP, CA). Quantification of the disulfide-linked and unlinked bands was achieved through the ImageJ software (National Institutes of Health, MA)." ] },{ "paper_id": "05513568bb7b58bb7df33023160838ac885a6144", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "05513da119ba8f48c1c468a8a40a591b731c4479", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We obtained written informed consent from all study participants. If these were less than 18 years of age we asked their parents or legal guardians to provide proxy written consent, with additional written consent from those participants aged 14 to 18 years of age. Children were defined as persons aged less than 14 years, adults were at least 14 years old.", "In general, we believe that our data for adherence and tolerability would support a recommendation to use non-pharmaceutical interventions in a pandemic." ] },{ "paper_id": "055bc4fbdbbe262da7684e89ea4cfcc154a42291", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Peptides were obtained from Bio-Synthesis (Lewisville, TX, USA) and included M 133-147 (GTVYVRPIIEDYHT), MOG (MEVGWYRSPFSRVVHLYRNGK), and MBP 60-80 (SHHAARTTHYGSLPQKSQR)." ] },{ "paper_id": "055df119df20e08c2830c0b300173e343a760d38", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "When calculating the proportion of confirmed and probable cases that presented with EVD symptoms, we assumed that patients for whom the presence or absence of at least one symptom was reported did not display any additional symptoms unless those were also reported.", "\u2022 Fever AND at least 3 symptoms (headache, vomiting/nausea, anorexia, diarrhoea, fatigue, abdominal pain, myalgia, generalized generalised joint pains, dysphagia, hiccups).", "\u2022 Any unexplained death.", "\u2022 All those (dead or alive) presenting with fever and any three of the following symptoms: ", "Further research is needed to understand why the likelihood of death is different for different age groups and to investigate the effect of the different routes of transmission of the virus on interventions such as vaccination." ] },{ "paper_id": "055ed1f10bcc96eacefe967b946a0b8c1674e197", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vero cells were maintained in minimal essential medium (GIBCO, USA) supplemented with 5% heat-inactived Fetal Bovine Serum and antibiotics in 5% CO 2 at 37\u00b0C. These cells were used for multiplication and titration of the virus.", "Data are shown as mean \u00b1 SEM. The Kaplan-Meier test was employed to compare survival rates. One-way ANOVA with Tukey's correction was used for multiple comparisons. Statistical significance was set at p < 0.05." ] },{ "paper_id": "05620ea699e7dcf77f750bbb52911ea18b005d8f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "05774f9508a8c3399ffb20e758f933ffadc40fbd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The closer the value of Levenshstein distance to zero, the closer are the species names.", "To share the information beyond our MySQL (v5.6.33) DBMS (Database Management System), we built a website using HTML, CSS, JavaScript and PHP (v5. 6 ", "No potential conflicts of interest were disclosed.", "Here, 'x' and 'y' are 2 strings and d(x,y) is the distance between 'x' and 'y' put as minimal cost of operations to transform 'x' to 'y'. The complexity of the algorithm is O(m \u00c3 n), where n and m are the lengths of 2 strings. 83 We used Perl extension for approximate matching (Search.cpan. org, (2016). String-Approx-3.27. Retrieved from: http://search.cpan.org/ CPAN/authors/id/J/JH/JHI/String-Approx-3.27.tar.gz)" ] },{ "paper_id": "0577bfc182ea9062ae7d4e4c419a84777b734a4c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The primary outcome was in-hospital mortality. The secondary outcomes were the length of stay in the intensive care unit (ICU) and total length of hospitalization.", "We defined ARDS according to the Berlin definition in 2012 [13, 14] .", "Pneumonia was diagnosed as an acute illness with fever, cough, or dyspnea/tachypnea, and at least one new focal chest sign that was supported by a finding of lung shadowing on a chest radiograph and without other noninfectious causes." ] },{ "paper_id": "057a931d8bfabff534eddd75a96af84a1b6b3deb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.ppat.1007836.g004" ] },{ "paper_id": "0586c9a5cbb333e62fb7e18d5239eae3be34d42a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The potential N-glycosylation sites were predicted within the S1, E, M, and N proteins. The analysis was performed using NetNGlyc server 1.0 software available at http://www.cbs.dtu.dk/services/ NetNGlyc [38] .", "Aligned nucleotide sequences of S1, E, M, and N genes were subjected to the Recombination Detection Program (RDP 4 Version 4.95) to detect potential recombination events by seven algorithms (RDP, GENECONV, Bootscan, MaxChi, Chimera, SiScan and 3Seq) in RDP 4.95 [4] . The detection of recombination breakpoints by at least four of these methods were considered as confirmation of any putative recombination event. The potential recombination events and breakpoints were further verified by similarity plots (SimPlots) analysis in SimPlot version 3.5.1 [7, 14] .", "HPD, highest probability density.", "Infectious bronchitis (IB) is one of the major viral diseases affecting the poultry industry globally. The causative agent avian infectious bronchitis virus (IBV) is a member of the genus Gammacoronaviruses, subfamily Coronavirinae, family Coronaviridae and is prone to mutate. There are multiple genotypes and serotypes of IBV isolates identified worldwide and limited cross-protection confers between serotypes of IBVs [1] [2] [3] [4] [5] [6] , which poses great challenge to the control of IB by vaccination." ] },{ "paper_id": "058b0cc7cecd43d80ed47196cb5376fa10efb58a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Competing Interests: The authors have the following interests. Edward Sumner and Colin Fink are employed by Micropathology Ltd. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.", "Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear.", "Several studies had shown that viruses can be found in children with no respiratory infections [6, 35] , and further research is needed to understand the natural history of respiratory viral carriage and infection. However, our findings were consistent in both independent cohorts very different between them, so this makes the outcomes more robust." ] },{ "paper_id": "058c0fc94ded8fa4e7a302081c3ea738d16a4b1a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Where \u03c9 is a weighting factor (default \u03c9 = 0.1). ", "Antifreeze proteins (AFPs) are functional proteins in a cell. With special antifreeze activity, AFPs make the organisms less sensitive to cold temperatures. AFPs bind to small ice crystals to inhibit growth and recrystallization of ice that would otherwise be fatal [1] . By contributing to both freeze resistance and freeze tolerance, AFPs have helped to increase species diversity in some of the harshest and most inhospitable environments. Freeze resistance involves the inactivation or removal of ice-nucleating agents in freeze-avoiding species, whereas freeze tolerance involves the activation or synthesis of ice-nucleating agents in winter in freeze-tolerant species [2, 3] .", "PROTEIN A R N \u2237 V T -4 -1 0 \u2237 0 V -1 -3 -3 \u2237 4 V 0 -3 -3 \u2237 4 F -2 -3 -3 \u2237 -1 C 0 -4 -3 \u2237 -1 G 0 -3 0 \u2237 -3 K -1 5 0 \u2237 -3 L -2 -3 -4 \u2237 -1 S 1 -1 1 \u2237 -2 G -1 -3 0 \u2237 -3 K -1 2 0 \u2237 -3 P -1 -2 -2 \u2237 -3 \u2237 \u2237 \u2237 \u2237 \u2237 \u2237 R -2 6 -1 \u2237 -3" ] },{ "paper_id": "058f046fec5eee31c9ed0bdacd37aa22ba485993", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The drugs that have been tested in humans included Interferon (alpha and beta), antiviral nucleoside analogues (Ribavirin), serine protease inhibitors (Camostat), immunosuppressant (cyclosporine, mycophenolate mofetil), monoclonal antibodies, and broad-spectrum antivirals (Nitazoxanide) [14] . In one study, multiple regimens were tested including mycophenolate mofetil, Interferon alpha and beta with or without ribavirin combination, and hydrocortisone [15] . Similarly, the efficacy of Interferon-beta with lopinavir-ritonavir has been the focus of an on-going clinical trial [16] . The most widely tested regimen, however, has been Ribavirin in combination with Interferon. This regimen has been found effective in reducing the virus replication 'in vitro' [17] . It has also modulated the host response and improved the clinical outcome in animal experiments [18] .", "We used the medical records of Buraidah Central Hospital (BCH) in the Al-Qassim region and adopted a retrospective cohort design for this study. BCH is the main centre in the region for the treatment of MERS-CoV infections; patients are referred here from neighbouring secondary hospitals (e.g., King Saud Hospital in Unaizah, Sulaiman Al Habib in Buraidah, and hospitals in ArRass, AlMuthnab, and Bukayriah) and tertiary hospitals (e.g., King Fahad Specialist hospital and Prince Sultan Cancer Centre in Buraidah).", "The Regional Ethical Committee of Al-Qassim and the administration of the BCH approved this study. The ethical committee did not require that we obtain informed consent from the patients since we examined archived medical records, had no direct contact with the patients, and ensured that the data collectors abstracted and recorded the patient data anonymously." ] },{ "paper_id": "05916d82efe1f937ee48f09df4e5d7c6fede83d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 5:10840 | DOi: 10.1038/srep10840" ] },{ "paper_id": "0596a285261bc529af5a4bea0447bc838f45866f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Levels of data: Epidemiological distribution of disease during outbreaks of viral infection [4, 22] no obvious association with virus infection [2, 9, 32] [132] found, that measles-mumps-rubella vaccination may trigger autoimmunity: neither the prevalence nor the levels of antibodies changed 3 months after vaccination [51] .", "These studies provide no evidence for a causative role for HFV in GD. However, the data do represent the possibility that HFV-like sequences may be implicated and this is a possibility especially in some geographically distinct populations [21] .", "Human foamy virus (HFV) is a member of the retroviral family of Spumaretroviridae. Three retroviral structural proteins of HFV -gag, pol and env -can be identified by indirect immunofluorescence." ] },{ "paper_id": "0597b458ac250cffe02827f4448a2bfd4e5e05f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our research returned 287 English articles and 305 Chinese articles after removing duplicates. After screening the titles and abstracts, 509 of these articles were excluded. The full texts of 83 articles were assessed, amongst which studies were excluded for the following reasons: the control group did not receive steroid therapy (26); reviews (8);", "We used the meta-analysis of observational studies in epidemiology guidelines in the present study [9] .", "non-SNP-related studies (5); basic studies (3); studies without frequencies or effect size results (2); non-steroid-related ONFH studies (2); case reports (2); microRNA-related studies (2); duplicated reports (2); and heredity SONFH study (1) . Ultimately, we included 30 studies that assessed a total of 7553 patients in our meta-analysis (Figure 1 , Table 1 )." ] },{ "paper_id": "0599be2719a0557e53ffb238765c811578a0cc9f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, SD RDT did not detect five patients with Ct values of 22-35. Although PCR showed a high performance in diagnosing RSV, it is still limited by its complexity and high cost [30] . Furthermore, upper respiratory infection is common in the winter months, indicating that acute and prior infection with these pathogens cannot be distinguished by PCR [31] .", "Therefore, simple, rapid antigen-detection tests offer potential advantages that are associated with point-of-care testing (POCT) over PCR, and our FICT method can improve the performance of POCT.", "RSV A (strain KUMC-41) and influenza A virus H1N1 (strain KUMC-76) were obtained from the Korea National Research Resource Center." ] },{ "paper_id": "059d5acb8af8bd2bedab06b5dcc0510691fe0f1e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "05a3101918abeee449871529fb0b788dd90df479", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "05a52fe28de83b331a2625473d6eabe95af62cc7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Whereas for the P42-segment of IDV (KF425664.1) the forward 5 -ATGCTGAAACTGTGGAAGAATTTTG-3 , reverse 5 -GGTCTTCCATTTATGATTGTCAACAA-3 and probe 5 -FAM-AAGGTTTATGTCCATTGTTTCA-BHQ1-3 were used. A standard curve of the P42-segment of Influenza C or D virus, cloned in pHW2000 plasmid, was included to interpolate the amount of genomic equivalents [30] . Measurements and analysis were performed using an ABI7500 instrument and software package (Applied Biosystems, Foster City, CA, USA).", "The Madin-Darby Bovine Kidney (MDBK) cells were maintained in Eagle's minimum essential medium (EMEM; (Gibco, Gaithersburg, MD, USA) supplemented with 7% heat-inactivated fetal bovine serum (FBS, Gibco), 2 mmol/L Glutamax (Gibco), 100 \u00b5g/mL Streptomycin and 100 IU/mL Penicillin (Gibco). Human rectal tumor 18G (HRT-18G) cells (ATCC, Manassas, VA, USA) were maintained in Dulbecco's minimum essential medium (DMEM; Gibco) supplemented with 5% heat-inactivated FBS, 100 \u00b5g/mL Streptomycin and 100 IU/mL Penicillin (Gibco). Both cell lines were propagated at 37 \u2022 C in a humidified incubator with 5% CO 2 .", "Primary human bronchial cells were isolated from patients (>18 years old) undergoing bronchoscopy or pulmonary resection at the Cantonal Hospital in St. Gallen, Switzerland, in accordance with our ethical approval (EKSG 11/044, EKSG 11/103 and KEK-BE 302/2015). Isolation and culturing of primary human bronchial epithelial cells was performed as previously described [26, 27] , with the minor modification of supplementing the BEGM with 10 \u00b5mol/L Rho associated protein kinase inhibitor (Y-27632, Abcam, Cambridge, UK)." ] },{ "paper_id": "05a94d5f5083ff58320c659cd519536d3e6aa4a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Three microliter of purified sample virus was adsorbed to a carbon-coated film (200 mesh grids). The grids with adsorbed virus were floated onto a solution of the negative stain (1% solution of uranyl acetate). The film was picked up by a copper EM grid and then air-dried. Specimens were examined under a HITACHI H7650 electron microscope operating at 80 kV and images were further processed using ImageJ software.", "At least in vitro, Ad infects cells by first attaching to primary receptors, including CAR, CD46 and sialic acid, via the fiber protein [22] . In some cells endocytosis of Ad may be triggered by penton base-mediated signaling through alpha(v) integrins [23] [24] [25] .", "siRNAs were purchased as duplexes from EuroGentec (only the reverse strand is shown): Scramble (59-CGCAAUUCGAUGUCCC-GUGdTdT), Nedd4.1 (59-AAACAACCCAGCCAGGCUCdTdA), Nedd4.2 (59-CUGUGACUUUGUGUUGUGGdTdA), were previously described by Segura-Morales et al. (2005) , AIP4/Itch siRNAs (59-UCAUCAUUCUGAGAAGCACdTdT, [54] , and WWP1 siRNA (59-CUUCUACGAUCAUCAACUCdTdT) was previously described by Chen et al. (2005) . The WWP2 siRNA was a Smartpool from Dharmacon." ] },{ "paper_id": "05ab8bd6ff732bea31fa673b450d37b58da78c46", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy ", "Sensitivity, specificity, PPV, NPV, and overall accuracy are shown in Table 8 ." ] },{ "paper_id": "05aeae1608e74b17f7c92bc7661e98742e0b3fb6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 7:40292 | DOI: 10 .1038/srep40292", "Scientific RepoRts | 7:40292 | DOI: 10.1038/srep40292" ] },{ "paper_id": "05b8deee7f76cda7511eb605e2ba84a8f46bc10f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CypA is a ubiquitously distributed intracellular protein found in all tissues in mammals, and it possesses peptidyl-prolyl cis-trans isomerase activity [20] . CypA has chaperon-like activity and takes part in protein-folding processes [21] . Further, CypA is the major intracellular receptor for the immunosuppressive drug cyclosporin A (CsA), and the CsA-CypA complex interacts with and inhibits calcineurin, a calcium-calmodulin-activated serine/threonine-specific protein phosphatase [22] , which in turn suppresses T-cell activation. In addition to its intracellular functions, CypA can be secreted into the extracellular environment [23, 24] . Extracellular CypA acts as a growth factor in several cell types. Furthermore, CypA is also involved in the pathogenesis of several diseases, including viral infection, cardiovascular disease and cancer. The extracellular functions of CypA are mediated by CD147, which is expressed on a wide variety of cells, including hematopoietic, epithelial and endothelial cells [25] [26] [27] [28] [29] . CD147 is a widely expressed type I integral membrane protein that is implicated in many physiological and pathological activities. Drugs targeting either CD147 or Cyps demonstrate a significant anti-inflammatory effect in animal models of acute or chronic lung diseases, suggesting a therapeutic pathway for some diseases.", "Accumulating evidence indicates that CypA is an important host factor for successful viral infection. CypA is involved in the lifecycle of several viruses, such as human immunodeficiency virus type 1 (HIV-1), influenza virus, hepatitis C virus (HCV), hepatitis B virus (HBV), vesicular stomatitis virus (VSV), vaccinia virus (VV), severe acute respiratory syndrome coronavirus (SARS-CoV) and Rotavirus (RV) [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] 30, 31] . CypA is also incorporated into several enveloped virus particles, such as HIV-1, influenza virus, VV and VSV [9, 14, 15, 32, 33] . However, the function of CypA in virus particles is still unclear.", "As was reported, CypA is also incorporated into influenza virions [9, 32] . However, the function of virion-associated CypA is still unclear. Recently, we found that the presence of CypA in the virions aids the infectivity of influenza virus particles, and CypA affects the ratio of M1/NP in the influenza virions (unpublished data). These results suggest that CypA may take part in the assembly of influenza virus and the uncoating process of the virus particles ( Figure 1 ). However, how CypA is incorporated into the virions and how CypA assists in the infection of the virion requires further studies. " ] },{ "paper_id": "05ba033423b8fcd8ca26cf0cf1611e128048f9db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cholera toxin and SV40 can also be internalized via raft microdomains into GPI-anchored protein-enriched endosomes. Mechanisms regulating this internalization pathway are unclear as of yet." ] },{ "paper_id": "05bdc3cf6dad125ad6539580352cb341eeaec2b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The cell fraction from the BALF were prepared on a slide by cytospin and differential cell counts were performed in a blinded manner, with a total of 300 cells counted per sample.", "All animal use procedures were conducted according to the guideline set by the Canadian Council on Animal Care. The Animal Care Committee at the Hospital for Sick Children, approved all protocols developed for this work. ", "The criteria for assessing mouse lung pathology score. (DOC)" ] },{ "paper_id": "05c54da3a4bd3e92c4d0e5286e331e333408c9a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Sections of formalin fixed tissue were cut and stained with haematoxylin and eosin, Giemsa and Periodic acid-Schiff stains using standard methods and examined by light microscopy.", "A conventional RT-PCR was run to produce template for in situ hybridisation (ISH) probe production. PCR template was created using conventional PCR primers targeting the gene encoding a putative viral membrane protein (M). Primer details were as follows: BRVMP forward: 5' ATGGAGTCCACCTCGA 3', BRVMP reverse: 5' TTATGGTAGGATG GCTGTT 3'." ] },{ "paper_id": "05ce1f7ae3a2051067e57e5e52f9cdad0e26a187", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "[ 35 S]-cysteine/methionine labeling mix was obtained from New England Nuclear (Massachusetts, USA).", "In vitro protein expression \u03b2TRCP protein was expressed in-vitro using pCDNA-\u03b2TRCP expression construct in a coupled transcriptiontranslation reaction (TNT kit, Promega Corp., Wisconsin, USA) following manufacturers protocol." ] },{ "paper_id": "05da888d78a628666b186a2f0773d8d4839a994e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Conceptualization: Jorge A. Hernandez. ", "Poultry pens are made of concrete or dirt floors, chicken-wire or wire mesh for fencing, galvanized metal roof, and tarp, roll-up side curtains for ventilation. Poultry pen bedding material is made out of wood shavings and is changed after each production cycle. Currently, there is no policy that prohibits the use of poultry litter as fertilizer on agricultural fields." ] },{ "paper_id": "05e4c2f6b0affdeef1b7d99d5b481bee1c244a7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Currently, it appears that all age groups can be affected by HBoV, although severe infections and infections requiring hospitalization occur primarily in patients with an underlying disease [76] [77] [78] [79] [80] [81] [82] [83] . Severe clinical cases have been described in children [76, 77] , adults with cancer [76] and other risk groups [84] .", "The seroprevalence of HBoV is strongly dependent on the age of the investigated patient cohort and ranges from ~40% in children between 18 and 23 months of age up to virtually 100% in children older than two years, with an average of 76.6% in children and 96% in adults [55, 56] . The seroprevalence is lowest for HBoV-4 (0.8-5%), followed by HBoV-3 (10-38.7%), HBoV-2 (34-49.3%), and HBoV-1 (66.9-96%) [55, 57] .", "These tools are a prerequisite for the search for answers to open questions, including questions regarding effective antivirals and disinfectants and the molecular pathogenesis of HBoV. These tools will also help to determine whether HBoV is in fact a serious pathogen and not simply part of the harmless microbiome of its hosts." ] },{ "paper_id": "05e6e7a72d16a7294079af8e96f5d6b42d8ce51f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics statement. Written informed consent for using the clinical specimens was obtained from all patients ", "Step 1 (Primary invasive reaction): A target DNA is firstly hybridized with an upstream probe (Up) and a downstream probe (Dp), forming a one-base overlapping structure at the 3\u2032 -end of the Up. The blue arrow indicates the site of cleavage.", "Step 2 (Secondary invasive reaction): The cleaved flaps from the target-specific primary invasive reaction are used to drive a secondary invasive reaction. Then the hairpin probe (Hp) is cleaved by AfuFEN.", "Simultaneous detection of multiple pathogens in one tube is without doubt cost-and time-saving. However, the differentiation of the ladder-like LAMP amplicons derived from multiple targets is still challengeable to date, although previous studies have described several methods for multiplex LAMP detection. These multiplex LAMP methods either used end point analysis, through gel electrophoresis 24 or pyrosequencing 25 , or used real-time detection, through annealing curve analysis 26 , DARQ 27 or MERT-LAMP technique 28 . However, these techniques all require complicated and specialized instrumentations, which diminish the point-of-care testing capability of multiplex LAMP." ] },{ "paper_id": "05e9af5c04c17b89fd8d65d62a381eb22e8316ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Difference between two categorical values was compared by Student's t-test. Statistical significance was set at < 0.05. The experiments were repeated at least three times.", "HepG2.2.15 cells with integrated full-length HBV genome were kindly provided by Professor Bo Qin (Chongqing Medical University, China), as previously described [17] , and were cultured in Dulbecco's Modified Eagle's Medium (DMEM) (Gibco, USA), supplemented with 10% heat-inactivated fetal bovine serum (Gibco, USA), 100 IU mL \u22121 penicillin (Gibco, USA), 100 IU mL \u22121 streptomycin (Gibco, USA), and 1 mg mL \u22121 G418 (Invitrogen, USA) in 5% CO 2 at 37 \u2218 C.", "Though mature form of ISG15 conjugation to target proteins was shown to be essential for ISG15-dependent antiviral effects, both free ISG15 (intracellular or extracellular) and" ] },{ "paper_id": "05eae269e7bd3b7b841a84c02b1c13a670faf012", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Early passage of HUVEC were obtained from Clonetics, Lonza and maintained in complete EBM-2 culture media (Allendale, NJ). KSHV-infected BCP-1 cells established from the peripheral blood mononuclear cells of a PEL patient [51] were maintained in culture in RPMI1640 containing 10% fetal bovine serum (FBS). Doxycycline-inducible iSLK cells, provided by Dr. Jae Jung at the University of Southern California, were maintained in DMEM supplemented with 10% FBS, 250 mg/ml of G418, 1,200 mg/ml of hygromycin, 1 mg/ml of puromycin, and 1% penicillin-streptomycin solution.", "Ubiquitination has been linked to diverse cellular functions including directing protein recycling [1, 2] . Addition of four or more ubiquitin moieties (polyubiquitination) provides the necessary signal for targeting protein for proteasomal degradation. Ubiquitination of target cell surface membrane proteins triggers its internalization and endocytic sorting in addition to proteasomal degradation. For examples, monoubiquitination, the addition of single ubiquitin moieties, of epidermal growth factor receptor (EGFR) cytoplasmic tail induces its internalization and transport to the lysosome for degradation [3] [4] [5] while ubiquitination of membrane receptors b2 adrenergic receptor and interleukin 2 receptor b chain is required for their correct internalization and processing [6] [7] [8] .", "Secondary antibodies AlexaFluor 568 goat-anti-mouse IgG1 and IgG2a, AlexaFluor 647 goat anti-mouse IgG1, AlexaFluor 488 goat anti-rabbit, and AlexaFluor 568 goat-anti-rat were from Molecular Probes, Invitrogen (Carlsbad, CA). DAPI was from BioChemika Ultra, Sigma." ] },{ "paper_id": "05f1c02ecdb1798e85e750ddfa81ede861f94cf6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Zika virus (ZIKV) was first isolated in monkeys in Uganda in 1947, and then detected in Aedes africanus mosquitoes in 1948. ZIKV belongs to a mosquito-borne flavivirus of the family Flavivirus, which spread from Africa to south-eastern Asia through transmission by Aedes mosquitoes, such as A.", "All data from 3 independent experiments were analyzed using Student's t-tests or \u03c7 2 tests. Statistical significance for each assay was judged at p < 0.05.", "TE671 (human, rhabdomyosarcoma/muscle), SF268 (human brain, glioblastoma/astrocytoma), and ARPE-19 (human, retinal pigmented epithelium) cells were cultured in minimum essential medium containing 10% fetal bovine serum, 2 mM glutamine, 1 mM pyruvate, and 1\u00d7 penicillin-streptomycin at 37 \u2022 C with 5% CO 2 ." ] },{ "paper_id": "05f2d4c337413ae496e31e2259020f3e328dcfa1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dengue virus (DENV) is a mosquito-transmitted virus that causes mild ((dengue fever (DF)) to severe disease ((dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS)) in humans [1] . DENV consists of four serotypes (DENV1-4) each comprising multiple genotypes and belongs to the genus Flavivirus of the family Flaviviridae [2] .", "Before 1970 DENV outbreaks were reported in nine countries but has since expanded to more than 100 countries, with an estimated 96 million apparent and 294 million unapparent cases in 2010 [3] . Two and a half billion people are at risk of infection worldwide [4] . Since specific treatment or a vaccine are currently not available [5] , early detection plays a key role for initiation of control and preventive measures in dengue endemic regions such as mosquito control and social mobilization [6] ." ] },{ "paper_id": "060201d43460ac305a26ac4b0acca66cd41c151a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "060833389f07819960d34c91e0dfdc92e053f6ac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine alveolar macrophages (PAMs) from the lavaged lungs of six-week-old PRRSV-negative pigs were kept in a medium of RPMI 1640 plus 10% FBS and 1% penicillin/streptomycin. PRRSV strain BJ-4, as a gift, was kindly obtained from Yang Hanchun of China Agricultural University.", "Plasmids for expressing PRRSV nsp1, nsp11, nsp11H129A, nsp11H144A, nsp11H173A, nsp1\u03b1, nsp1\u03b1C76S, nsp1\u03b1H146Y and nsp1\u03b2 have been described in our previous work [23, 27] .", "The firefly luciferase plasmid CMV-Luc for firefly luciferase expression was constructed by inserting the CMV promoter into the pGL-4.17 (Promega, Madison, WI, USA).", "Viruses 2015, 7, page-page amino acids could abolish the NendoU activity [32] . Furthermore, the active sites of PRRSV NendoU should be His-129, His-144 and Lys-173 for BJ-4 PRRSV after aligning the sequences of the proteins SARS-CoV nsp15, EAV nsp11 and BJ-4 PRRSV nsp11 [31] ." ] },{ "paper_id": "06094b031f02c0307da315a1428394c2c075ff2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The complete genome sequence of the MERS-CoV/KOR/KNIH/002_05_2015 isolate was deposited in GenBank under the accession number KT029139.", "The full genome sequence of a Middle East respiratory syndrome coronavirus (MERS-CoV) was identified from cultured and isolated in Vero cells. The viral genome sequence has high similarity to 53 human MERS-CoVs, ranging from 99.5% to 99.8% at the nucleotide level.", "is the first betacoronavirus lineage C member isolated from humans. It has been assumed that MERS-CoV was transmitted from bats and spread to humans through intermediate hosts (1) . The genome structure is a single-stranded RNA (ssRNA) encoding 10 proteins; two replicase polyproteins (open reading frames [ORFs] 1ab and 1a), three structural proteins (E, N, and M), a surface (spike) glycoprotein (S), and five nonstructural proteins (ORFs 3, 4a, 4b, and 5) (2)." ] },{ "paper_id": "06190bfcbc53a5d5d17e0a60a3a0f6488d8ae1db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Favipiravir Suppress viral RNA polymerase.", "(2) Favipiravir (T-705; 6-fluoro-3-hydroxy-2pyrazinecarboxamide)", "The authors declare that they have no competing interests.", "Immune evasion by the glycoproteins of the Ebola virus: implications on passive immunization and vaccine development", "Additional file 1: Multilingual abstracts in the six official working languages of the United Nations." ] },{ "paper_id": "061e49a521b8ea0acbd7c3a61360cc8e0b07e3ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Phylogenetic analysis. Sequence alignment and phylogenetic tree reconstructions of the sequences obtained were carried out using ClustalW alignment and maximum likelihood methods available within Geneious 8.1.5 (Biomatters) and IQ-TREE (21), respectively.", "Sample pretreatments and NA isolation. Prior to nucleic acid (NA) isolation, 100 l of clinical sample was treated with 2 U/l of Turbo DNase (Ambion, Life Technology, Carlsbad, CA, USA) and 0.4 U/l RNase I (Ambion) at 37\u00b0C for 30 min. Viral NA was then isolated from nuclease-treated materials using a QIAamp viral RNA kit (Qiagen GmbH, Hilden, Germany) and was recovered in 50 l of elution buffer.", "SUPPLEMENTAL FILE 1, PDF file, 0.9 MB." ] },{ "paper_id": "061eb24a1462aba7b53e6c099fe5d4bd046dd56a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "-Cationic porphyrin -Metabolic regulator nitrate assimilation." ] },{ "paper_id": "06249faa885cabbce6eccdf1e40ffe2f43fb5092", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "062a18fe6bcaad19bd60d8b47d3287079a915545", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Objective: The present study aimed to analyze clinical features and factors associated with treatment outcomes of H7N9 influenza A virus infection.", "Overall, few cases of H7 virus transmission to mammals have ever been reported in Asia and N9 virus infections in human have never been documented anywhere in the world [8] except H7N9 [7] . The H7N9 variants currently in circulation most likely evolved through a combination of genes from viruses in Beijing bramblings, Zhejiang ducks, and Korean wild birds according to report by Chinese scientists. Human infections with highly pathogenic H7 viruses generally resulted in conjunctivitis or uncomplicated influenza [3, 8] " ] },{ "paper_id": "062d0779c4b304f4188666a3989152d9f9557340", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Automated image acquisition was performed using an Opera confocal reader (model 5025-Quadruple Excitation High Sensitivity [QEHS], PerkinElmer, Waltham, MA, USA). Images were acquired as 2 exposures using a 10\u00d7 air objective and a bin factor of 1. The first exposure used the 488-nm and 640-nm lasers to excite the viral and cell body fluorophores, respectively, and was directed to the sample with a 405/488/640-nm triple dichroic. The emission light was split by a 580-nm SP dichroic mirror and collected on separate cameras through 562/40-nm and 690/70-nm band-pass filters. The second exposure used the 405-nm and 561-nm lasers to excite the nuclear and Alexa Fluor \u00ae 568 respectively, and was directed to the sample with a 405/561/640-nm triple dichroic.", "Viruses 2012, 4 1866" ] },{ "paper_id": "0638a299934da797243f6f35a516e172a38466a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "6 Pulmonary Medicine", "In cellular type of NSIP, chronic interstitial inflammatory cells involves alveolar walls, fibrotic form may include more advanced fibrosis. The histology is usually uniform. In AE of NSIP also DAD is present.", "Controlled prospective studies on the treatment of AIP are not available, not surprising since AIP is so uncommon and it is generally a very acute lung manifestation displaying some overlapping features with ARDS. " ] },{ "paper_id": "063f48cf2d9b53b075433f3bd1a63566feb240db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "If the sample points are presented as a discrete distribution, then the formula is:", "(e) (f)" ] },{ "paper_id": "06485dd45c17460af629f7c74234bef914fbbabe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by grants from the National Natural Science Foundation of China (grant no. 31670899 and 31070796) and the Natural Science Foundation of Chongqing (grant no. CSTC, 2011BB5029).", "JY collecting literatures and drafting manuscript. JW design of the work, collecting literatures, drafting, and revising manuscript. YW discussing literatures, design of the work, and revising manuscript.", "Plasma vRNA, another common agonist for NLRP3, may bind with NLRP3 and act to subsequently activate it. Although NLRP3 contains a nucleotide-binding domain (54), RNA-sensing molecules have been reported to participate in the process by which vRNA activates the NLRP3 inflammasome; these include the DExD/H-box helicase (DHX) family members (14, 41, 55, 56) and the 2\u2032,5\u2032-oligoadenylate synthetase (OAS, or 2-5A)/RNase L system (30) . However, some debate exists as to the exact role of DHX33, in particular, in VSV-induced NLRP3 inflammasome activation (29) ." ] },{ "paper_id": "06525dbe27937be0f8263a0e8ec743f68d9f1795", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "06589343cb2fcc62a39c587071c8a9e76836f993", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The paper is organised as follows. The next section outlines the research methods. Then the simulation results and analysis are presented, followed by a section that discusses the merits and limitations of our approach. The last section draws conclusions regarding the application of ISTAM and remaining research issues." ] },{ "paper_id": "0660d9281c1607ca1ca9cb62dfa00b56f49ddee1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Stable transformation has its own advantages such as reliable harvest of target proteins over multiple generations and optimized protocols for delivery of foreign genes into various plant species.", "[59] demonstrate the application of the classical Nicotiana benthamiana/A. tumefaciens transient expression system to accelerate the development of a malaria vaccine candidate, with screens for expression, solubility, and stability using fluorescent fusion proteins. In Marin Viegas et al.", "HBV is a hepatotropic DNA virus that replicates by reverse transcription. The human HBV is a small circular DNA molecule of 3.2 kb [2] . Its genome consists of four partially overlapping open reading frames (ORFs), namely the envelope gene (pre-surface/surface (pre-S/S)), the core gene (pre-core/core (pre-C/C)), the polymerase gene (pol) and the transactivating protein X (X). The ORF pre-S/S encodes pre-S1, pre-S2 and surface (S) proteins that form the surface antigen (HBsAg), and HBsAg protein is the main antigen to elicit virus-neutralizing and protective antibodies by the immune system [3, 4] . Understanding the HBV genome and structure is an essential prerequisite for preventive or therapeutic vaccination against HepB." ] },{ "paper_id": "06624de6d8b09e5db9ba01c4cc721583331a40b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1). Coinfections may induce more severe inflammation in the arthritic joint during the acute phase of disease, and/or.", "(2). They may prolong the self-limiting phase of the disease, and/or.", "The comprehensive research program outlined here is a prerequisite to understand the clinical implication of chlamydial coinfections in arthritis and SpA, and to develop therapeutic strategies directed against multiple persistently-infecting organisms.", "(3). They may cause relapse of the disease, and/or. (4) . They may support the chronic disease course because one or several of the coinfecting bacteria are not eliminated." ] },{ "paper_id": "066619641442d9c3f6a547301849bef0b8b12f2f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Enhanced communicable disease surveillance in hospital/ workplace environments", "Additional data and comments were collected, using Likert scales and free text responses. On completion of each round, participants' Likert scores were tabulated and free text answers analysed qualitatively, as described. The final stage of analysis during preparation of this report drew on the knowledge and professional experience of the research team, which includes expertise in health social science, bioethics, Australian health law, infectious diseases, microbiological laboratory and data sciences, and health protection. This study was approved by the University of Sydney Human Research Ethics Committee (#2016/819)." ] },{ "paper_id": "0666ca679df1885492aa1420fd995790d363b8a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following Env clones were obtained from the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: Env clones from early infection (QF495. 23M [3, 14, 50 ,51]) were gifts from Dr. Beatrice Hahn. We amplified the Rev-Env cassettes from these by PCR, TA-cloned them into pCR8 (Clontech), and then used Gateway cloning to move them into a gateway converted pCDNA3.1 (Invitrogen) mammalian expression vector. Further description of these Env clones, and those used in the fusion assay screens, are described in S1 Table. Nucleotide changes producing S375Y/W/H and A281V were introduced into BG505.W6M.B1 by site directed mutagenesis using overlapping PCR primers containing the mutation of interest, following standard methods.", "Introduction compatibility with primate CD4 receptors might be dynamic, given that CD4 is highly diverged in its protein sequence at the interaction interface with HIV-1 Env (Fig 1A) .", "https://doi.org/10.1371/journal.pbio.3000304.g006" ] },{ "paper_id": "06753b3e708ad76787b100b9009ccec622f267ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma rising at the post nasal cavity, which is prevalent in southern China, southeastern Asia, and Taiwan. Worldwide, approximately 80,000 cases of NPC are reported each year, 0.7% of all cancers [1] . In general, the 5-year survival rate of NPC is 60%. When treatment begins at an early stage, the 5-year survival rate can reach 80-95%; however, it is poor at a later stage of NPC [2] . Radiotherapy is the primary and effective treatment for NPC. The combination of radiotherapy with neoadjuvant chemotherapy is another pivotal treatment for NPC patients and increases the survival rate significantly [3] [4] [5] . Although the therapeutic efficiency of NPC management has largely been improved, how to avoid NPC metastasis is still an urgent unmet need. ", "Results" ] },{ "paper_id": "06795e24716acde6e56c25d7845c92a97fa0268c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The second moment is given as:", "Where \u03c1, the redundancy, is define to be equal to N\u03b1", "The standard deviation is then:" ] },{ "paper_id": "06989a9659f1b9b10abc5b92a90ecff38a778d55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell culture maintenance and growth conditions African green monkey epithelial kidney cells (Vero E6) obtained from ATCC were maintained in Dulbecco Modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37\u00b0C with 5% CO 2 . Madin-Darby canine kidney (MDCK) cells were routinely maintained in Eagle's Minimum Essential medium (EMEM) supplemented with 10% FBS and incubated at 37\u00b0C with 5% CO 2 .", "Pteropus giganteus field samples were obtained as a diagnostic submission. No live animal work was performed during this study.", "Although work has progressed toward understanding Afipia, it is unclear as to what niche these bacteria inhabit. Previous work has detected Afipia spp. in hospital and drinking water.", "doi:10.1371/journal.pone.0121274.g002 electron micrographs. In general, the overall cell structure and shape matches well with other members of the Afipia species [10, 12, 21, 22] ." ] },{ "paper_id": "069a3aebc920d5da476fef73fd5d47566c780885", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For 30 years it was thought the alphavirus 6K gene encoded a single 6 kDa protein.", "arthropod and mammalian host cells. Studies on 6K can now be facilitated by using mutants in the frameshift slip site which do not produce TF. " ] },{ "paper_id": "069b422b624f7d6bb46b8381030550a88a3b30dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bats are the source of multiple zoonotic viruses including severe acute respiratory syndrome (SARS) coronavirus [1] , Hendra virus [2] , Nipah virus [3] , and Marburg virus [4] . In fact, evidence suggests that bats host a greater proportion of zoonotic viruses than any other mammalian order [5] , highlighting the importance of identifying novel viruses in bats. Australian pteropid bats are becoming more urbanized and fewer bats are migrating, resulting in a greater chance of contact between bats and humans or domestic animals [6, 7] . This increased potential for exposure of non-reservoir hosts to bat-borne viruses leads to the increased probability of infection spillovers occurring [8, 9] .", "All procedures were approved by the CSIRO Australian Animal Health Laboratory Animal Ethics Committee. Study 1, project number 1814, was approved in August 2016. Study 2, project number 1865, was approved in June 2017.", "AlsPV" ] },{ "paper_id": "069bf4da8f0f4f540b9f6a16021e007442e7e027", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Ankle and spleen tissues were dissected and homogenized in TRIzol Reagent (Life Technologies) for RNA analysis with a MagNA Lyser (Roche). Viral RNA in tissues was quantified by RT-qPCR as previously described [23] ." ] },{ "paper_id": "069d6ce905dc7992f5bc8692218ca3969ab3e227", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.", "Thus, at present, the critical role of IFITM3 in antimicrobial defense appears to be limited to virus infections, though this remains an open question." ] },{ "paper_id": "06ad398fdbe5c8c55aafb34013ff47b35f0cee35", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Timber and plants are estimated to comprise nearly 70% of the known (broadly defined) wildlife global trade value, leaving non-aquaculture fisheries products responsible for 28% and ornamental fish, mammals, herpetofauna and other species responsible for roughly 2% (US $5.27 billion) (Engler and Parry-Jones 2007; Ahlenius 2008) .", "CITES maintains a database of reported trade of CITESlisted species only. The database is managed by the United Nations Environment Programme-World Conservation Management Center (UNEP-WCMC) and currently holds 7 million records of trade involving 50,000 scientific names of taxa listed by CITES. Currently, more than 500,000 trade records are reported annually (http://www.cites.org/eng/re sources/trade.shtml)." ] },{ "paper_id": "06b07a6407734edcb3af57da5fe2898ba61d1df8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each participant trialed both gowns, using a different gown for the 2 scenarios." ] },{ "paper_id": "06b3f93a98def37bdbfa4487060cd836fdf1070d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "06c0371d82953f5c35ee8bff3e5165d5aa1516de", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Paraffin-embedded tissue blocks were cut into 5 mm slices which were mounted on polylysine-charged glass slides. Endogenous peroxidase activity was blocked by exposure to 3.0% H 2 O 2 for 15 min. Antigen retrieval was performed in a citrate buffer ", "The serum FGL2 level from mice infected with or without MHV-3 was detected by using the mouse FGL2 ELISA Kit (Cat: E90512Mu; Uscn Life Science Inc., Wuhan, China) and following the manufacturer's instructions.", "All experiments were approved by and conducted in accordance with the guidelines of the Animal Care and Use Committee of the Third Military Medical University. All efforts were made to minimize animals' suffering." ] },{ "paper_id": "06c172a11ee30931ac537dfb70ce020dced50918", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Paleovirology is the study of ancient viruses.", "Outbreaks of ''new'' viruses are real causes of concern for human and animal health. But where do they come from? The vast majority of emerging viruses in the human population originate from other animals [1] . In fact, when a new virus appears, it is often a virus that already exists in one species, but then becomes established in another. For example, the transmission of a coronavirus (CoV) from bats to palm civets and raccoon dogs and ultimately to humans led to the emergence of severe acute respiratory syndrome (SARS-CoV), which created an epidemic in 2003, with 8,000 people infected and 700 deaths before it was finally eliminated in humans [2] . Another example is the transmission of influenza virus from birds to mammals (pigs and humans) in 1918 that was responsible for over 100 million deaths worldwide [3] , and many of the genes from this virus continue to circulate in human influenza to this day.", "While the main text describes the origins of the reticuloendotheliosis virus (REV) and its close relatives as pathogens, the study of these retroviruses has also contributed to several areas of basic science and basic virology. The original description of REV was from a tumor taken from a turkey that contained two viruses. One, REV-A, was replication-competent, and the other, REV-T, was defective, but carried an oncogene called Rel that allowed it to transform cells [23, 24] . Rel, it turns out, is a key component in the innate immune signaling pathway [25] , as a component of the NF-kB transcription factor [26] . The late Howard Temin adopted REV and related viruses as model systems to describe, among many other phenomena, the kinetics of retroviral infections [27] , the derivation of cell lines for making gene therapy vectors [28] , and retrovirus mutation and recombination rates [29, 30] ." ] },{ "paper_id": "06cf324e3d0f793e5c722894c6ea6949655b1f10", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Several species of this family are pathogenic to humans and are recognized as potential biological warfare agent (BWA) [5] . VEEV is classified as Bioterrorism Agent Category B by the center of Disease Control (CDC). Alphaviruses do not only have the potential for illness and transmission, but they can also be produced in large quantities and are moderately easy to disseminate. Furthermore, these virus species have the capacity to cause human epidemics [6] [7] [8] [9] [10] [11] . VEEV causes disease symptoms ranging from mild febrile reactions to fatal encephalitic zoonoses. Outcomes are significantly worse for young and elderly patients, with case fatalities ranging from 4 to 35% [12, 13] . These viruses are highly infectious as aerosols [14, 15] and an intentional release of sufficient quantities as inhalable small-particle aerosol is expected to infect a high percentage of individuals within an area of a least 10,000 km 2 [16] . They can replicate in cell culture to very high titers and are relatively stable to environmental influences [17] .", "Positive ELISA signals were obtained for the different VEEV strains with all tested scFv phage clones ( figure 6C ).", "A possible neutralisation activity of the selected scFvs has to be assessed in further studies. Normally, the protective immunity to Alphaviruses is associated with an antibody reactivity to the virion glycoproteins E2 and so far, six conformationally stable epitopes were identified as critical for virus neutralization [36] [37] [38] [39] [40] . Furthermore our antibodies are fully human and therefore better suited for applications like as passive vaccination than murine antibodies.", "Microtitre plate wells containing 200 \u03bcL 2xTY + 100 mM glucose + 100 \u03bcg/mL ampicillin (2xTY-GA) were inoculated with single E. coli colonies from the phage titration of the panning and incubated overnight at 37\u00b0C and with constant shaking at 1200 rpm. 200 \u03bcL 2xTY-GA was inoculated with 10 \u03bcL of the overnight culture and grown at 37\u00b0C and 1200 rpm for 2 h. Bacteria were harvested by centrifugation for 10 min at 3220 \u00d7 g. The pellets were resuspended in 200 \u03bcl 2xTY + 100 \u03bcg/mL Ampicillin + 50 \u03bcM isopropyl-beta-D-thiogalacto-pyranoside (IPTG), a substance that induces the prokaryotic lacZ promotor in E. coli, and incubated at 30\u00b0C and 1200 rpm overnight. Cells were removed from the scFv containing supernatant by centrifugation for 10 min at 3220 \u00d7 g and 4\u00b0C." ] },{ "paper_id": "06d210540bbdfe3b898f2ffbc4d1f9fb74a5a4d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "06d734de60efb9ac8c98cd02be9f667d0c535fb0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Comparisons between men and women of particle concentration and airflow were made using permutation tests (based on the Wicoxon rank sum statistic) rather than t-tests owing to the small numbers (4 men and 4 women).", "A further factor is the environment in which they are used; open situations with a strong draft or breeze will serve to rapidly dilute the aerosols produced but transmission risks may be considerably higher in enclosed arenas. A further risk factor for disease transmission will be the density of vuvuzela players and the prevalence of respiratory infections in the population.", "Coughing, sneezing, singing and talking can all produce aerosols capable of transmitting airborne respiratory diseases [17, 18, 30, 32] . Reports from earlier investigators suggest that coughs may produce up to 5,000 droplet nuclei and a sneeze may generate as many as 900,000 particles [21, 33] . The data we present suggests that blowing the vuvuzela for even a short time period has the potential to create more droplet particles than either coughing or sneezing." ] },{ "paper_id": "06e2a26a1925334deaf6621d3b2763924de55b14", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations GWAS: genome-wide association study; HCV: hepatitis C virus; MERS-CoV: Middle East respiratory syndrome coronavirus; MLST: multilocus sequence typing; MRCA: most recent common ancestor; MRSA: methicillin-resistant Staphylococcus aureus; PFGE: pulsed-field gel electrophoresis.", "Marc Lipsitch declares grants from PATH Vaccine Solutions and Pfizer (ongoing), and consulting income from AIR Worldwide (last 3 years; past). Yonatan Grad declares no competing interests.", "These advances can help address the following key questions that are of concern to the infectious disease epidemiologist (see Box 2):" ] },{ "paper_id": "06e89cafce095f075c8a197fbdfb78c259133a8b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LASV was first isolated in 1969 from a missionary nurse who worked in a clinic in a small town, Lassa, in northeastern Nigeria [34] . The nurse presumably acquired infection from an obstetrical patient residing in Lassa. She died approximately one week after the onset of symptoms. Subsequently, two more nurses that attended the first patient contracted the disease, which was later named Lassa fever and caused the death of one of them. Infectious virus was isolated from all three cases [35] .", "Additionally, multifocal adrenocortical cellular necrosis was detected that was most prominent in the zona fasciculata and was often associated with focal inflammatory reaction. However, in all examined cases adrenal necrosis was mild and \u2265 90% of the cells of adrenal cortex appeared viable [59] .", "Lassa fever is not considered to be associated with coagulation dysfunction, e.g., neither decrease in the coagulation factors nor disseminated intravascular coagulation (DIC) has been observed in infected patients. However, moderate thrombocytopenia with significantly impaired functionality of thrombocytes is detected in patients with severe Lassa fever [68] ." ] },{ "paper_id": "06ebe6e32a2e7241e23d3fb51c4dffeed389861d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The database search retrieved 2461 unique papers ( Figure 1 ). After screening the titles and abstracts, 302 papers met the inclusion criteria and were thus eligible for full text evaluation. Review of the full text publications resulted in the inclusion of 94 relevant papers based on our selection criteria. An additional two papers were identified via reference screening [11, 12] .", "A model in which random (stochastic) processes can affect whether certain events or processes occur (e.g. the rate at which individuals are infected can vary by chance) [61] .", "A model in which the population is divided into subgroups (i.e. compartments), which represent the average values of individuals in a particular state (e.g. susceptible, infectious or recovered). Within each compartment, all individuals are homogenous [9] ." ] },{ "paper_id": "06f33aa8d51ad1c6081cd855c8d274d47e1ee74e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleo-cytoplasmic transport of PTB is known to be regulated by the cAMPdependent Protein kinase A (PKA) through direct phosphorylation of PTB [41] .", "The Flavivirus genus of the Flaviviridae family of animal viruses contains more than 70 viruses including medically important dengue virus (DENV), tick-borne encephalitis virus (TBEV), West Nile virus (WNV), Yellow fever virus (YFV) and Japanese encephalitis virus (JEV). JEV is responsible for frequent epidemics of encephalitis in humans in most parts of Southeast Asia, China, Korea, Japan, and India. It is a neurotropic virus accounting for ,50,000 cases of encephalitis annually of which ,30% result in mortality and another ,30% in long lasting neuropsychiatric complications [1] . The treatment strategies upon diagnosis of JEV infections are mostly supportive and symptomatic as no specific therapeutic treatment is presently available. Greater understanding of the molecular mechanisms controlling JEV replication could help in designing novel interventions.", "Purified recombinant PTB was incubated in binding buffer (14 mM HEPES pH 7.5, 6 mM Tris-HCl pH 7.5, 1 mM EDTA, 1 mM DTT, 60 mM KCl) with 500 ng yeast t-RNA and 1 U RNasin in a 20 ml reaction for 10 min at 30\u02daC followed by the addition of 1 ng 32 P-labelled RNA and incubation for 30 min at 30\u02daC. The RNA-protein complexes were resolved by non-denaturing 6% polyacrylamide gel (PAGE) (acrylamide: bisacrylamide 50: 1) containing 2.5% glycerol in 0.5X TBE buffer (45 mM Tris-borate, 1 mM EDTA) at 4\u02daC. The gels were autoradiographed after drying." ] },{ "paper_id": "06f8316b5b1cd5f0737d5ada43c3dd9ebce27a91", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Meanings were organized into themes, and themes evolved into theme clusters and eventually into theme categories.", "\u2022", "The estimated sample for the interview was 15 as they met inclusion criteria and 10 participants agreed and consented to participate, and data saturation was reached with six participants. Interviews were terminated when data saturation was reached, that was when information was repeated and when the researcher probed, rephrased questions, and requested clarity but the information kept repeating itself." ] },{ "paper_id": "0700c01d64e50ef5ae5943328bd734718cf614f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In summary, the amounts of fluid expelled during a single expiratory event based on V 20 for breathing, coughing, or sneezing were 1.247610 28 ml, 2.04610 27 ml, and 5.27610 25 ml, respectively.", "The potential for international airline passengers to transport infectious diseases into the United States is a serious concern. In 2003, the severe acute respiratory syndrome (SARS) virus was largely spread by air travelers and became a global epidemic; at least 18 countries on 5 continents were affected, resulting in over 8,000 cases and 774 fatalities [1] . One conservative estimate of the economic damage to Asian countries was calculated as $11 billion [2] . Influenza viruses that can be spread by air travelers have the potential to cause far greater harm [3, 4, 5] . Deliberate infection of passengers by terrorists is also a possible threat [6] . A potentially powerful tool to mitigate disease threats would be rapid and accurate detection of a variety of airborne infectious pathogens onboard commercial aircraft before passengers and crew deplane.", "Table S1 Compilation of cough statistics. Notes: Chronic cough can include asthma, gastrooesophageal reflux, eosinophilic bronchitis, chronic obstructive pulmonary disease and chronic bronchitis. 1 Italics represent cases where median values are reported by primary literature. { Study reports cough frequency in cough seconds per hour. In this table, 1 cough second is assumed to be the equivalent of one cough. NR denotes not reported. Found at: doi:10.1371/journal.pone.0014520.s001 (0.59 MB TIF) content or accuracy of these views. Approved for Public Release; Distribution Unlimited. Case Numbers 10-4599, 09-0950, 09-0888, 09-0890, 08-0656, 08-1668. GMH thanks L. Morawska and G. Johnson for furnishing raw data on particles concentrations from human exhalations, and T. Korves for a critical reading of this manuscript.", "Unlike prior work, our study did not assume 50% evaporative loss for diameter ranges for cases where inputs came from the Morawska dataset. In diameter ranges where Morawska did not report any particles due to insufficient instrument signal (i.e., .10 microns for the cough scenario), we employed older data from Loudon and Rosenthal (see two points on Figure 6 )." ] },{ "paper_id": "0706374e8a8a5eaf3bff4d2555c0f0db11294755", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are expressed as mean\u02d8standard deviation (SD). Statistical analyses were performed using one-way analysis of variance. Dunnett range post-hoc comparisons were used to determine the source of significant differences, where appropriate. The SigmaPlot (Version 12.0) (Systat Software, San Jose, CA) program was used for statistical analysis. Values of p < 0.05 were considered statistically significant.", "Blood samples were centrifuged at 2000\u02c6g for 10 min at 4\u02ddC. The plasma was removed and placed into aliquots for analyses. Diagnostic kits for determining plasma levels of total cholesterol (TC; Cat. # 10007640) and triglycerides (TG; Cat. # 10010303) were purchased from Cayman Chemical Company (Ann Arbor, MI, USA). Kits for determination of plasma alanine aminotransferase (ALT; EC 2.6.1.2; Cat. No. A524-780TM) and aspartate aminotransferase (AST; EC 2.6.1.1; Cat. No. A559-780TM) concentrations were purchased from Teco Diagnostics (Anaheim, CA, USA). All experimental assays were carried out according to the manufacturers' instruction; all samples were analyzed in triplicate.", "Hepatic lipid content was determined from fresh liver samples. Liver (1.25 g) was homogenized with chloroform/methanol (1:2, 3.75 mL) and mixed well with chloroform (1.25 mL) and distilled water (1.25 mL). After centrifuging for 10 min at 1500\u02c6g, the lower clear organic phase was transferred into a new glass tube and then lyophilized. The lyophilized powder was dissolved in chloroform/methanol (1:2) and stored at\u00b420\u02ddC for less than three days [16] . Hepatic cholesterol and TG levels in the lipid extracts were analyzed using the same diagnostic kits used for plasma analysis.", "The flowering aerial parts of L. japonica were collected from Ligang Township (Pingtung County, Taiwan) in November 2014. Macroscopic and microscopic examinations, thin-layer chromatography, and high-performance liquid chromatography (HPLC) were used to confirm the authenticity of the plant material provided (this analysis was performed by Dr. Tang-Yao Hong, Department of Biotechnology, Collage of Pharmacy and Health Care, Tajen University). The voucher specimen (Lot No. LJ 20141121) has been preserved in our laboratory for future reference. The flowering aerial parts of L. japonica were air-dried, pulverized to a coarse powder in a mechanical grinder, and passed through a 40-mesh sieve to get powdered samples. Powdered samples (5 kg) were extracted at room temperature thrice with 10 L of 95% ethanol for 48 h on an orbital shaker to make the ethanol extracts. The L. japonica ethanol extract (LJEE) was evaporated to dryness under reduced pressure to completely eliminate alcohol and lyophilized, yielding approximately 582 g of dry residue (w/w yield: 11.3%). LJEE was stored at\u00b420\u02ddC until use and was suspended in distilled water. The content of chlorogenic acid in the samples was then analyzed using the Agilent 1100 HPLC system (Agilent Technologies, Inc., Santa Clara, CA, USA). The calibration equation of peak area against the concentration of chlorogenic acid was y = 6832.3\u02c6+ 117.2 (R 2 = 0.9998). The chlorogenic acid content in LJEE was 68.2\u02d80.3 \u00b5g/g of the dry extract." ] },{ "paper_id": "0712e5735c51991b7e0ce4bd5e63882703863459", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "D.M.E. is supported in part by CDC contract 200-2016-92313, and A.C. is supported in part by NIH grants 5R01AI052733 and 5R01HL059842.", "The mechanisms of pathogen geographic movement and dispersal are of great interest to ecologists, epidemiologists, medical historians, and others who seek to understand the causes of infectious disease emergences. These mechanisms can be natural or anthropogenic and can include anything from displacement or migration of reservoirs to the landscape, geophysical change, and climate changes to occurrences of natural disasters (as proposed here) ( Table 1) .", "(ii) Environmental evidence. (a) Trees and soils. The early environmental analyses of VGIIa in British Columbia identified that most C. gattii-positive environmental collections (soils and trees) were in the coastal Douglas fir forests and in coastal western hemlock forests bordering the coastal Douglas fir forest (16) (Fig. 1 ). While these studies were limited in geographical space, the identified contaminated landscapes did encompass the known locations of human and animal cases. Additionally, further ecological analyses have identified higher levels of soil and tree contamination at low-lying elevations close to sea level (25) . This is the expected pattern of a tsunami-caused dispersal from contaminated coastal waters.", "Here, we propose that a tsunami was responsible for the large-scale movement of ocean microbes into nearby coastal forests. While the evidence described above is largely circumstantial, the natural disaster dispersal hypothesis should be further explored and tested in other regions and with other microbial populations (see \"Hypothesis testing\" below). For example, the tsunami hypothesis may also explain how Cryptococcus was established in Western Australia following some mechanism of water transport from South America. Such mechanisms of dispersal can be considered \"black swans.\"" ] },{ "paper_id": "0715fd9f3fec7a2b86f3344c3c3a56611bcea4aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Immunohistochemistry and confocal microscopy. Intestinal tissues of mice were embedded in a frozen section compound (Surgipath FSC22, Leica Microsystems, Wetzlar, Germany). Thin sections (10 \u00b5m) were fixed in 4% paraformaldehyde, blocked in 1% BSA in PBS, and incubated for 2 h at room temperature with an anti-TLR4 mouse monoclonal antibody or an anti-villin rabbit polyclonal antibody with gentle rocking. After washing 3 times with PBS, appropriate fluorescent-conjugated secondary antibodies were used for visualizing the antigen. Nuclei were visualized by staining with 1 \u03bcM 4\u2032,6\u2032-diaamidino-2-phenylindole (DAPI) in PBS for 10 min. Confocal images were acquired on a ZEISS LSM 880 confocal laser scanning microscope (Carl Zeiss, Oberkochen, Germany). For z-stack analysis, images were obtained along the z-axis at 0.3-\u03bcm intervals and subjected to three-dimensional analysis using ZEN software (Blue edition, 2.3, Carl Zeiss).", "The authors declare that all other relevant data are available from the authors upon request." ] },{ "paper_id": "07177128e49e7d7440cebca1eb70294a3fc27cbb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This was a prospective study conducted from October 15, 2016 to May 14, 2017 at the Federico G\u00f3mez Children's Hospital of Mexico, a tertiary referral hospital in Mexico City providing care to the uninsured population. It has 349 beds, 2 ICUs, one neonatal ICU and registers more than 7,000 hospitalizations per year.", "The study protocol was approved by the ethical committee of Federico Gomez Children's Hospital of Mexico with registration number HIM 2016-082." ] },{ "paper_id": "0727980b80bddd2728174a65e08275cf73000f7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Funding: This research received no external funding." ] },{ "paper_id": "07330c35eb8beda0a4b515b8a0edce5d42662417", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "07396bda4a37d13aaf15fdf67d61971549f4162c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1) fever (axillary temperature$37.2); 2) cough, sore throat, wheeze, expectoration, chest pain; 3) moist/dry rales; 4) X-ray examination of lung inflammation showed punctate, patchy or uniform density shadow.", "Clinical information including demographic characteristics, symptoms, signs treatments, duration of hospitalization, clinical diagnosis were documented in case report forms (CRFs).", "The count data adopted constituted the ratio and frequency table description, and a non-normal distribution of measurement data using the median to describe the central tendency and percentiles to describe the discrete tendency. The group ratios were compared using Pearson's x2 test, with an inspection level a of 0.05." ] },{ "paper_id": "073bf7a5962595098cf9d08109b0db9ea1cb3303", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.ppat.1007860.g003" ] },{ "paper_id": "073cdd46009615f49f9c9c074e55ecebe8305d32", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "N-terminal sequencing. The thrombin-cleaved MERS S protein was separated by SDS-PAGE and subsequently electroblotted to polyvinylidene fluoride membrane with CAPS buffer (10 mM CAPS, pH 11, 10% methanol) at 200 mA for 1.5 h. The polyvinylidene fluoride membrane was stained with freshly prepared Coomassie Blue R250 (0.1% Coomassie Blue R250, 1% acetic acid, 40% methanol) for 50 s and destained with 50% methanol until bands were visible and the background was clear. Then the membrane was dried and the target bands were cut for the N-terminal sequencing with the Edman degradation method by using PPSQ-31A (Shimadzu Corporation, Japan).", "The data of SARS-CoV S was processed in the same way as mentioned above, and the shiny particles in class one and two were used to calculate a 3.2 \u00c5 with three-fold symmetry imposed and a 3.7 \u00c5 map without imposing any symmetry.", "Cryo-electron microscopy data collection and processing. Purified S protein (3 ml) with a concentration of B0.4 mg ml \u00c0 1 for MERS-CoV S or B0.3 mg ml \u00c0 1 for SARS-CoV S was placed on a glow-discharged holy carbon grid (GIG, 1.0 mm hole size, 400 mesh). After 4 s blotting with filter paper, the grid was flash plunged in liquid ethane using an automatic plunge device (Leica EM GP) with 10\u00b0C temperature and 99% humidity. Cryo-EM single particle data collection was performed using a 300 kV Titan Krios microscope equipped with K2 camera. Using the super resolution mode, each image was exposed of 11 s at a calibrated magnification of 38461 and an electron dose rate of B8 e per pixel per s, resulting in a total dose of B50 e \u00c5 \u00c0 2 that was fractionated into 32 movie frames. The images were binned before data processing, yielding a final pixel size of 1.3 \u00c5." ] },{ "paper_id": "073d6557ccb048fe248c2d4c09a21c33f8632371", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The human spleen and the classical pathway are integral for protection against infection by S. pneumoniae 39, [62] [63] [64] [65] .", "Human cadaveric spleens were donated from the Department of Anatomy, School of Medicine, Konkuk University (Seoul, Korea).", "Cells on coverslips or 10 \u03bcm OCT (Tissue-Tek) frozen spleen sections were fixed with 100% acetone (10 min, room temperature) and stained, where indicated, with DAPI (4\u2032,6-diamidino-2-phenylindole) (blue) or FITC-, PE-, AMCA-, or Alexa Fluor-conjugated donkey antichicken IgY, goat anti-hamster IgG, donkey anti-rabbit IgG, goat anti-rat IgG, and streptavidin as secondary reagents (purchased from Abcam, Jackson ImmunoResearch Laboratories, or Molecular Probes). Cells and spleen sections were examined for fluorescence with a deconvolution fluorescence BX61-32FDIC microscope (Olympus Corp., Tokyo, Japan). Images were acquired with a Coolsnap EZ system (Roper Scientific, Inc., AZ, USA).", "Mitomycin C-treated fluorescent bacteria (1 \u00d7 10 8 ) were intravenously administered to mice for the indicated times. Mice were sacrificed, and spleen sections were examined by deconvolution fluorescence microscopy.", "Lipid rafts (LRs) are small (10-200 nM) , highly dynamic, detergent-resistant membrane fractions enriched in cholesterol and glycosphingolipid content on the plasma membranes of eukaryotic cells 1, 2 . Although LRs comprise only a small percentage of the cell surface area 3 , their sizes can increase by coalescence with other raft units 4, 5 , providing spatiotemporal platforms for many molecular entities 6 . LRs play crucial roles in complex physiological processes, such as phagocytosis, receptor-receptor associations, receptor-pathogen associations, and signal transduction in many pathological situations 1,2,7-9 , modulating innate and acquired immune responses 10 ." ] },{ "paper_id": "073d9b195e4d3e325a8ec7cd30b9ec23bb0a00a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Other nonserious adverse events reported in more than 1% of the total population were in the OZ, O, and Z arms, respectively, nausea and/or vomiting (in 13, 4, and 5 patients), diarrhoea (in 2, 1, and 5 patients), and rash (in 1, 2, and 2 patients).", "Table S1 Proportion of false positive and false negative results for various viral load thresholds compared to viral isolation in the sample of GROG patients. " ] },{ "paper_id": "0741533a3a9c97880fb1d7f184d569a6e5191ef1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Age-and sex-matched controls were recruited among healthy patients undergoing elective surgery. Cases and controls were also matched according to procedure date (HSCT and elective surgery, respectively) \u00b1 1 week.", "The total cell count per sample was determined. T cell (CD45+, CD3+ CD56\u2212) and Natural killer (NK) cell (CD45+, CD56+, CD3\u2212) populations were identified using the following labelled antibodies: CD45-FITC/ APCCy7 (clone 2D1, BD Pharmingen), CD56-APC (clone NCAM16.2, BD Pharmingen) and CD3-PECy7 (clone UCHT1, Biolegend). Fluorescent cell viability dye 7-AAD (BD Pharmingen) was used to exclude dead cells. FlowJo v10.0.7 software (TreeStar) was used for data analysis.", "All HSCT were allogenic. Twenty-five patients underwent HSCT for the first time (93%) and two received their second HSCT (7%)." ] },{ "paper_id": "07420d39191900a262a4c5afff61e0ef80eac575", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ribosomal RNAs snoRNP:", "S-Adenosylmethionine SAH:", "S-Adenosylhomocysteine scaRNAs: Small Cajal body-specific RNAs snRNAs:" ] },{ "paper_id": "0749cab30d660b29d52b5346b02773a3f36fda0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Monoclonal mouse antibodies against CD9 (clone M-L13), CD63 (clone H5C6), and CD81 (clone JS-81) were obtained from BD Pharmingen. Rabbit anti-FLAG was obtained from Sigma Aldrich. Mouse anti-rhodopsin antibodies were obtained from Millipore. Rabbit anti-CD13 (APN) antibodies were obtained from Abcam. Mouse anti-CD26 (clone M-A261) was obtained from BD Biosciences. Rabbit anti-TMPRSS2 (clone EPR3681) was obtained from Abcam. Secondary antibodies were purchased from Invitrogen and include goat-anti-rabbit-AlexaFluor 488, goat-anti-mouse-AlexaFluor 488, and goat-anti-mouse-AlexaFluor 568. Donkey-anti-goat, goat-anti-mouse, and goat anti-rabbit HRP conjugated antibodies were purchased from Thermo Scientific.", "Quantitative reverse transcriptase-PCR Cellular RNA was isolated using the RNeasy Mini Kit (Qiagen) and 100 or 500 ng was reverse transcribed using an iScript cDNA synthesis kit (Bio-Rad). Quantitative PCR was performed using Power SYBR Green (Thermo Fisher) and primers specific to human CD9, DPP4, TMPRSS2, or HPRT.", "Statistical comparisons were made by two-tailed Student's t-test. Error bars in the figures indicate the standard error of the data. Non-linear regression analysis was used to fit a curve to the entry kinetics data and obtain the time of 50% infection. This analysis was performed using Minitab 17 software. " ] },{ "paper_id": "074a37594f93652c9db7cef967b21eaa5b70f731", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HIV [56, [89] [90] [91] has been a discussion topic in the microvesicle field for many years. Not only has it been hypothesized that HIV itself may have microvesicle features, but microvesicles also have been described to have immune modulatory functions on HIV-infected cells and to expand the infectivity of HIV.", "Being the first human tumor virus identified, EBV is in many aspects an extraordinarily benign pathogen and is best known as the causative agent of \"kissing disease\" or infectious mononucleosis. It is estimated that over 90% of the world population is persistently infected with EBV. The EBV life cycle begins by exchange through saliva and EBV virions that seem to preferentially infect na\u00efve resting B cells in secondary lymphoid organs, such as the tonsils. Occasionally isolated epithelial cells also become infected and presumably sustain lytic replication [72] , which is required for viral shedding into the saliva for transmission to new hosts [73] .", "Complexing of gB-DR effectively hijacks the cellular antigen presenting machinery, preventing further peptide loading and, in addition, increasing microvesicle production [37, 53] . This final step releases additional gB-DR complexes into the host immune microenvironment, promoting resistance of viruses to immune attack, and in some cases producing bystander T-cell tolergenicity or anergy [37, 53] . In the case of HIV, microvesicle packaging and spread of the virusencoded Nef protein impairs proper endocytosis of the immature MHCII/invariant chain, antibody class switching, and lysosomal degradation of viral peptides allowing HIV virus to evade immune recognition [37, 38] . EBV, human cytomegalovirus (CMV) and hepatitis C virus (HCV) have also found means to evade immune responses by exploiting microvesicles, as discussed below." ] },{ "paper_id": "074b685a347c109752be7efe757c3985190ec6c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A case was excluded if 1) it didn't meet the ILI case definition, 2) testing was performed more than five days after disease onset, 3) testing was performed within seven days after previous testing, 4) the clinical sample was lost, or 5) it presented before the week of the first PCR-confirmed influenza case.", "All patients who visited the outpatient department, presented with ILI, and had been administered the rapid influenza diagnostic test (RIDT) were eligible for the study. We modified the original case definition for ILI used in EU countries adapting to local context [11] ; a case was defined as ILI if the patient showed a sudden onset of fever and at least one of the following symptoms: cough, runny nose, sore throat, headache, myalgia, or fatigue. We aimed to recruit all age groups, but the number of child cases was limited because the hospital did not have a paediatric department.", "The phylogenetic tree was constructed using the Neighbor-Joining method. HA1 sequences from reference strains used in the phylogenetic analysis were obtained from the EpiFlu database of the Global Initiative on Sharing Avian Influenza Data (GISAID).", "In our setting, a commercial RIDT kit (RapidTesta Flu II, Sekisui Medical, Japan) was offered to every ILI patient to diagnose influenza A-and B-positive cases as a routine practice. The RIDT was performed by skilled nurses or laboratory technicians. Residual nasopharyngeal swabs were temporarily stored at 220uC in the laboratory department of the hospital after being used for the RIDT. Within a week, the samples were transported to the Institute of Tropical Medicine at Nagasaki University for storage in a deep freezer (280uC) until they were used for further molecular tests." ] },{ "paper_id": "075fc26a9bf29767e3e3e29e22121ce3980fcbf2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Library construction and TruSeq Illumina sequencing. The cDNA amounts in both samples were determined by a Qubit Fluorometer (Life Technologies, Thermo Fisher, Waltham, MA, USA). The two cDNA preparations were used to individually construct two libraries according to the manufacturer's instructions (TruSeq RNA Sample Preparation Kit, Illumina, San Diego, CA, USA). Briefly, the nucleic acids were ultrasonicated to generate fragments of less than 500-bp in length. The DNA fragments were end-repaired using T4 polynucleotide kinase, followed by adaptor ligation and loading onto the HiSeq 4000 (Illumina) for sequencing.", "Ethics statement. In Sample collection. In the Sichuan province of China in 2016, 26 nursery piglets aged 1 to 2 months were collected from 11 intensive commercial farms where acute respiratory disease had broken out. Animals that exhibited the clinical signs of acute respiratory disease (i.e., fever, rhinorrhoea, cough, laboured breathing, depression and ocular discharge) were considered to be PRDC cases after assessment by a veterinarian. The piglets were adequately sedated with azaperone (Melone Biotechnology, Dalian, China) to avoid distress. The pathological alterations observed during necropsy in the lungs included diffuse bleeding, cyanotic appearance, interstitial thickening, swelling, and hyperemia. Prior to testing, the nasal swab samples from the piglets were placed into viral transport medium (VTM) at \u221280 \u00b0C. Serum and lung samples were stored at \u221280 \u00b0C before they were tested.", "Metagenomic data assembly and phylogenetic analysis. The Illumina-generated raw sequence reads were trimmed to remove the adaptor-related reads, duplicate reads, and porcine genomic sequences, and a 150 bp minimum length was selected. Reads that passed the data processing procedure were considered useful sequences, and these were aligned with the sequences in the NCBI nonredundant nucleic acid and protein databases using BLASTn and BLASTx, respectively. The taxonomies of the sequences with the best BLAST values were selected and used for further grouping analyses. The viral abundances were scanned by SOAP aligner software. In parallel, all useful sequence reads were subjected to de novo contig assembly using SOAP assembly software (http://soap.genomics.org.cn/) with the criterion of a 90% minimum overlap identity. Individual viral contigs from both pools were reassembled into a larger contig or genome sequence using high-level sequence identity criteria. The assembled viral nucleotide sequences and open reading frame-translated peptides were aligned against the nonredundant database with BLASTN and BLASTP algorithms to calculate their percentage identities. The global multiple nucleic acid sequence alignments were constructed for the full or near-full length viral genomic sequences using MUSCLE v3.7. Pairwise identity values and phylogenetic analyses were carried out using MEGA 7.0 software (https://www.megasoftware.net/). Phylogenetic trees were constructed using the maximum-likelihood method and the tree topology evaluation was based on 1000 bootstrap replicates." ] },{ "paper_id": "0768babd4f340cc1b5eb49540be3decfc480eb8b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(c) Base composition. The frequency of A, T, G, C, and GC at first, second, and third positions of synonymously variable sense codons which can potentially vary from 0 to 1 was calculated. The variation of GC3s among genes was characterized by its standard deviation.", "The genetic code uses 64 codons to represent the 20 standard amino acids and the translation termination signal. Each codon is recognized by a subset of a cell's transfer ribonucleotide acid molecules (tRNAs), and with the exception of a few codons that have been reassigned in some lineages [1, 2] the genetic code is remarkably conserved, although it is still in a state of evolution [3] .", "Bacteriophages generally use the translational machinery of their hosts to synthesize both their structural and regulatory proteins. This indicates that the amount of codon usage in the protein coding genes in the phages and their bacterial hosts should be similar." ] },{ "paper_id": "076d18c2ee294256a400299b5c4631aac187d47a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The research presented here was approved by the Stanford University Non-Medical Human Subjects Institutional Review Board on 28 April 2009 (Protocol #16782).", "A concern regarding the relationship of people's self-reported anxiety and their protective behavior is that some people might generally be more anxious regarding health. We probed general anxiety by asking about respondents' anxiety with regard to a number of infectious, chronic, and violent threats to health. We asked a series of questions probing respondents' perceived subjective risk on a 5-point scale for a variety of health threats, including other infectious diseases (A(H5N1) ''bird flu'', seasonal flu, HIV/AIDS), chronic diseases (heart disease, diabetes, cancer), and violence (unintentional accidents, terrorism). We calculated the correlation matrix for answers to these threat questions and used Principal Components Analysis (PCA) to explore potential structure in the responses to different categories of threat [20] .", "We begin by presenting descriptive results of the survey and follow with our primary analytical questions from the survey, namely, testing the hypothesis that respondents' affective state mediates their protective action.", "An ongoing outbreak of novel influenza A(H1N1), colloquially referred to as ''swine flu,'' has caused over 200,000 confirmed cases (as of 28 August 2009 [1] ). Because of under-reporting, the actual number of people infected is substantially larger, particularly considering that many countries have ceased testing for A(H1N1) [1] . As human-to-human transmission became widespread in at least one region of the world, WHO rapidly declared the outbreak an imminent pandemic [2] and with widespread human infection, WHO declared a phase 6 pandemic on 11 June 2009, where it remains at the time of submission [3] . The virus appears to have a higher reproduction number and somewhat higher case fatality ratio than recent seasonal influenza viruses [4, 5] , and has certainly caused great concern in the population, fueled by both extensive media coverage and an initially high level of uncertainty about mortality rates and transmissibility of the virus." ] },{ "paper_id": "0771924722e625f8b49b2686a41e899954a962d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All results are presented as mean value 6 SEM unless otherwise specified. Significance of difference between any two groups was determined by two-sided Student t test, and a final value of p , .05 was considered significant.", "We thank Dr. Agnese Po and Dr. Giuseppina Catanzaro for technical assistance in confocal microscopy, and \"Fondazione Roma\" for continuous support. This project was supported by La Sapienza University funding to G.B.-Z. and G.F.", "I.C.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; F.P. and G.M.: collection and/or assembly of data, data analysis and interpretation; F.A., C.S., and V.P.: collection and/or assembly of data; E.D.F.: data analysis and interpretation, manuscript writing; M.P. and R.C.: data analysis and interpretation; M.I.: provision of study material; G.B.-Z.: financial support, data analysis and interpretation; E.M.: conception and design, manuscript writing; G.F.: conception and design, financial support, provision of study material, manuscript writing, final approval of manuscript." ] },{ "paper_id": "07899a6af647ba443bf04599aa35d111d0d08cb3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "3.2.6. Mitoxantrone (Novantrone \u00ae , Immunex/Amgen, Thousand Oaks, CA, USA)", "Dalfampridine (Ampyra/Fampyra \u00ae , Acorda Therapeutics)" ] },{ "paper_id": "078abb148599f16b6a3f8cfcf2599994dd9155f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "e results showed that about half of cases (629 (45.6%)) were linked to at least one place of exposure where 321 (23.3%) of them were linked to hospital outbreaks (Table 1) .", "e variables considered in this study were age, gender, patient type (whether the patient is a healthcare worker (HCW) or nonhealthcare worker), health outcome (dead or alive) as at the last day of follow-up, patient comorbidity status, types of exposure to known risk factors (animal contact and camel contact indirectly or directly or through consumption of camel products), and place of infection (classified as hospital, community, and household/ family). e data set was cross validated with information from WHO disease outbreak news and Saudi Arabia MOH MERS command and control website.", "e authors declare no conflicts of interest.", "To answer the questions about the relationships among the network centrality metrics, the results suggest that patient's degree centrality explains 90.2% of the variation in patient's closeness centrality, while 14% and 9.3% of the variation in closeness centrality were explained by eigenvector and betweenness centrality, respectively." ] },{ "paper_id": "078b6935fa30cd20a00da6c6182e85b41ab4d9c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following reagents were solubilized in sterile distilled H 2 O, stored at -20\u00b0C, and thawed immediately before use: adenosine (ADO, Abcam Biochemicals, Cambridge, UK), erythro-9-(2-Hydroxy-3-nonyl)-adenine hydrochloride (EHNA, Sigma-Aldrich), adenosine-5-triphosphate disodium salt (ATP, Sigma-Aldrich), apyrase (Sigma-Aldrich), adenosine-3',5'-cyclic monophosphate (cAMP, Sigma-Aldrich), 8-Bromo-cAMP (8BrcAMP, Abcam Biochemicals).", "doi:10.1371/journal.pone.0134943.g005", "doi:10.1371/journal.pone.0134943.g010" ] },{ "paper_id": "0792384d074cef963c808eacf3c63e3654776a2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SN, RW, and MK contributed to the conception, writing, and final edits of this manuscript.", "Interventions for either virus can be separated into primary prevention of infection, typically through vaccination, and reduction of infectious burden once transmission has already taken place.", "This work was funded by the National Institutes of Health (NICHD 5K12HD047349 and 5K08HL119359-02) to MK. " ] },{ "paper_id": "07ac15697a17a271224c7477de061f4ca6fc62aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LNs were fixed overnight at 4\u00b0C in freshly prepared 4% paraformaldehyde (Merck-Millipore) under agitation and subsequently washed in PBS for one additional day. Fixed tissues were embedded in 4% low melting agarose (Invitrogen) in PBS and sectioned with a vibratome (VT-1200; Leica). Forty \u03bcm sections were blocked in PBS containing 10% FCS, 1 mg/ml anti-FcR\u03b3 (BD), and 0.1% Triton X-100 (Sigma-Aldrich). Sections were incubated overnight at 4\u00b0C with the following antibodies: anti-gp38/PDPN, anti-B220 (Biolegend), and anti-YFP (Clontech). Unconjugated antibodies were detected using Alexa-fluor labelled secondary antibodies (Jackson Immunotools). To visualize nuclei, sections were stained with 4 0 ,6-diamidin-2-phenylindol (DAPI) (Sigma-Aldrich). Microscopic analysis was performed using a confocal microscope (LSM-710; Carl Zeiss), and the datasets were processed with ZEN 2010 software (Carl Zeiss).", "Results" ] },{ "paper_id": "07bf7b392feb438d436be66e2bdfe7513320231b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The total population size is denoted by N(t):" ] },{ "paper_id": "07ca288609eac312987db5e4e69de3c5a8b21e2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Epidemiological data including age, sex, symptoms, date of onset, and date of sampling were collected and entered into Excel worksheets. Descriptive analysis, frequencies and percentages were calculated using SPSS vr. 20 statistical software.", "Supporting information S1 Table. ", "The emergence of the Middle" ] },{ "paper_id": "07ddf570a1c38269ac3d1826cd8d013faeb6a339", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "07fc7bb8cbdb82bd4b17681aa92a6fc06d5fcf82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Isolation of viral RNA. Two different procedures were used to obtain viral RNA for RT-PCR and sequencing. Virions were purified from ;3 3 10 8 17Cl-1 cells that had been infected at a MOI of ;10 pfu/cell and incubated in low pH DMEM at 30-33 8C. The medium from the infected cells (;225 ml) was collected at 24 hpi and clarified at 4,000 rpm for 30 min. The virions were pelleted by centrifugation at 24,000 rpm for 3 h at 4 8C. The virus pellet was allowed to suspend overnight on ice in 0.4 ml/tube of 0.15M NaCl and 20 mM HEPES (pH 6.6). The suspended virus from six tubes was pooled and layered over one SW28 tube containing a linear gradient of 40% potassium tartrate (bottom) and 20% glycerol (top), in 0.0.2 M HEPES (pH 7.4).", "For most mutants, the revertant virus obtained from plaques formed at the non-permissive temperature had properties identical to wt MHV-A59. One exception was Alb ts17, which produced equal numbers of revertant viruses causing A59-sized plaques and revertant viruses with noticeably smaller plaques ( Figure S1 ). We isolated revertant viruses from a large (A59-sized) plaque (Alb 17R L ) and a small plaque (Alb 17R S ) for sequence analysis (see below). Some of the ts mutants did not produce revertant viruses (e.g., LA ts3, Alb ts19) or produced revertant viruses that were markedly different from the parental MHV-A59 virus.", "The cis-acting RNA elements involved in the different phases of MHV RNA synthesis have been studied quite extensively. It has been shown that 59-and 39-UTR, as well as [45] . The hatched box represents the common 59 leader sequence and the hatched circle represents the programmed (\u00c01) frameshifting element. The translation products of the genome and sub-genomic mRNAs are depicted and the autoproteolytic processing of the ORF1a and ORF1a/ORF1b polyproteins into non-structural proteins nsp1 to nsp16 is shown. A number of confirmed and putative functional domains in the non-structural proteins are also indicated: 3CL, 3C-like cysteine proteinase; ExoN, exonuclease; HEL, superfamily 1 helicase; MT, S-adenosylmethioninedependent 29-O-methyl transferase; NeU, endoribonuclease; PL1, papain-like protease 1; PL2, papain-like protease 2; POL, RNA-dependent RNA polymerase; X, adenosine diphosphate-ribose 19- ", "For our studies, virus stocks were derived from the original mutant isolates after plaque purification and propagation in 17Cl-1 cells cultured at 30 8C or 33 8C in low pH DMEM (pH 6.4) containing 6% FBS, 5% TPB, penicillin (100 units/ml), and streptomycin (100 lg/ml) [24] . Revertants were picked from plaques of mutants titered at 39.5 8C, followed by another plaque purification at 39.5 8C. The virus stocks used were first passage and were obtained by using virus from a single plaque (;10 7 pfu) to infect a dish of ;4 3 10 7 17Cl-1 cells to yield 30 ml of stock virus with a titer of 1-6 3 10 9 pfu/ml." ] },{ "paper_id": "0807d06a6db06216d0b9399f4658a4ffb581db03", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Spectrum analysis was carried out by selecting mutants (Can ) on selective minimum media drop-out plates containing canavanine [29] . Chromosomal DNA was isolated from the mutants and the relevant region of CAN1 was amplified by PCR and sequenced [30] . Sequence was carried out at MCLAB (San Francisco, CA, USA). Sequence analysis was carried out using Sequencher (Gene Codes, Ann Arbor, MI, USA).", "Yeast extract/ peptone/dextrose (YPD, 1% yeast extract, 2% peptone, 2% dextrose, 2% agar) and synthetic complete (SC, 0.67% yeast nitrogen base without amino acid, 0.087% amino acid mixture, 2% dextrose, 2% agar) media or the corresponding drop-out media were as described in [28, 29] . Homozygous haploid deletion strains library (Parental strain BY4741: MATa his3\u03941 leu2\u03940 met15\u03940 ura3\u03940) was obtained from Thermo Scientific (Pittsburgh, PA, USA).", "Adrienne P. Stephenson and Tryphon K. Mazu shared equally in this work." ] },{ "paper_id": "08174b668145c88e0e719dac2a03b30fb68f5de5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethical clearance for retrospective use of anonymized patient sera for test development and quality control was obtained from the ethical committee (Ethikkommission beider Basel)." ] },{ "paper_id": "082892d44934e61adfef5cd6d5867439e30b183b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "083d4f33c62061390ac7dafcc4e9a4e44518df3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "08467794d024d78c7981f7c39743a9faaa1adecb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are shown as the mean \u00b1 standard errors of three replicates per test in a single experiment repeated three times. Tukey's multiple comparison tests were used to analyze differences between groups. A p value less than 0.05 was considered statistically significant, and a p value less than 0.01 was considered highly significant." ] },{ "paper_id": "084df43c5fc9b52ac507f090c6d892b69e5b0999", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PID values for DNA and predicted protein sequences were calculated using the software package MatGAT (Matrix Global Alignment Tool) version 2.02 [78] .", "Nucleic acid extraction from blood, fecal, and tissue samples Total nucleic acids (TNA) were extracted from 200 ml of EDTA-blood, serosanguineous fluid, or fecal samples using the MagNA Pure LC Total Nucleic Acid Isolation Kit (Roche Diagnostics, Rotkreuz, Switzerland), or from tissues collected upon necropsy using DNeasy and/or RNeasy Tissue kits (Qiagen, Hombrechtikon, Switzerland) according to the manufacturer's instructions.", "Phylogenetic trees were constructed using MEGA3 [73] . Bootstrap support (1000 replicates) was calculated by the neighbor-joining/minimum evolution/MP methods and considered significant when .70% [76] . MP trees were obtained using the Close-Neighbour-Interchange algorithm [77] with search level 3 [76] , in which initial trees were obtained by random addition of sequences (10 replicates). All alignment gaps were treated as missing data. Branch lengths were calculated using the average pathway method [77] ." ] },{ "paper_id": "084f1464fd6c0885f64af9c09c1460ef50dddd01", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The above examples demonstrate that single-molecule spectroscopy can straightforwardly access physical quantities that seem to better correlate with pseudoknot-stimulated \u22121 PRF efficiencies, thereby providing unprecedented mechanochemical details for the underlying mechanisms [16, 31, 32] .", "Despite \u22121 PRF's ubiquity among infectious viruses, and its promising role for serving as an antiviral target [3, 4, 6, 27] , the precise molecular mechanism remains elusive. This paper aims to address how recent developments in biophysical tools, specifically single-molecule techniques and computational modeling, can help to elucidate the mechanochemical basis for \u22121 PRF.", "(\u0394G Stem 1, theory = \u221267.4 kJ/mol, 55% \u22121 PRF) actually stimulates \u22121 PRF more efficiently than that with a 13 bp Stem 1 (\u0394G Stem 1,theory = \u221280.0 kJ/mol, 47% \u22121 PRF) [49] ." ] },{ "paper_id": "085522850a68603e453f67deacac2be1293a483f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.pntd.0007231.g001", "https://doi.org/10.1371/journal.pntd.0007231.g002" ] },{ "paper_id": "085c71736d6b79717bb03aec375310d9e536f851", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Several cellular proteins bind to the 39UTR of HAstV-8 RNA", "The secondary structure modeling of the full-length 39UTR sequences of HAstV-1 to 28 (Accession Nos. Z25771, AF141381, AY720891, DQ028633, Y08632, and AF260508) were carried out with the RNA Mfold software release (version 3.2) [27] . The targets for the putative binding sites for cell factors were predicted utilizing the ESEfinder 3.0 [28, 29] , the ESRsearch [30, 31] , and the EBI-EMBL ASD-Alternative splicing search engines.", "Monolayers of CaCo2 cells (human adenocarcinoma HTB-37, ATCC) were grown at 37uC, 5% CO 2 in Advanced-Dulbecco's modified Eagle's medium (DMEM) (Invitrogen) supplemented with 5% fetal calf serum (FCS) (Biowest, France Labs), antibiotics (penicillin and streptomycin) and 2 mM L-Glutamine (Invitrogen). CaCo2 cells were infected with HAstV-8 strain Yuc 8 (kindly provided by E. Mendez, IBT, UNAM, M\u00e9xico). The Infections and the virus were obtained as previously described [20] ." ] },{ "paper_id": "085d2f0a23b102cb7492350434746878eb834785", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "0867cf1922a634eefb3a3ad07f4dc6c9c94828ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The raw data from the HTS assay were subjected to statistical analysis using cellHTS2 [52, 54] , a software package designed for the analysis of HTS data as part of the Bioconductor project for statistical computing [55] . Raw data were normalized using the plate median method [52, 56] . Next, a z-score transformation was applied to center and scale the data across the experiment. Replicates for a given compound at a given dose (N = 2 for each dose/compound combination) were then mean summarized. A zscore threshold of $2 was chosen to identify potential hits.", "The assay was automated in a 96-well format with a customized and fully integrated robotic system. The system equipment included: a Caliper Sciclone ALH 3000 workstation (Perkin Elmer) and a EL406 washer (BioTek) for liquid handling, an automated Liconic incubator (Thermo Scientific) for cold storage of plates, an automated Cytomat incubator (Thermo Scientific) for cell culture environment, a separate hotel for storage of plates at room temperature, a Synergy 4 plate reader, a Flexiseal plate heat sealer (K Biosciences, Beverly, MA), a Caliper Twister II, and a Beckman Sagian Orca robotic arm on a linear rail (Beckman Coulter, Fullerton, CA). Construction allowed for transfer of plates, reagents, and plasticware between all instruments, so that there was no need for any manual interference during screening assays. This entire system was enclosed in a custom-made laminar flow hood to allow for HTS screening capability under BSL2 sterile conditions. After the system demonstrated satisfactory performance in a 96-well format, the assay was miniaturized to a 384-well format and re-tested for reproducibility and stability under IFN-b and vehicle (1% DMSO) treatment conditions.", "To optimize the luciferase light reaction, we tested a series of flash and glow luminescent substrate systems in both lysed and live 2fTGH-ISRE-CBG99 and HEK293T-ISRE-CBG99 cells, including D-luciferin (Fisher Scientific, Pittsburgh, PA), the Chroma-Glo Luciferase assay system from Promega and the steadylite plus reporter gene assay system from Perkin Elmer (Waltham, MA) under a range of incubation conditions. The steadylite plus system was selected based on kinetic profile. Effects of IFN-b concentra-tion and treatment time were assessed with all other variables constant." ] },{ "paper_id": "08741b63c08d63c1a86dd3ef3ce3d1bfd39e560b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "in Dulbecco's modified Eagle's medium (DMEM, Invitrogen, Carlsbad, CA, USA) supplemented with 10% fetal bovine serum (FBS, Gibco, Carlsbad, CA, USA), 100 U/ml penicillin, and 100 \u03bcg/ml streptomycin at 37 \u00b0C in a 5% CO 2 humidified atmosphere. BTV1 strain SZ97/1 (GenBank accession numbers JN848759 to JN848768) was propagated in BSR cells.", "Statistical Analysis. Data were presented as the mean \u00b1 standard deviation (SD) from three independent experiments. All statistical tests were performed using GraphPad Prism 6 (GraphPad Software, Inc., La Jolla, CA, USA). Statistical comparisons were performed using Student's t test or ANOVA where appropriate. A P value of < 0.05 was considered statistically significant.", "to promote viral replication 14 . However, subsequent corresponding mechanisms underlying these observations have not yet been elucidated." ] },{ "paper_id": "0877aadd2c55095b8a663597fbb39150614f335e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mean values \u00b1 standard deviation (SD). No significant difference between the two methods of collection.", "The findings relating to the specimens collected by the parents and pediatricians were compared using SAS ver- The categorical data were compared between groups using the \u03c7 2 test or Fisher's test; the other between-group comparisons were made using Wilcoxon's signed-rank test, a non-parametric test for paired samples. P values of 0.05 or less were considered statistically significant.", "List of abbreviations CT: cycle threshold; CI: confidence interval; PDV: phocine distemper virus; PCR: polymerase chain reaction; SD: standard deviation." ] },{ "paper_id": "088207699688d96fe973df88c1add87ac8339645", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pidotimod follows a first order pharmacokinetic when administrated through oral route, while parenteral route follows second order pharmacokinetics, with a half-life of 4 h with and an oral bio-availability of 42-44%. It is eliminated through the kidneys without being metabolized. Plasma clearance is 5 l \u00d7 hE-1 with apparent distribution volume 30 l. Severeal types of oral route of the drug are available (tablets, sachets and vials) which are all bioequivalent [55] .", "Acute respiratory infections (ARIs) are still pandemics despite the introduction of new antibiotics and vaccines which contribute to reduce the risk of mortality and morbidity and they remain widespread and affect both young and elder people [1] . Furthermore, the socio-economic burden of ARIs remains high, considering the cost of symptomatic drugs, antibiotics, hospitalization and the indirect cost of absence from work or loss of school days [57] .", "In Europe, approximately 23% of the population is affected by allergic rhinitis (AR) [99] that is frequently accompanied by allergic asthma (AA), the prevalence of which increases from less than 2% in individuals without AR to 10-40% in those with AR; this combination of upper and lower respiratory symptoms increases the overall impact on the patient. There is now considerable evidence that the symptoms of AR and AA negatively affect patients' health related quality of life [100] [101] [102] .", "Allergen immunotherapy (AIT) is nowadays the only treatment specifically targeting the allergic inflammatory pathways and it represents a prototype of personalized medicine approach to respiratory disease patients [88] . AIT is highly effective and may induce long-term remission of symptoms. However, ongoing problems include the duration of treatment, the safety of immunotherapy, its cost and accessibility [103] .", "Adjuvants have the potential to modify the pharmacological and immunological effects of allergen vaccines. They may modulate allergen delivery, act as a depot, stimulate immune responses or limit antibody responses in order to reduce unwanted side effects.", "COPD results from complex interactions between environmental (mainly tobacco smoking and/or other pollutants) and molecular risk factors. Molecular risk factors for COPD include a plethora of gene polymorphisms, dysregulations of the antioxidants pool, metalloproteinase abnormalities and uncontrolled role of elastase. COPD exacerbations are triggered most often by respiratory viral infections, mainly rhinoviruses, even if bacterial component is present [77] [78] [79] . Moreover, exacerbations tend to be more severe and prolonged if caused by viral pathogens [80] ." ] },{ "paper_id": "088571fa032ef5eb915d17b62e106a698a301f2c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal experiments described in this paper were carried out in the BSL3 facilities of the Erasmus Medical Center in accordance with the Dutch guidelines for animal experimentation. A Dutch Government-approved and independent animal experimentation ethical review committee (Stichting DEC Consult) approved the animal studies (permit nr. EMC2838/122-12-29).", "Chikungunya virus (CHIKV) re-emerged in 2004 and has caused unprecedented outbreaks in Asia and Africa since 2005. The estimated number of cases exceeds 2 million and over a thousand infected travelers have returned to Europe and the USA since 2006 [1, 2] . CHIKV generally causes a fever that resolves within several days, a maculopapular rash, and a characteristic arthralgia that can be extremely painful and may persist for months. During the recent outbreaks also more severe clinical manifestations have been reported occasionally, such as neurological complications and even deaths, usually in the elderly, patients with underlying conditions, and newborns [3, 4] . A licensed vaccine or specific antiviral therapy are currently not available.", "Total protein samples were prepared by lysing 7610 5 cells in 0.5 ml of 46 Laemmli sample buffer (100 mM Tris-HCl, pH 6.8, 40% glycerol, 8% SDS, 40 mM DTT, 0,04 mg/ml bromophenol blue). Proteins were separated by SDS-PAGE in 12% polyacrylamide gels and were transferred to Hybond-LFP membranes (GE Healthcare) by semi-dry blotting. After blocking with 1% casein (Sigma) in PBS with 0.1% Tween-20 (PBST), membranes were incubated overnight with rabbit antisera against CHIKV nsP1 (raised using the peptide EVEPRQVTPNDHAN), nsP4 (raised using the peptide ASSRSNFEKLRGPV) or E2 [30] in PBST with 0.5% casein. Mouse monoclonal antibodies against b-actin (Sigma), or the transferrin receptor (Zymed) were used for detection of loading controls. Biotin-conjugated swine-a-rabbit (DAKO) or goat-a-mouse (DAKO), and Cy3-conjugated mousea-biotin (Jackson) were used for fluorescent detection of the primary antibodies with a Typhoon-9410 scanner (GE Healthcare)." ] },{ "paper_id": "08885e2da682c5d027e986aacc166975e01fc60c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Avian-origin influenza A (H7N9) virus was confirmed from nasopharyngeal aspirate, throat swab, and pleural ", "Our objectives are to describe lung ultrasound findings in two patients with severe respiratory failure from avian influenza A (H7N9) infection, provide clinical pathologic correlation, and to discuss the implications for viral pandemic preparedness.", "Serial lung ultrasound (Esaote MyLabFive) with an 11-to 3-MHz linear array transducer was performed on day 16, day 21, and day 24 of case 1's hospital stay. They were performed on hospital days 3 and 4 for case 2. A six-zone scanning protocol [4] was used to image the lungs in perpendicular planes (transverse and coronal or parasagittal) for the anterior, lateral, and posterior lung area \"AT the\" midclavicular line, midaxillary line and parasaggital line medial to the scapulae. A modified protocol scanning along the midclavicular line, anterior-axillary, and posterioraxillary lines described by Lichtenstein and Meziere was used in case 2 due to critical illness [8] . Lung ultrasound examinations were compared and correlated to the chest radiograph done that day for both patients (Figures 1 and 2) ." ] },{ "paper_id": "0892e16c218542d3a099d7b10aec24cab4bfce55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The statistical significance of the data was evaluated using ANOVA and Tukey post test using the IBM SPSS Statistics software version 20. P < 0.05 was considered significant.", "G.J.F and W.A.M have patents in the PD-1/ PD-L1 field. The other authors declare that they have no competing interests.", "have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative." ] },{ "paper_id": "0899b0f8df5f20c6a46ba1dc7675c85858b59a68", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vaccines 2019, 7, x 4 of 14 secondary antibodies (at the dilution of 1:5000) (Sigma, Ronkonkoma, NY, USA) at 4 \u00b0C for 30 min. Protein expression was visualized using a chemiluminescent substrate reagent (Thermo Scientific, Durham, NC, USA) according to the manufacturer's instructions.", "All data are presented as mean \u00b1 standard deviation (SD). The samples from each group (6 rabbits) were pooled and then analyzed as one sample in triplicate. Data were analyzed using two-way ANOVA with multiple comparison (LSD) test in SPSS. Different letters (a vs. b, a vs. c, b vs. c) indicate significant differences (p < 0.01) at the same time point.", "Rabbit hemorrhagic disease (RHD) is a comparatively new and economically important viral disease that affects adult rabbits [38] . It is important to develop effective strategies for preventing and controlling the spread of RHDV. However, because there is no efficient in-vitro system for propagating RHDV, it is difficult to produce this virus as a source of vaccine antigens [39] . At present, most commercial vaccines are produced using viral preparations obtained from the livers of experimentally infected rabbits [40] . This strategy raises numerous concerns with respect to animal welfare and biological safety [2] . To address these issues, and to develop an effective, safe, and convenient oral vaccine against RHDV, we constructed a recombinant L. casei expressing the RHDV VP60(VP1) protein." ] },{ "paper_id": "0899d745009fa75954f75b381c040aebd927832a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Citation: Glob Health Action 2014, 7: 23303http://dx.doi.org/10.3402/gha.v7.23303", "Recently, scholars have placed the classic transition within an expanded evolutionary framework. This recognizes a 'first' transition coincident with the Neolithic period and the agricultural revolution and a 'third' transition of emerging and reemerging infectious diseases occurring in the modern era (1) . In this expanded framework, Omran's classic transition becomes the 'second epidemiologic transition', as it is referred to here.", "Multiple modifications have been made to Omran's original theory. Omran (2) , attempting to accommodate variations from the theory, initially characterized three models for the progress of the transition. The 'classical model', featuring slow progression from high to low mortality and fertility, occurred in Western Europe, and was driven by economic development and advances in sanitation, public health, and medical knowledge. The 'accelerated model', seen in Japan, features more rapid progress, purportedly driven by the same factors. The 'contemporary model' applies to LMICs, wherein mortality has declined but fertility remains high and NCDs do not yet constitute the primary epidemiologic burden. Beyond the expansions suggested by Barrett and colleagues (1), Olshansky and colleagues have added a fourth stage, the 'Age of Delayed Degenerative Diseases', which recognizes a shift in NCDs to the elderly even as life expectancy increases, and a fifth, encompassing morbidity and mortality from HIV/AIDS and other emerging infectious diseases (22, 23) . Graziano (24) has proposed an alternative fifth stage, the 'Age of Obesity and Inactivity', in which increasing levels of weight gain and obesity alter the pattern of NCDs among the elderly (represented by Olshansky and Ault's fourth stage)." ] },{ "paper_id": "089acb4677633e0cf2d35fd728e686c8aa887bc0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pone.0219312.g005", "https://doi.org/10.1371/journal.pone.0219312.g006" ] },{ "paper_id": "08ac78608c5be04ef1cff3fba52a3c7648bfa21a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "AI initiated and planned the research. SI and MR collected the samples. MR and SA carried out the laboratory work. MKR and JF did a literature review, data analysis, and prepared the draft. SI, MMR, MAH, MMH, and AI made the necessary corrections over the entire manuscript. All authors read and approved the final manuscript.", "The Animal Experimentation Ethics Committee of Chattogram Veterinary and Animal Sciences Available at www.veterinaryworld.org/Vol.12/September-2019/24.pdf University (CVASU-AEEC) approved the study protocol and the approval number for the project was CVASU/Dir (R and E) AEEC/2015/07." ] },{ "paper_id": "08b862f9103eb1590d60bd0312f750729b3f2c7d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The severity of each respiratory episode was ranked as follows: 1) physician criteria (mild, moderate or severe); 2) Wood-Downes scale (0 to 10 points; mild < 3, moderate 4-7, severe > 8); and 3) a newly developed scale -named GENVIP score-(0 to 20 points) that assesses food tolerance, degree of medical intervention needed, respiratory distress, respiratory frequency, apnea, malaise and fever (article in preparation; data in S1 Table [10] )." ] },{ "paper_id": "08beca0f49f6c33cf0ea4544f6dfe34b5932214d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "08c1093aa1c393ee5364089d26278781dc3a3405", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The revised coding sequence annotations are available on-line at http://www.firthlab.path.cam.ac.uk/virad.html. More than two hundred of these revisions (restricting to, but not exhausting, ones with experimental support in at least one species) have already been submitted to and incorporated into GenBank.", "permissive approaches such as false discovery rate can be used to select a larger set of conserved regions.", "the results of applying synplot2 to each of the three alignments. All three alignments produced similar results, indicating that the plots are not greatly affected by the phylogenetic tree, nor, for large alignments, the exact choice of sequences." ] },{ "paper_id": "08d0057eaad519e3d6ef88ffbbc2187b2c11f126", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Phylogenetic analyses of either the complete sequence ( Fig. 1) a: determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) with the following primers/probe: ZIKV1086, ZIKV1162c and ZIKV1107-FAM. (10) b: sequence generated from P3. c: sequence generated directly from patient sera which is identical to P3 sequence. d: sequence generated from P0 which is identical to P3 sequence.", "A summary with information about the patient samples used for the ZIKV isolations and the GenBank accession numbers is presented in Table I ." ] },{ "paper_id": "08d822c186460651ee5f3a44d365b0701aff56e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The KSHV-positive B cell line bearing a doxycycline-inducible version of the major lytic transactivator RTA (TREX-BCBL-1) [55] was maintained in RPMI medium (Invitrogen) supplemented with 10% fetal bovine serum (FBS; Invitrogen), 200 \u03bcM L-glutamine (Invitrogen), 100 U/ml penicillin/streptomycin (Invitrogen), and 50 \u03bcg/ml hygromycin B (Omega Scientific). ", "Lysates were resolved by SDS-PAGE and western blotted with the following antibodies at 1:1000 in TBST (Tris-buffered saline, 0.1% Tween 20): rabbit anti-EST1A/SMG6 (Abcam), rabbit anti-NCL (Abcam), rabbit anti-HuR (Millipore), rabbit anti-actin (Abcam), rabbit anti-IGF2BP1 (Abcam), rabbit anti-YTHDC2 (Abcam), rabbit anti-hnRNPU (Abcam), rabbit anti-ZC3HAV1 (Abcam), rabbit anti-hnRNPD (Abcam), rabbit anti-STAU1 (Pierce), mouse anti-NPM1 (Abcam), rabbit anti-GADD45 (Abcam), mouse anti-GAPDH (Abcam), mouse anti-ORF59 (Adv biotechnologies), or rabbit anti-K8.1 (PRF&L, inc). Primary antibody incubations were followed by HRP-conjugated goat anti-mouse or goat anti-rabbit secondary antibodies (Southern Biotechnology, 1:5000).", "The GADD45B and IL-6 SREs assemble a partially overlapping ribonucleoprotein complex" ] },{ "paper_id": "08dd1169c7aa45621e5f48bf6246b049e071e445", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Ethical Review Board of the Sheba Medical Center, Tel Hashomer approved this study (SMC-8859). The samples and results were stripped of all links to personal details pertaining to, or which could be used to identify individual patients. All data were analyzed anonymously. The Ethical Review Board exempted this study from a requirement for obtaining informed consent.", "Small portions of fecal matter were vortexed for 15 seconds in stool suspension buffer, 2 ml 0.9% saline with glass beads (samples 1 to 93) or 5 ml of M199 containing 15.6 mg of dihydrostreptomycin, 15,625 U of Penicillin G, and 156 U of Mycostatin and 0.1 volume (v/v) of chloroform (samples 101-192). Suspensions were clarified by centrifugation at 2,5006g for 10 min and stored at 220uC until use.", "One of the trends in pathogen identification is the increasing reliance on molecular methods to achieve high throughput, high sensitivity and specificity of results in clinically relevant times [2, 16] . However, low pathogen copy number, inefficient extraction and the incomplete removal of inhibitors, reduce the sensitivity and specificity of the molecular assays. Among clinical samples, stool suspensions contain a wide range of materials that have the potential to inhibit RT and/or PCR chemistries [4, 6, 8, 9, 10, 11] . Thus, it is important to develop a reliable method to determine whether inhibitors are present in nucleic acid prepared directly from stool suspensions. An appropriate internal control does not exist because of wide differences in eukaryotic and prokaryotic composition in fecal material between patients." ] },{ "paper_id": "08e6541bee1b67eab1918bcbbe6f90463ecb651a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Agarose gel electrophoresis. The PCR products were electrophoresed on 2% agarose gel and visualized by staining with 0.50 \u03bcg mL -1 ethidium bromide by UV transilluminator (M-15; UVP, Upland, USA).", "PCR product purification. The PCR products were purified using PCR purification Kit (Roche, Mannheim, Germany) according to kit's manufacture instructions.", "RNA extraction Viral RNA was extracted from the directly pooled tracheal swabs in RLT buffer (Qiagen, Hilden, Germany) and 10 \u03bcL 2-mercaptoethanol (Merck, Darmstadt, Germany) per 1 mL buffer using RNeasy Mini Kit (Qiagen), according to the manufacturer's protocol." ] },{ "paper_id": "08e6a1b558bcb3962378851963c2e67681dabad6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "My-BatCoV-HKU6 7 0", "Miniopterus pusillus Mi-BatCoV-HKU8 8 0", "Rousettus leschenaultii Ro-BatCoV-HKU9 9 0" ] },{ "paper_id": "08e78c0222e84457195ccefb2e371f1847670436", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal work was conducted under conditions and with permits approved by animal ethics committees of the Australian Animal Health Laboratory and the Queensland Department of Primary Industries and Fisheries. ", "In all cases, cell medium was removed after 3-5 days and replaced with fresh medium supplemented with 10% BCS." ] },{ "paper_id": "08ee65d70ad0dae18dd402eb531103c2dfbbeffb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "0910e151cd1fb8d455e54cd4e97f867627f934c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "is the spatial weights matrix which considers three nearest neighbours ( is 1 if area and are within a distance of three nearest neighbours and zero if otherwise). The Moran's test was applied using the spdep package of statistical software [23] .", "Each Canadian FSA was assigned to the respective county and state based on the postal code conversion file (PCCF) available from StatCan.", "Currently, there are no solutions to fully overcome the effects of MAUP and related methodological issues have not yet been adequately addressed. Recommendations have been made to minimize MAUP effects in statistical inference by analyzing the aggregated covariates in hierarchical levels of areal units from the finest spatial resolution possible to a coarser resolution, verifying consistent model results across different scales, avoiding ecological fallacy, collecting data at the scale at which inferences is to be made, and using scale invariant statistics to make inferences [17, [44] [45] [46] ." ] },{ "paper_id": "092193fe026d59729062786d8f576b553e11a97d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Here r is 2 that means the (r \u00d7 n) matrix X lists points in 2-dimensional Euclidean space. We have applied the cost function \u03c3 to measures the squared differences between ideal (m-dimensional) distances and actual distances in r-dimensional space as follows:", "Our method presents a ripe opportunity to use data-driven approaches for advancing our current knowledge on disease mechanism and predicting disease comorbidities in a quantitative way.", "We suppose that what is happening for the comorbidities we investigate is similar to what found for prions [71, 72] . Similar to most infectious agents, prion causes inflammatory responses by activating innate immunity through glial cells in the brain." ] },{ "paper_id": "09242b23825a9c7e09660df99494b673e5abea3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "first micro second of up to \u223c 0.70 (Fig. 6b) . For Vpu-DD the sequence is reversed by assembly via TMDs of up to \u223c 0.50 oligomerization followed by cytoplasmic assembly which remains a ratio of \u223c 0.05 (Fig. 6c) .", "bilayer supported the experimental data in demonstrating that, in addition to a previously known role in downregulation of host factors, the phosphorylation sites of Vpu also modulate oligomerization.", "The thrombin enzyme cleaves the strep-His8 fusion tag from Vpu-WT and the mutants ( Fig. 2a lanes 2 , 4, 8 and 10 and Supplementary Fig. S1 ). The pattern mentioned for uncleaved Vpu does not seem to be affected by thrombin treatment." ] },{ "paper_id": "09340528717039c904847d959dd4ff0adcc308ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "International Journal of Cell Biology 7", "International Journal of Cell Biology that specific proteins, organelles, and invading bacteria are specifically degraded by autophagy (Figure 3 ).", "AgRP:" ] },{ "paper_id": "0938d2fb07611897abf38cea727ddbeea77b73d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author declares no conflict of interest.", "Regarding the real-time forecasting, we employed the so-called Richards model, an analogue to the generalized logistic model [4, 5] :", "where E(.) represents the expected value. As for fs, it is known that the mean and standard deviation are 5.0 and 3.0 days, respectively, best fitted by lognormal distribution [3] . Employing a step function, the incidence of infection was statistically estimated via a maximum likelihood method. The estimation was implemented independently by the history of contact and type of membership.", "We estimate the number of cases by time of infection, it. Using the probability mass function of the incubation period of length s, fs, the incidence of infection is known to satisfy" ] },{ "paper_id": "09403dce0f0c10723150a14e1ea2f00b11dc05fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition to the techniques included in the taxonomy [5] , session 2 included a core message intended to induce mild 'disgust' towards dirty hands in order to motivate hand-washing [8] . The page showed a photograph of a dirty hand and suggested that hands could be covered with 'dirty' viruses that were not visible.", "and previous experience of web-based intervention development, the first author identified likely key determinants of behavior and effective web-based methods of addressing these. The first and second author then drafted the webpages. An informal mapping process was employed to check that each of the relevant factors identified from theory and literature had been addressed (there was insufficient time to carry out an exhaustive, systematic reviewing and intervention mapping process). To check that the intervention was effectively addressing the right behaviors and determinants we also carried out four empirical studies, as follows:", "Following Green and Kreuter's 'PRECEDE-PROCEED' model [2] , we asked infection experts on our team to identify the behaviors most likely to be efficacious. We then carried out a qualitative study (N = 31) to determine which of these were also viewed as feasible and acceptable by our target population, and what factors would influence their adherence to the behaviors. Participants were invited to discuss their perceptions of infection transmission and likely adherence to infection control measures in both non-pandemic and pandemic contexts. Infection control measures discussed included handwashing, social distancing and cough hygiene (e.g. covering mouth, disposing of tissues immediately etc.). Thematic analysis revealed that handwashing was regarded by our participants as more feasible than cough and sneeze hygiene and more acceptable than social distancing, and identified a number of factors that were potential barriers to carrying out infection control behaviors." ] },{ "paper_id": "09417d5a567e93e35a80a241b9459f2b84ef0b0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell viability, cytotoxicity and enzyme activity assay on DOX/ GL-ALG NGPs", "At the time of sacrifice, tumor, liver, and heart were removed and fixed in 10% neutral formalin. The fixed tissue was dehydrated, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (H&E). The stained sections of each test sample were examined using light microscopy (OLYMPUS, Japan). Slides of the tumor were deparaffinized and rehydrated then immunofluorescence-stained using PCNA, Ki67 antibody and Immunofluorescence Detection Kit (Sangon Biotech, Co., Ltd., Shanghai, China) and TUNEL assay kit (Beyotime Biotech, Shanghai, China) according to the manufacturer's instruction.", "The protein expressions of Bax, Bcl-2, and Bcl-xL were analyzed by western blotting. HepG2 cells were collected by centrifugation and resuspended in extraction buffer of mammalian protein extraction kit (Sangon, China). Cell debris was removed by centrifugation, and the supernatant was collected to detect the protein concentration by BCA method (Pierce, USA). An amount of 40 mg cellular protein was electro-blotted onto a PVDF membrane following separation on a 10 % SDS-polyacrylamide gel electrophoresis. The PVDF membrane was transferred to incubate with blocking solution (5% skim milk) for 2 hours at room temperature, and then incubated overnight with a 1:1000 dilution of anti-Bax, anti-Bcl-2, anti-Bcl-xL, anti-\u03b2-actin antibody at 4 \u00b0C. Blots were washed five times with Tween 20/Tris-buffered saline (TTBS) and then incubated with a 1:1000 dilution of horseradish peroxidase-conjugated secondary antibody for 1 h at room temperature. Blots were washed five times with TTBS again and then developed by Horseradish peroxidase substrate (Millipore Corporation, USA) and data were captured by exposure to Kodak BioMax Light films." ] },{ "paper_id": "0943374130f5f8474d6d480d4d038615a0e36de3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasma HCV-RNA levels were assayed by Abbott RealTi-meHCV assay (Abbott Laboratories. Abbott Park, Illinois, U.S.A.). Moreover, HCV genotype was determined by Abbott RealTime HCV Genotype II Amplification Reagent kit.", "This study was approved by the Ethics Committee of the National Institute for Infectious Diseases ''L.Spallanzani'', and all enrolled individuals provided written informed consent.", "All experiments on monkeys were performed in accordance with the recommendations of the Weatherall report, and were previously approved by the regional ethical committee ( " ] },{ "paper_id": "0951f5ec3710990a5c181e04fa8fdf7d9a0376e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed by performing two-tailed non-parametric Mann-Whitney test using GraphPad Prism version 4.00. P-values#0.05 were considered significant." ] },{ "paper_id": "09525027db30dc3a6945da255f80b2099e239c48", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.ppat.1006314.g001" ] },{ "paper_id": "0953fa36903063f60627e07f7b4e07f0aec3c4d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After data extraction using Imagene 5.6 Software (BioDiscovery), Lowess normalization [57] was performed on mean spot-intensities in order to correct for dye and printtip biases [58] . The microarray data was analysed using ANOVA (R version 2.2.1/MAANOVA version 0.98-7) http://www.r-project.org [59] . Briefly, in a fixed effect analysis, sample, array and dye effects were modelled. Pvalues were determined by a permutation F2-test, in which residuals were shuffled 5,000 times globally. Genes with P < 0.05 after family wise error correction were considered significantly changed. Cluster analysis (standard correlation) was performed with GeneSpring GX 7.2 software (Silicon Genetics). When indicated, the confidence level was increased by applying a fold change cut-off. The resulting genelists were subjected to Genespring 7.2 software for further analysis." ] },{ "paper_id": "095424c03a6e78279e47488552d961bc328f9c84", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.pone.0227104.t005", "Supporting information S1 Table " ] },{ "paper_id": "09561ed721369a7a9e077f7bea9022499c12b13d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Many studies have attempted to measure the spatial dynamics of influenza spread, often in an effort to create better control strategies and predict the occurrence of specific strains in coming influenza seasons [6] [7] [8] . Implicit in this work is the reality that influenza transmission dynamics are not spatially uniform, though details of how transmission may vary spatially are lacking.", "The similarity measure can depend on geographical proximity and/or demographic proximity, and can also be informed by observed data on travel or contact patterns. The similarity matrix does not necessarily contain probabilities, but represents the relative similarity between two locations and/or demographic features. Additionally by similarity we are describing the potential for an infective event. Alternatively, we can also entertain a Bayesian formulation and attach a prior to the parameters of the distance measure. Below, we investigate some different measures." ] },{ "paper_id": "095cf0472e7f23349f22a1f538eb2c8d590d33e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nasopharyngeal (NP) and oropharyngeal (OP) swabs for detecting viruses and blood cultures for detecting bacteria were taken from eligible patients on admission using operating procedures described by the WHO [12] . Specimens were taken an average of 7 days after illness onset (range: 1-66 days).", "For influenza vaccination history; 832/1,075 (77.4%) cases did not receive the vaccine within the 12 months prior to hospital admission, while 243/1,075 (22.6%) were reported as unknown for an influenza vaccination status. Table 1 details these results.", "Fifty-three percent of patients had at least one underlying medical condition. These comorbidities included chronic respiratory disorders (asthma, COPD, bronchiectasis, and immotile cilia syndrome), cardiac disorders (heart failure congenital heart diseases, and cardiomyopathy), neuromuscular disorders (epilepsy, cerebral palsy, and myopathies), hematological disorders (thalassemia), endocrine disorders (diabetes mellitus, hypothyroidism, and morbid obesity), renal disorders (end-stage renal disease), and liver disorders (liver cirrhosis and hepatic failure)." ] },{ "paper_id": "0969d53ac7a447d43b431dbe9744e416de26df38", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There appears to be a genetic influence in exhibiting KD. Incidence is higher in some genetic backgrounds and consistently appears in males greater than females within those backgrounds [16] . By age five in the United States, 1 in 1000 African-American children and 1 in 2000 Caucasian children will have been affected [17] [18] [19] . In general, Asians have a much higher rate of KD, this is especially evident in Japanese children, whose lifetime incidence rate is near 1% [20] . This predisposition holds even for those persons of Japanese heritage raised in foreign lands, such as the United States [16] .", "In a recent network and pathway analysis, responses were consistent with global activation of the immune response [54] . Although genome wide searches and similar techniques have not been definitive, genes involved with B cell activation, such as CD40 and the B lymphocyte kinase (BLK), have been identified [55, 56] . There is a growing body of literature implicating specific B cell responses in the pathogenesis [57] . In this review we will focus on the literature surrounding these recent reports of antibody reactive cellular inclusions and B cell involvement.", "In addition to protein, the ICIs observed in the limited bronchial epithelial samples were also partially composed of RNA. While the RNA could be of viral origin it is important to note that many of the host-derived intracellular protein aggregates previously noted also contain host mRNA [113, 114, 116, 117] . It is reasonable to conclude that if the ICIs observed in KD patients were related to one of these structures, they would positively stain for RNA." ] },{ "paper_id": "096d707e74acc27426416dacf89d5d134a0b9866", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Allergic dermatitis APC:", "Antigen-presenting cells CHS:", "Contact hypersensitivity DNP: Dinitrophenyl ELISA: Enzyme-linked immunosorbent assay HRP: Horseradish peroxidase IFN:" ] },{ "paper_id": "0977f51bf118077aae3d344adbe019c40622beb4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "097b9b4ada3e89942ea196c59226e95da1b7969f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Serum samples were collected as reported previously [27] and submitted to the Diagnostic Center for Population and Animal Health (Michigan State University, Lansing, MI, USA) for quantitative VA concentrations by HPLC.", "Enumeration of total IgSCs and PEDV-specific ASCs was performed as described previously [16, 39] . Counts were averaged from duplicate wells and expressed relative to 5 \u00d7 10 5 MNC.", "Supplementary information accompanies this paper at https ://doi. org/10.1186/s1356 7-019-0719-y. " ] },{ "paper_id": "09b0945d4963d363bb670d75070c19a328fbfce6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at http://www.mdpi.com/2414-6366/4/3/99/s1, Table S1 : Bats collected and tested in this study. ", "Paramyxoviruses are negative-sense single-stranded RNA viruses capable of infecting a diverse host range including mammals, birds, reptiles and fishes [28] . The taxonomic classification of viruses in the Paramyxoviridae family has recently undergone several changes [29] . In an attempt to accommodate the rapidly growing number of paramyxoviruses described, the previously known Avulavirus and Rubulavirus genera were elevated to the sub-family level (Avula-and Rubulavirinae) each with two new genera. In addition, several unclassified rodent-borne viruses were classified to newly established genera (Narmovirus and Jeilongvirus) in the sub-family Orthoparamyxovirinae to which the Henipa-, Morbilliand Respirovirus genera belong.", "Sequencing was performed as previously described for molecular host species identification. Sequences were viewed, edited and a consensus generated using the BioEdit sequence alignment editor software version 7.2.5 [43] . CIPRES was used for ClustalX alignments, determining the best DNA substitution model for nucleotide sequence analysis using the jModelTest software and for constructing Bayesian phylogenies using the BEAST version 1.8 software [44] [45] [46] . Bayesian MCMC chains were set to 20 million iterations, sampling every 2000 steps for optimal ESS scores. Output files were visually inspected to check for convergence using the Tracer software version 1.7 [47] . The final phylogenies were constructed in TreeAnnotator with a burn-in value of 10%. For visualization and manipulation of the phylogenetic tree, the FigTree version 1.4.2 software was used. Pairwise similarities between sequences were analysed in MEGA X with complete deletion [48] ." ] },{ "paper_id": "09cba4ea15eda3c3bd33243487c9bd32928d9635", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hemocytin", "Basic transcription factor 3 BTF3-F 5 AGTGCATAAGCAGGCAACACCA3 BTF3-R 5 TACGTCGCCACCGAAATGAGTT3", "Real-time polymerase chain reaction (qPCR) was performed using SYBR Green PCR Master Mix (Applied Biosystems, Foster City, CA, USA) and the primers listed in Table 1 . Expression levels were determined through 2(-Delta Delta C(T)) method (DDCt) [34] , normalized using rp49 gene expression [35] , yielding the relative expression value. Statistical analyses were done using GraphPad Prism software, version 5.04 (GraphPad Software, Inc., San Diego, CA, USA). For comparison of the transfected and mock samples at different times after transfection, an unpaired two-tailed Student's t test was performed. * p \u2264 0.05, ** p \u2264 0.01, *** p \u2264 0.001. Table 1 . List of primers used for qPCR.", "Juvenile hormone-inducible protein JHIP-F 5 CCTTGCTGAGCTCCTTGAGAAACT3 JHIP-R 5 TACACATGGCCATTCCCATCTTCC3" ] },{ "paper_id": "09ccb3b9fece55e72c3acb85c4259de62a9c9e0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All serum samples were tested for BHV-1 antibodies using a commercial BHV-1 gB ELISA test kit, Herd-Chek* (IDEXX, Switzerland) having 100% sensitivity and 99.8% specificity. Suspect antibody test results (samples with blocking % greater than or equal to 45% but less than 55%) were considered as positive in the data analysis.", "Newly purchased animals can be the source of BRSV infection, which was confirmed in a Swedish study in which outbreaks of BRSV occurred most often after the introduction of purchased animals [7] .", "In each of the selected herds, serum samples from a representative number of randomly selected cows, and youngstock older than six months, were analyzed. In total, 9,637 serum samples were collected. A precise description about the selection of herds, and animals within herds, has been reported in Raaperi et al. [16] .", "The herd BVDV status was established by testing up to 10 serum samples from randomly selected animals, at ages from six months up to age at first calving, for BVDV antibodies as recommended by Houe et al. [17] . This enabled detection of a minimum prevalence of 20-28% depending on herd size. The PrioCheck BVDV Ab test kit (Prionics AG, Switzerland) was used for antibody testing. The test has a relative sensitivity and specificity of approximately 98% and 99%, respectively, compared to a virus neutralization test [18] ." ] },{ "paper_id": "09d2a697632210efee7bf9fe6ee07b66bb7248f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Resorcyclic acid lactones, namely radicicol (49, Figure 22) pochonin B (50, Figure 22 ) and C (51, Figure 22 ) isolated from H. fuscoatra exhibited a 92-98% reactivation efficiency of the latent HIV-1 ", "Marine organisms are well-established sources of natural alkaloids. Although the term 'alkaloid' seems puzzling and is prone to scientific controversy, alkaloids are generally defined as nitrogencontaining compounds derived from plants and animals. Relatively few alkaloids from marine sources have been found to possess antiretroviral properties and, so far, none have found their clinical use.", "Marine organisms are well-established sources of natural alkaloids. Although the term 'alkaloid' seems puzzling and is prone to scientific controversy, alkaloids are generally defined as nitrogen-containing compounds derived from plants and animals. Relatively few alkaloids from marine sources have been found to possess antiretroviral properties and, so far, none have found their clinical use.", "So far, the main anti-infectious activities documented for the fucose-containing SP are those against viruses [54] . More importantly, these polysaccharides are selective inhibitors of various enveloped viruses, including HIV [54] [55] [56] . FCSP acts during the early phase of infection by blocking the virus attachment and entry into the host cells, but may also inhibit subsequent replication stages in vitro [57] ." ] },{ "paper_id": "09db5b9c6d7c4f5d804c532939fb4f824c409bb6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "[B]", "[C]", "[D]" ] },{ "paper_id": "09de57e5401565a1e80361d32b09ce66b3a988c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A.A.Q); m.mckay@ust.hk (M.R.M.) \u2020 These authors contributed equally to this work.", "All sequence and immunological data, and all scripts (written in R) for reproducing the results are available online [33] ." ] },{ "paper_id": "09e25e413faba97b87efc701d1ab8d2a18386efb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "09e56ff472829444bd7a1670f61fb696fac7ba2c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "09e8d6985e74029c794e543bde68fba0d07133a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "09f23fe560ba923e5960707d0b4451df85253b36", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was carried out in strict accordance with the recommendations by Public Health Service Policy, United States Department of Agriculture Regulations, the National Research Council's Guide for the Care and Use of Laboratory Animals, and the Federation of Animal Science Societies' Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching. All the relevant institutional, state and federal regulations and policies were followed regarding care and use of animals at the Ohio State.", "All data were expressed as the mean value of 4 or 5 pigs \u00b1 SEM. Statistical analyses were performed using the GraphPad Prism 6 software by applying one way ANOVA followed by the Tukey's t-test. The statistical significance was considered at P < 0.05.", "Mycobacterium vaccae (ATCC#23027) was grown in endotoxin free 7H9 medium at 37 \u00b0C in accordance with ATCC instructions, and the whole cell lysate (WCL) was prepared as previously described [28] . CpG ODN 2007 (TCGTCGTTGTCGTTTTGTCGTT) in phosphorothioate backbone was custom prepared (Integrated DNA Technologies, IA, USA). Five conserved T cell peptides of PRRSV, nsp10 (aa 2578-2628) CPGKNSFLDEAAYC-NHL and (aa 2554-2604) VRILAGGWCPGKNSFLD; Nsp9 (aa 442-492) VRGNPERVKGVLQNTRF [29] ; GP5 (aa 445-489) KGRLYRWRSPVIIEK [30] ; and N (aa 187-213) VRHHFTPSE [31] were custom synthesized (Thermofisher Scientific, NY, USA)." ] },{ "paper_id": "09f32524e7d13409a47b77c3f7af60251df282f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The International Atomic Energy Agency (IAEA) standard soil 7 was equally pressed in similar manner as samples and these were used for quality assurance.", "Hospital wastes are generated as a result of patients' diagnosis and/or treatment or immunization of human beings or animals. Hospital wastes are a universal set having subsets like infectious and hazardous wastes.", "Soil is a very specific component of the biosphere because it is not only a geochemical sink for contaminants, but also acts as natural buffer controlling the transport of chemical elements and substances to the atmosphere, hydrosphere and biota. However, the most important role of soil is its productivity, which is the basis for the survival humans (Kabata-Pendias and Pendias 2001)." ] },{ "paper_id": "0a00a6df208e068e7aa369fb94641434ea0e6070", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As such, BCG-Prague is a natural phoP mutant.", "The duplication of ESX-5 in BCG-Tice, which could increase the residual virulence and immunogenicity, may partially account for the benefit associated with rBCG30 Tice.", "The mycobacterial strains used in this study were: ", "ASL, VT, ZW, and XY performed the experiments and participated in data analysis. DCA participated in data analysis and co-authored the manuscript. GFG oversaw the experiments. BZ oversaw the experiments and participated in data analysis. JL oversaw the experiments, analyzed the data, and wrote the manuscript.", "Mutation mapping microarrays were designed with Nim-bleGen algorithms that select a 29-mer oligonucleotide every 7 bases on each strand of the reference genome sequence (Genbank Accession AL123456) [29] . All probes were synthesized in parallel on a four-array set using a Digital Light Processor\u2122 (Texas Instruments, Plano Texas) and photoprotected by phosphoramidite chemis-try (Maskless Array Synthesis) (NimbleGen Systems, Madison WI) in a random probe layout [74, 75] ." ] },{ "paper_id": "0a01f5cf1c5cdc2711bcef74315dc54a6e143df0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting information S1 Table. SELDI-TOF " ] },{ "paper_id": "0a037565ead5cb2ee8dbdd7f6a0e381dd4b7ad83", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tissues sections from a total of 10 juvenile and 10 adult LBBs were subjected to lectin histochemistry for the detection of influenza virus receptors. No differences in SA receptor distribution between the juvenile and adult LBBs were found.", "Bats act as natural reservoirs for a variety of zoonotic viruses and they coexist with viruses through several mechanisms including elevated metabolism and body temperature 24 . It is believed that this unique feature of bats leads to the selection of viruses that adapt better at higher body temperature, and hence are more virulent to humans 24 . Bats carry a number of RNA and DNA viruses asymptomatically, and the detection rate of new viruses or virus sequences seems to be much higher in bats than any other mammals 25 . The perfect equilibrium between various zoonotic viruses and bats have been studied extensively in the past two decades 7, 26 .", "Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 660 |", "The prospects for bats contributing to IAV epidemiology came to light after the identification of two novel influenza-like viruses in fruit bats by next generation sequencing 10 . These two viruses are genetically distinct from all previously known IAVs and hence are designated as novel subtypes, namely H17N10 and H18N11. These novel IAVs have been recently recovered in cell culture using synthetic DNA 11 . However, these HA and NA subtypes have not been identified in birds serologically or virologically. Consequently, the reservoir(s) of these novel IAV subtypes is still undefined. Phylogenetic studies raised a possibility that bats have the capacity to harbor more influenza virus genetic diversity than all the other mammalian and avian species combined 10 . In addition, it was demonstrated that little yellow-shouldered bats in Central America could constitute a potential sylvatic mammalian reservoir of influenza 12 . Susceptibility of bats to IAVs has been confirmed by recent serological evidence of AIV H9 subtype in about 30% of frugivorous bats from Africa 13 . It is worth noting that detection of antibodies against one AIV subtype in 30% of the bats tested is very significant.", "Despite many rigorous scientific pursuits, we have been unable to understand the mechanism by which new pandemic influenza viruses emerge. Consequently, we do not yet have sufficient scientific understanding needed to accurately predict which IAV strains may cause the next pandemic. The extensive diversity of bat species globally and the limited understanding of the role of bats in IAV biology raises an urgent need for comprehensive epidemiological surveillance of IAVs across different bat species." ] },{ "paper_id": "0a05a7b95ce42f0b53c86a24842ecc9845a7d023", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral stocks were prepared and maintained as previously described [37] . Recombinant mKate-RSV expressing prototypic subtype A (strain A2) F genes and the Katushka fluorescent protein were constructed as reported by Hotard et al. [38] . HEp-2 cells (ATCC, VA) were maintained in Eagle's minimal essential medium containing 10% fetal bovine serum (10% EMEM), supplemented with glutamine, penicillin and streptomycin.", "Maxisorp plates (Nunc, 96 well) were coated with DS-Cav1 at 1\u03bcg/ml in PBS at 4\u02daC overnight.", "Supporting information S1 " ] },{ "paper_id": "0a0afb5dc02afa81689e0e75afe2f9a21ce09e70", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Page 15 and Figure 6 panels A and B \"In order to confirm the influence of p4b and p5 on virus replication, we performed loss of\u2026for the step-wise construction of an ORF4b-and ORF5-deleted MERS-CoV\" \"The deletion of p4b or p5 resulted in 10-fold lower replication efficiency 48 hours p.i. (Fig. 6B )\"", "Page 10 \"Targeting SKP2 INCREASED protein degradation\"" ] },{ "paper_id": "0a0cbd4cb08c862deadcb5aaef22a27b770c0791", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 225 infants hospitalized with respiratory symptoms were enrolled from September 2005 through May 2006. Samples from 222 children were available for study in both sites; three specimens were only available for RMA testing. Study children were 57% male with a median age of 13 weeks [IQR 7-33 weeks]. The admitting diagnoses of these infants were bronchiolitis (58%), upper respiratory infection (33%), and other (9%)." ] },{ "paper_id": "0a11a6e99c61da77f540fa28b3ab843761537711", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Inflammatory lung disease, also called COPD, includes a wide range of lung ailments. These related diseases include asthma, pulmonary fibrosis, and chronic bronchitis. They are influenced by a combination of environmental, genetic, and epigenetic components [82] . COPD is a chronic inflammatory disease of the airways. This disease is hallmarked by airflow that is not fully reversible. Systemic and local airway inflammation has been implicated in the pathogenesis of COPD [83] . COPD is mainly associated with tobacco smoking, and recent studies investigating the pathophysiology of emphysema have demonstrated that cigarette smoke can cause cells to enter cellular senescence.", "Moreover, Ezzie et al. researched the difference of miRNA profiles expressed in the lungs of smokers with and without COPD. They concluded that miR-223 and miR-1274a were the most affected miRNAs in subjects with COPD [126] . Yet, COPD is a complex, multi-component, and heterogeneous disorder with a number of different pathological processes and subgroups with their own characteristics and natural history [133] . A better understanding of the complexity of the disease and potential clinical relevance of the identified miRNAs is needed.", "On the other hand, lipid-based vectors can also induce toxicity and non-specific activation of inflammatory cytokine and interferon responses [62, 63] . Although polymer-based vectors elicit a relatively less strong immune response than lipid-based vectors, effective siRNA delivery to a local area in lung diseases requires more attention to the development of non-toxic delivery vectors. An important point for siRNA-mediated inhibition of gene expression is whether the observed effects are specific rather than due to off-target effects and free from potential interferon responses [64, 65] . Interestingly, some studies have shown that it was possible to administer \"naked siRNAs\" to mice and down-regulate an endogenous or exogenous target without inducing an interferon response [66] ." ] },{ "paper_id": "0a124d3aa26def70b2db71f68c89dfe1996daf3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We used the rubella virus with its G-and C-rich RNA genome (JN635295) to illustrate the skew plot analysis (Figure 1) .", "Data Availability e relevant databases ViralZone and GenBank used to support the findings of this study are included within the article (Materials and Methods). e GenBank IDs of the sequences are provided in the figures. e software used is mentioned by the references as provided by MAFFT and MEGA. Nucleotide randomization was performed by a BioWeb server application. e GenSkew algorithm was provided by Dr. T. Rattei. A web server version can be found at http://genskew.csb.univie.ac.at/.", "e authors declare that they have no conflicts of interest. " ] },{ "paper_id": "0a1533470817bc5ef0d0d0af56386a96b505dc0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Salmonid fishes are among the most widely studied model fish species but reports on systematic evaluation of reference genes in qRT-PCR studies is lacking.", "PAO was responsible for the experiment, data analysis and drafted the manuscript. KKL conducted the real-time RT-PCR analysis, and contributed throughout the experimental process. AEOJ constructed the qPCR assays for two of the genes. TON provided the cDNA from the smoltification experiment. IH participated as a supervisor in the study design, analyses and writing. " ] },{ "paper_id": "0a24f22d8d49dc503c52d43dbc51459fc06fbb14", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "sGP Can Subvert the GP 1,2 -specific Antibody Response", "Mutant ZEBOV GP plasmids for DNA immunization experiments were prepared using the EndoFree Plasmid Mega Kit (Qiagen) as per manufacturer instructions and redissolved in pure endotoxin-free water at a concentration of 4-6 mg/mL, and purity was verified by restriction analysis and spectrophotometry. For immunization, DNA was diluted in sterile PBS to 0.5 mg/mL and filter sterilized. Female BALB/C mice (Charles River Laboratory) at six mice per group received 50 mg of DNA intramuscularly (25 mg/leg) per immunization. Anesthetized mice were bled retroorbitally two weeks after each immunization and serum samples were stored at 280uC until use.", "sGP Differentially Interferes with Antibody-mediated Viral Neutralization by Antisera from sGP and GP 1,2 Immunized Mice" ] },{ "paper_id": "0a3ef8eca5d6cd4d7a0fef83335cc02a2347492c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protein samples were analyzed by performing electrophoresis on a 12% (w/v) SDS-polyacrylamide gel electrophoresis (SDS-PAGE) gel. For the immunodetection of the His-tag-fused scFv proteins, a monoclonal anti-His antibody conjugated to horseradish peroxidase (HRP) (Sigma-Aldrich) was used. An ECL kit (Amersham ECL Prime Western Blotting Detection Reagent, GE Healthcare) was used for signal detection.", "For enrichment of cells producing FlAsH tag (FLNCCPGCCMEP) from non-specific cells, cells harboring pMoPac16-MBP were diluted with non-specific cells harboring pMoPac16 at 1:10000 ratio. After labeling with with 25 mM of FlAsH-EDT 2 (Invitrogen), the mixed cells were applied to FACS and the fluorescent cells were sorted by the repeated FACS screening as described above.", "The GST-fused antigens were mixed with 0.05 M carbonatebicarbonate coating buffer (pH 9.6) to a final concentration of 2 mM. The antigen solution (100 mL) was loaded onto 96-well ELISA plate, which was then incubated for 2 h at 37uC. Subsequently, each well was washed four times with PBS-T (135 mM NaCl, 2.7 mM KCl, 4.3 mM Na 2 HPO 4 , 1.4 mM KH 2 PO 4 , and 0.5% Tween-20 at pH 7.2) and filled with 200 mL of 5% BSA solution, and the plate was incubated for 1 h at 37uC. After washing with PBS-T four times, each scFv sample (soluble lysate or purified sample) was loaded on to the plate, and the plate was incubated overnight at 4uC. Each well was washed four times with PBS-T, after which 1:5,000-diluted monoclonal Anti-His antibody conjugated to horseradish peroxidase (HRP) (Sigma-Aldrich, ST. Louis, MO) was added, and the plates were incubated for 1 h at 37uC. Finally, the wells were washed with PBS-T, and tetramethylbenzidien (TMB) was added for the colorimetric detection of the bound scFv clones. The reaction was arrested by adding 2 M of H 2 SO 4 stop solution. The absorbance was measured at 450 nm by using a TECAN Infinite M200 Pro ELISA plate reader (Tecan Group Ltd., M\u00e4 nnedorf, Switzerland). To confirm binding activity of scFv against inactivated whole FMDV, an FMDV serotype O kit (PrioCHECK FMDV type O, Prionics, Switzerland) was used; ELISA was performed in the same manner with the exception of the antigencoating step. " ] },{ "paper_id": "0a41b85153ef8a084f7b3476d4d38832f533e914", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Student's t-test for paired data was used to test for differences. Data given are the means and bars show standard deviations. Body weights were compared using non-parametric Wilcoxon-Whitney and Kruskal Wallis tests. All statistical calculations were performed with SAS vs. 9.1. (SAS Corporation, Cary, NC).", "Conclusions/Significance: siRNA treatment has potential for both prevention and early treatment of EHV-1 infections." ] },{ "paper_id": "0a4a2763f35864555a20b296c1daf1614f09e28f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The animal studies strictly followed the recommendations in ''Guide for the Care and Use of Laboratory ", ".", "been previously identified as an antifungal agent, was chosen for further study (Figure 4 )." ] },{ "paper_id": "0a4f30f5fd02ad89dc9ba18964325c6738807465", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Means and standard deviations were used to describe the distribution of continuous variables. Percentages were used to describe the distribution of categorical variables. A chi-square test was performed to examine the differences in educational background and MERS-related knowledge, diagnosis, and prevention between different major groups among medical students. SAS 9.3 (SAS Institute, INC, Cary, NC) was used for all statistical analyses.", "A structured questionnaire was adapted from the information released by the National Health and Family Commission of China and a previous MERS-related survey [7] . The questionnaire was comprised of 18 items including demographics and knowledge about MERS in three areas: diagnosis, treatment, and preventive measures. Response options for questions on knowledge about MERS included \"Yes\", \"No\", and \"Don't know\". A knowledge score was calculated by giving +1 for the correct answer (Yes/No), and 0 for \"Don't know\", with the highest possible score being 18. Higher scores indicated a greater level of knowledge.", "Our study had several limitations. Firstly, lacking the information about students' sources and the accessibility/availability of MERS-related knowledge (e.g., TV/internet/newspaper, etc.), as well as the varying levels of exposure (e.g., media/news time/day) to media, could be a limitation that potentially affects the reliability of the results. For example, the difference of knowledge scores between students in different majors could be confounded by students' individual habits of accessing information from media. Second, we did not have a general population for comparison. A comparison group consisting of randomly sampled non-medical general population might be needed in the study design to better understand the findings. Future studies addressing those points are warranted." ] },{ "paper_id": "0a4f344f96d5a21e3d0f33e199983738c37a1631", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The transition part, describing changes in state, is obtained from", ": : : : : : : : :", ": : : : : : : : : :" ] },{ "paper_id": "0a4ff36a0de0c6c9efdcc2f20e3223a31e4c05a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SRTI was assessed according to respiratory failure confirmed by an abnormal blood gas analysis result (based on the potential of hydrogen, partial pressure CO2, partial pressure O2, an oxygen saturation level of approximately 90% or less and the need for oxygen therapy) or by being a patient in intensive care unit (ICU) for mechanical ventilation treatment [14] ." ] },{ "paper_id": "0a617f5467e92a9a638ee23204247128635e32aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pone.0204865.g001", "d\u00bdPlk1 dt \u00bc k 9 \u00bdmass s \u00bdCycB\u00f01 \u00c0 \u00bdPlk1\u00de \u00c0 k 10 \u00bdPlk1; \u00f011\u00de", "https://doi.org/10.1371/journal.pone.0204865.g008" ] },{ "paper_id": "0a6d27149c1fc958d4f6a598cc165a7cb0ee0185", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Staphylococcus is a gram-positive bacterium that affects a wide range of avian species and widely spreads in poultry rearing environments, and presents itself as a part of normal flora of mucous membranes.", "Escherichia coli (E. coli) is a gram-negative, non-spore-forming, rod-shaped bacteria that grows both aerobically and anaerobically, and many strains are motile and have peritrichous flagella." ] },{ "paper_id": "0a789bc7f1713d549288d3effb72ff34cd3b0ab0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Images were obtained using a Axio Observer inverted microscope and a Compact Light Source HXP 120C with Filter set 49, 10 and 20 for blue, green and red fluorophores respectively (Zeiss) Image analysis was done using ImageJ version 2.0.0-rc-43/1.50e. Initial calculations were performed in Excel for mac version 15.18, afterwards data was transferred to Graphpad Prism 6 for further analysis." ] },{ "paper_id": "0a851d4005336287cd41901a8fcd0ba3bab686c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Infected cells :", "Data were extracted using www.WebPlotDigitizer.com. We fit each data set with a single virus model using custom-written software in Octave 3.6.4 [60] that uses either the leasqr function, which uses Levenberg-Marquardt nonlinear regression, or the nelder_mead_min function which uses Nelder-Mead minimization to minimize SSR.", "Eclipse cells :" ] },{ "paper_id": "0ab32c7726deaff1ef10c2ee762c2cb917d92929", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virion from culture supernatant was harvested and concentrated by centrifugation and viral RNA was extracted and purified using the QIamp viral RNA kit (Qiagen, Germany). For each virus, an aliquot of 15 mg RNA was run on a 10% SDSpolyacrylamide/Bis gel under denaturing and reducing conditions at 150 V for 4 hrs at room temperature. The gel was washed with distilled water, stained with ethidium bromide before the photo was taken.", "Respiratory tract infections remain the main infectious disease of humans and account for a large proportion of public health spending worldwide. Despite recent success in discovery of novel respiratory pathogens during the last decade [16] [17] [18] , there is still a substantial proportion of RTIs remaining undiagnosed.", "His throat swab was taken on August 21 for virus isolation as described below.", "Immunofluorescence antibody testing (IFAT) and virus neutralization assay were conducted as previously described [5] . Briefly, for IFAT a freshly confluent monolayer of MDCK was infected with KamV and at full CPE, the infected cells were harvested, washed four times and suspended in sterile PBS at a cell concentration of approximately 3000 cells per millilitre. An aliquot of the infected cell suspension was carefully spotted onto each well of Teflon coated slides, followed by air-drying over a warm plate and subsequent fixation in cold acetone for 10 min. Serial 2-fold dilutions of serum samples were then added to detect specific reactivity. For detection of IgM, IgG was removed by absorption with protein A prior to serum dilution. Bound antibodies were detected using fluorescein conjugated rabbit anti-human IgM or IgG (Dako, USA). Specific reactivity/labelling were read under a UV fluorescence microscope (Olympus BX50, Japan). For VNT, serial 2-fold dilutions of control and test sera were prepared in duplicate starting at 1:10. An equal volume of virus working stock containing 150 TCID 50 was added to the diluted sera and incubated for 30 min. The pre-incubated virus/ serum mix was added to confluent cell monolayers and incubated for 1 h. The inoculum was removed, monolayers washed three times with PBS and cell media replaced. Ability of sera to neutralize virus was determined by scoring the extent of CPE observed in duplicate wells three days later.", "In conclusion, the discovery and characterization of KamV corroborate our previous work on MelV and demonstrate the increasing risk posed by unknown bat viruses which are capable of infecting and causing disease in humans. This further highlights the urgent need to systematically survey bat-borne viruses in the international community so as to enable us to conduct more effective risk assessment, to provide forecast for potential future outbreaks and to devise better prevention and control strategies." ] },{ "paper_id": "0abbc904e7a1b2e1c3ea7be75ee2a61931e0a941", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Enteroviruses (EVs; genus Enterovirus, family Picornaviridae) are small positive-sense RNA viruses that include human enteroviruses, which comprise more than 100 serotypes and are among the most common pathogens that infect humans worldwide, especially children 1 . Most EV infections are asymptomatic, but some may lead to illnesses, ranging from mild to more severe, or even life-threatening, such as hand, foot, and mouth disease (HFMD), aseptic meningitis, encephalitis, myocarditis, pancreatitis, acute flaccid paralysis, and neonatal sepsis 1 . In recent years, outbreaks of HFMD caused by enterovirus A71 (EV-A71) or coxsackievirus A16 have occcured in China and several countries in Southeast Asia 2-6 . To date, there are no approved specific antiviral therapies available to treat diseases caused by EVs. Thus, there is an urgent need to identify safe and broad-spectrum drugs against existing pathogenic EVs.", "The data used to support the findings of this study are included within the article." ] },{ "paper_id": "0ac675fdff45bfddf5aea34d37f58ad7df4f78b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Comparative genomics of HAdV-B14p and two HAdV-B14p1 strains", "Amplified genomic fragments were purified using agarose gel electrophoresis with a QIAquick gel extraction kit, as per the manufacturer's instructions (Qiagen, Ltd.; Germany). Sangerbased DNA sequencing reactions were performed bi-directionally using an ABI Prism Big Dye Terminator v3.1 Cycle Sequencing Ready Reaction kit and AmpliTaq DNA polymerase (Applied Biosystems, Inc.; Foster City, CA). DNA sequencing ladders were resolved using an ABI 3730 DNA sequencer (Applied Biosystems, Inc.; Foster City, CA). Unresolved and ambiguous sequences were re-sequenced with additional custom primers located adjacent to the regions in question.", "Presented in Table 3 are the percent identities of select proteins spanning the genome. Proteins from all prototype genomes from all HAdV species are represented, with one from each but including all subspecies B1 and B2 prototypes. One chimpanzee adenovirus (SAdV-B21) is included, as it segregates into the subspecies B1 subclade." ] },{ "paper_id": "0acc757154434d8afc870e55c010962a61cc0af3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additionally, there has been an increased focus on minimising the impact of false-negative results; i.e., assuring that negative results truly represent absence of PCR diagnostic targets. This is because false-negative results can occur from failure of one of the test steps (nucleic acid extraction, reverse transcription reaction, PCR set up or amplification)." ] },{ "paper_id": "0add910e9efb81f7b906101a7790b812074dc8b3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A panel of 39 individuals was studied; 35 western chimpanzees, two eastern chimpanzees, one central chimpanzee, and one individual of unknown geographical origin. This study was approved by the Stanford University administrative panels on human subjects in medical research and laboratory animal care.", "Allele frequencies for C1-bearing HLA-B allotypes are from the Allele Frequency Net Database [69] ; when no population data were available, the country listed in the IMGT-HLA database [68] is given.", "The B46 distribution map was generated using the GMT software package [70] and a previously developed script [71] ; for this distribution, only anthropology studies were used, and data from recent migrant populations were discarded when the geographical location of the pre-migration population could not be precisely ascertained.", "The 3DL3 and 2DL8 genes are represented on each of the sequenced KIR haplotypes by alleles that encode the same" ] },{ "paper_id": "0ae65070d7cbfa7b5454181af026a8ea7391d5d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Female inbred BALB/c mice were used for the assessment of immunogenicity and ZIKV challenge. Mice were purchased from either Envigo (Bicester, UK) or from Charles River (Wilmington, MA, USA).", "The preparation of MVA vaccine stocks was performed by the infection of permissive CEF cells at low multiplicity of infection (M.O.I.). The supernatants were collected and the remaining cells lysed by successive rounds of freezing and thawing. The released virus was further concentrated by centrifugation through 36% (w/v) sucrose cushions and titres determined by routine plaque assay in DF-1 cell monolayers [24] .", "Week 0 " ] },{ "paper_id": "0aef63f4f4c4cb195e71b50d0c6e721aba9f2a81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antibody-dependent enhancement (ADE) is a mechanism by which viruses, such as dengue, HIV and Ebola, gain entry into some target cells through the use of host antiviral humoral immune responses [1] . Here, we studied the ability of severe acute respiratory syndrome coronavirus (SARS-CoV) [2] to use ADE mechanisms to enhance its infectivity towards cells of the hematopoietic lineage." ] },{ "paper_id": "0b0208d63d06379d846edf649d47041fc2c1aa86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethical approval for this study was obtained from the Institutional Review Board (IRB) of the Chinese Center for Disease Control and Prevention. The IRB approved that verbal consent should be obtained from all participants. Subjects from whom consent was obtained were asked to complete the questionnaire.", "The novel influenza A(H7N9) virus has caused 2013 spring and 2013-2014 winter waves of human infections since its first emergence in China in March 2013. Exposure to live poultry is a risk factor for H7N9 infection. Public psychobehavioral responses often change during progression of an epidemic.", "(DOCX)" ] },{ "paper_id": "0b05d3ede3351f8b3edb22c74b0cfe933ba408c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the detection of ZEBOV-GP specific antibodies in mouse sera, soluble ZEBOV-GP antigen (ZEBOV-GPDTM) was produced and used in an enzyme-linked immunosorbent assay (ELISA) as described before [32, 33] . For the detection of VSVspecific antibodies VSV was propagated in Vero E6 cells. VSV particles were harvested after 48 hrs, purified by centrifugation through a 20% sucrose cushion and treated with 0.05% Triton-X100 in PBS prior to storage at 280uC. The ELISA used VSV antigen in a 1:100 dilution. Sera from mice infected with MA-ZEBOV were inactivated by c-irradiation as per standard operating protocol.", "Animals were handled in the Biosafety Level 4 (BSL4) containment space of the Integrated Research Facility (IRF) at the Rocky Mountain Laboratories (RML), Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). Research was conducted in compliance with the guidelines of the NIAID/ RML Institutional Animal Care and Use Committee (IACUC). The facility, where this research was conducted, is fully accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC) with approved Office of Laboratory Animal Welfare (OLAW) assurance (#A4149-01). Research was conducted under a protocol approved by the IACUC. All procedures were conducted by trained personnel under veterinary supervision, and all invasive clinical procedures were performed while animals were anesthetized. Endpoint criteria, as specified by the IACUC approved scoring parameters, were used to determine when animals should be humanely euthanized.", "One-way ANOVA was performed using Prism 5 (Graph Pad Software Inc.)." ] },{ "paper_id": "0b0ce0d563375eba593f552fc31f82289982c829", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ADHS' Human Subjects Review Board determined this surveillance was part of public health practice." ] },{ "paper_id": "0b104ed7194e21c4ba47460db675b638b0d29bc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data generated or analysed during this study are included in this published article.", "reported in metabolic diseases where it decreased adiposity, serum insulin and increased insulin sensitivity 16, 17 ; and in renal diseases where it decreased acute renal injury and fibrosis 18 . It has recently emerged that apelin has pro-tumorigenic effects in various cancer models possibly by promoting angiogenesis and that inhibition of the apelin pathway was protective against tumour growth 14, 19 . However, these beneficial effects of apelin peptides are limited by the rapid in vivo metabolism.", "Oxidation of the methionine residue in [Pyr 1 ]apelin-13 was identified, however since this modification was also observed in the extracted standards, it could not be ascertained if they occurred in vivo or as an artefact of the extraction process." ] },{ "paper_id": "0b137fde2327ae4665db6aef52d1c98fc4053864", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Despite being an important issue for the GMP production of ATMPs, in the literature, there are few papers regarding specific validation strategies [6] [7] [8] with very different approaches.", "CV % = standard deviation mean * 100 3", "(iv) Detection limit (limit of detection, LoD): the lowest amount of analyte in a sample which can be detected but not necessarily quantitated as an exact value." ] },{ "paper_id": "0b14aca39651cc93fb2ca56a4ab433f57716ca37", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A particular problem are infections that are troublesome during pregnancy. There are few cases of cytomegalovirus (CMV) infection filed as OD. On the other hand, there are strict regulations concerning infectious diseases in pregnancy. For example, pregnant women with no natural immunisation against CMV need to stop working with young children in kindergartens or hospitals [43, 44] . It is beyond the scope of this analysis to decide whether these regulations are effective, as no systematic evaluation exists.", "A total of 124 influenza-related claims were registered throughout the whole period and 48 were confirmed as OD (Table 3 ). There was a spike during the H1N1 pandemic in 2009 (53 claims).", "A descriptive retrospective observational study was carried out about the mandatory claims and the confirmed ODs of infectious diseases of HWs, covering the last 22 years using insurance data." ] },{ "paper_id": "0b180c5c5edf329811114548e19a708303e7c1c2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were plated at a density of 10 4 cells/well in 2%FBS/ Medium in 96-well plates and were allowed to adhere overnight.", "Methods S1 Quantitative RT-PCR of TLR3 and apoptosis measurements in hPAECs. (DOCX)", "Numerical values are given as means 6 SD of n cells. Intergroup differences were assessed by factorial analysis of variance with post hoc Fisher's least significant difference test or Student's t-test (p values ,0.05 were considered significant).", "The major function of the vessel-forming endothelial cells is to maintain the blood-tissue barrier. Viral RNA has been identified as a pathogenic factor in different pulmonary diseases [39, 40] ." ] },{ "paper_id": "0b1af480d35b739da799df76a25463bc2ee4bbe5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The green pigment synthesized during conidiation in T. marneffei is dihydroxynaphthalene melanin" ] },{ "paper_id": "0b227d1996bc5dfd895b43f6c6e2449c58252c67", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The response rate to our survey questionnaire was relatively low (37.4%, N = 174); therefore, the results might be biased. However, our findings were similar to the findings reported by a study in the United Kingdom on the same topic [39] .", "Thus, our findings are relevant for other prefectures and are a good estimate for the level of preparedness among PCPs in Japan.", "Many PCPs (71.3%; n = 124) isolated patients with influenza-like illness from other patients, either using different consultation rooms or a physical barrier, and almost all institutions (94.8%; n = 165) provided pandemic vaccine to their patients." ] },{ "paper_id": "0b22db40e9e78fb29f6ae2938ed8ee2d00cd46b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Turbidity measurements of \u03c66 following the procedure described by Oster (1951) demonstrated that \u03c66 surface charge is negative at pH 7 (spectra not shown).", "42" ] },{ "paper_id": "0b26d9ec6dfae866ae3f1a3f773036b1c8627147", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The complete genomes of strains BR-I and Ma5 have been deposited in GenBank under the accession numbers KY626044 and KY626045, respectively.", "Because vaccination is a core tool for controlling AvCoV infection and due to the range of variables to be considered for this process (8) , the integration of experimental, field, and genomic data could improve the process of developing vaccines and predicting their behavior.", "This work was funded by CNPq (Brazilian National Board for Scientific and Technological Development) grants 400604/2016-7 and 301225/2013-3 and CAPES (Brazilian Coordination for the Improvement of Higher Education Personnel) grant 1841/2016. We are also grateful to the Swedish Research Links Program (grant 2013-6772)." ] },{ "paper_id": "0b3baf8685f86b7d620418cb17d29a60ce1d498a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scanner G2505C (Agilent Technologies, US). The sample labelling, microarray hybridisation and washing were performed based on standard protocols provided by the Shanghai Oebiotech Corporation.", "Microarray data analysis is a core technology in transcriptomics and is widely used in life sciences research. This type of analysis has also made invaluable contributions to research in chickens [21] . We first used a transcriptomics approach involving microarrays to study the -01 FGFR2, TRAF2, IL1R2, FGFR3, FGF14, FGF16, TGFB3, FGF10, NFKB1, FGF13, FGF12, NFKB2, MAP3K4, RAC2, PAK1, PRKACB, AKT3, PTPN5, CACNG4, CACNG3, CACNA2D3 ", "Supporting Information S1 " ] },{ "paper_id": "0b48e310b1f5d0205ad5ffa292d950d2808185c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The culture supernatants were collected from treated cells at the indicated time points and stored at \u221280\u00b0C. The protein levels of TNF-\u03b1, IL-1\u03b2, and IL-6 in cell cultures or mouse brain tissue lysates were measured by ELISA kits (eBioscience) following the manufacturer's instructions.", "Approximately 35,000-50,000 cases of Japanese encephalitis are reported annually in the region with 10,000 deaths, and nearly half of the survivors suffer from perpetual neuropsychiatric sequelae (3, 4) .", "Postnatal 3-4-day-old suckling BALB/C mice were infected with P3 strain of JEV. Upon onset of clinical manifestation of JEV such as poor brain response, limb paralysis, and whole body tremor, mice were killed and their brains were excised. Brain homogenate prepared in Dulbecco's modified Eagle's medium (DMEM) was centrifuged at 10,000g to remove cellular debris. The resultant suspension was filtered through 0.22 \u00b5m sterile filters to obtain viral suspension. Immediately, aliquots of filtered virus suspension were stored at \u221280\u00b0C until further use. The virus titer was determined by plaque formation assay on baby hamster Syrian kidney (BHK-21) cells as described previously (10) ." ] },{ "paper_id": "0b530925f860fe1a3191519482c19e8240834caf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The wild-type and mutant-type 3\u2032-UTRs of the ACE2 transcript were cloned into the psiCHECK-2 vector (Promega) through the NotI and XhoI restriction enzyme cutting sites. miRNA mimics were transfected into HEK293T cells using Lipofectamine RNAiMAX (Invitrogen). After 24 h, 1 \u03bcg of wild-type vector or mutant vector was transfected into ", "Plasma miRNA extraction and detection miRNAs were extracted from 400 \u03bcl plasma using an miRNeasy Serum/Plasma Kit (Qiagen, Hilden, Germany). A synthetic spike-in control, Caenorhabditis elegans miR-39 (cel-miR-39), was added to the lysed samples for internal normalization. cDNA was synthesized using the TaqMan MicroRNA Assays Kit and High-Capacity cDNA Reverse Transcription Kit (Applied Biosystems). PCR reactions were performed on a LightCycler 480 PCR system (Roche) using the TaqMan Universal Master Mix II (Applied Biosystems).", "NF-\u03baB p65/RelA-specific siRNA, p50-specific siRNA and nonspecific control siRNA were synthesized by GenePharma. The p65 siRNA duplexes (siRNA1: 5\u2032-GGACAUAUGAGA CCUUCAA-3\u2032; siRNA2: 5\u2032-CUUCCAAGUUCCUAUAG AA-3\u2032), the p50 siRNA (5\u2032-CGCCAUCUAUGACAGUAAA UU-3\u2032) or a control siRNA were transfected into cells (with a final concentration as 100 \u03bcM) with Lipofectamine RNAiMAX (Invitrogen) for 24 h, and then subsequent experiments were performed." ] },{ "paper_id": "0b65341c3090421acaac37ec4c93212277be55bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The analysis is derived from the Ingenuity Pathways Analysis (p < 0.05).", "\u00a9 The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver" ] },{ "paper_id": "0b6962f3ef4cb5e76d6ccd144af840b6aec67474", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pone.0219428.g007", "https://doi.org/10.1371/journal.pone.0219428.g008" ] },{ "paper_id": "0b7581ab8ae5da78a11692b4c7d9399ec6dea283", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "M. bovis (ATCC 25025) and M. bovirhinis (ATCC 5189985) were purchased from the ATCC (United Kingdom (U.K.), Guernsey, Ireland, Jersey and Liechtenstein) and cultured in Heart Infusion Broth Medium (Difco, Detroit, Mich.). All isolates were grown at 37\u00b0C and 5% CO 2 for seven days in a modified standard mycoplasma broth medium [20] ", "Calves (n = 44) with or without BRD (increased respiratory rate and/or dyspnoea) were sampled for diagnostic purposes. Sampling of the calves was granted an exemption from requiring ethics approval by the institutional Animal Experiment Commission \"Dier Experimenten Commissie (DEC) Lelystad (2013111.b)\" because sampling was performed for diagnostic purposes. BAL samples were obtained as described [21] . Approximately 35-75 ml BAL was obtained from each calf after instillation of 100 ml PBS with 10% Fetal Calf serum (FCS). Foam, large purulent exudates and blood clots were removed from the BALF samples under aseptic conditions. BALF (25 mL) was centrifuged (4600\u00d7g, 10 min, 4\u00b0C). Sediment was resuspended in 0.5 mL Dulbecco's minimal essential medium (DMEM) with 5% FCS, carefully added to 1 mL freeze medium (DMEM, 50% FCS and 20% DMSO) and frozen at \u221280\u00b0C. The BALF supernatants were also stored at \u221280\u00b0C.", "Differences in PCR results were analysed for statistical significance by the non-parametric Mann-Whitney U test in the GraphPad Prism version 5.0 software, with P < 0.05 considered significant." ] },{ "paper_id": "0b7d50ddfae18226d4a66c578d9235d872c85056", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. Data are summarized as mean \u00b1 SEM or graphically displayed as box and whisker plots. Statistical analysis was performed using Prism Version 6.0c software (GraphPad). Data were analyzed using Student's t test. Spearman's rank test was used for correlation studies. P < 0.05 was considered statistically significant.", "were injected (2.5 mg per 50 \u03bc l per mouse) subcutaneously with medroxyprogesterone (Greenstone LLC) 7 days prior to infection. On the day of infection, mice were anesthetized and infected through the intravaginal route with HIV-1 BaL (10,000 Infectious Units 2.54 ng \u22121 of p24 per mouse) in a maximum volume of 20 \u03bc l. A sterile micropipette tip was used to deliver the virus and care was taken to ensure that no mucosal abrasions or tearing occurred.", "Assessment of viral load. Blood samples were collected from humanized DRAG mice pre-and post-infection every 3 days for two weeks and then at weekly intervals for a total of 16 weeks. Viral load in the whole blood was determined using the Abbott RealTime HIV-1 Test (Abbott Molecular, Inc.) with minor modifications. Whole blood specimens were collected in tubes containing EDTA solution and then frozen. To determine viral load, frozen blood samples were thawed and lysed. HIV-1 RNA was extracted following the FDA cleared test method and quantified. Although whole blood was used, no inhibition of the assay was observed based upon the performance of the internal extraction control. As the blood volumes collected were slightly variable, the values obtained were adjusted by 1 log to account for an average dilution factor of 10." ] },{ "paper_id": "0b7de7591cf59d3b9e8f9db423431c0850eb0276", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1 Mathematical methods 1 ", "(", "In particular, 1" ] },{ "paper_id": "0b875918f93152038d3a87f24e51abc1fd99a348", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ifnw loci are also present in bat genomes and appear to have many tandem copies in species examined, unlike most other mammals [87] . Functional activities of bat IFN\u03c9 have not been described.", "Each program has advantages and disadvantages, so it is essential to carefully examine packages to determine which is most suited for a given dataset. Once the de novo assembly is completed, other software tools are employed to count reads from each sample for use in statistical analysis of transcript and isoform abundances. Several abundance estimation packages are freely available, including the Bioconductor package (composed of edgeR and DESeq) [114, 115] , and RSEM [116] and eXpress annotation [117] that provide quantitative and qualitative statistical analysis of differentially-expressed genes.", "Davis et al. [63] experimentally infected little brown bats (Myotis lucifugus) with rabies viruses and found that intramuscular infection led to rapid clinical progression of rabies, whereas subcutaneous infection led to delayed clinical progression. Notably, bats that developed rabies after subcutaneous infection were more likely to shed virus in salivary glands. Together, the data suggested that route of infection of rabies viruses among bats can influence clinical outcome and potential transmission among bats.", "Reactome mapping of differentially-expressed genes. Abundance of differentially-expressed IFN\u03b3 pathway transcripts in Pirital arenavirus-infected hamster livers relative to uninfected group were estimated by RSEM and statistically analyzed with DESeq. The symbols for the elevated genes were imported into the Reactome plugin of Cytoscape for pathway analysis. Genes in purple boxes were elevated in infected animals (author's unpublished data) and suggests this pathway is important in the host response to the virus." ] },{ "paper_id": "0b9583908e91f87840a0f844e7c4ebb546482c50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data were entered and verified using Microsoft Excel software and analysed using Stata version 12.0 (StataCorp, Texas 77845, USA) and R version 3.1.3 (R Foundation for Statistical Computing, Vienna, Austria). The categorical variables are summarized as frequencies and percentages. Different groups were compared using the \u03c7 2 test and Fisher's exact test. Student's t-test, the Wilcoxon-Mann-Whitney test and the Kruskal-Wallis test were used to compare different continuous variable between the groups. A p-value of less than .05 was considered statistically significant.", "This prospective case-control study was conducted from May to August 2016 at four major general hospitals in Quang Nam provincea rural area located in central Vietnam ( Figure S2 ). These included Quang Nam Central General Hospital, Quang Nam Provincial General Hospital, Quang Nam Northern Mountainous Region General Hospital and Quang Nam Regional General Hospital, which have approximately 2130 beds combined and serve 1,487,700 residents of Quang Nam province and thousands of people in the neighbouring districts of Quang Ngai province.", "Vector-borne infections, including emerging or reemerging infections, were frequently identified as the cause of AUF, as previously reported in Asia [1, 9] . " ] },{ "paper_id": "0b9b177210a4b23ff4745f2717083ba047a9e770", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed with SigmaStat 3.5 software (Systat Software) using non-parametric tests unless otherwise stated." ] },{ "paper_id": "0ba1801a150e25b029cf3c2a38573435b21dea80", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were harvested 24 h post-transfection and fixed in 0.1 M Cacodylate buffer containing 2.5% glutaraldehyde, post-fixed with 1% osium tetroxide, dehydrated in ethanol and embedded in Spurr resin. Thin section was cut with an ultramicrotome, stained with 5% uranyl acetate and 0.4% lead citrate. Concentrated viral samples were placed onto carbon-coated, UV-treated 200 mesh copper grids for 2 min. Sample-containing grids were rinsed for 15 secs in water, dried with filter paper, and stained for 1 min in filtered 1.3% uranyl acetate. Excess staining solution was removed by applying filter paper to the edge of each grid. Grids were allowed to dry before viewing with a JOEL JEM-2000 EXII transmission electron microscope. Images were collected at 20,0006 and 60,0006.", "The highly contagious severe acute respiratory syndrome (SARS) affected individuals in 30 countries in 2002 and 2003 [1] . Its causative agent was identified as a novel SARS-associated coronavirus (SARS-CoV) [1, 2, 3] that was initially classified as part of a separate coronavirus group [4, 5, 6, 7] , but is now described as a betacoronavirus [8] . As with most coronaviruses, SARS-CoV encodes four structural proteins: spike (S), membrane (M), envelope (E) and nucleocapsid (N) [4, 9] . Mature coronavirus particle assembly involves protein-protein and protein-RNA interactions. M, the most abundant structural protein [10] , is thought to play a central role in directing virus assembly and budding via interaction with E, S and N [10, 11, 12, 13, 14, 15, 16, 17, 18] . Translated on free polysomes, N is associated with newly synthesized viral genomic RNA to form helical nucleocapsids [19] . The M membrane glycoprotein is cotranslationally inserted into the endoplasmic reticulum (ER) and transported to Golgi complexes [20, 21] . M interacts with nucleocapsids on the cell membranes of ER or Golgi complexes [22, 23, 24, 25, 26] . In a similar manner, S and E proteins are translated on membrane-bound polysomes, inserted into the ER, and transported to Golgi complexes, where E and M interact and trigger virion budding with enclosed nucleocapsids [14, 19] . S is incorporated into virions via interactions with M. Virions accumulate in large, smooth-walled vesicles that are exocytotically released from cells [4] ." ] },{ "paper_id": "0baa7fbb346a50319eb57a4a1556c3f48938d0e6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "3) chemistry and synthetic oligonucleotides. If cloacal and oropharyngeal swabs of the same host had more than one subtype of influenza, then the infection was identified as a mixed infection.", "Where virus isolation was successful, sequence analysis [26] or hemagglutination inhibition (HI) assays [27] were performed to determine the subtype of influenza-positive samples. The Hartwell Center for Bioinformatics and Biotechnology at St. Jude Children's Research Hospital analyzed the sequences on Applied Biosystems' 3700 DNA analyzers by using BigDye Terminator (v.", "Seventeen H9N2-subtype isolates were tested using HI assays to determine the specific H9-antigenic group of the Bangladesh (12) Village-2 Ck 0 (7) 0 (7) 0 (7) 0 (7) 0 (7) 0 (7)" ] },{ "paper_id": "0bb181551513e8bfdac02b7936920ac3f50d01c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Xue et al. studied how flu changes in people with weak immune systems, who are infected for longer periods of time. Further studies are needed to reveal more about how flu viruses evolve in the more typical, shorter infections in otherwise healthy people. This kind of investigation is becoming easier because new methods are making it possible to examine the genetic material from many viruses at once. It is hoped that eventually, detecting mutations in individual infections could help predict how viruses will change worldwide, which might help researchers to design vaccines that will be more effective each year.", "We used the entire 20 mL volume of the reverse-transcription reaction as template in a 100 mL PCR reaction using KOD HotStart Reaction Mix (EMP Millipore) and a 24-primer cocktail as described in Figure 2 -source data 1 at a total concentration of 600 nM. We performed 35 cycles of PCR amplification with an annealing temperature of 55 degrees C and an extension time of 3 min.", "We purified the PCR product using 1X AMPure beads (Beckman Coulter) and prepared libraries for Illumina sequencing using Nextera XT (Illumina). We sequenced the libraries on a NextSeq 500 platform (Illumina) with 150 bp paired-end reads. We performed library preparation and sequencing in duplicate, starting from independent reverse-transcription reactions.", "The FASTQ files are available on the SRA as BioProject PRJNA364676. The computer code that performs the analysis is available at https://github.com/ksxue/parallel-evolution (with a copy archived at https://github.com/elifesciences-publications/parallel-evolution) and in Supplementary file 2 (Xue, 2017) ." ] },{ "paper_id": "0bca841af11fa978a07f916ec43b34d7c88b71c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Changes in cell surface glycosylation are known to be associated with a large number of chronic diseases and the cancer glycans represent a very promising field for biomarker discovery [1] [2] [3] . ", "Nonasaccharide azide 1 (Fig 1B) was prepared from egg yolk followed by enzymatic hydrolysis and azidation [15, 16] . 5.1 mg (3.1 \u03bcmol) of nonasaccharide 1 were disolved in 203 \u03bcl of phosphate buffer (100 mM, pH 6.8, 1 mM MgCl 2 ). 10 units of lyophilized \u03b2-galactosidase (EC 3.2.1.23) were added to the solution. The mixture was incubated at 37\u00b0C for 3 days (TLC: 2-propanol, 1 M ammonium acetate, 2:1). After lyophilization, the residue was purified by gel filtration (Superdex 30, 1.6 x 60 cm, 0.1 M NH 4 HCO 3 , 0.9 ml min -1 ). The peak, eluting at 86 min, was lyophilized and desalted by gel filtration (Sephadex G-25, 2.5 x 15.5 cm, 5% ethanol in water, 0.6 ml min -1 ). The peak, eluting at 75 min, was lyophilized yielding 2.9 mg (2.2 \u03bcmol) of heptasaccharide 2 (70%). ", "Ethanol-fixed human trachea, esophagus, duodenal junction, jejunum, colon, pancreas, liver, ovary, uterus and vagina samples were obtained from organ donors. 18 tissue samples from 10 different individuals were used to prepare a tissue microarray (TMA) of healthy tissues. Ethanol-fixed colorectal tumor sections were obtained after cancer surgery. Formalin-fixed paraffin-embedded human NSCLC samples (n = 3 squamous cell carcinomas, n = 3 adenocarcinomas) were also obtained. A breast tumor and a lung tumor TMA (formalin-fixed; 40 tumors, 10 paired metastasis and 10 paired adjacent \"normal\" tissue) were bought from SuperBiochip (Seoul, South Korea). Formalin-fixed canine mammary tumors were obtained from \"laboratory of animal histopathology of the Nantes Veterinary School, ONIRIS) Immunostaining analysis was performed on 3-\u03bcm-thick tissue sections." ] },{ "paper_id": "0bcbf352d92ce90e1c2595fb458ded32b45002a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples with high absorbance values in ELISA were also tested for hantavirus IgM antibodies and, in case of a positive result, RNA was extracted and screened by pan-hantavirus RT-PCR (Klempa et al., 2006) to target possible current infections which exhibit RNAemia.", "About 97% of people above 16 years participating in the study reported consumption of rodents and other small mammals. Professional exposure seemed not to play a statistically significant role within our study group, however, occupations in agriculture and meat preparation, usually having a higher risk for hantavirus infections (Mertens et al., 2011) , made up more than 70% of the probands, not including pupils. Many participants usually helped out in agriculture during harvest season, even if they work somewhere else, or they change occupation frequently. All these influencing variables might contribute to the postulated high exposure.", "In all 13 IgG-positive samples found to be also IgM-positive, no viral RNA was found by RT-PCR techniques. This is not surprising as hantavirus nucleic acid can be usually detected only up to 30 days after infection under good sampling and laboratory conditions (Ettinger et al., 2012; Korva et al., 2013) , while IgM can last for up to 2 years Hofmann et al., 2014) .", "Self-reported symptoms among the probands included problems common in African villages: 36% of the participants reported at least one type of recent health problem. Most common were malaria (n = 127), cough (n = 55), back pain (n = 47), and abdominal pain (n = 37). Four people reported fever. Of the hanta seropositive people four reported malaria, six reported cough, five reported back pain, two reported abdominal pain, and nine reported other symptoms. No hanta positive person reported fever only. Self-reported \"malaria\" is likely meaning symptoms that include fever. The self-reported medical information was not included into the statistical model due to the large number of different symptoms." ] },{ "paper_id": "0bd9e38537d45c72b8507471690027a78f8f4584", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LGP2 is an RLR, and the CTD structure of the protein is similar to that of RIG-I (14) . Initial studies reported that LGP2 is a negative regulator for RIG-I signaling (15, 47) . However, knockout and biochemical studies have revealed that LGP2 functions as a positive regulator of the RIG-I pathway (48, 49) .", "Evidence also suggests that TRIM25 produces unanchored K63-linked polyubiquitin chains in response to viral infection and delivered them to RIG-I (23) . The same study also showed that the K172 residue of RIG-I was important for non-covalent binding of RIG-I with unanchored polyubiquitin chains (23) .", "HO and MO wrote the manuscript. TK and YF helped the discussion." ] },{ "paper_id": "0bdae8c38f570965cc9a630a44b7089c2a5da0ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antibodies. Rabbit, goat, or mouse antibodies against cyclin D1, cyclin E, phosphorylated-Rb (p-Rb) (Ser795), p21, \u03b2 -actin were purchased from Santa Cruz Biotechnology. Horseradish peroxidase (HRP)-conjugated secondary antibodies were purchased from Sigma. Fluorescein isothiocyanate (FITC)-conjugated secondary antibodies were purchased from Dako.", "Western blotting. Whole PK15 cell lysate extracts at different time points after PCV2 infection were prepared with a nuclear extract kit (Active Motif) following the manufacturer's protocol. The cell lysate extracts were diluted in 2\u00d7 sample buffer and boiled for 5 min. 20 \u03bc g of each protein extract was subjected to 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to nitrocellulose membranes. The membranes were blocked in TBST blocking buffer (20 mM Tris-HCl [pH 7.4], 150 mM NaCl, 0.1% Tween 20) containing 5% dry skim milk powder at RT for 2 h to prevent nonspecific binding. The membranes were then incubated with the antibodies raised against cyclin D1, cyclin E, p-Rb (Ser795), p21, ORF2, and \u03b2 -actin at RT for", "Scientific RepoRts | 6:27917 | DOI: 10.1038/srep27917 miRNA quantification. Total RNA was extracted from synchronized PK15 cells after PCV2 infection using Trizol Reagent (Invitrogen). Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to determine the expression levels of miRNAs according to the protocol of miRcute miRNA cDNA kit (Tiangen Biotech, Co., LTD, Beijing). Briefly, the extracted RNA was polyadenylated and the first strand complementary DNA was synthesized using oligo (dT). U6 snRNA was used for normalization. The primers of miRNAs amplification include the universal primer and miR specific forward primers (ssc-miR-15a F: 5\u2032 -TAGCAGCACATAATGG-3\u2032 , ssc-miR-16 F: 5\u2032 -TAGCAGCACGTAAATATTGGCG-3\u2032 , ssc-miR-21 F: 5\u2032 -TAGCTTATCAGACTGATGTTG-3\u2032 , and ssc-miR-34a F: 5\u2032 -TGGCAGTGTCTTAGCTGGT-3\u2032 ). U6 snRNA F: 5\u2032 -CTCGCTTCGGCAGCACA-3\u2032 , U6 snRNA R: 5\u2032 -AACGCTTCACGAATTTGCGT-3\u2032 . Relative expression was analyzed using the \u0394 \u0394 Ct method." ] },{ "paper_id": "0be7b06a39aa31b27514a501ebdd477f42b0919a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "When accounting for an immediate reaction to challenge, antifragility thus contributes to fitness. A remarkable property of antifragility is the fact that, by definition, an antifragile entity will react to changes by providing a solution that is not exactly programmed. Hence it does not have a fixed fitness: its response is context and time-dependent. This type of behavior is also the hallmark of tinkering, giving credence to Taleb's reflection.", "The distribution of the length of the proteins important for stationary survival is compared in Figure 1 to that of all proteins in the E. coli proteome: it displays a remarkable bias both for short and long proteins.", "Birth, growth, maturation and senescence are the four ages of all cells. This is true of their components as well. In general the maturation step is ignored: cell's components are viewed as synthesized, used in their final form, then decaying and being either repaired or destroyed. Maturation and possibly functional improvement during ageing is rarely taken into account. Senescence and ageing are treated as equivalent. Yet, quite a few physico-chemical processes suggests that the state of cell components at any time should be seen as actively browsing through a series of ageing states. In fact, notwithstanding apoptosis (which may be a process to reset the system), most cells harbor a mixture of aged and young components, reflecting the overall history of their divisions (Figure 2 ).", "While the presence of short proteins is easy to understand (there is inherent robustness in being short as discussed by Galileo Galilei in his Dialogo sopra i due massimi sistemi del mondo) we need to account for the long ones. We will therefore be looking for unusual properties that could be a signature of antifragility rather than robustness. We explore now whether this unusual length distribution might suggest a direction to follow. ", "The recent dread of radioactive leaks near nuclear plants reminds us vividly of the vulnerability of life. \"Fragile\" is an epithet often associated with living organisms, perceived as delicate and easily damaged. But does this reflect reality? What would be the opposite of fragile? In a recent piece for Edge magazine [1] Nassim Taleb discussed another familiar attribute of life, tinkering. There he asserted that, contrary to the favored emphasis on intelligent engineering, \"tinkering outperforms design\". This property enables finding unexpected solutions, especially when challenged by \"normal accidents\" [2] , rare deleterious events (in terms of individual probability of occurrence) for which he himself coined the phrase \"Black Swan\" events [3] ." ] },{ "paper_id": "0bee52e6477404d2aed60b9ae06ac53bf92660de", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We next selected the 53\u00b0C treatment condition at neutral pH with different time points after incubation (0, 15, 30, 45, 60, and 120 min) to directly study the thermal stability and infectivity of all types of influenza viruses (Fig. 1C) . Significantly, only D/OK/13 was able to tolerate the high temperature of 53\u00b0C. All other types of influenza viruses, such as A/MN/08, A/CA/09 (pdm09HIN1), B/BR/08, and C/JHB/66, completely lost their capacity to survive when exposed to 53\u00b0C for 15 min (Fig. 1C) . Notably, D/OK/13 was able to maintain about 40% of its infectious titer for 2 h (Fig. 1C) . These results suggested that IDV is the most temperature-stable influenza type of all influenza virus types.", "IDV differs from all historically known influenza viruses in that it utilizes cattle as a primary reservoir. Adaptation to cattle may confer some unique features to IDV, which enhance its survival in this particular agricultural animal population. Such inherited characteristics through evolution may make IDV distinguishable from other types of influenza viruses circulating in ducks, pigs, or humans. As a first step toward identifying novel biological traits and better understanding the infection biology of newly emerging IDV, we directly compared the stability and infectivity of IDV to those of other influenza types following exposure to either high temperatures or low-pH solution. Interestingly, our experiments revealed that IDV was more resistant to high temperatures and highly acidic environments than the other three types of influenza viruses. Significantly, we found that the viral HEF glycoprotein is a primary force in dictating the exceptional stability of IDV infectivity at low pH and high heat.", "The viruses used in this study are listed in Fig. 1A , including two IAVs (originated from swine and human), one IBV (from human), one ICV (from human), and two IDVs (from cattle and swine). We started by investigating the effect of temperature on the stability and infectivity of the influenza viruses. Temperature gradients evaluated included 33\u00b0C, 37\u00b0C, 41\u00b0C, 45\u00b0C, 49\u00b0C, 53\u00b0C, 57\u00b0C, and 65\u00b0C. A temperature of 0\u00b0C was included as a control. All the viruses listed in Fig. 1A were treated under this set of temperatures for 1 h at neutral pH and then incubated on ice for another 30 min. After treatment, the infectivity of these viruses was determined by measuring viral 50% tissue culture infective doses (TCID 50 s) in MDCK (Madin-Darby canine kidney) cells using the standard protocol (6, 7) . Viral titers for all tested viruses were not impaired when treated at 33 to 41\u00b0C but started to decline at 49\u00b0C (Fig. 1B) . The 53\u00b0C treatment clearly discriminated IDV D/OK/13 (see Fig. 1A for the influenza virus strains and influenza virus abbreviations) from the three other types in that IDV retained a high residual infectivity (~2.5 log units of TCID 50 /ml), while IAV, IBV, and ICV were completely inactivated. Remarkably, IDV was still infectious when treated at 57\u00b0C, and the complete loss of its infectivity was observed only after 1 h of incubation at 65\u00b0C." ] },{ "paper_id": "0bf39c12d7c4576441079e2e758ec1eacfe015d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HFF cells were propagated as per standard laboratory protocols [40] .", "Recombinant human integrin \u03b19\u03b21 (R and D Systems); heparin, and fluorescein isothiocyanate (FITC) (Sigma) were used in this study." ] },{ "paper_id": "0c04a2b5c4c91d76c26736dd05ce6fc6385cc167", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The LILRA3 D1 crystal was cryoprotected in mother liquor containing 15% glycerol before being flash-cooled in liquid nitrogen. Diffraction data were collected using an in-house Xray source (Rigaku MicroMax007 desktop rotating-anode X-ray generator with a Cu target operated at 40 kV and 30 mA) and an R-AXIS IV++ imaging-plate detector at a wavelength of 1.5418 \u00c5 . The collected intensities were indexed, integrated, corrected for absorption, scaled, and merged using HKL-2000. Data collection and processing statistics are summarized in Table 1 .", "Key residues or structural elements crucial for influencing the binding affinity between Group 1 LILRs and HLAIs", "The atomic coordinates of LILRA3 D1 have been deposited in the RCSB Protein Data Bank with accession code of 3Q2C. ", "In all forward and reverse primers, a start or stop codon was introduced with NdeI or XhoI restriction sites accordingly. All of the PCR products were ligated into the pET21a vector (Novagen), transformed into E. coli strain BL21 (DE3) pLysS, and expressed in the form of inclusion bodies." ] },{ "paper_id": "0c0806be80c60f0e61f084f12ed847c265fc1d68", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed using Stata version 11.0 (Stata Corporation) and SAS version 9.1 (SAS Institute). p-Values of ,0.05 were considered statistically significant." ] },{ "paper_id": "0c0e91904a6c84a7ee80cc69fe83370aaa3ca708", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: The questionnaire." ] },{ "paper_id": "0c1318a0ed68a50f13ef04c2cd0741d2e7016104", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LH, JB, HSL, and HJL contributed conception and design of the study. JB and HSL performed the experiments and wrote the manuscript. YZ and JL performed the fluorescence experiments. GZ and YZ analyzed the data. LW and WJ made figures. HD, JY, and QX advised on experimental design and data interpretation. LH supervised the study, interpreted the data, wrote the manuscript and acquired the research funds. ", "HiScribe T7 Quick High Yield RNA Synthesis kit, Monarch RNA Cleanup Kit, NEBuffer 3.0, EnGen R Lba Cas12a (LbCas12a), and AhdI, EcoRI, and BamHI endonucleases were purchased from New England Biolabs (MA, United States). TaKaRa MiniBEST DNA Fragment Purification Kit Ver.4.0 and RNase inhibitor were obtained from TAKARA (Tokyo, Japan). The RAA kit was purchased from Hangzhou ZC Bio-Tech Co., Ltd. (Hangzhou, China). The constant temperature incubator purchased from Senxin (Shanghai, China) was set at 37 \u2022 C. Fluorescence intensity was measured by the Tecan Infinite M200 plate reader (Tecan, M\u00e4nnedorf, Sweden).", "The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher.", "African swine fever (ASF) is a highly contagious hemorrhagic disease of domestic pigs and wild boars. ASF is caused by a large, complex double-stranded DNA virus, the African swine fever virus (ASFV) (Galindo and Alonso, 2017) . The disease shares similar clinical signs with classical swine fever (CSF) and several other swine diseases (Oura et al., 2013) , making its diagnosis difficult, especially outside of a diagnostics laboratory By 5 September 2019, 156 outbreaks were detected in China and 1,170,000 pigs were culled in an effort to halt further spread (Food and Agricultural Organization of the United Nations, 2019). There is no effective treatment or vaccine against ASF yet, so controlling ASF mainly relies on animal slaughter and sanitary measures (Galindo and Alonso, 2017; Dixon et al., 2019) . Therefore, accurate and timely diagnosis of ASF infections is crucial for controlling epidemics." ] },{ "paper_id": "0c161375d1b822a44e873c134760ddb8600a550c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NO, CP, and ES conceived, wrote, and edited this review. FF, ED, and BC revised and extended the parts of the text -specifically in the areas of the biochemistry and structural biology, and provided various other useful suggestions and contributions. FF prepared ", "The assumption that the viable ZF1 mutant (H229C) possesses increased ExoN activity, which could explain the reduced levels of dsRNA in infected cells, seems premature. Alternative explanations for this phenotype include changes in the efficiency or kinetics of RNA synthesis. Moreover, the reported reduction of viral double-stranded RNA accumulation by this mutant should be interpreted with caution, as this conclusion was based solely on the in situ immunodetection of dsRNA using a monoclonal antibody with a poorly defined specificity for CoV dsRNA replication intermediates. For example, it remains unknown how changes in the protein composition or subcellular localization of the RNA-synthesizing complex may affect the accessibility of dsRNA epitopes during such immunolabeling experiments.", "As mentioned above, for most of the novel metagenomicsderived nidoviruses we only know genome sequences, and their replication properties and enzymes have remained biologically uncharacterized thus far. This is clearly different for CoVs, which have a track record as an important group of (zoonotic) human and veterinary pathogens. With some exceptions (Durzynska et al., 2018) , also the structure-function analysis of the nidoviral ExoN enzyme has been based on CoV-derived variants of the enzyme, on which we will focus our attention from this point forward.", "Currently, there are no FDA-approved antiviral drugs for the treatment of CoVs, which is mainly due to limited interest from the side of the pharmaceutical industry, despite the loss of human lives during the short-lived SARS outbreak and the continuing MERS epidemic. Moreover, antiviral hits identified so far often suffered from poor selectivity indexes. Drug development efforts were further restricted by the limitations of available animal models and potency failure in clinical trials (Zumla et al., 2016) . Taking into account the combination of ExoN and N7-MTase activities in a single protein, and its importance in viral replication, CoV nsp14 is an attractive target for antiviral drugs. Thus far, only two classes of compounds that (in)directly interfere with its activities have been analyzed in more detail: nucleoside analogs and methyltransferase inhibitors." ] },{ "paper_id": "0c22edd80a03a1b9de7f3d29b729ad1006d10674", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Arenaviruses have single-stranded, bisegmented ambisense RNA genomes and form enveloped virions [1] . Seven arenaviruses cause viral hemorrhagic fever in humans: the Old World arenaviruses Lassa and 'Lujo,' and the New World Clade B arenaviruses Machupo (MACV), Jun\u00edn (JUNV), Guanarito (GTOV), Sabi\u00e1 (SABV), and Chapare (CHPV) [2, 3, 4] . All of these viruses are US Select Agents and Risk Group 4 Pathogens [5, 6] . MACV, JUNV, and GTOV are also classified as US National Institute of Allergy and Infectious Disease Category A Priority Pathogens [7] . MACV causes human disease outbreak with high case-fatality rates. To date, at least 1,200 cases with <200 fatalities have been recorded [8, 9] .", "Currently there is no FDA-approved treatment to stop the spread of MACV once humans are infected. Defining interactions between the viral glycoprotein and a cellular receptor may allow for drug development that could limit viral spread in the infected individual and reduce infection during an outbreak. Our mutagenesis analysis of MACV GP1 experimentally elucidates the structure and functional interaction motifs of MACV GP1 and its receptor hTfR1. These studies therefore provide a solid platform for the future design and development of small molecule inhibitors and antivirals specifically targeting viral entry.", "Transferrin receptor 1 (TfR1) is the principle cell-surface receptor of MACV, JUNV, GTOV, and SABV [17, 18] , and a major determinant of host adaptation. However, studies on receptor use and cellular tropism suggest that the non-pathogenic Clade B viruses Amapari (AMPV) and Tacaribe (TCRV) can enter human cells in a human TfR1-independent manner [18, 19, 20] . Nevertheless, AMPV and TCRV use TfR1 orthologs of their principal host animals to infect nonhuman cells [21] . These studies reveal a complex pattern of receptor use for New World arenaviruses, suggesting the existence of additional receptor molecules, and a possible relationship between receptor use and disease potential.", "We have used purified MACV GP1 and MoMLV pseudotyped with the MACV glycoproteins in all experiments. Several studies suggest that retroviral vectors pseudotyped with the glycoproteins of arenaviruses adopt the receptor-binding characteristics of the corresponding viruses [17, 20, 27] . Therefore, we believe this surrogate system to be valuable for initial studies of viral cell binding and entry. However, it is important that the system is simplistic and uses only a few viral proteins in the absence of other viral-encoded proteins or genomic elements. Therefore, any results obtained with this system should be verified with infectious virus. Unfortunately, no reverse genetics system has been developed for MACV to date, making it impossible to evaluate the effect of the mutated residues on entry of infectious MACV.", "Arenaviral genomes encode at least four proteins from two segments (Large and Small). The Large segment encodes a matrix protein (Z) and an RNA-dependent RNA polymerase (L); the Small segment encodes a nucleoprotein (NP) and the glycoprotein precursor GPC [2] . GPC is cleaved by a cellular protease to a stable signal peptide (SSP), and two subunits, GP1 and GP2. The three cleavage products form a stable complex and mediate virus attachment to host cells and fusion of the arenavirion envelope with that of the cell [10, 11, 12, 13, 14, 15] . GP1 mediates the binding of the virion to a cell-surface receptor, whereas the class I fusion protein GP2 mediates membrane fusion after internalization of the virion into an acidified endosome [16, 17] . Interrupting the interaction of GP1 with its cell-surface receptor is a current focus of antiviral development since it would prevent the first and pivotal step of arenavirus host-cell infection." ] },{ "paper_id": "0c2489ea506fea5ac57b464c2a99f893cc867ff3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The protocol was approved by the institutional review board of each hospital.", "was based on patient self-report, which might not be totally reliable.", "On the other hand, strengths of our study include the participa- " ] },{ "paper_id": "0c3ceccabeff0296e424a649fe5931a1671f9905", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pone.0214871.g005", "Supporting information S1 " ] },{ "paper_id": "0c433c7c4e2e090b2d89d8456f9febed54b71966", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IFITM3 were synthesized as codon-optimized genes for expression in human cells (GeneArt) and cloned into the BamHI and NotI sites of the lentivirus vector pSIN-BNHA (derived from pHRSIN-CSGW; Demaison et al., 2002) .", "Cells. A549 cells were maintained in F12 medium, and 293T, NPTr (Ferrari et al., 2003) and FLN-R cells (Friedrich-Loeffler-Institut) were grown in Dulbecco's Modified Eagle's Medium (DMEM) with 10 % FCS. Primary lung cells from the microbat (M. myotis) were grown in DMEM containing 10 % FCS, penicillin (100 units ml 21 ) and streptomycin (100 mg ml 21 ) and 20 % amnioMAX (Gibco).", "Endocytic uptake of microbat and pig IFITM3 from the plasma membrane" ] },{ "paper_id": "0c4f848837c2e8eaf750682d4195cc9076d0cef5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Leishmania infantum infection in cats in Italy PLOS Neglected Tropical Diseases | https://doi.org/10.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "0c589675855cd6a533025c50fb319ecd269c2d0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal experiments were approved by the Hubei Administrative Committee for Laboratory Animals (permission number 00024534) and complied with the guidelines of Hubei laboratory animal welfare and ethics of Hubei Administrative Committee of Laboratory Animals.", "The one-way analysis of variance (ANOVA) was applied to analyze the experimental data. Data of three independent experiments were shown as the mean \u00b1 standard deviation (SD). Statistical significance was determined with a p-value < 0.01.", "YZ and SX designed research; YZ, KC, and DW performed research; YZ and LF analyzed data; YZ, HC, and SX wrote the paper. " ] },{ "paper_id": "0c58c5ce46bfa52188d231685cc1c6a440840b85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For comparisons of categorical data, \u03c7 2 test and Fisher's exact test were used where appropriate. All tests were twotailed and p<0.05 was considered statistically significant.", "The relationship between HPIV infection and neurologic disease has been studied for many decades. In a previous report, children hospitalized with HPIVs had serious febrile seizures [25] . In contrast, we found no significant difference in convulsion between HPIV-positive and HPIVnegative patients (p=0.726).", "Samples in this study were taken as part of standard care. The First Affiliated Hospital of Guangzhou Medical University Ethics Committee approved the experimental design and patient involvement in this study. Written informed consent was obtained from the patient for publication of this report and any accompanying images.", "This study explored characteristics of the four HPIV types and provided novel insights into the epidemiology and clinical implications of HPIVs." ] },{ "paper_id": "0c58e0eb436a3d0cb4c5acfa41babc03b3dfe825", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2)Ethical challenges", "(3)Legal challenges", "The political impetus for action in response to many EIDs is not necessarily scientific evidence but societal perceptions. Indeed, in the face of scientific uncertainty and ethical ambiguity, ideological perspectives and short-term political considerations often supplant efforts to devise effective long-term interventions [28, 37] .", "Rabies virus infects the central nervous systems of people, wildlife and domestic mammals. The disease is transmitted by bites from infected animals and once it becomes symptomatic, it is virtually always fatal. 55,000 people die and 7.5 million receive post exposure prophylaxis annually, costing $124 billion [91] . Rabies is endemic in much of South East Asia but its range is expanding. Focusing on Australia, the continent is free from Rabies, but the current expansion of the disease in Indonesia [92] is a genuine threat to northern regions. Although likely controllable in domestic dog populations [93] , if Rabies were to become endemic amongst wild or feral animals in this setting, current modelling indicates it would be almost impossible to eradicate [94] . Table 2 Significant historical (i.e. effectively eradicated) EIDs" ] },{ "paper_id": "0c6dfd6796df35e619aa7b8099bd54174415fb52", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analytical and preparative SFC separations were performed on a Waters Investigator SFC System controlled by ChromScope software (Waters, Milford, MA, USA). The system consisted of a FDM10 fluid control module, an Alias autosampler, a 10-port Thar columns oven, and a 2998 photodiode array (PDA) detector. Optical rotation of the separated enantiomers was measured by a Rudolph Autopol IV polarimeter.", "Carbon dioxide (food-grade) was obtained from Chengweifeng Inc. (Beijing, China). All the solvents were HPLC grade and were purchased from Merck (Darmstadt, Germany). (R,S)-goitrin (product number 111753) was from National Institutions for Food and Drug Control (Beijing, China). (R)-goitrin and (S)-goitrin were previously prepared by the NPLC method.", "Over the past decades, chiral separation has become an important research topic in the analytical science arsenal [9] [10] [11] . Individual enantiomers of chemical drugs may evince very different bioactivities and/or biotoxicities, so do natural products. While one isomer possesses a therapeutic effect, its enantiomer may be inactive and antagonistic or even has reverse effect. With this perspective in mind, it is imperative to investigate pharmacology and toxicology of (R)-goitrin and (S)-goitrin, respectively, which means large amount of resolved enantiomers need to be prepared for tests in vivo and in vitro." ] },{ "paper_id": "0c82e4a717a9242e0462b24a8759f98f0c83d677", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The mosquitoes, including Culex tritaeniorhynchus, Culex pipiens molestus, and Anopheles sinensis were collected from Yunnan province, China, in 2009. The samples were stored in liquid nitrogen until RNA extraction. No specific permits were required for the described field studies; the samples collected were not privately owned or protected and did not involve endangered or protected species.", "Total mosquito DNAs were extracted with TRIzol reagent (Introgen, Carlsbad, CA) according to the manufacturer's instructions. A pair of primers (forward primer: 59-ATA AAT TGA TCA GTC GTC CTC CAA C-39; reverse primer: 59-CTT GGG ATC ATT TCG GTC ATA T-39) were selected from the viral sequence assembled with the mappable reads. The PCR was conducted in a 50 ml reaction mixture containing 16Easy Taq PCR SuperMix (TransGen Biotech, Beijing, China), 1 mM each of the forward and reverse primers and 10 ng of template DNA. After pre-denaturation at 94uC for 3 minutes, 35 cycles of amplification (30 sec denaturation at 94uC, 30 sec annealing at 55uC, and 60 sec polymerization at 72uC) were performed, followed by a final incubation at 72uC for 5 min. PCR products were visualized on a 1% agarose gel stained with ethidium bromide." ] },{ "paper_id": "0c842a151c9e010a7c70151d029c91a118bde887", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dendritic cells (DC) are key antigen presenting cells that prime na\u00efve T cells and drive the adaptive immune response. They are very effective in sensing viruses through a wide range of surface, cytosolic, and endosomal receptors, and Toll-like receptors (TLR) are crucial DC pattern recognition receptors between those.", "Porcine macrophages express CD163, a scavenger receptor, CD169 (also known as sialoadhesin", "Funding: This research was funded by CSIC. Check carefully that the details given are accurate and use the standard spelling of funding agency names at https://search.crossref.org/funding, any errors may affect your future funding.", "As a whole, DC responses against PPRSV showed a general dysregulation of the IFN response, downregulation of activation and maturation markers with an induction of IL10 and Treg (Figures 1 and 2 ).", "Seven-week-old nursery pigs in a commercial setting were injected with MN 1-18-2, and at day 2 pi, approximately 50% of viremic pigs had greater than 50% reduction in NK cell mediated cytotoxicity. Reduced frequency of CD4\u2212CD8+ and CD4+CD8+ T cells and upregulated frequency of lymphocytes bearing natural Treg phenotype was detected in viremic pigs. All of the viremic contact pigs also had comparable immune cell modulation [100] ." ] },{ "paper_id": "0c917c3becd5b37cc4e44ad2c822ba132d339728", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Signal Transduction and Targeted Therapy (2020) 5:8", "Targeting cancer stem cell pathways for cancer therapy Yang et al.", "; https://doi." ] },{ "paper_id": "0c95f3083af8f4daf852527cc3d25b6b8af3a54c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting information S1 Table. Clinical characteristics and raw real-time data for sputum specimens. (DOCX) ", "Nucleic acid technologies are having a significant impact on the diagnosis, treatment, and control of drug-resistant Mycobacterium tuberculosis (M. tuberculosis), and there is a growing emphasis on developing and deploying molecular diagnostics outside of reference laboratories and closer to the point of need (e.g., [1, 2] ). Most tests for diagnosing pulmonary tuberculosis a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 are performed on sputum [2] [3] [4] , which as clinical sample matrix is also important for managing cyctic fibrosis patients [5, 6] ; detecting and diagnosing respiratory viruses [7, 8] , pneumonia [9] , and other lower respiratory tract infections [10] ; and even lung cancer diagnosis or screening [11] .", "Competing interests: Nitu Thakore \u00c3 , Ryan Norville, Christopher Cooney \u00c3 \u00a5, Darrell Chandler \u00c3 , and Rebecca Holmberg\u00a5 are all employees of Akonni Biosystems. Akonni Biosystems intends to manufacture the automated workstation as a commercial product. Those with asterisks are also shareholders of Akonni Biosystems. Those with \u00a5 have patents related to the extraction technology used in this research. This affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials." ] },{ "paper_id": "0ca5279816f66f7fd8c0bdb09d15f5953e019b68", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data Availability e data used to support the findings of this study are included within the article.", "e data was analyzed using SPSS 20.0. e statistical methods used are chi-square test for counting data and independent sample Kruskal-Walis test for measurement data.", "Disclosure e first author is Su Ma, the co-first author is Lili Feng, the co-first author is Wenxia Ding." ] },{ "paper_id": "0ca675e1d62eeff5188b3cfa32f4cf16ea634dc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Not until July 16, when WHO acknowledged that further spread of the pandemic was inevitable and that individual case counting was no longer essential, did the three MECIDS countries stop sharing daily reports of new cases.", "Recently, efforts have shifted away from Salmonella, toward other issues. Laboratory and public health professionals from all three countries have attended meetings dedicated to the identification and Alex Leventhal et al. characterization of another foodborne pathogen, Shigella; general laboratory safety and security issues; and the use of bioinformatics in microbiology and molecular epidemiology.", "MECIDS partners share a unique geographical situation. Located at the junction of three continents (Asia, Africa and Europe), between the Mediterranean Sea and Arabian Desert, the three countries act as a ''bottleneck'' through which a large portion of the world populations of certain migratory bird species concentrate on their way to and from their winter quarters in Africa ( Figure 2 ). These birds serve as a continuous source of viruses, such as West Nile and avian influenza (AI). It has been estimated that every year approximately 500 million birds pass through Israel alone." ] },{ "paper_id": "0ca8648d40bee3056b3f9840de6d34b57ed121d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "supplemented with penicillin (100 U/ml), streptomycin (100 mg/ml) and 5% fetal calf serum (FCS) (Sigma).", "Information concerning the specific role of VP5 during virus replication is somewhat controversial. Whilst some reports describe VP5 as a proapoptotic polypeptide [4, 5] , others provide experimental data supporting that it prevents IBDV-induced apoptosis [6, 7] . According to several reports VP5 expression enhances the virus progeny size and promotes virus release [6, 8, 9] .", "doi:10.1371/journal.pone.0123470.g003" ] },{ "paper_id": "0cafb384b401aeefaa3286bb0cf76309434e2288", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA interference (RNAi) technology is also being used to impair virus replication against respiratory syncytial virus, hepatitis viruses, influenza virus, poliovirus and HIV [109, 110] . Low molecular weight phenolic compounds such as flavonoids and phytochemicals isolated from plants were previously tested and are being used for anti-dengue therapy [111, 112] . An anti-viral inhibitory effect ranging from 50-75 % against DENV replication was observed when methanolic extracts of Momordica charantia and Andrographis paniculata were used in cultured primate cells [113] .", "The authors disclose that there is no conflict of interest.", "This Project is funded by the King Abdulaziz City for Science and Technology (KACST) under grant number ( \u202b\ufe8d\u202c \u202b\ufe95\u202c -33 -26 ). The authors are also grateful to the" ] },{ "paper_id": "0cc12d028d0f63383a4243bb73d76f70ae229daa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conservative amino acid motifs are bold and underlined. doi:10.1371/journal.pone.0049842.t002", "Care of laboratory animals and animal experimentation were performed in accordance with animal ethics guidelines and approved protocols. All animal studies were approved by the Animal Ethics Committee of Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences (SYXK (H) 2006-032).", "Amino acid sequence of the insert a" ] },{ "paper_id": "0cd1453fb9f28809b7544dcdcb0d6b3b4e42b3cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animal and Human Rights Statement This article does not contain any studies with human or animal subjects performed by any of the authors.", "Conflict of interest The authors declare that they have no conflict of interest.", "Abrahamyan LG, Chatel-Chaix L, Ajamian L, Milev MP, Monette A, Clement JF, Song R, Lehmann M, DesGroseillers L, Laughrea " ] },{ "paper_id": "0cd911d564b693ebedf57fa37c28b8ea5705c174", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are expressed as median with interquartile range (IQR) for continuous variables and count with percent for categorical variables. Fisher's exact test was used to analyze categorical variables. Statistical analyses were carried out using SPSS 12.0 (SPSS Inc., Chicago, IL, USA) and a P value of ,0.05 was considered to be statistically significant. " ] },{ "paper_id": "0cd96fd42139b22b63e5752eda2c38990a18763a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For real-time RT-PCR analysis, the total RNA of cells was extracted by using the RNA easy kit (Qiagen, Valencia, CA). Briefly, the total RNA (1 mg) of each sample was reversely transcribed in 20 mL using 0.5 mg of oligo dT and 200 U Superscript II RT (Invitrogen, Carlsbad, CA). The amplification was carried out in a total volume of 20 ml containing 0.5 mM of each primer, 4 mM ", "Table S1", "Found at: doi:10.1371/journal.pone.0002637.s001 (0.05 MB DOC) " ] },{ "paper_id": "0ce0b8bb68417974932e98c094ec93fbefc5193b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations AI: aromatase inhibitor; BAF: Brahma-associated factor; BRG: Brahma-related gene; BST2: bone marrow stromal cell antigen 2; CBP/p300: CREB-binding protein 300; CRCs: chromatin remodeling complexes; CREB: cyclic AMPresponsive-element binding protein; DAB: 3,3\u2032-diaminobenzidine; (D)" ] },{ "paper_id": "0ce2f11a7c4da992b9a8686bd3b2ed53064a2ac8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "0ce5bbc5edc608a6561d64e63edaad4a2bcad084", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Liquid chromatography-mass spectrometry (LC-MS) grade water, methanol, and acetonitrile were purchased from J.T. Baker (Center Valley, PA, USA). HPLCgrade chloroform was purchased from Merck (Darmstadt, Germany). Analytical grade acetic acid and commercial standards used for biomarker identification were purchased from Sigma-Aldrich (MO, USA). Internal standards (IS) including Arachidonic acid-d8, 15(S)-HETE-d8, Leukotriene-B4-d4, and Lyso-Plateletactivating Factor C16-d4 (PAF C-16-d4) were purchased from Cayman (Cayman Chemical, USA).", "The cell lipid extract was analyzed using an Acquity UPLC system coupled to a Synapt G2-HDMS mass spectrometer system (Waters Corp., MA, USA). The chromatography was performed on a Waters ACQUITY BEH C18 column (1. 1-40 min) . The column and auto-sampler temperature were maintained at 45\u00b0C and 10\u00b0C, respectively. The injection volume was 8 \u00b5l.", "Plasmids. FAS-Luc containing FAS promoter was a gift from Dr. Bruce Spiegelman (Addgene plasmid#8890). pSynSRE-T-Luc (named as HMGCS-Luc for clarity) containing the HMGCS promoter (Addgene plasmid#60444), pcDNA3.1-2 \u00d7 FLAG-SREBP-2 (Addgene plasmid#26807), pcDNA3.1-2 \u00d7 FLAG-SREBP-1c (Addgene plasmid#26802) were gifts from Dr. Timothy Osborne. The luciferase constructs IFN\u03b2-Luc and ISRE-Luc were provided by Dr. Dong-yan JIN (The University of Hong Kong). The LXRE reporter plasmid pGreenFire1-LXRE, named as LXRE-Luc in this study, was obtained from System Biosciences." ] },{ "paper_id": "0cec675c685c32258b42e915ab84a45851b6dd26", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleic Acids Research, 2016, Vol. 44, No. 15 7025 ", "Another reported early was the carlavirus, potato virus M (462) . However, as there are reasons for caution (463) , this will not be considered further here.", "One Shine Dalgarno sequence serves as both an initiator and frameshift stimulator in an IS element (194) . Mechanis- tic studies of their action are described in a separate section below.", "As introduced above with dnaX, transcription slippage in bacteria on runs of 9 As or Ts results in mRNAs with up to 6 extra nts, with translation of the subset of 3 or 6 additional nts generating zero frame encoded product containing one or two extra amino acids. Among other relevant cases of slippage are those in Shigella flexneri, human TGFBR2 and ATRX (381) , and the endosymbionts Buchnera aphidicola and Blochmannia pennsylvanicus (244) ." ] },{ "paper_id": "0ced1f946cce007aa319a0ba38aef2c4b14dab0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 9 mer peptides with a score exceeding 24 were selected in \"SYFPEITHI\"." ] },{ "paper_id": "0cf083b09e13b9c6d8fe008590784d479f67f2f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results show that FHV-1 genomes are highly conserved. The lack of recombination detected in the FHV-1 genomes suggests that the risk of attenuated vaccines recombining to generate virulent field viruses is lower than has been suggested for some other herpesviruses. The SNPs detected only in the vaccine isolates offer the potential to develop PCR-based methods of differentiating vaccine and clinical isolates of FHV-1 in order to facilitate future epidemiological studies.", "Author details" ] },{ "paper_id": "0cf8f9fb2f0481a0e6a4b83cbffb07acfa20d6b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fussenegger on gene therapy [65] , and Nielsen on systems biology in areas such as antibiotic production by microorganisms [66] .", "Workbook S1 Packaged Tableau Workbook for use with Tableau Reader 7.0. (ZIP)", "To achieve this objective we have exploited the increasing availability of digital tools for visualisation and interaction with scientific data to promote engagement with this field of research.", "In terms of the volume of publications network mapping reveals the prominence of the University of California at Berkeley, the Swiss Federal Institute of Technology (ETH), Harvard and MIT. The data does not discriminate by discipline with the social sciences represented in work at Berkeley, Exeter and Edinburgh while law is represented in work at Duke University [7, 10, 46, 47] ." ] },{ "paper_id": "0cf9f507a18a00de76b8bb61a2c5c2b66680dd50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The envelope protein Structure" ] },{ "paper_id": "0cfbd799dde9aedd35ace107455d6b0bee8fa640", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples were prepared for amplicon sequencing following the Illumina protocol for 16S rRNA gene sequencing (Part # 15044223, Rev. B) with modification to ensure sufficient amplification from samples that yielded low amounts of DNA. The recommended primers (forward: 5'CCTACGGGNGGCWGCAG, reverse: 5'GACT ACHVGGGTATCTAATCC) target the V3/V4 region of the 16S rRNA gene [39] with Illumina adapters attached ", "The associated non-parametric p-value describes the chance of seeing an m 2 value at least this extreme in 999 permutations using Monte Carlo simulations. A p-value of 0 means that no value as extreme as the calculated m 2 was observed in these permutations. This was carried out within QIIME and plotted with Emperor [57] .", "Species-level identification could not be achieved with the V3/V4 region. Some taxa contain multiple OTUs (which may not be the same species). It is also possible that multiple species have been classified as the same OTU if the sequences are more than 97% identical.", "The model included sex (Male/Female), recent antibiotic usage (within the past month; Yes/No) and length of breastfeeding (Never/Under 6 months/6 to 12 months/ Over 12 months/Current) to control for these potential confounders. All nasopharyngeal swabs from both groups were included in the analysis except those with missing data for the above covariates (n = 4), leaving 98 control NPS and 86 case NPS for comparison." ] },{ "paper_id": "0d0a0fdfcb384b60703d3ea329672f668d7c118e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "FACS based sorting of fluorescent parasites to purify populations of homogeneously expressing cells may represent another potential experimental approach but the low number of cells possible to recover in such a sorting experiment may be inappropriate for use in a drug sensitivity assay. Development of a superior inducible system in P. falciparum may also address these issues. A conditional protein stabilisation system has been used to excellent effect to address several questions of Plasmodium biology, but the applicability of this system to all subcellular destinations is uncertain [84, 85] .", "The drug sensitivity assays were performed using the SYBR Green staining method after 48 hours of growth as previously described by Smilkstein et al. [51] with some modifications as detailed in [52] .", "The parasite Plasmodium falciparum is the causative agent of severe malaria in humans, killing somewhere between 600,000 and 1.2 million people each year [1, 2] . The complex life cycle includes an asexual proliferation within human erythrocytes, characterised by three distinct stages: rings, trophozoites and schizonts. Adaptations to the intra-erythrocytic lifestyle have created new and in some cases unique organelles, such as an endosomal/lysosomal-like organelle, the food vacuole (FV) (reviewed in [3] )." ] },{ "paper_id": "0d12fa6f695fdb75443b00c49514e7850ef461e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Written informed consent was obtained from all mothers who participated in the study and the ZVITAMBO trial and the investigation reported in this paper were approved by The " ] },{ "paper_id": "0d1448dbed0b123a78907316826d116ad97cfbcf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "With regard to viral infections, however, our search of NCBI GEO revealed expression array studies in which human PBMC samples were devoid of TAAR1 at baseline ( Table 1) .", "All authors contributed to the writing of the manuscript. LF performed all meta-analyses and compiled all data presentation.", "When available, statistical analysis within a dataset was carried out using the Analyze Dataset tool located at the bottom of the dataset of interest's page." ] },{ "paper_id": "0d1ca8ed239b0d50c0dc8a21041a1a1c43045806", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Challenges for the Israeli approach to PCP involvement in pandemic management" ] },{ "paper_id": "0d1d6d059b8f14bab7c89cdcda4cda11e38233dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results of viral inhibition were calculated as a percentage of the negative control (medium plus drug diluent). All statistical analyses were performed by one-way ANOVA with Tukey's post-test using the GraphPad Prism 5.0 software (GraphPad Software, San Diego, CA, USA).", "Berberine is an isoquinoline alkaloid belonging to the structural class of protoberberines and is encountered in many plants including Berberis vulgaris [9] . It exhibits several pharmacological properties and is particularly effective against entry and replication of many viruses, including the human cytomegalovirus (HCMV) [10] , herpes simplex virus (HSV) [11] , influenza virus [12] , Chikungunya virus (CHIKV), and other Alphaviruses [13] . Emodin, an anthraquinone derivative, is also a naturally occurring compound derived from the Chinese herbs Rheum palmatum [14] , Polygonum multiflorum [15] , Aloe vera [16] , and Cassia obtusifolia [17] . Emodin possesses a wide spectrum of pharmacological effects, including antiviral activity, against Coxsakie B5 virus (CVB5), human respiratory syncytial virus (HRSV) [18] , influenza A virus [19] , Epstein-Barr virus (EBV) [20] , herpes simplex virus (HSV) [21] , hepatitis B virus (HBV) [22] , and Japanese encephalitis virus (JEV), which is another Flavivirus [23] .", "Stock solutions of Emodin and Berberine were diluted in 0.2% dimethyl sulfoxide (DMSO, Sigma-Aldrich, St. Louis, MO, USA). The working solutions were obtained by dilution, in different concentrations, of both drugs in Dulbecco's modified Eagle's medium (DMEM) (Sigma-Aldrich, St. Louis, MO, USA).", "Strategies to combat ZIKV infection include the development of vaccines [6] and the screening of molecules that inhibit the different phases of the viral lifecycle [7, 8] ." ] },{ "paper_id": "0d1d976e7073e6c1bbc69805f5c61a2f8607c911", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "More than 2 billion people worldwide are infected with the hepatitis B virus (HBV), of whom 400 million are chronically infected. A significant fraction of chronically infected individuals develop liver cirrhosis and hepatocellular carcinoma [1, 2] , and approximately 1 million die annually from HBV-induced liver disease [3] . HBV is a small, enveloped DNA virus belonging to the Hepadnaviridae family, which replicates preferentially in liver cells and utilizes a unique replication strategy involving the reverse transcription of pregenomic RNA (pgRNA) [4] .", "Several molecules, such as phenylpropenamide derivatives (AT-61 and AT-130) and heteroaryl-pyrimidines (HAP), have been developed to circumvent drugresistant CHB. Phenylpropenamide derivatives inhibit encapsidation of HBV wild-type (WT) and LMVresistant mutant pgRNA in vitro [21, 22] ; however, clinical trials were discontinued due to toxicity [23] . A Phase I clinical trial of HAP, which inhibits HBV core (C) protein dimerization and blocks nucleocapsid formation, has been conducted [24, 25] and both RNAi [26, 27] and inhibitors of a newly identified HBV receptor, sodium taurocholate polypeptide, are being tested [28] ." ] },{ "paper_id": "0d33d89c32913354f7164225a906ff85339293e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since the 1970s, NDV has been considered a useful laboratory virus for replication and virulence studies, as recently summarized [13] ." ] },{ "paper_id": "0d354b208fdfa2806bf33fd03e940e057b339de5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Screening Assays for Ebola virus (EBOV, Strain Kikwit).", "Immune-staining was used to visualize infected cells. Cells were treated with anti-GP specific monoclonal antibody (6D8) (1 to 1000 dilution) followed by anti-mouse IgG conjugated with Dylight488 (Thermo) (1 to 1000 dilution) in blocking buffer containing 3% BSA in PBS. Nuclei were stained with Draq5 (Biostatus) diluted in PBS buffer.", "Infection was done using Ebola virus (Kikwit) MOI = 0.5 (calculated for 4,000 cells/well, assuming one complete round of replication of HeLa cells at 15\u00b12 hrs after cell seeding) and 10ul of virus dilution was dispensed in each well except column 2, representing \"no infection control\". Cells were incubated with the virus for 24 or 48h. Infection was terminated by fixing samples in formalin solution." ] },{ "paper_id": "0d40afa4fc54a163858aeffbe43be47bf89b6f39", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Therapeutic antibodies currently approved as disease treatments", "By reviewing currently approved mAbs, one may easily see how sophisticated formats were developed in response to challenges posed by therapeutic indications. These mAb engineering solutions are highlighted by antibody-drug conjugates, glycoengineered mAbs, immunomodulators, bispecific mAbs, and CAR-T cells.", "Ublituximab is a glyco-engineered anti-CD20 antibody currently under clinical investigation in five late-stage clinical studies for different cancers (chronic lymphocytic leukemia, CLL, non-Hodgkin's lymphoma) and noncancer (multiple sclerosis) indications. Three Phase III studies are exploring the efficacy of ublituximab in combination with other anti-cancer agents. Among these studies, the UNITY-CLL Phase III study (NCT02612311) is evaluating the combination of ublituximab and TGR-1202, a PI3K delta inhibitor, compared to anti-CD20 obinutuzumab plus chlorambucil in untreated and previously treated CLL patients. Two other Phase III studies (UL-TIMATE 1, NCT03277261 and ULTIMATE 2, NCT03277248) are evaluating the efficacy and safety of ublituximab compared to teriflunomide in 440 patients with relapsing multiple sclerosis [70] .", "The mAb market enjoys a healthy pipeline and is expected to grow at an increasing pace, with a current valuation of $115.2 billion in 2018 [44] . Despite this high growth potential, new companies are unlikely to take over large shares of the market, which is currently dominated by seven companies: Genentech (30.8%), Abbvie (20.0%), Johnson & Johnson (13.6%), Bristol-Myers Squibb (6.5%), Merck Sharp & Dohme (5.6%), Novartis (5.5%), Amgen (4.9%), with other companies comprising the remaining 13% [44] ." ] },{ "paper_id": "0d5be5a4268da7c08b478ca36721d46bd67bbe69", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MiRNAs, a new class of endogenous, 18-23 nucleotide long noncoding and single-stranded RNAs, were recently discovered in both animals and plants. They trigger translational repression and/or mRNA degradation mostly through complementary binding to the 3\u2032UTR of target mRNAs. Studies have shown that miRNAs can regulate a wide array of biological processes such as cell proliferation, differentiation, and apoptosis [11] [12] [13] [14] .", "The data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus [38] and are accessible through GEO Series accession number GSE44455.", "The ", "Given the nature of viruses, being intracellular parasites and using the cellular machinery for their survival and replication, the success of the virus essentially depends on its ability to effectively and efficiently use the host machinery to propagate itself. This dependence on the host also makes it susceptible to the host gene-regulatory mechanisms, i.e. the host miRNAs may also have direct or indirect regulatory role on viral mRNAs expression." ] },{ "paper_id": "0d5f9dd2c1626d1d3a4228b838fc0bc666363a3c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The proteomes of 1,000 MERS-CoV genomes and 1,000 SARS-CoV genomes were retrieved from GenBank, respectively. After sequence alignment with MAFFT, the dominant amino acid for each site was elected as a reference sequence. The mutation frequency = the number of overall mutations for each amino acid/(the number of occurrences of the amino acid in the reference sequence\u00d7total number of sequences).", "Bats harbor many zoonotic viruses, including highly pathogenic viruses of humans and other mammals, but they are typically asymptomatic in bats. To further understand the antiviral immunity of bats, we screened and identified a series of bat major histocompatibility complex (MHC)", "The sequences of 56 MHC class I genes (including predicted genes) from bats were retrieved from the NCBI database (S1 Table) . Higher mammal MHC I heavy chain sequences were retrieved from the Immuno Polymorphism Database (IPD) (www.ebi.ac.uk/ipd/mhc) and the UniProt database (www.uniprot.org). Previously deposited marsupial (opossum, tammar wallaby, koala, Tasmanian devil) and platypus MHC I transcripts were included in these analyses (S1 Table) . Sequence alignments were generated with ClustalX [48] and ESPript [49] . Similarities were calculated using DNAMAN (https://www.lynnon.com/)." ] },{ "paper_id": "0d673eba8d23c47646d0f5b69937ee87716aa1df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Diverse paramyxoviruses in African fruit bats", "PCR products were cloned into pGEM-T Easy (Promega) and one or more clones from each sample were sequenced (Big Dye Terminator v3.1; Life technologies -Applied Biosystems). Obtained sequences were aligned with polymerase genes from the subfamily Paramyxovirinae using MUSCLE (Edgar, 2004) and CLUSTAL_X (Thompson et al., 1994) . Phylogenetic trees were constructed using Mr Bayes (Ronquist & Huelsenbeck, 2003 ) under the GTR+I+G model (as determined by MODELTEST; Posada & Crandall, 1998) .", "Although co-roosting with other species has not previously been observed, and sheeting was supervised throughout the sampling period, detection of these sequences in samples directly collected from individual bats would be required to confirm their origin." ] },{ "paper_id": "0d6a162406af842f2324077d73de17b2e85cffdb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The viruses and/or bacteria that could be detected by the 7 kits mentioned above are listed in Table 1 .", "When a signal was detected, it was considered as positive. The interpretation of the results obtained by each kit was validated with the acknowledgement of the corresponding supplier.", "The diagnosis of ARI relies both on clinical examination, radiological exploration and biological nonspecific inflammatory tests (including the level of protein C reactive or procalcitonin). The identification of the causative agent(s) is often omitted or limited to a few pathogens easy to detect by rapid antigen direct tests (influenza viruses and respiratory syncytial virus (RSV) in respiratory specimens, Streptococcus pneumoniae and Legionella pneumophila in urine specimens). However, the distinction between viral and bacterial infections is often impossible by using nonmicrobiological criteria [3] [4] .", "The global burden of acute respiratory infection (ARI) remains a huge problem of Public Health. In developed countries, the number of viral respiratory episodes per year has been estimated between 6 and 10 in children before school age versus 3 to 5 in those after this age and ARI represents the cause of 30 to 40% of hospital admissions in this category of patients [1] [2] . A wide range of pathogens are involved in ARI, including bacteria and viruses." ] },{ "paper_id": "0d76724747e4dd9c957017bb1dd628f087f652a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Inter-professional communication and teamwork skills.", "\u2022 Ability to recognize and treat zoonotic and vector borne disease \u2022 Ability to assess and improve patient environments Knowledge competencies: \u2022 Zoonotic and vector borne diseases \u2022 Animals as sentinels \u2022 Human-animal bond and role of service animals, therapy animals, etc.", "The one health concept-research and clinical aspects", "Mr. Glover, a 55-year-old real estate salesman, presents to the emergency room with chest pain that began earlier that day. He has a history of a myocardial infarction six months previously, reports gaining 20 pounds over the past year, and was reluctant to seek care when the pain started." ] },{ "paper_id": "0d7c95184b8a77a7fc0e35995ddc804ba4145429", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Primary antibiotic susceptibility testing is conducted using either automated or Kirby-Bauer tests. ETEST \u00ae is a method to supplement testing with antimicrobial susceptibility testing (AST) reagent strips that determine minimum inhibitory concentrations [54] . Recently, SeLux has developed a Next Generation Phenotyping (NGP) platform, which is a high-throughput, fully-automated AST testing system, enabling same-shift susceptibility testing of up to 50 antibiotics in parallel [55] . This assay differentiates antibiotic-induced bacterial growth modes with a surface-binding fluorescent amplifier.", "Urine antigen testing is also available for select pathogens, and is rapid with results in less than 1 h. Enzyme immunoassay and lateral flow assays are used to detect serogroup 1 of Legionella pneumophilia, the strain most common to cause infection, and enzyme immunoassay is available for S. pneumoniae detection [46-50].", "The gold standard for identification of bacterial, viral, and fungal pathogens remains culture. For bacterial pathogens, testing for antimicrobial susceptibility should also be conducted to ensure adequate therapy is being administered." ] },{ "paper_id": "0d80c3f53b8900bb8d958492553dc052c2b3c628", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CD3/CD16CD56, Simultest\u2122 Leucogate\u2122 (CD45/CD14) and Simultest\u2122 Control \u03b31/\u03b32a (IgG 1 FITC/IgG 2a PE). Lymphocytes were gated in the forward-side scatter plot and various cell subsets were estimated.", "Isolated human PBMC were suspended in HybridoMed DIF 1000 medium (Biochrom, Berlin, Germany) containing 10 \u03bcg/mL gentamycin, 100 \u03bcg/mL streptomycin, 100 U/mL penicillin and 10% FCS (HyClone Laboratories, Logan, UT, USA) and incubated at 37\u00b0C/5% CO 2 and finally cultured (1 \u00d7 10 6 cells/1 mL/well) in 48-well microtiter plates (Greiner Bio-one GmbH, N\u00fcrtingen, Germany). Cells were activated with agonistic CD3 (OKT3, mouse IgG1, Ortho Biotech, Bridgewater, NJ, USA), CD28 (clone CD28.2, mouse IgG1. Beckman-Coulter, Krefeld, Germany) and CD40 (clone B-B20, Trinova Biochem, Gie\u00dfen, Germany) mAb, 100 ng/mL each, or with hkSE (1.25 \u00d7 10 5 CFU/mL; ade -, his -, SALMOVAC SE \u00ae , Impfstoffwerk Dessau-Tornau, Rosslau, Germany).", "Vitality response of human PBMC to mAb or hkSE was evaluated by 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazoliumbromide (MTT)-reduction test as previously reported [26] ." ] },{ "paper_id": "0d82c429737f250a7bcd230fea2e4725edc2439a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The most studied alphacoronaviruses (alpha-CoVs) are the Transmissible Gastroenteritis Virus (TGEV) and Porcine Epidemic Diarrhea Virus (PEDV), which both infect suckling piglets and lead to a high mortality rate [72, 73] . Recurrent outbreaks of PEDV have occurred across Asia and the USA, causing significant economic losses [73] . Alpha-CoV also includes human pathogens such as HCoV-229E and HCoV-NL63, which are associated with respiratory tract infections such as the common cold to bronchiolitis [74, 75] . Despite their medical and veterinary relevance, however, the exact mechanisms of alpha-CoV replication and pathogenesis are not well characterized yet.", "Gammacoronaviruses (gamma-CoVs) are viruses that mainly infect poultry but are also transmissible to humans. They replicate in the respiratory tract and thus cause respiratory defects. The Infectious Bronchitis Virus, which causes major loses in the poultry industry, is the model virus for gamma-CoV. Similarly to other CoV, the IBV genome encodes several nsp proteins that help with replication and interfere with host cell functions.", "The two most studied Arteriviridae are PRRSV and the equine arteritis virus (EAV). The PRRSV strain, which was historically first characterized and is commonly referred to as atypical (i.e., AP PRRSV), causes the abortions in 10-50% of the sows, and fever and anorexia leading to the death of 5-10% of them [69] . However, in 2006, the emergence of a novel virulent highly pathogenic PRRSV (HP PRRSV) strain, carrying mutations in nsp1\u03b2, nsp2, and ORF5 genes, caused higher morbidity (50%) and mortality (20%) rates in piglets and sows [70] . The equine arteritis virus, in contrast, infects horses and donkeys, and can cause abortions in pregnant females and mortality in neonates [71] ." ] },{ "paper_id": "0d8784d230453109b9340461f2692f0f2d048927", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The subcultured osteoblast MC3T3 cells were seeded at a density of 5,000 cells/cm 2 in 40 mm dishes and cultured in \u03b1-Modified Eagle's Medium (\u03b1-MEM; Sigma-Aldrich) containing 10% (v/v) fetal bovine serum (FBS; Nichirei Biosciences Inc., Tokyo, Japan). On the next day, this was replaced with differentiation medium, containing 2 mM glycerophosphate and 50 \u03bcg/mL sodium ascorbate at final concentrations, to induce osteoblast differentiation. When necessary, 100 \u03bcM 2BP in less than 0.1% DMSO, or 0.1% DMSO alone was added to the differentiation medium at final concentrations. All cultures were incubated at 37\u00b0C in a humidified atmosphere containing 5% CO 2 for 27 days. Mineralized nodules were stained with Alizarin Red S (Sigma-Aldrich). The standard staining procedure was used. The mineralized nodules were checked every three days.", "Osteoblast-like MC3T3 cells were provided by the RIKEN, Cell Bank (RCB 1126). The procedures for cell culture, transfection, and protein expression were the same as reported previously. When necessary, 2-bromopalmitic acid (2BP; Wako, Osaka, Japan) and 17-octadecynoic acid (17-ODYA; Sigma-Aldrich) were dissolved in 99.5% dimethyl sulfoxide (DMSO; Wako) and added to differentiation medium at concentrations of 100 \u03bcM and 50 \u03bcM in less than 0.1% DMSO, respectively [30, 31] .", "In 2010, Dr. Yount and co-workers reported that the antiviral activity of IFITM3 is dependent on S-palmitoylation on the protein [10] . The S-palmitoylation [23] is a post-translational modification on proteins by C 16 saturated-fatty acids (palmitic acids) covalently attached to certain cysteine residues via a thioester linkage (Figure 1-B) . The modification is reversibly catalyzed by protein acyltransferases and acylprotein thioesterases, and confers unique properties to the protein, such as membrane binding and targeting, immunoreactivity," ] },{ "paper_id": "0dadaf875ce55724213796d3670ad73c5d8bd2a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "statistics. Student's t tests were calculated using GraphPad Prism software. Significance was set at p < 0.05 and denoted as *p < 0.05, **p < 0.01, ***p < 0.001 and ***p < 0.0001. All results are expressed as the mean \u00b1 standard deviation (SD).", "Results" ] },{ "paper_id": "0db6ae77cd580f4e8c3cb6728de4a2a6197a727c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(a) (b) (c) (d)", "Animal ID Infection 0 7 14 21 28 35 55 ", "PI506 2661 \u2212 \u2212 \u2212 + ++ +++ ++ 2664 \u2212 \u2212 + +++ ++++ +++++ ++++ 2665 \u2212 \u2212 + +++ ++++ ++++ +++ 2676 \u2212 \u2212 \u2212 ++ +++ ++++ ++++ 2682 \u2212 \u2212 \u2212 ++ ++ ++++ ++++ 2684 \u2212 \u2212 \u2212 +++ +++ ++++ ++++ Trangie 2675 \u2212 \u2212 \u2212 +++ ++++ ++++ +++ 2677 \u2212 \u2212 \u2212 ++ +++ +++ +++ 2685 \u2212 \u2212 \u2212 +++ +++ ++++ +++++ 2686 \u2212 \u2212 ++ +++ +++++ +++++ +++++ AO554 2666 \u2212 \u2212 ++ +++ ++++ +++++ ++++ 2668 \u2212 \u2212 +++ \u2212 +++++ +++++ +++++ 2669 \u2212 \u2212 +++ ++++ +++++ +++++ +++++ 2673 \u2212 \u2212 \u2212 ++ ++++ +++++ ++++\u2212 \u2212 + + +++++ +++++ ++++ 2674 \u2212 \u2212 \u2212 \u2212 ++++ ++++ ++++ 2680 \u2212 \u2212 + ++++ +++++ +++++ +++++ VR1112 2662 \u2212 \u2212 \u2212 \u2212 ++ ++ ++ 2678 \u2212 \u2212 +++ +++ +++++ +++++ +++++ 2683 \u2212 \u2212 \u2212 + + ++ ++ Contact 2663 \u2212 \u2212 \u2212 \u2212 \u2212 \u2212 \u2212 2681 \u2212 \u2212 \u2212 \u2212 \u2212 \u2212 \u2212" ] },{ "paper_id": "0dbb8e8757f40e57ded9443666880d99a63c8d7e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the obtained data was analysed using GraphPad prism 6.00 program (San Diego, CA, USA). Statistical significance was determined by one-way ANOVA (with Tukey's multiple comparisons tests). A non-parametric Chi square test was used to analyze significant differences in mortality of birds following SG challenge. Data are represented as mean \u00b1 standard deviation. p values of < 0.05 were considered statistically significant.", "\u00a9 The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver" ] },{ "paper_id": "0dbc8dd1c306474ee5d560eaab38a9500bceb7d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "0dbd0395f35ca86b7afb6e0325025b8741dfa771", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "0dbfaa6ddc08bef9b502de5cd6c0a2a3b7af0106", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "H.L.R. currently works for GeoVax, Inc., which is advancing a DNA prime-MVA boost vaccine. She owns stock in GeoVax as well as being on patents. S.L. is on DNA vaccine-related patents. E.F.F. is on DNA vaccine-related patents.", "The authors would like to acknowledge Joe Santoro for his technical support of the early DNA vaccine experiments in the Robinson laboratory.", "We are eternally indebted to Dr. Guido Majno for his provision of Departmental support for our early work on DNA vaccines and to the Howard Hughes Medical Institute for having supported postdoctoral work on DNA vaccines for S.L." ] },{ "paper_id": "0dc51a358655e78b2b47b4bc7c8b240556696a35", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords: RNA virus, dengue virus, funding models, interdisciplinary, vaccines, clinical trials as topic", "\u2022 generating definitive knowledge on immune responses that confer protection vs. those that do not.", "\u2022 delivery platforms that determine the breadth and longevity of immune responses." ] },{ "paper_id": "0dc958db13e5ac3b76b8204a8081ad0cec38bcfa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "0ddcebebb542f8a0905a3cf82a59f404158d3de2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To create positive controls, PCR products generated from whole organisms were purified and cloned into plasmids using the TOPO TA cloning system (Invitrogen, Carlsbad, CA), following the manufacturer's instructions. All positive controls were sequenced to verify the amplicon sequences and the possibilities of any mismatches generated during cloning. The positive controls were further amplified to generate large quantities that were purified using Qiagen Plasmid Midi Kit (Qiagen, Valencia, CA). The synthetic RNA standards were generated from linearized target sequence plasmids by using T7 in vitro transcription system (Promega, Madison, WI).", "The analytical testing of both multiplex assays demonstrated excellent LOD (1-10 input copies for all analytes) and no significant cross reactivity with a large number of agents that might be in clinical samples.", "For the BioT RNA assay, a two-step RT-PCR was performed in a GeneAmp 9700 thermocycler (Applied Biosystems). cDNA was synthesized in a 20 uL reaction mixture containing 2.5 mM random hexamers (Applied Biosystems), 4 mM dNTPs (Applied Biosystems), 4mM MgCl 2 (Applied Biosystems,), 1U/\u03bcL RNase inhibitor, 2.5U/\u03bcL MuLv reverse transcriptase (Applied Biosystems) and 3 \u03bcl RNA. The reaction mixture was incubated for 5 min at 25\u2103 and for 30 min at 42\u2103 and then the transcriptase was inactivated at 95\u2103 for 5 min." ] },{ "paper_id": "0ddcfc9bedfb0a87a7221dd2448bd41d3ba9cc51", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Even though the association is not statistically significant, we observe that Patients 3, 4 and 5 have the highest fraction of dead cells and also the highest symptom scores AUC ( Table 2 , Fig 3) .", "Our parameter estimates are of the same size as previous estimates from studies using comparable models (for example [11] ). As the parameters in these models tend to be highly correlated, the uncertainty around individual parameter estimates is generally large. Our analysis is limited by the small sample size which, however, is not unusual in studies fitting viral dynamics models.", "Both time to peak viral load and generation time were negatively correlated with initial viral growth. This means that an infection caused by slowly reproducing virus spreads more slowly and has a later peak than an infection caused by faster reproducing virus." ] },{ "paper_id": "0defab5b2520008da1413d0f75d29fe0ae656ea9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: A.C.F. and R.C.K. designed the study. A.C.F. and R.C.K. analyzed the data. A.C.F. and R.C.K. prepared the manuscript.", "Funding: This research received no external funding.", "The authors declare no conflict of interest." ] },{ "paper_id": "0df2a9766ade17a0d9a625ef02722fc167ee0526", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Microscopical examination of lungs. The lung tissues collected at 5dpi were fixed in 10% phosphate-buffered formalin for histopathological examination which was performed as described previously [37] [38] [39] . Briefly, samples were processed for paraffin embedding and cut into 5-\u03bc m-thick sections. One section from each tissue sample was stained with hematoxylin and eosin (H&E) stain. Another section was processed for immunohistological staining with a rabbit polyclonal antibody (orb176401; Biorbyt, USA) against influenza A virus NP. Specific antigen-antibody reactions were visualized by using DAB Detection Kit (Polymer) (ORIGENE, Wuxi, China) and counterstained with hematoxylin.", "Total RNA in PAM cells or lung homogenates were extracted using TRIzol reagent at specified time points according to the manufacturer's instructions (Invitrogen). Oligo-(dT) primed cDNA was generated from 1 \u03bc g of total RNA per sample using Superscript III First-Strand Synthesis SuperMix (Invitrogen). The qRT-PCR mixture for each sample consisted of 10 \u03bc l 2 \u00d7 SYBR green PCR master mix (Applied Biosystems), 7 \u03bc l of nuclease-free water, 0.5 \u03bc l of each primer, and 2 \u03bc l of cDNA template. Amplification was performed using the 7500 real-time PCR system (Applied Biosystems) with the following program: 1 cycle at 95 \u00b0C for 10 min, followed by 40 cycles of 95 \u00b0C for 15 s and 60 \u00b0C for 1 min. Expression values for each gene, relative to RPL4, were calculated using the 2 \u2212\u25b3\u25b3CT method. Each experiment contained three technical replicates for each sample, with two experimental replicates performed. Primers for qRT-PCR analysis of pig IFN-\u03b1 /\u03b2 are listed as following: IFN-\u03b1 , Forward, 5\u2032 -GCCTCCTGCACCAGTTCTACA-3\u2032 , Reverse, 5\u2032 -TGCATGACACAGGCTTCCA-3\u2032 ; IFN-\u03b2 , Forward, 5\u2032 -TGCAACCACCACAATTCC-3\u2032 , Reverse, 5\u2032 -CTGAGAATGCCGAAGATCTG-3\u2032 .", "The severity of microscopic lung lesions was scored by the distribution or by the extent of lesions within the sections examined as follows: 0, no visible changes; 1, mild focal or multifocal change; 2, moderate multifocal change; 3, moderate diffuse change; and 4, severe diffuse change 40 . The detection of swine influenza antigen in lung was executed through a ranked sore of 0-4, which was used to evaluate the number of positive cells per section taken from each block, as previously described 41 . The indication of the scores was as follows: 0, no SIV-antigen-positive cells; 1, 1-10 positive cells; 2, 11-30 positive cells; 3, 31-100 positive cells; and 4, = or > 100 positive cells. Two independent pathologists scored all lungs and slides from blinded experimental groups." ] },{ "paper_id": "0df659d4611fe09f4fa6ef2c22ec087985182ccb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "0e046152bb9c537c62ed4c4616a0b627ccfc992a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Murine macrophage-like cells, J774A.1, were obtained from the American Type Cell Culture Collection (ATCC TIB-67). Cells were cultured in complete medium: Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum, Glutamax, and penicillin/ streptomycin at 37\u00b0C with 5% CO 2 .", "(1-((PBS -\u03b1 PA83 IgG)/(PBS -50 ng LeTx))) \u00d7 100. ", "In humans, the anthracis bacilli can cause three types of infections: cutaneous via abrasions in the skin, gastrointestinal through ingestion of spores in contaminated meat and inhalation when spores less than 5 uM um are deposited into the lungs [1] . The mortality rates vary between each form of the disease with cutaneous anthrax presenting as a self-limiting and treatable infection with only a 20% case fatality rate. When left untreated gastrointestinal infections can progress rapidly and have over 80% case fatality rates. Inhalation anthrax infections are rare but have a high case fatality rate (over 75%) even with antibiotic treatment." ] },{ "paper_id": "0e08edfdafcee24569ce5be73cec8acb26142ba8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Confirmation of an organized NS2B protein structure on eukaryotic membranes", "Cells infected with DENV undergo a series of detrimental functional and structural changes, such as cell rounding, shrinkage, and dislodgment from the growth surface [3] . In addition, the membranes of DENV-infected cells are compromised during viral RNA replication, assembly, and egress, which induce remodeling and redistribution of distinct cell membrane structures [4, 5] including the rough endoplasmic reticulum (ER) and Golgi apparatus [6] . These phenomena result in dramatic cytopathic effects that compromise the viability of infected cells.", "Dengue viruses (DENVs) are enveloped (+) sense RNA viruses belonging to the Flaviviridae family. The DENV replication cycle initiates following receptor binding to the host cell membrane, which is followed by internalization via endocytosis and subsequent release into the cytoplasm. The genome is then translated into a large polyprotein, which is proteolytically processed to yield 3 structural proteins (envelope, membrane precursor, and capsid) and 7 non-structural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) [1, 2] ." ] },{ "paper_id": "0e1c072b035756104151484e6548cac0517cc5f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(a) Select a pattern, p, with maximal score in H. ", "1. J = \u2205", "V in {1... N} (a) Sort V by \u2211 k = 1...N c ik (b) generate_matrix(J, V) function generate_matrix(J, V) 1. While length(V) > 0 (a) k = shift(V) (b) if(|J| = 0 or \u2211 i\u2208J c ik > 0 or -\u2211 i\u2208J c ik 10 5 L \u22121 ), and considerable technical skill and expertise for accurate analysis." ] },{ "paper_id": "10829aeda495398ba475afbd713e36bdc58cfcd0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Having established that only intracellular signals are taken into account, it is still challenging to distinguish between intact and degraded forms of peptide or cargo. In two studies, a fluorescence-based quantification method was combined with either HPLC analysis [163] or \"cell activity by capillary electrophoresis\" [165] to verify the integrity of cargo and carrier.", "PEI covalently modified with the HIV-1 gp41-derived peptide HGP led to a 38-fold increase of gene expression after plasmid DNA delivery and also enhanced siRNAmediated knockdown of GAPDH by approximately 2-fold [199] . 30 % of cells incubated with PEI-HGP polyplexes showed not only the punctuate plasmid DNA staining observed with PEI polyplexes alone, but also a diffuse fluorescence throughout the cell, indicative of endosomal release of vectors. This would explain the observed increase in transfection efficiency, since the overall uptake was unaffected.", "In principle, either the peptide or the cargo can be labeled by a reporter group, e.g. a radioisotope [156] or a fluorophore [157] . Fluorescent peptides or cargos have been quantitatively evaluated by FACS [54] or fluorescence correlation microscopy (FCS) [158] or FRET [159] . In all cases, it is crucial to distinguish between internalized and membraneassociated signals. For this purpose, a simple wash step with just buffer is not sufficient to completely remove membranebound peptide/cargo-complexes [54, 55] . Extracellularly bound complexes can be efficiently removed for example by enzymatic digestion with trypsin [160] , acid wash [161] or heparin treatment [55, 162] . Alternatively, discrimination between intra-and extracellular material is possible through chemical modification of extracellular components [163] or fluorescence quenching [164] .", "In another approach, Jiang et al. [175] extended the 3' end of the sense strand of a siRNA with a nuclease-resistant DNA hairpin to obtain a so-called \"crook\" siRNA. This modification had no effect on RNAi-mediated reporter gene inhibition and served as a primer for a filling-in reaction followed by PCR. Parameters were chosen so that the initial rate of template amplification correlates with the initial con-centration of the \"crook\" siRNA. Under these conditions, quantification of attomolar siRNA levels per cell was possible after liposomal transfections with Oligofectamine." ] },{ "paper_id": "108b012df7e6ae774a2a83243c0662f376637426", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The experimental protocol was approved by the Iowa State University Institutional Animal Care and Use Committee (Approval No. 2-14-7742-S; approved on the 5 th of March 2014).", "The selected commercial SDPP was incorporated into a nonpelleted, complete feed, at a final inclusion of 5%. Based on average intake of 215 g/d for a 28 day old pig fed for 28 d, average plasma consumption was 10.5 g/d, for a total consumption of 301 g of SDPP per pig. In addition, a diet without SDPP was also produced to provide equivalent dietary energy and lysine compared to the diet containing SDPP.", "doi:10.1371/journal.pone.0104766.t004", "Porcine epidemic diarrhea virus emerged in North America in April 2013 [1] . Since the initial discovery, PEDV has spread rapidly through the pig population and is present in 30 U.S. States, Canada and Mexico as of May 2014. PEDV, an Alphacoronavirus, is a member of the Coronaviridae family which is a group of single-stranded, positive-sense RNA viruses [2] . PEDV isolates can be divided into genogroups 1 and 2 [3] ." ] },{ "paper_id": "108ebac20ee26fd05a2ba7ad43523957c34d871e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Here t~t{t i . At time t~t i ,", "From Eqn. 4, it can be determined that when", "then" ] },{ "paper_id": "10905e5423cc57fa9bd97aba8a348a3866953874", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication. ", "All these approaches have explored different scenarios to evaluate the more efficient therapeutic combination that seems to move toward personalized vaccinations for cancer patients." ] },{ "paper_id": "1090afa5b76644ce9e3be9d9d0e67ad651f846d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thiobarbituric derivatives were synthesized as shown in Fig 2. Reaction between benzoyl chloride 10, ammonium thiocyanate and the opportune amine led to intermediates 11a and 11b; consequent hydrazinolisis and coupling reaction with diethylmalonate 13 in basic conditions furnished monoalkylated thiobarbituric derivatives 14a and 14b. Finally Knoevenagel condensation with aldehyde 6 in refluxing acidic EtOH led to compounds 15a and 15b.", "The majority of emerging or re-emerging viruses are zoonoses, and it has been demonstrated that the passage among different species is easier for enveloped viruses in comparison a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "(Z)-4- (5-((1-benzyl-4,6- 179.42, 171.68, 162.05, 161.72, 160.30, 159.71, 158.73, 151.34, 138.28, 136.86, 134.45, 131.61, 130.83, 128.57, 127.31, 116.43, 114.46, 113.68, 113.38, 113. " ] },{ "paper_id": "10978f83e192204ea4f2347d49886969558a8b99", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Site-directed mutagenesis method was employed for the generation of ZIKV fragments containing the desired UFS mutations, the generated Not I-Avr II restriction fragments were then subcloned into the infectious clone of ZIKV strain FSS13025 (Shan et al., 2016) , which was kindly provided by Professor Pei-Yong Shi.", "The DENV4 mini-genomes were constructed by joining various 5 0 -300 nt fragments with the 3 0 UTR sequence using overlapping PCR techniques. The mutations targeting cHP and 5 0 CS were also introduced by overlapping PCR.", "The following source data is available for figure 9:" ] },{ "paper_id": "109a7800d93fdf2a2c64a261aab1182dd5b607af", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results were analyzed by a chi-square test the using SPSS 17 software. A P value < 0.05 was considered statistically significant.", "This study was performed in accordance with the principles expressed in the Declaration of Helsinki and approved by the Ethics Committee of the China-Japan Friendship Hospital. Informed consent was obtained from all patients.", "There are some limitations of this study. This study is limited by virtue of the retrospective analysis at only one center. And there was no randomized and blinded control group with conservative treatment in this study." ] },{ "paper_id": "10a769cac0a76b41a6a82be148c1a2675e9d4604", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The expression of various receptors was assessed with monoclonal antibodies and detected using the Accuri C6 flow cytometer (BD Biosciences). To measure endogenous hTIM1 expression, cells were stained with mouse anti-hTIM1 antibody (clone 219211, R&D Systems) or purified mouse Fc (mFc) as a negative control.", "Relevant SwissProt accession numbers are Q96D42 (hTIM1), Q8TDQ0 (hTIM3), Q96H15 (hTIM4), P30530 (hAxl), Q9BYF1 (hACE2), P02786 (hTfR1) and O15118 (NPC1).", "Text S1 Molecular causes underlying the inefficient viral usage of TIM3. (DOC)", "The plasmids encoding N-terminally myc-tagged human ACE2 (hACE2) and civet cat ACE2 were previously described [37] . Also previously described were the expression plasmids encoding the entry glycoprotein precursors of Zaire EBOV (Mayinga) and Lake Victoria MARV (Musoke), both lacking the mucin domains, Amapari virus (AMAV, BeAn 7063), Tacaribe [37] [38] [39] [40] [41] [42] [43] . The precursor of the Oliveros virus (OLIV) entry protein was synthesized by GenScript based on Genbank ID AAC54654.1 and was cloned into pCAGGS." ] },{ "paper_id": "10a9a18d6d821b917178be32b20f98c9e21d6028", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following human stool samples were provided by the National Reference Center (NRC) for HAV/HEV (Villejuif, France): HAV GIA (stools no. 780627147; 1181216151), HAV GIB (1280210015; 1280514230), HEV G3c (1280511146), HEV G3f (1280418084; 1280530128) and HEV G4 (1280615097; 1280522166).", "The Poisson distribution was used to estimate the average number of template copies per chamber in a panel [24, 25] . All samples were characterised by a corresponding absolute quantity. No positive chambers were observed in negative samples.", "Four viral strains were obtained from infected cell culture supernatants: two enterovirus strains (human B6 coxsackievirus (Schmitt strain: ATCC 1 VR-1037AS/MK\u2122) and human echovirus 19 (Burke strain)), one Adenovirus 40 strain (ATCC VR-931) and one Astrovirus GI strain.", "Nine nl of reaction volume mix were charged onto each of the 2304 chambers on the chip with the IFC controller MX." ] },{ "paper_id": "10abe76a05511196ea1f252383f0c70d592e7444", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lung weight and lung viral titres were compared across arms using ANOVA, with day of necropsy entered as a covariate. Differences between treatment groups were estimated using marginal means, with Sidak's adjustment for multiple comparisons. Statistical analyses were performed using SPSS version 15.0 (SPSS Inc. USA). Statistical significance level was set at a = 0.05.", "A complete macroscopic post-mortem examination was performed on all animals. This included examination of the external surfaces and all orifices; the thoracic, abdominal and pelvic cavities with their associated organs and tissues; and the neck with its associated organs and tissues. Lungs were weighed and all lung lobes were inspected and lesions described. The left lung (including trachea) was collected during autopsy, inflated with 10% neutral buffered formalin for fixation/histology and microscopic examination. Paraffin embedded tissue sections (left cranial lobe, left caudal lobe, right cranial-, middle-and caudal lobes and accessory lobe) were stained with haematoxylin and eosin and assessed by light microscopy for aspects like congestion, emphysema, presence of foreign body, haemorrhagy, bronchioloalveolar hyperplasia and inflammation, and oedema." ] },{ "paper_id": "10c5b88204b337e7d05aceba5fc73d041153d0d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RT-PCR was performed using a SuperScript II onestep RT-PCR Platinum Taq kit (Invitrogen, Carlsbad, CA, USA) to obtain cDNA. Conventional PCR was performed using Ex Taq polymerase (Takara, Otsu, Japan). All products were subjected to electrophoresis on a 2% agarose gel. PCR/RT-PCR protocols for each virus were available in detail (see Supplementary 1 available online at http://dx.doi.org/10.1155/2013/869521).", "Chi-square test with a significance level of < 0.05 was conducted to compare infection rates among different patient groups.", "The seasonal distribution of EV was regular, remaining at a stable detection rate (0.81%) throughout spring before reaching a peak in summer. No cases were observed from " ] },{ "paper_id": "10ce102dd3c76f690ebe84048a5d734598b3d2f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Facebook, the most popular social networking website [1], has invigorated a wide range of health sciences studies. Facebook use for disease surveillance [6] or public health issues [7] [8] [9] shows its broad scope for improving public health. Researchers have also used Facebook to address specific health concerns. For example, studies have been conducted to assess Facebook's potential in engaging smokers in smoking cessation treatment [10] and to evaluate it's scope in recruitment and retention of young adult American veterans into an online alcohol intervention study [11] . While most Facebook based health studies focus on information dissemination to individual users, surprisingly few have focused on how health agencies are involved in Facebook based communications [12] [13] [14] . This paper addresses this gap.", "We included features that are generally used in Facebook-based studies [12, 31, 32] as well as those that are seldom considered (see Table 1 ).", "The Facebook Graph API [30] was used to collect all posts from an account's timeline as of late January 2013. For each post, we recorded its unique identifier, number of likes, shares, comments and other metadata as described below.", "The Facebook Graph API provides information about the type of a particular post. Posts are classified into six selfexplanatory categories, namely link, music, photo, question, status (a post is an uncategorized status if it is simply textbased and does not belong to any of the other categories), and video/Adobe's ShockWave Flash format (SWF). ", "One aspect of Facebook analysis that is often overlooked is post content. We hypothesize that some topics are more attractive to a wider group than others. For example, a post about information dissemination of the outbreak of West Nile virus (\"West Nile virus is a potentially serious illness. What you need to know: http://go.usa.gov/r9g4\") generated far more activity compared to a job posting from U.S. Public Health Service Nurses (\"National Park Service has a Registered Nurse Manager position open in Yosemite, CA. This position closes on November 19. If interested, please send a cover letter and CV to S**** C**** at email@nps.gov.\").", "The coefficients of the logit regression in the zero portion of the model indicate how the features relate to crossing the 'hurdle' of obtaining at least one activity (i.e. either a like, share or comment). " ] },{ "paper_id": "10dab751e09a2f4ef5a81f68b82c76c8be09343f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "10dd2aeb61d54b45337a96f3c6243b72d6764732", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(ZIP)" ] },{ "paper_id": "10e691d6bf9cfc219bb72a2761d37ae5f1677f77", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "10f4664e4d1e58018892a7a2ab1eae868d59f2f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Simplifying gives", "Since", "Then we have g\u00f00\u00de \u00bc L \u00c0 m\u00f0s\u00fem\u00de\u00f0g\u00fem\u00de bs > 0 when R 0 > 1, g\u00f0 rsL d\u00f0s\u00fem\u00de \u00de \u00bc \u00c0 m\u00f0s\u00fem\u00de\u00f0g\u00fem\u00de bs < 0, and g 0 \u00f0M\u00de \u00bc h 0 \u00f0M\u00de\u00f0L \u00c0 d\u00f0s\u00fem\u00de rs M\u00de \u00c0 d\u00f0s\u00fem\u00de rs h\u00f0M\u00de < 0 holds true for any M satisfying L \u00c0 d\u00f0s\u00fem\u00de rs M > 0. Thus there must exist one and only one positive root M \ufffd < rsL d\u00f0s\u00fem\u00de that satis-" ] },{ "paper_id": "10f63acdd41437902fb627803c57d57dec2c4716", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Despite the global distribution of IBV, poultry in Finland remained free of clinical cases until April 2011 [9] after which outbreaks involving several CoV genotypes have occurred in Southern Finland.", "ARTICLE HISTORY" ] },{ "paper_id": "10f87d75360ca119636fcd75da502bcb0bf7845d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "[Male participant (P23), 65 years old]", "[Male participant (P8), 34 years old]", "[Male participant (P32), 35 years old]" ] },{ "paper_id": "10fbf7274b0bdfe7153269489851fc3d8f121bcd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rotavirus (RV) is the primary etiological agent of severe dehydrating diarrhea in young children worldwide, and is responsible for almost half a million deaths annually [1, 2] . In 2006, two live attenuated RV vaccines, RotaTeq and Rotarix, were introduced to the market and are now licensed for use worldwide. Studies thus far indicate that these vaccines are both safe and effective at preventing RV-associated disease and mortality although their efficacy is significantly diminished in the poorest countries of Asia and Africa [3] .", "Viral particles were first concentrated from RRV-infected MA104 cell lysates by genetron extraction and pelleting over a sucrose cushion. DLPs were then generated by treating the particles with 10 mM EDTA to remove the outer VP4/VP7 layer, followed by cesium chloride density gradient centrifugation as described [77, 78] . DLPs were dialyzed against tris-buffered saline (TBS). DLP concentration was determined by Bradford assay. DLPs were aliquoted and stored at -80\u00b0C.", "RV RNA synthesis is carried out by the endogenous, virionassociated RdRP, VP1, and the virion-associated guanylyltransferase and methyltransferase, VP3 [6] . RV transcripts possess a type I 5' cap structure, m 7 GpppGm [56] . We postulated that if capping by VP3 is not 100% efficient, some of the RV mRNAs extruded into the cytoplasm might have exposed 5' phosphates, a known RIG-I ligand [12, 13] . Second, if the VP3 methyltransferase activity is not completely efficient, then some of the transcripts may contain incompletely 2'-O-methylated 5' caps, a molecular signature that has been shown to induce IFN in an MDA5-dependent manner [24] ." ] },{ "paper_id": "11022b299f98034d0060f9c036333f1b9024d7a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and Oklahoma were the states with the most diagnostic case submissions testing positive for PEDV [10] . Subsequently, PEDV has continued to spread rapidly and as of June 2014 has been confirmed in 30 states in the USA [10] .", "Evidence of airborne transmission of enteric pathogens (bacteria and viruses) has been shown previously [12] . Drying of swine feces due to increase in temperature and resuspension of feed deposited on the floor of pig buildings can result in the generation of dust able to adsorb and carry microorganisms and odorous compounds [11] . We speculate that this is one likely mechanism by which PEDV became aerosolized and remained suspended in the air, and may contribute to both within farm transmission and area spread in high density pig regions. Furthermore, PEDV has a low infectivity dose and is able to survive in the environment for extended periods facilitating the risk of disease transmission [15] .", "To determine whether PEDV could become airborne under field conditions, 8 swine herds located in Oklahoma (US) and belonging to one production company were identified. Finishing and breeding herds that were experiencing acute PEDV outbreaks during each day of air collection throughout the study were purposively selected. Air collection was conveniently performed at different locations downwind, ranging from 0.006 to 15 miles (9.6 m to 24.14 km) from each of the farms starting from the furthest distances each day. A total of 62 samples were collected using an air cyclonic collector as described above for 30 min, with samples stored on dry ice and submitted to the UMN VDL for PEDV RT-PCR testing." ] },{ "paper_id": "11115aa43542f817d78ca0c8ec2b50e04eb7cc17", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It is known that the degree of pathogenicity depends on the virus species, with 5 species ( Zaire ebolavirus, Sudan ebolavirus, Bundibugyo ebolavirus, Tai Forest ebolavirus, and Reston ebolavirus) identified to date. Ebolaviruses belonging to Reston ebolavirus (REBOV) do no cause symptomatic disease, whereas those belonging Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 SCIenTIFIC REPORTS | (2018) 8:5495 |", "Statistical analysis. Student's paired t-test was used to determine the statistical significance of the differences. A p-value of less than 0.05 was considered statistically significant.", "Ebolaviruses comprises 5 species that exert varying degrees of mortality/infectivity in humans with" ] },{ "paper_id": "111968f7fb102882c193488965e41d5d0f0103dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Input buffers are continuously polled by the corresponding component and processing continued once data is available. An adjustable buffer length according to load expectation helps to prevent overflows.", "For instance, Figure 9 shows a screenshot of the implemented sequential workflow for a distance based phylogenetic analysis." ] },{ "paper_id": "111db95189df3fa90756c174fbb5abff1ca1bb01", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The performance of the prediction models were evaluated by several measures: sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), Matthews correlation coefficient (MCC) and the area under the ROC curve (AUC), which are defined as follows ", "where" ] },{ "paper_id": "111e82fd55d8b42cd523cf365b53dfcdaa2165d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HI Titer VN Titer LaSota 6.7 \u00b1 0.41 0 rNDV-IBV-T/B 6.6 \u00b1 0.32 6.82 \u00b1 0.26 PBS 0 0", "The ciliostasis activity of the tracheal explants was examined on 10 tracheal ring explants per chicken (5 chickens of each group) 5 dpc. The tracheas were carefully removed and examined for ciliary activity within 2 h after collection as described in the referenced papers [43, 44] . Briefly, 1 to 2 mm sections from the middle of each trachea were prepared and examined under a low-power microscope, and ciliary activity was scored as follows: 0, denotes all beating cilia; 1, 75% beating; 2, 50% beating; 3, 25% beating; and 4, absence of beating (100% ciliostasis). A maximum possible ciliostasis score of 40 suggested complete ciliostasis (total lack of protection).", "Vaccines 2019, 7, x 6 of 15" ] },{ "paper_id": "11227aa67f131d1b8220d5c45b4bf592f0a48ef4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Target peptide (2554.6) containing fraction obtained above were loaded onto a home-made C18 column (100 mm \u00d7 100 \u03bcm) packed with Sunchron packing material (5 \u03bcm) and followed with nano-LC-ESI-MS/MS analysis without digestion. The LTQ mass spectrometer (Thermo Finnigan, USA) was operated in a datadependent mode, in which the initial MS scan recorded the m/z ratios of ions over the mass range from 400-2000 Da firstly, and then the five most abundant ions were automatically selected for subsequent collisionactivated dissociation." ] },{ "paper_id": "112c03868171e79e5f64b72e7c837fd4875d88f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ZNA probes provide broad flexibility with respect to experimental design and represent an effective alternative to minor groove binder-DNA and locked nucleic acid probes [26] .", "Student's t-test was used to compare the viral loads between the various clinical symptom groups. The correlation between PRRSV and PRDC was evaluated using the chi-square test with Yate's correction. P values <0.01 and <0.001 were considered significant and highly significant, respectively. ", "A novel type of modified oligonucleotides known as ZNA was recently developed as a method for the clinical diagnosis of pathogens, such as the hepatitis B virus [27] . ZNAs are able to discriminate between complementary sequence that are a perfect match and those that are mismatched by a single base pair [25] . ZNAs are particularly efficient at low magnesium concentrations, low primer concentrations and high annealing temperatures [25] ." ] },{ "paper_id": "11416bee008daf3c42621002ba7f3a6939601b0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tetherin inhibits the release of not only HIV-1 but also that of a broad spectrum of other enveloped viruses, including alphaviruses, filoviruses, rhabdoviruses, arenaviruses, herpesviruses, paramyxoviruses, flaviviruses, orthohepadnaviruses, orthomyxoviruses, and other retroviruses (reviewed in [23] [24] [25] ). Many of these viruses have evolved diverse strategies to antagonize tetherin. HIV-1 Vpu counteracts human tetherin by reducing its cell-surface expression via lysosomal and proteasomal degradation [26] [27] [28] [29] [30] [31] [32] [33] [34] or by trapping tetherin intracellularly and/or preventing its recycling back to the PM [1,2,32,35-38]. The specificity of HIV-1 Vpu towards tetherin antagonism also varies from species to species. HIV-1 Vpu counteracts tetherins from human, chimpanzee, and gorilla; however, it is relatively inactive against tetherin from other non-human primates and non-primates [28, [39] [40] [41] [42] . Simian immunodeficiency virus (SIV) and HIV-2, which do not encode a vpu gene, antagonize tetherin through their Nef and envelope (Env) proteins, respectively, in part through an intracellular sequestration mechanism [29, 39, [42] [43] [44] [45] [46] [47] [48] .", "HeLa or 293T cells were transfected with HIV-1 molecular clones, virions were collected after 24 h, pelleted in an ultracentrifuge, cell and virus pellet were lysed in a buffer containing 50 mM Tris-HCl (pH 7.4), 150 mM NaCl, 1 mM EDTA, 0.5% Triton X-100, and protease inhibitor cocktail (Roche Life Sciences, Basel, Switzerland). After denaturation by boiling in sample buffer, proteins were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), transferred to polyvinylidene difluoride (PVDF) membrane, and incubated with appropriate antibodies as described in the text. Membranes were then incubated with horseradish peroxidase (HRP)-conjugated secondary antibodies, and chemiluminescence signal was detected by using West Pico or West Femto Chemiluminescence Reagent (Thermo Fisher Scientific, Waltham, MA, USA). The protein bands were quantified by using Imagelab-Chemidoc (Bio-rad Laboratories, Marnes-la-Coquette, France)." ] },{ "paper_id": "1146cc4ce6094ad35cc188166285b8c519986b6d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The complete genome sequence of PEDV strains JSLS-1/2015 and JS-2/2015 have been submitted to GenBank under the accession numbers KX534205 and KX534206, respectively.", "To our knowledge, this is the first report of a complete PEDV sequence isolated from dead pigs with a long-fragment deletion in ORF1b. So, further studies will be carried out to explore the virus's biological activities and pathogenesis in causing disease comprehensively.", "Two porcine epidemic diarrhea virus (PEDV) strains, JSLS-1/2015 and JS-2/2015, were isolated from piglets with watery diarrhea in South China. Two genomic sequences were highly homologous to the attenuated DR13 strain. Furthermore, JSLS-1/2015 contains a 24-amino-acid deletion in open reading frame 1b, which was first reported in PEDV isolates." ] },{ "paper_id": "114b18b271ebb99486d88b94f526864870ec4f11", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "11588188717735eb36e684003283dbe2d9832286", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Taken together, the NPC1 protein is a filovirus receptor with unexpected characteristics: In comparison to cell surface receptors used by other viruses, NPC1 is unique in recognizing the filoviral glycoprotein only after uptake into the cell and after proteolytic processing. The identification of small molecule inhibitors directly or indirectly inhibiting NPC1-usage by GP 1,2 for host cell entry [20, 129] makes it an attractive candidate for antiviral therapy.", "Integrins are cell surface expressed heterodimeric type I transmembrane glycoproteins, which are composed of two non-covalently linked subunits (\u03b1 and \u03b2) [122] . The integrin family in mammals comprises eighteen \u03b1 and eight \u03b2 subunits which can assemble into 24 different heterodimers [139] . These heterodimers, in turn, convey specificity to cell-cell and cell-extracellular matrix adhesion, immune cell recruitment, extravasation, and signaling events [121, 140] . Members of the integrin family have been discovered as attachment factors or receptors for a large number of enveloped and non-enveloped viruses, including herpesviruses [141] [142] [143] , adenoviruses [144, 145] , hantaviruses [146] [147] [148] [149] , picornaviruses [150] [151] [152] , and reoviruses [153, 154] . The association with viral surface proteins and microbial pathogens are followed by multiple signaling events, some of which promote cytoskeletal reorganization and thus facilitate receptor-mediated endocytosis (as reviewed in [155, 156] and references therein). It is not surprising that numerous viruses hijack integrins for infectious entry, as they are widely expressed in various tissues throughout the body ( Table 2) .", "Filovirus infection causes severe hemorrhagic fever in humans and non-human primates. Outbreaks of filovirus hemorrhagic fever occur in equatorial Africa and are associated with high case-fatality rates [1] . At present, neither vaccines nor antiviral drugs have been approved for combating filovirus infection. The filoviridae family comprises two genera, Ebolavirus (the ebolaviruses) and Marburgvirus (the marburgviruses). The genus Marburgvirus includes a single species, Marburg marburgvirus, which has two members, Marburg virus (MARV) and Ravn virus (RAVV). The genus Ebolavirus includes five species, each of which has a single member: Zaire ebolavirus (Ebola virus, EBOV), Sudan ebolavirus (Sudan virus, SUDV), Ta\u00ef Forest ebolavirus (Ta\u00ef Forest virus, TAFV), Bundibugyo ebolavirus (Bundibugyo virus, BDBV) and Reston ebolavirus (Reston virus, RESTV) [2, 3] . Filoviruses exhibit different virulence in humans: EBOV and MARV infection is associated with case-fatality rates of up to 90% [4, 5] while RESTV seems to be apathogenic [6] [7] [8] . Nevertheless, infection of non-human primates with RESTV can induce hemorrhagic fever [9] . Evidence is emerging that African [10] [11] [12] [13] , Asian [14] and possibly also European [15] bats are natural reservoirs of filoviruses and these animals could transmit the virus directly to humans or via intermediate hosts, including gorillas [16, 17] and swine [6, 14, 18] . Thus, filoviruses pose a threat to human and animal health in different continents, but virulence factors and pathogenesis are incompletely understood.", "Many viral GPs are synthesized as inactive precursor proteins which transit into a membrane fusion-competent state only upon proteolytic cleavage by host cell proteases, a process termed priming. A prominent example is the influenza virus, which depends on cleavage of its hemagglutinin by host cell proteases for acquisition of infectivity, and the nature of the cleavage sequences in HA determines the virulence of avian influenza viruses [166] . The subtilisin-like proprotein convertase furin is responsible for priming of several viral GPs in the Golgi apparatus of infected cells, and furin consensus sites are present in GP 0 of all filoviruses excluding RESTV, which harbors an incomplete furin recognition site [32] . Despite of its conservation, several studies indicate that this motive is dispensable for filoviral spread in cell culture and infected animals [46, 47] , and the reason for its presence is unknown." ] },{ "paper_id": "1174cadd31854c1128f0bbf2a61d31b2b72f61c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two investigators (KPK and SWHL) independently screened the titles and abstracts. Full texts of relevant articles were retrieved and reviewed independently to determine eligibility for inclusion in the review. Any disagreement was resolved through discussion.", "Data regarding study design, participants, interventions, clinical outcomes, and adverse events were independently abstracted by two investigators (KPK and SWHL) using a standardized data collection form. We also contacted five corresponding authors for additional information [17] [18] [19] [20] [21] and two responses were received [17, 20] .", "Supporting information S1 " ] },{ "paper_id": "118373b29085c6212547a34993be16eb98008dd0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1185137c3c9ddbc0c91aa718179dadd11039f771", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell culture. 293T Antibodies. The following antibodies were used as primary antibodies: Anti V5 (Invitrogen), anti \u03b2-actin (Sigma-Aldrich), anti VSV-M (Kerafast). As secondary antibody, an anti-mouse HRP (horse radish peroxidase) conjugated antibody was employed (Dianova). All antibodies were diluted in phosphate buffered saline containing 0.5% Tween20 (PBS T) and 5% skim milk.", "Plasmids. We employed pCAGGS-based expression plasmids encoding vesicular stomatitis virus (VSV) glycoprotein (VSV-G), wild-type (wt) MERS-S or cleavage site mutants 748 SSVR 751, 748 ASVA 751, 763 NYT 765, 884 ASAA 887 and 748 ASVA 751 + 884 ASAA 887 that have been described previously 10, 16, 21, 23 . Additionally, MERS-S-proteins containing single amino acid exchanges at the cleavage sites of the S1/S2 border, ASVR (R748A) and RSVA (R751A), or the S2\u2032 site, ASAR (R884A) and RSAA (R887A), were generated by overlap extension PCR (S protein mutants are summarized in Fig. 1 ). For all S proteins, we constructed versions with or without a C-terminal V5 tag. Further, we generated expression plasmids for human TMPRSS2 and human DPP4 N-terminally linked to DsRed (DsRed DPP4) by PCR-based methods and inserted the respective open reading frames and into the pQCXIP vector. In case of the expression vector for TMPRSS2, the vector encoded selection marker for puromycin resistance was exchanged by that for blasticidin resistance taken from the (pcDNA6/TR) vector. The integrity of the PCR-amplified sequences was verified by automated sequence analysis (Microsynth Seqlab).", "SCientifiC REPORtS | (2018) 8 :16597 | DOI: 10 .1038/s41598-018-34859-w sufficient for S protein-driven entry. The S protein is synthesized as an inactive precursor and is converted into its active form upon cleavage by host cell proteases 8, 9 . In fact, proteolytic processing of MERS-S might be sufficient to trigger the membrane fusion reaction and is subsequently referred to as activation. The host cell proteases responsible for MERS-S activation constitute potential targets for antiviral intervention and the identification of their cleavage sites might instruct the generation of inhibitors. Therefore, the proteolytic activation of MERS-S is in the focus of ongoing research endeavours." ] },{ "paper_id": "11855c4ce9640d35da8dd4c54e913843a41c9252", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Acute respiratory infections (ARI) are prevalent worldwide and infections by influenza virus are particularly responsible for morbidity and mortality among children and other groups considered at high risk for complications from viral infections [1, 2] .", "Routine clinical evaluations, including the Pediatric American College of Rheumatology 30% (ACRPed30) [14] were conducted during both surveillance periods prior to and at 30, 90 and 180 days after influenza vaccination.", "Nucleic acids were extracted from 200 \u03bcL of sample using the QIAamp MinElute Virus Spin Kit (Qiagen, Hilden, Germany) following the manufacturer's instructions. Detection of respiratory viruses was performed by real-time PCR (qPCR) using the TaqMan strategy (Applied Biosystems) with specific primers and probes (Additional file 1) [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] in a Thermocycler 7300 (Applied Biosystems). qPCR for the housekeeping \u03b2-actin gene was done in all samples as internal control. qPCR for HRSVA and B; HCoV OC43 and 229E; two sets of HRV serotypes; and HAdv and HBoV were done in duplex format, whereas single qPCR with only one pair of primers per reaction was done for HMPVA, HMPVB, influenza A, influenza B, HPIV1, HPIV3 and \u03b2-actin. For RNA viruses (HRV, influenza, HPIV, HRSV, HMPV and HCoV) reverse transcription was done prior to PCR using Multiscribe reverse transcriptase (Applied Biosystems) with 1 \u03bcg of RNA, primed with random hexamers, following the protocol proposed by the manufacturer detailed in the Additional file 1. [32] . Local symptoms at the injection site and systemic symptoms were recorded." ] },{ "paper_id": "1185a17f1cb650e0433ab8c84202cc242c54f6cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HCWs where effective pharmaceutical interventions may not be available, e.g. the 2003 severe acute respiratory syndrome (SARS) epidemic and the Middle East Respiratory Syndrome (MERS) outbreaks since 2012 [2, 3] .", "We would like to thank Abrar Chughtai for his contribution to the study." ] },{ "paper_id": "11914635e8fc7c041e815263d5e20ca4ad9166bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "to thank the broilers farm's owners for their cooperation and patience during samples collection.", "All Authors declare that they have no conflict of interest.", "ARTICLE HISTORY" ] },{ "paper_id": "119585987862e9f02ef0a1748462fb38ecb95b53", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Where do we go from here?", "Editorial" ] },{ "paper_id": "1196301d4e04f2283f18f95fbbbd6bc5cf6e341f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Goat and sheep sera were obtained from Innovative Research.", "Vero cells (African green monkey kidney epithelial cells) were grown in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% FBS, 1% penicillin/streptomycin, and 1% glutamax (DMEM+++) in a humidified environment containing 5% CO 2 at 37\u00b0C.", "The experiments described in this paper used a live attenuated vaccine (MP12) derived from the RVFV ZH548 strain that had been isolated in 1977 from a patient with uncomplicated RVFV. The virus was generated by 12 serial passages in MRC5 cells, inducing 25 nucleotide changes across the viral genome [14] ." ] },{ "paper_id": "11a3797796973b32b0763f8127b908f4783e5734", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The identity of the heavy and light chains of each MAb was determined using Pierce Rapid Isotyping Kit with Kappa and Lambda Mouse (Thermo, Rockford, IL, USA).", "Care of laboratory animals and animal experimentation was performed in accordance with animal ethics guidelines and approved protocols. All animal experiments were approved by the Animal Ethics Committee of Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences. The Animal Ethics Committee approval number was SYXK (Hei) 2011-022.", "Virus-infected cell lysates or expressed fusion proteins were subjected to electrophoresis on 12% SDS-PAGE after reduction with dithiothreitol (DTT) at 100uC for 5 min, then the samples were transferred to a nitrocellulose membrane. Nonspecific antibody binding sites were blocked with 5% skimmed milk powder in PBS overnight at 4uC. The membranes were incubated with MAbs as the primary antibody, after which each blot was washed five times with PBST and treated with IRDye 700conjugated goat anti-mouse secondary antibodies (LICOR Biosciences, NE, USA). Blots were visualized by scanning the membranes with a LICOR Odyssey infrared image system (LICOR Biosciences)." ] },{ "paper_id": "11ad2acc16067afbf2ce40d422647c3d899ecbd4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IRD are a leading cause of morbidity and mortality in humans. They cause great disruptions in many sectorseconomic, educational, recreational, and familial -and can bring worldwide healthcare systems to near collapse. IRD, whether bacterial, mycotic or viral, are transmitted to non-infected persons when an infected individual expels droplets loaded with pathogenic microorganisms during coughing.", "The end result of this debate will have a direct influence on social distancing (i.e. how far apart people should position themselves to prevent infection) and on whether current recommended primary prevention measures and commonly used personal protective equipment are effective barriers to transmission.", "This was an observational study in which all the participants, in an open bench format, were encouraged to give their best effort to voluntarily elicit a \"real cough\" three separate times.", "Textbooks in Medicine and in other health related areas teach that infectious respiratory diseases such as Tuberculosis and Influenza have a common symptom: cough. Those textbooks also teach that via cough is how these diseases are spread and transmitted to noninfected susceptible individuals. Cough mechanisms are described in those textbooks with emphasis in clinical diagnostic and management of the individual with cough [7] [8] [9] ." ] },{ "paper_id": "11ae714b01d105e39919f2a6d9b2471153963d25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MDRGN have previously been defined as Enterobacteriaceae with extended spectrum beta-lactamase (ESBL)phenotype, and Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa resistant against piperacillin, any 3rd/4th generation cephalosporin, and fluoroquinolones +/\u2212 carbapenems [7, 25] .", "Patient's entry criteria for NIMCU were a stable circulatory constitution and respiratory status without the need of invasive ventilation neither non-invasive continuous positive airway pressure (CPAP).", "Parents were encouraged to visit their neonate 24 h a day. The total amount of visitors/baby was limited to two persons. At their first visit, all visitors received a short instruction of the hygienic rules performed by the attending nurse." ] },{ "paper_id": "11bf75e973011d86b1039b707ed086b98deb5642", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MM wrote and conceived the manuscript. AC, DM, and SM contributed to conception and generated data. BO, SV, and SM revised the manuscript, read, and approved the submission.", "This publication is part of a project entitled CurB-Sviluppo di nuove molecole candidate alla cura di HBV, funded by Regione Lombardia, Programma Operativo Regionale 2014-2020, Obiettivo Investimenti in favore della crescita e dell'occupazione (cofinanziato con il FESR), Asse Prioritario I-Rafforzare la Ricerca, lo Sviluppo e l'Innovazione, Azione I.1.b.1.3-Sostegno alle attivit\u00e0 collaborative di R&S per lo sviluppo di nuove tecnologie sostenibili, di nuovi prodotti e servizi-R&S Per Aggregazioni. Call per l'Attivazione di un percorso Sperimentale Volto alla Definizione degli Accordi per la Ricerca, Sviluppo e Innovazione. art. 11 della Legge 241/1990 1 ." ] },{ "paper_id": "11ccc8d0c6d5b3297821a0e39535ce9dcb4810ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Inclusion (all criteria required)", "2. Diseases: epidemic and pandemic respiratory infectious diseases. Namely, avian influenza, swine influenza, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS).", "3. Behaviors: preventive, avoidant, and management health-related behaviors (reported, intended, or actual)." ] },{ "paper_id": "11d016e4272c8a89fe7986afde61e6fb91908304", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Interferences between pathogenic bacteria and specific commensals are known. We determined the interactions between nasopharyngeal microbial pathogens and commensals during viral upper respiratory tract infection (URI) and acute otitis media (AOM) in infants.", "We obtained a total of 20,976,078 high-quality bacterial sequences comprising 13,982 unique operational taxonomical units (OTUs). Of 971 sequenced samples, 948 (98%) yielded ! 1000 There was no association between with age or sample type (p > 0.2 and p > 0.3, respectively). SDI by bacterial culture results are displayed in Fig 2A. The median SDI was 2.49 for samples with no otopathogen, compared to 2.04 in samples positive for S. pneumoniae only (P = 0.022); 1.82 for H. influenzae (P = 0.040); 2.41 for M. catarrhalis (P = 0.620) and 2.09 for 2 or more otopathogens (P = 0.048).", "We analyzed 971 specimens collected monthly and during URI and AOM episodes from 139 infants. The 16S rRNA V4 gene regions were sequenced on the Illumina MiSeq platform." ] },{ "paper_id": "11d9deb4869385080d322af3026110247fb4d145", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The whole-genome sequence of the hPyV4/USA/AR001/2016 isolate has been deposited in GenBank under the accession number KX787894.", "We report here the complete genome sequence of a WU polyomavirus (WUPyV) isolate, also known as human polyomavirus 4, collected in 2016 from a patient in Arkansas with an acute respiratory infection. Isolate hPyV4/USA/AR001/2016 has a double-stranded DNA genome of 5,229 bp in length.", "Here, we describe a novel WUPyV isolate from a nasopharyngeal swab collected from a 13-month-old male (hPyV4/USA/AR001/2016) with no significant past medical history who was seen in the emergency department (ED) of Arkansas Children's Hospital in Little Rock, Arkansas, USA, on 15 March 2016. His symptoms included nonproductive cough, wheezing, and increased work of breathing. The patient was afebrile, had a heart rate of 160, respiratory rate of 36, and S A O 2 at 95%. He was given vaponephrine and albuterol in the ED. He improved and was able to be discharged home with albuterol as needed." ] },{ "paper_id": "11dcdcd827d9e2a609a7396a335d6c9891d99c28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "11dfd91790da005937371365098de726ddfaec98", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "11f13e2859eb22b349dbef68fd8124b8ba445aac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "11f2984bccfb6cb8952bceea9209357821a0583a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "11f3022ad1def6dfb1b29712112b96739ff3c498", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We would like to thank LetPub (www.letpub.com) for providing linguistic assistance during the preparation of this manuscript.", "Ethics approval and consent to participate Not applicable Consent for publication Not applicable", "The authors declare that they have no competing interests." ] },{ "paper_id": "11f8eeb589bf8737b2805b3bb50ca12b73884c64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ", "Results are presented as mean \u00b1 the standard deviations (SD). Statistical comparisons were made by using Student's t-test. p value less than 0.05 was considered statistically significant and p value less than 0.01 was considered highly significant." ] },{ "paper_id": "11fe16ac2f99335e81c64bb6b83761ed5b700963", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In D. melanogaster, among various lncRNAs, the hsw\u03c9-transcript was reported to form perinuclear omega-speckles in the nuclei in response to heat shock [21] , roX1androX2 found in the male-specific lethal (MSL) protein complex affected dosage compensation [22] , yellow-achaete intergenic RNA(yar) lncRNA influenced circadian rhythms [23] , CASK regulatory gene CRG lncRNA regulated Ca 2+ /calmodulin-dependent protein kinase (CASK) transcription [24] , and Sphinx lncRNA influenced courtship behavior [25] .", "The knowledge in the field of lncRNAs, and their mode of action and function can provide deep insight into the evolution and function of genomes during host-pathogen interactions.", "The success of insects in adverse environments indicates the advanced defense mechanisms employed by these organisms. With the passage of time, some insect species became resistant to most pathogens, and some remained susceptible to various infections. Insects exhibit both humoral and cellular immune responses against pathogens. The lack of an adaptive immune system has forced insects to choose immediate non-specific responses that include the production of antimicrobial peptides, phenoloxidase, apoptosis, phagocytosis, encapsulation, and nodulation. With the advent of molecular biology techniques, a large amount oftranscriptome data has been published and reviewed on the model organism Drosophila melanogaster, while other insect species have been investigated to a lesser extent. Transcriptome sequencing provides information on all transcripts occurring in different cells and tissues [1, 2] , while RNA sequencing provides data on multiple classes of non-coding RNAs (ncRNAs) [3] [4] [5] [6] ." ] },{ "paper_id": "1204dc3b147d4e4d5ccc3d4aff7551d39f5fe438", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Respiratory disease (Asthma, COPD a ) 8", "Immunodeficiency (common variable immunodeficiency, HIV) 2", "Cancer (multiple myeloma, synovial cell cancer) 2" ] },{ "paper_id": "120aebc8b074393770c411ebf774ed18a5a2a1da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recherche M\u00e9dicale (M.D.). This is manuscript number 21323 from the Scripps Research Institute. We apologize to authors whose work we may have misinterpreted or failed to cite. ", "The hepatitis C virus (HCV) is a major causative agent of acute and chronic liver diseases worldwide. 130-170 million people are persistently infected with HCV and have a high risk of developing liver cirrhosis and hepatocellular carcinoma [8] . A hallmark of HCV is its high propensity to persist with up to 80-90% of infected individuals failing to eliminate the virus. A prophylactic vaccine is not available and its development has been seriously hampered by the high genetic variability of the virus. Treatment options for chronic HCV infection are also limited. Indeed the current therapy, a combination of polyethylene glycol-conjugated interferon-\u03b1 and ribavirin, is associated with numerous side effects, has many contraindications and on average only approximately 50% of those patients who can qualify for treatment, tolerate its toxicity, and complete six months of therapy are cured [9] . A large number of direct-acting antiviral agents are under development at this time with the hope of eventually replacing interferon and ribavirin as the treatment of choice for chronic HCV infection.", "Recently, several papers have been published that shed light on the ability of HCV to modulate the autophagy pathway and on the capacity of several autophagy proteins to positively regulate HCV productive infection [41] [42] [43] [44] [45] [46] . Here we review these recent advances, present our understanding of the mechanism(s) by which autophagy proteins can enhance HCV infection, and discuss the implications of those concepts for the survival of HCV in infected cells." ] },{ "paper_id": "12127085d9546a704eb677320d4df5b44f4dce8f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "http://orcid.org/0000-0003-0400-8635", "ARTICLE HISTORY" ] },{ "paper_id": "121638b718d18f7bb5086223540f74cf61e49800", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Her physical examination revealed that she was obese, had a body temperature of 39.0\u00b0C, a pulse rate of 112beats/ minute and blood pressure of 145/90 mmHg. Her respiratory rate was 20 breaths/minute with oxygen saturation of 94% on room air. Her chest auscultation was unremarkable. She had a widespread, erythematous maculopapular rash with scattered petechiae on both legs. Examination of the oropharynx revealed erythema but no exudate.", "The chest radiograph at presentation was abnormal in 90% of patients. The most common pattern of abnormality was bilateral interstitial infiltrates (57%), although lobar consolidation was also noted reasonably frequently (24%).", "Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.", "Of the 21 cases retrieved in our literature search, 57% of the patients were men, and overall the patients' median age was 40 years (age range, 18 to 60 years). Where recorded, the commonest ethnic origin of patients was Caucasian (40%). Significant co-morbidity was uncommon among patients, but obesity was frequently noted as an examination finding.", "A 44-year-old Caucasian woman was admitted to our emergency department with a three-day history of a febrile illness associated with sore throat, dry cough, myalgia and diarrhea. One day prior to admission she had developed a widespread, non-pruritic, erythematous rash. Her medical history consisted of hypertension, for which she was taking atenolol, and several episodes of gout, for which she was taking allopurinol." ] },{ "paper_id": "121f06c44cde088607a6f4d16098eb6101513c01", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Methods: Seventy-two male adult Wistar rats were divided into three groups and treated as follows.", "All data are presented as the mean \u00b1 SD. Statistical analysis was performed using SPSS 13.0 software (SPSS Inc., Chicago, IL, USA). One-way analysis of variance (ANOVA) with Turkey's post hoc test was used to examine differences between groups. Statistical significance was set at P <0.05." ] },{ "paper_id": "12329a694934f5824e1ef7d695a7a1fa0310f52c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "B-Cell epitopes are antigenic residues that B Lymphocytes bind to. These antigenic determinants can be either continuous, or conformational. Continuous epitopes, also known as linear epitopes, are formed by continuous sequences of residues. The majority of epitopes (90%) are within the conformational class [4] , which are the result", "doing this search experimentally, searching exhaustively by brute force, is an extremely time consuming endeavour. Thus, computational approaches are employed, and are the primary subject domain of computational vaccinology. Epitope prediction, the ability to predict with some probability whether a particular amino acid belongs to an epitope, can guide our experimental based search and save us a significant amount of time.", "The SEQ194, HIV, Pellequer, and AntiJen sequences were all calculated by measuring the cross-reactivity between the intact protein and the peptide fragments. AntiJen and SEQ194 have extremely low epitope densities (1.4 and 6.6%, respectively); HIV and Pellequer have an order of magnitude higher epitope densities (37.1 and 37.6%, respectively); and SARS has the highest epitope density of the five datasets (63.7%). Thus, together these 5 datasets represent a realistic test of the classifier that is to be used to search for new epitopes within new protein sequences, covering a wide spectrum of possible epitope densities." ] },{ "paper_id": "123683340d6d91bf7251d4b91b7503f907dd56cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step " ] },{ "paper_id": "123db7e17bb17a0d4ff1e7ef87cb629d6ac78125", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human coronavirus OC43 (Nidovirales: Coronaviridae:", "Further human coronaviruses complete genome sequences included HCoV-HKU1 (KF686341.1), HCoV-NL63 (DQ445911.1), HCoV-229E (JX503061.1), HCoV-SARS (AY291315), and two HCoV-MERS (KJ156949 from a strain detected in a human patient and KJ713299.1 detected in a dromedary camel).", "Human coronavirus evolution " ] },{ "paper_id": "1244246ac28247b5674d6f4a8587e064bb565d7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Proportions standardized by age, gender and education attainment, and the corresponding 95% confidence intervals (95% CI) were calculated using logistic regression models for each type of behavior in the three residential areas and the total sample.The logistic regression model used for calculating the risk ratios of each behavioural outcome is showed below:", "50.1% of the respondents reported cleaning hands immediately after touching birds when buying and most say that they do this after touching backyard birds, bird cages or bird droppings. When slaughtering birds at home, the most frequently adopted protective measure was wearing aprons, outer garments or coveralls (13.7%, 95% CI: 6.2-27.3%), though a few reportedly wore gloves, boots or face masks (Table 1) .", "Live animal markets were found to be responsible for the spread of Severe Acute Respiratory Syndrome Coronavirus in 2003 [30] , and many H5N1 avian influenza virus infections [31] . However, perceived health risk from live animal sales did not increase from 2006 through 2013 even though human H7N9 cases were again closely linked with live bird exposures in wet markets [2, 3] . This suggests that knowledge deficiency or risk fatigue and adaptation may both be targets for public health education. However, compared with the 2006 survey, the proportion of respondents citing poor market hygiene as a cause of avian influenza infection had doubled in 2013, suggesting increased awareness of and attribution to poor hygiene rather than retail practice s that artificially concentrate and mix live animals as the main cause." ] },{ "paper_id": "12590435a221d10824ab106e66d0f9fec397db40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "FAD was released from recombinant proteins by heating at 75 C for 5 min in the dark and analyzed by highperformance liquid chromatography (HPLC). Briefly, HPLC separation was achieved with a Synergi 4u Fusion column (25 cm \u00c2 4.6 mm, 5 mm) using a gradient of 5 mM ammonium acetate, pH 6.5, to acetonitrile 50% and water 50% over 35 min at a flow rate of 0.6 ml/min. Flavins were detected by fluorescence emission (525 nm) using a Waters 474 scanning fluorescence detector set at 450 nm for excitation.", "Transfer RNAs (tRNAs) are highly and diversely modified, and each has a unique pattern of modification (1) (2) (3) . These modifications are post-transcriptionally introduced at precise positions by specific enzymes and play important roles in folding, stability, identity and in the functions of tRNAs.", "The acid resistance experiments were performed essentially as previously reported (39) . Briefly, strains were grown in LBT containing 0.4% glucose to stationary phase. The cultures were then diluted 1:1000 into EG medium [minimal E medium containing 0.4% glucose; (40) ], pH 2.0, supplemented or not with 0.7 mM glutamate. Samples were obtained at 0, 1, 2, 3 and 4 h post acid challenge and spotted on LAT plates.", "There are very few data available on the identity determinants required by TrmL. Methylation of the ribose The ratio was calculated as CFU/ml recovered on LAT supplemented with tetracycline versus CFU/mL recovered on LAT." ] },{ "paper_id": "125b3f6dd69d07e5dac7fa45b6567008bd1244ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Knowledge is always accompanied by uncertainty." ] },{ "paper_id": "126b264339dd9d8ee65cc747822e16c83af57e12", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Differences between two groups for VN antibody titers of individual pigs were analyzed using analysis of variance (ANOVA). A two-tailed P-value of less than 0.05 was considered significant." ] },{ "paper_id": "1275c64d711b3973f7e25ebc72bbc7c99341dd00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In conclusion, this work reveals some new mechanisms by which PNS neurons control the cytokine response during alphaherpesvirus infection and contribute to severe neuropathies.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "12834756cf70a24e0bc14906b131ca587f86dc02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tissue samples were collected from pigs died from diarrhea symptoms on farms, the small intestine was immersed in phosphate-buffered saline (PBS), washed several times to eliminate residual blood, and then placed in a centrifuge tube and stored at \u2212 80\u00b0C until use.", "The experimental procedure for virus isolation is in African green monkey kidney (VERO) cells according to reference [25] . The isolates were determined by more propagation until apparent cytopathic effects appeared.", "Prior to RNA extraction, frozen small intestine samples (~20 mg) were homogenized in liquid nitrogen. Then, total RNA was extracted by using a commercial extraction kit (EasyPure Viral DNA/RNA Kit; TransGen Biotechnology, Inc., Beijing, China) according to the manufacturer's instructions. The RNA was dissolved in DEPC-treated water for cDNA synthesis. The extracted RNAs were suspended in 100 \u03bcl of elution buffer and stored at \u2212 80\u00b0C until use." ] },{ "paper_id": "1291b42497aeef11d21f1fcf33ee7e910a3396dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "EVD in 2014 started and propagated in western Africa. Guinea was the index country which exported the infection to Sierra Leone and Liberia initially, and later to Nigeria, Senegal and Mali in addition to Spain and United States of America.", "In 2014 WPV was actively transmitted within at least ten countries with a risk of exportation and infection to others. Eastern Mediterranean Region is shouldering the greater portion of this burden particularly due to \"Pakistan to Afghanistan\" and \"Syria to Iraq\" exportations. While, \"Cameroon to Equatorial Guinea\" and \"Equatorial Guinea to Brazil\" are the other documented exportations in the rest of world during 2014 [18] . As a response, emergency committee of IHR (2005) on polio was conducted three times and has approved the temporary recommendations for three categories of countries.", "As per International Health Regulations (IHR-2005) [1] , Public Health Emergency of International Concern (PHEIC) is defined as \"an extraordinary event which is determined to constitute a public health risk to other States through the international spread of disease and to potentially require a coordinated international response\" [2] . PHEIC concept is one of the major update points in IHR (2005) version. It considers prevention, protection, response and containment of an event in such a manner that is fully aligned with human right's preservation and avoidance of unnecessary interference with international travel and trade [3] ." ] },{ "paper_id": "1292b5cdd7a8850cf1d0ceb1df706012c469da62", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "129341a52b43ccd59368d094950322d983ebe223", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Assumptions of normal distribution and equal variances of numerical data were tested using a Shapiro-Wilk W and a Brown-Forsythe test, respectively. All summary statistics are reported as medians and interquartile ranges (IQR) or as percentages.", "Positivity for tested gastrointestinal parasites ranged between 21 and 41%, whereas the study prevalence for both viruses evaluated reached approximately 20% (Table 1) ." ] },{ "paper_id": "1297127819be12e7f5319edd0a9b35fd5cc566b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Expression and purification of GST-E7 was undertaken following our previous published protocols [14] . Expression vectors for E7 with point mutations or deletions were also described previously [46, 63] ." ] },{ "paper_id": "12a4354b2c97189beca7e04d721508f420928396", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CM and WF contributed equally to this work. CM and WF wrote the manuscript and made the figures. LC-C edited the final version of the manuscript. ", "In addition to canonical initiation of translation, capindependent mechanisms of translation have also been described for DENV. Indeed, DENV can achieve vRNA translation and wild-type production of infectious viral particles when capdependent translation is inhibited by treating the cells with drugs that impair the phosphoinositol-3 kinase (PI3K) pathway.", "Downstream of IFN production and signaling, the sfRNA also plays a role in ISG expression at the post-transcriptional level. Indeed, host RNA-binding proteins G3BP1, G3PB2 and CAPRIN, which are involved in ISG translation are inhibited by their association with DENV sfRNA in Huh7 cells (Bidet et al., 2014) . G3BP proteins are core components of SGs (Anderson and Kedersha, 2006 ) whose formation and functions are modulated by flavivirus infection, as discussed above. Hence, it is tempting to speculate that, through the hijacking of SG components, flaviviruses remodel the host proteome by positively or negatively regulating the expression of pro-and anti-viral host proteins, respectively." ] },{ "paper_id": "12aa5eeb50296d810121cc1b2f87f053c39ce204", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(C) Predicted 3D structure of the MMTV SU in space-filled form generated using Swiss-Model is shown. The RBS is indicated in yellow, the glycosylation site in green, basic residues in blue and acidic residues in red. In the right panel, the RBS is enlarged and the charge change caused by G to E substitution at position 42 is highlighted.", "Knock-down of hTFR1 by small interfering RNA Hs578T cells (plated at a density of 3 \u00d7 10 5 cells per well of a six-well plate, one day before transfection) were transfected overnight with human TFRC SMARTpool (25 nM," ] },{ "paper_id": "12af3b3c07569926eb1ce96ebd4d5bffd05ce54a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the GST pull-down experiments, human serum were incubated for 2 h at 4uC with 5 mg of purified GST or GST fusion proteins bound to glutathione beads (GE Healthcare, Little Chalfont, Buckinghamshire, UK). The adsorbates were washed with lysis buffer and subjected to SDS-PAGE and immunoblot analysis. Purified AHSG protein was included as a loading control. ", "Two reporter plasmids encompassing 21091 to +22 bp of the human AHSG promoter were generated by PCR from two genomic DNA samples with either 2799A OR -799T, using the primers P1: 59-cgcagatctGGTCTCCATGAGAGGGCTTC-39 and P2: 59-cgcaagcttCAGGCGTGCAGGTGGTTG-39, respectively. The PCR product was digested with BglII and HindIII and ligated into a pGL3-basic promoter-probing vector (Promega) containing the firefly luciferase gene as a reporter. The constructs were sequenced to ensure correct cloning.", "Genotype Allele " ] },{ "paper_id": "12bc05b6a9ae2d8823f67b0a8200fb7f72c45f9b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.", "Medimmune, and payments from GlaxoSmithKline for participation in a DSMB. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed." ] },{ "paper_id": "12bc88e7428c240181f181ca0358dac85ae16289", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mitoxantrone, a cytotoxic drug with immunomodulatory properties, is used to treat progressive forms of MS [129] . Mitoxantrone increases the ex vivo production of the Th2 cytokines IL4 and IL5, but with no significant changes in IFN\u03b3, TNF\u03b1, IL10, or IL17 expression by PBMCs or CD4 + T cells, indicating that the immunomodulation afforded by mitoxantrone treatment in MS acts through the enhancement of Th2-type cytokines [130] .", "These advances in identifying unique therapeutic targets for MS have instigated numerous phase II and phase III clinical trials, for example, trials of various mAbs, including those directed against CD52 (alemtuzumab), CD25 (daclizumab), and CD20 (rituximab), and trials of disease-modifying therapies, such as teriflunomide, laquinimod, and fumarate [135, 155] . For example, alemtuzumab, a humanized mAb, targets the surface molecule CD52 on all T-cell populations and other cellular components of the immune system, such as thymocytes, B cells, and monocytes [156] .", "In summary (Figure 2 ), these immunomodulatory agents and neuroprotective therapies for MS have great value as clinical agents, to be tested in clinical trials or preclinical studies, and in the development of novel therapeutic strategies for MS [55] ." ] },{ "paper_id": "12c2a6ee1e3e7cf0f915e5c5454627b7e1ed9db3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are presented as the means \u00b1 standard deviations and are representative of at least three independent experiments. Differences between groups were analyzed by analysis of variance (ANOVA), and means were compared by Student's t-test. p-values less than 0.05 were regarded as significant. Results for percent initial body weight were also compared by using Student's t test. Comparison of survival was done by log-rank test using GraphPad Prism 6 version.", "The mice were intra-nasally infected with five times the 50% mouse lethal dose (MLD50) of H1N1, H5N2, H7N3 or H9N2 in 20 \u03bcl of PBS per mouse. Treatment and challenge experiments were conducted in an approved BSL-2 + facility. The body weight and survival were recorded up to 13 dpi. Mice showing a more than 25% body weight loss were considered to have reached the experimental end point and were humanely killed. At 3 and 5 dpi, three mice from each of the two groups from the H1N1-challenged set were randomly sacrificed to measure the lung virus titers.", "The animal study was conducted under appropriate conditions with the approval of the Institutional Animal Care and Use Committee of the Bioleaders Corporation, Daejeon, South Korea, Protocol number: BSL-ABLS-13-004. They are in accordance with Institutional, National and International laws for Laboratory Animal Experimentation." ] },{ "paper_id": "12c3660c37af4a311a3a14667a12ce48388dd6ce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Time from exposure to manifestation of symptoms within which concern for disease is valid 8-10d, never more than 21d", "Non-human animals that can harbor and/or spread Ebola Bats 6 Historical Information Information that has nothing to do with current outbreak Historical data on past outbreaks, information regarding nations involved, etc.", "Any statement that is factually inaccurate but stated as question of hearsay \"Some are asking if Ebola is spread through the air\"" ] },{ "paper_id": "12c70c4d576fce0b20fce2b35e47b05baea97e35", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After 40 years of reform, China's economic and comprehensive national strength have achieved breakthroughs, and resource allocation in all aspects has been strengthened overall; however, many structural problems have accumulated following years of sustained \"rapid development.\" A recent document shows that China has focused on the \"unbalanced and inadequate\" development and addressed it as a major social conflict [12] , which applies to the public health field.", "Suppose the sample containing n individuals is divided into K groups, each group is g k(k = 1, 2, 3\u2026K) , the number of individuals in g k of group k is n k , then P k k\u00bc1 n k \u00bc n, y i and y k represent the human share of an individual i and the total human share of a group k, respectively. T b and T w represent the between-group differences and withingroup differences, respectively, so the decomposition of Thiel T index is as follows:" ] },{ "paper_id": "12c7bde10bc2422a099a326c99cba1ec1e496431", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Primers used to generate the described plasmids are available upon request. Constructs ORFs were verified by DNA sequencing and protein expression confirmed by Western blot (WB).", "Viruses 2012, 4 2138 D471G mutation on viral infection, suggesting that NP self-association is an excellent target for the development of new antivirals against arenaviruses." ] },{ "paper_id": "12cbf7162f5525c020e909c85db4142007c64603", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "New approaches to benzotriazole derivatives are therefore expected to have a broad-ranging impact. Among the various N-substituted benzotriazolyl derivatives, as compared to N-alkyl and N-acyl compounds, those with a C-O-N bond are less common. Typically the latter are synthesized by the alkylation of BtOH with alkyl halides [17, 18] , quaternary alkyl ammonium salts [19] , or via a Mitsunobu reaction (Scheme 1) [20] .", "1919" ] },{ "paper_id": "12d267205009c178b6a50506db717ff650d93415", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "12d7a96036ca9e861d3636d55d3841452e455c73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study has been reviewed and approved by the Institutional Review Board of Samsung Medical Center and informed consent was waived by the board. Patient records/information were anonymized and de-identified prior to analysis.", "Conceptualization: KWS.", "Formal analysis: YBC." ] },{ "paper_id": "12f712c348c26e092759d804778defe2d2d4af6f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consistent with the responsiveness of MERS-CoV to interferon treatment in vitro, combinational treatment of IFN-\u03b12b and ribavirin reduced virus replication and improved clinical outcome in MERS-CoV infected rhesus macaques [30] . It was further demonstrated that IFN-\u03b21b treatment showed a better outcome in the virusinoculated common marmosets [31] .", "Unlike most other human-pathogenic coronaviruses, which mainly cause self-limiting upper respiratory tract infections, MERS-CoV is capable of causing severe disease with lower respiratory tract involvement and extrapulmonary manifestations [11, 12] . Patients with severe MERS often present with pneumonic symptoms including fever, cough and dyspnea, with some progressing to respiratory failure and acute respiratory distress syndrome [13, 14] . Extrapulmonary manifestations such as renal failure, hepatic dysfunction, and diarrhea are not uncommon [13, 15] . Additionally, deranged coagulation profile and hematological changes may also be observed in severe MERS [15] . The infectious virus could be recovered exclusively from patients' respiratory tract, whilst viral RNA could be detected extrapulmonary specimens such as blood, urine and stool by nucleic acid amplification tests [16, 17] . These clinical and laboratory findings are suggestive of possibly disseminated viral infection.", "While the cellular tropism of SARS-CoV in human respiratory tract resembles that of MERS-CoV [21, 22] , a number of immune cells displayed distinct susceptibility to MERS-CoV and SARS-CoV.", "The MERS-CoV mouse models have been utilized to test the efficacy of antiviral drug, neutralization antibody and vaccine. A Venezuelan equine encephalitis replication particle expressing MERS-CoV spike protein (VRP-S) was demonstrated to substantially reduce the virus titer in lung tissues of the immunized hDPP4 transduced mouse model [44] . The same group subsequent examined the VRP-S in a more permissive hDPP4 transgenic mouse model [59] . The VRP-S immunized hDPP4 transgenic mice were completely protected from lethal infection. Pretreatment with serum of the mouse immunized with VRP-S can also be protected from fatal infection [59] . Two fully human neutralization antibodies binding to distinct epitopes of MERS spike protein, which were generated using the mouse expressing human antibody, displayed the preand post-exposure protection efficacy from MERS-CoV infection in hDPP4 transgenic mice [61] ." ] },{ "paper_id": "12fc7df6445be6360090621b75df383ce86772af", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In vivo LPS injection CWE (20, 100 or 500 mg/kg of body weight) was given to mice via oral gavage for 6 days. Control mice received an equal volume of normal saline during the experimental period. Each group consisted of 12 mice. On day 7, LPS (serotype 055:B5; Sigma, St. Louis, MO, USA) (1.3 mg/kg) was injected intraperitoneally 1 hour before blood sampling. Blood was obtained by cardiac puncture. As a reference drug, dexamethasone (Sigma) (5 mg/kg) was injected intraperitoneally 18 hours before the LPS injection. Blood samples were centrifuged at 800 g for 20 min. The serum samples obtained were stored at \u221220\u00b0C until used.", "Chronic inflammatory responses found in most autoimmune diseases and metabolic diseases exhibit common characteristic processes where macrophages are initially activated and interferon (IFN)-\u03b3-producing type-1 T helper cells subsequently stimulate macrophages to release more inflammatory cytokines. Together with our previous findings that CWE prevented anti-CD3stimulated T cells from secreting IFN-\u03b3, our current study clearly shows that CWE is able to interfere with the chronic activation of macrophages [16] .", "For the use of in vitro culture of macrophages, normal mice were injected intraperitoneally with 2 ml of sterile thioglycollate medium (BD, France), and macrophages were collected three days later by peritoneal gavage with cold Dulbecco's modified Eagle's medium (DMEM). The recovered peritoneal fluid was washed by centrifugation. The cells were resuspended in DMEM with 10% fetal bovine serum and incubated for 3 hours at 37\u00b0C with 5% CO 2 . Non-adherent cells were removed." ] },{ "paper_id": "12fe4cca998a403e153ae872595eab2676c77d2f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After ethical committee agreement (Comit\u00e9 d'Ethique-H\u00f4pital Erasme, reference number P2007/175), AECII were isolated from macroscopically tumor free regions of lung tissues obtained following lobectomy or pneumectomy for lung cancer. The AECII isolation was adapted from a previously described technique [27] . After differential adherence of contaminating mononuclear cells, non-adherent AECII were plated at 5 \u00d7 10 5 cells/well in 48 wells flat-bottomed plates precoated with type I collagen (1%) to obtain pure AECII [28] . Cells reached confluence after 24 or 48 hours.", "The purity averaged 85.78% (81.78% -90.03%) (median, inter-quartile ranges) for the nine independent AECII isolations as assessed by flow cytometry (see below)." ] },{ "paper_id": "130c4c6c7faab2f0c0143b6f0cd0118b27c91dea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "131902a67f5e00ae13b9239427325dfd53413349", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protein modification was conducted as previously described [13] . Briefly, the proteins were dissolved in 0.1 M phosphate (final concentration, 20 mg/mL). Subsequently, 3-hydroxyphthalic anhydride (HP), maleic anhydride (ML) or succinic anhydride (SU) was added, respectively, in five aliquots with a 12-min interval, while pH was adjusted to 9.0. To optimize the condition of anhydride modification, HSA was modified with 2.5, 5, 10, 20, 40 or 60 mM anhydride (HP, ML or SU), respectively. The mixtures were kept for another 1 h at room temperature and then extensively dialyzed against PBS.", "Female BALB/c mice six to eight weeks of age were purchased from the Animal Center of Fudan University (Shanghai, China). Mice were housed in cages with barrier filters in certified rooms and were fed and watered ad libitum. The protocol for the use of animals in this study was approved by the Animal Center of Fudan University (Permit number: 2013N-067). The animal studies were conducted in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals." ] },{ "paper_id": "13194f8e42df83d260e53ad9bf7448577e9319e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The flaviviruses WNV, DENV, and JEV share some common features, such as transmission via mosquitoes, and cross-react with each other in serological tests.", "Japanese encephalitis virus (JEV) is the most important cause of epidemic encephalitis in most Asian regions. The virus belongs to the genus Flavivirus of the family Flaviviridae; about 35,000-50,000 cases of and 10,000 deaths from JEV infection are reported annually [1] . JEV was first isolated in Japan in 1935, following which it spread to most other Asian countries. At present, this virus is even found in regions beyond its ecological boundaries. Recently, JEV has spread to regions as far as northern Australia [2, 3] . Hence, there is a concern that JEV might become a global threat. In fact, it is not unusual to find 2 or more flaviviruses co-circulating in one area. In Southeast Asia, the most important flaviviruses are JEV and dengue viruses (DENV) [4] . In northern Australia, Kunjin virus is found to co-circulate with JEV [5] . In Vladivostok, Russia, studies have reported the detection of WNV in birds [6] . In addition, there is evidence that WNV infection in India from Japanese encephalitis nonendemic areas and endemic areas [7] .", "Ninety-six-well microtiter plates were coated with purified fusion protein or denatured inclusion body in 0.1 M carbonate buffer (pH 9.6) at 4\u00b0C overnight and blocked with 5% skim milk for 3 h. Subsequently, the plates were washed 3 times with PBST (phosphate buffered saline, PBS with 0.1% Tween 20). In the binding assay, the plates were incubated with diluted rabbit hyperimmune sera or swine sera at 37\u00b0C for 1 h followed by washing 3 times with PBST. Bound antibodies were detected with horseradish peroxidase (HRP)-conjugated secondary antibody. The reaction was stopped with 2 M H 2 SO 4 , and the absorbance was measured at 450 nm by using a microplate autoreader (Bio-Rad). In peptide ELISA, microtiter plates were coated with the synthesized peptide." ] },{ "paper_id": "131e5a7c8626d4fec5bfe8d77666d1d8556e5a4c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dengue virus (DENV), a member of the Flaviviridae family, is an enveloped virus containing a~11 kb genome of positive single-stranded RNA which encodes three structural proteins (C, pr-M, E) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5) [4] . Four serotypes of dengue virus (DENV1, DENV2, DENV3 and DENV4) cause dengue fever (DF) and more severe manifestations like dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) [1] .", "Solvents methanol, ethyl acetate, formic acid and dimethyl sulfoxide (DMSO) reagent or HPLC grade and silica gel (Kiselgel 69) were obtained from Merck KGaA (Darmstadt, Germany). Media and supplements for cell culture were purchased from Sigma-Aldrich Chemicals (St. Louis, MO, USA) and molecular grade agarose was obtained from Promega (Madison, USA). All other reagents used in analytical methods were purchased from Sigma-Aldrich Chemicals, except where otherwise indicated.", "For the chemical analysis, 100 mg of sample were mixed with 1.5 mL of methanol:water:formic acid (25:24:1, v:v:v) extractant, then vortexed and sonicated in an ultrasonic bath for 60 min at room temperature. The samples were kept at 4\u00b0C overnight and sonicated again for 60 min. A centrifugation was performed for 10 min at 10,000 rpm to separate the supernatant from the solid residue. The supernatant was filtered through a 0.22 \u03bcm PVDF filter before analysis (Millipore, MA, USA). The chromatographic analyses for identification of compounds were carried out on a Luna C18 column (250 \u00d7 4.6 mm, 5 \u03bcm particle size; Phenomenex, Macclesfield, UK)." ] },{ "paper_id": "131e6a035170ed5bd2dba6bec02649e9508a0c55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:34617 | DOI: 10.1038/srep34617" ] },{ "paper_id": "1329ea9b040bdc8af7c30f7ba4b5755e352deae8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequence alignment analysis was performed using the Clustal W program implemented in DNAStar software. A phylogenetic tree was then constructed by the neighborjoining method using the Molecular Evolutionary Genetics Analysis (MEGA) software version 5.1 with 1000 bootstrap replications set at 1000. Moreover, the possible recombination event was evaluated in the S and N genes by recombination detection program (RDP) 3.34 software.", "For the two enteric coronaviruses (PEDV and TGEV) in pigs, the recombination events were often detected. However, most of them were from intra-recombination [27] [28] [29] [30] . Recently, only one emerging recombinant/chimeric virus (named swine enteric coronavirus, SeCoV) was discovered in swine feces and resulted from inter-recombination of PEDV and TGEV, which had a TGEV backbone and a PEDV spike gene [31, 32] . In this study, there were no any possible recombinant events occurring in PDCoV strains. Maybe, the number and length of our obtained PDCoV sequences were limited. In the following study, the recombination event of PDCoV warrants further attentions.", "Before 2012, the subfamily Coronavirinae included three genera (Alphacoronavirus, Betacoronavirus and Gammacoronavirus). However, in 2012, an emerging genus, Deltacoronavirus, was found in many animal species including swine from Hong Kong [1] . At present, more than five different coronaviruses have been described in swine populations. Among them, porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine respiratory coronavirus (PRCV) belong to the genus Alphacoronavirus; meanwhile, porcine hemagglutinating encephalomyelitis virus (PHEV) and Porcine deltacoronavirus (PDCoV) are assigned to the genus Betacoronavirus and the genus Deltacoronavirus, respectively [1] . Numerous studies have shown that more than half of porcine coronaviruses (including PDCoV) were enteropathogenic and caused acute diarrhea and vomiting in pigs, which resulted in huge economic losses for the global swine industry [2] [3] [4] [5] [6] .", "This study reported the prevalence of PDCoV on swine farms in southern China. Phylogenetic analysis of currently circulating PDCoV strains in this region and other previously reported strains supported the theory of geographical clustering of PDCoV infection landscape. The origin of various PDCoVs in different countries and regions should be further studied." ] },{ "paper_id": "132d356a5461491379ccfb628fca604ef66b53e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. The authors declare that the data supporting the findings of this study are available within the article and its supplementary information files, or available from the authors upon request.", "Viruses and cells. All the B/Yamanashi/166/98 NS1/NP mutant viruses were generated by reverse genetics method, employing the eight-plasmid bidirectional transcriptional system as described by Hoffmann et al. 36 . Virus stocks were grown in 9-day-old fertilized chicken eggs, and virus titers were determined using plaque assays in MDCK cells. All eight segments of the recombinant viruses were sequenced. A549 (CCL-185) and MDCK (CCL-34) cells were obtained from the American Type Culture Collection (ATCC) and maintained in Dulbecco's modified Eagles' medium (Invitrogen) supplemented with 10% fetal bovine serum. To establish the IFN-b-inducible S-3F-ISG15GG A549 cell line, a plasmid was constructed by inserting into the pGL3 vector a KpnI-XbaI DNA fragment composed of a S-3F-ISG15-encoding sequence linked to an ISG15 promoter element at its 5 0 end. This DNA fragment was a product of PCR-mediated ligation of two smaller fragments: one fragment contains a ISG15 promoter sequence (bases -740 to 0) that was amplified from HeLa genomic DNA; the other fragment encodes S-3F-ISG15 generated by PCR-mediated addition of 3xFlag-S sequence to an ISG15-encoding sequence. The constructed plasmid (9 mg) was co-transfected with 1 mg of a linear puromycin selection marker (Clontech) into A549 cells. After selection with medium containing 1 mg ml \u00c0 1 puromycin, individual clones were selected, expanded, and the clone showing the strongest IFN-b-dependent induction of S-3F-ISG15 as well as its conjugates was used for virus infection experiments. The control IFN-b-inducible S-3F-ISG15AA A549 cell line was generated using the same procedure.", "Assay of association of ISGylated NP with NS1B and free NP. Cytoplasmic and nuclear fractions from USP18 siRNA-transfected, IFN-pretreated and virusinfected S-3F-ISG15GG A549 cells were prepared using the same procedure as described in assaying vRNP formation, except that RNaseOUT was replaced with Benzonase in presence of MgCl 2 to remove RNA. The resulting fractions were subject to double-affinity selection, and analysed by immunoblots probed with NP or NS1B antibody." ] },{ "paper_id": "132e94687b6ac1d68f3a33dcf090bc6f5865bb98", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We hope that this hypothesis-generating study will encourage the incorporation of pharmacokinetic data in future studies of bronchiolitis. Although validation studies in other populations are needed, this study underscores that the development of personalized approaches to the treatment of bronchiolitis may benefit from the analysis of specific genetic variants.", "Conclusions: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy." ] },{ "paper_id": "133933d03341e293921239f0d6a2b3ea4f1f574c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LoopampH DNA LAMP kits were purchased from Eiken Chemical Co. Ltd (Tokyo, Japan, Code No.: LMP206). The Eiken LoopampH Fluorescence Detection Reagent (Code No.: LMP221), a Calcein-based reagent that indirectly indicates the progress of DNA amplification in the LAMP reaction, was used for fluorescence experiments. LAMP primer sequences for P. falciparum (Integrated DNA Technologies , Coralville, IA, USA) were as described by Poon et al. [40] Genomic DNA from P. falciparum for preparing contrived samples was obtained from the PATH laboratory specimen collection.", "To verify that the device could incubate a LAMP assay, the Eiken kits were used as per package insert instructions, except where noted below. Clinically relevant dilutions of genomic DNA were made in Eiken kit buffer to yield the DNA concentration and approximate parasite count noted for each experiment. All dilutions were prepared as single solutions and then aliquoted across treatment conditions to minimize preparation variation. No template controls (NTC) were prepared first and immediately sealed to reduce the possibility of contamination. Mineral oil was layered on the tops of the samples to minimize evaporation. All reactions were incubated at 63uC." ] },{ "paper_id": "1340cfab5e9d9c4e29144766f379fe8f10e4cc29", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Members of the Coronaviridae family form a diverse group of enveloped, singlestrand, positive-sense RNA viruses. The Coronaviridae family is divided into the Torovirinae and Coronavirinae subfamilies, both characterized by their exceptionally large RNA genomes: 20.2 kb (Bovine nidovirus TCH5) to 33.5 kb (Ball python nidovirus) and 25.4 kb (Porcine deltacoronavirus HKU15) to 31.8 kb (Bottlenose dolphin coronavirus HKU22), respectively. Torovirinae and Coronavirinae subfamilies are able to infect a diverse array of vertebrate species. They have a distinct genomic architecture and replication strategy shared with other members of the Nidovirales order, which also includes the Arteriviridae, Mesoniviridae, and Roniviridae families (2, 3) . Coronaviruses (CoVs) are classified into four genera, with Alphacoronavirus and Betacoronavirus containing members that infect mostly mammalian species and Gammacoronavirus and Deltacoronavirus grouping viruses infecting both birds and mammals (4) .", "This work highlights the importance of incorporating biological data into sequencebased classifications for virus taxonomy. Within the Alphacoronavirus 1 species, this allows for more biologically relevant and useful virus groupings. We believe that this practice should continue to be encouraged and/or added once such data become available for viruses discovered solely through sequence information.", "While current criteria based on analyses of key replicase domains allow the definition of coronavirus species, we believe that it is useful to also provide subspecies classifications based on other genetic loci such as the S gene to allow for more functionally relevant classifications." ] },{ "paper_id": "1341e9e33488d304353f31081a8422ed8715b5b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protein phosphorylation is a reversible post-translational modification that can regulate the activity of enzymes, mediate protein-protein interactions, alter the subcellular localization, conformation, and/or oligomeric state of proteins, as well as regulate the addition or removal of other types of post-translation modifications [41] . This important type of modification is not limited to cellular proteins; a growing body of literature has demonstrated that phosphorylation of viral proteins has important consequences for different viral processes [42] [43] [44] [45] .", "Pathogens 2018, 7, 97 2 of 14 2008, outbreaks in Sierra Leone have resulted in an overall case fatality rate of 69% in hospitalized patients [12] . LASV infection results in fetal loss in most cases [13] . Further, pregnancy greatly increases the risk of fatality from Lassa fever for the mother [13] . Of Lassa fever survivors who were hospitalized, approximately one-third developed hearing loss, and in two-thirds of those patients, the hearing deficit was permanent [14] . Intravenous ribavirin treatment has been shown to reduce mortality from Lassa fever, particularly if administered during the first six days of fever onset, but there is a clear need for more effective therapies [5] . No United States Food and Drug Administration (FDA)-approved vaccines exist for the prevention of LASV infection.", "Supplementary Materials: The following are available online at http://www.mdpi.com/2076-0817/7/4/97/s1. Figure S1 : Mass spectra for identification of the Y97 and S98 phosphorylation sites in LASV Z, Figure S2 : Mass spectra for identification of the S18 phosphorylation site in LASV Z. ", "Arenaviruses have a simple, negative-strand RNA genome that encodes a total of four proteins on two segments. The small (S) segment encodes both the nucleoprotein (NP), which encapsidates the viral genome and is required for its replication, and the envelope glycoprotein (GP), which interacts with cell surface receptors to mediate cell entry and membrane fusion [15] [16] [17] [18] [19] [20] . The large (L) genome segment encodes the viral RNA-dependent RNA polymerase (L), which replicates and transcribes the genome, and the viral matrix protein (Z) [19] [20] [21] [22] . The Z protein is a structural component of the virion, forming a matrix layer on the inner leaflet of the viral envelope, and carries out an array of important functions during viral propagation [23, 24] . The Z protein of pathogenic arenaviruses antagonizes interferon production by binding to retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) to disrupt interactions between RIG-I-like receptors and mitochondrial antiviral signaling (MAVS) [25] . Z can inhibit the translation of capped cellular mRNAs and also regulate the activity of the viral polymerase [26] [27] [28] . Z is also an important coordinator of virus particle assembly by interacting with each of the other three viral proteins [29, 30] ." ] },{ "paper_id": "134da4eba94dc9b9f03a9244d62aee56abe0de56", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Allantoic fluid was collected, tested by hemagglutination assay [36] , and stored at \u221285 \u2218 C. Egg infectious dose (50%) was calculated by the formula of Reed and Muench [37] .", "The US Poultry industry annually produces over 43 billion pounds of high-quality broiler chickens and turkeys and over 90 billion eggs, which in 2010 had a market value of $34.7 billion [1, 2] . Avian diseases are a constant threat to the industry. Viruses are of particular concern because antibiotics cannot control them, although vaccines can control some avian viral infections. Avian vaccines are an important component of protecting the value of commercial poultry. However, many commercial birds are not vaccinated because of the cost, labor, and difficulty in differentiating infected from vaccinated animals.", "Weight loss or body temperature did not differ much among treatment groups, and therefore we believe that apparently these measures of health were not predictive of survival.", "Analysis. Data were analyzed using GraphPad software, Prism 4.0, and InStat 3.0. Serum means and tracheal plaques were compared using two-tailed, unpaired Student's t-test with Welch's correction. Correlation analysis between serum response and survival was done using Pearson's analysis (two-tailed), and a line was plotted using linear regression analysis. Survival was analyzed by the method of Kaplan and Meier using the logrank test. Temperature and weight change was analyzed using nonparametric ANOVA (Kruskal-Wallis test)." ] },{ "paper_id": "13580111f45eb6e4af4142774eb95f0e52350e92", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1358b278b691bdd7439d849fa8a002f9f9b8fe95", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "135f5ee5fba1a4280521d45e4fa882354f63e691", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "[\u2026]: an option for a 'long' format which is readily compatible with (Wickham, 2016) for ggplot2", "Comment 32:", "1." ] },{ "paper_id": "1363643127b0fd76d3c6b848e07cfc2ed3f75328", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The entire screen was performed twice in separate runs one week apart.", "The MTS was performed in duplicate with three compound libraries. The Spectrum Collection (MicroSource Discovery Systems) comprises 2000 compounds with a wide range of biological activities and structural diversity. The NIH Clinical Collection contains a total of 727 compounds previously used in human clinical trials (http://www.nihclinicalcollection. com). Finally, the Bio-active Lipid I Screening Library (Cayman Chemical) contains 846 bioactive lipids. Individual compounds for secondary confirmation of hits were purchased from Sigma, dissolved in DMSO, and diluted in OptiMEM for in vitro testing.", "Determination of reduced signal due to cell toxicity was a key aspect of the assay. Some compounds were toxic and reduced virus signal non-specifically as a consequence of reducing cell signal ( Figure 3 ). However, some compounds exhibited a clear virus-specific effect, with a reduction of virus signal but retained cell signal ( Figure 3 )." ] },{ "paper_id": "136f5dd69cd65fb0826ded4d9f51af7969dfcbcd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations", "Tumor necrosis factor GM-CSF Granulocyte macrophage-colony stimulating factor DTT Dithiothreitol G3PDH", "Glyceraldehyde-3-phosphate dehydrogenase IPTG Isopropylthio-b-D-galactoside" ] },{ "paper_id": "1378320afa873bdb81e3f3314a430c7a208d2d08", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Multilingual abstracts in the six official working languages of the United Nations.", "Please see Additional file 1 for translations of the abstract into the six official working languages of the United Nations.", "Rapid molecular markers for mass population screening and diagnosis-based triage and increasing the effectiveness of quarantine or other social distancing measures including the development of synthetic antibody techniques for monitoring infection-related changes in protein levels.", "More research in host-based early-warning alert models and understanding of the contribution of context, culture, and ecosystems on asymptomatic/ presymptomatic factors in Ebola pre-exposure diagnosis prior to the appearance of symptoms. Monitoring a person's blood serum chemistry for changes that suggest a compromised health status or non-invasive sampling of breath and saliva is attractive in theory." ] },{ "paper_id": "137b25ee1545c4b01332709ab1e24dcf935d6f96", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Proteins were harvested by using SDS-lysis buffer containing 1% Triton X-100, 0.5% NP-40, 150 mM NaCl, 10 mM Tris-HCl (pH 7.4), 1 mM EDTA, 1 mM EGTA (pH 8.0), 1% SDS, 0.2 mg/mL PMSF, 1 \u03bcg/mL aprotinin, 1 mM sodium orthovanadate, 2 \u03bcg/mL pepstatin, 2 \u03bcg/mL leupeptin and 10 mM sodium fluoride.", "Data obtained from two groups with different treatments were analyzed by two-tailed, paired Student's t-test (statistical significance if p < 0.05)." ] },{ "paper_id": "137c77a97b865b5d85e90b50782a1bdf78539ec4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/JCM .01658-17.", "SUPPLEMENTAL FILE 1, PDF file, 0.1 MB." ] },{ "paper_id": "138200f99f62c51776c9afec55d856e854ea8ff1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Another role for SPP in ERAD has come from a recent paper describing the cleavage of the unfolded protein response (UPR) regulator XBP1u by SPP (65) . XBP1u is a type II membrane protein and undergoes intramembrane cleavage within a conserved type II TM domain while integrated in a complex containing SPP, the protease Derlin-1, and the E3 ligase TRC8, which prime SPP for XBP1u cleavage. An ectodomain shedding of SPP substrates prior to SPP cleavage is thought to be required and normally performed by SP in signal sequences but such cleavage was unnecessary in the case of XBP1u, similarly to what we have described for Trh4 (52, 65) . In general, the UPR induces a strong downregulation of MHC class I molecules at the cell surface (66, 67) .", "Thus, SPP activity seems to have a direct impact on MHC class I peptide presentation by cleavage of leader sequences from nascent proteins and the liberation of some C-termini for MHC class I loading. A more indirect role that impacts on MHC class I presentation has been revealed and occurs through an ERAD pathway. This is also supported by a recent study using a systemslevel strategy reporting the involvement of SPP in the network that coordinates the ERAD response (68).", "What triggers the cleavage of Trh4 by SPP is not known yet. In addition to its liberation function of small transmembrane substrates, SPP has been shown to associate with misfolded membrane proteins in complexes where SPP is represented as a monomer, dimer, or multimer (57) . It was suggested that such high molecular weight complexes act as chaperones to dispose of membrane aggregates (57, 58) . The role of SPP in this degradation machinery might be to liberate such aggregates from the ER membrane. These discoveries were based on the viral US2 and US11 proteins, which successfully labels MHC class I molecules in the ER for retrograde transport to push this protein back to the cytosol for degradation by proteasomes (59, 60) . Interestingly, the SPP family member, presenilin 2, seems to be associated with this membrane proteolysis as well (61) . Since SPP and presenilin 2 have opposing preference for type I and type II transmembrane orientations, such a \"degradome\" machinery might be responsible to clear the ER membranes. This type of machinery is called the ERassociated degradation (ERAD) pathway. ERAD is an ER quality control system, which monitors the integrity of nascent or ERresident proteins and targets incorrectly folded or misassembled proteins to degradation. The disposal of misfolded MHC class I heavy chains also occurs through the ERAD pathway in the absence of viral interference (62) . Clearly, viruses take advantage of these existing pathways and hijack them in order to evade immune recognition by cytotoxic T cells (63, 64) ." ] },{ "paper_id": "1392d02729b5e2f1a63ff3ff259e10a8c45e5a55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The internal reliability of the pre and post-conference questionnaires was assessed separately. Cronbach's \u03b1 coefficients of 0.809 and 0.861 respectively were obtained, indicating a high internal consistency of the RIPLS questionnaire used.", "Traditionally, doctors have been trained to be self-reliant and independent, with the profession relying more on expertise, autonomy and responsibility rather than interdependence, deliberation and dialogue [1] . In recent years however, increasing focus has been placed on the importance of team-based care and collaboration between various healthcare professionals.", "(Additional non-IPE events held during the conference included a symposium on \"Surviving Medical and Nursing School\", as well as a scientific poster competition and a symposium on hospital residency for senior medical students.)" ] },{ "paper_id": "1399e34d62b515e482ccde6c4cae500b19546909", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, several newly emerged H5N1 AIVs in Egypt have been found to have acquired the human receptor SA\u03b1-2,6-Gal binding ability during their emergence in birds [76] .", "Like other influenza viruses, IDVs possess a negative-sense single-stranded RNA genome. However unlike IAVs that contain 8 segments, IDVs comprise seven genomic segments that are predicted to encode nine proteins, including glycoprotein hemagglutinin-esterase fusion (HE), polymerases PB2, PB1, and P3, nucleoprotein, matrix protein (M1 and CM2), and nonstructural proteins (NS1 and NEP) [59] . IDVs use 9-O-acetylated sialic acid as their cellular receptor on host cells such as ICVs [60] .", "Many viral pathogens have been implicated in BRD, which include bovine viral diarrhea virus, bovine herpesvirus 1, bovine respiratory syncytial virus and bovine parainfluenza 3. Experimental studies in calves with IDV showed damage that results in the induction of inflammation in the trachea. IDV could be a significant player in BRD and could facilitate coinfections with other bovine pathogens [59] . In addition to the animal health implications of IDVs, a recent study found IDV antibodies in 34 out of 35 persons that had contact with cattle and only 2 out of 11 that did not have any exposure to cattle [68] . The results of this study raised the possibility that IDV could be relevant from a public health stand point and that it could pose a zoonotic risk to cattle-exposed workers. With much still to be characterized about the new IDV species, exploring its impact on human an animal health through epidemiological studies will be vital to understanding spread of this virus.", "It is well established based on several epidemiological studies that cattle are the primary reservoirs of IDVs [50, 59] . In addition, IDVs have also been isolated from a range of animals including pigs, sheep, goat, horses and camelids. While the precise role of IDVs in clinical disease in animals is not yet fully investigated, their role in causing respiratory infections in cattle has been implied. Two recent studies carried out metagenomic characterizations of the virome associated with bovine respiratory disease in feedlot cattle and found correlation of IDV presence with Bovine respiratory disease (BRD) clinical signs, raising exciting new prospects for understanding and combatting this complicated disease [61, 62] .", "The International Committee on Taxonomy of Viruses (ICTV), which is responsible for developing, refining, and maintaining a universal virus taxonomy, has recently released revised classification of Orthomyxoviridae [57] . In earlier classification, Orthomyxoviruses belonged to any one of the five genera: Influenzavirus A, Influenzavirus B, Influenzavirus C, Thogotovirus and Isavirus [58] . However, the most recent classification of Orthomyxoviridae includes eight genera and nine species (Table 1) . Genus Alphainfluenzavirus comprises the species influenza A virus, Betainfluenzavirus comprises the species influenza B virus, Gammainfluenzavirus comprises the species influenza C virus, and Delatinfluenzavirus comprises the species IDV [58] . " ] },{ "paper_id": "139b81bc9c99d76cffc2014c4851942d2f592950", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "13a1c758877b216e51c51e9ee532ab5c3e0c12fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "into the cytosol where they activate a number of apoptotic pathways, ultimately leading to programmed cell death [18, 24, 44, 48, 60, 62] .", "\u2022\u2212 . Due to their high content of organic chemicals, ambient UFPs contribute proportionally more redox-cycling chemicals than larger particles [4, 24, 44, 60] .", "The \u2022 OH radical is more reactive than O 2" ] },{ "paper_id": "13a2da5074d1480d1e302628606afd1f17ac782e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A code was given to each enrolled participant and a physician examined each participant prior to the biological assessments, which included naso-pharyngeal swab collection for PCR analysis. The patient was interviewed directly to determine socio-demographic characteristics, patient's medical history and vaccination status, using a standard questionnaire. For children, these information were obtained from their mothers or care takers. For each enrolled study participant, paired nose and throat swabs were collected for pathogens detection. Symptoms presented by each participant on the day of survey, as well as data obtained from interviews and biological investigations were assigned on a case report form (CRF).", "Studies conducted in Africa, identified respiratory tract infections due to Streptococcus pneumoniae as a main cause of non-malaria febrile illnesses among other causes such as typhoid fever, urinary tract infection and other parasitic infections other than malaria [11] [12] [13] .", "Samples were collected by the study physician using a sterile nylon flocked swab and placed in viral transport medium (\"BD Universal Viral\"), labelled and transported on ice at Pasteur Institute Dakar for further processing and storage of the samples. " ] },{ "paper_id": "13ab857b7b076f5a00bb3becf27e9780fcecf26e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Among all the genetic human immunodeficiency virus (HIV) subtypes that exist in the world, subtype C is responsible for~50% of HIV-1 infections globally which included parts of Africa and Asia regions namely China, India etc., whereas in North America and Europe, the majority of HIV infections ligand, Bax, caspase 8, Receptor-binding cancer antigen expressed on SiSo cells (RCAS)-1, TNF-related apoptosis-inducing ligand (TRAIL), activation of cyclin-dependent kinases, microtubule alteration and inhibition of expression of manganese-dependent superoxide dismutase [39, 46, 47] .", "Authors declare that the data supporting the findings of this study are available within the paper and its Supplementary Information Files. The data are also available from the corresponding author upon request. The nucleotide sequences are available at GenBank with the accession numbers: HQ110625, FJ432073, HQ110614.", "T a t N 1 2 T a t V T 6 T a t D 6 0 T a t B T a t C" ] },{ "paper_id": "13af5f3171885fd9385c4320e14ce219aa345022", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "13b8c068799a93b4441116bb6cabae222d126d32", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Currently, standard immunological methods [7] or methods based on polymerase chain reaction (PCR) [8, 9] are widely used to identify the above mentioned viruses. Unfortunately, they can detect only one agent in a specimen.", "Avian viruses can cause diseases independently, in alliance with each other or in association with bacterial agents [12] . Thereby, rapid and sensitive methods of detection are required that are able to differentiate viral infections for surveillance of newly emerging avian viruses as well as for disease control.", "In assessment of laboratory tests effectiveness trueposi- [17] . Ninety-five percent confidence intervals (95% CI) were calculated according to Wilson [17] ." ] },{ "paper_id": "13b976db365e4973e7e0fe44646393b672c4a2db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Surface plasmon resonance binding assays. Surface plasmon resonance (Biacore) assays were performed on CM-5 dextran chips (GE) covalently coupled to the ligand via amine coupling. The running and injection buffers were matched and consisted of 150 mM NaCl, 0.01% Tween-20, 0.1 mg/ml BSA, and 10 mM HEPES at pH 7.5. Response unit (RU) values were measured as a function of analyte concentration at 298 K. Kinetic analysis was performed using the global fitting feature of Scrubber 2 (BioLogic Software) assuming a 1:1 binding model. For experiments using hAPN as a ligand, between 300 and 400 RU were coupled to the CM-5 dextran chips. For experiments using 9.8E12, 1900 RU was immobilized.", "Viral inhibition assay. HCoV-229E was originally obtained from the American Type Culture Collection (ATCC VR-740) and was produced in the human L132 cell line (ATCC CCL5) which was grown in minimum essential medium alpha (MEM-\u03b1) supplemented with 10% (v/v) FBS (PAA).", "Received: 29 May 2017 Accepted: 6 October 2017" ] },{ "paper_id": "13bc396fab607d24e0dfd5b38704463d13a85c08", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "13d39b597ef6853185ff1e43a4420984a8c6416e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vero cells were grown in high glucose DMEM supplemented with 10% heat-inactivated FBS and 1\u00d7 Antibiotic-Antimycotic solution (Gibco/Life Technologies, Carlsbad, CA, USA).", "The dose-response curves were fitted with four-parameter logistic functions (Equation (1)), where A min and A max are the upper and lower asymptotes (minimal and maximal drug effects), m is the dose that produces the half-maximal effect, and \u03bb is the steepness (slope) of the curve.", "We used a composite trapezoidal rule to estimate the area under the dose-response curve (AUC), which is a commonly used metric for the quantification of drug responses through multiple dose-levels [35] [36] [37] . This allowed us to calculate differential AUC (dAUC) between two dose-response curves (for example, plus minus virus).", "Several critical issues should be also considered while developing A-1155463 or its derivatives as antivirals. While A-1155463 may possess broad-spectrum antiviral activity in vitro and against some other viruses in primary patient samples ex vivo [12] [13] [14] , its antiviral efficacy should be evaluated in vivo. Also its side effects, including its immuno-and neuro-modulatory properties, " ] },{ "paper_id": "13d3cd2797da7eb9cc334821680a7b30badafa11", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Inducible Tregs are further divided into subclasses of iTregs, which are classified based largely on the mechanisms they use to mediate regulation (though the functional mechanisms of suppression utilized by these various iTregs are not strictly limited to each subpopulation -for example, multiple iTreg populations use surface molecules such as CTLA-4 or PD-1 to mediate infectious tolerance). Tr1 induced regulatory cells mediate suppression primarily through the secretion of the immunosuppressive cytokine IL-10, and are further characterized by their lack of Foxp3 and CD25 expression which are expressed by nTregs (7) . The second class of iTregs are Th3 cells, which were one of the earliest populations of Tregs and were identified as playing a role in mediating tolerance in experimental autoimmune encephalitis (EAE). These cells express CD25 and Foxp3 and predominantly utilize TGF-\u03b2 to mediate suppression, with minimal expression of IL-4 and IL-10 (8).", "While the Tr1 and Th3 populations of iTregs were long considered to be the only defined induced regulatory populations, research has identified another population of induced Tregs that can are potent mediators of suppression as well as in the propagation of infectious tolerance: iTr35 regulatory cells. These inducible regulatory cells were identified by Dario Vignali and colleagues and mediate suppression primarily through the expression of the regulatory cytokine IL-35 (9) . In this review, we will discuss the identification and characterization of IL-35, how it mediates suppression, the role it has been shown to play in disease, and the importance of IL-35 and more specifically iTr35 cells in propagating infectious tolerance.", "As clearly illustrated in Table 1 , IL-35 plays an important role in a variety of diseases. Furthermore, research from our group has identified that IL-35-expressing Tregs also play a central role in mediating tolerance in transplantation tolerance, immune responses to non-inherited maternal antigens (NIMAs), and prostate cancer [Ref. (23) ; and Olson et al., unpublished results], which we also found were dependent on the expression of CTLA-4. Interestingly, when we examined collagen type V-specific regulatory responses, we did not find a role for IL-35 [contrary to results obtained from other groups (16, 34) ] nor CTLA-4, though we did find that these responses relied heavily on TGF-\u03b2. This suggests that the regulatory responses we identified in the transplant, NIMA, and prostate cancer patients may have been relying on iTr35 cells, whereas the responses we identified to collagen V were nTregs, and suggests that potentially CTLA-4 and IL-35dependency may be a technique that can be used to identify this population of inducible regulatory cells." ] },{ "paper_id": "13e902f62fb20b66fbbc69e9ec434243342d16cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses (CoVs) are found in a wide variety of animals [1] in which they can cause respiratory, enteric, hepatic, and neurological diseases. Based on genotypic and serological characterization, CoVs were traditionally classified into three distinct groups [2] [3] [4] . Recently, the Coronavirus Study Group of the International Committee for Taxonomy of Viruses has replaced the traditional groups 1, 2, and 3 CoVs with three genera, Alphacoronavirus, Betacoronavirus, and Gammacoronavirus, respectively [5] . As a result of their unique mechanism of viral replication, CoVs have a high frequency of recombination [2, 6] . Their tendency for recombination and high mutation rates may allow them to adapt to new hosts and ecological niches [7] [8] [9] [10] .", "Viral RNA was extracted from the fecal samples using EZ1 Virus Mini Kit v2.0 (QIAGEN). The RNA was eluted in 60 \u00b5L of AVE buffer (QIAGEN) and was used as the template for RT-PCR.", "The authors declare no conflict of interest.", "The PCR products were gel-purified using the QIAquick gel extraction kit (QIAGEN). Both strands of the PCR products were sequenced twice with an ABI Prism 3700 DNA Analyzer (Applied Biosystems), using the PCR primers. The sequences of the PCR products were assembled manually." ] },{ "paper_id": "13f8fe9cd4b06843fce134699ecc8b89cf6a2353", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where T is the latest time of observation (i.e., December 22 in our case study) and c T = (c 1 , c 2 , : : : , c T ).", "where t in the right-hand side indicates the time since infection (or the so-called \"infection-age\"). We assume that c t follows a Poisson distribution. The likelihood to estimate u consisting of the parameters R 0 , n, and a t is derived as", "(1)" ] },{ "paper_id": "13fbc589f8307a0f1a6c7eccd2651743c780bd6a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The complete genome sequence of PDCoV strain CH/ JXJGS01/2016 has been deposited in GenBank under the accession number KY293677.", "The full-length genome sequence of CH/JXJGS01/2016 determined in this study will increase our knowledge of PDCoV virology, providing a basis for the development of diagnostic tools and vaccine candidates. Further in-depth phylogenetic analysis of PDCoV requires more complete genome sequences of PDCoVs originating worldwide.", "The complete genome sequence of a variant of porcine deltacoronavirus, isolated from a diarrheal piglet and designated CH/JXJGS01/2016, was sequenced and analyzed. Phylogenetic analysis demonstrated that CH/JXJGS01/2016 shares the highest nucleotide and amino acid identities with the Chinese strain NH (GenBank accession number KU981059)." ] },{ "paper_id": "140cdf5d99f486ccd0346d07cad3fa66b2567c42", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, is a negativestranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, while in livestock it causes fever and high abortion rates.", "The PCR product consisting of a wild-type ZH501 M-segment by M430F and M1041R was directly sequenced, or cloned into pSTBlue-1 by AccepTor Vector Kits (Novagen, Darmstadt, Germany) according to the manufacturer's instruction. Thirtyfive clones were sequenced by T7 primer." ] },{ "paper_id": "142a615ffb970d12beaa9597bff2b9c49da4bb96", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Funding received from Bill and Melinda Gates Foundation.", "ethical approval Not required." ] },{ "paper_id": "1434efe4d841738948735807bd1d1f1e9a36225e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "study participants from the Stockholm (Sweden) area entered the baseline step of the ILI study in the context of the Swedish national LifeGene project 1 .", "vaccine containing A/ H1N1/California/7/2009 (adjuvanted with ASO3, i.e. DL-\u03b1-tocopherol, vitamin E; squalene and polysorbate).", "Swedish residents who were offered the pandemic flu vaccine received Pandemrix (GSK)" ] },{ "paper_id": "14374db205f6934d9cba148624462000bc6ec7be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). RNA sequencing data have been submitted to the NCBI BioProject database under BioProject no. PRJNA394932 and SRA accession no. SRP113049.", "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .02469-18. ", "Statistical analysis. Statistical analysis was performed with the unpaired t test using GraphPad Prism version 5.03 (GraphPad Software). Values are depicted as mean \u03ee standard error of mean (SEM). A P value of \u03fd0.05 was considered statistically significant.", "Virus and bacteria. Influenza virus A/Puerto Rico/8/34 H1N1 strain (PR8) was obtained from the American Type Culture Collection and propagated in embryonated eggs. Viral titers were determined by plaque assay. Serotypes 3 and 19F of S. pneumoniae were derived from clinical isolates in Singapore and cultured in brain heart infusion broth (Sigma 53286) supplemented with 5% heat-inactivated fetal bovine serum (FBS) under anaerobic conditions until the mid-logarithmic phase." ] },{ "paper_id": "1449e7aedd623536a61d71bf1505622093774208", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Feline coronavirus (FCoV) is an enveloped RNA virus belonging to Coronaviridae. The disease is prevalent especially in catteries and multiple-cat household [1] . FCoV consist of two biotypes; Feline infectious peritonitis (FIPV) which is highly fatal and caused immune mediated complex, and feline enteric coronavirus (FECV) which caused from asymptomatic infection to severe enteritis [1, 2] .", "Although evidence of FIP have been reported among cat population in Malaysia [5, 6] , the circulating FCoV virus neither isolated nor characterized. Thus, the objectives of this study are to isolate and determine the FCoV biotypes occurring in Malaysia.", "Viral RNA was extracted from infected cell cultures or Ascites fluid using Trizol Reagent (Invitrogen, USA) according to manufacturer's instructions. RT-PCR was performed using Access RT-PCR system (Promega, USA) [6] with previously described primers p205 and p211 [16] . Positive samples were further differentiated into type I and type II FCoV using biotypes specific oligonucleotide primers targeting S-gene region [17] . All primers were synthesized by First Base Laboratories Sdn Bhd, Selangor, Malaysia." ] },{ "paper_id": "144bd370f94a0844a954100eb08bf1df9403ddaf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chloramphenicol acetyl transferase (CAT) activity assay using a mini-genome system", "All experiments were performed in 3-8 biological repeats. Statistical tests and graphical data presentation were performed using SigmaPlot 10.0 Software (Systat Software, Inc., USA), GraphPad Prism 5 Software (GraphPad Software, Inc., USA) and MS Excel 2010 (Microsoft Corporation, USA). All data are presented as the mean \u00b1 standard deviation of the mean (SD). The significance between two groups was determined via \"Student t-test\"." ] },{ "paper_id": "1455bb070334751379d26c7c161a1f17b8d07a0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although in vitro potency and lipophilicity of compounds are important parameters to evaluate, the concept of Lipophilic Efficiency (LipE) aids in establishing a more balanced relationship between the potency observed in vitro and lipophilicity properties of evaluated chemical compounds [27] . Ryckmans et al. [19] reported that high quality lead compounds possess higher LipE values.", "Human red blood cells infected with the P. falciparum clone W2 (chloroquine-resistant) were maintained in continuous culture as previously described [30, 31] . The human red blood cells and plasma were ceded by the Funda\u00e7\u00e3o Hemominas-Hemon\u00facleo Divin\u00f3polis [32] . The synchronization of the parasites was achieved by sorbitol treatment [33] and parasitaemia was determined microscopically in Giemsa-stained smears.", "In 2010, there were an estimated 219 million cases of malaria, a global infectious disease, and it was responsible for 660,000 deaths [1] . The arsenal of antimalarial drugs is limited and currently the most effective treatment against the pathogenic agent Plasmodium falciparum includes artemisinin combination therapies (ACTs), although resistance to artemisinins has been reported in four countries of the South-East Asia region: Cambodia, Myanmar, Thailand and Vietnam [2, 3] .", "One of the main challenges in the development of new antimalarial drugs is how to achieve a viable lead candidate with good pharmacokinetic properties: absorption, distribution, metabolism, excretion and toxicity (ADMET) [15] ." ] },{ "paper_id": "14597dad9c71c07579c0a5e5e9878aa1c003f50e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Provincial epidemiologists and local public health doctors conducted face-to-face interviews with all affected individuals, their family members and medical staff using a standard questionnaire designed by the Chinese Center for Disease Control and Prevention (China CDC). A variety of epidemiologic information was collected, including that which is related to personal information, comorbidity, and exposure condition and infection areas. Investigations generally began within 24 h of a diagnosis of suspected infection, clinical circumstances permitting.", "A cluster was defined as two or more persons with an onset of symptoms within the same 14-day period, who were associated with a specific setting such as a classroom, workplace, household, extended family, hospital, other residential institution, military barracks, recreational camp or live bird market [19] .", "Total viral RNA was extracted from the respiratory specimens using a Qiagen RNeasy Mini Kit, according to the manufacturer's instructions. The specific primer and probe sets were provided by the China CDC. All cases were confirmed by rRT-PCR methods." ] },{ "paper_id": "145bb000d606bc2ea82e7e11f79363796bc9b7b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To verify that the predicted platypus genes were expressed as mRNA and eliminate the possibility of amplification from DNA templates, gene-specific PCR primers were designed based on sequences on two separate exons.", "We used the CEACAM classification proposed by Beauchemin et al. (1999) [27] and Kammerer et al. (2007) [22] . If an orthologous relationship to human proteins could not be defined, the proteins were denoted by the generic gene name in the GenBank. In nonmammalian species, all CEACAM family genes were annotated with a Roman letter based on their chromosomal localization.", "Carcinoembryonic antigen cell adhesion molecules (CEA-CAMs) and pregnancy-specific glycoproteins (PSGs; also known as Schwangerschafts Protein 1) are characterized by an N-terminal immunoglobulin variable domain-like region followed by a varied number of immunoglobulin constant domain-like structures. The prototypic member, CEA (or CEACAM5), was initially discovered as a membrane-anchored tumor antigen [1] . CEACAM subfamily proteins have since been shown to play important roles in the regulation of immune responses, angiogenesis, the differentiation of mammary glands, insulin signaling turnover, tumorigenesis, and metastasis [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12] . By contrast, PSGs have been characterized as highly glycosylated major proteins from human syncytiotrophoblasts during pregnancy. High levels of human PSGs have been detected in maternal serum as early as 3 days postfertilization, coinciding with the attachment of the blastocyst to the uterine wall, and were believed to be critical for protecting the semiallotypic fetus from the maternal immune system during pregnancy in, at least, primates [13, 14, 15, 16, 17, 18, 19] ." ] },{ "paper_id": "1460431a11ae554624fded17f039eacbda52effb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1 \u30fbSupplementary Figure S1 Chromatograms of size fractionation HPLC 2 \u30fbSupplementary Figure S2 LC-ESI-MS and MS 2 spectra of 88 strial glycans 3 \u30fbSupplementary Figure S3 Positive ion mode MALDI-QIT-TOF-MS spectra of SALSA-4 derivatised glycans 5 \u30fbSupplementary Figure S4 LC-ESI-MS and MS 2 spectra of A3-13 species 6 7 \u30fbSupplementary", "GnM5 M a n \u03b1 1 -6 a r m M a n \u03b1 1 -3 a r m" ] },{ "paper_id": "14626b4b98947a5534bdcc578b6659c258f7e7dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Neutralizing Antibody Titer ED50 (AVG) ", "Vaccine candidates induced high titers of neutralizing antibody.", "Vaccines 2019, 7, x 5 of 13", "For the in vivo experiments, we treated mice (10 mice/group, 10 groups) with serial tenfold diluents of 100 \u00b5g crude toxins to monitor the survival rate. The minimal dose that caused complete lethality (MLD) in mice was calculated with the Reed-Muench method." ] },{ "paper_id": "1469710f9b5dce0601307791210b86a225dd1be1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza A virus is a remarkably promiscuous virus. Viruses circulating in birds, pigs and people garner the most attention, given their impact on public health, yet influenza virus naturally infects a diverse array of animals. These hosts include dogs, horses, cats, non-human primates, cattle, seals,", "whales, guinea pigs, ferrets, mink, giant pandas, pikas, raccoon dogs, anteaters, camels, and penguins (reviewed in [15] [16] [17] ). The detection of influenza A virus in bats, which represent ~20% of all known mammals, dramatically expands the host range of this virus.", "Influenza A virus is a member of the Orthomyxoviridae family with a segmented genome composed of eight single-stranded negative-sense RNAs [18] . The viral genome exploits splicing, frame-shifting and leaky scanning to code for at least 14 different proteins. Influenza viruses are classified into subtypes based on their two major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Prior to the identification of influenza virus in bats, 16 HAs and nine NAs had been identified, circulating primarily in avian reservoirs. Of these, only H1N1, H2N2, and H3N2 are known to have caused pandemics in humans." ] },{ "paper_id": "146fa23813d36d8da4ea4ab928d5cac594fdbd44", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The south and southeast regions of Jeju Island, especially Namwon-eup, showed the highest incidence of scrub typhus. Workers in mandarin orange orchards seemed to be the highest risk group for scrub typhus infection.", "The median age of the patients was 58-years-old (range, 8 to 91) and 43% of them worked in the agricultural, forestry or livestock industry. Regardless of their job, 87% of the patients had a history of either working outdoors or of other activities before developing scrub typhus.", "From January 2011 to December 2016, 446 patients were diagnosed with scrub typhus on Jeju Island. The patients' personal data and the environmental factors that might be related to scrub typhus were investigated and retrospectively analyzed." ] },{ "paper_id": "14723bfc42908c3f8f522692be41062a7cda62d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "147422b51b66a3e9c76f32fab4b4a004f67e8a16", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In some cases, VHHs are only effective or needed in a certain organ, cell type or cell compartment. Multiple formatting options are available to specifically target or deliver VHHs to one of these regions, e.g., linkage to antibodies or peptides, provide posttranslational modifications or in situ expression by bacterial vectors.", "The small size, single domain build-up and the presence of hydrophilic amino acids in FR2 go together with a typically high solubility and physical stability of VHHs. As a result, these proteins can ", "Some viral targets may be located inside the infected cell and thus hard to reach by antiviral VHHs. This problem can however be overcome by linking the VHH to a cell-penetrating peptide such as penetratin. This approach has been applied for the development of anti-hepatitis C virus (HCV) VHHs. Several intracellular viral proteins were considered as targets: the viral RNA-dependent RNA polymerase, the NS3 helicase/NTPase and the multifunctional HCV NS4B protein [84] [85] [86] [87] . In vitro, penetratin-linked VHHs directed against these targets could suppress HCV replication. These VHHs have not been tested yet in vivo." ] },{ "paper_id": "1477e7acddb857281705b48912ade3fd5b3f2a6e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "147b848766e7280950bd8ac4d1c02efb55e63ef3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The research proposal was approved by the ethics committee of the Sendai Medical Center (#26-03) and the ethics committee of the National Institute of Infectious Diseases (#873). The consents of participants were obtained verbally. When participants were under 20 years old, consents were obtained from parents or guardians.", "Multiple-sequence alignments were constructed with the MAFFT software (ver. 7.123b) using the default settings [41] . Phylogenetic analysis was performed with the maximum likelihood methods in the MEGA software (ver. 7.0.21) [42] . The statistical significance of the tree topologies was tested with bootstrapping (100 replicates).", "Human metapneumovirus (HMPV) is a major causative agent of acute respiratory infections especially in young children, older people, and patients with underlying conditions such as PLOS " ] },{ "paper_id": "14898820328acb4f3dcf85f33f3addb113d5a97d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Similar to HPV E6, the HTLV-1 oncoprotein Tax allows for sustained AKT phosphorylation under low serum conditions, and this may be due to Tax interacting with the regulatory p85 subunit of PI3K [70] . Another study showed that Tax-conferred growth factor independence through mTORC1 [71] .", "Several viral oncoproteins such as EBV LMP1 [15], KSHV vGPCR [242] , HBx [243] and HTLV-1 Tax [69] were shown to signal through the potential AMPK-activating kinase TAK1. TAK1-AMPK connections in the context of these viral proteins, however, have not been examined.", "The endoplasmic reticulum (ER) is the major cellular site for folding and maturation of secreted and transmembrane proteins. ER stress ensues when the number of unfolded and/or misfolded proteins that enter the ER exceeds the capacity of the ER chaperone machinery and triggers a regulatory response termed the unfolded protein response (UPR) that adjusts the ER work load to its folding/refolding capacity [279] . Moreover, the UPR also activates autophagy [139] . The signaling pathways that activate the UPR have been reviewed in detail elsewhere [279, 280] and are outlined in Figure 5 .", "In addition to inhibiting autophagy through formation of a vBcl2/Beclin-1 complex, KSHV also blocks this process via its FLICE-like inhibitor protein, vFLIP (encoded by ORF71/K13). vFLIP and its cellular counterpart cFLIP, inhibit death receptor-induced apoptosis [168, 169] and also suppress starvation-or rapamycin induced formation of LC3-decorated vesicles and cell death associated with autophagy [90] . Of note, the anti-autophagic activity of vFLIP and cFLIP were independent of their anti-apoptotic activities, and both vFLIP and cFLIP were found to bind the autophagy-protein ATG3 competitively with LC3. For vFLIP, it was shown that the ability to interact with ATG3 was required for inhibition of cell death associated with autophagy [90] ." ] },{ "paper_id": "1495c1fa93db3b9a5d12b5ae15ff0c8639b83452", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "What are the marketing networks? Biosecurity is generally quite low in both smallholder and larger commercial farms. What are some effective/feasible ways to reduce AI risk?", "How can these be tested in practice?", "What are antiviral drug and poultry vaccination policies?" ] },{ "paper_id": "14a0b8d9f05d4baef14cfa9178748cb9d504d523", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Doctor's Name; EGF: epidermal growth factor; ELISA: enzyme-linked immunosorbent assay; EPO: erythropoietin; FSH:", "follicle-stimulating hormone; GnRH: gonadotropin-releasing hormone; IFN\u03b3:", "interferon-gamma; IGF-1:" ] },{ "paper_id": "14ae1c8c866fcbdad5e965f296a90a8cbf41f689", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mouse anti-PRRSV N protein and monoclonal J2 anti-dsRNA antibodies were purchased from Jeno Biotech Inc. (Chuncheon, South Korea) and Scicons (Hungary), respectively. Cellular DNA, mitochondria and lysosomes were stained with DAPI, MitoTracker Red and Lyso-Tracker Red, respectively (all reagents were from Molecular Probes, OR, USA). Rabbit anticalnexin, anti-LC3 and anti-IgG Alexa Fluor were purchased from Cell Signaling Technology. A goat anti-mouse IgG-Gold antibody was obtained from Sigma-Aldrich.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "14b23be79f302d4603f64e7a45d56574a23b59f5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses that cluster within the family Coronaviridae (order Nidovirales). They infect a wide variety of species, including humans, livestock, and companion animals. In humans, they usually cause mild to moderate respiratory symptoms, although more severe cases occur mostly in individuals with impaired immune responses [1] . The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in China in the winter of 2002, and of Middle East Respiratory Syndrome coronavirus (MERS-CoV) in September 2012, reminds us that coronaviruses pose a significant threat, and that zoonotic transmission is common [2] [3] [4] [5] [6] .", "Subsequently, PCR was performed with using KAPA PROBE FAST qPCR Master Mix (Kapa Biosystem). Rox was used as a reference dye. The amplification program, specific probes and primers for each virus are listed in Table 1 .", "CRCoV nucleocapsid gene was codon optimized, synthetized, and cloned into pETDuet vector via BamHI and AatII sites. Plasmid identity was confirmed by sequencing. N protein was expressed in E. coli Origami cells following induction with 0.5 mM isopropyl-\u03b2-D-thiogalactopyranoside (IPTG) at 20 \u2022 C for 16 h. Protein was purified on Ni-nitrilotriacetic acid resin (IMAC Sepharose 6 Fast Flow)." ] },{ "paper_id": "14b4d32ff078c4db9661a587e43a30a7bf227ed9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Feline coronavirus (FCoV) belongs to the family Coronaviridae and the order Nidovirales [1] and affects both wild and domestic cats [2] . FCoV contains a positive polarity RNA genome approximately 29 kb in length, consisting of 11 open reading frames (ORFs). Two major ORFs encode a replicase, four ORFs encode the structural proteins S (spike), E (envelope), M (membrane), and N (nucleocapsid), and five ORFs encode the nonstructural proteins 3a, 3b, 3c, 7a, and 7b [3] .", "FCoV can cause a mild or sometimes apparently symptomless enteric infection, especially in kittens, and is also associated with a lethal, systemic disease known as feline infectious peritonitis (FIP) [4, 5] . FIP is characterized by fibrinous, granulomatous serositis, with protein-rich effusions in the body cavities of affected cats (effusive or \"wet\" FIP), as well as granulomatous-necrotizing lesions, periphlebitis and granulomatous inflammatory lesions in several organs, especially, liver, kidney, spleen, leptomeninges, and eyes (noneffusive or \"dry\" FIP) [6] .", "Brown et al. [18] have proposed yet a third hypothesis for FIP pathogenesis. These authors suggest, after phylogenetic 2 Advances in Virology " ] },{ "paper_id": "14c6dff031b3bcf8a7ea8486965b1dd888cf46a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study of animals was approved by the Institutional Animal Care and Use Committee at the New York Blood Center (Approval #194.14). All animal studies were carried out in strict accordance with the recommendations of the American Veterinary Medical Association (AVMA) Guidelines and the approved protocols.", "Mice were subcutaneously immunized with 10 \u03bcg/mouse of recombinant MERS-CoV S-RBD-Fc protein formulated with Freund's complete adjuvant (Sigma, St. Louis, MO) and boosted once with 5 \u03bcg/mouse of the immunogen and Freund's incomplete adjuvant at 2-week intervals. Sera collected at 10 days post-2 nd vaccination were used to detect neutralizing activity.", "Generated MERS-CoV pseudovirus was able to infect a variety of cell types from human and non-human hosts", "The codon-optimized genes expressing full-length S protein of MERS-CoV (humanbetacoronavirus 2c EMC/ 2012, hCoV-EMC, GenBank accession no. AFS88936.1) were synthesized by GenScript (Nanjing, China) by replacement of the N-terminal signal peptide (residues 1-17) with CD5 signal sequence and insertion into pcDNA3.1 vector (Invitrogen, Carlsbad, CA). The constructed recombinant MERS-CoV plasmid (rMERS-CoV-S) containing the S gene was confirmed for correct insertion by sequencing analysis." ] },{ "paper_id": "14c756dfe065a0ed1ff950195576f8975d209c93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Tables S1 and S2; Figures S1 and S2." ] },{ "paper_id": "14f427656a9898ce76f31cb012f258a9aa6d1ce3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Heifers, n (%) 44 (100) 11 (100) 12 (100) 14 (100) 7 (100)", "Median age (Years) 6 (4 to 9) 4 (4 to 7) 6 (4 to 9) 6.5 (4 to 8) 6 (5 to 8) ", "In this study" ] },{ "paper_id": "15029a39f0a27d1bbccb6fed1793ea25700d9e57", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "150e648964270067a1ea14caffbc3427f756dafb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics statement. As this research involved human blood, the aims of our study were explained to all the dengue patients involved (all were adults) and all provided written informed consent. The collection methods of clinical samples and epidemiological data were reviewed and approved by the Institutional Ethics Review Board of Southern Medical University and were carried out in accordance with the approved guidelines. Samples were selected randomly based on the laboratory diagnosis and clinical signs.", "Databases of E gene molecular evolution were created via a screening process based on epidemiologic and phylogenetic methods. Among them, 81 strains in Guangdong constituted the local database, whereas 403 strains in other countries made up the imported database.", "Based on DENV1 isolated from the outbreak in 2014, we systematically collected the E protein gene from 2005 to 2018 from GenBank. With the epidemiological data since 2005 supplied by the Guangdong Provincial CDC, we studied phylogenetics, molecular characteristics, and epidemiology to strengthen the foundational research of DENV1 for the prevention of large-scale dengue epidemics, providing preventive and control measures of DF with important evidence." ] },{ "paper_id": "1516a62bffb7478ad5cbec0bde15290baf5384a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HMGB1 Enzyme-Linked Immunosorbent Assay (ELISA) Serum HMGB1 was measured by ELISA using commercially available kits (HMGB1 ELISA Kit II; Shino-test, Sagamihara, Japan) following manufacturers' instructions. The sensitivity of the assay was 1.0 ng/mL.", "Hepatocellular damage was assessed by measuring serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) using a SPOT CHEM SP-4420 analyzer (ARKRAY, Kyoto, Japan).", "Two types of immunohistochemical controls were used. (1) Sections were processed by replacing the primary antibody with normal non-immune serum. (2) Sections were processed by replacing the primary antibody with an irrelevant antibody (GFP; Invitrogen). The immunoreactions were completely absent in control sections." ] },{ "paper_id": "15228615c1656f39a5ec8dcc8bc26ef0371d4040", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells on coverslips were fixed with 4% paraformaldehyde in phosphate-buffered saline (PBS) for 10 min and permeabilized with 0.2% NP-40 in PBS. The coverslips were soaked in 1% bovine serum albumin in PBS, and then incubated at room temperature for 1 hour with a primary antibody. After being washed twice with PBS, the coverslips were incubated at room temperature for 1 hour with a secondary antibody. The coverslips were then incubated at room temperature for 5 min with 3 mM 49,69-diamidino-2phenylindole (DAPI) and finally mounted on glass plates, and cells were observed under the fluorescence microscope.", "The virus transmission undergoes from infected to uninfected cells through either basolateral [36] [37] [38] or apical [39] [40] [41] [42] sides. In the case of influenza virus, cell-free progeny virions are released only from the apical surface of polarized epithelial cells [43] . This releasing polarity is achieved by directed transport of viral membrane proteins to the apical plasma membrane [44] . Indeed, that HA and NA glycoproteins are associated with lipid rafts, and the raft association has been implicated in apical transport [45, 46] .", "The production of rabbit polyclonal anti-NP antibody was described previously [53] , and this antibody was used as a primary antibody for indirect immunofluorescence assay. A goat antirabbit IgG antibody conjugated to Alexa Fluor 488 or Alexa Fluor 568 was purchased from Invitrogen and used as a secondary antibody for indirect immunofluorescence assay. A polyclonal antibody against influenza A virus was obtained from 2-month-old female rabbit immunized with 250 mg of purified virions of influenza virus strain A/Puerto Rico/8/34 [54] . The generation of antibodies was boosted three times and used as neutralizing antibodies to block the influenza virus infection." ] },{ "paper_id": "1522b3c191730bb3161a610fadb3bf06095ab902", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Supporting information S1 " ] },{ "paper_id": "15253c08a446817c195eab73473fc2f215528705", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was supported by the Agricultural Science and Technology Innovation Program (ASTIP) of Chinese Academy of Agricultural Science. We thank Accdon for their linguistic assistance during the preparation of this manuscript.", "WL wrote this manuscript and CD designed this project." ] },{ "paper_id": "1536008edcc909523ffc39c62b8389ba0ee76f95", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Similar results were found for hospitalizations, with 4 of 5 countries registering a decrease, with significant decreases in both Singapore (\u2424 1 \u03ed \u03ea0.090, P \u03fd 0.001) and Australia (\u2424 1 \u03ed \u03ea0.067, P \u03fd 0.001), whereas a significant increase was observed in Taiwan, ROC (\u2424 1 \u03ed 0.065, P \u03fd 0.001) ( Table 2) .", "The equations for the respective models of Poisson and linear regressions are shown together with Tables 1-4 (footnotes). The regression coefficients, \u2424 1 and \u2424 2 , each refer to the slope when the dependent variable-death counts, hospitalization rates, or C:R-is regressed on the independent variable, time in years or log(C:R). These regression coefficients (\u2424 1 and \u2424 2 ) would be interpreted as the average annual percentage change of the dependent variable in relation to the independent variable.", "The general decline in asthma mortality and hospitalizations across Asia Pacific (Figs. 1, 2) coincided with significant increases in C:R ratios across the region (Fig. 3) ." ] },{ "paper_id": "15372a2da42ddcb56ac4edc88090a6a425c5fad0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u25aa laboratory tests performed to investigate the illness;" ] },{ "paper_id": "153bc127b399f445ca2ec0e0709379efaada43bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "no clear source of infection to humans and an epidemiologic pattern that is more sporadic than the classic epidemic pattern of SARS [2] . Of further concern is the significant increase in reported cases since March 2014; in April 2014 alone, the number of reported cases exceeded the total number of cases that had been reported in the two years prior [2] .", "With MERS CoV there was no epidemic peak in the first 12 months as there was with SARS [12] . Instead, there were infrequent cases over a longer period than would be expected for a disease that is not highly infectious (see Figure 1 ). This pattern is suggestive of a sporadic rather than epidemic source of ongoing infection in humans. Estimates of the reproductive number, R0, are low, and range from 0.42 < R0 < 0.92 [33] , and 0.8 < R0 < 1.5 [34] , suggesting the infection does not have epidemic potential and cannot be easily sustained in the human population by human-to-human transmission alone [9, 35, 36] . A low reproductive number is supported by the epidemiologic pattern, however, the surge of cases in April 2014, inclusion of asymptomatic and mild infections and the increasing size and transmission generations of recent clusters would under-estimate this calculation.", "The first outbreak of MERS-CoV occurred in a hospital in Jordan in April 2012, with subsequent cases and clusters occurring throughout the Arabian Peninsula. Phylogenetic analysis of the virus has revealed that MERS-CoV has been in circulation since at least 2003 [4] , much longer than previously estimated based on the most common ancestor for the MERS-CoV strains found in humans [5] , and well before the first confirmed case in Jordon. Travel from the infected regions has resulted in additional cases in over a dozen countries, with limited local transmission occurring in the UK, France, Tunisia, and Iran. Furthermore, five of the highest travelled airports in the world are located in countries where MERS-CoV has been transmitted [6] , creating the possibility of a pandemic [7] ." ] },{ "paper_id": "1542e8e707bd5fa1cb6b3919722fc30ced018c1f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Percutaneous and transjugular liver biopsies and HVPG measurements were performed as we have previously described [5] . Fibrosis stage was scored using the Scheuer classification: no fibrosis (F0), minimal portal fibrosis (F1), periportal fibrosis (F2), fibrosis beyond the portal tract making septums (F3) and cirrhosis (F4) [6] .", "See (Data S1).", "See (Data S2)." ] },{ "paper_id": "1546fd2f004f233eea33c99a54f863ee80ffedaf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data were extracted from AEIS database and downloaded in Microsoft Excel and Access format. The statistical analyses were performed in SAS 9.1 and SPSS 14. The geographical distribution analysis was performed in Arc GIS 9.2." ] },{ "paper_id": "154880a8053db7adb802ae5350656b649496b4a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DC-SIGN is a transmembrane lectin receptor on dendritic cells with multiple immune modulation function [18] DC-SIGN can recognize many pathogens, such as viruses (HIV-1, dengue, and measles virus) [19] [20] [21] , bacteria (Helicobacter pylori, Mycobacterium tuberculosis) [22] , and fungi (Candida albicans and Aspergillus fumigatus) [23] contributing to generation of pathogen-tailored immune responses and immunosuppressive response by the MAPK pathway in DCs [24] . The real cause of KD remains unknown. It is generally accepted that KD results from an undefined infectious process trigger in a genetically predisposed individual [25] .", "Genotyping of CD209 rs4804803 SNP. Genomic DNA was isolated from heparin-anticoagulated blood samples using a standard phenol-chloroform extraction followed by 70% alcohol precipitation. Genotyping for the CD209 variant (\u2212336 A/G; rs4804803) was carried out using Custom TaqMan SNP Genotyping Assays (Applied Biosystems, Foster City, CA, USA). The primer sequences were 5 -GGACAGTGCTTCCAGGAACT-3 (forward) and 5 -TGTGTTACACCCCCTCCACTAG-3 (reverse). The Taq-Man minor groove binder probe sequences were 5 -TACCTGCCTACCCTTG-3 and 5 -CTGCCCACCCTTG-3 . The probes were labeled with the TaqMan fluorescent dyes VIC and FAM, respectively. The PCR was conducted in total volume of 15 \u03bcL using the following amplification protocol: denaturation at 95 \u2022 C for 10 min, followed by 40 cycles of denaturation at 94 \u2022 C for 20 s, followed by annealing and extension at 60 \u2022 C for one minute. After the PCR, the genotype of each sample was determined by measuring the allele-specific fluorescence in the ABI Prism 7500 Sequence Detection System, using SDS 1.1 software for allele discrimination (both Applied Biosystems). To validate the genotyping by real-time PCR analysis, 100 PCR products were subject to restriction fragment length polymorphism (RFLP) analysis with MscI restriction enzyme (New England Biolabs, Beverly, MA, USA) and showed a 100% identical result between these two genotyping systems as noted in our previous report [17] .", "The Scientific World Journal [27] [28] [29] , further investigation into other candidate SNPs contributing to KD morbidity is needed. Besides dendritic cells, IVIG was observed to affect many other cells, including endothelial cells, monocytes, neutrophils, and T and B cells [30] [31] [32] . The numerous effects of IVIG therapy also partly explain there not being an association of \u2212336A/G SNP of the DC-SIGN gene with IVIG resistance in KD.", "The Hardy-Weinberg equilibrium was first checked. The statistical differences between case and control in genotype and allele frequency were assessed by chi-square test. The statistical differences in the genotype and allele frequency of KD patients with and those without CAL formation, aneurysm formation, patients responding to IVIG, and those showing resistance were assessed using chisquare test. SAS 9.1 for Windows was used for data analysis." ] },{ "paper_id": "154eae1741c2ed718dec40b25f60eca4b56e0a74", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1552cf77b6385950e197c67c2ed55ed6e1879ced", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Received: 12 April 2010 Accepted: 10 August 2010 Published: 10 August 2010" ] },{ "paper_id": "155cca2a90a5430ac391b46983efa4c13f193289", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "WTA thus provides an isothermal alternative to random RT-PCR, and could become an invaluable method in diagnostic applications, particularly when used in conjunction with oligonucleotide microarrays. " ] },{ "paper_id": "155de81e6f3c3ca342aa733e289b749a5394a26b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Alpha-O Peptides did not fund any of this research. The paper is a mathematical paper that refers to self-assembling protein nanoparticle (SAPN), a technology that has been patented by P.B.", "Regarding D 3 symmetry, the necessary condition is", "Funding. Funding for G.I.'s visit to York via Italian National Group of Mathematical Physics (GNFM-INdAM) and by EPSRC grant EP/K028286/1 is gratefully acknowledged. R.T. also thanks the Royal Society for a Royal Society Leverhulme Trust Senior Research Fellowship (LT130088).", "Competing interests. P.B. is CEO of the company Alpha-O Peptides and has patents or patents pending on the technology." ] },{ "paper_id": "1560867701aecc60f73407501a5c5c85e53c8522", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All flow cytometry data were collected on either a FACSCalibur (BD Biosciences, San Jose, CA) or CyAn flow cytometer (Dako North America, Carpinteria, CA) and then analyzed by FlowJo software (Tree Star, Ashland, OR)." ] },{ "paper_id": "15640dc97f36ae7b410f731003235ee8a3cae495", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The kinetic parameters were determined with a published method (30) . In this assay, the initial velocity is given as a function of the enzyme concentration [E] with the following equation:", "IGF-1 and IGFBP3 were obtained from PeproTech Asia (USA). Anti-IGF1R b and anti-phospho-IGF1R (Tyr1135/1136)/insulin receptor (Tyr1150/1151) were from Cell Signaling Technology, Inc. (Danvers, MA). Antiinsulin Rb and anti-phospho-insulin Rb were from Santa Cruz Biotechnology (Santa Cruz, CA). Anti-IGFBP3 was from Abcam (Cambridge, UK). The polypeptide GPETLCGAEL was synthesized by Kelowna International Scientific (Taiwan). Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) analysis was carried out in the MASS core facility, NRPGM, National Science Council, Taiwan. CL1-0 cells were a gift from Dr Yang Pang-Chyr of the National Taiwan University (27) . NCI-H460, H520, and H661 cells were purchased from the American Type Culture Collection and cultured according to instructions.", "Reduction of the ligand concentration and a blockade of IGF1-IGF1R binding are promising anticancer strategies (26, 49) . Our results suggest that the proteolytic processing of IGF-1 is another alternative way to control the IGF axis. Consistent with this, the expression of the DPP-IV protease is reduced in certain cancer types (e.g., human lung SCC). Because DPP-IV inhibitors are currently used to treat human type II diabetes (50, 51) , their potential long-term impact on the balance between cell growth and apoptosis in this niche warrants further investigation." ] },{ "paper_id": "15724c0c0f8675d894aa76e25c9a29f4266d0440", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Colistin sulfate and resveratrol were obtained from Sigma-Aldrich (Saint Quentin Fallavier, France). Resveratrol (Thermo Fisher, Germany) was dissolved in dimethyl sulfoxide (DMSO) (Sigma-Aldrich, Saint Louis, USA) at a concentration of 20 mg/mL.", "-\"The content is object of Italian Patent Application No.", "102017000025738 filed on 08.03.2017\" -\"The content is object of International Patent Application No." ] },{ "paper_id": "15753984412d073dd4c6daed84e3d294f728b636", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "these mice is not ideal for studies seeking to understand innate and adaptive responses to viral infection. Therefore, a better model system for oral CVB3 infections is needed since some effects, such as those imparted by intestinal microbiota, can only be uncovered by using the natural oral infection route (30) (31) (32) (33) (34) .", "This work, including the efforts of Julie K. Pfeiffer, was funded by HHS | National Institutes of Health (NIH) (AI74668). This work, including the efforts of Julie K. Pfeiffer, was funded by Burroughs Wellcome Fund (BWF).", "Statistical analysis. Data throughout are shown as the mean \u03ee the standard error of the mean. The differences between groups were examined by unpaired two-tailed Student t tests. P \u03fd 0.05 was considered statistically significant. All analyses were performed with Graph Pad Prism 6.03 software (GraphPad Software, La Jolla, CA)." ] },{ "paper_id": "1575931c6fe7aea67ea3ced0ebe1df4d2604864c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1579fbff7af9b156c6f49fee0526e48f852ea460", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Infectious Bronchitis (IB) is an acute and highly contagious viral respiratory disease of chickens 1,2 . IB causes major economic losses in commercial chickens throughout the world 1,3 . It is one of the most prevalent diseases in the poultry industry. The disease is usually characterized by respiratory signs including ocular and nasal discharges, gasping, coughing and sneezing. However, the virus can also infect urogenital and reproductive tracts causing renal dysfunction and decreased egg production 3,4 .", "We performed all experiments involving virulent IBV in our USDA approved Biosafety level-2 and Biosafety level-2 plus facilities following the guidelines and approval of the Animal Care and Use Committee (IACUC), University of Maryland.", "Statistical analysis. Data were analyzed among groups by One-Way-ANOVA test. The student t-test was used to compare two groups. To avoid bias, all animal experiments were designed as blinded studies." ] },{ "paper_id": "15909c5986b0407310ef629ce19ebe562be7c20c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The baseline characteristics, symptom severity and degree of interference with daily life were similar in both arms (Table 1) . We identified an aetiology in the baseline sample of 73% (48/66) of participants (Table S1 ). Amongst these, 56% were rhinovirus and 31% were coronaviruses (COV), with the rest due to enterovirus, influenza A virus, parainfluenza virus type 3 (PIV-3), respiratory syncytial virus (RSV) and human metapneumovirus (HMPV). We detected dual infections of rhinovirus with an enterovirus/COV HKU1 in two.", "Published: xx xx xxxx opeN www.nature.com/scientificreports/", "We detected viruses in 73% of individuals, much higher than 40-55% reported by others [30] [31] [32] . This could be due to sampling within 48 hours of onset of illness. Though rhinoviruses and coronaviruses were the commonest, our study confirms that numerous viruses cause URTI. The viral load of the initial sample varied between individuals and sequential sampling is important to detect change in viral shedding. A larger study would help determine the relative efficacy of HSNIG against different viruses." ] },{ "paper_id": "159542778cfb78258a07f195a5b4aaf400cdcbcb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Group 1 consisted of 66 organisms, of which 22 were from the Salmonella genus. Parvovirus B19 had a moderate correlation with sunshine (mean r = 0.54), followed by Salmonella Enteritidis with sunshine (r = 0.52) and" ] },{ "paper_id": "15a1cb9e790f884e0513e9f0112a909e95a96c67", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "15a5a243bb623a17ee4f0c18c4e3bea8c065ed11", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Transmissible gastroenteritis (TGE) is a highly contagious infectious disease of pigs that is characterized by vomiting, diarrhea, and dehydration. Notably, the mortality rate of this disease in seronegative suckling piglets can reach up to 100% [1] . TGE is caused by the TGE virus (TGEV), which infects the gastrointestinal tract, causing villus atrophy and crypt hyperplasia, and disrupting intestinal nutrition absorption [2, 3] .", "\u03b2-tubulin was also analyzed.", "doi:10.1371/journal.pone.0165585.g002", "All results are presented as means \u00b1 SD of the results of three independent experiments. Significant differences between control and experimental groups were analyzed using Student's ttest. p-values < 0.05 were considered statistically significant." ] },{ "paper_id": "15be11732e317af7fa6c86abea963f89af68cc36", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "15ca0457de2d05a3796f024899edc9c55c86e4ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics Statement. The study design and methods were approved by the Institutional Review Board of Center for Clinical and Translational Research of Kyushu University Hospital (IRB serial number: . The methods were carried out in accordance with the approved guidelines. All patients or their relatives gave their informed consent within written treatment contract on admission and therefore prior to their inclusion in the study." ] },{ "paper_id": "15d37cf2a310ff8cce48b1c1f3eaea846b17bbd2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The descriptive statistics were presented as frequencies and percentages." ] },{ "paper_id": "15d52271667c76c6db91907ad72ecb65fb88ec84", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Early work on the viral sequences of Egyptian H5N1 used bioinformatics to model molecular phylogenetic evolution but did not consider geographic dispersion between different regions within the country [14, 15] . Phylogenetic analysis indicated a distinct clade of European-Middle Eastern-African (EMA) isolates [15] that is also classified as clade 2.2 [16] . EMA had three sub-clades with genetic similarities despite being geographically distinct [15] .", "By considering geography as a state within genotype evolution, it is possible to infer locations that are impacted by certain clades. This also enables epidemiologists to understand the migration from a given origin to a perceived endpoint; information that is vital for controlling spread of disease. Pinpointing specific trade routes leading to virus propagation within the country can enable targeted inspections and other disease control measures, improving the efficient use of public health resources.", "[35] to downloaded additional HA sequences from 2010-2012 in Egypt. For the HA gene, IRD considers a complete segment to contain at minimum 1,659 sequences. Thus, we specified this minimum segment length and also excluded sequences without a governorate name. This added 152 sequences to the final set for a total of 226." ] },{ "paper_id": "15d784a335abf0ea0266e9a2406b8d87f25c8f2f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are shown as the mean 6 SEM. Statistical tests, as described in the figure legends, were used to compare experimental groups, with p , 0.05 considered significant. GraphPad Prism 6 (GraphPad Software) was used for data analysis and preparation of all graphs.", "CD4 + cells from infected WT, Il27ra 2/2 , and Ifnar1 2/2 mice were enriched from lung homogenates using anti-CD4 microbeads (L3T4; Miltenyi Biotec) according to manufacturer's instructions. Purified cells were .95% CD4 + T cells as assessed by flow cytometry (data not shown). Cells were kept in 350 ml of RLT buffer (Qiagen) at 280\u02daC before processing. RNA was extracted using RNeasy Mini Kits (Qiagen) and reverse transcribed to cDNA with a high-capacity reverse transcription kit (Applied Biosystems). The expression of indicated genes was quantified by real-time PCR (ABI Prism 7900; Applied Biosystems) and normalized against Hprt1 mRNA levels. TaqMan primer probes (Applied Biosystems) for Il10 (Mm00439616_m1), Ifng (Mm01168134_m1), Csf2 (Mm01290062_m1), and Hprt1 (Mm00446968_m1) were used.", "M. tuberculosis experiments were performed under BSL-3 conditions. M. tuberculosis HN878 bacilli were grown to midlog phase in Middlebrook 7H9 broth supplemented with 10% oleic acid albumin dextrose complex (Difco), 0.05% Tween 80, and 0.5% glycerol before being quantified on 7H11 agar plates and stored in aliquots at 280\u02daC. Mice were infected via the aerosol route using a three-jet Collison nebulizer unit (BGI), calibrated to deliver \u223c100-200 CFUs to the lung. The infection dose was confirmed by determining the number of viable bacteria in the lungs of five mice just after the aerosol infection. For bacterial load determination, mice were euthanized by CO 2 inhalation and the lungs were aseptically excised, individually homogenized, as described previously (29) , followed by plating serial dilution of the organ homogenate on Middlebrook 7H11 agar supplemented with 10% oleic acid albumin dextrose complex. CFUs were counted after 3 wk of incubation at 37\u02daC, and the bacterial load per organ was calculated." ] },{ "paper_id": "15da0bac7ba69e867df1af947566ee74e80bdb0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "were adsorbed in a 300-mesh copper net for 2 min. The samples were observed via electron microscopy after negative staining.", "Recombination analysis was completed using RDP4 software. 18 Methods, including RDP, Bootscan and SiScan, were used. Likely parental isolates and recombination breakpoints were detected under default settings. Criteria for determining recombination and breakpoints were a P-value o10 \u2212 6 or a recombination score 40.6.", "In 2015, tissue from one small intestine and 14 anal tissue strips were harvested from a pig farm in Anhui Hefei (AHHF). The clinical symptoms were vomiting, yellow and watery diarrhea, rapid weight loss and dehydration. Intestinal content was collected from an infected piglet and was mixed with PBS at a ratio of 1:5. The suspension was then centrifuged at 6000g for 15 min at 4\u00b0C and was filtered using a 0.22-\u03bcm filter." ] },{ "paper_id": "15dd9abbe4084c12712f094415c5ca9980aaacda", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We successfully amplified and sequenced two partial DRA exon 2 sequences from three ancient dromedaries Table 2 ). The sequence recovered from AQ34 was identical to Cadr-DRA*02, while AQ30 showed an additional three C/T substitutions when compared with the reference sequence (Fig. 5) .", "All alignments and resulting phylogenetic trees are available at the TreeBASE (http://treebase.org/treebase-web/ home.html) under DOI http://purl.org/phylo/treebase/ phylows/study/TB2:S18850.", "All sequences were submitted to GenBank (http:// www.ncbi.nlm.nih.gov/genbank/) and are available under accession numbers KT936396-KT936421." ] },{ "paper_id": "15dddee0b99b7095553fde91f32e7ae83c15e9ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "15f2b1915443fff0466f0dd89c7c0ab6761833b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Resolved proteins were electro-blotted on 0.2 mm nitrocellulose membrane (Bio-Rad) using 20 mM Tris, 0.05% SDS, 150 mM glycine and 20% V/V isopropanol transfer buffer. Membranes were blocked with 5% skimmed milk, in Tris buffered saline (TBS: 25 mM Tris/HCl, 150 mM NaCl, 2 mM KCl, pH 7.4) and incubated over night with a dilution of 1/300 rabbit antisera. Membranes were washed three times with TBS-Tween-20 (TBS containing 0.05% Tween-20) and further incubated with monoclonal, anti-rabbit, peroxydase conjugate (Sigma), diluted at 1/750 in 5% skimmed milk. After 2 hours the membrane was washed three times with TBS-Tween-20 and developed using 4-chloronaphthol (Sigma) in presence of hydrogen peroxide.", "The genus Orbivirus currently includes twenty two distinct virus species, with genomes composed of 10 segments of linear double stranded RNA (dsRNA), that are vectored by Culicoides midges, ticks, phlebotomine flies, anopheline or culicine mosquitoes. The three economically most important orbiviruses: Bluetongue virus (BTV) (the Orbivirus 'type-species') African horse sickness virus (AHSV) and Epizootic hemorrhagic disease virus (EHDV) are all transmitted by Culicoides biting-midges [1] . Several tick-borne orbiviruses can infect humans, including members of the Changuinola virus, Corriparta virus, Lebombo virus, Orungo virus and Great island virus (GIV) species.", "SCRV, which persistently infects tick cells but does not grow in mammalian cells, appears to have a non-functional NS4 ORF that is interrupted by a stop codon. These observations suggest that NS4 expression could play a role in productive infection of mammalian cells." ] },{ "paper_id": "15f3676a843fc2b08f47c1e0c49d78f63519caeb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pumas from three study sites spanning coastal southern California, Colorado, and Florida were sampled and their FIV Pco status assessed.", "No explicit solution", "Further examination of co-infection patterns in puma would be a valuable direction for future research.", "with S the proportion of susceptible pumas, I the proportion of infected pumas, and parameters \u03b2 and \u03b3 describing the shape of the Weibull model. We used an ordinary differential equation solver (lsode) and then taking" ] },{ "paper_id": "15f3da54587d39ca8a3c8eabffb84fc463266ab0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The complete genome sequence of PEDV strain CH/ZMDZY/11 was submitted to GenBank under the accession no. KC196276.", "We report here the complete genome sequence of the porcine epidemic diarrhea virus strain CH/ZMDZY/11 isolated from central China. Our data, together with sequence data of porcine epidemic diarrhea virus (PEDV) isolates from other parts in China, will help to understand better the epidemiology and genetic diversity of PEDV field isolates in China.", "single-stranded RNA virus belonging to group 1 of the genus Coronavirus of the family Coronaviridae, is a causative of porcine epidemic diarrhea (PED), an acute and highly contagious enteric disease characterized by watery diarrhea, vomiting, dehydration, and high mortality in nursery piglets (1) . Since December 2010, PED outbreaks have been observed in most of the provinces in China. To date, the complete genome sequences of several PEDV strains from southern China have been reported (2) (3) (4) (5) (6) (7) (8) (9) (10) . To understand the diversity, as well as the epidemiological and molecular characteristics, of PEDV isolates in China, we sequenced the complete genome of CH/ZMDZY/11, a virulent PEDV strain that was isolated from a suckling piglet with severe diarrhea in Henan, a central province in China." ] },{ "paper_id": "160c4bd7c9401bed81b339157fa4ab54242ca8ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Whole blood samples were collected via jugular venipuncture in EDTA tubes from age matched chicks at 14-18 weeks old. At no time did the amount of blood harvested from each animal exceed 1% of body weight. and stored at -80\u02daC. The morphology of adherent cells was observed daily under bright field microscopy (20x objective).", "Purity of monocyte cultures using this culture method was confirmed by IFA and FACS using monoclonal antibody KUL01 as previously described as part of a different aspect of this study [13] .", "A 50 \u03c1g/ml ch-IFN\u03b3 solution (Invitrogen, Carlsbad, CA) was prepared in RPMI w/o Phenol Red culture medium (Invitrogen, Carlsbad, CA). After washing the cells twice with warm PBS, macrophage cultures were stimulated with 1 ml of RPMI-ch-IFN\u03b3 mixture [13] .", "Animal protocols were performed under the approval of the Institutional Animal Care and Use Committee at Western University of Health Sciences, Pomona, California (WesternU). Fertilized eggs, descended from Modified Wisconsin Line 3, were obtained from Dr. W. Elwood Briles, Northern Illinois University, and incubated and hatched under standard conditions at (38\u02daC/50-65% humidity) [10, 13] at WesternU. In addition to daily health monitoring, fresh food and water were provided ad libitum. Experimental animals were euthanized by insufflation of isoflurane gas (Butler, Dublin, OH)." ] },{ "paper_id": "1613fd55dff3cde4f7f32fd5b667e548f860b5d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Fevers of unknown origin constitute a substantial disease burden in Southeast Asia. In majority of the cases, the cause of acute febrile illness is not identified.", "Our findings demonstrate the utility of multiplex diagnostic assays for differential diagnosis of respiratory tract infections and underscore the increasing importance of EV-68 in respiratory disease.", "Mass Tag PCR data were analyzed using non-parametric statistics. The confidence score was calculated using fold inter-quartile range distance of the positive control or the test sample from the 95th percentile cut-point of the negative control distribution for a tag. The score is similar to parametric z-score but is distribution free." ] },{ "paper_id": "16145009d7725e0b39d5522f56ac9781d258eeb8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1621345a6fa32695580f1455de8a7f6284a0f9e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All tests are two-tailed unless otherwise indicated. P values less than 0.05 were considered statistically significant." ] },{ "paper_id": "1624c6455f4fb4a8e871403b0e27a217bcdc83b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Passive mixing principles are very attractive because they rely on diffusion or chaotic advection through specially-designed microchannels. They can also operated by avoiding the need of any external energy source. Active mixing schemes, on the other hand, improve the mixing performance by applying external forces to perturb sample flows and consequently to accelerate the diffusion processes. The latter configuration often leads to a complex device design [17] .", "Droplets help in achieving a rapid mixing of reagents: the rate of DNA hybridization in a homogeneous solution is about 40-fold faster than the hybridization rate in solid-liquid interfaces such as those of microarrays.", "NASBA utilizes two RNA target-specific primers and three enzymes (i.e., avian myeloblastosis virus reverse transcriptase, T7 DNA-dependent RNA polymerase (DdRp) and RNase H)." ] },{ "paper_id": "16283e25f01d47898ad2b82d56bd81d5ccf44a5d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical significance was determined using the Student's t test. For all data analyzed, a significance threshold of P < 0.05 was assumed. The values are expressed in some figures as means \u00b1 standard deviation (SD). ", "Cats with clinically diagnosed FIP have very rarely been cured, although several therapeutic strategies have been attempted. Some cats treated with prednisolone and phenylalanine mustard or cyclophosphamide have gone into remission [26] . Various immunosuppressants, such as glucocorticoids and cyclophosphamide, may prolong life but do not alter the fatal outcome [4] .", "Authors' contributions YT carried out all experiments, participated in the data collection and analysis, and prepared the manuscript. SO, MI, and ST carried out cell culture and virus preparation. YS performed some of the biochemical experiments and TS carried out luciferase assays. All authors read and approved the final manuscript." ] },{ "paper_id": "1628fb770b782044ef43a9c63252b5d3b25a38ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: Burtram C. Fielding and Aasiyah Chafekar made an equal contribution in the writing of this manuscript.", "[98]", "One pot RT-LAMP ", "Acknowledgments: Burtram C. Fielding receives funding from the National Research Foundation (NRF) (South Africa) and the University of the Western Cape Senate Research Fund. Any opinion, findings and conclusions or recommendations expressed in this material are those of the authors and, therefore, the NRF does not accept any liability in regard thereto." ] },{ "paper_id": "162c064dae8c02e477c00bbcd60b974ae794649f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Surveillance pyramid approaches: reconstruct conditional probabilities of appearing at one severity level conditional on reaching a lower severity level; combine data sources that have relatively complete ascertainment of higher severity levels (e.g., hospitalization, ICU, death) with those having relatively complete ascertainment of lower levels (e.g., seeking medical attention, hospitalization) [10, 11] . CFR can then be estimated as a product of conditional probabilities with associated uncertainties [17] .", "Serologic ascertainment of infection [18, 19] to provide a population denominator for infections regardless of symptoms, combined with active surveillance for more severe outcomes.", "Individuals identified before becoming cases (e.g., as healthy contacts of infected persons) and actively followed regardless of clinical severity could be analyzed separately as a prospective cohort for whom the course of disease could be observed and this restriction readily made." ] },{ "paper_id": "162d42b98a0abdf3d7ee609fe464918e457f55fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations BCG: Bacillus Calmette-Gu\u00e9rin; HSP: Heat shock proteins; IgM: Immunoglobulin M; KD: Kawasaki disease", "Here, we present a case report of a 7-month old infant with laboratory-confirmed measles who presented with erythema and induration at the BCG inoculation site.", "On admission, he looked unwell, was febrile (temperature 38.5\u00b0C) but had normal vital signs (pulse rate 125/min, respiratory rate 48/min). He had an erythematous maculopapular rash involving mainly the face, neck and trunk, with some areas of confluence (Fig. 1a) . In addition, a welldefined erythematous, indurated area measuring 2.5 cm in diameter was seen at the site of the BCG scar (Fig. 1b) . No conjunctivitis, cervical node enlargement, mucosal changes or extremity changes (swelling/erythema of the hands or feet) were found." ] },{ "paper_id": "162ffba72e95c4b2686b0b273b47c376aad61ba7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Another method for host recognition of viruses involves retinoic acid inducible gene-I (RIG-I) and melanoma differentiation factor 5 (MDA5) [46] . To clear viral infections, RIG-I-like receptors and MDA5 recognize cytosolic viral RNAs via the helicase domain [47] . In contrast to TLRs that are predominately present in leukocyte subsets, these receptors are ubiquitous in human cells. Neutrophils and monocytes themselves can become infected by viruses [48] and therefore possess cytoplasmic and endosomal mechanisms to recognize them, including RIG-I and MDA5 signaling cascades in the cytoplasm and endosomal TLRs. In fact, the double-stranded RNA mimetic poly(I:C) stimulates neutrophils to increase many antiviral genes, including type I IFN mRNA transcripts, IFN-responsive genes, TNF-\u03b1, and IFN regulatory factor (IRF)7 [49] . When infected with encephalomyocarditis virus (EMCV), MDA5-deficient mice mount significantly reduced TNF-\u03b1 and IFN-\u03b2 responses [49] . Similar results were also observed after infections with Coxsackie B virus (CVB) [50] and West Nile virus (WNV) [51] . Notably, TNF-\u03b1 and IFN-\u03b2 have the capacity to upregulate the expression of major histocompatibility complex molecules on antigen-presenting cells, which would make viruses more susceptible to T-cell-mediated clearance.", "Clearly, the cross-talk that is occurring between monocytes, neutrophils, and T-cells constitutes a crucial bridge between innate and adaptive immunity. Future investigations are encouraged to examine the full extent of communication between these cells, further elucidate the mechanisms, and the anatomical locations of these interactions. Depletion assays will be beneficial to determine which cell subsets can mount effective anti-viral responses, not just by T-cell and APC interactions, but also by direct interactions with neutrophils and monocytes.", "Myeloid cells are able to translate micro-environmental cues into an effector profile that initiates lymphocyte responses [123] . Innate lymphoid cells (ILCs) react to pathogens indirectly through myeloid or epithelial cell-derived cytokines and other inflammatory mediators including IL-12, IL-23, and IL-33 [124] . ILCs are derived from a lymphoid progenitor but do not contain either a B or T-cell receptor due to the absence of the recombination-activating gene [125] . There are three major subsets of ILCs: groups 1, 2, and 3. Group 1 includes cells that produce IFN-\u03b3 and TNF-\u03b1 and is predominately composed of classical natural killer (NK) cells. ILCs that require GATA3 and ROR\u03b1 to develop and express the cytokines IL-5 and IL-13 are denoted as group 2, while intestinal ILCs that express NKp46 and depend on ROR\u03b3 comprise group 3 [126] . Since evidence shows that ILCs are tissue-resident cell types with limited capacity to directly recognize PAMPs [123] , myeloid cells may play a crucial role in controlling ILC homeostasis and function [127] .", "Neutrophils, inflammatory monocytes, and their roles in mitigating bacterial infections have been extensively studied and well characterized. Exciting new research in immunology and virology has demonstrated that these first responders of the innate immune system are also crucial in limiting viral infections, replication, and associated off-target pathological damage. A multifaceted range of tactics is utilized to combat an equally diverse range of viruses, including phagocytosis, the formation of extracellular traps, the production of cytokines such as IFNs, and modulation of ILCs and lymphocytes." ] },{ "paper_id": "1638100b254164ee9af7d66be61794a7efa07b78", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Eight-wk-old female SPF BALB/c mice with body weight of 17-18 g were purchased from Beijing Laboratory Animal Research Center (Beijing, People's Republic of China), and housed in microisolator cages ventilated under negative pressure with HEPA-filtered air. During the experiments, mice were given food and water ad lib." ] },{ "paper_id": "16406822b5673734cefa5a986007b6fff662c7b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors would like to thank Sam Carding for creating Figure 1 .", "Declaration of personal interest: None. " ] },{ "paper_id": "164f04163f53a4fb15d74a03b6ab473b50c30989", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "164f0fed97b05b34ea5df0f4e4e9e204d05f7849", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Genotype distributions were tested for Hardy-Weinberg equilibrium using goodness-of-fit test (1 df). Informative missingness was checked by coding successful genotypes into one group and failed genotypes into another group followed by 262 Chi-square test for T2D and t-test for the quantitative traits of interest. One SNP (rs805264) with significant result (p,0.001) indicative of informative missingness (IM) was excluded for further T2D association analyses (Supplelmentary Table S2 ).", "Results from functional analyses were analyzed by Student's ttest for two-group comparison, and one way ANOVA for multiple group comparisons. A statistical significance is considered at p,0.05 level. All statistical analyses were performed using the SPSS program (SPSS version 15.0, Chicago, IL, USA) unless otherwise specified.", "Ectopic expression of APOM was achieved by transient transfection of APOM1 or APOM5 cDNA (cloned into the pCMV-Myc vectors) into cultured cells at 70% confluence using LipofectamineTM 2000 reagent (Invitrogen, Carlsbad, CA, USA) following the manufactorer's protocols [16] ." ] },{ "paper_id": "165cfcb6f439f6d779d1e94b0b8a3db96c79b22e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Having been identified to have been in contact with Case C in the hospital, 169 people (51 patients and 118 hospital employees) were subjected to either cohort quarantine or home quarantine for 14 days. However, there were no more newly infected people.", "We reviewed the MERS outbreak investigation report of the KCDC, and interviewed the healthcare worker who had recovered from MERS. Using the media interview data, we reaffirmed and supplemented the nature of the exposure." ] },{ "paper_id": "165d5a3cf0dc10f8229b0c6fcf149cd244cbd73a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quantitatively, according to this model, sporadic human cases subsequent to that date teach us very little more about whether the virus may ultimately adapt to humans.", "] m . 10 6 (May et al. 2001) .", "Together the parameters R 0 ( i ) and M (i ) define the stochastic process of evolution and infection as follows. For a given infected individual, there are three possible events that could occur next: transmission, pathogen adaptation, and host recovery/death. These have probabilities p i , q i , r i , respectively, where" ] },{ "paper_id": "166142fd39f6000cf789299a7df7fedc36b300cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Spleen leukocyte suspensions were prepared using DNAse I and collagenase D [23] , stained as detailed in S1 File, and acquired on a FACSCanto II Flow Cytometer (BD Bioscience).", "doi:10.1371/journal.ppat.1004897.g005", "The animal care and use protocols (ID no. 11-09/09/2011) were designed in accordance with national and international laws for laboratory animal welfare and experimentation (EEC Council Directive 2010/63/EU, September 2010), and approved by the Marseille Ethical Committee for Animal Experimentation (registered by the Comit\u00e9 National de R\u00e9flexion Ethique sur l'Exp\u00e9rimentation Animale under no. 14)." ] },{ "paper_id": "16627f4c7134394da448b1417a771d13ad7cca4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As post-disaster studies generally report a lack of baseline data as a major handicap to understanding the trajectory for psychosocial recovery, [17, 18] our study takes the first steps in establishing baseline for data vital for emergency planning, against which impact and recovery can be monitored.", "The survey data were weighted to adjust for probability of selection and for differing non-response rates among males and females and different age groups. [15] Data were manipulated and analysed using SAS version 9.2. [11] The SURVEYFREQ procedure in SAS was used to analyse the data and calculate point estimates and 95 per cent confidence intervals for the prevalence estimates. For pairwise comparisons of subgroup estimates, the p-value for a two-tailed test was calculated using the normal distribution probability function PROBNORM in SAS, assuming approximate normal distribution of each individual subgroup estimates with the estimated standard errors, and approximate normal distribution for the estimated difference." ] },{ "paper_id": "1664a9df618ca74e099245a2bd65f3172aeac284", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data are expressed as the mean \u00b1 standard deviation (SD). The statistical significance of data was analyzed using Student's t-test or one-way analysis of variance (ANOVA) by SPSS 19.0. Values of p < 0.05 was considered to be statistically significant.", "(Continued on next page)" ] },{ "paper_id": "16673eca9ff4c1f57f53126415ad2f89b8cab557", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved and consent was waived by the Beth Israel Deaconess Medical Center Institutional Review Board (protocol number: 2008-P-000412).", "Proportions were compared using the Chi-squared test and means were compared using the Mann-Whitney U test. Values of p < 0.05 were considered statistically significant and all tests were two-sided. The statistical analysis was performed in R (version 3.2.1; R Foundation for Statistical Computing, Vienna, Austria).", "Authors' contributions LDS, SFB, DM, and FP conceived of the study and participated in its design. DB and CH performed the statistical analyses. All authors participated in the interpretation of results and manuscript drafting or critical review. All authors read and approved the final manuscript." ] },{ "paper_id": "166ac544dda68154d0cfb96da75f30e457d6eda2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our study had the following three aims:", "For the evaluation of systemic and local antibody production two ELISA methods were used.", "The normality of data distribution were confirmed. Experimental groups were compared using non-parametric Man-Whitney test. Data from different dates were compared using non-parametric Wilcoxon test for paired samples. ", "MT, VC, JS, and MF designed the study. MT, LL, JS, and KN performed the experiments. LL, HK, LK, PO, and JF performed the lab work and analyzed the data. LK produced the figures and statistical analysis. MT wrote the manuscript. JS and MF participated in manuscript preparation. All authors read and approved the final manuscript.", "The virus neutralization test for detection of PRRSV neutralization antibodies was performed as follows. Samples of sera were diluted 1:4 in DMEM medium (Sigma-Aldrich) supplemented with 3% FBS. Then, heat inactivated sera (56 \u2022 C for 60 min) were diluted 2-fold serially in flat-bottom 96-well-microplate (NUNC). Next, equal volume (50 \u00b5L) of media containing 50 PRRSV PFU (Lelystad-CAPM V-490) was added to each well. Following incubation (60 min at 37 \u2022 C) MARC-145 cells were added to each well (3 \u00d7 10 4 per well) in 100 \u00b5L media per well. After 5 days of cultivation (37 \u2022 C, 5% CO 2 ), the cytopathic effect (CPE) of PRRSV on MARC-145 was evaluated by optical microscopy. The reciprocal value of the last sera dilution causing 50% reduction of CPE was defined as virus neutralization antibody titer." ] },{ "paper_id": "1673be3a6c0cd5762dcdabc21816f4acdc102e31", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "with other G2b PEDVs in other countries [7] . Therefore, development of the Taiwan G2b PEDV-based vaccines would be very helpful for controlling and reducing the disease burden.", "The results of IgG level, IgA level, body weight, antibody titer, and viral shedding were statistically compiled with SAS 9.4 (Statistical Analysis System, SAS Institute Inc., Cary, NC, USA). The differences between each group were compared by one-way analysis of variance (ANOVA). The significance was determined to have a p-value < 0.05 (p < 0.05)." ] },{ "paper_id": "1679d2d946adeb59a2ce943f067d4bde57f5577d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hemotropic mycoplasmas (hemoplasmas) are cell-wall free bacteria that attach to red blood cells and potentially induce hemolytic anemia [1] . In the domestic cat, at least three feline hemotropic mycoplasma species are known: Mycoplasma haemofelis (M. haemofelis), \"Candidatus Mycoplasma haemominutum\" (\"Cand. M. haemominutum\") and \"Candidatus Mycoplasma turicensis\" (\"Cand. M. turicensis\") [2] [3] [4] [5] . The pathogenic potential significantly varies among the three feline species; M. haemofelis is the most pathogenic of the three species, and an acute infection often results in hemolytic anemia [1, 6] .", "Long-term outcome of M. haemofelis infection: recovery in the absence of antibiotic treatment", "Serum chemistry was performed using a Cobas Integra 800 system (Roche Diagnostics, Rotkreuz, Switzerland) and included the laboratory's standard feline clinical chemistry panel: bilirubin, glucose, blood urea nitrogen (BUN), creatinine, protein, albumin, cholesterol, triglyceride, alkaline phosphatase, amylase, aspartate aminotransferase, alanine aminotransferase, lipase, sodium, chloride, potassium, calcium and phosphate. Globulin values were calculated by subtraction of albumin from the total protein concentration. Reference ranges are stated as 5% and 95% quantiles and were determined for routine purposes using identical methods and blood samples from 59 clinically healthy cats." ] },{ "paper_id": "167b459cba8933f49d8cb5585f442a68fe326361", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virions were absorbed to carbon-formvar coated grids (Electron Microscopy Sciences) by floating grids on 5 ml drops of sample for 30 seconds (s). Grids were blotted dry, stained with 2% uranyl acetate in water for 30 s, blotted to remove excess stain and airdried. Samples were visualized using a JEOL JEM 2100 LaB6 Transmission Electron Microscope.", "Syrian golden hamster kidney fibroblast cells (BHK-21; ATCC# CCL-10) were grown in monolayer cultures maintained in Minimum Essential Medium (Eagle's MEM, Cellgro) supplemented with 9% fetal bovine serum (FBS, Gibco), 0.3% glucose (w/v), 3.4 mM L-glutamine, 90 U/ml penicillin and 90 mg/ml streptomycin, and kept in a 5% CO 2 atmosphere at 37uC. Infectivity [plaque forming units (PFU) per ml] of virus stocks was determined by standard plaque assay on BHK-21 cells. Recombinant wild-type (wt) VSV (Indiana serotype) was generated previously [46] using pBS-L, pBS-P, pBS-N, and pVSVFL(+) plasmids, and was kindly provided by John K. Rose (Yale University) [47] .", "To grow and purify virus VSV, BHK-21 cells were infected with at a multiplicity of infection (MOI) of 0.001 and incubated at 37uC in media containing 5% FBS. Virus containing media was collected around 24 hours (h) post infection (p.i.) when most cells were infected but significant cell detachment had not yet occurred in order to maximize exclusion of cellular debris. The media was centrifuged at 3,0006 g for 10 minutes (min) to remove large cellular debris. The virus was then purified as described in [48] , with slight modifications. In brief, clarified supernatants were underlayed with 5 ml 20% (w/v) sucrose in HEN buffer (10 mM HEPES pH 7.4, 1 mM EDTA, 100 mM NaCl) and centrifuged at 28,000 rpm and 4uC for 3.5 h in a Beckman SW32 Ti rotor. The resulting virus-containing pellet was resuspended overnight in HEPES buffered saline, pH 7.5 [HBS; 21 mM HEPES, 140 mM NaCl, 45 mM KCl, 0.75 mM Na 2 HPO 4 , 0.1% (w/v) dextrose] and then centrifuged in a 7.5-27.5% continuous gradient of Optiprep (Axis Shield) in HBS at 26,500 rpm and 4uC for 30 min using a Beckman SW40 Ti rotor. The virus-containing band was removed from the gradient, diluted with ET buffer (1 mM Tris-HCl pH 7.5, 1 mM EDTA), pelleted by centrifugation at 27,000 rpm and 4uC for 1.5 h using a Beckman SW40 Ti rotor and resuspended in ET buffer.", "Recombinant wt VSV was grown in BHK-21 cells and purified using gradient centrifugation. The purity of the resulting material was then examined by electron microscopy (EM). As seen in Figure 1 , nearly all of the material present was clearly identifiable as VSV virions, although many of them were bent, a previously observed form that is generally believed to be infectious [57] and may represent an EM processing artifact [58, 59] . The titer of these purified virions on BHK-21 cells was 1.4610 11 PFU/ml, demonstrating this preparation was highly infectious." ] },{ "paper_id": "16844dca24405d3c94a4366cd94598a6a7357fc8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sanjay Chotirmall is a member of the editorial board (Section Editor). Dominik Hartl has an affiliation with University of T\u00fcbingen and Roche Basel ", "Consent for publication has been obtained from all persons for the included images.", "In the following two sections, we will focus on the microbiological (a) and immunological/inflammatory (b) findings associated with the pathogenesis of bronchiectasis." ] },{ "paper_id": "168667e863cc79cb44157edf0e39ca66a37b2b7b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For demographic analyses, differences between groups were assessed using Chi-square tests and analysis of variance (ANOVA).", "Two thousand eight hundred thirteen staff completed paper questionnaires while 235 completed electronic surveys. Three thousand forty-eight HCW participated (38%), which exceeded our target participation rate by three-fold.", "Although respondents reported that they believed the majority of their HCW colleagues would comply with IPC guidelines (61.5% \"mostly\" comply, 31.5% \"partially\" comply), there was wide variability in reported use of personal protective equipment and only 81-87% expected compliance with handwashing after interacting with patients with communicable respiratory diseases (Table 7) . Additionally, most respondents believed that patient charts would inaccurately report single or multiple HCW-patient interactions.", "Infection prevention and control practices were assessed with questions about regular compliance with IPC precautions as well as through the use of three HCW-patient contact scenarios involving a patient who is diagnosed with a) respiratory tract infection (e.g. RSV) that is spread by droplets; b) active pulmonary tuberculosis, who has a productive cough; and c) varicella (chickenpox). Respondents were asked about the precautions they would takesuch as wearing surgical mask, N95 respirator, face or eye shield, gloves, gown, or goggles -in each of these three scenarios. Additionally, for scenario (a), they were asked to provide a response in a situation when they are within 1 m (3 ft) of the patient with respiratory tract infection. Also, for scenario (c), they were asked to provide a response assuming they had immunity to varicella (e.g., via childhood infection). Quantitative responses were measured on a 1 to 10 scale. Charting practices regarding the accurate recording of number of daily patient-HCW interactions were also assessed." ] },{ "paper_id": "1686765b6847c2b132d0129be10f7263bac5973e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hamster No.", "For each of the prototype strains, virions were purified on discontinuous sucrose gradients [12] . The viral proteins were denatured and reduced and were separated on 10% SDS-Polyacrylamide gels and negatively stained using E-Zinc \u2122reversible stain kit (Pierce, Rockford, IL, USA). Each serotype was analyzed on a separate gel to avoid cross contamination. The N protein bands were excised from the gels and destained with Tris-glycine buffer, pH 8. The excised gel bands were minced in a clean pestle and mixed with elution buffer (50 mM Tris-HCl buffer pH 8, 150 mM NaCl, 0.5 mM EDTA, 5 mM DTT and 0.1% SDS) and transferred to the upper chambers of Nanosep centrifugal device (Pall Life Sciences, Ann Arbor, MI, USA). The proteins were eluted by centrifugation at 13000 \u00d7 g for 5 minutes, and the eluted proteins were quantified and 200 \u03bcg of each protein was mixed in complete Freund's adjuvant and injected subcutaneously into a rabbit. After two weeks, a booster immunization was given with 200 \u03bcg of protein in incomplete Freund's adjuvant and two weeks later the hyperimmune sera were collected. The sera were tested by western blot and were found to recognize specifically the homologous N protein (data not shown). The sera were stored at -80\u00b0C until further use.", "Hence, we have investigated the replication and pathogenicity of APMV-1 to -9 in hamsters inoculated intranasally. The intranasal route was intended to resemble the natural route of APMV infection as well as a likely route for vaccine vector administration. In this study, hamsters were chosen as the mammalian animal model because they are widely used to study replication and pathogenesis of a variety of viruses such as adenovirus [49] , herpes virus [50] , Nipah virus [51] , human RSV [52] , human parainfluenza viruses, SARS virus [53] , and Eastern equine encephalitis [54] .", "The other half of each tissue sample was used for IHC and histopathology. The tissues were fixed in 10% neutral buffered formalin, held for approximately seven days, and processed for IHC and histopathology. Paraffin embedded 5-micron sections of all the tissue samples were prepared at Histoserve, Inc. (Maryland, MD, USA). The sections were stained with hematoxylin and eosin for histopathology. Sections were also immunostained to detect viral N protein using the following protocol. Briefly, the tissue sections were deparaffinized in two changes of xylene for 5 min each, hydrated in two changes of 100% ethanol for 3 min each, changes of 95% and 80% ethanol for 1 min each, and finally washed in distilled water. The sections were processed for antigen retrieval in a water bath containing sodium citrate buffer (10 mM citric acid, 0.05% Tween 20, pH 6.0), at 95-100\u00b0C for 40 min and then allowed to cool to room temperature for another 60 min. The sections were rinsed in PBS-Tween 20, twice for 2 min each. The sections were blocked with 2% BSA in PBS for 1 h at room temperature. The sections were then incubated with a 1:500 dilution of the homologous primary N-specific rabbit antiserum in PBS for 1 h in a humidified chamber. After three washes in PBS, the sections were incubated with the secondary antibody (FITC conjugated goat anti-rabbit antibody) for 30 min. After a further wash cycle, the sections were mounted with glycerol and viewed under an immunofluorescence microscope." ] },{ "paper_id": "16874a8b95e04383b0ee7049220a36354ffab2ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analyses were performed using Microsoft Excel 2010 (Microsoft Corporation, Redmond, WA, USA), GraphPad Prism Software 4.0 (GraphPad Software Inc., La Jolla, CA, USA), and PSI-Plot V 7.0 (Poly Software International, Pearl River, NY, USA). Student's t-test was used to compare group means. p-values < 0.05 were considered as significant.", "Medicines 2018, 5, 79 2 of 15 is shown using various biochemical assays including cross-linking, nuclear magnetic resonance, and X-ray crystallography methods [6, 7] .", "Materials and Methods" ] },{ "paper_id": "168ee484462356a280cd7fe162b1b7a8d81e80c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Days post-infection FAN Fangchinoline HCoV-OC43 Human coronavirus OC43 IFN Interferon IL Interleukin TET Tetrandrine TNF Tumor necrosis factor ", "Statistical analysis was performed using GraphPad Prism Software V.6.05 for Windows (GraphPad Software, Inc., San Diego, CA, USA). Data are presented as mean \u00b1 standard error of the mean (SEM). Probability (p) values were calculated by one-way analysis of variance (ANOVA) followed by Tukey's test as indicated in the figure legends (* p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001)." ] },{ "paper_id": "1697f41650571796c51a52e8f5412d293f620c79", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All FilmArray Respiratory Panel reagents were purchased using Collaborative Research Grant Funds supplied by the Department of Laboratory Medicine and Pathology at Mayo Clinic.", "All statistical analysis was done using comparison of proportions online chi-squared calculator (https://www.medcalc.org/calc/comparison_of_ proportions.php)." ] },{ "paper_id": "1699f74dc5e3e5ee7417778d18f7f5a46fb7c879", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Both ERAV and ERBV are associated with respiratory diseases in horses and are therefore primarily found in nasal, nasopharyngeal and oral secretions [3] [4] [5] [6] . Infected horses develop fever, anorexia, nasal discharge, cough and lymphadenitis. These respiratory diseases in horses are of particular importance because of their effect on", "Real-time quantitative RT-PCR showed that the amount of ERBV RNA in the four positive samples ranged from 8.28 \u00d7 10 3 to 5.83 \u00d7 10 4 copies per ml of fecal sample (Table 1) .", "Viral RNA was extracted from the fecal samples using EZ1 Virus Mini Kit v2.0 (Qiagen, Hilden, Germany). The RNA was eluted in 60 \u03bcl of AVE buffer (Qiagen, Hilden, Germany) and was used as the template for RT-PCR." ] },{ "paper_id": "169ca2aef2c810471d33aa6522aa25a70594ae26", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mallard ducks are", "Chickens have a single polymorphic Mx gene with variable, but mostly weak anti-influenza activity that depends on chicken breed [235, [242] [243] [244] [245] . Schusser and colleagues showed that chicken Mx lacks GTPase activity [245] . It was previously shown that mutations disrupting GTP binding and GTPase activity also disrupt the antiviral activity of Mx, and it was assumed that GTP hydrolysis was necessary for antiviral function [228] . A more recent structural analysis found that MxA oligomerization is critical for viral nucleoprotein sequestration, and that GTP binding, but not necessarily hydrolysis, stabilizes MxA multimers [246] . In fact, MxA oligomerization reduced the rate of GTP hydrolysis, and antiviral activity was preserved when MxA bound a synthetic GTP analog that could not be hydrolyzed.", "LSm14A is the RNA-binding component of processing bodies that sequester non-translating mRNA, but can also act as a detector of viral RNA and induce IFN-\u03b2 production in humans [191] . Duck LSm14A is broadly expressed in tissues, and localizes to puncta (presumably P-bodies) in DEFs [192] . Overexpression of duck LSm14A induces IFN-\u03b2 and NF-\u03baB, and knockdown reduces poly(I:C) sensitivity.", "Ensembl ID" ] },{ "paper_id": "16a04dc7659daf72dfd1706f843b74d691048b6f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are shown as the means \u00b1 SD of three independent experiments done in triplicate. For each assay, student's ttest was used for statistical comparison. A value of P < 0.05 was considered significant.", "Mouse monoclonal antibodies against cyclin A, GRP78, NF-\u03baB p65, \u03b2-actin were purchased from Santa Cruz Biotechnology (Santa Cruz, Inc., CA, US). Porcine anti-PEDV polyclonal antibody was kindly provided by China Animal Health and Epidemiology Center (Qingdao, China). Mouse anti-GFP monoclonal antibody was purchased from Millipore (USA), Horseradish peroxidase (HRP)-conjugated secondary antibody was purchased from Pierce (Pierce, Rockford, IL, US). The MG132 proteasome inhibitor was purchased from Calbiochem (USA) and the nuclear staining dye Hoechst33342 and ER-Tracker\u2122 Red probe were obtained from Invitrogen (USA).", "Cells were harvested and washed with ice-cold PBS, then treated with ice-cold RIPA lysis buffer with 1 mM phenylmethyl sulfonylfluoride (PMSF). Cell lysates were centrifuged at 12 000 \u00d7 g at 4\u00b0C for 10 min. Protein concentrations were measured using BCA Protein Assay Reagent (Pierce, Rockford, IL, US). Equivalent amounts of proteins were loaded and electrophoresed on 8-12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, proteins were transferred to polyvinylidene difluoride (PVDF) membranes (Millipore Corp, Atlanta,GA, US). The membranes were blocked with 5% nonfat dry milk at room temperature for 1 h, and then incubated with indicated primary antibodies over night at 4\u00b0C, followed by HRP-conjugated secondary antibodies at room temperature for 1 h. The signal was detected by enhanced chemiluminescence (ECL) reagents (Pierce, Rockford, IL, US)." ] },{ "paper_id": "16ab54289da4d53548b4cf171a642e19fd81e660", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "16c14c63746634d9cc1a2d4257b7d7560af187ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments were performed in triplicate unless noted otherwise. Statistics, noted where applied, were performed in Microsoft Excel and GraphPad Prism. P-values.0.05 were considered non-significant (ns).", "Mammalian cell lines Vero, HeLa, and BHK-21 were maintained in DMEM (Gibco) supplemented with 10% newborn calf serum (NCS, Gibco) and 1% penicillin-streptomycin (P/S, Sigma), at 37uC with 5% CO 2 . Mosquito cell lines C6/36 and U4.4 (Aedes albopictus) and Aag2 (Aedes aegypti) were grown in L-15 media, supplemented with 10% fetal bovine serum (FBS, Gibco), 1% P/S, 1% tryptose phosphate, and 1% non-essential amino acids (NEAA), at 28uC with 5% CO 2 . Drosophila melanogaster S2 cells were grown in Schneider's Drosophila media (Gibco), supplemented with 10% FBS, 1% L-Glutamine, and 1% P/S at 25uC.", "Antimutator and mutator variants are valuable tools to study where the threshold of advantageous polymerase error exists for viruses facing different selective pressures. In this respect, arboviruses represent a special evolutionary position due to their need to replicate in disparate hosts, which is accompanied by distinct selective pressures. Arbovirus fitness is not necessarily reduced due to obligate host-cycling (alternating passages of CHIKV did not limit viral fitness), yet it has been shown that evolvability may be reduced due to these evolutionary constraints [33, 34, 35, 36, 37, 38] . For alphaviruses, evidence suggests that viral diversity is most restricted in the insect host, due to more stringent population bottlenecks and selective pressures [33, 34, 35, 37, 39, 40] . Since minority variants are thought to play important roles in arbovirus pathogenesis, transmission, and emergence [25, 41, 42, 43, 44, 45] , the implications of altered polymerase fidelity and mutation rates merit further study. Recently, this question was partially addressed using a chikungunya virus antimutator variant [25] .", "Drosophila melanogaster flies (strain w 1118 ) were reared on standard medium at 25uC. Three-to four-day-old female flies were injected with 50 nL of a virus dilution containing 400 pfu in 10 mM Tris-HCl (pH 7.5) using a Drummond nanoject injector as previously described [69] . Fly mortality at day 1 was attributed to damage produced by the injection, and these flies were excluded from further analyses. Mortality was monitored daily for 10 days, and every 3-4 days flies were transferred to fresh vials. In all experiments, 30-60 flies per genotype group were injected. Homogenates of individual flies were titrated on by plaque assay on Vero cells, as described above." ] },{ "paper_id": "16eb672447620efa83aa59f913d690a95240f488", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recent results indicate that PTX3 has therapeutic activity in chronic lung infections by Pseudomonas aeruginosa, a major cause of morbidity and mortality in cystic fibrosis (CF) patients. Treatment with recombinant human PTX3 causes enhanced clearance of bacteria from the lungs of chronically infected mice, reduced production of local pro-inflammatory cytokines and chemokines, www.frontiersin.org neutrophil recruitment in the airways and histopathological lesions. Also in this condition, the PTX3-dependent recognition and phagocytosis of Pseudomonas aeruginosa involves the interplay with complement and Fc\u03b3Rs (Moalli et al., 2011b) .", "C-reactive protein and SAP are the main acute-phase reactants in human and mouse, respectively. CRP is barely detectable in the plasma of healthy human adults (\u22643 mg/l) but its concentration increases by as much as 1000-fold in several pathological conditions. As opposed to this, the concentration of human (but not murine) SAP is substantially invariant (30-50 mg/l), even during the early acute-phase response. Human CRP and SAP are both produced by hepatocytes, where the pro-inflammatory cytokine IL-6 is a major inducer of CRP both on its own and in synergy with IL-1 (Pepys and Hirschfield, 2003) .", "As a consequence, these data point to a critical role of glycosylation in the modulation of PTX3 functions. It has been suggested that PTX3 can act as double edged sword. Following binding to microbial moieties, it has opsonic activity, activates complement and enhances leukocyte recruitment. On the other hand, PTX3 per se can act as a regulatory molecule of innate immunity and inflammation by dampening excessive neutrophil recruitment. This latter activity in particular is clearly dependent on PTX3 glycosylation .", "Here we review past and present literature on this family of proteins, with major emphasis on the long pentraxin PTX3 and the glycan-dependent mechanisms underlying its functions in pathogen recognition and crosstalk with other components of the innate immune system." ] },{ "paper_id": "16f4fcc0f008c01ee4711085e070b3dcb17040d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Herpesviruses (HVs) infect a wide variety of vertebrate hosts including mammals, birds, reptiles, amphibians and fish, and at least one invertebrate group, bivalve molluscs. HV share a characteristic virion structure, which consists of a large, linear, double-stranded DNA genome, an icosahedral capsid, a proteinaceous matrix (the tegument) and an envelope containing viral proteins [129] .", "Upon transmission to a new host species, viruses must usually adapt to a new genetic and immunologic environment in order to replicate and spread to other individuals within the species [1] . The high rates of mutation and replication of RNA viruses, such as human immunodeficiency virus (HIV) and influenza, facilitate the occurrence and fixation of those mutations that become beneficial under certain conditions [2] . Viral adaptations to new hosts primarily manifest as amino acid substitutions which can allow more efficient virus cell entry into the new host [3, 4] , block interactions with detrimental host proteins [5, 6] or promote escape from both the new and the old host's immune responses [7, 8] .", "The authors declare that they have no competing interests." ] },{ "paper_id": "16fb795aec2acb8b86ddac119772abde6392d40f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "16ffa1f7efaf96880e6f3c22d2de9c5672169303", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each\u00d1 i is calculated using N 0 , N 1 , \u2026, N i21 . Then the one-stepahead residuals are calculated as", ". .", "We present these residuals averaged over the T days observed." ] },{ "paper_id": "1703fbc6de47798061e7ec8d87182906fedab8e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Study approval. The Institutional Review Board at King Faisal Specialist Hospital and Research Center, Jeddah (KFSHRC-J), KSA, approved the study. Written informed consent was obtained from all study participants.", "Statistical analysis. Fisher's exact test was used to compare differences between groups, with P values of \u03fd0.05 considered statistically significant.", "We report no conflicts of interest.", "Clinical information. CW demographic and clinical data were obtained by one of the corresponding authors (A. N. Alagaili) at the time of blood collection, using a written questionnaire." ] },{ "paper_id": "170f0a7070650e42066d011135cc9e9d9f931223", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "170fc4f86244f8f795de48b349db6759add5a834", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\"EIDs have always been here around us. They are always here. It is just the trend of the infection that differs from time to time; that is, a strain of EID is dominant at this time, then another strain will take its place and become dominant later.\" (P15)", "(1) familiarizing with data; (2) developing initial codes;", "To access data for further analysis, please contact the Corresponding Author via stanleylam@twc.edu.hk." ] },{ "paper_id": "1713f0cf6cf8f5e4134cb4b78d5ab4d2c3cc8791", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our Institutional Research Ethics Board has approved this case report, and the need for informed consent has been waived.", "A 41-year-old female presented ambulatory to the Emergency Department at 11:41 PM with a 3-week history of feeling generally unwell. She complained of severe myalgias, chills, and a fever two days earlier. She had been unable to go to work for the previous 4 days due to her illness.", "Her investigations were significant for acute renal failure with a creatinine of 214 umol/L. Her white blood cell count was 7.2 \u00d7 10 9 /L, hemoglobin was 130 g/L, and platelets were slightly decreased at 115 \u00d7 10 9 /L. Her lactate was 1.5 mmol/L, and her venous blood gas showed a mild compensated metabolic acidosis with a ph of 7.32, a CO2 of 39 mm Hg, and a HCO3 of 20 mmol/L. Her urine b-HCG was negative. Liver function studies and liver enzymes were not performed on initial presentation." ] },{ "paper_id": "17192bd07c09aa9e70552f7f15f90f0a6b8180c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "To address these issues, we asked the following questions:", "Third, we manually checked overlapping genes, after having selected a single representative virus species per genus. Briefly, during this step, we identified 124 independent, putatively expressed overlaps out of 1207, and discarded 1016 homologs; we also excluded 114 other overlaps, being truncated forms of overlaps already considered. During the process of manual curation (see below), we then removed 72 overlaps out of the 124 initially identified, coming to a total of 52 proven overlaps." ] },{ "paper_id": "1731adb9524645ed8e10be851313f796f82459c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses (CoVs) are enveloped viruses with large positive-sense single-stranded RNA genomes. CoVs infect a variety of mammalian and avian species, and can cause serious disease in humans, as exemplified during the 2002-2003 outbreak of the severe acute respiratory syndrome (SARS).", "It is now clear that the CoV E protein has multiple functions during infection, although they are not clearly understood. Also, the role(s) for the E protein in different CoVs may not be identical. A comprehensive model of E protein function will provide a better understanding of CoV biology and the mammalian secretory pathway, and may provide a target for therapeutic intervention during CoV infection.", "bending scission A.", "Understanding the protein-protein interactions of CoV E is an important step in elucidating the functions of the protein. Since the sequences of the E proteins are quite divergent, it will be interesting to determine if different CoV E proteins interact with the same host proteins, or are able to elicit a similar effect through interactions with other proteins." ] },{ "paper_id": "17334b138ba80214847f144ebc57ce27ff9c23cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "On establishing the diagnosis of melanoma, the patient refused chemotherapy or surgery for lack of money. He died two months later. ", "His complete blood count showed a mild anemia level of hemoglobin 9.8 g/dL and mild leukocytosis with a white blood cell count of 10.46 \u00d7 109/L and neutrophils at 7.72 \u00d7 109/L. Metabolic panel was normal except for a serum potassium level of 2.89 mmol/L. Serum tumor markers, including CEA, SCC, CYFRA21-1, NSE, AFP, CA19-9, and CA72-4, were all normal. Serum antinuclear antibody test, anti-neutrophil cytoplasmic antibody test, thyroid function test, erythrocyte sedimentation rate, and T-SPOT were also all negative, as were tests for hepatitis, syphilis, and HIV. Serum lactate dehydrogenase was not detected. A pulmonary function test showed that his pulmonary ventilation function and diffusing capacity for carbon monoxide (DLco) were in normal reference ranges. Fractional exhaled nitric oxide concentration was 3.6 ppb.", "The authors declare that they have no competing interests.", "Written informed consent was obtained from a direct relative of the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the editor of this journal." ] },{ "paper_id": "173ce92cbc6f228d5bfbdbd7ba7137523ebe36bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "17413f651645c2b9c92555e9ce1404b9290eccab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hen eggs: Hen eggs were purchased from Valo BioMedia, Germany. At 48 h after inoculation with virus, the eggs were euthanized by an overnight incubation at 4\u02daC and the allantoic fluid was harvested. According to \" \u00a7 14 TierSchVersV-Geltung f\u00fcr Tiere in einem fr\u00fchen Entwicklungsstadium\" experiments conducted before the last third of the development of the animal commences do not require approval.", "Human lung: Human lung explants were obtained from patients who underwent lung resection for cancer or pulmonary hypertension at hospitals in Hanover, Germany (Hannover Medical School, Klinikum Siloah/ Nordstadt). All patients gave written consent. The experimentation with human lung tissue was approved by the ethics committee of the Hannover Medical School and Klinikum Region Hannover. Only lung tissue containing no tumors as qualified by medical pathologists was used for the experiments. Tissue was processed immediately on the day of resection.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "NHP lung: All animal work was conducted according to relevant national and international guidelines, in particular EU directive 2010/63/EU and the German animal protection law. The Animal Welfare and Ethics Committee of the German Primate Center approved the entire study and use of lung material from NHPs. Lungs originated from rhesus macaques (Macaca mulatta), cynomologus macaques (Macaca fascicularis) and common marmosets (Callithrix jacchus) of the German Primate Center. Animals were euthanized by an authorized veterinarian for animal welfare reasons, i.e. suffering from severe trauma after aggressive group conflicts, automutilation or marmoset wasting syndrome. Before euthanasia, animals were deeply anaesthetized using a combination of ketamine (Ketavet1, Pfizer) and xylazine (Rompun1, Bayer). Macaques were then euthanized by a lethal dose of sodium pentobarbital (Narcoren1, Merial GmbH) given intravenously. Marmosets were euthanized by a lethal dose of sodium pentobarbital (Narcoren1, Merial GmbH) given intracardially. Only animals with a healthy respiratory system were included in the study." ] },{ "paper_id": "176274e5fb44083ebc8c91d87e013d624533c7f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The bioinformatics approaches and rationale for the methodology adopted in this study have been previously described [20] and are summarized in Figure 1 .", "The global approach described herein provides a framework and methodology for large-scale and systematic analysis of conserved sequences of other pathogens, in particular for rapidly evolving viruses such as influenza A virus [75] and HIV [63] . These studies will offer insights into their diversity and evolutionary history, together with providing critical data for rational vaccine development, structure-based design of candidate inhibitory compounds, and improvement of the current diagnostic methods. ", "Background: Genetic variation and rapid evolution are hallmarks of RNA viruses, the result of high mutation rates in RNA replication and selection of mutants that enhance viral adaptation, including the escape from host immune responses. Variability is uneven across the genome because mutations resulting in a deleterious effect on viral fitness are restricted. RNA viruses are thus marked by protein sites permissive to multiple mutations and sites critical to viral structure-function that are evolutionarily robust and highly conserved. Identification and characterization of the historical dynamics of the conserved sites have relevance to multiple applications, including potential targets for diagnosis, and prophylactic and therapeutic purposes." ] },{ "paper_id": "1763110ecc1742f6158f410a0c4f0b923118fd79", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mouse embryonic fibroblasts (MEFs) deficient in Pik3cg were prepared as described [27] and maintained in DMEM (Sigma, St.", "AlexaFluor488-or AlexaFluor546-labeled dextran (Mr 10610 3 ), AlexaFluor546-labeled transferrin, LysoTracker Red, Alexa-Fluor594-conjugated anti-mouse antibody, and AlexaFluor647conjugated anti-rat or anti-mouse antibody were purchased from Invitrogen (Carlsbad, CA). LY294002 was obtained from Calbiochem (San Diego, CA). An antibody to EEA-1 was purchased from BD Bioscience (San Jose, CA), that to HA was from Roche, that to Ras was from Oncogene Research Product (Cambridge, MA), that for b-actin was from Santa Cruz Biotechnology (Santa Cruz, CA), and those to phospho-Akt and Akt were from Cell Signaling Technology (Danvers, MA). The anti-NP antibody was a kind gift from A. Takada (Hokkaido University, Sapporo, Japan)." ] },{ "paper_id": "1771673809c10324fde2768ce37d548a5077577f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasma Flavonols, Metabolites and Hormones. Plasma concentrations of flavonols (quercetin, isorhamnetin, tamarixetin and kaempferol) were measured via HPLC as previously described [26] with a detection limit of 2 nmol/L and a recovery rate of 92 \u00b1 2%. The intra-and inter-assay coefficients were 0.5 and 7.2%, respectively. Plasma metabolites were analyzed using an automatic spectrophotometer (ABX Pentra 400; Horiba ABX, Montpellier, France) and respective kits: glucose (#A11A01667), lactate (#A11A01721), albumin (#A11A01664) and triacylglycerides (#A11A01640) from HORIBA ABX, Montpellier, France; total protein (#553-412) and cholesterol (#553-127) from mti-diagnostics, Idstein, Germany; urea (#LT-UR 0010) from Labor+Technik, E. Lehmann, Berlin, Germany; and non-esterified fatty acids (#434-91795, #436-91995) from WAKO Chemicals, Neuss, Germany.", "Effects and differences were considered significant at P < 0.05.", "Experimental procedures were conducted in compliance with the German Animal Protection regulations with approval of the authorities of the state Mecklenburg-Western Pomerania, Germany (Landesamt f\u00fcr Landwirtschaft, Lebensmittelsicherheit und Fischerei Mecklenburg-Vorpommern; LALLF M-V/TSD/7221.3-1.1-044/12). Liver biopsies were performed under local lidocaine anesthesia and all calves received metamizole post-operatively for pain relief." ] },{ "paper_id": "17752cd197628ca49a7b800528bdd68532e4a148", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process.", "Ezrin is present at the site of entry of Spike-pseudotyped lentiviral particle", "The African green monkey kidney Vero E6, human embryonic kidney (HEK) 293T, human cervix carcinoma HeLa cell lines (ATCC, Manassas, VA, USA), and HeLa-F5, which stably express ACE2 [10] , were used in this study.", "S endodomains are accessible to cellular machineries i/ during production, maturation, trafficking, and assembly of viral envelope proteins (pre-budding steps), and ii/ at a critical stage of virus entry, just after formation of the fusion pore, and after fusion. We hypothesized that during these crucial stages of infection, interactions between the S endodomain and cellular machineries could participate in regulating infectivity and host cell susceptibility to infection." ] },{ "paper_id": "17787dbfbb012b537726971936c74cab0aa701b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Contemporary data on immunological, haematological and viral responses and predictors of reported therapeutic failure after initiation of free antiretroviral treatment in Cameroon were collected to evaluate existing treatmentmonitoring algorithms and to complement efforts to scale-up and improve the management of HIV/AIDS [20] .", "The categories", "A sum-up with respect to authorship reveals a total of 97 contributing scientists. Most of them contributed to a single piece (n = 90, 92.8 %), while the remaining seven authors were engaged with two or more articles, up to a maximum of four contributions [8, 11, 17, 26] ." ] },{ "paper_id": "177c9a5fa045b94ea25f72ab17240cdb82585946", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: People 65 years or older are at greater risk of serious complications from the seasonal influenza compared with young. To promote elderly people's behavioral compliance toward influenza prevention, the aim of the current project is to develop, implement, and evaluate a theory-based low-administration-cost intervention building on a leading psychological theory, the Health Action Process Approach (HAPA).", "Given the links the research team has established with the elderly centers (including District Elderly Community Centers, Neighborhood Elderly Centre) in our previous projects, we will make contacts (i.e., phones, emails, and faxes) with center-in-charges and employ their support in championing recruitment to the study. We plan to recruit participants who are registered as members of the elderly centers at the three main territories of Hong Kong (i.e., Hong Kong Island, Kowloon, and New Territories)." ] },{ "paper_id": "178363fb71ad0ae91e621e6e51fc03bb521f5695", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Enhanced version: This article can also be viewed as an enhanced version (http://plosone.org/enhanced/pone.0007165/) in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.", "Selenomethionine (SeMet) labelling of the protein was carried out using prepacked M9 SeMet growth media kit (Medicilon) following manufacturer's instructions.", "The ligand-free form crystals were grown at room temperature in sitting drops. A final concentration of 5 mM ADP, 1:100 chymotrypsin (w/w) were added into the protein stock solution and 0.5 mL protein solution was mixed immediately with 0.5 mL well solution containing 15% polyethylene glycol (PEG) 4000, 0.2 M ammonium acetate, 0.1 M sodium citrate, pH 5.6 and set up for vapour diffusion crystallization. The SeMet crystal used for structure determination was grown in 14.55% PEG4000, 0.2 M ammonium acetate, 0.1 M sodium citrate, pH 6.0, with 1:100 chymotrypsin (w/w) and 5 mM ADP in a sitting drop setup. Crystals grew to a mountable size within 24 hours. Paratone oil was used to cryo-protect the crystals." ] },{ "paper_id": "17889315db35509927f4fd1fb1d656b800365377", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No contact developed TB disease after contact with a TB case on an airplane.", "This level of risk is consistent with published data (0-4%) from 1993 to 2008 [10, [21] [22] [23] but much lower than the risk reported in the early 1990s (30%) [24, 25] .", "A binomial estimation of the 95% confidence intervals (CI) was performed using R software (Version 3.01, The R Foundation for Statistical Computing, Vienna, Austria) to compare the IGRA positivity between the age groups." ] },{ "paper_id": "179338a972eb486bae25e1898b54441c7534e0b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Combating antimicrobial resistance (AMR) is a national and international priority. The U.S. National Institutes of Health [1] , Center for Disease Control [2] , World Health Organization [3] , and United Nations [4] have prioritized the issue. On Sept. 18, 2014 former President Barack Obama issued AMR-focused Executive Order 13676 [5] , which was followed by a National Action Plan for Combating Antibiotic Resistant Bacteria [6] .", "Primers F1 and R1 (Table 1) were combined at a final concentration of 176 nM with control DNA (MGAS10394) dilutions at indicated concentrations, in 1X PowerSYBR (ThermoFisher Cat # 4367659) and run on an Agilent Stratagene Mx3005P. We used a 2-step program with 40 cycles of 30 s at 95\u00b0C and 1 min at 60\u00b0C. The total program time was 2 h 16 min.", "For specificity testing, human DNA was derived from primary adipose-derived cell line ASC080414A (commercially obtained from Zen-Bio, Raleigh, NC) cultured in a humidified 5% CO2 incubator at 37\u00b0C. The growth media consist of Dulbecco's Modified Eagle Medium (DMEM, ThermoFisher # 11965118) supplemented with 10% fetal bovine serum (ThermoFisher # 10082147), 1X Penicillin / Streptomycin (ThermoFisher # 15140122), and 1X Glutamax (ThermoFisher #35050061), changed every 3 days. Total DNA was purified using the Nucleospin Tissue kit (Macherey-Nagel, D\u00fcren, Germany) and quantified on a Qubit Fluorometer (ThermoFisher), which was also used to measure bacterial DNA liberated in crude lysates.", "For the experiment, 5 \u03bcl of overnight culture was mixed with 5 ml of BMI media (1000x dilution) in a sterile tray and gently mixed. This dilute culture was added at 180 \u03bcl per well of a 96-well plate pre-loaded with 20 \u03bcl of antibiotic solutions ranging, for erythromycin, from 0.5 to 32 \u03bcg/ml (10x) to produce the desired final concentrations of 0.05-3.2 \u03bcg/ml. For ampicillin, the stocks were 1.25 \u03bcg/ml-80 \u03bcg/ml resulting in final concentrations of 0.125 \u03bcg/ml-8 \u03bcg/ml. The 96-well plate was then transferred to a FilterMax F5 microplate reader for a 20 h incubation at a temperature of 37\u00b0C, with readings taken every 30 min. A 10-s orbital shaking was performed prior to each reading." ] },{ "paper_id": "17a425d3e66241ada9c347aa0e0387231be31dcd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The chemical analysis was performed on an Agilent RRLC 1200 series system (Agilent) equipped with a degasser, a binary pump, an auto-sampler, a DAD and a thermostated column compartment. The herbal extract was separated on an Agilent ZORBAX SB-C18 column (1.8 mm, 4.6650 mm) . An Agilent QQQ-MS/MS (6410A) equipped with an ESI ion source was operated in negative or positive ion mode. The drying gas temperature was 325uC; drying gas flow: 10 L/min; nebulizer pressure: 35 psig; capillary voltage: 4000 V; delta electro multiplier voltage: 400 V. Ten mL (after a 0.45 mm Millipore filter) samples were injected. In a negative mode, a linear gradient elution was applied from 15-20% B at 0-3 min, 20-30% B at 3-8 min, 30-40% B at 8-14 min, 40-75% B at 14-18 min, 15-15% B at 18.5-22 min. In a positive mode, a linear gradient elution was applied from 10-35% B at 0-5.5 min, 35-65% B at 5.5-6 min, 65% B at 6-10 min, 65-80% B at 10-14 min, 10% B at 14.5-18 min. Agilent Mass Hunter workstation software version B.01.00 was used for data acquisition and processing.", "The phagocytic capability of cultured macrophages was measured by using the Vybrant Phagocytosis Assay Kit (Molecular Probes, Eugene, OR). Macrophages (10 5 /well) were incubated with fluorescein-labeled E. coli K-12 bio-particles and intracellular uptake was quantified by measuring fluorescence emitted by engulfed particles. Extracellular fluorescence was quenched by trypan blue. The trypan blue was then removed, and the amount of bio-particles engulfed by the cells was quantitatively measured using Spectra Max Gemini EM ELISA plate reader at 480 nm excitation and 520 nm emission.", "RAW 264.7 murine macrophages (American Type Culture Collection, Manassas, VA) were cultured in high-glucose Dulbecco's Modified Eagle's medium supplemented with 100 U/mL penicillin/streptomycin, 10% heat in-active fetal bovine serum (all from Invitrogen). The density of Raw 264.7 cells in 24-well plate was 5,000/well. Cells were incubated under 5% CO 2 at 37uC for 24 hours before the transfection. pNF-kB-Luc was transfected to cultured RAW 264.7 macrophages by Lipofectamine 2000. Twently-four hours later, the transfected cells were challenged with different herbal extracts. The transfection efficient was over 80%, as determined by another control plasmid of having a bgalactosidase, under a cytomegalovirus enhancer promoter. -39 and 59-AGG TTG ACT TTC TCC TGG-39 for murine TNFa (251 bp; NM_013693) ; The GAPDH was used as an internal control in all cases, and its primer sequences were 59-AAC GGA TTT GGC CGT ATT GG-39 and 59-CTT CCC GTT CAG CTC TGG G-39 (657 bp; NR_0215885). SYBR green signal was detected by M63000ptm multiplex quantitative PCR machine (Stratagene, La Jolla, CA). Transcript levels were quantified, where the values of target genes were normalized by GAPDH expression in the same sample at first before comparison. The PCR products were analyzed by gel electrophoresis and melting curve analysis to confirm the specific amplification.", "After transfection with the luciferase reporter gene construct and drug treatment for 24 hours, the cells were stored frozen in 280uC, or solubilized in lysis buffer (100 mM potassium phosphate buffer, pH 7.8, containing 1 mM DTT) immediately and transferred into 1.5-mL eppendorf tubes. After vortex for 10 min in 4uC, the lysates were centrifuged in 13,2006g for 5 min in 4uC. Sixty mL of the cell lysates was transferred to the assay plate and set on the luminance reading machine (FLUOStar OPTIMA, Germany), which would automatically add luciferase reagent A and B (Invitrogen) into the lysates, and activated the luciferase activity. The readings of luminance intensity were equalized by the protein concentration of lysates, and the data indicated to the luciferase activities of the samples." ] },{ "paper_id": "17a5402664095260470c65dee52c38311b3ea399", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Critical to successful outbreak prevention and management is recognizing the need to identify, test, and employ biosafety and biosecurity measures that are sustainable and adoptable in local conditions, account for local infrastructure, laws, and social structure, and prevent accidental and deliberate release of studied pathogens. Outbreak investigations for Ebola virus, Middle East Respiratory Syndrome coronavirus (MERS-CoV), and SARS-CoV demonstrated the need for locally effective biosafety measures that protect healthcare workers, diagnostic laboratory workers, and animal health workers from exposure to the outbreak viruses, and biosecurity measures that prevent access to pathogens by malicious actors. Applied research may identify measures that enhance current risk management efforts, such as laboratory and clinical biosafety, biosecurity, and biorisk management.", "Approaches for improving communication between researchers and policy-makers, the funding landscape, and open access policies could help promote research that addresses key knowledge gaps in health security policy and practice, and translate funded research to global health decision-making.", "Although these results often are published in academic literature, decision-makers may not be aware that the studies exist, may not have access to the publication or the information contained therein, may not know how best to integrate the information into their decision-making processes, and/or may prefer to rely on scientific studies conducted by government, rather than non-governmental, researchers. Therefore, the existence of research, biosurveillance platforms, and official reporting mechanisms for infectious disease events does not necessarily indicate that these activities intersect and inform each other.", "The 2014-2016 West-African Ebola virus disease (EVD) outbreak reinforced the concept that a major pathogen outbreak in one country can affect other countries throughout the region and world, and highlighted the aforementioned gaps in leveraging existing knowledge and practices to facilitate outbreak response [13, 14] . This outbreak demonstrated that urban settings, socio-cultural traditions, and local migration affect outbreak dynamics. These lessons, along with the development and use of an experimental Ebola virus vaccine, contributed to very different responses in the 2018 outbreaks in the Democratic Republic of Congo (DRC) [15] . However, conflict and an unsafe public health response environment in the DRC towards the end of 2018 and into 2019 have led to a significant increase of known cases to over 1000 [16] . As long as the security situation ensues, the number of cases will continue to increase and the ability of researchers to collect information about circulating strains will be hampered." ] },{ "paper_id": "17a5e67e3855ae5fa7d1a711f3249b6813c28386", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human melanoma cells (MeWo [61] , from Charles Grose, University of Iowa) and fibroblast cells (MRC-5, American Type Culture Collection, Manassas, VA) were grown in Minimum Essential Medium with 10% fetal bovine serum (FBS). HeLa cells (American Type Culture Collection) were maintained in Dulbecco's Modified Eagle Medium with 10% FBS. SF9 or H5 (Spodoptera frugiperda) insect cells were cultured in TNM-FH medium (BD Biosciences Pharmingen, San Diego, CA).", "Expression and purification of polyhistidine-tagged human wildtype (IDE-w.t.) and mutant (IDE-E111Q) IDE proteins in E. coli were performed as previously described [12] with minor modifications. Briefly, plasmids pProEX-IDEwt and pProEX-IDE-E111Q [12] were propagated in E. coli Rosetta (DE3) cells and protein expression was induced with isopropyl-1-thiogalactopyranoside at a final concentration of 200 mM for 16 hrs. The cells were then lysed in RIPA buffer (10 mM Tris-HCl, pH 8.0, 100 mM NaCl, 1 mM EDTA, 0.1% NP40, 0.5% deoxycholic acid, 0.5% SDS), and polyhistidine-tagged IDE was purified through a Talon metal affinity column (Clontech, Mountain View, CA), eluted with 250 mM imidazole, and dialyzed overnight in PBS at 4uC.", "Insect SF9 cells were infected with a recombinant baculovirus expressing the extracellular domain of VZV gE with a C-terminal (histidine) 6 tag [64] . Three days after infection, tissue culture supernatant was harvested and gEt protein was purified through a Talon metal affinity column (Clontech, Mountain View, CA)." ] },{ "paper_id": "17b715fd64ea139c0ed35b555de365b47585da64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nipah \u00b7 MERS-CoV \u00b7 Chikungunya \u00b7 Rift Valley fever \u00b7 CEPI ", "Bundesgesundheitsbl 2020 \u00b7 63:65-73 https://doi.", "Coalition for Epidemic Preparedness Innovation (CEPI) Marcus Thranes Gate 2, 0473 Oslo, Norway gunnstein.norheim@cepi.net", "Today's world is characterized by increasing population density, human mobility, urbanization, and climate and ecological change. This global dynamic has various effects, including the increased appearance of emerging infectious diseases (EIDs), which pose a growing threat to global health security. Outbreaks of EIDs, like the 2013-2016 Ebola outbreak in West Africa or the current Ebola outbreak in Democratic Republic of the Congo (DRC), have not only put populations in lowand middle-income countries (LMIC) at risk in terms of morbidity and mortality, but they also have had a significant impact on economic growth in affected regions and beyond." ] },{ "paper_id": "17b8edaf62be1b907bf750a94c4b881f3db1f7be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that they have no competing interests." ] },{ "paper_id": "17bbe32558609da8c1aceab2b751383aa9c3c18b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A detailed understanding of the functional roles of P. falciparum novel merozoite antigens, their localization, and their fate during invasion is critical to the identification of targets of host immunity and prioritization of merozoite antigens for inclusion in blood-stage malaria vaccines.", "The C-terminal \u03b1-PfSRA human antibodies (\u03b1-PfSRA P3) were affinity-purified from plasma samples of malaria-exposed children as described previously [19] .", "Immunofluorescence microscopy was carried out using P. falciparum (3D7)-infected erythrocytes smeared onto glass slides and fixed in prechilled methanol for 30 minutes. Fixed erythrocytes were permeabilized using 0.1 % Triton X-100 formulated in phosphate-buffered saline. Nonpermeabilized, liquid immunofluorescence assay (IFA) was carried out as described previously [22] . After the washing step for both IFA conditions, the slides were blocked for 1 hour in PBS containing 3% bovine serum albumin. Slides were probed with primary and secondary antibodies for the respective antigens and mounted in vectashield (Vector Laboratories Inc) supplemented with 4\u2032,6-diamidino-2-phenylindole for staining the nucleus. Fluorescence microscopy was performed on an Olympus fluorescence microscope (BX41). Images captured were processed using the open access Fiji-Image J software (National Institutes of Health).", "To identify new blood-stage proteins as potential vaccine candidates, a systematic screening procedure was implemented. This included analysis of temporal gene expression relative to other well-characterized invasion-type genes and in silico interrogation of protein structural features. Once all of these selection criteria were ascertained, sequence alignment analysis was done to evaluate the conservation level of the target gene across the different Plasmodium species orthologs. Finally, we scanned the entire protein sequence using a current state-of-the-art online threading program to identify coiled-coil regions [15] ." ] },{ "paper_id": "17bcc640fec147856a5d625a1d17970429665b65", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Researchers conducting the experimental infection wore N-95 respirator masks, protective glasses and gloves when performing this procedure and throughout the entire study when they were accessing the pigs.", "Means and standard deviations from macroscopic and microscopic lung lesion scores were analyzed using ANOVA. The response variables that had a statistically significant effect (p \u2264 0.05) by treatment group were further analyzed through pair-wise comparisons using the Tukey-Kramer test. The analyses were performed using SAS (SAS System, SAS Inst., Cary, North Carolina, v 9.2).", "A triple reassortant H1N1 strain A/Sw/IA/00239/04 (IA04) belonging to the \u03b2 cluster used in previous studies [34] [35] [36] and isolated from field samples at the University of Minnesota Veterinary Diagnostic Laboratory was used for challenge. The IA04 influenza virus was grown in bulk quantities using Madin-Darby canine kidney (MDCK) cells using standard procedures [37] .", "Seeder pigs were infected intratracheally and intranasally with a total of 2 mL of the IA04 H1N1 challenge virus at a titer of 1 \u00d7 10 6 tissue culture infectious dose (TCID)50/mL. Before the inoculation, all piglets were sedated by an intramuscular injection of a dissociative anesthetic at the recommended dose of 6.6 mg/kg (Telazol \u00ae , Fort Dodge Animal Health, Fort Dodge, IA, USA)." ] },{ "paper_id": "17cfe7cc0c68b1002bb31a2b2afa988ab9cdc890", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Adenovirus (AdV) is a non-enveloped, double-stranded DNA virus, and is divided into five genera: Mastadenovirus, Atadenovirus, Ichtadenovirus, Siadenovirus, and Aviadenovirus. Recently, several novel members of Mastadenovirus were identified, and more than 40 species were registered in the International Committee", "Bat AdV-Mm32 Bat AdV-A Bat AdV-G Bat AdV-B Bat AdV-Vs9 Canine AdV1 Canine AdV2 Skunk AdV-A Equine AdV-A Human AdV-B Human AdV-E Human AdV-D Human AdV-C Human AdV-A Human AdV-F Bat AdV-C Tree shrew AdV-A Bovine AdV-B Ovine AdV-A Porcine AdV-C Bat AdV-F Bat AdV-D Bat AdV-E Murine AdV-A" ] },{ "paper_id": "17cff89c1672094997155613467334c9b1b410e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Researchers have addressed concerns about plant-specific glycosylation by altering the pathway that plant cells use to process the recombinant protein.", "Current methods in plant biotechnology cannot precisely control the expression level of transgenes in plants in a consistent manner and not every plant species is readily transformed. This means that the amount of pharmaceutical produced may vary in each plant species, or even in different plant parts (i.e., leaves, fruit, and seeds). Levels of expression in subsequent generations may also vary. Given this scenario, it is very difficult to accurately quantify the appropriate dosage of edible vaccines for children and adult patients. Edible vaccines can also trigger immune tolerance after oral administration. Lastly, most of the ingested protein will be degraded by digestive processes. Collectively, these disadvantages greatly restrict the clinical use of edible vaccines [30, 32] .", "A primary objective of PMF is to reduce the cost of producing novel therapeutic proteins. Using PMF to create a vegetable, seed or fruit health supplement could be a practical alternative to using PMF to develop a processed pharmaceutical drug. [57, 58] expressed lumbrokinase, an anti-thrombotic enzyme from earthworm, in sunflower kernels. Mice and rats that were fed the transgenic kernels exhibited a strong degradation of blood clots [58] . Unlike a vaccine or a therapeutic protein, lumbrokinase has been widely sold and used as a health supplement to dissolve blood clots and maintain healthy cardiovascular function in people. This makes lumbrokinase a good candidate for PMF since, in general, health supplements do not need a medical prescription and have less regulations for commercialization [59] ." ] },{ "paper_id": "17d0d25ab7105e239f9d13e41489d01d9a40c34a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "17d4c1e70195453379ed6529851c51d204fdc926", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total no. of pos. 5/6 2/6 2/6 5/7 7/7", "The plot of mean AAW over time, comparing 2011-2012 date by date (Fig. 4) , showed that the AAW of 2011 started higher, then fell to a lower level and stayed below the control year level for many months. When the groups were compared with respect to average FCR as well as ADG, the 2011 group had poorer figures (Table 4 ).", "Five of the six bulls with paired serum samples either seroconverted (four) or had a strong increase in BRSV antibody level in percent positivity of at least 70 % (one). Two of the six bulls seroconverted for BCoV and two of them had a strong increase in antibody level for BPIV3. The seven animals tested were positive for BRSV on nasal swabs (five) and/or BAL samples (seven) by RTqPCR (Table 1) ." ] },{ "paper_id": "17d6161faae981aa6c56ac58d9c1d30ed581b05f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Four virus genome sequences containing IRES element were tested in IRSS " ] },{ "paper_id": "17d92d371f5552921b86de6fb6cd7e65344ddb2e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Informed consent was obtained from the participants of this study and the study protocol was approved by the institutional review board of Ajou University Hospital (AJIRB-SBR-SUR-15-287)." ] },{ "paper_id": "17dbd5741595c1e5b7508063b31147be9263e7f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human bronchial epithelial cells were isolated from patients (. ", "cell proliferation assay, the selective index for K22, i.e. the CC 50 / IC 50 quotient, was 157. Compound J15, although showing anti-HCoV-229E activity similar to that of K22 exhibited a somewhat less favorable cytotoxicity profile in the cell viability assay ( Figure S1B ).", "The ChemBioNet diversity library of 16671 compounds was obtained from the Leibniz Institute for Molecular Pharmacology (Berlin, Germany). Library was provided in a 384 well plate format, each well containing 5 ml of a compound solubilized in DMSO to a final concentration of 10 mM. Hit compound K22 was purchased from ChemDiv (San Diego, CA; catalog number 4295-0370). The correct structure and purity of K22 (.95%) was confirmed in our laboratory by NMR and LCMS analyses." ] },{ "paper_id": "17e4de7b95ed440d0df3a87e85e9fca8b64b0de7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Then we define the media function, g, as follows:", "_", "Following infection, individuals recover after T R time periods. Therefore, if X i t\u00c0 1 \u00bc S and X i t \u00bc I, then:" ] },{ "paper_id": "17ef76b6acdc223229e3a6ed236bed4c2fc0f811", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author contributions-Y. L. and M. K. R. conceived the project. Y. L. designed and conducted the experiments. S. L. C. also conducted experiments. Y. L. and M. K. R. analyzed the data and wrote the manuscript, which S. L. C. helped revise." ] },{ "paper_id": "17fe16cf66ebbe693a2e75dda11d14513fec7519", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To date, the implementation of market closures has been based on viral surveillance data relying on virus detection alone.", "This study was financially supported by the United States Agency for International Development (USAID) under grant number GHA-A-00-06-00001. ", "Four of the eight markets located on open streets. In these street markets, traders pay a daily market fee of about 3,000-5,000 VND 3 per trader. Some of these street markets are nearby to official, enclosed marketplaces that do not sell live poultry. One market is neither indoors nor on a public street, but on an area of barren land. When it rains, the ground turns to mud." ] },{ "paper_id": "1803065327394f7f38931024cd4219d47f5f7d8b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2019, 11, x FOR PEER REVIEW 10 of 15", "Funding: Funding support came from NIH grants U19AI135995, AI132244, AI132223, U54 HG007480, U19 AI115589, U19AI142790, and contract HHSN272201400048C and grant INTU1901 from the Coalition for Epidemic Preparedness and Innovations." ] },{ "paper_id": "1804d84a48b0228ffdc40a1af0eb63d469630852", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1) Aged 30-69 years at study entry.", "Immune deficiency or auto-immune disease (eg. HIV/AIDS, lupus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease). Co-Investigator Dr. Muller will advise in questionable cases.", "Study visit checklists have been developed for the current study as tools used to ensure consistency and help study coordinators make sure all scheduled assessments/events are done for each particular study visit/time point. Please see Appendix E for a complete list of study visit checklists." ] },{ "paper_id": "18073920e12ee20d939dee5116c586da8accfd82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All laboratory testing was performed under a sterile hood in a Biosafety laboratory 3 (BSL3) according to standard operating procedures described in " ] },{ "paper_id": "1808454d2e8c7d1088e58a5e3a52111a8c507554", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All samples were extracted by using Qiagen RNA mini kit (Qiagen, Germany), in accordance with the manufacturer's protocol.", "Human enteroviruses (HEV) belonging to the Picornaviridae family are ubiquitous viruses responsible for a wide range of clinical syndromes ranging from mild respiratory symptoms to serious conditions, including aseptic meningitis, encephalitis and acute flaccid paralysis. Some serotypes support respiratory infections, and it has been confirmed that they are responsible for bronchopneumonias and occasional fatal cases [1] [2] [3] [4] . As for many RNA viruses, the genetic evolution of HEV occurs over time by means of point mutations and recombination phenomena allowing the virus to adapt to environment modifications and host selective pressure [2, 5, 6] . This genetic evolution is linked directly to virulence characteristics, tissue tropism and hence to the pathogenic potential of these viruses [5, 7] . More than 100 different serotypes of non polio enteroviruses have been recognized and recently two new enterovirus, the HEV104 and the HEV109, classified within HEV species C, were reported in association with respiratory diseases [8] ." ] },{ "paper_id": "1817050ed534376723c94abc3b5496beea55ed5b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Neonatal calf diarrhea (NCD) is a major disease worldwide when calves are reared intensively, and constitute substantial cost in terms of calf mortality, opportunity costs for labor and capital, veterinary costs and loss in calf value. The term NCD generally refers to a disease complex characterized by acute, undifferentiated diarrhea in young calves. It is a multifactorial disease where, besides the causative pathogenic agent, calf age, management and environmental factors, may influence the clinical outcome [1] .", "The samples were streaked on horse blood agar (5% v/v) and on MacConkey agar and incubated at 37\u00b0C for 18 h. From each sample, 25 colonies that morphologically corresponded to E. coli were sub-cultured on horse blood agar [15] . Isolates were confirmed as E. coli by testing for production of tryptophanase (indole) and \u03b2glucuronidase (p-nitrophenyl-\u03b2-D-glucopyanosiduronic acid, PGUA). Only lactose-positive isolates with typical morphology and positive reaction in both tests were selected for further analysis." ] },{ "paper_id": "18176d1030fff6410b83e0df1591b3617fc739cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our work highlights the importance of surveillance of circulating MERS-CoV in both camels and humans followed by functional analyses of the biological impact of variations uncovered. Further sequencing and functional studies should be conducted to characterize the frequency and effects of other variations.", "Middle East respiratory syndrome coronavirus (MERS-CoV) is the most recently characterized human coronavirus, causing over 1800 reported infections to date and with a high case fatality rate above 35%. First reported in 2012, human MERS infections are still occurring, with a main focal point in the Arabian Peninsula, but with occasional imported cases to other countries.", "Quantitative data were analyzed and plotted using GraphPad Prism 7 (GraphPad Software, La Jolla, CA, USA). Statistical significance analyses were performed using two-tailed Student's t-test. To describe P-value significance, the following convention was used: not significant (NS), P40.05; significant (*), P \u2264 0.05; highly significant (**), P \u2264 0.01; and very highly significant (***), P \u2264 0.001." ] },{ "paper_id": "181bef55321b315c053d17800f248442f38d15fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consider the Laplacian L at a point. It can be represented with its eigendecomposition:", "We use iterated gradient descent to calculate the mean:", "If \u03c4 \u2265 0.5, then", "Another computationally beneficial feature of the log-Euclidean metric is the closedform expression that it has for calculating the mean of a set of matrices:", "Once the spectrum has been plotted, techniques such as k-means clustering can identify communities. This should produce a sufficient approximation of the separatrices between maxima. However, if two eigenvectors are used, it may even be easier to identify communities visually." ] },{ "paper_id": "181d47c4050ebc63d4831f8dd0df88b785bf4985", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although the above findings have provided evidence for both direct and indirect antibacterial properties of P. sidoides, the pronounced anti-infective capabilities of this herbal medicine cannot adequately be explained merely on the basis of the observed antibacterial activities.", "The mucociliary system represents a defence mechanism of the nasal cavity and the bronchial tree for cleaning the air of bacteria and foreign particles, with the ciliary beat frequency (CBF) being an important parameter for determining its efficacy. EPs \u00ae 7630 significantly and concentration-dependently increased CBF of an adherent monolayer culture of human nasal epithelium cells. At 30 \u00b5g/mL, the increase was ca. 125% compared to the equilibrium phase [33] . After washing procedures the CBF returned to that of the equilibration period. However, subsequent examinations have to prove the effect under in vivo conditions with emphasis on the mucociliary clearance.", "Induction of protective immunity against Leishmania infection and other pathogenic agents is closely linked to the production of cytokines. The analysis of the data obtained from densitometric measurements revealed that the iNOS and cytokine (IL-1, IL-10, IL-12, IL-18, IFN-\u03b1, IFN-\u03b3 and TNF-\u03b1) mRNA levels of infected RAW 264.7 cells were significantly enhanced in response to LPS plus IFN-\u03b3 when compared with those of non-infected cells. Notably, EPs \u00ae 7630 produced similar transcript profiles with considerably increased and prolonged up-regulations distinctly expressed under infectious conditions ( Figure 5 ) [67] [68] [69] ." ] },{ "paper_id": "1821674721e32961f0f8c6aa3dc7c13c96b693c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All relevant data are within the paper. Any additional data use and transfer is monitored by ISGlobal's Data Management and Biostatistics Unit (contact e-mail: ubioesdm@isglobal.org).", "Minimum inhibitory concentrations (MICs) of a variety of antifungal agents were determined (Table 3 ). All triazole antifungal agents (fluconazole, voriconazole, itraconazole and posaconazole) had MICs less than or equal to the defined epidemiological cut-off values (ECVs) 26 . One isolate showed a MIC to flucytosine (16 \u00b5g/mL), one dilution higher than the ECV (8 \u00b5g/mL). Although all the isolates presented a MIC \u2264 1 \u00b5g/mL to amphotericin, the MICs of three C. neoformans molecular type VNI (1 \u00b5g/mL) and two C. gattii (1 \u00b5g/mL) were one dilution higher than the defined ECVs (0.5 \u00b5g/mL) 27 ." ] },{ "paper_id": "1829dd66176c20fb22a9d7186d62fa596cc93f9c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Airway epithelial damage [56, 57] and mucus metaplasia, both of which occur in asthma, may provide rhinovirus with increased access to more readily infected basal cells [58] and goblet cells [59] , thereby increasing viral replication.", "Infancy: Exacerbations of Preexisting Airways Disease or a Factor in Asthma Development?", "(This theory was also used to explain how nasal allergies promote asthma.) More recently, release of proinflammatory mediators from the nose and bone marrow into the circulation has been proposed [9] . (1) Viral infection (most commonly rhinovirus) (2) Allergen exposure (tree, grass, and weed pollens; mold; animal dander; dust mites; and cockroach particles) (3) Exercise (4) Irritants including environmental tobacco smoke exposure, smoke from wood-burning appliances or fireplaces, strong odors from perfumes, cleaning agents, air pollution, and occupational dust or vapors (5) Medications (aspirin and other anti-inflammatory drugs, and beta blockers) (6) Changes in weather (cold air, changes in temperature, and humidity) (7) Gastroesophageal reflux (8) Sinusitis" ] },{ "paper_id": "183e393843de9d6c653897f1039ad10af9750347", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since 2003/04, Ontario hospitals have reported day procedure events to NACRS rather than the DAD.", "The primary practical challenge that we faced was working with the large event-data files.", "In principle, it was straightforward to construct the desired distributions, i.e.,", "Infectious disease epidemics have substantial impacts on health care systems and economies. Mathematical models are extremely important for the purposes of planning [13] , because the best we can do is to make decisions based on comparing the effects of various interventions on simulated epidemics (real experiments are usually impossible or unethical). For example, planners may need to decide whether to close schools [8, 14, 15] (and for how long to close them) or how to prioritize the use of limited supplies of vaccine [5] ." ] },{ "paper_id": "18421f153f74c6b0f8f9efe88c2aad6b70547b99", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication.", "Sequencing and primary data quality control was performed at the Genomics Unit of the Centre for Genomic Regulation (CRG) in Barcelona, Spain. We thank Anna Menoyo, Anna Ferrer, Magda Montfort, Irene Gonz\u00e1lez, Manuela Hummel, and Sarah Bonnin for technical assistance, Avital Brodt and Roni Wilentzik for computational analyses, and Shirley Smith for scientific editing. We thank Tel-Aviv University for core funding and technical support.", "will require integration with additional genomic data, including proteomics, trans-acting polymorphic loci, and epigenetic data.", ": the higher the (absolute) founder effect on a certain eQTL target, the stronger the contribution of the DNA changes in the eQTL region of this founder strain." ] },{ "paper_id": "1842bb195a368132b3f4b433e1b1a71590fdc31e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Initially, approximately 20 adult bees from a heavily IAPVinfected colony were frozen in liquid nitrogen, ground to a fine powder, and homogenized in 10 ml extraction buffer (0.1 M potassium phosphate buffer, pH 7.5, 0.2% diethyldithiocarbamate, 1/5 volume of diethyl ether). Emulsification ensued by adding 5 ml carbon tetrachloride and centrifuging at 10,000 rpm for at 4uC for 10 minutes (Rotor: Sorvall RC-5B) and collecting the supernatant.", "One hind leg was removed from each pupa and stored at -20uC before DNA extraction to determine the subfamily (patriline) for each individual. DNA was extracted from each leg using a standard Chelex 100H method [43] . Briefly, each sample was incubated for 60 min at 55uC, 15 min at 99uC, 1 min at 37uC, and 15 min at 99uC in 150 ml of a 5% Chelex 100H solution with 5 ml 0.35 mg/ml proteinase K.", "Raw Data S1 Raw Ct values for all qPCRs run in the main experiment. (PDF) Results S1 The expression of genes evaluated by full, 3factorial ANOVAs indicated that developmental time is a significant factor, that was as important as treatment but for most genes interacted with treatment. (PDF)" ] },{ "paper_id": "1843389daffca2a8b5e04048821ce881eb068269", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request." ] },{ "paper_id": "184c8c4637d343cd81dddd0d3f5e6c922f538afe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The dichotomous analysis by identified virus is displayed in " ] },{ "paper_id": "18592fbe580d07f487157c4f81de8baecd9700e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "chromatograms. These data show the existence of different populations of viruses (quasispecies) in tissues and clinical isolates.", "Vero cells (ATCC #CCL81) and human primary fetal fibroblasts WI-38 (Coriell Institute, Camden, NJ) were maintained in DMEM supplemented with 5% and 10% Fetal Bovine Serum (FBS, Atlanta Biologicals), respectively.", "Rubella IgG titers were measured by an enzyme-linked immunosorbent assay (EIA) with the ZEUS ELISA Rubella IgG Test System (ZEUS Scientific, Branchburg, NJ) according to the manufacturer's instructions and expressed as IU/ml. Rubella IgM testing was performed with a Rubella IgM Capture EIA Kit (Diamedix, Miami, FL). Measles and mumps IgM testing was performed using in-house capture IgM EIA assays [74, 75] .", "The structures of the rubella E1 protein (PDB entries 4ADG, 4ADI and 4ADJ) were used as templates for computer modeling. The mutations were modeled as described earlier using the software package ECMMS (Energy Calculations for Macro Molecular Systems) for molecular mechanics modeling [83, 84] . The illustrations of protein structures were prepared using DS Visualizer (http://accelrys.com/products/collaborative-science/biovia-discovery-studio/ visualization.html; Accelrys Inc., CA).", "Primary immunodeficiency diseases (PID) are a group of hereditary disorders affecting different arms of the immune system [11] . PID patients usually have increased susceptibility to infections and have difficulties eliminating pathogens. Live vaccines, including rubella vaccine, are contraindicated for individuals with severe antibody deficiency, T-cell deficiencies or innate immune defects because they may cause severe or chronic disease [12] . Unfortunately, PID diagnosis often occurs after vaccination with MMR (usually given at the age of 12-15 months). Nevertheless, adverse outcomes related to MMR vaccination of children who are diagnosed with PID are thought to be rare [13] ." ] },{ "paper_id": "185b7ddc439bc3490a0c97ecc00861497c6bd481", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were washed twice with cold phosphate-buffered saline (PBS), and lysate samples were prepared in 350 \u00b5L T-PER Tissue Protein Extraction Reagent (Thermo Scientific Pierce, Rockford, IL, USA) in the presence of a protease inhibitor cocktail (Roche, Indianapolis, IN, USA) and centrifuged at 20,000\u00d7 g for 20 min at 4 \u2022 C.", "The following are available online at http://www.mdpi.com/2073-4409/7/11/222/s1, Figure S1 : Sequencing analysis of cell clones 1-10#, 1-19#, 1-22#, 2-3# and 6-18#, Figure S2 : Amino acid sequences alignment for wild-type, 1-10# and 1-19# cell clones. ", "The authors declare no conflicts of interest." ] },{ "paper_id": "185bc5c5addfa50d75d15b288537d11bd4a4aa5d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "PCR fragments were generated using 2X phusion master mix (M0531S, NEB, Ipswich, MA) and insert-specific primers that appended a 30 bp overlap with target DNA. Vector backbones were linearized by restriction enzyme and dephosphorylated by calf intestinal phosphatase (M0290S, NEB, Ipswich, MA). Prior to assembly, all DNA fragments were gel purified (D4002, Zymo Research, Irvine, CA). Linearized vector DNA (50 ng) was combined with isomolar amounts of purified insert(s); 5 ul of the resulting DNA mix was added to isothermal assembly master mix and incubated at 50\u02daC for 20 min [68] . Assembled product was transformed into NEB Stable competent cells (C3040H, NEB, Ipswich, MA) and plated on LB + agar plates (plus appropriate antibiotics) to isolate single isolates. Single isolates were grown in LB broth + antibiotics, and plasmid DNA was purified using a Qiagen miniprep kit (#27106, Qiagen, Hilden, Germany). Sequences were verified by Sanger sequencing (Eton Bioscience, San Diego, CA).", "Fluorescent images were obtained using a confocal microscope with Airyscan detectors (LSM880 with Airyscan, Zeiss) and a 63X PlanAPO oil-immersion objective lens (Zeiss, Oberkochen, Germany) and were processed with Zeiss Blue software (Zeiss, Oberkochen, Germany)." ] },{ "paper_id": "185e505daa1da8ee7ece18212693b2550410a190", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "African green monkey kidney epithelial Vero cells (ATCC, CCL-81) were grown in Dulbecco's modified Eagle's medium (DMEM; Mediatech, Inc) supplemented with 5% fetal bovine serum (FBS), 2 mM L-glutamine, 100 U/ml penicillin and 100 \u03bcg/ml streptomycin at 37 \u00b0C with 5% CO 2 ." ] },{ "paper_id": "1868242435edf92a6b0018f2569c2012f672ddf7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Corticosteroids have been used in some patients with HPAI H5N1, but no definitive role for steroids has been determined [25] [26] . The evidence for corticosteroid use in other severe viral pneumonias, including varicella-zoster virus infection and severe acute respiratory syndrome (SARS), is also insufficient [7] [8] .", "The isolated spleen cells (1610 6 per well) were seeded into 96well tissue culture plates and stimulated with LPS at different concentrations (10, 20 or 50 mg) or PBS for 12 or 24 h at 37uC and 5% CO 2 ; 2-[2-methoxy-4-nitrophenyl]-3-[4-nitrophenyl]-5-[2,4-disulfophenyl]-2H-tetrazolium monosodium salt (WST-8, Cell-Counting Kit-8H (Dojindo Molecular Technologies, Inc., Gaithersburg, MD) 10 ml per well) was added as described previously [50] . The plates were incubated for 4 h, and the optical density (OD) at 450 nm was measured using a microplate reader (BioRad, Hercules, CA). Each sample was analysed in three replicates, and the injury index was calculated using the following formula: injury index = (mean OD of control group-LPS-stimulated group)/(mean OD of control group).", "Comparisons among treatment groups were performed with a one-way-ANOVA test. A P value less than 0.05 was considered statistically significant." ] },{ "paper_id": "187062df058ff8a8110c008bc1f489986423ea1e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The cytomegaloviruses, classified within the Betherpesvirinae subfamily, are a group of species-specific herpes viruses that establish life-long infection of their hosts. Human cytomegalovirus (HCMV) can cause devastating disease and death in congenitallyinfected infants, and long-term neurological complications in survivors. In adults, HCMV can cause a spectrum of diseases in immune compromised patients involving multiple organs and tissues and is a primary cause of graft loss in transplant patients [1, 2] . In recent years, HCMV has been linked to lung injury in trauma patients [3] and is also postulated to act as a cofactor in atherosclerosis and some cancers [4, 5] . For these reasons, there is an urgent need for an effective vaccine and new antiviral intervention strategies that mitigate the toxicity and drug resistance shortcomings of current antiviral drugs [1, 6] .", "Ccl5 chemokine (C-C motif) ligand 5, RANTES 8.5", "Trank1 tetratricopeptide repeat and ankyrin repeat containing 1 8.4" ] },{ "paper_id": "187607fca4b1dc4e30fe91d36520432aec36f795", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Herpes varicella zoster (VZV)", "Viruses 2018, 10, x 9 of 30", "in childhood, it was clear that chickenpox was what he now had. No national alert was necessary, with all the widespread anxiety that would have followed. The speed and certainty of the diagnosis by EM offered a lesson that still has relevance." ] },{ "paper_id": "188337e43aa524493372f8769b6bac8b366850ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Excessive environmental and industrial development has created hazardous conditions, such as viral diseases (e.g., Middle East respiratory syndrome (MERS)) [1] and particulate matter air pollution, which has been classified as carcinogenic to humans (IARC Group 1) [2] . Thus, the importance of building a strong immune system is becoming more important for good health, and the demand for health supplements that can help improve the immune system has been rapidly increasing. There is a close correlation between immune responses and inflammation. When immunity decreases, the body is easily exposed to infectious and noninfectious inflammatory diseases.", "Cynanchum is a genus that includes approximately 300 species that are distributed worldwide, including east Africa, the Mediterranean, the tropical zone of Europe, and the subtropical and temperate zones of Asia [11] . Many Cynanchum species have been used as traditional medicines in Korea toprevent and treat various diseases such as rheumatic arthritis and geriatric, vascular, and ischemia-induced diseases [12] [13] [14] .", "In spite of advances in modern medical science, traditional herbal medicine has continued to be widely used for health maintenance, disease prevention, and even disease treatment in China, Japan, and Korea for thousands of years. Previous studies have shown that 1 out of 2 IBD patients turns to complementary and alternative medicine [7] [8] [9] [10] ." ] },{ "paper_id": "188a2e1351ceae0aa8347e1a1d7af1e3b7b66a02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RSV-positive samples were tested simultaneously for the following 17 respiratory pathogens: InfA, InfB, PIV1-4, ADV, EV, HMPV, HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, RV, HBoV, MP and CP. The testing procedure, using kits from Guangzhou HuYanSuo Medical Technology Co., Ltd, has been described in a previous report [17] .", "The study was approved by The First Affiliated Hospital of Guangzhou Medical University Ethics Committee for research on human beings, and the next of kin, caretakers, or guardians on behalf of the minors/children gave signed informed consent for participation in the study.", "As described in detail previously [17] , all statistical analyses were performed with the SPSS statistical software (version 19.0; SPSS Inc., Chicago, IL, USA). To compare categorical data, the \u03c7 2 test and Fisher's exact test were used, as appropriate. All tests were two-tailed, and p < 0.05 was considered statistically significant.", "doi:10.1371/journal.pone.0165108.t003 observed for the three target genes. Parallel standard curves (with almost the same slopes) increased the quality of the CVL calculation." ] },{ "paper_id": "18910856b917289b6bb3cc2cef0f78ff82ad4b02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Winter and annual influenza-associated excess elderly mortalities", "Model selection was based on Akaike's information criterion (AIC) and likelihood ratio test [11] . When modeling P&I mortality, both mean temperature and relative humidity were found to be without statistical significance and were thus excluded from the full model (Table 1) . The model was implemented by SAS (version 9.1; SAS Institute Inc, Cary, NC). The final model for ''influenza-associated deaths'' was devised as follows:", "To better understand why 2001-2002 exhibited the highest winter and annual excess P&I mortality rates, HA1 sequences of the 2002 epidemic influenza virus A (H3N2) Fujian strain (A/ Fujian/411/2002 (H3N2)), vaccine strains (red squared symbol) from 1999 to 2007, and other Taiwanese H3N2 isolates (circular symbol) from 1996 to 2008 were gathered from the National Center for Biotechnology Information (NCBI) for genetic comparison. We then constructed a phylogenetic tree of HA1 amino acids among Taiwanese A (H3N2) virus strains using the Neighbor-Joining method. This tree was bootstrapped 1,000 times with Mega 4.0 software [12] ." ] },{ "paper_id": "1894cac8794748c11482c059bc5a2c6d4f1e9527", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral nucleic acid from samples was extracted using an automated MagNa Pure LC 2.0 system (Roche Diagnostic Systems, Branchburg, NJ). HSV (2) Keratitis (2) HPV (2) Warts (2) CMV (8) Viremia (4), Pneumonia (6) Adenovirus (3) Viremia (2), Pneumonia (1)", "Enterovirus (3) Hemophagocytosis (1), Viremia (1), Pneumonia (1) Norovirus (1) ", "Immunodeficiency with centromeric instability and facial anomalies (2) Sapovirus (2) Enteritis (2) Adenovirus (2) Enteritis (1), Viremia (1) PREDOMINANTLY ANTIBODY DEFICIENCIES (n = 6)" ] },{ "paper_id": "18a116d870bd24c96d95317418946ce0873f2180", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Four-to six-week-old wild-type C57BL/6 mice were purchased from the South Medical University Animal Center (Guangzhou, China). Animal husbandry and experimental procedures were approved by the Animal Research Committee of the Zhongshan Ophthalmic Center, Sun Yatsen University (Guangzhou, China). All animals were housed in a specific pathogen-free biohazard level-2 facility maintained by the Zhongshan Ophthalmic Center in accordance with the Association for Assessment and Accreditation of Laboratory Animal Care guidelines.", "pathogenesis and immune reaction after intravitreal dispase injection in mice. In the present study, we analyzed these outcomes after intravitreal dispase injection during an 8 week observation period.", "Dispase, a proteolytic enzyme able to harvest and culture cells due to its ability to cleave the basal membrane in various tissues, can be used as an intravitreal injection material to induce proliferative vitreoretinopathy (PVR) in the eyes of mice [1, 2] and rabbits [3] [4] [5] [6] [7] [8] [9] . PVR is the most common cause of recurrent retinal detachment after retinal detachment repair, occurring in 5%-11% of patients [10, 11] . Basic research has indicated that PVR is characterized by the formation of scarlike fibrous tissue containing myofibroblasts derived from transdifferentiated retinal pigment epithelial (RPE) cells and other cell types, such as glial cells, that have entered the vitreous cavity and induced the contraction of cellular membranes within the vitreous cavity on both detached retinal surfaces [12] [13] [14] ." ] },{ "paper_id": "18a8af7a7be62a2ccc66a4f65c94ac94bf2f8639", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations: CI = confidence interval, HWE = Hardy-Weinberg equilibrium, MMPs = matrix metalloproteinases, OA = osteoarthritis, ONFH = osteonecrosis of the femoral head, OR = odds ratio, SNPs = single-nucleotide polymorphisms, TIMPs = tissue inhibitors of metalloproteinases. P values were calculated from 2-sided chi-squared test adjusted for age. \u2020 P values were calculated from Wald test. \u2021 P < 0.05 indicates statistical significance.", "Our study protocol adhered to the principles of the Declaration of Helsinki and was reviewed and approved by the Ethical Committee of Zhengzhou Traditional Chinese Medicine Traumatology Hospital. Informed consent was obtained from all candidate subjects." ] },{ "paper_id": "18c1ceb51b621792118f18381b9b3606b46717a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "18c21db94a22f1358057c6d797164ffe1585b395", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Note: Some patients do not show initial symptoms of fever, especially those who have had recent surgery or those having chronic diseases.", "(3) Routine laboratory examinations White blood cell counts are generally normal or below normal, with decreased absolute lymphocyte counts.", "Suspected cases: In accordance with 1.1+2+3, 1.2+2+4 or 2+3+4." ] },{ "paper_id": "18d519cf1ea884ddf381067f0733c18d8ad94c7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Further investigation is needed to establish a link between these observations and the correct activation of the immune system in ZIKV infection and to identify different intracellular signals induced by different ZIKV strains, responsible for different cytokine response.", "Zika virus (ZIKV) is an emerging mosquito-borne flavivirus, transmitted by different Aedes mosquito species, including Aedes aegypti. ZIKV tropism is various, and in addition to both skin fibroblasts and epidermal keratinocytes, dendritic cells (DCs) were found to be permissive to infection [1] . ZIKV was originally identified in Uganda in 1947 [2] and over the years limited ZIKV outbreaks were reported, especially in the Pacific islands [3, 4] . Phylogenetic studies have revealed that Zika virus has evolved into 3 distinct genotypes: West African (Nigerian cluster), East African (MR766 prototype cluster), and Asian [5] . In 2015, the largest ZIKV epidemic has begun in Brazil, spreading throughout the Americas and infecting nearly two million people; the virus that caused this epidemic was found to be most closely related to a 2013 isolate from French Polynesia, within the Asian clade [6] . Although ZIKV-associated illness was initially described as self-limiting mild illness characterized by rash, fever, conjunctivitis, arthralgia, and arthritis [7] , it is now generally accepted that ZIKV is responsible for neurological birth defects, including microcephaly in newborns [8] .", "In this paper, we analyze the ability of ZIKV to activate immune response in human PBMC, since it is well known that these cells represent the gatekeeper of virus spread in the body during systemic viral infections and include several subpopulations that may cooperate in the activation process [21, 22] .", "Following the recent outbreak raging in the Americas, ZIKV has become an emerging arbovirus with potential impact on human health, as supported by the WHO Declaration of PHC in February 2016 [18] . To our knowledge, limited and controversial information is available about the innate host immune response developed in response to ZIKV infection in humans. All vector-borne flaviviruses studied so far need to overcome type I IFN signaling to replicate and cause disease in vertebrates [19] and the mechanisms by which ZIKV interferes with the innate response are the object of intense investigation [20] and are still to be fully understood." ] },{ "paper_id": "18d6b41f2b9f5cad93519eb39f422f7f008a4ed3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 16S rRNA gene sequence data supporting the conclusions of this article are available by request to M.M. Pettigrew. The relevant de-identified raw sequence data will be made available to researchers wishing to use them for non-commercial purposes.", "Btrim software was used to sort, trim, and filter low quality sequences [10, 29] . Cleaned and filtered sequences were processed using customized analytic pipelines and open source packages available through the Ribosomal Database Project (RDP) [10, 11, 30] . Sequence reads were aligned using the RDP alignment tool. The command line RDP classifier tool was used for taxonomic assignment [30] . Sequences were classified in an iterative process. Taxa were defined by grouping together all sequences belonging to the same genus. Sequences that were unclassified at the genus level were classified and then grouped at the next lowest taxonomic level." ] },{ "paper_id": "18e4bf7e0c2d81caa5795174a4f25d5a035e09b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining", "The frozen tumor tissue sections were incubated with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling reaction mixture (Roche Diagnostics) at 37uC for an hour. The slides were counterstained with mounting medium with DAPI (Vector Laboratories). The slides were then visualized under a fluorescent microscope.", "Tissues were removed from treated mice, fixed with 4% paraformaldehyde and embedded with paraffin. Blood vessels were detected by staining of Lycopersicon esculentum (tomato) lectin conjugated to biotin (Vector, CA, USA). The biotinylated lectin was visualized with streptavidin-conjugated rhodamine (Pierce, IL, USA)." ] },{ "paper_id": "18efb24780930c0ee4343fd31b37b39ce3c3b315", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Optical aptasensors for virus detection can be classified into six categories based on the optical principles used for material detection. These categories are surface plasmon resonance (SPR) aptasensors, colorimetric aptasensors, chemiluminescence (CL) aptasensors, fluorescence aptasensors, surface-enhanced Raman scattering (SERS) aptasensors, and interferometry aptasensors.", "FUNDING Bai, C., Lu, Z., Jiang, H., Yang, Z., Liu, X., Ding, H., et al. (2018 ", "XZ, JW, JG, and LS conceived the work and discussed the content. XZ drafted the manuscript. JW, JG, and LS were responsible for revising it. LM critically reviewed, edited, and finalized the manuscript for submission.", "To mitigate HIV-associated cardiomyopathy, Lopes de Campos et al. (2014) employed an anti-gp120 aptamer UCLA1. By directly binding to HIV-1 and neutralizing the virus, the aptamer protected cardiomyocytes from apoptosis and indirectly prevented infection of monocyte-derived macrophages. Aptamers applied in antiviral therapy are summarized in Table 3 ." ] },{ "paper_id": "18f11e6900b1a76027c33f5e61ae9cb66d7d2370", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "18f3146e3ad376486f1ade8e5c89c086d434620a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Given the critical role played by EPAC in multiple pathologies, several EPAC-specific modulators have been screened to target EPAC proteins (vide infra). Despite their wide commercial availability and seemingly ubiquitous use in experimental studies, for several EPAC inhibitors, the molecular basis of their interactions with EPAC and the related mechanism of action are currently not fully understood, thus limiting further improvement on existing inhibitor design, lead optimization and EPAC-targeted drug development.", "EPAC regulates several critical cAMP-related signaling pathways, including cardiac calcium homeostasis, vascular remodeling, tissue homeostasis, regulation of smooth muscle contraction, insulin secretion from pancreatic \u03b2 cells, integrin-dependent cell adhesion, neuronal excitability and memory consolidation in the hippocampus [8, [18] [19] [20] [21] [22] [23] . Thus, EPAC inhibition has been recognized as a promising therapeutic route for a wide spectrum of diseases, including pancreatic cancer [24], breast cancer [25], cardiac hypertrophy [26], vascular inflammation [27], Alzheimer's disease [28], as well as infections, e.g., Coronavirus' [29] and malaria [30] . For further details about the physiological role of EPAC and subsequent disease implications, we refer to excellent reviews, which have been published in recent years [18, [31] [32] [33] .", "The existence of two ubiquitously expressed cAMP-dependent sensors, EPAC and PKA, necessitates the development of selective pharmacological interventions to modulate their discrete functions. Such EPAC vs. PKA selectivity was obtained for the first time through structure-based design, which led to the identification of a cAMP analog that functions as an activator for EPAC but not PKA [59] . However, in contrast to EPAC agonists, identifying EPAC selective antagonists has proven much more challenging, as cyclic nucleotide analogues often interfere with phosphodiesterase activities, which increases cellular cyclic nucleotide levels and counters the intended antagonistic effects." ] },{ "paper_id": "18f3b3f9f77227f4941079cdb605af4e5777c061", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "18fa3d1a5503e1943ce8e657416f9da8fe2cb475", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "cytoskeleton, calcium ion binding, the stress response, anti-oxidative stress, and macromolecular metabolism.", "A magnified comparison of eleven differentially expressed protein spots, representing ANXA1, HSPB1, MYLPF, TRIM27.2, EXFABP, ANXA5, PRDX1, TPM1, ENO1, ANXA2 and CALB, is shown in Figure 5 .", "the possible functional roles of some proteins identified during IBV infection in ovo.", "Avian infectious bronchitis (IB) is one of the most serious diseases of chickens. It is of economic importance in the poultry industry worldwide and is associated with respiratory disease, reduction in weight gain, poor egg production and quality, and decreased feed conversion efficiency. Its etiologic agent is the avian infectious bronchitis coronavirus (IBV), which is a Gamma coronavirus of the coronavirus genus and replicates primarily in the upper respiratory tract, kidney, and oviduct of chickens [1] [2] [3] .", "According to the UniProtKB and the Gene Ontology databases, the identified proteins could be classified into several functional categories, including cytoskeletal proteins, calcium ion-binding proteins, proteins related to macromolecule metabolism, anti-oxidative proteins, protein and nucleotide processing, the ubiquitin-proteasome pathway, immune response and antigen processing and presentation, response to stress, signal transduction, and metal ion binding. Detailed information about the PMF and MS/MS search results is listed in Additional file 1, Additional file 2, Additional file 3 and Additional file 4." ] },{ "paper_id": "18fb0cf6fba22d9478d4f5774f37f6b6bf09f3b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The intra-and interassay reproducibility were evaluated using three replicates of 10 6 , 10 4 , and 10 2 copies/ L plasmid standards of both pMD20-GD and pMD20-CH1a. Mean and coefficient of variation (CV) for the value were calculated. The results showed that neither the CVs of intra-assay nor the CVs of interassay were more than 5% (Table 2) , indicating the reproducibility of the two assays.", "Plasmid DNA. The conventional RT-PCR was performed by using the NSP2-F and NSP2-R primers described in Table 1 . 10 L reaction mixture contains 0.5 L cDNA, 5.0 L 2 \u00d7 PCR reaction mix, 0.4 L NSP2-F (10 M) primer, 0.4 L NSP2-R (10 M) primer, 0.1 L Taq DNA polymerase (2.5 U/ L), and 3.6 L H 2 O. The negative controls included the reagents without cDNA template. The reaction mixtures were performed at the amplification condition: 95 \u2218 C for 3 min, followed by 30 cycles of 94 \u2218 C for 30 s, 60 \u2218 C for 30 s, and 72 \u2218 C for 1 min, and a final extension step of 5 min at 72 \u2218 C. The PCR products were detected by 1.5% agarose gel electrophoresis in 1 \u00d7 TAE. Then the PCR products were cloned into the plasmid pMD20-T (TaKaRa) and propagated in competent Escherichia coli DH5 cells according to the manufacturer's instructions. Plasmid DNA was purified using the E.Z.N.A. Plasmid Mini Kit I (Omega) and quantified by measuring OD 260 using spectrophotometer ND-1000 (Wilmington, USA).", "531 serum samples showed that the TaqMan probe real-time PCR had the highest detection rate, whereas the conventional RT-PCR had the lowest detection rate. To evaluate comprehensively the practicality of this assay, clinical samples that span a broader geographical origin should be tested in the future." ] },{ "paper_id": "1904cb0e767c673c78ac5d6ebf6260c1d83bea13", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "High vaccination rates have helped to prevent many infectious diseases and resulted in less sickness and millions of lives saved (reviewed by Rappuoli et al.) [38] . Among the greatest success stories are the eradication of smallpox virus, rinderpest, and the polio eradication program, where poliovirus type 2 was already eradicated in 1999 [39] [40] [41] .", "The overall aim of this study is to generate data that will facilitate decision making on which substrate may be the best for the production of novel vaccine strains. As a first step for this, we investigated whether poliovirus, as a representative of the Picornaviridae family of viruses, can be propagated in the human suspension cell lines.", ", or K562 with a Low MOI. For vaccine production purposes it is important that, after infection of cells with a low MOI, a high viral yield in the culture medium can be achieved." ] },{ "paper_id": "190505ad74408b21fea8434a44a2f43b1ef198b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the commercially available reagents and solvents were used without further purification. 1,2-Diaza-1,3-diene (DD, 13) was synthesized as a mixture of E/Z isomers as previously reported [27] [28] [29] . Column chromatography was performed with Merck silica gel 230-400 mesh ASTM or with a B\u00fcchi Sepacor chromatography module (a prepacked cartridge system). TLC analysis was performed on pre-loaded (0.25 mm) glass-supported silica gel plates (Kieselgel 60); compounds were visualized by exposure to UV light and by dipping the plates in 1% Ce(SO 4 )\u00b74H 2 O, 2.5% (NH 4 ) 6 Mo 7 O 24 \u00b74H 2 O in 10% sulfuric acid followed by heating on a hot plate. 1 H-NMR and 13 C-NMR spectra were recorded in DMSO-d 6 or CDCl 3 solution on 200 (Bruker AC) or 400 (Varian Mercury) MHz instruments. Proton and carbon spectra were referenced internally to solvent signals, using values of \u03b4 = 2.49 ppm for proton (middle peak) and \u03b4 = 39.50 ppm for carbon (middle peak) in DMSO-d 6 and \u03b4 = 7.26 ppm for proton and \u03b4 = 77.00 ppm for carbon (middle peak) in CDCl 3 . The following abbreviations are used to describe peak patterns where appropriate: s = singlet, d = doublet, t = triplet q = quartet and m = multiplet. All coupling constants (J) are given in Hz. All melting points were taken on a B\u00fcchi-Tottoli capillary apparatus and are uncorrected; IR spectra were determined in bromoform or nujol with a Jasco FT/IR 5300 spectrophotometer. Mass spectra were recorded in the EI mode (70eV) on a Shimadzu GC-MS QP5050A spectrometer. Elemental analyses (C, H, N) were within \u00b10.4% of the theoretical values.", "3.1.1.1. General Procedure for the Preparation of 1,3-bis(Indol-3-yl)propane-1,3-diones 12a-e A solution of malonyl dichloride (1 mL, 10 mmol) in DCM (10 mL) was added dropwise to a cold solution of the appropriate N-methylindole 11a-e (20 mmol) in DCM (20 mL). The reaction mixture was stirred for 2 h at room temperature. The mixture was then added to 5% aqueous sodium carbonate and shaken for 2 min. This was extracted with DCM, dried and evaporated. The residue was purified by chromatography eluting with DCM/Ethyl acetate 9/1 to give derivatives 12a-e. Analytical and spectroscopic data are reported elsewhere [12] .", "To a solution of the appropriate 1,3-bis(indol-3-yl)propane-1,3-dione 12a-e (1.0 mmol) in THF (5 mL), 1,2-diaza-1,3-diene (DD, 13) as a mixture of E/Z isomers (1.0 mmol) and CuCl 2 \u00b72H 2 O (0.5 mmol) were added. The reaction was stirred under magnetic stirring at room temperature for 12 h, until the disappearance of the DD (as monitored by TLC). The crude mixture was concentrated under reduced pressure and the products 10a-e were purified by column chromatography on silica gel (eluent: ethyl acetate/cyclohexane = 1:1). " ] },{ "paper_id": "190bc9d8aadbfb5c848ccdb9f4fa98610780ba56", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Saikosaponin-d (Ssd) is one of the major triterpenoid saponins derived from Bupleurum falcatum L. (Umbelliferae), which is commonly prescribed for inflammatory and infectious diseases by Chinese and Japanese medical doctors, while its active component Ssd was reported to have immunemodulatory, anti-inflammatory, antibacterial, antiviral, and anticancer activities [18] . Recently, we have identified that saikosaponin-d (Ssd) could exhibit antiproliferative effect on the activated T lymphocyte via suppression of NF-B, NF-AT, and AP-1 signaling [19] .", "where = 0 is the area of wound measured immediately after scratching, and = end-point is the area of wound measured 16 or 24 h after scratching.", "Analysis. The data are expressed as means \u00b1 SD as indicated. The difference was considered statistically significant when the value was less than 0.05. Student'stest or one-way ANOVA analysis was used for comparison among different groups." ] },{ "paper_id": "191480bd880b13cbec0b421f7689e7d3f0fdc120", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DLSP current activities take place in three KEMRI laboratories, one in Kisumu and two in Nairobi (Fig. 1) . The KEMRI Kisumu facility houses zoonotic, biological safety level 3 (BSL3), respiratory and enteric laboratories. The Nairobi KEMRI facility has a BSL3 laboratory where Taqman Array Card (TAC), Next Generation Sequencing (NGS) and cell culture are performed. The KEMRI Kisumu and Nairobi laboratories also include HIV, malaria and TB laboratories. A third satellite microbiology laboratory is located in Kibera, an informal urban settlement in Nairobi. This microbiology laboratory supports population-based surveillance at the Tabitha Clinic, operated jointly with Carolina for Kibera, a non-governmental organization (NGO) providing health and other services for the people of Kibera.", "Lastly, DLSP provides laboratory capacity by mentoring interns and sponsoring training courses in coordination with pathogen specific subject matter experts from CDC. Over the last decade DLSP trained technical staff from Kenya and neighboring countries in PCR, ELISA and microbiology diagnostic techniques to detect multiple pathogens (Fig. 2 ). In addition, 6-10 interns from various local universities are accepted annually to train from 6 months to 1 year. These students then move on to other local or regional institutes to continue their careers as scientists and strengthen this capacity in Kenya and beyond.", "Other zoonotic studies that DLSP has supported include those on brucellosis in humans and animals and risk factors for brucellosis transmission such as ingestion of raw milk, exposure to goats, and handling of animal hides, as well as the risk of transmission of other enteric pathogens from animals to humans [17, 18] . DLSP has also evaluated serologic evidence of human exposure to Bacillus anthracis, Brucella spp., spotted fever group rickettsioses, and typhus group rickettsioses from persons aged 15-64 years and determined a high seropositivity suggesting frequent exposure to these pathogens in the Kenyan population. These studies allowed a recent prioritization of zoonotic diseases of public health importance in Kenya [19, 20] .", "In recent years as part of GHSA, DLSP through NPHLS, has transferred laboratory capacity country-wide to various tier level laboratories in strategic locations informed by our GHSA-sponsored laboratory mapping project and through expansion of surveillance for AMR, respiratory disease and AFI, to ultimately provide a network of decentralized laboratories and high quality reference laboratories prepared to respond rapidly to and prevent nascent public health events and threats to Kenya and worldwide. This capacity was recently recognized by the newly established African Centers of Disease Control which has designated Kenya as a regional collaborating center, to support disease prevention and outbreak response throughout the region." ] },{ "paper_id": "1926a717f92225eb7539c0fe190cefe1b067f08e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rice (Oryza sativa L. cv. Nipponbare) seeds were used throughout the experiments. After the disinfection with 0.1 % HgCl 2 for 1 h and thorough washing with RO (reverse-osmosis) water, seeds were soaked overnight in RO water and incubation at 25\u00b0C for 1 day. Seedlings were then grown on plastic chambers using Kimura B nutrient solution [48] , with a 14/10 h (day/night) regimes at 28 \u00b1 1\u00b0C.", "Using the RSV CP, SP gene and RBSDV P5-1, P9-1 gene, the dynamics of viral infection in rice plants was measured by reverse-transcription real-time PCR. The primer and products were shown in Table 2 .", "In our experimental conditions, geNorm analysis showed that GAPDH and UBQ 10 were ranked as the " ] },{ "paper_id": "192e7d37cf521798de0394c2ad593f2bb77f5a77", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data collection was done by using a questionnaire including 3 parts:", "Keywords: obvious anxiety\u201a hidden anxiety\u201a nursing\u201a anesthesia technician\u201a operating room technician Individuals, employed as health care workers including; physicians and nurses, are exposed to anxiety for www.ccsenet.org/gjhs" ] },{ "paper_id": "193361dba84bf8c443b6ebd5ead3b3eb54d49379", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 13 tissues samples including skin, muscle, fat, heart, liver, spleen, kidney, lung, dudens, jejunum, ileum, cecum, rectum from 5 healthy swines (Crossbred: Duroc \u00d7 Landrace \u00d7 Yorkshire) were collected, washed three times in phosphate buffered saline (PBS, pH 7.2) and immediately snap-frozen in liquid nitrogen before being stored at -80 \u2022 C for further use.", "Using this sequence, a pair of primers (F: 5'-ACTGTCGACAT GAACTGCGCTTCCCAGCCCTTC-3'; R:", "All results are presented as the mean \u00b1 standard deviation. SPSS (Statistical Package for the Social Sciences) statistical software (version 13.0) was used to analyze data (IBM SPSS Inc., Armonk, NY, USA). One-way analysis of variance (ANOVA) was employed to analyze the differences among groups. P-values less than 0.05 were taken to indicate statistically significant differences." ] },{ "paper_id": "194e09560f46554663015f54423f7f5d7822025b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For example, optical images in Figure 1a law gives the time-dependent concentration profile as a function of the distance from the absorbing wall [9] :", "Here, the drag force (F Drag ) results from the relative motion of a spherical particle under a fluid flow in a solution:", "Re \u2202u \u2202t" ] },{ "paper_id": "1951545d70e8568083cde219d2583c1aae0c4061", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The breadth and depth of arbovirus surveillance differs regionally, and several areas lack surveillance altogether. There is also a lack of interdisciplinary expertise on arbovirus diseases and understanding their vectors, and epidemiology. In addition, only a small number of arboviral diseases can be prevented using vaccines or specific antiviral drugs, and there are few validated diagnostic reagents, with which to monitor disease progress and control. Until such disease control reagents become available, the most effective alternative is to focus on practical procedures to reduce risks of exposure to arthropods.", "More than 100 species of arbovirus that cause human/animal or zoonotic diseases have been identified. 12 Four virus families, Togaviridae, Flaviviridae, Bunyaviridae and Reoviridae, contain most of the arboviruses that cause human/animal diseases. 12 Arbovirus infections are not always clinically obvious and often resolve spontaneously after 1-2 weeks. However, some arboviral infections result in high fever, hemorrhage, meningitis, encephalitis, other serious clinical symptoms, and even death. Therefore, they cause a large social and economic burden. A summary listing the arboviruses associated with human diseases and their geographic distributions was published previously. 21 ", "Arboviruses are transmitted between arthropods (mosquitoes, ticks, sandflies, midges, bugs\u2026) and vertebrates during the life cycle of the virus. 8 Many arboviruses are zoonotic, i.e., transmissible from animals to humans. [9] [10] As far as we are aware, there are no confirmed examples of anthroponosis, i.e., transmission of arboviruses from humans to animals. 9-10 The term arbovirus is not a taxonomic indicator; it describes their requirement for a vector in their transmission cycle. [11] [12] Humans and animals infected by arboviruses, may suffer diseases ranging from sub-clinical or mild through febrile to encephalitic or hemorrhagic with a significant proportion of fatalities. In contrast, arthropods infected by arboviruses do not show detectable signs of sickness, even though the virus may remain in the arthropod for life. As of 1992, 535 species belonging to 14 virus families were registered in the International Catalogue of Arboviruses. 12 However, this estimate is continuously increasing as advances in virus isolation procedures and sequencing methods impact on virus studies. Whilst many current arboviruses do not appear to be human or animal pathogens, this large number of widely different and highly adaptable arboviruses provides an immense resource for the emergence of new pathogens in the future." ] },{ "paper_id": "1952a38871ef31c0e837ff0ee666bd0350c8b32c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Injuries caused by used needles, scalpels or knives are coded as needlestick injuries (NSIs).", "Introduction: Healthcare workers (HCW) are exposed to infectious agents. Disease surveillance is therefore needed in order to foster prevention." ] },{ "paper_id": "1968f8d8ffe3f695372d919c9966b1ca412b83d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "EGTA, DTT, 5-aza-CdR, NS-398, and antibody against Flag were purchased from Sigma (St. Louis, MO). Antibody against COX-2 was from Cayman (Ann Arbor, MI, USA). Antibodies specific for \u03b2-actin, C/EBP\u03b2, GFP, and DNMT1 were purchased from Santa Cruz (Santa Cruz, CA, USA). Antibodies against DNMT3A and DNMT3B were purchased from Cell Signaling Technology (Beverly, MA, USA).", "Wild-type C/EBP: 5'-GCTTACGCAATTTTTT-TAAGG-3';" ] },{ "paper_id": "196d55353760e8e1ddbc2e2cce92f806351b747c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed by using the GraphPad Prism 5.0 software (GraphPad Software Inc. USA). Data were represented as Mean \u00b1 SEM. The comparison between the groups was performed by either one-or two-way ANOVA with Tukey or Bonferroni post-hoc test, respectively. Data presented here were representative of at least three independent experiments. p < 0.05 was considered as statistically significant difference between the groups.", "Taken together, the current data depict that CHIKV may induce p-c-jun via JNK pathway whereas induction of p-IRF-3 might be dependent on both p38 and JNK MAPKs." ] },{ "paper_id": "196eaa0045b36b7c0e56594ad4fbec1e8edd3e9c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "19717b7bfa9911835e3c0085633f6dec5453da9a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This model has been previously studied and applied to problems ranging from population dynamics to astronomy [18, 19, 21] . In particular, the expected final epidemic size for this model is [18] :", "and the distribution of extinction times, from which the probability density of the duration of outbreaks is obtained as the derivative with respect to time,", "where" ] },{ "paper_id": "19744eafb1b8520fa460274845713451ad539e91", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Similar sequences or common structural/functional motifs are located collinearly in the carboxyl terminal glycoprotein of Sandfly fever virus and Sindbis virus envelope glycoprotein E1.", ":", ". . ." ] },{ "paper_id": "197489ce2e74e5566e1cd13fdce4a26b4eba45f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MDCK, A549 and HEK-293T cells were purchased from the Cell Center, Institute of Basic Medical Sciences, Peking Union Medical College (Beijing, China) and cultivated in DMEM supplemented with 10% foetal bovine serum and 1% penicillin/streptomycin (all from Gibco).", "Animals. ICR mice (13-15 g) and Balb/c mice (18-22 g) were obtained from Vital River Laboratory Animal Technology Co., Ltd. in Beijing, China, and acclimated with standard feed and water in the following conditions (temperature: 20 \u00b1 2\u00b0C, humidity: 50 \u00b1 10%). All experiments were performed in compliance with the rules of the European Community Guidelines for the care and use of animals. The study was approved by the Ethics Committee at Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences.", "Disease Control and Prevention, Chinese Center for Disease Control and Prevention. The virus stock was prepared by infecting 10-day-old specific-pathogen-free embryonated chicken eggs (Merial Vital Laboratory Animal Technology Co., Ltd, Beijing, China) for 48 h at 35\u00b0C. The virus titre (expressed as 50% tissue culture infective dose, TCID 50 ) was calculated to be 10 \u22124.5 in the MDCK cells by the Reed-Muench method 64 ." ] },{ "paper_id": "19758fc382a2921a000c9d85a33300d3e3b0e2b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(forward), 5\u2032-TCGTCCAGGTCGTCGTCATCC-3\u2032 (reverse).", "All results are expressed as the means and standard deviations (SD). Statistical analyses were performed using Prism 5.01 (GraphPad Software). Significance was determined by two-way ANOVA followed by Tukey's multiple comparisons test." ] },{ "paper_id": "197679559a6aa8d3f30bde60d9387f1f9f975c0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Respiratory infections requiring hospital admission in surveillance centres in Bogot\u00e1, Colombia.", "In the group with more than one viral infection ( ", "A microarray diagnostic assay using CLART 1 PneumoVir equipment by Genomica (Madrid, Spain) was used to identify the viruses involved [6] . This assay detects and characterises viruses that most frequently cause respiratory symptoms in humans. The following viruses were analysed: Respiratory Syncytial Virus (RSV) A and B, Influenza A (H1N1, H3N2, 2009 A/H1N1 pdm), B and C virus, Parainfluenza virus subtypes 1, 2, 3, 4A and 4B, Metapneumovirus A and B, Adenovirus, Enterovirus, Rhinovirus, Coronavirus subtype 229E and Bocavirus. This kit amplifies specific fragments of the viral genome via a reverse transcription polymerase chain reaction (PCR) or via a PCR with hybridisation detection using specific capture probes [7] .", "At least one virus was identified in 63 patients (Table 3) . Influenza virus was the most common and was isolated in 28 patients (30.8%), of whom 21 (75%) had Influenza A and 7 (25%) had Influenza B (Table 3) . Of the Parainfluenza virus subtypes identified, five cases were PIV 3, and one case was PIV 1." ] },{ "paper_id": "198399348c2c6a7dafb438b3aaba23b43733b105", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For all multivariable models, putative risk factors with P < 0.20 in univariable analyses were entered forward stepwise and retained in models if P < 0.05. Correlated variables were not included in the same model but deviance measures were used to evaluate changes in model fit to the data with each parameter independently. In all models, variables with < 3 categories were evaluated for difference in magnitude, direction, and significance of effect between categories using the likelihood ratio statistic and similar categories were collapsed. Overall model fit was evaluated using Hosmer-Lemeshow goodness-of-fit test and measures of information criteria. Incidence rate and odds ratios were estimated with 95% confidence intervals. Univariable and multivariable statistical analyses were conducted using STATA 13.1 SE (College Station, TX, USA)." ] },{ "paper_id": "1986b0795d747225509369644cec05194d09a43c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2. Lysosome perturbants: bafilomycin A1 to inhibit the V-ATPase proton pump; chloroquine as a lysosomotropic alkalizing agent.", "The following five groups of compounds were tested:", "3. Cytoskeleton perturbants: nocodazole to depolymerize microtubules; latrunculin A to block actin polymerization; jasplakinolide to induce actin polymerization." ] },{ "paper_id": "1986e96f2be6bd012fcd4d0b731caf62c7a4dea2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Widely conserved pathways influenced by viroporin ion conductivity, and others that seem to be species-specific are now described and graphically summarized to facilitate their overview ( Figure 3 ).", "Taking into consideration the relevance of IC activity in viral production, and its direct effect in pathology and disease, ion conductivity and its pathological stimulated pathways can represent targets for combined therapeutic interventions.", "Taking into consideration the fast selection of drug-resistant viruses under drug pressure, the simultaneous inhibition of IC activity, and other signaling pathways stimulated by ion conductivity leading to pathology, may represent a better treatment option. Interfering with these pathological pathways constitutes a valuable approach, with the advantage that it is independent of the appearance of drug resistant viruses. Targeting exacerbated inflammatory responses, such as those triggered by IC activity leading to inflammasome activation in various respiratory infections, may reduce disease worsening and progression [23] . Novel specific inhibitors of NLRP3 inflammasome showing promising results for inflammatory diseases could be applied for these purposes [119] .", "Besides modifying cellular processes to favor virus propagation, the loss of ion homeostasis triggered by viral IC activity may have deleterious consequences for the cell, from stress responses to apoptosis [2, 14, 15] . That is why cells have evolved mechanisms to sense the ion imbalances caused by infections and elaborate immune responses to counteract viruses. Interestingly, the IC activity of several viroporins triggers the activation of a macromolecular complex called the inflammasome, key in the stimulation of innate immunity [16] [17] [18] [19] [20] [21] . Inflammasomes control pathways essential in the resolution of viral infections. However, its disproportionate stimulation can lead to disease. In fact, disease worsening in several respiratory viruses infections is associated with inflammasome-driven immunopathology [22, 23] ." ] },{ "paper_id": "198bdc284caeafc6bbff6f925f36eec10d3d033c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "for DIP entry with subsequent DIP replication in case of a co-infection.", "All datasets generated for this study are included in the manuscript/Supplementary Files.", "Cells total = T + I s + I d + I c" ] },{ "paper_id": "198ed53d956a2707716d175cc6516bb720f52d82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An instance of a class that contains unique properties" ] },{ "paper_id": "19a804b052b806f48b58c353d70c4bda178ad87f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The nucleotide sequences were first aligned in MAFFT v7.013 42 with published MERS-CoV sequences retrieved from GenBank. Phylogenetic trees were then inferred using the maximum likelihood method available PhyML version 3.0 43 assuming a general time-reversible model with a discrete gamma distributed rate variation among sites (Gamma 4 ) and a SPR tree swapping algorithm and visualized using MEGA version 6. 44", "The number of base differences per lineage and within lineage from averaging overall sequence pairs between groups were determined in MEGA6. The analysis involved 254 nucleotide sequences. Codon positions included were 1st+2nd+3rd+Noncoding. All positions containing gaps and missing data were eliminated. There were a total of 25 193 positions in the final data set. Evolutionary analyses were conducted in MEGA6. 44 ", "Next-generation sequencing data were analyzed using a custom workflow in CLC Genomics Workbench 8.5. Sequencing adapters were trimmed, then 26 bp were trimmed from each end to remove any residual PCR primer sequence. Remaining reads were trimmed from the 3\u2032-end using a CLC cumulative quality score of 0.05. Trimmed reads were aligned to a reference, either Jordan-N3/2012 (KC776174.1) or AbuDhabi_UAE_8 (KP209306.1). Consensus sequence was called based on regions that had 10 \u00d7 or greater coverage. Variants were called using the CLC consensus caller with cutoff values of 5, 10, 15 and 35%, with a minimum count of five reads. Further analysis of these sequences was performed with custom scripts written in-house at the CDC." ] },{ "paper_id": "19b9ee3dcd89f01eea3e48b333888b1ce70b296f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Second, there is a unique RNA replication mechanism using the TRS motif that is known as the ''copy choice'' mechanism, which induces homologous RNA recombination in CoVs [3] , [6] . Third, CoV possesses the largest genome (26-32 kb) among RNA viruses. Furthermore, heterologous recombination that Betacoronavirus subgroup A has the hemagglutinin esterase gene originated from influenza C virus [7] , [8] . These mutation and/or recombination events change viral properties, host range and pathogenicity.", "All animal procedures were conducted according to the Yamaguchi University Animal Care and Use guidelines and were approved by the Institutional Animal Care and Use Committee of Yamaguchi University. All efforts were made to minimize pain and suffering.", "CoVs frequently undergo mutation and recombination, and there are three reasons for this [4] . First, CoV RdRp has low fidelity. Although CoV encodes nsp14, which possesses 39R59 exonuclease activity for proofreading, the mutation rate approaches 2.0610 26 mutations per site per round of replication [5] ." ] },{ "paper_id": "19babdefd145a5becbc2a0b189eabdafa697de75", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As the human population expands and societal changes occur, human contact with wildlife will continue to increase. This increases the risk that emerging zoonotic viruses, including CoVs, pose to human and animal health. Surveillance combined with scientific studies to better understand zoonotic CoVs and spillover will enable us to stay a step ahead of the next epidemic. ", "Ecological and epidemiological studies to identify landscape changes and human practices that could enable a coronavirus to spillover from bats are also necessary [103] . Such studies enabled researchers to decipher the transmission cycle of Nipah virus in Malaysia and Bangladesh, which led to public health policies to change farming practices to control the spillover of Nipah virus from bats [104] [105] [106] .", "Coronavirus accessory proteins are dispensable for replication but they play an important role in pathogenesis and virus fitness under the natural environment of a host [13, 91] . Multiple studies with PEDV, SARS-and MERS-CoVs have identified accessory proteins that can effectively inhibit an IFN response in mammalian cells [12] [13] [14] [91] [92] [93] [94] [95] . However, to date, there have been no published studies looking at the role of these accessory proteins in modulating antiviral responses in bat cells." ] },{ "paper_id": "19bbeefa3a126f32fe8339a1fb11e3d9a1c7881c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Citation: Warren CJ, Sawyer SL (2019) How host genetics dictates successful viral zoonosis. PLoS Biol 17(4): e3000217. https://doi.", "nature, there are just too many protein-protein interactions to master by chance in a random encounter with humans.", "in a remote part of the world with low population density, then the virus may falter very quickly." ] },{ "paper_id": "19d93173c328e9ca42bd4238ccb39aa8da818422", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data underwent a quality assurance process and outlying or inconsistent data points were verified with the contributing investigators. All data were assessed for normality, with subsequent analyses performed using t-tests, non-parametric equivalents or analysis of variance." ] },{ "paper_id": "19dcbc62263225d430f506aa5745d23a66543de8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Preparation of monocyte-derived DC and treatment with recombinant gp120 treatment (gp120-DC)", "Table S1 Viral RNA copy numbers in the sera of HIV-1 infected individuals used for this study. Patient viral RNA copy numbers were retrieved from archived information. The following individual or pooled patient (#) samples were used to obtain the data shown in the respective figures: Figures ", "HIV-1 envelope protein gp120 binds to CD4 and chemokine receptors CCR5 or CXCR4 which are expressed by dendritic cells (DC) and which facilitate viral entry into the cells [1] . HIV-1 gp120 is also readily shed from the maturing virions [2] and forms immune complexes in the plasma of HIV-infected [HIV(+)] individuals [3, 4] ; consequently only a tiny portion (,0.1%) of circulating virions are actually infectious [5, 6] . HIV-1 gp120 additionally binds to DC-specific ICAM-grabbing non-integrin (DC-SIGN), initiating an intracellular signalling cascade that promotes viral infection and dissemination to T cells [7, 8] . A subset of CD14(+)DC-SIGN(+) DC has been identified in blood, which can bind HIV-1 and to transmit infectious virus to T cells [9] . The virus then actively replicates in activated CD4 T cells, which are chronically induced during HIV infection by various mechanisms [10, 11] ." ] },{ "paper_id": "19ddf65d65d5e172ac3ceda4662b68769633dbe6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ", for i = 1, . . . , K ,", ", for i, j = 1, . . . , K .", "where" ] },{ "paper_id": "19df6a2ae9a9070dd15404465eed98ad222b27f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The protease activity of cathepsins L, B and S in cells with or without GILT induction was determined by a fluorescence-based assay with selective substrate peptide conjugated with AFC according to the manufacturer's protocol (Bio-Vision Mountain View, CA, USA) as described previously [18] .", "In recent decades, cross-species transmission of numerous zoonotic viruses causes severe diseases in infected individuals and poses formidable threats to public health globally [1] [2] [3] . For example, outbreak of severe acute respiratory syndrome (SARS) in 2002/ 2003, caused by SARS coronavirus (SARS-CoV) transmitted from wildlife animal reservoirs, was associated with 774 deaths in 8096 infected individuals [4] . Ebola virus (EBOV) and Lassa virus (LASV) that cause Ebola disease and Lassa fever diseases, which are characterized with severe haemorrhagic fever, multi-organ failure, and high mortality rate, are currently circulating in West Africa and remain to be big challenges to medical community [5, 6] .", "All experiments were repeated at least three times with similar results achieved. For most figures, representative data or images were shown. Differences between control sample and tests were statistically analysed using oneway analysis of variance (ANOVA) with a Bonferroni adjustment for multiple comparisons. p-values less than 0.05 were considered statistically significant." ] },{ "paper_id": "19e45f3e51ee8f9151f7f3e901b2a579366abfd0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The current outbreak of ZIKV shows new modes of transmission with mother-to-fetus transmission and sexual transmission. Furthermore, infectious ZIKV has been detected in breast milk, and there are concerns of ZIKV transmission by blood products obtained from asymptomatic viremic persons or by organ transplantation.", "Given the time needed to develop and approve new antiviral drugs, clinicians are currently left empty handed in terms of targeted antiviral treatment for ZIKV infection. A major lesson from this outbreak and previous (re-)emerging RNA virus outbreaks is that we need safe, broad spectrum antiviral drugs that can be tested rapidly in phase III clinical trials during outbreaks to gain the time needed for the development of other control and prevention measures, particularly vaccines. " ] },{ "paper_id": "19e9c8796df362aa81ecfabf7730cfa4df5e5be6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethical approval for all of the capturing and sampling were confirmed by the competent authorities in the respective Federal Republic of Germany and Czech Republic. The Czech Academy of Sciences Ethics Committee reviewed and approved the animal use protocol No. 169/2011 in compliance with Law No. 312/ ", "A single M. myotis male was captured in Sloupsko-Sosuvske caves of the Moravian Karst (Czech Republic, coordinates 49u 249 40.880 and 16u 449 20.540). The bat was kept to minimize stress and handling between capture and euthanasia in a clean plastic box with soft mesh to enable roosting under temperature of hibernation torpor of 6uC and transferred to our laboratory at Veterinary and Pharmaceutical Sciences Brno (Czech Republic) within a day. It was anesthetized to insensitiveness using isofluranum (Isofluran, Piramal Healthcare, UK), and then transcription PCR (RT-PCR) using SV40T specific primers [35] . The protein expression was controlled by the immunofluorescence and western blot as described below. Briefly, cells were first fixed with 3% paraformaldehyde and permeabilized with 0.5% triton X. After washing with PBS, cells were stained with mouse anti-SV40T monoclonal antibody (Santa Cruz Biotechnology) and goat anti-mouse IgG Alexa Fluor (Invitrogen) as second antibody and visualized by fluorescence microscope. For western blot, the same mouse antibody was used as primary antibody and bound antibody was detected with goat anti-mouse IgG peroxidase (Sigma). Images were developed using the ECL kit (Thermo Scientific Pierce) according to the manufacturer's instructions.", "All data were presented as means 6 S.D. Statistical significant differences were analysed by one-way ANOVA using the SPSS software package. " ] },{ "paper_id": "19ebb3ea64083a71dcf7b9c2cd53bc49ec1a90ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "19eed2e91c17ea20e9cbda665e19fad13a948ecf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at www.mdpi.com/1999-4915/9/12/365/s1.", "The following plasmids were used: CD147 pLKO.1 lentiviral shRNA (A6) and non-target shRNA control plasmid (pLKO.1-NTC) were purchased from Open Biosystems (GE Healthcare, Little Chalfont, UK).", "CD147 " ] },{ "paper_id": "19f5eb39de2aef11b4e3b8c0fa4b92f048057d83", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1.", "The results indicate that cross ventilation by outdoor wind in central corridor inpatient ward could cause dispersion of infectious aerosols to indoor through airflow.", "Precautions are essential for every mode of unknown or known infectious diseases, especially in their early stages of outbreak. For example, the MERS-confirmed and MERS-suspected patients were quarantined in the negative pressure isolation wards that were primarily intended for airborne infection patients. The findings in this study can be used in initial epidemiological investigations and precautions, with respect to outbreaks of MERS or similar unknown infectious diseases." ] },{ "paper_id": "19ff77e874c0706f794908e9b6878314671d385a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1a0304e5340ef8d016dd2f73d730072c2559acbb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protocols for animal experiments were approved by the Animal Experiment Committee of Nagoya University (The approval number: 13122).", "Cxcl2, Mm00436450_m1; Ccl2, Mm00411241_m1;" ] },{ "paper_id": "1a07962f8472f03e5159e01b742cf39295db17f5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The operating conditions of the mass spectrometer were dry gas temperature, 350\u00b0C, flow rate, 50 L/min; nebulizer pressure, 30 psi; sheath gas temperature, 250\u00b0C, flow rate, 10 L/min; fragmenter voltage, 100 V; capillary voltage, 3,500 V; mass range, 50 -1,100 D.", "All datasets generated for this study are included in the article/ Supplementary Material.", "statistical Analysis" ] },{ "paper_id": "1a12f8004e57cbdc497edada74fdfd8431f4a9eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: During respiratory viral infections host injury occurs due in part to inappropriate host responses. In this study we sought to uncover the host transcriptional responses underlying differences between high-and lowpathogenic infections.", "We assembled a compendium of microarray data from 12 studies that measured host transcription in mouse lungs following infection with respiratory viruses ( Table 1) . Six of these studies contained experiments where 100% of the animals succumbed to infection; these involved influenza A subtype H5N1 (\"avian influenza\"), reconstructed 1918 influenza A, or SARS-CoV strain icHC/SZ/61/03 (Table 1) . After merging technical replicates the compendium comprised 733 individual transcriptome measurements with similar numbers of arrays associated with LPIs, MPIs, and HPIs ( Figure 1 ). Data were quality-controlled, further pre-processed, and converted to genelevel data.", "Additional file 4: Table S2 . Digital signature genes by modulemapping." ] },{ "paper_id": "1a19bed3bfcb373626804c55b111ca79e812efd1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The animal experiments in this study were approved by the Animal Ethics Committee (ACE) of the College of Life Sciences, Sichuan University (license: SYXK-Chuan-2013-185). All experiment procedures and animal welfare standards strictly followed the guidelines of Animal Management at Sichuan University.", "Purified VLPs were analyzed by SDS-PAGE, and three distinct protein bands were observed: An about 90 kDa band corresponded to rS, a 60 kDa band corresponded to rF, and a 25-35 kDa band corresponded to M (Figure 2A) .", "All the qPCRs were carried out quadruplicately." ] },{ "paper_id": "1a19e1b8f4e8c0fe67b2cab9eef2c95cfc44f5ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In 2014 the World", "of the limitations of these assessment systems and the flaws in biosecurity regimes and pandemic triage systems built on such entanglements of knowledge and practice.", "De Cock, a former director of the WHO's Department of HIV/AIDS and an expert on neglected tropical diseases with more than thirty years experience in the field, believes it was the evacuation of the American missionaries to Emory Hospital, coupled with the presentation in late September of a Liberian national infected with Ebola at Dallas Presbyterian Hospital, Texas, that finally shifted global perceptions of Ebola as 'some kind of obscure virus that you read about from time to time. . . [to being] an issue for global health security'. 100 292" ] },{ "paper_id": "1a29f97fc037ea6456b41d054e5603fbd4f76e94", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 " ] },{ "paper_id": "1a2c3991a18171055b98f12c29a2c1f5d5fef1bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A gene pool of bat SARS-related coronaviruses PLOS Pathogens | https://doi.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "1a383f04a8ddfeba2113f27e82c41d0582feb276", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "EI is a highly contagious virus and outbreaks of influenza may necessitate the cancellation of race meetings and other equestrian events [2] . However, in 1981, mandatory vaccination against EI was introduced for Thoroughbred racehorsesin Ireland and since then, no race meetings have been cancelled due to EI. However, outbreaks continue to occur in vaccinated horses, and young racehorses are particularly susceptible [3] [4] [5] . The return to athletic normality can be prolonged by damage to the mucociliary clearance mechanism and secondary bacterial infections [6] .", "A Chi-squared test was used to test the association of seroconversion with subsequent failure to race. The data was summarised in 2 \u00d7 2 contingency tables and an analysis was conducted in the R statistical software package version 3.5.1. The statistical significance was set at \u03b1 = 0.05.", "EHV-1 and -4 circulate in horse populations worldwide and are associated with respiratory disease in horses, immunosuppression, reduced performance, abortion and occasionally, neurological disease [7] [8] [9] . Although there is no mandatory vaccination programme for EHV-1 and -4 in Ireland, some trainers vaccinate their horses in an effort to reduce the virus challenge in their yards.", "There is a need for serological surveys to identify the viruses associated with economic loss in the racing industry. Longitudinal surveillance studies contribute to our understanding of the epidemiology of equine respiratory diseases in different countries and in different populations of horses. The aim of this serological study was to identify respiratory viruses circulating amongst elite racehorses of different ages in a training yard in Ireland and to determine their impact on health status and ability to race." ] },{ "paper_id": "1a465d982030d8f361dc914ff2defa359fdbe5f9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "demonstrated largely among camels and people in the Middle East 12 and travellers who visited the region could occasionally seed the virus to long-distance destinations in the Europe, Southeast Asia, and North America 9,13,14 .", "To detect putative recombinant regions in the MERS-CoV genome, we used the RDP4 program (v.4.39) 36 with a default (window size: 30 bp) and a higher window size of 1,000 bp, and the results obtained were confirmed by a manual bootscan method. Using the recombination breakpoints detected in the KOR002 strain by the default setting, we compiled new sequence datasets by dividing the complete genome sequences into five non-recombinant fragments. We subsequently reconstructed the phylogenetic relationships in each region using a maximum likelihood method (GTR+ I+ \u0393 , 500 bootstrap replication) implemented in MEGA5 37 . The trees were visualized using FigTree (v1.4.2)." ] },{ "paper_id": "1a485210a47a7eb2d39964a350d68ae52368c1df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Table S1 . Predicted genes of WIV19 and comparison to those of known adenoviruses. (DOCX 20 kb)", "Homologous recombination has been demonstrated to be an important evolutionary mechanism for AdVs, especially for HAdV-D members [20] . However, no signals of recombination were identified in the WIV19 genome, using RPD4 and SimPlot software [21, 22] .", "The potential host range of WIV19 was evaluated using cell infectivity assays. Seven cell lines were tested: A549 (human lung, ATCC CRM-CCL-185), HEK-293 T (human embryonic kidney, ATCC CRL-11268), NCI-H292 (human lung, ATCC CRL-1848), LLC-MK2 (Macaca mulatta kidney, ATCC CCL-7), MsIn (Miniopterus schreibersi intestine), RlKi (Rousettus leschenaulti kidney), and RsKi (Rhinolophus sinicus kidney) [24] . Cytopathic effects were observed in LLC-MK2, RsKi, and all three human cell lines, indicating that WIV19 has a wide host range." ] },{ "paper_id": "1a485fe46f5c18e940782aa60bb756d6ae2a6c0b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1a52cac849bdb5840d115cf513ec8cc63dc2d56c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pone.0186034.g002", "https://doi.org/10.1371/journal.pone.0186034.t003" ] },{ "paper_id": "1a5bdcd1c259d4b40800f9e96219641aafd5f6b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses are enveloped, plus-stranded RNA viruses that cause widespread disease in humans and animals. They tend to infect just one or a few closely related species and in their natural host exhibit marked tissue tropism. Often, the respiratory or gut epithelia are specifically targeted, causing localized infection, but disseminated infections leading to systemic disease are also seen. Together with toroviruses, arteriviruses and roniviruses, coronaviruses are members of the order Nidovirales .", "The species specificity of coronaviruses is, to a large extent, determined by the recognition of a functional receptor on the surface of the host cell (Kuo et al., 2000) ." ] },{ "paper_id": "1a5c7512b0e842a7b5f1d1511d0f035a0dbc3c25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RUNX1b plays a crucial role in development of myeloid and lymphoid lineage cells. It was originally identified at a break point on human chromosome 21 in the t(8;21) translocation. It is a most common target of chromosomal translocation in human leukaemias [16, 27] including acute myeloid leukaemia, B-cell acute lymphoblastic leukaemia and T-cell lymphoblastic leukaemia [28, 29] . Importantly, RUNX1b is involved in transcriptional regulation of several genes including cytokines and chemokines like IL2, IL3, GM-CSF, MIP-1a, CSFR etc. [19, 23, 30, 31, 32, 33, 34, 35] . It synergises with other transcription factors to activate transcription [36, 37, 38] and acts as a transcriptional activator or repressor depending upon its association with co-activators such as CBP, p300, MOZ [39, 40] and co-repressors, mSin3A [41] , TLE1 [42, 43] and NCoR [28] ." ] },{ "paper_id": "1a5f2c3f99d3607bf9170dcda0c54bc1b4400f6a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Implementation of analytical methods. All statistical and network analyses were implemented in the R computing environment 51 . Network analyses were implemented using the Network Analysis and Visualization (igraph) package 52 . Linear regression and descriptive statistics were calculated using base functions in R. Standard deviations and confidence intervals of proportions were calculated using the score interval approximation method 53 ." ] },{ "paper_id": "1a7751b196054ed357f5a0f16eeac17ad2def269", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animal studies were reviewed and approved by the ", "\"Contrat de Plan Etat-R\u00e9gion\" (CPER) grant named \"Infectio\"; and the \"Fondation pour la Recherche M\u00e9dicale\" (FRM, https://www.frm.org/). M.F. was supported by a PhD fellowship from the Government of Pakistan (Higher Education Commission). A.F. was supported by a PhD fellowship from the \"R\u00e9gion Bretagne\". M.S.E. was supported by a PhD fellowship from \"R\u00e9gion Bretagne\" and \"Minist\u00e8re de l'Enseignement Sup\u00e9rieur et de la Recherche\".", "Data were expressed as means \u00b1 SEM for all mice treated similarly. Mean differences between experimental groups were assessed using the non-parametric Mann-Whitney U-test. Statistical analysis for the in vitro experiments were performed using the unpaired Student's t-test. All statistical analysis was achieved with the GraphPad Prism5 software. Significance is shown as follows: *P < 0.05, **P < 0.01, ***P < 0.001." ] },{ "paper_id": "1a7d600387654c0315c076f74d8479adb4403d75", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest." ] },{ "paper_id": "1a8daad89d2701b4cf603e668f6aab1209b6237e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1a9fdd51745b132ee92107b4e9c68597d3767b7e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In 2002, the Uganda Ministry of Health piloted a new district level monitoring system in the southwestern highlands. Incoming clinical data from health centers are collated and entered onto a district level computer and compared with a baseline of historical illness data. An anomaly measure is used to provide the index of deviation, followed by electronic reporting. This simple system detected two malaria outbreaks in Kabale, in 2005 and 2006, more than two weeks before case numbers began to peak [20] .", "Syndromic surveillance often involves automated electronic reporting and statistical algorithms that sometimes require a complex information technology infrastructure. However, syndromic surveillance does not need to be highly computerized or technical; its tools can be simple, using few technological or human resources, and can complement existing surveillance programs [5] ." ] },{ "paper_id": "1aa091c222e1c37ab245b60ed6432ab597480149", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by the UW IRB (Study No. 00002488).", "Metadata such as the setting of care can potentially be gleaned from the type of microbiological organism sequenced. Pathogens of high public health importance-for which much high impact phylodynamic analysis has recently been performed-are likely to be tested for early in admission and may show higher correlations with admission date. For instance, both Ebola virus tests sent to our clinical laboratory in 2014 were sent the day of admission.", "The original identifiers obtained included name, medical record number, date of birth, sex, location of patient when the sample was collected, the classification of patient encounter (inpatient, outpatient, emergency room, or outside), sample collection date, patient admission date, patient discharge date, accession number, order code, order name, test code, test name, test result, and result time. All identifiers except sex, location, classification, admit date, discharge date, and collection date were expunged from the working dataset, although the original dataset was retained for chart review of select cases to ensure data validity.", "The degree of identifiability of a given patient or case can be fundamentally unknowable, especially when there exists a continuum of other metadata sources either on the Internet or in the community (Sweeney 2013) . Genomic sequences in NCBI's Genbank also frequently feature other sample collection information, like sex, age, and sampling hospital which can be combined with other information inherent in the sequence to reduce the statistical obscurity of these data by a very large degree. Different organisms, from Ebola virus and Pandoraea apista to human herpesvirus 2, may have different degrees of identifiability and different degrees of stigma associated with them. All of these give a strong rationale for the growing role and importance of Expert Determination for de-identification of data (Meyers et al. 2017 )." ] },{ "paper_id": "1ab0742b23affe5d2f9a5adc6b98e3f89defd930", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bacterial, fungal, and mycobacterial cultures of endotracheal aspirates and BAL fluid were performed. Respiratory viruses were tested by a multiplex reverse-transcription polymerase chain reaction (PCR) assay using a Seeplex RV15 ACE Detection kit (Seegene Inc., Seoul, Korea) and/or shell vial culture. PCR to detect Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila, and a urinary antigen test to detect Streptococcus pneumoniae and L. pneumophilia serogroup 1 species were also performed.", "Pneumonia was defined as the presence of an acute infiltrate on a chest radiograph and at least one of the following: fever (temperature $38.0uC) or hypothermia (temperature ,35.0uC), cough, pleuritic chest pain, dyspnea, and altered breath sounds on auscultation [15] . Pneumonia was categorized as communityacquired pneumonia (CAP), healthcare-associated pneumonia (HCAP), or hospital-acquired pneumonia (HAP), as defined previously [16, 17] ." ] },{ "paper_id": "1ac9aac4ecdf40363f1377cc08484db3dc4abf93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sample collection. Blood samples were collected on \u03ea7, 0, 3, 7, 10, 14, 17, 21, 28, 35 , and 42 days postinoculation (dpi) from the jugular vein or cranial vena cava using a single-use blood collection system (Becton Dickinson, Franklin Lakes, NJ) and serum separation tubes (Kendall, Mansfield, MA). Serum was separated by centrifugation at 1,500 \u03eb g for 5 min, aliquoted into 2-ml cryogenic tubes (Greiner Bio-One GmbH, Frickenhausen, Germany), and stored at \u03ea80\u00b0C until use.", "tality in piglets in TGEV/PRCV-naive herds. The virus was first described by Doyle and Hutchings in 1946 in the United States and subsequently reported worldwide (1) (2) (3) . Porcine respiratory coronavirus is a naturally occurring spike gene deletion (170 to 190 kDa) mutant of TGEV first isolated in Belgium in 1984 (4) . It infects the upper respiratory tract, tonsils, or lungs, with limited intestinal replication (4, 5) . Porcine respiratory coronavirus itself does not appear to be an important primary pathogen, with the exception of its contribution to the porcine respiratory disease complex (6) ." ] },{ "paper_id": "1adab26eb1167a39014dc503174f7d34f9087664", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rabbit polyclonal antibodies against Bax, Bcl-X L (B-cell lymphoma-extra large), caspase-3, caspase-8, cavoelin-1, CD4, CD28, cytochrome c, FADD (Fas-associated protein with death domain), Fas, FLIP ((FADD-like IL-1\u03b2-converting enzyme)-inhibitory protein), p53, Zap-70 (zeta-chain-associated protein kinase 70), and GAPDH (Glyceraldehyde 3-phosphate dehydrogenase were from Santa Cruz Biotechnology (Santa Cruz, CA, USA). AP-1, ERK (extracellular-signal-regulated kinases), JNK (c-Jun N-terminal kinases), p38, NFAT, and NF-kB p65 were bought from Cell Signaling Technology, Inc. (Danvers, MA, USA). All other chemicals were from Sigma (St. Louis, MO, USA).", "The data are expressed as copy numbers/mL. Known concentrations of HIV-1 (MN) viral RNA (serially diluted: 10 8 to 100 copies) were used as templates and quantitative RT-PCR performed to generate a standard curve. Each value represents the average concentration of six reactions in triple isolated repeats based on the standard curve.", "Cell viability was determined by Trypan blue exclusion analysis (Life Technologies, Waltham, MA, USA)." ] },{ "paper_id": "1adf578fb1c7019c2293b2e9c7cc3f036f9bc15b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "poor immunogenicity of candidate vaccines. For practical and compliant purposes, a single immunization with the highest immunogenicity in animals and humans will be preferred.", "As summarized in Table 2 , most of the aforementioned strategies require multiple immunizations which may pose additional logistic hurdles at the end point use. It is unclear whether these immunization strategies were empirically designed or due to relatively # Abbreviations for animal models: human DPP4 transgenic (hDPP4-Tg) mice with global/epithelial hDPP4 expression, human DPP4 knock-in (hDPP4-KI) mice with hDPP4 replacing mDPP4 in situ, mice transduced with human adenovirus 5 vector expressing hDPP4 (Ad5-hDPP4 mice), and non-human primates (NHPs).", "\u2191 indicates more, while \u2193 indicates less." ] },{ "paper_id": "1aea04847a4f34625beaf937ca06ff039a5d3a2e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Macrocystis pyrifera (Linnaeus) C. Agardh was collected in Bah\u00eda de Ensenada (Manto Jantay) in front of the Salsipuedes beach (31. ", "The discovery of antivirals with high efficacy, low cost, and low cytotoxicity is a long-pursued goal in drug discovery. The marine environment is a wealthy source of biological and chemical diversity of natural antivirals; the investigation of natural antivirals isolated from marine sources is an interesting approach in the development of new antiviral agents [1] .", "The strategy of simultaneously attacking multiple targets is a studied approach in the control of viral diseases [11] . Combining targeted therapies have demonstrated multiples advantages in this field, such the reduction of individual drug doses, the decrease in the side effects of antiviral agents, and the prevention of the emergence of drug-resistant viruses [12] ." ] },{ "paper_id": "1aeb1b6c5213c80ebd33f69021776928ee1fc315", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The MHC-B region was examined in an Australorp population for an influence in avian leukosis virus (ALV) group-specific (gs) antigen shedding related to virus infection. Haplotype frequencies for three MHC-B haplotypes were B8a = 66.7%, B9a = 15.6, and B21 = 17.8% in a base population. The data supported differential susceptibility to horizontal virus transmission based on MHC-B complex type but no MHC-B effect on vertical transmission (Yoo and Sheldon, 1992) .", "Investigations into disease responses have been carried out in various ways. Some compare responses in inbred congenic and sometimes MHC-B recombinant lines. Others examine populations in which MHC-B types are segregating either in selected lines or, occasionally in natural or semi-natural populations. Here we attempt to provide a very brief overview of investigations into MD as well as diseases caused by Rous sarcoma virus (RSV), v-src DNA, other viruses, several bacterial infections, coccidiosis, and an infestation with avian ectoparasites. More information is available for the role of MHC-B in MD and RSV than in other diseases.", "This finding further highlights the resistance conferred by B2 haplotype." ] },{ "paper_id": "1aec943a21b8dc9decd07bd0039e10e5bd87ef00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The samples were fixed in 4% neutral formalin for 72 h at room temperature and subsequently dehydrated through a graded ethanol series and then cleared with xylene and finally embedded in paraffin. Serial tissue sections were cut at 4 lm thickness and six non-successive sections mounted on each slide (Fisher Scientific, USA). The sections were deparaffinized, rehydrated and rinsed in distilled water. Finally, they were stained with haematoxylin for 5 min and then eosin for 40 s, dehydrated and mounted.", "a,b", "The data were analysed by one-way ANOVA. Duncan's multiple comparison was used for the detection ", "Different letter superscripts mean significant difference (P < 0.05). " ] },{ "paper_id": "1aef4c8a0b31ddf10ab37a448fc90808218fa9d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1af8d169cf2d572b46f2b94b1e83c66686973297", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ramachandran plot also supported the quality of monomeric MBL protein model.", "Deleterious and damaging effect of nsSNP was predicted using web based tools SIFT (Sorting Intolerant from Tolerant) and Polyphen-2 (Polymorphism Phenotyping v2).", "Muster v1.0 (http://zhanglab.ccmb.med.umich.edu/ MUSTER/) provides the Z-score and complete full length models by using Modeller v8.2 (Wu and Zhang 2008) . The corresponding template is considered good if the calculated Z-score is greater than 7.5." ] },{ "paper_id": "1af9746ea8f584f3f58da4f59d6dba8185f8be4b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "( Then," ] },{ "paper_id": "1b02698e082376846f59c99c449161a7a7eb737f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mice B6.Drak2 -/mice were previously described and backcrossed 19 generations to C57BL/6 [1] . OT-II mice were obtained from Kristin Hogquist, TGF-\u03b2DNRII mice were obtained from Hongbo Chi, C57BL/6, CD451/1, and OT-I mice were purchased from Jackson Laboratories. Mice were held under specific pathogen-free conditions at St. Jude Children's Research Hospital.", "Drak2 is a serine/threonine kinase expressed highest in T cells and B cells.", "All studies were reviewed and approved by the St. Jude Animal Ethics Committee under protocol number 486-100303-05/14. St. Jude is AAALAC accredited and complies with all federal, state, and local laws." ] },{ "paper_id": "1b050ba5ac020c50042f89a5f4936404ab2f507f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Basic reproduction number R 0" ] },{ "paper_id": "1b08674379f9805e1ab55ce13c056b716433b8a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.pcbi.1006554.g005 the performance of the method (mean average between sensitivity and specificity greater than 93%, Fig 5C) ." ] },{ "paper_id": "1b1b133fc211d0bf8af604d58bedafd5fac7cde9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DF1 cells seeded onto Thermanox coverslips were transfected and processed as before. Sections 250 or 300 nm thick were cut from the resin-embedded blocks and collected on 50 mesh copper hexagonal grids coated in formvar or pioloform-coated copper slot grids. Ten or 15 nm gold particles were applied to the grids to serve as fiducial markers for subsequent alignments. Data was recorded on a JEOL 2100 F TEM (Jeol, Welwyn Garden City, UK) used at 200 kV with a TVIPS F416 digital camera, or on a Tecnai 20 TEM (FEI) used at 200 kV with a FEI 4 k \u00d7 4 k Eagle CCD camera. Samples were mounted in a JEOL high angle tilt holder or a Fischione double tilt tomography holder, respectively. A single axis tilt series was collected using Serial EM or FEI software. Each single axis tilt series was collected over 100 \u2022 to 130 \u2022 in increments of between 1 \u2022 and 2.5 \u2022 and subsequently aligned and reconstructed in IMOD [43] .", "BeauR. DF1 cells were infected with BeauR for 24 h, fixed, and processed for electron microscopy (EM). Viral particles are indicated with arrowheads, double membrane vesicles (DMVs) with asterisks, and zippered endoplasmic reticulum (zER) and associated spherules with arrows. Scale bar represents 500 nm.", "Supplementary Materials: The following are available online at http://www.mdpi.com/1999-4915/10/9/477/s1, Table S1 : Cells expressing each nsp compared to the total number of cells counted, Video S1: Electron tomographic reconstruction of paired membranes in an nsp4-expressing cell, Video S2: Electron tomographic reconstruction of paired membranes in an nsp3 and nsp4-expressing cell. " ] },{ "paper_id": "1b2079db92924c2ee758d437394789b4822d0327", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Informed consent was originally obtained by the National Health Research Institutes in Taiwan. To avoid the potential for ethical violations related to the data, the privacy of each individual's information was protected by de-identifying the data. Thus, informed consent was not required, and an exemption was obtained from the institutional review board of Chi Mei Medical Center (IRB No. 10402-E01).", "The categorical variables that are presented as frequencies and percentages were compared using Pearson's \u03c7 2 test. Continuous variables, presented as means \u00b1 standard deviation (SD) or medians with an interquartile range, were compared using Student's t test or the Wilcoxon rank-sum test. The Cochran-Armitage trend test was used for categorical data analysis to test the association of trends in proportions over specific periods. Cumulative mortality during the first 90 days of each patient's hospital stay was characterized using Kaplan-Meier plots, with the log-rank test used for the comparisons between genders and between different age groups. SAS 9.3 (SAS Institute, Cary, NC) was used for all statistical analyses but the Kaplan-Meier curves, which were plotted using STATA 12 (Stata Corp., College Station, TX). Significance was set at p < 0.05 (two-tailed).", "Based on their first two ICD-9-CM discharge diagnosis codes, six major comorbid diseases for hospitalized patients treated with IABP were identified: acute coronary syndrome (ACS), " ] },{ "paper_id": "1b21437159e00cfbc7a48cfb1cc4c27a818e2157", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceptualization: Mario Recker.", "OPEN ACCESS" ] },{ "paper_id": "1b248ec38c2c12737c005fd38db1bec556675707", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "File S1 Supporting Tables. Table S1 , List of 403 cytotoxic siRNAs which caused significant cell death. ", "Six wells of a 96 well plate were transfected with a siRNA SMARTpool and, 48 h later, infected with VACV-A5eGFP as described above. At 24, 36 and 48 h post infection cells were scraped into the overlying media, collected and then frozen and thawed three times and sonicated for 30 seconds (Misonix sonicator 3000). The resultant lysate was titrated on BS-C-1 cell monolayers and virus titre quantified as plaque forming units (PFU) per ml [19] .", "VACV, like all other viruses, harnesses the cell to enable its replication. It turns off or subverts multiple crucial anti-viral pathways including cytokine production, Toll-like receptor pathways, NF-kB activation and the dsRNA PKR response [2] [3] [4] [5] [6] [7] [8] . In addition VACV suppresses both intrinsic and extrinsic proapoptotic pathways [9] and activates numerous anti-apoptotic, pro-survival pathways including the PI3K/Akt pathway [10, 11] , the MEK/ERK pathway [12, 13] , the p38 MAPK pathway [14] and the MAPK/JNK pathway [14, 15] . Modulation of so many different signalling pathways prevents viral-induced premature cell death and contributes to the ability of poxviruses to replicate in a wide range of cell types.", "The AMP-activated kinase complex (AMPK) is a key regulator of energy metabolism. It is activated by a reduction in ATP which prompts phosphorylation of many target proteins, resulting in the activation of catabolic pathways and inhibition of anabolic pathways [73] . It has also been linked to regulation of the actin cytoskeleton [74] . AMPK is a heterotrimer comprising a catalytic a subunit and regulatory b and c subunits. In mammals each subunit has several isoforms (PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2, and PRKAG3) [73] . The druggable RNAi screen reported here screened all seven genes and identified three (PRKAA2, PRKAB1, and PRKAB2) as promoters of VACV replication whose depletion led to fewer and dimmer accumulations of cytoplasmic eGFP (Figure 6d ). This result is in broad agreement with a recently published RNAi screen of 440 cellular kinases and phosphatases in a nonpermissive Drosophila cell model of VACV infection [36] , which identified seven hits including three AMPK subunits.", "Another HF that affects both VACV and influenza A virus replication is MAP2K3 (also known as MKK3 and MEK3), which activates the p38 MAPK signalling pathway and is involved in low pH-dependent entry of influenza virus and VSV [31, 47] . VACV also has a low pH-dependent entry mechanism [52] which may be similarly reliant on MAP2K3. Alternatively, it may be required to activate the p38 MAPK pathway to promote cell survival post infection [14] ." ] },{ "paper_id": "1b2d0c795271b2dffeba58396e52cca462185d78", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1b3ea086b81a5e0c4dd22aa41653befc358d7163", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data from multiple timepoints was analyzed by ANOVA and Dunnett's multiple comparisons post test, using GraphPad Prism version 5. Microarray data was analyzed by one-way ANOVA, and Benjamini and Hochberg FDR method was used for multiple testing correction. p,0.05 was considered statistically significant.", "The Kikwit 95 isolate of ZEBOV was produced and titrated on Vero E6 cells as previously described [6] .", "ZEBOVForward -CAGCCAGCAATTTCTTCCAT; ZEBOVReverse-TTTCGGTTGCTGTTTCTGTG; ZEBOVProbe FAM-ATCATTGGCGTACTGGAGGAG-CAG-NFQ.", "Some of the worst haemorrhagic fever outbreaks in humans, great apes and nonhuman primates (NHPs) have been caused by Ebola viruses (EBOV) and Marburg virus (MARV). These enveloped filamentous, negative sense single-stranded RNA viruses belong to the family Filoviridae. The African EBOV species, including Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV), Cote d'Ivoire ebolavirus (CIEBOV) and Bundibugyo ebolavirus (BEBOV) have been associated with disease of varying morbidity and mortality in humans. So far ZEBOV has had the highest case fatality rate ranging from 60 to 90% [1] . The only EBOV species found outside of Africa is Reston ebolavirus (REBOV) [2] . Though REBOV can infect humans, it has never been associated with clinical disease in people [1] . However, it can cause disease and mortality in cynomolgus macaques [3] ." ] },{ "paper_id": "1b41bb775aaf552e944aceaa31f52814e264c78d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Treatment of a variety of human ailments using mAbs is revolutionizing our ability to ameliorate human suffering. For infectious disease, the Ebola epidemic highlighted the potential utility of a cocktail of three neutralizing (n)mAbs that block infection by the Ebola virus [29] . Most convincingly, the administration of a single nmAb up to five days post infectious virus exposure prevents the development of disease in Ebola-infected macaques [30] . Because mAbs can be engineered to prevent antibody-dependent enhancement by incorporating the L234A and L235A (LALA) mutations which reduce Fc\u03b3R binding [31] , they are a promising intervention in flaviviral therapies. Our long-term goal is to use a cocktail of LALA-mutated nmAbs to prevent ZIKV infection in at-risk individuals, primarily pregnant women.", "Unfortunately, despite our efforts, we were unable to map P1F12's binding site. We first employed an in vitro escape assay [65] , which did not result in a single mutated consensus sequence. Also, P1F12 did not bind to the prM/E proteins expressed in cells, precluding our ability to map this interaction using an Ala-mutated envelope panel [66, 67] . Characterizing this interaction will, thus, require a significant effort that is beyond the scope of the current manuscript. Because the P1F12 mAb retains the ability to bind virions, our conclusion is that it binds to a conformational epitope.", "Therapeutic nmAbs must be potent in order to be clinically viable, and most nmAb isolation strategies are based on the identification of high-titer, antigen-selected repertoires. Somatic hypermutation (SHM) in germinal center (GC) B cells provides the basis for selection of B cells producing Abs with increased affinity-a hallmark of the adaptive humoral response. This feature is conserved among mammals, highlighting the importance of Ab affinity enhancement for evolutionary fitness [32] . Thus, it is unsurprising that the vast majority of human Abs in the memory immunoglobulin (Ig)G pool have undergone affinity maturation and have, on average, 10-26 nucleotide substitutions from precursor genes [33] . The contribution of SHM to Ab-mediated viral neutralization is particularly clear for the chronicallyinduced broadly neutralizing antibodies to HIV [34] [35] [36] [37] . Reversion of these anti-HIV nmAbs to precursor germline antibodies results in a drastic reduction or complete loss of viral neutralization [38] [39] [40] [41] . Although mutated mAbs are found after secondary DENV infection, the role of these mutations in acute virus-neutralization and clearance is less clear [42] [43] [44] [45] . Still, the prevalent thought is that antiviral Ab response involves the engagement of poor-or non-neutralizing germline clones generated by V(D)J rearrangement, followed by SHM-mediated refinement in germinal centers to enhance neutralization potency." ] },{ "paper_id": "1b42f78eee63e2f5c5a58a59759dc119ef1f73da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Table S1 . Physical-chemical characteristics of PAMAMs used in this study.", "The development of nanotechnology has rapidly accelerated, with an estimated market of approximately one trillion US dollars within the next few years [43] . Safety problems associated with nanomaterials have recently attracted attention, highlighting the urgent need for protocols that protect workers, consumers, and the environment [44] . We propose here a valuable strategy using ARB drug to address potential acute lung injury might be induced by application of PAMAMs.", "mouse \u03b2-actin forward primer: 5'-CTCTCCCTCAC GCCATCC-3' mouse \u03b2-actin reverse primer: 5'-CGCACGATTT CCCTCTCAG-3' mACE2 forward primer: 5'-GGCTACAACTATAAC CGTAAC-3' mACE2 reverse primer: 5'-TATCCATCAACTTCC TCCTC-3'." ] },{ "paper_id": "1b482a5e57ac1d83844e7204c907109483603516", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses (CoVs) are found in a wide variety of animals in which they can cause respiratory, enteric, hepatic, and neurological disease of varying severity. In humans, CoVs cause a large fraction of common colds [1] , as well as more rare, but serious disease such as the outbreak of Severe Acute Respiratory Syndrome (SARS, caused by SARS-CoV) in 2003, and the polymerase (RdRp) were generated using methods described in [14] or [15] , and sequences generated in this study have been deposited in GenBank under accession numbers KT882615-28. Resulting sequences were aligned using the MAFFT algorithm [16] implemented in Geneious R7 (Biomatters, New Zealand). The nucleotide substitution model was determined in MEGA 5.2 [17] and maximum likelihood trees were constructed using PhyML [18] with aLRT branch support in SeaView [19] . Trees were projected using FigTree v1.4 [20] .", "A total of 764 birds from 11 species of Anserifomes (ducks, geese, swans, n = 691) and 11 species of Charadriiformes (gulls, terns, shorebirds, n = 143) were sampled in this study. Overall, the prevalence of CoV was high, at 18.7%, but species, groups and orders were unevenly represented. Diving ducks had the highest prevalence (39%), driven by high prevalence in Greater Scaup (Aythya marila; 51.5%), however the sample size was small (n = 37). Dabbling ducks of the genus Anas also had high prevalence; Mallard, in particular, had a prevalence of 19.2%. While Anseriformes had the highest prevalence, in the order Charadriiformes, CoV was detected in a Black-headed Gull (Chroicocephalus ridibundus), but absent in tern and wader species sampled (Table 1) . Eleven sequenced Mallard CoV and three sequenced Scaup CoV were gammacoronaviruses.", "Despite few studies, small samples sizes and differences in prevalence, what is clear, is that in the Northern Hemisphere waterfowl species, especially dabbling and diving ducks are important in the epidemiology of avian CoVs. It is interesting to note that these patterns are very similar to those found in low pathogenic influenza A viruses: high prevalence in waterfowl and gulls in the Northern Hemisphere [30] , and little host species and temporal structuring within waterfowl derived viruses in the conserved polymerase genes (such as PB2, PB1) [31] . Further, detection in fecal or cloacal samples suggest these viruses may also replicate in the gastrointestinal tract, which is the true for Turkey Coronavirus [9] . As demonstrated by years of influenza sampling [32] , to better understand the eitiology, epidemiology and ecology of these viruses more systematic surveillance needs to be undertaken and more viruses need to be sequenced, particularly full genomes. Given the importance of coronaviruses as human pathogens, as exemplified by SARS and MERS-CoV and the potential for wild birds as reservoirs, spreaders and mixing vessels, further studies of coronaviruses in wild birds are warranted. " ] },{ "paper_id": "1b5d310d0656503b1d2fbc612625496a3266ae16", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Week 12 (Panels E and F). Signal strength against 141 and 327 increased in sera from Week 5 post-infection (Panel C), but returned to pre-immune levels by Week 9 (Panel D).", "Although the samples were boiled in SDS-buffer containing 2-mercaptoethanol, putative dimeric and trimeric forms of the HA protein are apparent as slower-migrating species.", "Week 26 following the final HA immunization at Week 10." ] },{ "paper_id": "1b62107420aac57e1b7e2d496183036dec1ab905", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Transport/Transmission models Epidemiology studies can link disease cases together and develop a disease transport and transmission model [8] .", "From the AirPath point of view, to carry out an exposure assessment -that is, to estimate and measure the amount of infectious pathogens entering our bodies through inhalation -is already a complex and multidisciplinary science without the added component of using exposure data and disease outcomes to predict risk factors. We think that Air-Path has contributed towards forming a technical network, as shown in the output in Table 1 , as well as a medical network to further clarify a comprehensive and systematic exposure assessment. ", "Detection and identification of pathogens has changed since the development of different molecular methods and innovative approaches other than culture methods [5] . The existing detection methods can be divided into two levels: generic and specific. Generic detection gives information about whether the particles are biological materials, microbes or living cells, e.g. bioluminescent measurement of ATP using continuous flow luminometer and mass-spectrometry. Specific methods such as micro-arrary and immuno-assays can tell us what kind of microbes are detected and identified. Other new techniques have been proposed for bio-detection, for instance, by characterising the size and shape of bioaerosols, pollens and fungal spores under microscope [18] and analysing fluorescence spectrum of bacteria [5] ." ] },{ "paper_id": "1b64709bd4f9ba56a4209bd32c07a89d1beec6c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Smallpox is a category A bioterrorism agent, despite being declared eradicated in 1980 [1] . The virus is retained in high security biosafety level 4 laboratories in the United States and Russia [2] . The variola genome is fully sequenced and could be synthesized in a laboratory [3] . This a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Results showed for 95% of new infected isolated.", "https://doi.org/10.1371/journal.pone.0217704.g005" ] },{ "paper_id": "1b64cf541af6560335b092dc63f67dd4cd81691a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleic acid was extracted from swabs or respiratory samples using EZ1 Virus mini kit (Cat No. 955134, Qiagen, Germany) performed on a semi-automated system (EZ1, Qiagen, Germany), and stored at -70\u00b0C for more detailed molecular testing. Besides routine standard clinical testing, additional multiplex real-time PCR testing was performed for each extracted sample.", "Abbreviations APACHE II: Acute Physiology and Chronic Health Evaluation II; CAP: Community-acquired pneumonia; PCR: Polymerase chain reaction", "Anyplex " ] },{ "paper_id": "1b7c700ee3a33c0a675a5f7e71a20ce62467b900", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "described here, and also its immunogenicity, if it is to be used as a candidate HIV-1 vaccine.", "Approximately 50 to 100 ng of recombinant plasmid was electroporated into host A. tumefaciens GV3101::pMP90RK cells as described by Maclean et al. [52] Recombinant A. tumefaciens colonies were selected on plates incubated at 27\u00b0C containing kanamycin (30 \u03bcg/ml), rifampicin (50 \u03bcg/ml) and carbenicillin (50 \u03bcg/ ml).", "This work was carried out using 2-4 week-old Nicotiana tabacum cv. Petite Havana SRI plants grown in a greenhouse under a 16 hr light and 8 hr dark photoperiod at light intensity of 60-80 \u03bcE/m 2 /s and 22\u00b0C." ] },{ "paper_id": "1b8a085682d10dad4baf90417a8cbcde144cc8c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analysis of residues is performed, and the ACF model must show the nonexistence of a significant autocorrelation or a partial autocorrelation between residues. The Portmanteau test could be applied as a complementary means to evaluate the adjustment; a positive test might indicate an inadequate model (15) .", "Some parameters can present no statistically significant values (p\u22650.05); in such cases, these parameters could be taken away from the study in order to improve the arrangement of data.", "A avalia\u00e7\u00e3o do gerenciamento de doen\u00e7as infecciosas e n\u00e3o infecciosas pode ser realizada por meio da an\u00e1lise de s\u00e9ries temporais. Com isso, espera-se que sejam medidos os resultados e previstos os efeitos da interven\u00e7\u00e3o sobre a doen\u00e7a. Os estudos cl\u00ednicos t\u00eam se beneficiado do uso dessas t\u00e9cnicas, visto a grande aplicabilidade do modelo ARIMA. Esse texto apresenta de maneira resumida o processo de uso do modelo ARIMA. O uso dessa ferramenta anal\u00edtica oferece grande contribui\u00e7\u00e3o para os investigadores e gestores de sa\u00fade na avalia\u00e7\u00e3o das interven\u00e7\u00f5es de sa\u00fade em dadas popula\u00e7\u00f5es.", "A stationary series has a \"white noise\" when mistakes consist of a sequence of uncorrelated random variables. One can understand white noise in errors as the inexistence of patterns, which is equivalent to establishing that mistakes are not correlated. The partial ACF (PACF) is used to measure the associative degree between an observation ( ) and an observation made in two periods before ( ) removing the intermediate period ( ) (15) . PACF enables the evaluation of the correctness degree of current variables with its previous values, whereas other constant values are kept." ] },{ "paper_id": "1b8bd44173742cd254617aabc5fdf20fb98f4072", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Lower respiratory tract infection (LRTI) is a major cause of pediatric morbidity and mortality, especially among non-affluent communities. In this study we determine the impact of respiratory viruses and how viral co-detections/infections can affect clinical LRTI severity in children in a hospital setting.", "Demographics were summarized as mean or median and range according to their distribution. Characteristics among groups were compared, accordingly, using twosample t-test, Mann-Whitney, Chi-square or Fisher's exact test.", "This study was approved by the local Institutional Ethics Committees (06/03467 -Pontif \u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul and 4856/2004 -Universidade de S\u00e3o Paulo). Parents or legal guardians read and signed an informed consent approved for this study." ] },{ "paper_id": "1b92fda04723ae9d30a58f10b054cc1b7971e870", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell lysates were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (BioRad, Hercules, CA), and were transferred onto a PVDF membrane (Millipore, Billerica, MA). The membrane was treated with an anti-cystatin C or anti-actin antibody (Santa Cruz Biotechnology, Santa Cruz, CA), and then with a horseradish peroxidase-conjugated protein G (BioRad). Protein G-bound polypeptides were visualized by ECL Western blotting detection reagents (GE Healthcare, Buckinghamshire, UK).", "Total RNA was isolated from cells by using TRIsol reagent (Invitrogen). First strand cDNA was synthesized from the total RNA with random hexamers by means of a reverse transcriptase (TaKaRa). Semi-quantitative PCR was performed using the first strand cDNA as a template to detect cystatin C, cathepsin B, and GAPDH mRNAs. The nucleotide sequences of the PCR primers (Genenet) for the cystatin C mRNA were 59-TCC TAG CCG ACC ATG GCC-39 and 59-CGG TAC AGA CCC CTA GGC-39, those for cathepsin B mRNA were 59-GTG TAC CAA CAC GTC ACC GGA-39 and 59-CAG GCC CAC GGC AGA TTA-39 [19] , and those for the GAPDH mRNA were 59-AGG TCG GAG TCA ACG GAT TTG GT-39 and 59-GTG GGC CAT GAG GTC CAC CAC-39.", "Target cells were pretreated with inhibitors for 4 h, and then starved in presence of inhibitors for 1 h. Cy3-conjugated transferin (4 mg/ml) (Jackson Laboratories) was added, and incubated for 10 min. Surface-bound transferin was removed by trypsin treatment of the cells for 15 min. Fluorescence intensities of the cells were measured by a flow cytometer (BD Biosciences)." ] },{ "paper_id": "1ba33d95f798c3f591766786b165215875278bc7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Raw sequences were analyzed and edited in Geneious Pro v5.1.7 and MEGA 5.03. Multiple sequence alignments were constructed using ClustalW and phylogenetic comparisons made using Neighbor-Joining (NJ) and maximum likelihood (ML) algorithms. ModelTest was used to select the most appropriate nucleotide substitution model. Support for branching order was evaluated using 1,000 nonparametric bootstrap support. Sequence identity was calculated using uncorrected p-distances in PAUP* and BLAST.", "The USFWS specimens from 2006 included an additional 20 NHP tissues from 16 individual animals including 10 baboons (Papio sp.) and 6 African green monkeys (AGMs; Chlorocebus sp.) all confirmed by phylogenetic analysis.", "Nucleic acids were extracted from 10-30 mg of tissue using mechanical disruption (Qiagen tissue lyser II or Next Advance Inc Bullet Blender), followed by proteinase K treatment until complete digestion of the tissue was achieved. Purification of subsequent homogenates was performed using the Qiagen All-Prep DNA and RNA extraction kit or DNeasy Blood and Tissue kits according to the manufacturer's instructions. Nucleic acid quality was determined using the Agilent BioAnalyser (Agilent RNA nano 6000) or \u00df-actin PCR as previously described [16] ." ] },{ "paper_id": "1bab633e4d3ab1ed30599369e8654c235256c5cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hematology. For monitoring of hematological parameters, hearts were punctured and blood was collected in EDTA tubes. Numbers of lymphocytes (Lym), granulocytes (Gr), and monocytes (Mon) in the blood were determined immediately by using a VetScan HM5 hematologic system (Abaxis)." ] },{ "paper_id": "1bb908e3833b1882de4b7a04593005dbe9e5cd1e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1bd1b038d7ed985902aeef21bc1493eda76cdab5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human erythrocytes were separated from whole blood of healthy donors. After isolation and washing, 50 \u00b5l of a 0.75% human red blood cell (RBC) suspension was added to 50 \u00b5l volumes of 2-fold serial dilutions of purified rHA proteins in a U-bottom 96well plate (BD Falcon, USA; total volume, 100 \u00b5l). Agglutination was read after incubation for 60 min at room temperature. As a control, phosphate-buffered saline (PBS) was used instead of rHA.", "All data are presented as the means \u00b1 SEMs. Measurements at single time points were analyzed using ANOVA, and if these measurements demonstrated significance, they were further analyzed by a two-tailed t-test. Survival data were subjected to Kaplan-Meier survival analysis. All statistical tests were performed with GraphPad Prism 5.0 (GraphPad Software, San Diego, CA, USA). P < 0.05 indicates statistical significance.", "Western blotting following viral infection. Data are presented as the means \u00b1 SEMs. *P < 0.05, **P < 0.01 and ***P < 0.001, Student's t-test.", "Tenfold dilutions of the virus were used to inoculate MDCK cells in a 96-well plate, and infected cells were maintained in culture for 72 h. Viral titers were calculated using the Reed-Muench method and are expressed as the tissue culture infectious dose (TCID50) per milliliter of supernatant." ] },{ "paper_id": "1bd2f6497996fc0fccd8dffd7f84846d3d36f964", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "F laviviruses are taxonomically classified in the genus Flavivirus and family Flaviviridae.", "These viruses comprise over 70 different pathogens, such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), dengue virus (DENV), West Nile virus (WNV), and yellow fever virus (YFV). Most flaviviruses are arthropod borne and cause public health problems worldwide (1) . The development and usage of vaccines against some flaviviruses, such as JEV, YFV, and tick-borne encephalitis virus (TBEV), have decreased the rates of morbidity and mortality from infections caused by these viruses (2) ; however, flavivirus-induced diseases are still pandemic, and few therapies beyond intensive supportive care are currently available.", "Flaviviruses have an approximately 11-kb positive-stranded RNA genome containing a single open reading frame (ORF) flanked by untranslated regions (UTRs) at both termini. The ORF encodes three structural proteins, including the capsid (C), membrane (premembrane [prM] and membrane [M] ), and envelope (E), and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) (3) . These seven nonstructural proteins participate in viral replication, virion assembly, and virus escape from immune surveillance." ] },{ "paper_id": "1be8f67d3b7d2730be96799adfc38746474b0a3b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA was extracted from AMs using TRIzol reagent (Life Technologies, Paisley, Scotland, UK), reversetranscribed to cDNA, and amplified by PCR with the following primers: porcine Fas (sense: ", "The terminal deoxynucleotidyl transferase (TdT)mediated dUTP nick end-labeling (TUNEL) assay was performed according to the manufacturer's instructions (in situ cell death detection kit, fluorescein; Boehringer Mannheim, Mannheim, Germany) and counterstained with 1% Hoechst 33258 (Sigma) as described previously [14] . " ] },{ "paper_id": "1bebd833b3535712b5d13f9ed985e3491d3c96c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vero cells (continuous cell lineage originated from the kidney of African green monkeys) were grown in Leibovitz-15 (L-15) culture medium (Invitrogen, New York, USA) supplemented with 10% Fetal Bovine Serum (FBS), 1% L-glutamine 200 mM, 1% penicillin G (100 U/mL), streptomycin (100 g/mL) and 10% triptose 2", "2.6. Viral RNA Extraction. Viral RNA was extracted from 140 L of each supernatant sample using the QIAamp Viral RNA kit (QIAGEN, USA) according to manufacturer's directions.", "Thus, as chloroquine is considered a safe and effective drug, used to treatment many diseases, including malaria, their therapeutic use is promising because it was shown in this study that the drug has significant antiviral effect on the replication of dengue-2 virus in cells culture." ] },{ "paper_id": "1bef85a33a74c3d1765752da0e715fc3a46e00d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Concept, design, data acquisition, data analysis and data interpretation. AL, PB, PC: Concept, design, data analysis and data interpretation. YSL, RH, JB: Concept, design, data interpretation. AR: Concept, design, data acquisition. AT, MB, ALQ, YK, VD: Data acquisition; data analysis and data interpretation. Drafting or revising manuscript. PC, AT, AL, PB, JB, YSL: Drafting and revising. AR, MB, RH, ALQ, YK, VD: Revising. All authors read and approved the final manuscript.", "Not applicable.", "Author details" ] },{ "paper_id": "1c07f420a5a01bec7481025a89f2621596a99782", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "V.M. and R.B. wrote the paper.", "The authors declare no conflict of interest.", "Viruses 2015, 7 4462" ] },{ "paper_id": "1c0ae4beee003ecb59ff15f81ed8f22cd9451353", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, another open-format item asked about habitual actions taken when sick or dead poultry was found on the farm.", "If Nepal were hit by pandemic flu as a consequence of re-assortment or adaptive mutation of the virus and ensuing full human-to-human transmissibility, consequences could be severe. Depending on the planning scenario, fatality numbers are estimated between 15,000 and 130,000 and large numbers of people in need of clinical care might be faced with a severe shortage of hospital beds [4] . Beside the expected toll on human life, a pandemic is bound to incur disastrous economic losses in a country where sectors like farming and tourism, which make a significant contribution to the overall economy, are expected to be particularly hard hit [5, 6] .", "In January 2009 Nepal faced the first localized outbreak of highly pathogenic avian influenza (AI) among poultry, followed by a second outbreak in another area in February of the same year [1, 2] , but no human cases were registered [3] ." ] },{ "paper_id": "1c2e5c34faa703640900893c58254c63361bd29b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Y K S N NQ Y K S N NQ Y K S N NQ Y K S N NQ Y K S N NQ Y K S N NQ", "Transporter of antigenic peptide SMM:", "Stabilized matrix method HLA:", "Epitope-based immunizing agents are often an inexpensive choice to thwart enteric Shigella infection. The identification of specific epitopes derived from infectious pathogens has considerably advanced the event of epitopebased vaccines (EVs). Higher understanding of the molecular basis of substance recognition and human leukocyte antigen-(HLA-) binding motifs has resulted in the advancement of rationally designed vaccines that solely depends on algorithms predicting the peptide's binding to human HLA." ] },{ "paper_id": "1c363c20418dda4f6c674f6d7af16f92b5dce974", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1c39727d1bf8a4e67e43fccecf8dafcd9b960b70", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Unless otherwise noted, statistical analyses were performed using Student's two-tailed t test. Difference was considered statistically significant at P < 0.05. Data Availability. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request." ] },{ "paper_id": "1c3e28d4bd170a986bb5566cb9f9616410f67763", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1c5b9b791b402f44f6229f9d420d6a10dc173d39", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Yu Ping Feng (YPF) decoction, a classic herbal formula, has been used in clinics to treat various diseases, such as respiratory tract infection 8,9 , nosocomial pneumonia 10 , chronic bronchitis 11 , and perennial allergic rhinitis 12,13 .", "Understanding the scientific basis and therapeutic mechanisms of herbal formulas from traditional Chinese medicines (TCMs) is essential since they play a vital role in complementary and alternative therapies in clinical practice to cure diseases or restore the whole-body balance; additionally, they provide a rich source for drug discovery. Owing to the complexity of the constituents in TCMs, reductionism, which individually considers each ingredient, cannot adequately explain the effects generated by an entire formula, and therefore faces several challenges comprehending and illustrating the mechanisms of herbal formulas. With the rapid development of bioinformatics, a combined attempt based on system/network biology and polypharmacology has created a new paradigm called network pharmacology (NP).", "In recent years, NP has been proposed as a promising approach for understanding herbal formulas 1,2 and predicting potential new drugs or targets 3-5 . To some extent, NP-based research on the underlying therapeutic mechanisms of herbal formulas has been well-accepted 6,7 and accounts for the strong compatibility of different scales of systems. A distinct advantage of network analysis is that it can excavate underlying information from multilevel interactions, especially when dealing with big data." ] },{ "paper_id": "1c5f2a7a584371461fa19a49e49c99ecd0ef7743", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 70 rectal swab samples were collected from 70 piglets infected with PEDV from October 2010 to March 2012. These infected piglets were chosen from 16 different swine farms located in 6 different provinces in China. Samples were subgrouped according to the geographic regions ( Table 1 ). The rectal swabs were soaked in PBS buffer supplemented with penicillin G (10,000 IU/mL) and streptomycin (2 mg/mL) and centrifuged at 1,500 \u00d7g for 15 min to collect the supernatant fluids. The supernatant fluids were stored at -80 \u2218 C until used.", "RNA was extracted from the supernatant using TRIzol Reagent (Invitrogen Corp., Carlsbad, CA, USA) following the manufacturer's instructions. Briefly, the supernatant (200 L) containing PEDV was mixed with 1 mL of TRIzol Reagent. Then, 200 L of chloroform was added to the mixture, and the suspension was centrifuged for 15 min at 12,000 \u00d7g. The RNA-containing aqueous phase was precipitated with the same volume isopropanol, maintained at -20 \u2218 C for 1 h, and centrifuged for 10 min at 12,000 \u00d7g. The resulted RNA pellet was washed with 1 mL of 75% ethanol, centrifuged for 10 min at 12,000 \u00d7g and dried, and resuspended in 30 L of diethyl-pyrocarbonate-(DEPC-) treated deionized water.", "Step Buffer, 2 L each specific primer (10 pmol), 2 L PrimeScript 1", "were performed with reverse transcription at 50 \u2218 C for 30 min and predenaturation at 95 \u2218 C for 5 min, followed by 35 cycles of denaturation at 95 \u2218 C for 1 min, annealing at 50 \u2218 C for 1 min, and extension at 72 \u2218 C for 1 min, and a final extension step of 72 \u2218 C for 10 min. For the M gene, the amplification conditions were the same as above; however, the annealing temperature used was 56 \u2218 C for 1 min. RT-PCR products were visualized via electrophoresis in a 1.5% agarose gel containing ethidium bromide. Bands of the correct size were excised and purified using TaKaRa MiniBEST Agarose Gel DNA Extraction Kit Ver. 3.0 (TaKaRa Biotechnology Co., Ltd., Dalian, China) following the manufacturer's instructions. The purified products were sequenced by BGI Biological Engineering Technology & Services Co., Ltd. (China, Shenzhen)." ] },{ "paper_id": "1c60d93cd686bb14fac65510ad3de47cf8b9332c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although C31 is not more potent against all Flaviviridae than against HCV, this compound represents a good candidate for further chemical optimizations.", "Drugs. Alisporivir (ALV) and ledipasvir (LDV) were purchased from AGV Discovery (Clapiers, France), while cyclosporine (CsA) was purchased from Sigma-Aldrich (St. Louis, MO, USA).", "(This work was presented as an oral communication at HCV2016, the 23rd International Symposium on Hepatitis C Virus and Related Viruses, Kyoto, Japan, 11 to 15 October 2016.)" ] },{ "paper_id": "1c7230a768a9650c409a13c25b42dcf5f7f3392c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step 3: The emulsion is broken and double stranded library beads are magnetically collected.", "Step 2: PCR is conducted within the droplets.", "The developments in ePCR, described in the section above, have allowed for the generation ", "The dissociation constant of the novel structure switching aptamers was slightly stronger (4.1 \u00b5M) than that of the aptamer on which the initial library was based (5 \u00b5M) [16] . These relatively high K d are understandable given the size and hydrophobicity of steroid molecules and the fact that simple unmodified DNA aptamers were used." ] },{ "paper_id": "1c7b536966e355206379e97fd0e8ef71d71fb143", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2\u00b75, which does not permit commercial exploitation. R. A. Velarde et al.", "Sequences (N = 35) representing the diversity of NR2E, 2B, and C/D subfamily proteins were aligned using CLUSTALX (Jeanmougin et al., 1998; Hall, 2001) . The multiple sequence alignments were then inspected and manually refined with JalView (Clamp et al., 2004) . Only complete sites were used for the phylogenetic analysis. Phylogenetic tree reconstruction was performed using the minimum distance heuristic algorithm in PAUP* v4.0b10 (Swofford, 2003) .", "In addition to identifying and/or reconstructing orthologs for each of the Drosophila receptors, we also identified a nuclear receptor not present in any Drosophila sequence database. This receptor has relatively high sequence similarity to the photoreceptor-specific nuclear receptor (PNR) of vertebrates, and will be discussed in detail in a subsequent section." ] },{ "paper_id": "1c7c9d9c03f404119c5cc1dd98e0ebe17ea3bb3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "For RNA sequencing (RNAseq) quality and integrity of total RNA was controlled on Agilent Technologies 2100 Bioanalyzer (Agilent Technologies; Waldbronn, Germany). The RNAseq library was generated from 500 ng total RNA using Dynabeads mRNA DIRECT Micro Purification Kit (ThermoFisher) for mRNA purification followed by ScriptSeqv2 RNA-SeqLibrary Preparation Kit (Epicentre) according to manufacture\u00b4s protocols. The libraries were sequenced on Illumina HiSeq2500 using TruSeqSBS Kit v3-HS (50 cycles, single ended run) with an average of 3 x10 7 reads per RNA sample.", "Human subject research. Human primary hepatocytes were isolated from liver specimens obtained after partial hepatectomy of adult patients, following written informed consent of the patients (approved by the ethic commission of Hannover Medical School/Ethik-Kommission der MHH, #252-2008)." ] },{ "paper_id": "1c7d1097a0fc23516fc084e127333ec4bbf9ca94", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chlorpromazine is an anti-psychotic drug that interferes with EBOV infection [86] , probably by inhibiting the internalization of virions [87] .", "Until 2014, EVD was considered a neglected disease, causing small outbreaks in remote African villages. EBOV research was focused mainly on biology aspects of viral infection or preparedness due to its potential use as bioweapon, and was limited to few laboratories equipped with biosafety level-4 (BSL-4) facilities. However, the recent large outbreak of EVD (Western Africa, 2013-2016) characterized by 28,616 cases and 11,310 deaths, highlighted the worldwide danger of this disease and its impact on global public health and economy [5] ." ] },{ "paper_id": "1c7db6e51155dadaaffd563ef1e560011b25ae92", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Prob(sustained transmission | m imported cases, \u03b3 i ) (4)", "The risk of sustained transmission given multiple imported cases was calculated by considering the possibility that none of those cases led to sustained transmission. Consequently,", "The infectious agent driving the ongoing pneumonia outbreak (the 2019-nCoV) appears to have transitioned from animals into humans, with the Huanan seafood wholesale market in Wuhan, China, representing the most likely source [1] [2] [3] [4] [5] . Since then, cases have been recorded in other countries, and initial estimates suggest a hospital fatality risk of around 14% [6] , although estimates of disease severity early in an outbreak are often imprecise [7] [8] [9] . Even countries without confirmed cases have been on high alert. For example, even prior to the two cases in the United Kingdom on 31 January 2020, officials were reported to be attempting to trace as many as 2000 visitors that had travelled to that country from Wuhan [10] ." ] },{ "paper_id": "1c857d4493720168ac6eba2bbeb2fbfa31433d91", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Table S1 Distribution of FCGR2A SNP (rs1801274) in atopy + and atopysubjects. (DOC) " ] },{ "paper_id": "1c8a0fb2f60c243f71d16d5fefb5b51d7978869e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Venom allergen acid phosphatase (Api m 3)", "Major royal jelly protein 9 precursor (Api m 11)", "The " ] },{ "paper_id": "1c8afcb822dac8e8e5b33a85c2c2e9c7cc24a25a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The GenBank accession number for the MD27 sequence is FJ008695. The accession numbers for other IBV gene sequences used in this study are as follows: (a) complete structural genomes: ", "DNA from various clones was sequenced by dideoxy chain termination method using an automated DNA sequencer (Applied Biosystems Inc., Foster City, CA). At least three independent clones were sequenced for each amplicon to exclude errors that can occur from RT and PCR reactions. The assembly of contiguous sequences was performed with the GeneDoc software [32] . Comparative sequence analyses of MD27 with other IBVs and coronaviruses were conducted using the BLAST search, NCBI, and Vector NTI Advance 10. Phylogenetic analyses were carried out using the MEGA4 program [33] . The phylogenetic tree was constructed from aligned nucleotide and amino acid sequences using the neighbor-joining method with 1000 bootstraps.", "Virus isolation was done in Dr. Marquardt's laboratory by passaging tissue (trachea or kidney) homogenates into 9-10-day-old chicken embryos by the allantoic cavity route of inoculation and at S1 S2 3a 3b E M 5 N 3'UTR X X X X SE17-like SE17/JMK-like Conn -like Ark99/ Gray/? Conn-like Putative recombination site least three passages were done before declaring samples as negative. Two of the isolates were named as Md27, and these were propagated by inoculating into 9-day-old embryonated specific-pathogen-free (SPF) chicken eggs and allantoic fluid was collected 72 h post-inoculation. The fluid was clarified by low speed centrifugation and clear supernatant was stored at -80 \u00baC until further use.", "Numerous IBV serotypes, such as Arkansas, Massachusetts, Connecticut, Florida, Georgia and others, referred to as variants, exist in the United States of America (USA). These variants have practical significance for controlling the disease because immunity following infection or vaccination with one serotype often is not protective against subsequent infections with heterologous serotypes [7, 8] . Many serotypes have been described for IBV, probably due to the frequent point mutations that occur in RNA viruses and also due to recombination events [9] [10] [11] . It is essential to characterize field isolates for the selection of appropriate vaccine strains." ] },{ "paper_id": "1c956bc94ce590a7ca6c2ace2c0766bbbbfaa0e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords: hepatitis A virus; soybean agglutinin linked-magnetic bead separation; lectin; oyster", "All statistical analyses was carried out using SPSS software (IBM Corp., Somers, NY, USA) [51] and Excel software (Microsoft Corp., Redmond, WA, USA) [52] . All samples were analyzed in triplicate and represent three independent experiments to ensure assay consistency. Analysis of variance was used to compare groups. Significant differences among means were determined using Tukey's HSD test. Values of p < 0.05 were considered significant.", "Viruses are a major cause of foodborne illness, due in large part to the contamination of shellfish by hepatitis A virus (HAV) [1] . HAV, the prototype of the Hepatovirus genus within the Piconaviridae family, is composed of an icosahedral capsid that contains a positive sense single-stranded RNA genome [2, 3] . HAV infection is associated with the consumption of virus-contaminated bivalves, including oysters, clams, cockles and mussels, which accumulate the virus from seawater as they filter-feed [4] . Moreover, the increasingly widespread incidence of oyster-related HAV infection is attracting greater attention to the mechanisms underlying the interaction between HAV and oyster [5] ." ] },{ "paper_id": "1c995ac4ae70bbcc5da53211e20df4398d1ce55d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cleavage of the caspase substrate was monitored using a spectrofluorimeter (Hitachi F-2000 fluorimeter, Hitachi LTD, Tokyo, Japan) at excitation/emission wavelengths of 380/460 nm. Activity was expressed as fluorescence units per milligram of protein per min of incubation.", "Autophagy vesicles were detected in RHDV-infected hepatocytes by transmision electron microscopy", "For transmission electron microscopy (TEM) analysis, liver tissues were dissected into 1-mm 3 pieces for good penetration of the fixative, and then immersed in a modified Karnovsky fixative (2% glutaraldehyde + 4% buffered formalin (0.1 mol/L phosphate buffer)) overnight. The samples were post-fixed in 2% osmium tetroxide for 2 h at 4\u00b0C and dehydrated with ascending grades of alcohol. The tissue block was then infiltrated and embedded in epon resin at 60\u00b0C for 72 h. Ultrathin sections (70 nm) were cut with an automatic ultra-microtome (Reichert Ultracut E, Vienna, Austria) using a diamond knife. The sections were collected on copper grids (200 meshes) and stained with uranyl acetate and lead citrate solutions. TEM images were obser ved under a transmission electron microscope (JEOL Ltd, Tokyo, Japan) operating at an accelerating voltage of 80 kV." ] },{ "paper_id": "1ca045bd7724943ce8c268353153bd522358625d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "normalized positions showed no systematic effects (supplementary Fig. S3 ).", "We then grouped the epitopes retrieved with the query by viral species. As described below, we want to map all epitopes from one species to a single reference proteome. Therefore, we excluded all viruses for which we do not have reference proteomes available, resulting in a total of 93 different viruses.", "To derive a measure of epitope position that is independent of protein length, a normalized position, x, is defined as follows:" ] },{ "paper_id": "1cb0c02329d10e7513faabdc57113172591d5406", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sequencing data has been deposited to NCBI Sequence Read Archive (SRA) under accession numbers: SRR10292736 to SRR10292741." ] },{ "paper_id": "1cbc073d7288259db8f24cd19ee27052c1eece02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "UPR-Cytokine Intersection Impacts Infection and Autoimmunity", "Frontiers in Immunology | www.frontiersin.org March 2018 | Volume 9 | Article 422 acute phase response (37) . For a basic summary of the three UPR pathways, see Figure 2 .", "Overall, the precise role of UPR pathways in supporting or limiting IFN or other cytokine production during viral infection, and the ultimate effect on pathogenesis remain important areas for further investigation.", "Spondyloarthritis encompasses a group of genetically and pathologically related inflammatory diseases which manifest with axial (spinal) arthritis, enthesitis, uveitis, gut inflammation, and psoriasis (219) . SpA is highly linked to an MHC protein HLA-B27 that misfolds during biogenesis: in patients with the prototypic SpA, ankylosing spondylitis, 80-90% of subjects are HLA-B27 positive vs 6% of the United States population (220, 221) . Although ankylosing spondylitis is a polygenic disease, the presence of HLA-B27 accounts for the preponderance (67%) of the currently identified heritability, conferring an odds ratio of >50 (222, 223) . This misfolding propensity and prolonged association with BiP in the ER results from specific amino acids in its peptide-binding B pocket and unpaired cysteines (224) (225) (226) . The subtypes of B27 with differential disease association also exhibit variance in biochemical features including thermos-stability, folding rates, and intracellular aggregation (227) (228) (229) ." ] },{ "paper_id": "1ccc635c4d6c62091bbf7df3f8e4f36803ea1a32", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Reoviridae family consists of two subfamilies: Spinareovirinae and Sedoreovirinae, including 9 and 6 genera, respectively. These are icosahedric non-enveloped viruses with a segmented genome of 10 to 12 doublestranded RNA (dsRNA) segments [1] . Viruses belonging to this highly diverse family infect a variety of host species including mammals, reptiles, fish, birds, protozoa, fungi, plants, and insects.", "MRVs have long been considered non-pathogenic, although mild respiratory and enteric diseases have occasionally been reported in young animals and children. Several evidences have recently shown that MRVs can cause severe diseases. Cases of neonatal diarrhea and neurological symptoms in children were associated both with MRV2 and MRV3 in Europe and North America [3] [4] [5] . These findings highlight the zoonotic potential of MRVs, though the mechanisms of their pathogenicity are not fully understood [5] .", "Full genome sequencing was conducted using an Illumina MiSeq platform from the isolated virus. Briefly, 100 \u03bcl of cell culture supernatants were treated with 250 units of Omnicleave endonuclease (Epicentre, Tebu-bio, Milan, Italy) at 37\u00b0C for 2 h. Viral RNA was extracted from treated supernatants using One for all Vet kit (QIAGEN, Milan, Italy). Sequencing libraries were prepared using TruSeq RNA sample preparation kit v2 (Illumina Inc. San Diego, CA, USA) and sequencing was performed on a Miseq Instrument with MiSeq Reagent Nano Kit v2, 300 cycles (Illumina Inc. San Diego, CA, USA). Sequencing reads were de-novo assembled by Seqman NGen DNASTAR application (version 11.2.1) (DNASTAR, Madison, WI, USA). Genome sequences were available into GenBank under accession numbers KX343200-KX343209." ] },{ "paper_id": "1ccf19a7957dd88ddcce92605007ad16f26d28ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "doi:10.1371/journal.ppat.1005373.g008 system are probably promoting expansion of the fusion pore connecting an envelope and endosomal membrane." ] },{ "paper_id": "1cd1d321b575ccec089326f7b5d66d44e5c99bed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1cdf5f7fb665c7d9efaf8562af501d3b3bdd9273", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1ce01bfd8909920c3da397b92d9803389f043268", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "3D EcoRI-R AAT TAA TTC ATC GAT GAA TTC GGG CC 3D BglII-F GGC AAA GAA GTG GAG ATC TTG GAT GC" ] },{ "paper_id": "1cedf8c2a09236302e9b5717604bdb98bae977ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The metatranscriptomic data were deposited at NCBI GenBank SRA under BioProject accession no. PRJNA320636. The metagenomic libraries were deposited in iMicrobe under project code CAM_P_0001109.", "Support is acknowledged from Science for Life Laboratory, the Knut and Alice Wallenberg Foundation, the National Genomics Infrastructure (funded by the Swedish Research Council), and Uppsala Multidisciplinary Center for Advanced Computational Science for assistance with massively parallel sequencing and access to the UPPMAX computational infrastructure. Support by BILS (Bioinformatics Infrastructure for Life Sciences) is also gratefully acknowledged. The Ask\u00f6 Laboratory (Ask\u00f6, Stockholm Archipelago, Sweden) is acknowledged for permission to use their field and laboratory facilities. We thank Mark D. Adams for providing feedback on data interpretation and the manuscript and the Sorcerer II staff and crew for sample collection.", "Supplemental material for this article may be found at https://doi.org/10.1128/ mSystems.00125-16. " ] },{ "paper_id": "1cf0ff471514dc73eaa490d65d0d4a35f1345f6e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This research protocol was approved by the Departmental (IFR48) Ethic Committee and did not require patient consent. Only biological archival material was used (no specific sampling, no modification of sampling procedures). All information contained in databases was de-identified. ", "Sequences were analysed and compared with H1N1sw 2009 HA and NA sequences available in databases at mid-October 2009. Complete HA and NA amino-acid sequences were aligned with ClustalX [18] and phylogenetic trees were built using nucleotide or amino-acids alignments with MEGA version 4.1 [19] using various methods (Neighbor-Joining, Maximum Parsimony and UPGMA) with 1,000 bootstrap replicates. ", "The biological material studied here was used only for standard diagnostic procedures following physicians' prescriptions (no specific sampling, no modification of the sampling protocol). Analysis of data was performed using an anonymized database. Following local regulations, this procedure did not require a specific consent from patients." ] },{ "paper_id": "1d034e288cb8c4eb1f407a4f61d9c553ea30a670", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1d05dbf38f98918269d71020f0c9ff616548c2df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1d0c8b03f2da34c55161d6205a97d06d373762c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The weighted trachea specimen was ground (parameter: 30 tps) into a homogenate with a beveller (type: QIAGEN, Spoorstraat, Netherlands), and then the products were ground for 3 minutes (parameter: 30 tps) again, to which serum-free MEM was added. The supernatant obtained from a 5-minute centrifugation (at 4 \u00b0C and 5000 rpm) was fractionated into two centrifuge tubes for later tests.", "The cultured cells were harvested and fixed in 2.5% glutaraldehyde for transmission electron microscopy (TEM) examination (JEM-1200, Tokyo, Japan).", "Viruses 2014, 6" ] },{ "paper_id": "1d105041da2d3a6e6e16cd0dce1f0a672066d407", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by the National Key R&D Program (2017YFD0500600) of China and the Key Program for Natural Science Foundation of Heilongjiang Province (ZD2017007).", "After infecting the MDCK cells with CAdV-2 at a multiplicity of infection (MOI) of 10 and incubating them at 37 \u2022 C for 24 h, the infected and uninfected cells were fixed with 4% paraformaldehyde for 15 min and probed with different mAb supernatants (SP2/0 supernatants as control) for 1 h at 37 \u2022 C. Bound antibodies were visualized using fluorescent-conjugated antibodies against mouse IgG (TIANGEN, Beijing, China) on a fluorescence microscope.", "XC and KY conceived the study and designed the experimental procedures. SW, YW, GD, and XL performed the experiments. YW, GD, MS, and JG acquired the data. SW, YW, TA, and XL analyzed the data. SW, MS, XL, and JG contributed reagents and materials. SW, TA, KY, and XC wrote the manuscript. SW, TA, GD, MS, KY, and XC approved the version to be published.", "samples was detected as positive and 19 of the 20 tested serum samples were detected as negative. Identical results can be seen for strips from the same batch and different batches after different times in storage. Table 3 ). The positive rates of the PCR and ICS tests were Times 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4" ] },{ "paper_id": "1d13029ab155210da6e202f8cb5d902d7eabe226", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MB, SKP, PKS, APA and RCP designed the experiments. MB, SD and SP carried out the experimental work. SKP, PKS and MB were involved in scientific discussion and analysis of the data. MB, SKP, ******** PKS and APA drafted and revised the manuscript. All authors read and approved the final manuscript.", "Ethical approval was not necessary. All the animals under this research were clinical cases and were examined, diagnosed and treated as per standard treatment and examination procedure.", "Dogs in and around Bhubaneswar suffering from diarrhea and vomiting were selected for the study as " ] },{ "paper_id": "1d14e19f66d1a9c36b98aa2365aab80e9845616e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This is an immunodiffusion-based approach used to measure antibody responses to influenza virus internal proteins NP and M, following vaccination or infection [22] . Due to lower sensitivity, complement fixation has been replaced by HAI, VN, and EIA assays.", "Serological assays most commonly used to detect influenza virus-specific antibody responses include hemagglutination inhibition assay (HAI), microneutralization or virus neutralization assay (VN), single radial hemolysis (SRH), complement fixation assay, enzyme linked immunoabsorbant assay (ELISA) and Western blotting.", "SRH is a technique commonly used to determine the induction of antibodies following natural infection or vaccination. It is used to measure complement-mediated hemolysis induced by antigen-antibody complexes. SRH is considered more sensitive than the HAI assay and does not require pretreatment of the serum to inactivate non-specific inhibitors." ] },{ "paper_id": "1d14fd3be698da4aa12b91523c9d099f76775604", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "C57/B6 mice were purchased from Charles River. All animal procedures were approved by the University of North Texas Health Science Center Animal Care and Use Committee.", "Neutrophils were lysed and proteins were separated by Tris-Glycine polyacrylamide gel. The proteins were transferred to a nitrocellulose membrane, and the membrane were blocked for 1 hour with 5% non-fat dry milk in PBS and incubated over night at 4\u00b0C with primary antibodies. The membranes were repeatedly washed with PBS prior to incubation with secondary horseradish peroxidase-conjugated secondary antibodies. The blots were developed with an enhanced chemiluminescence reagent. The images were acquired and analyzed by a Western blot imaging system (UVP, upland, CA).", "CXCL2: Forward 5' gccaagggttgacttcaagaac 3' Reverse 5' aggtcagttagccttgcctttg 3' TNF-\u03b1: Forward 5' gcctcttctcattcctgcttgt 3' Reverse 5' caggcttgtcactcgaattttg 3' IL-1\u03b2: Forward 5' ggtgtgtgacgttcccattaga 3' Reverse 5' tcgttgcttggttctccttgta 3' IL-6: Forward 5' gacttccatcgagttgccttct 3' Reverse 5' ttgggagtggtatcctctgtga 3'" ] },{ "paper_id": "1d2a06d34c1ae369008931acca5000233e246011", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tobacco or cigarette smoke regulates airway gene expression via two main mechanisms, by altering the status of (i) chromatin remodeling, and (ii) DNA methylation of the target genes (Figure 1 ) (52-54).", "The First Line of Defense in the Lung-The Innate Immunity and Inflammasome", "The lungs are vital organs involved in gas exchange between the vascular system and the external environment, thus they are greatly exposed to the environment-derived microorganisms, including fungi, viruses, and bacteria. The bronchial tree and parenchymal tissues of the lungs, that until recently were considered as sterile, are colonized by phylogenetically-diverse microbes.", "AECOPD is a complex yet multifactorial consequence of COPD. Most of the exacerbations could be triggered by infectious (up to 80%) or non-infectious agents (\u223c10%) (AECOPD with known etiology), whereas up to 30% of cases are of unknown etiology (132, 133) . Respiratory tract infections are the major causes for AECOPD with known etiology and are mainly attributed to infections by viruses, bacteria, and atypical bacteria (not detected with conventional Gram-staining) (11, 134, 135) . Non-infectious causes of AECOPD include air pollution, environmental factors, meteorological effects, and comorbidities of the patients, all of which are partially contributing to COPD exacerbations (133, 135, 136) .", "In this review we will focus on NTHi, one of the dominant genera that is relatively abundant in the total COPD-dependent lung microbiome, due to its role of infection in COPD immunological responses (136, 149, 192-195, 198, 204-206) ." ] },{ "paper_id": "1d2c4cd6798ba4eb5e8e062248a7853df4bc74ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Of these species 37 had a confirmed or suspected human host, 6 were parasite or animal viruses, 12 were plant viruses and 49 were bacteriophages.", "Our protocol, including viral capture probes followed by metagenomic sequencing, was evaluated on airplane sewage from 19 long distance airliners.", "Sampling was done as previously described [25] . Briefly, airplane toilets were sampled from 19 long distance flights arriving in Copenhagen between June and September 2013, from the nine cities: Bangkok, Beijing, Islamabad, Kangerlussuaq, Newark, Singapore, Tokyo, Toronto, and Washington DC, with permission from the airline (SAS) cleaning service. Three 0.5 L samples of toilet waste were obtained from each airplane, pooled, aliquoted, and stored at -80\u02daC until nucleotide extraction (Fig 1) .", "In addition, the negative controls also had large numbers of bacterial Thermus sp. reads, most likely being a DNA contaminant of the used Taq polymerases as this protein was originally isolated form Thermus aquaticus YT-1 [38] , stressing the importance of the inclusion and analysis of negative controls to reduce false positives [39] ." ] },{ "paper_id": "1d32215c90a79509e66eb1f6e3e05b077d08ee1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "were maintained in Dulbecco modified Eagle medium (DMEM; Sigma) supplemented with 5% fetal bovine serum (FBS; Invitrogen). The stable cell line BSR-VP6 was grown in DMEM-5% FBS supplemented with 7.5 g/ml of puromycin (Sigma). Equine dermal (E. Derm) cells (NBL-6, ATCC CCL-57) were cultured in Eagle minimum essential medium (MEM; Sigma) supplemented with 10% FBS and 1% nonessential amino acids. Mammalian cell lines were cultured at 37\u00b0C in a 5% CO 2 humidified atmosphere. Insect KC cells, derived from Culicoides midges (26) , were maintained at 28\u00b0C in Schneider's insect medium supplemented with 10% FBS.", "Plasmids. For the AHSV1 RG system, the coding regions of the corresponding segments were inserted in the pCAG-PM vector (18) using AflII and PacI restriction sites. The corresponding expression plasmids were designated pCAG-AHSV1VP1, pCAG-AHSV1VP3, pCAG-AHSV1VP4, pCAG-AHSV1VP6, pCAG-AHSV1VP7, pCAG-AHSV1NS1, and pCAG-AHSV1NS2 and confirmed by sequencing. T7 plasmids carrying AHSV transcripts were generated using a sequenceindependent cloning system as previously described (17) . Briefly, genomic dsRNA was ligated to a self-annealing primer before reverse transcription (RT)-PCR amplification with an adaptor primer. Each cDNA amplified from AHSV segments was cloned into the pUC19 vector and sequenced.", "IMPORTANCE" ] },{ "paper_id": "1d39fce3c09c95c13c9b8e18c1ab9a85c24ff7c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "How to cite this article: Ismail ZM, El-Deeb AH, El-Safty MM, Hussein HA (2018) Enhanced pathogenicity of low-pathogenic H9N2 avian influenza virus after vaccination with infectious bronchitis live attenuated vaccine, Veterinary World, 11 (7): 977-985.", "All applicable institutional guidelines for the care and use of animals were followed in the Central Laboratory for Evaluation of veterinary Biologics (CLEVB).", "The interpretation of ELISA results was as follows:" ] },{ "paper_id": "1d44b78805f7baf17f811f8e5957c546c020abbc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We conducted a case-control study in one large metropolitan pediatric hospitals, located in Rome, Italy, between June 2012 and February 2018. Bambino Ges\u00f9 Children's Hospital is the largest pediatric research hospital in Europe. It accounts for nearly 600 beds and admits several patients from outside the Lazio Region, especially those with chronic and severe diseases. It performs every year a total of over 1 million and 690 thousand pediatric clinical encounters.", "Nasopharyngeal aspirates were performed and processed using a specific panel detecting the following viruses: RSV, influenza virus A and B, human coronavirus OC43, 229E, NL-63, and HUK1, adenovirus, hRV, parainfluenza virus 1-3, human metapneumovirus-hMPV, and human bocavirus-hBoV.", "Samples of nasopharyngeal aspirate were collected within 24 h from hospital admission and processed immediately, or stored at \u221270 \u2022 C until performing the test." ] },{ "paper_id": "1d45a0c89997d27fe2e01fbee4b407e01cc595c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Information and phylogenetic groupings of sequences used in this study. 1, 2, 3, and X denotes groups 1, 2, 3, and unclassified (early viruses; see main text for explanation). Empty entries indicate the unavailability (e.g., no sequence found, too short, too many ambiguous codes, and too many gaps) of the sequence. ", "We found previously unrecognized phylogenetic discordance between gene trees involving human and cat isolates (n = 25, denoted in red in Figures 1, S1-S3)-the main focus of our study-suggesting that they are reassortant viruses descending from group 2 and 3 lineages. In addition, the placement of two avian viruses isolates from Java (Ck/IDN/Semerang1631-62/07 and Ck/IDN/Magelang1631-57/07, shown in blue in Figures 1A and S2C ) differed between HA and NA phylogenies, suggesting another reassortment event.", "The BSP analyses ( Figure 3E-3H) indicate that the reassortant viruses follow a logistic-like growth curve, which is typical for virus invasion and maintenance, especially in a structured population [24, 25] . In contrast, the group 2 viruses followed a more continuous and relatively slow growth in diversity. There was insufficient data in our samples to definitively discriminate between alternative population growth models and provide narrow confidence intervals for parameter estimates, but our results are suggestive and future sequencing will add to the needed statistical power.", "The H5N1 highly pathogenic avian influenza (HPAI) virus was originally isolated from a farmed goose in Guangdong province of China in 1996 [1] , and soon spread to live-poultry markets in Hong Kong [2] , resulting in 18 cases of human infection in 1997, 6 of which were fatal [3, 4] . The first wave of H5N1 infection ceased after the depopulation of all poultry in Hong Kong, although the H5N1 virus was later found to circulate continuously in Southern China without causing apparent disease symptoms among infected poultry [5] . H5N1 outbreaks recurred in 2003, persistently affecting poultry farms in many Southeast Asia countries, such as China, Thailand, Vietnam, Indonesia and Cambodia. The viruses also spread outside Asia, including to some European countries. More importantly, occasional zoonotic transmissions to humans occurred in most of the affected Asian countries and the virus continued to pose a serious threat to global public health [6] ." ] },{ "paper_id": "1d4793842e3eeae37f34abb1541b0cee61ff976d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The research protocol was reviewed and approved by the Argentina Ministry of Health and the Argentina office of the Pan American Health Organization. Health authorities strived to maintain case-patient confidentiality by protecting data elements that help third parties identify them. Health utilization survey participants provided verbal informed consent prior to participation.", "Introduction: While there is much information about the burden of influenza A(H1N1)pdm09 in North America, little data exist on its burden in South America." ] },{ "paper_id": "1d55a99be0e217434aa3a7bfafb4d83c83d12525", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Direct transmission occurs mainly by the oral route, e.g. through ingestion of feed contaminated with the virus [10, 11] . Indirect transmission could occur through fomites e.g. contaminated trucks and equipment [3, 12] .", "The model was developed in @Risk 6 (Palisade Corporation). Runs were made using 10,000 iterations and Latin hypercube.", "Herd incidence in SDPP producing countries from where pig plasma is imported (HerdInc)", "In Europe, in the 1990s, serological surveys made in different Member States showed a low prevalence of the virus. During the last decade a few recent outbreaks have been reported from the EU (e.g. in Italy, Germany, Belgium, The Netherlands and Ukraine) [3, 7, 8] .", "The incubation period of the disease is between 1 and 4 days. The infectious period can last between 1 and 5 weeks [4, 21, 22] , and growing pigs can recover within 1 or 2 weeks. Maternal antibodies can protect piglets and re-infection might occur after immunity wanes [4, 6, 7, 23] ." ] },{ "paper_id": "1d572b31e29c16909825aa14dc9e462020d95303", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1d613eb26d86e376a5f8cb5fdb673b7254110936", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "4. Calculate B(T a ) using Eq 5.", "We evaluate whether H a,b is more plausible than H T by calculating the Bayes factor [20] , using the corresponding likelihoods. When our initial beliefs are a priori equally probable, pr(H a,b ) = pr (H T ), the Bayes factor", "3. Use the average hRi a,b as an estimate of the parameters R a,b .", "1. Let T a consist of the first i trees in T and T b = T\\T a ;", "2. Estimate the pair of posterior distributionsp\u00f0R a;b j\u03a4 a;b \u00de using Eq 3; Numerical integration of the normalization constant was performed using the trapezoidal rule." ] },{ "paper_id": "1d6e09ce2559ff9fcb55f3351110880446b477fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quantitative mass spectrometry-based proteomic analysis of RNAinteracting proteins (qTUX-MS)" ] },{ "paper_id": "1d720a06cad9b69f7f45a4e7549142738114287e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The stability of IgY when subjected to feed processing", "1) They are highly effective." ] },{ "paper_id": "1d75590848a42f84359d8ff9631fdc3145efd631", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All cells used in the study were grown in Dulbecco's Modified Eagle Medium (DMEM, Lonza, Verviers, Belguim) containing 20% (v/v) heat-inactivated fetal calve serum (FCS) (Hyclone, Lonan, Utah) and penicillin (100 IU/mL)/streptomycin (100 mg/mL) (P/S) Invitrogen-Gibco) at 37 \u2022 C in a humidified 5% CO 2 incubator.", "Simian rotavirus SA11 was used and prepared as described previously [39, 43] .", "All numerical results are reported as Mean \u00b1 Standard Error of Mean (SEM). The statistical significance of differences between means was assessed with the Mann-Whitney test using GraphPad Prism 5 (stationary-pc/mac version; GraphPad Software Inc., La Jolla, CA, USA). The statistical significance was defined as P \u2264 0.05." ] },{ "paper_id": "1d7f8850c5244fdc9b387038e7eeae9bcbbde6d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1.", "where x t i defines the pollen i at iteration t. L denotes the pollination's strength or the step size. F * is the target position or best solution. In some cases, insects can fly with different distance steps for a long space; therefore, Levy fly distribution is applied to simulate this movement.", "SSA is an optimization technique introduced by [48] . It simulates the Salps' behavior in nature. This behavior is called salp chain. The mathematical model of SSA begins by splinting its population into a leader group and followers group. The leader is the front salp, whereas, the followers are the other salps. The search space is determined in n-dimensions with n variables. Equation (10) works to update the salps' positions." ] },{ "paper_id": "1d8b7f079d5b7a6f9ecd1a0999f16582df84fd8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA substrates were prepared as described earlier [12] .", "Chikungunya virus (CHIKV) (family Togaviridae, genus Alphavirus) is transmitted by Aedes mosquitoes. It causes an acute febrile illness associated with severe joint pain that can persist for a long time even after viral clearance. Due to changing patterns of vector distribution, abundance in response to climate change and increased vectorhuman contact, CHIKV is regarded as a potential worldwide public health problem, with no preventive or therapeutic means available.", "The RNAs were separated from unincorporated radioactive nucleotides by two rounds of gel filtration through Sephadex-G50 columns.", "Viral RNA was isolated from infected C6/36 cell culture supernatant (Virus: Andhra Pradesh strain, isolated during 2006 outbreak in India, Genbank accession number: EF027134.1) using QIAamp viral mini kit (Qiagen, Germany) as per the manufacturer's instructions. Purified RNA was reverse-transcribed using Superscript II reverse transcriptase (Invitrogen). Truncated nsP2 region (2161-3552 nt, spanning 166-630 a. a. of the CHIKV nsP2) was PCR amplified using Pfx polymerase (Invitrogen) and cloned in NdeI/BamHI sites of pMal-5cX vector (New England BioLabs) (NEB)." ] },{ "paper_id": "1d8d4fed8118f54a4a5db8892cc5e5bbbf19afa4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by the Ethical Committee of Nippon Veterinary and Life Science. University (Permission number: 29-5). We confirmed in the revised manuscript that this treatment meets the standards set out in NC3Rs primate guidelines and follows veterinary care best practice guidelines.", "Written informed consent was obtained from the owner of the patient dog for publication of this case report. ", "Abbreviations CIBDAI, canine inflammatory bowel disease activity index; FMT, fecal microbiota transplantation; IBD, inflammatory bowel disease; GI, gastrointestinal." ] },{ "paper_id": "1da61ea537e7b6a6b56a2ac371e9e95442078672", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We applied the non-probability sampling strategy for our specimen collection with incidental assignment approach as previously described [24] ." ] },{ "paper_id": "1da81f5357aef31dd451b4ed90e7fb255c9af8ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Three locations were selected, at different administrative levels, i.e. province, municipality and barangay; a barangay is the smallest administrative division in the Philippines and is equivalent to a village.", "Methods: Three locations were selected, at the scale of province, municipality and barangay (i.e. village). Data on disease incidence, programme activities, and programme management were collected on-site through meetings and focus group discussions." ] },{ "paper_id": "1dad67bd586092707fb9e7d311d465b82b85425f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Semliki Forest virus (SFV), and some flaviviruses induce spherules or invaginated vesicles (9) (10) (11) (12) (13) (14) (15) .", "Citation Maier HJ, Hawes PC, Cottam EM, Mantell J, Verkade P, Monaghan P, Wileman T, Britton P. 2013. Infectious bronchitis virus generates spherules from zippered endoplasmic reticulum membranes. mBio 4(5):e00801-13." ] },{ "paper_id": "1db4560940a913194230a37755d10fa154b09d15", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral haemagglutinin binds to cell surface receptors in susceptible host cells. In humans, virus binds to sialic acid \u03b12, 6-galactose (SA\u03b12, 6-Gal) linked receptors whereas avian viruses preferentially bind to sialic acid \u03b12, 3-galactose (SA\u03b12, 3-Gal) linked receptors [10, 11] . SA\u03b12, 6-Gal linked receptors are the predominant type in the trachea of chickens, while duck tracheas contain more SA\u03b12, 3-Gal linked receptors [12] . This may be one reason why chickens have the potential to act as an intermediate host for human infection.", "HPAI H5N1 remains a concern, with new strains continually evolving and increasing the pandemic threat from this subtype. Worryingly, the recently emerged H7N9 subtype also poses a risk of being the vector by which a human influenza epidemic occurs. The first human infections by this virus were reported early in 2013, and by June 2013, the mortality rate was over 30 % -a level still being seen as cases continue to be reported. The World Health Organization (WHO) has identified H7N9 as \"\u2026an unusually dangerous virus for humans\" [8] . Although not posing an imminent threat, H10N8 has also recently been identified as having the potential to spread from birds to humans if the necessary viral mutations occur [9] .", "Samples were prepared for mRNA sequencing using 5ug of total RNA starting material following the Illumina mRNA sequencing 8 sample preparation kit protocol. Resulting libraries were quality checked on an Agilent DNA 1000 bioanalyzer (Agilent Technologies, South Queensferry, UK) and then clustered onto a Single Read flowcell using the Illumina v2 cluster generation kit at a 4.75pM concentration. Thirty-six cycle single-ended sequencing was carried out on the Genome Analyser IIx using Illumina v3 Sequencing by Synthesis kits (Illumina, Little Chesterford, UK)." ] },{ "paper_id": "1db51d8c217cae965ebad4dabf0651a2ecd62e53", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since various blood-feeding animals may accumulate viruses of interest, VEM surveillance efforts should not be limited to mosquitoes exclusively. Here we summarize several groups of hematophagous arthropods and leeches that might be useful for surveillance purposes.", "Barbazan et al. reported a first targeted approach for vectored vertebrate virus detection using mosquito blood meals. They collected blood-engorged mosquitoes near a poultry farm during an outbreak of avian influenza in Thailand and found H5N1 virus sequences in the mosquito pools tested by using RT-PCR [25] ." ] },{ "paper_id": "1dc4f757f425b080168840089f1f4d29bac75f51", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where i X is the sample mean and \u03c3 i X is the SD for the sampling period. The meteorological effects are related to \u03b2t using the following linear component:", "Rather than fixing a value, mid-year population (Nyear) was used for each wave, so as to reduce the impact from natural mortality and birth.", "We conducted a sensitivity analysis addressing two aspects:" ] },{ "paper_id": "1dcfe803d2660b1fdfa8006aace78d485512e156", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We gratefully acknowledge the financial support of the Biotechnology and Biological Sciences Research Council (BBSRC) of the UK. RLI and SM-L are funded by BBSRC grant: BB/L006952/1. AT is funded by BBSRC grant: BB/J014567/1.", "It is known that SGTA promotes the deubiquitination of client proteins and hence appears to facilitate their rescue, or at least enables further attempts at promoting the acquisition of a functional fold. This relies on deubiquitinating enzymes (DUBs) that collaborate with components of the SGTA/BAG6 cycle. Further investigation is necessary to identify these DUBs and understand their contribution to this process.", "The complete lack of high-resolution structural information on this region of SGTA means molecular details pertaining to its interactions with hydrophobic substrates remain unclear. There are many outstanding questions with regard to this vital, yet poorly understood, substrate-binding domain of SGTA. These include mechanisms of TA-protein recognition and sorting, and the binding and release of MLPs determining their ultimate fate." ] },{ "paper_id": "1dd28ef7fb600a0ca94980bcf6e5cbccf52a77fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Zika virus (ZIKV) was a neglected, mosquito-borne flavivirus because of its assumed small geographical spread and mild clinical symptoms [1] such as fever, headache, rashes and etc [2] . The first biological ZIKV sample was isolated from a sentinel rhesus monkey in the Zika PLOS ONE | https://doi.org/10.1371/journal.pone.0180632 July 10, 2017 1 / 22 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "To allow comparison with the NS2B-NS3pro complexes of four Dengue serotypes (17), we selected three fluorophore-tagged substrates previously used (17) : namely Bz-Nle-Lys-Arg-Arg-AMC, Boc-Gly-Arg-Arg-AMC and Boc-Gly-Lys-Arg-AMC (Bachem AG, Bubendorf), which were dissolved in dimethyl sulfoxide for preparing stock solutions (100 mM). All enzymatic experiments were performed in triplicate and data are presented as mean \u00b1 SD, while IC 50 , Km and Ki were obtained by fitting with GraphPad Prism 7.0 [61] ." ] },{ "paper_id": "1dd7096290bcbcc5aa830706c5396155ef51bd39", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "September/October 2019 Volume 4 Issue 5 e00474-19 msphere.asm.org 13", "where g i is the gravitational acceleration and f 12 and f 13 are the surface tensions.", "Finally, \u2423 1 and \u2423 2 were obtained by equation 11 and equation 12:" ] },{ "paper_id": "1ddf28f6c2bc0a7db607b0771748e34fb6659f51", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SJ and LD conceived the idea and revised and edited the manuscript. NW and LD collected information and drafted the manuscript. JS performed the structural analysis. All authors read and made final approval of the manuscript.", "This work was supported by the NIH grants R01AI137472 and R01AI139092.", "Numerous subunit vaccines against SARS-CoV have been developed since the outbreak of SARS, the majority of which use the S protein and/or its antigenic fragments, in particular, RBD, as the vaccine target (Table 1) ." ] },{ "paper_id": "1de0f645bef4bb4fa6244abca0b1e0396fdea449", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conventional methods for determining etiology, such as bacterial culture of blood or nasopharyngeal swabs, and/or selective application of serological tests for a few organisms, are limited by poor sensitivity, or low specificity, or both. On the other hand, diagnostic techniques with greater specificity are limited by technical difficulty, invasive procedures, and high cost.", "A blood sample was drawn by venepuncture for routine investigations (hemogram, blood biochemistry). One to three ml blood was processed for bacterial culture using BACTEC 9240 (Becton Dickinson, Haryana, India) in Peds plus/F culture media (Becton Dickinson) [18] . The bottles were incubated at 37 \u00b0C for seven days and isolates were identified to species level by conventional biochemical and serological tests." ] },{ "paper_id": "1de438fe6e455f606c21b859df1769e2807c3546", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the UK, Tailby reports that 80% (of 185 000) nurses registered with NHS nurse banks had another nursing job, and 60% worked occasionally or regularly additional shifts paid at bank or agency rates [43] . In a survey among nursing magazines' readers in 2013 [45] , 54% declared taking up extra nursing work, and 10% another full time job outside nursing; 5 years later, 47% of the 900 nurses participating in another online magazine readers survey declared engaging in bank and/or agency shifts [37] .", "What are the consequences for health systems, specifically for the delivery of quality and safe nursing/health care? What are the consequences for nurses' welfare? What are the consequences for patients? What are health workers', managers', and patients' perceptions around this practice?", "From 228 records retrieved, 159 (70%) were excluded after reviewing their titles and abstracts (Fig. 1 ). An additional four articles were identified through snowballing search strategies, resulting in a total of 73 full texts assessed for eligibility. Of all these, a total of 35 (48%) articles finally met the inclusion criteria for addressing dual practices of nurses: 20 using predominantly quantitative methods and 15 using mostly qualitative designs. The vast majority of the studies were in English, with only four published in Portuguese and one in Spanish. Additional file 2 provides spreadsheets for the (a) list of included articles organised by study-type, (b) the data extraction table, and (c) list of articles excluded with the respective reasons.", "Based on the overarching aim of the paper, the preliminary knowledge of the literature, and a priori consultation with health professionals [13] , we developed the following set of questions to guide the data extraction for the review:" ] },{ "paper_id": "1de4de4c1b8a4d3c18f20867febc8f4a2758dfd9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(e.g., daf-2), Drosophila melanogaster (under dietary restriction, rapamycin treatment or insulin-like mutants), mice (under dietary restriction and IRS1 long-lived mutants) and human muscles biopsies (under modest dietary restriction) showed the small nucleoli phenotype [30]. On the other hand, cells from Hutchinson-Gilford progeria syndrome (HGPS) patients and cells from aged healthy individuals showed the expanded nucleoli phenotype [31]. In yeast, nucleolar structure goes through two different phases during aging as well: first, expansion and, secondary to this, fragmentation [32,33]. The above observations, conserved throughout evolution, could be employed as a predictive cellular marker for aging in both healthy and aged individuals [34,35].", "The size and shape of the nucleolus are tightly related to the growth and proliferation status of the eukaryotic cell, and this is known since several decades ago [16, 17] . An increase in size correlates with a high growth and proliferation rate [18] , and this feature has been used by pathologists over decades as a prognostic marker in tumour tissue samples [19] . In fact, for a specific type of cancer, the Clear Cell Renal Cell Carcinoma (ccRCC), the nucleolus is used as the main marker to establish the histological grade [20, 21] . Tumour samples with a normal nucleolar number, size and shape correlates with a good prognostic, while an enlarged size and/or irregular shape correlates with a bad prognostic [22] [23] [24] [25]. Ribosome biogenesis is thus becoming an important aspect of cancer biology [26][27][28]. Remarkably, nucleolar size and aging are also correlated; small nucleoli and reduced ribosome biogenesis are hallmarks of longevity, whereas expanded nucleoli, elevated ribosome biogenesis and increased protein synthesis are hallmarks of aging [29]. On the one hand, long-lived mutants of Caenorhabditis elegans Cells 2019, 8, 779 3 of 22", "As in Saccharomyces cerevisiae, different nucleolar rearrangements do occur in higher eukaryotes during stress, the cell cycle or as a result of cell aging. These morphological changes take place despite obvious differences in nuclear and nucleolar physiology; namely, a closed mitosis without nucleolar disassembly in the case of the budding yeast versus an open mitosis with transient nucleolar disassembly in higher eukaryotes [10] . Another major difference lays on the different architectural complexity of the nucleolus. In higher eukaryotes a define set of compartments can be easily distinguished under the microscope: the fibrillary center (FC), the dense fibrillary component (DFC) and the granular component (GC), i.e., a tripartite compartmentalization. By contrast, in the budding yeast only a bipartite compartmentalization, comprising fibrillar and granular components, is present. The main differences are summarised in Table 1 . Each compartment undertakes a specific task; traditionally, FC is where rDNA transcription occurs, DFC where rRNA processing takes place and GC is dedicated to late rRNA processing and pre-ribosomal particles assembly [11] . Thus, the alteration and reorganization of these spatial structures are indicative of alteration in nucleolar function [196] . Remarkably, nucleolar morphology, visualised by NORs silver staining (AgNORs), is correlated to tumour DNA content and ploidy; aneuploid tumours have higher AgNORs counts [197, 198] . This could be due to amplification of the five human acrocentric chromosomes (13, 14, 15, 21 and 22) , where the NORs are located, as proposed in [23] . On the other hand, rDNA copy number variation, increasing the copies of 5S genes while decreasing the 45S copies, have been linked to nucleolar activity, proliferation and inactivation of p53 [199] . All these rDNA changes may operate as a tumour adaptive strategy to promote genome instability." ] },{ "paper_id": "1df0f9012de37de02b7af4bd23931f626c7bbc71", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1dfc1d885254d7df5f71844b7de87fb6c9539662", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supernatant titrations were performed with TCID 50 / ml, using Reed & M\u00fcnch formula [16] .", "The thermocycler was preheated to 50\u00b0C for 2 min, after which the reaction tubes were placed, reverse transcription was carried out at 50\u00b0C for 30 min, and reverse transcriptase was inactivated for 15 min at 95\u00b0C. The reaction was carried out under the following conditions: 94\u00b0C 2 min, (94\u00b0C 1 min, 55\u00b0C 1 min, 72\u00b0C 90 min) for 40 cycles, with a final period of 10 min at 72\u00b0C. Selected primers and their specifications are shown in Table 1 .", "The authors declare that they have no competing interests." ] },{ "paper_id": "1e0851ed44e0459ff83448af23b81560a41ede72", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A sample was defined as bacteriologically positive if the bacteria were present at 10 7 CFU/mL or more for sputum, 10 6 CFU/mL or more for bronchial aspirates and 10 4 CFU/mL or more for bronchoalveolar fluid.", "Quantitative variables were presented using the median (quartile 25-75) and were compared by t-test or variance analysis. Qualitative variables were compared using a Chi2 test or a Fisher-exact test. Outcomes were compared using a logistic regression multivariable model, with adjustment for time since transplantation, age and sex. A sensitivity analysis was carried out excluding patients who had had a BOS before inclusion. All of the statistical analysis was done using R software, version (3.1.1).", "Pseudomonas aeruginosa (n = 4), Corynebacteriae striatum (n = 2) and others (n = 2). Three patients had more than one detected virus and eight patients had more than one detected bacteria." ] },{ "paper_id": "1e1f8ec1fffc3e243c9c5b53baf146f0e7c6ddb0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells and Viruses-Mouse leukemic monocyte-macrophage (RAW264.7) cells (European Collection of Cell Cultures) were grown in Dulbecco's modified Eagle's medium (DMEM) with 4.5 g/liter D-glucose \u03e9 L-glutamine \u03e9 pyruvate (Invitrogen), supplemented with 10% (v/v) FBS and 1% (v/v) penicillin/streptomycin (5000 units ml \u03ea1 penicillin G sodium; 5000 g ml \u03ea1 streptomycin sulfate in 0.85% saline (Invitrogen)) at 37\u00b0C in 5 % CO 2 . MNV1 strain CW1, propagated in RAW264.7 cells, was described previously (38) . Virus titers were estimated by determination of the 50% tissue culture infectious dose (TCID 50 ) units per ml. For a multiplicity of infection (MOI) equal to one, cells were infected with 1 TCID 50 unit/cell.", "SDS-PAGE and Immunoblotting-Protein concentrations of the cell lysates were determined by a bicinchoninic acid (BCA) assay using the Pierce BCA protein assay kit (Thermo Scientific) as per the manufacturer's instructions. The samples were adjusted to the same concentration of between 20 and 50 g of protein and made up to 30 l with NLB and SDS (3\u03eb) sample buffer (New England BioLabs, Hitchin, UK). The proteins were then separated by SDS-PAGE (Mini Protean TGX gels; Bio-Rad) and transferred to polyvinylidene fluoride (PVDF) Immobilon-P membrane (Merck Millipore) for subsequent immunoblotting using conventional methods (40) . Following incubation with primary antibodies, washes, and incubation with secondary antibodies, the membranes were probed for chemiluminescence using SuperSignal West Pico Chemilumi-nescent Substrate (Thermo Scientific), and the signal was detected on radiographic film (Fuji RX, Fisher).", "The phosphorylation of eIF4E plays a critical role in controlling protein translation. Results: MNV1 infection results in activation of p-eIF4E, its relocation to polysomes, and translational regulation. Conclusion: MNV1 manipulates the host cell translation machinery by controlling eIF4E activity. Significance: Regulation of cellular response to infection may contribute to viral pathogenesis and persistence. 4 The abbreviations used are: VPg, viral protein, genome-linked; MNV, murine norovirus; FCV, feline calicivirus; eIF, eukaryotic initiation factor; 4E-BP, eIF4E-binding protein; TCID 50 , 50% tissue culture infectious dose; MOI, multiplicity of infection; hpi, hours postinfection; p-eIEF4E, phosphorylated eIF4E; qPCR, quantitative PCR." ] },{ "paper_id": "1e2493a8e26be4ff934b96dedc32dc7cf5728370", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were harvested and disrupted on ice by sonication (VCX 750, SONICS, Newtown, CT, USA) using a program (45 cycles of 2 sec On/5 s Off, amp 20 %) and centrifuged at 20,000 g for 15 min at 4\u00b0C. The pellets and supernatants were separately stored at \u221220\u00b0C until use. Protein concentration was measured by Bradford assay (BioRad, CA, USA) using bovine serum albumin (BSA) as a standard. Protein expression was evaluated using band intensities of recombinant protein on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) from independent and/or parallel induction samples.", "The Student's t test was used for all statistical analyses, and p-values of less than 0.05 were considered statistically significant." ] },{ "paper_id": "1e2989b7156dc944d0a24b596fd17aaa08b3b56c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(page number not for citation purposes)", "The bronchoscope was wedged in the distal airway. The initial 25 ml of warm saline injected was discarded. Five further 25 ml aliquots were instilled and aspirated. A portion of the aspirated fluid was spun at 1,500 \u00d7 g for 10 minutes at 4\u00b0C. The supernatant was stored at -80\u00b0C. Samples were assayed by ELISAs for PTF levels (Enzygnost F1 + 2 monoclonal assays; Behring, Marburg, Germany) and for t-PA antigen levels (Tin-tElize tPA, Biopool International, Ventura, CA, USA)." ] },{ "paper_id": "1e39b7b66d19b0beaf607a0ea98ea1d13c402ad9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The nsp12 gene was amplified by PCR and inserted into vector pMAL-c4X (New England Biolabs). MBP-nsp12 was expressed in E. coli and purified using Amylose Resin (New England Biolabs) according to the manufacturer's instruction.", "HC and XX conceived and designed the research. HN, JL, MT, SD, JT, and LL performed the Y2H screening. HN, JL, and JT conducted the BiFC assays. HN and JL carried out pull-down assays. HC, XX, HN, and JL analyzed the data. HC wrote the manuscript.", "The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmicb. 2018.00970/full#supplementary-material" ] },{ "paper_id": "1e4181fec183b68f1c863a6465c4a39c867008dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition to the Online Report, the ICTV is also partnering with the Journal of General Virology to publish short summaries of each report chapter (21) . These ICTV Virus Taxonomy Profiles are published at the same time as the Online Report chapters, and consist of a two to three-page review of the properties of each virus family. These profiles serve as citable references for the Online Report chapters (22) .", "In the past, the ICTV has continually modified and modernized its approach to virus taxonomy through, for example, moving to sequence-based characters as the primary source of information needed for classification (30) ; developing and utilizing automated computational methods to facilitate the grouping of viruses into taxa (existing and new) based on a comparison of their genomic sequences (10, (32) (33) (34) (35) ; operating more efficiently and shortening the time taken to approve proposals for new taxa; and now, basing taxonomic decisions solely on the information contained in genomic sequences (30) . It is only through this process of continued evaluation of the current state of virus discovery and research, responding to new data and new understanding by updating policies and procedures, that the ICTV will be able to remain current and continue to be relevant to the scientific community.", "The complete taxonomy for any one release (the Master Species List) is also available for download as an Excel spreadsheet (http://ictv.global/msl.asp). These spreadsheets are available for every release back to 2008. Each new taxonomy release is also shared with the National Center for Biotechnology Information (NCBI) of the National Institutes of Health so that the taxonomy database they main- tain and use for the annotation of virus sequence records can be kept up-to-date with the most recent ICTV taxonomy." ] },{ "paper_id": "1e6d38b98619d0d315d728291e97acde6c0012e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The model parameters describing transmissibility and clinical severity were chosen based on data from the 2009-H1N1 pandemic, with a basic reproduction number of 1.32 [23] [24] . Under the parameter values chosen (see Table S1 and [22] ), in a population with sufficient resources (i.e. when there are no shortages of oseltamivir, hospital beds, or ventilators), the scenario predicts an overall attack rate of 35.6%, a clinical attack rate of 24.9%, a peak prevalence (of symptomatic cases) of 0.94%, and a case fatality rate of 0.018%. In the absence of any resources, the case fatality rate is substantially higher at 0.029%, while attack rates and peak prevalence remain very similar." ] },{ "paper_id": "1e71a51670cdda3d92a1f182967d78dca3bb5d44", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The digestive tract is the entry site for transmissible gastroenteritis virus (TGEV). TGEV transmission can be prevented if local immunity is established with increased lymphocytes. The current parenteral mode of vaccination stimulates systemic immunity well, but it does not induce sufficient mucosal immunity.", "Specific IgG and IgA detection. The TGEV-specific IgG and TGEV-specific secretory IgA (sIgA) levels" ] },{ "paper_id": "1e7bcacaa32d4c0f5ed60e5e56897404d3896d81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No amplification was detected with heat-treated uninfected whole blood (data not shown)." ] },{ "paper_id": "1e7e3df5deec55ed5c2fa7f9cba8854c6aeb7ab6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Age and gender specific incidence I[i, j] per 1,000 residents were calculated using population P[i, j];", "Informed consent was obtained in accordance with international guidelines." ] },{ "paper_id": "1e8198cb2eac9d910c4f14712025d90ddb958204", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "R.A.B.); Vincent.munster@nih.gov (V.J.M.) \u2020 These authors contributed equally to this article.", "Materials and Methods", "Supplementary Materials: The following are available online at" ] },{ "paper_id": "1e863993819f87abe5cee255ccb97d623838542a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Parvoviruses consist of small non-enveloped, autonomously replicating, single-stranded DNA viruses with genome length between 4.5 -5.5 kb [1] . Bocavirus, a genus of the family Parvoviridae, is characterized by the presence of a third major ORF named NP1. Bocaviruses are known to infect multiple mammalian species including humans [2] , cows [3] , pigs [4] [5] [6] , gorillas [7] , chimpanzees [8] , California sea lions [9] , dogs [10] [11] [12] [13] , cats [11] , bats [14] , and pine martens [15] . Bocavirus infections can cause respiratory and gastrointestinal symptoms in young animals and humans, but are also often subclinical in adults [2, 16] . While many bocaviruses were initially identified in feces or respiratory secretion they can also be found in blood [2, 16] .", "Bocaviruses are believed to replicate through the parvovirus rolling hairpin model, which generate replication intermediates of concatemers with head-to-head or tail-to -tail structure [17] . Recent experimental evidence showed the presence of head-to-tail concatemers or circularized genomes of human bocavirus (HBoV) 1&3 [18, 19] and porcine bocaviruses [20] , indicating that some bocaviruses may use a rolling -circle replication model." ] },{ "paper_id": "1e88d68fd702c8accc72cece9a8df345c64b0b8c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All in vivo studies were performed in accordance to the guidelines of the Institute for Laboratory Animal Research (ILAR). These studies were part of an institutional animal care and use committee (IACUC)approved protocol and animals were housed in an AAALAC International accredited research facility. Since all experimental key readouts were terminal, all study animal groups were used once only and were euthanized at the end of each study.", "Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), also known as CD66a or biliary glycoprotein-1, is a multifunctional transmembrane protein expressed in diverse cell types, including epithelial cells and certain cells of the immune system. CEACAM1, like other structurally related CEACAM 3-8 proteins, is a member of the Ig superfamily with a basic structure of sequentially ordered Ig-like domains. This protein serves as an adhesion molecule via homophilic and heterophilic interactions and participates in multiple physiological and pathophysiological cell to cell processes [1] [2] [3] [4] . Moreover, direct immunomodulatory consequences have been suggested based on immune cell expression and the presence of ITIM motifs in the intracellular domain of the protein [5] .", "Early experiments investigating CEACAM1 in tumorigenesis denoted a pivotal role for CEACAM1 as a tumor suppressor. For example, prostate cancer cell line PC-3 transfected with CEACAM-1 demonstrated significantly lower growth rates and less tumorigenicity in vivo relative to controls [6] . Nittka et al. found that the Research Paper www.oncotarget.com absence of CEACAM1 on hyperplastic tumors correlated with reduced apoptosis of malignant cells [7] . Moreover, a lack of CEACAM1 in WAP-T tumor cells resulted in increased Wnt signaling, promoted cellular invasiveness, and strongly enhanced the rate of metastasis of mammary adenocarcinomas in vivo [8] . On the other hand, other investigations have suggested a role for CEACAM1 in angiogenesis and suppression of the neoantigen-specific anti-tumor response [3] ." ] },{ "paper_id": "1e8ec294fcc4507fcc89872f84adcf4633bb10e6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analytical evaluation using the quality-control panel", "Analysis of variance (ANOVA) and t-test were performed using Prism 5 (GraphPad Software, USA), and statistical significance was defined as p < 0.05. Positive and negative agreements and the related 95% confidence interval (95% CI) were calculated using MedCalc 13.0 (Med-Calc Software bvba, Belgium).", "The study protocol and informed consent documents were reviewed and approved by the Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University (ZJU Hospital), the Shanghai Public Clinical Health Center (SPHCC), the Nanjing Municipal Centers for Disease Control and Prevention (Nanjing CDC), the Zhejiang Provincial Centers for Disease Control and Prevention (Zhejiang CDC), the Guangdong Provincial Centers for Disease Control and Prevention (Guangdong CDC), the Guangzhou Municipal Centers for Disease Control and Prevention (Guangzhou CDC) and the Jiangsu Provincial Centers for Disease Control and Prevention (Jiangsu CDC). Written informed consent for the research use of clinical samples was obtained from all of the patients involved in the study." ] },{ "paper_id": "1e8fd672db3be95e223c83ea48b923fadb9d5d4f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1e912d2c58583bb9540a560d237fca233aefde70", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Huh7.5 cells stably expressing Firefly luciferase (Huh7.5 Fluc) were cultured in Dulbecco's modified minimum essential medium (DMEM, Gibco, Thermo Fisher Scientific, Schwerte, Germany) containing 2 mM L glutamine, 1% minimum essential medium nonessential amino acids (MEM NEAA, Gibco, Thermo Fisher Scientific, Schwerte, Germany), 100 \u00b5g/mL streptomycin, 100 IU/mL penicillin (Gibco, Thermo Fisher Scientific, Schwerte, Germany), 5 \u00b5g/mL blasticidin and 10% fetal bovine serum. Cells were maintained in a 37 \u2022 C environment with 5% CO 2 supply. Cells were infected with Jc1-derived Renilla reporter viruses in the presence or absence of compounds as described [44] . Infected cells were lysed and then frozen at \u221280 \u2022 C for 1 h following measurements of Renilla and Firefly luciferase activities on a Berthold Technologies Centro XS3 Microplate Luminometer (Bad Wildbad, Germany) as indicators of viral genome replication and cell viability, respectively.", ". Summary of all isolated and identified bacteria grouped on a phylum level as well as its source of isolation.", "An individual of both Holothuria leucospilota and Stichopus vastus were collected in Sari Ringgung, Lampung, Indonesia (coordinates: S 05 \u2022 33.706' E 105 \u2022 16.220') on the 19 April 2016. Sea cucumbers were kept cold on ice until the bacterial isolation was carried out." ] },{ "paper_id": "1e9719d2d1a523240172b19f822f7a956c553fdf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1e981bc1ac8d6a8ea0f8e21991e3f525ae0a16a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The global burden of inter-pandemic influenza is high. It is estimated to affect 1 billion people annually, with 3-5 million severe cases requiring hospitalization or intensive care treatment, resulting in approximately 0.5 million deaths [1] . Worryingly, drug-resistant influenza strains are emerging at a rapid rate that will severely hamper the ability of our healthcare systems to contain influenza outbreaks [2] . Therefore, alternative strategies are needed against severe influenza infections during both seasonal and pandemic influenza outbreaks.", "All human RNAs were analyzed on the Agilent Bioanalyzer (Agilent, Santa Clara, CA, USA) or the Perkin Elmer Labchip GX system (Perkin Elmer, Waltham, MA, USA) for quality assessment with RNA Integrity Number (RIN) or RNA Quality score range from 6.8-9.7 and median of 9.0. cDNA libraries were prepared using 2 ng of total RNA and 1 \u00b5L of a 1:50,000 dilution of ERCC RNA Spike in Controls (Ambion \u00ae Thermo Fisher Scientific, Waltham, MA, USA) using SMARTSeq v2 protocol [16] , except for the following modifications: ", "FASTQ files were mapped to the human genome build hg38 using STAR. Gene counts were computed using featureCounts (part of the Subread package) using annotations from GENCODE version 26. Differential gene expression analysis was performed using edgeR in a paired fashion under R version 3.3.3. Multiple testing correction was done using the method of Benjamini and Hochberg and p-values (False Discovery Rate; FDR) less than 0.05 was deemed to be significant." ] },{ "paper_id": "1e9929bbb08fb46de40a699d0c2d2aa7c287e5b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HRV-A strains case control ", "Further, when the HRV types were compared among the asymptomatic and RTI controls separately, there were no significant differences for any of the demographic, clinical, or molecular markers (Table S1 and S2) .", "HRV-C strains case control by performance of a bronchodilator nebulizer inhalation challenge prior to study enrollment; i.e., children in whom the lower chest wall indrawing resolved post-B2agonist nebulization challenge, regardless of its effect on wheezing, were not enrolled. These associations of HRV-A with more-severe LRTI and HRV-C with more wheezing disease have also been reported from a study in Burundi, where HRV-A was more prevalent among pneumonia and bronchitis cases and HRV-C among cases with acute wheezing (37) . An association between HRV-C and wheezing disease was also seen in a study which characterized the cell receptors for HRV-C infection in humans, namely, the CDHR-3 receptors, which facilitate HRV-C adhesion and replication (16) . A mutation (cysteine-to-tyrosine mutation at amino acid 529) in CDHR-3 enhances HRV-C binding and replication in vivo and has also been associated with increased susceptibility to wheezing and asthma illnesses (38) ." ] },{ "paper_id": "1eadeab29c774bb8b5935c5ce5d741855a8080a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(Emma -nurse)", "(Annanurse)" ] },{ "paper_id": "1eb37c6ac1e51907a8a1d5f31c45fff08737cb36", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Systems Biology: beginning to piece together the life sciences puzzle ", "The Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifies COPD into four stages; mild, moderate, severe and very severe according to spirometric measurements [16] . Spirometry, however, is believed to correlate poorly with symptoms [17] , quality of life [18] , exacerbation frequency [19] and exercise intolerance [20] .", "The authors declare that they have no competing interests." ] },{ "paper_id": "1eb822e2417937f3273c3423e25cd1344ba9a1e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To sequence SPAV-2, PsNV and CAV, the samples were prepared using the same method as above but sequenced by BC Cancer Agency using a HiSeq (2 \u00c2 125) protocol (four different samples indexed over one lane).", "Here, virus-discovery was implemented to screen for viruses associated with mortality. Together, sequencing of dead or moribund aquaculture salmon and live-sampled wild salmon, in-situ hybridization, and epidemiological surveys revealed that previously unknown viruses, some of which are associated with disease, infect wild salmon from different populations.", "The distribution of CAV was markedly different from SPAV. CAV was not detected in any juvenile wild or hatchery Chinook salmon, despite being detected in farmed fish on both the west and east coasts of Vancouver Island. Over 20% of moribund Chinook aquaculture fish tested positive for CAV, with most detections occurring in fish at least 1.5 years after ocean entry, well past the time when migratory salmon were sampled. Hence, infection by CAV may take a considerable time to develop, or be an infection that is only acquired by older fish. CAV was also detected in a small number of farmed Atlantic salmon (seven positive detections of 2816 fish tested). The monophyletic grouping of CAV with other disease causing aquareoviruses and the consistency with haemorrhagic disease suggest that the virus is important to monitor in cultured fish, and potentially wild adults returning after several years at sea." ] },{ "paper_id": "1ec08de8b92b3b6c9be98dcd92db0ddf3efdad44", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequences of PCR primers and TaqMan probes specific for feline immunomodulators and the housekeeping gene \u03b2-actin were either designed as previously reported [19, 22] or obtained from the literature [17, [23] [24] [25] [26] . The primer/probe sequences are listed in Table 2 .", "Precisely-regulated placental and decidual immunomodulatory molecules such as cytokines and chemokines are necessary to establish and maintain pregnancy [1] [2] [3] [4] [5] [6] . While many of the immunomodulators expressed at the maternal-fetal interface are products of decidual leukocytes such as T cells, NK cells, dendritic cells, and macrophages [2, 5, 7] , leukocytes are not exclusive producers of these molecules. Trophoblasts, including both cytotrophoblasts and syncytiotrophoblasts, are fetalderived cells of epithelial origin that form the placental chorionic villi. These cells contact and attach to the maternal endometrium and serve as a barrier between maternal and fetal blood supplies in human pregnancy [8] . Trophoblasts are a source of many cytokines and other immunomodulatory molecules that support both placental development and parturition [9] [10] [11] ." ] },{ "paper_id": "1ed4c31d7ee724f9937c3f91d2a91b01579a853c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. All statistical analyses were performed with GraphPad Prism 7 software (Graph-Pad Software, CA, USA). Statistical significance was ascribed to P values of less than 0.05.", "Accession number(s). Raw NGS data are available from the NCBI Sequence Read Archive under BioProject entry PRJNA453810. Pipeline and in-house scripts are available at https://github.com/ kasenriemersma/CHIKV-NGS-diversity.", "K.K.R. and L.L.C. conceptualized and designed experiments. K.K.R., C.S., and A.S. conducted experiments and data collection. K.K.R. performed data analyses and drafted the manuscript and figures. K.K.R., C.S., A.S., and L.L.C. edited and reviewed the manuscript. CACACGTAGCCTACCAGTTTC 1601R CCCGCTCTGTCCTCAAGCTG 60 2 1417F GAGGACTAGAATCAAATGG 2807R GATGCGGCTGCTGTCATGAC 55 3 2480F GTGCGGCTTCTTCAATATG 4151R CACTGTTCTTAAAGGACTC 55 4 3982F ACTGAATGCAGCCTTCGTAG 5423R GAACGTCTCGCTTGATGCT 60 5 5041F AGCGTTGATGGCGAGATAC 6568R CCACATAGGTATGCTGTCGCC 60 6 6444F CACTACAGGAAGTACCAATGG 7706R GTTTGGGTTGGGATGAACT 55 7 7570F GCAGAAGCCGACAGCAAGTA 9736R GCCATACCCACCATCGACAG 60 8 9486F CAACGAGCCGTATAAGTATTGG 10726R CGCTCTTACCGGGTTTGTTG 60 9 10418F TTCAGCCTGGACACCTTTC 11756R GGAAGAGTTCGGTATGCTATG 60 " ] },{ "paper_id": "1ed7ba58402344abc5e614e344d03a30c03164af", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1edab5890fbff22ad353739d3d1e80a86d482820", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The United Nations Children's Fund reports that 1.7 million children under the age of five die annually of diarrhea and pneumonia [1] . Acute respiratory infections account for 4.0 million deaths in children under five worldwide [2] .", "The 2013-2014 surveys were conducted to establish statistical data necessary for setting up handwashing programs and policies related to infectious disease control planning pursuant to the Infectious Disease Control and Prevention Act.", "The 2014 handwashing observational survey was performed in subway/railway station restrooms in Seoul and six other municipalities selected by systematic sampling. During the one-week observational period (September 12 to 18), a total of 1,120 restroom users were observed and checklist completed. The observational survey checklist contained three categories: \"restroom conditions,\" \"task and handwashing afterwards,\" and \"handwashing behavior.\"" ] },{ "paper_id": "1ee81584a0fbdae5f787c41b02ba330bc46b545c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HEK 293T cells obtained from CCTCC (China Center for Type Culture Collection, Wuhan, China) were grown in Dulbecco's modified Eagle's medium (DMEM, GIBCO, Grand Island, NE, USA) supplemented with 1% penicillin/streptomycin (GIBCO) and 10% fetal bovine serum (FBS, GIBCO) at 37 \u2022 C with 5% CO 2 . The HSV-1 strain 129 (H129) was used in this study, and virus was stocked at \u221280 \u2022 C.", "IFN-inducible transmembrane (IFITM) protein 3 was a member of the first identified ISGs. A wealth of data has suggested that IFITM3 strongly protects host cells against a broad range of viruses, including SARS coronavirus, influenza A virus, human immunodeficiency virus type 1, and Zika virus [23] . The antiviral effects of IFITM3 might be attributed to the blockage of virus entry by inhibiting the fusion of the virus membrane, though the mechanisms are still unclear. One possible mechanism is that by binding with vesicle-associated membrane protein-associated protein A (VAPA), IFITM3 disrupts intracellular cholesterol homeostasis and blocks viral release to cytosol [24] . This is consistent with our data and explains our finding that HSV-1 increases IFITM3 expression, and knockdown of this gene leads to higher virus proliferation.", "MS spectra were submitted to ProteinPilot version 5.0.1 (AB SCIEX) to perform peptide identification and quantification. The UniProt_Human database (download at 201701) containing HSV-1 proteins was used. The search parameters were as follows: sample type: SILAC (Lys+4D, Arg+6; Lys+8, Arg+10); cysteine alkylation: iodoacetamide; digestion: trypsin; instrument: tripleTOF 5600; miss cleavages tolerance: 2; fixed modification: carbamidomethyl Cys; variable modification: none; MS1 initial mass error tolerance value: 0.05 Dalton; MS2 initial mass error tolerance value: 0.1 Dalton. The false discovery rate (FDR) analysis in ProteinPilot uses a \"decoy database searching\" strategy, and the FDRs of the ProteinPilot search results were all set as lower than 1% of the protein level." ] },{ "paper_id": "1eef10e356884a9f63b17f13df74ac185700ab06", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Health has become a global issue because viruses such as HIV and SARS do not respect international borders [1, 2] . The failure of immunization delivery in one country can precipitate the return of a disease in surrounding countries, as the recent example of polio in Nigeria shows [3] . Malaria eradication schemes in one area are ineffective unless neighbouring countries adopt similar strategies [4] .", "Access to uncontaminated water is a fundamental prerequisite for good health. Conflict zones, water supply dis-putes and lack of engineering infrastructure prevent large areas of the world's population from achieving a reasonable health status [5] .", "The outcome for premature babies in resource-poor countries used to be very unfavourable. In South America, the \"kangaroo care\" model was developed. Premature babies are placed between their mother's breasts. A woollen hat is provided to minimize heat loss through the baby's scalp, and the mother's body acts as an incubator (Additional file 2). Breast milk is expressed directly into the baby's mouth, or onto cotton wool and then squeezed gently into the baby.", "The Malawian health care system has to prioritize which patients are suitable for expensive treatments, including antiretroviral therapy for HIV or anti-TB therapy. In order to be accepted on to a treatment programme, patients have to give a commitment to try to maintain their nutrition, take their medication as directed and be present for follow-up appointments. To facilitate these, patients must nominate a \"guardian\" -usually a close family member. The guardian must then accept responsibility for ensuring that the patient takes the right sort of nutritious food, checks medication compliance and makes sure the patient is present for follow-up. Some clinics even provide a shelter and cooking facilities for the guardians [13] ." ] },{ "paper_id": "1ef024725b588f435abcc6c51189d14b223d24fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data Accessibility. Raw sequence data for transcriptome assemblies can be found at NCBI PRJNA383875." ] },{ "paper_id": "1ef187d95b5c98c9ef187f3b5cf23e276bf1b018", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The reagents were purchased from TaKaRa. Triplicate recombinant DNA positive clones from each PEDV isolate were sequenced by Sangon Biotech, China.", "Primers used in this study were designed to target the conserved regions of the S gene and were synthesised by Sangon Biotech. The primers are listed in Table 1 . For the PCR reactions, 1 \u03bcl of cDNA, 10 \u03bcl ExTaq DNA polymerase (TAKARA), 1 \u03bcl of each primer (10 pmol) and RNase-free water in a total volume of 20 \u03bcl. The amplification was carried out as follows: 95\u00b0C for 5 min, followed by 33 cycles of 95\u00b0C for 1 min, 57\u00b0C for 1 min and 72\u00b0C for 1 min and finally 72\u00b0C for 10 min. The products were examined by electrophoresis using a 1.0% agarose gel.", "We also examined the three major epitope regions, viz : aa 498-637, aa 747-754 and aa 763-770. The sequences at aa 747-754 were conserved between the latest Chinese PEDV isolates and CV777 attenuated strain, however the sequences at positions 498-637 and 763-770 were variable (Table 4 ).", "Sequencing of the S1 and ORF3 genes" ] },{ "paper_id": "1efc2d5258eb4387f65e85a5b9bde50cdcd104fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1efd8ee0124faf388961ff309a10ca2cfba5268c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Demographic characteristics, underlying diseases, medical history, clinical examination at enrollment, radiological findings, vaccinations, and outcome were recorded prospectively for each patient on a standardized form.", "With : Pr c \u00bc Prevalence of microorganim detection in controls; OR \u00bc crude odds ratio:", "Supporting Information S1 STROBE Checklist. (DOC) S1 " ] },{ "paper_id": "1f1c43d3f7a43ad4a16b8ded2b2ac384f3db3b4c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1f23a8772f471052f70a35fe6921865c014cad71", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1f28ddf08dc9bb5b9b4c291f15d3d42ecdf9cde4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Infectious bronchitis virus (IBV) causes avian infectious bronchitis, a highly contagious disease that affects poultry and produces severe economic losses worldwide. IBV belongs to the order of Nidovirales, family Coronaviridae and to genus of Gamma-coronavirus group 3 [1] . The genome is positive-sense single stranded RNA of about 27.6 kb and contains 5\u2032 and 3\u2032 untranslated regions [2] [3] [4] .", "The presence of serine, threonine and tyrosine residues, with the right context for potential phosphorylation was " ] },{ "paper_id": "1f29ce1525b32b7b954901bc5c04aaffe615ccd9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "for an improved understanding of the virus. Furthermore, studies of NDiV as part of mosquito monitoring programs in a greater number of areas are required to enrich the resources available for such research." ] },{ "paper_id": "1f2bbc79b56c51c0ae26ced2d7d8ccf10360fa72", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus (Cooper et al., 2014) and are accessible through GEO Series accession number GSE52489 (51).", "Superscript III (Invitrogen) and a DNA primer (5 0 -AAT GAT ACG GCG ACC ACC GAG ATC TAC ACT CTT TCC CTA CAC GAC GCT C-3 0 ) were incubated with the gel-purified RNAs to make cDNA (per the manufacturer's instructions). Exonuclease I (0.5 U) and recombinant shrimp alkaline phosphatase (0.25 U) (USB/Affymetrix) were added to each RT reaction, followed by additional incubation at 37 C for 30 min, to remove excess DNA primer and dNTPs. RT reactions were then heated to 95 C to inactivate the enzymes. RNAs were hydrolyzed using 1 N NaOH treatment at 100 C for 10 min and neutralized with 1 N HCl. cDNA was P:C:I extracted and ethanol precipitated.", "Following the ligation and Tpt1 reactions, RNAs were resuspended in denaturing sample buffer (95% formamide, 18 mM EDTA, 0.025% SDS and 0.025% each bromophenol blue and xylene cyanol), heat denatured (10 min at 65 C) and fractioned on a 6% urea-polyacrylamide gel. RNAs in the gel were visualized using SYBR-Gold (Invitrogen) and blue light transillumination. RNAs 100-500 nt in length were excised from the gel, crushed into a slurry with 0.3 M sodium acetate and incubated at 42 C for 2 h. RNA was purified from polyacrylamide by running samples through DTR cartridges (EdgeBio) followed by ethanol precipitation.", "A DNA linker was attached to the 3 0 -end of the cDNA in reactions (10 ml of volume) containing 1 mM miRNA cloning linker 1 (5 0 -rApp-CTG TAG GCA CCA TCA AT-ddC-3 0 [Integrated DNA Technologies]), 10 units of T4 RNA ligase I (New England Biolabs) and T4 RNA ligase buffer (50 mM Tris-HCl [pH 7.5], 10 mM MgCl 2 and 1 mM DTT). Linked cDNAs were P:C:I extracted and ethanol precipitated. Linked cDNAs were resuspended in formamide sample buffer and fractioned on a 6% urea-polyacrylamide gel. cDNAs >150 bases long were gel purified and resuspended in 30 ml of water." ] },{ "paper_id": "1f3077db9137fe7b7cc858899628f1625cbf0644", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "N-total number of analyzed samples, nd-not detectable, b LOD -limit of detection (see Experimental Section).", "The prevalence of mycotoxin-induced nephropathy is still unknown, and epidemiological studies must be carried out on a large scale in livestock population where ochratoxin A levels in feed are high, as they are also relevant for the understanding of human nephropathies.", "The occurrence and mean concentrations of ochratoxin A in swine serum, kidney and liver are summarized in Tables 1 and 2." ] },{ "paper_id": "1f31c7be736309949bbd0cf4a0c39841f3f67bd6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Currently, PRRSv control and prevention activities are unregulated in the U.S., which, combined with the varied and rapid biological properties of this RNA virus and the limited effectiveness of available vaccines, jeopardize the effectiveness of those mitigating measures 17 . Hence, risk-based interventions against emerging strains are required to minimize their impact on the industry 5 . Current swine production systems are commonly not separated by well-defined geographical boundaries and are characterized by highly frequent, often long-distance movement of pigs and supplies. Indeed, geographical distribution and dynamics of PRRSv spread are influenced by system-level decisions and needs, as well as environmental risk factors including, mainly, pig density and climate [18] [19] [20] .", "are commonly characterized by annual seasonal increases in the number of observed outbreaks, with incidence of cases being low during spring and summer and high during fall and winter 15 . However, the emergence of new virulent viruses is also a common characteristic of PRRSv (referred to as emerging strains), with \"spreader events\" being recognized for different United States regions 16 ; those emerging strains are of considerable concern to the swine industry as they cause severe economic losses. It is currently unknown if alternative transmission routes are equally important for emerging and endemic PRRSv strains.", "Another limitation of the present study was attributed to the lack of information related to spatiotemporal patterns of pig movements. Such information would substantially improve the inferences of the methods presented here. With the continuous advancements in the phylodynamic methods, described above, the inclusion of pig movement into future phylogeographic models of PRRSv will soon be possible as it would, indeed, yield a more realistic inference about the spatiotemporal evolutionary patterns of PRRSv endemic and emerging strains. Finally, data represented only a sample from the region, and data from other farms and systems may have helped to improve our predictions; noteworthy, however, the quantity of data available to us is unprecedented." ] },{ "paper_id": "1f33cc82e136a1cc89b2382e6fcc6ae520e364ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bacteriological examinations were carried out for Escherichia coli, Salmonella enterica, and Clostridium perfringens, and parasitological examinations were carried out for Coccidia and Cryptosporidium parvum, as described previously [21] .", "Fecal specimens were diluted with Eagle's minimum essential medium to 10% suspensions and clarified by centrifugation at 1 500 \u00d7 g for 10 min. The supernatant was collected and total RNA was extracted from 250 \u03bcL of the fecal suspensions using TRIzol LS (Invitrogen Corp., Carlsbad, CA, USA). Recovered total RNA was suspended in 50 \u03bcL of RNase/DNase-free water and stored at -20\u00b0C until use for reverse transcription-polymerase chain reaction (RT-PCR) and polyacrylamide gel electrophoresis (PAGE).", "PAGE of the extracted RNA was performed with 7.5% precast gels (e-PAGEL; Atto Corp., Tokyo, Japan). The gels were stained using a Silver Stain Plus kit (Bio-Rad Laboratories, Hercules, CA, USA). GAR electropherotypes were determined by comparing the individual RNA migration patterns of genome segments on the gel [23] ." ] },{ "paper_id": "1f345c5a7a02b742ca70ce9233c80a200af974b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.", "DS devised study design, analysed data, and drafted the manuscript, supervised by PJ, PN, GP, and AR. NW is a coinvestigator on the grant funding this work, and assisted with revising the manuscript. FS-V and SD are co-investigators of the wider SAVSNET project, assisting with revising the manuscript.", "This work is funded by The Veterinary Medicines Directorate (VM0520), the University of Liverpool and SAVSNET." ] },{ "paper_id": "1f4c7f7b1707f71e188cc621e323bd5751b3e6a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "3.1.1. Terminal 3\u2032-3\u2032 and 5\u2032-5\u2032 Internucleotide Linkage" ] },{ "paper_id": "1f4d59790ebb50fad78486e25156bcbb6b1edb40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1f4ec41f723e758522faa99829a52f00ea45a9e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hotels and cruise ships share the same concerns as an office building or aircra\ue09d cabin, as these venues have in common enclosed spaces with large, dense populations. \ue062ey are thus susceptible to airborne and droplet transmission via any of the mechanisms described above [38, 174] .", "Regarding environmental controls, several strategies are available to reduce exposure to infectious particles, including natural ventilation, mechanical ventilation, and upper-room ultraviolet light [132] [133] [134] [135] . Mechanical ventilation delivering negative pressure and 12 air changes per hour is the standard of care for respiratory TB isolation [128] , but these systems require delicate design and have high costs associated with installation. \ue062ey also require ongoing maintenance, necessitating both resources and expertise. Unfortunately, poorly maintained mechanical ventilation systems have been widely documented in resource-rich settings [136, 137] and implicated in several TB outbreaks [124, [138] [139] [140] .", "Facility Setting" ] },{ "paper_id": "1f534cb2b4a2d3482affcb6d7a1dd23be34f9321", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. The statistical significance of lethality was analyzed using the Kaplan-Meier method. Groups of data are presented as mean \u00b1 S.D. One-way analysis of variance followed by Dunnett's test or Student's t-test was used to determine the statistical significance of difference in measured parameters. Difference was considered significant at Po0.05.", "To induce non-lethal liver inflammation, mice were intraperitoneally injected with LPS (3 \u03bcg/kg body weight) and D-GalN (200 mg/kg body weight). Blood and liver samples were collected 5 h after treatment.", "Endotoxin-induced fulminant hepatitis model. Fulminant hepatitis in mice was established by intraperitoneal injection of LPS (5 \u03bcg/kg body weight; Sigma-Aldrich, St. Louis, MO, USA) and D-GalN (500 mg/kg body weight; Sigma-Aldrich). To determine the survival rate, the animals were monitored continuously after LPS/D-GalN injection until their death. For assessment of liver damage, the animals were killed 5 h after treatment with this dose to obtain blood and liver tissue.", "Western blot analysis. Proteins were extracted following the procedure described previously. 50 The proteins were separated by SDS-PAGE on 8-12% polyacrylamide gels and subsequently electrically transferred to a PVDF membrane. After blocking with 5% (w/v) BSA in TBST at room temperature for 1 h, the membranes were then incubated with an appropriate specific primary antibody (anti-HA, 1 : 2000; anti-PPAR-\u03b3, 1 : 1000; anti-PER1, 1 : 200; anti-\u03b2-actin, 1 : 1000) at 4\u00b0C overnight, followed by incubation with an HRP-conjugated secondary antibody (1 : 10 000). Detection was performed using an enhanced chemiluminescence kit (Thermo Scientific, Hudson, NH, USA).", "Animals. Per1 \u2212 / \u2212 mice 45 were obtained from Dr. CC Lee at Baylor College of Medicine, Houston, TX, USA. Ccr2 \u2212 / \u2212 mice were obtained from Jackson Lab (Bar Harbor, ME, USA). The Per1 \u2212 / \u2212 ; Ccr2 \u2212 / \u2212 (DKO) mice were generated at the expected Mendelian ratios and developed normally. All of the animals were backcrossed for at least five generations before the first pilot study to ensure a largely homogenous C57BL/6J background. Male WT C57BL/6J mice and gene knockout mice at 8-10 weeks of age were used in this work. The animals were maintained in cycles of 12 h of light and 12 h of darkness with free access to food and water ad libitum. All animal care and use procedures were in accordance with the guidelines of the Institutional Animal Care and Use Committee at Nanjing University of Science and Technology.", "Clock regulators appear to have an intimate role in the innate immune response aside from their role in circadian control." ] },{ "paper_id": "1f60f032bad1fcfb8d48b20527c347ec774d255e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Point-of-care cardiac ultrasound showed hyperdynamic function and an ultrasonic cardiac output monitor (USCOM\u00ae) calculated a cardiac output of 19 liters/minute, with stroke volume of 120 milliliters and systemic vascular resistance of 550 dyn\u00b7s/cm, 5 Using point-of-care ultrasonography, we found that the inferior vena cava was neither distended nor collapsed and the painful hip showed no excess joint fluid.", "Prekker et al.", "Empiric Treatment for Fulminant Pneumonia" ] },{ "paper_id": "1f63075aa219ae29132b49a0c7277632b9b31ba8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1f7224df292f2dcbfb805602296acd9aba317f24", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CORT, corticosterone; DAPI, 4', 6-diamidino-2phenylindole; DMEM, Dulbecco's Modified Eagle's Medium; FBS, fetal bovine serum; H&E, hematoxylin and eosin; IFITM3, interferon inducible transmembrane 3; IFN, interferon; IL, interleukin; ISGs, IFN-stimulated genes; LD50, median lethal dose; MAVS, mitochondrial antiviral signaling; Mfn2, mitofusin-2; MMP, mitochondrial membrane potential; NA, neuraminidase; NP, nucleoprotein; PAMPs, pathogen-associated molecular patterns; p-IRF3, phosphorylation interferon regulatory factor 3; PRRs, pattern recognition receptors; RIG-I, retinoic acid-inducible gene I; siRNA, small interfering RNA; STING, stimulator of interferon genes; TCID50, median tissue culture infective dose.", "A549 cells, a carcinomic human alveolar basal epithelial cell line, were cultured in Dulbecco's Modified Eagle's Medium (DMEM) (Biological Industries, CT, USA) containing 10% heat-inactivated fetal bovine serum (FBS) (Biological Industries, CT, USA). The CO 2 concentration of incubator was 5% and the temperature was at 37 \u00b0C.", "Lungs were removed and fixed in 4% paraformaldehyde with a hand-held 5 mL syringe to pump out air. Then the lung tissue was embedded in paraffin wax and sliced in 4 \u03bcm thickness. The slices were stained with H&E. Histopathologic changes were observed using \u00d710 objectives (Olympus, DP70, Japan).", "Specific-pathogen-free male Kunming mice (threeweek-old, 13-15 g) were obtained from Guangdong Medical Laboratory Animal Center (Guangzhou, China, Approval ID: SCXK 2013-0002). The animals were raised in plastic cages with bedding material of corn straw and lived at 23 \u00b1 2 \u00b0C with a cycle of equal light and dark. The relative humidity was 50 \u00b1 10%. Animal experiments conformed to the Animal Care and Use Committee of Jinan University (Approval No: 20150310001), as well as the National Institute of Health's Guide for the Care and Use of Laboratory Animals (7 th edition, USA)." ] },{ "paper_id": "1f7b47ec5e68a274a145bddd152303eba2f9d035", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the purpose of analysis, the individual scores were summed up to yield a total score. All statistical analyses were performed using SPSS 16 for Windows (SPSS Inc, Chicago, IL), with the level of significance set at 5%. Age was computed from the information on date of birth and date of interview. Chi-squared tests of significance were used to find the association of knowledge, attitude and behavior in relation to different age groups and different educational levels.", "Both practices and knowledge level towards preventive measures on H1N1 were only affected by different types of races and education levels. The reasons may be because the campaigns were done in Malay or English language, which most of the other races do not understand, thus, they do not get the knowledge needed to practice the preventive measures recommended by the Ministry of Health.", "" ] },{ "paper_id": "1f7d12535c961aa81e3719db27546b741674c1aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Primary CK cells were prepared by The Pirbright Institute cell culture department from chickens produced in the Institute's poultry production unit. The chickens were sacrificed by trained staff under a schedule 1 procedure, cervical neck dislocation, a procedure that does not fall under any UK Home Office licence requirements as no procedures were carried out on live animals and therefore did not fall under any local or EU ethical requirements. The kidneys were removed from the sacrificed chickens for preparation of the primary CK cell cultures. The work was done in a designated establishment, The Pirbright Institute, Compton Laboratory.", "Primary chicken kidney (CK) cells were prepared from 2-3 week old specific pathogen free (SPF) Rhode Island Red chickens as described previously [43] . All IBVs were propagated and titrated on primary CK cells using BES (N, N-Bis(2-hydroxyethyl)-2aminoethanesulphonic acid) cell maintenance medium [44] .", "Viral RNA was extracted from cell supernatants using the RNeasy Mini Kit (Qiagen) following the manufacturer's instruction for the RNA clean up protocol. cDNA was synthesised using SuperScript III (Life Technologies) and a random primer as per manufacturer's instructions. cDNA was amplified by PCR using primer pairs that flanked the inserted reporter gene: for D5ab recombinant viruses (59-GAGCTATTAACGGTGTTACC-39) and (59-AATCTAATCCTTCTCTCAGA-39), for DIR recombinant viruses (59-GAATGGTGTTCTTTATTG-39) and (59-TCTAACACTCTAAGTTGAG-39), and for D3ab recombinants (59-TGACGAATTGTCAAAATG-39) and (59-AGACAGA-CACGCAAACACTG-39). PCR cycling parameters were as follows: 1 cycle of 94uC for 2 min; 25 cycles of 94uC for 30 sec, 50uC for 30 sec, 72uC for 30 sec; and a final extension step of 72uC for 2 min." ] },{ "paper_id": "1f7f414d82475a8c5b2272163e6f31b474904486", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1f8a1700ee536e43e65c9ba4df7f87b0461ee999", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The IL6/STAT3 signaling pathway has been implicated in cancer cachexia, a multifactorial condition that presents with skeletal muscle wasting, adipose tissue atrophy, and anorexia. Cachexia is defined by the loss of 5-10% or more in body weight associated with cancer or other inflammatory conditions [63, 64] . The prevalence of cachexia accounts roughly for 80% of upper gastrointestinal cancer patients and 60% of lung cancer patients at the time of diagnosis. Cachexia correlates with diminished quality of life and a high mortality rate in cancer patients [65] .", "Physical activity and exercise training are important for maintaining muscle mass and function. In addition, healthy skeletal muscles and adequate physical activity levels are essential to general health and maintaining metabolic homeostasis. Previous studies showed that IL6 upregulation and STAT3 activation are essential components for the adaptive responses to resistance training [22] [23] [24] . The IL6 and STAT3 activation was also shown to be directly associated with increased glucose transport in both in vivo and ex vivo experiments [25] . For instance, vastus lateralis muscle strips from healthy men, incubated with IL6 (120 ng/mL), had greater glucose transport, glucose incorporation into glycogen, and glucose oxidation compared to control samples.", "Regulatory Target ", "The phenotypic characteristics of cancer cachexia are well recapitulated in several animal models, including the colon cancer model Apc Min/+ , the Kras-induced lung cancer mouse, Lewis lung carcinoma, C26 adenocarcinoma, and B16 melanoma, where the cachexia level is dependent upon the increasing level of circulating IL6 [67] [68] [69] . In vivo evidence of the specific involvement of IL6/STAT3 in causing cachexia-associated muscle wasting is that Apc Min/+ mice lacking IL6 do not develop cachexia [3, 42] . Moreover, systemic overexpression of IL6 in cancer-free mice or pre-cachectic Apc Min/+ mice accelerates the onset of cachexia [67] . Circulating levels of IL6 in Apc Min/+ mice were significantly correlated with Apc Min/+ mouse body weight, and with the level of STAT3 phosphorylation in slow oxidative and fast glycolytic skeletal muscles [70] . IL6 plasma levels have also been examined in cancer patients, and they were found to be variably but consistently elevated in cancer patients compared to healthy controls [71] [72] [73] [74] . Moreover, plasma levels of IL6 were significantly correlated to the degree of tumor progression and symptoms of cachexia (loss of lean mass, severe fatigue, and anorexia) in humans. However, the studies limited their analysis to serum IL6 and did not analyze total or activated STAT3 protein, in either skeletal muscle or other tissues." ] },{ "paper_id": "1f91af10bd4371cfb8d9e08a8a1518d8bbd6d4f5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Next generation sequencing (NGS) platforms offer exceptional depth, speed and accuracy of sequencing, resulting in a significant increase in the rate of new pathogen sequences that have been identified from tissues or fluids [Fig 1] . The decline in sequencing costs [1] now makes this technology broadly accessible, with some recent viral discoveries having potential health and economic benefits [1] [2] [3] [4] [5] . NGS is also useful as an unbiased tool with the ability to identify previously undetected or unsuspected causative agents without prior information and has the potential to become a diagnostic tool overcoming inherent a priori limitations of conventional molecular diagnostics such as PCR and microarray technology.", "Human liver samples were acquired from the Institute of Liver Studies, Kings College Hospital, London, University of London, UK. Samples were obtained with patient written consent. This work forms part of a broader project with ethical approval provided by the UK National Research Ethics Service, Cambridge 3 Research Ethics Committee, Cambridge CB21 5XB (REC reference numbers 09/HO306/52, 09/HO306/60) and Kings College Hospital Research Ethics Committee, London SE5 9RS (REC reference number 04/Q0703/27).", "Prior to sequence assembly and / or host sequence read removal, we trimmed all Illumina paired read data sets using CLC Bio v5.5 Trimmer (Aarhus, Denmark). SISPA PCR primers used for random priming and amplification [11] were removed (+/-strand search setting). Other settings chosen included: max ambiguity/read = 3, reads discarded if <38nucleotides in length (following all other trim functions). Quality control analysis revealed sequence read level (arithmetic mean) PHRED score averages of over 40 for all sets, with no single read mean PHRED score less than 30." ] },{ "paper_id": "1f92a01ead66646392c85f3abe57d3ea5ef8125a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Phylogenetic analysis is widely used for taxonomic classification, characterization, and revision 15,16 . However, for prokaryotic genomes, phylogenetic trees based on small subunit rRNAs often do not agree with those based on different genes. Conflicts among gene trees have increased as more genes and genomes are sequenced 17 . This incongruence can have many causes, including tree-building errors, incomplete lineage sorting, hidden paralogy, and horizontal gene transfer. As early as 1996, inconsistent phylogenetic trees were obtained for viruses when using different numbers of isolates, or when different lengths of aligned sequences were used (as in a study of hepatitis C viruses 18 ). Similar inconsistencies have been reported for human papillomaviruses 19 , SARS coronavirus 20 , and some plant viruses 21 .", "The second circle shows the hosts' kingdoms, including archaea, bacteria, fungi, animal, plants, protists, and the environment. As shown, the host kingdom with the most dsDNA viruses is bacteria. The plant viruses are mainly ssDNA viruses and ssRNA(+ ) viruses. The animal viruses distribute around the whole dendrogram, and respond to various sequence structures and reference orders, which suggests their possible origin from transmission. Different levels of genome sizes color the outside circle. The overall trend is that genomes with similar sizes are easier to group together, although the colours mix as locality changes.", "The innermost circle of the dendrogram is coloured by reference taxonomy at different Orders, including Caudovirales, Herpesvirales, Ligamenvirales, Mononegavirales, Nidovirales, Picornavirales, Tymovirales, and unclassified families. Supplementary Table S1 shows that ~60% of viruses in our dataset are Caudovirales (excluding the 2,171 viruses whose reference orders are unclassified or unassigned). In general, the Caudovirales viruses group well (ignoring the unclassified orders), with a few member discrepancies. It is interesting to note, however, that Herpesvirales viruses form a small clade to split the largest clade of Caudovirales. Other Herpesvirales viruses also group inside the Caudovirales clades as discrepancies. The Ligamenvirales, Mononegavirales, Nidovirales, Picornavirales, and Tymovirales orders separate from each other to form small sporadic groups." ] },{ "paper_id": "1f972484a578ead6c95a1dfff150894e935cad9d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus inactivation. Figure 1 shows representative fluorescent 40\u00d7 images of mammalian epithelial cells incubated with airborne viruses that had been exposed in aerosolized form to far-UVC doses (0, 0.8, 1.3 or 2.0 mJ/cm 2 ) generated by filtered 222-nm excimer lamps. Blue fluorescence was used to identify the total number of", "Airborne-mediated microbial diseases represent one of the major challenges to worldwide public health 1 . Common examples are influenza 2 , appearing in seasonal 3 and pandemic 4 forms, and bacterially-based airborne-mediated diseases such as tuberculosis 5 , increasingly emerging in multi-drug resistant form.", "Scientific RePoRtS | (2018) 8:2752 | DOI:10.1038/s41598-018-21058-w A range of far-UVC exposures, from 3.6 \u00b5J/cm 2 up to 281.6 mJ/cm 2 , were used to define a response calibration curve. Films were scanned as 48 bit RGB TIFF images at 150 dpi using an Epson Perfection V700 Photo flatbed scanner (Epson, Japan) and analyzed with radiochromic film analysis software 32 to calculate the total exposure based on measured changes in optical density.", "The entire irradiation chamber was set up inside a certified class II type A2 biosafety cabinet (Labconco, Kansas City, MO). All air inputs and outputs were equipped with HEPA filters (GE Healthcare Bio-Sciences, Pittsburgh, PA) to prevent unwanted contamination from entering the chamber as well as to block any of the virus from releasing into the environment." ] },{ "paper_id": "1fa8ee295da509bade53e2988275c9a5ad214d3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Studies that define these immune features are required to improve disease management and prognosis, as well as to contribute to vaccine development.", "Consistently, the immunization of Syrian hamsters with adenoviral vectors expressing the Andes virus nucleocapsid or glycoprotein, protected them against a viral challenge, with an important contribution from cytotoxic T-cells [155] . A similar protection was observed in bank voles immunized with Puumala virus nucleocapsid protein [156, 157] . Strikingly, immunization of bank voles with nucleocapsid protein from different hantavirus strains elicits cross-protective T-cell responses against Puumala virus [158] . Collectively, these studies underline the importance of T-cell immunity for protection against hantavirus infections and support the relevance of nucleocapsid protein for the generation of cross-protection using novel vaccine candidates.", "The authors declare no conflict of interest.", "In summary, the magnitude and quality of the T-cell response, as well as host characteristics, determine the final outcome of hantavirus infections." ] },{ "paper_id": "1faad9ed0f7640ab69cac98df7db103f99e66066", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Gini index \u00bc 2 \u00c2 P t\u00c01 n\u00bc1 \u00f0A i!j;n \u00de \u00fe A i!j;t \u00c0 t t \u00c0 1 (12)", "f 110 \u00bc a 0 \u00fe a 2 \u00fe a 3 \u00fe a 23 f 111 \u00bc a 0 \u00fe a 1 \u00fe a 2 \u00fe a 3 \u00fe a 12 \u00fe a 13 \u00fe a 23 \u00fe a 123", "Combining inequality (14) and (20) gives" ] },{ "paper_id": "1fb1a2388d4c9483abb1b390bb0410c941bfd1b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A minimum number of studies showed the development and validation of serological tests. Two reports have published limited information about indirect enzyme-linked immunosorbent (ELISA) tests using recombinant PCV-3 Cap protein (21, 106) . More recently, a PCV-3 specific monoclonal antibody has been produced, presumably working on formalin-fixed, paraffin-embedded tissues by means of immunohistochemistry (72) .", "We would like to acknowledge the funding of the E-RTA2017-00007-00-00 project, from the Instituto Nacional de Investigaci\u00f3n y Tecnologia Agraria y Alimentaria (Spanish Government). The funding from CERCA Programme/Generalitat de Catalunya to IRTA is also acknowledged.", "The evolution of emerging diseases is associated with factors embedded in the concept \"host-agent-environment triangle\" (1) . To infect the host and cause disease, the pathogen needs to evade host defenses, which may occur through single point mutations, genome rearrangements, recombination and/or translocation (2) . Genetic uniformity generated through genetic selection of the host (3) and the fact that demographic changes, intensification of farming, and international commerce have occurred markedly over the last decades, must be also considered as essential factors for the development of emerging diseases (4) (5) (6) .", "FK and JS did the majority of the writing and communicated with the coauthors to coordinate the document editing. JS designed the outline of the manuscript. GF provided the phylogenetic analyses. FC-F, GF, MS, and JN revised the manuscript, did partial writing and approved the final version for publication." ] },{ "paper_id": "1fb48248ba087b62ed753f63f4ff046e68828bf9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "1fb6893b7abf4b147f4185c6f94a06c79773d3ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The infection status of farms part of MSHMP in the studied area over the study time span is shown in Figure 5 . This data show two periods in which vaccine usage increased, the first one in mid-2012, and a second in approximately mid-2014. Not all farms that reported its status to MSHMP contributed to sequences to this analysis.", "IP and KV analyzed, conceptualized, and designed the study. CC, JS, CV, and KV contributed to acquisition of the data. IP, CC, AR, JS, CV, DS, and KV interpreted the data. MM aided in early interpretation of data. All authors but MM were involved in drafting the manuscript and revising it critically for intellectual content and have given final approval of the version to be published. ", "The sequence dataset used here is available in GenBank under the accessions numbers MN498289-MN502669." ] },{ "paper_id": "1fb860b35fac03bc319a2d12de832b65ca392c55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reporting summary. Further information on research design is available in the Nature Research Reporting Summary linked to this article.", "* Values in parentheses are for highest-resolution shell. One crystal was collected for structure NATURE COMMUNICATIONS | https://doi." ] },{ "paper_id": "1fceaf9f2102c71bf508ebd46c18c9b0cb48e6c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceptualization: AK MT.", "Data curation: PD. " ] },{ "paper_id": "1fddc1d4d4d31015df5e948d0119947b8bd681d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For pharmacokinetics (PK) study of oral verdinexor treatment, n = 3 male CD1 mice per time point (~28 g of weight) [BK Laboratory Animal Co. Ltd., Shanghai, China; qualification no. SCXK(SH) 2008-0016 12470] were used. Plasma verdinexor concentrations were determined by an ultrahigh-performance liquid chromatography-mass spectrometry method as previously described [18] .", "Total RNA was isolated from nasal wash cells using the RNeasy Mini Kit (Qiagen) and cDNA were synthesized using the Verso cDNA Synthesis Kit and random hexamers as primer (Thermo Scientific). Quantitative PCR was performed using ferret IFN-\u03b3, IL-12p40, TNF-\u03b1, and GAPDH gene specific primers [21] and RT 2 SYBR Green qPCR Master Mix (SABioscience) in MX3005P thermocycler as previously described [18] . Ct values for cytokines were normalized to GAPDH and their expressions relative to basal samples were calculated using 2 (-\u0394\u0394Ct) formula.", "Statistical analyses were done using student's t-test and results were presented as means \u00b1 standard errors (SE). Values of p 0.05 were considered significant." ] },{ "paper_id": "1fdefb8aa4368ef11e32bad469c37591b0eb24bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Therapeutics targeting RNA-dependent RNA polymerase (RdRP) complex", "EV-71 infections usually manifest as mild hand, foot and mouth disease (HFMD), characterized by fever, mouth ulcers, and vesicles on the palms and feet. Unlike other HFMD-related enteroviruses, EV-71 also causes severe neurological manifestations, such as poliomyelitislike acute flaccid paralysis and brainstem encephalitis in infants and children below 6 years old [17, 18] . The fatal brainstem encephalitis is characterized by rapid progression of cardiopulmonary failure. Patients with neurological involvement who survive often have permanent neurological sequelae, with delayed neurodevelopment and reduced cognitive function [19, 20] .", "Authors' contributions CWT, JKFL, ICS and YFC drafted the manuscript. All authors read and approved the final manuscript." ] },{ "paper_id": "1ff255719ae770ac447902320cf19bd3c7e895b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The significance of the difference between any two different groups was assessed by the Mann-Whitney test using Prism 5 (GraphPad Software, CA). P value of < 0.05 is considered statistically significant.", "Pertusis is another vaccine-preventable disease and pertussis vaccination has been given to all newborns in Singapore since 1957 [19] and sero-prevalence of pertussis antibodies in the adult population of Singapore (18-45 years) was 97% in 2002 [20] . In 2015, there was a total of 56 local cases of pertussis reported in Singapore, a rise from the 19 cases in 2014. As vaccine-induced antibodies begin to wan significantly 4 years after the last dose [21] , a booster could be beneficial for optimal protection of the recruits against this highly contagious bacterial disease." ] },{ "paper_id": "1ff2f23a621ca476cd59ade285f8b9198ca178fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Low High" ] },{ "paper_id": "1ff38c46bce64adb553080443f72ff90e61dcbc3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Subject 2 Fever (6), Lymphopenia (6), Thrombocytopenia (6) Thrombocytopenia (10) ", "Fever is defined as a temperature more than 2.5 uF over baseline or at least 1.5 uF over baseline and $103.5 uF.", "Day 0-8 Day 9-10 Day 11-28" ] },{ "paper_id": "2000b147cb90354ba98206dffbc47deddddcc84d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Descriptive statistics are presented as numbers of cases, percentages, and means with standard deviation (SD). Pearson's chi-square (\u03c7 2 ) test, analysis of variances (ANOVA), and post-hoc ANOVA (Scheff\u00e9 test) were used to evaluate the significance of differences; the Mantel-Haenszel (M-H) \u03c7 2 test was used to examine trends. All statistical calculations were performed using the Statistical Package for Social Sciences for Windows (SPSS for Windows 13.0).", "Conclusions: The frequency of major health problems diagnosed at ED visits varied by age: more complicated complaints and multiple diagnoses were more frequent in older patients. In Taiwan, the ED system remains overloaded, possibly because of the low cost of an ED visit." ] },{ "paper_id": "2000b56ab7a60199d3bbb2148295370ae87b3d58", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where we neglected the usual S(t)/N , for simplicity -its inclusion does not change the discussion.", "The duration of the infectious period \u03b3 \u22121 is usually estimated from direct patient observation." ] },{ "paper_id": "2005ffa70562f5f03b57f0d19f4d63e807762964", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2028c33a99d25b4388a27d93fa0d4e2fe2563b54", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(3) Nucleus internalization 5 3 5 3", "RNase: Ribonuclease RI: RNase inhibitor protein ACTB:", "-Actin GAPDH: Glyceraldehyde-3-phosphate dehydrogenase RNP:", "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." ] },{ "paper_id": "202f004261b2489f0e28acebc96cba9ebb576860", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was funded by Alexander von Humboldt foundation (project ID: 3.4 -Fokoop-DEU/1144102). The funding agency has no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.", "Veterinarians rely mainly on the appearance of clinical signs for LSD diagnosis [8] . Establishment of a rapid diagnostic test to identify early stages of an LSD outbreak would allow rapid execution of control measures.", "Several loop-mediated isothermal amplification (LAMP) assays have been established to identify capripoxviruses [36] [37] [38] . The design of LAMP assays requires four to six oligonucleotides and a minimum of four binding sites. The LAMP results can be read by naked eye, if turbidity read out is used [39] after about 60 min. In contrast, the RPA assay developed here was very fast (15 min) and required two primers and one probe.", "Lumpy skin disease (LSD) affects primarily cattle and occasionally buffalo [1, 2] . It causes pyrexia, generalized skin and pox lesions of internal organs, as well as generalized lymphadenopathy [3, 4] . The disease exists in three forms, acute, subacute or unapparent [5] . LSD is caused by an enveloped double-stranded DNA virus called LSD virus (LSDV), which together with sheep poxvirus (SPV) and goat poxvirus (GPV) constitutes the genus Capripoxvirus of the Chordopoxvirinae subfamily of the Poxviridae family [6, 7] ." ] },{ "paper_id": "20308c2a1349e993e82115a8dc869c011298dd06", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The island of Corsica, a land bridge between Europe and Africa, is an important crossing area for infectious agents, which increases the public health importance of establishing an efficient and reliable surveillance system in the region.", "The ILI consultation rates are reported in Figure 2 ", "The continuous circulation of influenza viruses in animal species carries the potential to cause severe human illness through crossspecies transmission [1] . It is also possible that virus adaptation to enable efficient and sustainable human-to-human transmission could possibly lead to worldwide pandemics [2] [3] . Past episodes have confirmed the need for supporting influenza surveillance networks throughout the world [4] [5] ." ] },{ "paper_id": "20317b47f1178792d735b4202fc343721d1ff4a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "20320bc56f02e0fc4bc6430ddb0efa564db40cd1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pntd.0006349.g002", "14. Guito " ] },{ "paper_id": "2032190765972c590630a370d6d2f088270ee9db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "the above-described detection methods, new approaches to detect folding or unfolding of single molecules emerge and include time-resolved NMR, which becomes a powerful tool to study folding of small RNAs.", "Hfq encompasses an Sm-domain, which is highly conserved among various species and usually is found in eukaryotic spliceosomal RNPs. Crystallographic studies of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus Hfq proteins showed that Hfq forms homohexameric ring structures with a central cationic pore that forms the RNA binding site [68] [69] [70] .", "HnRNP K is also a multifunctional protein that is a transcriptional factor for c-myc and c-src [56] [57] [58] ; it enhances splicing [59] and is a translational regulator [60] ." ] },{ "paper_id": "2034ca5a9941b6e3d8b0ba9280a5b2fae192778d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Activities of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), blood urea nitrogen and creatinine were analyzed using a Cobas C311 Analyzer (Roche) or a 747 Automatic-Analyzer (Hitachi).", "For detection of IFN\u03b1, sera were 1:10 prediluted and analysed by ELISA using rat \u03b1-mIFN-\u03b1 capture antibody (PBL Interferon Source 22100-1), rabbit \u03b1-mIFN-\u03b1 detection antibody (PBL Interferon Source 32100-1), \u03b1-rabbit HRP secondary antibody (Jackson ImmunoResearch 711-036-152) and TMB solution (Life Tech 002023).", "\u03b1-CD45 (30-F11), \u03b1-CD8a (53-6.7), \u03b1-CD11c (N418), \u03b1-F4/80 (BM8), \u03b1-MHCII (M5/114.15.2), \u03b1-NK1.1 (PK136), \u03b1-PDCA-1 (eBio927) and \u03b1-TCR\u03b2 (H57-597) were from eBioscience; \u03b1-CD45.1 (A20), \u03b1-CD45.2 (104), \u03b1-CD4 (RM4-5), \u03b1-Ly6G (1A8) and \u03b1-Ly6C (HK1.4) were from BioLegend. \u03b1-CD11b (M1/70) and \u03b1-siglec-F (E50-2440) were from BD Bioscience. Samples were acquired on a FACS LSR Fortessa or FACSCanto II (Becton Dickinson), data was analyzed with FlowJo (Tree Star)." ] },{ "paper_id": "204a803a89944c81ecd8b50ddfb85e78db5df7f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chick placement [1, [17] [18] [19] [20] [21] [22] Increased stocking density [23] [24] [25] [26] [27] [28] [29] [30] [31] Weighing, grading, group formation, catching, transferring to breeder houses [1, 18, 19] Prolonged egg storage, egg transportation, inadequate egg storage conditions, incorrect incubation regimes [1, 18, 19] ", "Inadequate temperature [32] [33] [34] [35] [36] [37] [38] [39] Inadequate ventilation and increased dust [1, 18, 19, 40, 41] Inadequate lightning [1, 18, 19, 42, 43] ", "Thioredoxin system (Trx, Trx peroxidase (peroxiredoxins), sulfiredoxin and TrxR);" ] },{ "paper_id": "206121388211d800150c316cd04daeaec547032b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "206231b403edaaa8ff0fd1a23ca2428dd261507b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Infectious and parasitic diseases account for approximately half of the deaths worldwide (Menpara and Chanda, 2013) .", "This study was supported by the Agricultural Research Center, Ministry of Food, Forestry, and Fisheries, Republic of Korea.", "JKP, SG, GD, and SS wrote the manuscript. H-SS and JKP designed the concept, edited the manuscript. All the authors read and approved the manuscript." ] },{ "paper_id": "20651c857a793c827bc2d32bbbf6392e8285b84d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For comparison of VSV-G expression, fusion frequency, and fusion product morphology versus controls, a normal distribution was assumed and oneway analyses of variance and Student's t-test were used. Data were analyzed with Microsoft Excel (Microsoft, Redmond, WA, USA).", "Merge CMs ", "This paper was supported by funding from the National Institutes of Health (HL089679)." ] },{ "paper_id": "20656a048091de934d0fb432f8d070304a1664dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequences (Note that this transcript was prepared from a hammerhead construct to allow efficient transcription of the gene carrying a 59A residue, and so has a 59-OH start) [66] .", "PKR was originally described as the double-stranded RNAactivated protein kinase [62] . While this moniker still holds, it has become clear that PKR is activated by much more than dsRNA.", "Interferon-inducible PKR is a vital component of innate immunity, which provides the first line of defense against pathogens [1, 2] . PKR consists of two functional domains: an Nterminal double stranded RNA (dsRNA) binding domain (dsRBD) comprised of two dsRNA binding motifs (dsRBMs) and a Cterminal kinase domain. These domains are separated by a flexible 20 amino acid linker [3, 4] . The dsRBM recognizes dsRNA with no sequence specificity via minor groove interactions [5, 6] , while the kinase domain helps mediate dimerization of PKR as well as possessing the kinase catalytic activity [7] [8] [9] ." ] },{ "paper_id": "206b5371a11c4b903ed2600b579171a3e6873764", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All specimens were also screened for human respiratory syncytial virus (HRSV), human metapneumovirus (HMPV), influenza viruses A and B (IFVA, IFVB), parainfluenza virus types 1 to 3 (PIV1-3), human rhinoviruses (HRVs), and human coronaviruses (NL63 , HKU1) using a standard reverse-transcription PCR technique [16] [17] [18] [19] , and human Bocavirus (Bcov) using traditional PCR methods [20] .", "The objective of this study was to describe the epidemiological and clinical features of HAdV ARTIs over a period of 3 years.", "Informed consent was obtained from the parents of all children who provided specimens. The study protocol was approved by the hospital's ethics committee (The Ethics Committee of the First Hospital of Lanzhou University)." ] },{ "paper_id": "2076515c446601717239a974bc7bfc84f455e62c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sialic acids are compounds derived from neuraminic acid which belong to a large family of complex nine-carbon sugars usually bound to other carbohydrates through \u03b1-ketosidic bonds. In mammals, sialic acids are found at the non-reducing end of glycoconjugates [1] . Influenza viruses are the oldest and most important examples of viruses that recognize sialic acids as the surface receptor for entry into host cells and their binding and propagation through interaction with these receptors have been well documented [2] .", "On April 21 st , 2009 the Centers for Disease Control and Prevention (CDC) reported two cases of infection with a new influenza virus strain which had occurred in California, USA [12] . This strain rapidly spread around the world and gave origin to the first influenza pandemic in the 21 st century [13] . In this pandemic, the fact that the incidence of severe disease was higher among young adults than among individuals older than 50 years called attention [14] and differed from observations made during annual epidemics caused by other human viral subtypes [15] .", "In order to evaluate the putative effect of both variants in ST3GAL1 regulation, in sillico analyses using HaploReg 3.0 [23] and Human Splicing Finder 3.0 [24] were performed to analyze the putative role regulatory function and on splicing activity respectively. HaploReg is a tool for exploring annotations of the noncoding genome at variants on haplotype blocks, draw on comprehensive data from the Encyclopedia of DNA Elements (ENCODE). Using LD information from the 1000 Genomes Project, genetic variants can be visualized along with their predicted chromatin state, their sequence conservation across mammals, and their effect on regulatory motifs [23] . Human Splicing Finder 3.0 tool [24] , is a tool that helps studying the pre-mRNA splicing. It combines 12 different algorithms to identify and predict mutations' effect on splicing motifs including the acceptor and donor splice sites, the branch point and auxiliary sequences known to either enhance or repress splicing. These algorithms are based on either PWM matrices, Maximum Entropy principle or Motif Comparison method." ] },{ "paper_id": "207885268ef61365fc89820ecb7c854a3dc23d9a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "The replication ability of these viruses was first assessed in L2 fibroblasts in which IFN-\u03b2 expression is not induced by MHV [49] . WT, mutant, and chimeric viruses all replicated with comparable kinetics and to similar final titers, indicating that neither the mutations in ns2 nor the replacement of NS4 by L \u00c3 affected viral replication (Fig 8B) .", "Expression vectors used in this study are summarized in Table 1 ." ] },{ "paper_id": "2079a44557da9aa2ce74d6af8ac0e8a344c1ad8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "207bf71776ac6427c03a4dffa991148bb6dd4833", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A stochastic susceptible -infectious -recovered (SIR) model was used to investigate epidemic behaviour on the livestock network. The probability of farm i becoming infected is defined as", "Simulations are carried out in the same way as detailed in \u00a72d with the one exception that we only run outbreaks for the length of one infectious period. The increased transmissibility from the inclusion of markets results in substantially larger epidemics, and therefore one infectious cycle is sufficient to analyse the effects of the different sampling methods.", "Subject Areas: health and disease and epidemiology, computational biology", ": This method explicitly depends on knowledge of the total weight of the network." ] },{ "paper_id": "207f7aeed7a6907c94d4b00ed07e2ce3ded10ded", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The nucleotide sequences of the MRV obtained from environmental sewage described here have been deposited in the GenBank database under the following accession numbers: KR296769 to KR296785.", "To detect sewage viruses growing in the cell culture, viral RNA and DNA were extracted from cell culture lysates using a ZR viral RNA kit (ZYMO Research) and a QIAamp DNA mini kit (QIAGEN) according to the manufacturer's instructions.", "This study was reviewed and approved by the Centers for Disease Control, Department of Health, Taipei, Taiwan. Permission was obtained from the wastewater treatment plants before conducting the study." ] },{ "paper_id": "2089844227bd2ff234044e4b311bf1c2bcb3838c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The human microbiome was firstly defined by Joshua Lederberg in 2001, as a community of microorganisms that live in our organism, establishing a relationship of commensalism, symbiosis or pathogenicity [1] .", "Patient demographics, comorbidities, Acute Physiology and Chronic Health Evaluation (APACHE) II score and Simplified Acute Physiology Score (SAPS) II, admission diagnosis and ICU clinical outcome were recorded.", "Not applicable." ] },{ "paper_id": "208f4d527c8ac85c04dd9e431babfaaa54e66428", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conduct an Arctic-wide disease outbreak table top exercise to describe stakeholders, processes communication, collaboration and structure as a gap analysis process", "Define/characterize local and regional processes and initiatives addressing Arctic health challenges", "Collect and share experiences of Arctic stakeholders,current situation across the region on One Health initiatives/programs", "The findings and conclusions are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention." ] },{ "paper_id": "20905ce137d4d5735c25f22352a653f3ebcbc4fc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The genome sequence was deposited in GenBank under the accession no. KJ614529.", "T.K., V.P.M., and G.N.D. are employees of the U.S. Government, and this work was prepared as part of their official duties.", "The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the US. Government." ] },{ "paper_id": "2094652c2eeb8a55eee12afad81cb3ecb86a2bcf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "209fd978d66d8ffe04712de07dc7e07b779baa08", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There have been an increasing number of studies supporting an important role for thiol (\u2212SH)/disulfide (\u2212S-S-) exchange in the entry of multiple viruses into susceptible cells, including Sindbis virus [1] , Baculovirus [2] , Vaccinia virus [3] , equine arteritis virus [4] , Moloney murine leukemia virus [5] , Newcastle disease virus [6] [7] [8] , hepatitis delta virus [9] and HIV-1 (reviewed in [10, 11] )." ] },{ "paper_id": "20a5ebd5341de218798e2defbca3e14ba15895cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. aseptic techniques, 2. patient screening and evaluation, 3. personal protection, 4. instrument sterilization, 5. immunization against hepatitis B virus, 6. surface disinfection, and 7. equipment asepsis.", "Aim: Dental students have increasing patient contact during their education and clinical years, putting them at high risk of cross-infection;", "The study was approved by the Review Board and Ethics Committee of Riyadh Elm University. A total of 400 questionnaires were distributed among clinical students and interns at Riyadh Elm University, Riyadh, Saudi Arabia. The questionnaire was designed to cover different aspects of infection control practices in dental clinics including:" ] },{ "paper_id": "20ae5549ea5761744ffac3015a31a03816699a49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Shwetank, EF, and AL contributed to the conception and design of the study and wrote the manuscript. Shwetank, EF, TM, HR, MT, ML, CN-W, GJ, and JC performed experiments, analyzed data, and performed the statistical analysis. All authors contributed to manuscript revision, read and approved the submitted version.", "Funding for this work was supported by grants from The National Institutes of Health (R01 NS088367 and R01 NS092662 to AL, R01 AI096879 to BE, F31 NS083336 to EF, and F32 NS106730 to CN-W), and the Young Investigator Award from Adaptive Biotech Inc. to Shwetank.", "p-values were determined by Mann Whitney, Wilcoxon matchedpairs signed rank test, or one-way or two-way ANOVA using GraphPad Prism software (La Jolla, CA). All p < 0.05 were considered significant." ] },{ "paper_id": "20af160641510a4c79b9a23b06ea83d27ebba059", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plaque formation assay. Cells were mock-infected or exposed to viruses in mixture supplemented with DMEM. After 90 min the inoculum was replaced with 2% FBS of DMEM. Yields of infectious virus were determined by plaque assay for 48 h. Following incubation, plaque numbers were counted. Data represent the mean of three independent experiments.", "Preparation of cell lysates and immunoblots. The cells were collected by centrifugation, rinsed with phosphate-buffered saline (PBS) containing protease inhibitor cocktail (Roche) and dissolved in 200 \u03bc l lysis buffer (pH7.5 20 mM Tris-HCl, 150 mM NaCl, 1% Triton X-100, 1 mM EDTA, 2.5 mM Sodium pyrophosphate, 1 mM \u03b2 -Glycerrophosphate, 1 mM NaVO4, 1 \u03bc g/ml Leupeptin) in the presence of the protease inhibitor cocktail and finally disrupted by sonication. Solubilization of protein was harvested from cells, electrophoresis in denaturing polyacrylamide gels were transferred to polyvinylidene fluoride (PVDF) and reacted with appropriate antibodies. The protein bands were detected with secondary antibodies conjugated to HRP, and actin expression was used as a loading control. Quantitave real-time PCR (qRT-PCR). Replicate cultures were harvested and total RNA was extracted with Trizol (Invitrogen). A two-step qRT-PCR (SYBR Green I technology, Applied Roche) was performed using SYBR green supermix (Toyobo) according to the manufacturer's protocol to measure transcription levels for several genes of interest. The primers used were as follow. GAPDH: 5\u2032 -CTG GTG ACC CGT GCT GCT T-3\u2032 (forward), 5\u2032 -TTG CCG CCT TCT GCC TTA-3\u2032 (reverse). NDV-N: 5\u2032 -TGA TGA CCC AGA AGA TAG ATG GAG-3\u2032 (forward), 5\u2032 -CTG TGA GTG GGA GCA TAA AAG AGA-3\u2032 (reverse). IBV-N: 5\u2032 -GGT TGC TGCT AAG GGT GC-3\u2032 (forward), 5\u2032 -GCC TTT GTA ATG CGG GAG-3\u2032 (reverse). Relative fold changes were automatically calculated by the Step One Plus real-time PCR system software (Applied Biosystems), following the \u0394 \u0394 C T method. GAPDH was also determined and used as internal control." ] },{ "paper_id": "20b02257b13e1631fe457bc81ed2b6033baee43e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our data do not suggest a role for MASP2 polymorphisms in SARS susceptibility in northern and southern China.", "Our analysis indicates that MASP2 polymorphisms is not directly related to SARS-CoV susceptibility in northern and southern Chinese." ] },{ "paper_id": "20b5fc51aef8b077346c4587aad3811eebf8b11b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceived and designed the experiments: JSB QY. Analyzed the data: QY. Contributed reagents/materials/analysis tools: GP BL. Wrote the paper: QY EON. Developed and evaluated the model: QY EON. Edited and revised the manuscript: JSB QY EON RC.", "In (1), index j represents the search index for j keywords, y denotes influenza case counts, a 0 ,a 1 ,e denote the intercept, coefficient and error term respectively.", "No ethics committee approval is required to obtain the data since it is publicly available. In addition, only count data is presented, no personal information is revealed, thereby maintaining confidentiality.", "The coefficients b 0 b 1 b 2 for model (2) are 0.56 (P = 0.001), 0.25 (P,0.001) and 20.14 (P = 0.004) respectively. Note the model's Rsquared is 0.95 and the AIC is 18.50. In addition, the Durbin-Watson test statistic is 1.89 suggesting that autocorrelation is not an issue (see Table 4 ). The null hypothesis of the Durbin-Watson test is that the autocorrelation parameter is zero." ] },{ "paper_id": "20c2e99b2e557513c61d82a9d291b809eafaf70e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "20c5f4025a94ca3a48d6d8a23a9db2ebc8b5ec03", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords Bronchiolitis, caspase, disease severity, lactate dehydrogenase.", "Background Bronchiolitis is the leading cause of hospitalization in infants. Biomarkers of disease severity might help in clinical management.", "Further work exploring the balance between necrosis and apoptosis has been done in in-vitro studies showing that virally infected human lung epithelial cells release both LDH and caspases. 24 Additional studies would likely include further clinical work with hospitalized infants over time, demonstrating the overall trajectory of these biomarkers relative to clinical status.", "Supported in part by Department of Defense Grant W81XWH1010146 (R.P.G.). R.M. was supported by a Postdoctoral fellowship from the NIEHS (T32-07254). The contents are solely the responsibility of the authors and do not necessarily represents the official view of the granting agencies." ] },{ "paper_id": "20d1c063410f32eb59b3f3063d506c4888c80bec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To determine if glycosylation contributes to the observed differences, we generated a dCAT-1 clone from which the N-glycosylation sites had been removed." ] },{ "paper_id": "2106f8105f3cb30bf479fdcb6d78e4891a204080", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Graphical programs. Figures 1 to 5, 8 , S1, S3 and S8 were produced using the programmes UCSF Chimera 75 and Adobe Illustrator (Adobe Systems Inc., San Jose, California, USA). Figures 6, 7 and S2, S4 to S7 were produced using Adobe Illustrator." ] },{ "paper_id": "21083480591a0f89c6c6a1ee575c79ef9eeaeb75", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A DNT producing Pm isolate, which originated from a pig with the clinical form of progressive atrophic rhinitis, was cultured on blood agar at 37\u00b0C for 24 h. A suspension of this culture to 0.7 McFarland turbidity (which corresponds with approximately 1.5 \u00d7 10 8 colony forming units (CFU)/ml) was prepared in PBS. A plate count was also performed to quantify the accurate number of viable bacteria (final result 1.5 \u00d7 10 8 CFU/ml).", "Whole blood samples were analyzed for different leukocyte proportions and concentrations on a Abacus Junior Vet 5 hematology analyzer (Diatron, Hungary). Proportions of lymphocytes, monocytes and granulocytes were calculated as a percentage of leukocyte concentration." ] },{ "paper_id": "210a892deb1c61577f6fba58505fd65356ce6636", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data were processed using R version 3.6.2 [12] , MLE was computed using Julia version 1.3 [13] , and the Markov chain Monte Carlo (MCMC) simulations were performed in Stan (cmdStan version 2.22.1 [14] ). All code is freely available at the github repository: http://github.com/aakhmetz/ WuhanIncubationPeriod2020.", "Here, r is the exponential growth rate (estimated at 0.14 [11] ), T is the latest time of observation (31 January 2020), and F(.) is the cumulative density function of f (.).", "The authors declare no conflicts of interest.", "Here, in the case of (a) g(.) is the probability density function (PDF) of exposure following a uniform distribution, and f (.) is the PDF of the incubation period independent of g(.). D represents a dataset among all observed cases i, where exposure and symptom onset fall within the lower and upper bounds (E L , E R ) and (S L , S R ). We fit the PDF f (.) to lognormal, Weibull, and gamma distributions." ] },{ "paper_id": "210ebd55fd095ff2fb393e871fea70815a9ead75", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To determine transfection efficiency, we monitored GFP fluorescence intensity of transfected cells using fluorescent microscope analysis. Culture supernatants were collected for virus titration. Six days post infection, supernatants was harvested from the infected cultures and virus titer (TCID50) was determined three times on Vero cells.", "This study provides not only an experimental basis for the development of a new anti-GTPV strategy, but also for a new approach to the study of GTPV infection and replication.", "Cells were further subjected to fluorescence-activated cell sorting (FACS). At 48 h posttransfection, the transfected cells and the controls were washed gently in phosphate-buffered saline (PBS), trypsinized and resuspended in PBS. EGFP positive cells and EGFP expression signal were evaluated by the FACS Calibur Flow Cytometry System (Becton Dickinson, USA).", "Blasting ORF095 sequence in GenBank revealed that there were 8 Capripoxvirus isolates containing identical sequence corresponding to ORF095. In view of the sequences of the ORF095 genes of GTPV strains from the same genotype, they all share high homology (95-100%). Therefore, ORF095 gene is a good target to suppress GTPV replication by RNAi." ] },{ "paper_id": "21133fab598928cee990ee06d660b1d00f317175", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza virus causes substantial disease in low-and middle-income countries each year, but data on the disease burden are limited [1] . Data on influenza from country-level surveillance can show the distribution of disease among the population and identify groups at high risk of infection. This information can subsequently help policy makers make evidence-based decisions on how to target influenza treatment and prevention programs, such as vaccination, and can lead to more effective allocation of resources within a country [2] .", "Supporting Information S1 " ] },{ "paper_id": "21268687c8044a9acd561589e1f291f0843c6678", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pathogen proteases are important virulence factors that facilitate infection, diminish the activity of lysozymes and quench the agglutination capacity of hemocytes. Because protease inhibitors play important roles in invertebrate immunity by protecting hosts through the direct inactivation of pathogen proteases, many bivalves have developed protease inhibitors to regulate the activities of pathogen proteases [1] . Some genes encoding protease inhibitors were identified in C. gigas [57] , A. irradians [58] , C. farreri [59] and C. virginica; in the latter a novel family of serine protease inhibitors was also characterized [60] [61] [62] .", "After annotation, Blast2GO software [89] was used to assign Gene Ontology terms [90] to the largest contig of a representative cluster (minimum of 100 bp). This strategy was used to avoid redundant results. Default values in Blast2GO were used to perform the analysis and ontology level 2 was selected to construct the level pie charts.", "Pyrosequencing. After stimulation, hemolymph was centrifuged at 1700 g at 4uC for 5 minutes, the pellet was resuspended in 1 ml of Trizol (Invitrogen) and RNA was extracted following the manufacturer's protocol. After RNA extraction, samples were treated with Turbo DNase free (Ambion) to eliminate DNA. Next, the concentration and purity of the RNA samples were measured using a NanoDrop ND1000 spectrophotometer. The RNA quality was assessed in a Bioanalyzer 2010 (Agilent Technologies). From each sample, 1 mg of RNA was pooled and used for the production of normalized cDNA for 454 sequencing in the Unitat de Gen\u00f2mica (SCT-UB, Barcelona, Spain).", "Antimicrobial peptides (AMPs) are small, gene-encoded, cationic peptides that constitute important innate immune effectors from organisms spanning most of the phylogenetic spectrum. AMPs alter the permeability of the pathogen membrane and cause cellular lysis [63] . In bivalves, they were first purified from mussel hemocyte granules [64, 65] . In mussels, the AMP myticin C was found to have a high polymorphic variability as well as chemotactic and immunoregulatory roles [66, 67] . In clams, two AMPs with similarity to mussel myticin and mytilin [68] and a big defensin [69] are known." ] },{ "paper_id": "212b5e2ca9c78f0864f5a8540b36b3c18ad06d27", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All media were supplemented with 10% fetal bovine serum (Hyclone Laboratories), 2 mM L-glutamine, 100 U/ml penicillin, and 100 \u03bcg/ml streptomycin.", "2.8. Histology and Immunofluorescence. For histological assessment, samples of dorsal skin from the disease model (day 7) were fixed in 10% formalin for \u226524 h at 23\u00b0C and embedded in paraffin. Deparaffinized 5 \u03bcm sections were stained with hematoxylin erythrosine saffron and assessed by light microscopy." ] },{ "paper_id": "213313b5fe57d1ecf1930503ed0e7fd8e1dc73e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine coronaviruses, particularly PEDV, transmissible gastroenteritis virus, and porcine deltacoronavirus, have caused devastating losses at the global level [10] . New swine coronaviruses, e.g., swine acute diarrhea virus (SADS-CoV), continue to emerge with effects yet to be determined [11] . Highly transmissible and stable in the environment [10] , these viruses have moved rapidly across pork-producing regions of the world. The exception to the rule, Canada has been effective in slowing the spread of PEDV and PDCoV and may ultimately succeed in eliminating both viruses [12] . The Canadian effort is based on extensive surveillance of animals, farms, and the production chain, i.e., livestock assembly yards, abattoirs, truck wash stations, and livestock trailers, by RT-rtPCR. If control and elimination is successful, other regions may choose to follow suit. However, swine coronaviruses will continue to circulate widely in swine populations in much of the world. Thus, inexpensive but effective surveillance methods will be needed to detect incursions, guide program responses, and maintain freedom from these pathogens.", "In the context of surveillance, meat juice-based testing presents significant advantages. Porcine muscle specimens are readily collected at the abattoir and avoid the biosecurity risks inherent to on-farm visits. The disadvantage of this approach is that infection is only recognized retroactively. Regardless, meat juice is easily recovered by thawing the frozen meat sample and is compatible with high-throughput testing.", "S=P ratio \u00bc sample OD \u00c0 blank well control mean OD \u00f0 \u00de positive control mean OD \u00c0 blank well control mean OD \u00f0 \u00de" ] },{ "paper_id": "213fdedff656134ff3dbe24a7d7bbba61d13baa1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Intracellular staining for analysis of CD4 + Th1, Th17, and Treg cells" ] },{ "paper_id": "2142f50e9a7ace971bc142fe4067a52c91b7af28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses belong to the order Nidovirales, family Coronaviridae, and subfamily Coronavirinae [1] , and are characterized by their large genome, helical nucleocapsids, and unique method of gene expression [2] . The subfamily includes four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and the more recently discovered Deltacoronavirus [3] . a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Three valid replicates were used to evaluate how well the model fit with the experimental data by calculating the adjusted R 2 (Adj. R 2 ) as follows:", "Conceptualization: SMG GCS PEU. " ] },{ "paper_id": "21469fd00f33c1dcdde68abf4b8da0508b7fe2d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The designs of the animal experiments are shown in Table 2 .", "For the control of PPR, four attenuated vaccines are available commercially. In endemic areas, the virus is currently controlled using the Nigeria 75/1 strain (Nig75/1), which has been attenuated by serial passage in Vero cells. In India, three other live attenuated vaccines are currently licensed for use: Sungri 96, Arasur 87, and Coimbatore 97 [9] . However, a major disadvantage of these attenuated vaccines is that they cannot be used for differentiating infected from vaccinated animals(DIVA).Recently, subunit vaccines have been developed based on the incorporation of PPRV immunogens into various vector systems, such as sheep or goat pox, vaccinia virus, adenovirus, or baculovirus vectors [10, 11, 12, 13] .", "The data were analyzed with one-way ANOVA in GraphPad Prism version 5.00 (GraphPad Software, San Diego, CA, USA); pvalues less than 0.05 were considered statistically significant.", "Similarly, a bacmid transfer vector,p-MF, which permitted expression of both the M and F genes, was prepared by cloning the F gene, as a 1.6-kb BamHI-XbaI DNA fragment, downstream of the P H promoter, into p-M (Fig.1 )." ] },{ "paper_id": "215d86822474f970baa8ed894e23940bc4a85c79", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA extraction. Viral RNAs were extracted using RNeasy mini kit (Qiagen, Hilden, Germany) according to the manufacturer's instruction. Extracted viral RNAs were used in subsequent reverse transcription for synthesizing cDNA or stored at -70 \u02daC for later use.", "Virus strains. In this study for developing duplex-PCR, two standard field strains of NDV (Razi institute), a vaccinal strain of IBV named IB88 (Merial, Lyon, France) and one field strain of IBV named 793/B (Faculty of Veterinary Medicine, Tehran, Iran) were used.", "Field samples. Clinical samples including trachea, liver and kidney were collected from chickens with respiratory symptoms from 12 broiler farms. All farms had a routine history of vaccination against IBV and NDV. Six birds were collected from each broiler farm. Mucosal layer of trachea was scratched by scalpel blade. Tissues of 0.5 cm 3 was removed from each liver and kidney and then crushed in a sterile mortar with one mL sterile PBS buffer." ] },{ "paper_id": "215e667edcc02054361258755a4db8bca18a4e9b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As shown in Fig. 3 , public health enrollment increased at a rate of 7.3% per year, which was much lower than the other health-related disciplines such as nursing (31.9%), integrated Chinese western medicine (28.9%), stomatology (21.8%), and pharmacy (17.8%).", "The dataset generated and analysed during the current study are not publicly available because it is the asset of the Ministry of Education of People's Republic of China and the authors are not authorized to share it to the public. Researchers who are interested in the dataset for academic purpose may contact JH: houjianlin@bjmu.edu.cn.", "Our analysis of the MOE dataset was focused on higher education institutions (HEIs) that offer education for public health, with at least one program in the first-level discipline: public health and preventive medicine. These programs are offered through junior college, bachelor, master, or doctorate degrees." ] },{ "paper_id": "215fb42f8f5f2ede1ed7e7b1561e51f494593578", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Authors' contributions AM designed the concept, carried out the literature search, and drafted the manuscript. AW designed the figure, participated in the literature search, and helped draft the manuscript. MB performed an independent literature search and helped draft the manuscript. All authors read and approved the final manuscript.", "The mammalian response to injury occurs in three distinct phases [8] . The initial inflammatory phase occurs immediately following insult and involves activation of the coagulation cascade, fibrin deposition, and infiltration of macrophages and neutrophils [9] . Following this, the proliferative phase is defined by angiogenesis, fibroblast proliferation, and differentiation [10, 11] . Finally, in the remodeling phase, fibroblasts and myofibroblasts deposit a collagen-rich extracellular matrix that will ultimately become a scar that replaces the injured functional tissue. This process of healing is highly conserved across tissue types.", "The authors declare that they have no competing interests." ] },{ "paper_id": "217114455f564a37a057840d761b901fd372bef3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The newly determined sequences have been deposited in the NCBI nucleotide sequence database and assigned the following accession numbers: KC340952 (farm numbers 1 and 2); KC340953 (farm number 7); KC340954 (farm numbers 8 and 11); KC340955 (farm number 10); KC340956 (farm number 13); KC340957 (farm number 14); KC340958 (farm number 18).", "To confirm the specificity of the fragments obtained by RT-PCR, PCR products were purified and used for sequencing. The purposed band, about 450 bp, was excised and then purified using Biomed gel extraction kit (BEIJING BILOMED CO., LTD) according to the manufacturer's instructions. The resulting products were cloned into pMDT-19 simple vector (Takara) for sequencing.", "Using Table 2 ." ] },{ "paper_id": "217e7ecb495478a12b89de6ab9d03e629f478752", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The statistical difference between the groups was determined by AVOVA and Tukey's Studentized Range test. Differences among groups were considered statistically different at P < 0.05. ", "From our results, we can deduce that cell apoptosis induced by lycorine is a very complex process involving the interaction of multiple signal transduction pathways and it deserves further study.", "The human acute promyelocytic leukemia (APL) cell line HL-60 (ATCC Number: CCL-240) was cultured in RPMI-1640 medium containing 10% fetal bovine serum (FBS), 100 U/ml penicillin, and 100 mg/L streptomycin at 37\u00b0C with 5% CO 2 and saturated humidity. When the cell density reached 5 \u00d7 10 5 to 1 \u00d7 10 6 /ml, the cells of the experimental group were treated with lycorine, untreated cells represented the control." ] },{ "paper_id": "2181d2f31f1f4b8c6203668dee4f6b3f382af799", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hologram QSAR (HQSAR) offers the ability to rapidly generate QSAR models of high statistical quality and predicted value by SYBYL line notation (SLN), cyclic redundancy check (CRC) and partial least squares (PLS) [33] [34] [35] . The premise of HQSAR is that since the structure of a molecule is encoded within its 2D fingerprint and that structure is the key determinant of all molecular properties (including biological activity), it should be possible to predict the activity of a molecule from its fingerprint.", "The structures and inhibitory activities (IC50) of 25 andrographolide derivatives ( Figure 1 ) were collected from the literature, and served as the database to build QSAR models [13, 14, 31] . PLogIC50 was used as the dependent variable of QSAR model. PCA, HQSAR, CoMFA, CoMSIA were performed by Sybyl7.03 (Tripos Co., LTD) program. ", "QSAR [21] has been widely used for years to provide quantitative analysis of structure and activity relationships of compounds. Statistical methods are applied in QSAR modeling to establish correlations between chemical structures and their biological activities. Once validated, the findings can be used to predict activities of untested compounds. Recently, computer-assisted drug design based on QSAR has been successfully employed to develop new drugs for the treatment of cancer, AIDS, SARS, and other diseases [22] [23] [24] [25] [26] [27] [28] [29] . With the availability of large commercial databases and highly efficient programs including Sybyl, Discovery studio, MOE and so on, it is estimated that QSAR modeling as a tool could remarkably reduces the cost of drug discovery [30] .", "The distribution pattern of the 25 andrographolide derivatives is shown in Figure 2 . There were different population densities in the Figure. Eighteen compounds (1, 3-8, 11, 13, 16-21 and 23-25) were selected as the raining set by the MDC method. The rest of them (compounds 2, 9, 10, 14, 15 and 22) were used as the test set whose biological activities were covered by the training set. " ] },{ "paper_id": "21823032c216c8f7e08c918373d49518c68aaab1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Outbreak Timeline 2013-present May-July 2015 ", "Poor, conflicted among boards Good, standardized", "Information Unavailable Mandatory masks, gloves, gowns for visitors and staff" ] },{ "paper_id": "2183478af3f9343c0f566eee8b5d95a1abea6754", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Approximately 20-30 ng of each amplimer was used for direct sequencing using a 9800 Fast Thermocycler, a Big Dye automated DNA sequencing kit, and a 31306l Genetic Analyzer (Applied Biosystems, Foster City, CA).", "The GenBank accession numbers for the F5 nIgG light and heavy chain variable region sequences are HM047070 and HM047071, respectively." ] },{ "paper_id": "2188208efc7ac8e7721dfc5cbea787d5b62c3537", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "2191141163dc621f5b160f741d880e9ce6342e3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The time to result was compared with the Wilcoxon signedrank test, using IBM SPSS Statistics version 23 software for Windows. A p-value < 0.05 was considered statistically significant.", "Currently, the diagnosis of respiratory infections is usually based on (a combination of) molecular amplification methods and bacterial culture. In our laboratory, laboratory-developed real-time polymerase chain reaction (PCR) multiplex assays (LDT) are used that show excellent sensitivity and specificity. However, this approach is limited by the number of targets per multiplex reaction and the need for batch-wise testing. The assays are performed once daily, with a time to result of approximately 20 h.", "Respiratory tract infections are a leading cause of hospital admission, morbidity, and mortality [1] [2] [3] [4] . At presentation, etiological agents of the respiratory tract infection cannot be identified solely based on clinical signs and symptoms. Therefore, and awaiting microbiological confirmation, empirical antibiotic and antiviral treatment is initiated based on severity score and the influenza season [5] . Since only a minority of the infections is being caused by bacteria, this empiric antibiotic treatment approach is redundant and can lead to an increase in antibiotic resistance. Moreover, empiric isolation precautions are installed to protect other patients and healthcare workers from a possible (viral) infection. Altogether, there is a need for rapid identification or exclusion of a viral respiratory tract infection to reduce inappropriate (unnecessary) hospital hygienic interventions and focus (shorten) antibacterial/antiviral treatment." ] },{ "paper_id": "219db23666b8e31245a5a93f4c8bda3606449296", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "William R Strohl declares that he has financial interest in Johnson & Johnson, for whom he was recently an employee, but no other potential conflicts of interest. This article does not contain any studies with human or animal subjects performed by the author.", "The 864 unique antibody-based molecules/cells in development or approved for therapeutic use (Table 3 ) target 328 unique antigens (Table 4 ). Because several targets are important for multiple disease areas (e.g., vascular endothelial growth factor [VEGF] as a significant target in both oncology and ophthalmology indications), there are more uses listed than antibodies. Thus, 864 unique molecules are used in 884 different major therapeutic area indications (Table 4) , and the 328 unique targets are distributed amongst 351 major uses (Table 5) .", "Finally, not all cancer cells within a tumor are target antigen-positive (Singh et al., 2016) , thus allowing potential Abbreviations: BBB, blood brain barrier; CDC, complement-dependent cytotoxicity; CDRs, complementarity determining regions; CNS, central nervous system; ERT, enzyme replacement therapy.", "Antibody-directed modulation of immune cell checkpoint receptors has become one of the most exciting and important new areas in antibody therapeutics over the past few years. Most efforts have been focused on T cell checkpoint modulation, but there is increasing interest in B cell, NK cell, and myeloid cell checkpoint modulation as well." ] },{ "paper_id": "21a539cc5e6c5ce8c39d80a59033791d7860a8b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine kidney PK15 cells (free of PCV-1 and PCV-2) were grown in Eagle's Minimum Essential Medium (Lonza, Levallois-Perret, France) supplemented with 5% of fetal calf serum (FCS) and Penicillin and Streptomycin (Gibco, Life technologies, Cergy-Pontoise, France), the growth medium.", "Mutations introduced in the primers are in bold and underlined. Five-week-old specific-pathogen-free (SPF) piglets, from the Anses SPF herd, were used. The SPF piglets were free from porcine circovirus type 1 and 2 (no DNA and no PCV-antibodies detected), virus of African swine fever and classical swine fever, virus of bovine viral diarrhea, Border disease virus, Aujeszky's disease virus, parvovirus, porcine reproductive and respiratory syndrome virus, swine influenza virus, virus of transmissible gastro-enteritis, porcine respiratory coronavirus, M. hyopneumoniae, P. multocida, B. bronchiseptica, A. pleuropneumonia, H. parasuis, S. suis, T. hyodysenteriae. The experiment was performed in accordance with EU and French regulations on animal experimentation.", "Regarding relative daily weight gain (rDWG) no differences between any groups were observed (data not shown).", "Research grade plasmid DNA (endotoxin \u2264 100 E.U./mg DNA) from the four constructions was produced at a concentration of 0.5 mg/mL by Plasmid Factory (Bielefield, Germany). For the trial, each DNA suspension was diluted " ] },{ "paper_id": "21a9444b2cd05fcac9c082ca87fac36e91086b6c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "chronic infection in \u03fe71 million individuals worldwide, which are at risk of developing liver cirrhosis and hepatocellular carcinoma (3) . The genus Flavivirus encompasses 53 species and comprises a number of vector-borne, zoonotic agents responsible for acute and self-limiting diseases, which can, in some cases, lead to severe symptoms (vascular leakage, hemorrhage, encephalitis, meningitis) (4) . As has been observed for Zika virus (ZIKV), which has recently spread throughout South and Central America and the Caribbean (5) , several flaviviruses are considered emerging or reemerging pathogens and can rapidly become endemic, thereby leading to serious short-or long-term health consequences (6) . Hepaciviruses and flaviviruses are therefore a major human health concern. The newly proposed genus Pegivirus as well as the genus Pestivirus mainly comprises virus species of veterinary relevance that cause gastrointestinal, respiratory, and reproductive diseases in animals, which are associated with major economic losses (7) (8) (9) .", "Supplemental material for this article may be found at https://doi.org/10.1128/AAC .01206-18.", "SUPPLEMENTAL FILE 1, PDF file, 5.0 MB." ] },{ "paper_id": "21c5b88a655bb1b5b8c3c3cd1dc1aefcf2c75cbd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SCIentIfIC RePoRtS | (2018) 8:15000 | DOI: 10 .1038/s41598-018-32984-0" ] },{ "paper_id": "21caf0c49864b6af4c62e68e3ff7374e14c16537", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequences of each PCR product were assembled using SeqMan II program (DNASTAR, Inc). The identification of open reading ", "Members of the Parvoviridae family are small non-lipid enveloped viruses with a diameter of 18-26 nm, icosahedral symmetry (T = 1), encoded by a single-stranded linear DNA genome of approximately 4,000 to 6,000 nucleotides (nt) [1] . The family includes two subfamilies: Densovirinae, Parvovirinae. The subfamily of Densovirinae contains four genera: Densovirus, Iteravirus, Brevidensovirus and Pefudensovirus, which infect only invertebrates [1] . The Parvovirinae subfamily is currently subdivided into five genera: Parvovirus, Erythrovirus, Dependovirus (adeno-associated virus), Amdovirus, and Bocavirus, infecting vertebrates [1] .", "Random RT-PCR DNA products ran as smears on agarose gel and were gel purified (Axygen, CA, USA), then subcloned into pMD-18T plasmid vector (TaKaRa, Japan) for sequencing. The sequences were then screened for sequence similarities using tBLASTx and BLASTn against the nr database in GenBank. " ] },{ "paper_id": "21d0dff90077800702fb5a6502246e9d512b6fe8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a The enzyme kinetic parameters were determined by GraphPad Prism by the equation", "(" ] },{ "paper_id": "21da52646864c1ad3303daf10f0b3e4c9d12fa5c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Surprisingly, we did not detect any peptide corresponding to gN either in MuHV-4 or in BoHV-4 virions. However, as previously mentioned, gN and gM form a complex in herpesviruses [43, 44] and gN is needed for the proper processing of gM. Moreover, we readily detected gN by Western blotting on the same MuHV-4 virions preparations even after the proteinase K treatment [29] . The absence of gN in our analyses is therefore likely due to a detection failure by our mass spectrometry approach.", "Proteomics is a highly valuable tool for studying virus structure and understanding mechanisms by which viruses can replicate and spread using the host cellular machinery. Frequently, the cellular response to virus infection is analyzed by looking at changes in cellular protein abundances and post-translational modifications but also viral-host protein interactions (for a global review see [3, 4] ). The contribution of proteomic analyses to the understanding of the life cycle of alphaherpesviruses have been recently reviewed by Engel et al. [5] . In addition to understanding the host response to viral" ] },{ "paper_id": "21e12783ad4aac6ecf757de6c644368ad999cd58", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bolaji Thomas is supported by a Research Laboratory and Faculty Development Award, College of Health Sciences and Technology, Rochester Institute of Technology. This work also received additional funding from Miller Chair in International Education (BNT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.", "The following grant information was disclosed by the authors: Research Laboratory and Faculty Development Award. College of Health Sciences and Technology. Rochester Institute of Technology. Miller Chair in International Education (BNT).", "The following information was supplied regarding data availability: This is a review paper. No raw code or raw data is involved." ] },{ "paper_id": "21e6d4c42e4375fcb05eeebb140a805461688542", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "21f0073aa9c5c592c81fd9db4e11d61a35865cf7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "21fd38266c7336a6ace6ca87ee9ac07a580cfdeb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pooled gut homogenates were clarified via centrifugation (2400 \u00d7 G and 5500 \u00d7 G; 15 min each, 4\u00b0C, SLA 1500 SuperLite rotor, Sorvall) and clarified supernatant was subjected to stepwise filtration through 0.8 micron and 0.45 micron cutoff syringe or bottle filters (Nalgene). The clarified, filtered homogenates were then spun at 41K for 4.5 hours at 4\u00b0C (Beckman Type 80 Ti, 113,000 \u00d7 G). The resulting supernatant was removed and the virus pellet was re-suspended in sterile phosphate-buffered saline (PBS) via shaking at 4\u00b0C. The re-suspended pellet was aliquoted into cryogenic tubes and held at -80\u00b0C. DNAse and RNAse treatment of re-suspended viral particles was performed to minimized the amount of unencapsidated nucleic acid in the preparations: 450\u03bcl of the re-suspended pellet, 50\u03bcl 10X Turbo DNAse buffer (Ambion), 2.5\u03bcl Turbo DNAse (2Units/\u03bcl), 0.25\u03bcl RNAse A (20mg/ml, Invitrogen), 37\u00b0C for 1 hour. Following the nuclease treatment, total RNA was isolated from the viral particle suspension using a hybrid protocol with Trizol reagent and MagMax kit (Life Technologies) as described previously [29] . Multiple MagMax extractions were performed in concert using a KingFisher instrument (Thermo Scientific) to collect 250\u03bcl of viral RNA. Total viral RNA was precipitated via sodium acetate/ethanol precipitation, re-suspended in 50\u03bcl TE buffer, and stored at -80\u00b0C.", "PCR and 454 pyrosequencing of the V1-V3 regions of 16S rRNA genes were performed using tagged amplicon methods as previously described [34] . Briefly, sequences were de-multiplexed and preprocessed with the Galaxy toolkit [35] and our own custom tools [36] ; additional quality controls per recent recommendations and standard protocols [37] were completed using Perl and Bioperl scripts to trim pyrosequencing tag sequences, screen for presence of the forward PCR primer sequence, and remove sequences with any ambiguous base calls. Based on expected amplicon sizes and frequency distributions of sequence lengths in v108 of the Silva reference database [38] , sequences were further limited to a range of 325-425 bp. Putative chimeric sequences were identified with usearch [39] and ChimeraSlayer in mothur [40] .", "Preparation and amplification of viral cDNA cDNA first strand and second strand synthesis using random hexamers and oligo dT was performed on the total viral RNA using the SuperScript Choice System cDNA kit (Invitrogen). cDNA was ligated to the included EcoRI/NotI double-stranded oligonucleotide adapter and sephacryl-column purified to remove excess adapters to select for cDNA size (>500bp). Total viral cDNA was then subjected to a PCR amplification step using a single oligonucleotide (5'-CGG CCG CGT CGA C-3') directed toward the ligated adapter sequence. The PCR reaction (50ul) was aliquoted into five equal reactions and subjected to thermal cycling (94C for 30s, 55C for 30s, 72C for 2 min for 35 cycles; final extension at 72C for 7 min); the aliquots were pooled following PCR and purified (Qiagen MinElute PCR cleanup kit). PCR amplicons were checked via agarose gel electrophoresis. Purified, amplified cDNA representing the total viral RNA was submitted directly for high-throughput sequencing. Prepared cDNA was barcoded and sequenced using the Ion Xpress Library Kit (Life Technologies) and the Ion Torrent Personal Genome Machine (PGM) platform." ] },{ "paper_id": "222534164391422210b3089109605e8ff4d1d46c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human MMP2 5\u2032 -CCCTGATGTCCAGCGAGTG-3\u2032 5\u2032 -ACGACGGCATCCAGGTTATC-3\u2032 Human MMP9 5\u2032 -CCAACCACCACCACACCG-3\u2032 5\u2032 -GCAGGCATCGTCCACCG-3\u2032 Human IL-17 5\u2032 -CGCAATGAGGACCCTGAGAG-3\u2032 5\u2032 -GCCCACGGACACCAGTATC-3\u2032 Human GAPDH 5\u2032 -AGCCACATCGCTCAGACAC-3\u2032 5\u2032 -GCCCAATACGACCAAATCC-3\u2032 Mouse TGF-\u03b2 1 5\u2032 -CAACAATTCCTGGCGTTACCTTGG-3\u2032 5\u2032 -GAAAGCCCTGTATTCCGTCTCCTT-3\u2032 Mouse vimentin 5\u2032 -CTGTACGAGGAGGAGATGCG-3\u2032 5\u2032 -AATTTCTTCCTGCAAGGATT-3\u2032 Mouse TSP-1 5\u2032 -TGACCCTGGACTTGCTGTAG-3\u2032 5\u2032 -CGGCTGCTGGACTGGTAG-3\u2032 Mouse Egr-1 5\u2032 -GGAGCAAAGCCAAGCAAAC-3\u2032 5\u2032 -ACGGAACAACACTCTGACAC-3\u2032 Mouse GAPDH 5\u2032 -TGAGGCCGGTGCTGAGTATGTCG-3\u2032 5\u2032 -CCACAGTCTTCTGGGTGGCAGTG-3\u2032" ] },{ "paper_id": "222f2de4774452963b9c8b640faf80dced073b64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The experimental setup was approved by the University of New England, Animal Ethics Approval Committee under Authority No. AEC15-022. The protocol was carried out in accordance with the guidelines specified in the Australian Code for the Care and Use of Animals for Scientific Purposes 8 th edition 2013.", "Time " ] },{ "paper_id": "22371f1a9a91782adf48ffc5ad7d54d9a7a61b13", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This general, internet-based survey conducted with healthy volunteers from the general population did not require formal, medical ethical approval, according to Dutch law [26] .", "Background Q fever is a zoonosis caused by the bacterium Coxiella burnetii. The primary reservoirs of the bacterium are farm animals, including goats, sheep, and cattle [1] . Acute Q fever typically presents as an influenza-like illness, but severe infections, like pneumonia and/or hepatitis, may also occur [2, 3] . Approximately, 1-5% of all Q fever cases may progress to a chronic infection, which often leads to lifethreatening endocarditis. Although Q fever is associated with substantial morbidity, mortality is uncommon (1-2% of cases) [1, 4] .", "Data sharing data are available on request from MB m.bults@rotter dam.nl" ] },{ "paper_id": "2239f23b3b6738f24cd381b0ee59faaf39a8a027", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A paired t-test was performed to determine statistical significance using GraphPad QuickCalcs software (GraphPad Software Inc., La Jolla, CA).", "Confocal images were acquired with a Nikon PCM 2000 (Nikon Inc. Mellville, NY, USA) using the Argon (488) and the green Helium-Neon (543) lasers. Serial optical sectioning was performed with Simple 32, C-imaging computer software (Compix Inc, Cranberry Township, PA, USA). Z series sections were collected at 0.5 mm using a 606 PlanApo objective and a scan zoom of 26. Images were processed in NIH Image J (National Institutes of Health, Springfield, VA, USA).", "For transfection of 253-NT cells, 1610 6 cells at 75% confluence were transfected with 7.5 mg of plasmid DNA in Lipofectamine LTX reagent (Invitrogen) following the manufacturer's recommended protocol. After incubation for 24 hours in complete medium, stable transfectants were selected by maintaining cells in complete medium containing geneticin (Invitrogen) at 600 mg/ml with medium changes every 48 hours. For all subsequent experiments, geneticin resistant cells were maintained in complete selection medium." ] },{ "paper_id": "223d9fa8ef42ff808b3301ec2f96cb0a13bf059e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, CPV has been taxonomically segregated as an unclassified virus as well as caprine pneumovirus and ovine pneumovirus [7] ." ] },{ "paper_id": "22450e467873a3cf4f2627d36d6f71aa779520c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "-4-O-acetylneuraminic acid V 5-N-Acetyl-7-O-acetylneuraminic acid V, Pz, B 5-N-Acetyl-8-O-acetylneuraminic acid V, B 5-N-Acetyl-9-O-acetylneuraminic acid V, E, Pz, F, B, H [31] 5-N-Acetyl-4,9-di-O-acetylneuraminic acid V 5-N-Acetyl-7,9-di-O-acetylneuraminic acid V, B, H [32] 5-N-Acetyl-8,9-di-O-acetylneuraminic acid V, H [32] 5-N-Acetyl-4,7,9-tri-O-acetylneuraminic acid V 5-N-Acetyl-7,8,9-tri-O-acetylneuraminic acid", "Funding: S.S.P. acknowledges support received through the Earl C. Anthony Fellowship (University of California, Davis)." ] },{ "paper_id": "2246e28681bde69c65dc9081df367bb661997f19", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Strain typing was attempted for all WB and skin samples obtained from SS patients, which were Tp-positive by diagnostic PCR. PCR amplification and sizing of the 60-bp tandem repeats within the arp (acidic repeat protein) gene and PCR-restriction length polymorphism (RFLP) analysis of tpr (T. pallidum repeat) E, G, and J genes was done as previously described by Pillay et al. [26, 27] , with two modifications. First, the tandem repeat region within the arp gene was amplified with a new primer pair, N1 (59ATCTTTGCCGTCCCGTGTGC39) and N2 (59CCGAGTG-GGATGGCTGCTTC39) using the existing PCR conditions for the arp assay. Second, all PCR amplicons were analyzed on an Agilent 2100 Bioanalyzer (Agilent Technologies, San Diego, California).", "PCR amplification was performed using forward primer TP-1 (59CAGGATCCGGCATATGTCC39), reverse primer TP-2 (59AAGTGTGAGCGTCTCATCATTCC39), and probe TP-3 (59CTGTCATGCACCA GCTTCGACGTCTT39) as previously published [24] with some exceptions. The probe was labeled with Cyanine (Cy5) at the 59 end and black-hole quencher 3 (BHQ3) at the 39 end. PCR was performed in 50ml reaction volumes containing the following: 4ml of deoxynucleoside triphosphate mix (2.5mM of dATP, dCTP, dGTP, and 5.0mM of dUTP), 6ml of MgCl 2 (25 mM), 0.2mM of each primer, 0.6U uracil Nglycosylase, 5U of AmpliTaq Gold polymerase, 5ml of 106 PCR buffer (All Applied Biosystems, Foster City, CA), 0.2mM of probe, and 12ml of template DNA. Thermocycling was performed in a Rotor-Gene 6000 instrument (Qiagen) as follows: 50uC for 2 min and 95uC for 10 min and 45 cycles of 95uC for 20 sec and 60uC for 1 min. Each PCR run included positive and negative (no template) control reactions. The Tp copy numbers for each WB specimen were extrapolated from the standard curve generated using ten-fold serial dilutions of purified Tp DNA. A human ribonuclease (RNase) P gene PCR assay was used, as previously described [25] , to test for PCR inhibition in blood samples that were negative by the polA real-time PCR assay. ", "None of the WB samples analyzed had sufficient quantity of Tp DNA to satisfactorily perform molecular strain typing. On the other hand, six of the eight positive skin samples were amenable for typing. By combining the 60-bp arp repeat sizes and the tpr E, G, and J RFLP patterns, we identified four different strain types; two each were 14d and 16d, and one each was 13d and 22a, respectively. The remaining strain was partially typeable by tpr RFLP analysis (pattern a). Although it is not possible to generalize our results due to the small sample size, our data suggests high strain diversity, which reflects the pattern seen in South Africa [27] , where syphilis is known to be highly endemic." ] },{ "paper_id": "225d47cea0dca6f6211b16f9bf8911e2360fb75b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Real-time PCR specific for CPV-2 was performed on the ABI 7500 instruments described previously with some modifications [18] . Premix Ex Taq\u2122 (Takara Co., Ltd., Dalian, China) was applied in the real-time PCR and the reaction was performed as follows: 95\u00b0C for 3 min, followed by 40 cycles of 95\u00b0C for 10s and 60\u00b0C for 32 s.", "The real-time RPA reactions were performed in a 50 \u03bcL volume using a TwistAmp\u2122 exo kit (TwistDX, Cambridge, UK). Other components included 420 nM each RPA primer, 120 nM exo probe, 14 mM magnesium acetate, and 1 \u03bcL of viral or sample DNA. All reagents except for the viral template and magnesium acetate were prepared in a master mix, which was distributed into each 0.2 mL freeze-dried reaction tube containing a dried enzyme pellet. One microliter of viral DNA was added to the tubes. Subsequently, magnesium acetate was pipetted into the tube lids, and then the lids were closed carefully. The magnesium acetate was centrifuged into the rehydrated material using a mini spin centrifuge. After briefly vortexing and centrifuging the reaction tubes once again, they were immediately placed in the Genie III scanner device to start the reaction at 38\u00b0C for 20 min. The fluorescence signal was collected in real-time and increased markedly upon successful amplification.", "For the determination of analytical sensitivity of the real-time PRA assay by the molecular DNA standard, a semi-log regression was calculated using Prism software 5.0 (Graphpad Software Inc., SanDiego, CA). For exact determination, a probit regression was performed using the Statistical Product and Service Solutions software (IBM, Armonk, NY, USA). The evaluation of exo RPA with clinical samples data is presented as R 2 value." ] },{ "paper_id": "2264a7f6a968665b70a4a06c73e096e0710fc3f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A novel comorbidity mouse model of asthma and influenza PLOS ONE |", "doi:10.1371/journal.pone.0173008.g006" ] },{ "paper_id": "2269f102137c683d0a7871a9ea5110298bd3598c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Aerosol therapy is recognised as an effective method of administrating pharmaceuticals. The procedure involves generating an aerosol for drug delivery to the lungs to aid in the treatment of respiratory diseases. Nebulised medical aerosol has a typical particle size distribution of 1 to 5 \u00b5m [1]. If such aerosol particles escape into the indoor environment, they may remain airborne for periods of several hours [2] [3] [4] .", "Room temperature and relative humidity in the laboratory room were measured using a digital hygro-thermometer-datalogger (Model DHM200, Pacer Instrument, Chippewa Falls, WI, USA) and values recorded were in the ranges 18.5 to 23.8 \u00b0C and 47.3 to 66.9%, respectively. The experiments took place over a three-week period.", "Room temperature and relative humidity in the laboratory room were measured using a digital hygro-thermometer-datalogger (Model DHM200, Pacer Instrument, Chippewa Falls, WI, USA) and values recorded were in the ranges 18.5 to 23.8 \u2022 C and 47.3 to 66.9%, respectively. The experiments took place over a three-week period." ] },{ "paper_id": "226a0c0674dd9f9ad4a4e90ff6f03decb03457ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA integrity upon poly I:C stimulation was measured by capillary electrophoresis using the the Agilent RNA 6000 Pico Chip kit (Agilent Technologies) in an Agilent 2100 Bioanalyser, according to manufacturer instructions.", "ELISA IFN-b and IL-6 quantification in culture supernatant was performed using the Mouse Interferon Beta ELISA kit (PBL InterferonSource) and Mouse Interleukin-6 ELISA kit (eBioscience) respectively, according to manufacturer instructions.", "Rabbit polyclonal anti-eIF2a[pS 52 ] and Cystatin C were from Invitrogen and Upstate Biotechnology, respectively. Mouse monoclonal antibodies for b-actin and HDAC1 (10E2) were purchased from Sigma and Cell Signaling Technologies. Secondary antibodies were from Jackson ImmunoResearch Laboratories." ] },{ "paper_id": "2271ecb14bddddc60f33827495cb727858789ba9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The preliminary sequence management and analysis were carried out using Geneious version 9.1.3 (Biomatters Ltd., Auckland, New Zealand) and the sequence alignment and editing were performed using MAFFT [13] . The phylogenetic analysis of hepadnavirus used the neighbor-joining " ] },{ "paper_id": "228650bc0429064d800d4b9c5fb0e00c2533a579", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Prior to beginning studies involving animals the protocol was reviewed and approved by Purdue University's Institutional Animal Care and Use Committee (Protocol #1605001416). All animals used came from the Purdue University Animal Sciences Research and Education Swine facility, and standard farrowing protocols were followed prior to identification of experimental piglets and milk collection from sows. All sample preparation and lipid analysis were completed at the Proteomics and Metabolomics Core Facilities in the Bindley Bioscience Center at Purdue University.", "Blood samples were collected from gilts at 48 h postnatal. A 22 g x 1.5-inch needle and a 3 ml serum Vacutainer 1 (BD Life Sciences) tube was used to collect blood by jugular venipuncture. Blood samples were refrigerated and allowed to clot overnight. Serum was collected following centrifugation (Horizon Model 614B Centrifuge; Fisher Scientific) for 25 minutes at 2,500 g and stored at -20\u02daC until analysis.", "Lipid identification. Precursor ion/product ion pairs were tentatively assigned identities using attributions in Metlin (https://metlin.scripps.edu) and Lipid Maps (http://www. lipidmaps.org/). Potential identities were assigned using the associated functional group and biological information. Metlin MS/MS Spectrum Search was used with the following settings: precursor ion mass from the mass spectrometer reading for m/z value, maximum tolerance at 100, collision energy at 10 eV or 20 eV, MS/MS tolerance at 0.5, peaks included the product ion mass m/z with an intensity of 100, positive mode, and M+H was selected for the adduct. If the suspected ion pair was a TAG, M+NH 4 was also selected as an adduct to account for ammonium acetate." ] },{ "paper_id": "2286b53045dda4309a7f4da297e7d1974b1cb0d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "(Po = Accuracy, Pe = hypothetical probability of a chance agreement) ", "Supporting information S1 " ] },{ "paper_id": "22977df2b5a35dfe536faa4bd77a21ab316dc9f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All work with ANDV-infected hamsters and potentially infectious material was conducted in the BSL4 facility at the Rocky Mountain Laboratories, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health. Sample removal from the BSL4 was performed according to approved standard operating procedures. This animal experiment was approved by the Institutional Animal Care and Use Committee and performed following the guidelines of the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC) by certified staff in an AAALAC-approved facility.", "To determine whether vaccination resulted in significant protection from ANDV-induced disease, we compared the survival curves between mock-vaccinated and VSV\u2206G-ANDV-GPC-vaccinated animals using a log-rank (Mantel-Cox) test with significance set at 0.05. Analysis was performed using Prism software version 6 (GraphPad Software, Inc., La Jolla, CA, USA).", "To measure the neutralizing antibody response to vaccination, 2-fold serial dilutions of sera were mixed 1:1 with approximately 100 FFU of ANDV and incubated for 1 h at 37 \u00b0C in a humidified chamber. This mixture (200 \u03bcL) was then used to inoculate Vero E6 cells (ATCC) for 1 h at 37 \u00b0C, 5% CO 2 . The inoculum was then removed and 500 \u03bcL of 1.2% carboxymethylcellulose in Modified Eagles Medium (MEM) containing 2.5% FBS was added to the cells and incubated at 37 \u00b0C, 5% CO 2 . Seven days later, an immunofocus assay was performed and sera resulting in a greater than 80% reduction in foci were considered positive (FRNT 80 ) as previously described [15] . To examine whether hamsters that survived challenge (42 days post inoculation) developed anti-ANDV antibodies, we performed an ELISA to detect antibodies directed against the ANDV nucleocapsid protein (N) as described previously [10] ." ] },{ "paper_id": "229bb9dc175fcc4d90e46d9ad90b67ab3e49a536", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "T he interferon (IFN) system is an integral component of innate immunity and an important first-line defense against invading viruses. The IFN system is triggered by sensors that recognize pathogen-associated molecular patterns and, upon ligand binding, induce signaling cascades that trigger the production of IFN (1, 2) . Binding of IFN to IFN receptors then induces the expression of IFN-stimulated genes, several of which encode proteins with antiviral activity (3) . Understanding how these antiviral effectors block viral spread may allow devising novel antiviral strategies and is thus the focus of many current research efforts.", "The family of IFN-induced transmembrane proteins (IFITMs) comprises five members (in humans), including the antivirally active proteins IFITM1, -2, and -3 (4). These proteins inhibit host cell entry driven by the glycoproteins of many enveloped viruses, including influenza A viruses (FLUAV), coronaviruses, and filoviruses (5) (6) (7) (8) (9) (10) (11) (12) . Expression of IFITMs blocks entry at the stage of glycoprotein-driven fusion of viral and cellular membranes, specifically during hemifusion or the formation of fusion pores (13, 14) . This blockade might be due to IFITMs modifying the physical properties of cellular membranes, potentially via IFITM-IFITM interactions (15) or by altering membrane cholesterol levels (16) ." ] },{ "paper_id": "22a7db49b1d6a2856d8737d3739af18b715cd399", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest." ] },{ "paper_id": "22b2cb7ff5ea6e57e41098d8cf66aa69a5d04bc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1)", "(3)" ] },{ "paper_id": "22b6982820cdeb330dc2086ea69713f6e109a671", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BHK-pAPN cells grown to 90% confluence in 35 mm plates were transfected using 4 \u00b5g of the corresponding pBAC and 12 \u00b5L of Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA), according to manufacturer's specifications. At 6 h post-transfection (hpt), BHK-pAPN transfected cells were trypsinized, washed twice with DMEM, and plated over confluent Vero monolayers grown in 35-mm-diameter plates. One hour later, trypsin was added to a final concentration of 10 \u00b5g/mL. After a 3-day incubation period, the cell supernatants were harvested (passage 0) [49] . The rTGEVs were cloned by limiting dilution method, grown, and titrated as previously described [50] .", "PEDV genomic RNA (gRNA) levels were measured by RT-qPCR analysis using a custom TaqMan assay detecting a conserved ORF1a region (TaqMan Probe 6-FAM-TGTACT GGCTTACTGGTGTT-MGB; forward primer 5 -TGTTGCTATGTTTGTGCATTGG-3 ; reverse primer 5 -TCTGAATCACTAGGCTGACCTTTG-3 ). TGEV gRNA was evaluated using a custom TaqMan assay set up in our laboratory [52] . The porcine \u03b2-glucuronidase (GUSB) gene (TaqMan code Ss03387751_u1) was used as a reference housekeeping gene, since its expression remains constant in infected cells compared to that in non-infected cells [ [53] and data not shown]. Data were acquired with a 7500", "Reverse Size (bp)", "Fixed jejunum sections were washed twice with PBS and stored in 70% ethanol at 4 \u2022 C. Paraffin embedding, sectioning, and hematoxylin-eosin staining were performed by the histological laboratory (Autopsy Path Kft., Budapest, Hungary). Samples were examined with a ZEISS Axiophot fluorescence microscope. Determination of the jejunum damage was obtained from unbiased measurement of three full-length perceived villi and crypt per location. At least two different locations per section per animal were measured. The villous height to crypt depth (VH/CD) ratio was calculated from the measurements." ] },{ "paper_id": "22bc83fbc25560c43305c1995aad1e805821e054", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "geNorm NormFinder BestKeeper Geomean Gene M value Gene SD Gene SD Gene Value Shell", "In the current study, all ten reference genes were selected from the literature published for chickens (Table 3) . Specific amplifications of the primers were assessed by generation of a single peak of melting curve using uMelt web based tool for predicting DNA melting curves and denaturation profiles of PCR products 70 . Furthermore, primer specificity was confirmed by obtaining a single band of appropriate size in Agilent 2100 Bioanalyzer (Agilent Technologies, Waldbronn, Germany) using Agilent DNA 1000 Kit per the manufacturer's instructions. PCR amplification efficiencies and correlation coefficients (R 2 ) were determined with the amplifications of a series of six 10-fold dilutions of RNA based on the following equation [71] [72] [73] [74] ", "SciENTific REPORTS | 7: 14271 | DOI:10.1038/s41598-017-14693-2 NormFinder, the data are pre-processed for quality control, such as inter-run calibration, amplification efficiency correction, missing data handling, failing replicates (>0.5 Cq difference) removal and conversion to mean relative quantities. An Excel based BestKeeper (Version 1.0) software was used to determine the most stable reference genes based on Pearson correlation coefficient (r), coefficient of variance (CV) and standard deviation 42 . The overall ranking of the 10 reference genes was calculated by assigning an appropriate weightage value to individual gene ranking obtained in the three different statistical applets 75 . The principles of individual software (algorithms) have been detailed in the introduction section." ] },{ "paper_id": "22c4eb219966e3ab37726362c48b0d8f918d4b52", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "22d734ce865dda20bbbbd2695ffe67cb5bb10445", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal procedures were performed according to national and international guidelines approved by the Institutional Bioethics Committee from the Autonomous University of Yucatan (authorization number CBI-CIR-11-04).", "In Mexico, the Ministry of Health reports an incidence of 500-900 cases annually, although the disease is likely to be under-reported [5, 6] . Drug treatment for infected patients is complicated, with only few drugs available with limited efficacy, and a vaccine is still in early experimental stages [1, 5, 7, 8] .", "Infected animals were euthanized at week 15 postinfection, when lesions had healed except in one dog, and necropsy was carried out to detect any gross abnormality. All analyzed tissues appeared macroscopically normal. Spleen was weighted and the data normalized to body weight. Four of the six dogs (three males and one female) presented a splenomegaly outside the normal range ( Figure 2) ." ] },{ "paper_id": "22d812dbf1b71eb834f1244bdd26db698fed6a34", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After single colony purification in 5% sheep blood agar, the positive colonies were grown in bouillon medium for 48 h at 37\u00b0C, and the number of colony formation units (CFU) in the culture was calculated post the inoculation.", "The current study was approved by the Animal Care and Use Committee at China Agricultural University and was carried out in accredited animal biosafety level 3 facilities. The trachea and lungs were aseptically obtained from ORT serum-positive broilers. Streak cultures were performed using standard I nutrient agar (Merck, Germany) with 5% sheep blood and were incubated at 37\u00b0C under aerophilic conditions for 24-48 h. The positive colonies were identified by Gram stain and biochemical assays [1] . The biochemical tests assayed for oxidase, catalase, lysine, urea, indole, sulphuric acid (H 2 S), nitrate, gelatinase, motility, and carbohydrate fermentations, including glucose, mannose, lactose, sucrose, maltose, and galactose [2, 7] .", "In this study, a total of 291,000 chickens from 8 intensive farms in 5 provinces of China were evaluated, including 70,000 affected breeding broilers, 100,000 affected breeding layers, 95,000 broilers with pneumonia and 16,000 affected layers. In addition, 10,000 unaffected broilers were used as controls. In total, 193 serum samples were collected for the detection of antibodies against ORT using a commercial testing kit. The samples originated from Liaoning, Inner Mongolia, Hebei, Shandong and Beijing represented the ORT prevalence in Northern China." ] },{ "paper_id": "22d9a77f7eb015a61ad58babdd9a9a68c29a3176", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that there are no conflicts of interest regarding the publication of this paper.", "The \"host-parasite continuum\" framework [28] , which suggests that wildlife and domestic animals and human populations coexist and that disease spillover occurs within a finely balanced host-agent continuum, provides the basis for exploring bat-human interactions in this paper. The framework highlights the ways in which underlying factors such as agricultural intensification, translocation, and human encroachment are responsible for emerging infectious diseases (EID).", "Journal of Environmental and Public Health 5", "During focus group discussion, one petty trader who operated under one of the trees at the market reported the following:" ] },{ "paper_id": "22e6bf7b64a17d055dca239d9fdac04edfb1414c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "22f1e46f69ea11771ee26f499b234bd3ff1bb88b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Controlling the pandemic spread of newly emerging diseases requires rapid, targeted allocation of limited resources among nations. Critical, early control steps would be greatly enhanced if the key risk factors can be identified that accurately predict early disease spread immediately after emergence.", "Our current report is the first published analysis of H1N1 spread to include indirect flight data, and this significantly increased the predictive power of our model. Our analysis suggests that airports serving as major hubs could be targets for disease surveillance, and could become facilities that train people and stockpile medicines in preparation for pandemics. This approach differs from previous reports that focus on the role of travel restrictions at hubs [6, 17] .", "For all analyses, dates were transformed to Julian day since February 15 th , and all predictor variables were standardized (mean subtracted, then divided by standard deviation) in order make possible the direct comparison of coefficients. This standardization has the added advantage of canceling out the x factor in equation 1 for the statistical analysis; thus, our analyses do not require any assumptions about the number of passengers who make connecting flights.", "One consequence of lower health care resources is that the threshold for detection (i.e., the number of cases that need to occur before a case is detected, tested and confirmed by medical authorities) is likely higher in lower-income countries that cannot afford to invest as much in public health and healthcare infrastructure. Similar socioeconomic factors have been shown to play an important role in determining spatiotemporal patterns of diseases such as tuberculosis, schistosomiasis, West Nile virus, and HIV/AIDS [12, 13, 25, 26] ." ] },{ "paper_id": "22faab96b423cab9df3cd453727e6a7763de4bb6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Informed consent was obtained from parents/legal guardians on admission to hospital.", "All the described tests were done as diagnostic tests during hospitalization. Informed consent was obtained from parents/legal guardians on admission to hospital.", "This article does not contain any studies with human participants performed by any of the authors. This study is done based on analysis of patients' medical records; all tests were done as diagnostic tests during hospitalization." ] },{ "paper_id": "2305cbae32a50cf9923356cd30ca3152944d6d38", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bacterial strains and growth conditions L. monocytogenes EGDe (BUG1600, ATCC BAA-679), L. monocytogenes isogenic mutant DpgdA (BUG2288, [25] ) and L. monocytogenes DpgdA complemented strain (BUG2382) were grown in brain heart infusion (BHI, Oxoid), aerobically at 37uC and 200 rpm.", "For inhibition of bacterial internalization, cell monolayers were pretreated either for 2 h with 100 mM cytochalasin-D (Sigma-Aldrich), or 30 min with 80 mM dynasore (Sigma-Aldrich) or 30 min with 100 mM chloroquine (Sigma-Aldrich) prior to infection assays.", "The aim of the present study was to decipher the signaling pathways involved in this response to DpgdA infection. We reveal that IFN-b production in peritoneal macrophages requires TLR2 signaling and the TRIF adapter protein." ] },{ "paper_id": "2318d71622cd266fdbd9a9d80f25e689ff6f61ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Trypsin specificity was used in MS/MS search with up to two missed cleavages. N-terminal acetylation and methionine oxidation were selected as variable modifications, while carbamidomethylation of cysteine was selected as a fixed modification. Precursor ion mass accuracy was set to 15 ppm, fragment ion mass tolerance to 30 mDa. Automatic decoy database search and builtin Percolator algorithm (version 2.01) [31] were used to rescore search results and calculate posterior error probabilities for each peptide-spectrum match. All results were filtered to achieve global FDR #1%.", "Proteomics easily detects contamination with, in principle, any virus or other foreign organism.", "Conceived and designed the experiments: RZ AC. Performed the experiments: AC. Analyzed the data: AC RZ. Contributed reagents/ materials/analysis tools: AC. Wrote the paper: AC RZ. ", "In view of the deficiencies of the above extreme approaches, a balanced procedure is needed that assigns higher (but less than 100%) a priori probability to human sequences compared to viral sequences." ] },{ "paper_id": "232dc9f3baa927facbe91722ae717e0738a73981", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Several microarray-based studies have demonstrated transcriptional changes in fungal genes following mycovirus infection, although most of these studies examined only CHV1-713 infecting the chestnut blight fungus Cryphonectria parasitica. Initially, a polymerase chain reaction (PCR)-based approach demonstrated that elevation of cAMP levels by CHV1-713 resulted in reduced accumulation of the GTP-binding (G) protein subunit CPG-1 [25] . In addition, cDNA microarrays containing 2,200 genes from C. parasitica showed transcriptional change in G-signaling pathways following hypovirus infections showing different virulence or phenotypes [27] [28] [29] .", "Virus-free and FgV1-DK21-infected F. graminearum strain-DK21 were stored in 15% (v/v) glycerol at \u221280\u00b0C and reactivated on PDA at 25\u00b0C with a 12 h light-dark cycle. F. graminearum cultures used for RNA extractions were grown as described previously [9] . Freshly grown mycelia from PDA media plates were inoculated in 50 or 200 ml complete media (CM) broth [6] and incubated at 25\u00b0C for 36 h or 120 h in an orbital shaker (150 rpm). Hyphae were collected by filtering through 3MM paper, washed with distilled water, dried by blotting with paper towels, and frozen at \u221280\u00b0C.", "Conidia of virus-free and FgV1-DK21-infected F. graminearum strains were harvested in 50 ml of CMC broth at 4 days after inoculation. Conidial suspensions (2 \u00d7 105 conidia per dish) were grown in 20 ml of defined media containing 5 mM of agmatine [47] in 90 \u00d7 15 mm Petri dishes for 7 days prior to filtrate harvests. Three replicates were used for this treatment. Mycotoxin was extracted from the isolates and analyzed with a Shimadzu QP-5000 gas chromatograph-mass spectrometer, as described previously [48] . The trichothecenes were measured based on biomass produced by each strain." ] },{ "paper_id": "232e85eda8060808405e79f0dbe13309eccddf58", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Parasites were cultured in O-positive RBCs at 5% hematocrit in RPMI 1640 medium (Sigma) supplemented with 25 mM HEPES, 4.5 g/L glucose and 2.1 g/L NaHCO 3 , 0.5% AlbuMAX II (Thermo Fisher Scientific), and gentamicin (50 mg/ml). The medium was replenished every 24 h.", "The membranes were exposed to HRP-labeled anti-rabbit IgG secondary antibodies (1:5,000) (BioRad) for 1 h at RT and detected by enhanced chemiluminescence detection system and visualized using GE image quant 4000 chemiluminescence system (GE Healthcare Lifesciences).", "This observation is in agreement with the study that malaria patients have suppressed T-and B-cell functions (Zander & Butler, 2013) ." ] },{ "paper_id": "23393085181dbde8039e7123f35b67d4b2e9f6ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our final workflow is depicted in Fig. 4 .", "Availability of data and materials Raw sequencing data are available on the Zenodo repository (10.5281/ zenodo.814807). The analysis pipeline \"VirMet\" is available on github (https://github.com/ozagordi/VirMet/releases/tag/v0.3.3).", "Authors' contributions DWL, AT, and MH conceived and designed the study. DWL, FDG, VK, and SS performed experiments. DWL, OZ, JB, KJM, and MH analyzed the data. DWL and MH wrote the manuscript. All authors read, commented on, and approved the final manuscript.", "The optimized metagenomic sequencing protocol detects the majority of virus species in a highly multiplexed viral pathogen reagent" ] },{ "paper_id": "233b6a7c5234ef4a8bb7918dab6d5ea8fe0b1aad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "235451b60cac00666f0e69e9d196d090da8609a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(SF) variant that was isolated as described previously [15] , and was used for these studies. The viruses were propagated in African green monkey kidney (MA-104) cells (from ATCC).", "Mice were anesthetized with ketamine/xylazine (50/5 mg/kg) by intraperitoneal (i.p.) injection for i.n. treatments and i.n.", "Homogenization of soft tissues was performed in 1 ml of cell culture medium using a stomacher. Snouts were ground in 1 ml of medium using sterilized mortars and pestles. Samples were serially diluted in 10-fold increments and plaque titrated in 12-well microplates of Vero cells. Plaques were stained at three days with 0.2% crystal violet in 10% buffered formalin, followed by counting the plaques with the aid of a light box. Plaque numbers were converted to PFU per gram of infected tissue." ] },{ "paper_id": "235855da90347b259f4d6b244821f3c1c264c04e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cattle serum were collected at 7, 14, 21and 28 days postvaccination (dpv). Antibody against FMDV was detected by LPBE method (as above) and SNT.", "The results suggest that this strategy might be used to develop the new subunit FMDV vaccine." ] },{ "paper_id": "235fab2608254fb0e97f003cef3b4694bc003756", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A549 cells, JNK phosphorylated Bcl-2 to inhibit its antiapoptotic activity, and also phosphorylated Bax. Phosphorylated Bax then translocated to the mitochondria and activated Bak to promote apoptosis (130) . Thus, CHOP can cooperate with IRE1\u03b1/TRAF2/ASK1/JNK to regulate the occurrence of apoptosis.", "Cell death induced by ER stress also can be mediated through exogenous pathways. Death receptor-mediated apoptosis occurs via death ligands (Fas, TNF, and TRAIL) combined with death receptors. The receptor protein, Fas-associated death domain protein, is recruited to form a death-inducing signal complex, which activates the cytosolic caspase-8, which then activates the downstream caspase to induce apoptosis.", "HH, MT, and CD drafted the review. SY critically revised the review. All authors read and approved the final manuscript. " ] },{ "paper_id": "23696844593c72dd8c4d74607ff26049336fe9b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We analyzed data analysis using STATA 12.1 (StataCorp, College Station, TX). This research received human subjects review approval by the University of Pittsburgh." ] },{ "paper_id": "236bd666a76213bc131969e1d5b66e410fc1cd45", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "237cdea88e640a5848e7abb82992894618315d63", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This systematic review was reported in line with the proposal for reporting Meta-analyses Of Observational Studies in Epidemiology (MOOSE checklist) [9] ." ] },{ "paper_id": "238d2be0d4db41b5460bd3a50a0a374549c189aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were harvested in RIPA lysis buffer (50 mM Tris-HCl [pH 7.4], 150 mM NaCl, 1 mM EDTA, 1% Triton X-100, 0.1% SDS, 1% sodium deoxycholate, 1 mM PMSF, and protease inhibitor cocktail) and the protein concentration was measured by the BCA protein assay (BioRad). Proteins were resolved by 12.5% sodium dodecyl sulfate polyacrylamide gel electrophoresis, transferred onto PVDF membrane, blocked with 5% skimmed milk in Tris-buffered saline (TBS) ( ", "RNA isolation, reverse transcription, and real-time PCR RNAs were extracted from virus-infected or mock-infected cells by Trizol reagent (Invitrogen) and treated with DNase I (Promega). 1 mg total RNA was subjected to reverse transcription by SuperScript II First-Strand Synthesis System (Invitrogen) according to the manufacturer's instructions. The expression level of viral genes was measured by SYBR Green-based real-time RT-PCR. The PCR primer pairs sequences for ICP0 were cited as described [36] . The primer pairs for UL52 and UL13 were UL52F (5'-GACCGACGGGTGCGTTATT-3')/UL52R (5'-GAAGGAGTCGCCATTTAGCC-3') and UL13F (5'-GCGACCTGCTGGTCATGTG-3')/ UL13R (5'-TGCGAGCCAATCCTTGAAG-3').", "The pure compounds, quercetin, isoquercitrin, quercitrin, hyperin, rutin and acyclovir (ACV), were purchased from Sigma-Aldrich, dissolved in dimethyl sulfoxide (DMSO) or absolute ethanol and diluted with sterile deionized distilled water before use.", "Quercetin is a small molecule, and our study showed that it could inhibit HSV binding to the cell surface. We hypothesize that this small molecular compound may compete for the gD binding site with a cellular receptor such as heparin sulfate or nectin-1. However, more work will be needed to test this hypothesis. " ] },{ "paper_id": "23904278d806ced4d6fd0ea9b264d495562cf7e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A representative sample of 60 GPs from the French Sentinelles Network [21, 22] was recruited to enrol ARI patients from all over mainland France.", "Insufficient information about the prevalence of GI symptoms in ARIs, their clinical features and their potential risk factors may lead to diagnostic errors and inadequate treatment.", "Gastrointestinal (GI) symptoms, such as diarrhea, vomiting, abdominal pain and nausea are not an uncommon manifestation of an acute respiratory infection (ARI) [1] [2] [3] [4] [5] [6] [7] [8] (Additional file 1) and have been reported as a hallmark of severe influenza in childhood [9] ." ] },{ "paper_id": "2392e0e02b81ed3565b792e9794d50994acc8535", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The inhibition of processing and incorporation of Env into nascent virions was suggested as an antiviral mechanism of IFN-I against HIV-1 many years ago (223) . Recent studies have implicated this process as a target for two ISGs (224, 225) .", "All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.", "The Neil laboratory is funded by the Wellcome Trust." ] },{ "paper_id": "239cd6dbc4b75c51256acc527ae69394b891bc1d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tissue sections were photographed with Optronics camera attached to Ziess Axioskop 2 plus microscope using the Zeiss Achroplan 20X objective and images were captured using MagnaFire SP 2.1B software. Fluorescence images were photographed with Axiocam MRC camera (0.63X magnification) attached to Zeiss Axioplan 2 microscope using a 10x, 20X, 40X or 63X objectives. For fluorescence quantification all of the images were acquired at the same exposure.", "The data were represented as mean \u00b1 s.e.m. of the indicated number of measurements. Statistical differences between groups were analyzed by using unpaired, two-tailed t-test or One-Way ANOVA. Differences were considered significant at p < 0.05.", "Non-invasive measurements of superficial hindlimb perfusion were obtained before and 0, 3, 7, 14, and 21 days after ligation using a Laser Doppler perfusion imager (model LDI2-IR, Moor Instruments, Wilmington, DE) that was modified for high resolution and depth of penetration (2 mm) with and 830 nm wavelength infrared 2.5 mW laser diode, 100 \u03bcm beam diameter, and 15 kHz bandwidth. At each time point, an average of 4 measurements per animal was made on anesthetized (1.5% isofluorane on an isothermal heating pad). To avoid the influence of light and temperature, the results were expressed as a ratio of perfusion in the right (ischemic) vs. left [non-ischemic (NI)] limb (Limbourg et al., 2009 )." ] },{ "paper_id": "239f4596308a1247bf27a034c3cab95e0771215f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The next generation approach yields an expression for R 0 that agrees with the formula given in [14] and can be decomposed as follows [20] [21] [22] .", "\u03c1 FH : rate of pathogen deposit from hand to fomite", "All code used to produce the results of this paper has been uploaded as additional materials." ] },{ "paper_id": "23a2c32c86891deabe9176b41434f3ed202a5055", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was registered with ClinicalTrials.gov (NCT03443102) and was authorized by the Ethics Committee of Peking University People's Hospital (2018PHB010-01). All recruited patients provided written informed consent to participate.", "Bone Research (2020) 8:8", "; https://doi." ] },{ "paper_id": "23a6cc5f5c3babf3e187374eca3be2a5e052669b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animals were implanted subcutaneously with temperature-sensing microchips (Lifechip \u00ae ). Staff wore powered air purifying respirators, coveralls, impervious gloves and boots while in animal rooms.", "Virus isolation. Vero cell monolayers were grown in 96 well tissue culture plates to 80% confluency in cell media (Minimal Essential Medium containing Earle's salts and supplemented with 2 mM glutamine, antibiotic-antimycotic and 10% fetal calf serum).", "Data availability. The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request." ] },{ "paper_id": "23acad3bdcee7563f22da647aae639dbee1d56e6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Many naturally-occurring networks like the Internet, the World Wide Web, and biological networks are scale-free and are thus well described by Barabasi's preferential attachment model [23] . Others argued, however, that social networks are different as they show strong clustering of nodes (also called community structures) and their degree distributions are not power laws [24] . To specifically reproduce the community structures seen in social and social-like networks, Holme and Kim modified the preferential attachment model to incorporate clustering [25] . Newman et al., on the other hand, started out with random graphs and progressively build the social-like degree distribution [26] , whereas Boguna et al. and Jin et al. proposed friendship-formation dynamics models to generate social-like networks from scratch [27, 28] .", "Since the preliminary EGP result in Section 3.1 is encouraging, we tried EGP mitigation on the larger networks despite the poor estimation accuracy.", "Citation: Hadidjojo J, Cheong SA (2011) Equal Graph Partitioning on Estimated Infection Network as an Effective Epidemic Mitigation Measure. PLoS ONE 6(7): e22124." ] },{ "paper_id": "23b1f3033a86c0f53ee90b9ba14634e956f8610b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "d~ffi ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi", "Chikungunya virus (CHIKV), which causes CHIKF, is an alphavirus of the Togaviridae family, with a 12,000-nucleotides linear, positive-sense, single-stranded RNA genome containing two large open reading frames (ORF). The first, ORF1, encodes 4 non-structural proteins (nsP1, nsP2, nsP3 and nsP4) while ORF2 encodes structural proteins that include 1 capsid protein (C), 2 major envelope surface glycoproteins (E1, E2) and 2 small proteins (E3, 6K) [8, 9] . CHIKV is transmitted by Aedes mosquitoes (mainly A. albopictus and A. aegypti)." ] },{ "paper_id": "23d0641f1f78528bbf3fa7b0b749abc1299a9cb4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To assess the indirect and direct protection afforded by a given decision strategy D at a given R 0 , we calculate a quantity we call the herd effect, given by" ] },{ "paper_id": "23d8bce7be2d5afed730addd3b4531f1bc721da6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Residues 157 to 165 of hNTCP are critical for pre-S1 binding and viral infections", "Virus-related experiments were conducted in a BSL-2 facility at the National Institute of Biological Sciences, Beijing." ] },{ "paper_id": "23dcdd1995567d482009f9eafaffc887da09701d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "12 29362479 see Table S9 ADCD Table S13 Total gene number 390-91 = 299", "Frontiers in Oncology | www.frontiersin.org The red highlights indicate increased fold changes, and green highlights indicate decreased fold changes.", "This work was supported by the hospital fellowships to BL and JW." ] },{ "paper_id": "23e37316e27cec6fe0e71647552b1f7b0e9255b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All oligos and primers were custom synthesized by Invitrogen. The sequences and the relative position with respect to an scFv of various oligos and primers were detailed in Table 1 and Figure S1 , respectively.", "Recombinant SCoV-N protein was cloned, bacterially expressed and purified as described in our previous publication [34] .", "For expression analysis, scFv clones were subcloned into pCantab His vector, transformed into E Coli HB2151, and periplasmic His-tagged scFvs were purified using Ni-NTA agarose beads as described in our previous publication [35] .", "The protocol for animal work was approved by the Animal Experimentation Ethics Committee of the Chinese University of Hong Kong (Permit Number: 03/015/MIS). BALB/c mice (,25 g) were sacrificed by cervical dislocation and the spleens were immediately removed. After punching holes with a G21 needle, splenocytes were squeezed out and resuspended in an icecold phosphate buffered saline (PBS) containing 4% BSA (Sigma). For isolation of CD19 + cells, splenocytes (2610 7 cells/ml, 5 ml) were incubated with a fluorescein isothiocyanate (FITC)-conjugated rat anti-mouse CD19 + monoclonal antibody (0.5 mg/ml, 100 ml, BD Bioscience) on ice for 30 min to label B-lymphocytes carrying rearranged immunoglobulin genes. After washing to remove unbound antibodies, labeled cells were resuspended in 5 ml of RPMI-1640 medium (Gibco) supplemented with 10% fetal bovine serum (FBS, Gibco). The CD19 + splenocytes were sorted and captured using a FACS VANTAGE SE cell sorter (Becton Dickinson)." ] },{ "paper_id": "23f1565e1f4f6a5e0c92d96dc454299a9e37400b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To examine pathological changes, the right side of the lung was embedded in paraffin, sectioned at 4 \u00b5m for haematoxylin and eosin (H&E) staining. The severity of histological changes was scored according to a semiquantitative scoring system [47] , which was further showed in 'Supplement material of Methods'.", "Oxymatrine (OMT, C 15 ", "The pNF-\u03baB-luc reporter plasmid was purchased from Beyotime Institute of Biotechnology (D2206, Shanghai, China)." ] },{ "paper_id": "23f5f98892b12255b20f4b0a0ec1f3e7b29d5d72", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ACE2 is a type 1 integral membrane glycoprotein [8] that is expressed and active in most tissues. The highest expression of ACE2 is observed in the kidney, the endothelium, the lungs, and in the heart [2, 8] . The extracellular domain of ACE2 enzyme contains a single catalytic metallopeptidase unit that shares 42% sequence identity and 61% sequence similarity with the catalytic domain of ACE [2]. However,", "ACE2 is an integral component of the RAS. It is highly expressed in the vasculature, the kidney, lungs, and heart where its actions on peptide signals balance and offset those of ACE. Its actions appear critical in a variety of disease states, including hypertension, diabetes, ageing, renal impairment, and cardiovascular disease. ACE2 deficiency leads to modest physiological changes. However, in states of RAS activation, the loss of ACE2 appears far more important in the development and progression of disease. By contrast, augmentation of ACE2 expression, either directly with recombinant ACE2 or indirectly via agonists like XNT, may have important benefits relevant in the treatment of a range of conditions." ] },{ "paper_id": "2402b2a0cb8aef3abb2e103f0997c61dec6511a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2405180506967da1f4007e49ad653c3c356a823a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In southern European countries, canine and human leishmaniosis are mainly caused by L. infantum zymodeme MON-1 [9] . This occurs also in FeL [10] [11] [12] [13] [14] , but zymodemes MON-72 and MON-201 have also been isolated in two single cases from Sicily [10] .", "Based on these studies, cats are apparently less susceptible than dogs [47, 48] to the development of disease after established experimental infection with species of the L. donovani complex or are even resistant to infection [15] .", "It often has a diffuse pattern and the epidermis may present hyperkeratosis, acanthosis and ulceration [56, 68] . A nodular to diffuse arrangement of the granulomatous dermatitis is also reported [26, 60] . However, in a retrospective case series from Spain, two cats presented different histological findings [68] . The first one had granulomatous perifolliculitis with a high number of lymphocytes and plasma cells surrounding the cutaneous adnexa. It was associated with a marked hyperplasia of epidermis and sebaceous glands. The other cat was diagnosed with a lichenoid interface dermatitis typically represented by infiltration of lymphocytes, plasma cells and a few neutrophils and macrophages at the dermoepidermal junction. In this case, epidermal necrosis and epidermal microabscesses were also observed. A perivascular infiltration of superficial skin layers by macrophages, mast cells, neutrophils and eosinophils was also observed in another case [12] ." ] },{ "paper_id": "2410516def70473a479454501fab2cdaf95d88d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Another well-described path is caveolin-1 mediated endocytosis. Caveolae are flask-shaped cholesterol-and sphingolipid-rich smooth membrane invaginations stabilized with caveolin-1 27 . Loading of the caveolae with cargo results in recruitment of dynamin-2 28 , which cuts off the invagination, forming a neutral-pH vesicle called caveosome. The vesicle can be either transferred into Golgi complex, endoplasmic reticulum (ER) or progress to early endosomes 27 . Recently, besides these two canonical pathways, numerous alternative routes have been described, including entosis, flotillin-dependent entry, FEME, and IL2R\u03b2-like mechanisms.", "There are currently six human coronaviruses described. The well-known human coronaviruses (HCoV) 229E and OC43 were described in 1960's and for almost 40 years were considered to be the only representatives of Coronaviridae infecting humans. Emergence of Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV) in 2002, followed by identification of HCoV-NL63 and HCoV-HKU1 revealed that these viruses are far more common and clinically relevant than previously expected. Further, emergence of the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 proved that these pathogens frequently cross the species border and may pose a significant healthcare risk.", "HCoV-OC43 remains incessantly one of the most important etiological factors for respiratory tract diseases in humans 1,2,36 . Considering lack of effective vaccine or therapeutics, and zoonotic potential of animal coronaviruses, understanding of the virus' biology seems to be of importance." ] },{ "paper_id": "241ba286b5b231ad009c7e9a28c85aacbdff49a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The differences between the cases were assessed using \u03c7 2 analyses to compare categorical variables and the Mann-Whitney U test to compare continuous measures. Statistical analysis was carried out using the SPSS software package (SPSS Inc., version 17.0, Chicago, IL, USA). A two-sided test with a significance level of 0.05 was used to determine statistical significance for all analyses." ] },{ "paper_id": "241bbd33b32abf0cc6adb68b9c80381f0856cddd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 Dataset. Pig batches produced by the 18 flows that broke with PED during the study period (March 2013-June 2014) in the 120 days before the first PED+ batch. (XLS)", "ADG and FCR were significantly worse in case batches, with a 0.16 lb mean decrease of the former (95% CI = 0.07-0.26) (Fig. 3a) and a 0.55 increase in the latter (95% CI = 0.30-0.79) (Fig. 3b) . ADFI remained largely unaffected (p = 0.9). Again, differences observed in WF batches were larger than those observed in nursery pigs, but differences were not significant (p>0.3).", "Mortality was significantly (p<0.001) higher in PED-positive batches compared with the control pigs, with an overall mean difference of 12.5% (95% confidence interval = 6.4-18.4) (Fig. 2) . Difference observed in WF pairs was not significantly different from that found in nursery pairs. The difference in mortality between control and infected batches increased for those cases in which control batches left the sow farms in the previous 14-60 days compared with 61-120 days (Fig. 2) ." ] },{ "paper_id": "24259e03c484aa60752b90e228fe92f90bf2143d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2431c74630bb92f71e47e7f1c89054cef368ace0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Seven pigeons, free of any nematode infection in their alimentary tracts, were kept in separate cages. They were divided in 2 groups: P1 (n=5), P2 (n=2) and each bird was fed 40-50 nematode larvae, which were collected from naturally (P1), and experimentally (P2) infected beetles. In the second month post infection, their feces were examined daily. In addition, the infection rate of larvae fed to pigeons were determined by collecting and counting the larvae from the alimentary tract, especially gizzard, proventriculus and the region between them in two pigeons which died in days 9 and 18 after infection; and also by counting the collected nematode adults from the remained pigeons until 4 months after infection.", "Collected beetles were identified morphologically and the mean length as well as width of 70 beetles were measured. To confirm natural infection of the beetles and evaluation of the possibility of experimental infection, 133 adult beetles from litter samples (natural group, A) and 51 from cultured larvae (experimental group, B) were killed and their exoskeletons removed under stereomicroscope by means of forceps and dissection needle. Their haemocoel in the abdomen, thorax, and head regions were examined for the presence of the nematode larval forms. Collected free larvae or cyst forms of each beetle were counted and active forms (third stages) of them were used for further experiments. Third stage larvae were also measured by micrometer.", "After collecting the bedding litter (fecal layers, soil, piles and broken feathers) from the pigeon houses, they were placed into plastic bags, transported to the laboratory and examined under a stereomicroscope. Numerous adults and larval stages of the beetles were observed in litter samples. The larvae and adult beetles were collected from the litter samples by sieving them with common sieves. The beetles were cultured with the modified method of Rice et al 2009 (21) . The beetle larvae were put into a plastic box (measuring 135\u00d7 195 \u00d7 80 mm) that contained 250 ml of culture medium (up to 15% sieved dust of litter, 15% wheat bran, 70% layer and semimoist fecal pellets from cage ' s tray of pigeons infected with the nematode) and a number of H washed apple halves placed faced down on the medium. The plastic boxes were sealed with gauze and lid of the box, which closed the vent while allowing passage of air, and maintained for up to 5 months under 27-34 \u00b0C temperature and relatively high humidity." ] },{ "paper_id": "243532558bf1aeed5200836620159cf37f91ab26", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "[0 0 1], \u03c1 I will decay faster than the case of \u03b2 = ." ] },{ "paper_id": "2448743a5de075f6a1816e46fe72b69cc791da18", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .02490-19. ", "Quantification of Sia variants. The Sia composition of cells were determined by incubating with 2 M acetic acid at 80\u00b0C for 3 h, filtration through a Microcon 10-kDa centrifugal filter (Millipore), and drying in a SpeedVac vacuum concentrator. Released Sia were derivatized with DMB (Sigma-Aldrich) for 2.5 h at 50\u00b0C (39) . HPLC analysis was performed using a Dionex UltiMate 3000 system with an Acclaim C 18 column (Thermo Fisher) under isocratic elution in 7% methanol, 7% acetonitrile, and 86% water. Sia standards included bovine submaxillary mucin and commercial standards for Neu5Ac and Neu5Gc (Sigma-Aldrich). Statistical analyses were performed in GraphPad Prism software (v8).", "Characterization of A549 conditioned media. Conditioned medium from A549 cells was prepared by washing a fully confluent flask of cells to remove any serum and allowing the cells to grow in serum-free medium for 5 to 7 days. The conditioned medium was collected, dialyzed with 3 volumes of PBS, and concentrated using a 30-kDa centrifugal filter (Pall Corporation). The protein concentration was determined by using a Qubit 4 fluorometer (Invitrogen). To determine Muc5B presence, 2-fold dilutions of conditioned media were compared to purified human Muc5B using a 8% SDS-PAGE gel and probed with an anti-human Muc5B antibody (both purified protein and antibody were gifts from Stefan Ruhl, University of Buffalo). Conditioned medium was analyzed for total Sia using the HPLC methods listed above." ] },{ "paper_id": "2468815380ef0da6656eafec81936b459b5b210e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The mystery patient drill scenarios were designed by PCEPN with input from their advisory group, which has representation from all five NYC boroughs (Bronx, Brooklyn, Queens, Manhattan, and Staten Island). Scenarios were designed describing a patient walking into a community health center and reporting either (1) fever, generalized body aches, and respiratory symptoms (e.g., cough, shortness of breath) or (2) fever and rash on the trunk and back in the context of attending a children's birthday party 1-2 weeks prior during which a child may have been sick. These scenarios corresponded to influenza-like illness (ILI) and measles, respectively. Clinics chose their preferred patient scenario in advance of their own drill.", "All PCEPN-affiliated community health centers were invited by e-mail to participate; an announcement was also included in PCEPN's quarterly newsletter. Clinics were enrolled on a first-come, first-served basis, with the number of drills allotted per round dependent on available funding. If a clinic network (defined as the lead institution governing the operation of multiple clinics) participated in multiple rounds, different clinics within the clinic network were prioritized for selection for each round of the drill. The project was exempted by the NYC DOHMH institutional review board.", "Mystery patient drills for infectious disease of public health concern can serve multiple functions. First, they can provide a practical assessment of emergency preparedness using both quantitative and qualitative methods. Qualitative data are valuable because they can enable triangulation when evaluating quantitative associations, as we show by analyzing participant feedback regarding the exercise that suggests a causal factor to our finding that measles patients were less likely to be masked." ] },{ "paper_id": "246a98b042ab326afd859e0e14579431f078894b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "246d1372657ab63d6f10a57907fcda07c1ddbc3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Emerging infectious diseases (EIDs) are responsible for a substantial burden of mortality and morbidity globally, and a majority of EIDs (60.3%) are caused by zoonotic pathogens [1] [2] [3] . In the past decades, high impact outbreaks have occurred with introductions from wildlife and livestock reservoirs, respectively, exemplified by the wildlife-borne outbreaks of Severe Acute Respiratory Syndrome (SARS) [4] , Nipah disease [5, 6] , and Lassa fever [7] , and outbreaks resulting from contact with livestock animals, such as Middle East Respiratory Syndrome [MERS] [8] , avian influenza [9] , Rift Valley fever [10] , and swine influenza [11, 12] . Livestock animals that live in close proximity to humans can facilitate transmission of infectious diseases through the wildlife-livestock-human interface [3] ." ] },{ "paper_id": "24708179db3a64c831215a30805bf37e6d27ccf7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Closeness is the sum of the graph--distances from one node to all other nodes in the network 3 .", "(1" ] },{ "paper_id": "247a9eae1e4452f7f969ab41a88f335fda54fbc9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "247d3262ad1b15f331a89f70eec56b34dbe6b8b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "zeroes To simulate the possible under-reporting of individuals who cause no secondary infections, it was assumed that all individuals who caused x i = 0 cases can be overlooked with some fixed probability p z , while all other individuals have their full case-count recorded. NB samples were generated as in section 2.1.1, then any value x i = 0 was deleted with probability p z and replaced by another NB random variate. If the new value was also 0, then it was again replaced with probability p z . This process was repeated until a sample of n values was generated, in which each remaining value x i = 0 had avoided replacement exactly once.", "Four types of simulated datasets were examined. In all cases, the datasets comprised n values, x i (i = 1, 2, \u2026, n), generated as described below. In the epidemiological context that motivated this study, these values x i correspond to the numbers of secondary cases that were infected by n different infectious individuals, but similar data could arise from many other processes. All simulations were conducted using Matlab v6.1 (MathWorks, Cambridge MA).", "x i ." ] },{ "paper_id": "247d7378386c4c48cf327c151a9ea73040df0403", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability statement. The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.", "Our study has implicated miR-4289 as a prostate cancer diagnostic biomarker for the first time. To date, only two studies investigating the role of miR-4289 in congenital obstructive nephropathy as an exosomal biomarker 35 36 which may provide further clues to explore its therapeutic potential in prostate cancer.", "Recent studies have indicated the importance of miR-98 in colon 39 , lung 40 , liver 41 and prostate 42 cancer. Meta-analysis of six miRNA datasets revealed up-regulation of 15 miRNAs, miR-98 being one of them, in recurrent compared to non-recurrent prostate samples suggesting the predictive ability of miR-98 along with other miRNAs 42 . To the best of our knowledge, we are the first to demonstrate plasma miR-98-5p as a candidate for early diagnosis of prostate cancer.", "Evidence suggests that the target genes discussed so far play a vital role in prostate cancer and their regulation by miRNAs may be crucial in prostate cancer pathogenesis. Some of these miR-152-3p targets are oncogenes while some are tumour suppressors and this suggests that miRNA target modulation is dependent on various aspects such as genetic alterations, transcriptional/ post-transcriptional regulation, post-translational modification, target stabilisation, indirect regulation as well as cell type. Moreover, validation of target genes and further functional studies are necessary to understand the mechanistic role of our identified miRNAs in cancer progression." ] },{ "paper_id": "248e6ce743867edebd9fb8d241a56f542732888a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Stereocontrolled synthesis of vidarabine [23] and several analogues/derivatives with antiviral activity has been described [24] [25] [26] . Its biosynthesis from Streptomyces antibioticus has also been reported [27] .", "Antiviral compounds are currently of particular interest since viral diseases (e.g., HIV, H1N1, HSV, etc.) have become major human health problems in recent decades. The ability of a virus to rapidly evolve and develop resistance to existing pharmaceuticals calls for continuing development of new antiviral drugs. Several lead antiviral compounds have been isolated from marine sponges, and there has been a consistent effort to identify new compounds.", "This compound (Figure 9 ) was isolated from the marine sponge Hamigera tarangaensis (family Anchinoidae) from the Hen and Chicken Islands in New Zealand and showed 100% in vitro virus inhibition against both the herpes and polio virus with only slight cytotoxicity at a concentration of 132 \u00b5g per disk [51] . Syntheses of hamigeran B have been reported by several groups 1 [81] [82] [83] . " ] },{ "paper_id": "24a525b0319b028b8898f731d49b84f467ae2c73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "24a8a71cbe308f92fd40a91b81fd4483363bd36b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A textbook on animal husbandry dating from 1906 observed: \"Swine appear to have a craving for what might be called 'unnatural substances'. This is especially true of hogs that are kept in confinement, which will eat greedily such substances as charcoal, ashes, mortar, soft coal, rotten wood etc. It is probable that some of the substances are not good for hogs, but there is no doubt that charcoal and wood ashes have a beneficial effect, the former being greatly relished\" (Day, 1906) .", "This study predominantly selected research papers published between 1980 and 2019 but included also a selection of historical articles and books published between 1905 and 1979. Some rare oral communications were included to reference and illustrate farmer and feed certifier experiences.", "1. Adsorption of proteins, amines and amino-acids.", "Charcoal is one of the oldest remedies for digestive disorders, not only for humans but also for livestock. Cato the Elder (234 -149 BC) was one of the first to mention it in his classic On Agriculture: \"If you have reason to fear sickness, give the oxen before they get sick the following remedy: 3 grains of salt, 3 laurel leaves, [ : : : ], 3 pieces of charcoal, and 3 pints of wine.\" (Cato, 1935, \u00a770) . Besides the administration of medicinal herbs, oil or clay, charcoal was widely used by traditional farmers all over the world for internal disorders of any sort. Apparently, it never did any harm but was mostly beneficial (Derlet & Albertson, 1986) . For some animals like chicken or pigs, the charcoal was administered pure; for others it was mixed with butter (cows), with eggs (dogs) or with meat (cats)." ] },{ "paper_id": "24b20768feb528be2a620b4afcd761cdfabcb183", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In contrast, potently neutralizing, type-specific antibodies did not require the formation of aggregates for effective neutralization [26] . Type specific neutralizing antibodies can be detected even 60 years after a primary infection [27] ." ] },{ "paper_id": "24beb94c313a07be6b0c745a6ca8a3d810618506", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "of the Russian Federation (State Assignment no. 056-00108-18-00).", "The HEK293 and A549 cell lines were obtained from the Russian collection of vertebrate cell lines (Russia). The HEK293T and Vero E6 cells were obtained from ATCC (USA). All cells were cultured in DMEM (Dulbecco's modified Eagle medium) supplemented with 10% fetal bovine serum at 37\u00b0C with 5% CO 2 .", "IgG2b IgG3", "All animal experiments were performed in strict accordance with the recommendations of the National Standard of the Russian Federation (GOST R 53434-2009; Principles of Good Laboratory Practice). Six-week-old female C57/BL6 mice (18-20 g) were obtained from the Pushchino Breeding Facility (Russia). The mice had free access to water and food. The mice were housed in an ISOcage system (Tecniplast, Italy)." ] },{ "paper_id": "24c20b8ab487acad45bb797b2ae0a2a910b31043", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Suppression of virus-induced cytokine production in mice treated with celecoxib", "2.1. Prostaglandins. PGs are generated when phospholipase A 2 (PLA 2 ) releases arachidonic acid (AA) from membrane glycerophospholipids ( Figure 1 ). Released AA is oxidized to the intermediate prostaglandin H 2 (PGH 2 ) by cyclooxygenase (COX). COX exists in three isoforms. COX-1 is generally constitutively expressed, while COX-2 expression is rapidly induced by growth factors and cytokines [5] . COX-3 is a recently discovered isoform whose biological role, if any, remains poorly understood [6, 7] . Once formed, PGH 2 can be converted by specific synthases to thromboxane A 2 (TXA 2 ), PGD 2 , PGE 2 , PGF 2 , and PGI 2 . As described below, PGE 2 has multiple effects on host immune function. PGE 2 is transported from the cell by multidrug resistance protein (MRP) 4 and possibly by other unknown transporters [8] .", "The prostaglandins and leukotrienes modulate many host immune responses that are important contributors to viral pathogenesis, such as cytokine signaling, neutrophil and macrophage phagocytosis, trafficking and activation of DCs and T cells, and antibody production by B cells." ] },{ "paper_id": "24c4787033b7069da07ce6b0b8f85f6fd5ad84b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Selection of sampling locations varied by Round as follows:", "The surveillance period extended from September 2011 to December 2015 and was divided into six \"Rounds\" ( Table 1) .", "then \u03b8, the empirical Bayes-smoothed prevalence for the ith province, was calculated as follows:", "(3)" ] },{ "paper_id": "24c739b85e7c9082d00e9680cf7a99070c427d55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PLOS ONE |", "Blank experiments and chamber cleaning", "PFU=ml genomes=ml WithVirucide , PFU=ml genomes=ml WithoutVirucide\u00f03\u00de" ] },{ "paper_id": "24d4ea00f8f0e950b98a668d62f780396d3cad68", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 7: 3576 | DOI:10.1038/s41598-017-03799-2" ] },{ "paper_id": "24d774f5b08d9ca987d0d23927d92ba23f131931", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total genomic RNA was extracted using Trizol Kit (Invitrogen, USA). DNA was extracted by DNA Blood Mini Kit (Qiagen, Germany). After elution in 20 \u03bcL Nuclease-free Water, RNA/DNA samples were stored at -70\u00b0C before use. The original concentration of RNA/ DNA sample was about 50 ng/\u03bcL.", "Swine Transmissible Gastroenteritis Coronavirus (TGEV, strain H), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), Pesudorabies (PRV), Porcine Parvovirus (PPV) derived from their passages in cell culture were provided by Shanghai Entry-Exit Inspection and Quarantine Bureau (SHCIQ); nucleic acids of Footand-mouth Disease Virus (FMDV) and Classical Swine Fever Virus (CSFV) were obtained from Chinese Academy of Inspection and Quarantine (CAIQ).", "LAMP primers were designed using the Primer Explorer V3 software based on a conserved fragment of the nucleocapsid gene (Fig. 1) . The primers including Outer Primers (F3 and B3), Inner primers (FIP and BIP) and Loop primer (LF and LB) were shown in Table 1 ." ] },{ "paper_id": "24d7fe6bbb9945f1536fef5b281d074fe69cfc6a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Table S1 Questions used to measure AI knowledge, risk perception, and preventive behavior. (DOC)" ] },{ "paper_id": "24d93589f9edba05a3f0a95b350bc91cb551814a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Respondents were asked which of 11 specific surveillancerelated activities or capacities are priorities for their country, MBDS, and/or the WHO IHR:", "They feel the XB model should be strengthened and expanded-by strengthening local human, laboratory and communications technologies and expanding to more counterpart XB sites along the expansive MBDS " ] },{ "paper_id": "24db4d088787fb5c43f2f60604e1f1463d4b4082", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each experiment was repeated at least three times. The data are shown as mean \u00b1 s.e.m. , and the statistical significance was determined using one-way analysis of variance (Dunnett's T3 test) (Davis, 2001) . Statistical analysis was done using SPSS (www.ibm.com/analytics/).", "In summary, a continuous cell line from A. anguilla kidney has been established and showed its potential impact for studying infectious viral diseases of Anguillidae fishes and for immune genetic, toxicological and pathological researches, benefitting the protection of A. anguilla.", "The internal control gene \u03b2-actin showed no significant change." ] },{ "paper_id": "24de2f3f8107492057953a49ec7182514e9ff95a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses that belong to the subfamily Coronavirinae within the Nidovirales order, which are further subdivided into four genera: alpha, beta, gamma and delta. Human coronaviruses belong to the alpha and beta genera [4] .", "Asymptomatic cases were those with no reported symptoms at the time of a positive test recorded by a healthcare provider in the medical chart. However, these patients showed symptoms subsequently in the clinical course. In contrast, in symptomatic cases, patients reported their symptoms during hospital admission.", "A suspected case was defined as any instance of hospitalization for bilateral pneumonia and any one of the following clinical symptoms at admission: fever (>38\u00b0C), cough, shortness of breath (SOB), sore throat, vomiting, diarrhoea, haemoptysis, chest pain and/or infection, respiratory failure, loss of consciousness, runny nose and any asymptomatic cases with a history of contact with confirmed symptomatic cases." ] },{ "paper_id": "24e8a04adeb7f1142768d4de1e10d8ac48afcd03", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It has long been known that a variety of oligomannose-specific lectins have potent in vitro HIV-1 inhibitory activities, and therefore have been proposed as microbicide candidates for topical prophylaxis of HIV-1 infection, and as potential therapeutics [8, 9] . However many lectins possess lymphocyte mitogenic activities incompatible with their use as pharmaceuticals, and some are known human and animal toxins, although the pharmacological basis for their toxicity is poorly characterized [10, 11] . The antiviral potency of lectins has been correlated to their capacity to bind multiple glycans simultaneously, often facilitated by their ability to form dimers and higher order multimers [12, 13, 14] .", "In unstimulated cells, about 15% of CD4 positive PBMC expressed the late activation marker HLA-DR and treatment with GRFT and ConA did not affect this number in a significant fashion (Fig. 6 , right panel and Fig. S2C ). PHA treatment of cells yielded more than twice the number of CD4 + /HLA-DR + cells (33.4%) compared with unstimulated PBMC.", "When freshly-isolated PBMC were pre-incubated for 24 hrs with GRFT at various concentrations, washed and then infected with HIV-1 R5 strain BaL (without adding new compound), GRFT inhibited viral replication for 9 days of cell culture (Fig. 2) . As a control maraviroc (MVR) at 2 mM was included and this also showed anti-HIV activity after 9 days in culture, as this compound is known to bind specifically to the CCR5 receptor. However, lower concentrations of maraviroc (at 0.4 mM) did not retain its antiviral activity in this assay protocol (data not shown).", "Freshly isolated PBMC were cultured in the presence of GRFT, CV-N and maraviroc for 24 hrs. Then the cells were collected, washed in culture medium, suspended in RPMI medium with 2 ng/ml IL-2 and seeded in a 48-well flat bottom plate (5610 5 cells in 450 ml) and 50 ml of the CCR5-tropic clade B HIV-1 BaL stock was added at 100 TCID 50 . The supernatant of each sample was collected after 9 days and viral replication measured by a specific p24 Ag ELISA (Perkin Elmer, Zaventem, Belgium)." ] },{ "paper_id": "24ea6063ca2c39579eef84d27b3170e6d33a7e27", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "24ed22a878649ce74463bf63090563093d002c86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Unpaired Student's t-test and One-way ANOVA were used for determination of statistically significant differences. The use of the term significant in text refers to a comparison of values for which p,0.05.", "Production of VLPs. To generate influenza A/PR/8/H1N1 b-lactamaseM1VLPs (PR8 b-lacM1 VLPs), 293T cells were cotransfected with 3 mg each of pCAGGS-HA, pDZ-NA, and pCAGGS-b-lacM1 PR8 using FuGENEH HD (Roche Applied Science, Indianapolis, IN) according to manufacturer's instructions. The supernatant containing the VLPs were collect 48 h post-transfection and clarified of floating cell debris by centrifugation at 3,000 rpm for 10 min. The VLPs were concentrated once by low-speed centrifugation through an Amicon Ultra 100 kD centrifuge filter unit (Millipore; Billerica, MA), and the retentates were aliquoted and stored at 280uC." ] },{ "paper_id": "24f1d3b412c3e8fcbbd6807643cc193ef00b5ed8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scenario 4 represents the highest risk of secondary transmission and may also reduce the chance of a positive clinical outcome for the sick individual.", "We developed open-source software, including a freely-available web application at http:// iddynamics.jhsph.edu/apps/shiny/activemonitr/. The source code for the web app, the data for the analyses, and the code to reproduce this manuscript itself are all freely available online under an open-source license at GitHub https://github.com/reichlab/activemonitr, with a static version in an open-access digital library 22 . All analyses were run in R version 3.4.1 (2017-06-30) 23 . These tools enable others to easily implement our model and reproduce our results.", "We present a framework for assessing the cost of active monitoring, which is one possible public health strategy for combating an emerging epidemic. However, alternate strategies such as quarantine, pharmaceutical interventions, or increasing risk communication could also be implemented. These different interventions could also be assessed under a similar framework to that presented here. We hope this paper provides the key underpinnings needed for a formal cost-effectiveness analysis. Such an analysis, that synthesizes model-based estimates of costs, benefits, and risks, could provide additional valuable information about the value of each possible strategy." ] },{ "paper_id": "24f3fb94ffa06167fa87ba73f357916cc88359b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Primer sequences were as follows: forward primer sequence ATGACYCTCTATGGGAAACTCCTT, reverse primer sequence GTGCCTRGCAACAACCTCCAA, and a minor groove binding probe sequence FAM-TTGGCCAYAACCTCCCTGA-MGB. The eluted RNA and the PoAstV3 and XIPC specific primers and probe were mixed with commercial reagents TaqMan ", "Identification of risk factors associated with PoAstV3-associated neurologic disease requires additional investigation but could include exposure dose, genetic determinants, intestinal microbiota and/or immune suppression as a result of co-infections, co-morbidities, and stress. Further studies are also needed to understand the infection dynamics and antibody response over time, comparative sensitivity of sample types, and efficacy of commercial disinfectants. This information would provide foundational knowledge required to prevent and control disease.", "Fecal samples were collected using sterile polyester tipped swabs (Puritan \u00ae , Catalog no. 10805-165, Puritan Medical Products Co., ME, USA) placed in a 5-mL polystyrene round bottom tube (FALCON, Catalog no. 352054, Corning Incorporated Life Sciences, MA, USA). Each tube contained 1 mL of phosphate buffered saline (Gibco TM , PBS pH 7.4 (1\u00d7), Catalog no. 10010023, Grand Island, NY, USA) and samples were stored at \u221280 \u2022 C until testing." ] },{ "paper_id": "24f49539fad81e8f8b10650eb9cbfd60c8ee23f5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virion RNA from wild type and CP variants was subjected to Poly-A tailing using E. coli poly A polymerase according to the manufacturer's protocol (NEB). Following inactivation of poly A polymerase by heat (95 \u00b0C for 2 to 3 minutes), first strand cDNA was synthesized using a reverse primer (5\u2032 GGGAGGACACAGCCAACATACGTATTTTTTTTTTTTTTTTTTTTT 3\u2032 ; SnaB I site is underlined) and M-MulV reverse transcriptase (New England Biolabs). The resulting product was subjected to PCR using a forward primer (5\u2032 TACGTAAACTTACCAATCAAAAG 3\u2032 ) and a reverse primer (5\u2032 GGGAGGACACAGCCAACATACGTA3\u2032 ; SnaB I site is underlined). PCR products were analyzed by agarose gel (1%) electrophoresis then visualized and photographed under UV light following ethidium bromide staining." ] },{ "paper_id": "24f4f393fb59daab089844e7af64e913d2951034", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data acquisitions and analyses were carried out using a FACSCalibur device and Cell-Quest software (BD Biosciences).", "For analysis of PBMC proliferation, total cell numbers after treatment were assessed by flow cytometry.", "To test the significance of pairwise differences between the treatment groups, the Wilcoxon matched-pairs signed-rank test was used (SPSS software, IBM). A p-value of p 0.05 was considered as indicator of significance.", "All cell cultures were performed using RPMI culture medium supplemented with 2 mM L-Glutamin and 10% fetal bovine serum (Biochrom). The study of EPs 7630 effects, the collection and usage of the blood samples were approved by the clinical institutional review board of the University Hospital Charit\u00e9 Berlin, and written informed consent was obtained from donors." ] },{ "paper_id": "24fc42faaa7cf3f1b483806e77056a1d253715c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Within the past five years epidemic prone diseases such as the pandemic (H1N1) in 2009 which originated in Mexico, the Middle East Respiratory Syndrome Corona Virus which was isolated in 2012 in Saudi Arabia, the Chikungunya virus which emerged in the Americas in Saint Maarten in December 2013 and the Ebola Virus in West Africa in March 2014, were introduced into nonendemic areas by travel [5] [6] [7] [8] [9] . These public health events further emphasise that international travel can quickly and extensively affect global health [10] [11] [12] [13] .", "The Barbados Port Health Department is the government agency responsible for enforcing the International Health Regulations (2005) and regulating public health conditions on vessels transiting through Barbados' territorial waters.", "The findings of this study show a high predominance of infectious diseases such as gastroenteritis and influenzalike illness in both passengers and crew passing through a busy Caribbean cruise port and highlight the need for continuous surveillance at points of entry.", "Ethical approval to undertake this study was applied for before commencing the data collection in June 2014. Ethical approval was formally obtained by written correspondence from the Institutional Review Board (IRB) of the University of the West Indies on the 18 th May 2014." ] },{ "paper_id": "25037be00789070e126164a9f939b64aeede0a64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "250615c975f713cb3e2b09e7e9718fa2eb095a79", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The samples were stored at -20\u02daC and coded for blinded analyses.", "If cats less susceptible to T. gondii infection could be selected for breeding, it could have a major impact. Preferring such cats could potentially decrease the risk of infection for other hosts, including humans, by limiting the production of T. gondii oocysts. Furthermore, as T. gondii can cause severe disease and mortality in domestic cats [24, 29] , decreasing susceptibility to the parasite would also be beneficial for feline welfare and health.", "Supporting information S1 " ] },{ "paper_id": "250c1f24a22bcb81973ea532f8236838987e0872", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2522231ac6a1faeccfaf8f71e1bdc7cc81c7c647", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "252e6f853b7025fa235432baf9869ae4f51a020d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The recipient array block, containing 60 holes of 2 mm diameter, was prepared by first pouring paraplast X-TRA (Sigma, Aldrich, The Netherlands) into an array mold (IHC world, USA). Selected cores from the donor blocks were subsequently transferred to the recipient array block (Fig 1) . The array blocks were trimmed and sectioned into 4 \u03bcm TMA sections mounted on KP plus glass slides (Klinipath, The Netherlands). A TMA from every array block was stained with H&E and lectins MALI (Maackia amurensis lectin I) and MALII (Maackia amurensis lectin II) (Vector Laboratories) for quality control and to identify the different cell types in each tissue.", "The tissues used for this study were obtained from the tissue archive of the Veterinary Pathologic Diagnostic Center (Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands). This archive is composed of paraffin blocks with tissues maintained for diagnostic purposes; no permission of the Committee on the Ethics of Animal Experiment is required.", "Tissues were selected from Canada goose, graylag goose, guineafowl, mallard duck, partridge, pheasant, pigeon, quail, teal, turkey, and white leghorn chicken. The donor blocks were sectioned to 3-4 \u03bcm. Sections were stained with hematoxylin and eosin (H&E) assessed microscopically to analyze the quality of preservation and to select areas from organ systems devoid of pathological changes for transfer into recipient blocks." ] },{ "paper_id": "2530bf775255e8026438e91645aba95d0506928e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2020, 12, 64 2 of 15 development against SUDV infection. Further, these horse anti-SUDV purified immunoglobulins lay a foundation for SUDV therapeutic drug research.", "The impact of SUDV outbreaks in recent years, and the potential for viral spread to non-endemic regions or countries, makes the development of safe and efficacious vaccines urgent.", "The authors declare no conflict of interest.", "The mechanism of natural immunity against EBOV remains unclear. The efficacy of different types of vaccines may vary depending on the vaccine platform: antibody is the major immune correlate factor of the rVSV-ZEBOV vaccine [33] . Meanwhile, CD8 T cell responses have been attributed to protection by the Ch-Ad5 vaccine [34] . Previous VLP vaccine studies showed it is efficacious against lethal Ebola challenge, however, with different adjuvants to save antigen and enhance vaccine-induced immune responses [35, 36] ." ] },{ "paper_id": "25397e5a50461221e9a0706147a6b6e3ad449ac9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data set supporting the results of this article is available in the LabArchives repository, DOI: 10.6070/ H4DR2SHR. ", "As the public health community has rushed to understand the etiology and natural history of this disease over the past several years, insights have begun to emerge. A first point is that bats appear to play some sort of ultimate role in the long-term hosting of a diverse community of coronaviruses [e.g., [8] ], including virus lineages closely allied to that found in MERS-affected humans [9, 10] . This bat origin and long-term hosting coincides with the apparent conclusions regarding the identity of the long-term host of the preceding SARS-CoV virus that caused disease across East Asia [11] ." ] },{ "paper_id": "253cfd411f93ef88f702accd0fa195f24d1d2925", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes of SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained from previous outbreaks, perhaps the world is better equipped to deal with the most recent emergent group 2B coronavirus.", "Building from the sequence, the nucleotide alignment quickly distinguished the novel virus as a group 2B CoV, distinct from the SARS-CoV strains [4, 5] . Examining the whole genome, 2019-nCoV maintains~80% nucleotide identity to the original SARS epidemic viruses. Its closest whole genome relatives are two bat SARS-like CoVs (ZC45 and ZXC21) that shared~89% sequence identity with 2019-nCoV; these CoV sequences were deposited in early 2018 from Zhejiang province in R. sinicus bats in China. Comparing across the deposited 2019-nCoV strains finds > 99.5% conservation; the lack of diversity suggests a common lineage and source with emergence not likely having occurred that long ago [28, 29] . A recent report has subsequently identified a bat CoV sequence, RaTG3, with 92% sequence identity with the novel virus which argues for bat origins for the 2019-nCoV [30] .", "The rapid sequencing of the nearly 30,000 nucleotide 2019-nCoV genome by Dr. Zhang's group at Fudan University and several other groups in China illustrate the dedication and increased capacity of the scientific infrastructure in China [4, 5] . For SARS-CoV, the causative agent was unknown for months and subsequently took over four weeks until a full genome was released [26] . Similarly, MERS-CoV was only identified after several months of testing and a full-length genome available about a month later [27] . In contrast, time from the first date of patient onset (12 December 2019) to the report of several 2019-nCoV full-length genomes took less than one month. Combined with the immense pressure of an ongoing outbreak with an unknown agent, the effort of these scientists should be considered nothing less than remarkable." ] },{ "paper_id": "2544d85288aa39f592b1e172f8c62040bc1b2ba6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Immunofluorescence. PAM were grown on coverslips and treated or untreated with cGAMP (20 g/ml) or mock or ASFV infected at the indicated MOI. At the indicated times postinfection (1 or 6", ", and lysates were separated by 7 to 20% SDS-PAGE, followed by immunoblotting with anti-p-STING, anti-STING, anti-p-IRF3, anti-IRF3, anti-ASFV p32 (viral early p32), and anti-actin antibodies. Graphs below the panels B and C indicate the relative phosphorylated-STING versus total STING protein. Densitometry was performed using ImageJ." ] },{ "paper_id": "2557b13f557e15081960d49034d890a790943b38", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reagents used were Nocodazole (Sigma-Aldrich), taxol (paclitaxel; Sigma-Aldrich), BODIPY 493/503 (Invitrogen Molecular Probes), 4',6-Diamidino-2-phenylindole (DAPI; Invitrogen Molecular Probes) and wheatgerm agglutinin (WGA) Alexa Fluor 647 conjugate (Invitrogen Molecular Probes).", "A CellTiter96A Queous One solution cell proliferation assay kit (Promega) was used to evaluate cell viability, which was performed as described previously [40] .", "Cells were gown on glass chamber slides. Cell fixation and immunostaining were performed by the methods described by Listenberger L. L. and Brown D. A. [41] . Photographs of the cells were taken with a confocal microscope (Zeiss Confocal Laser Scanning Microscope LSM 510META-NLO)." ] },{ "paper_id": "2558f92b15a62a49fdd0e7621ba97f1a4aa0080d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "255e2bd7406726ccde903239d96011c340330634", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fragments of 130 nt and 196 nt from three Brucella positive cases and two PPV positive cases were sequenced and compared with sequences available from the GenBank database demonstrating a nucleotide identity of \u226595% (data not shown).", "PCVAD was defined as a significant increase in the postweaning mortality and 'wasting' rates and detection of PCV2 nucleic acid by polymerase chain reaction (PCR) in 50% of pigs that died with clinical signs of PCVAD in the post-weaning period." ] },{ "paper_id": "25615501bc9f54fd01b72047cec1f8ec619b1e69", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "I.n. immunization was performed under anesthesia by 0.06-0.07 mg/g pentobarbital. There were 4-7 mice in each group.", "Monolayers were grown in 12-well Corning Costar Transwell plates (Corning Inc., U.S.) with 0.4-mm or 3-mm pore filter inserts. Cells were cultured for 14-16 days after becoming confluent (which took about 2 days). The medium was changed every other day so that would be well polarized. The TER readings were about 600 Ohm/cm 2 (as measured by a Millicell-ERS voltmeter; Millipore Corp., U.S.).", "All statistical analyses were conducted using GraphPad Prism, version 4. Statistical comparisons were conducted using the 2tailed unpaired t test. P values ,0.05 were considered significant.", "Each monolayer was rinsed with PBS and fixed with 2% formaldehyde and 0.1% glutaraldehyde in 0.1 M sodium phosphate buffer, pH 7.2, at 4uC for 2-4 hours [32] . Following fixation, the cells on filters were cut free of the plastic inserts, postfixed in OsO 4 , contrasted en bloc with 1% uranyl acetate, dehydrated in a graded series of ethanol solutions, and embedded in epon. Sections were cut perpendicularly to the filter, collected on Formvar-coated mesh grids, and examined under a JEM-1230 electron microscope." ] },{ "paper_id": "25621281691205eb015383cbac839182b838514f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional methods can be found in the supplementary information.", "Data availability. Any reagent will be shared and distributed to other investigators upon request for research purposes and upon signing of a standard material transfer agreement from the relevant institute if necessary." ] },{ "paper_id": "2563d232b59f44a5431f582cdc965b3de048e8dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "256425602cf068d42a6473d317890d0c0ac6a464", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A number of emojis have been created that could be related to infectious diseases. In 2017, the \"mosquito\" ( ) emoji was proposed with the objective to improve communication and research regarding mosquito-borne diseases and to monitor mosquito-borne disease outbreaks [36] . \"Face with thermometer\" ( ) and \"sneezing face\" ( ) are among the smileys that may be used to represent a hospital patient, person with a cold or flu or other physical diseases. New health-related emojis in other categories including \"lab coat\" ( ), \"microbe\" ( ), \"test tube\" ( ), \"petri dish\" ( ) and \"DNA\" ( ) have also been added as part of Unicode 11.0 in 2018 to facilitate scientific communication in the digital world.", "The ever-evolving medical language, which is globally accepted as medical English, has faced significant changes over time [10] . But despite all the developments that have taken place, language barriers still hinder disseminating knowledge worldwide [11] by preventing sufficient quality of care among patients and healthcare providers who speak different languages and come from different cultures [12, 13] . Numerous pictographs have been developed to enrich verbal communication and facilitate digital communication by substituting for nonverbal cues [8] . They received so much attention that in 2005, a number of medical emoticons were recommended instead of abbreviations and acronyms used in medicine [14] . Emojis are a step further than emoticons. For example, \":-O\" is an emoticon for surprise while \" \" is the emoji with the same meaning. More natural in design, emojis have attracted scientific attention as they are able to transmit emotion, attitude and attention when added to text [1, 15] . As emojis are easily distributed by users around the world, they enable researchers to conduct studies and surveys across geographical boundaries using this language [6] .", "Emojis may empower IPC in different aspects such as raising awareness with no language barrier, educating people to adopt healthy behaviors, and enhancing surveillance systems to monitor infectious diseases. It is recommended to evaluate the relevance and appropriateness of the current set of emojis to use for hand hygiene promotion in order to harness the potential beneficial impact of these symbols. Medical emojis that are standardized as a new category of emojis offer much hope for the future, especially in the field of IPC.", "Considering the significant role of person-to-person transmission of infectious diseases and the necessity of behavioral adherence to IPC interventions, behavioral science is directly associated with infectious disease models [37] . Therefore, the existing set of emojis may be useful for showing behaviors associated with IPC such as hand hygiene. Bearing in mind the limited number of health-related emojis, positive effects of the currently available symbols in the field of IPC are questionable." ] },{ "paper_id": "256b5eac8bfa8c9641d0d210032e64b82294b597", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protein-coding messenger RNAs (mRNAs) are highly conserved even between phylogenetically distant organisms [20, 21] .", "Viruses are likely the most abundant biological entity and the known global virosphere is greatly expanding [1, 2] . Viral infections cause significant morbidity and mortality worldwide. Socio-economic and environmental changes increase the frequency and impact of outbreaks, as recently seen for Zika virus (ZIKV), chikungunya virus (CHIKV), Ebola virus (EBOV), and severe acute respiratory syndrome coronavirus (SARS-CoV) [3] [4] [5] . As obligate intracellular pathogens, viruses make extensive use of host cell machinery to replicate. The interfaces between host and virus have provided extraordinary insights to molecular mechanisms of pathogenesis and yielded valuable therapeutic targets. Viruses further constitute a unique opportunity to advance our understanding of mechanisms of cell biology. Virology already provided numerous tools and basic discoveries in cellular biology [6] . The simple genetic architecture, high diversity, and fast evolution of viruses have made them perfect for subtractive and comparative studies [7] [8] [9] . Most systematic studies of virus-host interactions have focused on proteins whereas RNA interactions are a more recent focus area.", "Thus, several types of cellular ncRNA, including miRNAs and lncRNAs, are regulated upon viral infection-as a cellular response to infection or as a viral evasion strategy-and the outcome can be either pro-or anti-viral. Many more such cases of miRNAs and lncRNAs may await discovery, and future studies will show whether other regulatory RNA molecules exhibit similar responses to infection.", "Sequence analysis of the mammalian transcriptome uncovered a vast transcriptional landscape of regulatory lncRNAs both overlapping (sense or anti-sense) and outside known protein coding and small RNA genes [25, 123, 124] . Depending on their sub-cellular localization, lncRNAs can modulate metabolism and gene expression by coordinating architecture of nuclear domains, mediate epigenetic modifications, and regulate translation and stability of target mRNAs and protein functions [124, 125] . Although less conserved than protein coding genes [126] , the expression of specific lncRNAs, such as XIST or FENDRR, is essential for embryonic development and organ homeostasis [127] [128] [129] ." ] },{ "paper_id": "25707e09aa87bb548138776e263ab037f4e6cda0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical comparisons of data among groups of control and treated BM-DCs were performed with the nonparametric Mann-Whitney U test. Values of p < 0.05 were considered significant. All statistical tests were performed by SPSS for Windows, version 13.0. (SPSS Inc., Chicago, Ill., USA).", "(TIF)" ] },{ "paper_id": "25742d7fc7e3a5dfd8af95c2dbc9731494d13e67", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "McGahie, D: employee Virbac, Carros, France. His contribution for this work was mainly as a Consultant. The other authors declare that they have no competing interests.", "Authors' contributions ROL, SG and MTVB carried out the clinical follow-up of both cases, making substantial contributions to the clinical management of the cats. ROL and SG were involved in data acquisition, analysis and interpretation and the drafting of the manuscript. DMcG contributed the treatment protocol. DMcG, MN and LT were involved in revising the manuscript, contributing to its intellectual content. All authors read and approved the final manuscript.", "Authors' information RL is a PhD fellow (FCT SFRH / BD / 62917 / 2009 Portugal) at CIISA/ Technical University of Lisbon (FMV-UTL). His current research is focussed on immune-modulation therapy in feline medicine, particularly in naturally retrovirally-infected cats. Concurrently with finalizing his PhD thesis, RL is also a clinical assistant at the Teaching Hospital (FMV-UTL), working being involved in the endocrinology service. SG is a research assistant in the Programa Ci\u00eancia 2007 (FCT-Portugal). Concurrently with her research activity, SG is also a clinical assistant at the Teaching Hospital (FMV-UTL) working in the infectious diseases service." ] },{ "paper_id": "257c4916d1ec89f09d6d2b42b42042b6aeaa41bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by St. Jude institutional review board. All samples were fully anonymized before initiation of the study and the IRB committee waived the requirement for informed consent.", "Lymphocytes play an important role in viral respiratory infection [42, 54] . An ALC count below 100/mm 3 or 300/mm 3 is significantly associated with increased risk of progression to LRTI [42, 55] . In addition, patients receiving T-cell therapy have decreased viral loads, viral clearance, and resolution of clinical symptoms [56] . Although symptomatic patients had a lower lymphocyte count than did asymptomatic patients, this difference was not significant by age or virus.", "Another study showed that the relationship between viral loads and multiple virus infections is virus specific [52] . The limited sample size of our study did not allow us to further explore viral load in relation to each different virus, which might explain why we did not see an overall change in influenza or RSV viral loads in cases of viral coinfection." ] },{ "paper_id": "257d3ac44f72e298b1b0c5f46561948b973ac3d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nested-PCR onset dpi (duration) Feces Serum Feces Serum", "For assessment of the antigen distribution of rotavirus, IFA was performed in each organ sampled from virus- ", "The Genbank accession numbers for the 11 genome segments of strains used in this study are shown in Additional file 2." ] },{ "paper_id": "2585403015b1b1b31ab187eace93d67f4441e3cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Next, we summarized workflow performance by aggregating benchmark results on simulated viral data from different publications (Figure 2) . Twenty-five workflows had been tested for sensitivity, of which 19 more than once. For some workflows, sensitivity varied between 0 and 100, while for others sensitivity was less variable or only single values were available. For 10 workflows specificities, or true negative rates, were provided. Six workflows had only single scores, all above 75%. The other four had variable specificities between 2 and 95%.", "Precision, or positive predictive value was available for sixteen workflows. Seven workflows had only one recorded precision score. Overall, scores were high (>75%), except for IMSA+A (9%), Kraken (34%), NBC (49%), and vFam (3-73%).", "This work was supported by funding from the European Community's Horizon 2020 research and innovation programme under the VIROGENESIS project, grant agreement No 634650, and COMPARE, grant agreement No 643476." ] },{ "paper_id": "258b69aa1d0bb32cf913f8124f8c053442522f6b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: In Madagascar, despite an influenza surveillance established since 1978, little is known about the etiology and prevalence of viruses other than influenza causing influenza-like illnesses (ILIs).", "File S1 Laboratory Details. (DOC) ", "The protocol and oral consent were determined as routine surveillance activity, and therefore non-research by the National Steering Committee for Surveillance of Fevers, an entity representing MoH, IPM, WHO and Clinicians in compliance with all applicable National regulations governing the protection of human subjects. Data were collected in an objective of surveillance and are anonymous. Collections of non-sensitive data or an observation from normal care in which participants remain anonymous do not require ethics committee review. Only physician could withdraw anonymity. Before each sample, physician gave information about surveillance system and objectives to prevent disease spread in community. After that, patients could refuse to participate and no specimen will be taken. Oral consent was documented in the patient form." ] },{ "paper_id": "258dc6960914cb934076d169f8c02d51883cf571", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study has identified ACE2 as a potential surrogate marker of CV outcomes, and possibly a target for therapeutic intervention. Whether targeting patients with increased plasma ACE2 levels for more intensive therapy would lead to improved outcomes has yet to be tested." ] },{ "paper_id": "2590692fa24c429d02c8d67f6100a132c3915473", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Compound 5 was prepared according to our procedures published earlier [43] .", "3.1.6. Synthesis of N-(4-((6-Methoxyquinolin-8-yl)amino)pentyl)hydrazinecarboxamide (6) The title compound was prepared following previously published procedure [46] .", "The authors declare no conflict of interest. " ] },{ "paper_id": "259ac67e44e833ea06564160ee399b76985f1145", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All chemicals used in these studies were analytical grade or equivalent and were obtained from Sigma (St. Louis, MO) unless otherwise noted. Milli Q water (18.2 M\u03a9) was used throughout. ", "All data are representative of at least three independent experiments with twenty individuals in each group and are expressed as means \u00b1 standard error of the mean (SEM). Comparisons between two groups were performed using unpaired Student's t-test. The criterion for statistical significance was p < 0.05 for all comparisons. ", "Fasting venous blood samples were collected in the morning (8-10 am). Blood samples were drawn into tubes containing K2EDTA and then immediately centrifuged at 1300 \u00d7 g and 4\u00b0C for 10 min according to HUPO plasma proteomics project recommendation [28] . Supernatant was removed to a new tube and one tablet of complete protease inhibitor cocktail (Roche, Mannheim, and Germany) was added. Then, sample were promptly frozen in aliquots and stored at -80\u00b0C until used." ] },{ "paper_id": "25a160364a2e056a097e4520f64c49c63140da6c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Interferon IFN-\u03b2 was produced and quantified, as described previously, from 293T cells transfected with pcDNA3-IFN-\u03b2 [25] , and diluted in culture medium at 5 units of IFN per ml for cell treatment.", "To construct these vectors, the coding sequences of Apol9b and Apol9a were PCR-amplified from C57BL/6 mouse spleen cDNA, using Phusion polymerase (Finnzymes) and cloned in pTM942 using AgeI/BsiWI restrictions sites introduced in the PCR primers.", "The plasmid used to express C-terminally FLAG-tagged mouse IFN-\u03b1A is pcDNA3-IFN-\u03b1A-FLAG (or pAGE2) [12] . ", "For Brefeldin A treatment, GolgiPlug (ref 555029, BD Biosciences) was diluted 1000-fold in the culture medium 20 hours after transfection of the cells and 4 hours prior to cell collection for western blot analysis." ] },{ "paper_id": "25a348f34236403317091db876b29fd5063528ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pandemic planning resources generally describe the nature of the anticipated threat, highlight the role of government and health authorities, outline essential business continuity planning and response requirements, and describe specific measures that may be implemented to limit or prevent disease spread. Specific strategies recommended to limit disease spread within the workplace include promoting improved hygiene and infection control practices, using social distancing measures and flexible work arrangements to minimise contact between individuals within the workplace and the community, using personal protective equipment, restricting workplace entry and isolating individuals who may be infectious [4] ." ] },{ "paper_id": "25ad3917e35438350dc5fdd7f64a4a1cdaea39f9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "entering the healthcare facilities. These data are being used further to predict atypical patterns of hospital admissions to detect outbreaks ( Figure 2 sopharyngeal swab) are collected and subjected to a bacteriological and viral diagnostic algorithm for each clinical syndrome. This diagnostic process is conducted within Vietnam (both at study sites and at Oxford University Clinical Research Unit (OUCRU) laboratories) and was designed to identify the major known causes of the four specific syndromes of interest. Cases are subsequently categorized as being associated with a known causative agent or as a DUO. At the time of writing (May 2015), we have recruited >6500 patients across the four syndromes.", "To deliver the aims of VIZIONS, we established two fundamental components: a hospital disease surveillance program to characterize endemic infections, novel infections and DUOs, and a high-risk sentinel zoonosis cohort to assess disease incidence and pathogen transfer ( Figure 1 ).", "(1) known pathogens that were not tested for or misdiagnosed; (2) previously unrecognized but common pathogens (e.g., parechoviruses and human metapneumovirus); and (3) newly emerging or re-emerging pathogens (e.g., filoviruses, henipaviruses, and coronaviruses). All three categories are relevant to policymakers when trying to allocate resources for prevention. While the third category accounts for the smallest number of infections, the impact of emerging pathogens, particularly those with potential for human-tohuman transmission, may range from disruptive to catastrophic. Developing an infrastructure to tackle these issues is challenging and costly, yet interventions that are implemented without supporting data on DUO frequency and population risk may prove ineffective." ] },{ "paper_id": "25affabb80bcf3e1a60c00fc09fd5d2e8f89ec48", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A study by van den Wijngaard et al." ] },{ "paper_id": "25b2a50598fe741c4092ca239bacca5e72e79972", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hepatitis A is a virus causing mild to severe liver disease. Globally, there are an estimated 1.4 million cases of hepatitis A every year. The virus is transmitted mainly via the fecal/oral route through the ingestion of contaminated food and water, or through direct contact with an infected subject. There is evidence to suggest that hepatitis A can be acquired by swimming in contaminated water.", "2013 [23] ", "A number of considerations emerge:" ] },{ "paper_id": "25b38d2f44283253d1e8d320c8389c069c5ae906", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human epithelial cervical cancer (HeLa) and Madin-Darby Canine Kidney (MDCK) cells were cultured with Dulbecco's Modified Eagle's Medium (DMEM; LGC Biotecnologia, S\u00e3o Paulo, Brazil) and Minimum Essential Eagle's Medium (MEM;", "HIV-1 production was evaluated in cell-culture supernatants by a commercial enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturer's instructions (ZeptoMetrix). HIV-1 RNA was detected and as described elsewhere [40] .", "The results of this study were prepared using Excel 2010 for Windows software (Microsoft), from at least three independent experiments. Means 6 standard error of the means (SEM) are displayed. Statistical analysis calculations were performed using the same software, and the comparisons between means were considered significantly different when the P value was less than 0.05, by means of Student'st test." ] },{ "paper_id": "25bdd8095f71bd8c6be54898b437e16896ea3790", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To determine the biological pathways with significant enrichment of the input proteins, algorithms in GeneSpring software package performs a standard hyper-geometric calculation to obtain p-value, which signifies the enrichment. Prior to analysis, manually curated biological pathways from Reactome, Biocarta, NCI and PathwayCommons (in Biopax level 2 format) were populated in GeneSpring's database. Pathways with significance pvalue (p,0.05) were chosen for subsequent analysis and interpretation. We used GeneSpring's pathway database to create Shortest Connect network from the selected pathways. The Expand Selection algorithm was performed on the above network to include first and second degree neighbors. Expand Selection uses the GeneSpring pathway database for finding expansion on entities and takes a series of expansions to connect processes/ functions/other biomolecules to the given entities (proteins). This algorithm allows listing all processes and functions in which the given entities participate.", "The gene ontology (GO) categories for 30 proteins was assigned using GeneSpring software package (version 11.5; Agilent Technologies, Santa Clara, USA). Since, GO vocabulary is organized in a hierarchical fashion, the second level of GO terms were presented as a balance between GO term for specificity and maximal coverage. GO terms that were enriched in two or more proteins were considered. In addition, a significance p-value of the enrichment was computed using the hypergeometric probability distribution, which identifies GO categories represented by the 30 proteins relative to their representation on the Biological Genome for Human created using information available at NCBI (ftp://ftp. ncbi.nlm.nih.gov/gene/DATA).", "According to the molecular function analysis by GeneSpring, most of the differentially expressed proteins identified in FM are related to binding (59.5%) and enzyme regulation activity (24%). A small fraction is involved in transport (9.5%) and antioxidant activity (7%) ( Figure S7A ; Table S6 ). Majority of the proteins reside in the extracellular region (61%), while some are located in cell (15%), organelle (11%), macromolecular complex (9%), and lumen (4%) as depicted in Figure S7B by cellular component analysis (Table S6 ). Biological processes analysis by GeneSpring indicated that identified proteins are involved in following biological process: response to stimulus (20%), biological regulation (20%), localization (14.5%), cellular process (11.5%), metabolic process (9%), immune system (9%), multi-cellular organismal process (8.5%), biogenesis (3%), signaling and development process (,4%) ( Figure S7C ; Table S6 ).", "Subsequent to enrichment and purification through the Zip-Tip pipette tips, peptide mixtures were dissolved in 0.5 mL of CHCA matrix solution (5 mg/mL CHCA in 50% ACN/0.1% TFA) and spotted onto a freshly cleaned MALDI target plate. Spots were allowed to dry for 30 mins at room temperature. After air drying, the crystallized spots were analysed using a 4800 MALDI-TOF/ TOF mass spectrometer (AB Sciex, Framingham, MA) linked to 4000 series explorer software (version 3.5.3). All mass spectra were recorded in a reflector mode within a mass range from 800 to 4000 Da, using a Nd:YAG 355 nm laser. The acceleration voltage and extraction voltage were kept at 20 kV and 18 kV respectively. Six point calibration of the instrument was automatically performed by a peptide standard Kit (AB Sciex) that included des-Arg1-bradykinin (m/z 904.468), Angiotensin I (m/z 1296.685), Glu1-fibrinopeptide B (m/z 1570.677), ACTH (18-39, m/z 2465.199), ACTH (1-17, m/z 2903.087), and ACTH (7-38, m/z 3657.923). All the MS spectra were obtained from accumulation of 900 shots. MS/MS spectra were acquired for the 15 most abundant precursor ions, with a total accumulation of 1500 laser shots and collision energy of 1 kV. Once the MS survey scans were completed, the data were processed to generate a list of precursor ions for interrogation by MS/MS. The combined MS and MS/ MS peak lists were searched using the GPS TM Explorer software version 3.6 (AB Sciex). Protein identification was performed by MS/MS ion search using MASCOT version 2.1 (http://www. martixscience.com) search engine against the Swiss-Prot database. Searches were carried out with the following parameters; all entries taxonomy, trypsin digestion with one missed cleavage, fixed modifications: carbamidomethylation of cysteine residues, variable modifications: oxidation of methionine residues, mass tolerance 150 ppm for MS and 0.4 Da for MS/MS. Identified proteins having at least two unique matched peptides were selected for further analysis. We have reported only those proteins with a protein identification confidence interval of $95%." ] },{ "paper_id": "25c68946a75609c08c00a639ba839a67316cd034", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "25d0bd17e76d262df4c2948ef2d8a5270f00871a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA was extracted using a GenElute\u2122 Total RNA Purification Kit (Sigma-Aldrich) following the manufacturer's instructions. Polyacrylic acid amine gel electrophoresis was used to identify the RNA samples having no degradation or DNA pollution. Samples with OD (260/ 280) ratios in the range of 1.8-2.0 and OD (260/230) ratios from 1.8 to 2.2 met the requirement of sequencing as identified using a NanoPhotometer spectrophotometer. RNA samples with RNA integrity numbers (RINs) greater than 7 were selected for subsequent RNA sequencing which was performed using an Agilent 2100 bioanalyzer.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Supporting information S1 ", "The swine reference genome (NCBI genome database: Sus scrofa 11.1) was used as the reference genome for our RNA sequencing data. Genome mapping was performed using HISAT software (http://www.ccb.jhu.edu/software/hisat/index.shtml). The instructions of the HISAT software website was followed to prepare the data to be uploaded and also for the running analysis protocol." ] },{ "paper_id": "25d4af008525a27cff170cac5381937b1a65dc83", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "R-Mix ReadyCells Vials with coverslip (Diagnostic Hybrids Inc. OH, USA) were used for rapid virus isolation according to the manufacturer's instructions." ] },{ "paper_id": "25d8592c8527ce05463209c6e0c3f61c75b65f86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Longitudinal analyses of prospective samples showed that of the 10 viruses found before the start of chemotherapy only 2 were still present during neutropenia (one in a patient with, and another in a patient without, neutropenic fever). In both cases it concerned RV.", "Looking at different sample types, nasal swabs had a positivity rate of 14% (16/117), compared to 6% (6/106) for throat swabs and 9% (14/148) for throat gurgles. The difference between nasal swabs and throat swabs was statistically significant (p < 0.05 chi square test). When multiple samples were taken, more than one sample was positive in 49% of the paired samples.", "Over the last decade molecular techniques, such as polymerase chain reaction (PCR), have revolutionized the diagnosis of viral infections. PCR has enabled rapid and highly sensitive detection of a large number of respiratory viruses, including those that cannot, or are difficult, to culture, such as human Bocavirus (hBoV) and human metapneumovirus (HMPV) [12] [13] [14] . In patients with hematological malignancies, PCR has shown to be far more sensitive than viral culture [11, 15] , but these studies have not looked into viral prevalence during neutropenic fever." ] },{ "paper_id": "25e0a5092935b57609da913715f5e1e5e6ecb91f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plaque assays with different incubation times ", "Double concentrated Dulbecco's modified Eagle medium (DMEM) was prepared by mixing DMEM (PAA) with 9.48 g/L DMEM Powder (Biochrom, Berlin, Germany), supplemented with 20% Foetal Bovine Serum \"GOLD\" (PAA), 2% Penicillin/Streptomycin 100 \u00d7 concentrate (Penicillin" ] },{ "paper_id": "25e53f84ee9bb3d0f9be47a740938c12dbbd559b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ribavirin (CAS no. 36791-04-5; PubChem CID 37542) was obtained from MP Biomedicals (order no. 02196066), arbidol hydrochloride (CAS no. 131707-23-8; PubChem CID 131410) from Waterstone Technology, USA (order no. 49823), and T-705 (favipiravir; CAS no. 259793-96-9; PubChem CID 492405) was custom synthesized by BOC Sciences, Creative Dynamics, USA." ] },{ "paper_id": "25eb6cba256ef7c1dce823fc897b29a642aa0d5c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "25eca606303e4a141d7f3f4a1c2e4e8138e9667c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The antiproliferative activity of the purified protein was determined as follows. The cell lines L1210 (leukemia) and MBL2 (lymphoma) were purchased from American Type Culture Collection.", "Protease inhibitors have been isolated from the seeds of different monocots and dicots, including maize [1] , wheat [2] , wampee [3] , bitter gourd [4] , Momordica cochinchinensis [5] , and legumes [6] [7] [8] . Some of them display a variety of biological activities including antifungal [9] , immunomodulatory [5] and antitumor/antiproliferative [8, 10] activities. Thus, they have drawn the attention of many researchers.", "One class of protease inhibitors is trypsin inhibitors. Trypsin inhibitors are divided into Kunitz type [11] , Bowman-Birk type [12, 13] , and squash type [4] . The three types have a molecular mass of about 20 kDa, 8 kDa, and 3 kDa, respectively. The soybean produces both Kunitz and Bowman-Birk inhibitors [6] , while melons belonging to family Cucurbitaceal produce squash-type inhibitors [4] ." ] },{ "paper_id": "25f4a5990fcb174f80bc472629eb47be50d5b3f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "260203fe9a476037ca41765c677af4b844573d36", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The EtOAc extract (41 g) was subjected to CC (7.0 \u00d7 60 cm) on silica gel, eluted with a gradient of dichloromethane (CH 2 Cl 2 )-methanol (MeOH) (100:1 to 10:1, v/v) to give ten fractions (Fr. E1-Fr. E10). Fr. E3 (2.630 g) was purified on silica gel CC (2.2 \u00d7 70 cm), eluted with hexane-EtOAc (30:1 to 1:1, v/v) to afford (61.0 mg), (28.0 mg), (23.0 mg), (7. The PE extract (80 g) was subjected to CC (6.5 \u00d7 40 cm) on a silica gel, eluted with a gradient of hexane-EtOAc (10:0 to 1:3, v/v) to give thirteen fractions (Fr. P1-Fr. P13). Fr. P4 (9.920 g) was subjected to a silica gel CC (4.0 \u00d7 50 cm) with a hexane-EtOAc gradient (250:1 to 40:1, v/v) as the solvent to gain (200.0 mg). Fr. P8 (3.190 g) was firstly performed on a silica gel CC (2.2 \u00d7 70 cm) and then purified by recrystallization with hexane-EtOAc (7:1) to afford (50.0 mg) and (100.0 mg).", "The data used to support the findings of this study are available from the corresponding author upon request.", "The chemical structures of compoundsare shown in Figure 1 ." ] },{ "paper_id": "2616c5aef5cc1449e5a6b07264e1611efc93f4df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The influences of crystal packing and structural water on docking", "Supramolecular chemistry deals with creation of a large molecule assembled with noncovalent bonding among small molecular units, in contrast to organic synthesis that involves breaking and making covalent bonds to create a new molecule [13] . Such noncovalent bonding is reversible and comprises hydrogen bonding, metal coordination, hydrophobic force, van der Waals force, p-p interaction, cation-p interaction, and/or long-range electrostatic interaction to assemble small molecules into a multimolecular complex. Supramolecular chemistry principles have been used to develop new materials, molecular sensors, and multimolecular complexes designed to disrupt protein-protein interactions." ] },{ "paper_id": "2618f1868d3eaf92f7f306467b9c8d91ec7572ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "x (Pearson's correlation, RMSE), for a module from all predictions from 10 folds of cross validation. We then assembled a null distribution of statistics by running the method on N = 40 random permutations of protein data and real module gene expression data, obtaining the null mean \u03bc 0 and variance \u03c3 0 . We calculated the Z-score for the statistic as", "For some modules, the union of candidate paths resulted in small and visually interpretable subnetworks, as in Fig 9. However, for most modules, the resulting subnetwork was not visually interpretable (as in Fig 7) . Our ILP-based method can identify high-confidence interpretable subnetworks for all modules that had paths, regardless of size.", "Networks in figures were developed using Cytoscape [112] and supporting website visualizations were developed with Cytoscape.js (http://cytoscape.github.io/cytoscape.js)", "We performed 40 randomizations, and calculated the FDR of a protein or an edge at a particular confidence level as the fraction of the random subnetworks that included it in a path of that confidence level." ] },{ "paper_id": "26300f1df41b1308ba14cd9d83f7729a52283e7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cyclodextrins also interact with collagen, which makes them promising modulators for medicinal biomaterials. Under development are biomimetic corneas prepared by growing collagen in a CD-containing medium as well as filling materials for arthritis-damaged joints made of CDs in association with collagen and glycosaminoglycan.", "Randomly methylated \u03b2-cyclodextrin SIV Simian immunodeficiency virus TRIMEB Heptakis-2,3,6-tris-O-methyl-\u03b2-cyclodextrin TNF-\u03b1 Tumour necrosis factor alpha U937", "Homo sapiens pleural myelomonocyte cell line VZV Varicela-zooster virus (chickenpox virus) WHO World Health Organisation TGF-\u03b21", "With the turn of the new millennium, developments in cyclodextrin biomedical research have once more surprised the scientific community by demonstrating that these molecules are not quite so inert and they that may, in fact, be used to treat some human ailments. Such medicinal properties are the main topic of this review and are presented in detail in Section 2." ] },{ "paper_id": "263a93d919f1c783a014ddb3f1b15d7ad3a3553b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA extraction was done using Trizol (Ther-moFisher scientific, 15596026) following the manufacturers protocol. Two micrograms of extracted RNA was used the same day for cDNA synthesis using the Omniscript RT Kit (Qiagen, 205113). Quantitative realtime PCR (qRT-PCR) was performed in 10 ul reactions containing 2\u00d7 SYBR Green Master Mix, diluted cDNA, and PCR primers. The primers used for qRT-PCR were as follows:", "Cells were treated with 500 \u03bcl 1.5% formaldehyde solution for 7 min at RT and then pelleted at 1800xg for 3 min at RT, resulting in 10 min of exposure to formaldehyde. The cross-linking reaction was quenched by treating the cells with 0.5 ml ice-cold 1 M glycine in phospate-buffered saline twice, and cells were then lysed in 250 \u03bcl RIPA buffer (50 mM Tris-HCl, pH 8.0, 150 mM sodium chloride, 1% NP40, 0.5% sodium deoxycholate, 0.1% SDS, 1 mM EDTA, protease inhibitors) for 60 min on ice. After 30 min, cell lysates underwent 20 strokes using an injection syringe. Lysates were spun for 15 min at 3000 rpm and 4\u00b0C to remove insoluble debris. The supernatant was either used directly or stored at \u221280\u00b0C. Lysates were separated by SDS-PAGE and analyzed by immunoblotting.", "The following primary Abs were used for western blotting: Anti-Myc Epitope Tag ", "GAPDH ATP6V1H: F\u2032: GGAAGTGTCAGATGATCCCCA, R\u2032: C CGTTTGCCTCGTGGATAAT. Reaction mixtures were incubated at 95\u00b0C for 10 min, followed by 40 cycles of 95\u00b0C for 10 s and 60\u00b0C for 1 min, followed by a melting curve stage. A threshold cycle (Ct) was observed in exponential phases of the amplification, and quantification of the relative expression levels was determined by the 2 \u2212\u25b3\u25b3Ct method." ] },{ "paper_id": "26401aab640b61b28b31696b3540662e5e1428d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ZIKV testing was conducted using diagnostic assays developed and validated by CDC [23] . Acute sera collected within 10-14 days post-onset from symptomatic individuals were first tested for the presence of virus by RT-PCR [23] with samples considered positive if both the gene targets in the PCR were positive. If negative, sera were tested by an IgM-antigen capture enzyme-linked immunosorbent assay (MAC-ELISA) and confirmed by plaque reduction neutralization test (PRNT) [23] . The PRNT assay was conducted in parallel with a dengue virus PRNT assay and only samples that yielded a 4-fold or higher titer for ZIKV were considered positive.", "The proportions of travellers testing positive after travelling to Zika-affected countries with an estimated R 0 \u2265 2.76 and < 2.76 were 11.2% (67/596) and 0.85% (25/ 2955), respectively.", "The dataset used in this study comprised all ZIKV tests performed at NML on individuals returning to Canada with a travel history to a ZIKV affected country or territory up to June 21, 2016. The de-nominated dataset included a case ID, the date the test sample was received by NML and information on country/territory or countries/territories to which the case had recently travelled (although precise dates of travel were not available). A total of 5157 unique test samples (of which 111 were positive) with a history of travel were received between May 27, 2015 and June 17, 2016. However after eliminating samples that did not precisely identify countries or territories of travel, travel to potentially Zika-affected countries or territories outside of the Americas and those from travellers who visited multiple Zika-affected countries or territories there were 4533 test results available for the analysis." ] },{ "paper_id": "264b30686ef5ca001923b9820e7d96fdb74e268e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "264e7bc2caec36fca2b89d1f21198b8abb4a2d3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are presented as percentage or fold increase from the paired vehicle and LPS treated blood samples at each time point. All data are presented as mean 6 SEM; n = number of animals used in each experiment. Statistical significance was evaluated by paired or unpaired two-tailed Student's t-test. Statistically significance was accepted at P,0.05. " ] },{ "paper_id": "265121b026dccf527cd9cc00dbd28a425ba5510f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Breastfeeding provides protection against infections in newborns and infants, and it is associated with low levels of morbidity and mortality in developing countries (7) (8) (9) . This effect can substantially decrease when the child is fed other than maternal milk, including even water or tea. The reason for this is that the child who is not exclusively breastfed receives less protection factors that exist in mother's milk, besides receiving food or water that are frequently contaminated (9) (10) (11) .", "At the HCPA, the usual criteria for withdrawal of oxygen is the absence of respiratory distress and haemoglobin saturation of >94% in room air. This decision, and that of discharging the patients, was taken by the paediatrician-in-charge.", "The p value of 0.05 was considered significant, and the analyses were carried out using the SPSS software (version 10.0) (SPSS Inc., Chicago, IL)." ] },{ "paper_id": "26670350d15f4a1f0a7072ad985d98b21c28fd5a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recent outbreaks of SARS and H5N1 influenza have underlined the threat that viruses in the animal reservoir pose to the human population. Fortunately, neither SARS nor H5N1 influenza have become endemic in humans. Nevertheless, these and other events have stressed the importance of being prepared for emerging and reemerging infectious diseases.", "Text S1 Model structure and details of the model analyses Found at: doi:10.1371/journal.pone.0001558.s001 (0.10 MB PDF)", "When will a prophylactic antiviral control program be able to prevent an epidemic? Several studies have addressed this question using simulations of metapopulation models that include household structure and other population and pathogen details [6] [7] [8] ." ] },{ "paper_id": "266c1240291949d87000170237a0de20daacec67", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "in contact mapping tools and in statistical methods to infer epidemiologically linked case pairs 9, 10 . Furthermore, household demographic characteristics may differ between developed and developing settings 11 .", "There were 22 infants from the 20 HHs." ] },{ "paper_id": "266da81290486b68fea7c553e21fa6a5d46aa6b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "8. Repeat the above steps until a stopping criterion (e.g. t > t max ) is reached.", "5. If t E \u2265 t next , set t = t next , and resimulate t E as described in Step 3.", "1. Draw a waiting time t I in class I from a specified infectious period distribution, and set the time of recovery t R = t + t I ." ] },{ "paper_id": "266e97136335f2ef19dd7d372fe0472afa2af17c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "THP-1 monocytic cells were purchased from ATCC and grown in supplemented RPMI-1640 (10% FBS, 1% Penicillin/Streptomycin).", "Purified genital mucosal IgG from HIV-1+ women was prepared as described [16] .", "Biotinylated HIV-1 Envelope antigen was conjugated to Neutravidin fluorescent beads (Invitrogen) as described [50] . Briefly, 10 \u03bcl of 0.1% BSA/PBS-washed beads were incubated with 20 \u03bcg biotinylated antigen overnight at 4\u00b0C on a rotator. Unbound antigen was removed by washing twice with 1 ml 0.1% BSA/PBS." ] },{ "paper_id": "267084b4bdfd4a3d8fbdb8d7e4c935715f3e7171", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lysates were routinely prepared by solubilisation of cells in RIPA buffer (0.1 M Tris-HCl, pH 7.4, 0.15 M NaCl, 1% (v/v) Triton X-100, 0.1% (v/v) Nonidet P-40). Protein concentrations were determined by bicinchoninic acid (BCA) protein assay [60] . Bovine serum albumin was used as a standard with a 50:1 ratio of 4% (w/v) CuSO 4 .5H 2 O.", "Results are expressed as mean +/2 standard error of the mean (SEM). Significance was assessed by Student's t test or one-way ANOVA and p#0.05 was considered significant. ", "All routinely used reagents were purchased from Sigma unless otherwise stated. Cell culture reagents were purchased from Lonza (Slough, UK). Cell Extraction Buffer and Elisa (pFAK) kit were purchased from Invitrogen (Paisley, UK) along with lipofectamine and BCECF reagent (2979-bis-(2-carboxyethyl)-5-(and6)-carboxyfluorescein). Roche (Welwyn, UK) supplied protease inhibitor tablets. Fluorescent ACE2 substrate Mca-APK-Dpn was supplied by Enzo (Exeter, UK) and MTS reagent by Promega (Southampton, UK). Secondary antibodies, the chemiluminescence system used and Protein G Sepharose 4 fast flow were supplied by GE healthcare (Chalfont St. Giles, UK). DTBP (Dimethyl 3,39dithiobispropionimidate) was purchased from Pierce (Cramlington, UK). The ACE2 inhibitor 416F2 [53] was a generous gift from Prof V. Dive (CEA, Gif sur Yvette, France). Polyclonal ACE2 antibody raised in goat was purchased from R&D systems (Abingdon, UK). Integrin antibodies raised in mice against ITGB1 and ITGA5 antibodies were bought from Santa Cruz Biotech (Heidelberg, Germany). Polyclonal ADAM17 antibody raised in rabbit was purchased from Calbiochem (Nottingham, UK), while Akt antibody raised in rabbit was purchased from Cell Signaling (Hertfordshire, UK). Purified ACE enzyme was a kind gift from Prof N. Hooper (The University of Leeds, UK) and Prof S. Danilov (University of Illinois at Chicago, USA) generously provided the ACE monoclonal antibody [54, 55] ." ] },{ "paper_id": "26762988147d906e873f16c6e03cbb2ad7c46ea1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experimental procedures were performed with approval and under the guidelines of the US Meat Animal Research Center (USMARC) Institutional Animal Care and Use Committee (IACUC approval numbers 5438-31,000-082-04 (24) and 3040-32,000-031-07 (5)).", "Analysis of variance (class regression) models for differences in weight, age, and maternal antibodies Differences between weaning weights, weaning ages, or maternal BCV IgG antibodies (log) across herds were analyzed in a model where location was fixed and animals were the residual.", "Two challenge strains were used for the VNT: the cell culture adapted US reference enteric strain, Mebus (kindly provided by Dr. Linda Saif; The Ohio State University, Columbus, OH); and a respiratory strain isolated in 2014 from a naturally-infected calf in the same research herd as the serum samples to be tested (BRCV_2014). BRCV_2014 was propagated six times in HRT-18G cells. The Mebus virus strain has been passaged in multiple cell types and the passage number was unknown." ] },{ "paper_id": "2686a3eb4a97b4cd2f1d9b05018dbe2b28df410d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "268d325d7a8003c4b0474e6a605d6655ab370b6f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Then from (1) and (4) and y rec = y pred , we have", "To plot time series from different stochastic simulations on a common time scale, we used the time at which growth became nearly deterministic in each simulation as time zero for that simulation.", "where P is the probability that we can trace a particular pair of cases back to a single case before the last transmission event. We have", "Simulation source code is available from the authors upon request. The code made use of the GNU scientific library [20, version 1.13+dsfg-1] to generate random numbers and the igraph library [21, version 0.5.3-6] to construct networks." ] },{ "paper_id": "26945898e55a1c496ddbbf74d0fdec3eeafef9e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RVA RNA was detected by a previously described real-time RT-PCR [29] . PEDV and TGEV were detected by a real-time multiplex RT-PCR for the simultaneously detection of both viruses, following manufacturer recommendations (virotype PEDV/TGEV RT-PCR Kit, Qiagen, Denmark).", "Faeces from the swab were streaked out on blood agar (Columbia agar with sheep blood; Oxoid: PB5008A) and Gassner agar (Oxoid: PO5021A) for the isolation of Escherichia coli. Inoculated plates were incubated aerobically at 37\u00b0C for 24 h. Suspected E. coli isolated colonies were confirmed by morphological characteristics; in addition, blue colonies (lactose-positive) on Gassner agar were further confirmed by negative oxidase testing. Haemolysin presence was identified by haemolysis on blood agar.", "E. coli strains were isolated from all submissions tested. However, only 11 of them were classified into defined pathotypes (ETEC and EPEC). Specifically, 9 isolates were classified as ETEC and 2 as EPEC ( Table 2) . Within ETEC isolates, 7 different virulence factor profiles were found; among ETEC strains, the most frequently detected virulence factors were STII (7 isolates), STI (7 isolates) and F4 (5 isolates). Both EPEC strains showed the same combination of virulence factors, Intimin and escV.", "For the immunoblotting, 5 colonies were suspended in 5 mL TYCG-medium plus TYCG-supplement (liquid media for Clostridium spp.) and incubated 6 to 8 h at 37\u00b0C under anaerobic conditions; 1 mL was centrifuged at 11.000 x g for 5 min. The supernatant was used to detect \u03b1-, \u03b2and \u03b22-toxins by immunoblotting [27] ; \u03b1 and \u03b2 toxin presence was defined by positive or negative, and only \u03b22 production was semi quantitatively recorded (strongly positive, positive, weakly positive and negative) [28] . For genotyping purposes, a single colony from a pure agar culture was selected and suspended in 150 \u03bcL lysis buffer, incubated for 90 min at 60\u00b0C and then heated at 97\u00b0C for 15 min. Lysate cooled at room temperature and genotyping (cpa, cpb, and cpb2 genes) was performed following a previously published method [28] ." ] },{ "paper_id": "26a222223bf9fe6164feaa2f4231923c9abcc77e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We declare no competing interests. ", "We thank Ricardo Montesinos, \u00c1ngela Montalv\u00e1n, and Edison Huaccachi for their outstanding technical support.", "The VFAR-047 genome will facilitate future development of new vaccines and other infection control strategies in the poultry industry." ] },{ "paper_id": "26a931d514eb3f80a779ec6d06997e1d77278dd4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "hood gain, in comparison with the null hypothesis that involves collapsing the branch under study but leaving the rest of the tree topology unaffected [64] .", "One Way ANOVA, Tukey post hoc tests for non equal n, and standard errors were calculated using Statistica 6.0 software package (StatSoft 2001)." ] },{ "paper_id": "26b43aa70c7a8314456956b5ada051dc6807dc56", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author(s) declare that they have no competing interests.", "YN performed the computational analyses and the target mRNA cleavage assays, participated in the design of the study, and drafted the manuscript. KN and TO performed the viral replication assays. RU analyzed the data. KU-T participated in the target mRNA cleavage assays, and was", "We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains." ] },{ "paper_id": "26ba0cb6190e2a4b476ebf7122a0e439bbe80229", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analysed statistically using GraphPad software, as described in the figure legends.", "Mink enteritis virus (MEV) is an autonomous parvovirus that causes important disease in mink, leading to huge economic losses worldwide. MEV is a single-stranded negative sense DNA virus belonging to the family Parvoviridae, with a genome of about 5 kb containing 2 main open reading frames (ORFs). MEV, a variant of feline panleukopenia virus (FPV) and highly homologous with canine parvovirus (CPV), causes a highly infectious acute disease of mink characterized by extensive virus replication in mesenteric lymph nodes and intestinal crypt epithelial cells, with an associated loss of intestinal mucosa, diarrhea, and a high rate of morbidity and mortality [1] [2] [3] [4] [5] .", "Screening of miRNAs targeting TfR mRNA 3\u2032UTR" ] },{ "paper_id": "26bdc177821e0161d138236656dafefe2f9f6900", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses as obligate intracellular parasites rely upon the host cell for different steps in their life cycle, including attachment, disassembly, transcription, translation, reassembly, and egress. Consequently, characterization of these cellular processes will be essential for any understanding of viral life cycles, and may provide cellular targets for new antiviral therapies.", "GGGGAGCTTGTTGACACGCTTCAGTTTGTCTGTTCGGACCGCGGCTTCTAC" ] },{ "paper_id": "26d8317a46bcbe3ec8ff5aa98de2a848fbd358ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary information accompanies this paper athttps://doi.org/10. 1186/s12931-019-1181-0." ] },{ "paper_id": "26d93683447b88c154664f5f80b35cd7991ba106", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "-IFN also is secreted by Th1 cells; it can reflect the basic status of cellular immunity and humoral immunity of organism to certain extent.", "MTT method is one kind of methods to detect the survival and growth of cells. Its detection principle is that the exogenous MTT could be reduced to water Therefore, the larger 570 value is, the more live cells are [16] . Experiment in vitro designed three drug-adding patterns, and those are, respectively, corresponding to prevention, sterilization, and treatment of three clinical administrations.", "After adding pattern ", "Determination. Viral genomic DNA was extracted from the tissue of challenged guinea pigs using RNA/DNA Extraction Kit Ver. 3.0 (TaKaRa, Dalian, China) according to the protocol of manufacturer. A series of tests was performed to optimize the RTFR PCR protocol, including PCR cycling parameters and reagent concentration. Optimization of each singleplex real-time PCR assay of PPV was essential for the subsequent PCR reaction. Water instead of template DNA used as negative controls using was run with each test. All RTFR PCR reactions were performed in triplicate. A total of tissue and serum samples were tested for PPV by RTFR PCR and conventional PCR assays. The conventional RTFR PCR assays conditions were the same as the standard plasmid template preparation described [15] ." ] },{ "paper_id": "26dbe2acce338b3bbb79096eba3893d99b5398f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "26e8ef0fab0bc606adadae018a73d8490c8e1cd5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are expressed as mean +/-SEM. Each experiment was performed at least three times and the number of experiments is represented by n. statistical analysis was done with the unpaired student's test. Differences between groups were considered statistically significant when p < 0.05.", "At this stage we conclude that the induction of MMPs by BASIGIN as it has been initially hypothesized by Biswas [17, 31] is not proven and we propose to abandon the misleading acronym EMMPRIN." ] },{ "paper_id": "26ee25b06063d12c5685b764db2c72fbb17fc31f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Geometric means (GM) were used as measures of central tendency. Data were analyzed for larval growth by multifactorial analysis of variance ANOVA with post-hoc Fisher's Least Significant Difference (LSD) testing in Systat v.11 (Systat Inc., Evanstown, IL, USA). Probability values less than 0.05 were considered statistically significant. All experiments were performed a minimum of 2 times." ] },{ "paper_id": "26f219a1d536118b973f8948cd564b53beb649fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HPVs infect and replicate in cutaneous and mucosal epithelium (skin and oral/genital mucosa). Of the hundreds of HPV types [1] [2] [3] , a set of about 15 HPV \"high-risk\" types are associated with cervical, anogenital, and oropharyngeal cancers. An additional set of \"low-risk\" mucosal types cause benign anogenital warts. HPVs are currently the most common sexually transmitted infection, and collectively, these viruses account for 5% of cancers worldwide [4] [5] [6] .", "Acid-dependent cathepsin proteases further cleave and process the L1 capsid within the endolysosomal compartments." ] },{ "paper_id": "26f8c5fbd310c95c2e1fb04c34ed6f5d10901d07", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step 3: Removal of Links After averting the cases that have been vaccinated, all subsequent secondary individuals stemming from vaccinated cases are therefore considered averted.", "Vaccination strategy 1 (healthcare workers)", "Vaccination targets healthcare workers, but the target vaccination coverage is lowered to 50%.", "Our algorithm employed to simulate the effects of vaccination strategies consists of the following four steps: (see Fig. 3 )." ] },{ "paper_id": "27053e838296b253c42a6b343940a6aec83a7ebb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are shown as the means \u00b1 standard errors of three replicates per test in a single experiment repeated three times. Tukey's multiple comparison tests were used to analyze differences among the groups. A p-value of <0.05 was considered statistically significant, and p < 0.01 was considered highly significant.", "All applicable international and national guidelines for the care and use of animals were followed. Approval (2016NEFU-315, 13 April 2017) was obtained from the Institutional Committee of Northeast Agricultural University for the animal experiments.", "On day 35 post-immunization, splenocytes from three mice from each group were prepared for a lymphocyte proliferation assay as previously described [34] . Briefly, 100 \u00b5L of splenocytes (5 \u00d7 10 7 cells mL \u22121 ) was suspended in Roswell Park Memorial Institute (RPMI) 1640 medium containing 10% fetal calf serum and then transferred to a 96-well flat-bottom plate; the cells were re-stimulated for 72 h with 1.0, 5.0 or 25 \u00b5g mL \u22121 TGEV-6D protein and PEDV-COE protein (produced by Escherichia coli prepared in our lab), using 5.0 \u00b5g mL \u22121 concanavalin A (ConA) and culture medium as positive and negative controls, respectively. The plates were supplemented with 10 \u00b5L of 3-(4,5-dimethylthylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) per well and incubated for an additional 4 h, and then proliferation was measured using OD 490 values. The experiment was carried out in triplicate, and the lymphocyte proliferation index in the spleen (SI) was calculated as the mean reading of triplicate antigen stimulation wells divided by the mean reading of triplicate negative control wells." ] },{ "paper_id": "2718d50101d585d27c5c817dfe2fb1dded056e1a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2019, 11, 958 2 of 16 assess the hygienic management [15] . In veterinary facilities or research catteries, nobody has so far investigated environmental contamination with FCV.", "The cat beds were cleaned with a small brush to remove hair, and, if obviously stained, brought for washing at 60 \u2022 C and autoclaving. No additional cleaning or disinfection was performed in-between the two FCV challenges.", "Materials and Methods" ] },{ "paper_id": "271eaab0cdf64e3274bd45a4264eeac8f2d1b0d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "272b73f1f4852e9c37a862eab96131a5d27e1892", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics statement. This study was approved by the Committee of Experiment Operational Guidelines and Animal Welfare of Sichuan Agricultural University. Experiments were conducted in accordance with approved guidelines." ] },{ "paper_id": "272c6cc36e652db7f8d263194c13b2a5c92ed92e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The pipeline described below was designed to integrate a wide range of analytical tools into a single automated process (Fig. 2) .", "The only access to the backend computing cluster is via a Secure Shell (SSH) connection, with a PKI key, ensuring that the data remains secure in transit. Data is not encrypted while stored on the computing cluster, but the cluster is located in a secure location on a military installation." ] },{ "paper_id": "27373ff091fe4a81ee4d6bfc09ece3995080c2ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "While many bat borne pathogens cause severe and often fatal diseases in humans, bats demonstrate no clinical signs of disease when infected with these agents.", "Real-time PCR of ISG54 following Poly I:C stimulation", "iTRAQ" ] },{ "paper_id": "2738ed5788b2eb1a42164c7ddff227105d5ae617", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Blood collection of sows occurred at 5 weeks prepartum and 3 weeks postpartum. Blood was collected from the jugular vein into EDTA Vacutainer\u00ae tubes (BD, Franklin Lakes, NJ, USA). Colostrum was collected from all sows within 2 hrs of farrowing. Teats were scrubbed with alcohol wipes (70%; Medline, Mundelein, IL, USA) and gloves were worn to minimize sample contamination. Colostrum (25 ml) was collected manually from all functional teats.", "None of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper.", "Authors' contributions MB conceived the study, participated in its design, sample collection, immunoassays and data analysis, and drafted the manuscript. KT participated in study design and sample collection, coordinated the farm site, and carried out immunoassays. TWM participated in study design and its coordination and helped to draft the manuscript. All authors read and approved the final manuscript." ] },{ "paper_id": "2739ea989ec040104223cfb49d2a13d7d89dc79a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Genbank Accession number species Sequence Product size (bp) Ta (\u00b0C) % homology", "Histone H2A [15] U62674", "182 60 82 % TBP [33] NM_003194" ] },{ "paper_id": "273ed1bf60b19e3db4ab3894a20598336b7e0ef4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total serum proteins were measured by trained personal to evaluate passive transfer of immunity. A 5 ml blood sample was collected from the jugular vein in calves 3 to 7 days old in a tube without anticoagulant.", "Dehydration status was assessed daily using a calf dehydration chart [27] . The scores were assigned as 1 for non-dehydrated animals (< 6% water body loss) with a normal attitude, strong suckle reflex, appetite, no eyeball retraction into the orbit and skin tent lower than 2 s. Score 2 was described as moderate dehydration (6 to 8% of water body loss) were the calf was depressed with weak suckle reflex, dropped ears, dry and slightly recessed eyes into the orbit and skin tent duration of 2 to 6 s. Score 3 was described as severe dehydration (> 8% of water body loss), when the calf showed signs of depression no suckle reflex, skin tent > 6 s, dry and recessed eyes into the orbit and recumbency.", "Least square means (PROC GLM) were calculated for ADG and IgA concentration. IgA results were firstly Log10 normalized. Statistical significance was defined at P < 0.05. Tendency was defined at 0.05 < P < 0.1. " ] },{ "paper_id": "2748111c3683cdd338b098c0b5d2aa6becfc0fee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LSu designed the experiments. HL, RB, QL, LY, TP, and LSa performed the experimental work. IBA, HK, and LSu analyzed the data and wrote the manuscript.", "the Japanese MEXT (16H06436, 16H06429, and 16K21723) to HK.", "We express our deep gratitude to Drs. Zhonghua Ma, Donald L. Nuss, Nobuhiro Suzuki, and Qingmei Guan for providing research materials." ] },{ "paper_id": "274eab479084dcb79951d6fdde012c9eab9bb469", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One optimization was to precompute and store as much information about the trilinear interpolations as possible before docking is executed. These computations take less than a few seconds but come with a significant time savings later. The only cost is additional memory usage as eight times the memory is necessary. Furthermore, special attention was paid to the memory layout and access patterns of this precomputed data so as to maximize availability in local CPU cache. This amounted to reorganizing the 3 dimensional grid of data and various access loops to maximize spatial and temporal locality.", "The Shoichet Lab cluster of over 800 CPUs was used for all processing. CPU times should be taken with a caveat as the cluster is heterogeneous, containing 32 bit and 64 bit nodes, with varying levels of processing speed. ", "The focus on screening multi-million compound libraries has motivated rapid calculations in the DOCK3.x programs, but as ambitions increasingly turn to docking across families of proteins or even the proteome [89] the need for further optimization remains pressing. Whereas previously we have investigated methods to optimize efficiency in sampling orientations [82] or conformations [79, 80, 94] or in their scoring [95] , here we investigated compiler-level optimization and code efficiencies to increase raw speed. Whereas this may seem inelegant, it has the virtue of being applicable to most other programs.", "A key to exploring the variation of enrichment with sampling was a code base optimized for speed. Whereas it may seem easy to optimize compiler flags and grid interpolation, as opposed to fundamental algorithmic efforts, the result is a program that is three-fold faster. This not only enabled extensive testing on a large and challenging benchmark, the DUD-E set, but also ambitious prospective campaigns against multiple targets. For instance, a longstanding goal in chemical biology has been to screen the world's chemistry against all of the pharmacologically relevant targets. This remains infeasible for empirical screening, but it is feasible, even today, for docking. To dock the 2 million ZINC lead-like available-now compounds against the 3000 or so pharmacologically interesting targets for which structures are available, with 50 orientations sampled per ligand, would demand about seven months for a 1000 core cluster, which is no longer considered a large cluster in the field.", "Though it may only be of special interest, some readers may find additional technical details of the optimizations made useful. The optimization techniques generally fell within four categories: 1. Precomputation 2. attention to data structure layout to accommodate the underlying memory architecture of the computer 3. changes to the underlying operating system to better accommodate the needs of DOCK and 4. trial and error with various heuristic based compiler switches." ] },{ "paper_id": "2750bbcb6ecf63b2519523a2a63145167c5f8d38", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2019, 11, 326 2 of 16 two single-stranded genome fragments such as the Arenaviridae (e.g., LASV), three fragments such as the order Bunyavirals (formerly the family Bunyaviridae, e.g., CCHFV), or multiple fragments such as the Orthomyxoviridae (e.g., influenza). Examples of families of non-segmented negative-sense RNA viruses with a single-stranded RNA genome (Mononegavirales) include the Filoviridae (e.g., EBOV), the Paramyxoviridae (e.g., Nipah virus (NiV)), and the Pneumoviridae (e.g., RSV).", "All RNA primers and templates used in this study were purchased from Dharmacon (Lafayette, CO, USA). 2 C-methyl-ATP and remdesivir-TP were chemically synthesized by Gilead Sciences (Foster City, CA, USA). Ara-ATP was purchased from TriLink (San Diego, CA, USA). NTPs were purchased from GE Healthcare (Cranbury, NJ, USA)." ] },{ "paper_id": "27548472c288a185911a8907c927d18f3c9b0abe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Spleen cells were prepared by gently flushing the spleen with IMDM supplemented with antibiotics (100 U/ml penicillin and 100 mg/ml streptomycin), 10% FCS, 50 mM b-ME, and 2 mM Lglutamine. Erythrocytes were lysed for 2 min in ACK buffer (0.15 M NH 4 Cl, 10 mM KHCO 3 , and 0.1 mM EDTA) and cells were washed two times with PBS. Cell clumps were removed by passaging through a 50 mm nylon filter. Preparation was conducted strictly at 0uC.", "Mouse care and experimental procedures were performed under the approval of local authority Nieders\u00e4 chsisches Landesamt f\u00fcr Verbraucherschutz und Lebensmittelsicherheit (LAVES). Permit numbers for this study are 33.11.42502-04-067/07 and 33.42502-071/06." ] },{ "paper_id": "2757ce8aa9cfdd87202c39c244d8f8313f4a2ca3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The statistical analyses (Student's t test) and generation of graphs were performed with the GraphPad Prism \u00ae 6 software. Data are presented as mean \u00b1 standard deviation. *P < 0.05, **P < 0.01.", "Mouse monoclonal anti-hemagglutinin (anti-HA), anti-FLAG, and anti-\u03b2-actin antibodies were purchased from ABclonal Biotechnology. Anti-FLAG polyclonal antibody (Macgene, China), anti-DHX36 polyclonal antibody (Proteintech, China), anti-TRIF polyclonal antibody (Proteintech, China), anti-MyD88 polyclonal antibody (Proteintech, China), anti-HSP90 polyclonal antibody (Proteintech, China), anti-LaminA + C polyclonal antibody (Proteintech, China), anti-I\u03baB\u03b1, anti-NF-\u03baB P65, and anti-phosphor-p-P65 polyclonal antibodies (Cell Signaling) were purchased and used according to the manufacturers' recommendations. Horseradish peroxidase-conjugated anti-mouse or anti-rabbit IgG antibodies were purchased from Beyotime Institute of Biotechnology (Jiangsu, China). PRRSV N protein monoclonal antibody was produced from hybridoma cells derived from Sp2/0 myeloma cells and spleen cells of BALB/c mice immunized with recombinant N protein from PRRSV strain WUH3.", "The FLAG or HA epitope tag was amplified by PCR and cloned into the pCAGGS-MCS vector to generate the pCAGGS-FLAG or pCAGGS-HA plasmid, encoding an N-terminal FLAG or HA tag. Expression plasmids for FLAG-tagged DHX36 were constructed by PCR amplification of the cDNA from PAMs. Plasmids encoding truncated DHX36 were constructed by PCR amplification using the specific primers listed in Table S1 in Supplementary Material. The HA-tagged expression plasmid encoding the PRRSV N protein (pCAGGS-HA-N) used in this study, and its expression was confirmed with HA-tag immunoblotting (23) . Reporter plasmids NF-\u03baB reporter plasmid and pRL-TK were described elsewhere (21) . All constructs were confirmed by DNA sequencing." ] },{ "paper_id": "2759426af4c8df595f4b5e76b614712fda6da5d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We define the (prior) predictive probability", "To simplify the notation, we denote the probability in equation 2 as p jhrk . The likelihood function can now be compactly rewritten as", "To define the conditional prior distribution for Z, we follow a hierarchical approach. Let c5(c 1 , c 2 , c 3 ) T denote our prior probabilities for a column to represent noise, weak signal or strong signal, respectively. Then, c h \u00a2 0 and h P c h \u00bc 1\u00f0h \u00bc 1; 2; 3\u00de. Note that these properties are column-specific and they are not affected by any particular partition under consideration. Also, note that the array Z satisfies " ] },{ "paper_id": "275d7a25357ea46699072167d4ca109108132068", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. Specimens collected as part of an influenza surveillance programme should also be tested for RSV." ] },{ "paper_id": "275dd71da13e09fcace07d5824ac14a2c38d1df1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In April 2014, a first group of healthcare experts was deployed with an anthropologist in an area where MSF had just installed an ETC, in a context of almost 100 % mortality. There were rumours that MSF was killing people and an anti-MSF demonstration had been planned. Anthropological activities with communities used community leaders to sensitise the population. Then, central government local representatives organised a large public meeting. As a result, the anti-MSF demonstration was cancelled.", "Weekly conference calls took place between the various centres treating the patients to exchange experiences and learn from each other.", "The first published results of the four VEBCON trials were based on 138 healthy adult volunteers who had all been followed for at least four weeks [86] . It could be seen that viremia increased very rapidlyusually within 24 hamong subjects who had received a dose of several million PFU (doses ranged from 300,000 PFUfor which viremia increased lessto 3-50 million PFU where viremia peaked after 1-3 days at several thousand RNA copies/ml). However, whatever the initial dose, the virus appeared to have been cleared from the blood by day 7. Although very few participants had no adverse events, almost all were mild or moderate (fever or feverish feeling, flu-like symptoms including myalgia and fatigue) and lasted no more than one or two days.", "The authors declare that they have no competing interests.", "The HUG started preparing for receiving a possible EVD patient in April 2014. Personnel from the intensive care and emergency departments were trained for EVD ahead of time (see video \"Ebola PPE coaching\" at http:// tinyurl.com/EbolaPPEcoaching). Training and simulations were carried out long before it was known whether a patient might ever be admitted. Furthermore, the Swiss National Reference Centre for Emerging Viral Diseases, part of the Laboratory of Virology at HUG, was experienced in PCR-based investigation of viruses such as Ebola.", "On 18 November 2014, WHO called the Swiss Federal Office of Public Health to suggest the transfer of a patient with EVD. The transfer took place on 20 November. The patient was admitted to HUG on 21 November with high fever and swollen face features, and was in a semi-delirious state. Central and bladder catheters were already in place. Three hours after the patient's arrival at the hospital, he received his first medication. We refer the reader to a complete description of the clinical and laboratory observation published elsewhere [30] ." ] },{ "paper_id": "27636c830ab9c45d38454d50312227747652f70e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis" ] },{ "paper_id": "2765b43f0c431c63acf11a93ddb513f0332ca22b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2769723b9b497b45c8178f8f68dc48a5fed06db6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This breakpoint divides the BAGV genome into two regions: one that encodes the structural proteins and another that encodes the non-structural proteins. Phylogenetic trees were constructed using 1000 bootstrap replications and midpoint rooted for clarity only (Figure 7 ). This recombination event led to a mismatch between NJ phylogenetic trees constructed using comparison of nucleotides sequences of recombinant (positions 2202-4908) and non-recombinant genomic regions (positions 1-2201 and 4909-10,281). ", "(RRAA and GRIWNA, respectively) and ARD260266_Barkedji_SEN_2014 (RRSS and RTDMEC, respectively) ( Figure 2 ). ", "MCMC convergence was obtained for three independent runs with 100 million generations, which were sufficient to obtain a proper sample for the posterior at MCMC stationarity assessed by effective sample sizes (ESS) above 200 for each gene. Furthermore, the evolutionary rates (\u00b5) and the highest posterior densities (HPD with 95% of confidence interval) were 1.226 \u00d7 10 ", "Nevertheless, to ensure the potential of BAGV to be involved in human encephalitis cases, it would be important to evaluate its pathogenicity on human induced pluripotent stem cell lines (iPSC) capable of differentiating into brain microvascular endothelial cells (BMECs) and constituting a robust model of the human blood-brain barrier [109] . Otherwise, the iPSC cells can also generate primitive neural stem cells (NSCs), which can differentiate into neurons, astrocytes, or oligodendrocytes [110] . These BAGV sequences data obtained in our study could be used not only in future viral studies, but also in development of reverse genetic reagents or reliable diagnostic tools for investigation of this virus in human populations." ] },{ "paper_id": "27785fc9727a9c538b279d2c940f72ab5b9a3423", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "277e85da79677586ae01bb02ea6e410ebc97fd29", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Expression of proteins in their native configurations is exceptionally advantageous when it comes to vaccine production as this would allow the retention of not only the rightly exposed linear epitopes, but also those conformational ones. This, hence, makes BVES a very attractive option for vaccine production.", "EV71 is classified into three major genotypes (A-C), which are further subdivided into 11 subgenotypes, namely A, B1 to B5, and C1 to C5. Such classification of EV71 into its subgenotypes is dependent on its VP1 sequence variations [5] .", "Vaccinations are only suitable for individuals with immune systems capable of raising an immune response against the foreign targets/particles. This fundamental criterion for successful vaccinations keeps immunocompromised people, such as X-Linked Agammaglobulinemia (XLA)-and Common Variable Immune Deficiency-affected individuals, unprotected even if an EV71 vaccine is made available on the market, since their bodies are unable to produce sufficient and/or functional immunoglobulins.", "Making the issue regarding the existence of only few universal epitopes worse, some of these precious epitopes were lost during the production process, since formaldehyde destroys the native structure of the proteins [27] . The effectiveness of EV71 inducing cross-immunity and cross-neutralization among all subgenogroups may be further limited." ] },{ "paper_id": "2786687808083b1a23083be32dae8229ff545179", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(a) Twenty-four hours after HCl instillation, the mice were sacrificed and the following analysis were performed (detailed methods are described in Additional files):", "Procedures involving animals and their care were conducted in conformity with the institutional guidelines complying with national and international laws and policies. The experimental protocol was submitted to the Italian Ministry of Health and approved by the Animal Care Unit of the University of Milan-Bicocca, Monza, Italy.", "In particular, we performed as follows:" ] },{ "paper_id": "278697db1668e58b24cd105be09208d7f1bc1119", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There were peaks in RSV-associated hospitalization during the last four months of the year in 2011 through 2014 when the temperature was cooler. Influenza activity peaked during June-July which is the rainy season in Bangladesh. There was no clear distinct seasonality for the other viruses (Fig 3) .", "We also collected respiratory specimens from asymptomatic children beginning in 2012, we used descriptive statistics to present the distribution of respiratory viral pathogens in these control children.", "Sample collection and laboratory analyses. Surveillance physicians collected nasal and throat swabs from each enrolled child (symptomatic and control). Immediately after collection, field assistants stored the samples in nitrogen dewars and transported to icddr,b within 15 days of collection. At the icddr,b virology laboratory, specimens were tested for RSV, PIV types 1-3, HMPV, influenza viruses (influenza A and B), rhinovirus and adenovirus by real-time reverse transcription polymerase chain reaction (rRT-PCR) using primers and probes supplied by the U.S. Centers for Disease Control and Prevention (CDC) [19, 20] . However, due to logistical constraints we could not test the samples for rhinovirus in 2014.", "The study was a combination of prospective hospital based surveillance and community based health care utilization survey." ] },{ "paper_id": "27869d617d1c3766400b9f33f31e28f8fb1bdbd0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Expression analyses of S100A8, S100A9, S100A12, and", "Iron is an essential nutrient for most microbial pathogens." ] },{ "paper_id": "27966ec51b51b6fd67959b36c4a51300360865e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The negative control vector contains a nonsense sequence which has no significant homology with the target sequence. It was 5\u2032-GTTCTCCGAACGTGTCACGT-3\u2032. All of the plasmids were designed and synthesized by Shanghai Gene Pharma (Shanghai, China)." ] },{ "paper_id": "27969ab6c34a3d9b630666d5876256a9641bc05a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "27ac134e8e678f379d1550477ea87257c9c2ed2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DN and MK designed the focus of the review, DN did the literature search and drafted the manuscript, MK reviewed and revised.", "having influence on gut health and therefore expression of disease (Cadwell, 2015) . Because of under and miss-diagnoses, clinical surveillance likely only captures the tip of the iceberg of foodand waterborne viral disease cases.", "European Union's Horizon 2020 research and innovation program under grant agreement No. 643476 (COMPARE). ZonMW TOP project 91213058." ] },{ "paper_id": "27ada359a2b9536a180bd93585f47a13d5b82517", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "27b4bbbc97d4660bbfef9e12bf3c3b9790df9014", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses are positive-sense, single-stranded RNA viruses found in humans and a wide variety of animals. In humans, coronaviruses are mainly causes of respiratory tract infections, whereas in animals, they can cause respiratory, enteric, hepatic and neurological diseases of varying severity. As in other RNA viruses, the infidelity of RNA-dependent RNA polymerase results in high mutation rates. In addition, coronaviruses possess a unique mechanism of viral replication that leads to high frequencies of recombination, as well as the largest genome size (26.4 to 31.7 kb) among all known RNA viruses that gives this family of viruses extra plasticity [18, 22, 43] . All these factors have allowed the coronaviruses to adapt to new hosts and ecological niches. Traditionally, coronaviruses were classified into groups 1, 2 and 3, with groups 1 and 2 consisting of mammalian coronaviruses and group 3 being avian coronaviruses [2, 22, 47] . In 2008, the Coronavirus Study Group of the International Committee for Taxonomy of Viruses proposed three genera, Alphacoronavirus, Betacoronavirus and Gamma-coronavirus, to replace these three traditional groups of coronaviruses (http://talk.ictvonline.org/cfs-filesystemfile.ashx/__key/CommunityServer.Components.PostAttachments/00.00.00.06. 26/ 2008 .085_ 2D00_122V.01.Coronaviridae.pdf).", "Viruses 2009, 1 58 expressed recombinant nucleocapsid of HCoV-HKU1 have been used for IgG and IgM detection in sera of patients and normal individuals, using Western blot and enzyme-linked immunoassay." ] },{ "paper_id": "27b5819a442f4af88897625612d73a398b439bfd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dot blot assays. Filtered supernatants from transfections were serially diluted 2-fold and applied to a phosphate-buffered saline (PBS)-washed nitrocellulose filter in duplicate using a Minifold Micro-Sample Filtration Manifold (Schleicher & Schuell). Samples were allowed to bind; they were washed twice with PBST and blocked, probed, and quantified as described above.", "MuLV proviral clone. The full-length MuLV Moloney strain proviral clone pNCA (31) (GenBank accession number AF033811.1) was a kind gift of S. P. Goff, Columbia University." ] },{ "paper_id": "27bafe2069fadba9638ec9eb5ae1afaf3c78cfb8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Fishers Exact test was used to associate genetic and immune factors with viraemia and non-progressor status.", "Methods for HLA and chemokine receptor polymorphisms [30] and toll-like receptor (TLR) and Fc\u03b3RIIA polymorphisms [31] [32] [33] have been described elsewhere." ] },{ "paper_id": "27d79d16bc5eee9c79ee05ee5997d031e15d72bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1 H-NMR and 13 C-NMR spectra were recorded for the intermediates at 400 MHz and 100.5 MHz, respectively, in CDCl 3 with CHCl 3 as the internal reference for 1 H (\uf064 7.24) and CDCl 3 as the internal reference for 13 C (\uf064 77.00) or DMSO-d 6 with DMSO as the internal reference for 1 H (\uf064 2.49) and DMSO-d 6 as the internal reference for 13 ", "Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/17/5/5346/s1.", "All apparatus was oven-dried and cooled in a desiccator. Reagents were purchased from commercial suppliers and used without further purification except reagent grade CH 2 Cl 2 that was distilled from CaH 2 before use. Thin layer chromatography (TLC) was performed on 250 \u00b5m glass-backed silica gel plates and visualized using UV. Column chromatography was performed on silica gel (Merck, grade 9385, 230-400 mesh, 60 \u00c5). The columns were prepared in plastic 20 or 30 mL syringe bodies and filled to approximately 2/3 of their capacity with silica gel." ] },{ "paper_id": "27ea5838cb5cf114ddeecd9972be98813834ef9c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "on the need for data collection, sharing and analysis to be conducted in a more open and cooperative fashion and under a one-health framework among relevant parties, such as public health agencies, animal surveillance agencies and non-governmental research institutes.", "Data on human cases with H7N9 and H5N1 virus infections. The data regarding all laboratory-confirmed cases infected with avian influenza A (H7N9) and (H5N1) in China from 2003 to 2014 were collected from the World Health Organization 23 , and the consistency with the data from Health Map (http://www.healthmap.org/ zh/) and Flu Trackers (https://flutrackers.com/forum/) was checked to ensure data quality and reliability. The date of onset, age, gender and location of each confirmed patient was extracted and used in this study. The definitions of H5N1 and H7N9 human infections have been described as previously 15, 24 . As in previous studies 14, 15, 22 , each confirmed case was geo-referenced and linked to a digital map of China according to each patient's residence at the time of symptom onset using GIS technologies. Monthly cumulative numbers of cases based on their symptom onset dates were plotted over time to display the temporal trend of the epidemics caused by the two viruses.", "The important role of the density of human population for both H7N9 and H5N1 is not surprising. A higher density of human population is usually associated with a higher volume of poultry trading and consumption 21 . The coverage of built-up land is also positively related to poultry trading and might have increased the chance for human exposure. Relative humidity and precipitation played significant roles in human infections for both viruses, but temperature only affected the occurrence of human H7N9 infections, consistent with our previous studies for the two viruses in early years 15, 22 ." ] },{ "paper_id": "27ed601fcd2be1e67274e57dcc4ea6b01040e5ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "OR gated LAMP-to-Glucometer detection was performed using Protocol 1 as detailed above. RT-LAMP amplicons were generated from the same amount of MERS-CoV RNA (60 PFU) by using either no primer, upE primer (upE.9) only, 1A primer (ORF1A.55) only, or both upE.9 and ORF1A.55 primers, respectively." ] },{ "paper_id": "27ee6e389b8f87a3545232db8b8fe385f73e5003", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "While it is not covered here, we want to emphasize that as with any other experiments, proper experimental design should be carefully conducted before the start of infections and RNA-seq analysis.", "In summary, the large number of less studied lncRNAs represent a great opportunity for uncovering novel insights into virus-host interactions and potentially new targets for intervention.", "Viral infections remain a major world-wide concern. Even though we have all but eradicated some once deadly viruses, many still elude effective treatment. HIV-1 is becoming a chronic disease since current anti-retroviral therapy can suppress the infection but cannot clear the virus. Influenza is still a major global concern that evolves rapidly and kills thousands of individuals every year. As shown by recent examples, like Zika and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), the threat of emerging viral infections is constant. A better understanding of virus and host interactions is needed to accurately define viral pathogenesis and to rapidly develop new therapies." ] },{ "paper_id": "27ee82e4db05cf49d789f25d14660daffe743cfd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Immunosuppressed rhesus macaques", "Frontiers in Microbiology | www.frontiersin.org ", "CY and HO wrote the manuscript. SY, KH, and WT reviewed, edited, and approved its final version. " ] },{ "paper_id": "27f21a68a6f074f434e506aee9492fa2c772847c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Initiator integrated poly(dimethylsiloxane) (iPDMS) membrane 26 ( ", "Not applicable " ] },{ "paper_id": "27f21ae7789e41a6de01554cdae09cb93ef8524f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results are expressed as the number of cases. Statistical analyses were performed using StatFlex software (ver. 6, Artech Co., Ltd., Osaka, Japan). Significant differences between groups were determined by the Mann-Whitney U-test and \u03f0 2 test." ] },{ "paper_id": "27fb200a637c8fff339f06399be1d563e365a7a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal studies were carried out in accordance with the UK Animals (Scientific Procedures) Act 1986 and with the approval of the Agri-Food and Biosciences Institute Northern Ireland Ethical Review Committee.", "100 \u03bcL of plasma was added to a well in an Ostro protein precipitation and phospholipid removal plate (Waters Corporation, Milford, MA, USA). 100\u03bcL of 1% formic acid/acetonitrile (v/v) was added to the sample well, the plate shaken for 30 sec and extracted metabolites drawn through under vacuum into a 96 well 2 mL collection plate.", "HPLC grade acetone and analytical standards were purchased from Sigma Aldrich (Dorset, UK). LC-MS grade acetonitrile, water, methanol and chloroform were purchased from Fisher Scientific (Loughborough, UK)." ] },{ "paper_id": "28040123483f1f80ef9b612102f0b2083eac4ec4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The pathogenesis of multiple sclerosis (MS) is probably triggered by a combination of genetic and environmental factors [1] [2] [3] [4] [5] . Frequent childhood infections, lower socioeconomic status and higher sibling exposure lead to a lower MS prevalence, remarkably similar to observations made in childhood leukemias [6] . Children experiencing viral infections later in life are at risk for developing this disease [1, 3, 4, [7] [8] [9] . More sensitive detection methods have enabled earlier recognition of pediatric MS, leading to an estimated 2-5% of cases developing before the age of 16 years [10] [11] [12] . The disease has even been diagnosed in children between 2 and 5 years of age [13, 14] .", "Infection-induced molecular mimicry has been implicated in several autoimmune diseases including MS [41] [42] [43] [44] . CD4 + T lymphocytes responding to the latent EBV nuclear antigen-1 (EBNA-1) are increased in patients with MS [45, 46] and these cross react with myelin antigens [47] . Our previous study [43] demonstrated the response of clonally expanded CD4 + T cells isolated from an MS patient to the poly-arginine motif present in the open reading frame 1 (ORF1) of certain torque teno virus (TTV) types. Serum samples from this patient, taken during exacerbation and 24 months later, harboured TTV DNA sequences. In addition, we demonstrated TTV DNA in 6 of 13 brain samples, 12 from MS brain and one in HHV-6 encephalitis brain.", "The enhanced replication of TTV-HD14b and TTV-HD14c in the presence of EBV is independent of the EBV copy number" ] },{ "paper_id": "2804ea9b709694627657763fd17564d0323a5dcf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Peptide data was filtered by peptide matching quality scores (given by the VIPER software) STAC (>0.6), UP (>0.5), and Peptide Prophet tag score (>0.9), which resulted in a matrix of 184 sample rows by 9326 peptides. Sample replicates were combined by taking the mean over replicates.", "A second round of filtering was performed by assessing the quantity of missing data. Missing data are encountered when peptides are identified in a subset of samples. \"Missingness filtration\" involves removing any peptide with greater than X% missing data across samples. Peptides were filtered by missingness, taking peptides with not more than 20% missing data, resulting in a matrix of 90 samples by 2273 peptides. This process eliminates a large proportion of the measured peptides (86.5%), however, for statistical analysis that depends on nearly complete matrices, many peptides are unusable since they are identified in a very small number of samples.", "The matched microarray data were processed using the Agilent Preprocess Bioconductor package (Lopez-romero, 2010) . After considering quality measures, 31,416 probes passed probe QC flags for all replicates of at least one infected time point." ] },{ "paper_id": "280a11fb6a3cd27873efa93e4600bc4227e7ee0b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "**assessed for each particular pathogen in question, e.g., the criterion \"Treatment possibilities and needs\" refers to availability and adequacy of treatment for each case of an illness caused by a particular pathogen but does not take into account the incidence of illnesses or the availability of preventive measures.", "The weighting step was removed. This was the other modification of the German method in addition to those mentioned in the \"Scoring\" paragraph.", "doi:10.1371/journal.pone.0136353.t001" ] },{ "paper_id": "2810296105b6ae2ca21d299d27f83c6d1b071f28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "281303193aa29253bb0b00328b48e892d0cf4f85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical tests. Unless indicated otherwise, each experiment was performed in technical triplicate and repeated three times (biological triplicate). All tests were performed using Microsoft Excel and GraphPad Prism. P values of \u03fe0.05 were considered nonsignificant.", "IMPORTANCE" ] },{ "paper_id": "2813c9a864720f35199261a3ab219750d3a5daeb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fecal consistency was monitored daily and scored visually as 0 = normal, 1 = loose, 2 = semi-fluid, and 3 = watery, as described previously [15] . The body weight of each piglet was measured weekly.", "The porcine epidemic diarrhea virus (PEDV) is an enveloped, positive-sense and single-stranded RNA virus, belonging to the order Nidovirales, family Coronaviridae, and genus Alphacoronavirus [1] . The genome of PEDV is about 28 kilobase pairs in length and comprises of seven open reading frames (ORF), including ORF1a and b genes that constitute the 5 two thirds of the genome and encode the replication complex; the spike (S) gene that governs viral entry; the envelop (E), membrane (M), and nucleocapsid (N) genes that are responsible for virion assembly; and the accessory ORF3 gene with an undetermined function [2] .", "The results of body weight, antibody titers, viral titer of growth kinetics at each time point, and fecal viral shedding were analyzed statistically on GraphPad Prism 6.0 (GraphPad Software, San Diego, CA, USA) with Two-way ANOVA by time. A p value less than 0.05 was considered statistically significant." ] },{ "paper_id": "281520c659ef5b7b5561307d5a91a00526e994f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Availability of data and materials Data and materials supporting the findings of this study can be shared on request." ] },{ "paper_id": "281ed09feadb379021bb0d63faa25b484ca482f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Gender, age, ethnicity, marital status, and education level were included in the analyses.", "Following the protocol of most studies on natural disasters [16, 17] , participants were asked the following questions to examine the intensity of the flood: Have you lost at least one family member? Have you or your family members been physically injured? Have you or your family lost most of your property? Have you or your family lost your livelihood? Have your homes been destroyed? These five questions were treated as dichotomous variables answered with either \"Yes\" or \"No\"." ] },{ "paper_id": "28223ad437aa22ac2285bd9dd775e1415a69411a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2822c9550311df8e6325df17b17cfde48c9ab6ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We then repeated the blank experiment 20 times in order to calculate the standard deviation (SD). We took 3 times the value of the SD and divided it by the slope of the calibration curve, and got the LOD of 4.67 pmol mL \u22121 . Up to now, we have assumed that IgG-FITC proteins are all uniformly labelled with fluorescent FITCs. Because the quality of antibodies and percentage of FITC labelling on IgG may vary in different batches and from different manufacturers 20 , the LOD could in principle be improved with well-controlled and uniform labelling of IgG by FITC. However, this is beyond the scope of this paper.", "Conventional enzyme-linked immunosorbent assay (ELISA) has been widely used in analytical biochemistry and clinical diagnosis. However, the accuracy of ELISA is affected by a few shortcomings intrinsic to the technique. For example, the uncertainty of the recognition between antibody and antigens could cause false signals 1-3 the ELISA plates made of polystyrene lack definitive chemical surface properties to provide chemical binding of the protein 4 ; and intricate procedures such as \"plate cleaning\" increase opportunities for systemic and human errors. In recent years, many research groups have tried to improve the accuracy of ELISA by synthesizing new ELISA polymer substitutes 4 , introducing nanomaterials 5, 6 , employing more sensitive biomarkers 7 , and applying monoclonal antibodies 8 . All of these studies were restricted by the framework of traditional ELISA, which still relies on ELISA plates, and the problems mentioned above remain unsolved. Obviously, new immunosorbent assay techniques call for quantitative surface sites for antibody binding and fewer steps or reagents in the whole process to avoid the above-mentioned drawbacks.", "Antibody-conjugated GO was synthesized by a classic two-step EDC-NHS (1-Ethyl-3 -(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide) method [21] [22] [23] . Briefly, 1 mg of GO was ultrasonically dispersed in 5 mmol of L \u22121 2-(N-Morpholino) ethanesulfonic acid (MES) buffer (pH = 4.0). Then a MES buffer solution containing 4 mg mL \u22121 of EDC and 6 mg mL \u22121 of NHS was added into the GO-dispersed MES solution to activate the GO. The mixture was first stirred for 30 min at 15 \u00b0C, then centrifuged and washed with 20 mmol L \u22121 of phosphate buffer solution (PBS, pH = 7.4) 3 times to remove unreacted coupling reagents. The activated GO was redispersed in PBS to react with 50 \u03bc g of rabbit anti-human IgG so as to modify the GO with the antibody. The samples were mixed on an electronic shaker at 15 \u00b0C for 2 h. Remaining active sites of GO were blocked with 2% BSA in 20 mmol L \u22121 of PBS buffer solution for 30 min. The solution was then centrifuged at 16,000 rcf for 10 min to remove any unbound biomolecules in the supernatant.", "Atomic force microscopy (AFM) was introduced to measure the various stages of the surface modification of GO. According to the works of Lee et al. 19 and Hosseini et al. 4 , the height of GO would obviously increase after being activated by EDC-NHS and further upon conjugation by antibodies. These studies served as reference points for us to use AFM to characterize the surface morphologies of bare GO, EDC-NHS-activated GO, and antibody-conjugated GO to provide evidence of the EDC-NHS coupling reaction and the presence of antibodies on the GO surface." ] },{ "paper_id": "283047560dd3e30f1161338e0f4f2fcc335328f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hemotropic mycoplasmas (hemoplasmas) are noncultivable epierythrocytic bacteria that infect a variety of mammalian species worldwide [1] . In recent years, hemoplasmas have attracted scientific attention due to their host diversity and pathogenic potential [1] . The main pathogenic feature of hemoplasmas is hemolysis, and clinical signs such as lethargy, anorexia, pale mucosal membranes, pyrexia, jaundice and pigmenturia may be present in severely affected animals [1] . Reports of hemoplasma infections in humans emphasize the need to characterize these agents in more detail [2] [3] [4] [5] [6] [7] . Feline hemoplasmas can thereby serve as a model because of their extensive molecular and clinical characterization within this group of organisms.", "Flow cytometry was performed using a guava easy-Cyte \u2122 8HT Flow Cytometer (Millipore, Darmstadt, Germany) using the GuavaSoft 2.5 software. Gates representing the lymphocyte population were set based on forward and side scatter, and 10 000 events were acquired for each sample. The absolute number of each lymphocyte subset was calculated by multiplying the absolute lymphocyte number from hematology by the subset percentage as previously published [38] .", "Flow cytometric analysis was performed on day 0 and on days 3, 7, 14, 21, 28, 42, 56, 70 and 98 pi. Three different staining combinations of primary antibodies were used: (1) Fluorescein isothiocyanate (FITC)-conjugated mouse anti-feline CD5 antibody (f43, Southern Biotech, Allschwil, Switzerland); (2) an R-phycoerythrin (RPE)conjugated mouse anti-feline CD4 antibody (Vpg34, AbD Serotec, Puchheim, Germany) and a FITC-conjugated mouse anti-feline CD25 antibody; and (3) a FITC-conjugated mouse anti-feline CD8 antibody (fCD8, Southern Biotech) and a RPE-conjugated rat anti-mouse CD45R/ B220 antibody (RA3-6B2, AbD Serotec). CD5 is a marker for feline T lymphocytes [34] , and CD4 + -and CD8 +positive T lymphocytes represent helper and cytotoxic T lymphocytes, respectively [35] . CD4 + CD25 + T lymphocytes represent activated CD4 + T lymphocytes, and CD45R/B220 antibody was used to identify B lymphocytes [36, 37] ." ] },{ "paper_id": "2835b0f9f06e3e829cfa7d3f1e3805af94249d65", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For flow cytometry, L. plantarum cells were cultured in MRS broth overnight at 37 \u2022 C. The cell pellets were sequentially incubated with gp85-specific mouse monoclonal antibody (1:800) and fluorescein isothiocyanate (FITC)-conjugated antimouse IgG secondary antibodies (1:5,000; Sigma). Finally, 3 \u00d7 10 4 cells were analyzed with a FACS Calibur platform (Becton Dickinson, Oxnard, CA, USA) equipped with CellQuest software.", "Blood samples were collected from the wing vein on Days 1 (before immunization), 7, 14, 28, 35, 42, and 49. Blood samples without additives were centrifuged and the serum was stored at \u221280 \u2022 C for subsequent analysis.", "L. plantarum HQ542228 was purchased from China Center of Industrial Culture Collection (CICC) and grown anaerobically at 37 \u2022 C, without agitation in MRS broth medium (250 g, Hopebiol, Qingdao, China). The E. coli strains were cultured at 37 \u2022 C with continuous shaking in Luria-Bertani (LB) medium (250 g, Hopebiol)." ] },{ "paper_id": "283604cd89c223271768c0a2fb065cba3a015b13", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DNA was extracted by TIANamp Genomic DNA Kit (TIANGEN biotech, Beijing, China). RNA was extracted by MiniBEST Universal RNA Extraction Kit (TaKaRa, Dalian, China).", "Frontiers in Microbiology | www.frontiersin.org ", "Conceived and designed the experiments: YD, YT, and JY. Performed the experiments: JY, HC, and ZW. Analyzed the data: JY, XY, and XN. Contributed reagents/materials/analysis tools: JY and HC. Wrote the paper: JY." ] },{ "paper_id": "284790100b67133f3228466016a8f98ad096e24d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Approval for animal experiments was obtained from the Institutional Animal Welfare Committee and performed according to Dutch guidelines for animal experimentation.", "RNA labeling, microarray hybridization, scanning and data preprocessing Pooled total RNA (2.4 mg) from one-three separate lung pieces of all animals (including previously infected animals), with substantial SARS-CoV replication (.10 5 fold change), was labeled using the One-Cycle Target Labeling Assay (Affymetrix) and hybridized onto Affymetrix GeneChip Rhesus Macaque Genome Arrays (Affymetrix), according to the manufacturer's recommendations. Image analysis was performed using Gene Chip Operating Software (Affymetrix). Microarray Suite version 5.0 software (Affymetrix) was used to generate .dat and .cel files for each experiment. All data were normalized using a variance stabilization algorithm (VSN) [64] . Transformed probe values were summarized into one value per probe set by the median polish method [65] . Primary data is available at http://www.virgo.nl in accordance with proposed MIAME standards.", "Serial 3 mm lung sections were stained using mouse-anti-SARSnucleocapsid IgG2a (clone Ncap4; Imgenex) 1:1600, mouse-antihuman neutrophil elastase (clone NP-57; DAKO) 1:10, mouseanti-human CD68 (clone KP1; DAKO) 1:200, mouse-anti-human pankeratin (clone AE1/AE3; Neomarkers) 1:100, rabbit anti p-NF-kB p65 (Santa Cruz) or rabbit control and isotype antibodies (clones 11711 and 20102; R&D), according to standard protocols [22, 23] . Quantitative assessment of SARS-CoV infection in the lungs was performed as described previously [22] ." ] },{ "paper_id": "284a7df2b370e893122a58ce3af9a9d2daaab704", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At the indicated times post-infection/transfection, cells were briefly washed in phosphate buffered saline (PBS) collected by centrifugation (2000 rpm, 10 min, 4\u00b0C) and lysed in reporter lysis buffer (Promega, Madison, WI) according to the manufacturer's guidelines. Lysates were spotted to 96-well dishes, mixed with Luciferase Assay Reagent (Promega) and arbitrary light units (LU) were measured using an Envision 2102 Multilabel Reader with Wallac EnVision Manager software (version 1.12; PerkinElmer, Waltham, MA). All experiments were performed at least three times.", "Chemicals X-gal, nocodazole, vincristine, PYR-41, and MG132 were obtained from Sigma-Aldrich (St. Louis, Mo) and dissolved in dimethylsulfoxide (DMSO). AraC (Sigma) was dissolved in sterile water. Recombinant IFN-\u03b1 solution was from Sigma. X-glu (Clontech, Palo Alto, CA) was dissolved in DMSO. Compounds were diluted to their final concentration in cell culture medium or in a 1:1 mixture of 2 \u00d7 Dulbecco's minimal essential medium (DMEM; Invitrogen, Carlsbad, CA) and 1.7% agar (X-gal; X-glu) immediately prior to use.", "\u0394A51R, \u0394A51R FREV , \u0394A51R/\u0394J2R, \u0394A51R/\u0394J2R FA51R , and \u0394A51R/\u0394J2R FMVAA51R strain construction" ] },{ "paper_id": "284b00ca025a939e64aefb5129b9e942c065baaf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The eaeA gene was amplified from pEB310 using primers SW20H3:", "LGA, FCF, and SJL are funded co-applicants who designed the study and edited the manuscript. All authors read and approved the final manuscript.", "Shedding of Salmonella was monitored by collecting daily fecal swabs, followed by enrichment in tetrathionate broth (Beckton Dickinson and Company, Franklin Lakes, NJ), and in Rappaport-Vassiliadis R10 broth (Beckton Dickinson and Company, Franklin Lakes, NJ). Bacteria were enumerated by plating serial dilutions onto XLT-4 plates (Beckton Dickinson and Company, Franklin Lakes, NJ)." ] },{ "paper_id": "28564e89afd6423e291c68867dd52654258b29f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Several steps are needed to accomplish the above-suggested approach:", "noses should be connected to the Internet, which allows for synchronization with the breath-cloud. \u2022 The electronic noses should be readily available in the areas where the first signals of an outbreak are visible.", "As conventional diagnostic methods such as viral culture and detection of antigens or antibodies have limitations due to low sensitivity and delay in time, the officious gold standard for laboratory diagnosis is detection of viral nucleic acids by reversetranscriptase polymerase chain reaction (RT-PCR; George, 2012 Ryoo et al., 2013) . Of course, one could decide to quarantine and treat every critically ill patient who presents with influenza-like symptoms empirically (Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 Influenza et al., 2010) . Potential side-effects of treatment and high costs associated with quarantine, however, are arguments against such \"unselected\" treatment, especially on a large scale." ] },{ "paper_id": "2857cb1d4c6c446ac30ab4d0cabca0b42d62c465", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 126 nasopharyngeal aspirates were collected from children under two years of age who were hospitalized at the Children's Hospital of Beijing, China, during June, 2008 and March, 2010 with a diagnosis of pneumonitis or bronchopneumonia and a fever of 38\u00b0C or greater. A total volume of 0.5 ml of nasopharyngeal aspirate was collected in 3.5 ml of transport medium. This study was approved by the Beijing ethics committee. Sample collection was agreed by child's parents or grandparents with informed consent.", "Extraction and purification of RNA/DNA Total RNA/DNA was extracted from 200 \u03bcl of viral stocks or clinical samples using the QIAamp Viral RNA Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. The extracts was eluted in 50 \u03bcl of DNase-and RNase-free water and stored at \u221280\u00b0C.", "Viral respiratory tract infections, which have a considerable morbidity and fatality rate, are common diseases that especially affect infants and the elderly [1] . Common respiratory viruses include influenza A virus, influenza B virus, parainfluenza virus, human rhinovirus, adenovirus and respiratory syncytial virus. New respiratory viruses important to public health, such as metapneumovirus, coronavirus (subtypes SARS-Cov and CoV HKU1) and human bocavirus [2, 3] , have emerged over the past decade. The clinical presentation of respiratory infections caused by different viral pathogens can be very similar, making etiological diagnosis difficult [4] ." ] },{ "paper_id": "286bea94529dca847214023bb3eabc8b2bc59760", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics. The study protocol, informed consent statement, clinical research form, amendments, and all other study documents were submitted to and approved by the institutional research ethics committee of each site.", "Overall, 70.5% tested positive for urinary antibiotics at admission. Among the 402 (99.3%) patients given antibiotics during hospitalization for a median duration of 7 days (IQR = 5-10 days), 298 (74.5%) received monotherapy, with some also getting multiple antibiotic lines. The main drugs were ceftriaxone (N = 135, 26.0%), amoxicillin (N = 120, 23.1%), ampicillin (N = 51, 9.8%), amoxicillin/sulbactam (N = 36, 6.9%), amoxicillin/clavulanic acid (N = 35, 6.7%), oxacillin (N = 35, 6.7%), and vancomycin (N = 22, 4.2%).", "Study sites and design. Findings from a prospective, hospital-based, multicenter, longitudinal study, conducted at five sites in four countries located on three continents, were analyzed: Lucknow and Vadu in India, Antananarivo in Madagascar, Bamako in Mali, and San Lorenzo in Paraguay. The participating sites are members of the GABRIEL (Global Approach to Biological Research, Infectious Diseases and Epidemics in Low-Income Countries) Network established by Fondation M\u00e9rieux. 11 The study protocol and sites are described elsewhere. 12 Pneumonia cases from the original case-control study were followed up during hospital stay and constituted the analyzed cohort." ] },{ "paper_id": "286ffc3b37fa763b765bb3d8403fd4deacff80c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2870d8384735793d033aac6c0621f35540b59736", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "DNA virus confirmatory nucleic acid analysis was performed for the Adenoviridae and Herpesviridae families as described in Li et al. [37] and Van Devanter et al. [38] , respectively. PCR products of appropriate size were excised, purified (Zymoclean\u2122 Gel DNA Recovery Kit, Zymo Research) and sequenced on an ABI 3130 sequencer (Applied Biosystems) at Inqaba Biotech (Pretoria, SA).", "Bt [25] .", "https://doi.org/10.1371/journal.pone.0194527.g007" ] },{ "paper_id": "2871cf7a741e9af5c94009d2cf5f368932f6f47e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Three-quarters of this departmental funding is allocated to the stockpiling of antiviral drugs and vaccines for use in the US, while only 3.8% is dedicated to \"international activities.\" Poor countries are understandably concerned that the stockpiling of tools for pandemic infl uenza control will be the preserve of the rich world.", "We surely need WHO more than ever.", "Under IHR 2005, WHO member states are now required to notify WHO of \"all events which may constitute a public health emergency of international concern,\" which can include noninfectious events (such as chemical or radiation hazards) [5] .", "In WHO terms, this time scale was miraculously quick, but there is clearly room for improvement-an even quicker time frame is likely to be needed for future health emergencies. The process could be expedited, say the authors, by identifying or establishing collaborating centers skilled in producing evidence-based guidelines and by building in-house capacity to reduce the time needed to organize a review team. It will also be vital for this new rapid advice group to make its process of panel selection as transparent as possible if the group is to garner the trust of the public health community. WHO has previously come under fi re for allowing industry to unduly infl uence its expert committees, and for failing to ensure that committee members declare their competing interests [3] . The rapid advice group must not sacrifi ce transparency in the interests of urgency." ] },{ "paper_id": "287daad100931cefff81e066860bac399a008cbb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Moreover, aptamers may be applicable in drug development. One example in this regard is RNA aptamers developed against aminoglycoside by in vitro selection to discover the interactions between aminoglycoside and natural RNAs, including HIV RNAs, which may have similar mechanism in their interactions. The in vitro selected aminoglycoside aptamers seem to have valuable applications in the discovery of the pathogenesis and treatment of HIV infection, including molecular mechanism of interaction with aminoglycoside antibiotics, and screening of efficient anti-HIV drug candidates [95] .", "Aptamer-siRNA/miRNA conjugates Short interfering RNA (siRNA) are 21-23 base pairs (bp) in length and as an exogenous agent can experimentally manipulate gene expression. siRNAs, compared to similar therapeutic agents, exhibited minimal toxicity and high stability. siRNAs had demonstrated to have a promising modulatory effect on virulence, drug resistance and pathogenesis [63] . The use of siRNA-aptamer conjugates for drug delivery can result in the increase of favorable therapeutic efficacy and safety [24] .", "Bacterial specific aptamers can be a promising agent in the prevention of pathogen invasion to immune cell (Fig. 5) . Some of the examples were illustrated in following section.", "Aptamers can bind specifically to cell surface receptor molecules. Therefore, aptamer-based delivery systems can improve the cellular entrance of therapeutic agents. Aptamers can be designed for a wide range of applications through coupling with nanoparticles, drugs or other nucleic acids (nano carrier/ drug carrier) and play a major role in cell internalization (Fig. 4) [53] ." ] },{ "paper_id": "287efc07973e7b2d046c7664771dc2e2a00b501b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses are phenotypically and genotypically diverse [6, 10] . All coronaviruses possess a common genome organisation in which the replicase gene encompassing the 5' two-thirds of the genome is comprised of two overlapping open reading frames, ORF1a and ORF1b. The structural gene region, which covers the 3' third of the genome, encodes the canonical set of structural protein genes in the order 5'-spike (S) \u2192 envelope (E) \u2192 membrane (M) \u2192 nucleocapsid (N)-3' [1, 10] . The S proteins is the most immunodominant CoV protein [1, 6, 10] .", "Coronaviruses are positive-sense, single-stranded RNA viruses found in humans and a wide variety of animals [1] . In humans, four respiratory coronaviruses, namely human coronavirus (HCoV) -229E [2] , -OC43 [3] , -NL63 [4] , and -HKU1 [5] , are endemic worldwide. These four common strains cause diseases from mild, febrile upper respiratory tract illnesses to severe outcomes, such as croup, bronchiolitis, and pneumonia, and attribute to about 10% of all upper and lower respiratory tract infections in hospitalised children [1, 6] . In 2003, a previously unknown coronavirus caused an outbreak of severe acute respiratory syndrome (SARS) in humans [7, 8] . More recently, the novel betacoronavirus species HCoV-EMC was identified from a man with pneumonia in Saudi Arabia [9] .", "Statistical analysis was performed using the Statistic Package for Social Science(SPSS) statistic 17 package with \u03c7 2 -test and Fisher's exact test. Differences between the mean values of each group were considered significant at p < 0.05 when assessed using Tukey's test." ] },{ "paper_id": "2883a8e6fafe65f0dc49b8e2aa1b1f4640f1a8d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All blood samples were collected prior to or during surgery. Blood samples were collected in BD Vacutainer SST tubes (Becton, Dickinson and Company, Franklin Lakes, NJ, USA) and were centrifuged at 1300 rcf for 20 min at room temperature within 50 to 60 min of venipuncture. Serum samples were stored in aliquots at \u221280 \u2022 C until use. Only serum samples without hemolysis were used.", "In the last decade, various efforts have been made to discover circulating biomarkers for breast cancer, including microRNAs (miRNAs) [10] . MiRNAs are evolutionary conserved, single-stranded non-coding RNAs (with 19 to 25 nucleotides) with a primary function in mediating the degradation or translational repression of mRNA targets [11] . Apart from its critical roles in the normal physiological state, dysregulated miRNAs are also associated with the hallmarks of cancer through their tumor suppressor or oncogenic activities, and the aberrant expression of miRNAs has been demonstrated in a variety of malignancies [12] [13] [14] . Circulating miRNAs have been proposed as clinically useful biomarkers not only due to their expression levels changes that are associated with cancer development, but also attributable to their stability in different body fluid sources and extreme conditions (e.g., RNAse digestion, multiple freeze-thaw cycles, and prolonged storage period) [11, 13] .", "Hence, in this study, we aim to identify a miRNA signature with high discriminative ability between malignant and benign breast lesions. Our approach utilized next-generation sequencing (NGS) of 2,083 miRNA transcripts, followed by the identification of significantly differentially expressed miRNAs and the development of a miRNA-based classification model for malignant breast lesions.", "In addition, there are other significant miRNA biomarker candidates that have been published. The study by Shimomura et al. (2016) is the largest breast cancer miRNA discovery to date, which reported a five-miRNA signature-miR-1246, miR-1307-3p, miR-4634, miR-6861-5p, and miR-6875-5p-that could recognize breast cancer cases from non-cancer controls at an AUC of 0.9710 [24] . Nevertheless, the downside of the study is that the biomarker signature was profiled and developed using a microarray-based platform which is known to have poor specificity [25] , and only one of the five miRNAs could be validated in 26 serum samples by qRT-PCR." ] },{ "paper_id": "2884fdee6db20fa38c7ad56008b0ff4b84eeb41d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Susceptible patient direct transmission", "GK is a paid employee of Bode Chemie GmbH & Co. KG, Hamburg, Germany. ", "All authors contributed to the conception, review of studies, and analysis of data. All authors were involved in drafting and revising the manuscript. All authors approved the final version of the manuscript. " ] },{ "paper_id": "288e7bf5d16ac18731d2f1ee7db6d6ed2a720cc2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Note: FeLV01-FeLV14 sequences were amplified from plasma viral RNA while the remaining local sequence (FeLVUPM13-FeLVUPM29) were amplified from proviral DNA.", "Failure to detect FeLV viral RNA in about 13% p27 antigen-positive cats (p27-positive/viral RNA-negative) could result from atypical infection, wherein the virus is sequestered and replicates locally in tissues such as salivary gland, mammary gland, and urinary epithelium, causing intermittent or low-grade antigenaemia, although there is no ", "In both inner and outer PCR steps, the target gene regions were amplified using the following conditions: reverse transcription: 45 \u2218 C (45 min) (only in the case of RNA), initial denaturation: 94 \u2218 C (2 min), denaturation: 94 \u2218 C (45 sec), annealing: 58 \u2218 C (30 sec), extension: 72 \u2218 C (1 min), 35 cycles of repeats, and final extension: 72 \u2218 C (7 min). PCR product was electrophoresed using 1.5% agarose (SeaKem LE USA), stained with 0.5 g/mL ethidium bromide (Bio-Rad USA), and visualised under UV light (Geldoc system, Bio-Rad, USA). Extraction and amplification procedures were carried out in separate hood to reduce chances of contamination.", "The PCR mixture was prepared in 25 L reaction volume containing 10 mM each of dNTPs mix, 0.2 mM Tfl DNA polymerase (5 U/ L), 0.1 U AMV (5 U/ L), 0.1 U recombinant RNasin ribonuclease inhibitor (400 U/ L), 0.8 U MgSO 4 (25 mM), 20 pmol of each of the forward and reverse primer, 5.0 L of 1 times buffer, and 1 L RNA or DNA template. Nuclease-free water was used to bring the mixture to its final volume of 25 L. AMV reverse transcriptase enzymes and RNasin ribonuclease inhibitor were included only when RNA was a starting template for the PCR assay. In the nested PCR step, 1 L of outer PCR product was used as template." ] },{ "paper_id": "2890249daa0601affd680a8aadee19b50ed2044d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Y-DT, P-FL, and J-YL performed most experiments, and L-FL (Figures 5A,B) , S-YK (Figure 4E ), C-WH and C-HW (Figures 5C,D) performed the remaining experiments. TCGA data was analyzed by C-HL, H-TC, and MH. C-WS prepared the figures, interpreted data, and wrote the manuscript." ] },{ "paper_id": "2895e9bc46487b11d2e514ed42fca059df5ec7a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Provincial health services authority, within which the British Columbia center for disease control is situated." ] },{ "paper_id": "2896c5193ae79e31e46c2eb50590dc8d58fe9a44", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GenBank accession numbers of the sequences obtained in this study are indicated in S1 Text.", "In patient 53, the first two specimens were unavailable for typing, therefore only specimens 53C to G are reported.", "Demographic data (age, sex) and data on underlying diseases and immunosuppression were retrospectively obtained from hospital records." ] },{ "paper_id": "289edbe9e28f26ea1d2de597c085e0f6e3009aed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There are several well-known risk factors for severe adenovirus infections, including: allogeneic stem cell (or solid-organ) transplantation, particularly with T-cell depletion; treatment with anti-CD52 monoclonal antibody (alemtuzumab or Campath) or anti-thymocyte globulin (ATG); severe immunosuppression used to treat graft-versus-host disease; and any other cause of severe lymphopaenia that reduces the ability of the host's cell-mediated immunity to defend against adenovirus infection [1] .", "Finally in such immunocompromised patients, all pathogens: bacteria, fungi and viruses, should be screened for in the initial investigation of an acute infective episode, to allow prompt intervention as required. ", "This patient's chemotherapy regimen included fludarabine which has severe lymphopaenia as a recognised adverse effect, and which has been present in treatment regimens where various other viral reactivations have occurred, including hepatitis B [10] [11] [12] , BK virus [13] , herpes simplex and Epstein-Barr viruses [14] , cytomegalovirus [15] , as well as adenovirus [16] . Yet in this case, it was noted that throughout this period during which he acquired and was infected with adenovirus, his total lymphocyte count remained within or even above the normal range of 1-4 \u00d7 10 [9]/L, though their specific functionality was not tested." ] },{ "paper_id": "28a0bf1e235fe876fff1127346bb3bac0b6e5072", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although important data has been generated by mapping studies, the biological significance of these interactions is the scope of further experimentation. Nevertheless, these associations can prove to be valuable starting points for understanding CHPV biology and designing antiviral strategies. Components blocking the N protein interacting regions may represent a novel class of molecules suitable for a therapeutic intervention in Chandipura-mediated disease. ", "PiSQRD web resource was used to subdivide CHPV N protein structure in quasi-rigid fragments. This server uses an algorithm introduced by Potestio and coworkers [20] and subdivides proteins into regions that behave approximately as rigid units in the course of protein structural fluctuations. Default values were used for all the parameters with captured mobility threshold of 80% and 10 lowest energy essential modes.", "Plasmids. The putative nucleocapsid (N) fragments (N1, N2, and N3) were amplified using specific primers (as listed in Table 1 ) designed to incorporate NdeI and BamHI restriction enzyme sequences at their 5 ends to facilitate cloning in yeast expression vectors pGBKT7 (BD, bait) and pGADT7 (AD, prey), Clontech, USA. These primer pairs span nucleotides 1-90 bp (N1), 61-894 bp (N2), and 693-1260 bp (N3) of the complete nucleocapsid ORF cloned in pET33b vector [7] . The clone of CHPV N gene was a kind gift from Dr. Dhrubajyoti Chattopadhyay of Dr. B. C. Guha Centre for Genetic Engineering, Kolkata, India.", "During the life cycle of viruses, the encoded proteins extensively interact with one another to perform their functions. These protein-protein interactions (PPIs) are achieved through specific regions that are responsible for the physical interactions. These regions which mediate different interactions are considered as building blocks of interaction networks. Domain mapping has been carried out for several viruses such as Herpes Simplex Virus type I (HSV), Epstein Barr Virus (EBV), Kaposi's Sarcoma associated Human Virus (KSHV) [27] , Murine Coronavirus [28] , Rabies Virus (RV) [29] , VSV [8, 30] , and Sendai virus [31] and for certain proteins of CHPV as well [12, 13] . These studies have highlighted the importance of identifying the regions which can be targeted for therapeutic strategies." ] },{ "paper_id": "28a98145eda693bae14b52abfc3d37ced6c5fd90", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. Raw microarray data for these studies were deposited in publicly available databases at the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (37) and are accessible through GEO series GSE65574.", "Clustering and functional enrichment. Genes identified as differentially expressed were used to generate clustered expression heat maps. Hierarchical clustering (using Euclidean distance and complete linkage clustering) was used to cluster gene expression according to behavior across experimental conditions. The David online resource (https://david.ncifcrf.gov/) was used to acquire functional enrichment results for the genes in each cluster. David output was manually summarized for each cluster. Plots were generated with R.", "RNA isolation, microarray processing, and identification of DE. RNA isolation and microarray processing, quality control, and normalization from Calu-3 2B4 cells were carried out as previously described (36) . Differential expression (DE) was determined by comparing virus-infected replicates with time-matched mock-treated replicates. Criteria for DE in determining the consensus ISG list were an absolute log 2 change of \u03fe1.5-fold and a false-discovery rate-adjusted P value of \u03fd0.05 for a given time point." ] },{ "paper_id": "28af8fb783b6180c247285955b5e48df75947819", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Practice of meditation or exercise may enhance health to protect against acute infectious illness.", "https://doi.org/10.1371/journal.pone.0197778.t002 " ] },{ "paper_id": "28b64c3ea5c13cbcaae132a45661fb8bf5c25c62", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In most VNTR, the N-terminal repeat unit (H1) and C-terminal repeat unit (H4 followed by H5) are highly conserved. Most alleles has H1 and H4 followed by H5 (or their transition variants) in these two locations ( Figure 2 ), which is supportive that these subunits are important for the formation of oligomer of CLEC4M [9] .", "The VNTR polymorphism of the neck-region was genotyped as described in Li et al [18] . The genotype was determined by separating the PCR products in 3% agarose gel with ethidium bromide staining. To validate the genotyping results, 10% of the samples were re-genotyped by duplicated genotyping experiments.", "The clonal sequence of the 290 chromosomes of the worldwide population sample then called according to the subunit haplotype (H1 to H8). For example, the common 7-repeat VNTR allele is formed by one H1, three H2, one each of H3, H4, and H5 in the order of H1-H2-H2-H2-H3-H4-H5 ( Figure 2 and Table 1 )." ] },{ "paper_id": "28b906cb5b5dd66df68bdd155ccc2ab514180c2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HAI assays were performed on a 100-\u03bcl aliquot of the samples at University Health Network (UHN), Toronto, Ontario, Canada. as previously described [16] using inactivated pandemic influenza A/California/07/2009 antigens [17] .", "List of abbreviations GM-CSF: granulocyte macrophage colony-stimulating factor; IFN: interferon; IL: interleukin; IL-1RA: interleukin receptor antagonist; IP-10: interferongamma inducible protein-10; MCP-1: monocyte chemoattractant protein-1; MIP-1\u03b2: macrophage inflammatory protein-1\u03b2; MV: mechanical ventilation; NMV: non mechanical ventilation; TGF-b: Transforming growth factor -beta; VEGF: vascular endothelial growth factor." ] },{ "paper_id": "28bec3efe92c8567992ee35baecf2dc42bbc34ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results of our analyses are available on our website, and provide a foundation for understanding the genome and biology of Mtb in a comparative context.", "Our whole-genome alignments, coupled with RNA-seq and microarray data, allowed us to predict novel noncoding features, including small RNAs (four of which we have validated experimentally), and potential transcription factor binding sites.", "1. All Mycobacteria (excluding M. leprae because of its massive gene loss)." ] },{ "paper_id": "28cfe86a8fa13dacd3f447dcb095ac9a9f99a33a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "28d395784208073fa0bd75540cfed74a2018061d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "28d59a7490b8337301262db257c5cfe98ddede06", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Zika virus (ZIKV) is a mosquito-borne flavivirus in the family Flaviviridae, which not only affects human adults by causing Guillain-Barr\u00e9 syndrome but also induces microcephaly and death in congenitally exposed fetuses [1, 2] . The recent ZIKV outbreak in South America has resulted in an unprecedented large number of infection cases [3] . ZIKV has emerged as a public health threat.", "The experiments were conducted in strict accordance with guidelines of the AAALAC accredited Laboratory Animal Research Center at Utah State University and approved by the Institutional Animal Care and Use Committee of Utah State University (IACUC Protocol: 2667; approval date: 27 September 2016).", "Following de-paraffinization, tissue sections were blocked with normal goat serum for 60 min at room temperature [17] . Either mouse anti-flavivirus group antigen monoclonal antibody (Millipore, Temecula, CA, USA) or mouse monoclonal antibody to ZIKV NS1 protein (Aalto Bio Reagents, Dublin, Ireland) was incubated on the tissues for overnight. After a brief wash with PBS, sections were incubated with a fluorescence-conjugated secondary antibody (Invitrogen, Grand Island, NY, USA) at room temperature for 2 h. Images were captured using Zeiss microscope, AxioVision 4.0.1 and processed using Adobe Photoshop. Hematoxylin and eosin (H&E) staining was performed to study the morphological diagnoses (Table 1 ) and it was read by a veterinary anatomic pathologist (Dr. A.V.W).", "Currently, there are no countermeasures available for the prevention or treatment of ZIKV infection, except for symptom relief management. Vaccine development is still at its early stages and it is unknown when an approved ZIKV vaccine will be available." ] },{ "paper_id": "28deef160eb2e879ffa3a4f025898a9690be0e7e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "28e355b80d2d62c5314e8d97e92fbd67f77679d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA from the tissues samples was extracted using an Axygen total RNA extraction kit (Axygen, USA) as described in the manufacturer's instructions. Briefly, 400 ml of lysis buffer was added to 30-40 mg of ground tissue. The nucleic acids were eluted in 50 ml nuclease-free water and stored at 220uC. For every five samples, one negative control (water) was included to detect any possible contamination.", "After informed consent was obtained, the cadaver was stored at 4uC and underwent autopsy about 18 h after death. The autopsies were done following conventional protocols with strict adherence to biosafety procedures [48] . Twenty-four tissues were collected from respiratory, digestive, nervous, urinary and lymphatic organ systems. Duplicate tissue samples were collected; one sample was fixed in diethylpyrocarbonate (DEPC) treated 10% formalin for pathologic analyses, while a second sample was frozen at 280uC for virus isolation and molecular analyses.", "The patient was laboratory confirmed as an H5N1 infection by China CDC on February 20, 2008. He is a 42 years-old Chinese male living in Guangxi, China with a history of 6 days of fever, cough and dyspnea. Two weeks before hospital admission, he bought 3 hens at an open-air market, one of which died later at same day. The remaining birds exhibited symptom of chicken attack next day. The patient killed and cooked the birds, and ate them together with other family members who later did not experience any clinical symptom. On admission, the patient was febrile with a temperature of 40.3uC, had infiltration of lower left lung lobe based on chest radiography, bilateral lower lung moist rales, and substantially reduced oxygen saturation. He was placed on a ventilator and treated with antibiotics, spasmolysis, corticosteroids, and the dissipatation of phlegm and fluids. Despite treatment, the patient presented with function damage of multiple organ (lung, heart, liver and kidney) on the second day after admission, and died 59 h after admission, and 8 days after the onset of symptoms. Throat swabs were collected and performed RT-PCR and rRT-PCR detection at the day patient died. No antiviral drug treatment was given since the patient died before finally laboratory diagnosis." ] },{ "paper_id": "28f13f534ff3d7fccd966a9bb1158a0a1ed95967", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The coldspots were mainly limited to three areas: Table 2 , and the reason for listing hotspots in provincial level is we mainly discussed cluster in this level." ] },{ "paper_id": "28f89ac0fa6a72cf3dc315817c2e670c10dec347", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Materials and Methods cDNA constructs and RNA transcription SGR-Gluc was previously described as pYSGR-JFH/Gluc [65] . The noncytopathic VEEV vector 5'VEEVrep/L/GFP/Pac [84] , a kind gift of Dr. Ilya Frolov (University of Alabama, Birmingham), was modified to replace the GFP insert with a short multi-cloning site. Briefly, oligos YO-0779 and YO-0780 (S1 Table) were annealed and ligated into the XbaI/BsrGI sites of p5'VEEVrep/L/GFP/Pac to yield pVEEV/MCS.", "PLOS Pathogens |" ] },{ "paper_id": "28fbe1da18bb4a2e0f8a42013e14794b6f3038f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. Symptomatic illness exceeding two weeks (14 days) at time of enrollment. 2. Negative rRT-PCR from respiratory secretions or blood within 48 h prior to assessment of eligibility. 3. History of allergic reaction to blood or plasma products (as judged by the investigator). 4. Known IgA deficiency. 5. Medical conditions in which receipt of 500 mL intravascular volume may be detrimental to the patient (e.g., actively decompensated congestive heart failure).", "Clinical and laboratory data will be collected at baseline, 30 min after first dose, 30 min after second dose, study days 1, 3, 5, 7, 14, and 28.", "We will conduct exploratory stratified analyes based on (1) the time between symptom onset and CP therapy initiation, (2) comorbidities, (3) co-intervention; and (4) baseline severity (SOFA scores) at treatment initiation. The SAS System for Windows version 9.3 (SAS Institute, Inc., Cary, North Carolina) and R will be used for all analyses.", "This protocol was developed collaboratively by King Abdullah International Medical Research Center (KAIMRC), Gulf Cooperation Council (GCC) Infection Control Center Group and the World Health Organization-International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO) MERS-CoV Working Group. It was approved by the Ministry of the National Guard Health Affairs Institutional Review Board (IRB) (approval number IRBC/13/244, 5th June 18, 2014) and has been registered at clinicaltrials.gov (NCT02190799)." ] },{ "paper_id": "290408ae0dcc207b221cee5bd2b86763ac593a1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Proteasome inhibitors MG132 (carbobenzoxy-L-leucyl-Lleucyl-L-leucinal) and lactacystin were purchased from Sigma.", "XH and YH carried out the main experiments, analyzed the data, and drafted the manuscript. SW and SN performed the viral titer assay and participated in the qRT-PCR experiments. YH and QQ designed the experiments and reviewed the manuscript. All authors read and approved the final manuscript. ", "Immunoreactive bands were visualized with diaminobenzidine." ] },{ "paper_id": "2906d781d6cac5a07bf2826f620a788e3f8432ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At the end of the experiments, the lungs were removed and processed for routine histologic analysis. Briefly, the lung tissue was fixed with 10% formalin and embedded in paraffin. Four-micrometer sections were cut and stained with hematoxylin and eosin (H&E) and Periodic Acid-Schiff (PAS). Inflammatory infiltrates were examined by light microscopy and corresponding images were shot using an Olympus BX51 microscopic/DP71 Digital Camera System (Nagano, Japan).", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "290c2714886f1aaa00c374d3315381b0f0aa8033", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2911b1cc77f7c2bf1f8743673d3d2df7d7993aee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work is supported by grant MOST 105-2311-B-005-002 from the Ministry of Science and Technology, Taiwan.", "I-HC wrote the section on the plus-strand RNA synthesis. Y-WH wrote the section of subgenomic RNA synthesis. C-HT wrote the rest part of the manuscript.", "Bamboo mosaic virus (BaMV) has a single-stranded positivesense RNA genome that is approximately 6.4 kb in length with a 5 -cap structure and a 3 poly(A) tail. The genome contains five open reading frames (ORFs) (Figure 1 ). ORF1 encodes a replicase for viral RNA replication, ORF2 encodes a 28-kDa protein (a silencing suppressor) required for viral movement, ORF3 and ORF4 encode membrane-anchoring proteins required for virus movement, and ORF5 encodes a 25-kDa capsid protein for viral encapsidation, movement, and symptom development." ] },{ "paper_id": "2934008a223a07e3fd3c886db120eb1fe3aab567", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the ethics committee of The First Affiliated Hospital of Guangzhou Medical University and informed consent was obtained for all subjects.", "Statistical software (SPSS 13.0; SPSS, Chicago, IL, USA) was employed for statistical analysis. Quantitative data were presented as median and interquartile range (IQR) and compared by non-parametric Kruskal-Wallis test. The categorical variables were reported as frequencies and percentages and compared using the Fisher's exact or Chi-square test." ] },{ "paper_id": "293854bf36effa5c8080201deaa19b213d4465c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Information on the participating doctors was also collected and included doctor's gender, age and training grade.", "Ethical approval was obtained from the Joint CUHK-NTEC Clinical Research Ethical Committee (Ref. no.: CRE-2011.306-T) before the start of the trial." ] },{ "paper_id": "2943228f12c0cb46c035893d848410ff23686595", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). Wild-type DENV1 and DENV4 sequences were derived from GenBank accession numbers U88535. 1 ", "rDENV1ic-EDI mutant construction. For mutant virus generation, 12 predicted contact residues of 5H2 (24, 25) were identified that differ between DENV1 and DENV4 (Table 1 ). rDENV1ic plasmid A fragment was redesigned to encode these 12-amino-acid changes in the envelope protein to create rDENV1ic-EDI. The new plasmid A was digested and ligated with WT rDENV1ic plasmids B, C, and D as described above to generate the rDENV1ic-EDI mutant virus.", "Supplemental material for this article may be found at https://doi.org/10.1128/ mSphere.00380-16. " ] },{ "paper_id": "295d0e530c6b6d9df5c46872c36bf15dc85507fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "295d1050a0d5e811698a853c29cc8b388d4d92f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by the German Research Foundation (SFB-TR84 B2, SFB1021 C05, KFO309 P2/P8, EXC147), by the German Center for Lung Research (DZL), and by the German Center for Infection Research (DZIF).", "Respiratory syncytial virus is an important cause of respiratory tract infections especially in children worldwide. Generally, there seem to be virus-elicited anti-apoptotic mechanisms active in the lung epithelium, as RSV-infected primary human airway cells show a minimal cytopathic effect (173) . However, several cell lines including small airway cells, primary tracheal-bronchial cells, and A549 and HEp-2 showed increased expression of TRAIL and its ligands DR4 and DR5 in an in vitro RSV infection model (174) . Moreover, soluble TRAIL released from leukocytes was elevated in the bronchoalveolar lavage fluid of patients with RSV-associated respiratory failure, suggesting that similar to IAV, TRAIL contributes to RSV-induced epithelial injury and disease progression (137) .", "CP and SH performed bibliographic research and drafted the manuscript.", "Importantly, the activation of proapoptotic and pro-necroptotic pathways in respiratory infection can result in a structural disruption of the airway and the alveolar epithelial barrier, which is a major hallmark of respiratory disease and its progression to the acute respiratory distress syndrome (122, 123) . In virusinduced lung injury, especially expression of TRAIL, which can initiate both apoptosis as well as necroptosis has been correlated with more severe outcomes.", "Respiratory viral infections are major causative agents for lung injury and ARDS; however, in many cases antivirals are not sufficient to limit disease (208). Besides the fact that most viruses are subject to strong selective pressures that favor quickly evolving, drug-resistant virus variants, recent advances in understanding the processes that contribute to tissue injury and ARDS highlight a crucial role of immune-related, IFN-driven events. Therefore, novel therapeutic strategies often aim to improve the outcome of severe respiratory infection by modulating host cell responses; however, to date, clinical trials trying to improve severe viral infections or ARDS outcomes by targeting host pathways have not resulted in approval of new drugs (122) ." ] },{ "paper_id": "29621887690af716dac0c244eeb95bce74fa8755", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "H5N1 and H7N9 outbreaks have remained a spillover event, but the potential of these novel avian IAV strains to develop the ability to efficiently transmit human-to-human through aerosol droplets exists (3) (4) (5) ; thus, increasing the threat of new global pandemics.", "Are virus entry and Replication in Mast Cell Required for Activation?", "Mast cell granules contain histamine, TNF-\u03b1, amines, \u03b2-hexosaminidase, serotonin, antimicrobial peptides, and proteases (tryptases and chymases) bound to either heparin or chondroitin sulfate through electrostatic interactions (29, (31) (32) (33) . Upon stimulation, the granules are released from the cell via a calcium-dependent exocytosis process. Once expelled, the granules can either discharge the stored mediators into the immediate environment or intact granules can travel through the IL-17, and VEGF (32, 52) . These mediators activate tissue-resident cells, while recruiting additional effector leukocytes and lymphocytes to maintain the inflammatory state for a prolonged time." ] },{ "paper_id": "2965d872997d38cdfcde8b9bb17c8c659b0a16f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Other articles in this Issue cover various other antiviral approaches against influenza virus, including traditional and current ones, which will offer a more comprehensive perspective of our battle against this prehistoric pathogen.", "As in any therapeutic regimen, however, intranasal applications need to be optimized for potential side effects. The previously mentioned Zanamivir, as sold under the name 'Relenza' by GlaxoSmithKline, is applied via a hand-held nasal inhaler and is generally well-tolerated. However, its side-effects may include exasperation of asthma, bronchospasm, coughing, dizziness, headache, nausea, sinus inflammation, sore throat, stuffy nose and facial swelling, although the exact mechanism of these reactions remains unclear.", "The path of the pharmaceutical development of anti-influenza siRNA shares the general hurdles that confronts all siRNA.", "The IN route is particularly promising for the prevention and therapy of influenza and other respiratory viral infections [13, 31, 32] since it delivers the siRNA directly to the lung, the primary site of infection, thus ensuring the specificity of delivery and minimizing systemic siRNA loss and toxicity (see below)." ] },{ "paper_id": "296e24d0dc3c17633eeffea57bd23e968a1c8a5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Histopathological features of osteonecrosis in ON+ group ", "Steroids are indicated for many inflammatory and autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus and severe acute respiratory syndrome. One of the most serious complications for steroid administration is osteonecrosis (ON), that most frequently presents in femoral heads and often advances to subchondral bone collapse and needs arthroplasty [1] [2] [3] . However, there is a high failure rate in steroid-associated ON patients [4] . Prevention of ON is a very important strategy. However, the unclear pathogenesis of ON is still the stumbling block for developing effective prevention modalities." ] },{ "paper_id": "2975cca0a160177ac01195442ee8f6a55c59bd24", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In a univariate analysis with Poisson generalised linear model, we found that weekly URI incidence was significantly associated with weekly average temperature (RR for 1\u00b0 increase of temperature=1.048, 95% CI 1.030 to 1.066) and humidity (RR for 1% increase in relative figure S3 ). Temporal correlation of weekly incidence was well controlled for URIs and also relatively well controlled for LRIs in the full GAMM models (online supplementary figure S4 ).", "Our study has limitations as the findings were generated using routine data of from hospitalised patients. Therefore, are finding may be generalisable for outpatients, especially for URIs, as many patients with URI may not be admitted to hospital. The findings for LRIs may be more generalisable as LRIs are more severe than URIs and more likely to be hospitalised. Second, the databases contained mostly general ICD-10 codes and very limited specific diagnostic information regarding the ARI pathogens. Different pathogens can cause differing URI and LRI disease presentations and different pathogens may be influenced differently by climatic, environmental, population factors as well as host immunity. Therefore, further surveillance and studies investigating different groups of pathogens for ARIs are necessary. ", "The district level incidence over the entire study period of ARIs was significantly lower in the districts located further away from the hospitals (mean district incidence=26.7 per 1000 population, RR for two times increase in distance to hospital=0.88, 95% CI 0.80 to 0.96) and in rural districts (RR for urban vs rural districts=1.54, 95% CI 1.10 to 2.15) ( figure 1A) . Other district characteristics were not significantly associated with district ARI incidence.", "A large proportion of ARI admissions in these data were URIs, two-third of these were diagnosed with acute pharyngitis. These conditions can usually be treated in outpatient settings and do not typically require hospitalisation. However, the decision to hospitalise patients with ARI in these tertiary hospitals is not strictly based on WHO Integrated Management of Childhood Illness (IMCI) guidelines and is also dependent on the preferences of caregivers and the subjective patient evaluation of the attending physicians. Therefore, there should stricter policies for applying IMCI guidelines and other clinical criteria to reduce unnecessary URI admissions in these hospitals, as well as to improving outpatient care and follow-up." ] },{ "paper_id": "298d325e27d8cafcd150d56a199a5ce099ee2b07", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "From 2004 to 2014, 15 CNIC staff received training in CDC Atlanta, from one month to 1.5 years in length, on topics including influenza surveillance and laboratory management, reverse genetic techniques, serological techniques, pathology, antigenicity characterization, and drug resistance surveillance. CNIC provided lecture-based training to 2320 staff from network laboratories and sentinel hospitals, and hands-on training to 450 lab specialists on cell culture, virus isolation, and serology testing and gene sequence analysis with USCDC support.", "A year after WHO's assessment of CNIC in 2007, the Chinese Ministry of Health submitted an application for CNIC to become a WHO Collaborating Centre (WHO CC) for Reference and Research on Influenza. CNIC implemented performance improvement measures based on WHO requirements, and launched a one-year assessment in November 2008. In October 2010, CNIC was officially designated as the world's sixth WHO CC for Influenza, joining laboratories in Australia, Japan, the United Kingdom and the United States.", "The emergence of severe acute respiratory syndrome (SARS)", "In this report, we review the China-US laboratory collaboration on influenza from 2004 to 2014, to share best practices and lessons learned, and to assess how this collaboration builds capacity in the prevention and control of influenza in China and globally." ] },{ "paper_id": "298ebce4397c9735f69cb5fcf9ad82881eead18f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CD measurements were performed by using an Applied Photophysics spectropolarimeter. The spectra were scanned using a thermostatic quartz cuvette with a path length of 1 mm. Wavelength scans were performed at 25uC; the average recording time was 15 s, in 1 nm steps, through the wavelength range of 195-260 nm. Peptides were scanned at a concentration of 50 mM in buffer only (HEPES 5 mM) or in a membrane mimetic environment of 1% Lysophophatidilcholine (LPC) in buffer.", "The following sequences were used for quantitative mRNA analysis:", "TNFa Forward: CTTGTGGCAGGGGCCACCAC Reverse: CCATGCCGTTGGCCAGGAGG MCP-1 Forward: TCACCTGCTGCTACTCATTCACCA Reverse: AGCACAGACCTCTCTCTTGAGCTT" ] },{ "paper_id": "2990612686e9b3dc6819d62a2daeec9c857a98e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author declares that he has no competing interests.", "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.", "What is \"inflammaging\" as opposed to \"immunosenescence\"?" ] },{ "paper_id": "29ada2d0f89dbeee105c3f95b7df0ab204d9a444", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mosquito pools were homogenized for RNA extraction and virus isolation as previously described [11] .", "Tilt series were collected using a Tecnai F30 FEG-TEM (FEI) operating at 300 kV with a 4 k lens-coupled camera (Direct Electron). Tilt series data were collected over a range of 660u at 1.5u increments along two orthogonal axes and recombined computationally to produce a 3D tomogram using the etomo software package.", "For IFA analysis, monolayers of C6/36 and Vero cells grown on glass coverslips were inoculated with CASV, WNV or mockinfected as described above. After 48 hrs, the cells were fixed in acetone and probed with a cocktail of two monoclonal antibodies that are specific for double-stranded RNA (dsRNA; O'Brien, Hobson-Peters, Hall et al., unpublished) using methods described previously [17] .", "No specific permits were required for the described field studies and no specific permissions were required for the locations/ activities for mosquito trapping because they are public lands and are not privately owned or protected. The sites of mosquito trapping are those where the Northern Territory Department of Health conducts regular mosquito monitoring and has done so for many years. These field studies did not involve endangered or protected species." ] },{ "paper_id": "29b6131c0d572d383cbc6774b12e4471aa612b07", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The World Health Organization provides guidance, archives, and other information resources on SARS Information from the US Centers for Disease Control on SARS Wikipedia (an internet encyclopedia anyone can edit) has an entry on SARS Collected resources from MedLinePlus about SARS", "Lungs were weighed and homogenized in four equivalent volumes of PBS to generate a 20% solution. The solution was centrifuged at 13,000 rpm on a tabletop centrifuge for 5 min, the clarified supernatant serially diluted in PBS, and 200-ll volumes of the dilutions placed onto monolayers of Vero cells in 60-mm dishes. Following a 1-h incubation at 37 8C, cells were overlaid with 1% agarose-containing medium. Two days later, plates were stained with neutral red and then plaques counted.", "Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed. 0030525.", "The GenBank (http://www.ncbi.nlm.nih.gov/Genbank) accession number for the GD03-S glycoprotein sequence is AY525636." ] },{ "paper_id": "29baaba300edea006f7b4d287edd3426d6573a26", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "29bdff5ccc8a7e0a2b20a3d1ed9354ed29c553a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "host innate immune response, thus providing the greatest opportunity for clinical success.", "Supplemental material for this article may be found at https://doi.org/10.1128/AAC .00629-17.", "SUPPLEMENTAL FILE 1, PDF file, 0.4 MB." ] },{ "paper_id": "29cc49c0a88d00ecc54d45ff5bf9128e47e9a444", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It should also be noted that cross-reactivity between antibodies against severe acute respiratory syndrome (SARS) coronavirus and HTLV has been observed on occasion [27] . The HTLV antibody response was exhibited when numerous serology tests were performed on samples from patients admitted to a hospital in Taiwan for SARS. However, this was immediately following the SARS outbreak in 2003, and has not been observed in other regions.", "With further in depth research involving these newer methodologies, the significance of these HTLV-I/II seroindeterminate banding patterns will become clearer. As it becomes apparent that the prevalence of seroindeterminates is more widespread than originally thought, it becomes increasingly important to clarify the meaning of these results. If HTLV-I/II seroindeterminates (or subsets of these subjects) represent exposure to prototype HTLV-I or HTLV-II, the frequency of infection in the general population will be greater than previously believed. It remains to be seen whether the incidence of exposure is also associated with any clinical disease outcome.", "As research progresses, reports of large numbers of HTLV-I/II seroindeterminates have come from Iran, Brazil, Japan, Argentina, Taiwan, the Caribbean, Central Africa, and the United States, indicating a higher prevalence than originally thought [15] [16] [17] [18] [19] [20] [21] . Importantly, the reasons for these blotting patterns remain unclear. Several possible explanations have been proposed for the occurrence of HTLV-I/II seroindeterminates that include cross-reactivities to other known retroviruses or a novel virus, antibody responses to a malaria parasite with epitope homology to HTLV-I, a defective HTLV-I or HTLV-II, and low copy numbers of prototypic HTLV-I in the affected patient yielding the indeterminate antibody response." ] },{ "paper_id": "29d51bb07c2434b1a2f2adf2a0ea52d82c8dfd24", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "29d776d7a6f03cf59887534629dcbe5014f09aed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "On another level, following the September 2001 terrorist events in the US, many federal and local spatial databases, e.g., \"critical infrastructure\" spatial data, were assessed by their holding agencies as a potential liability to national security and withdrawn from the Internet or public dissemination. The current concern is to find an appropriate balance between public access to spatial information and protection of information considered a priority for national security [17, 23] .", "Along the same vein, Amazon.com is now also providing A9 Block View http://a9.com/-/company/Yellow Pages.jsp, an online Yellow Pages/map service that offers US maps with street-level photos.", "programming expertise to use them can also be built using the existing APIs.)", "But despite all these undeniable, legitimate and real concerns about Internet GIS and map data privacy and confidentiality, many of the doubts and misgivings that are raised concerning these aspects of Internet GIS seem to be ill founded, or at least exaggerated. Entchev [19] has wisely stated, \"Let us not cripple the GIS system to meet some vague privacy perceptions\"." ] },{ "paper_id": "29d98c8c19182d261f0f0fd59e09dd466cfcaade", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the authors approved the final version of the manuscript.", "Competing interests MC, YL, DW, AS, RFC, GB, and UBRB declare no competing interests. CT, PAL, PC, HGC, and HTW are affiliated with GeneReach USA, Lexington, MA. However, this does not alter our adherence to BMC Infectious Diseases policies on sharing data and materials." ] },{ "paper_id": "29da5f5d00af5c47f9b3a0a49d561f8caffb0cf3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusions: GUE cures rotaviral enteritis by coordinating antiviral and anti-inflammatory effects. Therapy of this herbal medicine can be a viable medication for curing rotaviral enteritis in animals and humans.", "Porcine K85 (G5[P7]) strain which was originally isolated from fecal sample of a diarrheic piglet [35] was cultured in fetal rhesus monkey TF-104 kidney cell (a cloned derivative of MA-104 monkey kidney cells). Virus titer was determined by cell culture immunofluorescence assay with monoclonal antibody against the VP6 protein of the porcine rotavirus strain OSU, and was expressed as fluorescence focus units per milliliter (FFU/ml)." ] },{ "paper_id": "29e5350bd66573e9e7d304b12b1f551fe59e05f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "29e75f8938836f57cbdfa2e73f05939ee5f561a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Surveillance began on October 1, 2011, and the results were reported weekly by an electronic data reporting system throughout the following year.", "RNA extraction from the viral transport medium was done using NucliSENS easyMag (BioM\u00e9rieux, France), and cDNA synthesis was performed using AccuPowerH CycleScript RT PreMix (Bioneer, Korea effects of independent variables on clinical outcomes. A p-value of ,0.05 by the two-tailed test was considered statistically significant.", "The number of laboratory-confirmed cases and the distribution of influenza types were estimated serially." ] },{ "paper_id": "29e893a01ad314a8432d5948be971e13e48b9103", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Emerging infectious diseases continue to pose serious threats to global public health. So far, however, few published study has addressed the need for manpower reallocation needed in hospitals when such a serious contagious outbreak occurs.", "All claim data in the research database, which we applied for this study, were anonymized and de-identified before its release. According to the local regulations, informed consent is not required in this situation. This study was reviewed and exempted from full review by the institutional review board of Taipei Veterans General Hospital, Taipei, Taiwan." ] },{ "paper_id": "29e94dee0df31f591c6f09c590e4c3523a14e647", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "29f305ed687e42fc04b6707fbcc31d95f5588ab7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In order to examine the sensitivity of parameter assumptions, the following distributional assumptions were considered:", "and", "s:t:" ] },{ "paper_id": "29f7f8a096554d3f4cd512b9e825b72130520f12", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "186 G-V V V V V V G186VPA 100 V-A A A V V A Species-associated signature positions 36 336 L-M L L L L L Increased polymerase activity in mice 37 356 K-R K R R R R Species-associated signature positions 38 409 S-N N N N N N Species-associated signature positions 36 PB1 368 I-V V V V V V Increased transmission in ferrets 18 PB1-F2 66 N-S N N N N N Induction of apoptosis 39 PB2 627 E-K E E K K K 701 D-N D D D D D D701N", "Ethics Statement. Swab sampling and experiments were approved by the Institutional Animal Care and Use Committee of Guangzhou Medical University. All methods were performed in accordance with the relevant guidelines and regulations.", "Some limitations of this study are noteworthy. First, because of the necessary biosafety restrictions, we did not attempt to isolate and culture the AIVs collected from positive swab samples. However, since their full genomes have been obtained, these novel AIV can potentially be reconstructed through reverse genetics (e.g., in collaboration with researchers with a BSL-3 lab) for further basic virology research. Secondly, sample collection was carried out in a single day at one LPM; therefore, the results could not be generalized to the whole region and for a longer period of time. Additional surveys with longer time frame and in more sampling sites (e.g., in poultry farms and LPMs in southern China, including but not necessarily limited to Fujian, Hunan, Guangxi and Hainan provinces besides Guangdong province) are being planned. The results from these additional studies will be described in subsequent reports." ] },{ "paper_id": "29fdfade9c2f2ec46e06085777de897e0a613984", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Principal component analysis (PCA) reveals that RSCU patterns are related to GC and codon-end binucleotide content", "The parity rule 2-bias plot was constructed using the values obtained from the formulae A3/(A3 + U3) and G3/(G3 + C3). These data were visualised in a scatter diagram with a plot root of 0, and thus all data points were distributed into four quadrants." ] },{ "paper_id": "29ffe6751373335a54c9d02cec1af4cfdf049ea8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PRNT assays were performed against CHIKV-LR as previously described [29] . Sera were heat-inactivated at 56 \u2022 C for 1 h; then, diluted 2-fold in media after an initial 10-fold dilution. A known amount of virus was incubated with each serum dilution for 1 h, after which each virus-serum dilution was used to infect Vero cell monolayers in a 12-well plate. Plates were treated like a virus titration from that point on. The number of plaques in un-neutralized wells was 136, making a 50% reduction (PRNT 50 ) yield 68 plaques and an 80% reduction (PRNT 80 ) yield 28 plaques. The LOD was a titer of 1/20 and any titer below this was set at half of the LOD (titer of 1/10).", "The most commonly used strain to perform in vivo vaccine efficacy studies is the LR strain. However, multiple lineages of CHIKV are found worldwide and have slightly different phenotypes in the A129 mouse [15] . Regardless, all known CHIKVs are comprised of one serotype and antibody immunity against one lineage can be cross-neutralized by another [29] . Pre-challenge serum was tested by PRNT only against the LR strain here but future studies will expand upon this panel to confirm high-neutralizing antibody titers against all known lineages to add further evidence of the cross protective efficacy of the mosaic antigen evaluated.", "Vero CCL-81 cells (American Type Culture Collection, Manassas, VA, USA) were maintained in Dulbecco's minimal essential media (DMEM, Gibco, Thermofisher Scientifc, Waltham, MA, USA) supplemented with 10% fetal bovine serum (FBS, Atlanta biologicals, Flowery Branch, GA, USA) and 1% penicillin/ampicillin (Gibco, Thermofisher Scientific, Waltham, MA, USA). Cell cultures were maintained in an incubator set to 37 \u2022 C with 5% CO 2 ." ] },{ "paper_id": "2a1e091e9ed956fa71921a76e014e1694c855d04", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Saliva and mouth-to-mouth contact were the most frequently mentioned modes of transmission.", "\"If my mother has TB, I am more likely to get the disease than my wife. My mother and I have the same blood type.\"", "Participants mentioned poor living conditions, low quality and lack of food, and stress as factors contributing to TB.", "Ethical approval for the study was obtained from the Ethical committee of the School of Medicine, University of Belgrade.", "Participants (especially those having someone close with TB) had heard of the term cavity and knew that patients with cavity are contagious." ] },{ "paper_id": "2a246ea75b64133cf7210fa8971a6d43917da132", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Despite the impressive wealth of studies assessing GRFT's therapeutic value, little is known about its pharmacokinetic profile, which could limit its use as a drug. Therefore, this study aimed to evaluate the pharmacokinetic properties of this promising antiviral, after administration by different routes.", "Recombinant GRFT produced in Nicotiana benthamiana plants as described previously [15] was purified to >99% purity in phosphate-buffered saline (PBS, pH 7.4) with <0.05 endotoxin units (EU) per milligram.", "Sprague Dawley (SD) rats (Rattus norvegicus, Charles River Laboratories, USA) weighing 250 g were housed in a temperature-and humidity-controlled room with an alternating light/dark cycle of 12 h, with standard diet and water ad libitum. All animal procedures were approved by the University of Louisville's Institutional Animal Care and Use Committee." ] },{ "paper_id": "2a2a3087f3f753cbfdab460a0a31c0ac64b0cc52", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Empirical risk factor analysis ", "Where u is equal to a uniform random number between 0 and 1and t 1/2 is equal to the half-life of seroconversion.", "The primary motivation behind this study was to emphasize that not all cattle movements and not all cattle herds are epidemiologically equal. Although BVDV was used as a case example, the basic principles and methodologies are equally relevant to the many other infectious cattle diseases that spread through cattle movement networks, such as bovine tuberculosis, bovine paratuberculosis, bovine herpesvirus 1, bovine leukaemia virus, and contagious mastitis. Most importantly, this analysis demonstrates how the basic records of individual births, deaths, and movements available through national cattle movement databases can be used in future research studies to better quantify disease specific risk factors for infectious diseases and to determine the relative importance of high risk movements to disease transmission dynamics at the population level." ] },{ "paper_id": "2a3a08fcd21eb4e6ed6251960b7e1e6cf1a7f18a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Four \u03bcLs of cDNA or extract was amplified in a total volume of 20 \u03bcL with 0.5 \u03bcM of each primer and 0.2 \u03bcM of each probe and 10 \u03bcL of Lightcycler Probes Master (Roche Diagnostics GmbH) in the LC480 microwell plate. Primers and probes were designed in-house or chosen from previous publications [9] [10] [11] and optimised so that all targets were efficiently amplified under the same conditions. The assay was evaluated against a panel of known positive and negative respiratory specimens [12] . To increase the sensitivity of detection of the commonly known serotypes of rhinoviruses, enteroviruses and adenoviruses, two sets of primers and/or 2 probes were used for each of the virus groups ( Table 1 ). The Taqman real-time PCR assay conditions consisted of denaturation (95\u00b0C -10 min) and amplification (40 cycles of 95\u00b0C -10 sec, 58\u00b0C \u221215 sec, 72\u00b0C -20 sec).", "The emergence of a novel pathogen of pandemic potential, as occurred in 2009 with the influenza A(H1N1) pdm09 virus, requires the development of clinical case definitions to assist in managing the clinical, laboratory and public health responses to the new disease. A (H1N1)pdm09 virus is a quadruple reassortant virus of mostly swine-origin influenza genes that was first reported in the United States of America (USA) on 24 th April 2009 [1] , although it was believed to have emerged in Mexico earlier [2] .", "In conclusion, laboratory testing specifically targeting only the new virus will miss other clinically important cocirculating respiratory pathogens in the very early stages of a pandemic. Detecting the presence of other viruses may provide important information on the impact of preexisting viruses when a new pandemic virus is circulating." ] },{ "paper_id": "2a3a68a67776a01043a6a156b69be803c7118a6d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:24934 | DOI: 10.1038/srep24934" ] },{ "paper_id": "2a3e6aaf35057f4222ef436b616e9d05106e076e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The mabs against pigeon CD3 + , CD4 + and CD8 + T lymphocytes are not commercially availble. For this reason they were developed and provided by Dr. Arkadiusz Miazek, M.Sc.Eng. Marta Lisowska and Dr. Andrzej Rapak from Hirszfeld Institute of Immunology and Experimental Therapy (Wroc\u0142aw, Poland) as an external service (see Acknowledgments for details).", "Before the experiment, the optimal concentration of monoclonal antibodies was evaluated by staining isolated mononuclear cells with serial dilutions (1 to 10 \u00b5L per one million cells) of mabs. The optimal concentrations of mabs were 7 \u00b5L/ one million cells (anti-CD3 and anti-CD8 antibodies) and 8 \u00b5L/ one million cells (anti-CD4 antibodies). The cross-reactivity of goat anti-chicken IgM-FITC polyclonal antibodies (AbD Serotec, Kidlington, UK) and their optimal concentration were evaluated in the previous study [37] .", "Funding:", "The production of monoclonal antibodies in mice was carried out in observance of the I Local Ethics Committee in Wroc\u0142aw (Authorization No. 70/2015), whereas experiment trial with pigeons was carried out in strict observance of the Local Ethics Committee on Animal Experimentation of the University of Warmia and Mazury in Olsztyn (Authorization No. 64/2014). The researchers made every effort to minimize the suffering of birds." ] },{ "paper_id": "2a40cae1982703e2b3f357d3721982eef57e0258", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was conducted over a period of two years following the approval from the Institutional Review Board from the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. There was no specific approval number assigned at that time. Informed patient consent was obtained prior to treatment.", "FES is one of the leading causes of morbidity and mortality following skeletal trauma, particularly in long bone and pelvic fractures [13] [14] [15] [16] . Symptoms of FES include a triad of respiratory failure, sensorial disturbances, and petechiae. The majority of mortality is preventable if diagnosed early and treatment is initiated in a timely manner.", "The aerosol therapy is a modality of drug administration where the main advantage is that for a given therapeutic response, the drug dose is several-fold lower, and the systemic absorption is negligible [8] [9] [10] . The aerosol preparations of steroids have the advantages of better pulmonary deposition efficiency, high systemic clearance, and selective binding to the glucocorticoid receptors. The efficacy of inhaled corticosteroids has already been proved in parenchymal lung injury due to chlorine gas [11] and acute respiratory distress syndrome [12] .", "Ciclesonide is an inhaled corticosteroid administered via a metered-dose inhaler (MDI). It can reach the lung parenchyma, unlike most of the previous steroid inhalers that were unable to go beyond the bronchial tree and had minimal effect on endogenous cortisol. It has already been used successfully in the treatment of allergic rhinitis and asthma." ] },{ "paper_id": "2a423f15be9162d939e0402df6f74c31ee2e9486", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although JC virus has been rarely implicated as a cause of nephropathy either alone or in combination with BK, it is more commonly seen as a cause of Progressive Multifocal Leukoencephalopathy, a demyelinating process involving the cerebral white matter. Presenting symptoms include progressive neurologic impairment, which can progress to dementia [108] .", "Biopsy is necessary to confirm a diagnosis of PTLD and to rule out other neoplastic or infectious lesions [73] . Histochemical stains are helpful in narrowing the differential diagnosis. Immunohistochemistry is somewhat less reliable, since viral proteins such as LMP1, LMP2, EBNA1, and EBNA2 may be expressed focally or inconsistently in PTLD cases with EBV infection [78] .", "Clinicians and pathologists should be vigilant and aware of AV nephritis in renal allografts. Diagnosis can be difficult. Few laboratories perform immunohistochemistry for AV.", "Early diagnosis with close monitoring of renal function andserial determinations of Vm continue to represent the most efficacious tool to control PVAN. Systematic reduction in immunosuppression has not been associated with clear evidence of increased chronic rejection but longer times of followup and more stringent studies are necessary to determine the longterm impact of the interventions for PVAN on long-term graft outcomes." ] },{ "paper_id": "2a46fb28bde7f183808bb47ec90ffd8d97511a73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The presence of parasites (Cryptosporidium spp, Giardia spp, Cystoisospora suis and Strongyloides ransomi) was examined using standard diagnostic criteria.", "Positive associations between diarrhoea and microbiological and pathological findings were evaluated using one-sided Fisher's exact tests (\u03b1=0.05). When considered relevant, associations between histopathology and necropsy were also evaluated by Fisher's exact tests (\u03b1=0.05). Since the piglets originated from four different herds, associations within herds were also assessed." ] },{ "paper_id": "2a5d09bdb532096261be55490d99eb996e05ea18", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples were collected from consenting ILI patients at each sentinel site, and subjected to multiplex PCR targeting 16 respiratory viruses for virological surveillance. A two-step realtime RT-PCR was performed using the CFX96 Real-time PCR system (Bio-Rad) and Anyplex II RV16 Detection kit (Seegene ", "Further investigations were carried out if a change was detected. The first step in any outbreak investigation is to confirm the signals. Actually, the use of text message codified to identify affected patients may result some mistakes with inclusion of patients whose main medical complaints would be unrelated to the syndromes under surveillance.", "Specimens (n = 1427) were collected from all the age groups. However, the percentages of sampled ILI patients were statistically different between the age groups with respectively 12% (133/ 1132) of sampled ILI patients among the under 1-year olds, 32% (651/2042) among 1-4yr olds, 38% (368/960) among 5-14yr olds, 43% (138/319) among 15-24yr olds and 19% (137/693) among the over 24yr olds (p,0.001)." ] },{ "paper_id": "2a5f81ece752816e85edfe177f324c522228f292", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting information S1 ", "Prospective observational cohort study." ] },{ "paper_id": "2a6a9de82dc0494f32530e1ee8ee7509367a04fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2a71668dd2b73cbbeb5005a2905688ed276603a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DNA methodology has specific limitations that are similar to those presented with bacterial culture. Advancement in this field would require the capture and amplification from a smaller number (maybe even a single organism) from blood or other bodily fluids. Such a task is not insurmountable but it will be a challenge to make it cost effective.", "Typhoid (enteric) fever is still a common disease in many developing countries but current diagnostic tests are inadequate. Studies on pathogenesis and genomics have provided new insight into the organisms that cause enteric fever. Better understanding of the microorganisms explains, in part, why our current typhoid methodologies are limited in their diagnostic information and why developing new strategies may be a considerable challenge." ] },{ "paper_id": "2a7617954fb5dc66e2d7d62b1e5ea2c54f4e02ce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical evaluation was performed using the statistical software package GraphPad Prism 3.02 (GraphPad Software, San Diego, CA, USA). The results were expressed as mean \u00b1 standard error of the mean (SEM) and t test or the Mann-Whitney test were used. Probability values (P < 0.05) were considered as statistically significant.", "IL-8 is a powerful chemotactic and paracrine mediator for neutrophils, and infiltration of activated neutrophils play a key role in pulmonary inflammation and oxidative injury [34] , a characteristic feature of respiratory viral infections [35, 36] ." ] },{ "paper_id": "2a79ac3a49714d75cfc75c28df0a4e33d9362969", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical and laboratory data were recorded on paperbased case record forms and subsequently entered into an Access 2003 database (Microsoft, Redmond, WA, USA) and systematically checked for errors by comparison with the original case record forms. Data were analysed by Stata/IC version 12.1 (StataCorp, College Station, TX, USA).", "Proportions were analysed by chi-squared or Fisher's exact tests as appropriate. Logistic regression was used to calculate odds ratios (OR) and their 95% confidence intervals (CI). Multivariate models were constructed to determine relationships between age, viral detection, pneumonia severity (<5 years old only), and antimicrobial use prior to admission. Two-tailed p-values of < 0.05 were considered significant.", "Virus detection varied by season. RSV, influenza viruses, and hMPV were all detected in the wet (June-October) and cool (November-February) seasons, whereas adenovirus detection occurred year round and peaked in the late cold and hot (March-May) seasons ( Figure 2 ).", "Interestingly, in an age-adjusted analysis, patients who had received an antimicrobial in the two weeks preceding admission were more likely to be RSV PCR positive (AOR 1.7, 95% CI 1.2-2.5, p = 0.003). No such association was seen for the other viruses. (Figure 3 ). Twenty five patients with influenza A associated pneumonia (admitted May-October 2009) have been described in detail in a previous manuscript [14] ." ] },{ "paper_id": "2a7c951e191425fd9fa5ac108f07a1f02eb75872", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Microglia-T cell crosstalk: key determinants for the trend of immune response", "Whether microglial activation is neurotrophic or neurotoxic is context-dependent", "So far, what we know is that not all microglia respond in the same way, even to the same stimulus, and microglial function is tailored in a context-specific manner [171] . Numerous elements are involved in this context; most likely there are many more beyond what we have discussed here. Identifying these elements and clarifying their interactions or crosstalk with microglia is essential before we are able to design a strategy to control inflammation through the manipulation of microglia. The simple therapy of inhibiting all microglia without differentiating their function in a context-dependent manner surely should be abandoned." ] },{ "paper_id": "2a7fdc03389aef740cb9d6de762e96e52473b236", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza B viruses are divided into two antigenic lineages (Victoria/87 and Yamagata/88) since 1983. Both of them frequently co-circulate during epidemic periods [9] and segment reassortment between strains of both lineages is frequent, making it difficult to produce robust complete-genome phylogenetic analyses. Here, evolutionary trees were reconstructed from the alignment of 485 HA sequences and showed that ten out ", "Influenza A(H1N1)pdm09 Figure 5) .", "To obtain influenza B virus sequences, we used a similar protocol and one set of primers (BM-NS-1 and BM-NS-2) to amplify the HA, NA and NS segments [29] and another set of newly designed primers (M-2eFor: AG AAGYASAGCATTTTCTTGTGA and M-2eRev: TAAA CACCCACATYCCAAACGT) to amplify the M segment." ] },{ "paper_id": "2a8339ac2c0891d5113f221ebd214f2b1d903d38", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Store aliquots as cell pellets peptidyl-prolyl-cis-trans-isomerase SlyD. Such impurities cannot be eliminated easily and are independent on the immobilization support. The higher an expression level of a recombinant protein, the lower the competitive binding effect of host endogenous proteins. In this study, we examined wash buffers to minimize protein impurities resulting from non-specific binding." ] },{ "paper_id": "2a8a6ddd84f0c80ce33fed8960c3201c08e56854", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Then, we verified that NS1 targets the nucleolus in vivo. We infected two-week old Pekin ducks orally with (Figure 2 ) revealed the presence of viral antigens in enterocytes 6 days post-infection. Anti-NS1 antibodies detected with a peroxidase-coupled secondary antibody revealed with diaminobenzidine stained the cytoplasm and subnuclear structures, corresponding to nucleoli ( Figure 2) . Thus, the subcellular localization of NS1 in vitro is consistent with its nucleolar localization in duck intestinal epithelial cells.", "In mammalian cells, nucleolar localization of influenza A NS1 requires the presence of a C-terminal nucleolar localization signal. This nucleolar localization signal is present only in certain strains of influenza A viruses. Therefore, only certain NS1 accumulate in the nucleolus of mammalian cells. In contrast, we show that all NS1 tested in this study accumulated in the nucleolus of avian cells even in the absence of the above described C-terminal nucleolar localization signal. Thus, nucleolar localization of NS1 in avian cells appears to rely on a different nucleolar localization signal that is more conserved among influenza virus strains.", "The nucleolus is a highly dynamic multifunctional subnuclear compartment [1] . It is the site of ribosomal RNA synthesis and ribosomal subunits assembly. In addition, the nucleolus is increasingly recognized as a critical regulator of many other cellular functions, including the regulation of mitosis, cell growth and response to stress [1] [2] [3] . The nucleolus is also emerging as an important target of various viral proteins [4] . Viral proteins targeting the nucleolus are for example implicated in the regulation of apoptosis, as shown with West Nile virus capsid protein, and in the regulation of viral mRNA export, as shown with human immunodeficiency virus Rev protein and with herpesvirus saimiri ORF57 protein [5] [6] [7] . However, for most viruses, consequences of viral protein localization in the nucleolus remain largely unknown [3, 4] ." ] },{ "paper_id": "2a8e26038c98efac0a61629aa6b768fefad5a573", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ligase-like enzyme (33) . EcAtg5 possesses all the characteristic features of canonical ubiquitin ligase, including two ubiquitinlike domains, a helix-rich domain, and the conserved calpain cleavage sites (32, 33) .", "QQ and JW designed the experiments. CL performed the majority of the experiments, analyzed data, and wrote the manuscript. JL and XZ contributed experimental suggestions. SW, YH, and XH helped to design the experiments. All authors revised the manuscript. ", "The datasets for this manuscript are not publicly available because this data has not been published. Requests to access the datasets should be directed to Jingguang Wei, weijg@scau.edu.cn." ] },{ "paper_id": "2a90543a82ae4b2916e12f6294b7a37aa8142942", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations DFA: direct immunofluorescence assay; ADV: adenovirus; RSV: respiratory syncytial virus; IFA: influenza A; IFB: influenza B; PIV 1-3: parainfluenza viruses 1-3; hMPV: human metapneumovirus; picorna: respiratory picornaviruses;", "All samples were analysed at the Institute for Infectious Diseases, University of Bern. The methods used have previously been described [24] .", "An epidemiological year was defined as May 1 st to April 30 th of the following year. Summer was defined as the months July to September, and winter as January to March. Epidemiological years were designated \"odd\" if the month of January was in an odd year, and they were labelled \"even\" if the month of January was in an even year." ] },{ "paper_id": "2a98b0a9e3e89d1aff14a6f64e25374b4e2855a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Staphylococcus aureus [11] and Enterobacteriaceae assays [12] had low sensitivity. An Escherichia coli assay [12] hit Shigella and Vibrio sequences.", "Year Target Pseudomonas aeruginosa, Escherichia coli, and Neisseria meningitidis.", "Black bars indicate the mean, grey bars indicate the median. Top and bottom of each box indicates 75th and 25th percentiles, and grey lines at whisker ends denote min and max values. The wide ranging sensitivities demonstrate both inconsistency in genetic diversity at a given taxonomy level, and inconsistency in signature design approaches." ] },{ "paper_id": "2aa31ef3d9d80509a965846122911a3fc53f7a99", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ribonucleases (RNases) form a very large group of bacterial or eukaryotic enzymes that have been deeply studied in the last 50-60 years (1) . RNases catalyze the hydrolysis of a variety of different RNA substrates (2) , so that a logical and suitable classification in families may not be easy or immediate. Furthermore, a cell contains a large number of distinct RNases, approaching as many as twenty members, often characterized by different or sometimes overlapping substrate specificities (3) . However, notwithstanding this complexity, a useful classification may descend from differentiating intracellular RNases from the ones secreted in extracellular fluids that are also called secretory RNases (1, 4, 5) , on which we will focus our attention.", "Finally, and interestingly, we note that BS-RNase has a high binding affinity also toward the extracellular matrix (ECM), since its cytotoxicity against CHO cells grown in suspension is quite lower than the one exerted vs. the same adherent cell subtype (128) .", "Monomer1-C-term-peptide linker-N-term-Monomer2", "influence of the N-and C-termini in their swapping behavior (16, 267, 273, 274) , in line with RNase S (259): indeed, this derivative dimerizes upon acidic lyophilization, but less than RNase A and obviously only through the swapping of its C-terminus (275) ." ] },{ "paper_id": "2aabf3a6ba52bfdd83a884673fd6e48c67b8727b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A Mann-Whitney (two-tailed) test was performed using GraphPad Prism (GraphPad Software, San Diego California USA). Significance of the data is represented as follows: * p < 0.05, * * p < 0.01, * * * p < 0.001, * * * * p < 0.0001.", "Though birds resistant to influenza transmission have recently been engineered by the incorporation of interfering RNA into the avian genome 41 , there is considerable consumer resistance to this approach, while conventional selective breeding for many traits has existed since the domestication of poultry. Furthermore, as human genetic determinants for influenza are comparatively unknown 42 , a better understanding of the genes and mechanisms involved in susceptibilities identified as a result of animal models could lead to improved therapeutic options in humans 10 .", "Chicken cell lines were produced and maintained at the Pirbright Institute (Compton, UK). Chicken Embryo Fibroblasts (CEFs) of 3 different birds each of Lines C-B12 and 0 were harvested from 10-day old embryos, washed and grown in T25 flasks (Nunc) in a culture media containing Medium 199 supplemented with TPB Glutamine (Sigma), 100 U/ml Penicillin, 100 \u03bc g/ml streptomycin and 10% heat inactivated fetal bovine serum (FBS), equilibrated to neutral pH with sodium bicarbonate and maintained in 5% CO 2 at 41 \u00b0C. Confluent monolayers of cells were washed with warm PBS and infected with a solution of culture media (without FBS) 0.5 \u03bc g/ml TPCK trypsin (Sigma) containing H7N7 strain at different Multiplicity of Infection (MOI) of 0.1 and 0.01. After 1 hour incubation at 41 \u00b0C, cells were washed again and culture media solution was added to the monolayers. After incubation at 1, 6 and 24 hours at 41 \u00b0C, supernatant of infected cells were harvested, centrifuged at 300 \u00d7 g for 10 min to remove dead cells and frozen at \u2212 80 \u00b0C.", "immunological reagents 4 . Mice have been widely employed to study host-genetic determinants and have helped to identify many candidates of the genetic host regions involved 9, 12 , including the influence of Mx gene in susceptibility to influenza 10 . However, it is a poor model for virus transmission 13 . The chicken is a natural host of AIV and obviates the need to use model species." ] },{ "paper_id": "2aad3ed695f9313c14066aa2c385092c7cf814b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Embryo (E) timing was based upon identification of coital plugs (equal to E0.5). Immunohistochemical methods were as described . Embryos were fixed in PBS/2% paraformaldehyde/5% sucrose, cryoprotected with sucrose in PBS to a final of 30%, embedded and sectioned using a Microm EM550 microtome. The 12-lm sections were mounted on glass slides, blocked, and permeabilized with 1% deoxycholate and 0.2% Triton X-100 in PBS, and then incubated overnight at 4\u00b0C with the appropriate primary antibodies. After washing, sections were incubated with secondary antibodies conjugated to fluorescent markers (Jackson Immuno-Research, West Grove, Pennsylvania) for 1 h at room temperature. The sections were again washed, and mounted in prolog gold antifade reagent (Invitrogen, Grand Island, New York; P36930) and cover-slipped before being photographed using fluorescence microscopy . Images were collected using a Microfire 24-bit CCD camera (Optronics, Goleta, California) and imported into Photoshop C2 for preparation of figures.", "All animals were used and housed in accordance with protocols approved in advance by the Institutional Animal Care and Use Committee at the University of Utah . This includes adherence to the Guide for the Care and use of Laboratory Animals of the National Institutes of Health.", "Generation of alpha7-HA-IRES-tauGFP and alpha7-HA-IRES-Cre mice" ] },{ "paper_id": "2ab24bbc71562ee67437db9fee7f83edb40f4de9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The culture supernatant of Vero cells, in which CPE appeared, was used for electron microscopic observation. Samples were fixed with 4% glutaraldehyde, negatively stained with 2% phosphotungstic acid, and then observed using a JEM-1400 transmission electron microscope (JEOL Ltd, Tokyo, Japan).", "Viral dsRNAs were purified as previously described [19] . RNA genomes were purified from each virus solution by using TRIzol (Life Technologies). Each of the purified RNA was mixed with LiCl at its concentration of 2 M, followed by incubation of the mixture at 4uC overnight. The mixture was then centrifuged at 14,000 rpm for 30 min for separation of ssRNA from dsRNA. The supernatant fraction containing dsRNA was treated with ethanol precipitation. Precipitated dsRNA was solubilized with water and separated by 10% SDS-polyacrylamide gel electrophoresis. Genome segments were visualized by ethidium bromide staining.", "Neutralization antibody titers rose significantly against the isolated virus; from 10 in the acute phase to 320 in the convalescent phase.", "The patient of the present study was a 38-year-old Japanese man, who visited Bali, Indonesia in November 2007. After returning to Japan, he presented to a local hospital with high fever, joint pain, sore throat, and cough.", "We found no evidence of human-to-human transmission of the virus among the family members and hospital caregivers, who were in contact with the patient. Given that only a small number of possible human-to-human transmission episodes were reported in the sporadic outbreaks of Melaka, Kampar, and Sikamat viruses [3] [4] [5] , currently the risk of human-to-human infection of these orthoreoviruses would seem to be low." ] },{ "paper_id": "2ab40cd143985f0fe1f581a31c3aa4009e94e759", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Netica software (Norsys Software Corp) was used to perform model construction and inference. Receiver Operating Characteristic (ROC) curve analysis was performed to ", "Dengue is considered a global public health threat due to its potential to rapidly spread across countries [1] . Currently, dengue is endemic in more than 100 countries, with approximately 2.5 billion people at risk. [2, 3] . Dengue infections lead to a wide range of clinical outcomes. The large proportion of asymptomatic and mild dengue infections can lead to underreporting of dengue cases by routine passive surveillance systems [4] [5] [6] .", "In addition, dengue monthly incidence in Bangkok during 2013 to 2014 was obtained from the Ministry of Public Health, Thailand. This information was used as prior knowledge that might influence a physician's diagnosis of dengue.", "A total of 397 patients were recruited in this study, with 171(57%) of them female. Almost one fourth of the patients were students with age between 15 and 20 years. Most of patients (69%) reported that they had no underlying disease ( Table 2) . Among the 214 non-dengue febrile patients, for more than half of them (61%) it was not possible to specifically identify causal agents. About 7%-10% of non-dengue patients had influenza, murine typhus, or leptospirosis (Table 3 )." ] },{ "paper_id": "2ab5a9cc48131a2a4fc4c2e8be6fabc68aa6397c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2ab6b5e2628c1979ae2e65f9a0f9870cb3773d61", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The RVP simultaneously detects influenza A virus (subtyped as H1, H3 or H5), influenza B virus, RSV-A and -B, adenovirus, hMPV, PIV-1, -2, -3 and \u22124, coronaviruses 229E, NL63, OC43 and HKU1, picornavirus (enterovirus and rhinovirus) and human bocavirus. The assay also includes an internal positive control added to each specimen at the extraction step (phage MS2) and a positive run control that is added to each plate (phage lambda DNA) [16] .", "In order to simulate clinical-relevant multiple infections as well as to analyse possible competitive amplification reactions between the different viruses, PBS-buffer was further inoculated with only 4 different viruses in one assay ( Table 3) Table 1 .", "The qualitative Respiratory Validation Panel Global (NATRVP-2, ZeptoMetrix Corporation, Buffalo, New York) was quantified by real-time qPCR. External plasmid standards were used to determine the concentration of the different viruses. Plasmid standards of adenovirus (from position 18895 to 18968, accession number AC_000008), influenza A virus (from position 144 to 238, accession number CY041531), RSV-A (from position 1801 to 1949, accession number M11486), enterovirus (from position 455 to 602, accession number D00820) and rhinovirus (from position 356 to 563, accession number D00239) were established [15] . Samples were analyzed in triplicate in three independent PCR assays. The viruses hMPV, PIV-1, PIV-2 and PIV-3 were quantified by LightMix assays (TIB MOLBIOL, Berlin, Germany).", "The detection of respiratory viruses by multiplex PCR has been described as an important tool for the identification of the pathogens in respiratory tract infections.", "The Legionella pneumophila PCR was carried out in glass capillaries containing 15 \u03bcl reaction mix and 5 \u03bcl DNA extract. The reaction mix consisted of 5 \u00d7 FastStart DNA Master Plus Hybridization Probes (Roche Diagnostics, Mannheim, Germany), 200 nM of each target primer, 150 nM of the target probe, 300 nM of each IC primer for lambda, 100 nM of the IC probe and 0.01 U of UNG (Roche Diagnostics, Mannheim, Germany). PCR was performed on the LightCycler 2.0 system (Roche Diagnostics, Mannheim, Germany) with an UNG activity step at 37\u00b0C for 10 min, preliminary denaturation at 95\u00b0C for 10 min, followed by 45 cycles of denaturation of 95\u00b0C for 2 s, annealing at 55\u00b0C for 10 s and extension at 72\u00b0C for 15 s, with a single fluorescence acquisition step at the end of the annealing step, and a following melt analysis (95\u00b0C for 60 s and 40\u00b0C for 30 s)." ] },{ "paper_id": "2acdee7df15edf13c1f992bc7aed50fa3a193ae6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2ace5853970e68deefd9800fdd135a266237884a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by Harbin Veterinary Research Institute and was performed in accordance with animal ethics guidelines and approved protocols. The animal Ethics Committee approval number is Heilongjiang-SYXK-2006-032.", "The pCold-TGEV-M plasmid was constructed using the F-GST-M and R-GST-M primers (Table 1) ", "Four BALB/c mice were immunized subcutaneously (s.c.) with RS-15-KLH, YT-16-KLH, or YV-20-KLH (100 \u00b5g per mouse) emulsified in complete Freund's adjuvant (Sigma). The mice were immunized four times at two-week intervals. The sera were evaluated using ELISA plates coated with RS-15-BSA, YT-16-BSA, or YV-20-BSA (2 \u00b5g/well). " ] },{ "paper_id": "2ad6ccc77d12ec8c8f91076fd337a01d734e578e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Of note: Reduced immunogenicity in participants with pre-existing immunity against Ad5", "Phase I Dec 2014", "120" ] },{ "paper_id": "2ad8032804b3deb79b634cfbad52efbf2f90da76", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Both active molecules in our study are structurally related to chlorquinaldol (unique chemical structure identifier CID: 6301). According to the PubChem database (https://pubchem.ncbi. ", "Synthetically, substituted quinolines can be accessed from quinoline or quinoline N-oxide precursors.", "Molecules 2018, 23, x FOR PEER REVIEW 2 of 11" ] },{ "paper_id": "2af1bd7a71e67484330a168ec2aa07e383cef140", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using GraphPad Prism (version 8.0.2, GraphPad Software, San Diego, CA, USA). Data were analyzed using Student's t-test or the non-parametric Mann-Whitney test to determine the significance of differences (*p < 0.05, **p < 0.01, ***p < 0.001, n.s. non-significant)." ] },{ "paper_id": "2af9fe633f4839d908785d15bac5c5233a53aca0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Moderate ARDS (partial pressure arterial oxygen/fraction of inspired oxygen ratio = 123 mmHg with positive endexpiratory pressure \u2265 5 cm H 2 O) with bilateral pneumonitis was diagnosed.", "At the 6-month evaluation, the patient displayed only mild exertional dyspnea, stage 1 of the modified Medical Research Council (mMRC) classification, but her physical activity was limited by pain from a sternal fracture caused by a road accident (August 2016). The chest CT scan confirmed residual bilateral basal consolidations.", "All the authors disclose that they do not have any conflicts of interest." ] },{ "paper_id": "2afa3da371e5495dd55f0b4dde4ae7700eaf99d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Concern about possible health effects of indoor air pollution has been increasing especially with respects to allergies and asthma. The dwelling is an important indoor environment, since it is where we spend most time, usually 15-16 h per day [1] .", "The study and the consent procedure were approved by the Regional Ethical Committee in Uppsala, Sweden. All participants gave informed consent. An information letter sent together with the questionnaire stated that if the subjects answered and returned the questionnaire it meant they had given informed consent.", "(1) Gender (female/male); (2) Age;" ] },{ "paper_id": "2afcf2ab2330cb56ec493f82d87fa0c5b5f076e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A two stage pre and post intervention cohort study, and a time series analysis", "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "2aff265697682af71816737a2fd85f1d9bc9a0c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Subsequently, the cumulative incidence can be estimated by: c(t)/q.", "Clarifying the full spectrum of disease is of utmost importance to understanding the expected burden of the ongoing epidemic to the world. The meticulous effort of screening and testing Japanese passengers on evacuation flights indicated that about 90% of infections were not initially ascertained as cases, which must be kept in mind when analyzing the confirmed case data in China. ", "The authors declare no conflicts of interest." ] },{ "paper_id": "2b0d5260ad731335898da719538d30d414a9e39f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vero 76 cells (African green monkey kidney cells, CRL 1587 American Type Culture Collection) were seeded on round plastic coverslips (13 mm diameter, Bibby Sterilin, Stone, UK) and cultured in GM without gentamycin at 37\u00b0C until they reached confluence. Before inoculation, the cells were washed once with phosphate buffered saline (PBS).", "Coverslips from all experimental conditions were fixed in 2.5% glutaraldehyde (Electron Microscopy Sciences, Ft. Washington, USA) for 1-2 h, and processed by routine methods for embedding in epoxy resin (Fluka). Appropriate areas for ultrastructural investigation were selected using semithin sections (1 \u03bcm) stained with toluidine blue (Fluka, Buchs SG, Switzerland). Ultrathin sections (80 nm) were mounted on gold grids (Merck Eurolab AG, Dietlikon, Switzerland), contrasted with uranyl acetate dihydrate (Fluka) and lead citrate (lead nitrate and tri-natrium dihydrate; Merck Eurolab AG) and investigated in a Philips CM10 electron microscope.", "From duplicate samples of three independent experiments uniform random sampled images were acquired using a widefield microscope (Leica LX, Leica Microsystems Mannheim, Germany). Cells and inclusions were automatically detected according to size, shape and intensity and counted using Imaris (Bitplane AG, Z\u00fcrich Switzerland)." ] },{ "paper_id": "2b10c237281a6e5d61e8fff995dc8920465eda56", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Inter-assay coefficient variation. doi:10.1371/journal.pone.0048972.t004" ] },{ "paper_id": "2b244041ab6f2ab167b76c5b17332c5598b56431", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "doi:10.1371/journal.pone.0126510.g002", "Supporting Information S1 Dataset. Genotype sequence and multiple alignment. " ] },{ "paper_id": "2b2903114784318062dabce86e330fbbe9309aa8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found ", "Data availability. Cryo-EM maps have been deposited in the Electron Microscopy Data Bank (EMDB) under accession codes EMD-20671 and EMD-20672. The atomic model has been deposited in the Protein Data Bank (PDB) under accession code 6U7K.", "renewed interest in the development of antiviral therapeutics (5, 6) . Reports of protection against PEDV reinfection and passive transfer of lactogenic immunity to suckling piglets suggest that vaccination would be an effective means of preventing future outbreaks, although there is currently no such approved vaccine in the United States or Europe (7) . Recent efforts in Asia have produced both live attenuated and inactivated vaccines, but their efficacies have yet to be thoroughly evaluated (8) ." ] },{ "paper_id": "2b2b4954a960745a09009e9de6d1cb87358bfa6a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Immunochromatographic strips were generated by assembling a glass fiber (sample pad), conjugate pad, nitrocellulose membrane, and liquid absorbent pad. To compare each combination of antibodies, antigen proteins were diluted to 12.5 ng/0.1 mL in 40 mM phosphate buffer containing 150 mM NaCl and applied to the strips. The color intensity of red lines at the test and control position and the background of the membrane were visually observed and evaluated after a 15 min reaction.", "The purified protein was used to immunize BALB/c mice. After 4 weeks, splenocytes were isolated and hybridomas were generated ( Figure 1B) . Ultimately, 48 stable hybridomas were obtained and designated #1-#48. Among the 48 clones, seven (#5, #13, #20, #25, #29, #45, and #46) were selected for further investigation based on their reactivity to MERS-NP in immunoblot analysis (Figure 1C ).", "YY designed and performed the research, analyzed the data, and wrote the manuscript. SM and SF performed the research, contributed the virus preparation, analyzed the data. SM performed the research, analyzed the data. YM performed the bioinformatics analysis. HK, HK, MT, and TC edited the manuscript. AR directed the research, analyzed the data, and wrote the manuscript." ] },{ "paper_id": "2b2e83d49677c03c836133b83b909f5db0423cc9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The media used for sample collection and storage was supplied by the University of California Davis' Veterinary Medical School's Biological Media Service (BMS). The viral transport media (BMS product #5404) contained minimal essential medium, sodium bicarbonate, HEPES buffer, Gentamycin, Amphotericin B, and water. The Brucella broth (BMS product #5571) contained pancreatic digest of casein, peptic digest of animal tissue, dextrose, yeast extract, sodium chloride, sodium bisulfite, and 10% glycerol.", "(1)", "The decision rule to interpret the score results was to classify a calf as test positive if the total score was greater than a critical point, S cp , and test negative otherwise." ] },{ "paper_id": "2b2ec303d28afd9e460b710dd23efe264a5359f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nasal MucilAir HAE cell cultures from four individual donors (59701, 48401, 43601, 19702) were purchased from Epithelix S\u00e0rl (Geneva, Switzerland) (Tapparel et al., 2013) . Upon receiving the well-differentiated 24-well format transwell HAE inserts, they were cultured for 1 week at air-liquid interface before performing the infection experiments. The MucilAir culture medium (Epithelix S\u00e0rl) was refreshed every 2-3 days.", "The data discussed in this publication has been deposited in NCBI's Gene Expression Omnibus (Edgar et al., 2002) and is accessible through GEO Series accession number GSE117183 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE117183 ", "The downregulated HPeV3-specific DEGs were annotated with various processes such as ones involved in protein translation (translational initiation, SRP-dependent cotranslational protein targeting to membrane), RNA degradation (nuclear-transcribed mRNA catabolic process) and cell metabolism (oxidation-reduction process, mitochondrial ATP synthesis coupled proton transport) ( Figure 5C ).", "Gene Ontology over-representation analyses of biological processes described by the selected DEGs were performed using the topGO R package (Alexa et al., 2006) . Significance for each individual GO-term was computed by means of the weight01 algorithm and Fisher's exact test." ] },{ "paper_id": "2b38999c47f55f18f27ce6dc678dc2b4df381043", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. All relevant data are available from the authors upon request.", "(5 0 -TTGGTCATGATACTGCTGATTGC-3 0 ) and ZIKV 911c (5 0 -CCTTCCACAA AGTCCCTATTGC-3 0 ) and probe ZIKV 860FAM (5 0 -CGGCATACAGCATCAGG TGCATAGGAG-3 0 ) using the TaqMan Fast Virus 1-Step Master Mix (Applied Biosystems, Foster City, CA, USA). A standard curve was generated in parallel for each plate and used for the quantification of viral genome copy numbers. The StepOnePlus Real-Time PCR System (Life Technologies Corporation, Carlsbad, CA, USA) software version 2.3 was used to calculate the cycle threshold values, and a cycle threshold value r38 for at least one of the replicates was considered positive, as previously described.", "Statistical analysis. Results were analysed and graphed using Prism 7 software (Graphpad Software). As appropriate, statistical analyses were performed using two-way ANOVA with Bonferroni's post-test, one-way ANOVA with Dunnett's test or the Mann-Whitney test." ] },{ "paper_id": "2b420869104820f327acb9db991fb1fe7ec281b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Acute bacterial and viral respiratory infections are a leading cause of childhood morbidity and mortality globally [1] [2] [3] [4] . Frequently detected viruses include respiratory syncytial virus (RSV), influenza virus, parainfluenza virus, rhinovirus, human metapneumovirus, and human coronavirus [5] [6] [7] . Six coronavirus species are known to infect humans: Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), associated with zoonosis and high mortality [8] [9] [10] [11] , and Human coronavirus (HCoV)-NL63, -OC43, -229E, and -HKU1, with higher prevalence but reduced mortality [12] [13] [14] [15] ." ] },{ "paper_id": "2b4696bf4bc923a139e8508086f854ca52b690d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We are evaluating new methods for computational annotation of function based on based specifically on their domain architecture (DAAC, or Domain Architecture Alignment and Classification) (22, 25) or any combination of sequence properties and features (ARBA, or Association-Rule-Based Annotator).", "We describe the major developments that we have made since our last update published in this journal in 2017 (1) with a focus on how we are positioning the UniProt database to address the challenges of the increased volume of sequence data entering the database.", "We greatly value the feedback and annotation updates from our user community. Please send your feedback and suggestions to the e-mail address help@uniprot.org or via the contact link on the UniProt website." ] },{ "paper_id": "2b46b2e0798f4e27871c942a86515bdcc64a4a44", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2b532466bcad2dea4891e62bb86097a2089d95ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sequences were assembled with SeqMan and then aligned using MegAlign software (version 7.0; DNASTAR Inc., WI, USA). Pairwise sequence identity calculations were performed using Clustal W software within DNAStar 7.0 software (available at https://www.dnastar.com/). The phylogenetic tree was analysed using MEGA 7.0 software (available at http://www.megasoftware.net/) with the neighbour-joining method with 1,000 bootstrap replicates. Meanwhile, recombination events among BNoV strains were further investigated using RDP4 software with seven different algorithms, RDP, Bootscan, MaxChi, GeneConv, Chimaera, SiScan, and 3Seq [36] .", "Faecal suspensions of each sample were prepared by diluting faeces 1:10 (w/v) in sterile phosphate-buffered saline (pH 7.2). These sample suspensions were mixed for 30 s and centrifuged at 8000 g for 10 min at 4\u00b0C. The supernatants were collected and maintained at \u2212 80\u00b0C until further processing." ] },{ "paper_id": "2b6524fc0ce858d2db326b94ff9bf48cc14cd9a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human embryonic kidney 293T cells and HeLa cells were purchased from ATCC (Manassas, VA, USA) and cultured at 37\u00b0C with 5% CO2 in Roswell Park Memorial Institute-1640 medium (HyClone, China) supplemented with 10% fetal bovine serum (FBS) (PAN-Biotech, Germany), containing 100 U/ml penicillin, and 100 mg/ml streptomycin (GNM15140 Cell lysates and the immunoprecipitates were resolved by 10-12% SDS-PAGE and transferred to pure nitrocellulose membranes (GE). The membranes were blocked in 1% bovine serum albumin (BSA) in TBST buffer for 1 h at room temperature and probed with indicated primary antibodies for 1-2 h at room temperature. After hybridizing with either goat anti-rabbit or goat anti-mouse secondary antibodies at a dilution of 1:10,000 in TBST buffer, the membranes were washed with TBST buffer for four times (10 min each) before visualized with ECL reagents (Advansta).", "Three siRNA oligonucleotides against TRAF3 and the corresponding negative control siRNA were obtained from GenePharma. Sequences are as follows: si-1, 5\u2032-CCACUGGAGAG AUGAAUAU-3\u2032; si-2, 5\u2032-GUUGUGCAGAGCAGUUAAU-3\u2032; and si-3, 5\u2032-CUGGUUACUUUGGCUAUAA-3\u2032. Transfection of siRNA into 293T cells was performed by Lipofectamine 2000 according to manufacturer's instructions.", "The results are expressed as means \u00b1 SD. Statistical analyses were performed on data from triplicate experiments by using twotailed Student's t-test. A P-value of less than 0.05 was considered significant and a P-value of less than 0.01 was considered highly significant." ] },{ "paper_id": "2b6ea0603deab65ea1e0ddf4367985f6061bac9b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Survey methods. Participants were recruited by random digit dialing of all fixed land-line based residential telephone lines. Each telephone number was dialed for a maximum of 5 times until there was a response. Upon a successful telephone connection, we delivered a brief introduction of the study to the respondent. The respondent was then asked about his/her household composition. One eligible household member was chosen randomly from the pool of people who would fulfil age and sex quotas, and invited to participate in our study. Recruitment continued until we met our predefined target sizes by age and sex.", "Ethical approval. The study was approved by Institutional Review Board of The University of Hong Kong/ Hospital Authority Hong Kong West Cluster (HKU/HA HKW IRB). The reference number is UW 14-537. All methods were performed in accordance with relevant guidelines and regulations. Informed consent was obtained from all participants and/or their legal guardians. Data availability. The data collected as part of this survey will be made available to the scientific community via the zenodo data repository as part of a social contact data collection initiative www.socialcontactdata. org thanks to ERC grant TransMID (grant agreement 682540) awarded to Niel Hens (Hasselt University and University of Antwerp).", "Then we applied propensity score analysis to reduce the potential effects due to selected mode of questionnaire medium 37 . The propensity of choosing a paper questionnaire was estimated for each participant in the logistic regression model shown in the above Step 2 (Supplementary Figure S1 ). We created a synthetic sample by matching the resulting propensity scores using the \"MatchIt\" package in R 3.3.3 38 . In the matched sample, we compared the subjects in paper and online questionnaire group by computing the standardized difference of their demographic variables (Supplementary Table S3 )." ] },{ "paper_id": "2b7d5e5ebeba8a9731ed1e98a3ee177499fed7db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Axis I clinical syndromes were diagnosed using the Mini International Neuropsychiatric Interview-Brazilian Version 5.0.0 (M.I.N.I. PLUS), a short, structured diagnostic interview compatible with DSM-IV and ICD-10 criteria [46] ." ] },{ "paper_id": "2b84b189357f940efd105bcfe6e45ea14bdcc95c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For studies where close contacts of confirmed influenza cases (e.g., household contacts of confirmed cases; " ] },{ "paper_id": "2b8c0be4a3bed5dbeea46401dcebe6c1263ead10", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "interconnected for which it is not meaningful to evaluate their independent roles in the present study." ] },{ "paper_id": "2b91f521c12a736203029e85675120740c3c1810", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "On Day 7 pI, animals were euthanized and the upper and lower left lobes of the lung tissues were harvested and formalin-fixed by perfusion followed by paraffin embedding and sectioning. Tissue slides were then stained with hematoxylin and eosin for histopathology assessment.", "All work with animals was conducted in strict accordance with the Institutional Animal Care and Use Committee (IACUC) guidelines from Southern Research Institute (SRI) or Lovelace Respiratory Research Institute (LLRI). For SRI, ferret studies were approved by the Southern Research Institute's Institutional Animal Care and Use Committee. Southern Research Institute has Veterinary Medicine tasked to monitor and support all animal experiments. Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals, National Research Council, 1996. The facility where this research will be conducted is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International. For LLRI, The animal work was reviewed and approved by the LRRI Institutional Animal Care and Use Committee under protocol number 06-017. All work involving infectious agents are reviewed by the LRRI Infectious Agents Committee and approved. All infections and sample collections were performed under 5% isofluorane anesthesia and all efforts were made to minimize suffering.", "Table S1 Genes significantly changed over time in SARS-CoV infected ferret lungs following reinfection. (DOC)" ] },{ "paper_id": "2ba96cb3fe11b62cac4ae9816383256395239409", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Many middle-aged adults have undiagnosed medical conditions, such as diabetes mellitus, and are at higher risk of severe influenza-related complications [9, 10] .", "The questionnaire was designed with reference to past vaccination questionnaires from health authorities [14, 15] and relevant studies [16] [17] [18] . The draft questionnaire was then sent for comment to a multi-disciplinary team, comprised of an infectious disease specialist, an epidemiologist and general practitioners. The questionnaire was in Chinese and English and had 38 questions including 11 on demographic data and 27 covering the factors (variables) to be examined.", "Multi-dimensional factors have contributed to people's choice of whether or not to receive vaccination. These factors comprise of social, environmental and economic dynamics in a specific context. The factors were put in a multiple logistic regression model and statistically adjusted for age, employment status, in receipt of social security, and all independent variables. Before statistical adjustment, most of these factors had statistically significant crude odds ratios. The variables affected each other and many became non-significant after adjustment. There would be a confounding effect between variables.", "The sample size was calculated with a significance level of 0.05 (two-sided) and a power level of 0.80. The calculation of the sample size was done by the Fleiss formula for unmatched case-control studies with dichotomous exposure variables. A minimum sample size of 510 was required with a case-to-control ratio of 1:2 [13] ." ] },{ "paper_id": "2ba9b89e1cab4bfe6b3b82046e458fec8eb12bbd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Data were analyzed using Prism software (GraphPad, San Diego, CA) and Microsoft Excel. Data are representative of three or more experiments and are presented as means \u00b1 SEMs. Data were evaluated statistically with ANOVA or the Student's t-test, with Bonferroni correction for multiple comparisons. Significance was considered at a P value of less than 0.05." ] },{ "paper_id": "2baa5a272429873854470fa3f3cec0c91264f5d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Both experiments were conducted in line with the AR-RIVE guidelines for planning and reporting in vivo experiments and the concept of the 3R's (Reduction, Replacement and Refinement) [15, 16] . In both experiments, efforts were made to minimize the stress and discomfort for the animals. The animals were closely monitored and medical treatment were administered in line with national Norwegian and Swedish recommendations for treatment of pneumonia and diarrhea in calves.", "BRSV RNA was extracted from 200 \u03bcl of Amies medium, using the automated NucliSens easyMAG protocol (Biom\u00e9rieux, Marcy l'Etoile, France), according to the manufacturer's instructions. Quantification of BRSV genomes was " ] },{ "paper_id": "2bc264fbfdad15fb4ef382db12714a5ed5ceabe0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2bc2fe97aaf88704800806bac58b85cfdc39a6e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronavirus prevalence data was analysed using R [14] , investigating the effects of season (spring or autumn), year (2013-2016), and bat gender. Odds-ratio [15] and Fisher's exact test were performed for each variable of season, year, and gender. A significance level of 0.05 was used in the statistical analysis.", "All generated coronavirus sequences belong to the genus Alphacoronavirus, as determined by BLASTn searches and phylogenetic analysis, and they are deposited in the European Nucleic Archive (ENA) database under study accession no. PRJEB28001, PRJEB28437, and PRJEB28438.", "Coronaviruses (CoVs) are a diverse group of large, single-stranded, positive-sense RNA viruses in the family Coronaviridae, order Nidovirales. Certain CoVs can cause severe diseases in animals and humans. Most recently, the SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) epidemics in humans have sparked a renewed interest in coronaviruses. Nucleotide sequencing and phylogenetic analyses have enabled the discovery of spill-over events and back-tracing of the origin of these viruses from their animal hosts." ] },{ "paper_id": "2bc8716c8d60412f241f096246127275b734635b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Teach your friends about bats. vi Be more environmentally conscious (reduce pollution, stop littering, consume less palm oil, conserve energy etc.).", "(f) How do you generally feel about bats? (g) How scary are bats to you?", "Attend another event put on by OBC. v" ] },{ "paper_id": "2bce7709e22e3d5a110cb77501f6d97db10d9c05", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Authors' contributions DT, JP and APB co-wrote this review. All authors read and approved the final version of the manuscript for publication. ", "Maintenance of gut barrier function is critical for normal nutrient absorption while excluding toxins and microorganisms [40] . Mucosal permeability depends mainly on the capacity of tight junctions to efficiently seal the apical poles of epithelial cells. The permeability of the intestinal epithelium is regulated by several stimuli and its increase is associated with secretory diarrhea [41] . Proinflammatory cytokines, such as IFN-\u03b3 and TNF-\u03b1, increase epithelial permeability by reducing the expression of tight junction proteins [42, 43] . Moreover, an impaired intestinal barrier function contributes to disease pathogenesis especially when luminal antigens challenge the intestine.", "Spray dried plasma (SDP) is a protein rich product obtained from the industrial fractionation of blood from healthy animals. Blood is collected with an anticoagulant and centrifuged to separate the blood cells. Plasma is then concentrated and spray-dried under high pressure to achieve a minimum of 80\u00b0C throughout its substance (Fig. 1) . With this procedure, proteins preserve most of their biological activity [1, 2] ." ] },{ "paper_id": "2bd1d7992ad099b99b495fdd79493a00210bcbe0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "would provide useful information on infection control during resuscitation of potentially infected patients with impending respiratory arrest.", "We measured exhaled air dispersion distance using a threshold of 20% normalized smoke concentration because this is a common procedure in flow visualization studies 22 . The arbitrary threshold allows us to eliminate background contamination and provides a clear and distinctive contour for defining the boundary of dispersion. Using this method, exhaled air was shown to disperse by 0.8 and 1.0 m after application of jet nebulizer and non-invasive ventilation, respectively 11, 13, 14 . These data are remarkably consistent with the dispersion of 1.0 m, measured by droplet counts, in patients with influenza and chronic lung diseases receiving the same respiratory therapies 23 ." ] },{ "paper_id": "2bd6e33d92632dfcba4056a2d7355ced5b7ab1fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These interventions were implemented using the following algorithm." ] },{ "paper_id": "2bdf40e784ab64290491a7b7f0dfb785c84c2082", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Comparison of total amount of handled tubes and wrong combinations.", "Simulated glovebox sitting II -pipetting a defined volume from three coloured water reservoirs into a 96-well plate following a certain amount and pattern.", "Comparison of total amount of filled wells and wrong or omitted wells." ] },{ "paper_id": "2be4d8ed799f2556c53e6946720e3033d41060e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "China has four administrative levels -town, county, prefecture and province from low to high in rural, corresponding to community, district, city and municipality in urban area [17] ." ] },{ "paper_id": "2bf3f075175c307923fc400707b30616a676419c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An ubiquitin plasmid with a HA tag (HA-Ub) was a kind gift from Dr. Benhur Lee (David Geffen School of Medicine, University of California, Los Angeles). Transfections were performed using Attractene Transfection Reagent (Qiagen, 301005) as per manufacturer's instructions. As a control plasmid pUC19 was used. Transfections were performed for 24 to 48 hours for optimized protein expression. Preparation of whole cell lysates has been previously described [28] .", "Whole cell lysates were separated on a 4-20% Tris-Glycine Gel and transferred to a polyvinyl difluoride (PVDF) membrane using the iBlot gel transfer system (Invitrogen). Primary antibodies to VEEV Capsid, Ubiquitin (Abcam, ab7780), and Anti-Ubiquitin (linkage-specific K48) antibody (Abcam, ab140601) were used according to the manufacturer's instructions. The blots were incubated with respective secondary HRP-coupled antibody. The membranes were visualized by chemiluminescence using SuperSignal West Femto Maximum Sensitivity Substrate Kit (ThermoScientific) and a BIO-RAD Molecular Imager ChemiDoc XRS system (BIO-RAD).", "LC-MS/MS analysis was carried out as previously described [28, 33] . Briefly, samples were first lysed in 8M urea, after which, they were reduced using DTT and acetylated using iodoacetamide. The reduced and alkylated proteins were trypsin digested (Trypsin, Promega) for 4 hours at 37\u00b0C. The digested peptides were eluted using ZipTip purification (Millipore) and analysis of the peptides was performed by LTQ-tandem MS/MS equipped with a reverse-phase liquid chromatography nanospray (ThermoFisher). After sample injection, the column was washed for 5 minutes at 200 nl/min with 0.1% formic acid; peptides were eluted using a 50-minute linear gradient from 0 to 40% acetonitrile and an additional step of 80% acetonitrile (all in 0.1% formic acid) for 5 minutes. The LTQ-MS was operated in a data-dependent mode in which each full MS scan was followed by five MS-MS scans where the five most abundant molecular ions were dynamically selected and fragmented by collision-induced dissociation using normalized collision energy of 35%. Tandem mass spectra were matched against the National Center for Biotechnology Information human database by Sequest Bioworks software (ThermoFisher) using full tryptic cleavage constraints and static cysteine alkylation by iodoacetamide." ] },{ "paper_id": "2bf62ecb50fd95973de0bf6c1285ac3475fc4cc8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One-to-null probesets 2203 925", "IPI entries and their mappings to external protein accession numbers were acquired from the International Protein Index (IPI) database [21] (release 3.17). Also obtained there were the mapping relations between IPI numbers and transcript IDs (GenBank, RefSeq, and Ensembl). The counterpart file for human was downloaded there too (release 3.16).", "Sum 18894 15288" ] },{ "paper_id": "2bf72671f78524129acb86ceef6c598e10c7daa7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:31176 | DOI: 10.1038/srep31176" ] },{ "paper_id": "2bf9a03995b1056dc5d3e353461d3a31a9348885", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The PBZ was recently discovered to be a specific and high affinity PAR-binding module [40] and possesses the motif consensus sequence", "Poly(ADP-ribosyl)ation regulates many important processes and therefore this signal must be recognised in a timely fashion to allow the appropriate functioning of the cell. The recent discovery of protein domains that specifically recognise and bind to different forms of ADP-ribose and/or a part of the PAR polymer, has significantly improved our understanding of the complex roles of poly(ADPribosyl)ation signalling. Over the last decade, four evolutionary conserved PAR-binding modules have been discovered within numerous proteins with various functions, providing an insight into the regulation of the cellular processes mediated by poly(ADP-ribosyl)ation.", "The PBM was the first discovered protein motif with the ability to recognize and bind PAR [29] . It consists of only 8 amino acids with the following sequence: [53] . It is loosely defined and therefore it is difficult to predict this motif from genome sequences with a high degree of certainty. The X-ray repair cross-complementing gene 1 (XRCC1) is a prominent example of a DNA repair factor that is recruited to DNA strand breaks, through the interaction of its PBM with the PAR synthesized by DNA damage inducible PARPs. In silico predictions indicate the presence of the PBM in more than 800 proteins. Although the functional role of the PBM in the vast majority of these proteins has yet to be confirmed, the broad presence of this motif implies its general role in PAR mediated processes. Although some PBM containing polypeptides have been crystallized, a crystal structure of the PBM in complex with PAR or a PAR fragment is not available, and therefore the precise molecular nature of this interaction is not clear [54] . However, current data implies that the PBM, through its basic residues, forms an electro-positive surface that non-specifically binds to the negatively charged PAR polymer [55] ." ] },{ "paper_id": "2c0c7b9bdc81461fbf533ae6b89fd78326651306", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The human embryonic kidney cell line 293 (Microbix Biosystems, Toronto, ON, Canada), the human lung carcinoma cell line A549 (ATCC # CCL-185) and the type I IFN indicator cell line MxRAGE7 ( [20] , Werner M\u00fcller, German Research Centre for Biotechnology, Braunschweig, Germany) were propagated in Dulbecco's modified Eagle medium (DMEM) with high glucose. A murine fibroblast cell line from Mus dunni [50] was maintained in RPMI medium (Invitrogen/Gibco, Karlsruhe, Germany). Cell culture media were supplemented with 10% heatinactivated fetal bovine serum (Invitrogen/Gibco) and 50 \u03bcg/ml gentamicin. Cell lines were maintained in a humidified 5% CO 2 atmosphere at 37\u00b0C (293, M. dunni) or 32\u00b0C (MxRAGE7).", "The adenoviral vector Ad5.Henv contains a codon-optimized full-length env based on HIV clade C isolate CN54 and was obtained using the AdEasy system after cloning of synthesized DNA into pShuttle-CMV plasmid. Ad5. Hgpsyn contains a codon-optimized HIV gag-pol based on the HIV clade B isolate BH10 that was described before [52] and was constructed using the AdEasy system and vectors pShuttle-CMV and pAdEasy-1.", "For the analysis of F-MuLV-binding antibodies, Maxi-Sorp ELISA plates (Nunc, Roskilde, Denmark) were coated with whole F-MuLV antigen (5 \u03bcg/ml), blocked with fetal calf serum, and incubated with serum dilutions. Binding antibodies were detected using a polyclonal rabbit-anti-mouse HRP-coupled anti-IgG antibody and the substrate tetramethylbenzidine (TMB+; both Dako Deutschland GmbH, Hamburg, Germany). Sera were considered positive if the optical density at 450 nm was 3-fold higher than that obtained with sera from na\u00efve mice." ] },{ "paper_id": "2c0c9617097af6391e34b3f30dde6c1e6845d722", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This large and diverse group has been more formally organized (https://talk.ictvonline.org/ files/ictv_official_taxonomy_updates_since_the_8th_report/m/plant-official/6694). It comprises ten different families that include segmented negative strand virus species infecting plants, arthropods, and vertebrates. This group includes tri-segmented negative-strand RNA viruses, commonly known as bunyaviruses of which several members are important pathogens of animals and humans.", "Arboviruses are arthropod-borne viruses that exhibit worldwide distribution and are a constant threat, not only for public health but also for wildlife, domestic animals, and even plants.", "The Togaviridae family are composed for linear, non-segmented, single-stranded, positive sense RNA viruses. Among this family, only the genus alphavirus, are transmitted by arthropod vectors. Sindbis, Semliki, chikungunya, Mayaro, O'nyong-nyong or Ross River alphaviruses are known to cause human diseases in which rheumatic complaints are a major feature, while eastern equine encephalitis, and Venezuelan equine encephalitis viruses can cause arthritis disease and encephalomyelitis, a potentially fatal inflammatory disease of the CNS with frequent long-term neurological deficits in survivors [116] [117] [118] [119] [120] ." ] },{ "paper_id": "2c1d22afddf9c0d5ea6ae358aab7171b06fbdf0f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The natural course of syphilis begins with an inoculation period of 21 days on average, rarely exceeding 6 weeks. Syphilis can present itself in three different stages, specifically primary, secondary, and tertiary syphilis, with each stage characterized by unique clinical manifestations.", "On physical examination the patient's vitals on admission were a temperature of 37.2 degrees Celsius, a heart rate of 110 beats per minute, a blood pressure of 130/80 mmHg, and a respiratory rate of 40 breaths per minute. General and systemic examinations were significant for a patchy, macular hyperpigmented rash on the dorsum and pedal areas of his foot and on his shins bilaterally ( Figure 1 ) and both decreased breath sounds and vocal fremitus in the right lower chest region.", "Syphilis is a sexually transmitted illness caused by the organism Treponema pallidum. The infection itself is acquired mainly via sexual contact with clinical manifestations such as a chancre or skin rash. However, although less common, the infection can also be contracted by nonsexual contact, organ transplantation, blood transfusion, or in utero infection [1] . With the introduction of penicillin therapy to counter syphilis infection, the number of cases in the developed countries such as United States has decreased by 95% since 1943 [1] ." ] },{ "paper_id": "2c20b67e10309a26ad07fdb1ff5c86c9f966230a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus is transferred by contact with a contaminated intermediate object (fomite).", "Direct transmission Virus is transferred by contact from an infected person to another person without a contaminated intermediate object (fomite)." ] },{ "paper_id": "2c2c2d6a805a6ea5cdd4568c9bedeedc705e1043", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ON-TARGETplus SMARTpool, containing four different siRNA sequences specifically targeting each of murine Irf1 (siRNA Irf1, L-046743-01-0005), murine Cebpb (siRNA Cebpb, L-043110-00-0005), human IRF1 (siRNA IRF1, L-011704-00-0005) and the corresponding non-targeting control (siRNA NEG, D-001810-10-05), were designed and synthesized by Thermo Scientific Dharmacon.", "GRN inference was performed using three distinct approaches:" ] },{ "paper_id": "2c332ca9f08d552ef49e6945655e9059e82ba13d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the 3\u2032-end, we used primer HINGEIgG2rv [previously used and described for phage display library (3)] and HINGEIgG3rv: 5\u2032-AATTGTGTGAGCGGCCGCACCAAGTGGGGTTTT GAGCTC.", "An additional 3\u2032-end primer was used: lib-IgG2/3-CH3-AS: 5\u2032-CTGACCTGGTTCTTGGTCATCTCCTC.", "lib-3-23/53-S: 5\u2032-GTGTCCAGTGTGAGGTGCAGCTG-3\u2032, lib-3-11-S: 5\u2032-GTGTCCAGTGTCAGGTGCAGCTG-3\u2032, and lib-1-46-S: 5\u2032-GTGCTCACTCCCAGGTGCAGCTG.", "Sequencing of the positive DNA clones was done using primer CAG seq2-s 5\u2032-GCTGGTTATTGTGCTGTCTCATC-3\u2032." ] },{ "paper_id": "2c33d7f0e90a4a8a7e7be1d56308496b7e13dad5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All variables were collected and entered into the database before randomization codes were opened. The database was created using the Epi-INFO 3.5.1 software. SPSS 14.0 was used for statistical analyses.", "Randomization for this clinical trial was performed using the Random Allocation Software and simple randomization into two groups by means of a table of random numbers, which generated a simple randomization spreadsheet.", "Placebo: One capsule was administered every 4 hours during waking hours between 7 a.m. and 11 p.m. (five daily doses) for 2 to 3 consecutive days." ] },{ "paper_id": "2c3faeb0d5d8690917ef67e2f36bb59a93072c7b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical significance was determined using one-way ANOVA or Student's t-test. P-values <0.05 * and <0.01 * * were considered to be significant.", "(3) MyD88 is critical in early control and late clearance of the organism.", "IFN-\u03b3 levels in the culture supernatants were determined 72 h post stimulation using sandwich ELISA kits (PeproTech Inc., Rocky Hill, NJ) according to the manufacturer's instructions (Pei et al., 2008) .", "At 8-week post infection (p.i.), one-half of the spleen from each euthanized mouse was used to produce single cell suspensions as previously described. The cell density was adjusted to 2 \u00d7 10 6 per ml using complete RPMI-1640 containing 10% (v/v) heatinactivated FBS, 1 mM non-essential amino acid, 100 \u03bcg/ml of penicillin and 100 U/ml streptomycin. The cell suspension was dispensed to 24-well plates with 1 ml/well and stimulated with heat killed Brucella (HKB) or ConA (2 \u03bcg/ml) for three days. Following stimulation, supernatants were collected and cytokine synthesis characterized. Cells collected from 100 \u03bcl of the suspension were lysed using 1% (v/v) Triton X-100, and the LDH released from live cells was determined using CytoTox 96\u2122 Nonradioactive Cytotoxicity Assay kit (Promega) following the manufacturer's instructions." ] },{ "paper_id": "2c3fc2c522ed72e939effed158240c1c971fbdad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Substrate specificity of NA was affected by altered HA-receptor specificity", "Influenza viruses (H1N1pdm or H9N2) were incubated in 0.1 M acetate buffer (pH 5.0 and 6.5) at 37\u00b0C for 1 h and were neutralized to pH 6.5 by the addition of HEPES buffer. The buffer was then exchanged to phosphate buffered saline (PBS, pH 7.4) through Amicon centrifugal filter unit (Millipore). HA assays were performed in 2-folds dilution using 0.5% TRBC on V-bottom 96-well plates.", "Expression plasmids containing HA or NA were constructed with DNA sequences corresponding to HA (GeneBank accessions: GQ117044(H1N1pdm); EF541403(H5N1/VN1203)) and NA (GeneBank accessions: FJ969517(H1N1pdm); EF541467(H5N1/ VN1203)) cloned into mammalian expression vector pcDNA3.1 (Invitrogen). Both NA and HA proteins were FLAG-tagged at the C-terminus. Site-directed mutagenesis was applied for the constructions of HAdefective mutant at RBS of H1N1pdm (\u0394H1) with L194A and Y195F amino acid substitutions, and \u03b12,6 SA-binding mutant of H5 (H5 mut ) containing Q226L and G228S double mutations in amino acid sequence.", "Cleavage of 3 \u2032 SLN in solution was detected using NMR spectroscopy as previously described [22] . Virus and VLP samples were reconstituted in HEPES-d18 buffered saline and 1 mM 3 \u2032 SLN-BSA was added. 1 H NMR spectra were acquired at 10-min intervals with 64 scans over a spectral width of 6,000 Hz using a Varian 700 MHz NMR System." ] },{ "paper_id": "2c468e84bbaa10edb38eb112ab8088e74073c02f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Specimens from patients and healthy volunteers were collected with informed written consent. The work was conducted in strict accordance with study design approved by the Guy's Research Ethics Committee, St. Thomas' Hospital, London, UK.", "B cells were plated at 500 cells per well on 96 well U-bottom microplates (Nunc, Rochester, NY) along with 3x10 4 cells per well of irradiated (30 Gy) ", "Videos S1 and S2", "Malignant melanoma, the most fatal form of skin cancer, arises from malignantly-transformed melanocytes in the basal layer of the epidermis. The incidence of melanoma has been increasing at an accelerated rate in the past few decades amongst fair skinned populations [1] and advanced forms of the disease are highly resistant to treatment [2, 3] . Thus, an urgent need exists for novel therapies and earlier diagnosis." ] },{ "paper_id": "2c5983eedfe4431e007a45dcf0103176ed1d9ff8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cilnidipine is a dual blocker of L-and N-type calcium channels in vascular smooth muscle or sympathetic nerve terminals that supply blood vessels [28] . It is effective for treatment of essential hypertension and has been approved in Japan [29] . The toxicity of cilnidipine is low (MLD50 .5 g/kg) and has a low incidence of unfavorable side effects in humans [30] . In the present study, cilnidipine also showed effective inhibition of JEV. The replication of JEV was almost completely inhibited by 20 or 15 mM cilnidipine. So, cilnidipine might be a candidate anti-JEV drug.", "Japanese encephalitis virus (JEV), a member of the genus Flavivirus in the family Flaviviridae, is a mosquito-transmitted and zoonotic pathogen that causes 50,000 cases and 10,000 deaths per year [1] . There are .70 arboviruses in the genus Flavivirus including JEV, dengue virus (DENV), West Nile virus (WNV), and yellow fever virus [2] . JEV can cause severe central nervous disorders such as poliomyelitis-like paralysis, aseptic meningitis, and encephalitis in humans. The fatality rate caused by JEV is 10-50% and half of the survivors have severe neurological sequelae, including persistent motor defects and severe cognitive and language impairments [3] . The geographic range of JEV is still expanding with an enhanced threat, and JEV infections have been reported in Australia [4, 5] , Pakistan [6] , and Saipan [7] in the past 30 years. Therefore, JEV is still an important pathogen that has global health significance.", "BHK-21 cells were cultured in Dulbecco's Modified Eagle's Medium (Sigma-Aldrich, St. Louis, MO, USA) supplemented with 10% fetal calf serum (FCS) (Invitrogen, Grand Island, NY, USA), 100 U/mL penicillin (Sigma-Aldrich), and 100 mg/mL streptomycin (Sigma-Aldrich). JEV (P3 strain, Genbank accession no. U47032.1) was propagated in BHK-21 cells with maintenance medium containing 1% FCS, 100 U/mL penicillin, and 100 mg/ mL streptomycin." ] },{ "paper_id": "2c5d1ebec404ad8061eb81e94effbe52a6dbe809", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "N-ethyl maleimide (NEM) was obtained from Sigma. PEOmaleimide biotin (PMB) and Sulfo-NHS-biotin (SNB) were obtained from Pierce.", "residues. Peptide fragments containing NEM-modified SU Cys38, Cys292, and Cys309 were identified ( Figure 2C and 2D). These results conclusively demonstrate that Cys-S \u00c0 residues in SU are targets for sTva-dependent modification by thiol-reactive agents." ] },{ "paper_id": "2c5f5500b79b97672aca47a26df7996390c30459", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "with PTB and CAP and evaluated how well the DNI value predicted PTB compared with other commonly used inflammatory blood markers.", "The diagnosis of PTB was considered definitive when: (1) microbiological examination (acid-fast bacillus stain, polymerase chain reaction, or acid-fast bacillus culture) using respiratory tract specimens confirmed infection with M. tuberculosis 3, 19 ; or (2) the patient's clinical presentation met the criteria for clinical active PTB established by the World Health Organization, when microbiological tests for tuberculosis were negative 20 . Tuberculosis pleurisy was defined when the lymphocytic exudate with pleural fluid adenosine deaminase level was \u226540 U/L and clinical improvement was observed after anti-tuberculosis treatment. CAP was defined as the presence of a new infiltrate on chest radiography without evidence of PTB plus at least one of the following: (1) respiratory symptoms including cough, sputum, dyspnea, or pleuritic chest pain; (2) fever (body temperature \u226538.0 \u00b0C) or hypothermia (body temperature <35.0 \u00b0C); or (3) abnormal breath sounds on auscultation 21 .", "Patient management and data collection. The microbiological etiologies of all patients suspected of having PTB or CAP were evaluated in peripheral blood, sputum, bronchoalveolar fluid, nasopharyngeal or oropharyngeal specimens, or pleural fluid using the following tests; microbiological culture for bacteria; a multiplex real-time polymerase chain reaction (PCR) test for bacterial agents including Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, and Chlamydia pneumoniae etc.; a multiplex real-time PCR for common respiratory viruses; and a urinary antigen test for Streptococcus pneumoniae or Legionella pneumophila." ] },{ "paper_id": "2c6d1fc20495ba6b8b43ffe06cc0d9bb80244d96", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All values were presented as mean \u00b1 S.D. Statistical significance was evaluated using the two-tailed Mann-Whitney U-test; P < 0.05 was considered significant.", "As a rapid developing technology, RNAi has not only become a powerful tool for studying gene function and development of gene-based therapies, but also been widely used in anti-virus researches. Precious studies suggested that, at the molecular, cellular and individual levels, RNAi can potentially be used to block viral transmission and thus prevent the viral diseases [12, 18] . With the high efficiency, specificity and low cytotoxicity, RNAi offered a new promise of anti-viral therapy.", "Background: Dengue viruses (DENs) are the wildest transmitted mosquito-borne pathogens throughout tropical and sub-tropical regions worldwide. Infection with DENs can cause severe flu-like illness and potentially fatal hemorrhagic fever. Although RNA interference triggered by long-length dsRNA was considered a potent antiviral pathway in the mosquito, only limited studies of the value of small interfering RNA (siRNA) have been conducted." ] },{ "paper_id": "2c6d57a5c31e345cd689687255b13506d71df902", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses and software. Statistical analyses were performed on the results of triplicate experiments using GraphPad Prism software version 5.03 (GraphPad Software Inc., La Jolla, CA, USA) and a one-way analysis of variance (ANOVA) test. P values of less than 0.05 were considered statistically significant. The figures were generated using Adobe Photoshop CS3 and Prism 5 version 5.03.", "PSaV can dissociate the lateral surfaces of LLC-PK cells early in infection and that addition of bile acids enhances the disruption of TJs.", "Construction of mutant plasmids. Wild-type pmRFP-occludin plasmid (a generous gift from Jerrold R. Tuner, University of Chicago) was used to construct the plasmid encoding the wild-type occludin tag with GFP at the N terminus. Using a primer pair specific for the coding region of occludin (Table 1) , the occludin gene was amplified by PCR from a plasmid encoding wild-type pmRFP-occludin. After enzymatic digestion and purification, the occludin gene was inserted into a pEGFP-C1 expression plasmid (here designated GFP-WT-OCC). Using the plasmid encoding GFP-WT-OCC, two mutant plasmids (GFP-M1-OCC and GFP-M2-OCC) containing four silent-mutation sites corresponding to each siRNA were generated by site-directed mutagenesis (GeneTailor site-directed mutagenesis; Invitrogen) using primertargeting mutation sites according to the manufacturer's instructions. The mutation sites are shown in Fig. 7A ." ] },{ "paper_id": "2c7260dadc28671d3ba4e14120b63a5232765805", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Includes all participants with known source of payment. \u00a7 Statistically significant. ", "Hajj is a large annual mass gathering that attracts more than two million Muslims from around the world to congregate within confined areas in Makkah, Saudi Arabia. A highly crowded and congested environment during Hajj amplifies risks associated with mass gatherings, including transmission of respiratory organisms, notably Neisseria meningitidis [1, 2] .", "All n/N * (%) Domestic Pilgrims n/N * (%) Overseas Pilgrims n/N * (%) p-Value ", "No identifiable personal data were collected, and respondents' completion of the survey was considered implied consent. This study was reviewed and approved by the Institutional Review Board of King Saud University College of Medicine, Riyadh, Saudi Arabia (E-17-2534)." ] },{ "paper_id": "2c798963aaa2245c095624af78d5638bebf60c2f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The paediatric team were therefore concerned whether this would affect the child's psycho-social development as only the staffs' eyes but no other facial expressions were visible to the child, each time they visited.", "Although infection prevention and control guidelines are necessarily precautionary and generally universal to avoid confusion, supplemental near-patient air sampling can sometimes be used to refine or reassure the need for PPE requirements in specific patient cases, where the need arises.", "Although air sampling has been extensively used in research studies [1] [2] [3] [4] [5] and in specific clinical situations (e.g., to assess the risk of aerosol-generating procedures-AGPs) [6, 7] , it is still not routinely used in hospital infection control situations, though this application is being explored currently by some teams [8, 9] ." ] },{ "paper_id": "2c7f8c9a78ec06b29ea61f2dd02730d2c3af1cfb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analysis of immune cell populations BALF or whole lung homogenate was collected from PBS control and influenza inoculated mice at 2, 5, 6, or 7 dpi.", "Vascular permeability assays. BALF was collected and total protein content quantified by BCA assay (Pierce), and albumin concentration measured by ELISA (Bethyl, Montgomery, TX).", "BALF preparation. Total cell infiltrate into the BALF was counted by Trypan blue exclusion staining." ] },{ "paper_id": "2c9a3072e8533ac8c5a74abfc595966d516a7878", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "AN would like to thank members of the Computational Biology and Bioinformatics Group at COMSATS, Islamabad, for their support.", "The spread of each viral FSF in proteomes was calculated by an f -value, which represents the number of proteomes in a superkingdom (or virus group) encoding an FSF divided by the total number of proteomes in that superkingdom (or group). The resulting statistic is given on a scale from 0 to 1 indicating range from either complete absence (i.e., f -value = 0) to ubiquitous presence (f -value = 1). The index does not evaluate how heterogeneous is that distribution.", "AN conceived the study. AN, KMK, and GCA designed the experiments. SSM and SAZ performed the preliminary experiments and wrote the first draft. AN, KMK, and GCA edited and improved the manuscript. All authors approved the study, final manuscript, and conclusions. " ] },{ "paper_id": "2ca39f3627583a75a4cd19f770b697714a89b686", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Depending on the cell type, the ER can adopt a wide range of organizations to adapt to different functions. Thus, the sheet-to-tubule ratio varies in different cell types reflecting the need for biosynthetic processes occurring in these two structures. In general, cells involved in synthesis and secretion of large amounts of protein (e.g., pancreatic or salivary gland cells) possess many ribosome-studded sheets [7, 19] , whereas poorly secreting cells (e.g., neurons, muscle cells, epithelial cells) contain an abundant tubular network [7, 70] .", "72 73" ] },{ "paper_id": "2ca680635b3f3dcf21ea32eca2ef05b3ef44d3ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The current studies were approved by the Institutional Biosafety Committee (IBC), Protocol ID: 1601-33271H (PI: Davydova, Julia) and the Institutional Animal Care and Use Committee (IACUC), Protocol ID: 1612-34382A.", "As oncolytic adenoviral technology has matured, engineering of tropism-modified viruses utilizing species B (Ad3, Ad35, Ad11) binding domains has emerged as a crucial step to improve the efficacy of conventional Ad5-based vectors. This retargeting has improved infectivity of oncolytic adenoviral therapeutics across a broad range of tumors including pancreatic, gastric, ovarian, melanoma, esophageal, breast, prostate, and others [10, [14] [15] [16] [17] [18] [19] [20] . As the field now moves to bring tropism-modified viruses to clinical practice, the appropriateness of current preclinical animal models must be questioned, and a species B receptor permissive species identified.", "Oncolytic adenoviruses (Ad) have emerged as a promising new therapy in the fight against cancer. Adenoviruses are a family of non-enveloped DNA viruses comprised of 51 different serotypes organized into 6 species (A-F) [1] . The viral capsid is an icosahedron which is composed of hexon and penton base proteins. Attached to each penton base is a fiber protein which consists of three shown in multiple studies to be semi-permissive to human adenoviral infection and oncolytic effect was demonstrated in this animal model [25, 29, 30] . Their widespread use has been hampered because they are a difficult species to work with and have limited commercial availability [26] . Syrian hamsters have emerged as an essential animal model for evaluation of species C serotypes [26, [31] [32] [33] [34] [35] [36] . These animals have been studied extensively and are known to support Ad5 replication. This immune-competent model has enabled the evaluation of Ad behavior in situ with natural host immune responses." ] },{ "paper_id": "2cb1a471e9f1ba5fe1623c8143f8847c0b12dbe6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There are numerous mechanisms of the transmission of zoonoses, and some diseases are transmitted in various ways, which significantly hinders the diagnostic process ( Figure 1) [7] . [7, 8] .", "Sequencing of the C. jejuni NCTC 11168 genome demonstrated the existence of genes that code some proteins with infectious potential. Despite numerous studies on the molecular genetics of Campylobacter spp., their mechanisms of pathogenicity and virulence remain poorly understood [37] .", "Zoonoses, or diseases of animal origin, are defined as diseases transmitted between animals and humans as a consequence of a direct contact, indirect environmental contact, or through food [1]. Among recognised pathogens causing human diseases, almost 60% are of animal origin. They cause such diseases as toxoplasmosis, anthrax, rabies, Ebola haemorrhagic fever, severe acute respiratory syndrome (SARS), and primary HIV infection [2, 3] ." ] },{ "paper_id": "2cb75a42281bf540c142bec979a4bc66da597a3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2cb893552a3e4a8aa105a96476b02c16bf7bef42", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "fAPN/pcDNA3.1D/TOPO and hAPN/pCiNeo plasmid DNAs were provided by Dr. Kathryn V. Holmes (University of Colorado Health Sciences). For standard transfection, 0.6 \u00b5g of plasmid DNA were premixed with 2 \u00b5l of Lipofectamine 2000 (Invitrogen) in 300 \u00b5l of Opti-MEM (Gibco) at room temperature according to manufacture's instructions. Cell monolayers were transfected at 37\u00b0C for 24 hours before fixation or virus infection." ] },{ "paper_id": "2cbb038739adbd4487fa3c529e404189637e59d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each PCR reaction contained: [5, 10, 15, 19] ." ] },{ "paper_id": "2cbcfb658251f2d2873e1ec118deea4167283c0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vaccines represent an effective strategy in the fight against infectious diseases and recent estimates suggest that vaccination prevents 2-3 million deaths every year [1] . The need for rapid and large scale vaccine production during epidemics against emerging pathogens is a major challenge in vaccine development [2] , including effective vaccines for antigenically diverse and versatile pathogens that successfully subvert host immunity such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and malaria [3] [4] [5] .", "A majority of the studies on experimental DNA vaccines with genetic adjuvants have been studied in animal models such as mice (Table 1) , and very few of these have been clinically tested ( Table 2) . Limited published data on clinical trials pose difficulty to compare efficacy between adjuvants in animals and humans. ", ") and humoral (MVA-specific IgG) responses were not significant [85] . Thus, the ability of such an adjuvant to enhance immunogenicity of DNA vaccines in humans is still debated." ] },{ "paper_id": "2cd037e5b6e8f285b0a68b5d10c627d407046c0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Waste management for EVD is a significant hurdle. EVD results in copious amounts of vomit and diarrhea with up to 10 liters of fluid lost by patients each day. Up to 40 large \"bags\" per day", "\u2022 Our experience as an academic health center with EVD emphasized the importance of preparation, communications, and implementation:", "To achieve the lowest risk to health care personnel, the highest level of biosafety was initially employed. This included MAXAIR powered air-purifying respirators (PAPRs), fluid-resistant body suits along with cover aprons, double gloves and shoe covers, and wiping down all Box 1. The SCDU" ] },{ "paper_id": "2cd9b37d110968368ce6f837e002788ac6158af8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These issues are illustrated by interview responses included in the Additional file 2.", "The medical records included demographic characteristics such as age, sex, address, and occupation ( Table 2) ." ] },{ "paper_id": "2ce201c2ba233a562ee605a9aa12d2719cfa2beb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Multiple sequence alignments were performed with ClustalW, 15 and alignments were manually edited with Aliview. 16 For whole genome sequences, MAFFT software was used for alignment with default parameters (http://mafft.cbrc.jp/alignment/server/). Maximum likelihood (ML) trees were estimated in RaxML 17 using the generalized time-reversible (GTR) nucleotide substitution model with gamma distribution among site rate heterogeneity. 18 ", "Data analysis was performed with spss 15.0 (SPSS Inc., Chicago, IL, USA). Differences with an error probability of P<.05 were regarded as significant. For categorical data, we used chi-square testing and Fisher Exact testing as appropriate." ] },{ "paper_id": "2ce32d388ce40b7b9645329a2a2f0edfff7367ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Various approaches have been used to prevent ETEC PWD, including passive administration with specific antibodies, dietary supplementation such as prebiotics and probiotics and dietary preventive measures, genetic breeding for ETEC-resistant herds and live oral nontoxigenic E.coli vaccines [3] .", "When ETEC sustains neonatal diarrhoea, large quantities of watery to a creamy consistency scour are observed, with a distinctive smell and often white to yellow in colour.", "A complete serotyping of H (flagellar protein antigen) and O antigens, with the additional identification of K antigens (capsular polysaccharide), is the standard method for the definition of all serotypes, but in general is carried out in few reference laboratories.", "[28] ( Table 5) ." ] },{ "paper_id": "2cedf6edf59b93290a68074986ee680c8c8e89a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The analyses could not take into animals being bought and sold on to more than one country i.e. the chain of infection [16] and assumed that an animal moved once between countries in its lifetime.", "The poultry and pig sectors had the greatest number of LSU movements, which are being used to indicate" ] },{ "paper_id": "2cf982b22e1f2deebca01ece2c70b0e4828ebc21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis performed using GraphPad Prism software for the Students t test per individual time point of each graph. Any comparisons between timepoints of the same experiment utilize a two-way analysis of variance test with Bonferonni post-tests for multiple comparisons. * p,0.05, ** p,0.01, *** p,0.001.", "This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Institutional Animal Care and Use Committee of The Ohio State University.", "Ready-Set-GO! Spot-forming units (SFU) were enumerated with an ELISpot plate counter (C.T.L.)." ] },{ "paper_id": "2d1c0935153f0c1139529c1c05373504028abd4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Figure 1. JEV NS5 forms a dimer in the asymmetric unit and is monomeric in solution. A) Surface representation of the NS5 dimer in the asymmetric unit viewing down the pseudo 2-fold axis. Coloring scheme: molecule I MTase -lime, RdRP -", "green; molecule II MTase -cyan, RdRP -blue; linker -grey. B) Maximum likelihood superimposition [1] of the two NS5 molecules in the asymmetric unit (RMSD=0.5 \u00c5) shown as cartoon representation. Coloring scheme is as in panel A. C) NS5 has a retention volume around 68 mL in a superdex 200 gel filtration column, consistent with a monomeric state. that motif G of JEV NS5 adopt a canonical conformation. In a very recent report [2] , binding of an inhibitor helped resolve the missing part of motif G in the original DENV RdRP model. However, the observed conformation deviates significantly from the JEV model." ] },{ "paper_id": "2d1d0fbb79973ccbe29af6ae067aa91d05599a4f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All small interfering RNAs (siRNAs) (Gene-Pharma, Shanghai, China) were transfected by PerMute (UcallM, Jiangsu, China) at 50 nM according to the manufacturers' instructions.", "Statistical analysis was carried out with SPSS 13.0. All data are shown as the mean\u02d8SD. The mean values from each group were compared by Student's t-test. In all tests, p-values of less than 0.05 were considered statistically significant.", "Mouse anti-Flag (M2) (Sigma-Aldrich, St. Louis, MO, USA), mouse anti-hemagglutinin (HA) (Merck Millipore, Darmstadt, Germany), anti-GAPDH (BioWorld, Atlanta, GA, USA), anti-HACE1 (Abcam, Cambridge, UK) and anti-GFP (Neobioscience, Shenzhen, China) were from the indicated manufacturers.", "To determine the efficiency of protein knockdown, at 48 h post-transfection, cells were harvested, lysed and immunoblotted with rabbit anti-HACE1 Ab. The sequences of the individual siRNAs were as follows: nonspecific control, 5 1 -UUCUCCGAACGUGUCACGU-3 1 ; HACE1 #1, 5 1 -UAUAGCGCUGAUGUCAACA-3 1 ; HACE1 #2, 5 1 -GGUCUGUUUCUGAACUACU-3 1 [20]." ] },{ "paper_id": "2d1d4b3eee10123a6c8567dbac2705659b8047bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "From April 2012 to December 2015, 12,714 samples were collected: 6,087 stool, 5,827 blood, 661 oropharyngeal, and 139 CSF. Throughout this period, cholera was the main cause of diarrhea among sampled patients 5 years or older and under 5 years old, with 69.3% and 29.0% of samples testing positive by culture, respectively. During this same period, rotavirus was the second most common pathogen in children under 5 with diarrhea (13.9% positive by Premier Rotaclone qualitative EIA) (Figure 4) . Although suspect malaria represents about 25% of all febrile illnesses reported to routine surveillance, from 2012 to 2015, only 2.9% of samples from febrile patients tested positive for malaria by rapid diagnostic test (RDT) (Malaria P. falciparum test First Response Ag [113FRC25]) ( Figure 5 ). Dengue represented 1.9% of cases of febrile illness reported to NESN, 1.9% samples testing positive for IgM and NS1 by RDT (SD Bioline Dengue Duo Rapid Diagnostic Test) ( Table 2) .", "Haiti's Field Epidemiology Training Program (FETP), established in 2011, has trained over 200 MSPP employees including physicians, nurses, laboratory technicians, computer scientists, pharmacists, veterinarians, and surveillance officers in epidemiologic methods, disease surveillance, and outbreak response. These trainees, working closely with departmental epidemiologists, have been involved in detection and response to over 100 outbreaks such as cholera, vector-borne diseases, and food poisoning since the establishment of the program.", "Received December 4, 2016. Accepted for publication May 1, 2017." ] },{ "paper_id": "2d21f74120d056518c96f23fc9df39320c2d598a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. Clinical characteristics and laboratory variables were compared using the Student's t test and Fisher exact test. A 2-sided value of p < 0.05 was considered statistically significant.", "Regarding previous clinical history, 49 out of 346 patients had an underlying disease (leukemia, multiple myeloma, lymphoma, cystic fibrosis, liver transplantation, congenital heart disease, and asthma or recurrent wheezing). Of them, 28/172 patients were infected by EV-D68 (16.3%) and 21/174 by EV-A or B (12.1%) (p = 0.1654). Only 4 of these patients required admission to the ICU.", "Phylogenetic analysis. A total of 201 EV-D68 sequences obtained in this study and detected between 2014 and 2018 were included in a phylogenetic analysis with different EV-D68 sequences available in GenBank in the same 3'-VP1 region from American, Asian and European countries (N = 89). The prototype strain Fer-monUS/1962 was included as the outgroup. The phylogenetic tree was constructed with MEGA 7.0 software using a neighbour-joining distance method under the maximum composite likelihood substitution model with 1,000 bootstrap resamplings. The sequences obtained in this study have been deposited in GenBank under accession numbers MN403103 -MN403299." ] },{ "paper_id": "2d266d6c9ef81ffefa8fc5ba319851d220e71cbd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Respiratory samples were collected during the GRACE study. Flocked nasopharyngeal swabs (Copan) were collected in universal transport medium (UTM). In addition, a single nasopharyngeal specimen was obtained at the Academic Medical Center from a patient with an upper respiratory tract infection.", "Real time PCR for ribosomal RNA was performed as described [5] using primer set 5/6 and the rRNA28S_3674 probe. The platinum quantitative PCR Supermix-UDG system (Invitrogen) was used.", "Virus infections are a continuous threat to the human population; e.g. HIV, hepatitis viruses, and influenza viruses constitute a large proportion of morbidity and mortality each year. Apart from infection with well-described viruses, outbreaks with previously undescribed viruses occur regularly (e.g. SARS-CoV, MERS-CoV) [1] [2] [3] [4] . Furthermore, respiratory tract infections and diarrhoea in young children or immunocompromised persons often test negative for known viruses, and could very well be caused by yet unknown pathogens." ] },{ "paper_id": "2d2670b7397637426c285d293f7e5671d95e0e80", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All cynomolgus monkeys were housed in the South China Primate Research & Development Center (Guangdong, China) and were clinically asymptomatic for known diseases. Peripheral blood samples were collected from over 30 unrelated Vietnamese-origin cynomolgus macaques. The experiments were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of Guangdong Landau Biotechnology Co. Ltd. (project number: IACUC-003).", "with 41 of them (17 Mafa-A, 24 Mafa-B) being identified in our laboratory (Zhang et al., 2012; Zhou et al., 2011; Wang et al., 2011) .", "Total RNA was extracted from peripheral blood mononuclear cell samples of 30 animals using E.Z.N.A. TM Blood RNA Kits (OMEGA bio-tek). cDNA was synthesized using a PrimeScript TM II 1st Strand cDNA Synthesis Kit (TaKaRa Bio, Kusatsu, Japan). Amplification of the full length of exons 2 and 3 sequences was investigated using specific primer pairs (Mafa-A: 'A-F' 5 -AACCCTCCTCCTGGTGCTCT-3 , and 'A-R' 5 -GGAAGGTTCCATCTCCTGCAG-3 , Mafa-B: 'B-F' 5 -AACCCTCCTCCTGCTGCT-3 , and 'B-R' 5 -TGGACTGGGAAGATGGCT-3 ) The two upstream primers are both located in exon 1 and the two downstream primers are located in exon 4. PCR employed a denaturation process for 3 min at 94 \u2022 C, followed by 32 cycles at 94 \u2022 C for 30 s, 58 \u2022 C (Mafa-A) or 56 \u2022 C (Mafa-B) for 30 s, 72 \u2022 C for 1 min, with a final process at 72 \u2022 C for 8 min. Ex Taq DNA polymerase (TaKaRa) was used in this reaction. PCR products were purified and cloned into the pMD18-T vector (TaKaRa). For each animal, about 30 clones were selected for Mafa-A and Mafa-B respectively and then were sequenced bidirectionally by the service provider (Beijing Genomics Institute, Shenzhen, China). Nucleotide sequences of cDNAs were assembled and processed using SeqMan (DNASTAR, Madison, WI, USA Burland, 2000) and aligned using the Clustal W program (BioEdit (Hall, 2015) ). To ensure authenticity, each sequence was uniquely named if three or more identical clones were observed from at least two individuals, or from two independent PCR for an individual. These sequences were then submitted to the GenBank for accession numbers and to the IPD-MHC database for allele nomenclature (Robinson et al., 2013; De Groot et al., 2012) ." ] },{ "paper_id": "2d298d793c2521ceebdcd2c4be960591032ae0d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Monoclonal ELISA was then performed to select for positive clones. One hundred clones were screened for each antigen from each format. Only clones displaying an OD405.2.0 were selected for plasmid preparation and sequencing.", "This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose." ] },{ "paper_id": "2d2b70166db15be7908f748930e9c56a300e5851", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2d2d787fd72d87b38275e4deb4b160ad8c80338c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceived and designed the experiments: HSY. Performed the experiments: WTC YLW. Analyzed the data: WTC HLC HCC. Contributed reagents/materials/analysis tools: WTC YWC. Wrote the paper: HSY WTC TC CSC." ] },{ "paper_id": "2d315ee4d1e5819f972a999a7cc1a1c83a8993e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "is also empty. This simple partition holds the key to computing distance distinguished partition functions below.", "-1", "To simplify, we extend the definition of " ] },{ "paper_id": "2d32032f8498219617634b8b4e5f5c7d214d2ebb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In medicine, analysis of case reports can provide useful information for the general practitioner on the way an outbreak has emerged. New lessons might be learned. In terms of research, the case report can contribute to better understanding of a new and emerging infectious disease through a case series review. Publication in this area is highly welcomed by the journal and can serve as a future point of reference.", "Case reports on infection have a long history. Some case reports can be found in the ancient literature. A good example is the description of a condition that is believed to be \"malaria\" in the papyrus [2] . In ancient Chinese and Egyptian papers, a condition that is believed to be \"syphilis\" is also recorded [3] . Hence, there is no doubt that infection has been focused on by physicians and medical scientists for many centuries.", "The case report is a specific kind of publication in the medical literature. This specific kind of article is seldom seen in other non-medical literature. The case report is usually a short article describing \"an interesting case\" in medicine [1] . This might be a new medical condition, a new diagnostic approach, a new treatment or a new disease. In general, case reports usually describe a specific group of medical disorders including metabolic diseases, malignancies, infections and genetic disorders." ] },{ "paper_id": "2d5916f47ca6cc70ac9f50a2cb85be34b6f8e029", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "http://www.ajlmonline.org Open Access", "The elements of an effective laboratory quality system include organisation, standard operating policies and procedures, a quality control system, planned quality improvement activities, external quality assessments, document control, and a plan for accreditation. These are described in detail below:", "Biologic risk management includes laboratory biosafety and biosecurity, which share the common goal of safe handling of biologic materials and keeping valuable biologic materials safe and secure during use, storage, and transport. 23" ] },{ "paper_id": "2d5a036da3eec69cf318ee695e8bd53347a61a1e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest." ] },{ "paper_id": "2d5fdcbc3c2b82ecef0748012b73fc1aa7a2ad96", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Values were presented as mean with SD. Statistical significance among different groups was calculated by Student's t test using Stata statistical software. P values less than 0.05 were considered significant.", "The animal studies were carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory ", "For N-PAGE analysis, the proteins were first separated by 6% N-PAGE gels using N-PAGE sample buffer and running buffer (Invitrogen), followed by the same protocols as above. For protein cross-linker detection, 4.5 mg of a purified protein was mixed with 20 ml of 0.1% glutaraldehyde (final concentration 4 mM) and left at room temperature in the dark for 2 h before SDS-PAGE and Coomassie Blue staining as described above." ] },{ "paper_id": "2d73c30f41bb0fd24d5ddf1e71a472d971ce4d6f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics Statement: All experiments were approved by the Colorado State University Institutional Animal Care and Use Committee. Work with infectious MERS-CoV strains under ABSL3 conditions was approved by the Institutional Biosafety Committee (IBC). Inactivation and removal of samples form high containment was preformed according to IBC-approved protocols.", "RNA was extracted from swabs, fecal samples and serum samples using the QiaAmp Viral RNA kit (Qiagen) according to the manufacturer's instructions. For detection of viral RNA, 5 \u03bcl of RNA was used in a onestep real-time RT-PCR upE assay using the Rotor-GeneTM probe kit (Qiagen) according to manufacturer's instructions [22] . Standard dilutions of a titered virus stock were run in parallel, to calculate TCID 50 equivalents in the samples.", "Tissues were collected from Bactrian camel 2 and fixed for >7 days in 10% neutral-buffered formalin and embedded in paraffin using standard techniques. Histopathologic evaluation was performed on slides stained with hematoxylin and eosin. Other slides were deparaffinized and immunostained using a rabbit polyclonal antiserum to MERS-CoV (EMC/2012) as primary antibody. Slides were evaluated by a boardcertified veterinary pathologist." ] },{ "paper_id": "2d78b0600b84cfd57e11ba249ee58c159fe517ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It would be of interest to further investigate the association between BCV/BRSV infections and herd health parameters on a larger scale. It would be beneficial to follow herds over time and compare uninfected herds with herds that have shown primary infection during the study period.", "A pooled milk sample from five home-bred primiparous cows was collected from each herd [24] . We used 10ml test tubes containing 1.5 mg of the preservative agent Bronopol (2-bromo-2-nitropropane-1.3-diol). The milk samples were stored at -20\u00b0C until analysis.", "The predictor variables were tested for collinearity by pair-wise Spearman rank correlation test; a test result of <0.6 was considered as negative i.e. no strong correlation. There were no collinearities found between the explanatory variables. No interactions were tested in the statistical model because of the small sample size. To evaluate the fit of the models with significant outcome we plotted the studentised residuals against the predicted observation. The statistical analyses were done using Stata Software (StataCorp. 2006; Stata Statistical Software: Release 9.0; College Station, TX, USA: StataCorp LP)." ] },{ "paper_id": "2d85ecf540b138ba2c5dd735bcf986c58ede052e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analysis. Data were analyzed using GraphPad Prism software (ver. 5.0 GraphPad Software, San Diego, CA, USA). Results are expressed as the mean \u00b1 standard error of the mean (SEM) and were evaluated using Student's t-test or analysis of variance (ANOVA). A value of less than 0.05 was considered statistically significant.", "Ethanol extract of Sanguisorbae Radix AD:", "Atopic dermatitis DNCB: 2,4-Dinitrochlorobenzene H&E:" ] },{ "paper_id": "2d874577cfbe77f483ae4988cda1975f8d470c91", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consistently, the HMC3 cells were also found to have phagocytic properties [29] . In this study, the HMC3 cells were exposed to tetramethylrhodamine (TRITC)-labeled Staphylococcus aures, and phagocytosis was assessed by flow cytometry and confocal microscopy. The HMC3 displayed a significant capacity to uptake the bacterial particles, with two distinct populations indeed detected by flow cytometry. However, the overall phagocytic activity of HMC3 cells was lower if compared to peripheral dendritic cells [29] .", "In contrast to all the evidence reviewed above, none of the following transcripts was detected in the CHME-5 cells by semi-quantitative RT-PCR using human specific primers: IL-1\u03b1 and \u03b2, IL-6, IL-10, IL-12, TNF\u03b1, TGF\u03b2, IFN\u03b3, MIP-1\u03b1, and MCP-1 [105] . In addition, it has recently been shown by genotyping and amplification of a key human gene CyCT1 that several aliquots of CHME-5 cells (in use in different laboratories) are cross-contaminated by rat glioblastoma cells [19] . This observation further highlights the importance of authenticated cell lines as experimental models. This process, which has recently been performed by ATCC\u00ae on the HMC3 cells, ensures for the origin of the cell line excluding cross contamination by other species. In addition, it allows researchers to control the genetic drift that can possibly occur with serial passaging of the cells, contributing to cell heterogeneity in cultures [107] . Genetic drift may explain the subtle differences observed among different laboratories using the same cell line.", "Finally, the expression of classic neurotransmitter receptors has been detected in resting CHME3 cells, with respect to the cholinergic receptor \u03b17nAcR [44] . Interestingly, the expression level of this receptor varied in response to different inflammatory stimuli, including an up-regulation with LPS treatments and down-regulation in response to 10-100 \u03bcg/ml A\u03b2 1-42 . On the other hand, the observation of a direct inhibition of cFos expression obtained with dexmedetomidine, a specific \u03b12 adrenergic receptor agonist, would suggest the presence of these receptors on the HMC3 cell membranes [32] . In addition, it has been documented the expression of functional neurotensin receptor 3 in the aliquot of cells named C13-NJ [46] . Accordingly, neurotensin stimulated microglial migration and cytoskeleton remodeling, via activation of ERK signaling." ] },{ "paper_id": "2d91222fa8318aa7814fe7ad58b9d97c09eb6330", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ": L'ACTIVIT\u00c9 ANTIPALUDIQUE DE LA FERROQUINE : DE LA RECHERCHE \u00c0 LA CLINIQUE La ferroquine (FQ, SSR97193) est actuellement le candidat m\u00e9dicament organom\u00e9tallique le plus avanc\u00e9 dans son d\u00e9veloppement industriel et, en tant que traitement du paludisme non compliqu\u00e9, il devrait bient\u00f4t voir s'achever des \u00e9tudes cliniques de phase II. Ce compos\u00e9 \u00e0 base de ferroc\u00e8ne est extr\u00eamement actif contre des isolats et/ou des clones de Plasmodium falciparum et de P. vivax sensibles ou r\u00e9sistants \u00e0 la chloroquine. Cet article pr\u00e9sente la d\u00e9couverte de la FQ, son activit\u00e9 antipaludique, les hypoth\u00e8ses li\u00e9es \u00e0 son mode d'action, l'absence actuelle de r\u00e9sistance in vitro et, enfin, les r\u00e9cents essais cliniques.", "This mini-review will focus on the discovery of FQ, its antimalarial activity, the hypothesis of its modes of action and recent clinical trials.", "ENANTIOMERS As FQ is a racemic compound. The two stereoisomers were synthetized and showed an antimalarial activity similar to that of the parent compound in vitro (Delhaes et al., 2002) ." ] },{ "paper_id": "2d9482a26d740c255bf3108d1c628e97fae3cc7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The complete genome sequence of the CRCoV K37 strain was deposited at GenBank under the accession no. JX860640.", "In summary, phylogenetic analyses of the genome sequences of CRCoV K37 and the reference coronaviruses obtained from GenBank revealed genetic lineages through Mega 4.1 program analyses (5) . CRCoV belongs to the 2a subgroup, with HCoV, BCoV, BRCoV, mouse hepatitis virus (MHV), pigeon herpes encephalomyelitis virus (PHEV), and coronavirus HKU1 (CoV-HKU1) of coronavirus group 2.", "Total RNA for CRCoV K37 was extracted using the microcolumn-technique-based QIAamp viral RNA minikit (Qiagen), and cDNA was amplified using a one-step reverse transcriptase (RT)-PCR kit (Qiagen). Specific primers for amplification of the genome were designed based on the genome sequences of BCoV. RT-PCR amplification products were cloned into the pGEM-T plasmid and were sequenced with T7 and SP6 sequencing primers using an Applied Biosystems (ABI) Prism 3730xi DNA sequencer." ] },{ "paper_id": "2db670e443cdceb7fb2ff63b6331df5d12efef99", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments were carried out in accordance with protocols (Animal protocol A07-0106) approved by the UBC Committee on Animal Care and the Canadian Council on Animal Care.", "Proteases of the caspase family are known as important mediators of apoptosis and have been commonly subdivided based on their roles in apoptosis or inflammation (apoptotic initiator, apoptotic executioner or inflammatory caspases). This definition however has become somewhat inaccurate as an increasing number of non-apoptotic roles for both initiator and executioner caspases have been identified that mediate cell differentiation, maturation and signaling events [1] .", "For assays using MEF or MCF-7 cell lysates, lysates were diluted in PBS to 0.2 mg/ml, 5 ml were spotted in each well of a Mesoscale ELISA plate and the plate was developed as described above." ] },{ "paper_id": "2dcb2c53f12e45bb92c07e5b47d82dbe495bede9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We used a multiple stakeholder qualitative design (n = 35), conducting interviews with largely tertiary and policy sector health care professionals, as well as primary care physicians, Table 1 . We report study methods following the Consolidated Criteria for Reporting Qualitative research (COREQ) checklist [18] . Data were collected by a senior social scientist and experienced qualitative researcher (ZH), and trained female researchers (SS, JJ and QT), from clinical, bio-sciences and public health backgrounds. ZH initially lead the interviews, supported by the clinical team members who later co-led them together or conducted them independently.", "Capacity is broadly referred to in respect to crowding, and as such is known as the quantitative arm of surge management [13] and having enough of what is needed such as beds, medicine and people to manage it [14, 15] . Capacity was readily understood by our participants as such, for example: 'So I suppose Surge is a statistical term laah, so it refers to incident within a period of time.' -C2.", "Staffing: Manpower management and willingness to work; Space: Institutional roles and national level policy; Supplies: Equipment and stockpiling; Systems: Financing for innovation, communication, monitoring and surveillance, as well as logistics and operations." ] },{ "paper_id": "2dd6dd3a860b840098976e99c1124ea89466e77c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Late ALS 78 \u00b1 2 4(M), 4(F) 4(S), 1(B), 3(-) 29 \u00b1 10 14 \u00b1 5 8", "Late Controls 77 \u00b1 4 2(M), 6(F) n/a n/a n/a 8", "Early ALS 47 \u00b1 6 2(M), 2(F) 1(S), 3(B) 37 \u00b1 11 15 \u00b1 4 4" ] },{ "paper_id": "2ddd50da1dd398931c5db3d1734948ef27b705bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where dow(t) and \u03b4 x,y are described in equation 2, moy(t)", "The value of \u03bb was an adjustable model parameter.", "The predicted threshold for day T was E T + \u03bb\u00b7\u03c3 T ." ] },{ "paper_id": "2de3df4bc6bfab602038165ccb45368768071956", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This provides a chronological list of references to the 80 cellular studies.", "Plasmodium falciparum malaria by identifying and characterizing Plasmodium spp. DNA sequences in faecal samples from wild-living apes: 'Importantly, all currently available human P. falciparum sequences comprised a single lineage nested within the G1 clade of gorilla parasites. This finding indicates that human P. falciparum is of gorilla origin and not of chimpanzee, bonobo or ancient human origin.'", "Ethical approval: Not applicable Guarantor: EM Contributorship: EM" ] },{ "paper_id": "2debc2b3a63c04c798cb30f704911b63d44ec841", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Depending on the required inputs, existing programs for analyzing virus composition can be roughly divided into two groups. One group take assembled contigs as input for functional and compositional analyses. Another group of tools classify reads first and then conduct assembly for classified reads. Below we describe both types of tools and their limitations.", "Additional file 1: Supplementary information for LCS sizes, iterative search, complete assembly results for SARS-CoV data, and tool commands. (PDF 790 kb)", "To test this, we assume that the bat coronavirus (NC_014470.1) was sequenced and available to use as a reference, although it was actually sequenced after the breakout of SARS.", "With T and BWT(T), the backward search can be used to detect overlaps between a query read and all other reads. After matching \u03c4 (the overlap threshold) characters, we search for the delimiter '$' to find the prefixes overlapping with the query's suffix." ] },{ "paper_id": "2df184bde7ca6083d8a33a2b1ce05e302685dc72", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were MIAME compliant and have been deposited in a respective database. The Gene expression omnibus (GEO) number of the microarray data associated with this paper is GSE29061." ] },{ "paper_id": "2df20f5c298fe15e93bc70a752c8566c367f0faa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2e0b69d338fec7a243a0b2c02a7f2a9722e07054", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2e0fdaf23e6de0d6787519f671bc198d47f3acb1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Flu case definition: include only hospital diagnosed cases of the flu, namely ICD9 codes 486XX and 488XX.", "We can also incorporate the evolutionary information into statistical models [43, 30] to understand the how viral evolution affects the disease spread process. Further, these patterns can be examined to identify regions that are vulnerable to specific strains and target them for early intervention. Such enhancements will be evaluated in forthcoming publications from our group.", "For this study, we analyzed the IMS Health claims data from Apr 1, 2009 -Mar 31, 2010, with a total of nearly one billion records. The claims data was processed for flu-related records using the definition shown below:", "The Google Flu Trends (GFT) project [14] builds an automated method for discovering influenza-related search queries by aggregating historical logs of online web search queries and developing a log-linear model that estimates the probability that a query is related to ILI. This model was validated across CDC-observed ILI percentages and made available for the public from http://www.google.org/flutrends/us/#US. We downloaded the weekly information available for the same period covered by the IMS Health claims data (Apr 1, 2009 -Mar 31, 2010)." ] },{ "paper_id": "2e237dc7ffdacf42c76c0671bea72fae2a3ec9e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The threshold level of germline transmission \u03c4* is a monotonically decreasing function of mutation rate \u03bc, mutant replicative advantage \u03c3, and time to transmission T ( Figure I) ", "Europe PMC Funders Author Manuscripts germline transmission, \u03c4) makes it more likely that the germline will be favoured by natural selection.", "With extremely short generation times and high mutability, many viruses can rapidly evolve and adapt to changing environments." ] },{ "paper_id": "2e27f1de90668d3c54ffb49720a9a978383cc78b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fluorescent Au nanoclusters were synthesized using ovalbumin-CpG oligodeoxynucleotides (ODNs) conjugates as templates [71] . The nanoclusters can act as self-vaccines to assist in generation of high immunostimulatory activity.", "Hydrophilic gold nanodots were used to control lipopolysaccharide assembly to ease the formation of stable endotoxin nanovesicles, which are stable precursors of cubosomes and hexosomes with specific immunological effects that might be useful in vaccine development [72] .", "Cancer is one of the main causes of death worldwide, that can affect people at all ages, even small children and foetuses, the risk usually increasing with age [32, 79] . The present treatments consist of surgery, chemotherapy, or radiotherapy, which can have adverse side effects, due to a lack of specificity for tumors [80] . An ideal treatment should aim only at the target tumor cells and have limited detrimental effects on normal cells [32, 79] . [47] )." ] },{ "paper_id": "2e28d846c5181c13e9ff54ef725fb009dd966b47", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Considering health indicators, disease was more severe among cases tested and positive for H1N1 (Table 1) .", "In the current study, we couldn't accurately establish any of the above conditions, since we did not collect data on clinical symptoms (fever, cough) neither obtained the results of those specific laboratory findings or imaging. The diagnosis of H1N1 influenza was also not standardized through all hospitals included. We understand that timing of sample collection, quality of sample and laboratory procedures are key for the accurate diagnosis and unfortunately we do not have data on details regarding these procedures.", "This was not a population based study, however, there was a concern to reduce the impact of nonrandom sampling and an effort to consider representativeness of the national territory (with health facilities from all five macro-regions of the country) and of facilities from public and private sectors, university and non-university hospitals. All selected hospitals had to provide information concerning their characteristics, including location, complexity of level of care, population covered, number of maternity beds and availability of resources for severe cases." ] },{ "paper_id": "2e2de8d6ebd368c062fed5770aa26a780bdc25b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author(s) declare that they have no competing interests." ] },{ "paper_id": "2e313159ccde7f6fbd8d036a04beb2ce3a2809e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The carcass of this pig from Minnesota was submitted for autopsy and diagnostic work-up to the UMN-VDL on May 2016. The pig was 9-to 10-weeks of age and had a history of respiratory disease and rectal prolapse.", "A group of 1000 pigs from a commercial operation in Missouri included 2 % of animals which showed clinical disease of anorexia, weight loss and swollen joints beginning at approximately 1 week post-weaning. Pathological examination of three such animals showed that a variety of known etiologies could account for the signs of two while myocarditis lesions remained unexplained in the third animal who was selected for further studies. Tissues from this 3-week-old pig were submitted to the University of Minnesota Veterinary Diagnostic Laboratory (UMN-VDL) for diagnostic workup in May of 2015. Varied fresh tissues were processed for bacteriology and virology.", "All PCV3 infected pigs in this report were between 2-3 and 9-10 weeks of age. This suggests that animals probably contracted the infection at a young age after birth, although congenital transmission should also be considered. Interestingly, some forms of PCV2-associated disease such as \"porcine multisystemic wasting syndrome\" occur more commonly in pigs between 5 and 12 weeks of age [30] . Agedependent susceptibility to PCV2 infection has been associated with declining levels of maternal immunity obtained through the colostrum in juvenile pigs [31] ." ] },{ "paper_id": "2e32842d3ebcee3ffaf4b6822dbac0f41f82130a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This research involved the use of BALB/c mice. The mice were purchased from Jackson Laboratory (Bar Harbour, ME, USA). All animal experiments were approved and carried out according to the Institutional guidelines for animal care (Christian Medical College, Vellore, India). Studies were conducted on mice housed at 22-24uC in individual ventilated cages. Mice had free access to water and food. All efforts were made to minimize any suffering during our studies.", "Highly purified stocks of recombinant single stranded (ss) and self complementary (sc) AAV2 vectors or scAAV1 or scAAV6 viruses comprising enhanced green fluorescent protein (EGFP) driven by chicken beta-actin (CB) promoter (a kind gift from Dr Arun Srivastava, University of Florida, Gainesville, USA) were generated by triple transfection of AAV-293 packaging cells (Agilent technologies, Stratagene, La Jolla, CA, USA) using The vectors were finally concentrated to a final volume of 0.5 ml in phosphate buffered saline (PBS) using Amicon Ultra 10 K centrifugal filters (Millipore, Bedford, MA). Physical particle titers of recombinant AAV2 stocks were determined by quantitative DNA slot blot analysis [38] .", "The human cervical carcinoma cell line, HeLa, was obtained from the American type culture collection (ATCC, Rockville, MD, USA). The cell line was maintained as monolayer cultures in Iscove's-modified Dulbecco's medium (IMDM, Life technologies, Invitrogen, Carlsbad, CA, USA) supplemented with 10% fetal bovine serum and 1% (by volume) of 1006 stock solution of antibiotics (10,000 U penicillin+10,000 mg streptomycin). Rabbit monoclonal primary antibodies specific for PERK (C33E10), IRE1a (14C10), Phospho-elF2a (Ser51) (119A11), BiP (C50B12), beta-actin (8H10D10) and the anti-rabbit horse radish peroxidise conjugated IgG secondary antibody were from Cell Signaling TechnologyH, Inc. (Danvers, MA, USA). ER stress inducing agents tunicamycin and metformin were from Sigma-Aldrich (St Louis, MO, USA) while dithiothreitol (DTT) was procured from Life technologies." ] },{ "paper_id": "2e34c8495ee4de8e0607b48585b97fa0c0da9dc9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasmids and Antibodies-Plasmid pCMV6-FLAG-CCND3 was generated by subcloning the CCND3 open reading frame (ORF) (Homo sapiens, GenBank TM accession number NM_ 001760.4) from plasmid pCMV6-CCND3-GFP (Origene Technologies) into the pCMV6-Entry vector at the MluI and SgfI restriction sites. Plasmid pCAGGS-M2-FLAG, pCAGGS-M1-HA, and rabbit anti-M1 polyclonal antibody (pAb) were kindly donated by Prof. Adolfo Garc\u00eda-Sastre (Icahn School of Medicine at Mount Sinai).", "TPCK-treated trypsin. Three days after incubating the plates in an upside down manner, plaques were visualized by staining with crystal violet (84) ." ] },{ "paper_id": "2e3c6d9e2a2a8d2d9b43d5ae7b882c9a82557274", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethical approval was obtained at UCLA Fielding School of Public Health and the Kinshasa School of Public Health.", "Human embryonic kidney 293T, human muscle RD, and African green monkey COS-1 cells were grown in Dulbecco's modified essential medium (Hyclone) supplemented with 10% fetal bovine serum, l-glutamine, nonessential amino acids, and antibiotics penicillin and streptomycin (all Gibco) and incubated at 37\u00b0C with 5% CO 2 . For PRNT50 assays: African green monkey kidney cells (VERO C1008 (E6), ATCC, CRL-1586) were maintained in DMEM high glucose with l-glutamine (Lonza 12-604Q) containing 10% heat-inactivated fetal bovine serum (Sigma Life Sciences, F2442). The cells were seeded one day prior at 4 \u00d7 10 4 cells/well in 96-well plates (Greiner bio-one 655948) and 1 \u00d7 106 cells/well in 6-well plates (Corning 3506), respectively, and incubated at 37\u00b0C with 5% CO 2 .", "Univariate analysis was performed for categorical variables using \u03c7 2 or Fisher's exact test, as appropriate using SAS software, Version 9.4 (SAS Institute, Cary, NC)." ] },{ "paper_id": "2e3d6708bedf2af3d3b900329871c910308b0b7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authentication of selected clones, as well as of parental cell lines, was conducted at Genetica DNA Laboratories, Burlington, NC.", "Accession number(s). The genome sequence of Hom-1 was submitted to GenBank and assigned accession no. KY114613.", "Supplemental material for this article may be found at https://doi.org/10.1128/ mBio.00031-17. " ] },{ "paper_id": "2e45e30b65fd34a5727e967dda22436bffc2b57e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequences from bovine CEACAMs are available at NCBI GenBank accession numbers MH684294 -MH684297.", "Bovine peripheral blood lymphocytes and granulocytes were isolated from blood of healthy cattle by centrifugation through a Ficoll-Paque gradient 1.077 g/l (GE Healthcare, Chalfont St Giles, UK). Lymphocytes were taken from the interphase of the gradient and separated from monocytes by plastic adherence for one hour. Granulocytes were collected from the top of the red blood cell (RBC) pellet and further purified by RBC lysis with ammonium chloride. Different bovine tissue samples were collected from freshly slaughtered healthy cattle and stored in the RNA stabilization reagent RNAlater \u00ae (Invitrogen, Carlsbad, US) at 4 \u00b0C for 24 h or at \u221280 \u00b0C for long term storage.", "Bovine ceAcAM cDnA cloning and sequencing. Primers used for amplification of full length cDNAs are shown in Table 1 . For cDNA cloning the RT product was amplified by PCR with Easy-A High-Fidelity PCR Cloning Enzyme (Agilent) and analyzed by agarose gel electrophoresis. Specific bands were extracted from the agarose gel using QIAEX II Gel Extraction Kit (Qiagen). The PCR products were cloned using the StrataClone PCR Cloning Kit (Agilent). Plasmid DNA isolated from various clones were analyzed by PCR and sequencing. Nucleotide sequencing was performed with the BigDye Terminator Cycle Sequencing Kit (PE Applied Biosystems, Weiterstadt, Germany)." ] },{ "paper_id": "2e50303039d019b3f817743da8a21e60f3b99130", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bacterial strains and antibiotic susceptibility testing A total of 400 carbapenem-resistant (with resistance to imipenem or meropenem) Acinetobacter were isolated at Nanfang Hospital in Guangzhou, southern China. Three hundred and fifty of them were collected from different clinical specimens from diverse units of the hospital, between January 2010 and December 2014, and the other 50 were collected from the stool specimens of inpatients, between January 2014 and December 2014. Species identification and antimicrobial susceptibility testing were performed with the BD Phoenix 100 Automated Microbiology System (Becton, Dickinson and Co., Franklin Lakes, NJ, USA). The results of susceptibility testing were interpreted according to the Clinical and Laboratory Standards Institute (CLSI) guidelines (CLSI-M100-S23). The isolates were stored at -80\u00b0C in nutrient broth containing 30% (v/v) glycerol.", "Supporting Information S1 ", "Conceived and designed the experiments: YR QY. Performed the experiments: QY. Analyzed the data: QY. Contributed reagents/materials/analysis tools: QY. Wrote the paper: QY. Critically revised the paper for important intellectual content: YR." ] },{ "paper_id": "2e5bfe1233f49b63cd653c03a695b24f42adaedd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mice FVB mice were purchased from the Frederick National Lab, Maryland. Mice were housed under specific pathogen-free conditions under a 12-h light/dark cycle with access to food and water ad libitum. All the procedures used in this study were approved by the NIH Animal Care and Use Committee.", "Spheroid culture is a common method to detect stem cell features in vitro [19] . Spheroid colony formation was tested by serial dilution technique. Both CCSP + and CCSP 2 cellular fractions were able to form sphere clones. However, following 10 days of culture ( Figure 5 ) CCSPcells demonstrated a larger colony size and higher efficiency of colony formation than CCSP + cells. Dissociation of spheroid colonies into single cells resulted in reformation of the spheroid colonies, indicating that this phenotype was stable (data not shown).", "Total RNA from sorted cells was isolated using an RNeasy minikit (Qiagen, Valencia, CA) by following the manufacturer's protocol. One microgram of RNA was reverse transcribed in a total volume of 20 ml using the QuantiTect RT kit (Qiagen). PCR was performed in triplicate in a MyiQ single color real time PCR detection system (Bio-Rad, Hercules, CA) using SYBR Green PCR kit (Qiagen) according to the manufacturer's protocol. Amplification was confirmed by ethidium bromide staining of the PCR products on an agarose gel. The expression of each target gene was normalized to the expression of 18 S RNA and presented as the ratio of the target gene to 18 S RNA, expressed as 2 2DCt , where Ct is the threshold cycle and DCt = Ct Target " ] },{ "paper_id": "2e6797f37268c2339ab73addc0e9ef77efd3c557", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are reported as mean \u00b1 standard deviation (SD) of at least three independent experiments performed in duplicate. Unpaired student t-test using GraphPad Prism 5.0 (GraphPad software) was used to calculate p values. Differences of P < 0.05 were considered significant.", "West Nile virus (WNV), a mosquito-borne flavivirus that causes lethal encephalitis has emerged as a significant cause of viral encephalitis in the United States [1] . Since its introduction to North America in 1999, outbreaks of WNV fever and encephalitis have occurred in regions throughout the United States [1] . The fatality rate is approximately 10% for hospitalized encephalitic cases with increased risk in patients with compromised immune systems, older age and having underlying conditions such as diabetes mellitus [2] . Currently there are no therapeutic agents or vaccines approved for use against WNV infection in humans. Following peripheral infection, WNV replication is first thought to occur in skin Langerhans dendritic cells. These cells migrate to and seed draining lymph nodes, resulting in primary viremia [3] . By the end of the first week after infection, the virus is largely cleared from the peripheral organs, but in a subset of patients the virus enters the brain and causes a spectrum of neurological sequeale.", "The levels of IL-1\u03b2, -6, -8 and TNF-\u03b1 were measured in the cell supernatant by ELISA, using the Quantakine kits (R&D Systems). The tests were conducted according to the manufacturer's instructions and the plates were analyzed using a Victor 3 microtiter reader equipped with Workout 1.5 software as described previously [31] ." ] },{ "paper_id": "2e6e30e494cf5e2216a4ac5cd2878a17ce8fc4b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Student's t test and the Pearson chi-squared test were used to assess intergroup differences. Statistical analyses were performed with EpiInfo software (V 3.5.1 CDC). A test was considered significant when the p value was < 0.05. The newly obtained sequences were analysed and compared with sequences available in GenBank.", "PIV-3 was detected in seven patients (median age, 16 months; range, 5-48 months) and PIV-1 in four infants (median age, 11 months; range, 3-24 months) between April and November 2010 ( Figure 2B ).", "Background: Acute viral respiratory illnesses in children in sub-Saharan Africa have received relatively little attention, although they are much more frequent causes of morbidity and mortality than in developed countries." ] },{ "paper_id": "2e7571bccf8e71340eae54a7254aa136d0cbbcb3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each parameter is described below.", "Birth and death rate (\u03bc)" ] },{ "paper_id": "2e7a5d9a03e6fdbce778e489686a2533d47f7463", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This review was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases/ National Institutes of Health.", "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.", "Curiously, extensive serological evidence indicates that CCHFV can productively infect numerous vertebrate species, including both wild and domestic animals 5 , yet humans seem to be uniquely susceptible to severe or lethal disease. Even within humans, CCHFV infection may result in a mild or subclinical infection 9 , and why some patients develop a serious or fatal disease whereas others develop an asymptomatic infection is unknown." ] },{ "paper_id": "2e83f16bbbc37d4cf2eba3dd0479e4ec7da6fc41", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Peripheral blood (5 mL) was collected from the jugular vein of each dog and transferred to tubes containing EDTA as anticoagulant. The absolute count of lymphocytes in each sample was obtained using a BC-2800 VET auto hematology analyzer (Mindray, China). Blood samples were stored at room temperature for up to 12 h prior to processing.", "Statistical analyses were performed using Prism 5.0 software package (Prism Software, Irvine, CA, USA). Normality of the data was detected using a Kolmogorov-Smirnoff test. One-way analysis of variance and Tukey post-tests were used to determine the differences between groups. In all cases, the differences were considered significant when p values were < 0.05." ] },{ "paper_id": "2e84c01cad3e1f37940539a14a1f043fadf5b36d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The descriptive analysis was conducted by using R software [6] and Quantum GIS [7] . Geographical data on the administrative boundaries for the whole world were obtained from a spatial database named GADM (http://www.gadm.org/).", "\u2022 Topic 1: Discussion about PE definitions and examples of its successful application.", "We provided two definitions and participants were asked to select the preferred definition, attempt to improve it, or to provide an alternative definition." ] },{ "paper_id": "2e87670d524b1b76e2af6090d5cba472a6448f85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Minimal expenditure on support structures and faculty. Flexible and integrated.", "Students may endeavor to stay in host country. Limited overall improvement to existing health profile.", "Premedical programs for undergraduate students. Example: New York University Abu Dhabi [54] Students in existing or new university can take premedical course." ] },{ "paper_id": "2e8855a1b4fa41526eac0e93264c024aef7f6c9d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using the SPSS software program 20.0. Qualitative variables were compared using the \u03c7 2 test. Quantitative variables were analyzed using the ANOVA test or the Kruskal-Wallis test. Values of p \u22640.05 were considered statistically significant. Length of stay was dichotomized as short (\u2264 7 days) or long stay. FACED and BSI were dichotomized as severe (\u2265 5 and \u22659 points respectively) and not severe.", "The microbiological diagnosis was performed with the following tests: sputum (208 patients), urine antigen test for S. pneumoniae (126) and L. pneumophila (128), two blood samples (87) and nasopharyngeal swabs (125) (for influenza A and B, parainfluenzae, syncytial respiratory virus, adenovirus). Sputum and bronchoalveolar lavage (11) were processed for Gram and Ziehl-Neelsen stains and for cultures of bacterial, fungal and mycobacterial pathogens. Sputum samples were considered acceptable if there were more than 25 leukocytes and fewer than 10 squamous cells per low-power microscope field. Invasive samples were obtained if requested by the attending physician. Microorganism identification was consider positive as in previous publications. [9] Briefly, bacterial identification was achieved by means of the MALDI-TOF MS (Biomerieux, Marcy l'Etoile, France). Antimicrobial susceptibility was tested by the Kirby-Bauer disk diffusion technique on Muller-Hinton or sheep blood agar, depending on the microorganism growth requirements; E-test and in-house PCR were used to assess unexpected resistance patterns.", "The most frequent pathogens found during exacerbation are described in Table 2 . MDR pathogens isolated during an exacerbation were found in 32 out of 241 microorganism, representing 13.2% of all microorganisms isolated: 16 (50%) MDR Pseudomonas aeruginosa, 6 (18.7%) methicillin-resistant Staphylococcus aureus, 2 (6.2%) extended-spectrum beta-lactamase-producing Enterobacteriaceae (Proteus mirabilis and Serratia marcescens) and 8 other bacteria (2 Achromobacter xylosoxidans, 2 Stenotrophomonas maltophilia, 1 Brevundimonas diminuta, 1 MDR Escherichia coli not ESBL, 1 Haemophilus influenzae ESBL and 1 MDR Mycobacterium abscessus).", "Concept of Multidrug resistant pathogens (MDR) [10] MDR pathogens were classified according to European Centre of Diseases Prevention and Control: P. aeruginosa was considered MDR if non susceptible to at least 1 agent in 3 or more antimicrobial categories; MRSA was defined when S aureus was resistant to oxacillin corresponding to a minimum inhibitory concentration (MIC) of \u22654 mcg/mL. Enterobacteriaceae was defined as ESBL+ when they presented resistance to most \u03b2-lactam antibiotics, including penicillin, cephalosporins and aztreonam." ] },{ "paper_id": "2e8bc0044aba50cc5c208dbab92d35493e05eb74", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ACAACTTT GGTATCGTGGAAGGAC and R (5\u2032 to 3\u2032): AGGGATGATGTTCTGGAGAGCC, IFITM1, F (5\u2032 to 3\u2032): ACTGAAACGACAGGGGAAAG and R (5\u2032 to 3\u2032): GAACAGGGACCAGACGACAT.", "The data were expressed as means \u00b1 standard deviations (SD). All the statistical tests were performed using GraphPad Prism software (version 6.0). Statistical significance of differences were determined using the Student's t-test or one-way analysis of variance (ANOVA). P < 0.05 was considered statistically significant." ] },{ "paper_id": "2e905d86f4b7a8cb748864eb560c6555816fb0f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NGS metagenomics has also been used in several environmental studies to discover new species of viruses [24, 25] . These studies estimated an abundance of 10 7 viruses per milliliter of water in marine environments [24] . Others have identified a series of giant viruses in addition to the Acanthamoeba polyphaga mimivirus [26] and characterized virophages as small viruses that infect larger viruses [27, 28] .", "Plasma samples were obtained from patients who read and signed the consent form according to protocols that were reviewed and approved by the Human Research Ethics Boards of the University of Alberta.", "(XLSX)", "Supplemental Tables S29-S42 Summary description of top hits to the virus database from scaffolds alignments with BLASTx. The content of each column is as follows: Scaffold: ID of scaffold after assembly with SOAPdenovo-Trans;" ] },{ "paper_id": "2eb06838c62a16822b1a0aa7be0a43d380025f50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The immune system has evolved to protect multicellular organisms, including humans, from pathogens. Immunostimulatory effects are regulatory actions that counteract reduced immune responses caused by immunodeficiency diseases, viral infections, malnutrition, tumors, and aging. Two strategies have been developed to stimulate the immune system. One method is to increase antigen-specific or nonspecific immune responses, and the other method involves the use of appropriate immunosupplements for antigen administration [1] .", "The data used to support the findings of this study are available from the corresponding author upon request.", "The authors declare that there are no conflicts of interest." ] },{ "paper_id": "2eb279d1dfd4b3649ed0ff00c4e5a72261d445a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2eb55c914df79a8b8cee977bac85d06eb07507d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Trial registration: NCT02605109, date of registration: 11th November 2015." ] },{ "paper_id": "2ebb6c8bf24d0955f26398dcc7653b0f6fb5c9f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 ", "Formal analysis: SX XW YW SL CB AS MO YL. Funding acquisition: KK YL. Investigation: SX XW YW YL. Methodology: SX XW YW MO YL." ] },{ "paper_id": "2ebf1526911eca26db1a7933e592260302caa3b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal experiments were carried out in accordance with the Guidelines for Animal Experiments of the National Advisory Committee on Laboratory Animal Research (NACLAR). Experimental protocols were reviewed and approved by Institutional Animal Care and Use Committee of the Temasek Life Sciences Laboratory, National University of Singapore, Singapore. (IA-CUC approval number TLL-IACUC-2013/002).", "Reverse-genetically (RG) constructed viruses were propagated in RD cell cultures. Harvested supernatants were purified by sucrose gradient centrifugation: cells were pelleted by centrifugation at 8,0006 g for 40 mins, after which the supernatant was", "Brain samples were collected, fixed in formalin, embedded in paraffin blocks, cut at 5 mm thickness (Leica Microsystems, Germany), and attached to coated glass slides. The slides were stained with hematoxylin and eosin (H&E) and observed under light microscopy.", "PLOS Neglected Tropical Diseases | www.plosntds.org hybridomas were subcloned by limiting dilution, and their supernatants were analyzed for the presence of neutralizing antibody." ] },{ "paper_id": "2ec6a171036b53b0c21a39abdfd12756fd02ace6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2ec6d0d83b08c9b4e1784e319978aff1930d5484", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2ed23e6fe433d2ce14436eaa68a9ab6240a00500", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Other than indicated, all programs were run with default parameters (9, 10, 13) .", "The datasets generated for this study can be found in NIH Short Read Archive linked to a BioProject with an accession number of SRP033717.", "Porcine tissues and primary cells used for gene expression and activity assays were cryopreserved samples from a previous study (9) . The Institutional Biosafety and Institutional Animal Care and Use (IBC and IACUC) committees approved all recombinant DNA procedures and animal procedures, respectively. Samples of various tissues were collected, immediately snap frozen and stored in liquid nitrogen until used for nucleic acid or protein extraction (9, 13, 21) ." ] },{ "paper_id": "2ee32c492fb088bca33f2b2409baa37d488dae5c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following antibodies and streptavidin, purchased from BD Biosciences, eBiosciences and BioLegend, were used in this study: ", "expression on M133 Tregs within 1-2 generations of division ( Figure 3F ).", "Brains harvested after PBS perfusion were dispersed and digested with 1 mg/ml collagenase D (Roche) and 0.1 mg/ml DNase I (Roche) at 37uC for 30 min. Dissociated brain was passed through a 70-mm cell strainer, followed by Percoll gradient (70/ 37%) centrifugation. Mononuclear cells were collected from the interphase, washed, and resuspended in culture medium for further analysis." ] },{ "paper_id": "2ee77e390b7b181cef6dfca17f4a6aeab09d0064", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An interferon-induced antiviral RNA binding protein which can selectively bind viral mRNAs and prevent translation [112, 113] .", "A double-stranded RNA (dsRNA) binding protein, recognizes and binds dsRNA before recruiting RNaseL [114, 115] .", "LGALS16 2.00 A galectin protein found specifically within the syncytiotrophoblast [116] that induces T cell apoptosis as a mechanism of immune tolerance [117] ." ] },{ "paper_id": "2efa5dad7a6606eece48c0c389fdd45b2f7c90e6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In summary, most information available for influenza viroporins is centered around AM2, followed by BM2. For the latter, structural data are increasingly available, but protein-protein interaction data studies comparable to AM2 are lacking. Viroporins in ICV and IDV have attracted much less interest, concomitant with their lower virulence in humans and biomedical relevance. Nevertheless, their mode of action, and those of lesser known viroporins, can help to better understand ionic transport across membranes. ", "The authors declare no conflict of interest." ] },{ "paper_id": "2efafa52eab6095a1d2e48ae5acd7f295b634db2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2efb2e64e0fb3039c9fd9bd5abbebaf9d48ed216", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data were statistically analyzed using GraphPad Prism software (GraphPad Software). P value < 0.05 ( * ) and P value < 0.01 ( ** ) were considered statistically significant.", "RS and SCV conceived and designed the experiments; RS performed the experiments and acquire the data; RS and SCV analyzed the data and wrote the paper.", "Copyright: Sarkar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited." ] },{ "paper_id": "2f00227d35cee08706713c7085ec576b74ff2f9a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ii) Removal of host sequences. The program SMALT (Wellcome Trust Sanger Institute, 2012) was used to align the reads against mitochondrial, human genome, and bacterial ribosomal RNA to remove them, using 90% coverage and 90% identity.", "To avoid misclassification, the first 100 hits were obtained for each sequence. Reads that did not map were considered as unidentified.", "v) Assembly. Reads assigned to the same virus family level were subsequently used for de novo assembly with Velvet 1.1.04 to increase the accuracy of classification. Each assembly contig was aligned against BLASTn database." ] },{ "paper_id": "2f071bf96a0a2a1c4fc270a41ca7f4535f474ec5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics. Our work using Merino sheep followed Australian Government guidelines with ethical approval obtained from the FD McMaster Laboratory, Chiswick, Animal Ethics Committee. Approval number AEC0373.", "Data accessibility. All the data described in this study are available from the Dryad Digital Repository: https://doi.org/10.5061/dryad.1802hj0 [60] .", "JL, 0000-0002-2640-1027; MEV, 0000-0002-4857-1238" ] },{ "paper_id": "2f09116d82b287cf3731d3baacc75895e7999203", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Abbreviations: MERS, middle east respiratory syndrome; CoV, coronavirus; ISH, in situ hybridization; IHC, immunohistochemistry; DDP4, dipeptidyl peptidase 4; CD, cluster of differentiation." ] },{ "paper_id": "2f0c1ffd323fc118bfa8cdd80142b126416423f9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:34379 | DOI: 10.1038/srep34379", "Dengue viruses (DENV), which are four mosquito-borne Flaviviruses distributed throughout the tropics, typically cause classical dengue fever (DF), but can also cause dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) 1,2 . Other Flaviviruses include the Yellow fever virus (YFV), West Nile virus (WNV), the Japanese encephalitis virus (JEV), and Zika virus (ZIKV) 3 ." ] },{ "paper_id": "2f132252da880c9c19d5548ef6ab4ac752a90244", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2f2921851e825705103320bf3d61f9d76e4c6b45", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Environmental air was circulated through National Institute of Occupational Safety and Health (NIOSH) BC 251 Personal Aerosol Samplers by AirCheck XR5000 Sample Pumps (Cat. # 210-5000, SKC, Inc., Eighty-Four, PA). Each NIOSH Sampler featured two stages of collection for pathogens greater than 4 and 1-4 \u00b5m in size, and a polytetrafluoroethylene (PTFE) backup filter (0.03 \u00b5m pore, 37 mm) to capture pathogens less than 1 \u00b5m, producing three specimens for each sampler during each run. Pathogens filtered greater than 4 \u00b5m and 1-4 \u00b5m had the potential for remaining viable after capture.", "This study was supported by Duke University discretionary funding (Gray PI).", "Emergency Departments (ED) are often at the frontline of clinical care for many who are seriously ill, unable to be seen acutely by a primary care provider, or are uninsured (1) . Particularly during respiratory virus and seasonal influenza outbreaks, EDs are tasked with the evaluation and treatment of sick individuals. As there is increasing evidence to suggest that respiratory viruses may be transmitted in air (2) (3) (4) , novel surveillance targeting bioaerosols has been suggested as a non-invasive clinical sampling technique (5) ." ] },{ "paper_id": "2f2f4654524b26b1b253d2ca5a6f6bf7e7455f36", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PCV13 vaccination was launched in Vientiane in November 2013, just one month before the beginning of our study. Therefore, it is highly unlikely to see the impact of PCV on pneumonia with such a small cohort and only 1 year post vaccine introduction.", "Although a significant number of studies on respiratory viral infections have been published, there is still a poor evidence-base for understanding the impact of these infections and of potential pharmacological interventions 6 .", "Human ", "In 2012, the World Health Organization (WHO) launched the Battle against Respiratory Viruses (BRaVe) initiative in response to increasing evidence that viruses play an important role in acute respiratory infections (ARI). WHO emphasized the need to prioritize research to gain a better understanding of the epidemiology, pathogenesis, prevention and clinical management of respiratory virus infections across different populations and resource settings 1 ." ] },{ "paper_id": "2f314a77ea26734587af46d6ed32345b0160760e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thirty grams of D. brittonii leaves were mixed with 300 mL of distilled water (DW), and extraction was performed at 110\u00b0C and 39.23 kPa for 15 min in an autoclave (Daihan Scientific, Wonju, Korea). The aqueous phase was collected and filtered with a 0.2 \u03bcm syringe filter (Minisart, Sartorius, Goettingen, Germany).", "Cell culture 3D4/31 macrophages (ATCC-CRL-2844; ATCC, Manassas, VA, USA) were cultured in complete Roswell Park Memorial Institute (RPMI) 1640 medium (supplemented with 10% [v/ v] fetal bovine serum and 1% [v/v] penicillin streptomycin) in a CO 2 incubator (95% air and 5% CO 2 , 37\u00b0C).", "We certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript." ] },{ "paper_id": "2f32fb8cf3cf8e48df1d344dbdd9dd86a00605cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2f38704ef0009750d4c48d1cd7ac81e898023527", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All datasets generated for this study are included in the article/supplementary material.", "The studies involving human participants were reviewed and approved by The Research Advisory Council (RAC) at King Faisal Specialist Hospital and Research Center (RAC# 2121053). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.", "Patient V:5 underwent HSCT from a fully matched sibling (10/10) at 19 months of age. To save his life and because of the disseminated BCGitis, he received no conditioning and no GVHD prophylaxis. The CD34 dose was 9.2 \u00d7 10 6 /kg. He " ] },{ "paper_id": "2f38b7690f9e7ab1069f6b9e28c103de5f6adb96", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, although new lyssaviruses are also being described, the genus forms a well-delineated cluster within the family and does not have any close relationships with other rhabdoviruses.", "A conundrum over lyssavirus origins, emergence, perpetuation-and extinctions?", "All phylogroup I lyssaviruses circulate in bats. Among these, only RABV is also adapted to perpetuation in carnivores. Within phylogroup II, both Lagos bat virus (LBV) and Shimoni bat virus are bat-borne whereas the reservoir of Mokola virus (MOKV) remains unknown 10 . MOKV was isolated on a few occasions from shrews and from spill-over infections to cats and a dog 11 . The West Caucasian bat virus (WCBV) was isolated from a bat, and LLEBV genetic material was identified in a bat as well. Ikoma lyssavirus (IKOV) was isolated from an African civet, but phylogenetic relatedness of this virus to WCBV and LLEBV suggests that it might be a spillover infection, such that IKOV is actually a bat-borne virus as well 8 . Enhanced surveillance activities may help to resolve this point.", "Lyssaviruses are bullet-shaped, single-stranded, negative-sense RNA viruses and the causative agents of the ancient zoonosis rabies." ] },{ "paper_id": "2f405ed2109c2b706eb85413816893558100afba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Noroviruses are positive sense non-enveloped RNA viruses in the Caliciviridae family (51) . In humans, they are the most common cause of epidemic gastroenteritis and are a significant contributor to childhood mortality worldwide (52, 53) . In addition to causing acute symptomatic infections characterized by vomiting and diarrhea, they can persist in both immunocompetent (54) and", "Enteric viruses, including rotavirus (RV), reovirus, norovirus (NoV), and others, generally infect via the fecal-oral route, though other transmission routes have been described. As such, the IECs comprising the mucosal barrier of the intestine likely represent the first eukaryotic cells with which an enteric virus interacts. Here, we describe what is known about specific enteric viruses and their relationship with both the intestinal epithelium and IFN-\u03bb ( Table 1) .", "All authors contributed equally to this work. SL and MB conceptualized, wrote, and edited the manuscript. " ] },{ "paper_id": "2f4331d2427906e96afeb82ef5c4a90dda236470", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "General 1D and 2D NMR experiments were performed on a Bruker Avance 2 (500 MHz) instrument at 500 MHz for 1 H and 125 MHz for 13 C. All spectra were recorded in CD 3 OD using the signals of residual non-deuterated solvent as internal reference. Mass spectrometric analyses were performed using a Bruker micrOTOF-Q II mass spectrometer (Bruker \u00ae Daltonics, Billerica, MA, USA), equipped with ESI. Multi-point mass calibration was carried out using a mixture of sodium formate from m/z 50 to 900. Data acquisition and processing were carried out using the Bruker Compass Data Analysis version 4.0 software supplied with the instrument. All the analytical solutions (0.5 mg/mL) were prepared using methanol LCMS grade. Compounds were infused into the source using a KDS 100 syringe pump ( ", "HSV-1 (KOS strain, Faculty of Pharmacy, University of Rennes, France) was propagated in Vero cells. Viral stocks were stored at \u221280 \u00b0C and titrated based on plaque forming units (PFU) counted by plaque assay as previously described [53] .", "The drug of choice for the prophylaxis and treatment of Herpex Simplex Virus (HSV) infections is acyclovir (ACV), which selectively inhibits HSV DNA replication with low host-cell toxicity. However, the intensive use of antiviral drugs has led to the emergence of resistant viruses [1] [2] [3] . Recently, De Clercq [4] described the evolution of antiviral agents against some viral infections, including HSV, confirming that the search for new antiviral agents is still relevant." ] },{ "paper_id": "2f446f5b176d426f14b28a4898d83c43291ae82d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were stained with fluorescein isothiocyanate (FITC)labeled anti-mouse CD8 + monoclonal antibody and phycoerythrin (PE)-labeled anti-mouse CD4 + monoclonal antibody; Tlymphocyte subsets were measured by a Beckman Coulter FC500 Flow Cytometer (Beckman Coulter, USA).", "The authors declare that they have no competing interests." ] },{ "paper_id": "2f464f69ee34fff67b35b41170660a4e3dac0654", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2f48db348bec8a09f6a83d949d1a3294fbe44008", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A Chi-square test was applied to evaluate the differences in percent positivity between the compared groups. A p-value < 0.05 was considered statistically significant. All analyses were performed using IBM \u00ae SPSS \u00ae Statistics software (Version 23, SPSS Inc., Chicago, IL, USA), SAS (SAS 9. ", "The samples were obtained as part of influenza surveillance conducted in accordance with the Public Health Ordinance in Israel. The institutional review board (IRB) of the Sheba Medical Center approved this research, under Helsinki protocol number 4375-17-SMC (Date of approval, 19 September 2017).", "Despite its circulation in the Middle East and recent eruption in South-Korea, no MERS-CoV has been reported in Israel since its first detection in Saudi-Arabia in 2012 [14, 19] . However, other types of HCoV were detected during the 2015-2016 winter (HCoV-OC43, -NL63 and -229E) and spring-summer (HCoV-HKU1) seasons. It is difficult to predict the combination and dominancy of each HCoV type for the next season.", "December to February of the same period ( Figure 1C ). All HCoV sub-types distributed similarly during this time frame, whereas the highest number of infections for HCoV-OC43 were in weeks 51-52, for HCoV-NL63 was week 2 and for HCoV-229E weeks 53 and 1 ( Figure 1D )." ] },{ "paper_id": "2f4ea657c6c2e9ee90b6ef1af40e2626e5bb488b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author declares that there is no conflict of interests regarding the publication of this paper.", "Concerning autoantibodies, despite the statistically significant associations of their presence during ARM (i.e., the very early stages of AMD), CNV, and GA [43, 44] , their role during AMD remains a subject of debate [45] . More studies are needed to determine their exact role(s) during disease evolution.", "Altogether, evidence presented here suggests that autoimmunity is one of the main risk factors in AMD. Therefore in the future instead of age-related macular degeneration, the three letters A, M, and D may stand for autoimmune macular disease." ] },{ "paper_id": "2f5ad2dee412dbb5a043d1a1c7aa2e0389bb2c7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LX performed the data analysis and drafted the manuscript. YZ, YD, TH, ZH, and CL performed the laboratory experiments. ZX and XJ participated in the study design and coordinated the drafting of the manuscript. All the authors read and approved the final manuscript. ", "Because unequal amounts of reverse primers were used in the asymmetric PCR process, after PCR amplification, large amounts of ssDNA that could be directly hybridized were generated using the signal probes (100 \u00b5M each), 10 \u00b5L of foetal bovine serum (FBS), and 20 \u00b5L of sodium perchlorate for 30 min without heat denaturation." ] },{ "paper_id": "2f5c3733e35cbcc1bb8c2eaded2796d59d94ff2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Participatory epidemiology (PE) is a concept that has increasingly been used in health surveillance in recent years. It uses community involvement to improve the understanding and control of diseases and was most prominently brought to attention by work conducted in Africa investigating animal health from information gathered by local farmers (8) .", "The operating environment of FluMob can be divided into two components: software environment (SE) and hardware environment (HE).", "Technical Specifications" ] },{ "paper_id": "2f5fb10362e86dbf302d8677f4c106c5287bf704", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Molecules 2019, 24, x; doi: www.mdpi.com/journal/molecules", "Molecules 2019, 24, x; doi:", "www.mdpi.com/journal/molecules" ] },{ "paper_id": "2f724b7cfad10b8e35297cd8f000b88f67939d72", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. The complete genome sequence reported here was deposited in GenBank under the accession no. MH817484 and in the SRA under accession no. SRR8352624.", "The genome was assembled using a hybrid methodology of de novo assembly and reference mapping with the Minia (kmer-size \u03ed 32, abundance-min \u03ed 3, abundancemax \u03ed 500, nb-cores \u03ed 8) (6) and Geneious (with default parameters) version 8.1.9 (7) programs, respectively.", "We identified a strain of Alphacoronavirus 1, FCoV-SB22, from a pool of fecal samples from domestic cats from a rural settlement in the municipality of Santa B\u00e1rbara, Par\u00e1, Brazil. The nucleotide identity with feline coronavirus was 91.5%. The present study reports the first complete genome sequence of a feline coronavirus from Brazil." ] },{ "paper_id": "2f74928e0d29d3724e184de8839982d6a44fe8bf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2f8012db8f2100bb1876e19722d6c131849e2315", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CoV PLPs antagonize STING-mediated activation of IRF-3", "In summary, the results of this study indicate that HCoV-NL63 and SARS-CoV PLPs inhibit host IFN-b production by targeting and nullifying STING. Blocking this key scaffolding protein prevents activation of IRF-3 and subsequent transcription of IFNb. The antagonism functions of CoV PLPs are important negative regulators of the innate immune response and may be important in the virulence and pathogenesis of human coronavirus infection. Further characterization of the PLP-STING interaction may provide new targets for antiviral interventions.", "The innate immune system is the first line of defense that protects the host against viral infection. Viral infections are sensed by pattern-recognition receptors (PRRs) of the innate immune system that recognize pathogen-associated molecular patterns (PAMPs) and then trigger an antiviral response [1] . Viral nucleic acids, such as the viral genome or replicative intermediates produced during viral replication, can be recognized by toll-like receptors (TLR3/7/8/9) or the retinoid acid-inducible gene (RIG)-I-like helicase (RLH) family members RIG-I and melanoma differentiation-associated protein 5 (MDA-5) [2, 3] . Viral double stranded RNA can be sensed by membrane bound TLRs or cytosolic sensors like MDA-5, whereas RIG-I detects intracellular viral RNAs bearing 59-triphosphate ends with basepaired structures to activate antiviral signaling [4] [5] [6] [7] . Upon engagement with viral RNA, these PRRs recruit different adaptor proteins (MAVS/IPS-1/VISA/Cardif for RIG-I, and TRIF for TLR3 and MyD88 for TLR7/8/9), and transduce signals to the downstream kinase complexes which activate IFN regulatory factor-3 (IRF-3), nuclear factor kB (NF-kB) and ATF-2/c-jun. These transcription factors coordinately regulate the expression of type I Interferons (IFN-b and -a). Type I IFNs induce the activation of STAT transcription factors that induce the expression of hundreds of IFN-stimulated genes (ISGs) which establish an antiviral state in surrounding cells, thereby limiting viral replication and spread." ] },{ "paper_id": "2f855365da2675234802a5f218bda88aacc089b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Summary of therapeutic proteins expressed by lactococci and lactobacilli and validated in animal studies.", "As for protein delivery, the use of food-grade lactococci and lactobacilli as DNA delivery vehicles is a promising alternative to attenuated pathogens.", "The advantage of DNA vaccines relies in their ability to induce both cellular and humoral Th1 immune responses [67, 68] . In contrast to bacteria-mediated delivery of protein antigens, bacteria-mediated delivery of DNA vaccines leads to the expression of post-translationally modified antigens by host cells resulting in presentation of conformationally restricted epitopes to the immune system [69] ." ] },{ "paper_id": "2f8c155ac0b65122bf485baf2bd6c2fe78e21373", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nanoviridae-like virus. A single read of 252 bp showed weak similarity to the replication initiation protein of banana bunchy top virus (AAG44003). The two sequences were 45.2% identical throughout the amino acid alignment with an e-value of 5e-10. In comparison, the lowest e-value obtained when excluding viral hits was 7e-04. Nanoviridae are currently only known to infect plants. However, sequence homology between Nanoviridae and porcine circovirus suggests that porcine circovirus is distantly related to nanovirus [31] and we cannot exclude the possibility that this fragment could originate from a mammalian virus.", "A schematic overview of the entire process from sample collection and preparation throughout the data-analysis is given by Figure 1 . The first two steps describe sample collection up to sequencing and the following steps (3 to 6) describe in silico analyzes.", "Pre-processing of data and de novo genome assembly.", "Homolog searches. The homolog searches conceptually consisted of searching against both a nucleotide and protein database, translating the nucleotide sequences in all six possible frames, see 'Step 5' of Figure 1 . The similarity search was partitioned into three levels of homology-search, where at each level; any sequence that could be reliably classified was removed from downstream analyzes. For nucleotide homology search, the NCBI nt (minimally non-redundant nucleotide) database (Jan 2010) [13] was used and for the six-frame translated nucleotide homology search the NCBI nr (non-redundant protein) database (Jan 2010) [13] was used.", "Table S2 Assembly information. The number or reads, sequences, longest sequences and total bases for assembled sequences (contigs) and singletons. Note that 10,951 of the sequenced reads did not form contigs and were too short to be included as singletons for further analysis (the exclusion process is described further in Materials and Methods). (DOC) " ] },{ "paper_id": "2f9d66c86c6ef08d8e3679e2cd01c2b140e68a32", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One Liter Bioreactor and Micro24 cultivations were performed as described previously [25] .", "mAbs were purified using a one-step, 96-well format STREAMLINE rProtein A methods described in [26] .", "Proteins were resolved using LabChip\u00ae GX II (PerkinElmer, Waltham, MA)." ] },{ "paper_id": "2f9f32fc7d8af64617d6bbd88c7a42dec0e13a90", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As greater numbers of prokaryote and virus genomes are solved, genomic signatures have become better defined." ] },{ "paper_id": "2fa46e22a7460345c3a4aed5aca12df56667cb56", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "2fac2663c1643fe03479ddfc4122ec63bf269803", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The supplement quantifying method by the relative characteristic fingerprint (RCFP)", ", then the actual results can be revised back again. That is the reason why we could obtain the same results. The RCFP can also cancel the systematic differences in the different HPLC machines.", "Correlating LQTS with LQLS" ] },{ "paper_id": "2fadcd6b5c3ddc519094af150095be7578d8499b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dr Huichen Guo is an associate professor in Lanzhou veterinary research institute, CAAS, China. She has focused on the pathogenesis of animal virus including Classic swine fever virus (CSFV), Foot-and-mouth disease virus (FMDV) and porcine circovirus (PCV2) after doctor graduation. At present, she is studying on viroporin of CSFV and FMDV and apoptosis induced by PCV2 ORF3. ", "DA and HCG conceived the idea, compiled the information, and drafted the paper; SQS critically reviewed and revised the paper. All of the authors agreed to the final version of the manuscript.", "The authors declare that they have no competing interests." ] },{ "paper_id": "2fba918741f8128e992b17b14c8a631b36801e3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CB contributed to the initial design of the CCL3 overexpression studies and carried out the experimental work. " ] },{ "paper_id": "2fc84e709c4978a92c3f4168a6c145080d1b046b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Also, these IBV isolates represent a group distinct from the LX4 IBV type and from QXIBV and IS/1201 (a Middle Eastern strain) related to it. These strains share only 79% nucleotide sequence identity. The lowest nucleotide identity was seen with the DEL072 strain (58%) and with the N1/88 strains (63%) from Australia.", "In the Middle East, the common circulating IBV strains are Mass serotype vaccine isolates, H120 serotype vaccine isolates, D274 [14] [15] , along with other unique strains like IS/885/00 [3] and the Egypt/Beni-Seuf/01 strain found in Egypt. By the end of 2009, variant 2 and variant 2-like strains appeared in Jordan (unpublished data) and in northern Iraq (Sul/01/09) [16] .", "Infectious bronchitis virus (IBV) is a positive sense singlestranded RNA virus, belonging to the genus Coronavirus, group 3 (gamma coronaviruses) [1] . Infectious bronchitis virus is not only an important pathogen of the respiratory system, but also can be nephropathogenic and cause infection of the reproductive system [2] [3] [4] . IBV was first recognised as avian respiratory pathogen in 1930, after that many IBV vaccines were introduced to tackle this problem (H52, H120, M41, 4/91(793/B), and other strains). Recently, different IBV variants have emerged causing nephropathogenic and reproductive problems which require a dramatic change in vaccination programmes [5, 6] ." ] },{ "paper_id": "2fd0fccb43ad3cb1634370734ba27eaed2cf015a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Comparisons of means were performed with ANOVA with Sheffe's multiple comparison test, or where appropriate with Students t test. p<.05 was considered statistically significant.", "Upon euthanasia at 4 d post infection, mouse corneas were removed surgically, rinsed in PBS, and fixed with 10% neutral buffered formalin for 24 hr at room temperature. After paraffin embedding, whole eyes were cut into 5-\u03bcm-thick sections, mounted on positively charged slides and air dried overnight. After deparaffinization and rehydration, slides were stained with hematoxylin and eosin for histology, coverslipped, and photographed (Axiovert 135; Carl Zeiss Meditec, Inc.), using a 40\u00d7 objective.", "Primary human corneal fibroblasts were derived from human donor corneas as previously described [97] . Cells from multiple deceased donors from multiple eye banks were pooled and the cell monolayers used at passage two or three. The A549 cells and HAdVs used in this study were purchased from American Type Culture Collection (ATCC, Manassas, VA). Virus purification was performed by cesium chloride gradient. Cy3labeled virus was prepared as previously described [98] ." ] },{ "paper_id": "2fd379bd7d8ce15f444b2fa608e6c5899441d52a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2014, 6 3684 proteins and demonstrate that mechanisms other than accumulation of endosomal cholesterol can contribute to viral entry inhibition by IFITMs.", "Human embryonic kidney 293T cells were maintained in Dulbecco's minimal essential medium (DMEM), supplemented with 10% fetal bovine serum (FBS; PAA, Pasching, Austria; Biochrom, Berlin, Germany), 100 U/mL penicillin and 100 \u00b5g/mL streptomycin (Cytogen, Sinn, Germany). A549 cells stably expressing IFITM3 were created by transducing A549 wild type cells with the retroviral vector pQCXIP-IFITM3. Transduced cells were selected using the puromycin-resistance-cassette of the pQCXIP vector [14] and were maintained in DMEM containing FBS, penicillin/streptomycin and 2.5 \u00b5g puromycin/mL (Cayman chemical, Ann Arbor, MI, USA)." ] },{ "paper_id": "2fe52e4cee440e3ca69f615221a85064b0641e0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At least 3 days of ICU management before making end-oflife decisions (ICU trial)", "Close relationship and collaboration need to be developed with hematologists and oncologists to increase the skills of both sides in the overall management of patients with cancer", "Many unanswered questions deserve future observational and interventional studies ( Table 4 ). As experts in the management of critically ill cancer patients, we suggest a research agenda to address the following ten burning issues:" ] },{ "paper_id": "2ff4902f8704407bd2f72325ee5ea75908919a54", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(3) For engineered mAb, only two mutations that prevent internalization of immune complexes, i.e., LALA and N297A substitutions, have been identified. More such mutations must be identified for optimal efficacy and synergism.", "Since the declaration of the Zika epidemic as an international public health emergency by WHO in 2016, research on ZIKV has increased many fold. However, there are areas that still need to be addressed.", "All the authors acknowledge and thank their respective Institutes and Universities." ] },{ "paper_id": "300684bd7c47e1f3e8373cb250c6ad82a359955d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Amplification and sequencing of the VP2 gene", "For all sera, the mean value of the results from the duplicate HI tests was calculated. If the mean value of the result from one sera was included between two successive dilutions, the lower titre was reported. Cats with an HI titre \u22651:8 were considered positive and cats with an HI titre \u22651:80 were considered to be protected from infection.", "A melting curve analysis showed a solitary peak between 81.8\u00b0and 82\u00b0C for standard plasmid dilutions and between 81\u00b0and 82\u00b0C for each positive cat sample." ] },{ "paper_id": "300738e128112ee5721442ca851bc5769f1a9b64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Besides, Xu isolated four new lignans from the aerial parts of Justicia procumbens (Acanthaceae) and tested their activity against HIV-1. One of the new secoisolariciresinol dimethylether acetate exhibited anti-HIV-1 activity with an IC50 of 5.27 \u00b5M in vitro [31] . ", "Besides, Xu isolated four new lignans from the aerial parts of Justicia procumbens (Acanthaceae) and tested their activity against HIV-1. One of the new secoisolariciresinol dimethylether acetate exhibited anti-HIV-1 activity with an IC 50 of 5.27 \u00b5M in vitro [31] .", "Yatein was isolated from Chamaecyparis obtuse (Cupressaceae). It could significantly suppress HSV-1 replication in HeLa cells without apparent cytotoxicity [37] . MOA showed that yatein can inhibit HSV-1 alpha gene expression, including the expression of the ICP0 and ICP4 genes, by arresting HSV-1 DNA synthesis and structural protein expression in HeLa cells [38] ." ] },{ "paper_id": "300778fc251628966c3c027308a7d3fe5a02f84c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Development of a screening assay for antiviral compounds.", "CsA (Sigma) was dissolved in DMSO and a 10 mM stock was stored in aliquots for single use at 220 uC. Peg-interferon a-2b (PEG-IFN; Pegintron) was prepared according to the manufacturer's instruction as a 100 mg ml 21 stock and stored at 4 uC.", "Immunofluorescence microscopy. Cells were grown on coverslips and fixed with 3 % paraformaldehyde in PBS or with 4 % formaldehyde and 70 % ethanol (p-STAT1 experiments), permeabilized with 0.1 % Triton X-100 and processed for immunofluorescence microscopy as described previously ( First, the samples were maintained at 290 uC for 6 h in this medium and then slowly warmed to 220 uC within 14 h, kept at 220 uC for 1 h, warmed to 0 uC at a 5 uC h 21 rate and left at 0 uC for 1 h before letting the samples reach room temperature. After washing with acetone, the samples were gradually infiltrated with epoxy resin LX-112 and polymerized at 60 uC. The samples were cut into thin sections (100 nm) and counterstained with uranyl acetate and lead citrate. Imaging was performed in an FEI Tecnai12 TWIN electron microscope operating at 120 kV and equipped with an Eagle 4k cooled slow-scan charge-coupled device camera (FEI Company). The images were acquired using binning mode 2." ] },{ "paper_id": "3012e3f833915e67993777c3a69d90013bff8c1e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These results encouraged us to test other potential inhibitors of SKP2. Autophagy-inducing, FDA-approved drugs and drugs from clinical trials were of particular interest as these could become more readily available for treatment in humans. Of note, valinomycin (VAL), which has been shown to target SARS-CoV in vitro 45, 56 , is also known to act as an SKP2 inhibitor 44 .", "I maxNIC = 23,000 fold and I maxVAL = 93,000 fold; Fig. 9c , Supplementary Fig. 10 ) and moderate to high potency (IC 50SKP2i = 9 \u00b5M, IC 50NIC = 0.32 \u00b5M and IC 50VAL = 84 nM).", "M acroautophagy (subsequently referred to as autophagy) is a conserved cytosolic degradation process in eukaryotes that maintains macromolecule, energy and organelle homeostasis 1 . It requires a fine-tuned sequence of molecular actions largely executed by autophagy-related genes (ATGs). In the initial steps, a phagophore consisting of a double-membrane sheet is nucleated, amplified and finally closed to form a vesicular structure called an autophagosome that engulfs cellular material for degradation 1 . Degradation is accomplished after the fusion of autophagosomes (AP) with lysosomes to form autolysosomes (AL)." ] },{ "paper_id": "30215fe783662edff46565307706587b3bdd60a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "While most successful vaccines in use today mediate protective immunity through the induction of antibodies, optimum protection against many pathogens requires the generation of appropriate cellular immune responses, including CD4 T cells.", "KM and MW co-authored this article.", "This work was supported by a Science Foundation Ireland (awards 11/PI/1036 and 16/IA/4468 to KM)." ] },{ "paper_id": "3024739cfc1f411186c0844a254501c14301c935", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background", "\u2022 Exposure: An event reported by a case in which the case came into contact with an ill or dead person or attended their funeral. Cases could report more than one exposure.", "All data cleaning and analyses were performed using R software [22] ." ] },{ "paper_id": "3025f11897040ad8046b2a7ef8e94fc8615df214", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We calculated the mean week of the epidemics (MWE) to compare the epidemic peak time in the pre-and post-pandemic seasons [12] :" ] },{ "paper_id": "30292ad7f0b45c12878cab23e909fcdeb38bdf7e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, despite the large biological potential, a comprehensive SAR would be necessary to " ] },{ "paper_id": "303c666ccc5e060cf609a6d6acbe0ef7b5e508cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflicts of interest." ] },{ "paper_id": "303dd57924047b30670081699eb8c991bf0f41b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Summary", "where X~I 1,0 z P n i~1", "City :" ] },{ "paper_id": "3041ba0d88fceebd32a14e0b62b443961a64a82b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To assess the significance between two mean correlation coefficients the z-score and P-value were calculated using:", "Data availability. The data that support the findings of this study are available from the corresponding author upon reasonable request.", "Received: 28 July 2016 Accepted: 30 January 2018" ] },{ "paper_id": "3041d890310a050dfc5725636a7b26a23b9d40aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Confluent monolayers of CK cells in 6-well plates were infected with viruses at a MOI of 0.1 PFU in triplicate for each time point. Following attachment, for 1 h at 37uC, the cells were washed twice with phosphate-buffered saline (PBS) to remove residual virus and incubated at 37uC. Samples of media were collected at 24, 48, 72 and 96 h post-infection and assayed in triplicate for progeny virus by plaque assay using CK cells.", "All experiments were carried out in accordance with the UK Home Office guidelines using SPF Rhode Island Red chickens obtained from the Poultry Production Unit of the Institute for Animal health. Four groups (n = 12) of 1-day-old SPF Rhode Island Red chickens were inoculated via the conjunctival (eye drop) and intranasal routes with 10 6 PFU/ml of each virus in a total of 0.1 ml serum-free BES (N,N-Bis(2-hydroxyethyl)-2aminoethanesulphonic acid) medium. The chickens were housed in positive-pressure, HEPA-filtered isolation rooms, and each group was housed in a separate room. The birds in the mockinfected group were inoculated with serum-free BES medium.", "Avian infectious bronchitis virus (IBV) is a member of the genus Coronavirus, family Coronaviridae, order Nidovirales [1, 2] . Together with the genetically closely related Turkey coronavirus [3] [4] [5] [6] , Pheasant coronavirus [7] , and recently identified coronaviruses from several species of wild birds [8, 9] , a beluga whale [10] and an Asian Leopard cat [11] form the Group 3 coronaviruses. IBV is a highly infectious pathogen of domestic fowl that replicates primarily in the respiratory tract but also in epithelial cells of other organs, including the gut, kidney and oviduct [12] [13] [14] , and is the causative agent of infectious bronchitis, a disease that is responsible for economic losses in the poultry industry throughout the world [15] ." ] },{ "paper_id": "30420a081a88b98988e277a508b07af7e7acde41", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u00c3 \"" ] },{ "paper_id": "304d61d063b602c2971b9df3ce167445c9880645", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Copies/\u00b5l ", "Regarding competing interests we do have neither financial competing interests nor Non-financial competing interests.", "Peste des petits ruminants (PPR) is an economically important disease of small ruminants such as sheep and goats. The disease is characterized by severe pyrexia, oculo-nasal discharge, pneumonia, necrosis and ulceration of the mucous membrane and inflammation of the gastrointestinal tract leading to severe diarrhea [1] .", "The causative agent of this disease, peste des petits ruminants virus (PPRV), is a member of the Morbillivirus genus in the Paramyxoviridae family. It has a negative sense single-stranded RNA genome encoding eight proteins [2] ." ] },{ "paper_id": "3053529090a8974edc1ad695d3be4d407eef9674", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MUP bands were detected using SDS-PAGE (Fig. 2a) . MUP levels were significantly decreased by castration but restored by T treatment (P < 0.001, F = 24.204;", "Background: In rats, urine-borne male pheromones comprise organic volatile compounds and major urinary proteins (MUPs). A number of volatile pheromones have been reported, but no MUP pheromones have been identified in rat urine." ] },{ "paper_id": "3053729be9dadd6180b0b30ed2048dec12bd0401", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasmids containing a 1773 bp and a 1737 bp region of the NS1 encoding gene of HBoV-1 and HBoV-3 respectively were used for assay optimisation and as controls. Control material was kindly provided by R. Ratcliff, Adelaide, Australia.", "The qPCR assay targeted the NS1 gene (Ratcliff et al., unpublished method, personal communication) and was performed using an ABI Taqman7500. Oligonucleotide primer and probe sequences and positions are described in table 1.", "Sequence ( ", "HBoV-1, 2 and 3-specific primer pair and probes were designed in house through alignment of sequence data available in GenBank. The reaction conditions are as follows; 1X Platinum Quantitative PCR Supermix-UDG (Invitrogen), HBoV-NS1-1F, HBoV-1R, HBoV2-R and HBoV3R primers each at a concentration of 20 mm, the HBoV1,2 and 3 probe at 10 mm concentration, ROX 25 mm (Invitrogen), 2.5 ml of template and RNase free water was added to a final reaction volume of 25 ml. The amplification conditions for the typing assay are the same as those described in the HBoV NS1 detection assay above." ] },{ "paper_id": "30556242d064131f0f2b645a727d42c55dc1c71e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For characterization of binding specificity, the selected Fc-binding Fab was studied their reactivities with type VI collagen (Sigma), lipopolysaccharide (LPS; Sigma), keyhole limpet haemocyanin (KLH; Sigma), thyroglobulin (Sigma), and calf thymus single-stranded DNA (ssDNA; Sigma) simultaneously. The ELISA analysis was carried out as described above. The amount of these antigens used for coating was 0.5 ug/well.", "Abbreviations: (s) and (m) denote the side chain and the main chain, respectively. * Denotes the residue of somatic mutation.", "2.1. Antibody Library. Two antibody libraries were constructed to express antibody binding fragment (Fab) from patients with Sj\u00f6gren's syndrome associated with hepatitis C infection. Library sizes for and light chain were 1.3 \u00d7 10 7 and 2.1 \u00d7 10 6 , respectively. Equal amount of phage particles was taken from two libraries and mixed evenly for subsequent panning cycles." ] },{ "paper_id": "305cf1019ca9c81126b2e527fedf79969c2c522f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cloning, expression, and biochemical analysis of elaD and G. zeae SENP8", "One possible explanation for these observations is that CE proteases originally derived from a deubiquitinase, a protease specific for this most conserved eukaryotic protein. As CE peptidases in eukaryotes structurally diversified to accommodate the evolving family of Ubls, protease counterparts in bacteria, viruses, and some deeply branched eukaryotes retained their specificity for the ''ur-substrate'' ubiquitin.", "Protein and DNA sequence data were obtained from the National Center for Biotechnology Information (www.ncbi.nlm.nih.gov), the Institute for Genomic Research (www.tigr.org), and the University of Wisconsin E. coli Genome Project (www.genome.wisc.edu). Protein sequence identifiers are listed in Table 2 . Sequences containing and surrounding the catalytic core of the proteases were aligned with the ClustalX algorithm (default parameters) (bips.u-strasbg.fr/fr/Documentation/ClustalX) [52] , manually edited with Genedoc (www.psc. [53] . Secondary structures were predicted with JPred (www.compbio.dundee.ac.uk/,www-jpred/) [54] . Phylograms were constructed with the MEGA software package [55] , using the Neighbor-Joining Method with Poisson correction (all substitutions, homogeneous pattern, c-distribution 2.0) and pairwise deletion of gaps. Figure 1 shows a consensus tree based on 100 bootstrap replications." ] },{ "paper_id": "3060dac173270e62020e18ce6fcdcb4b8bf4fd8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There are small differences in how sex chromosomes are treated by the pipeline. For males, the forward-backward HMM has only 8-states for the X-chromosome, but when merged with the female obligate ancestors they are extended to 36 with the heterozygous states set to 0 probabilities, and they are then combined into strain probabilities as before.", "Whole genomic DNA was isolated as described in Srivastava et al. (2017) from tail tissue of a single male from the following six CC strains: CC078/TauUnc, CC079/TauUnc, CC080/TauUnc, CC081/ Unc, CC082/Unc and CC083/Unc. Samples were sequenced at the UNC High Throughput Sequencing Facility (HTSF). DNA was sheared by ultrasonication, and size selection was targeted at 350 bp using a PippinPrep system. The HTSF generated sequencing libraries using Kapa (Kapa Biosystems) DNA Library Preparation Kits for Illumina sequencing. Each CC sample was run in two lanes of HiSeq4000 (Illumina). Paired end 150-bp sequencing was performed on these samples.", "All sequenced samples and MRCAs were genotyped using GigaMUGA (Morgan et al. 2015) . Three additional mice (two females and one male) were selected from 72 CC strains and were genotyped using the MiniMUGA platform (Neogen, Lincoln NE). To ensure the correct mice were sequenced and genotyped on MiniMUGA, each sample's genotype was compared to the sequenced mouse's genotype for concordance (Table S2) ." ] },{ "paper_id": "3065f9bd3f5cbaad08a1f0e35f5781ccd0857cd7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In February 1996, more than 100 elderly people living alone in Hong Kong died during an unexpected long cold spell, which is excessive in comparison to the same period in the previous years. In response to this incident, in the same year a non-government organization, the Hong November 2007 the accumulated number of users of this service has reached 100,000.", "The data supplied by SCHSA consist of the daily numbers of PE link calls that lead to hospital admission and effective service subscribers from 1 January 2000 to 31 December 2005. The daily weather information such as minimum temperature (in degrees Celsius) and relative Fig. 1 for time series plots of the data.", "We have made an attempt to model the time series of the daily numbers of PE Link calls that lead to hospital admissions in Hong Kong. A negative binomial generalized linear auto-regressive moving-average model was found to afford adequate fit to the data. Our analysis reveals that temperature is a significant predictor for call numbers. We found the effect of the average temperature to be highly nonlinear and roughly U-shaped. The finding aligns wells with previous researches about the effect of weather on various measures of health status. By inspecting the effect function of temperature, we were able to identify a cold temperature threshold of about 15\u00b0C, which triggers excessive PE Link calls. Our findings are potentially useful in assisting the SCHSA with service planning and resource allocation." ] },{ "paper_id": "306840cf9baaaf3a2e493a39f3ebd67529b8cb2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Crystallization and diffraction data collection. The endoglycosidase H-treated (16 h, 30 \u00b0C) pAPN (pAPNeh) ectodomain was crystallized by the sitting drop technique with a crystallization solution of 5% polyethylene glycol (PEG)-1000 and 10% PEG-8000 (pH ~6) and a 15 mg/ml protein sample. Alternatively, native glycosylated pAPN ectodomain crystals were prepared with a crystallization solution of 20% PEG-3350 and 100 mM sodium acetate pH 5.6. The hAPN ectodomain (15 mg/ml) was crystallized with a solution of 20% PEG-6000, 50 mM imidazole-HCl pH 8.0. Crystals were frozen in crystallization solutions containing 20% ethylene glycol for diffraction data collection at the European Synchrotron Radiation Facility (ESRF; ID14 and ID23) and Swiss Light Source (SLS; PXII) beamlines. Diffraction data were processed with XDS 36 and scaled with SCALA programs 37 . For statistical data, see Table 1 ." ] },{ "paper_id": "306bedd61bce68752ab0206d35b28c79f4eebb0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Article submitted to Royal Society T E X Paper 2. Alternative disease severity formulations 9.4 9.5 9.6 9.7 9.8 9. ", "Here we consider a more complicated model of IFN, namely one which uses Michaelis-Menten dynamics to describe the secretion of IFN as a function of infected cells. We again assume that IFN decays at some rate dF and that NK cells kill infected cells at a rate proportional to \u03baIF . The model is given by:" ] },{ "paper_id": "306c2b4690eb9e399d2f301c7ca36eca27cad013", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis and graphical representations were performed using GraphPad Prism 5 software (GraphPad Software, USA). Data analysis was performed using Student's t test for the comparison of two groups. The log-rank (Mantel-Cox) test was used for statistical comparison of the survival between groups.", "Influenza virus, a respiratory pathogen, contributes to a high rate of morbidity and mortality in humans globally. As such, while antiviral therapy has been available, vaccination is still the most effective strategy for the prevention and control of influenza. There is growing interest in mucosal vaccines due to their advantages over conventional injectable vaccines. Side effects associated with conventional vaccines, such as local reactions at the injection site are potentially reduced with implementation of mucosal vaccines. The need for needles during vaccine administration is also avoided, eliminating the possibility of blood transmissible infections [29, 30] . Moreover, mucosal vaccination can be easily administered without a trained personnel, thus considered a more favorable approach for mass vaccination [31] .", "Enzyme-linked immunosorbent assay (ELISA) for detection of mucosal and systemic immune response HA1-specific IgG and IgA antibodies were detected by enzyme-linked immunosorbent assay (ELISA) following the protocol described by Joan et al. [28] with some modifications. Briefly, 96-well microtiter plate (Costar Corporation, USA) was coated with 100 \u03bcl of HA1/L/AcmA recombinant protein (1 \u03bcg/well) at 4\u02daC for overnight. The wells were blocked with 3% (w/v) BSA for 1 h. Sera or mucosal samples were added and incubated for 1 h. Bound antibody was detected using HRP-conjugated goat anti-mouse IgG (Abcam, UK) at 1:10,000 dilution or HRP-conjugated rat anti-mouse IgA (Abcam, UK) at 1:1,000 dilution. The plates were washed 3 times with PBS between steps. TMB peroxidase substrate system (KPL, USA) was added for detection. After incubation for 20 min, TMB stop solution (KPL, USA) was added and absorbance value at 450 nm was measured using a microplate reader (Tecan, Switzerland). The assay was performed with 3 technical replicates. " ] },{ "paper_id": "306d48f87402c3759c22d1c5fbfe4ddce3fd5967", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The primary aim of this study is to identify the views and potential setbacks to successful ASP implementation at CHS which has limited resources. The secondary aim is to identify priorities of future infection-related service needs.", "\"If the strain shows good susceptibility to an antimicrobial, I would choose the antibiotic with a narrow spectrum.\" (IDphy3-3-76).", "\"We don't have time to confirm if antibiotic changes are being made correctly. We barely have time to evaluate oral antimicrobial agents for patients.\" (pharm2-9-216)", "\"In university hospitals and large hospitals, research and education are a big part of the task, but in local community hospitals like us, that function is a bit weak.\" (phy9-1-10).", "\"During my consulting (ID) round, I often find patients who have been prescribed incorrect doses; there was a case where one-fifth of the dose should have been prescribed, but the regular dose had been administered instead. There are cases when medications are administered without adjusting the prescriptions despites of changes in organ function.\" (phy3-4-109)." ] },{ "paper_id": "307179cebf2bf9f9107f745af8f2899db6c51ca9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "the end-point titer that was expressed as the reciprocal of the dilution that provided complete neutralization. Titers Z1:20 were considered positive.", "The microneutralization assay was used to determine antibodies against MERS-CoV. The assay was conducted as previously described and positive and negative camel antisera were included in all runs. 14 Results were only accepted if results from the positive and negative antisera were as expected. Test samples (milk and sera) were initially screened at a dilution of 1:10 in duplicate. Any sample that had a positive result when screened was then repeated in duplicate to obtain A microneutralization positive sample was that with a neutralizing antibody titer \u2265 1:20. A positive RT-PCR sample was positive by the upE RT-PCR assay and another confirmatory RT-PCR assay. a P-value is 0.003 when the unknown category is excluded. b P-value is o0.0001 when the unknown category is excluded.", "More female camels were seropositive than males when the analysis was performed by camel origin, that is, imported vs local. Females had consistently higher seroprevalence even when data were further analyzed by age strata. This translated into lower detection of MERS-CoV in females as compared with males. Our data does not allow us to provide a biological explanation for this observation, however, it could be potentially explained by the close link of cows and calves. As calves are more susceptible to infection, the cows become exposed to virus repeatedly, increasing their antibody titer." ] },{ "paper_id": "3078165241b24fed34596efa9f563661f1caa00c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mouse monoclonal antibody against PHEV was generated in our laboratory. Mouse monoclonal anti-beta actin was purchased from Proteintech, and rabbit polyclonal anti-SDC1 was obtained from Abcam. Horseradish peroxidase secondary anti-mouse and rabbit IgG antibodies were obtained from Proteintech. Goat antimouse IgG-Alexa 568 and goat anti-rabbit IgG-Alexa 488 were purchased from Cell Signaling Technology.", "The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation to any qualified researcher.", "The animal study was reviewed and approved by the Animal Welfare and Research Ethics Committee of the College of Veterinary Medicine, Jilin University, China.", "SH and WH designed and supervised the experiments. SH, ZL, and YL performed most of the experiments and interpreted the data. JG cultured cells and conducted the statistical analysis. KZ and DC carried out the bioinformatics prediction analysis and prepared the figures. FG and YG drafted the manuscript and GF and WH revised it critically for important intellectual content. " ] },{ "paper_id": "30793ddad13205696658bbb0a2083c1cd400aab7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was obtained from GeneMark (GMbiolab Co., Ltd., Taichung, Taiwan). FFA was purchased from Sigma-Aldrich Company (St. Louis, MO, USA). Fenofibrate and chloroquine were obtained from Cayman (Cayman Chemical Co., Ann Arbor, MI, USA). Compound C was obtained from ENZO Life Sciences, Inc. (Farmingdale, NY, USA). Toosendanin was purchased from Wuhan ChemFaces Biochemical Co. Ltd. (Wuhan, Hubei, China).", "TSF and TSB were collected locally in spring from 2015 to 2018 (Yulin, Taiwan) and identified by Professor Hseng-Kuang Hsu, Physiologist and Botanist, Kaohsiung Medical University, Taiwan." ] },{ "paper_id": "3083af632db7cfbddd6ac1b939fcf076d545e783", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3083f7cc3a62acaf4a94a4da4eceb84081d70329", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Maps were generated using RegioGraph Analyse 13; StataSE 14, Microsoft Visio and Microsoft Excel were used for other graphs and analyses.", "Three different case definitions were developed.", "Not applicable." ] },{ "paper_id": "308e91d0c4575362a0d169b9ed31c60f79a86437", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tear collection: Tear secretion was stimulated with onion vapors, and tears were collected from the lower conjunctival", "cul-de-sac from healthy human donors as previously described [15] ." ] },{ "paper_id": "30a8e34179b5cc12c971eaa2b40015a446f10621", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A single cell suspension from spleens was prepared by passing through a nylon 40 mm cell strainer (BD, San Jose, CA). Suspensions were washed with RPMI complete (10% FCS, 1%Pennicilin/Streptomycin, 1% Glutamine, 1% Sodium Pyruvate, 1% nonessential amino acids, 0.1% B-mercaptoethanol) (Life Technologies, Grand Island, NY) and centrifuged for 5 minutes at 1200 RPM at 4uC. Red Blood Cells were lysed using 0.86% ammonium chloride solution, centrifuged and resuspended in RPMI complete. BMNCs were prepared as previously described [89] .", "BMNCs or splenic cells were incubated with various conjugated antibodies against CXCR3, CD3, CD4, CD8, CD11b, IL-10, and CD45, (eBioscience, San Diego, CA) and MMR (Biolegend, San Diego, CA). Cells were analyzed using the BD FACSCanto II flowcytometer (BD Biosciences, San Jose, CA) and FlowJo analysis software v.8.7.3 (Treestar Software, Ashland, OR). Cell populations were determined by gating on CD4+, CD8+, CD45 hi / CD11b+ (macrophages) and CD45 int /CD11b+ (microglia) from live cell gate.", "Total RNA from brain tissue samples was extracted with TRIzol reagent (Life Technologies, Grand Island, NY) according to manufacturer's instructions. DNase1 treatment and first strand cDNA synthesis was performed using cDNA synthesis kit (BioRad, Hercules, CA) according to the manufacturer's instructions. CXCR3, CXCL9, CXCL10, CCL2, CCL5, AMCase, Arg1, and Chit1 specific primers for Real Time PCR were purchased from IDT's primer Quest (http://www.idtdna.com/Scitools/ Applications/Primerquest/). Primer sequences were as follows: " ] },{ "paper_id": "30abdf7a423427b001aee5d319abecfb5ad1671b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells in the immune system detect the viral pathogens via several recognition strategies. Of which, the most well characterized is the pattern recognition receptors (PRR), which engage various microbial pathogens via evolutionarily conserved structures known as pathogen-associated molecular patterns (PAMPs). PRRs are mainly categorized into three classes, namely Toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and nucleotide oligomerisation domain (NOD)-like receptors (NLRs).", "When the cells are exposed to pathogens such as viruses, immune responses are induced as a form of host defence. The immune response is modulated during pathogen exposure in a cell-type dependent fashion. Innate immunity is the first line of defence mounted against the virus before the adaptive immune system is generated. Both the host and virus can manipulate innate immune mechanisms as a form of defence or evasion strategy [95, 96] . ", "When the cells are exposed to pathogens such as viruses, immune responses are induced as a form of host defence. The immune response is modulated during pathogen exposure in a cell-type dependent fashion. Innate immunity is the first line of defence mounted against the virus before the adaptive immune system is generated. Both the host and virus can manipulate innate immune mechanisms as a form of defence or evasion strategy [95, 96] ." ] },{ "paper_id": "30b285a628c951e7c2d73848be13204f59b2fa73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author details 1 School of Public Health, Georgia State University, Atlanta, Georgia, USA." ] },{ "paper_id": "30b4defc3cb6deb9e7b1a2719d0537ca01081159", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Financial support: This research was supported by the National Institutes of Health (contract no. HHSN266200700006C).", "design. Prospective study." ] },{ "paper_id": "30b4f6254119ea425c5370fe40f3def0500fa359", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "30c57af407724c03de7e5b24b175c3de44ea79a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Authors' contributions STY conceptualized the study. JHC performed the statistical analysis. STY, YRL, MYW, PSY and HRY contributed to the interpretation of the TCM data and pharmacological mechanisms. TCH contributed to the interpretation of Western medicine data. STY, YRL and HRY drafted the manuscript. STY and HRY finalized the manuscript. All authors read and approved the final manuscript.", "The ancient CM literature did not use the word \"TB\", but rather considered this pulmonary condition to be related to a syndrome of lung consumption characterized by cough, hemoptysis, tidal fever, night sweats and emaciation due to consumptive or exhaustive overstrain. It was reported that Chinese medicines combined with conventional medicine has beneficial effects for inhibiting Mycobacterium, strengthening the immune system of the body, enhancing the effect of anti-TB drugs, reducing drug resistance, and being relatively safe [23] [24] [25] .", "Not applicable." ] },{ "paper_id": "30d216d33a2ead14fe0230f40fd76f6ae2d3b79c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Figure S16: Phylogenetic tree obtained by ClustalW method using 58 genome datasets from different species.", ": Phylogenetic tree of 41 mitochondrial genome sequences based on multiple encoding vector method [b] . The 8 clusters are Primates (red), Cetacea (green), Artiodactyla (pink), Perissodactyla (light green), Rodentia (black), Lagomorpha (dark red), Carnivore (blue), and Erinaceomorpha (grey). Figure S15: Phylogenetic tree obtained by ClustalW using 24 Eutherian mammal sequences [d] .", ": The phylogenetic tree of the 11 AMF sequences constructed by ClustalW method using MEGA package[a]. Figure S2: The phylogenetic tree of the 16S rDNA sequences from 40 bacterial isolates constructed by ClustalW method using MEGA package[a]." ] },{ "paper_id": "30d6338f9b3366f9d76e5cc76e6a79a4aa3f8c13", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All diagnostic and therapeutic procedures involving live animals were performed by an approved veterinarian in the course of routine veterinary health management.", "Here, we report the first detection of PEDV in pigs on an Austrian fattening farm and provide information about disease symptoms, diagnostic test results, possible route of PEDV entry and genetic relatedness of the newly detected Austrian PEDV to published sequences.", "During and after these follow-up studies on the index farm, PED was confirmed in our laboratory on three additional pig finishing farms located in Upper Austria in February -June 2015. In addition, PEDV was detected in an intestinal sample collected from a finishing farm in neighboring Slovenia in February 2015. Veterinarians reported highly varying degrees of mortality (7-100 %), but absent or low (<1 %) mortality. All affected farms were specialized on finishing pigs. Permission for taking samples was granted by all farm owners." ] },{ "paper_id": "30e4b834f1684fcc9ba26d41316a44b90aa287a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These data indicated that expression of 3b protein blocked or delayed the progression of cells from G0/G1 phase into S phase, and induced cells toward apoptosis.", "Next, using similar method, we investigated the effects of p3b/EGFP-N1 on cell cycles in 293 and Vero cells. In these cells, the p3b/EGFP-N1 positive cells were arrested at G0/ in Vero cells at 48 h), but the percentages of sub-G1 phase in positive and negative cells were all too low and comparable. These data indicated that the role of 3b protein in inducing cell cycle G0/G1 phase arrest was a conserved character, but the apoptosis induction of 3b protein might be a cell type specific.", "Published data showed that massive necrosis was found in lung, spleen and lymph nodes in SARS patients. As compared with normal tissues, apoptosis cells increased significantly in the spleen, liver, lung, and lymph nodes of SARS patients. The apoptosis cells were further demonstrated to be pneumocytes, lymphocytes, and monocytes [10, 11] . Taken together, the data we presented here, as well as the apoptosis and necrosis data of SARS patients, suggest that 3b is an apoptosis-related gene in SARS genome, which induce cell or tissue specific apoptosis in transfected cells." ] },{ "paper_id": "30e8d03a5cf6907154b5a3d7c7b23cdc96cf1952", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by internal funding." ] },{ "paper_id": "30f0103086a7458f1bdb18024f372814d88a9b4e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dengue is one of the most important vector-borne viral diseases in humans. However, the interaction between dengue virus (DV) and host cells is only partly understood. Therefore, there is an urgent need to develop new tools to gain insight into the viral journey through host cells.", "Thus, our observations indicate that expression of prM and E DV1 envelope proteins induces the formation of RSPs in an ERderived compartment.", "HeLa-prME cell line was fixed at 28 hours post-trypsination and processed for EM and immuno-EM.", "For the endoglycosidase treatment, RSPs or HeLa-prME cell lysates were treated with 500 U of EndoH or PNGase F at 37uC for 3 hours according to the manufacturer's instructions (New England Biolabs, Beverly, MA, USA), and subsequently analyzed by Western blot." ] },{ "paper_id": "30f0d89777ce7543d7b37544544c810b896c4821", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) was identified in Saudi Arabia in 2012 and it belongs to Coronaviridae family and mostly reported among the Middle Eastern people. This virus causes the respiratory illness called the Middle East Respiratory Syndrome (MERS) [1] . Phylogenetic studies show that bats are the reservoir of this virus and camel is the only host through which the virus spreads to humans [2] .", "(i) Wimley-White interfacial hydrophobicity scale (WWIHS > 0), (ii) interfacial helical hydrophobic moment (iHHM > 0).", "The authors declare no conflicts of interest.", "The model refinement has improved its quality of the theoretical models developed for selected AMPs. Further, Ramachandran plots from Rampage server determined the stereochemical quality of best scored four defensin models. The aim of model refinement using Rampage Ramachandran plot was to determine whether the theoretical model acquired the quality and side chain configuration [30] . This program helps researchers to evaluate the accuracy of the predicted models [31] ." ] },{ "paper_id": "30f8d46cca4f068ecc358d99115a885d458ad9b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The generation of MDMs has been described in previous studies [28, 29] . Briefly, PBMCs were isolated from human whole blood by density-gradient centrifugation over Histopaque (1.077 g/ml, Sigma-Aldrich, St. Louis. MO). Monocytes were purified using human CD14-specific microbeads (Miltenyi Biotec, San Diego, CA, 130-050-201) following manufacturer's instructions. CD14 + monocytes were differentiated into MDMs by culturing for 6-7 days with recombinant human macrophage colony-stimulating factor (Bio-Techne, Minneapolis, MN, 216-MC-005) and conditioned medium from KPB-M15 cells (kind gift from Dr. Atsunobu Hiraoka, SCGF Research Laboratory, Kyoto, JP). Media were replaced every 2-3 days during the incubation for a total of 6-7 days. The cells were harvested and plated on desired 96-well plates 1 day prior to the drug screen assay. The differentiated MDMs were characterized by flow cytometry before assay initiation. Toremifene citrate (oral solution) tested in this study was purchased from Sigma-Aldrich (CAS 89778-27-8; T7204-5MG).", "To effectively identify potential compounds of interest from large libraries of chemical compounds, share more reliable and reproducible data between laboratories, and provide data to the international community, appropriate methods or models need to be established. Furthermore, these models should be evaluated to determine how predictive they are for identifying compounds most likely to be efficacious in humans. For EVD, indications of efficacy could include successful treatment and survival of patients, alleviation of disease severity, or mitigation of clinical symptoms associated with EBOV infection.", "https://doi.org/10.1371/journal.pone.0194880.g001", "A trend towards higher EC 50 s with increasing input virus and longer assay time was observed. The data indicate that if the amount of virus present in cells or tissues is high enough, the drug will be less active. Also with longer time for the virus to replicate, drugs may be unable to stem high viral replication. In contrast, the EC 90 values were less affected by high MOI or longer time points, which may, therefore, be a more reliable parameter for comparing data sets between laboratories." ] },{ "paper_id": "30fc9806c9b1ba0d786a31cad4a1d98b6642462d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022", "Second, there are potential biases from key informants' selection. These were mitigated by including resource persons from different health system levels and sectors to allow for the triangulation of results from various sources. Additionally, the data collection including interviews was carried out by both external and local experts to balance the views and to provide systematic, robust, contextual understanding." ] },{ "paper_id": "310122c497498a3be55d1984730142fcf414a4c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "M2 ion channel blockers (for example, amantadine and rimantadine) and neuraminidase (NA) inhibitors (for example, oseltamivir, zanamivir, and peramivir) are commonly used for the prevention and treatment of influenza [6] . Amantadine and rimantadine, however, have been associated with neurologic toxicities and gastrointestinal * Correspondence: nanshan@vip.163.com \u2020 Equal contributors 1 side effects [7] . Moreover, overuse of these medicines has been found to result in drug-resistant strains [8] . Up to 2003, M2-resistant variants had even spread to countries where these drugs are used infrequently [9] . Pandemic (H1N1) 2009 has demonstrated resistance to amantadine and rimantadine [10, 11] . Our previous study suggested that clinical isolates of H1N1 and H3N2 developed amantadine resistance at 93.1% and 100%, respectively, in Guangzhou, China [12] . NA inhibitors, in comparison with M2 ion channel blockers, are more commonly used but they (i) can also cause respiratory side effects and even death (for example, oseltamivir [13] ) owing to intensive use and (ii) have a higher barrier for resistance if overused. A survey from 1999 and 2007 showed a very low level (<1%) of resistance to oseltamivir [10, 14] , but a survey between 2008 and 2009 reported the resistance to be \u226590% [15] [16] [17] [18] . Resistance to zanamivir has been (albeit rarely) reported among immunodeficient patients [19, 20] . Whether such antiviral agents can be used to address influenza epidemics is not clear. Furthermore, the true effectiveness of oseltamivir treatment against influenza is controversial [21] .", "The placebo group will receive BLG analogous granules, twice a day, 30 min after eating, taken with an analogous oseltamivir phosphate capsule.", "Drug efficacy was determined using patient symptoms, body temperature, and virus detection." ] },{ "paper_id": "31042ccf8374ad96d39d8156d9e2ced042734ba9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All 74 patient samples and clinical information were collected under IRB-approved protocols. Most cases (66) were recruited from clinical centers: 25 patients from Ohio (J. Greinwald), 20 from Massachusetts (H. Rehm and M. Kenna), 12 from Belgium (G. Van Camp), 5 from Israel (K. Avraham), 2 from Iowa (R. Smith), 2 from Nebraska (P. Kelley), and the remaining 8 represented anonymized samples obtained through clinical testing at the Laboratory for Molecular Medicine at the Partners Center for Personalized Genetic Medicine. All patients had previously tested negative for biallelic GJB2 mutations, except for 3 patients who had heterozygous mutations in the GJB2 gene. All patients had bilateral SNHL and were either recessive cases (e.g. with affected siblings) or singletons. DNA and clinical information was collected on most patients (de-identified clinical information for those cases that were anonymized) and included demographic information, audiometric profiles, family history, neuro-otologic history and physical examinations.", "Abbreviations SNHL: sensorineural hearing loss; SNP: single nucleotide polymorphism; PCR: polymerase chain reaction; GDAS: GeneChip DNA Analysis Software; GSEQ: GeneChip Sequence Analysis Software; Indel: insertion/deletion; sPROFILER: strand-specific PRObe cell intensity comparison for FILtERing GDAS/GSEQ calls", "We developed two resequencing microarrays containing 13 unique genes implicated in nonsyndromic SNHL. Array base calls were compared to dideoxy sequencing to determine accuracy. Through optimization of protocols and data analysis methods, similar high-quality performance measures could be achieved for microarrays developed at two independent research facilities and containing different sets of genes.", "Our work focuses on evaluating the effectiveness of resequencing arrays as a tool for variant detection and discusses the impact on base-calling of adopting additional computational algorithms and laboratory protocols. This study presents the results from hearing loss arrays developed in two different research facilities and highlights some of the approaches we adopted to enhance the applicability of the arrays in a clinical setting." ] },{ "paper_id": "310c97d16197e1ab6ff3227b706bed41f079b8ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Oral squamous cell carcinoma (OSCC) is a tumor of the oral cavity epithelial in origin that affects more than 400,000 people per year worldwide. The mortality rate has not been improved over decades, and the 5 year survival rate is under 70% 1 . Tumor microenvironments comprise cancer cells and various normal cells including immune, inflammatory, and stromal cells 2-4 . Several studies indicated that M2 macrophages infiltrate into the tumor microenvironment and promote tumor immunosuppression, cancer progression, angiogenesis, invasion and metastasis. This phenotype of macrophage called tumor-associated macrophage 5-7 .", "CD204 is a prototypic member of a family of structurally different transmembrane receptors conjointly termed as scavenger receptors and is primarily expressed on macrophages and dendritic cells 31 . CD204 recognizes modified lipid proteins, and exogenous pathogen-associated molecular patterns, and apoptotic cells. We previously reported that CD163 + CD204 + TAMs promote T-cell apoptosis and immunosuppression via IL-10 and programmed death-ligand 1 in OSCC patients 19 ." ] },{ "paper_id": "310f2c636d121f3a0e48ccaf6b97e4c3c8ce5abe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All 26 subjects completed the study, and their demographic characteristics and experience of performing endotracheal intubation are summarized in Table 1 . Nineteen subjects were fitted with a model 1860 respirator and seven with a model 1860S respirator according to their face and lip measurements.", "During outbreaks of infectious disease and bioterrorism attacks, it may be necessary to wear respirators for prolonged periods of time. Rebmann et al. reported that although longterm use of a respirator did not result in a clinically relevant physiologic burden for the wearer, it was associated with many subjective symptoms [28] . Thus, compliance may be determined by selection of a respirator that is comfortable for the wearer. In this context, low-pressure facial seal areas are more comfortable to wear but are prone to leakage, whereas high-pressure facial seal areas cause discomfort that negatively affects wearer compliance [26] . Compared with fold-type respirators, cup-type respirators are more rigid and include a head strap that generates higher pressure, which could increase facial discomfort.", "Supporting information S1 File. The consort checklist of information to include when reporting a randomized trial assessing non-pharmacologic treatments (NPTs). " ] },{ "paper_id": "3115260ab0b83020627a59f8e6c47d8e33337d3d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although lower respiratory infections, including pneumonia, are one of the main causes of death worldwide [21] , real-time surveillance systems and situational awareness are generally lacking.", "The current Zika outbreak (2015) shows how important an effective arbovirus surveillance system is, as the IHR requires countries to report unusual Zika-related cases [26] .", "Combining syndromic surveillance together with the outcomes of laboratory tests increases the probability of timely detection and proper assessment. Further strengthening a combined syndromic and laboratory surveillance system can be further explored by both countries." ] },{ "paper_id": "3118aa53f6b7e539049e2a52e973f4124ba121e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "doi:10.1371/journal.pone.0117496.t006", "Nowadays, natural-product-based antiviral agents are more popular than those produced by chemosynthesis. Since plants have evolved multiple mechanisms to resist pathogens by producing secondary metabolites with antimicrobial activities, natural products from plants have been proved to be a rich resource of antiviral agent. Moreover, nature-derived plant substances have less negative impact on the environment, as they are readily broken down and have shortlasting residual periods [6, 7] . With the increasing worldwide concern on virus diseases, exploitation of new nature-derived anti-viral agents received increasing attentions.", "Finally, two bioactive compounds were obtained from ethyl acetate extract. Both the compounds were identified by physical, chemical properties and organic spectroscopy ( 1 H NMR, 13 C NMR), as well as contrast with the standard compounds. Their structures were identified as Gossypol and \u03b2-sitosterol. NMR data were shown in Tables 3-5 ." ] },{ "paper_id": "311aaa859b69a54fba2d8a532fcf632599002edb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "VIRSorter_NODE_210_length_3873_cov_4_79189-cat_1", "VIRSorter_NODE_388_length_2881_cov_7_17939-cat_1", "VIRSorter_NODE_8_length_45832_cov_51_2672-cat_1" ] },{ "paper_id": "311d15fee68d2a591ffc4e7cc0187b8dae872f9c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As the outbreak of severe acute respiratory syndrome (SARS) [1] and the continued threat of novel influenza strains that could produce pandemics illustrate [2, 3] , human populations remain vulnerable to epidemics of acute respiratory infections (ARI). These outbreaks must be discovered as soon as possible if control measures are to be implemented in time to curb morbidity, mortality and socioeconomic disruptions [4] .", "The Maryland (n = 5,127) and the Utah (n = 10,250) study samples were representative of their respective outpatient populations and included mostly male veterans. They differed in racial composition: the Utah population was more than 90% Caucasian, whereas almost half of the Maryland veterans were African American (Table 1) ." ] },{ "paper_id": "3128ce331b8e280214991a3c775c895045ccfa70", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Many probiotic bacteria have been described as promising tools for the treatment and prevention of inflammatory bowel diseases (IBDs). Most of these bacteria are lactic acid bacteria, which are part of the healthy human microbiota. However, little is known about the effects of transient bacteria present in normal diets, including Lactococcus lactis.", "The authors declare that they have no competing interests. " ] },{ "paper_id": "312f1e49512a7626113891f7796d4c2c318c7e39", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HTNV is a spherical, enveloped virus with a genome consisting of three segments of single-stranded, negativesense RNA. The three segments are designated as large (L), medium (M), and small (S) segments that encode RNAdependent RNA polymerase, respectively [4] ]. It is indicated that the glycoprotein (GP), which was encoded by M segment, could elicit organism to produce neutralizing antibody and could protect infected animal and human body from Hantavirus lethal infection [5] . Moreover, the neutralization sites of GP mainly exist in G2 [6] .", "To construct the eukaryotic expression plasmid DNA vector for IL-2 DNA, the full-length IL-2 DNA was amplified from plasmid PUC19-IL-2 (Department of molecular biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China) encoding human IL-2 gene by PCR using IL-2 primers (forward, 5'-GGCATCGCAAGCTTATGGCACCTACTTCAA-3'reverse, 5'-GCTCTCCGGTACCCTGCAGTGTTGAGATGA -3'), which also introduced an Hind III and KpnIrestriction sites, respectively (underlined) to the amplicons. The PCR-amplified IL-2 DNA fragments were digested with restriction endonucleases Hind III and KpnI and annealed by ligation with T4 DNA ligase (TaKaRa, Japan) to Hind III and KpnI-digested pcDNA3.1 (+) expression vector (Invitrogen\u2122 Life Technologies) DNA, downstream of the CMV promoter, hereafter referred to as pcDNA3.1/IL-2.", "Differences between assays are analyzed using one-tailed or two-tailed pair t-test as appropriate (GraphPad Prism). Probability values of \u03f9 0.05 are considered to represent significant differences.", "The Hantaan virus (HTNV) is a member of the genus Hantavirus of the family Bunyaviridae and a causative agent of hemorrhagic fever with renal syndrome (HFRS) [1, 2] . More than 100,000 cases of HFRS are reported annually, with a mortality rate between 2% and 10% [3] . However, no effective vaccine has been developed to prevent this disease." ] },{ "paper_id": "31444b90fc581b9b42bfbbb70e4ad4dcf1aca613", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Key indicators: single-crystal X-ray study; T = 120 K; mean (C-C) = 0.003 \u00c5; R factor = 0.048; wR factor = 0.127; data-to-parameter ratio = 12.4.", "The C-bound H atoms were geometrically placed (C-H = 0.95-0.99 \u00c5) and refined as riding with U iso (H) = 1.2U eq (C).", "Cg1 is the centroid of the C10-C15 ring. Symmetry codes: (i) x; \u00c0y \u00fe 1 2 ; z \u00fe 1 2 ; (ii) x; \u00c0y \u00fe 3 2 ; z \u00fe 1 2 ; (iii) \u00c0x \u00fe 1; \u00c0y \u00fe 1; \u00c0z \u00fe 2." ] },{ "paper_id": "31491f82bfaa808144e856d7a21308cfa971b558", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Amplification and sequencing of partial bat DPP4 mRNA transcripts", "The collection of bat samples for developing bat cell lines was approved by the Committee on the Use of Live ", "The nucleotide sequences of bat DPP4 obtained from this study have been deposited in the GenBank sequence database under accession numbers MH345671-MH345676." ] },{ "paper_id": "315303952d93ba93f55029cca73e2f483bc16362", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Numerous parasites species circulate simultaneously in natural populations. Many of them are able to infect a same host species and a host individual can therefore be infected by several parasites at the same time. These multiple infections are not only common in nature but usually more frequently encountered than infections by a single parasite [1] . Within a host individual, parasites can thus interact, either in a synergistic manner (parasite A favours infection by parasite B or worsens the symptoms caused by B) or in an antagonistic manner (parasite A decreases the infection risk by parasite B or reduces the symptoms caused by B) [2] . As these interactions can have important epidemiological, biological and clinical consequences (e.g., [3] [4] [5] [6] [7] ), detecting, understanding and evaluating them is essential to understand the phenomena and to control and manage infectious diseases.", "The theoretical contingency table is then deduced from these probabilities:", "Step 1: Estimated seropositivity probabilities (p p p,x ) are used to generate in silico serological data for both pathogens independently." ] },{ "paper_id": "3154395f4f53dd3c358e5ba72e394f9334430cef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These selected measures are useful for estimating epidemic impact and decision making regarding selection and introduction of control measures for optimal effectiveness [8, 10] .", "Steps ii and iii are repeated until convergence. We describe methods and processes involved in fulfilling each of these steps.", "The SIMOP procedure can be described in three steps:" ] },{ "paper_id": "3159f6ba739648bbaa0b8b7eb498924a8d21cf8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Source data are available for this figure.", "Source data are available for this figure. " ] },{ "paper_id": "315f0a94d6ac0655e0e5defec4f9526641c76037", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "were used for sequencing of both strands. Amplicons were assembled on a scaffold sequence using Vector NTI ContigExpress and polymorphisms were identified by visual inspection.", "PLOS ONE | https://doi.org/10.", "132 (6-907) Death with AIDS-related symptoms (%) 34 (72.3) Mamu-A1 \ufffd 001 positive (%) 10 (21.2)" ] },{ "paper_id": "317f9c2b15b77682a875328e023b5b62a9eb2896", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "of intracellular signals (IGF receptor coupled to IP 3 formation) discretely to the nucleus in cardiomyocytes (111) . The apparent advantages of this system may reflect a more selective activation of the signaling cascade and independence from the intracellular generation of the peptide ligands (112) . The latter study adds another potential mechanism to the complex pathways of the intracellular receptor system for angiotensins and other peptides, as well as emphasize the need for additional studies to elucidate their organization and function.", "Immunofluorescent (IMF) staining and protein immunoblot for rat angiotensinogen (Aogen) and renin. Immunoblots of Aogen and renin in nuclei (lanes 1-3) and cytosol (lanes 4-6) were from three separate passages of NRK-52E cells. Major bands for Aogen and renin were identified at approximately 55 kDa. Renin activity (conversion of Aogen to Ang I) in isolated nuclear fractions was increased threefold following activation by trypsin (TRP) and was essentially abolished by the renin inhibitor aliskiren (ALK). Conversion of 125 I-Ang I to 125 I-Ang-(1-7) in the isolated nuclear fraction was predominantly blocked by the thimet oligopeptidase inhibitor CPP. Renin activity data are mean \u00b1 SEM; n = 4; *P < 0.05. Ang I metabolism representative of data from n = 4 separate cell passages. Adapted from Alzayadneh and Chappell (107) .", "100-fold higher than that of PC or POP. In this regard, the soluble form of ACE2 has been utilized as a therapeutic agent to reduce blood pressure and attenuate target organ damage in hypertensive and diabetic animal models (34) (35) (36) (37) . ACE2 mRNA expression was increased in the brain medulla following long-term AT1-receptor blockade (38) . It is unclear whether the beneficial effects of ACE2 administration reflect the reduction in Ang II, the enhanced formation of Ang-(1-7) or the increased ratio of Ang-(1-7) to Ang II. Moreover, Turner and colleagues report that soluble ACE2 attenuated the integrin-dependent stimulation of focal adhesion kinase (FAK) and increased the expression of the Akt kinase suggesting the peptidase may have direct cellular effects apart from its peptidase activity (39) ." ] },{ "paper_id": "318eb743359acf11f860f81255d3a1625f33e484", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The syntheses of compounds 1, 2, 8-21, and 25 are described in [17] .", "Melting points were determined in open capillary on a melting point apparatus, model 530, from B\u00fcchi, Switzerland. NMR spectra were recorded on an AVANCE 400 MHz spectrometer from Bruker Biospin GmbH, Germany [solvent CDCl 3 (unless otherwise noted); 1 H-NMR, 400.13 MHz; 13 C-NMR, 100.61 MHz]. The optical rotation values were determined on a Perkin-Elmer 241 polarimeter. ESI mass spectra were recorded on an Agilent 1100 ion trap equipped with an Agilent HPLC system. Hydrostatic column chromatography was performed with silica gel 60 (0.063-0.2 mm). All solvents were purified and dried prior to use according to standard literature procedures. Chloroquine, E64 and DMSO (dimethyl sulfoxide) were obtained from Sigma-Aldrich, Deisenhofen, Germany. Alamar Blue \u00ae was purchased from Trinova Biochem, Giessen, Germany. DMEM (Dulbecco's Modified Eagle's Medium) high glucose was delivered from Gibco/Sigma-Aldrich, Deisenhofen, Germany. Hygromycin was obtained from Merck, Darmstadt, Germany.", "Malaria is still a major cause of global human morbidity and mortality, with Plasmodium falciparum being the deadliest among the four Plasmodium species that infect humans. Annually 350-500 million clinical malaria episodes occur, causing more than 1 million deaths each year [1]. The" ] },{ "paper_id": "319896275e7fe7dacb19138689294224c13a1aeb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hemagglutination titres were measured using 0.75% suspensions of human (type O), horse and guinea pig red blood cells, as previously described [30, 43] .", "Results are presented as mean values 6 SD of the indicate number of observations. Statistical difference between groups was determined by the unpaired Students's t-test with a 0.05 significance level." ] },{ "paper_id": "319da4b3a356bea3794d401087176bcd055ba23d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Brain samples were collected and tested for confirmation wherever possible, but despite efforts to obtain diagnostic samples, most cases reported here were suspected rather than confirmed. Inadequate sample preservation such as storage at room temperature and long intervals between sample collection and testing (during which samples underwent repeated freeze-thaw cycles) probably caused specimens to deteriorate. Composite samples of each brain necessary to achieve the highest test reliability were also rarely available. Nevertheless, a high percentage of samples from suspected cases of rabies were confirmed by laboratory diagnosis (;75%) suggesting that use of epidemiological and clinical criteria is justified and reliable [18] . Researchers are encouraged to contact the authors regarding data availability.", "(2) Epidemic tree reconstruction. We used an algorithm for probabilistically constructing epidemic trees based on the location of cases in space and time [38] . For each suspected case (i), we chose a progenitor ( j) at random with probability p ij from all n cases preceding that case, where:", "G\u00f0s\u00dee \u00c0rs", "Rabies is an acute viral encephalitis that is spread through the saliva of infected hosts [2] . Clinical manifestations vary, but the neurological phase often includes increased aggression and the tendency to bite and thereby transmit infection; rapid progression to death is inevitable [4] . These distinctive signs make transmission of rabies easier to track than that of most other diseases and provide an unusual opportunity to explore epidemiological patterns at the scale of the individual." ] },{ "paper_id": "31a744d5cdf4b8901ea26a847bbc3cc76d6e02d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rectal swabs were homogenized in 300 \u03bcl of PBS. After centrifugation at 10000xg/10 min, the supernatant was collected and stored at \u221280\u00b0C. Blood samples were centrifuged at 4000xg/10 min to separate plasma from blood cells. Plasma was stored at \u221220\u00b0C until processing.", "Relating to the genetic variability of CDV, it would interesting to identify the different CDV genotypes in positive samples, in order to differentiate between vaccine and field strains, and determine which lineages circulate on this island.", "For CDV the OD values had correspondence with the indirect immunofluorescence (IIF) method, and the values were divided into three categories: 1) low titer (IIF values: 1/20-1/40), 2) medium titer (IIF values: 1/80-1/160) and 3) high titer (IIF values: \u2265 1/320).", "Records were only available for the specimens sampled in 2011. Of the 125 dogs, all them of undetermined or mixed breeds, 65 were females (52%) and 57 males (46%). For 3 dogs (2%) no data was registered regarding gender.", "Only two samples, collected in each year of the survey, tested positive for CCoV-RNA, (2010 (1/53, 1.9%) and 2011(1/93,1.1%)). The percentage of positivity in each group is indicated between brackets." ] },{ "paper_id": "31a8187c739fcc29ee62764d0c8da44bdc1b4d8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Other possibilities for GBF1 function during viral replication include mechanisms unrelated to Arf activation. For example, GBF1 function during poliovirus replication has been demonstrated not to depend on its catalytic Sec7 domain and therefore on Arf1 and COP-I activation [166] . This suggests that in addition to Arf activation GBF1 has unknown cellular functions that viruses could hijack.", "HCV infection affects lipid metabolism and cholesterol homeostasis in particular. The association of HCV with lipid metabolism has long been noticed in clinical practice. Liver biopsies of infected patients present an increase of neutral lipids in cytosolic lipid droplets [3] . Non-A and non-B hepatitis has been associated with liver steatosis, frequent hypobetalipoproteinemia and reduced blood levels of cholesterol (reviewed in [4] ). It is worth noting that patients infected by genotype 3 viruses are more prone to severe steatosis, suggesting that specific viral sequences are responsible for lipid accumulation in the liver (reviewed in [5] ). Although several mechanisms have been proposed to account for the viral steatosis, no experimental model clearly recapitulates the phenotype observed in humans. HCV treatment by interferon alpha and ribavirin restores the cholesterol and the lipoproteins levels in patient sera [6] . At the same time, initial virus purification from infected patients sera revealed the low density of the virions and their association with apolipoproteins [7] .", "Hepatitis C Virus (HCV) affects over 150 million people worldwide. The majority of infections evolve to chronicity and liver disease starting from steatosis and fibrosis to cirrhosis and hepatocellular carcinoma [1] . Until recently, the standard for therapy has been represented by pegylated interferon alpha plus ribavirin. The treatment had significant side effects and variable efficacy depending on the viral genotype. In the last two years, HCV therapy has been profoundly improved with the approval of direct acting antivirals in the clinical practice (reviewed in [2] ). The new gold standard for treatment has a better sustained virological response rate with significant reduction of the treatment period and less side effects. Despite significant advances in HCV therapy, the drug resistance and genotype specific efficacy are still issues to be considered.", "The late stage of HCV assembly debuts with core, the NS2 complex and the replication complexes in close proximity of LD. We may assume that virion budding probably derives from a combination of the pulling force resulting from lateral interactions of envelope proteins and the pushing force of the nascent nucleocapsid. Until now, our knowledge of HCV nucleocapsid envelopment is quite limited. However, as mentioned before, PLA2G4A might have a role in capsid envelopment and particle infectivity [191] ." ] },{ "paper_id": "31b039f27dbcd96df12be89f281f576d26fe80e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Gene prediction was performed by Glimmer [39] version 3.02, and results post-processed using TICO [40] for improving predictions of translation initiation sites. Automated annotation of the finished sequence was performed by a modified version of AutoFACT [41] , supplemented by analysis by InterProScan [42] . Manual curation of annotation results was done with support from the software tool GenDB [43] . In addition, annotation of membrane transport proteins was done by performing BLAST search of all predicted genes against the curated TCDB [44] . Ribosomal RNA genes were annotated using the online RNAmmer service [45] . Putative prophage sequences were identified using Prophage Finder [46] . Frameshift errors were predicted using ProFED [47] . CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats) were searched by using PILER-CR [48] , CRISPRFinder [49] and CRT (CRISPR recognition tool) [50] .", "The genome sequence of L. hongkongensis HLHK9 was determined with the whole-genome shotgun method. Three shotgun libraries were generated: one small-insert (2-4 kb) library and one medium-insert (5-6 kb) library in pcDNA2.1, and a largeinsert (35-45 kb) fosmid library in pCC2FOS. DNA sequencing was performed using dye-terminator chemistries on ABI3700 sequencers. Shotgun sequences were assembled with Phrap. Fosmid end sequences were mapped onto the assembly using BACCardI [38] for validation and support of gap closing. Sequences of all large repeat elements (rRNA operons and prophages) were confirmed by primer walking of fosmid clones.", "The nucleotide sequence for the complete genome sequence of L. hongkongensis HLHK9 was submitted to Genbank under accession number CP001154." ] },{ "paper_id": "31b6292728805572de28133c6eb02ed1d44ef211", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\"LA is different, and hopefully represents a kind of scientific publication machinery that removes the hurdles from free flow of scientific thought.\" Your paper will be: \u2022 Available to your entire community free of charge \u2022 Fairly and quickly peer reviewed \u2022 Yours! You retain copyright http://www.la-press.com" ] },{ "paper_id": "31c0ee2b6dff1699d251316667c0b56c7b8f09a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Primary antibodies used in cattle were: non-labeled CD3 (MM1A, IgG1), TCR\u03b3 \u03b4 (GB21A, IgG2b), CD21 (BAQ15A, IgM) (all from VMRD) and Alexa Fluor 488-labeled CD335 (AKS1, IgG1, AbD Serotec). Secondary antibodies used were: goat anti-mouse IgG1-FITC (Santa Cruz Biotechnology), goat anti-mouse IgG2a-APC (Invitrogen), rat anti-mouse IgG1-APC (BD Biosciences), rat anti-mouse IgG2b-FITC (Southern Biotech), rat anti-mouse IgM-APCCy7 (Biolegend) and goat anti-mouse IgG2a-PE (Invitrogen).", "Antibodies used for mice were: CD3-PECy7 (clone 145-2C11), CD4-Biotin (clone RM4-5) and CD8a-PECy7 (clone 53-6.7) from eBioscience, and CD3-APC (clone 145-2C11), CD335-AlexaFluor647 (clone 29A1.4), CD19-Biotin (clone 1D3) and TCR\u03b3 \u03b4 -FITC (clone GL3) from BD Biosciences. Biotin-conjugated antibodies were fluorescently labelled using streptavidin-APC-eFluor780 (eBioscience).", "Recombinant ASP was produced in Pichia pastoris as previously described 36 and will be referred to as pASP." ] },{ "paper_id": "31cc00c5c0a5298a2e22068195971a9e5f3a4fe4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The checklist resulting from workgroup deliberations is organized around recommendations for reporting background, search strategy, methods, results, discussion, and conclusions (TABLE) .", "Participants Twenty-seven participants were selected by a steering committee, based on expertise in clinical practice, trials, statistics, epidemiology, social sciences, and biomedical editing. Deliberations of the workshop were open to other interested scientists. Funding for this activity was provided by the Centers for Disease Control and Prevention.", "Assessment of the usefulness of recommendations for reporting is dependent on a well-designed and effectively conducted evaluation. The workshop participants proposed a 3-pronged approach to determine usefulness and implementation of these recommendations." ] },{ "paper_id": "31ce4647dd3ce32716212b10cfa8b05724dc32fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:39010 | DOI: 10 .1038/srep39010" ] },{ "paper_id": "31cfa31a4d8a26ca083257be0e6dce51562d8c6d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "31d093e41e871ccc4472ec4bcfccb4a94a46653e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To infer statistical differences in the serological results, the Fisher's exact test was applied, whereas for survival rates the Mantel-Cox test (log-rank test) was used as implemented in GraphPad Prism version 7.00 (GraphPad Software, La Jolla California USA), with p-values < 0.05 considered significant.", "There was a significant difference (Fisher's exact test, p = 0.0031) in the parenteral versus the DOA vaccinated group. In general, with < 31.4% the DOA vaccinated animals showed only a 1.3 fold increase in ELISA mean PB values at days 28 and 56 p.v. compared to day 0 and remained below the ELISA cut-off of positivity. Though there was a 1.7-2.0 fold increase compared to day 0 the GMT of VNAs of orally vaccinated animals remained below 0.5 IU/ml until challenge (Tables 3, S3, Fig. 5) .", "There is no other country in the world with such a large population of Kudus than Namibia. The high population density as a result of game farming is thought to favor rabies epidemics among this species. Experiments involving large, highly stress-sensitive wild-caught species like Kudus are typically limited by space and cost. Also, the lack of suitable research facilities able to house these large antelopes under quarantine conditions restricted this study to a relatively remote holding site that is normally used for temporary housing of wild game for sale and auctioning, hence complicating observations, sampling, sampling storage and -transportation. The precautions and safety measures specifically developed for the purpose of the study were of high standard and have proven to be useful in preventing contact to free-roaming wildlife in adjacent areas (Fig. 2) .", "Animals and housing conditions. Adult free-living Kudus (n = 46) were caught by mass capture or by individual darting from a helicopter on game farms in three different Conservancies and transported to the experimental holding facility on the Okosongoro Safari Ranch located about 265 km northwest of Windhoek (Fig. 1 ). Blood samples were taken on the day of capture to assess the immunological status of the animals." ] },{ "paper_id": "31e1410cb8c22cfaae254381a16e88ec633086e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "31f30e0bd74035d9bbae69437e8af989fa78966c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2018, 10, 36 8 of 20 spermidine synthase; SMS, spermine synthase; SMO, spermine oxidase; SAT1, Spermidine/spermine N(1)-acetyltransferase). Ornithine decarboxylase antizyme (OAZ), the first rate-limiting step in polyamine synthesis, binds and inhibits ODC. Difluoromethylornithine (DFMO), currently in clinical trials for cancer treatment, is an irreversible inhibitor of ornithine decarboxylase. T bar indicates inhibition. Blue dotted circle, nucleus. Consult text for more detail.", "Prior to its discovery as an antiviral factor against viruses, SAMHD1 gene mutations were found to associate with the autoimmune neurological condition, the Aicardi-Gouti\u00e8res syndrome (AGS) [119] . AGS affects new-born infants and mimics a congenital viral infection with elevated interferon\u03b1 levels in cerebrospinal fluid [120] .", "An alternative cellular mechanism involves a membrane protein called CD81 that binds to SAMHD1 and interacts with SAMHD1 and directs SAMHD1 toward proteasomal degradation [137] ." ] },{ "paper_id": "31f33e2c73a467477e3a4a72e6ee128703946fe5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study adopted a qualitative approach, particularly valuable when seeking to explore processes of implementation [25] .", "Seven categories of factors which influenced TB service integration were: historical context, clinical capacity, motivation for integration, resource allocation, incentive and staffing, management coordination, and technical exchange." ] },{ "paper_id": "31f9d7bce1db40d866a3e93b06ff9515c34fc3b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data management, statistics and creation of map shape-files were performed using SAS 9.2 (SAS Institute, Inc., Cary, NC, USA) and ArcGIS 9.1 (ESRI Inc., Redlands, CA, USA)." ] },{ "paper_id": "31fa7844fdceee15b185eb734a7e1a09527431e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The family Coronaviridae is divided into the subfamilies Coronavirinae and Torovirinae. Torovirinae includes the genera Bafinivirus and Torovirus, infecting fish and mammals respectively, while Coronavirinae includes the genera Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus, commonly infecting mammals and birds. SARS-CoV and MERS-CoV are members of the genus Betacoronavirus. Therefore, a useful model for these two viruses, especially with regard to their structure and replication, is Murine coronavirus, a betacoronavirus that is commonly referred to as mouse hepatitis virus (MHV).", "The sequencing data have been deposited in the ArrayExpress database (http://www.ebi.ac. uk/arrayexpress) under the accession number E-MTAB-4111." ] },{ "paper_id": "31fabefa068bca926a43f94ef80df1daf41aa806", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal trials were carried out at CSIRO Black Mountain Laboratories according to the Australian Code for the Care and Use of Animals for Scientific Purposes (2013) and approved by the CSIRO Ecosystem Sciences Animal Ethics Committee (permit identifiers: CESAEC 13-01, DOMRAB).", "Amplicons for each virus (i.e. from each individual animal) were quantified using the Qubit dsDNA BR assay (Life Technologies) and pooled in equimolar ratios, before dilution to a final concentration of 0.14 ng/\u03bcl in UltraPure DNase/RNase-free distilled water (Life Technologies).", "https://doi.org/10.1371/journal.pone.0173727.g005" ] },{ "paper_id": "31fd4d2067fb03f503ce03d16e323020b9f1d219", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "32011a9e06d16f2e8bf8f86977aaa8143e9fc692", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The SDSG strain (Accession number: KJ740747.1) was isolated from a duck farm in Shandong province in 2013. The virus titer was 10 4.8 ELD50/ 0.2mL (Median embryo lethal dose), calculated according to the Reed and Muench method (Reed and Muench, 1938) . The duck and mouse sera against TMUV were also provided by Dr. Ke-Xiang Yu. ", "This research was approved by the Committee on the Ethics of Animal of Shandong (permit number 20147620)." ] },{ "paper_id": "3207d738e32216ee810dcb38fdbdf73d47eafaca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. Data are presented as the mean \u00b1 standard deviation. The SPSS 17.0 statistical package (SPSS, Inc., Chicago, IL, USA) was used for the statistical analysis. Student's t-test was used for comparisons between groups. P<0.05 was used to indicate a statistically significant difference.", "Glycyrrhizin, a naturally occurring licorice flavonoid glycoside extracted from licorice (Glycyrrhiza uralensis Fisch) root has been reported to have multiple functions (1) (2) (3) ; it can scavenge free radicals, have anti-bacterial, anti-inflammatory, antiviral and anti-ulcer effects and protect cytochrome enzymes as an antioxidant (1) (2) (3) (4) (5) (6) . Studies have shown that glycyrrhizin can regulate the secretion of various cytokines and the functioning of immunomodulatory effects in the central nervous system (6, 7) . Glycyrrhizin can also improve intracerebral ischemic injury (6, 8, 9) . During 20 years of anti-inflammatory application for the treatment of liver diseases, glycyrrhizin has not generated any toxicity or side-effects (10) (11) (12) . However, the effects of glycyrrhizin on functional recovery following peripheral nerve injury are not well understood.", "Electroneurophysiological testing. Affected sciatic nerves underwent electroneurophysiological testing using an electromyograph and evoked potential machine (Keypoint \u00ae , Medtronic A/C Inc., Skovlunde, Denmark) prior to the mice being sacrificed, as previously described (20) , with certain modifications. Briefly, the sciatic nerves were exposed at 24\u02daC, then pin electrodes were pierced into the musculi soleus for wave recording (M point) and grounding electrodes were placed on the tails. A single current stimulus (10 mA) was employed to stimulate proximal anastomotic ischial tuberosity (P point) and the distal sciatic nerve bifurcation point (D point), respectively, using a parallel stimulating electrode with a fixed space of 3.3 mm between two tips. Motor nerve conductive velocity (MNCV) equaled the distance between the P and D points divided by the difference value of potential latency." ] },{ "paper_id": "322b92b3fe13a75501b634f427892409246de419", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All swabs were kept on ice and stored at \u2212 80\u00b0C within one hour, until analysis.", "No animals seroconverted towards BCoV or BPIV-3.", "The inoculation procedure was performed on non-sedated calves via manual restraint. The head was kept in a horizontal position while 5 ml inoculum was nebulized intranasally by use of a perforated plastic tube with a diameter of 1.57 mm and an inner channel of 1.14 mm. The tube was inserted 15 cm into the left nostril. After nebulization, the left nostril was closed by hand to avoid outflow of the inoculum." ] },{ "paper_id": "322e9f87ee07bd71dd82ebf7e431c34580feef25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are shown as the means \u00b1 standard errors of three replicates per test in a single experiment repeated thrice. GraphPad Prism V5.0 (San Diego, CA, USA) was used to perform statistical analyses. Tukey's multiple comparison tests and one-way analysis of variance (ANOVA) were used to analyze the significance of the difference between means. p-Values less than 0.05 (p < 0.05) were considered significant and p-values less than 0.01 (p < 0.01) as highly significant.", "Lactobacillus casei ATCC 393 (L. casei 393) was cultured in our laboratory in de Man, Rogosa and Sharp (MRS) broth at 37 \u2022 C without shaking. PEDV LJB/15 strain was isolated and identified from clinical samples by our laboratory and was propagated in Vero cells at 37 \u2022 C with 5% CO 2 . The constitutive expression plasmid pPG-T7g10-PPT (Figure 1Aa ), was constructed in our laboratory. ", "As shown in Figure 2B , DCpep protein can be detected with COE-DCpep antiserum which wasdiluted at 1:2-1:64. With the increase of dilution of COE-DCpep antiserum, the immunoreactive is weakened. Moreover, we showed that there is no cross-reactivity between the mouse anti-COE monoclonal antibody and synthetic DCpep protein. ", "Intestinal DC subsets regulate of the intestinalimmune homeostasis through linking humoral and cellular immune responses [12] . It was confirmed that an intestinal DC-targeting oral vaccine could elicit highly efficient antigen-specific immune responses, protecting the mucosal membrane against pathogen infection [13] . Currently, the vaccine strategy of using Lactobacillus to express DC-targeting peptide (DCpep) conjugated with Bacillus anthracis PA antigen [14] and Newcastle disease virus HN antigen has been investigated to show improved immunogenicity." ] },{ "paper_id": "3236c24e4656add3fbf17ed686d2b7c73bb52de9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Serial plasma specimens were collected from 12 US donors who became HIV-1 infected during the collection period. The seroconversion panels were obtained from SeraCare Life Sciences (n = 7) (Gaithersburg, MD) and ZeptoMetrix Corp. (n = 5) (Buffalo, NY) [24, 25] . ", "An HIV-1 RNA linearity panel was created using the supernatant from 8E5 cells (ATCC, Manassas, VA), which contain a single defective proviral genome of HIV-1 per cell, but still ", "The presence of amplified product was determined visually by observing fluorescence in the reaction tubes using the UV lamp from a GelDoc XR+ Imaging System (BioRad Laboratories, Hercules, CA)." ] },{ "paper_id": "323c52cddef7a35732afdc41dac2a1aa6cb60f16", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In conclusion, this bioinformatics approach demonstrates the superiority of BA and UPGMA models over MP model for phylogenetic analysis using different regions of mtDNA or other datasets of this size. However, the implication of these fi ndings to different data structures e.g. multiple sequences and more numbers of taxa or outgoups is not clear and needs further investigations.", "The results of Tajima's neutrality are given in Table 1 . Both the number of segregating sites (S) and nucleotide diversities (\u03c0) were directly correlated and were in the order of 16S rRNA (S = 17, \u03c0 = 0.025) \u03fd cyt-b (S = 125, \u03c0 = 0.058) \u03fd d-loop (S = 270, \u03c0 = 0.122) ( Table 1 ). The test of homogeneity of substitution patterns showed certain identities and certain variations in disparity index as well as Monte Carlo probability for different mitochondrial markers ( Table 2) .", "The UPGMA model also produced similar phylogenies to BA model for 16S rRNA and d-loop sequences however cyt-b inferred a different phylogeny (Fig. 3) . These differential phylogenies may be associated with comparatively high variations in non-coding d-loop than coding cyt-b due to reduced functional constraints and relaxed selection pressure. Although, increased polymorphism in d-loop segment may render it superior to cyt-b for species or sub-species level identifi cation, the possibility of reduced phylogenic information due to back mutations and parallel substitutions in rapidly-evolving d-loop may not be ruled out. It is also important to mention that changing the outgroup species or the length of d-loop segment can signifi cantly alter the topology of phylogenic trees (Iyenger et al. 2006 )." ] },{ "paper_id": "323e747a1a351a6ec4053512e45718fc27d242d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An increased use of maternity services in local community hospitals occurred during the SARS epidemic in Taiwan. However, we observed no increase in neonatal and maternity mortality associated with these increased demands on local community hospitals.", "Linear regressions were estimated using data from the years 1998 to 2002 to examine the changes in neonatal mortality rates for the pre-SARS period. A total of 22 counties were included in the analysis. We excluded the data from three isolated islands with no advanced medical institutions and small populations because the expense of transportation in these locations may have prevented expectant mothers from voluntarily selecting advanced hospitals and little shifting would have occurred. Furthermore, the SARS patients were found only on Taiwan's main island.", "SHH contributed to the design and the analysis of the data, commented on the interpretation of the results, and completed the writing of the article. LKC collected the data and contributed to the interpretation of the results and writing of the article. All authors reviewed and approved the final draft of the manuscript." ] },{ "paper_id": "3240298a10e4834230eabe0b7cb5a728c00779af", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Transformation, selection, and regeneration of transgenic plants", "Spleens from orally immunized mice were minced with a razor and added to 1 ml ice cold endotoxin-free PBS containing a protease inhibitor cocktail (Roche) and 0.1% Igepal CA-630 nonionic detergent (Sigma) [34] ." ] },{ "paper_id": "324224a860eb73492e4207926e5ea62cd1a910d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consistent with previous observations, recent experiments performed in mammalian cells using IBV showed that this avian coronavirus is also capable of inducing autophagy during infection [55] .", "Here, further work was performed and individual expression of viral nsp6 was also capable of inducing autophagy, whereas nsp4 and nsp10 were not. Nsp6 induced autophagosomes fused with LAMP1 labelled lysosomes and autophagosomes were susceptible to wortmannin treatment. This indicates that bone fide autophagy was induced. Interestingly, nsp6 homologues from SARS-CoV, MHV and arterivirus porcine reproductive and respiratory syndrome virus (PRRSV), also induced autophagy.", "Coronaviruses are single stranded positive sense RNA viruses belonging to the order Nidovirales, and are known to infect a variety of hosts. Several human coronaviruses have been identified, causing mainly mild respiratory infections, with the exception of severe acute respiratory syndrome coronavirus (SARS-CoV). In addition, coronavirus infections have an economic impact on livestock industries worldwide. The avian coronavirus, infectious bronchitis virus (IBV), causes infectious OPEN ACCESS bronchitis (IB), a mild respiratory infection, but as a consequence is responsible for serious effects on the global poultry industries due to poor weight gain in broiler chickens as well as reduced egg production and egg quality in layers. In addition, some strains of IBV are nephropathogenic whilst others result in severe pathology in the reproductive organs. Bovine coronavirus (BCoV) causes respiratory infection and diarrhoea in cattle, transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhoea virus (PEDV) cause diarrhoea in pigs and porcine haemagglutinating encephalomyelitis virus (PHEV) causes vomiting and wasting disease in pigs." ] },{ "paper_id": "324deb63a4686d7efc7c32b8e20bdc7e96e1fb7e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experimental groups were composed of 10 animals. Data are expressed as mean \u00b1 standard deviation Analyses were performed using Student's t-test and repeated measures one-way analysis of variance (ANOVA) with computer software SPSS 13.0. The values were considered to be significantly different as p < 0.05.", "One-year-old roots were collected and identified according to the botanical morphology of Glycyrrhiza uralensis Fisch, characteristic and microscopic character description of the roots recorded in Chinese Pharmacopoeia.", "To study the influence of space flight on the components of licorice, chromatographic fingerprint with good resolution of adjacent peaks was obtained. The chromatogram acquired by HPLC-DAD at 254 nm was showed in Figure 1 . The differences of main components were found in the groups of H to HCK and A to ACK.", "and anti-inflammatory activity is one of the most important pharmacological activities." ] },{ "paper_id": "32501343a772539b8477e17940f7333e8678fe5f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where is the sampling time (seconds postinjection). The function starts at (0) = 1 (thus assuming no metabolism before injection) and has an asymptotic value (\u221e) = .", "Rather than imposing a specific model on these tracers, we examined the applicability of three different models for each tracer ( Figure 2) ." ] },{ "paper_id": "325688eb32f8e6875a930f831c4cea02b2a556c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3256ad6795fb323a3711f3d3d6f7ae85657fc5ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. Two-tailed Student's t test was applied to evaluate the statistical significance of differences measured from the data sets obtained in 3 independent experiments. p < 0.05 was considered statistically significant.", "Influenza A viruses (IAVs) constantly circulate in animal hosts including birds, human and pigs. Seasonal IAVs are one of the major causes of respiratory tract infections and responsible for 3-5 million clinical infections and 250,000-500,000 fatal cases annually 1 . IAV is a negative sense single-stranded RNA virus with segmented genomes 2 , which belongs to the family Orthomyxoviridae and is subtyped based on its surface glycoproteins haemagglutinin (HA) and neuraminidase (NA). So far, 18 HA and 11 NA subtypes have been identified 3 , with the H1N1 and H3N2 subtypes being the seasonal IAVs currently circulating in human 4 .", "AlphaScreen-based dsRNA binding inhibition assay. A 21nt-siRNA previously reported to form complex with NS1(RBD) 34 was purchased from Thermo Scientific Dharmacon (Dharmacon, Lafayette, CO). The siRNA was biotinylated at the 5\u2032 end of the sense strand and the siRNA sequences were as follows:" ] },{ "paper_id": "3268f252e2559df8ea83c97725a4412a003670ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bronchial alveolar lavage (BAL) fluid was collected using a protocol modified from (35) . Briefly, the tracheae were cannulated with a 22-gage catheter tube (attached to a 5cc syringe) and then washed once with 1 mL of sterile PBS. Samples were stored at \u221220 \u2022 C until analysis.", "BN, TW, and KL conceived the research. ZZ, TW, and KL designed the experiments, analyzed data, and interpreted the results. ZZ conducted the experiments. EH provided technical assistance with processing of tissue samples and flow cytometry. KR, JG, and BN manufactured the IAV-nanovax. ZZ and KL wrote the manuscript and ZZ, KR, JG, TW, BN, and KL edited the manuscript. All authors reviewed and approved the manuscript. ", "Lung viral titers were analyzed by plaque assay on whole lung homogenates. Briefly, serial dilutions of homogenized lung samples were applied to confluent Madin-Darby canine kidney epithelial cell layers and incubated for 1 h at 37 \u2022 C. Cell layers were washed and a minimum essential media agar overlay was applied and incubated for 3 days at 37 \u2022 C. Cell layers were fixed in 4% formaldehyde, blocked with 5% milk, and plaques were detected with polyclonal anti-IAV A/Puerto Rico/8/34 (H1N1) chicken antiserum (NR-3098; BEI Resources), peroxidase-conjugated AffiniPure rabbit antichicken IgY (Jackson Immunoresearch, West Grove, PA), and TrueBlue R peroxidase substrate (KPL, Gaithersburg, MD)." ] },{ "paper_id": "3273d1af75cb33dbbec0d61dded9d576fe946030", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where X ij represents the distance from i virus strain to j virus strain in distance matrix of gene X; X represents the mean of all X ij values; Y ij represents the distance of strain i to strain j in the distance matrix of genome Y; Yrepresents the mean of all Y ij values; and N represents the number of viral strains in the matrices.", "constructed from the other genes in the same genome, in both their topologies and branch lengths in a way.", "For HEV, all the correlation values were less than 0.990, relatively lower than those for the other viruses ( Table 1 ). The MJ-C region had the highest value (0.983) with the genome whereas the KLY-B region had the lowest r-value (0.933)." ] },{ "paper_id": "327803ba593def74cf64634bc148a46935a3dd10", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza-related death 2 (9 %) 2 (18.2 %) 0 0 Week ( " ] },{ "paper_id": "3289d3f6963ba040c68dbbde3120156d73e1e5b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In accordance with Dutch law, no informed consent was required for this study using anonymised routine surveillance data.", "helps to assess whether there is endemic circulation or new introductions of mumps viruses in the country.", "In addition to the NEWC reports, clusters 2 and 3 are described in references [33] and [32] , respectively." ] },{ "paper_id": "328b36edcc6169a2aceba2c7e6859d1770d6a81d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Participants could refuse any of these options, as well as any questions posed to them during the interview itself. All participants were de-identified to maintain confidentiality.", "A few participants articulated that rather than forcing a top-down policy approach, AMR could be better tackled by the sharing of best practices through communities of practitioners and creating social movements to encourage and sustain behavior change.", "(4) through independent agencies and expert bodies; (5) and by adaptive policies, resilient structures, and foresight.", "Laying the foundation of surveillance in public hospitals and making the data transparent was appreciated by all participants. Participants also shared recent advances in the capacity to implement stewardship and infection prevention and control policies among different Singapore institutions including nursing homes.", "\"We are looking to reaching out to even nursing homes to provide that kind of bold infection prevention, but also infection control.\" -I03, Human Health", "\"We had this roundtable discussion. Everybody, all the movers and shakers, public health systems . . . and they were asked to state these priorities. And believe it or not, infection, the scourge of infection wasn't one of the top five.\" -I02, Human Health" ] },{ "paper_id": "32b10bf8534bb8843320576bbf033d983e89f692", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "32b29df5230354c35d8734b996e5e45501a5111b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mean values and standard deviation were calculated. Statistical analysis was performed using the paired Student's t-test. P,0.05 was considered significant.", "A plasmid-based rescue system [27] was used to generate a Gdeleted VSV driving expression of firefly luciferase and eGFP. The previously described genomic plasmid pVSV*DG(HA) containing 6 distinct transcription units (N-P-M-HA-eGFP-L) [28] was modified by replacing the influenza virus HA gene in the fourth position with eGFP taking advantage of MluI and BstEII endonuclease restriction sites upstream and downstream of the HA ORF, respectively. The firefly luciferase gene was amplified from the pBI-L plasmid (Clontech) by Pfu PCR and inserted into the fifth transcrition unit using XhoI and NheI endonuclease restriction sites. The resulting plasmid was designated pVSV*DG(Luc) and contained 6 genes in the order N-P-M-eGFP-Luc-L (Fig. 1) .", "Cells BHK-21 cells were obtained from the German Cell Culture Collection (DSZM, Braunschweig, Germany) and grown in Earle's minimal essential medium (EMEM) supplemented with 5% fetal bovine serum (FBS). BHK-G43, a transgenic BHK-21 cell clone expressing VSV G protein in a regulated manner, was maintained as described previously [23] . The porcine kidney cell line PK-15 (ATCC, Manassas, VA) was propagated in Dulbecco's modified Eagle medium supplemented with nonessential amino acids, 1 mM Na-pyruvate and 5% horse serum. D-17 canine osteosarcoma cells (ATCC), Calu-3 human lung adenocarcinoma cells (ATCC), and NHDF normal human dermal fibroblasts (Lonza, Cologne, Germany) were maintained in EMEM with 10% FBS. The UMNSAH/DF-1 (DF-1) chicken fibroblast cell line (ATCC) was maintained in Dulbecco's Modified Eagle's Medium and 10% FBS. All cell lines were cultured at 37uC in a humidified atmosphere containing 5% CO 2 , except DF-1 cells which were kept at 39uC. BALB 3T3 fibroblasts (subclone A31) were kindly provided by N. Pringle, University College, London, UK, and maintained in Dulbecco's Modified Eagle's Medium." ] },{ "paper_id": "32c5106b9647b0d72f6c6fb15bf114e15d71736d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine epidemic diarrhea (PED) is a highly contagious enteric disease characterized by vomiting, acute watery diarrhea, and in particular, a high mortality rate in suckling piglets, resulting in substantial economic losses [1] . The etiologic agent of this disease is the PED virus (PEDV), which is an enveloped, positive-sense, single-stranded RNA virus that belongs to the order Nidovirales, family Coronaviridae, and genus Alphacoronavirus. The disease was initially reported in England in 1971 [2] and Belgium in 1978 [3] . Since then, it has been identified in many swine-producing countries such as those in Europe and Asia, notably Belgium, Czech a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "The samples were obtained from a naturally infected animal in the field by qualified veterinarians as a part of normal veterinary care and diagnostic testing procedures. Samples of intestine used were collected from dead piglets and the fecal samples were non-invasively collected immediately after excretion. Therefore, no aggressive operation had been conducted against pigs for sampling purpose. No piglets or other animals were sacrificed for the purposes of this study. The University of Miyazaki DNA recombinant Committee approved the protocol for our cloning work of PEDV (protocol number 2014-464).", "All sequences were determined in both directions, and sequencing reactions were performed using BigDye Terminator v3.1 Cycle Sequencing Kits and an ABI PRISM 3130xl Genetic Analyzer (Applied Biosystems, US). Nucleotide and deduced amino acid sequences were edited, assembled, and analyzed using Geneious v9.0.4 software (http://www.geneious.com) and molecular evolutionary genetics analysis (MEGA) software version 6.0 [34] . The resultant nucleotide sequences were deposited in GenBank under the following accession numbers: KU363044-KU363130. Phylogenetic trees based on the nucleotide sequences of the full-length S gene and ORF3 gene were constructed by the maximum likelihood method using the Tamura-Nei substitution model with a discrete gamma distribution; then gaps/missing data treatment was done by complete deletion, and bootstrap tests of 1000 replicates in the MEGA program." ] },{ "paper_id": "32c89e23750b5dbc17e97eecfc5e916c15600ebe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The article follows with a methods section on literature review and documentary analysis. This precedes a results section that presents the main findings from our four regions under study, a discussion of these findings and final conclusion.", "The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.", "Moreover, the literature shows that framing these narratives can be instrumental in introducing an issue into political agendas potentially leading to the institutionalisation of norms (Boas and McNeill, 2004; Finnemore and Sikkink, 1998) . For instance, the Millennium Development Goals (MDGs) are an example of an initiative that emerged from a norm regarding poverty as morally unacceptable and something that should generate collective action for its eradication (Fukuda-Parr and Hulme, 2009; Ottersen et al., 2014) ." ] },{ "paper_id": "32d5699f514f8d58fa7939fefaea6ef9fce1121c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was carried out in Excel 2003 (Microsoft), and statistical significance was determined with two-tailed Student's t tests for comparing two independent groups, or with one-way ANOVA using \u03b1 = 0.05 for comparing more than two groups. In all experiments P < 0.05 is considered statistically significant; *, P < 0.05; **, P < 0.01; ***, P < 0.001." ] },{ "paper_id": "32d5b5c7b38c1dd14b316de97bce86e5ab252f91", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All recombinant (r) flavivirus NS1 antigens used in this study were purchased from NativeAntigen (Oxfordshire, UK). Recombinant sumo protein was purchased from LifeSensors (Malvern, PA, USA).", "Rapid tests such as the NS1 enzyme-linked immunosorbent assay (ELISA) are commercially available for DENV with relatively good sensitivity and specificity [3] .", "Mice immunization, and isolation of anti-DENV-4 NS1 MAbs secreting hybridoma clones" ] },{ "paper_id": "32da24606ad160166f08cf05349eaadd580ccff0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The HCoVs occupy two of four genera in the subfamily Coronavirinae [4] . Human coronavirus 229E and Betacoronavirus-1 subspecies HCoV-OC43 have been known for more than 50 years, while Human coronavirus NL63 and Human coronavirus HKU1 were first characterised in 2004 and 2005, respectively.", "Receptor binding and fusion to cell Antigenic Trimeric ", "The rarity of seropositive donors, sometimes low antibody titres, and a lack of clinical evidence have made the use of convalescent sera from recovering MERS patients a possibility for treatment, but one with significant limitations [39] . Instead, human monoclonal antibodies targeting the RBD and polyclonal antibodies may provide treatment options for those at risk of severe outcomes [107] [108] [109] [110] . Clinical trials are awaited." ] },{ "paper_id": "32e54e86db8e7cc46844319fb3dba6d9a02a86f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cost of pandemic with no border closure 14.4 120.6", "We explored two additional scenarios in which import/export trade: (i) was reduced by 50%; and (ii) ceases completely:", "\u2022 The method used monetized QALYs (based on GDP per capita valuation as used in WHO CHOICE work) which although having an element of resource realism, is still somewhat arbitrary. Also some societies may use different discount rates than the 3% that was applied to both costs and health gains in this study.", "An expected value for each input variable was calculated and a distribution estimated. We ran a probabilistic sensitivity analysis (PSA) on the base case using values sampled randomly from the distributions for all variables and 1000 iterations. For this the Excel add-in tool Ersatz (Epi-Gear, Version 1.3) was used. The cost-benefit results for other scenarios were calculated using expected values for the variables." ] },{ "paper_id": "32e9da5d0766c5b192ba52080d05a9d91edf74eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The nucleotide sequence of BRBV_SWE1 has been deposited in GenBank under the accession no. KY432299.", "A bovine rhinitis B virus, identified in a calf from Sweden, was genetically characterized. The complete polyprotein was recovered, and phylogenetic analysis showed that this virus has the highest similarity to a bovine rhinitis B virus previously identified in Mexico.", "B ovine respiratory disease (BRD) is a complex condition that is costly for the cattle industry worldwide. Several viruses have been associated with BRD, such as bovine coronavirus (BCoV), bovine respiratory syncytial virus, bovine parainfluenza virus 3, and bovine herpesvirus type 1 (1, 2) . In a sample from an experimental study investigating BCoV (3), a nearly full-length genome of a bovine rhinitis B virus (BRBV) was identified." ] },{ "paper_id": "32ffbe671caf791831bb7516b550b4b27240a5f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Despite the mentioned limitations, data were aggregated directly from medical charts rather than public source databases.", "There are no conflict of interests. " ] },{ "paper_id": "33019198857c41e85955b2b731077ab3ea57c85b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The rising of antibodies to PToV antigens after weaning can be explained as a consequence of the animal grouping in livestock facilities for fattening purposes that provides", "Protein concentrations in the cell extracts were determined by Bradford reaction (Bio-Rad Protein Assay) using known amounts of purified bovine serum albumin (BSA) as standards.", "Cells, viruses and antisera BSC40 (African green monkey kidney cells) cells were grown in Dulbecco's modified Eagle's medium (DMEM), supplemented with 5% heat-inactivated neonatal calf serum (NCS), non-essential amino acids (1%), gentamicin (50 \u03bcg/mL), penicillin (100 IU/mL), streptomycin (100 \u03bcg/mL) and fungizone (0.5 \u03bcg/mL)." ] },{ "paper_id": "330c656592e9917ebc7c9c1703ddaa3d9df809bf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author(s) declare that they have no competing interests." ] },{ "paper_id": "3319b5fd5749bba0f2fa25f335cc8c19b351a403", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All immunoblots, and immunofluorescence images shown are representative of reproducible experiments. Differences between groups were determined using Student's t-test (p < 0.05 was considered significant), and all statistical analysis was performed on GraphPad Prism 6.0. All experiments were performed a minimum of three times.", "The following primary Abs were used for immuno Alexa 568 conjugated polyclonal antimouse (Thermo Fisher, A11004) and anti-rabbit (Thermo Fisher, A11011) were used as secondary Abs prior to fluorescent imaging. For immunoprecipitation experiments, we used GFP antibodies coupled to magnetic beads (MBL, D153-9) and Flag antibodies coupled to agarose (Sigma, A2220) to pull down tagged proteins prior to immunoblotting. Cyclosporin A (R&D Systems, 1101) and Z-VAD-FMK (Sigma, V116) were used at 10 \u03bcM overnight, and Bafilomycin A1 (Sigma, B1793) at 100 nM for 4 h.", "Cell death assay 0.4% Tryptan Blue (Sigma T8154) was added to cell culture plates and incubated at room temperature for 2 min. Percentage of non-viable cells (cells that had taken up Tryptan Blue) was determined manually by light microscopy and recorded; a minimum of three fields with >50 cells per field were quantified." ] },{ "paper_id": "331d9c08ce93e1ca8843610514f7ecb1d83dd883", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The plasmids encoding SARS spike (phCMV-SS) and ACE-2 (pFLACE-2/T7RLuc) were described before [14] . Plasmids encoding mutant spike proteins were created by using the Quikchange method (Stratagene) and the products were verified by sequencing.", "SWT KWPWYVWLGFIAGLIAIVMVTILLCCMTSCCSCLKGACSCGSCCKFDEDDSEPVLKGVKLHYT SG1201K Sins1202K Sins1202A SA1204K SV1210K SV1210A SL1216K Sins1217K SS1221K SS1221A SS1224K SS1224A SK1227A 1238 Aromatic Central Cysteine A Cys Box1 Cys Box2 1189 SWT KWPWYVWLGFIAGL... SW1 F SW12 F SW123 F SW2 F SW23 F SW3 F SW13 F SW123 A S ARO F F F F F F F F F F F F K GFIAGL... A A A K K K A K K A K A A KWPWYVWLGFIAGLIAIVMVTILLKCCM.. SWT KWPWYVWLGFIAGLIAIVMVTILLCCMTSCCSCLKGACSCGSCCKFDEDDSEPVLKGVKLHYT S C27 KWPWYVWLGFIAGLIAIVMVTILLCCMTSCCSCLKG B KWPWYVWLGKFIAGLIA... KWPWYVWLGAFIAGLIA..." ] },{ "paper_id": "331efc82eb143a10c93bb64327998b525bc461a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All datasets generated for this study are included in the article/Supplementary Material.", "LAB are characterized by producing lactic acid and metabolites, including antioxidants, organic acids, and antimicrobial compounds, modulating and improving intestinal microbial balance (15) . LAB feed supplementation improves meat production through growth rate promotion, increased feed conversion, and disease prevention (2) . For example, probiotics have been used in pig feed for improving the immune status by reducing harmful microbes in their intestines (16) . Moreover, the administration of probiotics to dairy calves results in improvement daily weight gain and resolution of diarrhea (17) . Similar results have also been reported in other animals, including poultry (2, 18) , ostriches (19) , raccoon dogs (20) , and silver foxes (20) . LAB have widely been applied in animal feed. At present, screening for new probiotics, especially from some undeveloped species has become an ongoing practice (21) .", "The data analysis was performed using the program SPSS 22 Statistics. A one-way analysis of variance (ANOVA) was used to compare the data. Statistical significance was defined at P < 0.05." ] },{ "paper_id": "33222702ba2e2e7e5f526c667d64beb5bd2cda96", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "is the fraction of surviving target cells.", "All protocols involving human subjects were reviewed and approved by the Kyoto University institutional review board. Informed written consent from the human subjects was obtained in this study.", "The estimated parameter values of each individual mouse are given in Tables 2 and 3 . Using the best-fit parameter estimates the behavior of RQS and PWT models is depicted together with the individual data in Figures 4A and B , respectively, which confirms that both models reasonably describe the acute phase of HIV-1 infection in humanized mice.", "where the replication phase (Eq. (7)) is identical to the initial phase of the standard model (see the remark above). Thus, at the price of one additional parameter, we can generalize the depletion of target cells to mechanisms (e.g., inflammation, activation and redistribution of target cells) other than infection only, and have a model with very similar parameters characterizing the acute viral infection." ] },{ "paper_id": "3330a6e81c27b196cb5171baf11239a9560ff6e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nasal washes from each side of the nose were taken from consenting participants by trained medical staff, placed in viral transport media and refrigerated. The samples were transported to the laboratory on ice for etiological testing within 24 hours.", "The basic demographic data are described in Table 1 . Participants were mostly young male adults, with other characteristics largely similar. However, there were significantly less recruits amongst controls than amongst other groups." ] },{ "paper_id": "3331e1bb231ae4227e4b6e8e98412b17468747a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3339f4bb346bfa3070ae5fc7dc745ef051535b0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Text S1 Supporting information.", "The MHV fusion inhibitor HR2 peptide has been described before [100] and was synthesized by GenScript. The peptide was diluted in Tris/HCl 50 mM, pH 7. from Sigma-Aldrich. A stock of 125 mM CPI in PBS was made [76] and used at 5 mM final concentration.", "(PDF)" ] },{ "paper_id": "333a04fb2ab37297b4591e7d6179fd731f5c1bf3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequences obtained in this study have been submitted to GenBank under accession numbers KR002657 to KR002671." ] },{ "paper_id": "3341998ccda48a6464d056736f52a967b45df144", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Jaguarundis (Puma yagouaroundi) are small diurnal felids that have several unpatterned color morphsbrownish-black, gray and reddish-yellow furand are protected across most of their range. The species occurs at low densities and has a decreasing population in the wild, despite being widely distributed throughout South and Central America and occupying a broad range of habitats [1] . Mainly due to displacement from nature and, to a lesser extent, to captive breeding, jaguarundis are commonly found in zoos and similar captive settings in Brazil [2] .", "FeLV viral RNA loads and proviral loads were investigated using real-time RT-PCR and PCR and primers targeting the U3 region of exogenous FeLV, as previously described [30] . For tissue samples, the total copy numbers detected per reaction were normalized to the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene as described [38] .", "For sample prevalence, 95% confidence intervals (CI) were calculated. Fisher's exact test was used to compare frequencies between infected and uninfected animals. Pvalues <0.05 were considered significant." ] },{ "paper_id": "3345fa1a77d9ad2f4bce48138490e60a462fe18b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Historically, plant lectins have been characterized as hemagglutinin-or mitogen-acting toward animal cells (e.g., Griffonia simplicifolia lectin I (GSL-I) A4 hemagglutinin specific for blood type group A [1] [2] [3] and the plant toxin ricin known as Ricinus communis agglutinin II (RCA60) [4] [5] [6] ). Plant lectins exist as multiple molecular species (i.e., isolectins such as Ricinus communis agglutinin I (RCA120), RCA60, GSL-I A4, and GSL-I B4 [1, [7] [8] [9] [10] [11] ). These plant lectins have long been utilized in the glycoscience field, especially when no methods are available other than anti-glycan antibodies. Therefore, knowledge about glycan-binding properties is crucial to interpret the results obtained by their use.", "pNP glycosides Gal\u03b21-4GlcNAc\u03b2 (LacNAc-\u03b2-pNP), GlcNAc\u03b21-4GlcNAc\u03b21-4GlcNAc\u03b21-4GlcNAc\u03b21 (chitotetraose-\u03b2-pNP), and GlcNAc\u03b21-4GlcNAc\u03b21-4GlcNAc\u03b21-4GlcNAc\u03b21-4GlcNAc\u03b21 (chitopentaose-\u03b2-pNP), were obtained from Toronto Research Chemicals, Inc. (North York, ON, Canada).", "For the determination of B t and K d values for each lectin column, an appropriate pNP-saccharide was diluted to various concentrations (2-100 \u00b5M) and was used for concentration-dependent analysis. Using the resulting V values, Woolf-Hofstee-type plots, i.e., (V \u2212 V 0 ) vs. (V \u2212 V 0 )[A] 0 , were constructed to determine B t and K d values from the intercept and the slope of the fitted curves, respectively, as described previously [9] ." ] },{ "paper_id": "334adcddbb251335c86c3a5d79a0f66b526109ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession numbers. The complete genome sequences of CBR1 and EAS1 have been deposited in Gen-Bank under the accession numbers KR610993 and KR610991, respectively.", "Thailand was a new variant containing an insertion and deletion in the spike gene. Herein, full-length genome sequences are reported for two variants of PEDV isolates from pigs displaying diarrhea in Thailand.", "The results of the whole-genome sequence demonstrated that novel PEDV variants are circulating in Thailand. Studies investigating the molecular epidemiology, prevalence of either variant, and evolution of PEDV in Thailand are urgently required." ] },{ "paper_id": "334b38e4803085738b38d29775edea658bfb309b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additionally, very sophisticated multilayered nanoparticles could be designed to include targeting molecules, as both biosensors for detecting surrogate molecules expected in infected cells prior to the delivery of a nanoparticle cargo, and moreover, as a feedback control mechanism for the amount delivered [19] .", "Tuberculosis is a major health problem worldwide, especially in undeveloped countries, and about 3 million people are estimated to remain undiagnosed or untreated. In addition, Mycobacterium tuberculosis strains are associated with higher morbidity and mortality in infected patients, making their prevention, diagnosis and cure crucial [27, 28] .", "Food poisoning produced by bacteria is an important cause of disease and death. The bacteria that cause the most illnesses and deaths are Salmonella enterica, E. coli and Clostridium sp.", "Hence, the functional criteria defining a QS system is: a cell density-dependent accumulation [143] of a small diffusible molecule that is recognized by adjacent cells, in which it triggers a specific transcriptional response [144] . Autoinducers synthesis increases with bacteria population density (b) and when a thresthold level is achieved the response is activated (a) [134] . Reproduced with permission." ] },{ "paper_id": "334bc72deded9b157e7f7fcc108fe0671cc41b50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Studies were excluded if they: included seasonal influenza infection cases; were in vitro tests, animal experiments, case studies, case series, and review or letter articles; and targeted special crowds, such as pregnant women and patients with HIV infections.", "The sponsor of this study had no role in the study design, data collection, data analysis, data interpretation, writing of the report, or decision to submit the paper for publication. The corresponding authors had full access to all data in the study and had final responsibility for the decision to submit the paper for publication.", "Novel influenza A (H1N1) spread around the world in spring 2009. Although influenza A (H1N1) infection has a mild clinical course, the pandemic virus is capable of leading to severe illness, requiring hospitalization. As an example, the hospital admission rate for children with 2009 H1N1 influenza was twofold the rate for seasonal influenza [1] . Additionally, approximately 9 to 31% of hospitalized patients were admitted to an ICU, where 14 to 46% of patients died [2] [3] [4] [5] . The disease caused 284,500 deaths globally [6, 7] . Accordingly, there is an increasing need for the development of an effective therapy and treatment to improve upon the prognosis of severe cases.", "We conducted a comprehensive literature search both for English-language and Chinese-language articles examining the effect of corticosteroid treatment in influenza A (H1N1) published up until October 2014. Electronic databases searched included: MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Clinical Trials, University of Saskatchewan Library System, China National Knowledge infrastructure, Wan fang Data, and CBM disc. We contacted article authors for further information or clarification when necessary. No attempt was made to include unpublished data. All searches were executed independently by two skilled researchers. The search strategy consisted of the terms (' A (H1N1)' or ' A/H1N1' or 'influenza' or 'viral pneumonitis') and ('corticosteroids' or 'steroids') as medical subject-heading key words. In addition, the reference lists of retrieved original articles and of relevant systematic reviews were manually checked. No ethics board approval was deemed necessary for a meta-analysis of previously published studies." ] },{ "paper_id": "334dad2c93659c3ffac791c39b0282e7fbe18c52", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "33542ce3cc964e6621e0ce35fedd41b34367de76", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As methodologies for proteomic, metabolomic and lipidomic studies, as well as necessary bioinformatics approaches, are constantly being adapted and improved, it is expected that these \"omic\" technologies will play an increasingly important role in infectious disease research.", "Comprehensive acetylome studies have revealed that histone and non-histone protein acetylation is comparable in frequency to phosphorylation [12, 13] . One study alone identified over 3,500 acetylations across three human cell types using immunoaffinity isolation of acetylated substrates coupled with mass spectrometry analysis [13] . Interestingly, acetylations within several important effectors of innate immunity-RIG-I, IRAK4, OAS2, TRIM25 [13] and, most recently, IFI16 [70] -have been identified, suggesting that acetylation provides dynamic control of important mammalian innate immune functions. Indeed, increasing evidence suggests that HDACs are regulators of inflammatory response, immune signaling and myeloid differentiation [71] [72] [73] [74] .", "In this review, we summarize the mechanisms employed by herpesviruses to perturb the functions of this important family of host transcriptional regulators, the histone deacetylases. Next, we discuss the roles of acetylation in regulating host defense mechanisms against herpesvirus infection. Finally, we provide a perspective on the promise of emerging \"omic\" technologies for gaining a systems biology view of infection and an in-depth understanding of virus-induced changes within cellular pathways.", "Altogether, these studies have demonstrated that gamma-herpesviruses EBV and KSHV co-opt HDAC complexes to repress viral gene expression. These mechanisms likely allow for maintenance of the viral genome in a latent state until conditions are advantageous for viral replication. Viral infection further alters HDAC activity through activation of phosphorylation signaling cascades, thereby modulating the phosphorylation states and activities of individual HDAC enzymes." ] },{ "paper_id": "3359ea81b72a9d6002755539aa7f91bde5fc87bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, inadvertent effects of transgene insertion are not always disadvantageous. As discussed more fully below, the original HSV-1 VP26 capsid fusion, reported by Desai et al. [41] , contains an inadvertent deletion of an upstream promoter element. The resulting decrease in fusion protein expression is actually beneficial for viral replication [45] .", "Table+3.\"Typical\"pH\"of\"intracellular\"compartments.\" ", "First described in 1942, the method of detecting and localizing antigens in cells or tissues using fluorescent antibodies has proven invaluable in molecular and cell biology [159] . Immunofluorescence was first used to visualize VZV infected tissues and cells in 1954 [160] , and HSV in 1956 [161] . However, to visualize intracellular antigens, immunofluorescence protocols require destructive fixation and permeabilization steps, typically accomplished by aldehyde crosslinking of proteins, protein precipitation and lipid extraction by organic solvents, and/or lipid extraction using detergents. Variability in fixation and permeabilization can easily introduce artifacts, ranging from over-extraction leading to loss or relocalization of proteins of interest, to under-permeabilization leading to poor antibody accessibility [162] .", "GFP was first discovered in 1961 from Aequorea victoria jellyfish [1] . The GFP gene was cloned in 1992 [2] , demonstrated to function as a transgene in other organisms in 1994 [3, 4] , and by 1995, many groups reported functional fusions between GFP and a variety of cellular proteins [5] . An enhanced GFP (EGFP) was described in 1996, widely disseminated, and remains the most commonly used \"workhorse\" FP today. EGFP contains mutations that increase expression in higher eukaryotes, improve protein folding, accelerate chromophore maturation, and shift its excitation maximum from 395 nm (ultraviolet) to 488 nm (blue-green). Variants were also engineered creating blue, cyan, and yellow FPs. Subsequently, the mutation A206K was identified, which suppresses the weak dimerization of EGFP variants [6] . Monomeric versions containing this mutation are frequently identified by a lowercase \"m\" prefix to the FP name (e.g., mEGFP). Many of the best FPs available today are only a few amino acids different from the parental EGFP.", "It has been shown that the original HSV-1 strain containing an EGFP-VP26 fusion harbors an inadvertent 65 bp deletion upstream from the VP26 start codon [45] . Nagel et al. took the effort to recreate the virus mutant as originally designed [41] using a BAC recombination approach, and surprisingly found that this mutant was highly attenuated. Because the deleted region contains transcriptional enhancers [45] , it is likely that this deletion is a compensatory mutation that causes reduced expression of the fusion protein." ] },{ "paper_id": "335b0a3f21f764adcbe20ff71e422d823c410098", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "By contrast, CHV, a herpesvirus, produces life-long infections characterized by periods of latency where the virus is present but does not provoke a strong immune response [39] . A negative CHV test result most likely reflects an uninfected individual, although a latent infection cannot be ruled out, whereas a positive result suggests exposure, a more recent infection, or recrudescence [19, 40] ." ] },{ "paper_id": "335e894a725e26adfe71b89170e3fc1301eafb1c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A model (Fig. 10 ) based on our results explains the key steps involved in the macropinocytic entry pathway of IAV, which are described in more detail below.", "An unpaired Student's t-test was used for detemination of statistically significant differences. The use of the term significant in text refers to a comparison of values for which p,0.05. ", "Stocks of bafilomycin A1 (BafA1), dynasore, cytochalasin D, cytochalasin B, Blebbistatin, 17-AA-geldanamycin, ML-7, ML-9, PP-2, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), IPA-3 (all obtained from Sigma-Aldrich), Latrunculin A (Enzo), jasplakinolide, wiskostatin, NSC23766 (all obtained from Calbiochem) and pirl1 (Chembridge) were prepared in dimethylsulfoxide (DMSO). All stocks were stored at 220uC. A kinase inhibitor library composed of 80 kinase inhibitors was obtained from Biomol (2832A[V2.2])." ] },{ "paper_id": "335f41145ff784047aa5a0ae829be50613c65038", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All research protocols and survey instruments were reviewed and approved by the institutional review boards at the University of Michigan and Peking University.", "The survey included administering a demographic and health questionnaire and the Life Orientation Test (LOT-R).", "The Demographic and Health Questionnaire measured patient characteristics including age, number of pregnancies, other medical conditions, and self-perceived health status." ] },{ "paper_id": "3370214f4f7242b2a6ef23df718ef0f8b863a04c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The FMDV genome sequences have been submitted to the GenBank/EMBL/DDBJ and assigned the accession numbers EU448368 to EU448381. ", "Total RNA was extracted directly from a 10% epithelial suspension using the RNeasy Mini Kit (Qiagen, Crawley, West Sussex), or from blood or oesophageal/pharyngeal scrapings using TRIzol (Invitrogen, Paisley, UK). Reverse transcription of the RNA was performed using Superscript III reverse transcriptase (Invitrogen) and an oligo-dT primer (see Table S2 ). Twenty four PCR reactions per genome were performed with Platinum Taq Hi-Fidelity (Invitrogen), using 23 primer sets tagged with forward and reverse M13 universal primer sequences, and one primer set with a oligo-dT reverse primer to obtain the very 39 end genomic sequence (Table S2 ). The PCR products overlap such that each nucleotide is covered by two products. The reactions were run on a thermal cycling programme of 94uC for 2 min, followed by 40 cycles of 94uC for 30 s, 55uC for 30 s, 72uC for 1 min, with final step at 72uC for 7 min. Sequencing reactions were performed using the Beckman DTCS kit, with M13 universal forward and reverse primers and specific forward and reverse primers for each PCR product. This resulted in an average of 7.4 times coverage of each base.", "Foot-and-mouth disease (FMD) is an economically devastating vesicular disease of domesticated and wild cloven-hoofed animals. FMD is caused by a 30 nm un-enveloped virus belonging to the genus Aphthovirus in the family Picornaviridae. Its genome consists of a single strand of positive-sense RNA approximately 8.3 kb in length [1] encoding a single polyprotein which is post-translationally processed by virally-encoded proteinases [2] . FMD viruses (FMDV) are divided into seven immunologically distinct serotypes known as O, A, C, South African Territories (SAT) 1, SAT 2, SAT 3 and Asia 1. FMDV has a high mutation rate resulting in rapid evolution and extensive variation between and within serotypes [3] .", "The molecular epidemiology of FMDV has been extensively studied [4, 5] ; and has allowed the tracing of outbreak origins on a global scale [4] . Most of these studies have been conducted using nucleotide sequences of one of the three major capsid-coding genes (VP1) which represents less than 10% of the genome. However, VP1 sequence data alone does not have the required resolution for within-epidemic transmission tracing. In common with some other RNA viruses, for example, human immunodeficiency virus (HIV) [6] , hepatitis C virus (HCV) [7] and SARS coronavirus [8] , full genome sequence for FMDV has recently been used for high-resolution molecular epidemiological studies [9] . To date, fine scale tracing of pathogen transmission has focussed on retrospective analysis; production of full-genome sequences during the course of an outbreak (in real-time) may assist in the interpretation of field epidemiology data and directly influence measures to control the spread of the disease." ] },{ "paper_id": "3373c12fcd9f891217dec7833378f696637b6ddd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Endocytosis of host cells is required for the retroviral infection.", "MI, HK, EH, Y. Koizumi, KY, and Y. Kubo performed experiments. TS helps the experiment of electron microscopy. MI, HH, KA, and Y. Kubo analyzed the data. MI and Y. Kubo wrote the manuscript." ] },{ "paper_id": "3380c2147c090bd81525c67d4200fb3860517008", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using Mann-Whitney U-test. P,0.05 was considered as significant.", "Animals BALB/c 6-week old male mice were purchased from Japan SLC Co. (Shizuoka, Japan) and used at 7-week. Animal care was performed according to ethical guidelines, and approved by the Institutional Board Committee for Animal Care and Use of Mie University.", "DCt method was used to standardize the transcripts to GAPDH, and the ratio to that of control mice was calculated." ] },{ "paper_id": "3380d0cb8447aa4741878f8a3d300a3765ed9a40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MB and HL contributed to the literature review and writing of the manuscript. MB prepared all Figures and Table. FUNDING This work was supported in part by NIH NIAID grant R01 AI131586 to HL and by a pre-doctoral NIH fellowship T32 DA007097 to MB.", "In addition to vaccine development as a preventative measure, the discovery of anti-viral drugs is a burgeoning area of arenaviral research. Currently, the only anti-viral treatment clinically in use that is specific to mammarenaviruses is convalescent plasma therapy against JUNV (175) . Standard anti-viral nucleoside analogs, such as Ribavirin and Favipiravir (69, (371) (372) (373) (374) have seen moderate clinical success, but are only effective when given in the earliest stages of infection when symptoms are primarily non-specific (173) . Peptideconjugated morpholino oligomers have also been tested as alternative nucleoside analogs, reducing the titers of several arenaviruses in cell culture and LCMV-infected mice (375) . Nevertheless, recovery has been documented with symptom management in place of nucleoside analogs due to a delay in diagnosis being reached after the resolution of symptoms (376) , limiting the desire for using nucleoside analogs as anti-viral compounds.", "The authors wish to thank Dr. Y. Liang for her helpful comments and suggestions about the manuscript. ", "The family Arenaviridae is divided into 3 genera based on their natural hosts-Mammarenaviridae, Reptarenaviridae, and Hartmaniviridae that include viruses infecting mammals, reptiles, and fish, respectively (1, 2) . Mammarenaviridae are further classified into the regions of their origins, such as the Old World (OW) viruses found in West Africa (3-9) and the New World (NW) viruses found in South America (5, (10) (11) (12) (13) (14) (15) (16) (17) , which are believed to have originated <23,000 and 41,000 years ago in those continents, respectively (18) (Figure 1) . Additionally, several NW arenaviral strains have been discovered in the United States, which are suspected to potentially cause human FIGURE 1 | Taxonomy and location of arenaviruses. The phylogenetic tree for OW and NW arenaviral strains and their geographic locations. Tree was generated from full-length genomic sequences for the L polymerase protein aligned by Clustalw analysis. Asterisks designate strains that cause natural human diseases, whereas hashtags designate strains that can cause laboratory-acquired diseases in animals.", "Significant progress has been made in recent years to understand the role of modern means of travel in inadvertently exporting deadly arenaviruses from endemic regions, the basic biology of these viruses, their genomic evolution and modes of transmission and immune suppression, and the disease pathogenesis for which they are responsible. A detailed level of understanding of the viral life cycle, evolution, and interactions with the host's immune signaling pathways is necessary in order to design effective therapeutic and preventative measures against this group of deadly human pathogens." ] },{ "paper_id": "33813052430b7faada17882d12fc343aad02981e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The initial values of theta were inferred from the comparison of human and chimp orthologous sequences for each 10kb region using a mutation rate based on the average number of substitutions per site (with the Jukes and Cantor correction) as assessed by DnaSP v5.1 (Librado and Rozas 2009 ). The rho parameter was estimated from the deCODE Genetics sexaveraged recombination-rate track in the UCSC Genome Browser (https://genome-euro.ucsc.edu). Uncertainty in the estimates of theta and rho was considered by generating a random and normally distributed set of values for these parameters, with mean equal to the estimated value and variance equal to the mean, from which we sampled a pair of values in each simulation.", "./msHOT 28 5000 -t tbs -r tbs 10000 -I 4 0 0 0 28 -n 1 1.68202 -n 2 3.73683 -n 3 7.29205 -n 4 3.73683 -g 2 116.010723 -g 3 160.246047 -ma x 0.881098 0.561966 0 0.881098 x 2.79746 10 0.561966 2.79746 x 0 0 1 0 x -es 0.0005 4 0.1 -ej 0.0005 5 2 -en 0.0005 4 0.068 -ej 0.0135 4 1 -ej 0.028985 3 2 -en 0.028985 2 0.287184 -eM 0.028985 28 -ej 0.197963 2 1 -en 0.303501 1 1 < random_thetas-rhos.txt > output_file.ms", "Supplementary data are available at Molecular Biology and Evolution online." ] },{ "paper_id": "338d45deb88de8cc7f4cf5158c4752fb3533a0b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pneumonia is a common clinical entity, particularly among the elderly [1] . In addition, among young children in many developing countries, community-acquired pneumonia (CAP) is responsible for a significant number of deaths [2] . More than 2 million children under age 5 are killed by pneumonia every year worldwide-more than AIDS, malaria, and measles combined [3] . For each child who dies of pneumonia in a developed country, more than 2,000 die in developing countries [4, 5] .", "Citation:", "RT reactions were performed in 20-\u00b5l volume containing 500\u00b5M each dATP, dTTP, dGTP and dCTP, 50ng of random hexamers, 1x RT buffer, 5mM MgCl 2 , 10mM DTT, 40U of RNaseOUT, 200U of SuperScript III (Invitrogen Life Technologies, Carlsbad, CA), 10,000 copies of in vitro transcribed TIM RNA and 2\u00b5l of the extracted clinical specimen. Reactions were carried out in a Px2 Thermo Cycler (Thermo Electron Corp, Vantaa, Finland) using the manufacturer's recommended protocol." ] },{ "paper_id": "338d5cc4af296ec1ecd8ed7c63f6ac522ff583db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ubiquitin and NEDD8 conjugates decrease following infection with Listeria while ISG15 sites increase a-d) SDS-PAGE of liver homogenate from wild type or USP18 C61A/C61A mice either uninfected or infected with 5 x 10 5 Listeria for 72 hours (three mice of each genotype and condition). e) SDS-PAGE of ubiquitin, NEDD8, ISG15 and ACTIN from MEFs (wild type or Isg15 -/-) uninfected or infected with", "Listeria for 24 hours f) Pie chart showing the distribution of the quantified GlyGly(K) sites between clusters 1 to 4 and the non-significantly regulated sites after two-way ANOVA test (Respectively cluster 1 to 4: 8%, 15.5%, 5.5%, 25.4% and 45.6% of non-significantly regulated sites). g) Volcano plots showing significantly regulated GlyGly(K) sites after pair-wise t-test. The fold change (in log2) of each GlyGly(K) site is shown on the x-axis, while the statistical significance (-log P value) is shown on the y-axis (FDR=0.05, S=1). From left to right: Listeria infection upregulated 746 sites in wild type animals while 435 sites were downregulated. In Isg15 -/animals Listeria upregulated only 168 sites while 1,137 sites were downregulated. No sites were significantly regulated between uninfected wild type and Isg15 -/mice. Finally, Listeria infection led to 886 upregulated sites in wild type and 54 sites were upregulated in Isg15 -/mice. Raw data are available in the source data file.", "Proteomics data for input and ISGylome a) Heatmap showing significantly regulated proteins after non-supervised hierarchical clustering. On the right side, the heatmap is shown with missing values in grey. Two major clusters can be observed corresponding to proteins that are upregulated or downregulated during infection, listed in Supplementary Data 3. b) Since only two major clusters were observed in the heatmap, a t-test was performed (FDR=0.05 and S0=1) to compare protein intensities between all infected and all non-infected samples. Quantified proteins (n=3,055) and the results of the t-tests are listed in Supplementary Data 4. The fold change (in log2) of each protein between the nine infected and nine non-infected samples is shown on the x-axis, while the statistical significance (-log P value) is shown on the y-axis. According to this t-test, 490 proteins were upregulated during infection and 558 were downregulated. c) Distribution of the total proteome, ISGylome (cluster 1 and 2) and ubiquitylome (cluster 3 and 4) in liver from wild type mice infected or not with Listeria, based on LFQ intensity (x-axis) and on the cumulative protein counts (y-axis). Although there is a slight bias towards more abundant proteins, proteins at all expression levels were well represented in both the ISGylome and ubiquitinome, independent of infection. Figure 3 : General properties of ISGylation sites a-b) All lys residues in the proteins within cluster 1 and 2 were categorized into ISGylated sites (\"ISG15\") or non-ISGylated sites (\"Other\"). a) The sequence conservation among orthologs for each Lys site was computed. The distributions of sequence conservation were compared between the two categories. b) The relative solvent accessibility (RSA) for each Lys site was computed if structural information is available. For those Lys sites with multiple structures, the reported RSA was the average among all structures. The distributions of RSA were compared between the two categories. Two-tailed t-test was employed to compute the p-value. c) ISGylated site Lys19 of nicotinamide phosphoribosyltransferase (uniprot ID: Q99KQ4) is shown on the structure (PDB 2H3B) 1 Supplementary Figure 5 : Validation of proteins modified by ISG15 a-c) Ectopic expression of ISG15 (either conjugation competent ISG15GG (wild type) or non-conjugatable -ISG15AA) with Ube1L, Ubc8, HERC5 and respective substrates: Myosin 9 and HSP90 in HEK293T or glucose phosphate isomerase in HeLa. Asterisk indicates FLAG-HERC5. d) Immunoblot of mTOR following immunoprecipitation with endogenous mTOR. eg) Immunoblot of mTOR IP with ISG15, ubiquitin and NEDD8 reveals a more slowly migrating band for ISG15 but not for ubiquitin or NEDD8. Raw data are available in the source data file." ] },{ "paper_id": "338ea249f053b957f0681c987b83322a96a7350b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In order to capture as much useful information from a molecular fingerprint as possible, we can also convert the above 256-bit hexadecimal string into a 1024-bit binary vector, which is a digital sequence only including 0 and 1, and consider two different digital signal characteristics for the digital sequence as follows.", "where has the same meaning as in (10) .", "Incorporating the above 400 dipeptide components into (11), we have +20 = (2) ( = 1, 2, . . . , 400) .", "where" ] },{ "paper_id": "3391fcc4d89196ca239c043cfb37e68d8d2e370a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The milk samples were thawed and heated to 37\u02daC in a water bath. The milk components, including protein, fat, total solids (TS), lactose and acidity, were then analyzed using a MilkoScan FT120 instrument (Foss, Denmark).", "No difference (P > 0.05) in the nutrient contents of sows' milk was found between the control and infected groups (Table 1) .", "Porcine epidemic diarrhea (PED), a disastrous gastrointestinal disease, causes great financial losses due to its high infectivity, morbidity and mortality in suckling piglets [1] [2] [3] . The major clinical symptoms of PED are severe enteritis, vomiting and watery diarrhea [4] . Porcine epidemic diarrhea virus (PEDV) rapidly spreads among piglets through the fecal-oral route [5] . Although various vaccines have been developed and applied, PED outbreaks still occur in some immunized swine herds [6, 7] . Therefore, the identification of new preventive measures as well as further research and development of new vaccines are necessary." ] },{ "paper_id": "339f0cd12ca08506c22c8b62eb4b3283a437271a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The protocol for this study was reviewed and approved by the Institutional Review Boards (IRB) of the University of California, Berkeley, and the Nicaraguan Ministry of Health. Parents or legal guardians of all subjects provided written informed consent, and subjects 6 years of age and older provided assent.", "DENV was propagated in Aedes albopictus C6/36 cells as previously described [9] . Cell supernatants were concentrated by centrifugation through Amicon filters (50 kDa, 3,2506g for 20 min at 4uC) or by ultracentrifugation (90,0006g for 2 h at 4uC, Beckman SW28) and resuspended in PBS. DENV2 (strain N172, passage 3) and DENV3 (strain N7236, passage 3) are clinical strains from Nicaraguan patients isolated in the National Virology Laboratory in Managua and passaged minimally. Raji-DC-SIGN-R cells (gift from B. Doranz, Integral Molecular, Philadelphia, PA) were grown in RPMI-1640 medium (Invitrogen) with 5% FBS at 37uC in 5% CO 2 for use in neutralization assays [38, 39] .", "The four serotypes of the flavivirus dengue virus (DENV1-4) cause the most common mosquito-borne viral disease in humans worldwide, with 50-100 million people infected annually and over 3 billion people at risk [1] . DENV infection can be asymptomatic or cause a spectrum of disease ranging from classical dengue fever (DF) to more severe, life-threatening forms termed dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) [2] . Approximately 500,000 dengue patients require hospitalization annually, of whom a large proportion are children [3] . Although several antiviral and vaccine candidates are in various phases of preclinical and clinical evaluation, current treatment remains supportive care [4] ." ] },{ "paper_id": "33a39cbf4221c9373bc07bf09d325c066fbe97a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2) A probable exception is the superior IFN complexity recently identified in amphibians, which may primarily cope with the dramatic environmental changes during terrestrial adaption from water life [8, 38, 41, 42] .", "(3) All other comparable natural species, such as wild birds and underground rodents, have a very basic number of functional IFN genes/subtypes ( Figure 2 ).", "Funding: This work was supported by USDA NIFA 2018-67016-28313 and USDA NIFA Evans-Allen-1013186 to Y.S., and in part through reagent sharing of NSF-IOS-1831988 to Y.S." ] },{ "paper_id": "33b0c24cb03b515296b278e96fd7de32151b9511", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Development of the 17D vaccine strain of YFV and its first human trials. Max Theiler, son of South African bluetongue researcher Sir Arnold Theiler, received a Nobel Prize in 1951 for this work.", "In 1960, the RF made a decision to phase-out its Virus Program and to devote more of its efforts and resources to other projects, such as population control and increasing food production (\"the green revolution\"). Over the next 10 years, the RF-funded investigators working in overseas laboratories were withdrawn and the respective laboratories were turned over to local institutions or governments. In 1964, the RF made arrangements with Yale University to transfer its Arbovirus Group to New", "Discovery that the rhesus monkey and the white mouse are susceptible to infection with YFV, providing models for subsequent studies on the pathogenesis, transmission, epidemiology, and control of the disease; 3." ] },{ "paper_id": "33b590b2a517896a894c71c1c0b86c593804c034", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using Prism 6.0 (GraphPad Software, Inc.).", "Plasmids were sequenced at the University of Michigan sequencing core (http://seqcore.brcf.med.umich.edu/). Chromatograms were analyzed and assembled with the Sequencher software (Gene Codes Corporation). Sequence analysis was performed using Vector NTI (Invitrogen\u2122 Life Technologies\u2122).", "The clinical progression of disease was found to be very similar for both organisms and can be divided in the 3 stages" ] },{ "paper_id": "33bee45e93ec92d0813e39a07e158605af679215", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Autophagy is an intracellular \"self-eating\" process that targets the cytoplasmic components via the double membrane vacuoles to lysosome for degradation. As a regulated catabolic process, autophagy exerts a broad range of impacts on cellular pathways to counteract stresses, e.g., nutrient starvation, accumulation of damaged cytoplasmic components, pathogen infection, or ER stress, thus maintaining cellular homeostasis and enabling cell survival [56, 57] . Activation of autophagy initiates with the sequestration of cytoplasmic components within a membranous structure, called isolation membrane (IM) or phagophore, that expands to form a double-membraned autophagosome ( Figure 4A ). Finally, autophagosome then fuses with endosome and lysosome, forming the autolysosome where the engulfed material is degraded by lysosomal proteases [56, 57] (Figure 4A ).", "Pathogenesis of HCV-associated liver diseases. Approximately 3% of the population has been infected with HCV worldwide. In the majority (about 50-80%) of infected individuals it becomes a persistent-infection and the chronic-infected hepatocytes in liver progressively develop into liver steatosis, and liver cirrhosis. Ultimately, the chronic infection leads to hepatocellular carcinoma formation in nearly 3-5% of viralinfected patients.", "Signaling transduction of UPR. Three major signaling transducers of UPR, including inositol-requiring protein-1 (IRE1), activating transcription factor-6 (ATF6), and protein kinase (PKR)-like ER kinase (PERK) are indicated. Left column: Upon sensing accumulation of unfolded proteins, IRE1 oligomerizes and processes autophosphorylation, leading to X-box protein-1 (XBP1) mRNA splicing. The spliced XBP-1 (XBP-1s) subsequently transactivates gene expressions of chaperones, lipogenic genes, and ER-associated degradation (ERAD). Middle column: In response to ER stress, PERK also undergoes oligomerization and autophosphorylation processes. The activated PERK then transduces the signaling to activate eukaryotic translation initiation factor 2\uf061 (eIF2\uf061) via phosphorylation, resulting in suppression of global protein translation and activations of UPR genes that function in amino acid transporter, oxidative response, and apoptosis. Right column: When cells facing ER stress, the precursor form of ATF6 is first translocated from the ER to Golgi apparatus and processed into the cleaved form of ATF6 (cATF6). Then the cATF6 is shuttled into nucleus to transactivate UPR target genes, such as ER chaperons." ] },{ "paper_id": "33bfc254b350a34f254ea0c56d349ddae719048b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A/Duck/Czech/56 (H4N6), a low pathogenic avian influenza virus (LPAIV), was used in this study. The virus was propagated in 11-day embryonated chicken eggs. Virus propagation and titration were carried out as previously described [32] .", "Statistical analysis of log transformed virus titers was performed by one-way ANOVA (SAS version 9.3) followed by Tukey's post hoc test for multiple comparisons to examine the effects of TLR ligands. p values <0.05 were considered to be statistically significant. For gene expression, fold changes and standard errors were calculated using REST (Relative Expression Software Tool) software version 2009 (Qiagen, Toronto, ON, Canada). The REST software compared control (medium or non CpG ODN) and treatment groups using pair-wise fixed reallocation randomization based on the PCR efficiencies and the mean crossing point deviations between the control and treatment groups. Statistical analysis of Nitric oxide production was performed by two-tailed Student's t-test.", "Total RNA was extracted from five tracheal rings using Trizol reagent (Life Technologies, Burlington, ON, Canada), according to the manufacturer's recommendations. There were 6 biological replicates in each group and each replicate contained five rings of trachea from the same individual embryo. DNA-Free\u2122 kit (Ambion, Austin, TX, USA) was used to remove contaminating DNA from RNA samples before cDNA synthesis. One microgram of RNA was used for cDNA synthesis. Superscript II First Strand Synthesis kit (Life Technologies) and Oligo(dT)20 primers were used for cDNA synthesis according to the manufacturer's protocols. Quantitative real-time PCR was performed on diluted cDNA (1:10 in DEPC treated water) using a SYBR green dye in a LightCycler 480 II (Roche Diagnostics, Laval, QC, Canada) as previously described. Specific sequences of primers were described previously [29] [30] [31] ." ] },{ "paper_id": "33c50b9e506abf3c1db6bf58bd77b97155f9e903", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Middle East Respiratory Syndrome. The Middle East Respiratory Syndrome-Corona virus (MERS-CoV), a newly recognized corona virus, emerged in Qatar and Saudi Arabia with a high fatality rate (50%) in 2012 (141) .", "Plague. Plague is caused by Yersinia pestis. Plague pandemics have killed millions of humans in Africa, Europe, Asia and America (168, 169) .", "Different surveys of animals have revealed the Leptospirosis infection rate to be up to 43% in horses (211, 212) , 37% in cattle (213-217), 37 % in dogs (218), 18.5% in sheep and goats (219, 220) , as well as infections in cats and donkeys (212, 221, 222) .", "Over the past century, even thought there was considerable development regarding prevention, control and elimination of some of the infectious diseases through proper use of hygiene and sanitation practices in addition to development of antibiotics and vaccination, some infectious diseases remained as the leading causes of morbidity and mortality worldwide. Furthermore, amongst the challenges in controlling these infectious diseases, emerging infectious diseases (EIDs) and reemerging infectious diseases (RIDs) could be pointed out (1) ." ] },{ "paper_id": "33cf03ea72e45ea6d6beeccc91c5145807544728", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In Vivo Activities", "Enhanced chemosensitivity toward Olaparib-resistant Brca1-deleted tumor cells [168] .", "Inhibiting the initiation stage of rRNA synthesis and inducing both senescence and autophagy [170] , blocking replication forks and inducing ssDNA gaps or breaks [147] ." ] },{ "paper_id": "33d46081e98cd5a3b1152ecee6361ae8f9f89ea9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Maternal RSV Infection PLOS ONE |", "IRB approval for the study was obtained from the Johns Hopkins University Bloomberg School of Public Health, Seattle Children's Hospital, Cincinnati Children's Hospital, the Institute of Medicine at Tribhuvan University, and the Nepal Health Research Council. Oral consent was obtained from study participants due to low literacy rates in the population. This procedure was approved by the IRB." ] },{ "paper_id": "33e9e969d555d597b3af0d6c4bdb38010ce3996d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "33ea5a062d23a8c46b7d6e9ba23f1c82f40fde29", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Alpaca (Vicugna pacos, also known as Lama guanicoe pacos) are domesticated members of the New World camelid species (Lamini), which also include guanaco (Lama guanicoe), vicuna (Vicugna vicugna), and llama (Lama glama). The natural habitat for alpaca is at high altitude (3500-5000 m) in South America (Peru, Ecuador, Bolivia, and Chile) where they are kept as livestock in herds and their fiber is used much like wool. Approximately 300,000 animals [1] are in the U.S. Compared to other livestock, e.g., about 96 million cattle [2] , their number is still relatively small.", "Recently developed approaches to virus detection have the potential to further expand understanding of viral disease in animals, including alpaca. Many of these approaches are based on non-specific PCR amplification used in conjunction with standard or high-throughput sequencing to identify PCR products.", "We utilized such a method [17] [18] [19] to investigate an outbreak of a respiratory infection in alpaca, identifying a bovine enterovirus (EV-F), named Enterovirus F, strain IL/Alpaca, after other techniques had failed to detect any pathogen." ] },{ "paper_id": "33f0a6576216e3c8ff02dcb1affaa66c9f08e30b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author(s) declare that they have no competing interests. " ] },{ "paper_id": "33f48f3ce2b476338c67cddb65732d26806377bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study protocols were approved by the independent institutional review board at each study site.", "Open Access 262" ] },{ "paper_id": "33f569ebbee2a937504860dcfb7bb7801965f1f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Effective Reproduction Number (Re): Re values were calculated using follow formula (1)", "Phylogenetic Analysis" ] },{ "paper_id": "33fbcefc12a3f06bf2e20b88ac1b69d481746250", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All analyses were performed using IBM SPSS Statistics (version 25). Two-tailed Mann-Whitney U exact test and two-tailed Student's t exact test were used to calculate the 95% confidence interval (CI) of positive rate. The association p values between viral seropositive samples and camel information were calculated using Chi-square test followed with Yates correction twotailed test and Fisher's exact test.", "Lysates of MERS-CoV infected Vero cells were generated in the biosafety level 3 laboratory at WIV, loaded onto 12% SDS-PAGE gels, and transferred onto nitrocellulose membranes. Membranes were incubated with selected MERS-CoV RBD positive and NP positive or negative camel sera for 1 h at 37\u00b0C (1:100 dilution) after blocking. Membranes were then washed and then incubated with anti-camel IgG-HRP secondary antibody (as above) for another 1 h at 37\u00b0C, followed by three more washes.", "Viral RNA was extracted from camel nasal swabs using a viral RNA extraction kit (Roche, Germany) according to the manufacturer's instructions. Three primer pairs were used to screen the samples in RT-PCR, two targeting the conserved RNA-dependent RNA polymerase gene of CoVs and another targeting the MERS-CoV S2 region [20, 21] . Twelve pools of RNA were made from 139 MERS-CoV negative samples (roughly every 10 samples were pooled) and libraries for next-generation sequencing were prepared using Illumina Truseq mRNA kit (TruSeq Stranded mRNA Library Prep Kit, Cat # RS-122-2101) following the manufacturer's instructions. The sequencing was performed on a HiSeq 3000 sequencer and data was analysed using the Galaxy platform.", "There are two studies which have previously tested both S and NP IgG antibodies in Middle East camels. Of the two studies, one reported a strong correlation between NP positives by Western blot (97%) and Sbased VNT positives (98%) using camel samples from the United Arab Emirates [12] . The second study tested camel sera from Saudi Arabia, and found more samples seropositive for S than NP by ELISA, Western blot or the Luciferase Immunoprecipitation System (LIPS) [13] . The latter study did not proceed with further analysis." ] },{ "paper_id": "340036a465efeb78d0b0160bf6dddd2322f293ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "34081c03e48678c7d7633e81cecdeb0b6dbf30e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Working with community health workers in Uganda", "The consensus amongst academics and practitioners alike that the most important determinants of health are the wider social, economic and environmental factors is not new. Modern conceptualizations of health start with prevention, rather than cure or care and the importance of a reinvigorated public health sector is regularly impressed upon us. Increasingly, single issue approaches to promoting health have come to be seen as limited.", "We have always conceptualized the relationship between NTU, MakSPH and other partners as one of mutual respect and learning from each other. From our experience, trust among partners, with volunteers and community members takes time. MakSPH's long term working relationship with local communities including where partnership activities are based has been profound in fostering trust with local communities and responsible authorities." ] },{ "paper_id": "341032e0d9e1730bdf19b1742d4f9e32c544d083", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "34190b8df3ed825e3c49e41a3782d04acf1e21e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethical issues are hardly considered in emergency department setting. A study by Anderson-Shaw et al has suggested that patients hospitalized through ED often present with ethical dilemmas significantly impacting their inpatient care and overall health outcomes [13] . There is need of more research regarding the proactive use of ethics consultation in ED.", "Waiting long for a consultation can increase pain and suffering and, at times, worsen the outcome and thus, result in indirect harm. Psychosocial harm includes stress, fear, feeling neglected or not being taken care of." ] },{ "paper_id": "341a9a57e865081e81a9c60b97802773761ce8c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Subtracting the first equation from the second equation", ", which is equivalent to Equation 1. This derivation makes clear that the estimator (1) measures the rate along the path from sequence i to sequence j, with only incidental dependence on sequence k.", "We note that the term t i + t j -1 is used rather than t i + t j to account for the expected error coming from the uniformly" ] },{ "paper_id": "341fd3d94baafcde2e5e7c0b1d166028d69523e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Response 02 Mar 2015 , Collaborations in Chemistry, USA" ] },{ "paper_id": "34201b73f0586cc43cf1a416647ba6fc39c35486", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "342160459c20d71ef6f3da97763dd855a5357b1e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The safety, pharmacokinetics and antiviral effect of Civacir, an immune globulin enriched in human hepatitis C polyclonal antibodies (HCIG), were studied in patients undergoing LT for chronic hepatitis C [42, 44] (Table 1) . A phase II \"proof-of-concept\" clinical trial was initiated in 2007, involving 20 patients receiving 400 mg/kg of Civacir. During this trial, the progression of liver fibrosis was studied on biopsies. Liver enzymes and HCV RNA levels were analyzed in liver and serum; safety and tolerance were evaluated. However no result has yet been made public.", "Targeting cellular receptors could constitute a good strategy since it could limit mutational resistance and reduce viral escape. Nevertheless, this strategy may be delicate because the targeted host proteins play cellular roles.", "Arbidol (Arb), a broad-spectrum antiviral which demonstrated activity against a number of enveloped and non-enveloped viruses, was initially used for prophylaxis and treatment of infections by influenza A and B viruses [110] [111] [112] .", "A recent study revealed that mAbs directed against the domain III of DENV E protein potently neutralized infection in a mouse model of lethal dengue fever, illustrating the strong potential of an antibody-based therapy on severe forms of the illness [45] ." ] },{ "paper_id": "3422bab59932dcb046a0dfe931eb71173130979f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "infections. Simple paper-based sample pre-treatment systems for on-site diagnosis have been reported [17] [18] [19] , but they did not eliminate completely the risk of infection and only chemical lysis on paper may not enough to liquefy and lyse a highly viscous sputum sample. There are very few studies that developed a sputum pre-treatment system to allow for point-of-care testing of respiratory infections." ] },{ "paper_id": "34277d7f5f84c871e13853e830eb07b2186f8fec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SCIEnTIFIC REPORTs | 7: 8582 | DOI:10.1038/s41598-017-09119-y", "H37Rv and M. bovis BCG Pasteur were grown at 37 \u00b0C in Middlebrook 7H9 medium (BD) supplemented with 0.5% glycerol, 0.02% Tyloxapol, and 10% albumin-dextrose-catalase (ADC) or on solid Middlebrook 7H11 medium (BD) supplemented with oleic acid-ADC." ] },{ "paper_id": "343aeda9b3a81a9db2f40386f3991ef6c48338ce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:22420 | DOI: 10.1038/srep22420", "ij from equation (10), where the B ij have the same meaning as above Because the explicit expression of \u03c7 p ( ) is very complex, we provide only the derivation process." ] },{ "paper_id": "344057fa7bef9619bf39e1d681ab054048949e75", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since May 20, 2015, when a patient was first diagnosed with Middle East Respiratory Syndrome (MERS) in Korea, the num-ber of patients affected with MERS drastically increased and led to diagnosis of MERS in 186 patients within 45 days, followed by eventual deaths in 38 patients, leaving a record of a 20% mortality rate.", "Anger status was defined as a STAXI total score of 14 or higher, which is equivalent to the average score of a prison inmate with moderate to severe symptoms of depression (28.1%), suicidal thoughts (33.6%), and alcohol abuse (39.1%) [17] ." ] },{ "paper_id": "3442b139e80c8351c89a9398709090db63edb8fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Serum samples were submitted to a commercial laboratory (IDEXX BioAnalytics, Columbia, MO, USA) to detect antibodies against the following agents using a multiplex fluorescent immunoassay ", "This study was conducted at Ross University School of Veterinary Medicine (RUSVM), Basseterre, St. Kitts, West Indies, adhering to a protocol approved by the Institutional Animal Care and Use Committee (protocol no. 17-01-04)." ] },{ "paper_id": "34483f6b88d4999066d631b65cdf0f256d305b6f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Context dependence is another phenomenon in CASs. CASs are nested systems with fuzzy borders, meaning that each system can be a subset for a bigger one and a supra system for a smaller one, and agents there can exchange information cross-border [41] . Agents' mental models or other rules in their mind are influenced by their history, culture, values, and norms even illogical or incomprehensible when viewed by others. Likewise, the transition of external environment have impact on agents, and their actions inevitably create ripple effects. As a result, complexity of the systems is generated from the dynamic coevolution.", "Policy documents and reports from local health facilities were collected to extract the information about local management models and some general statistics. The backgrounds of history, culture, population and socio-economics were gathered from the county annals.", "County A and B are relatively developed eastern regions. Particularly, county B lies in seaboard having several harbors. Both of them are well-known for prosperous business throughout history. Compared to agents in other midland counties, health care executants there had stronger sense of innovation. Furthermore, they preferred to consider cautiously and predict outcomes prior to conducting a policy." ] },{ "paper_id": "345180770287ab9188e2dcfa2fd2ba0cd58214bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The symmetric binary 1-mode commune network includes 191 nodes, has 1.77% density and 322 links.", "\u2022 Some LPT's introduce poultry to other flocks as part of their normal trade practice.", "Given the above, current disease prevention and control interventions would benefit from dissemination of information about outbreak risk and the implementation of a formal data recording scheme at LBM's for all incoming and outgoing LPT's." ] },{ "paper_id": "3455e9fd57dea013498de20c236c15b7bf19b424", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "KEYWORDS: H1N1, H1N2, influenza A virus, molecular epidemiology, nomenclature, swine, virus evolution I nfluenza A virus (IAV) is one of the most important respiratory pathogens of swine.", "We gratefully acknowledge the laboratories that deposit swine influenza virus sequences into publicly available databases and the OFFLU network and contributing support staff at all participating organizations and institutions. ", "Phylogenetic methods, clade annotation, and clade comparisons. From these data, a maximum likelihood tree was inferred using RAxML (v8.2.4 [54] ) on the CIPRES Science Gateway (55) employing the rapid bootstrap algorithm, a general time-reversible (GTR) model of nucleotide substitution, and \u232b-distributed rate variation among sites. The statistical support for individual branches was estimated by bootstrap analysis with the number of bootstrap replicates determined automatically using an extended majority-rule consensus tree criterion (56) ." ] },{ "paper_id": "345a04a8633d593b5a400b559d533a6b4595f490", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Forward Primer Reverse primer", "doi:10.1371/journal.pone.0155341.t001 ", "Supporting Information S1 " ] },{ "paper_id": "347209baac4ddbcc1533979d1a496128d7834f5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "True", "Salmonella can predominantly be found on chicken, raw vegetables, and fruit. True 61.0%", "After you have eaten Salmonella-contaminated food, it can take weeks before you become ill. False 52.5%" ] },{ "paper_id": "347d44e7849c7abbf867722925ffc5996b0f9a11", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Can We Exploit DCs to Improve Immune Responses during Vaccination?", "Langerin (CD207) is a membrane marker expressed solely by Langerhans cells, which do not express DC-SIGN [30] . In stark contrast to DC-SIGN, langerin was shown to internalize HIV-1 virions into Birbeck granules and degrade them [31] .", "Distinct stages of DC generation may be altered by viral infection, from hematopoietic progenitor differentiation, to maturation, or even both (Figure 2 ) [38] . In mice, DC progenitors generated under the influence of IL-10 are able to give rise to a DC subset that induces antigen-specific expansion of functional CD4 + CD25 + Treg cells with strong suppressive functions [44] . The role of Treg cells is normally to downregulate immune and inflammatory responses as part of the healing process, but they may be activated to create an immunosuppressive environment during certain viral infections." ] },{ "paper_id": "347f19fee8147e17a853627c99decbeada4660dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In conclusion, this study provided a better understanding of paramyxoviruses infection and highlighted the correlation with climate factors, revealing the potential for modeling and risk assessment. The findings of this work will help public health authorities and clinicians to improve strategies for controlling paramyxoviruses infection.", "In general, the prevalence of viruses can vary because of factors such as geographical location, climatic conditions, population, and social activity [29] . Guangzhou, which is located on the subtropical coast of China, has a maritime subtropical monsoon climate. Guangzhou is China's first gateway hub to Southeast Asia and Oceania. The city is densely populated and frequent exchanges of domestic and international personnel and materials take place in the area. Guangzhou has been a hotbed of activity for various respiratory pathogens. Investigation of respiratory pathogen epidemics in the region is critical.", "In this study, we analyzed paramyxovirus infection among children hospitalized with ARI over a 7-year period in Guangzhou, and we collected local meteorological data for climate correlation analysis. These data will be helpful for the prevention and control of these viruses.", "Real-time PCR for detection of RSV, PIV, HMPV, and common respiratory pathogens TaqMan real-time PCR was conducted to detect RSV, PIV1-4, HMPV, and other 12 common respiratory pathogens, including influenza A virus (infA), influenza B virus (infB), human rhinovirus (HRV), enterovirus (EV), four types of coronaviruses (HCoV-229E, -OC43, -NL63, and -HKU1), adenovirus (ADV), human bocavirus (HBoV), MP, and CP, as previously reported [13] . Briefly, real-time-PCR and RNA/ DNA extraction kits were purchased from Guangzhou HuYanSuo Medical Technology Co., Ltd. RNA/DNA was extracted from 200-\u03bcL samples, according to the manufacturer's protocol. The cycling conditions were 48\u00b0C for 10 min, 94\u00b0C for 2 min, and then 40 cycles of 94\u00b0C for 10 s and 55\u00b0C for 35 s. The amplified products were detected using the Applied Biosystems 7500 Real-Time PCR System (Life Technologies, Singapore). The sensitivity of the detection kits was 500 copies/mL and 1000 copies/mL for the target DNA and RNA, respectively." ] },{ "paper_id": "348e9d5eb25a7d8b2b9597d7a24642eb67abc034", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 ceftriaxone or cefotaxime are recommended for \u03b2-lactamase-producing H. influenzae and high-level penicillin-resistant pneumococcus.", "\u2022 Vancomycin is recommended for empyema owing to S. aureus.", "Issues of surveillance. Globally, there are difficulties in surveillance of antimicrobial resistance (AMR) owing to limited laboratory capacity, harmonised diagnostic procedures and a lack of surveillance networks. Mapping AMR in under-resourced countries requires focus on specimen shipping conditions, data standardisation, absence of contamination and adequate diagnostics [34] ." ] },{ "paper_id": "3498e7e96b742565d9041107cae12e667b394f9f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The secreted protein levels of IFN\u03b3, IL-6, IL-8 and TNF\u03b1 were determined by testing culture supernatants with the respective commercial ELISA kits (R&D Systems,", "All animals' tissue collection procedures were performed according to protocols approved by the Hubei Province PR China for Biological Studies Animal Care and Use Committee. Three 3-week-old Large White piglets were obtained from a herd in Hubei province, which tested negative for both PCV2 and porcine reproductive and respiratory syndrome virus (PRRSV), and were raised in controlled lab conditions. For the first three days of containment, the pigs were administered daily doses of enrofloxacin (1 mL of 5% solution) and lincospectin/spectinomycin (1 mL of 5 or 10% solution) to eliminate any residual bacterial pathogens [67] . Seven days later, the piglets were sacrificed. PAMs were collected by bronchoalveolar lavage and frozen in liquid nitrogen, as previously described [68] . Prior to use, the cells were confirmed as negative for PCV1, PCV2, parvovirus, pseudorabies virus (PRV), classical swine fever virus (CSFV), and PRRSV variously by PCR and RT-PCR [69, 70] . The PAM phenotype was confirmed by flow cytometric detection of the macrophage markers SWC3, CD169, and SLAII [68] .", "Background: Porcine circovirus type 2 (PCV2) is the causal agent of postweaning multisystemic wasting syndrome (PMWS), which has severely impacted the swine industry worldwide. PCV2 triggers a weak and atypical innate immune response, but the key genes and mechanisms by which the virus interferes with host innate immunity have not yet been elucidated. In this study, genes that control the response of primary porcine alveolar macrophages (PAMs), the main target of PCV2, were profiled in vitro." ] },{ "paper_id": "34b2b1fe3361c684f52c9a60f48f579edb8f52dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After infection, in a 24-well plate, supernatants (500 \u03bcl) were subsequently removed and cells were lysed, after three washing steps, using a 15 min incubation with 500 \u03bcl PBS 1% TritonX-100 followed by centrifugation (10 min 400 \u00d7 g). Cell-free supernatants and supernatant from cell lysates were measured using a PAI-1 antigen and VWF ELISA kits according the manufacturer's instructions (both from Zymugen, Hyphen Biomed, France).", "(Mann-Whitney U; p = 0.0022) adhered to plates directly coated with PUUV compared to plates coated with a virus control (VSV), which was cultured under the same conditions as PUUV.", "plates coated with 5 days old vero E6 virus free medium. Binding of the neutralizing IgG antibodies was confirmed by incubation with a goat-anti human HRP labeled conjugate and subsequent TMB reaction." ] },{ "paper_id": "34b8edf90b257de03bb8a408b8fc58544b479d4c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Improving clone stability. . .", "1010" ] },{ "paper_id": "34c5a299626d47493cf1bd35b16debc3f12ca798", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "is study was approved by Nepal Health Research Council (reg. no. 180/2015).", "Statistical analysis was performed using SPSS version 11.5. Descriptive statistics, frequency, and percent were generated. Age-wise distribution of coinfection cases, influenza single-infection, and coinfection with other pathogens were described.", "e authors declare that there are no conflicts of interest." ] },{ "paper_id": "34c60b33c493dfe1545112d9f4b1107576f11dbd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For purity control of isolated pmATII cells, IF staining was performed on cells cultured overnight on chamber slides (BD Bioscience). Cells were subsequently fixed with acetone/methanol (1:1), and blocked with 3 % (w/vol) bovine serum albumin (Sigma Aldrich) for 30 min at room temperature (RT). Primary antibodies (proSFTPC (Merck Millipore, Darmstadt, Germany), panCK (Dako, Hamburg, Germany), T1\u03b1 (Podoplanin; R&D Systems, Minneapolis, MN, US), CD45 (BD Bioscience), CD31 (Abcam, Cambridge, UK), \u03b1SMA (Sigma Aldrich)) were diluted in PBS containing 0.1 % (w/vol) BSA and incubated for 1 h at RT. Fluorescently labeled secondary antibodies (polyclonal goat anti-mouse FITC, Dako, Hamburg, Germany; goat anti-rabbit Alexa 555 or goat anti-rat Alexa 555, both Life Technologies) were diluted in PBS containing 0.1 % (w/vol) BSA and incubated for 1 h at RT. DAPI staining (Roche, Basel, Switzerland) was performed to visualize cell nuclei.", "Additional supporting data are shared as Supplementary Data.", "The authors declare that they have no competing interests. " ] },{ "paper_id": "34ccc1c615fa5697b5926c7ce5f1ea21bc06f5fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Commentary to: Maier HJ, Hawes PC, Cottam EM, Mantell J, Verkade P, Monaghan P, Wileman T, Britton P. Infectious bronchitis virus generates spherules from zippered endoplasmic reticulum membranes. MBio 2013; 4:e00801-13; PMID:24149513; http://dx.", "No potential conflict of interest was disclosed.", "paper type 288 Bioengineered Volume 5 Issue 5 COMMeNtary" ] },{ "paper_id": "34dfd4d983484d85d797e915cb47041aeb4ced86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The mild HFMD outpatients were defined as patients with fever and vesicular lesions on their palms, feet and mouth. Severe cases usually presented with neurologic complications, which were defined as having two of fol-lowing clinical manifestations: brainstem encephalitis or aseptic meningitis; continuous high fever (temperature of at least 38\u00b0C); weakness, vomiting, irritability, myoclonus and acute flaccid paralysis; pulmonary edema or hemorrhage, heart and lung failure. Encephalitis, aseptic meningitis, pulmonary edema, pulmonary hemorrhage, acute flaccid paralysis, myocarditis were characterized by the same definition as described previously [2] .", "The first HEV71 infection was reported in 1969 in the US [1] . Although HFMD is usually a mild disease, several HEV71 outbreaks associated with severe neurological complications have been reported in Western Pacific countries or regions, including Malaysia in 1997; Taiwan in 1998, 2000 and 2001; Australia in 1999; Singapore in 2000; Japan in 1997 and 2000; and Shandong of China in 2007 [2] [3] [4] [5] [6] [7] [8] .", "Human enterovirus 71 (HEV71) is one of the member in HEV-A species of Enterovius genus in the family Picornaviridae. The genome of HEV71 consists of a single-stranded positive-sense RNA of approximately 7400 nucleotides. The viral genome contains a 5'-and 3'untranslated regions (UTRs) which are essential for viral RNA replication. The genome is translated as a single large polyprotein that is composed of four capsid proteins, VP1 to VP4, and seven nonstructural proteins, 2A, 2B, 2C, 3A, 3B, 3C, and 3D. VP1 to VP4 capsid proteins were encoded by P1 region. The P2 and P3 regions encode nonstructural proteins and the RNA-dependent RNA polymerase, 3D, is a major component of the viral replication complex [9] ." ] },{ "paper_id": "34e11e290d25709bbe4a448c970b54162f457902", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After alignment by ClustalW with MEGA 7.0 [28] , phylogenetic trees were constructed using the Maximum Likelihood method with the Tamura-Nei model by using MEGA7.0, and bootstrap values were calculated with 1000 replicates.", "Chromatograms were checked with Chromas 2.5.1 (Technelysium, Tewantin, QLD, Australia) to exclude double peaks, and sequences were analyzed with the BLAST programme (http://blast.ncbi.nlm.nih.gov/Blast.cgi).", "Briefly, bats were anesthetized for collecting blood samples, and were then killed with overdosed anesthetic to collect organs." ] },{ "paper_id": "34e218f77932d4c7a4c29c7a18010d846ee3f4a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lung lobes were isolated and fixed in phosphate-buffered formalin (4% v/v) and sectioned for H&E and PAS staining performed by Histopathology, Great Ormond Street Hospital. Semiquantitative histological assessment was performed blind by two independent observers to score for cellular infiltration of the airways and mucous production. H&E staining was scored for cellular infiltration: 0, normal aspect; 1, mild infiltration around the airway; 2, moderate infiltration around the airway; 3, strong infiltration around the airway; and 4, severe infiltration around the airway and extravasation, majority of airway involved. PAS staining was scored for mucous production: 0-1, minimal; 1-2, moderate; and 2-3, severe. Pictures were photographed by Zeiss AxioCam digital camera with Zeiss Axioplan (NDU) Microscope, 20\u00d7 Objective lens (Plan-Neofluar/0.5NA) and 40\u00d7 Objective lens (Plan-Neofluar/0.75NA) and acquired by software AxioVision v4.8 (Zeiss) and analyzed using ImageJ software.", "www.eji-journal.eu t-statistics, followed by removal of false positives by the false discovery rate (FDR) method to identify DEG with fold change greater than two, which were then filtered for those with a minimum range of at least 250 units (RMA normalized nonlog value) to identify 920 DEG. CCA was carried out as previously described [39, 44, 45] . We used the CCA function of the CRAN package library \"vegan\" for the calculations. All microarrays are publically available (GEO: GSE90494)." ] },{ "paper_id": "34e4b49c46c5462089f516983eeb19a6aff69d01", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Monocytes are classified into two phenotypically and functionally distinct subsets", "Authors' contributions RLT drafted the manuscript. DRG, CD, CVV, ILC and NJCK contributed to the interpretation and critical evaluation of content and revision of the manuscript. All authors read and approved the final manuscript.", "The authors declare that they have no competing interests." ] },{ "paper_id": "34f0507e2d36312bb0a90c6c9a66acd14d9154c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The innate immune system recognizes invading infectious agents through an array of so-called pattern-recognition receptors (PRRs). These molecules detect pathogen-associated molecular patterns (PAMPs) and initiate a downstream signaling cascade that ultimately triggers antiviral/antimicrobial programs. PRRs belong to diverse molecular families including Toll-like receptors (TLRs), Nod-like receptors, RIG-I-like receptors, and AIM2-like receptors (ALRs).", "DNA alignments were generated using RevTrans (Wernersson and Pedersen 2003) and screened for the presence of recombination using GARD (Kosakovsky Pond et al. 2006) . No breakpoint was detected for any gene.", "Parallel Evolution at OAS1, OAS2, and cGAS", "Supplementary tables S1-S4 and figures S1 and S2 are available at Genome Biology and Evolution online (http://www. gbe.oxfordjournals.org/)." ] },{ "paper_id": "350bf76f2ecfc9322c9c8b59af3b7a14a6e51c0f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 63 interviews were conducted with pig traders operating from Wambizzi between October 2015 and October 2016. No traders declined participation in the study.", "Therefore, the objectives of this study were to (1) describe pig trader characteristics, trading practices, biosecurity practices, pig health management, and reporting practices and (2) map source locations of pigs purchased to supply pork through the major abattoir in Uganda.", "Wambizzi Cooperative Society Limited is located in Nalukolongo, southwestern Kampala, Uganda's capital city." ] },{ "paper_id": "35105bb6ba037441c3366e7ea8d59dbcb9245c1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "None of the authors has a financial or personal conflict of interest related to this study.", "For all participants, respiratory samples were collected after informed consent, under the supervision of local sanitary authorities.", "The ethical aspects of this study were approved by Charles Nicolle's Hospital ethic committee." ] },{ "paper_id": "35173a96f21f1e674e63d473864215d025f76d0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The presence of G4s has been recently reported in viruses 31 , such as SARS coronavirus 32 , human papilloma, Zika, Ebola and hepatitis C genomes [33] [34] [35] [36] , Epstein-Barr virus 37, 38 and herpes simplex virus 1 39, 40 .", "The evolutionary history was inferred by using the Maximum Likelihood method based on the General Time Reversible mode 71 . The analysis involved 41 nucleotide sequences of the pol gene extracted from different lentiviruses (relative accession numbers in Table 1 ), which were multiple aligned with clustalW 72 . The percentage of trees in which the associated taxa clustered together is shown next to the branches (for values > = 70 on 500 bootstrap replicates 73 ) (Fig. 3) . The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. All positions containing gaps and missing data were eliminated. There were a total of 2380 positions in the final dataset. Evolutionary analyses were conducted in MEGA6 74 .", "within the viral context was established by assessing the degree of base conservation among different isolates of the same virus strain (Supporting Table S3 ). Only viruses with more than 5 complete LTR sequences and from different strains were considered. An extremely high degree of G-base conservation, especially within G-tracts, was found for almost all 5\u2032-LTR PQSs (generally higher than 70% and in most cases higher than 90%) (Fig. 2 ). In particular, the potentiality to form G4 was maintained in all viruses." ] },{ "paper_id": "3518ccc719fac30ad9a95930985cb000a0018ae5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary information accompanies this paper at https://doi.org/10. 1186/s12889-019-7707-z." ] },{ "paper_id": "351ea0aee67d40885b15698e3c38134f67590a9a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data was entered into a secure web-accessible on-line database (MARVI) as well as into paper case report forms for back-up and quality verification purposes.", "Of " ] },{ "paper_id": "35229a458e5e6c73b9bcc155eedb15c62a24ce17", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Comfort should be an important selection criterion because when a person is comfortable using a respirator, he would probably wear it more accurately. Respirator masks may impose physiological stress on mask wearers.", "Members of content validity were experts in ergonomics, occupational medicine and Occupational Health Engineering.", "The term reliability generally refers to the consistency of a measurement specified by a tool at same conditions (18, 19) . Reliability coefficient ranges from zero to one.", "Content Validity Index (CVI) CVI is equal to the CVR mean of valid items. It represents integrity of judgments about the validity or enforceability of the final tool." ] },{ "paper_id": "352fc70d79c0668a5a7583538fe0167c1fd785d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Research on bats represented an average of 55.7% \u00b1 1.4 of the research activities of our studied population, with these activities being divided as follows: field activities (30.0% \u00b1 1.0), laboratory studies (19.4% \u00b1 0.9), and desk activities (51.7% \u00b1 1.1) (Q2 and Q21). The most extensively studied bat family was Vespertilionidae, followed by Molossidae ( ", "The survey was performed in compliance with the Helsinki Declaration [9] , i.e. all participants were informed about the aim of the questionnaire and were free not to participate or to withdraw at any stage of the process. Responses were analysed in an anonymous manner.", "As illustrated in S1 Fig, respondents showed a worldwide distribution in their research activities on bats, with Eurasian (18.6%) and North American (16.1%) regions being the most represented." ] },{ "paper_id": "35346aa2228281a39b64a6185827e497e57296a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the graphs were created with GraphPad Prism 6 software. All the data are presented as the means \u00b1 standard deviations (SDs) from at least three independent experiments. Significance was estimated using one-way ANOVA with multiple comparisons to control. P values less than 0.05 were defined as the threshold for statistical significance. P values between 0.05 and 0.01 were marked with one asterisk, P values between 0.01 and 0.001 were marked with two asterisks, P values between 0.001 and 0.0001 were marked with three asterisks, and P values less than 0.0001 were marked with four asterisks.", "Coronavirus entry is inextricably linked with proteolytic processing of the S protein. In most cases, PEDV is trypsin dependent. Thus, we investigated the trypsin dependency of both strains used in our research. As shown in Figure 1A , GDS01 strain needed trypsin while GDS09 strain is trypsin independent. So, we added trypsin in the following assays to explore the invasion mechanism of PEDV." ] },{ "paper_id": "354a4b199eb297756554a8967154ea32f07e88d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3557b5b8c5052a1f7fbb18130ace9427201e0fe4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Three investigators (FM, JVK and PF) independently reviewed the combined laboratory and clinical data from all PICU patients, based on the previously defined selection criteria, to decide on inclusion. Disagreement was resolved by consensus.", "This study was approved by the Medical Ethical Committee of the Erasmus MC, Rotterdam the Netherlands (MEC 2013-221). Informed consent was waived because this was a retrospective case-chart study. Data were stored anonymously and cannot be retraced to individual patients." ] },{ "paper_id": "35593b9b140bf1c91c758584ed4e924dd7798436", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(DOC) PRISMA Flow Diagram S1 (DOC) " ] },{ "paper_id": "3559efd0d0327a8262022dcdd40d01a6f468cb82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Serum samples and organs were stored at \u221280 \u2022 C until virological examinations were performed.", "Representative tissues of Buddha were collected and fixed in 10% neutral formalin. Fixed tissue was processed routinely into paraffin blocks and sections were stained with hematoxylin and eosin and reviewed by a board of certified veterinary pathologist.", "The appearance of new variable sites over time can also be noted, like at codon position 645 where a polymorphism appeared only in 2008. Interesting to notice is that kidneys and, most of all, the intestine are the locations where most polymorphic sites characterizing earlier time points were conserved (positions 742, 763, and 777).", "To detect possible differences between sequences obtained from various organs or different years, all positive samples were subjected to a specific amplification of a 1231 nt long portion of the VP1 gene using DreamTaq DNA polymerase (Thermo Scientific) with primers Buddha_VP_5F-ATGTCT CCACTCATTCTGGTG-and Buddha_14_R-ACGATCTGG GTAGATGACTTC. Amplicons were diluted 1:10 and directly sequenced employing the Big Dye terminator chemistry (BigDye\u00ae Terminator v1.1 Cycle Sequencing Kit, Applied Biosystems).", "The start codon of NS1 as well as the stop codon of VP1 are highlighted in gray. The sequence of the small hairpin unique to the 3 side non-coding region is underlined and in boldface." ] },{ "paper_id": "355eb5b5bf565e8e432d8746982b5100764db289", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The dominant viral etiologies responsible for acute respiratory infections (ARIs) are poorly understood, particularly among hospitalized patients. Improved etiological insight is needed to improve clinical management and prevention of ARIs.", "Patient with respiratory viral infection usually develop clinical symptoms, including fever and cough, which further develop pneumonia and bronchitis. We found that RSV (75.61 %) and PIVs (72.34 %) infection were more likely to be associated with pneumonia than were ADV (57.89 %) and HCoV (59.09 %), while IVB shared the same chance to develop pneumonia and bronchitis (43.33 %).", "The viral nucleic acid was directly extracted from the clinical specimens by using a QIAamp mini viral RNA extraction Kit (Qiagen, German). The cDNAs were synthesized by PrimeScript TM 1st strand cDNA Synthesis Kit (Takara # 6110), all samples were tested by multiple RT-PCR screening according to Seeplex\u00ae RV12 ACE Detection manufacture (Seegene Cat No. RV6C00Y). The detected respiratory viruses included IVA, IVB, ADV, RSVA, RSVB, PIV1-3, hMPV, HCoV-229E/NL63, OC43/HKU1, and HRV." ] },{ "paper_id": "356381d431c775e013710e6bff7ab89a507eb013", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dual or multiple infections were common (range, 13.4%-17.4%). A prospective cohort study in a daycare center in the United States using comparable molecular techniques reported a coinfection rate of 27% among symptomatic young children [20] , indicating that this high burden of viral coinfection, especially among children, is global. Detection of coinfection was higher among the symptomatic cases, as has been reported in hospital-based surveillance studies [21] [22] [23] .", "Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author." ] },{ "paper_id": "3568da162b8d9f5356c9264193b6292efa3d9556", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All nsp1 subdomains are critical for transcription, while the ZF and PCPa domains are also important for virus production", "Following inactivation of the enzyme, we added an excess of 32 P-labeled transcripts of positive polarity, which were derived either from a region unique to the EAV genome, or from the leader-body junction regions of RNA6 and RNA7. The samples were then subjected to a second round of RNA denaturation, hybridization, and digestion with RNase A and T1, after which the protected fragments were analyzed by electrophoresis." ] },{ "paper_id": "356b49eeee107ff0397b374e29cdd8f133b2688f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Ensembl Genome Browser (http://www.ensembl.org) referring to the GRCh37.p13 version of the NCBI database contributed all DNA sequences that were used for primer design. Tandem Repeats Finder software was used to identify repeated sequences in the CLEC4M gene region (http://tandem.bu.edu/trf/trf.html) and masking of repeated sequences used the Ensembl Genome Browser. Primers were designed using Primer-BLAST (http://www.ncbi.nlm.nih.gov/tools/ primer-blast/) and purchased from DNA Technology A/S (Risskov, Denmark). ", "Identified variants in the CLEC4M gene were compared to publicly available data in dbSNP (http://www.ncbi.nlm.nih.gov/SNP/) and 1000Genomes databases (http://www.1000genomes. org/). The 1000Genomes database consisted of 26 populations from different geographic regions. We extracted information from three of these populations: Utah residents of [20] using the 106 type 1 VWD index cases and the C 1 and C 2 individuals as controls. Haplotypes, haplotype blocks and linkage disequilibrium (LD) plots were constructed using Haploview 4.2 [21] . The functional consequences of missense variants were evaluated using SIFT [22] , PolyPhen-2 [23] and MutationTaster [24] .", "Supporting information S1 ", "Complete VWF resequencing showed that 45% of the 482 patients with historical type 1 VWD diagnosis carried a rare variant in the VWF gene compared to 62% of the 310 patients fulfilling the modern criteria. Thus, this type 1 VWD population is very similar to our type 1 VWD population [18] ." ] },{ "paper_id": "356f0fd788357570d8316ea566c88002554745b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Slightly blocked" ] },{ "paper_id": "3576b9e0d1895a2d2cb0231304425e1633e86e82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis of RT activities was performed by Student's t test using Stata statistical software. Results were considered significant at P#0.05.", "Reverse transcriptase (RT) of human immunodeficiency virus (HIV)-1, encoded by pol gene, is a multifunctional enzyme that possesses RNA-and DNA-dependent polymerase activities as well as RNase H activity [1] . RT is indispensable for HIV-1 and it converts the single-stranded viral RNA into double-stranded DNA upon viral entry into host cells. Due to its important role in viral life cycle, RT is one attractive target for antiviral drug design [2] .", "RT sequences of 1083 HIV-1 strains obtained from the HIV complete sequence database (http://www.hiv.lanl.gov/content/ sequence/NEWALIGN/align.html) were aligned and compared. Based on the X-ray crystal structures of HIV-1 RT (1RTH) from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), structural models of wild type and mutant RTs were analyzed using Swiss-PdbViewer software (http://spdbv.vital-it.ch/)." ] },{ "paper_id": "357a008270023e621d758ada372b14e676edb782", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Running and Coordination", "Chair of GP network participates and gives advice in national/sub-national crisis committee.", "Identify the vulnerable and at risk groups for necessary health protection." ] },{ "paper_id": "357d43fba827a0d33c5810a56e193149df4777f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were analyzed with SPSS 25.0 software (IBM, USA). Categorical variables were described with counts and percentages. Differences between medians were tested by the Mann-Whitney U test, and the Chi-square or Fisher's exact test was used to compare categorical variables. A P value of less than 0.05 was considered statistically significant.", "Point mutations associated with resistance in domain V of 23S rRNA were detected. Genomic DNA of all M. pneumoniae was extracted using a QIAamp DNA minikit (Qiagen, Hilden Germany). The extracts were distributed into aliquots and saved at-20\u00b0C. A forward primer extending from position 1758 to position 1775 (GCAGTGAAGAACGAGGGG) and a verse primer extending from position 2684 to position 2664 (GTCCTC GCTTCGGTCCTCTCG) in the sequence of M. pneumoniae 23S rRNA were used to amplify the domain V region of the 23S rRNA gene by PCR methods, as previously described [22] . The amplification products were sequenced by the Invitrogen Life Technologies (Shanghai, China).", "The median hospitalization period was 11 days (range = 2-28 days), and the median duration of disease was 16 days (range = 6-34 days).Among the 55 cases, the overall median time interval between onset to first visit to any medical institution was 1 day (range = 0-10 days), the time interval before June 8 was longer than cases onset on and after June 8 (Z = -3.238,P < 0.001)." ] },{ "paper_id": "357f5b1caf114fdb8a60870473af88bc9017bf14", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Equine influenza (EI) is an acute, highly contagious viral disease which can cause rapidly spreading outbreaks of respiratory disease in horses and other equine species. It does not infect humans, but the virus can be physically carried on skin, hair, clothing, shoes, vehicles and equipment and through these means can be transferred to other horses. In addition, the windborne virus can be spread for distances up to eight kilometres [1] .", "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "35808155b612d2189d338168dc1cc0e0b7401661", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PAO was responsible for the experiment, data analysis and wrote the manuscript. KKL participated in planning, sampling, and contributed throughout the experimental process. LS contributed in the statistical analysis of the data. All authors read and approved the final manuscript." ] },{ "paper_id": "35906518687a56bbe629ae4b4c9002b0267d8a93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Experimental autoimmune encephalomyelitis (EAE) is one of the most studied animal models of MS which is induced by inoculation of rats or mice with antibodies against myelin binding protein (MBP), proteolipid protein (PLP) or myelin oligodendrocyte glycoprotein (MOG) 10-12 . After inoculation, animals develop pathological features of inflammation and demyelination in the spinal cord and brain, with infiltration of the spinal Statistics. All data are presented as mean \u00b1 SE. Results were statistically analyzed using paired t-test to compare the parameters from the same group at different time points, and unpaired t-test to compare the parameters between different groups (Systat Software, Inc. San Jose, CA). Data with p \u2264 0.05 difference were considered statistically significant.", "cord with inflammatory cells expressing pro-inflammatory cytokines [10] [11] [12] . EAE-driven demyelination is mostly mediated by CD4 T cells of a Th17 phenotype 13 , which is a population of immune cells known to be associated with more severe pathology of MS 14, 15 . Several previous studies investigated micturition abnormalities in animals with EAE. In rats with MBP-induced EAE, both detrusor areflexia and detrusor hyperactivity were observed and correlated with spinal cord inflammation and hindlimb paralysis 16 . Using cystometric analysis, Mizusawa et al. showed that EAE caused detrusor areflexia in 52% of female rats in comparison to 12% which developed detrusor overactivity 16 . Another group established that the majority of female rats showed symptoms of detrusor areflexia prior to EAE onset but that detrusor overactivity developed at the onset of the disease 17 . Additional animal models of neurodegeneration and demyelination include a murine model of coronavirus-induced encephalomyelitis (CIE) 18, 19 . Mice inoculated with neurotropic strain A59 of mouse hepatitis virus (MHV) develop CIE accompanied by severe central nervous system (CNS) demyelination and axonal degeneration 20, 21 . The viral nature of CIE model reflects a spontaneously occurring demyelination in the CNS in comparison to induced models (e.g. EAE). MHV-driven demyelination is mediated by interferon-gamma (INF-\u03b3) of a Th1 phenotype 18, 19, 22 . Compelling preponderance of Th1 cytokine responses has been previously reported in a majority of MS patients 15, 23, 24 .", "In conclusion, our study identified several phenotypes of neurogenic bladder dysfunction based on the patterns of neurological impairment development in CIE mice suggestive of high clinical relevance of the viral murine model to the human MS. The mechanistic differences between the subgroups of CIE mice make the model suitable for studying the relationship between voiding dysfunction and progressive neurological impairment over the course of virus-induced demyelinating disorder, and to test novel therapeutic approaches for the treatment of human MS." ] },{ "paper_id": "359417eec03774de55b638845646f0f377f35de8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Study design and data source. We investigated data from 594 COPD patients who were enrolled in the Korean COPD subgroup study (KOCOSS) cohort between December 2011 and March 2014. Patients were eligible if they had been diagnosed with COPD by a pulmonologist, were aged \u226540 years, had post-bronchodilator FEV1/FVC < 0.7, and if respiratory symptoms, such as cough, sputum, or dyspnoea, were present. Detailed information regarding KOCOSS cohort is described in a previous publication 33 .", "Results", "Baseline patient characteristics. Supplementary", "The Korean National Institute of Health (KNIH) monitors the trends of virus activity on a nation level. KNIH has surveyed respiratory viral infection status since 2000 and provided information to the public on a weekly basis (detection rate, %). Data on the activities of influenza adenovirus, parainfluenza virus, respiratory syncytial virus, influenza virus (IFV), human coronavirus (hCoV), human rhinovirus (hRV), human bocavirus, and human enterovirus were collected from the KNIH database for the 2007-2012 period.", "We also collected primary weather variables, including levels of particulate matter <10 microns in diameter (PM10, \u00b5g/m 3 ), daily minimum ambient temperature (\u00b0C), and daily precipitation for 2007-2012. Daily local meteorological weather data, measured at the local weather stations, were provided by the Korean Ministry of the Environment. All the information amassed was matched to the patients' addresses. Matching was performed at province level. The area of the respective provinces (n = 16) ranged from 501 to 19,031 km 2 (median: 6,628 km 2 , interquartile range: 827-10,362 km 2 )." ] },{ "paper_id": "359aef6ff466266be0ea21eb665fb887cec16713", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The methods described herein are similar or identical to those published for our previous studies [6, 7, 8, 9, 25, 26, 27] .", "Analyses were carried out using the SAS software system (SAS Institute, Inc., Cary, NC) and the PLINK whole genome data analysis software package." ] },{ "paper_id": "359d79257b07cb81eddbcbcc2882bbb43362cfe4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "359e2466c6424f9b5ca2f4eb46fbf2a011a9a6c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Regional Animal Research Ethical Board, Stockholm, Sweden, approved protocols involving extraction of cells from mice, following proceedings described in EU legislation (Council Directive 2010/63/EU). The Regional Ethics Committee, Stockholm, Sweden, approved protocols involving human cells. All donors received written and oral information upon donation of blood at the Karolinska University Hospital. Written consent was obtained for utilization of white blood cells for research purposes.", "AH performed experiments and analyzed data. M-AH provided crucial reagents. AH and AB conceived experimental design and wrote the manuscript.", "We acknowledge Dr. Manuel Varas-Godoy for input on shRNA design and all the members of the Barragan lab for providing critical input." ] },{ "paper_id": "35a1fc9f21b1fd513fd01f015e091a023d50dd7e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "35b1d29a27113b46ea93b8cd542cb09a9da6a0c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "35c05762c68e41518351ac579286703662345575", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "35c31daa44cb7fd28aeea422bb15d1a3858a2378", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza A virus infection is responsible for annual influenza epidemics and intermittent pandemics that are associated with significant morbidity and mortality [1] . The ability of IAV to constantly change in response to immune pressure or antiviral treatment limits the effectiveness of currently used antiviral interventions. Thus, vaccines against seasonal influenza need to be annually reformulated and will provide little if any protection against pandemic influenza [1] . Moreover, the effectiveness of antivirals targeting the viral proteins M2 and neuraminidase a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 is compromised by the frequent emergence and transmission of resistance mutations [1, 2] . Therefore, novel approaches to combat influenza are urgently needed.", "The production of MLV particles for transduction of cells followed an established protocol [25, 28] . Briefly, 293T cells seeded in T25 flasks were transfected with 6 \u03bcg of retroviral vector (e.g. pQCXIP-PB2), 3 \u03bcg MLV-gag-pol plasmid and 3 \u03bcg VSV-G expression plasmid, employing the calcium phosphate transfection method. The culture medium was exchanged at 8 h after transfection. After 48 h, MLV particle-containing supernatant was harvested, cleared by passing through a 0.45 \u03bcm filter, aliquoted and then stored at -80\u02daC.", "Images were taken on a Zeiss LSM800 equipped with a 10x/0.45 plan-apochromat objective, 488 nm and 561 nm diode lasers and ZEN imaging software (Zeiss). Fluorescent signals (red channel, 561 nm laser) were detected with GaAsP detector employing the same sensitivity for all images of a series, while bright field signals were recorded with an ESID detector (photodiode) with individually adjusted sensitivity." ] },{ "paper_id": "35ccd353aa1b7ee2a015dc8012a3bcc19a8f9a20", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An early diagnosis in this patient could have been secured in the presence of serology. Serological methods are the most sensitive available diagnostic tools. A variety of antigens have been used to develop serological tests. ELISA test had a negative predictive value of 98% and is an excellent screening test for strongyloidiasis [24] . A number of studies demonstrated high sensitivity with specificity of >90% in most of reports. These tests can be used to make the diagnosis and screening and more importantly as a possible test of cure [22] . This underscores the importance of maintaining serological tests in all transplant centers in order to avoid this serious infection.", "Treatment options include albendazole, thiabendazole, and ivermectin. In a recent Cochrane review, ivermectin has been proven to be more effective than albendazole (RR: 1.79; CI: 1.55 to 2.08) and equally effective to thiabendazole but more tolerable than it (RR: 1.07; CI: 0.96 to 1.20) [25] . It is usually given orally; subcutaneous injection (veterinary formulation) and retention enema were used, too. The duration of treatment of hyperinfection syndrome is variable. The CDC recommends ivermectin, 200 g/kg per day orally, until stool and/or sputum exams are negative for 2 weeks. If possible, immunosuppressive therapy should be stopped or reduced.", "To the best of our knowledge, this is the first case report of Strongyloides hyperinfection with concurrent (CMV) infection and Gram-negative sepsis in a Saudi patient. Despite a very aggressive disease, this patient had a favorable outcome and is now evaluated for a second transplant." ] },{ "paper_id": "35cd13c57dc46df01a1cae4ee1edbff7774cfe9b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication.", "The authors' work was supported in part by Institut Pasteur, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Institut National de la Recherche Agronomique, Universit\u00e9 Paris Diderot, Agence Nationale de la Recherche (Grant Proantilis, Laboratoire d'Excellence ANR-10-LABX-62-IBEID), European Research Council, Howard Hughes Medical Institute, Fondation Le Roch and Louis Jeantet Foundation. LR is a long term fellow of the Human Frontier Science Program and European Molecular Biology Organization.", "Cytosolic sensing of pathogens is essential to a productive immune response. Recent reports have emphasized the importance of signaling platforms emanating from organelles and cytosolic sensors, particularly during the response to intracellular pathogens. Here, we highlight recent discoveries identifying the key mediators of nucleic acid and cyclic nucleotide sensing and discuss their importance in host defense. This review will also cover strategies evolved by pathogens to manipulate these pathways.", "The importance of inhibiting the inflammasome to promote viral infection has been demonstrated by revealing the critical role of the Poxvirus M13L immunomodulatory protein in infection of monocytes and lymphocytes and in disease (Johnston et al., 2005) . Poxvirus M13L is a member of the pyrin domain-containing superfamily of proteins. It interacts with host pyrin domain protein ASC-1 (apoptosis-associated speck-like protein containing CARD-1), inhibiting caspase-1 activation in monocytes, thereby disrupting the intracellular pathways leading to IL-1\u03b2 processing and secretion." ] },{ "paper_id": "35cf9c43b3b1028de85e24946f7bbc0436b24190", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "35d2665a9d06c67cd85ff2ed458c9df80902d4bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Using assumption 2, we may write ", "P\u00f0C 1 ! C 2 ji changes; t\u00deP\u00f0i changesj\u0398; t\u00de \u00f08\u00de" ] },{ "paper_id": "35d7e6d1717c9b8604c8370ffdf26ea9569aa75d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A plasmid encoding segment 8 from strain A/PR/8/34 New York (kindly provided by Stephan Ludwig) was generated after RT-PCR amplification from virion RNA using primers fluA AarI-NS-1 5-CGATCACCTGCTCGAGGGAGCAAAAGCAGGG-TG-3 and fluA AarI-NS-890R 5-CGATCACCTGCTCTCTAT-TAGTAGAAACAAGGGTGTTTT-3, and subsequent Golden Gate cloning [24] into pHW2000-GGAarI.", "The eight plasmid system for low and high virulent strains A/ lvPR/8/34 (H1N1) or A/hvPR/8/34 (H1N1) and expression plasmids for influenza A/Thai/1(Kan-1)/04 replicase (PB1, PB2, PA and NP in pCAGGS) were described previously [52, 53] .", "For immunoblotting, cell lysates were separated by SDS-PAGE and blotted onto nitrocellulose membranes. Membranes were blocked with 5% milk powder in PBS/0.1% Tween. NS1 proteins were detected using an antibody against NS1 protein from A/ California/06/2009 (H1N1) [57] . Bound antibodies were detected with horseradish peroxidase-(HRP-)-conjugated secondary antibody (Dianova) at a dilution of 1:5000 and reacted with a luminescent substrate (Amersham ECL reagent, GE Healthcare, M\u00fcnchen).", "Retroviral vectors for expression of IFITM1, 2 and 3 have been described previously [17, 55] . A version of pQCXIP-IFITM2 with correct stop codon was amplified with IFITM2-5NA 5-CCCG-CGGCCGCACCGGTACCATGAACCACATTG-3 and IFITM2-3BE 5-CGAATTCCGGATCCCTATCGCTGGGCCTGGAC-3 and cloned in pQCXIP using NotI and EcoRI. For construction of the control vector pQCXIP-Cat, pENTR-2B-Cat was digested with NotI and BglII and ligated to pQCXIP digested with NotI and BamHI. The cat gene had been amplified with primers EN-TRcat3Xho and ENTRcat5Acc and cloned into pENTR-2B-Dual (Invitrogen, Germany) via Acc65I and XhoI. Plasmids for viral envelope proteins from Vesicular stomatitis virus (VSV), Mouse leukemia virus (MLV) and Lassa virus (LASV) have been described previously [56] ." ] },{ "paper_id": "35d8d53b4907862f8ad0c6f72e6905204d4c9562", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was supported in part by funding from the Iowa Pork Producers Association (NPB no. .", "Nucleotide sequence accession number. The complete genome sequence of PEDV strain USA/Iowa/18984/2013 was submitted to GenBank under the accession no. KF804028.", "Porcine epidemic diarrhea (PED) was recognized in U.S. swine for the first time in early 2013. A plaque-purified PED virus (PEDV) isolate (USA/Iowa/18984/2013) was obtained from a diarrheic piglet. The isolate is genetically close to other previously reported U.S. PEDVs and recent Chinese PEDVs and was virulent when inoculated into neonatal pigs." ] },{ "paper_id": "35dd113e67ede7d921128d82d5a0077071a8ee78", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "35e064b054a771d099132d43c9ebb75cfee837b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For public data sources see [43, 44] Monthly mean precipitation Alaska (taken from SNAP)" ] },{ "paper_id": "35f029b40611c03be25c0c2e0e8a9731e7ed4643", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Age <5 months preferably. Normal body temperature of 38\u223c39.5 \u2022 C (rectal temperature).", "We thank all present and past members of Yan Laboratory who have contributed comments and ideas.", "Frontiers in Microbiology | www.frontiersin.org Frontiers in Microbiology | www.frontiersin.org", "JH and LC wrote the paper with the help of all authors. JH, LC, YT, CX, BX, MS, WZ, SZ, XW, LL, YY, TY, YN, QH, and XX prepared the materials for this manuscript. XY revised this manuscript. All authors read and approved the final version of the manuscript. " ] },{ "paper_id": "35f06fe8870be0c3cd7f0e9b47872a59c7590d7d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vitamin D also modulates the adaptive immune response, and acts as a key intermediary between innate and adaptive immunity due to its influence on antigen presentation.", "The manuscript was conceived by both authors. CLG wrote the draft manuscript which was subsequently edited by ARM.", "The authors declare no conflict of interest." ] },{ "paper_id": "35fa07c7c7d1803f22859f6647d5d743e7ad7652", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "balanced accuracy specificity sensitivity = + 2" ] },{ "paper_id": "35fd455662a4a9c03d3791ee3a390c163a53f242", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Biopanning for screening of combinatorial phage display libraries", "Bacteriophages with RNA genomes have also been applied to develop vaccines. QB and MS2 are RNA viruses that antigens fused to their surface coat proteins have been used for the production of vaccines against drug addiction [92, 93] and HIV infection [94] .", "Viruses are biochemical complexes made up of genomic and proteomic materials. All of the physical, chemical, and biological characteristics associated with the structure and function of these biological entities are specified by their genetic sequences. Viruses infect their hosts through recognizing specific receptors on the surface of host cells and subsequently transfer their genetic information into the cells. The delivered viral genome hijacks the host metabolism in order to produce more virions, thereby propagating the viral population [1] . Within the recent decades, a considerable body of data has accumulated with regard to the molecular basis of structural and functional features of viruses. These findings have led to a paradigm shift in our understanding of viruses from disease-causing pathogens to health-giving biomedical tools." ] },{ "paper_id": "35fd57d62eba3f9b7de6cd27ac5fe63a478a4197", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA was extracted from virus-infected cultures using TRIzol reagent (Invitrogen, Carlsbad, CA, USA), and cDNA was reverse transcribed with reverse transcriptase (Takara, AMV, Kusatsu, Japan) using random primers (Takara, Kusatsu, Japan, 6 mer). All the fragments were amplified by polymerase chain reaction (PCR) with Phanta Super Fidelity DNA polymerase (Vazyme, Nanjing, Jiangsu, China).", "(ORFs), which encode polyprotein 1a (pp1a), polyprotein 1ab (pp1ab), spike (S) glycoprotein, envelope (E) protein, matrix (M) protein, and nucleoprotein (N) [10, 11] .", "Coronaviruses (CoVs) are single-stranded, positive-sense RNA viruses closely related to animal and human health [1] [2] [3] . CoVs belong to the Coronaviridae family, which consists of the Alpha-, Beta-, Gamma-and Deltacoronavirus genera [4] . Since 2003, CoVs, including severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and porcine epidemic diarrhea virus (PEDV), have swept across the world and caused considerable global economic losses [5] [6] [7] [8] [9] . As the largest RNA genome viruses, CoVs have at least six typical overlapping open reading frames" ] },{ "paper_id": "360991ff283a6ec08b264813dba65427cecfa615", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2018, 10, 425 2 of 10 and associated clusters in other regions of the world. Outbreaks of non-sustained, human-to-human transmission have primarily occurred in healthcare settings [2].", "The case-patient data reported to WHO by member states is anonymized, thus, neither informed consent, nor approval from an institutional review board were required." ] },{ "paper_id": "360ab35f1a888c57572270161254de77913951be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Differentially Affects MG, Spleen, Mesenteric Lymph Node, and Ileum ASC", "Studies were approved by the Institutional Animal Care and Use Committee (IACUC) and performed on gestating and lactating gilts and piglets aged 0-5 weeks, in accordance with USDA and OSU IACUC guidelines.", "LS, KL, and SL contributed conception and design of the study. SL conducted the experiments, analyzed the data, and wrote the manuscript. LS and AG supervised the work and contributed critical analysis to the results. FP, MA, AB, and AVG assisted with daily animal work, collected and processed samples and conducted RT-qPCR experiments and analysis. MA and SL conducted IHC experiments and analysis. All authors contributed to manuscript revision, read, and approved the submitted version. " ] },{ "paper_id": "360d7a85fefdad638d52a705f668d2047fc63ce7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "360e2ae0c8c522d48cb5414c1e982d96e40165b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "unit with an YM-10 membrane (Millipore, USA), followed by dialysis against PBS. E. granulosus somatic antigen (Sm) was obtained by sonication of adult parasites in PBS supplemented with ULTRA Protease Inhibitor Tablets (Roche, Indianapolis) on ice, centrifugation and filtration (0.22 mm). Antigens from T. hydatigena were similarly prepared. Protein content was determined using a BCA kit (Pierce, Rockford, Illinois).", "The parasite antigens were prepared essentially as described by Casaravilla et al. [16] . ", "(DOCX)" ] },{ "paper_id": "360fb902fea73a294614ebd95276b59de868786c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although frequently used, invasive MV has several complications, such as ventilator-associated pneumonia, which is a risk factor for mortality and for diaphragmatic dysfunction, which may lead to diaphragm myofiber atrophy [9] [10] [11] .", "NIV was delivered by a specific ventilator, BiPap \u00ae Vision \u00ae (Philips -Respironics) providing a pressure support ventilation through a total face mask. The respiratory therapists were responsible for this therapeutic intervention. Our ICU has a respiratory therapists:bed ratio of 1:5.", "Categorical variables were expressed as absolute and relative frequencies (percentages). The quantitative variables were expressed as mean and standard deviation if normally distributed, or as median and interquartile range if distributed otherwise. The software R, version 10.1 was used to compute the descriptive statistics [16] ." ] },{ "paper_id": "3619c9e99ff6ceb2fa038d13239e6fce4e818995", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IBV was propagated in 9-11-day-old embryonated specific pathogen-free chicken eggs as described previously [30] . The allantoic fluid was harvested 48 h post-inoculation and stored at \u221280 \u00b0C until RNA extraction. The different viruses used in this study are listed in Table 3 ." ] },{ "paper_id": "362f9e6b508a42ffebfd1a95d146955d59c7cea0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The estimations of w and b are obtained by transforming Eq. (3) into the primal function:" ] },{ "paper_id": "362ff59c268fdb40d5a9689c370beca4f2a16d66", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics approval. Ethical approval for this study was obtained from the University of Malawi College of Medicine Research Ethics Committee (P.07/10/958), Liverpool School of Tropical Medicine (10.76), and the CDC through an ethical reliance. All participants provided written informed consent.", "Climatic data. Data on rainfall (millimeters), temperature (degree Celsius), and relative humidity (percentage) were obtained from the Malawi Department of Climate Change and Meteorological Services for 2011-2013.", "A single virus was isolated in 253 (22.5%) patients, whereas 154 (13.7%) individuals had two or more viruses detected. The highest proportion of viral co-detection was observed for bocavirus (21/24, 87 .5%) and enterovirus (27/32; 84 .4%), whereas the lowest proportion was observed in influenza A (26/108; 24.1%)." ] },{ "paper_id": "3633ffe6e8c7f4af342b1a5d23821169f7f9e1b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "36469337a42a7feb9bdefa958b364d2e269ec2ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "None of the experiments in our study involved human participants.", "PCR assay for ALV-J detection was carried out with the subgroup-specific primers H5:H7(ALV-J) described by Smith et al [30] . The PCR primer sets for subgroups A, B, E are designated as H5: Cap A (ALV-A), H5: Cap B (ALV-B), H5: AD1 (ALV-E) , described by Zavala et al [31] . All PCR reactions were performed in accordance to the methods described for detection of ALV [31] . The PCR products were visualized in a 1.5 % agarose gel with ethidium bromide.", "The ", "DNA was extracted from the clinical tissue samples using a UniversalGen DNA kit (CWBIO, Beijing, China), according to the manufacturer's operation manual. These DNA extractions were stored at -20\u00b0C utilized as a template for the LAMP assay and routine PCR detection." ] },{ "paper_id": "3646ec7d036646a765d5afe60f4644346c4a001e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "364b968c148ee72c7336bf89c06974a646683fd3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Deep sequencing of field-collected mosquito bloodmeal-derived DBS RNA extracted from individual mosquito bloodmeal-derived DBS (M-DBS, 30 \u03bcl each) were pooled together (n = 24-57). The pooled RNAs were concentrated to a volume of 20 \u03bcl by precipitation with sodium acetate and ethanol followed by DNase treatment (Ambion) and RNA purification using Agencourt RNAclean XP beads (Beckman Coulter Genomics, Pasadena, CA). The RNA pools were prepared for NGS using the NuGEN Ovation RNA-Seq System V2 (San Carlos, CA) and Nextera XT DNA Sample Preparation Kit (Illumina, San Diego, CA) according to the manufacturer's recommendations. Each library was constructed with a unique barcode and subsequently combined into pools of four and sequenced on two lanes of the Illumina HiSeq (Beckman Coulter Genomics, Danvers, MA).", "PLOS Neglected Tropical Diseases |" ] },{ "paper_id": "364f3e45183f362e8398724c29d3b010436ce375", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We would like to thank Dr. Wannasiri Lapcharoensap for her contributions to editing and critical review of the manuscript.", "This work was funded in part by NIH grants NHLBI HL085526 (K23) (Sapru) and NHLBI HL114484 (R01) (Sapru) . The authors have no disclosures related to financial interests in any drugs, devices, or studies discussed herein.", "The main focus of this review is to assess the current knowledge of biomarker patterns in acute lung disease/injury and their association to patient outcomes, with a specific focus on the pediatric and neonatal patient population.", "Drs. BO and AS conceived of the project and jointly prepared the abstract proposal. Dr. BO drafted the manuscript. Dr. AS provided subject matter guidance and critically reviewed and revised the manuscript. All authors approved of the final manuscript prior to publication." ] },{ "paper_id": "3650b941642ddc9c3627fdb8d415f8c8b69a4158", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3654aa0ea8709bb844a9dd36d67c4e5d89ba3c83", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IAVs were labelled with R18 (Molecular Probes, Eugene, USA) as follows.", "A549, MDCK, and 293T cells were subcultured using Dulbecco's modified Eagle's medium (DMEM, Nissui, Tokyo, Japan) containing 10% fetal calf serum. Zanamivir was provided by GlaxoSmithKline Research and Development Ltd. (Stevenage, UK).", "Scientific RepoRts | 7:45043 | DOI: 10.1038/srep45043" ] },{ "paper_id": "3656fed9d1f687fd87440d7da4f3d852aa1dcdc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The number of individuals in each experimental group (n = 12 per group) was calculated using Fisher's exact conditional test for two proportions (as implemented by Proc Power twosamplefreq, SAS software) and power 1-b = 0.80 (a = 0.05). A Wilcoxon matchedpair signed-rank test was used to analyze differences in mean values between groups. Mann-Whitney and Mantel-Cox tests were also used as described in legends. P-values of < 0.05 were considered statistically significant.", "Blood samples were collected from participants vaccinated against rabies. All donors gave written informed consent for research use of blood samples, following approval by the Cantonal Ethical Committee of Cantone Ticino, Switzerland. Animal studies were performed in strict accordance with the relevant national and local animal welfare bodies [Convention of the European Council no. ", "Expanded View for this article is available online." ] },{ "paper_id": "365ab3e4ca40537484abf16d4d33d88f63635404", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Develop methods and/or tools for real-time monitoring during the outbreak Others 1. Promote planning and policy-making by health services 2.", "Investigate psychobehaviors 3.", "Other epidemiological studies ", "Investigate transmission (determine the modes and routes of transmission, estimate the transmission probability and variability andpredict future trends of the present outbreak) Intervention 1." ] },{ "paper_id": "365b0a8e08cc9c93c6e5b33e23ef3d4399953870", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study received a review exemption from the institutional review board (IRB) of Seoul National University Hospital (IRB No.1508-064-694)." ] },{ "paper_id": "3660a0a14f82558378797b8a86fb7d0854bd1ab4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Diagnostic testing PEDV RNA extraction and real-time reverse transcriptase PCR (rRT-PCR)", "The data is available upon request from the corresponding author.", "For each site, all samples were completely randomized (random.org) within specimen type and submitted for testing at the end of the collection period." ] },{ "paper_id": "36767ebe8e566a75a7fe9561206af5e722006b46", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Safety was evaluated during the study through analysis of adverse events (AEs), vital signs, and physical examinations.", "The mean changes in vital sign and physical examination values from baseline were small, and no clinically The \"bold data\" are statisticly significant significant trends were observed between treatment groups. No pregnancies were reported during the study.", "Current pharmacological interventions for the prevention and treatment of respiratory viral infections are primarily limited to vaccines and antivirals for influenza. Available antiviral treatments for influenza infection are M2 ion channel inhibitors (eg, amantadine and rimantadine) and neuraminidase inhibitors (eg, oseltamivir and zanamivir) [6] . If the infection is caused by bacterial pathogens, treatment can involve antibiotics and also medications that provide symptomatic relief. However, in case of viral aetiology, only medication for symptomatic treatment can be provided. [7] ." ] },{ "paper_id": "367aa0244a4b97d04590b92ba9dba13fccd07ce3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Categorical variables were expressed as percentage of outcomes of interest over total observations for each quantitative indicator. Furthermore, 95% confidence intervals for proportions were calculated using the binomial distribution. The statistical analysis was implemented using Stata version 14.2 (StataCorp, College Station, Texas, USA).", "Calculation/data inputs Data source Indicator value Score \u2022 Estimation of burden of influenza-associated illness using surveillance data Not applicable Publication on burden of influenzaassociated ILI and SARI.", "\u2022 Contribution to influenza Regional/Global studies Not applicable Publications on Regional/Global studies with DRC influenza data 3 [14, 15] 3 the African region and are expected when a geographically representative coverage is attempted. Overall, the timeliness of the system in relation to its geographical coverage is considered satisfactory." ] },{ "paper_id": "367af6bb9a8bbda02206506a819656bb6f14ce4c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "d." ] },{ "paper_id": "367e3d844bd06915e08d9082a3b720dcc6ac845f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dengue virus (DENV), which includes four serotypes (DENV1-4), is transmitted to humans by Aedes mosquitos and is the etiological agent of dengue fever and dengue hemorrhagic fever [1] . DENV causes an estimated 50-100 million cases of dengue fever, 500,000 cases of severe dengue (dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS)), and more than 20,000 deaths each year in tropical and subtropical regions, representing a considerable public health threat in over 100 countries worldwide [2] . However, there are still no specific antiviral drugs or licensed vaccines against DENV infection.", "The ORF is flanked by highly structured 5 1 -and 3 1 -untranslated regions (UTRs), which play regulatory roles in translation of the viral proteins and viral RNA genome replication. In DENV and other flaviviruses, the presence of complementary sequences at the ends of the genome mediates long-range RNA-RNA interactions [5] . DENV RNA displays two pairs of complementary sequences (CS) required for genome circularization and viral replication [6, 7] . The downstream 5 1 CS pseudoknot (DCS-PK) elements enhance viral RNA replication by regulating cyclization [8] .", "Some researchers have conducted studies in which the luciferase gene is replaced with the enhanced green fluorescent protein (EGFP) gene for construction of DENV replicon cells [41, 42, 44] . In this replicon assay system, readouts are easy to monitor by measurement of the fluorescence intensity of living cells. Indeed, Leardkamolkarn et al. carried out HTS and identified new anti-DENV compounds using this DENV replicon system." ] },{ "paper_id": "36885622f4e863ce69c521612093f1682fed1a5d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The presence of H. pylori in stomach tissues was identified by visualization of spiral microorganisms in histology sec-tions and/or by immunohistochemistry. Four-micron tissue sections were de-waxed in xylene and decreasing grades of ethanol. Antigen retrieval was by heating in citrate buffer, pH 6.0. The primary antibody against H. pylori (1:50 dilution; DAKO A/S, Glostrup, Denmark) was followed by the secondary antibody polymer link (Envision Chem Mate, DAKO) and visualized using diaminobenzidine as chromogen." ] },{ "paper_id": "368cbceb0d0e8ad64b484f330c03d950394bf397", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Complete tables of results for Google Correlate Searches, Google Trends data, Spearman Correlations and cross correlations." ] },{ "paper_id": "3691c1e9130028008093d3d62e16a43883631cae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3695704554777889f8232a9ea086df70bf17ff58", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data S1 Solid-phase fractionation data. (XLS) Data S2 Liquid-phase fractionation data. (XLS)", "Malaria parasites were detected and counted by microscopy following Giemsa staining of thick and thin blood films [15] . Malaria Parasite (MP) densities were calculated as follows MP/ Table 1) . The microscopic criterion for declaring a participant to be free of malaria was the absence of parasites in 100 high-power (1000X) fields. One in 10 thick blood films were randomly selected and independently reviewed by local experienced microscopists not part of the research team." ] },{ "paper_id": "369914e87f682579eb3a5efeb43dc0184a88b5d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses, unpaired, two-tailed student t-tests and Extra sum-of-squares F test, were performed using Graphpad Prism software (version 7, La Jolla, CA, USA).", "Extracellular supernatants were collected at the indicated time points and stored at \u221280 \u2022 C. Viral titers were determined by plaque assay using Vero cells as previously described [43] .", "Rift Valley fever virus (RVFV), an emerging pathogen and public health threat, was identified as the causative agent of an outbreak of viral hemorrhagic fever in Kenya in 1930 [1, 2] . RVFV was initially only found in Sub-Saharan Africa, but since its discovery, it has spanned the African mainland, crossed over to Madagascar, and moved into the Arabian Peninsula [3] [4] [5] [6] [7] [8] [9] [10] [11] . The footprint of RVFV mosquito vectors has expanded, and this, in combination with the ubiquity of competent mammalian hosts [4, [12] [13] [14] [15] [16] , makes the likelihood of this virus spreading globally a distinct possibility [17, 18] . The alarming escape of other arthropod-borne viruses (West Nile virus, chikungunya virus, Zika virus) from their ecological niches, into and throughout the Americas [19] [20] [21] [22] [23] [24] gives us a potential harbinger of future events. Based on these concerning trends, governments and public health authorities across the globe have identified a need for FDA approved vaccines and treatments for RVFV [1, 25] ." ] },{ "paper_id": "36ac477a0485cd6f631502a5fe2e471db2210799", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The " ] },{ "paper_id": "36b168d717a2816e60feb1b2b833cd0f02163cef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analyses were performed with GraphPad Prism 6.0 software (GraphPad, La Jolla, CA, USA). Results are expressed as the mean AE SEM. Statistical differences were analysed using analysis of variance with Bonferroni adjustment. P values less than 0.05 were considered significant.", "At the end of study, fore paws, hind paws and knees were harvested, fixed in 10% neutral buffered formalin for 1-2 days, and then decalcified in 5% formic acid for 4-5 days before standard processing for paraffin embedding. Sections (8 lm) were cut and stained with toluidine blue (T blue). Hind paws, fore paws and knees were embedded and sectioned in the frontal plane. Six joints from each animal were processed for histopathological evaluation. The joints were then assessed using 0-5 scale for inflammation, pannus formation, cartilage damage, bone resorption and periosteal new bone formation as previously reported [19] . A summed histopathology score (sum of five parameters, 0-25 scale) was also determined. ", "Accession numbers (UniProtKB/Swiss-Prot knowledgebase, http://www. uniprot.org/) for the protein sequences discussed in this Research Article is as the follows: human TREM-1, Q9NP99; human apo A-I, P02647." ] },{ "paper_id": "36b5106f87b0cf684bca0e39767d48caedc47d43", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However lectin pathway activation does not only depend on MBL function. Some authors have observed how deficient mice models, without the capability to activate MBLindependent lectin cascade (i.e., ficolins and other collectins), are more susceptible to develop severe systemic pneumococcal infections [53] .", "Another recent Korean study in ICU patients investigated whether MBL2 gene polymorphisms and serum levels might influence severity and prognosis of sepsis [64] .", "These polymorphisms determine the production of unstable proteins, with shorter half-life, mainly due to the absence of the high-ordered oligomeric structure. These variants are not able to efficiently activate the complement pathway [15] .", "Regarding fungal diseases, the protective role of this lectin was also observed in murine models of invasive pulmonary aspergillosis after ex vivo MBL administration [52] ." ] },{ "paper_id": "36bb7f8a45356e1a6d2da97b78155d0d45646cc0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest." ] },{ "paper_id": "36c09af15d4a614f954aae5a5f8a4199f1ff8b2f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Monitoring the effectiveness of the measles control policy is done by surveillance. In China, measles is a category B infectious disease which indicates it is highly contagious and must be reported to the surveillance system within 24 hours after confirming the laboratory samples [8] . Since 2004, China has a direct network reporting system and automatic warning information system for infectious diseases. The system focusses on the number of reported cases, but does not evaluate the transmissibility of measles.", "Despite several immunization efforts, China saw a resurgence of measles in 2012. Monitoring of transmissions of individuals from different age groups could offer information that would be valuable for planning adequate disease control strategies. We compared the agespecific effective reproductive numbers (R) of measles during" ] },{ "paper_id": "36c123eb9cf765e87991924a21da9bdf32e7dc85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sputum and conjunctival culture grew heavy growth of beta-lactamase-producing nontypeable Haemophilus influenzae (NTHi) that was susceptible to levofloxacin and amoxicillin-clavulanate. A FilmArray\u00ae Respiratory Panel 2 (RP2) polymerase chain reaction (PCR) system test did not detect 14 viruses (adenovirus, coronavirus HKU1, coronavirus NL63, coronavirus 229E, coronavirus OC43, human rhinovirus/enterovirus, human metapneumovirus, influenza A, influenza B, parainfluenza virus 1, parainfluenza virus 2, parainfluenza virus 3, parainfluenza virus 4, respiratory syncytial virus) and four bacteria (Bordetella pertussis, Bordetella parapertussis, Chlamydophila pneumoniae, Mycoplasma pneumoniae).", "He experienced repeated episodes of sustained elevated blood pressure (up to 210/110) and tachycardia (112/minute). This was managed by administration of clonidine 0.1 mg as needed (1-2/day).", "His fever started to decline 48 hours after antimicrobial therapy was started. The conjunctivitis improved within 36 hours. The sputum production declined and became less viscous over time, but persisted for 5 days." ] },{ "paper_id": "36c1c6bc314487fe898f76a7093175d90347ac20", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DNA was extracted using the Masterpure DNA Purification kit (Epicentre, Madison, FL) in accordance with the manufacturer's instructions, and a 50 \u03bcL final elution volume after purification. The extracted DNA was quantified using Picogreen reagent (Life Technologies, Monza, Italy) and an Infinite M200 PRO fluorimeter (Tecan Italia, Cernusco Sul Naviglio, Italy). Following the nucleic acid purification procedures, the samples were stored at \u221220\u00b0C until use." ] },{ "paper_id": "36c57bd8ded4b2dc1a5859c15dea5c3800e23413", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "While the mouse antisera neutralized the homologous virus with 20-160 serum neutralizing titer, they did not neutralize the heterologous virus (Table 2 ).", "Bats are considered a reservoir of severe emerging infectious diseases. Severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), Nipah virus, Hendra virus, and Ebola virus are all thought to be bat-borne viruses 1, 2 .", "forward primer: PVM-F5\u2032-CCCAGGAGTATGGTTATCAAGTGAGG-3\u2032; reverse primer: PVM-R 5\u2032-TCCA TTGGGCTCTCTTTGTTTGC-3\u2032; Taqman probe: PVM-P 5\u2032-FAM-CCCATCCCAGACCAGCCACCA GACCC-TAMRA-3\u2032" ] },{ "paper_id": "36c6a493ce71b4e2df91b9b486cc847833a4ed25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples originated from 12 Brazilian states from the north-east, east, and south-east regions. Table 9 . ", "RT-PCR and PCR products were analyzed by electrophoretic diffusion in 1.5% Ultrapure TM Agarose (Invitrogen) gels submerged in 0.5X Tris-borate-Ethylenediamine Tetraacetic acid (EDTA). The size of DNA fragments was estimated by comparison with the 100 bp DNA Ladder (Invitrogen). A UV trans-illumination camera was used to visualize the DNA bands.", "1 + - - - - - - 22 8.1% 2 + - - + - - - 1 0.4% 3 + - - - + - - 2 0.7% 4 + + - - + - - 2 0.7% 5 + - - + + - - 1 0.4% 6 - - - + - - - 19 7% 7 - - - + + - - 3 1.1% 8 - - + + - - - 1 0.4% 9 - - - + - - + 1 0.4% 10 - + - + + - - 7 2.6% 11 - - - + + - + 3 1.1% 12 - + - + - - + 1 0.4% 13 - - + + + - + 2 0.7% 14 - + + + - - + 1 0.4% 15 - + - + + - + 1 0.4% 16 - + + + + - + 1 0.4% 17 - - + - - - - 15 5.6% 18 - - + - + - - 6 2.2% 19 - - + - + - + 1 0.4% 20 - - - - + - - 164 60.7% 21 - + - - + - - 1 0.4% 22 - - - - + - + 2 0.7% 23 - + - - - - - 8 3% 24 - - - - - - + 4 1.5% 25 - - - - - + - 1 0.4%" ] },{ "paper_id": "36c9f0d81abca39d9decec0de264ad9b5e8be161", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Methods: Clinical sequencing was performed on a cohort of patients presenting with variable immune phenotypes lacking molecular diagnoses. Hypothesis-free whole-exome sequencing (WES) was selected in the absence of compelling diagnostic hints in patients with variable immunological and haematological conditions.", "In four patients belonging to three families, we have detected five novel variants in known TBD-causing genes (DKC1, TERT and RTEL1). In addition to the molecular findings, they all presented shortened blood cell telomeres. These findings are consistent with the displayed TBD phenotypes, addressing towards the molecular diagnosis and subsequent clinical follow-up of the patients. Conclusions: Our results strongly support the utility of WES-based approaches for routine genetic diagnostics of TBD patients with heterogeneous or atypical clinical presentation who otherwise might remain undiagnosed.", "Background: The telomere biology disorders (TBDs) include a range of multisystem diseases characterized by mucocutaneous symptoms and bone marrow failure. In dyskeratosis congenita (DKC), the clinical features of TBDs stem from the depletion of crucial stem cell populations in highly proliferative tissues, resulting from abnormal telomerase function. Due to the wide spectrum of clinical presentations and lack of a conclusive laboratory test it may be challenging to reach a clinical diagnosis, especially if patients lack the pathognomonic clinical features of TBDs.", "Additional file 1: Figure S1 . Categorization of the clinical phenotypes of the patients in the studied dataset (n = 212 patients). Categories defined according to the 2017 Primary Immunodeficiency Disease Committee Report [25] . " ] },{ "paper_id": "36ce44a073e35fa159c1aa4fa86286643a6e9993", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "How old are the major human pathogens?", "Where are the resistance-conferring genes in the human genome?", "We know relatively little about the underlying genetic changes required for a pathogen to infect a new host, though, interestingly, only a few mutations can be required for a host jump. For example, avian influenza is only around five mutations away from being able to transmit in mammals [5] , and a single amino acid change was sufficient for the humanadapted bacterium Staphylococcus aureus to become a pathogen of rabbits [6] ." ] },{ "paper_id": "36dce9f7118e056798289b0019752f51e83568d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 22 control samples were tested for TBE-C by EIA, and any samples with above-baseline OD ratios reflexed to confirmatory IFA.", "(ii) IFA method. An in-house strain of Powassan virus lineage II, sequence-confirmed deer tick virus (DTV) isolated from an I. scapularis tick pool, along with viral reference strains Powassan LB and DTV CT390 (World Reference Center for Emerging Viruses and Arboviruses, Galveston, TX), was cultured in Vero cells and used to prepare IFA substrate slides. Three different culture techniques were tested to determine the best slide manufacturing conditions. Vero cells infected with POWV were grown on eight-well chamber slides using optimized culture conditions. Slides were fixed in 2% neutral buffered formalin (NBF) followed by 100% cold methanol and stored at \u03ea20\u00b0C until use. Prior to testing, substrate slides were warmed for 30 min in a humidity chamber at room temperature and blocked with 2% normal goat serum (Vector Laboratories, Burlingame, CA) for an additional 30 min. Patient serum and/or plasma samples, positive and negative controls, were diluted 1:40 in 2% normal goat serum for IgG analysis and 1:20 in Eurosorb (Euroimmun US) anti-human IgG antibody buffer for IgM analysis, added to slide wells, and incubated for 60 min at 37\u00b0C. After 1 h of incubation, the slides were washed 3 times with phosphate-buffered saline (PBS), and 50 l of DyLight 488 anti-human IgG (Vector Laboratories) diluted 1:300 or 50 l of fluorescein anti-human IgM (mu-specific) secondary antibody (Vector Laboratories) diluted 1:200 was added to each well. The slides were incubated for 30 min and washed three times in PBS. The slides were counterstained with Evans blue, rinsed with distilled water, mounted using Vectashield mounting medium (Vector Laboratories), and examined using an epifluorescence microscope. Positive-and negative-control samples were included in all IFA runs.", "(iv) WNV method. Samples were tested for the presence of IgG and IgM antibodies to WNV by qualitative EIA (Euroimmun US), and results were analyzed per the manufacturer's recommended protocol." ] },{ "paper_id": "36de1c611ceee1af5ceddea2e4041691829cf7ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Funding: This research received no external funding.", "Author Contributions: Study concept, P.R.; Acquisition of data, analysis and interpretation of data, writing of the manuscript, E.B. and P.R.", "All these data were obtained with cells cultured in vitro. The rare investigations performed on liver biopsy specimens from HCV-infected patients have not addressed the question of the membranous web, essentially describing an enlargement of the ER compartment [8] and aberrant mitochondria [9] , a feature of the major stress induced by HCV in host cells. To address this question, we therefore used electron microscopy to re-examine a series of liver biopsy specimens from patients chronically infected with HCV." ] },{ "paper_id": "36def2d37441d9ab0833ba1a1a48c68184bae246", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Based on obtained next-generation sequencing data, specific primers of the novel rhabdovirus, theilovirus, and amdovirus were designed to confirm and partially extend the obtained sequence data. Products were sequenced as described previously and primer sequences are available upon request [49] .", "Bunyaviruses are segmented, negative-sense single stranded RNA viruses. Genomes consist of three different segments, the Large (L), Medium (M) and Small (S) segment. At present the ICTV has recognized five different genera, Orthobunyavirus, Hantavirus, Nairovirus, Phlebovirus, and Tospovirus [22] . The genus Phlebovirus consists of a genetically diverse group of viruses, some of which were described very recently [32] [33] [34] . A few members of this genus were identified as important pathogens in humans and domestic animals, including Rift valley fever virus and the Severe fever with thrombocytopenia syndrome virus or Huaiyangshan virus [35, 36] ." ] },{ "paper_id": "36e757c81ded2a278e917ab9030d1f682e4c4b9f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study covers the patients attending just one facility at Arafat, hence does not give a comprehensive picture of the situation as there are many other hospitals an out patient clinics in the area. As such the results cannot be generalized.", "Cases related to cardiac problems were expected. A gradual increase in admissions due to cardiovascular diseases has been noted in the last few years among the Hajj pilgrims. 21 We encountered cases of Ischemic Heart Disease (IHD) and arrhythmias besides numerous patients having hypertension.", "Patients presenting with kidney related problems were 21 in number which included chronic renal failure, renal colic and urinary tract infection. There was no case of snake bite but one patient reported with scorpion bite. Four out of 75 female patients were pregnant though only one presented with threatened abortion." ] },{ "paper_id": "36eedeee8fd40eda2f7f1d0c0cb0e2a4971439a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3702eb1540a20656d1f723b180c1a8607c6cb4a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "TEXT S1, PDF file, 0.1 MB. ", "Screening of yeast two-hybrid libraries. Commercially available Mate & Plate cDNA libraries of human liver and fetal brain were screened against the viral proteins expressed in the Y2H gold strain, following the instructions of the manufacturer (Clontech, Mountain View, CA, USA). Details are provided in Text S1.", "Supplemental material for this article may be found at https://doi.org/10.1128/ mSystems.00135-17.", "Hepatitis E virus (HEV) is a positive-strand RNA virus that infects humans and many other animals, usually causing an acute self-limiting hepatitis (10) . In organ-transplant patients or immunocompromised individuals, it causes chronic infection (11) . In HEVinfected pregnant women, the mortality rate is up to~30% (12) . All HEV genotypes contain three open reading frames (ORFs), namely, ORF1, ORF2, and ORF3. Recently, we identified an additional ORF, ORF4, in genotype 1 HEV (g-1 HEV), which is located in the \u03e91 reading frame position (with respect to ORF1) within ORF1 and produces a 158-amino-acid (aa)-long protein by an internal translation mechanism. ORF1 encodes a polyprotein containing distinct domains such as methyltransferase (Met), Y domain (Y), papain-like cysteine protease (PCP), V domain (V), X domain (X), helicase (Hel), and RNA-dependent RNA polymerase (RdRp). The ORF2 gene codes for the ORF2 protein, which is the major capsid protein of the virus, and the ORF3 gene codes for the ORF3 protein, which plays an important role in virus egress and is also believed to be involved in multiple signal transduction processes (13) ." ] },{ "paper_id": "37142e322bc30493a97e2aff05533919897e39ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Exercises presented participants with a future scenario that involved an unfolding pandemic influenza crisis at different stages. They were required to respond to the scenario with the actions they would take if the scenario were actually occurring. Exercise facilitators were given discussion points and probes to keep the discussion focused and moving forward. Each section of the exercise ended with participants being asked to make concrete decisions for the topic area being discussed before moving on. The exercise concluded with a debriefing in which all participants evaluated their own response in light of what they learned during the exercise.", "Since 2001, there has been a dramatic increase in the use of disaster preparedness exercises among public health agencies in the United States [1, 2] . These exercises have explored a wide range of topics from foodborne toxoplasmosis outbreaks [3] , chemical disasters [4] , acute blood shortages [5] , bioterrorism [6] , and severe acute respiratory syndrome (SARS) [7] . Exercises have been designed to assess and improve a variety of capabilities such as regional disaster preparedness among rural hospitals [8] , knowledge and confidence of legal authorities [9] , resource allocation [10] and risk communications [11] . A large number of these exercises have been focused on the spread of infectious diseases especially the threat of pandemic influenza because the common challenges pandemic influenza shares with other types of public health emergencies [12] [13] [14] [15] [16] .", "We developed pandemic influenza tabletop exercises that built on the \"Day After\" methodology developed by Millot, Molander and Wilson [25] and described elsewhere in greater detail [1] . Countries in three different geographic regions participated: Southeast Asia (Cambodia, China, Lao PDR, Myanmar, Thailand and Vietnam), the Middle East (Israel, Jordan and Palestine) and East Africa (Burundi, Kenya, Rwanda, Tanzania and Uganda). Countries that participated in the exercises were included because they were all part of sub-regional disease surveillance networks established in part through funding from the Rockefeller Foundation. Some countries not included in these networks were invited to observe the exercises. Countries ranged in their past experience with preparedness exercises with some countries having extensive past exercise experience (such as Israel, Vietnam, China and Thailand) and other countries having minimal past exercise experience (such as Cambodia, Lao PDR, Myanmar and Uganda). Exercises were developed and conducted by exercise planning teams that included external exercise development experts from the RAND Corporation as well as senior health leaders from each of the respective localities and/or countries represented in the exercise. There were three different levels of exercises: sub-national (e.g., one or more provincial areas), national (e.g., one country) and sub-regional (e.g., multiple countries from one geographic region)." ] },{ "paper_id": "371c9fd77329f6bd62e32c702dfbed1bb5ae2401", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Monoclonal antibody production. For expression of m336 IgG1, the previously described m336 IgG1 vector 23 was used to infect CHO-K1 cells (ATCC, Manassas, VA) with PolyFect transfection reagent (Qiagen, Valencia, CA). After screening of 960 clones for antibody productivity by ELISA and subsequent characterization, a stable cell line was generated and inoculated into a Bioflo 410 bioreactor (New Brunswick Scientific, NJ) for large-scale production of m336 IgG1. Purification was carried out by using a protein G column (GE Healthcare), and endotoxin was removed by Detoxi-Gel Endotoxin Removing Columns (Thermo Scientific) according to the manufacturer's instructions.", "Scientific RepoRts | 6:31629 | DOI: 10.1038/srep31629 treatment with either dose of m336 were graded 1 (Fig. 4, right panel) , compared to the grade 2 assigned to mice received control antibody treatment prior to infection (Fig. 4, left panel) .", "Scientific RepoRts | 6:31629 | DOI: 10.1038/srep31629 and long-term threat to people, particularly those who interact closely with camels in the Arabian Peninsula. Even though MERS-CoV presently has limited human-to-human transmission 2, 16 , the high mortality rate of this virus and limited information on the mechanism able to confer increased human-to-human transmission have raised concerns of a potential MERS pandemic. Indeed, the recent outbreaks in Korea and the appearance of super-spreading events indicate that MERS-CoV has the ability to cause large outbreaks outside of the Arabian Peninsula [17] [18] [19] . Currently, no approved vaccines or drugs are available to treat this viral infection. These facts highlight an urgent need to develop potent prophylactic and therapeutic agents to fight this lethal virus.", "Taken together, these results suggest to us that the MERS-CoV RBD protein-specific m336 mAb is an excellent candidate for passive immunotherapy to provide immediate and effective protection to individuals who may be exposed to MERS-CoV and to treat patients who have been exposed. Testing in humans is needed for its potential use as a therapeutic for the treatment of MERS-CoV-infected patients." ] },{ "paper_id": "37215fa618869df1820d22f28bace99ea9ceb1fc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "F81 (feline kidney cells) [28] and 293T cells were both purchased from ATCC and cultured in Dulbecco's modified Eagle's medium (DMEM; Gibco, Thermo Fisher Scientific, Waltham, MA, USA) supplemented with 10% foetal bovine serum (FBS; Excel, Australia) in a 37 \u2022 C incubator with 5% CO2. HR-1, an FHV-1 strain saved in our laboratory, was separated from a domestic cat in Harbin [13] . The titres of virus stock were measured by TCID50 assay. Multiplicity of infection (MOI) represents the number of viruses per cell (plaque-forming unit (PFU)/cell).", "Supplementary Materials: The following are available online at http://www.mdpi.com/1999-4915/12/1/2/s1. Table S1 : Sequences of miRNA mimics, inhibitors and siRNAs, Table S2: Table S2 . Sequences of primers used in the research; Table S3: Table S3 . Some differentially expressed miRNAs obtained from the high-throughput sequencing. ", "F81 cells were lysed on ice for 30 min using RIPA lysis buffer (moderate) (Beyotime, Shanghai China) supplemented with PMSF (Beyotime, China) and cocktail protease inhibitor II (MedChemExpress, MCE, Monmouth Junction, NJ, USA) before boiling with 5\u00d7SDS loading buffer for 10 min. Then, the proteins were separated by 10% SDS-PAGE gel and transferred onto BioTrace\u2122 NT Nitrocellulose (NC) Transfer Membrane (Pall Life Sciences, New York, NY, USA). Next, the membrane was blocked using 5% skimmed milk for 1 h and incubated with primary antibodies as follows for 1 h at room temperature or overnight at 4 \u2022 C: rabbit anti-cGAS (ab176177), rabbit anti-p-STAT1 (phospho Y701) (Abcam, Cambridge, UK, ab109457, 1:1000), rabbit anti-STAT1 (Abcam, ab92506, 1:1000), rabbit anti-SOCS5 (Abcam, ab97283, 1:500), rabbit anti-GAPDH (Sigma-Aldrich, St. Louis, MI, USA, G9545, 1:3000), mouse anti-Flag (Sigma-Aldrich, F1804, 1:3000) and mouse anti-FHV-1 UL42 (1:200). After washing with TBST buffer, the membrane was incubated with IRDye \u00ae 800CW goat anti-rabbit or anti-mouse secondary antibodies (LI-COR, Lincoln, NE, USA) for 1 h at room temperature. After washing again with TBST buffer, the proteins were detected using Odyssey CLx Image Studio 3.1 (LI-COR, USA). The anti-FHV-1 UL42 antibody was generated by immunizing six-week-old BALB/c mice with prokaryotically-expressed FHV-1 UL42 protein for three times at two weeks intervals. The serum of mice was served as polyclonal antibodies against FHV-1 UL42." ] },{ "paper_id": "3725a278a669559c9fd096a9a7dd5f35c6928c6c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human HeLa cells containing 10-50 proviral copies/cell of HPV-18 [29, 30] were grown in E-MEM (Sigma-Aldrich) containing 10% inactivated fetal bovine serum (FBS), 120 IU penicillin/ml, 120 \u03bcg streptomycin/ml, and 2mM L-Glutamin. Human 8E5 cells containing a single copy/cell of proviral HIV-1 [31, 32] were grown in RPMI-1640 with Glutamax-I (Invitrogen) containing 120 IU/ml penicillin, 120 \u03bcg/ml streptomycin, 24 \u03bcg/ml gentamycin, 6 IU/ml nystatin, and 10% inactivated FBS. ", "High-throughput sequencing (HTS) requires no prior knowledge of the target sequences. In theory, unbiased HTS investigation should increase the probability of identifying novel viruses in various diseases, such as cancers and in infections, when conventional tests fail.", "Adapter sequences were removed and overlapping read pairs merged using AdapterRemoval [34] . Reads were mapped onto the human genome (hg19) and a reference collection of viral genomes (AC_000008.1, GU109481.1, NC_001802.1, X05015.1, the 208_p_MV_tag genome and enterovirus aRNA sequence) using bwa [35] . Quality trimming was invoked both during removal of adapters (-trimqualities and default-minquality (2) in AdapterRemoval) and mapping (-q 20 in bwa). Read pairs or merged reads with identical start and end mapping positions were considered to be of clonal origin, and only one representative for each mapping coordinate set was kept for analysis of unique reads." ] },{ "paper_id": "3727230a23a43b18086004127d3d288db1ba3bf5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This medicinal has been tested for cancerological and dermatological activities. Its application to disease conditions proved to exhibit an activity that slowed down cancer tumor growth and to cure serious cases of dermatosis. It was also found to have an effect on postoperative analgesia [9] [10] [11] [12] .", "Potassium inwardly-rectifying channel J3 1", "Classification Frequency", "The 33 compounds were aligned over, under the superimposition of the common moiety and Template Compound 6. The statistical parameters for database alignment-q 2 , r 2 , F, and SEE-were The whole framework of the comprehensive in silico method for screening potential targets and studying the quantitative structure-toxicity relationship (QSTR)." ] },{ "paper_id": "3727f751c9cf944c8e6ddf578f5644629ed50d45", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tilapia lake virus (TiLV) causes high mortality rates in wild and farmed tilapia. The disease caused by TiLV was first reported in Israel in 2009, while the virus was first characterized in 2014 [1] . Since then, TiLV infections have been reported from different countries around the world [2] [3] [4] [5] . It is an icosahedral virus made of a trilaminar capsid with a diameter of 55-110 nm, which is morphologically similar to orthomyxoviruses [1] . Its genome is made of -ssRNA consisting of 10 segments, of which segment 1 has a weak homology with the influenza virus C PB1 subunit (~17% amino acid identity, 37% segment coverage). In addition, it has four motifs (I-IV) conserved in RNA-dependent RNA and RNA-dependent DNA polymerases that are homologous with influenza A, B, and C viruses [6] .", "Different orthomyxoviruses bind to different Sia receptors on host cells. In human influenza A and B viruses, the HA1 subunit binds to Sia receptors attached to either \u03b12-3 or \u03b12-6 linkages [19, 21] , avian and equine influenza viruses bind Sia containing the \u03b12-3 linkage [17] , and swine influenza ", "The observed ISAV properties are in line with observations made by Falk et al. [25] , showing that ISAV only agglutinated piscine RBCs and not avian RBCs. Similarly, it was shown by the same authors that influenza virus A agglutinated both avian and piscine RBCs, which corroborated our findings." ] },{ "paper_id": "372caa549b07492de5fd7064e9cadc62bef0f478", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Some PRRs, such as NACHT, LRR, and PYD domains-containing protein 1 (NLRP1), NLRP3, NLR family CARD domain-containing protein 4 (NLRC4), and absent in melanoma 2 (AIM2), recruit apoptosis-associated speck-like protein (ASC) and caspase-1 to form the inflammasome-a multimeric platform of proteins that initiates inflammation as well as some forms of cell death (3) . Among all the inflammasomes discovered, the NLRP3 inflammasome is the most extensively studied and it plays an important role in both inflammation and antiviral responses.", "Viroporins are small, highly hydrophobic proteins derived from viruses, which interact with membranes to modify the host cell's permeability to ions or other small molecules (48) . Several viroporins are observed to localize to the Golgi apparatus and other cytoplasmic structures during viral infection (49) (50) (51) . Examples include 2B proteins from EMCV, poliovirus, enterovirus 71 (EV71), and human rhinoviruses (HRV), the envelope (E) protein of severe acute respiratory syndrome coronavirus (SARS-CoV), as well as influenza virus M2 protein.", "Accumulation of misfolded protein aggregates is an important activation signal of the NLRP3 inflammasome. A wellknown example is that of Alzheimer's disease (AD), which is characterized by the accumulation of amyloid-\u03b2 peptide (60) . The ORF 8b of SARS-CoV forms intracellular aggregates through the valine residue at position 77 (61) . This complex acts as the danger signal to induce endoplasmic reticulum stress and lysosomal damage, resulting in NLRP3 inflammasome activation." ] },{ "paper_id": "372f3a4aac120be6b70f0b3d51481ab2679a6b92", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Canine infectious respiratory disease (CIRD) is a multifactorial disease affecting dogs of all ages, which is typically induced by simultaneous viral and bacterial infections [1] . Apart from wellknown canine respiratory pathogens, such as canine adenovirus type 2, canine herpesvirus [2] , canine distemper virus [3] , and canine parainfluenza virus [4] , novel viruses are being continuously associated with CIRD occurrence in dogs. These include canine influenza virus [5] , canine respiratory coronavirus [6] , canine pantropic coronavirus [7] [8] , canine bocaviruses [9] , and canine hepacivirus [10] .", "CnPnV positive samples were inoculated into semiconfluent canine fibroma (A-72) cells, as previously described [14] .", "Respiratory specimens were submitted to molecular detection of other respiratory pathogens of dogs, such as canine parainfluenza virus (CPiV) [18] , reoviruses [19] , CAdVs [20] , CDV [21] , canine respiratory coronavirus (CRCoV) [22] , canine pantropic coronavirus [23] [24] , canine minute virus [25] , canid herpesvirus type 1 [26] , canine influenza virus [27] , canine hepacivirus [28] , canine bocaviruses [9] , Bordetelella bronchiseptica [29] , Streptococcus equi subsp. zooepidemicus [30] , Mycoplasma cynos and Mycoplasma canis [31] .", "Inoculated cells were maintained in D-MEM supplemented with 5% FCS and monitored daily for the occurrence of cytopathic effect (CPE). After 6 days of incubation, the monolayers were tested for CnPnV antigen by an immunofluorescence (IF) assay using a monoclonal antibody targeting HRSV (MonosanH, Sanbio BV, Uden, The Netherlands). The cells were sub-cultured every 6-8 days for 5 consecutive passages." ] },{ "paper_id": "3735055ce30bb1cb8aa6ef4fb1731dcc8219df35", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Research Ethics Board of the University of Guelph approved the study. Data for this study were obtained from Swine Health Ontario under an appropriate data sharing agreement based on secondary data usage.", "The assumption of the Cox's proportional hazard model was evaluated graphically showing the logarithm of the estimated cumulative hazard function. Goodness-of-fit was evaluated using a Hosmer-Lemeshow test and a Harrell's C concordance statistic. Deviance and score residuals were evaluated.", "Ninety-four cases (65.2%, 90/138) reported that they were confirmed PED-positive. Of these 90 cases, 92.2% (n = 83) reported that they eliminated PEDV and therefore gained a presumed-negative status. Forty-eight cases (34.8%, 48/138) reported that they were initially presumed PED-positive, at their initial date of infection. Of these 48 cases, 97.8% (n = 47) reported that they eliminated PEDV during the study period and achieved a presumed-negative status." ] },{ "paper_id": "373811bcfe3a46dc6d49b2a1725f1dde8a59e8a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "t\u00bc0 \u00c0l j;t ! \u00f01 \u00c0 exp\u00f0\u00c0l j;t j \u00de\u00de:", "We used a Bayesian framework for statistical inference.", "ln P t j \u00c0 \u00c1 :" ] },{ "paper_id": "37485356ce87c19f6d32121ed6b64b28c3041c24", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "374861bab555d907099146fb05867d810fca1ad1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study protocol, informed consent statement, clinical research form, any amendments and all other study documents have been submitted to and approved by the institutional ethics committee of each site: Brazil ( " ] },{ "paper_id": "375b438ae6250e39e16ed60349f924b2693f1d25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "376004b900cd163891128558e6c275dab9ecf34d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 3D structures were rendered using PyMOL (The PyMOL Molecular Graphics System, Version 1.8.4.0 Schr\u00f6dinger, LLC).", "The Supplementary Material for this article can be found online at:" ] },{ "paper_id": "376ac2d5c7446918fdc12ef89696687b8a2b23d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data represent the mean \u00b1 SEM and were plotted using Graphpad prism 5.0 software (Graphpad Software Inc., La Jolla, CA, USA). Statistical analysis was performed using a Mann-Whitney test, Dunn's multiple comparison test, and ANOVA with Bonferroni post-test. p-Values <0.05 were considered statistically significant.", "After PBS perfusion, spinal cords were fixed in 10% zinc formalin, divided into six sections (two per cervical, thoracic, and lumbar regions) prior embedding in paraffin. Then, 6 \u03bcm cross sections were stained with Luxol fast blue (LFB) to visualize demyelinated lesions. To determine the percentage of demyelination, LFB-stained sections of all six levels per individual mouse were scanned with an Aperio ScanScope (Vista, CA, USA) at 40\u00d7 and areas of demyelination within the white matter tracks were quantify using Aperio software.", "Altogether, our study demonstrates the importance of distinct Treg populations in controlling SR T cells both at the induction and effector site during chronic encephalomyelitis. These are the" ] },{ "paper_id": "376c6616538eb3ae465dbf8ebe62c99193ba5e42", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition to tick-borne transmission, non-vector-borne transmission of SFTSV has also been reported. A number of case clusters linked to nosocomial or intra-familial transmission have been described. While the majority of the secondary cases in these clusters were likely infected through unprotected direct contact with the index patients' blood and/or bodily fluids with high viral loads, possible transmission of the virus through exposure to contaminated hospital environment surfaces and aerosols have also been reported recently [3] [4] [5] [6] .", "The 3D structure of hexachlorophene (ID code: DB00756) was downloaded from the Drugbank database (https://www.drugbank.ca/). The crystal structure of SFTSV Gc protein (PDB code: 5G47) was used to build up the docking receptor [20] . Bond orders were assigned, hydrogens were added, and cap termini were included with the Protein Preparation Wizard module as implemented in Maestro [21] . Protonation states of side chains were predicted by using PROPKA3.1 server [22] . Partial charges over all atoms were finally assigned within the AMBER99 force field scheme as implemented in AmberTools. Ligand binding sites were predicted with Metapocket2.0 server [23] . Ligand-receptor docking was performed with LeadFinder version 1804 [24] . The top-ranked pose was visualized with Pymol. Intermolecular interactions were visualized with Ligplot+ [25] .", "Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus in the genus Banyangvirus, family Phenuiviridae, order Bunyavirales. It was first identified in Huaiyangshan, a mountainous area in Huaiyang County in the Henan province of China [1] . Subsequently, the virus has also been isolated from infected humans, ticks, and mammals in Japan and South Korea. SFTSV is so named as it causes severe fever with thrombocytopenia syndrome (SFTS), an acute febrile illness characterized by high fever, thrombocytopenia, and hemorrhagic complications in infected humans. Patients with SFTS may also develop other clinical manifestations such as systemic upset, coma, slurred speech, gastrointestinal upset, hepatosplenomegaly, and lymphadenopathy, as well as abnormal laboratory findings including leukopenia, prolonged activated partial thromboplastin time, deranged liver function tests, proteinuria, hematuria, and elevated creatinine kinase and lactate dehydrogenate levels. The mortality rate of SFTS may be as high as 17% to 30% [1, 2] .", "The CellTiterGlo luminescent assay (Promega Corporation, Madison, WI, USA) was performed to detect the cytotoxicity of the selected drug compounds as previously described [12] . Briefly, Vero cells (4 \u00d7 10 4 cells/well) were incubated with different concentrations of the individual compound for 72 h, followed by the addition of substrate and measurement of luminance 10 min later. The 50% cytotoxic concentrations (CC 50 ) of the drug were calculated by Sigma plot (SPSS) in an Excel add-in ED50V10." ] },{ "paper_id": "3775869c0c45f1f0c92eec1d68f9b10827d299f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quality assessment of included randomized controlled trials: sequence generation, allocation concealment, blinding of participants personnel and outcome assessors, incomplete outcome data, selective outcome reporting, and other sources of bias.", "Twenty-four out of twenty-six trials mentioned the adverse effect except two trials [22, 24] . Twentyfour trials reported the twenty-seven specific symptoms including diarrhea, dizziness and headache, somnolence, dry mouth, Bloating, constipation, tachycardia, blurred vision, insomnia, prolonged QT, naupathia, fatigue, anxiety, tremor, anorexia, palpitation, asthenia, oscitancy, sweat, akathisia, tetter, excitation, hypertension, bellyache, dysuria, transaminase increased, and sexual dysfunction (Figure 3) .", "Depression is a common mental disorder that presents with depressed mood, loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep or appetite, insomnia or hypersomnia, fatigue or loss of energy, and poor concentration or difficulty making decisions. These problems can become chronic or recurrent and lead to substantial impairments in an individual's ability to take care of his or her everyday responsibilities." ] },{ "paper_id": "377bace754b08919a4139b9f1070f8ab422f90bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "377c6ff0f04a67152f6029e2836500abddac3d57", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistics were performed using software from Scientific Python, namely SciPy and pandas through the Jupyter Notebook interface (Oliphant, 2007 " ] },{ "paper_id": "377d9d0d1f580860076b5799e30babd834eda260", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "According to World Health Organization (WHO) statistics, influenza occurs globally with an estimated annual attack rate of 5%-10% in adults and 20%-30% in children [1] . These annual epidemics are estimated to result in approximately 3 to 5 million cases of severe illness worldwide and around 250 000 to 500 000 deaths, which is a major cause of losses in human lives and a grave global public health issue.", "Based on our results, we make the following observations:", "Supporting Information S1 Table. (XLSX) S1 Text. (DOCX)" ] },{ "paper_id": "378082edc2f3e85e6cc8941c81030a70c65c7f8f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Generation of recombinant MHV vectors is based on reverse genetic systems established for MHV-A59 [51] . Molecular cloning and production of recombinant coronavirus particles was performed as previously described [18] .", "Experiments were performed in accordance with federal and cantonal guidelines under permission numbers SG09/92, SG11/06, and SG11/10 following review and approval by the Cantonal Veterinary Office (St. Gallen, Switzerland).", "Statistical analyses were performed with Graphpad Prism 5.0 using non-paired, two tailed Student's t test. Comparison between different groups was done using one way ANOVA with Tukey's post test or with Bonferroni multiple comparison test as indicated. Statistical significance was defined as p < 0.05." ] },{ "paper_id": "379317c0c8b61dd88b6faa235b21dd861436edcf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Position specificity Alpha CoV TGEV Independent [127] Dependent [127] No specific position [127] Beta CoV MHV Dependent [123, 124] Dependent [123, 124] Specific position (CRM1B) ** [123] Specific position (CRM2) [124] No specific position [125] ** SCoV Independent [122, 126] Dependent [122] Specific position (CRM2B) [122] * This table is a modification of a table in reference 120. ** The mutants show little or no infectivity, although S incorporation is not affected [123] or not studied [125] .", "Alpha CoV TGEV YxxI motif Main retention signal. Not I.S. [109] KxHxx motif Not main retention signal [109] Retention of reporter protein [38] PEDV YxxF motif Not studied", "We summarize here the many excellent reviews on protein trafficking through the secretory pathway, from the ER to the plasma membrane though the Golgi complex [53] [54] [55] [56] [57] [58] , and on the mechanism of intracellular retention [59, 60] . Figure 2 shows a schematic of this trafficking pathway." ] },{ "paper_id": "3799479a8ad2b8db9f21c68f88dfae6410d0fed0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For tools which use different models/matrices in their prediction for different organism group [16, 17, [24] [25] [26] [27] [28] [29] [30] , the appropriate matrix is selected accordingly. Signal-3L, in particular, allows for six selections: (i) human; (ii) plant; (iii) animal; (iv) gram-positive; (v) gram-negative; (vi) \"other-eukaryotic\". We use the authors' categorization method as shown in (Online Supporting Information B: http://www.csbio.sjtu.edu.cn/bioinf/Signal-3L/Data. htm to classify and select the corresponding matrix for a given input sequence." ] },{ "paper_id": "379dc32e1a173ffb789b66c9dccea4219ace8fde", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Association with dysregulation of inflammatory response (2107), alteration of NLRP3 mRNA stability and enhancer activity [33, 34] HLA Various alleles Influenza-specific CTL responses exhibit varying frequency and magnitude across various HLA alleles [35] times higher than that reported for local North American Caucasian populations [26, 27] . Given the small sample size available in this cohort, further studies will be required to conclusively determine the impact of CCR5 deficiency on pH1N1 susceptibility and severity.", "When a novel strain of influenza emerges, the preexisting antibody response directed largely at the surface glycoproteins is rendered ineffective. In these cases, the mechanisms underlying heterosubtypic cross-protection assume a dominant role and it is, therefore, not surprising that immune dysfunction caused by underlying genetic polymorphisms may lead to impaired responses and would therefore be associated with adverse outcomes. During the 2009 H1N1 pandemic, several immunogenetic determinants of severe disease were identified.", "Polymorphisms previously linked to IgG2 deficiency, but not corroborated in H1N1 patients [28] [29] [30] NLRP3", "Infection. The 1918 H1N1 as well as the recent 2009 pandemics were both notable for the comparatively high rates of morbidity among healthy, young adults not typically observed with seasonal influenza [11] . During the recent pandemic, several studies of confirmed pH1N1 cases in Canada and the US reported the median age of severe infections to be 23-27 years old [8, 10] . In Canada, 30%-48% of infections also presented in persons with comorbidities; diabetes, heart disease, and immunosuppression were associated with the highest risk of severe infection, while lung diseases and obesity were among the most common underlying conditions [10, [12] [13] [14] . The role of pregnancy as a risk factor, regardless of the stage, was also supported by a myriad of reports; among hospital admissions, pregnancy accounted for roughly 30% of female cases aged 20-39 years old [9, 12, 15] ." ] },{ "paper_id": "37a69d36617af76ae26d7801efb776af8f7488a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the International Medical University Research and Ethics Joint Committee, project number BP I-01-14 (23)2017. The names and identity card numbers of participants were excluded to ensure anonymity and confidentiality. Before the survey, a study information sheet was shown, and individual verbal or written consent was obtained.", "Healthcare professionals in the public sector were not included in this study as access to public hospitals could was not approved within the stipulated timeframe during the study. Future studies should focus on public healthcare professionals. Convenience sampling may cause selection bias and effects outside the control of the researchers. Therefore, caution should be exercised in generalizing these findings. All data were self-reported, and no cross verification of actual competence of methods and techniques were made.", "The Asian region is susceptible to epidemic Zika transmission because of various reasons like; widespread distribution of relevant mosquito vectors, the large amount of travel to, and from, Zika-affected areas, local conditions conducive to transmission, and limited health resources [13, 14] . Zika virus infections have affected Southeast Asian countries, such as Indonesia [15] , Singapore [16] , Vietnam [17] , and Thailand [18] , and Microcephaly, associated with Zika infection [19] , has been also reported in Southeast Asian countries. Previous literature has furthered the knowledge, attitude, practice, and vigilance of healthcare professionals from Malaysia and some Southeast Asian countries [20] [21] [22] [23] [24] [25] . However preparedness and response studies among healthcare professionals is still lacking in Malaysia and other Southeast Asian countries.", "Epidemics of infectious diseases are a major concern for global health [1] and the recent epidemic of Zika virus Brazilhas gained attention globally [2] [3] [4] [5] , due to its complications associated with congenital malformations [6] . The recent outbreaks suggest that Zika virus, one of the arboviruses transmitted by Aedes aegypti mosquitoes, is mainly spread all over tropical and sub-tropical counties worldwide [7] . Presently, there is no treatment or preventive vaccine to manage the consequences of Zika virus infection [8] ." ] },{ "paper_id": "37a7937db6ae6abd28ead7c4956ae68850faa8ce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The complete genome sequence of the human coronavirus NL63 CN0601/14 strain is available in GenBank under the accession number MG772808.", "Altogether, the complete genome sequence data of CN0601/14 indicate that variations in HCoV NL63 occur in South Korea. This information will aid in the understanding of the genetic diversity of HCoV NL63 in South Korea and in manufacturing an infectious CN0601/14 clone construct based on Korean vaccine candidate development.", "We report here the complete genome sequence of the human coronavirus NL63 CN0601/14 strain, first isolated from South Korea. It contains 18-nucleotide discontinuous deletions of the open reading frame 1a (ORF1a) and spike regions. This study will aid in our understanding of the complete genome sequences of isolated coronaviruses in South Korea." ] },{ "paper_id": "37bc284af4f2f731792f44339253abc79c6d2782", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "37c5a8f3c1c22335e7a3569c243cf4185295fc54", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2018 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.", "DNA extraction was performed using a DNeasy \u00ae Blood and Tissue Kit (QIAGEN) according to the manufacturer's recommendations. DNA concentration and purity were assessed using a NanoDrop\u2122 2000 full-spectrum UV-vis spectrophotometer (Thermo Fisher Scientific). DNA extracts were stored at -20\u00b0C until testing was performed.", "Poisson mixed-effects models for all species did not reveal any significant factors related to host community richness or species presence/absence in determining MPXV-positive count when both museum and year bin were included as random effects." ] },{ "paper_id": "37cae647fffbd8ed2ba338d805a6029577621c1d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "3. Helper T cell-rich germinal centers (GCs) are greatly reduced in PRRS.", "4. Non-neutralizing antibodies in PRRS are of low affinity.", "Described below are four studies that test tenets of our major hypothesis plus one that tests our secondary hypothesis.", "With exception of some new data presented in Figure 5 , all of the methods employed and materials used in obtaining the data presented are provided in the cited publications. In regard to Figure 5 , samples collected during previously published experiment (34) from animals infected by PRRSV strain VR-2332 were used as a starting material. Frozen material included cDNA prepared using random hexamer primers on total RNA from cell suspensions isolated using TRI Reagent according to a protocol recommended by the manufacturer (Sigma-Aldrich). Analysis of these samples are described below.", "Each cDNA preparation was amplified in three concurrent analyses for one of three V\u03b2 super-families (V\u03b2I-V\u03b2III families, V\u03b2IV-V\u03b2VI families, and V\u03b2VII family) (34, 47) . The 1st round PCR targeted the original cDNA preparation while the 2nd round PCR targeted the 1st round PCR products. After checking PCR product on 1.5% agarose gels stained by GelRed, the diversity of the V\u03b2 CDR3 regions was inspected by CDR3 length analyses. Technically, the second round of PCR products for each V\u03b2 superfamily was subjected to the 3rd round of PCR that involved incorporation of radioactive adenosine 5'-ATP \u03b3-32P triphosphate nucleotide labeled C\u03b2 primer (34) . The products were separated on sequencing gels that were subsequently dried and their radioactive images were obtained by Storage Phosphor Screens BAS-IP MS scanned in fluorescent Image Analyser FLA-7000 (Fujifilm Corporation, Yokyo, Japan). All primers and PCR conditions used for amplifications were published earlier (34) ." ] },{ "paper_id": "37ce6523b9d7806ed86759bc36b5c6efcfa6dda3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DNA ligase and restriction enzymes BamH I and Sal I (Takara Co., Ltd, Dalian, China), QIA quick Gel Extraction Kit (QIAGEN, Duesseldorf, Germany), unstained or pre-stained molecular weight markers (Thermo Fisher Science, Waltham, MA, USA), 0.2 \u03bcm nitrocellulose membrane (Whatman GmbH, Dossel, Germany), and enhanced chemiluminescence (ECL) plus western blotting detection kit (GE Healthcare, Buckinghamshire, UK) were obtained.", "The DNA fragments encoding these short peptides were synthesized by Wuhan Tianyi Huiyuan Biotechnology Co., Ltd. Each fragment contained a BamH I site at the 5' end, a Sal I cleavage site linked with a TAA termination codon at the 3' end. All DNA fragments encoding each short peptide were cloned into the pXXGST-3 vector expressing GST188-tagged protein in E. coli, respectively [21, 22] .", "The GTV genome contains three single-stranded minus-strand RNA fragments, comprising small (S), medium (M) and large (L) RNA fragments [9, 15] . As occurs with known Banyangvirus genus members, GP protein encoded by GTV-M gene is cut into two mature Gn and Gc proteins. However, knowledge about the antigenicity and immunodominant region of the GTV-encoded protein is still lacking." ] },{ "paper_id": "37d2a557fe2029d7bf6e32dde8fe5728e27ba4a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequencing viral quasispecies for genetic diversity analysis was one of the first applications of nextgeneration sequencing (NGS) technologies [3] . Applying whole genome shot-gun sequencing to viral quasispecies does not require cultivation and can sequence divergent strains from known virus families. It thus has become a favored choice for characterizing the diversity of quasispecies.", "The iterative clustering algorithm contains four steps as shown below:", "Step 3: post-processing", "(2) calculate relative abundances in each window and apply a clustering algorithm to group clusters of the same haplotype." ] },{ "paper_id": "37d6ce7eabf4b6177b9462771494c7c2fc36e5ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "37dcd4f6316a14205dd4887216b931a3877a0f50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "37e17a2bab698f8850dc89f7689eda93502821fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "37e2ecefeffdf8d95f1509809b59fe0464abba44", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Real time PCR was performed to assess whether PDK1 expression was modulated by PGE 2 . Total RNA was isolated using the RNA Bee kit (Qiagen, Inc., Valencia, CA) as per manufacturer's instructions. One \u03bcg of total RNA was reverse transcribed as per protocol using TaqMan\u00ae RT reagents (Applied Biosystems) at 37\u00b0C for 120 min followed by 25\u00b0C for 10 min." ] },{ "paper_id": "37f723594fc45504f7f8d4fc7ca0190513a639c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Image 2 | Detailed Phylogenetic Trees of five clade in Figure 1 ", "Homeodomains Reflect the Evolutionary Relationship from AP2L to AP2 and TOE1", "The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fpls.2016. 01383", "The 2-132 mutation was mapped using plants with a wildtype-like phenotype in the F2 generation from a cross of an 2-132/+ plant with the Columbia ecotype. The initial mapping was done using CAPS markers from The Arabidopsis Information Resource (http://www.arabidopsis.org). The dCAPS markers used for fine mapping of the 2-132 mutation were generated based on the information available from CEREON. " ] },{ "paper_id": "37fe4be4d997e01fa069ab31bbe1a0090356500a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ecological study Determination of the adaptation strategy of a parasite (e.g., evolution of vivax malaria owing to seasonal selection pressure)", "This is rearranged as:", "Further, considering different values of t, e.g., t+h, yields:", "Estimation of the transmission potential and infectiousness relative to disease-age (e.g., estimation of the relative infectiousness of smallpox)" ] },{ "paper_id": "380e9f8318abdddde5c3c6b30802f48f4d3540c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors state that we have no competing interests." ] },{ "paper_id": "380ffac0468974d60549293c37047bd307218587", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Intestinal tracts of PDCoV positive piglets were investigated after H.E staining, and some obvious pathological changes were found. Sections of middle jejunum to caecum showed diffuse intestinal villus blunting, fusion and enterocyte attenuation ( Figure 5 ). No lesions were seen in other organs. The mean VH: CD was 2.33 + \u2212 0.58 in duodenum, 1.71 + \u2212 0.81 in jejunum, 1.88 + \u2212 0.74 in ileum and 3.02 + \u2212 0.11 in cecum, respectively.", "The (Table 2 ). We chose one positive sample in each farm for sequencing, and the three samples were identified as PDCoV.", "During necropsy, the small intestines (duodenum and ileum) and large intestines (cecum and colon) and other major organs, including lung, heart, kidney and spleen were examined grossly. Samples collected from these tissues were fixed by 10% neutral buffered formalin for 48 h and for histopathological examination as described previously [23] . Fixed tissues were embedded, sectioned, and stained with Mayer's H.E for light microscopy examination. The length of ten villi and crypts of jejunum was measured and the mean of jejunum villous height: crypt depth (VH: CD) ratios was calculated as described [23] ." ] },{ "paper_id": "3811a68dda2911cb406a2fbb448530aa2319ee21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Student's t-test and Steel-Dwass test using JMP 10 software (SAS Institute Inc., Cary, NC) was applied for unpaired or multiple comparisons. Significant differences were defined as P<0.05.", "HIV-1 is predominantly transmitted at mucosal surfaces, but vaccine design and evaluation have focused primarily on systemic immune responses. The mucosal immune system is, in many respects, independent of the systemic immune system. In humans, 90% of intestinal and 50% of vaginal IgA is produced locally and induction of mucosal immunity is best achieved via mucosal infection or vaccination [1] [2] [3] . Passive transfer studies using broadly neutralizing antibodies (BnAb) have shown protection against mucosal transmission (reviewed in [4] ). Induction of BnAb has proven extraordinarily difficult because neutralizing epitopes are often structurally complex and difficult to faithfully recapitulate, long-term immune maturation is needed to acquire the extensive hypermutation described for most neutralizing IgG, and some neutralizing antibodies show autoreactivity [5, 6] . However, BnAb may not be essential for protection at the mucosa.", "There is strong evidence that protection by IgA typically does not rely on classical virus neutralization. IgA can sequester virus in mucus, sterically hinder binding to mucosal epithelia, and target virus for destruction via the polymeric immunoglobulin receptor (pIgR). There is also growing interest in the protective potential of non-neutralizing IgG [7] [8] [9] [10] . Mechanisms of non-neutralizing protection include antibody-dependent cellular cytotoxicity, antibodydependent cell-mediated virus inhibition, and other innate immune functions such as phagocytosis that are mediated by the Fc domain of the antibody. Whether mucosal vaccination can induce a protective antibody response of any sort against HIV-1 is uncertain." ] },{ "paper_id": "3819c9d30c75527e915470a797c69fa83934fa06", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.ppat.1008079.g008", "The sequences of siRNA and gRNA are as following. " ] },{ "paper_id": "381bb3c674e68a97e38efe5d6f9952c7a64522d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Swine influenza is a highly contagious acute respiratory viral disease of pigs, caused by H1N1, H1N2 and H3N2 subtypes of Influenza A virus (IAV). The disease is responsible for significant economic loss to the swine industry [1] . Pigs also play a critical role in the emergence of new strains of influenza viruses by acting as a \"mixing vessel\" [2] . Current swine flu vaccines are strain specific and they have been failed to induce cross-protection against genetically variant flu viruses [3] . Moreover, intramuscularly delivered flu vaccine induces poor mucosal IgA antibody and T cell responses [4] .", "Dulbecco's minimum essential medium (DMEM, Lonza) supplemented with 10% fetal bovine serum (Atlanta Biologicals) at 37\u00b0C with 5% CO 2 . For virus infection DMEM containing TPCK (L-1-tosylamido-2-phenylethyl chloromethyl ketone) trypsin (1 \u03bcg/ml) and without fetal bovine serum was used. For preparation of nanoparticles, polylactic-co-glycolic acid (PLGA) 75:25 (MW 40,000-75,000) (Lakeshore Biomaterials, AL), poly-vinyl alcohol (MW 30,000-70,000) (Sigma-Aldrich) and dicholoro methane (Acros Organics) were used. Micro BCA (bicinchoninic acid) protein assay kit (Pierce) was used for estimation of the peptides concentration.", "SwIV H1N1 challenged pigs were observed daily for clinical signs of influenza at DPC 1 to 7 and the rectal temperature was recorded daily beginning 1 day before challenge. During necropsy the lungs were examined for gross pathological changes and scored for virus induced consolidation as described previously [27] .", "All the data were expressed as the mean of 6 or 7 pigs \u00b1 standard error of the mean (SEM). Statistical analyses were performed using one way analysis of variance (ANOVA) followed by post-hoc Tukey's test using GraphPad InStat Prism (software version 5.0) to establish variations among MKC, PEP, NPP and NPA pig groups. Statistical significance was assessed at P<0.05 ( \u00c3 ), P<0.01 ( \u00c3\u00c3 ) and P<0.001 ( \u00c3\u00c3\u00c3 )." ] },{ "paper_id": "381f1d10b47e89d45a1008b53292c66c034b6960", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recent individual-based simulation models of pandemic influenza transmission have attempted to model the effectiveness of social distance measures, including travel restrictions [38, 39] . While eliminating travel in and out of affected areas along with imposing border restrictions may provide some relief by delaying spread by up to 8 wk [38] , drastic reductions in domestic travel are required to have much impact internally [38, 40] . Although these simulation studies have found that these strategies may not have a significant impact on the course of a pandemic, the models lack parameterization of the underlying relationship between air travel and influenza spread based on experimental data. Future work using simulation will benefit greatly from parameter estimates based on empirical findings such as those presented here.", "Although the sequence of infection varied among regions from year to year, certain spatial-temporal patterns emerged in the seasonal component of P&I mortality (Figure 3 Effect of Airline Volume on Influenza Inter-Regional Spread and Peak", "We did not find a significant relationship between climate and inter-regional influenza spread. Although we did find a 2001-2002 warm temperature spike and a positive relationship between hot temperatures and late peaking, this relationship was not significant and dropped out of the However, the 1999-2000 season was the warmest November-February period since 1895 and yet had an earlier than average national influenza peak. We also considered winter months separately, as well as overall minimum mean winter temperature, but none were significant predictors. In addition, strain type did not account for any significant amount of the variability in transnational spread or peak time of influenza mortality. Finally, first region affected was also not a significant explanatory variable (see Protocol S1)." ] },{ "paper_id": "3838015252b0ac31630c87d5cb719869e1569aa3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "38486671848611786384f2cc0a49066c5fca595f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3849786c8c14c11ae4b19b4543672421e5d169fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\"\u2026an accelerated and integrated effort to deliver effective interventions for pandemic influenza\"", "Authors' information EPR conceived, wrote, edited and communicated the review." ] },{ "paper_id": "384cdcda67c8a385d6a571ba5f9fb09e16d130b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were expressed as means \u00b1 standard deviations (SD) of 3 independent experiments. The statistical significance was tested by student 's t-test and p-values less than 0.05 were considered statistically significant.", "The African green monkey kidney cell line VeroE6 and swine small intestine epithelial cells (IECs) [30, 31] were respectively cultured in Dulbecco's modified Eagle's medium (DMEM) and Dulbecco's modified Eagle's F12 Ham medium (DMEM-F12) supplemented with 10 % fetal bovine serum at 37\u00b0C in a humidified atmosphere of 5 % CO 2 . PEDV strain CV777 was propagated in VeroE6 cells in DMEM containing 2.5 \u03bcg/mL of trypsin." ] },{ "paper_id": "3855de3900dee3cecb63982884763c5dac76b8cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Selecting the right intrabodies to perform these roles for antiviral development is not trivial and requires identification of appropriate candidates from panels of pre-existing clones that not only express well but also have the desired inhibitory function. Alternatively, intrabody selection campaigns can be introduced to enrich high-expressing clones for screening of inhibitory function (12) . More recently, direct selection of clones that allow cell survival after virus challenge with cytotoxic viruses can identify clones with antiviral activity (13) .", "aUThOr cOnTriBUTiOns TD, LS, and AH designed experiments, performed the work, and analyzed the data. AH wrote the paper.", "This work was supported in part by National Institutes of Health grants R21AI105568 and R01AI112851, a Texas Biomedical Research Institute Forum Award, and internal funding. " ] },{ "paper_id": "386c21f11ae0c9199c26218e334373932f3fa0c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The age group most frequently bringing animal products (Table 2 ) was between 35 and 55 (p = 0.0207). The odds ratio comparing this group with all others was 1.64 (Confidence limits 1.12-2.42).", "The second most frequent country was the China. Portugal and Italy also showed a large movement of people. Many Brazilian descendants of Portuguese origin still travel to Portugal and return to Brazil with, for example, Portuguese Bacalhau (dried salted cod) without a valid animal health certificate. This food, even if certified abroad, cannot enter Brazilian territory without approval of the Brazilian Ministry of Agriculture, Livestock and Food Supply.", "The largest values for the quantity of baggage were respectively 3, 1, 2 and 4 volumes ( Table 5 ). These were mainly suitcases and bags of some sort (Table 6 )." ] },{ "paper_id": "386d7389837dbaa87d3b0119af4d965b197651f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "38709b5c18e24c3287a6b1b97ddbe8899cdab432", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "x (i th marker appears in t ik ) , j~1,2, . . . ,", ", if E is true; 0, otherwise:", "We find the optimal coefficient vectorb b by minimising RSS(b).", "where b j 's are the coefficients of regression. The residual, the error of the linear estimator, is" ] },{ "paper_id": "38771dc09043758e9f76b1c8746495874d2a41bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Routing of astrovirus sequence data from GenBank to PAML input data files Figure 4 Routing of astrovirus sequence data from GenBank to PAML input data files. " ] },{ "paper_id": "388bf10627c470191554ffe46e7fcddbf00aa054", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A one-tailed student's t-test was used to examine statistical significance.", "https://doi.org/10.1371/journal.pone.0179177.g005 protein activation. Conversely, residue R797 did not impact SARS S cleavability by TMPRSS2 but was essential for virus activation by this protease. In the following we will discuss and provide potential explanations for these at first sight paradoxical findings.", "Retroviral particles encoding a firefly luciferase reporter and harboring SARS S in their envelope (pseudotypes) are commonly used to study SARS S-driven host cell entry. Since we sought to employ pseudotyping to investigate the proteolytic activation of SARS S mutants, we next determined whether the mutations studied modulated SARS S incorporation into retroviral particles. These particles bud from the plasma membrane and one would thus expect that only S proteins expressed to appreciable levels at the cell surface are incorporated into particles.", "Human embryonal kidney 293T cells and African green monkey derived COS-7 cells were grown in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), penicillin, and streptomycin (1%) at 37\u02daC in a humidified atmosphere containing 5% CO2. The identity of the 293T cell line was verified by short tandem repeat (STR) analysis. COS-7 cells were obtained from collaborators. All cells were tested negative for mycoplasma." ] },{ "paper_id": "389053111a32e148f8b7c07c883818f70525aa73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Microscopy Sciences (EMS), Hatfield, PA, USA) and 2% glutaraldehyde (16020; EMS) in a 0.05 M sodium cacodylate buffer (SCB; pH 7.2) (11652; EMS) at 4\u00b0C for 2 hours, followed by washing with 0.05 M SCB at 4\u00b0C for 2 hours. Post-fixation, the samples were treated with 1% osmium tetroxide (19152; EMS) in 0.05 M SCB at 4\u00b0C for 2 hours, and then washed with distilled water at room temperature. The samples were dehydrated at room temperature in a 30-100% ethanol series with 10-minute exposure to each concentration. The ethanol was then replaced with hexamethyldisilazane (16700; EMS). Following dehydration, each sample was spread onto polycarbonate membrane filters with a pore size of 0.4 \u03bc m (Isopore Membrane Filters HTTP01300; Millipore, Billerica, MA, USA) and coated with osmium by chemical vapor deposition (HPC-1SW; Vacuum Device Inc., Ibaraki, Japan)." ] },{ "paper_id": "3892a126c127795e96e4e071cf14fd7fdc2e4231", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2.9. Statistical Analysis. All data are presented as mean \u00b1 SD. Statistical analysis was performed with SPSS 16.0 (SPSS, Chicago, USA). Multiple comparisons were performed using the Kruskal-Wallis test, or ANOVA, followed by the LSD-t test, as appropriate. A value less than 0.05 was considered significant.", "Rats were monitored and weighed daily by two independent observers to evaluate clinical scores of EAE after immunization. Neurological signs were assessed as follows [23] : 0 = no clinical score; 1 = loss of tail tone; 2 = hind limb weakness; 3 = hind limb paralysis; 4 = forelimb paralysis; 5 = moribund or death.", "2.1. Animals. Female, 6-7 week-old Wistar rats were purchased from Shanghai Xipuer-Bikai Experimental Animal Company, China, and housed in the aseptic laboratory of the Experimental Animal Center of Henan, China. All efforts were made to minimize the numbers of animals used and to ensure minimal suffering." ] },{ "paper_id": "389612b52a4489f9be2109a5eb0060499a0f7c15", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Student's t test analysis was used to determine the significance of the results. Values of p#0.05 indicated statistical significance. ", "For flow cytometric analyses of various lymphocyte populations in the peripheral blood, we used our previously published protocols [17] .", "Analysis of binding antibodies against whole SARS-CoV lysates or N protein, and S glycoprotein-specific neutralizing antibody (Nab) were conducted as previously reported [11] ." ] },{ "paper_id": "3899c4aad46100ad273f70ecf65f5454806d5117", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "br (A.A.d.S.-J.); Tel.: +55-084-3342-9820 (A.A.d.S.-J.); Fax: +55-084-3342-9833 (A.A.d.S.-J.) \u2020 These authors have the same contribution in this manuscript.", "This ability of colloidal nanocarriers to preserve the entrapped drug into the polymeric matrix is a promising characteristic for drug targeting intended for specific affected cell or tissue, mainly considering the internalization of nanoparticles by endocytosis [43, 56, 57] ." ] },{ "paper_id": "389b75fa8272ae7d2ab3d90ae8c1edbdf55c0463", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "WNV pp9", "doi:10.1371/journal.ppat.1005009.g007 " ] },{ "paper_id": "38a24f1500fcb5cfbac618720eb8996fd27029a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All datasets generated for this study are included in the manuscript/Supplementary Files.", "Both examples clearly illustrate the need to harmonize methodologies at international level in order to discuss data collected in different countries. Such discussions currently take place within the AACTNG network (www.aacting.org).", "RS did all the calculations presented in this work. LC helped with the repartition of sales between species, expert advice and biomass distribution. Raw sales data and advice regarding their use was provided by DH. The study was designed by CM and supervised by KE and HN." ] },{ "paper_id": "38a33f302357e8dced322858ad61fe20b876d445", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary information accompanies this paper at https://doi.org/10. 1186/s12889-020-8279-7.", "Additional file 1. Ebolarelated stigma Questionnaire.", "Not applicable." ] },{ "paper_id": "38aa050ad79d8a1d7022c33535255ce9d47914e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Arenaviruses are enveloped RNA viruses with bi-segmented, negative-sense genomic RNA [1] . Based on the antigenicity, phylogeny, and geographical distribution, they are divided into the Old World (Lassa-Lymphocytic choriomeningitis complex) arenaviruses and the New World (Tacaribe complex) arenaviruses. Recent studies have identified several snake-borne arenaviruses that are highly divergent from known arenaviruses [2] [3] [4] . The lymphocytic choriomeningitis virus (LCMV) from the Old World (OW) arenaviruses is the prototype arenavirus. The New World (NW) arenaviruses are further classified into clades A, B, and C NW arenaviruses. Arenaviruses often chronically infect their natural rodent hosts [1] . Infection in humans is mostly acute and occurs probably through mucosal exposure to aerosols or by direct contact of abraded skin with infectious materials.", "The role of IFN response in JUNV pathogenesis is still not well understood. High levels of IFN-a have been detected in serum samples from Argentine hemorrhagic fever (AHF) patients and have been associated with severe and lethal disease outcomes [9] . IFN has been linked to some of the clinical symptoms including thrombocytopenia [33] . In natural rodent host, the role of IFN in JUNV pathogenesis and persistent infection remains unclear, largely due to lack of laboratory inbred animals [13] .", "Wild-type MEF cells and IRF3/7 knockout MEF cells were infected by Romero and Candid#1 viruses at MOI of 0.1 or 0.001. Supernatants from infected cells were harvested daily and subjected to plaque assay as described previously [18] . Statistical analysis of virus growth kinetics was performed by two way ANOVA test." ] },{ "paper_id": "38b50147abf86a5818c6bb5e09b1f07edf51352b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "in (M.M.K.); jayanta@jncasr.ac.in (J.H.) 4 BerGenBio, Jonas Lies vei 91,", "FDA issuance of an approval letter after their review of the NDA or BLA application submitted by the sponsor for the pharmaceutical documents this criterion.", "None. Continue surveillance." ] },{ "paper_id": "38bed8a14f2f6103cf5f8ddc6db772c8ab52f7c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Generally the short incubation period for IBV varies with infective dose and route of infection. For example, while infection via the tracheal route may take a course as short as 18 hours, ocular inoculation leads to an incubation period of 36 hours [33] .", "Other clinical outcomes associated with IB infection include frothy conjunctivitis, profuse lacrimation, oedema, and cellulitis of periorbital tissues. Infected birds may also appear lethargic, with evidence of dyspnoea and reluctance to move [36] . Nephropathogenic IBV strains are most described in broiler-type chickens. Clinical signs include depression, wet droppings, and excessive water intake. Infection of reproductive tract is associated with lesions of the oviduct, leading to decreased egg production and quality. Eggs may appear misshapen, rough-shelled, or soft with watery egg yolk ( Figure 2 ). Unless effective measures are instituted, decline in egg production does not return to normal laying, thus contributing to high economic loss [1, 37] . tracheal mucosa and extrapulmonary bronchi ( Figure 3 ) [38, 39] .", "The authors declared no conflict of interests regarding the present paper." ] },{ "paper_id": "38c1c195de7abd1d3319ab5dfedb585f6cbbda85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "38c9ad4d6eb48945732f8519c795b39b4bdb0c93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Here again, therapeutic antibodies can also be used for prophylaxis, affording immediate and reliable protection." ] },{ "paper_id": "38cbb822fbce17d5cbd5d12896d8ffa7848e8229", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. All relevant data are available from the authors on request.", "More versatile than traditional drugs, Z2 may be converted into bullets to target the virus in the fetal brain. Coupled with blood-brain barrier shuttle peptides, such as angiopep-2, glutathione, or peptides derived from transferrin (TfR1), or low-density lipoproteins (LDLRs) 54 , Z2 may acquire the ability to penetrate through the fetal blood-brain barrier.", "In recent years, development of peptide drugs has attracted growing attention because of their better safety and lower development cost compared to small-molecule-and antibody-based antiviral drugs. We previously identified the first highly potent anti-HIV C-peptide, SJ-2176 (refs 17,18) and the patent was licensed to Trimeris Pharmaceutical Inc. for development of the first HIV fusion inhibitor, enfuvirtide, which was approved by the US Food and Drug Administration in 2003 for the treatment of HIV infection 19, 20 . Furthermore, the use of enfuvirtide, either alone or combined with other antiretroviral drugs, could successfully prevent mother-to-child HIV transmission during pregnancy [21] [22] [23] , indicating that antimicrobial peptides could be developed as safe and effective antiviral therapeutics and/or prophylactics. Therefore, we aimed to design and identify an effective anti-ZIKV peptide." ] },{ "paper_id": "38d4184fcc07afbf2bd269491da88687764e86f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As an alternative to full-length polypeptides, expression and purification of protein domains may improve yield of stable products for use in microarrays. In one reported study, a total of 212 protein domains (SH3, SH2, PDZ etc.) were immobilized on nitrocellulose and screened with peptides [55] . The results proved that the immobilized domains were stable and could be used for binding studies.", "Kaushansky et al. [56] constructed an array based on protein interaction domains such as Src homology, phosphotyrosine binding domains, and mouse PDZ domains produced from recombinant E. coli. These arrays required low sample consumption and may reduce false positive rates. Advanced knowledge of the specific recognition events will be required to substitute peptides or single protein domains for full-length proteins to ensure that important epitopes are not missed for the purpose of studying antibody interactions.", "The high efficiency, low cost, and high-throughput nature of chemically synthesized peptides are significant advantages compared to production of recombinant polypeptides. Therefore, peptide microarrays have been explored as another alternative to recombinant proteins, with a limited degree of success. A chemically synthesized peptide microarray representing the major antigens of hepatitis B and C viruses, human immunodeficiency virus, Epstein-Barr virus, and syphilis was constructed on a glass slide and antibody responses were simultaneously detected [53] . The assay showed very high sensitivity and specificity for the diagnostic identification of these viruses. Another proof of principle study [54] was reported to identify diagnostically relevant peptides using a peptide array deduced from bioinformatics data for Echinococcus granulosa (tapeworm) infection, achieving only 57% sensitivity and 94% specificity compared to ELISA." ] },{ "paper_id": "38d6c3ecce86e079e55dcb9a1b33f2a239b3ba81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The time has come to set up appropriate measures and put machineries in motion to combat and possibly subdue influenza pandemics; starting from Africa, and to the rest of the world.", "Controlling the disease in animals is the first step in decreasing risks to humans [4] , and this will include among others:", "OGF: Coordinated the study and drafted the manuscript. FAB and OGF: Searched for relevant literatures. FOF and IAO: Critically reviewed the manuscript. All author read and approved the final manuscript." ] },{ "paper_id": "38df3b1f635f3643d1a818ea62ac60915d71e92c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Common goal was based on Fisman and Laupland [2] and Kahn [3] and has a construct reliability score of 0.89. Participants were asked the following:", "Apart from a number of open questions (related to age or the number of working years), all items were based on a Likert scale (1-7) and can be interpreted as continuous variables, thus following the fundamental Ordinary Least Square (OLS) principles. The sevenpoint scale was used to obtain greater dispersion and hence more nuance in the data [52] . Table 1 reports the general descriptives of the variables (mean, SD, alpha and correlations).", "The study sample consisted of 368 respondents. This size is acceptable in view of the rule of thumb provided by Barclay, Higgins and Thompson [60] , which suggests using ten times the maximum number of paths aiming at any construct in the outer model (this is not applicable as no formative constructs were used) and the inner model. All construct variables (Collaboration, Common Goal, Recategorization, Decategorization, Mutual Differentiation, and Knowledge Sharing) are reflective constructs." ] },{ "paper_id": "38eee3781e1192464696b9a1164834259214cde9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The population attributable fraction, PAF (proportion of cases in the total population that would be avoided if the exposure was removed, assuming the exposure is causal), was estimated using the punafcc package for Stata [12] .", "Of the 440 confirmed BNP cases in this study, 20 cases (4.5%) had dams that were not PregSure-vaccinated and had not previously had a BNP calf, had received only dam's colostrum, and came from farms with no history of PregSure vaccination or BNP cases.", "(DOCX)", "All procedures on animals used in this study were in concordance with the ethical conditions for animal experimentation as mentioned in the European legislation (Directive 86/609/ EEC). The blood samples collected from calves on the farms were taken for diagnostic purposes at the request of the owner as part of clinical veterinary practice and therefore were not considered to be experimental, so no formal approval of the protocol by an ethical committee in any of the four countries was required." ] },{ "paper_id": "38f12e7be8d0f29aabe77ac96fa19d62407c0898", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It is expected that a large proportion of ribosomes should scan past the CUG codon and initiate at the ORF1a AUG codon -thus allowing synthesis of the replicase polyprotein -though the additional possibility that the CUG-initiation efficiency may be temporally regulated as part of the virus lifecycle can not currently be discounted [16, 22] .", "Overlapping genes are common in RNA viruses where they serve as a mechanism to optimize the coding potential of compact genomes. However, annotation of overlapping genes can be difficult using conventional genefinding software [7] . Recently we have been using a number of complementary approaches to systematically identify new overlapping genes in virus genomes [7] [8] [9] [10] [11] . When we applied these methods to the toroviruses, we found strong evidence for a new coding sequence -overlapping the 5'-terminal region of ORF1a ( Figure 1 ). Here we describe the bioinformatic analyses.", "Overlapping genes are difficult to identify and are often overlooked. However, it is important to be aware of such genes as early as possible in order to avoid confusion (otherwise functions of the overlapping gene may be wrongly ascribed to the gene they overlap), and also so that the functions of the overlapping gene may be investigated in their own right. We hope that presentation of this bioinformatic analysis will help fullfil these goals. Initial verification of ORFX product could be by means of immunoblotting with ORFX-specific antibodies, bearing in mind, however, that it may be expressed at relatively low levels." ] },{ "paper_id": "38f94d6ff230d6a00680940606d559f893701898", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Madin-Darby canine kidney (MDCK) cells were cultured in Dulbecco's modified essential medium (DMEM) containing 10% (v/v) fetal bovine serum (Hyclone, tah, USA) and maintained at 37\u00b0C and in a 5% (v/v) CO 2 atmosphere.", "Fifty-percent tissue culture infective dose (TCID 50 ) assays", "BALB/c mice (6 weeks old, female) were purchased from the Animal Experiment Center, Yangzhou University. All animal experiments complied with the guidelines of the Animal Welfare Council of China, and the Animal Ethics Committee of Nanjing Agricultural University approved the study." ] },{ "paper_id": "38fec468e30f4e956339345baeef4f15c7541cf5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The analytical detection limit of the combined RNA preparation/RT-PCR/MALDI-TOF MS system was determined by probit analysis [12] using the Statgraphics Plus 5.0 software package (Statistical Graphics, Jena, Germany).", "A primer extension genotyping assay was designed for each SARS-CoV SNV using SpectroDesigner software (Sequenom, San Diego, California, United States) and analyzed using the MassARRAY system (Sequenom) and the recommended protocol for the MADLI-TOF (matrix-assisted laser desorption ionization/time-of-flight) MS-based genotyping analysis [11] .", "Citation: Liu J, Lim SL, Ruan Y, Ling AE, Ng LFP, et al. (2005) SARS transmission pattern in Singapore reassessed by viral sequence variation analysis. PLoS Med 2(2): e43." ] },{ "paper_id": "39063a51b2de47e1b2ef019d04eac54ca1c3f2d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Blood smears were stained with Diff Kwik (eosin and methylene blue) and microscopically examined at 40x and 100x (oil) magnification for cellular abnormalities and haemoparasites.", "No potential conflict of interest was reported by the authors. ", "Jonas Malmsten is a veterinarian currently employed at the Swedish University of Agricultural Sciences. He is specialized in wildlife population health in mammals and birds, and does research related to wildlife disease, management, and welfare." ] },{ "paper_id": "390b4e40d86e389acf5cb47705c7c02eca264c8a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SA-H, LG, DoA, SB, and DeA have participated in writing and preparation of the manuscript, and approved it for publication. ", "Thus, in addition of being safe and immunogenic on its own, a nanovaccine should have a size similar to viruses while incorporating relevant antigens (54) .", "The use of particles as nanoplatforms displaying relevant antigenic moieties is appealing as an alternative approach to conventional vaccines. These nano-sized materials can be obtained from biological sources and/or can be synthetic.", ". Other examples of SAPNs as potential nanovaccines against respiratory viruses include the capsid protein of the papaya mosaic virus (PapMV), the purified coronavirus spike protein and ferritin, which are selfassembling proteins that form rod-shaped and nearly spherical nanostructures, respectively (96, (130) (131) (132) (133) (134) (135) (136) (137) (138) (139) (140) . Recently, assemblies composed of four tandem copies of M2e and headless HA proteins were prepared and stabilized by sulfosuccinimidyl propionate crosslinking, showing the possibility of generating protein nanoparticles almost entirely composed of the antigens of interest (141) . VLPs are spherical supramolecular assemblies of 20-200 nm diameter, which result from the self-assembly of viral capsid proteins. These particles are free from genetic materials and have the advantage of mimicking perfectly the structure and the antigenic epitopes of their corresponding native viruses. Therefore, this repetitive antigen display promotes efficient phagocytosis by APCs and subsequent activation (142) (143) (144) (145) (146) ." ] },{ "paper_id": "390b508dfbde0fbf9b91e67cc77fcd3bf0e391ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The formation of a hybrid population through the mixing of two ancestral, or long-separated, populations.", "A discipline which uses next-generation sequencing technologies to characterize the entirety of genomic material found in environmental samples.", "The relations among a set of sequences showing which shares a most recent common ancestor with other sequences." ] },{ "paper_id": "3911541ad43c2734d7e64deb63e319e085e54357", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The microarray analysis procedures for group R were performed as described previously for groups S and C .", "The authors would like to thank Gogoleva N.E. and Gogolev Yu.V. (Kazan Institute of Biochemistry and Biophysics, Federal Research Center \"Kazan Scientific Center\" of RAS, Kazan, Russia) and Volkov K.D. (Kazan State Medical University) for assistance in some of the experiments. Kazan Federal University was supported by the Russian Government Program of Competitive Growth.", "The animal protocols including euthanasia were reviewed and approved by the Commission on Bioethics at the Institute of Mitoengineering of the Lomonosov Moscow State University (Protocol No. 35 of November 1, 2012) " ] },{ "paper_id": "3929d5fe37521db29b4d747ab3c9376f6865be16", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bioinformatic analysis of metagenomic datasets. Obtained raw reads were analysed using the software RIEMS 28 to get an overview of the taxonomic composition of reads.", "Published: xx xx xxxx OPEN www.nature.com/scientificreports/" ] },{ "paper_id": "393091a75a8617bf9fd5127a834c16743a9e89cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: P.-S.Y. and A.-B.F. contributed to conceiving, performing the analysis and writing the paper. C.-H.C., V.S., and A.K. helped in interpreting the data. A.K. helped editing the paper. All authors reviewed the paper. " ] },{ "paper_id": "3941bfed937029a31746847f195aeb98631f8d0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The majority of enveloped viruses release viral internal genomes and proteins into the intracellular compartment through fusion processes induced by viral surface proteins between viral and cellular membranes immediately after virus attachment to receptors or the endocytic pathway.", "Rotaviruses, pathogens of severe diarrhea in infants and young children, recognize several molecules on the epithelial cell surface, including glycolipids, N-glycoproteins, HSC70 protein, and \u03b1 V \u03b2 3 integrin localized in membrane rafts [128, 129] .", "GM1 expression and asialo-GM1 expression in membrane rafts of T cells and natural killer (NK) cells are differentially regulated by these cells in the context of RSV infection. Asialo-GM1 may increase RSV clearance by increasing IFN-\u03b3 levels in mouse lungs [229] .", "The pseudorabies virus Us9 protein interacts with membrane rafts and then promotes targeting of viral structural proteins to neuronal axons. Consequently, the virus spreads from presynaptic to postsynaptic neurons and cells of the mammalian nervous systems [108] ." ] },{ "paper_id": "3949a9e9a8c6c26ed1b9aa4bd9b02291dbeefe4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The school population distribution of ages (S c ) with elements signifying the probability of encounters between two ages within school was obtained using", "PLOS Computational Biology | https://doi.org/10.1371/journal.pcbi." ] },{ "paper_id": "394b9e259a4a871f49e3ab9209a05059fb6347ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples were prepared as 20% suspensions in DEPCtreated water and centrifuged at 5,000 \u00d7g/15 min at 4 \u2218 C, and the supernatant was stored at \u221280 \u2218 C prior to analysis.", "Amplicons for each gene (HE: 441bp; S: 488bp; and N: 306bp) were purified from agarose gels with the GFX PCR DNA and GB Purification Kit (GE Healthcare Bio-sciences Corp, Piscataway, NJ, USA) and submitted to bidirectional sequencing with BigDye version 3.1 (Applied Biosystems, Carlsbad, CA, USA) according to the manufacturer's instructions. Sequences were resolved in an ABI-377 sequencer.", "Chromatograms were submitted to Phred analysis (http:// asparagin.cenargen.embrapa.br/phph/), and positions with scores >20 were used to assemble sequences with CAP-Contig in BioEdit 7.0.9.0 [15] .", "Thus, one can speculate that successive natural passages of the strain E17 amongst horses, without the participation of cattle, led to different host-parasite relationships due to differences in receptors, in viral replication, and in the intracytoplasmic content [29] , and probably, this distance has a tendency to rise over evolutionary time.", "In the nested RT-PCRs, DEPC-treated water was used as a negative control every five samples, also added to the mix, and placed in a thermocycler in order to monitor contamination by DNA amplicons. Each step of the study (RNA extraction, nested RT-PCR, electrophoresis, and DNA sequencing) was carried out in different rooms with materials and reagents exclusive for that specific step in order to prevent DNA carryover." ] },{ "paper_id": "395fef2b73d1c568f900de94f5f6d908bc305f24", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In mammals and birds, CoVs are associated with upper and lower respiratory illnesses or gastroenteritis. In humans, CoVs infections are commonly caused by HCoV-229E and HCoV-OC43 which generally cause mild respiratory illnesses [3] . A new CoV that causes severe acute respiratory syndrome (SARS-CoV) emerged in humans in 2002-2003 and infected more than 8,000 individuals with mortality rates estimated at around 10% [4] . The emergence of SARS-CoV and its mortality rate have raised the risk of a new pandemic that could threaten public health. For this reason, the scientific community invested considerable interest in the identification and characterization of CoVs especially within mammal reservoirs. Subsequently, two novel human CoVs were discovered: HCoV-NL63 in 2004 [5] and HCoV-HKU1 in 2005 [6] . In June 2012, a third novel coronavirus named HCoV-EMC/2012 (renamed MERS-CoV) was isolated from patients presenting with acute respiratory distress and pulmonary inflammation [7, 8] .", "Although estimates of the most recent common ancestors (MRCAs) proved inaccurate in our study, most likely as a result of a limited sequence availability from the identified viral strains, standard evolutionary analyses have estimated CoV origins to date to somewhere between 500-10,000 yrs. in the past [41] [42] [43] . Nevertheless, further investigations into the relevance of MRCA prediction methodologies are required and a great level of caution must be employed in the interpretation of MRCA data. .", "Although we were not able to evaluate risk of human infection, the strains detected here may be considered as potential human pathogens, as bats are natural reservoirs of some pathogenic CoVs. Isolation of Malagasy CoVs using cell culture and molecular analysis of spike (S) gene could better evaluate risk of human infection. Also, a longitudinal study amongst people who frequently handle live bats (e.g. bat hunters, bat bushmeat purveyors, and scientists), and who represent populations at higher risk of infection, would be interesting to establish possible cases of transmission to humans and public health risks." ] },{ "paper_id": "396312dfae0562afce275a99e96c903e91aa96c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. It was cohort study or case control study in design.", "4. All patients were definitively diagnosed with influenza confirmed by viral genome polymerase chain reaction (PCR) assay, and able to give informed consent.", "1. Repeatedly published literature." ] },{ "paper_id": "39683dd78bcf6b301cbed610b6e3213a5ce33380", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following on their work with monomeric GRFT, Moulaei and co-workers created several GRFT tandemers [24] . The tandemer proteins were constructed by linking GRFT monomers to one another through covalent linkages formed by insertion of Gly-Thr-Gly linkers. The tandemers were analyzed by electron microscopy that showed the double and triple repeats to exist in a linear arrangement while the tandemer containing four mGRFT repeats formed a more globular structure. In HIV neutralization assays, improvements in potency were observed for the double and triple tandemers but potency plateaued there, with no increase in potency observed for the 4\u00d7 mGRFT construct.", "Studies on mouse-adapted MA15 SARS-CoV showed that mice that received daily doses of intranasally administered GRFT had 100% survival rate, with no loss in weight, improved lung histopathology scores, and reduction of lung tissue virus titers, compared to the control group that experienced weight loss and had only a 30% survival rate [30] . Further studies might prove GRFT as a good candidate molecule to treat respiratory infections [30] .", "In a study investigating the effects of three lectins on delta and gamma retroviruses including human T cell leukemia virus, GRFT had no effect [51] .", "Interestingly, even though the monomeric GRFT had comparable affinity towards nonamannoside, it showed decreased ability to bind to gp120 and even more dramatic decrease in inhibiting HIV infection in CEM-SS cells [19] . This indicates that crosslinking of multiple high-mannose sugars is responsible for the high potency of the lectin GRFT." ] },{ "paper_id": "396a42500c39667896d3e7b918422af5854d7439", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 701088.", "A recent prospective study including 284 children and 232 adults with RTI, aimed to determine antibiotic misuse, showed that viral infection was more common in children than in adults, while antibiotic overuse occurred both in children (37%) and, at a significantly higher level, in adults (83%). The study highlights the needing for effective interventions to decrease antibiotic overuse in RTI patients of all ages (van Houten et al., 2019) .", "The Allplex Respiratory Panels (Allplex; Seegene, Republic of Korea), a recently released one-step real-time reverse transcription-PCR method for the simultaneous detection of multiple pathogens, has been demonstrated to be a rapid and accurate method for detecting respiratory viruses, particularly in case of multiple viral infections (Lee and Lee, 2019) . A study comparing Allplex RP1 assay with ProdesseProFlu+ and ProFAST+ (Hologic, Madison, WI, USA) , and GeneXpert Flu/RSV XC (Cepheid, USA) for IV and RSV detection, found accuracy of 95, 91, and 96% and sensitivity of 94, 88, and 95%, respectively. The three assays showed a 100% specificity and positive predictive value (PPV), while the negative predictive values (NPV) were 84, 73, and 86% for Allplex RP1, Prodesse and GeneXpert, respectively (Gimferrer et al., 2018) .", "SE wrote the first draft of the manuscript. AM, EC, and BC gave a substantial scientific contribution. ES performed the literature review. NP co-wrote the first draft of the manuscript and supervised the project. All authors approved the final submitted version of the manuscript." ] },{ "paper_id": "396b05e6ede13dc6078ddf0eae5c14ceae695600", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. The t-test statistics, Spearman's correlation coefficients, Fisher's exact text, and chi-squared test were analyzed using SPSS software (Version 17, IL). P values less than 0.05 were considered significant. The critical point for positive definition was a number with a higher value than that of the healthy controls (Mean 1 3 SD).", "B eh\u00e7et's disease (BD) is a chronic multisystem vasculitis of unknown etiology 1 . This disease has global epidemiology but is more prevalent in regions spanning from East Asia (Japan, Korea and China) to the Mediterranean basin, including Turkey and the Middle Eastern countries 2, 3 . Similar to other classical autoimmune diseases, such as systemic lupus erythematosus (SLE), Sjogren syndrome (SS) and rheumatoid arthritis (RA), BD also exhibits a diversity of clinical manifestations, indicating the co-existence of a large number of autoantigens 4, 5 . In fact, efforts by other groups have led to the successful identification of some autoantigens, including the retinal S-antigen, IRBP, HSP70, a-tropomyosin, SBP, Mtch1, and annexin V [6] [7] [8] [9] [10] [11] .", "The newly identified 36-kDa autoantigen was cut from a polyacrylamide gel and digested with trypsin. The peptide fragments were identified using LC-MALDI-TOF-TOF mass spectrometry and then analyzed using the Mascot bioinformatics database to obtain the amino acid sequence of all the detective proteins. It was shown that the target protein shared the most significant sequence homology with annexin A2 (estimated molecular weight/pI, 38780/7.57; NCBI accession number, gij18645167; Mascot score, 606; matched unique peptides, 19) , which was accurately determined with over 95% confidence interval (.95 C.I.%) indicating credible results (Fig. 2c) ." ] },{ "paper_id": "39772fc7033bdfcfd0a6fb689d7a5c8bff2d80e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Liposomes were prepared by freeze-thaw and extrusion through 200 nm polycarbonate filters [66] , and were stored at 4uC in TAN buffer under N 2 and used within 2 weeks of preparation. Liposomes were composed of a 1:1:1:3 molar ratio of 1-palmitoyl-2-oleoylsn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-snglycero-3-phosphoethanolamine (POPE), sphingomyelin (bovine brain) (Avanti Polar Lipids; Alabaster, AL), and cholesterol (Steraloids, Inc.; Wilton, NH), plus trace amounts of 3 H-cholesterol (Amersham; Arlington Heights, IL).", "We also produced and purified a dimeric ectodomain form of DENV2 E protein containing all three domains (E9), a monomeric form containing E domains I and II (DI/II), and E domain III (DIII) (Fig. 1A and 1C ), all as previously described in detail [30, 41] .", "SDS-PAGE analysis was performed using 10-12% acrylamide gels with a Bis-Tris buffer system (Invitrogen). Western blots were performed with Alexa Fluor 688-conjugated secondary antibodies (Molecular Probes), and were quantitated using an Odyssey Infrared Imaging system and Odyssey InCell Western software (LI-COR Biosciences) [30] . Standard curves with purified E proteins confirmed the linearity of this analysis (data not shown)." ] },{ "paper_id": "397fe94fcd6118c9d0b40283a806525300c16156", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where\u0108", "Thus there are three key results which have implications for decision-making:" ] },{ "paper_id": "39809942de9e0dd4d8449754015aa6f9aec3e2c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The QIAamp Viral RNA Mini Kit (Qiagen, Hilden, Germany) were used for viral RNA and DNA extraction. To guarantee RNA integrity, samples were lysed under highly denaturing conditions to inactivate RNases. Alcohol was added and lysates loaded onto the QIAamp spin column. Viral RNA and DNA bind specifically to the QIAamp silica membrane while contaminants pass through. Pure viral RNA/DNA were eluted in a 60 \u03bcl buffer. Wash buffers removed impurities and pure, ready-to-use RNA/DNA was then eluted in water or low-salt buffer. Total nucleic acid extracts were stored at -80\u02daC until further processing by PCR.", "FTD Respiratory Pathogens 21 (Fast Track Diagnostics) multiplex Real-Time PCR diagnostic strategy was used to detect influenza A, pandemic influenza A/H1N1 (A/H1N1pdm09 or A/H1pdm09), influenza B, rhinovirus, coronavirus NL63, 229E, OC43, HKU1, parainfluenza 1, 2, 3, 4, human metapneumovirus A/B, bocavirus, respiratory syncytial virus (RSV) A/B, adenovirus, enterovirus, parechovirus, and Mycoplasma pneumoniae. The CFX96\u2122 Real-time PCR System (Bio-Rad, Hercules, CA, USA) that detects five different fluorescent dyes simultaneously was used for multi-pathogen detection in one clinical sample. To identify A/H3 virus, we used a real-time RT-PCR Influenza A subtyping kit donated by the US CDC.", "The dataset was analyzed in SPSS version 20 (IBM Corporation, Armonk, NY, USA)." ] },{ "paper_id": "39855ca915f908855de8577baf009e5b1acf5f5c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experimental protocols were approved by the Institutional Animal Care and Use Committee of Beijing Institute of Microbiology and Epidemiology (ID: SYXK2010-005) and carried out in accordance with the approved guidelines.", "Ang II levels were measured as described elsewhere 22 . Western blotting. Lung tissues were lysed in RIPA buffer. The following antibodies for Western blotting were used: rat polyclonal anti-ACE2 antibodies and rabbit monoclonal anti-ACE antibodies (all R&D Systems)." ] },{ "paper_id": "398cbb196acb9f8ee91a22edcca3b32c044878b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In some contexts, the challenge of genetic engineering goes beyond synthesis and function. Any self-replicating genome is subject to evolution, and if that genome is grown as a population of individuals-as it must be in many of these applications-evolution may reverse the engineering toward unwanted ends. The second challenge of genetic engineering is thus to predict that evolution and take measures to avoid or reduce it. Yet predicting evolution represents its own set of difficulties, and designing genomes to avoid that evolution poses others.", "The probability that a vaccine strain evolves above the epidemic threshold depends on transmission chain length and the probability that viruses at that stage of transmission will have the mutations necessary for R 0 > 1 (Fig. 1) . As with any adaptive evolutionary process, the magnitude of evolution is expected to increase with population size and with increasing time to extinction. Vaccines whose intrinsic R 0 (before evolution) are 0.4 or less are expected to die out quickly (they have a very low probability of transmission chains of 4 or more from a single infected individual), whereas those of R 0 > 0:6 have a much higher probability of long chains (Farrington and Grant 1999) . Viruses with an R 0 near 1 are especially prone to evolve above the epidemic threshold both because they are likely to experience long transmission chains and because they need little increase in R 0 to exceed the threshold (Antia et al. 2003) . Based on population size considerations, it might also seem that adaptive vaccine evolution increases directly with the number of individuals vaccinated, but herd immunity generated by mass vaccination will reduce opportunities for transmission and thus restrict evolution.", "5 The old way: haphazard, no control over attenuation or recovery" ] },{ "paper_id": "399cef5a5c8ca96a0ac33ee31dec722eac145a7b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mycelial plugs of Magnaporthe oryzae strain S-0412-II 1a, naturally infected with Magnaporthe oryzae chrysovirus 1 strain A (MoCV1-A) (45) were incubated in 0.5% yeast extract and 2% glucose liquid broth (YG broth) with reciprocal shaking (60 rpm) at 25\u00b0C for 2 weeks in the laboratory of Prof. Teraoka (Tokyo University of Agriculture and Technology). Colonies of a diatom on tidal rocks in Tokyo Bay (35.3405\u00b0 N, 139 .6396\u00b0 E) were sampled in April 2014. After washing with distilled water, the colonies were stored at -80\u00b0C.", "The data sets supporting the results of this study are available in the GenBank database repository (accession nos. DDBJ: AP014890-AP014920) and Short Read Archive database (accession no. DDBJ: DRA003723 and DRA003724).", "Multiple alignments based on the deduced aa sequences of putative RNA-dependent RNA polymerase (RdRp) genes in dsRNA contigs were obtained using ClustalX 2.0 (23) and MEGA5 software (42) . Phylogenetic analyses were conducted using MrBayes 3.2.3 (36) with the model of aa substitution, RtREV+I+G+F, selected by ProtTest2.4 (1), as judged by the Akaike information criterion (33) . Bayesian analyses with the covarion parameter were run with one run and four chains for 1,000,000 generations.", "Ultrasound was used to fragment cDNA in Snap-Cap micro-TUBEs at 4\u00b0C using a Covaris S220 (Woburn, MA, USA). The fragmentation conditions were as follows; run time 55 s, peak power 175.0 W, duty factor 5.0% and 200 cycles/burst. The Illumina library was constructed with KAPA Hyper Prep Kit Illumina platforms (Kapa Biosystems, Woburn, MA, USA). The quantity of the library was evaluated using the KAPA library quantification kit (Kapa Biosystems). Each 300 bp of the paired-end sequences of each fragment were determined with the Illumina MiSeq platform (San Diego, CA, USA)." ] },{ "paper_id": "39a1d7e4cf03a63037800c831965232d1d259e0f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pol II-transcribed host RNAs are selectively degraded by PA-X during IAV infection", "doi:10.1371/journal.ppat.1005427.g005" ] },{ "paper_id": "39ab5e6b24f55e696076c53f96fc5704ff3ff0f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Using primary cells of conventional cats holds the risk that cultured cells are already infected with FCoVs. Therefore, mock-infected cells were accurately screened to exclude the presence of inherent infected cells. All cells were negative for inherent coronavirus.", "Since cats are euthanized every day in practice, tissues of these animals can be used in research in order to reduce the number of laboratory cats. Therefore, the intestines of euthanized conventional cats were used in this study and were a kind contribution to research by the owners. This study was approved by the Local Ethical and Animal Welfare Committee of the Faculty of Veterinary Medicine of Ghent University (EC2012/043) and informed consent was obtained from all owners. Faecal extracts from SPF cats (Harlan laboratories, Indianapolis, IN, USA) experimentally infected with FECV UCD were used as a source of this enteric field strain. These infection experiments were approved by the Local Ethical and Animal Welfare Committee of the Faculty of Veterinary Medicine of Ghent University (EC2012/042).", "In conclusion, we established cultures of both feline small and large intestinal epithelial cells, providing new and reliable in vitro models for studying enteric pathogenesis processes of FCoVs. These enterocyte cultures were susceptible to different enteric serotype I field strains, while FIPVs were clearly restricted in their replication in intestinal epithelial cells. Two of the enteric strains were further propagated, providing relevant enteric strains for future FCoV research." ] },{ "paper_id": "39aba27d479a1340c398f332053951fb33606dcd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The inherent limitations of using solely publicly available mammalian RLRs sequences should be highlighted, although several studies have used the same source of data for general conclusions about other genes in mammals [43] [44] [45] [46] [47] [48] [49] . The analyses performed ahead use only an individual representative of each included species and therefore, any drawn conclusions should be carefully considered.", "Regarding the LGP2 gene, no clear evidence of recombination was detected. The ML tree obtained (Figure 3 ) supported the monophyly of the nine mammalian orders collected for this gene.", "By detecting the extension of acting positive selection on mammalian RLRs, this study provides further insights into their biological functions in host defense against viral pathogens in general. Differences in these genes across mammalian species may consequently impact downstream immune responses and, as a result, contribute to the species-specific resistance/ susceptibility profiles against many diverse viral pathogens." ] },{ "paper_id": "39ac63ed0923e3bc5533c2f7998d5b62a828173a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "39ad6d2aa80498b55d03ac9d7f5a4adaaaaf574b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 BECs construct cortical blood vessels and capillaries, including high endothelial venules (HEVs)", "These are a type of BEC PNAd + in histology" ] },{ "paper_id": "39b4ca41bed615d00441db0664ce67e473e74ba5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The server is implemented on Red Hat Linux and Apache (2.2.17) in back-end and front-end of web interface is implemented with PHP (5.2.14).", "Where n is the size of test set, E i pred and E i act is the predicted and actual efficacy respectively." ] },{ "paper_id": "39b557ab42e265c37acee079b474c73708f197c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Decreased fluorescence intensity of 1-anilino naphthalene-8-sulfonic acid (ANS) with SsTroA upon metal loading" ] },{ "paper_id": "39c58dbaa3f69e91698b2efe6d3b12504aa3904d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "39cf0b0febc53a4655489e3e458a93585b68093d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The dry tubes were centrifuged (4380\u00d7 g, 5 min), and serum free from any apparent hemolysis was aspirated for further analyses. AST and CPK activity were determined using automated clinical biochemistry analyzer (Miura One, ISE. S.r.l., Albuccione, Italy). TSP concentration was measured by refractometer technique (Reichert Rhino Vet 360, Munich, Germany). For all measurements, Pointe Scientific (Canton, USA) reagents, standards, calibrators, and controls were used.", "Endurance riding is an equestrian sport, involving completing the distances from 40 km to 160 km, depending on the age and sport level of horses, confirmed by previous finishing competitions required by the regulations. All distances are divided into loops, 20 km to 40 km each, with a time check and obligatory veterinary inspection (vet gate), in order to detect if the horses are fit to continue the ride. Horses with irregular gait or metabolic abnormalities are eliminated from competitions.", "Another parameter that increased significantly only after competition was WBC. Higher WBC values are likely to be a combined result of hemoconcentration and the release of neutrophil marginal and splenic pool triggered by adrenaline, noradrenaline, and cortisol [29] ." ] },{ "paper_id": "39cf63270ea4247abd489125c9d3c78d8f400987", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Modified Eagle Medium (DMEM), while COS7 cells (ATCC CRL-1651) were cultivated in Minimal Essential Medium (MEM). All cell culture media were supplemented with 10% fetal calf serum, 2 mM L-glutamine, 100 U/mL penicillin and 100 \u00b5g/mL streptomycin. The cell lines were obtained from collaborators, and the identity of the human cell lines was verified by STR typing [48] .", "Rabbit anti-GFP polyclonal serum (BioVision, Milpitas, CA, USA) was used for immunoblot at 1:500 dilution. IFITM proteins were detected with a mouse monoclonal anti-IFITM1 antibody (Proteintech Group, Manchester, UK; diluted 1:500) and a rabbit anti-IFITM2 antiserum, which is cross-reactive with IFITM3 (Proteintech, Chicago, IL, USA; diluted 1:1000).", "Oligonucleotides were purchased from Sigma-Aldrich (St. Louis, MO, USA): hIFITM5-5Not 5 -CCGCGGCCGCACCATGGACACGGCGTATCCCCGCGAG-3 , hIFITM5-i3 5 -ACCACCTTCTGATCTCGGGCCTTGATGGAGTAGGCCAGCG-3 , hIFITM5-i5 5 -CGCTGGCC TACTCCATCAAGGCCCGAGATCAGAAGGTGGT-3 , hIFITM5-3Eco 5 -CGAATTCTCAGTCATA GTCCGCGTCATCAAAC-3 , Mem-AccAge-for 5 -GTACCACCATGCTGTGCTGTATGAGAAG AAC CAAACAGGTTGAAAAGAATGATGAGGACCAAAAGATA-3 , Mem-AccAge-rev 5 -CCGGTATC TTTTGGTCCTCATCATTCTTTTCAACCTGTTTGGTTCTTCTCATACAGCACAGCATGGTG-3 , Myr-Pal-GFP-5E 5 -CGAATTCACCATGGGCTGCATCAAGAGCAAGCGCAAGGACAACCTGAACGAC GACGAGCCACCGGTCGCCACCATGGTG-3 , SV40pAseq 5 -GAAATTTGTGATGCTATTGC-3, HCM Vep-seq 5-GCAAATGGGCGGTAGGCGTG-3 , ScyFP-Ger 5 -GGAATTCTCACAAGACAAGGCACCC AGAAGATCTGAGTCCGGACTTG-3 , EIF3-5Esp 5 -GACGTCTCAGGCCACGCGTGCTAGCACC ATGGTGAGCAAGGG-3 , SV40pAseq 5 -GAAATTTGTGATGCTATTGC-3 , IFITM3-5N 5 -GCGCG GCCGCACCATGAATCACACTGTCCAAACC-3 , mut-IFITM3-F75AF78A-rev 5 -GACTTCACGGAG TAGGCAGCTGCTATGGCGCCCAGGCAGCAGGG-3 , mut-IFITM3-F75AF78A-for 5 -CCCTGCT GCCTGGGCGCCATAGCAGCTGCCTACTCCGTGAAGTC-3 , pCAGGS-3 5 -CAGAAGTCAGATGC TCAAGGG-3" ] },{ "paper_id": "39d94b291715335c79664305706e67a752304121", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A prospective, hospital-based, study was conducted at CEN-HOSOA from November 2010 to July 2012.", "The case definition and eligibility criteria used during this study are described in figure 1 .", "Demographic, socio-economic, clinical and epidemiological data were recorded in case report forms (CRFs). Paediatricians completed the CRFs which were then validated by a clinical research officer. Instruction sheets were provided to clinical research officers to ensure accurate data collection. The data collected was managed by a senior medical epidemiologist." ] },{ "paper_id": "39e066c95d89964b9cd608c14fc5e2077706e72e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ng also shared the requirement for clinical practice: sequencing results should ideally be available within 1 day to stop and/or prevent outbreaks.", "The panelists were Patrick Wilson (University of Chicago), Oon Tek Ng (Tan Tock Seng Hospital, Singapore), Colin Brenan (HiFiBio), and Evan Newell (Singapore Immunology Network). The panel was moderated by Katja Fink (Singapore Immunology Network)." ] },{ "paper_id": "39e643e0263bee019519c0c51f4ae17f1fe1a0a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data generated or analyzed during this study are included in this published article.", "Ethics approval and consent to participate Not applicable.", "The authors would like to thank college student Simba Mugadza for offering encouragement." ] },{ "paper_id": "39e7645f7139f5677b413f08ef3bfecf1a1e9e66", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "According to the international health regulations, this case has been notified to the European Union Member States and the European Centre for Disease Prevention and Control (ECDC) through the Early Warning and Response System (EWRS) and to the World Health Organization (WHO).", "The initial diagnostic routine was limited to testing for the influenza A virus matrix gene, without subtyping. In view of the severe course of illness, the child was resampled for repeated testing including typing of the haemagglutinin (HA) gene by quantitative real-time PCR for H1 (seasonal and pdm2009), H3, H5, H7 and H9. All typing PCRs were negative.", "Severe acute respiratory infection caused by swine influenza virus in a child necessitating extracorporeal membrane oxygenation (ECMO),", "We here describe that transmission of SIV to humans, though rare, can occur and cause severe disease requiring life support through ECMO. Monitoring of people in direct contact and not wearing personal protective equipment revealed no secondary cases." ] },{ "paper_id": "39eadd11ec6d5021711bcfa21f0cb6e183242c71", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.", "SARS-CoV S protein mediated entry is restricted by IFITM1, 2, and 3" ] },{ "paper_id": "39f1634046dffbbb7da9f5ef69fa08bdb7b7096f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "39f33cf580fe6ce842e2c9005570d08115c3ed4b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cultures were harvested at 48 h post-drug treatment, which was 72 h postinfection.", "Statistics. Statistical tests were performed using GraphPad Prism 7 software (La Jolla, CA) as described in the respective figure legends.", "Viruses. All work with MHV was performed using the recombinant WT strain MHV-A59 (GenBank accession no. AY910861) (54) . SARS-CoV expressing green fluorescent protein (SARS-GFP) and MERS-CoV expressing red fluorescent protein (MERS-RFP) were created from molecular cDNA clones according to protocols described previously (29, 57) ." ] },{ "paper_id": "39fae6df128e98e970b22ea35cebdaaac78a647e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "To be able to incorporate spatial covariate and to model the continuous variable, age using smooth function, we adopt the logistic model with structured additive predictors defined as:", "Middle East respiratory syndrome coronavirus is a contagious respiratory pathogen that is contracted via close contact with an infected subject. Transmission of the pathogen has occurred through animal-to-human contact at first followed by human-to-human contact within families and health care facilities." ] },{ "paper_id": "3a1c74872d4e0aa20076dc1f3970d9ff42991847", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics. This study has been approved by the Institutional Review ", "Social encounter patterns are an important driver of the spread of infectious diseases requiring close contact for transmission, particularly for respiratory viral pathogens [3] . Quantifying such behaviours enables improved modelling of epidemics for a variety of purposes, and helps identify effective interventions aimed at reducing transmissions.", "Interviewers reviewed the contact event information and confirmed the information with the participant where multiple contacts had the same or similar names or descriptions. In turn, eligible participants in the household were interviewed. The above procedure was repeated in each wave of recruitment. Participants who agreed to complete the questionnaire were compensated with HKD20 of supermarket vouchers for each interview in which they participated. Individuals were permitted to participate in subsequent waves even if they missed one or two waves." ] },{ "paper_id": "3a2f058d14f4b6db1e7191a2ed2634d5c5699455", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Transfection. Transfection was done using Lipofectamine 2000 or 3000 (Invitrogen) as per the manufacturer's protocol. For transfection related to immunoprecipitation, after 6-7 h post transfection, MG132 was added to the transfected cells to a final concentration of 0.5 \u03bcM and incubated for further 30-40 h.", "ImageJ image analysis. Western blot densitometry: an area of interest was selected on the smeary part above the protein bands shown in the immunoblots. Mean density of the selected area was then calculated.", "For endogenous protein detection, mock or HCMV-infected HFFs (grown in sixwell plate) were lysed in 30 \u03bcl of standard cell cell lysis buffer and~8 \u03bcg of protein was loaded to each well." ] },{ "paper_id": "3a324b07dddba6a95b23d5cf90c4f0756b87afe4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Using these parameters, the expression for the expected number of case counts for a given week, E (Y) is given by:" ] },{ "paper_id": "3a39684ab2bd22b39597a985ed3c57794a941a82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For a more detailed description of this materials and methods section, we refer to Additional file 6: Supplementary Methods.", "For the microbiota data, statistical significance between contrasts with regard to taxonomy abundances was tested by a non-parametric (unpaired) Mann-Whitney U (MWU) test, corrected with false discovery rate (FDR) for multiple testing; unless stated otherwise. Multivariate redundancy analysis (RDA) and principal component analysis (PCA) was done using Canoco 5.04 [52] . For all other experimental data (i.e., protein measurements, metadata, etc.), statistical significance was tested likewise using a non-parametric Kruskal-Wallis one-way ANOVA, with Dunn's correction for multiple testing (GraphPad Prism 5.0), unless stated otherwise." ] },{ "paper_id": "3a3c6a9ff71461bd81862fc711d5605cfbbb975d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We are thankful to the R community for sustaining the development of free, open-source statistical software, to github (http://www.github.com) for providing code hosting facilities, and to travis (https://travis-ci.org/), appveyor (https://www.appveyor.com/), and codecov (https://codecov.io/) for providing free resources for unit testing. The funders had no role in the design of the study, the collection, analysis, and interpretation of data and in writing the manuscript.", "Determining 'who infected whom' during an outbreak can yield precious insights into transmission dynamics of an infectious disease and subsequently inform infection control policies. Transmission tree reconstruction has been used to specify the contribution of individual cases and locations to overall transmission [1] , characterise heterogeneous infectiousness within outbreaks [2, 3] , evaluate the impact of control measures on transmission intensity [4, 5] and identify transmission routes [6] . Consequently there exists significant interest in designing methodologies for the inference of transmission trees from outbreak data, including temporal data (e.g. date of symptom onset), contact data, pathogen whole genome sequences (WGS) and geographic locations.", "A prior distribution describes the probability of observing a parameter given our previous knowledge of the infectious disease under observation. In outbreaker2, custom priors are specified as functions with a single argument of class outbreaker_param, which return a log-probability of a given parameter value (all probabilities are treated on a log scale). Custom priors can take any shape as long as this structure is satisfied. Priors can be specified for each parameter in the model by passing a named list of functions to the priors argument of the outbreaker function. " ] },{ "paper_id": "3a4cf1cc2f583dea77288aa7e114c117a00660b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results of investigations performed on presentation included chest radiography (signs of consolidation and pneumonia), simple hematologic blood analysis including hemoglobin level (Hgb) and leukocyte count (WBC), and C-reactive protein (CRP). Because we did not have sufficiently complete data (>60%) on some laboratory determinations for the entire sample (including platelet count, other serum biochemistry tests and clotting profile), we excluded these determinations from the analysis for all patients.", "Additional information collected included age, sex, history of any poultry exposure, including exposure to live poultry markets within two weeks of symptom onset, influenza vaccination history, smoking history, pregnancy, history of underlying medical conditions, height (m), weight (kg) and clinical symptoms.", "Our objective in this study was to develop a clinical prediction rule that would accurately identify patients with A(H7N9) influenza on their first presentation to a hospital emergency setting and to evaluate the predictive performance of this rule.", "The collection of data from confirmed A(H7N9) cases was determined by the Chinese National Health and Family Planning Commission as part of public health investigations of emerging influenza outbreaks and was exempted from institutional review board assessment. Collection of data of SARI cases was approved by the ethical review committee of the China CDC. Therefore, informed consents from the cases were not required.", "In the context of preparing and responding to further waves of this evolving epidemic, the importance of early detection, diagnosis, isolation and reporting of A(H7N9) infections has been repeatedly emphasized [8] . Accurate and objective risk prediction can help physicians to guide clinical management and inform triage decisions * Correspondence: yuhj@chinacdc.cn \u2020 Equal contributors 1 for optimizing the utilization of valuable clinical and public health resources that may easily be overwhelmed during an epidemic. However, no simple and reliable decision tool has yet been available for predicting the risk of A (H7N9) influenza in an objective and timely manner." ] },{ "paper_id": "3a5bfccbd47694771018f0ee03b0eeedfeeb2ef9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "with c i indicating the country of district i. The observed incidence I i (t) is assumed to be Poisson distributed [32] . The dispersion term m i,j distributes the migrants over the other districts following a gravity-type model [19] :", "The model parameters are estimated in a Bayesian MCMC analysis. For the reproduction numbers R, a vaguely informative gamma prior is used with mean 1 and shape parameter 2." ] },{ "paper_id": "3a60c19b5cc401e24f815f8924010e77bed7579d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasma was separated from peripheral blood samples by centrifugation. Plasma samples were aliquoted and immediately frozen and stored at \u2212 80\u00b0C for later determination of cytokine concentrations.", "Remaining cells were resuspended in RPMI (Roswell Park Memorial Institute)-1640 medium (Sigma-Aldrich, St. Louis, MO, USA). Cells were incubated with PMA (phorbol 12-myristate 13-acetate) (50 ng/ml), ionomycin (1 \u03bcg/ml), and BFA (Brefeldin A) (10 \u03bcg/ml) for 6 h at 37\u00b0C to allow intracellular accumulation of cytokines.", "In this paper, we present four NAIS cases, in whom detailed analysis of intracellular and plasma cytokine levels are available from immediately after birth until the first month of age. To our knowledge, no such information is available in humans in NAIS; therefore, the data presented could serve as a basis for future, larger-scale case-control studies." ] },{ "paper_id": "3a676f4ebe85b17d5aedd055c0af967760e13e64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Antagonism of viral assembly, e.g., competitive inhibitors of trimmer formations or required cleavages.", "\u2022 Cell-targeting antibodies (CTAb) that require Fe receptor (FeR) interaction for manifestation of antiviral effect.", "Presaged in mice newly designed with knock-in human FcR to examine tumor immunity (26) threshold of activity that is itself variable. Some of these are more widely familiar than others, as described next.", "In experimental animal models, a range of Ab doses is preferred." ] },{ "paper_id": "3a693a23a7b7c13330611d995ea9d8861203c8b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The possibilities of transmission are potentially high during capture, transport and release. Emerging parasites in new hosts are becoming more evident as diagnostic techniques are refined, wildlife-human-domestic animal interactions increase and new diseases are identified [18] .", "Anaplasma phagocytophilum (formerly Ehrlichia phagocytophila, Ehrlichia equi and Anaplasma phagocytophila) is the causative agent of granulocytic ehrlichiosis (anaplasmosis) in humans, horses, sheep, cattle, dogs and cats.", "Bartonella vinsonii subsp. berkhoffii was originally isolated from a dog with infectious endocarditis and was recently identified as a zoonotic agent causing human endocarditis. An epidemiological study was conducted following a child bitten by a coyote who developed clinical signs compatible with Bartonella infection in California. Among 109 coyotes from central coastal California, 31 animals (28%) were found to be bacteremic with B. vinsonii subsp. berkhoffii and 83 animals (76%) presented antibodies. These findings suggest these animals could be the wildlife reservoir. Further studies are necessary to elucidate the mode of transmission especially to identify potential vectors and to determine how humans become infected [31] ." ] },{ "paper_id": "3a6f6369bb9df09d06938f9ef8fdceb72de53a21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Respiratory tract infection etiology is complex and diverse, and new pathogens are continuously being reported. Over the past few years, several novel respiratory viruses including human metapneumovirus (hMPV) [1], severe acute respiratory syndrome (SARS) coronavirus [2] , human coronavirus NL63 (HCoV-NL63) [3, 4] , and coronavirus HKU1 (HCoV-HKU1) [5] [6] [7] have been identified." ] },{ "paper_id": "3a6fd660f0d9555bdf2ba3b89120c82911386f51", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antimicrobial resistance gene profiling of Salmonella ser.", "In the summer of 2016, several Midwestern premises raising bottle-fed calves experienced striking losses in dairy bulls purchased from sale barns. Death rates, usually dictated by neonatal diarrhea which is very common in sale barn calves, increased 5-10-fold. Illness was subsequently found in dairy heifers as well. Disease was apparent even when best practices were used: it affected quality calves given space and comfort, on a good plane of nutrition, with no failure of passive transfer. Sporadic cases were also found dating back to 2014 in our database (see Table 1 ).", "Sequencing library was prepared using Nextera XT kit (Illumina Inc. San Diego, CA). Concentration of the DNA samples were adjusted to 0.3 ng/\u00b5l prior to processing. After bead normalization, DNA libraries were pooled at equi-molar concentration. Pooled libraries were then sequenced on Illumina Miseq platform (Illumina Inc., CA) using V2 chemistry to generate 2\u00d7 250 paired end reads." ] },{ "paper_id": "3a744992aeec8bfdcfc35035187791f3c8613f41", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3a83391556631ba5fbdbef16900ceed1619d69f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Laboratory-acquired infections (LAIs) are caused by accidental exposure to infectious aerosols and contact with mucous membranes, even though LAIs have been decreased due to personal protective measures and biosafety training [1, 2] . Pike et al. reported that 4,079 LAIs resulting in 168 deaths occurred in the United States from 1930 to 1978 [3, 4] . Thereafter, Harding and Byers identified 1,267 LAIs resulting in 22 deaths [5] . According to Siengsanan-Lamont et al., 27 LAIs occurred between 1982 and 2016 in the Asia-Pacific region [6] . In these instances, the a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.pone.0225177.g003", "https://doi.org/10.1371/journal.pone.0225177.g006" ] },{ "paper_id": "3a8c6a1683a063b6fc3c1bd689ff9c1b83723b4e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Demographic and clinical information was obtained from participants using a standardized questionnaire." ] },{ "paper_id": "3a8f3c3b8c4be0144795e7dc34472a9a7dd35cc5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data describing C. jejuni counts and in vitro assays were analyzed using one-way ANOVA followed by Tukey's Multiple Comparison adjustment. A value of P < 0.05 was considered statistically significant for all experiments. Measurements were expressed as mean \u00b1 SE (standard error) and represent averages of three replicates. For microarray data analysis, linear regression models were used for comparisons among different treatment groups.", "mild growth: less than 100 CFU), ++ = (moderate growth: less than 300 CFU), +++ = (heavy growth: too many to count), -= (No Growth), N/A, Not applicable; a Ewe (G3-V-2) no C. jejuni was isolated from any tissues; however, at postmortem this ewe was found to be heavily infested with tapeworm.", "S. Intestine --+ + + + + + + + + + + + + + + + + + -(highly congested) - " ] },{ "paper_id": "3aa75376556fa96324ad4cacb0b862ad86b7a11e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "genome [58] . This vector contains DsRed under the control of a late p11 promoter to allow for visual based selection and permits an easy distinction between recombinant (red) and wild-type (green) viruses (Fig. 1A) .", "Background: Chikungunya virus (CHIKV) is a re-emerging arbovirus associated with febrile illness often accompanied by rash and arthralgia that may persist for several years. Outbreaks are associated with high morbidity and create a public health challenge for countries affected. Recent outbreaks have occurred in both Europe and the Americas, suggesting CHIKV may continue to spread. Despite the sustained threat of the virus, there is no approved vaccine or antiviral therapy against CHIKV. Therefore, it is critical to develop a vaccine that is both well tolerated and highly protective." ] },{ "paper_id": "3aae9e36468d7e3e26825d23997b612d7ce755b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords: CD9, tetraspanin, inflammation, hematopoietic cells, cancer, lung allograft dysfunction, infections, hypersensitivity", "Tetraspanin proteins are ubiquitously expressed and consist of 4 transmembrane domains, an intracellular terminus and 2 extracellular loops (1) . Tetraspanins function as organizers of the cell surface by recruiting specific partner proteins into tetraspanin-enriched microdomains (TEMs) (2) . Bringing together a large variety of molecules and amplifying their activities, tetraspanins regulate various cellular processes, such as cell adhesion, motility, growth, differentiation, signal transduction, and sperm-egg fusion (3-5) (summarized Table 1 ). ", "Finally, anti-CD9 is also tested for its anti-adhesive properties to inhibit bacterial adhesion to keratinocytes and has been shown to be effective in a tissue-engineered model of human skin infected with Staphylococcus aureus suggesting that CD9 inhibitors may be a valuable addition to current treatments of skin infection and underscore the potential of targeting CD9 in bacterial infectious diseases (99) .", "The extravasation of leukocytes from the bloodstream to sites of infection involves a complex series of events, which are dependent on interactions between the leucocyte and the apical membrane of the endothelial cells (36) . CD9 promotes endothelial-leucocyte adhesion by co-localizing with adhesion molecules ICAM-1 and VCAM-1 at the apical endothelial cell surface, reinforcing the adhesion of the leucocyte to facilitate extravasation (37) (Figure 5) . Furthermore, knockdown of CD9 results in reductions of ICAM-1 and VCAM-1 surface expression, thus reducing leucocyte adhesion and transmigration (64) . Taken together, CD9 appears as a key regulator of leucocyte recruitment during the inflammatory cascade." ] },{ "paper_id": "3ab1d505d3521db73f63ef84163a41fa2f3dbdf6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analgesic, anesthetics and tranquillizing drugs were used when appropriate under supervision of Veterinary Services. Veterinarians and herdsmen used cattle chute for restraining when needed. Cattle were not restrained for more than four hours per day.", "The bovine genomic BAC library (CHORI-240) was purchased from Children's Hospital Oakland Research Institute and screening was performed, according to their instruction.", "(XLSX)" ] },{ "paper_id": "3ab8bf523ee26f6e2f7d3cf11d757f8b449d9dcd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3ac512d142c583daae040f2dc71312ea804b4f0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All virus and host phylogenetic trees and virus sequence alignments are available at github. com/jemmageoghegan.", "Virus genera were excluded either due to lack of available data or because we were unable to obtain a reliable alignment of sufficient length for phylogenetic analysis (i.e. at least 100 amino acids after trimAl pruning). (DOCX) S3 Table. Overall nPH85 distances, means and 95% percentiles between two unrooted phylogenetic trees for each virus family determined using the normalized Penny and Hendy [14] topological distance method, implemented in in NELSI v0.1 [45] . The overall nPH85 distances are illustrated in Fig 2 in ", "Emerging infectious diseases are often characterized by host switching events, in which a pathogen jumps from its original host to infect a novel species. However, given the ecological and genetic barriers a virus must overcome to jump species and adapt to new hosts, it might be reasonable to assume that successful cross-species transmission is a relatively rare occurrence and that viruses are instead more likely to co-diverge with their hosts. Using a comparative co-phylogenetic analysis performed at the scale of virus family a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Gene sequence data of viruses were obtained from GenBank (Table 1; see S1 Table for all Gen-Bank accession numbers). Following a broad and comprehensive survey of all virus genomic data available on GenBank, a total of 19 family-level virus data sets passed our selection criteria and were included in the analysis. These selection criteria, which are independent of whether the viruses have evolved by co-divergence or cross-species transmission, were: (i) the availability of virus sequence data that included a wide range of distinct and diverse virus species that is representative of the virus genera currently available; (ii) the availability of data with informative genomic regions that can be used to reveal evolutionary relationships (e.g. the RNAdependent RNA polymerase-see Table 1 ) and that were not so divergent as to prevent reliable sequence alignment; and (iii) the virus sequence data met a minimum length requirement of 100 amino acids following alignment and the removal of any ambiguously aligned regions." ] },{ "paper_id": "3acb357dc20a411ef495ab53d242e5a0454cd1fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2) local, unilateral, or bilateral coarse breath sounds, with or without local moist rales, central cyanosis, tachycardia (>100/min), and tachypnea (>24/min);", "(5) arterial blood gas analysis showing continuous hypoxemia accompanied by mild respiratory alkalosis;", "(4) routine blood test findings include an increased white blood cell count and an increased neutrophil count;" ] },{ "paper_id": "3acc047295ee11b02f13aac787a12fe114d58558", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequence data were analyzed using computer programs such as DNAMAN and DNASTAR. Phylogenetic analyses were performed by the neighbor-joining method using MEGA (version 5.05; http://www.megasoftware.net/). Previously published GETV sequences used in this study include sequences YN08 isolates MM2021 (from Malaysia,", "Acute encephalitis syndrome (AES) was observed in suckling mouse with growth retardation, panting, abdominal breathing, and arthritis (data not shown). Negative-staining electron microscopy (EM) of the supernatant from infected suckling mouse brain (named YN08) revealed virus-like particles ( Figure 1 ). These particles were spherical in shape, with an envelope, and approximately 50-70 nm in diameter, consistent in size and morphology with that of Togaviruses or Flaviviruses.", "GETV was observed by EM. Preparation of the sample from a 1/10 volume of the brain extract from suckling mice included extraction with chloroform and incubation of the mixture for 30 min at 4\u00b0C. The extract was then centrifuged at 13 800 \u00d7 g for 30 min. The precipitate was resuspended in 5 mM phosphate buffered saline (PBS; pH 7.2) and negatively stained with 2% phosphotungstic acid. Specimens were examined using a transmission electron microscope (Hitachi-8100, Japan) at 80 kV." ] },{ "paper_id": "3adfcb05fa2004182d3c232a69429d2b1adfe12f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Electrochemical synthesis 4.8 Dry oxygen-free solvents were used under an argon atmosphere. [55] .", "The film, as a cathode, was ion exchanged to desired Ag contents in AgNO 3 solutions and then reduced electrochemically [56] .", "A platinum was employed as cathode and anode [57] ." ] },{ "paper_id": "3ae4cc1c1b639a21e95972d63cfe5822b96d136d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The associated risks can be reduced through the correct use of protective equipment such as face masks, gloves and sterile utensils to prevent contact with raw and bloody poultry. Further intervention should include the provision of additional education to the population through a range of health promotion mechanisms (including social media) as to how to handle potentially infectious meat to hygiene standards imposed as a feature of standard food preparation HACCPs in the retail food industry.", "Approximately 80% of the Vietnamese population live in rural areas and almost 80% of these rural households participate in small-scale (backyard) poultry production [12] . The Red River and Mekong River deltas are major poultry producing areas from which poultry and their products (e.g. eggs, faeces, feathers) may be transported directly to the point of sale by the breeder or pass through a number of middle-men in the trade chain.", "The H5N1 virus can survive in poultry carcasses kept at room temperature for several days or longer at cooler temperatures [26] . Human infection with the H5N1 virus is associated with recent exposure to live poultry [25] , direct contact with dead poultry [27] and the preparation or cooking of sick or dead poultry [28] [29] [30] . As a result, poultry market workers and poultry slaughterers are at particular risk of human HPAI H5N1 infection [24] .", "Preparing poultry for human consumption is the first stage of the trade chain when non-farmers are introduced to a high-risk opportunity to contract HPAI viruses. Two key CCPs concern poultry slaughtering and carcass preparation; this refers to the slaughter of poultry both at home and in the wet markets." ] },{ "paper_id": "3aeb264d986c987ced699cb2c711eb022b697d5a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and", "where a,b,c,d are parameters,", "The equations that fit the curvilinear patterns of the base distributions with reasonable statistics are of the form" ] },{ "paper_id": "3aeb4a0f6893b933dc061157d196e5618380c63b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral DNA was extracted from 200 \u00b5L of positive cell culture supernatants using a BioSprint 96 One-For-All Vet Kit (Qiagen S.p.A., Milan, Italy). Sequencing libraries were made with a Nextera Flex kit (Illumina Inc. San Diego, CA, USA) in accordance with the manufacturer's instructions. Libraries were sequenced on a MiSeq Instrument (Illumina Inc. San Diego, CA, USA) by using a MiSeq Reagent Kit v2 in a 250 cycle paired-end run. Data were assembled de novo by the CLC Genomic workbench v.11 (Qiagen S.p.A., Milan, Italy).", "When the seven conserved genes-RPO147, RAP94, mRNA capping enzyme large subunit, P4a precursor, RPO132, VETF-L, and DNA primase-were considered individually, the value of nt similarity with EPTV ranged from 90.5% to 98.5%. The above conserved genes that have been used for phylogenetic analysis in previous studies [10, 12] are presented in bold in Table 3 .", "In recent decades, bats have been increasingly recognized as reservoirs of emerging viral infections, which has important ramifications for animal and public health [3] . However, the majority of bat-borne viruses that can cause severe diseases in humans and other mammals, do not cause apparent clinical signs in bats. Consequently, it has been assumed that bats may have a \"special\" relationship with viruses based on physiological, ecological, evolutionary, and/or immunological aspects, which allow them to act as special viral reservoirs with exaggerated viral richness [4] [5] [6] [7] ." ] },{ "paper_id": "3aed588044335032787a5eb91ee61afadcd4a006", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As stated, all the antagomiRs employed successfully reduced the pathological changes, starting from cellular level, in vivo, without evidence of inefficacy on the samples studied.", "\u2022 Strong evidence confirmed that miRNAs play a crucial role in several pathologic mechanisms, therefore they have been proposed as diagnostic or prognostic biomarkers and therapeutic targets for future treatments. \u2022 AntagomiRs are chemically modified oligonucleotides able of silencing microRNAs and are now emerging as novel therapeutic agents in several conditions.", "Coherence between these groups has been demonstrated, thus suggesting the importance of developing new studies on these agents as target therapies." ] },{ "paper_id": "3af2a50a4711db48012cf6972cb579f85cf1da40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The classification of an infectious agent as airborne and therefore 'aerosol-transmissible' has significant implications for how healthcare workers (HCWs) need to manage patients infected with such agents and what sort of personal protective equipment (PPE) they will need to wear. Such PPE is usually more costly for airborne agents (i.e. aerosol-transmissible) than for those that are only transmitted by large droplets or direct contact because of two key properties of aerosols: a) their propensity to follow air flows, which requires a tight seal of the PPE around the airways, and b) for bioaerosols, their small size, which calls for an enhanced filtering capacity.", "One should note that \"aerosol\" is essentially a relative and not an absolute term. A larger droplet can remain airborne for longer if ambient airflows can sustain this suspension for longer, e.g. in some strong cross-flow or natural ventilation environments, where ventilation-induced airflows can propagate suspended pathogens effectively enough to cause infection at a considerable distance away from the source.", "For human influenza viruses, the question of airborne versus large droplet transmission is perhaps most controversial [54] [55] [56] [57] . In experimental inoculation experiments on human volunteers, aerosolized influenza viruses are infectious at a dose much lower than by nasal instillation [58] . The likely answer is that both routes are possible and that the importance and significance of each route will vary in different situations [16, 20, 21] .", "Chickenpox Chickenpox is a febrile, vesicular rash illness caused by varicella zoster virus (VZV), a lipid-enveloped, double-stranded DNA virus, and a member of the Herpesviridae family." ] },{ "paper_id": "3b124808cb49c3530b23b6fda834fcbbc8af1988", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Optimal control and stochastic programming models", "These are dynamic optimization techniques that aim to find the optimal way to control a system over time.", "Additional file 1: Figure S1 . PRISMA 2009 study flow diagram." ] },{ "paper_id": "3b1fca9311e0efc4368f3775dd878f57c5978a5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and LDLR probe, FAM-AC-CTGTGTCTGCCAGCTCCACA-3IABkFQ.", "b-actin F, CCCACGCCATCCTGCGTCTG;", "b-actin R, GTAGCCCCGCTCCGTCAGGA;" ] },{ "paper_id": "3b2a2a17eb789fee6c46ff6cdc7b6e794f7d545c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Epidemics of acute respiratory infections (ARI), whether due to influenza [1, 2] , coronaviruses [3, 4] , or other pathogens [5, 6] , could overwhelm even the most developed health care systems. It is imperative to recognize these epidemics as early as possible, as the passage of time quickly degrades the effectiveness of mitigating measures [7] .", "where t is the time series index, Y (t) is the observed case count on that index day, Y Y (t) and S(t) are respectively a 7-day moving sample mean and a standard deviation calculated with a 2-day lag from the index day. The value of S(t) was replaced by 1 if S(t),1. The method signaled when the value of the W2c statistic exceeded a given threshold." ] },{ "paper_id": "3b3bb498af6f356f4389825f4f3b026edcaef4f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical tests were two-sided. A p-value of < 0.05 was considered to indicate statistical significance. All of the analyses were performed using R version 3.5.1.", "Supplementary information accompanies this paper at https://doi.org/10. 1186/s12931-019-1201-0." ] },{ "paper_id": "3b4888c664b3d2fa758325160b185a453b6f8bb4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Several viruses may cause infectious and postinfectious complications in the nervous system (Table 1) . Despite advances in molecular techniques a specific cause is found in less than half of the cases [32] .", "Despite effective antiviral therapy for certain chronic viral infection (e.g. Hepatitis B), the virus can integrate its genome into the host cell and become latent. Therefore, new therapies that can completely remove viral components integrated in host cells are needed [13, 113] .", "The authors report no competing interests. ST is a principal investigator in a multinational, multicenter clinical study evaluating zanamivir vs oseltamivir, sponsored by GSK. " ] },{ "paper_id": "3b5ea760c63aaff964de32541643d92c69dfc05e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In July 2015 raw sewage (130 L) was collected at the waste water treatment plant BIOFOS Lynetten in Copenhagen, Denmark, receiving waste water from about 550,000 inhabitants. Approval was granted from BIOFOS Lynettefaellesskabet A/S before sampling. The sewage was mixed thoroughly in a single container and spiked to a concentration of 1.74\u00d710 8 RT-PCR units/L of murine norovirus (MNV) (kindly provided by Dr Virgin, Washington University School of Medicine, USA), and 2.13\u00d710 9 genome copies/L of human adenovirus 35 (HAdV). The sample was mixed for 5 min before aliquoted and stored at-20\u02daC until further processing.", "To investigate the correlation between viral concentrations and RPM, qPCR data was compared with read counts from the two spiked viruses, HAdV and MNV. There was a strong correlation between RPM and qPCR enumeration for HAdV (R 2 = 0.82). However, no relationship was observed for MNV (R 2 = 0.07).", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Nucleic acids were extracted from 200 \u03bcL-portions of the respective viral concentrate using four different extraction kits; NUC (Macherey-Nagel, D\u00fcren, Germany), QIA (Qiagen, Valencia CA, USA), MIN (BioMerieux, Herlev, Denmark) or POW (MO BIO, Carlsbad, CA, USA). In all cases, extractions were carried out according to manufacturer's instructions." ] },{ "paper_id": "3b6d78d18468508dd0b85bc9fc2e1b2e3079ec05", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hypothesis 9 (H9). Individuals with more health resources are likely to perceive risk less than those with less health resources are.", "Hypothesis 5 (H5). Individuals holding a higher vulnerability have an increased risk perception of MERS.", "We calculated Pearson's correlation coefficients to examine the relationships among variables. These results have been presented in Table 3 ." ] },{ "paper_id": "3b7e06a340e084847e969e188f5d2a7789af2f25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "B. " ] },{ "paper_id": "3b9aeb17bc120925271e7443ebaa19f69ed34a25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The intensities of bands from Western blot analysis were quantified using the ImageJ program (National Institutes of Health) according to the developer's instructions.", "The data were presented as mean \u00b1 standard deviations (SD) of three independent experiments. The differences between groups were assessed by Student's t test. A P value < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS.", "Submit your next manuscript to BioMed Central and take full advantage of: " ] },{ "paper_id": "3b9e6b4d9ba3f58a882e5e25dd12d8aed9b5b4d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In 6 out of 12 patients of group A from whom sputum culture was received, a pathognomonic isolation (>10 6 CFU) of bacteria was achieved (3 Streptococcus pneumoniae species, 2 Mycoplasma species and 1 Moraxella catarrhalis). On the other hand from group B only in 8 out of 15 patients a pathognomonic isolation was achieved (5 Streptococcus pneumoniae species and 3 Mycoplasma species).", "Lastly the mean young age of the patients in both groups, and the small number of co-morbidities observed in our sample of patients, possibly were also responsible for having overall mild clinical course.", "All the patients in general, had a mild clinical course and none of the patients had to be admitted in the ICU." ] },{ "paper_id": "3ba1be6ad61854f68d5d05c1bd9b046479a9dafd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "AL and MO planned and designed the whole study. AL and HM collected samples, performed technique, and analyzed the data. KO and MO supervised the project and helped during manuscript writing, crosschecking, and revision. All authors read and approved the final manuscript." ] },{ "paper_id": "3ba2641160cb0acdca16991443017f11d2d848c2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lungs from sacrificed mice were fixed by instilling formaldehyde solution (4%, pH 7.2) through the trachea. Inflated lungs and livers were removed and fixed in phosphate buffered formalin. Tissues were embedded in paraffin and sections (4 mm) were stained with hematoxylin and eosin before being evaluated by light microscopy.", "This study was carried out in strict accordance with German regulations for animal experimentation (German Animal Welfare Act). ", "(TIF)", "Supernatants of the first BAL instillations were collected and pooled from 3 mice. Detection of different cytokines used undiluted BAL fluids for ELISA in triplicates. Measurement of interleukin-6 (IL-6) used a Quantikine ELISA Kit purchased from R&D Systems (Wiesbaden-Nordenstadt, Germany). ELISA for detecting interferon-a (IFN-a) was purchased from PBL Inter-feronSource (distributed by tebu-bio GmbH, Offenbach, Germany). Assays were performed according to manufacturer's instructions and repeated at least three times." ] },{ "paper_id": "3ba5a8bec872feebb62f6a1f384690ba1cd63a8b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For Western Blot analysis, Vero cells cultured in 6-wells were lysed two days post infection (MOI = 0.03) and immunoblotted as previously described 67 . A polyclonal antibody reactive against full-length CLDN6 (1:100) (IBL Co., LTD., Gunma, Japan) was used as primary antibody for mCLDN6, a rabbit anti-Ovalbumin polyclonal antibody (1:20,000) (Novus Biologicals, CO, USA), a rabbit anti-MV-N polyclonal antibody (1:25,000) (Abcam, Cambridge, UK) for MV-N, and a goat \u03b1-rauscher leukemia virus (RLV) p30 antibody (1:20,000) (ATCC). HRP-coupled donkey anti-rabbit IgG (H&L) polyclonal antibody (1:10,000) (Rockland, Gilbertsville, PA) and a HRP-coupled rabbit anti-goat polyclonal antibody (1:10,000) (Dako, Glostrup, Denmark) served as secondary antibodies, as appropriate.", "A lentiviral transfer vector encoding mCLDN6 controlled by hEF1\u03b1 promoter was generated by shuttling mcldn6 ORF into pLenti6.4/R4R2/V5-DEST together with the EF1\u03b1 promoter cassette of pENTR5\u2032 using Gateway \u00ae cloning (Invitrogen). Using conventional cloning techniques, the vector was further modified to encode a hygromycin-T2A-GFP fusion protein downstream of the hPGL promoter to yield pL64B42E(EF1\u03b1-mCldn6) Hygromycin-T2A-GFP. Likewise, the PCR-amplified ORF of hCD46 BC1 was cloned together with an IRES-puro R cassette into pSEW 63 to yield pSEW-hCD46-IRES-puro." ] },{ "paper_id": "3bac7494aeafbb2f2cff25690dac67e99c120029", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Regular methods for identifying GPV include agar-gel diffusion precipitin test, virus neutralization (VN) assay, and enzyme-linked immunosorbent assay (ELISA) [5] . However, these methods have certain limitations; they are tedi-ous and are not always reliable because of the requirement of specific-pathogen-free (SPF) gosling embryos and standard positive anti-GPV serum [7, 8] ." ] },{ "paper_id": "3bad4716622640d66aad1bf65067abc5b5a2cb01", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Highly pathogenic avian influenza (HPAI) viruses such as H5N1, H7N7, and H9N2 can result in poultry and occasionally in human mortality [1] . The first instance of human HPAI H5N1 virus infection occurred in Hong Kong in 1997; it re-emerged in 2003 and has triggered sporadic human infections in Asia, the Middle East, Europe, and Africa with a mortality rate that could be as high as 60% [2] but the true mortality rate of H5N1 infected individuals is currently unknown [3] . Humans can be infected with H5N1 from close contact with infected poultry, and virus mutations have been identified in cases of cross-human transmission. Recent reports indicate that the involvement of HA and PB2 amino acid substitutions leads to easier transmission in ferrets, suggesting that HPAI H5N1 viruses have the potential to evolve and be transmitted between mammals, thus posing the risk of a human pandemic [4, 5] . Accordingly, an effective H5N1 vaccine is urgently needed to reduce pandemic potential.", "For splenocytes isolation, spleen was removed from mouse and mashed through 70 mm cell strainer to release cells. Cells were spun down and re-suspended in 5 ml ACK lysis buffer (Invitrogen) for 5 min at RT. After cells spun down, dead cell mass in supernatant was removed; splenocytes (.80% CD3 + cells) were re-suspended and used for all experiments.", "Bone Marrow cells were isolated from femurs and tibias and seeded in 24-well plate with 1 ml supplemented RPMI-1640 medium (10% FBS, 2 mM L-glutamine, nonessential amino acids, sodium pyruvate, HEPES) (all from Invitrogen), 0.5 mM 2-ME (Sigma-Aldrich), and 15 ng/ml recombinant mouse GM-CSF (Invitrogen). On day 3, 1 ml of medium containing 15 ng/ml GM-CSF was added, and half the cell-free supernatant was exchanged by fresh medium containing 10 ng/ml GM-CSF on day 5. The 7-day-cultured bone marrow-derived DCs (.70% CD11c + cells) were used for all experiments." ] },{ "paper_id": "3bb7cd6590ad3a1d77205ad58c2c014934ee2364", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The qPCR was done on an Agilent Mx3005P qPCR System (Agilent Technologies). A qPCR master mix was made for each reaction with 12.5 \u03bcL 2\u00d7 GoTaq Master Mix (Promega), 0.5 \u03bcL of 10 \u03bcM forward and reverse primer (P009/P010) ( Table 1) , 0.125 \u03bcL of 5 \u03bcM Taqman probe (Table 1 ), 1.25 \u03bcL 50 mM MgCl 2 and made up to 20 \u03bcL with RNase-free water. The primers and probe were produced by Metabion (Metabion International) and were described previously by Dye et al. [19] .", "Historical samples were collected with full informed consent from owners that samples could be used for research purposes. The project has been approved under ethical review by the University of Bristol Animal Welfare and Ethical Review Board (VIN/14/013).", "Feline coronavirus (FCoV) infection is ubiquitous in domestic cats, particularly in multi-cat households where up to 90% of animals may be infected [1] [2] [3] . The majority of FCoV infections are asymptomatic or are associated with mild enteric disease [4] . However, approximately 5-12% of infected cats develop the invariably fatal disease, feline infectious peritonitis (FIP) [5] [6] [7] ." ] },{ "paper_id": "3bb907cbe9deee5e9585de1c0c7f04d15a82fafd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3bc70642b00cb1e53c8a6c83a584e429d626d199", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To get high quality clean reads, reads containing adapters, low quality reads, and rRNA reads were removed and then mapped to Sus scrofa reference genome (Sus scrofa 10.2) by TopHat2 (version 2.0.3.12) with default options." ] },{ "paper_id": "3bc7abde53bcbdc7ca555c835d5ad34a67941a80", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ovarian cancer represents 4% of all female cancer. It has the highest fatality to case ratio of all gynecological cancers because the majority of cases are diagnosed in the late stage. Despite of significant efforts to improve the early detection and advances www.frontiersin.org ", "WA and AK were responsible for drafting and revising the manuscript. GH was involved in critical reading of the manuscript.", "The amino acids sequences of each protein were submitted to SWISS-MODEL server to build a 3D model (10).The highest resolved structure, 1.67-\u00c5 X-ray-derived eEF1A protein structure from yeast (Saccharomyces cerevisiae) with PDB ID: 1f60 and E -value 0.0 (sequence identity: 80.371%) was used as a template for modeling. Structurally, each model consists of three domains, domain I, domain II, and domain III as shown in the above cartoon. Domain I (residues 1-240) is made up of Rossmann-fold topology. Domain II (residues 241-336) and domain III (residues 337-443) are made up of entirely from beta-strands; each domain contains two beta sheets that form a beta barrel (7)." ] },{ "paper_id": "3bd02864e1ab4b40712401ac5a0c8580dc98c0c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasmid encoding the soluble form of ACE2, pCDNA3-ACE2-ecto, was kindly provided by M. Farzan from Harvard Medical School, Boston, Massachusetts. VTF7.3 is a kind gift from C. Broder, USUHS, Bethesda, MD. Expression vectors pSecTag2 series were purchased from Invitrogen (Carlsbad, California). The monoclonal anti-c-Myc epitope antibodies (unconjugated and conjugated to HRP) were obtained from Invitrogen (Carlsbad, CA).", "Various plasmids were transfected into 293 cells using the Polyfect transfection kit from Qiagen (Valencia, CA) following the manufacturer's protocol. Four hours after transfection, cells were infected with VTF7.3 recombinant vaccinia virus encoding the gene for the T7 polymerase. The soluble S fragments were obtained from the cell culture medium.", "The author(s) declare that they have no competing interests." ] },{ "paper_id": "3bd416cb6ace33b8879fa9e93778de31ae256773", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3bd56ae4a76caf910da9be6266e18b74308364b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 Fig. 50 year-old man with adenovirus type 55 pneumonia. " ] },{ "paper_id": "3bd73eb99e264efe1eb26301ea1fe67e8916aa6c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "p e xp 2 0 2 in which the intensity I(s) was modified by subtraction of an appropriate constant from each data point, forcing the s -4 decay of the intensity at higher angles for homogeneous particles demanded by Porod's law 53 ." ] },{ "paper_id": "3bda17d21aee670c29e22635d622b780820572af", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Increasingly however, the sensitivity of nucleic acid amplification techniques for diagnosis has become recognised [5] [6] [7] [8] [9] [10] . However widespread concerns about contamination issues [11, 12] and perceived cost [13] have slowed their widespread adoption. An added problem for acute respiratory tract infections is the relatively large number of viruses that need to be accounted for, a problem which presents specific technical challenges.", "Although touchdown PCR has been used successfully to help overcome some of the uncertainties associated with the thermal amplification of microbial nucleic acid targets [19] [20] [21] [22] , its use in this study has extended its role further and in so doing brought closer the goal of undertaking molecular diagnostics in a routine setting. Previously its main impact has been seen where multiplexing [23, 24] or degenerate primers have been needed [25] [26] [27] and where the problems of choosing correct annealing temperatures are at their most difficult." ] },{ "paper_id": "3be0bd1914203f4536b93862e93434e84e531335", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3bf0902346541d9c58458ab14fc97d2f95e2f63d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It seems logical to assume that the more educated people are, the higher their cognitive ability. Gan and colleagues (2006) [5] , however, reported that depressive participants with higher educational qualifications exhibited lower levels of coping flexibility. In fact, when stressful events were encountered in daily life, active-inflexible coping was the dominant strategy employed by Chinese university students perceiving most situations as controllable [12] .", "The current study was approved by the ethics committee of the Institute of Psychology of the Chinese Academy of Sciences. Participants were given a general introduction to the study as well as the opportunity to ask questions about the study. Written consent was obtained prior to the administration of questionnaires. Questionnaires were administered to groups of students.", "The results of a Chi square analysis indicated that the two groups (i.e. depressed and non-depressed) did not vary in terms of gender composition (\u03c7 2 (1, n = 112) = 0.358, p = 0.085). The results of a multivariate analysis of variance (MANOVA) revealed a significant effect of group status on all variables (F (18, 91) = 13.777, p < 0.001) with the effect size being large (partial \u03b7 2 = 0.732). At the same time, neither gender (p = 0.249) nor the interaction between gender and depressive symptoms (p = 0.348) exhibited significant effects.", "Coping refers to the \"thoughts and behaviors that people use to manage the internal and external demands of situations that are appraised as stressful\" [1] . A large body of research has accumulated in the past three decades [1] demonstrating that coping is a crucial determinant of psychological well-being with its outcome depending largely on the types of strategies employed [2] [3] [4] . Effective coping is achieved only if the situation has been appraised accurately and the coping strategies that are used are appropriate for the situation [5] . When the appropriate coping style is used, positive emotion can occur even when depression and distress are frequent [1] . A failure, however, of effective coping with stress may lead to psychological problems [4, 6] ." ] },{ "paper_id": "3bfdf7dff1f50821c7fd782b0c6c0b4d56bf1815", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following outbreaks of severe acute respiratory syndrome (SARS) and avian flu (H5NI) in 2004\u00c12005, the World Health Organization (WHO) adopted the International Health Regulations (IHR), whose goal is 'to prevent, protect against, control and provide a public health response to the international spread of disease' (24). The WHO also published a checklist designed to help countries prepare effectively for infectious emergencies (25) .", "Regarding experimental treatments, it is important to formulate and adhere to ethical rules (64, 67, 69) in order to mitigate inadvertent damage, which could worsen already strained relationships between health professionals and their patients (64) .", "The findings will help promote emergency preparedness in every country.", "An additional aspect of the legislative infrastructure relates to counterfeit medicines. Despite the efforts of the WHO (42), the regulatory structures prevailing in LMICs cannot cope with the problem of counterfeit drugs and their use (43) ." ] },{ "paper_id": "3c082fd7a87e4e55f001e749fa9ce2a3481b0f5f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Studies investigating anopheles target-organ resistance is recommended, in addition to strategies to combat insecticide resistance must be kept a priority. Crossresistance should be also investigated, as well as, the ecology of the target pest, novel biochemical targets, and new chemical approaches for pest control and the implications of utilizing more and newer insecticides. ", "Collaboration between countries was presented as percentage of single country publication (SCP) and percentage of multiple country publication (MCP). The SCP represents intra-country collaboration while MCP represents inter country collaboration. Citation analysis for countries and journals was presented using VOSviewer technique [54] . The technique generates map that are either as density or network visualization maps. The map can be generated based on certain criteria set by the researchers. The impact of retrieved articles was assessed using Hirsch-index (h-index) [55] . The strength of journals publishing articles on malaria vector resistance was assessed by impact factor (IF) obtained from Journal Citation Report 2015." ] },{ "paper_id": "3c1893f7c0ec143b4f173980381354e5cfe6416f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HCWs. A structured questionnaire was administered to HCWs through a face-to-face interview or by telephone interview if a respondent was in quarantine or had left their job.", "Approvals for both studies were obtained from The Mount Sinai Hospital Research Ethics Board as well as the Research Ethics Boards/Committees of the following institutions: Sunnybrook Health Center. North York General Hospital, The Scarborough Hospital, Rouge Valley Health Care, Humber River Regional Hospital, Markham Stuffily Hospital, St. Michael's Hospital, St. Joseph's Health Center, Southlake Regional Health Center, Toronto East General Hospital, University Health Center, and Lakeridge Health Center." ] },{ "paper_id": "3c20c596797997337c0e8ed472cf7847dc467c65", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We explored three digital indicators for collective attention and awareness corresponding to different communities: general population, professionals and health authorities. Digital sources have been recently used in the context of early detection and surveillance [49, 50] . They have also been used as a source to study public concern in response to an ongoing epidemic threat [49, 51] .", "All indicators of attention yielded similar results, with more rapid isolation in periods of high attention (Fig. 6d) . ", "TUN1 A A A A A GE1 A A A A B UK1 A B B B B B C C C SK1 A A A B B B C D D D FR1 A A A B A A C C PH1 A A A A A A A A US2 A MA1 A B C US1 A A A1 (*) A A B B C NETH2", "We studied the factors affecting the risk of transmission following importation. We used bias reduced logistic regression to analyse the outcome of each imported case, classified as \"with secondary case\" vs. \"without secondary case\" [25] ." ] },{ "paper_id": "3c3068bf6e652c02d85923d2438ad4c84d53071a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "-several cases of non-Ebola deceased sent to cremation because of fear;" ] },{ "paper_id": "3c3f097f19bb3dbbf56eb0f099af81054b305752", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "16.9% (104) 16 .2% (47) 17.6% (57) 18.4% (38) 22.2% (10) 14.8% (4) 10.8% (4) 16.7% (1) 0% (0) 0.56 2 Intubation 3.7% (23) 3.4% (10) 4.0% (13) 3.9% (8) 4.4% (2) 7.4% (2) 0% (0) 16 (15) 2.2% (7) 1.4% (3) 2.2% (1) 3.7% (1) 0% (0) 16.7% (1) 50 ", "Viral respiratory illnesses are responsible for large numbers of hospital admissions each year leading to substantial morbidity and mortality [1] . The etiologic agents include a diverse group of viruses, such as influenza A which is responsible for intermittent pandemics [2] . Reassortment of swine-origin and human strains led to circulating pH1N1 [3, 4] and a significant increase in hospital admissions during the 2009-2010 influenza season.", "An age-adjusted analysis was performed to assess if any factors were found that significantly impacted the likelihood of patients (11) 38.5% (10) 51.9% (14) 100.0% (5) 0% (0) ,0.01 1. (29) 20.0% (7) 30.8% (8) 22.2% (6) 0% (0) 50.0% (1) (24) 55.6% (15) 56.8% (21) 33.3% (2) 50.0% (1) ,0.01 4.11 [2.88-5. (21) 37.0% (10) 27.0% (10) 16.7% (1) 50.0% (1) ,0.01 0.59 [0.43-0.82]", "All predictors were tested for an interaction with different age categories (,5 years, 5-18 years, 19 years and older) with regards to predicting pH1N1 in logistic regressions. Models included main effects for the predictor, age, and the interaction of the two. When a statistically significant interaction was detected, the simple effects of the predictors were described in terms of their effects within age categories. Those which did not significantly interact with age were described in terms of their main effect." ] },{ "paper_id": "3c43e9e66c5b384ac03f0067bc8d16a9efdd5fb9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The conservation of mass for the CSPG concentration gives", "In summary, we have the following governing equation for the virus density,", "In this section we develop a system of partial differential equations with initial and boundary conditions, for the variables introduced in Section 1, in a spherical tumor V(t) and boundary C(t).", "Cell density (x,y,n)", "Ly Lt z+ : (y u )~bxv |{z}", "Ln Lt z+ : (nu )~dy |{z}", "Text S1 Detailed description of the models and parameters used. " ] },{ "paper_id": "3c440b07b2bc59e8483537e994bbd7ac0030801a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A DI RNA-free stock of the Mebus strain of BCoV (GenBank accession no. U00735) was plaque-purified three times and grown in a HRT-18 cell line, as described [54, [66] [67] . Persistently BCoVinfected HRT-18 cells were established by infection at a multiplicity of infection (MOI) of 5. After acute infection, the surviving cells (,10%) were passaged at every fourth day thereafter. Total cellular RNA was extracted with TRIzol (Invitrogen) during acute and persistent infection.", "The DNA constructs were linearized with MluI, transcribed in vitro with the mMessage mMachine T7 transcription kit (Ambion) according to the manufacturer's instructions, and passed through a Biospin 6 column (Bio-Rad), followed by transfection [41] . For transfection, HRT-18 cells in 35-mm dishes at ,80% confluency (,8610 5 cells/dish) were infected with BCoV at a multiplicity of infection of 5 PFU per cell and transfected 2 h later with 3 mg of transcript RNA using Lipofectin (Invitrogen) [19] . After transfection, proteins from HRT-18 cell lysates were harvested, electrophoresed through 12% SDS-PAGE gels, and electrotransferred to nitrocellulose membranes (Amersham Biosciences). DI RNA fusion proteins were detected using an antibody specific to the histidine tag or b-actin (Serotec) as the primary antibody and goat anti-mouse IgG conjugated to HRPO as the secondary antibody (Jackson Laboratory). The proteins detected were visualized using Western Lightning TM Chemiluminescence Reagent (Perkin Elmer NEL105) and X-ray film (Kodak) [69] .", "and not from a recombinant molecule, RT-PCR using primers that anneal to the reporter sequence in DI RNA (for RT) and the M protein gene in the coronavirus genome was used to test for a potential recombinant generated during infection [49] . No RT-PCR product was observed (Fig. 2E , lanes 2-3), thus ruling out the expression of the protein from a recombinant molecule. These results suggested that the translation of leaderless DI RNA is less efficient than that of DI RNA with a leader during infection." ] },{ "paper_id": "3c44fe859327f5e7b02cc27a10a228ae5288d65b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Specific antibodies against IBV were detected with an ELISA kit (IDEXX Laboratories Inc., Westbrook, ME, USA), and serum titers were calculated according to the manufacturer's instructions.", "The SNU8067 titer was determined by inoculating 10-fold serial dilutions (10 \u22121 -10 \u22127 ) of the virus into five 10-d-o SPF ECE via the allantoic cavity. The inoculated ECE were observed for death and dwarfism for 5 days and the 50% chicken embryo infectious dose (EID 50 /mL) was calculated using the Spearman-Karber method [18] .", "Phylogenetic analysis of the S1 genes of infectious bronchitis viruses. The phylogenetic tree was constructed by the neighbor-joining method (Kimura-2 distance, 500 repeats of bootstrapping)." ] },{ "paper_id": "3c4505f3ce59be775697d87a10f448ac2afc7ad7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Identifying the most productive and influential research, can be useful to anyone involved on the field of aflatoxin. Drawing on these insights may aid understanding of historical progress in aflatoxin research over the last 20 years and offer guidance researchers, and policy makers, regarding best scientific and publishing practices for future health research of this scientific field.", "The evaluation of the collected sample involved weighing the following indictors: (1) publication output by years, (2) top 10 countries with their h-index and collaboration pattern, (3) top 10 most influential journals with their Source Normalized Impact per Paper (SNIP), and impact factors (IF), (4) top 10 most influential institutions, and (5) top 20 cited publications.", "Supplementary information accompanies this paper at https://doi.org/10. 1186/s12995-019-0248-7. " ] },{ "paper_id": "3c51c5a11684d15c9f3d39dc99b0fdf9f7a73847", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Worldwide demographic changes drastically impact global health, and can increase the cost of healthcare delivery systems across the planet until these systems become unsustainable. The pattern of diseases is substantially different between developed and developing nations.", "The healthcare expense will increase both from population growth and ageing: there are more people being born, and more older people staying alive.", "The following sections define Cybercare; describe its technologies and applications, and provide a case study of how Cybercare would improve care in a pandemic.", "Telecommunications and IT have been applied to support the delivery of health care for more than 20 years. The term telemedicine has been generally applied to this activity and may be considered synonymous with e-Health, Telehealth, Telecare, etc. Telemedicine has generally been seen as connecting a patient to a provider or a provider to another provider/specialist. When telemedicine is on a network then it comes under the umbrella of Cyberhealth/Cybercare." ] },{ "paper_id": "3c51ef8a5ac17b4e6d461b5997f29a8324dd8a02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SureSelect probes covering the chicken IFITM locus (40Kb region) were purchased from Agilent and samples processed for targeting pulldown according to the Illumina and PacBio protocols. ", "Poultry accounts for almost half of all meat consumed in the UK, with 875 million chickens, 17 million turkeys, 16 million ducks and 250,000 geese a year supplied by over 2500 poultry farms [1] . Their production can be adversely affected by infection with avian specific viruses such as infectious bursal disease virus (IBDV), infectious bronchitis virus (IBV) and Newcastle virus (NDV) [2] [3] [4] [5] [6] [7] . Poultry can also serve as the source of zoonotic, or potentially zoonotic, infections with viruses such as H5N1 and H7N9, transmitted to humans through contact with poultry. To reduce the threat to the global food supply and to minimize the risk of zoonotic events, there is an ongoing need to better understand the biology of avian viral infections, the mechanism of natural resistance (viral intrinsic and innate immunity) and the characterization of the biological factors that might be involved." ] },{ "paper_id": "3c568d47a1d134908dc09e454a5a52655d3a9434", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The etiology of ACS is multifactorial. The three primary studied mechanisms include pneumonia or systemic infection, fat embolism, and direct pulmonary infarction from HbS-containing erythrocytes [6, 11, 18] . The management of this condition is still largely determined by the experience of individual practitioners, and currently there are no conclusive randomized controlled clinical trials to guide therapy [19] . The most common therapy includes nonspecific supportive care strategies aimed at hastening recovery to baseline, including: hospitalization, hydration, analgesics, broad-spectrum antibiotics, bronchodilators, incentive spirometry, supplemental oxygen, and blood transfusions [6, 11, 18, 19] .", "Abbreviations ACS: Acute chest syndrome; Hb: Hemoglobin; SCD: Sickle cell disease; SSA: Sub-Saharan Africa; VOC: Vaso-occlusive crisis.", "ACS is an acute lung injury syndrome that occurs frequently in patients with SCD. Indeed, it is the second most common cause of hospitalization, and the leading cause of death, contributing to almost 25 % of SCD-related mortality [7, 8] . Moreover, nearly half of deaths due to ACS occur in SCD patients less than 20 years of age [9] . Repeated episodes of ACS negatively impact long-term lung function, resulting thereby in chronic lung diseases [10] ." ] },{ "paper_id": "3c5dd991f2d7b334cc56b2715d73af3fcf1cdca4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The coronavirus sequences described in this study have been deposited in GenBank under the accession numbers MH687934-MH687978.", "Note that screening using specific PCR targeting the conserved RNA-dependent RNA polymerase (RdRp) gene had previously identified CoV sequences in some of the same samples (29). The RdRp sequences generated in that study were closest to the bat Alphacoronavirus NC_009657 (Scotophilus bat coronavirus 512) and the rat Betacoronaviruses NC_026011 (Betacoronavirus HKU24) or KF294372 (Longquan Rl rat coronavirus). These are likely to be the same viruses described here at the full genome level.", "Advances in nucleic acid sequencing technology (commonly termed Next-Generation Sequencing, NGS) are providing large sets of sequence data obtained from a variety of biological samples and allowing the characterization of both known and novel virus strains. Algorithms that can accurately and rapidly detect and classify low-frequency virus sequences amidst a highsequence background are useful. The desired features of these classification algorithms are the ability to rapidly process large number of sequences and to accurately identify more distantly related sequences. Use of such tools in the field during outbreak sequencing is common, thus methods that are stand-alone requiring no internet connection are desirable.", "The Coronaviridae family comprises enveloped positive-sense single-stranded RNA viruses of the order Nidovirales with a genome of up to 32 kb in length. The family is divided into Coronavirinae and Torovirinae sub-families, which are further divided into six genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, Deltacoronavirus, Torovirus, and Bafinivirus. While viruses in the genera Alphacoronaviruses and Betacoronaviruses infect mostly mammals, the Gammacoronavirus infect avian species and members of the Deltacoronavirus genus have been found in both mammalian and avian hosts (de Groot 2012; Drexler, Corman, and Drosten 2014) ." ] },{ "paper_id": "3c67252392670f7eb8bd7ec3c01daf8e2b3a6da9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3c787e585321cc1d3d62aacb1c74713a4c77e9cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Whole brains, collected and fixed in 4% paraformaldehyde were immunolabelled as previously described [47] . In brief, they were sectioned at 50 mm thickness with a Leica Vibrating Microtome and stored in PBS at 4uC. Sections were treated with 0.1% Triton X-100 (Sigma-Aldrich) in PBS for 1 hour and blocked with 0.5% Bovine serum albumin (Sigma-Aldrich) in PBS (PBS/BSA) overnight at 4uC. Primary antibodies were diluted in 0.5% PBS/BSA and incubated on sections for 2 hours at 37uC. Antibodies and dilutions were: rabbit anti-IBA1-microglia marker PBS. Mouse Ig Blocking Reagent (Vector Laboratories) was used with mouse primary antibodies: anti-Human Neurofilament protein (DakoCytomation) 1:50, anti-NeuN, (Millipore) 1:50, and a mouse monoclonal antibody raised against whole HeV (AAHL). Bound primary antibody was detected with species-specific secondary antibodies conjugated to Alexa 488 or 568 (Invitrogen) diluted 1:200 in PBS/BSA for 2 hours at 37uC. Sections were washed 3 times for 5 minutes with PBS and nuclei labelled with DAPI diluted 1:1000 in dH 2 O for 30 minutes. Sections were rinsed twice with dH 2 O, mounted with Vectashield Mounting Medium (Vector Laboratories) and coverslips sealed with nail varnish.", "For all studies reported in this paper, the animal husbandry and experimental design were approved by the CSIRO Australian Animal Health Laboratory's Animal Ethics Committee. All animal experimentation was conducted following the Australian National Health and Medical Research Council's Australian Code of Practice for the Care and Use of Animals for Scientific Purposes.", "Ten juvenile (8 weeks) and ten aged (12 months) C57BL/6 mice were each divided into two groups and challenged with 50,000 TCID 50 HeV using either an intranasal or subcutaneous route of exposure and monitored daily for 21 days post infection (DPI).", "Taken together, this data suggest that HeV replication is restricted to neurons during infection of the brain.", "We have now confirmed progressive involvement of the mouse CNS by HeV which is most likely established via a nonhaematogenous route of neuroinvasion, as has been established or proposed for other paramyxoviruses including Sendai virus in mice [24] , Canine distemper virus in ferrets [25] , and the closely related Nipah virus in pigs [26] ." ] },{ "paper_id": "3c78f14566e94220797611e80ca9136e070bbe45", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Paired-like homeodomain transcription factor 2 (PITX2, RefSeq NM 000325.5, MIM# 601542) is located at 4q25 and is expressed in the developing eye, brain, pituitary, lungs, heart, and gut [1] . Mutations in human PITX2 or the forkhead box transcription factor C1 (FOXC1; 6p25, RefSeq NM 001453.2, MIM# 601090) underlie the autosomal dominant disorder called Axenfeld-Rieger syndrome (ARS; MIM# 602482) [2] [3] [4] [5] . ARS is a full penetrant, but clinically and genetically heterogeneous disorder characterized by developmental anomalies involving both ocular and non-ocular structures [6] . To date, 87 identified including deletions, insertions, splice-site mutations, and coding region frameshift, nonsense and missense mutations [7] [8] [9] [10] [11] [12] [13] .", "Citation: Seifi M, Walter MA (2018) Accurate prediction of functional, structural, and stability changes in PITX2 mutations using in silico bioinformatics algorithms. PLoS ONE 13(4): e0195971. https://doi.org/10.", "Molecular models for the homeodomain of wild-type and variant-containing PITX2 proteins were designed using threading algorithms to assess impairment of PITX2 structure by missense variants." ] },{ "paper_id": "3c7a2bc73e390cf72261519f241cd12b363c7444", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BLI-delivered epitope clustering using the in-tandem strategy was developed for therapeutic antibody discovery to study a glucose-dependent insulinotropic polypeptide (GIP) receptor with the purpose of possible diabetes and obesity treatment [20] . The flexibility of BLI is useful for a variety of epitope studies and mAb selection.", "This study shows how BLI can greatly contribute to the understanding of functional studies of proteins involved in viral recognition, which can lead to improved vaccine efficacy in the future.", "Understanding the interaction between microbes and their host is a big step in improving or developing new vaccines. Epitope design and epitope capture approaches focus on the microbial molecular structure and how different epitopes may have different potency, functions, and targets that ultimately impact vaccines. The following examples show strategies that employ BLI and how they contribute to the understanding and characterization of epitope design toward vaccine development and improvements." ] },{ "paper_id": "3c7d045c73a10e8b81cc58d86d7cf5d144f83b1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Subsequently, previous studies have extensively characterized the antioxidant properties of the heme oxygenase (HO) system and its isoform, HO-1, which is a crucial stress responsive protein.", "Funding: This research received no external funding.", "The authors declare no conflict of interest. " ] },{ "paper_id": "3c83a45d3f3e227de8b5e0e88022352385dd78e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Therefore, we considered the following model [13, 14] ," ] },{ "paper_id": "3c8a38879c8d9910167b2dab37c2d98e17701141", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This RNA-Seq compendium extends the analyses of previous gene expression atlases performed using Affymetrix GeneChip technology and provides an example of new methods to accommodate the increase in transcriptome data obtained from next generation sequencing [29, 31, 32] ." ] },{ "paper_id": "3c8f08f49903aa46c23718a59a6bb221879aa1d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All cell cultures were routinely screened for Mycoplasma spp. contamination using Hoechst 33258 staining.", "RNA from viral and control cultures was extracted using GeneJet RNA purification kit (Thermo Scientific, Lithuania), according to manufacturer's protocol. Isolated RNA was stored at -80\u00b0C. DNA fragments were synthesized by a third party (Genomed, Poland).", "Isolated viral RNA was reverse transcribed using High Capacity cDNA kit (Life Technologies, Poland) and used as a template for subsequent amplification." ] },{ "paper_id": "3c988a00ed94308e36a8814b391ead01480efb60", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We next determined if there was any flexibility in the amino acid required at position 16 in IBV E. A multiple sequence", "Multiple sequence alignment of CoV E proteins was carried out using ClustalW2 at the European Bioinformatics Institutes server [51] . The figure was generated using jalview version 2 [52] . Tris-HCl [pH 6.8], 8% SDS, 60% glycerol, 0.2% bromophenol blue) was added to each sample prior to separation on 10% SDS-PAGE. Labeled proteins were visualized by using a Molecular Imager FX phosphorimager (Bio-Rad) and quantified using Quantity One software (BioRad).", "Coronaviruses (CoVs) are enveloped, positive strand RNA viruses that infect a variety of mammalian and avian species. In humans, CoVs are responsible for nearly 20% of common cold cases. CoVs can also lead to more serious disease as seen during the outbreak of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. To better prepare for the emergence of another highly pathogenic CoV it is important to increase our understanding of CoV biology." ] },{ "paper_id": "3c9d07cac8fdfacf5199e81f35aa6dd4dc7e49ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The rapid emergence of AIDS in humans during the period between", "In the north of the continent a single study was performed in 52 domestic cats on Isabela Island, Galapagos, Ecuador's coast. It was demonstrated using serological methods that none of the tested animals was infected with FIV [36] .", "It is important to emphasize that FIV strains infecting 9 species of the Felidae have been at least partially sequenced and molecularly characterized [3, 10, 11, 25, 34, 38, 42, 43, 66] . Genetic analysis indicates that different felid species are infected by different strains of FIV [8, 11] . Analysis of pol gene sequence of FIV from lions (Panthera leo), pumas (Puma concolor) and domestic cats indicated that each species has a specific strain of FIV and that the strains are related but distinct [7, 43] . Also, strains from African lions (subtype B and E) differ in their abilities to replicate in feline cell lines [59] , their sensitivity to receptor antagonists [71] , and their requirement for ectopic expression of CD134, the primary cellular receptor, for productive infection [41] ." ] },{ "paper_id": "3c9db7ee30074667f9fe308de9910b013aa1f163", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All procedures performed in this study were approved by the Jordan University of Science and Technology Animal Use and Care Committee.", "Data for ELISA and fold changes were expressed at mean \u00b1 standard deviation. One-way ANOVA and t-test were used to compare different values in all groups using OpenEpi software (Emory University, USA). Parameter differences were considered statistically significant at p<0.05. Parameter differences were indicated by small letters labeled within each group; different letters indicated significant differences at p<0.05.", "Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging human coronavirus that was discovered in 2012 in a 60-year-old Saudi Arabian man [1] . Following its discovery, many cases were identified in different regions of the Arabian Peninsula and worldwide thereafter [2, 3] . The most recent outbreak occurred in June 2015 in South Korea and was linked to a South Korean man who had recently traveled to the Middle East [3] . The infection then rapidly spread to 26 persons through close contact in a hospital. Within a few months, many cases (n=186) were reported in hospitalized and non-hospitalized persons in South Korea [3] . The disease showed a high mortality rate that reached up to 40%, which was higher than that of the severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak in 2002-2003 (10%) [4] ." ] },{ "paper_id": "3ca43ade94501268228e5239d1717d4f6333d462", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "By late 2003, Vical had completed all of the appropriate activities and compiled the requisite documentation for filing an investigational new drug application (IND) with the U.S. FDA. IND allowance occurred in early 2004 followed shortly by initiation of a phase 1 trial.", "In that setting, the vaccine was well tolerated, with no serious adverse events (SAEs) and no discontinuations due to vaccine-related adverse events (AEs). The most frequent AEs were injection site pain, myalgia, headache, and malaise and were of mild to moderate severity. Systemic reactions included mild to moderate malaise and myalgia. Local reactions included injection site pain, induration, swelling, and erythema [38] .", "During production of DP for testing in phase 1 and phase 2 trials, improvements in CMC-related processes and refinements in analytical testing methods and assay specifications were identified and implemented prior to phase 3 testing. Furthermore, the DP lot sizes sufficient for phase 1 and phase 2 CTMs had to be increased by scaling up the manufacturing procedures to meet the CTM demands for phase 3. Process improvements enhanced manufacturing efficiencies and lot-to-lot consistency by streamlining/simplifying procedures, upgrading equipment, and enriching product yield. Some assays underwent refinements that resulted in increased sensitivity, precision, ease of use, and reagent stability and availability. Each plasmid-specific DS and DP release assay was validated in preparation for use in phase 3. All of the CMC-related changes were submitted to the FDA under the current IND in 2012.", "The combination of CRL1005 and BAK self-assembles into stable nanoparticles. The formulation appearance is a milky white suspension at room temperature that becomes clear as the temperature drops below the CRL1005 cloud point (5 \u00b0C-7 \u00b0C). The final bivalent vaccine formulation was designed to be a 1-mL intramuscular (IM) injection consisting of a 5-mg total plasmid dose (2.5 mg of each plasmid), 7.5 mg of CRL1005, and 0.1 mg/mL of BAK, all dissolved in phosphate-buffered saline (PBS) and stored frozen [36] . This formulation provided key practical advantages compared to an alternative cationic lipid-based formulation undergoing development during that time: A higher DNA dose could be formulated (up to 5 mg/mL) and a single vial formulation was possible, in contrast to a multivial format (up to 1 mg/mL) with reconstitution of dried lipid film and mixing for the cationic lipid formulation.", "The final drug product (DP) was manufactured by mixing each monovalent bulk DS at a 1:1 mass ratio to create a bivalent bulk DS that was then formulated with CRL1005 and BAK under aseptic conditions, resulting in the bulk DP. A challenging aspect of the formulation development was the requirement to maintain the temperature of the CRL1005-containing solution below the cloud point during filtration. During early development the bulk DP was sterile filtered below the cloud point. However, significant product losses were incurred, leading to optimization of the process prior to phase 3. Sterile filtration of a premix containing BAK and CRL1005 below the cloud point was implemented, followed by introduction of sterile-filtered bulk DS to form the bulk DP." ] },{ "paper_id": "3ca853dca7e2037fb95acf0b90ce59c9776979b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleic acids were extracted from each DNS using the commercial kit QIAamp \u00ae Viral RNA Mini Kit (Qiagen S.p.A., Milan, Italy), according to the manufacturer's instructions, and were stored at \u221280 \u2022 C until tested by Real Time quantitative PCR (qPCR). Primers and TaqMan probe for qPCR assay were used as previously described [13] , in the same reaction conditions, including reaction mix component and thermal cycling (Supplementary Table S1 ).", "Supplementary Materials: The following are available online at http://www.mdpi.com/2076-2615/9/12/1093/s1, Table S1 , Primer and probe sets for the detection of BRD pathogens. " ] },{ "paper_id": "3caab8234843e6047eacf1f7d1efc1db1d40d11b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "-" ] },{ "paper_id": "3cba082e1f0b91d9143ea8e72eada78be0474064", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All amplified products were separated by 1% agarose gel in 1X Tris-borate-EDTA buffer by electrophoresis and stained with ethidium bromide (0.5 \u00b5g/ml). Standard molecular size marker (100 bp DNA ladder) was included in each gel. DNA fragments were observed by ultraviolet transilluminator and photographed in a gel documentation system (Alpha Imager, Germany)." ] },{ "paper_id": "3cbc04dc1d9cc8faffc2328df66ac20e09e93661", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3cbeb11d471dd6cebf2b65c42c00fd66a6cb5dc0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that the research described herein was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.", "The study design was approved by the ethics committee for animal experiments at the Guangdong Institute of Applied Biological Resources (reference number: GIABR20170720, 20 July 2017) and followed basic principles outlined by this committee.", "Viruses 2019, 11, x FOR PEER REVIEW 5 of 16", "As raw sequencing reads always include some low-quality data, it is necessary to perform processing to improve the accuracy of reads for follow-up analyses. To this end, we used SOAPnuke version 1.5.6 [19] to remove adapter sequences and reads (i) with more than 5% Ns; (ii) those with 20% base quality values less than 20; (iii) those arising from PCR duplications; as well as (iv) those with a polyA sequence." ] },{ "paper_id": "3cc1733c40062f59a5d1e9c7c9fd318c8041c0a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Swab results. Beta-hemolytic Streptococci were isolated in 35/169 (20.7%) throat swabs: 11 (6.5%) GAS, four (2.4%) group B, four (2.4%) group C, one (0.6%) group F, 14 (8.3%) group G, and one (0.6%) non-groupable.", "In all, 164/169 (97.0%) patients were diagnosed with a single respiratory tract syndrome, of which 94/164 (57.3%) had a common cold, 42/164 (25.6%) had pharyngitis, 26/164 (15.9%) had tonsillitis, and 2/164 (1.2%) had bronchitis.", "nickd@tropmedres.ac, and yoel@tropmedres.ac. Clare Ling, Nuffield" ] },{ "paper_id": "3ccac237e5fa57c9d28f59f0b9b8e58188edd29b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All constructs were verified by Sanger sequencing. The sequences of the oligonucleotides used for amplification and sequencing can be provided upon request." ] },{ "paper_id": "3ce03de615e79f44ac9d8193429f9f6be86be3a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Epidemics of flavivirus and alphavirus occur globally on an annual basis with different degrees of severity. Table 1 shows a small selection of recent flavivirus/alphavirus outbreaks worldwide.", "The global distribution and severity of flavivirus and alphavirus infection requires accurate surveillance tools and timely diagnosis to ensure infected patients obtain the best medical treatment options and alert authorities to possible outbreaks of disease.", "The " ] },{ "paper_id": "3ceddc72c46d0c69ff2718e3780a0d987da91cab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "respiratory syndrome (SARS) outbreak. However, infectious diseases still remain a major", "Increased rainfall favors mosquito development by providing aquatic breeding sites, subsequently increasing mosquito populations and the potential incidence of malaria and dengue [44] . Although excessive rainfall and flooding may destroy the existing mosquito breeding sites and restrict disease transmission in the short term, it is likely to create more breeding habitats for mosquitoes and increase disease incidence over time [44] .", "In summary, strengthened disease surveillance infrastructure, better trained health workers and further consideration of underreporting are needed to improve the infectious disease surveillance system. The importance of improving the system is further accentuated by the likely impacts on infectious disease transmission of two important issues facing this nation: urbanization and climate change." ] },{ "paper_id": "3cf1d3f730cadc87a4392893ee1a6d4da9cb5efb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3cf41b596058f2d1b07760563aa6c5316b014af2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses (CoVs) have been recognized as emerging pathogens that cause significant morbidity and mortality, leading to major economic losses in both humans and animals [1] . They are currently classified into four genera, the Alpha-, Beta-, Gamma-, and Deltacoronavirus, identified in diverse animal species including humans [2] . With its origin still unknown, porcine deltacoronavirus (PDCoV) is a recently emerged deltacoronavirus in swine. It particularly targets neonatal piglets, causing acute diarrhea, vomiting, dehydration and high mortality [3] [4] [5] [6] [7] . In 2012, PDCoV was first identified in swine herds in Hong Kong and was subsequently reported as an enteric pathogen causing diarrhea in the United States in 2014 [2, 3, [7] [8] [9] [10] [11] . Shortly thereafter, PDCoV has been reported in South Korea, mainland China and Thailand [4, 12, 13] . Currently, PDCoV, together with other enteric viruses including porcine epidemic diarrhea virus (PEDV), rotavirus (RV) and transmissible gastroenteritis virus (TGEV), is causing enormous economic losses in the swine industry worldwide [9, 14] .", "Assembly of a full-length cDNA clone of PDCoV", "No potential conflict of interest was reported by the authors. " ] },{ "paper_id": "3cff423d90d10aed4310a7d726a6a873d37b2693", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "evidence of weight loss (Figures 5c,d) . The infection of control mice with ZIKV-PR209 virus produced a marked decrease in body weight along with decreased mobility, hunched posture, hindlimb knuckle walking and/or paralysis of one or both hind limbs (Figures 5e,f) .", "Differences in fold increases in antibody titres were compared using Mann-Whitney analysis. Statistical analysis was performed using Graphpad, Prism 4 ZIKA virus prM envelope-based DNA vaccination K Muthumani et al (Graphpad software, Inc. San Diego, CA, USA). For all the analyses, Po0.05 was considered to be significant. Log 10 transformations were applied to end point binding ELISA titres and whole-virus PRNT 50 titres.", "with ZIKV-prME plasmid at 48 h post transfection with anti-ZIKV-prME specific antibodies ( Figure 1e )." ] },{ "paper_id": "3cffdde62288c2bedae29c7291a5304f9cb9279b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As a multivariate statistical method, PCA is normally applied to study the relationship among variables and samples, which transform relative indices into small number of uncorrelated indices, thus, the so called principal components. In this study, each dimension represents a sense codon relative synonymous codon usage (RSCU) value [69] . PCA analysis was performed using GraphPad Prism 5.0.", "The correlations among the A%, T%, G%, C%, A 3s, T 3s , G 3s , C 3s , GC 3s , ENC, Aroma and Gravy were calculated using Graphpad Prism 5.0, with an extremely significant relationship (**) of p < 0.01 and a significant relationship (*) of 0.01 < p < 0.05.", "ARTICLE HISTORY", "A total of 52 completed genomes of PCV3 available until the 9 th of November 2017 were retrieved from the GenBank database (https://www.ncbi.nlm.nih.gov/gen bank/) and considering the opposite direction of ORF2, the individual ORF1 and ORF2 gene were concatenated for the analysis. The detailed information of each strain including the accession number, strain name, country and collection-date are listed in Table S1 ." ] },{ "paper_id": "3d0778430adbbbc96d00837831f9a1ce1d4ff35b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Yeast transformation by spheroplast formation. The S. cerevisiae strain VL6-48N (14) (MAT\u2423 his3-\u0394200 trp1-\u03941 ura3-\u03941 lys2 ade2-101 met14 cir\u00b0) was used for all yeast transformations and grown in YPD (yeast extract, peptone, dextrose) medium supplemented with adenine. S. cerevisiae spheroplasts were prepared using previously described methods with the following modifications (16) . Overnight cultures were grown to an optical density at 600 nm (OD 600 ) of 1. . DNA for transformation-associated recombination (TAR) cloning or assembly was added to 200 l of spheroplasts, followed by the addition of 900 l of 20% PEG solution (20% PEG 8000, 10 mM CaCl 2 , 10 mM Tris-HCl). The suspension was incubated at room temperature for 20 min, the PEG solution was removed, and the cells were then incubated at 30\u00b0C for 30 min in SOS medium (1 M sorbitol, 6.5 mM CaCl 2 , 0.25% yeast extract, 0.5% peptone). Transformed yeast spheroplasts were plated with selective top agar with sorbitol.", "The P7 Toledo-F, P7 Toledo-P, Assembled Toledo-F, Reconstituted Toledo-F, Assembled Toledo-P, and Reconstituted Toledo-P were aligned in Geneious (Biomatters Ltd., Auckland, New Zealand) using the PhyML package to the reference strain (HCMV Toledo, GenBank accession number GU937742.2) available from NCBI and to each other for identification of insertions, deletions, and single nucleotide polymorphisms (SNPs).", "Supplemental material for this article may be found at https://doi.org/10.1128/ mSphereDirect.00331-17. " ] },{ "paper_id": "3d09812aba24146255e664c9ed4ed7d5dcd9e3b3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Authors' contributions SZ conceptualized, designed the methodology, and implemented the study, and did the analysis and write-up. Then read, and approved the final manuscript.", "The author declares that he has no competing interests." ] },{ "paper_id": "3d0d60d3d1906b4086ca3e10bcf5dde7b4db69b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3d1d14a7dc9189add63df0501822830a3291a850", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Largely responsible for the diversity of RNA viruses [12] RNA-RNA recombination was observed in several positive-sense, ssRNA human and animal viral taxa including caliciviruses, coronaviruses, hepatitis, dengue, enteroviruses and astroviruses [13] [14] [15] [16] [17] [18] [19] [20] [21] . For example, genetic exchange in ssRNA viruses was first demonstrated in polioviruses [22, 23] .", "Each strain was plaque purified and further enriched using Escherichia coli HS(pFamp)R as host [4] . Approximately 1-2 mL aliquots of the purified viral supernatant were frozen at &75 \u00b0C. Coliphage RNA was extracted from purified virus as described [26] using a QIAamp viral RNA mini kit (Qiagen, Valencia, CA, USA). Purified RNA was stored frozen at &20 \u00b0C.", "Sequence data were analyzed using BioNumerics Software v.3.5 (Applied Maths, Saint-Martens-Latem, Belgium). Phylogenetic trees were built by global cluster analysis performed on multiple aligned sequences and clustered by unweighted pair group method using arithmetic averages (UPGMA). A bootstrap analysis, based on 10,000 substitutions, was used to measure cluster significance. The reliability of each cluster was expressed on a percentage basis [3] .", "Nucleotide percent similarity and dendrograms were constructed using BioNumerics Software v.3.5 (Applied Maths, Saint-Martens-Latem, Belgium). Phylogenetic trees were built by global cluster analysis performed on multiple aligned sequences and clustered by UPGMA using the Jukes and Cantor correction [28] . Cophenetic correlations and cluster Cutoff method were employed to measure faithfulness and relevancy of the clusters (Applied Maths, Saint-Martens-Latem, Belgium). Average similarities with standard deviations were calculated for the relevant clusters.", "Deduced amino acid sequences for each of the four genes were determined using a computer-generated DNA-to-protein translation tool, ExPASY (http://ca.expasy.org/). Prediction of protein sequence motifs were identified by PROSITE (http://ca.expasy.org/) and protein families and domains were modeled in Pfam (http://pfam.janelia.org)." ] },{ "paper_id": "3d2962558f0a2ed4ddc00989168efe60856bd792", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total nucleic acid was extracted from the specimens using NucliSens easyMAG extraction system (bioMerieux, Netherlands) according to manufacturer's instructions.", "They were examined daily for cytopathic effect, and immunofluoresence was done on fixed cell smears when CPE appeared or at the end of the incubation period [1] .", "Madin-Darby canine kidney (MDCK) cell monolayers in culture tubes were inoculated with 200 \u00b5l of the nasal swabs-virus transport medium suspension and the cells were maintained in serum-free minimum essential medium (MEM, Gibco, N.Y., USA) containing tosylsulfonyl phenylalanyl chloromethyl ketone-treated trypsin (2\u00b5g/ml) (Sigma, St. Louis, MO), and incubated at 33 o C for 7 days (MDCK cells)." ] },{ "paper_id": "3d2fae37d61a2e45cf0dff9bc0abee361bbf9a8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results shown are the mean \u00b1 SD. A P-value <0.05 was considered to indicate statistically significant differences. Statistical analyses were calculated using SPSS 11.5. Each experiment was repeated 3 times.", "Cell culture. The SGC7901 human gastric cancer, SHG44 glioma, SHI-1 leukemia, A549 lung adenocarcinoma, and HO8910 ovarian cancer cell lines were obtained from Shanghai Cell Bank (Shanghai, China). They were cultured in RPMI-1640 (Gibco, USA) containing 10% fetal bovine serum (FBS) in a humidified atmosphere with 5% CO 2 at 37\u02daC. They were selected as all these poorly differentiated cells often have aberrant terminal sugar structures of O-glycan chains.", "Total-RNA was isolated from equal cell numbers using Tri Reagent (Sigma) following the manufacturer's instructions. Reverse transcription was as previously described and 5 \u00b5l of the resultant cDNA was used as template for PCR (16) . The sequences for primers with annealing temperatures indicated in brackets were as follows: ppGalNAc-T2, 5'-AAGAAAGACCTTCATCACAGCAATGGAGAA-3' (forward) and 5'-ATCAAAACCGCCCTTCAAGTCAGCA-3' (reverse) (60\u02daC); MMP-2, 5'-AGATCTGCAAACAGGACA TTGTATT-3' (forward) and 5'-TTCTTCTTCACCTCATTG TATCTCC-3' (reverse) (56\u02daC); MMP-14, 5'-TGGCGGGTGA GGAATAAC-3' (forward) and 5'-GGGAACGCTGGCAGT AGAG-3' (reverse) (56\u02daC); TGF-\u03b21, 5'-TGTGGCTACTGGT GCTGAC-3' (forward) and 5'-ATAGATTTCGTTGTGGG TTTC-3' (reverse) (56\u02daC); \u03b2-actin, 5'-CATGTACGTTGCTA TCCAGGC-3' (forward) and 5'-CTCCTTAATGTCACGCA CGAT-3' (reverse) (52\u02daC). The number of PCR cycles used was 30 and the expected product size after primer amplification was as follows: ppGalNAc-T2, 669 bp; MMP-2, 332 bp; MMP-14, 690 bp; TGF-\u03b21, 317 bp; and \u03b2-actin, 330 bp. The PCR products were separated by electrophoresis on 10 g/l agarose gels and visualized by ethidium bromide staining." ] },{ "paper_id": "3d3886831b542dfc9d1b6428ac48d96589d0ae61", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The time-dependant method, proposed by Wallinga & Teunis [13] , computes reproduction numbers by averaging over all transmission networks compatible with observations. The probability p ij that case i with onset at time ti was infected by case j with onset at time tj is cal-", "After briefly recalling the principle of these methods, we illustrate their use, propose some tools to critically examine results and finally discuss applicability and limitations.", "While several methods for estimating reproduction numbers exist, sometimes with code provided by their authors, no common framework was available to allow easy and direct comparison of the results. Developing an R package provide this framework and allow widespread distribution. It will complement package developed for epidemiological surveillance [4] and cost-effectiveness analyses [5] . Furthermore, R packages are easily extensible, so that additional methods can be easily included in future releases." ] },{ "paper_id": "3d4b0d8d4ac0c8419efb82278b823952e94d1393", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Ebolavirus genus comprises five species that are named after the regions in which they were first observed. These viruses are Bundibugyo virus (BDBV; species Bundibugyo ebolavirus); Ebola virus (EBOV; species Zaire ebolavirus); Sudan virus (SUDV; species Sudan ebolavirus); Tai Forest virus (TAFV; species Tai Forest ebolavirus) and Reston virus (RESTV; species Reston ebolavirus), with the newly discovered Bombali virus (BOMV; species Bombali ebolavirus) currently unclassified but may form a ", "Influenza B, SARS-CoV, and Vaccinia viruses are all reported to escape the inhibitory effects of ISG15 through unique mechanisms involving NS1, papain-like protease (PLpro), and E3, respectively [161] [162] [163] . In these cases, viral antagonists prevent ISG15 from performing its homeostatic role in protein production [161] [162] [163] . However, there are no reports of a viral antagonist that targets ISG15 to restore EBOV budding. Nevertheless, the precedent set by Influenza B, SARS-CoV, and Vaccinia viruses makes it an intriguing possibility worthy of further investigation.", "The authors declare no conflict of interest.", "Ebola virus and Marburg virus are among the deadliest viral pathogens known to infect humans, being transmittable primarily through contact with infectious bodily fluids [1] . These viruses can be transmitted between humans and from non-human hosts. The latter include non-human primates, as well as African fruit bats, which are the known and suspected natural reservoir of Marburg and Ebola, respectively [2, 3] . Both viruses are members of the family Filoviridae of the order Mononegavirales." ] },{ "paper_id": "3d758d41ef57c3d1e9ffe346ece0dd6b59e68cd8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Funding: This study was funded by the ZonMW's Meer Kennis met Minder Dieren grant (114021506).", "All picornavirus capsids adopt an icosahedral structure (see Figure 1 ) [5] . The three capsid proteins assemble into a protomer and five protomers together form a pentamer [5] . A total of 12 pentamers ", "The authors declare no conflict of interest. " ] },{ "paper_id": "3d7aeae7fc9f39f80a461b590c16fd9ea37aa9d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Entire tracheal explants were prepared from 29 days old embryonated specific pathogen free (SPF) Muscovy duck eggs (just before hatching) and after several careful washing steps, maintained at 37\u00b0C in minimal essential medium supplemented with antibiotics until use.", "At 4 and 8 h post-infection (p.i.), tracheas were washed with cold PBS and then crushed directly into Trizol LS reagent (Invitrogen) using a tissuelyser and a stainless bead. RNA extraction was performed following standard Trizol protocol instructions.", "Trachea infection was performed by injecting the inoculum directly into and all along the lumen of trachea using a fine needle. Trachea was then incubated at 37\u00b0C, 2% CO 2 in inclined plates in order to keep trachea into the medium." ] },{ "paper_id": "3d8ad2b7cceac3f97d193df3beb627b05860c499", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Province. The approval ID is NKYVET 2015-0066, granted by the Jiangsu Academy of Agricultural Sciences Experimental Animal ethics committee. All efforts were made to minimize animal's suffering. The immunization, challenge, collection of serum samples and separation of pig PBMCs were performed in strict accordance with the guidelines of Jiangsu Province Animal Regulations (Government Decree No. 45).", "IFN-\u03b3 release assay. The isolated lymphocytes (1 \u00d7 10 6 cells/mL) were cultured in 24-well plates at 37 \u00b0C with 5% CO 2 , with or without 20 \u03bc g/mL PRRSV proteins. After 72 h incubation, culture supernatant was harvested and the presence of IFN-\u03b3 was tested with a commercial porcine IFN-\u03b3 immunoassay ELISA kit according to the manufacturer's instructions (USCN Business Co., Ltd., Wuhan, China). The concentrations of IFN-\u03b3 in the samples were determined from standard curves.", "Scientific RepoRts | 7:41886 | DOI: 10.1038/srep41886" ] },{ "paper_id": "3d91360fc7a5df1058b9db9e8615ffef804edacf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "From the 2095 references gathered from all the sources searched, a total of 97 English and non-English articles in Dutch, French, German, Japanese, and Spanish were accepted for inclusion ( Fig. 1) .", "Two authors independently reviewed the title and abstract of all articles resulting from the searches and the retrieved full texts of the relevant articles. The reviewers appraised the published full-text articles for inclusion according to the five criteria described below; articles were rejected if they did not meet all of the criteria. Disagreements during title and abstract screening and full-text review were resolved through thirdparty adjudication.", "While significant progress has been made in preventing device and procedure-related healthcare-associated infections (HAI), the threat of antimicrobial resistant organisms (ARO) and Clostridium difficile continues. In the USA, the prevalence rate of HAI was 4 % in 2011 [1] , and it has been estimated that there are at least two million ARO-related infections and 23,000 deaths each year [2] , resulting in $26-$33 billion additional medical costs [3] . An estimated 220,000 HAI and 8000 related deaths occur in Canada per year [4] . Healthcare-associated C. difficile and vancomycin-resistant Enterococci infections increased from 2007 to 2012, and carbapenemase-producing organisms appeared in 2010 [5] . The cost of readmissions alone due to nosocomial C. difficile-associated diarrhea is estimated to be at least $128,200 CDN per year per facility [6] . These observations highlight the need for more effective prevention and control practices and better therapy." ] },{ "paper_id": "3d91cc711f18ce05f6d63c11760e3ff4fd88928a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Female BALB/c (H-2 d ) mice aged 6-8 weeks were purchased from The Animal Resource Centre (Perth, WA) and maintained under standard conditions. All studies were approved by the Queensland Institute of Medical Research Animal Ethics Committee (protocol P1111).", "Conclusions: This work provides proof of concept for the potential of high-throughput approaches to identify T cell targets of complex parasitic, viral or bacterial pathogens from genomic sequence data, for rational vaccine development against emerging and re-emerging diseases that pose a threat to public health." ] },{ "paper_id": "3d950119c81a03ac40e3d304f3fee12617a3316c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following source data and figure supplement are available for figure 6:", "The following figure supplements are available for figure 3: marginally more severe phenotype than vector control, implying that the UBZ mutant may still interact with PCNA or some other factor(s) that could lead to increased nascent DNA degradation.", "Isolation of protein on nascent DNA (iPOND) is a powerful technique to identify proteins bound to nascent DNA in the vicinity of the replisome during unperturbed replication (Sirbu et al., 2012) ." ] },{ "paper_id": "3d9b665ff94e800c03f3051567312a3921a76e81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "suggesting that other factors, possibly host derived, render the endothelium unable to regulate barrier integrity, leading to pulmonary edema (6) .", "Plaque assay. Hantavirus plaque assays were performed as previously described (33) ." ] },{ "paper_id": "3daf73ca2c2bb003b6f6201b1924660cc2fd75a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In this review, we focused on the relationship between CsA and the replication of CoVs, and introduce some of the recent advances in this area.", "CoV replication relies on a variety of host factors, which also constitute potentially interesting targets for antiviral therapy [28] . Feline CoV (FCoV) is classified into two biotypes, the ubiquitous feline enteric CoV (FECV) and infectious peritonitis virus (FIPV). The widely accepted theory from in vitro studies is that FIPV arises by mutation from parental FECV in the gastrointestinal tract of infected cats [29, 30] . Many strategies for curing FIP have been attempted. Interferon \uf077 inhibits FIPV in vitro, but is ineffective in vivo [28] . Various other immunosuppressants, such as glucocorticoids and cyclophosphamide, have also been investigated; however, although these agents can prolong life, the outcome of FIPV infection remains fatal [31] . Thus, an effective vaccine and therapeutic medicine against FIPV are still needed.", "CD147-CypA interaction plays a critical role in HIV-1 infection [46] . The CD147-CypA complex could induce phosphorylation of the matrix protein (MA) to regulate the detachment of the reverse transcriptase complex from the membrane or promote transition from the step of hemifusion. Moreover, it is proposed that CD147-CypA interaction might indirectly affect capsid conformation. Efficient incorporation of CypA into the HIV-1 virion is mediated by a direct prolyl peptide bond between the CypA and a proline-rich loop in the HIV-1 capsid protein [47] . Disruption of CypA incorporation by Gag mutations or by treatment with CsA attenuated the infectivity of progeny viruses [48] . However, there is no evidence that the CD147-CypA complex affects the step of fusion in CoVs." ] },{ "paper_id": "3db2c3d613104b23711a28ea5f8f6a414d303376", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Strengths of present study are adequate sample size and children being recruited over 2 consecutive years including all the seasons. Limitations include children presenting to the health facility only were recruited, reinfection rate by the viruses were not considered, and simultaneous/secondary bacterial infections were not studied.", "Although viral etiology of ARIs and their impact on health care are much studied in developed countries, there is a gap in knowledge regarding the same in developing countries including India [8] . From the public health point of view, it is important to know the most common viral agents causing ARIs, their manifestations, how often they cause severe disease, and how severe ARIs can be prevented. In this study, we aimed to characterize the viral spectrum and pattern of upper and lower ARIs in children under five from eastern part of India.", "In LRIs, out of 174 cases (LRI = 101; severe LRI = 51; very severe LRI = 22), 161 were cured and 13 died. Of 13 cases who died, 10 had coinfection with more than 1 respiratory virus (IFV + RSV = 5; RSV + RV = 3; IFV + hCoV43 + RV = 2). In URIs, all were cured." ] },{ "paper_id": "3db3a962e710f4712e14a5162a9e7f3f136696f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The experiments described in this manuscript did not involve human subjects or nonhuman primates, so no institutional review board approval was required. The use of mice in the study was approved by the Animal Care and Use Committee at the Beijing Institute of Microbiology and Epidemiology.", "Two-day-old specific-pathogen-free Kunming mice, maintained together with the mother mice under specific-pathogen-free conditions, were purchased from the Animal Center of the Academy of Military Medical Sciences of China. Ten suckling mice were assigned to two groups, each containing five mice. The infection group was inoculated intracranially with 2610 6 TCID 50 of BYD1 in 20 ml of PBS. The mock infection group was inoculated intracranially with 20 ml of PBS. All the treated mice were observed daily, euthanized on the eighth day postinoculation, and their brains, hearts, lungs, and kidneys excised, fixed in 10% formalin, and embedded in paraffin blocks. The tissue sections were stained with hematoxylin-eosin (H&E) for blind pathological analysis by a veterinary pathologist.", "Phase-contrast images and fluorescent images of the transfected 293 T cells were captured at a magnification of 6200 using an Olympus inverted microscope and a Canon digital camera. Hep-2 cells infected with BYD1 and mock-transfected controls, and 293 T cells transfected with different vectors were fixed with 2% glutaraldehyde-0.5% paraformaldehyde in 0.1 M cacodylate buffer (pH 7.2) for subsequent standard processing, infiltration, embedding, ultrathin section preparation, and staining for highcontrast transmission electron microscopy (TEM). Electron microscopic images were taken with a Philips Tecnai-10 electron microscope." ] },{ "paper_id": "3dc77148a29d1caf25a7a345f04d61d160385734", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sample processing and total nucleic acid (TNA) extraction Upon arrival, the cytobrushes and swabs were incubated at 40\u00b0C for 10 min. The cytobrushes and swabs were then turned upside down and centrifuged for 1 min at 6440 \u00d7 g. The samples from each patient (oropharyngeal cytobrush and nasal and conjunctival swabs) were pooled and subsequently divided as follows: two aliquots of 200 \u03bcL were used for TNA extractions and 400 \u03bcL were used for virus isolation. TNA extraction was performed using 200 \u03bcL of sample or cell culture supernatant with the MagNa Pure LC (Roche Diagnostics AG, Rotkreuz, Switzerland) using the MagNa Pure LC Total Nucleic Acid Isolation Kit (Roche Diagnostics) following the manufacturer's instructions. In each batch of extraction, a negative control that consisted of 200 \u03bcL of PBS was used to monitor for cross-contamination. TNA was stored at -20\u00b0C until qPCR analysis.", "TNA from swab/cytobrush from each cat was also tested for FHV-1 [43] , C. felis [44] , B. bronchiseptica [15] and M. felis [45] by qPCR using previously described methods. Moreover, the samples were also tested for FeLV [46] and FIV viral RNA [47] by RT-qPCR because both infections can lead to increased susceptibility to other infections and can be associated with inflammatory oral disease. Three samples from FCV-suspect cats could not be analyzed for B. bronchiseptica, M. felis, FeLV and FIV because of a lack of material.", "An association of FCV with intact reproductive status has been reported in an earlier study [52] . Although no clear explanation can be given for this association, possible reasons postulated earlier include hormonal effects, which might alter the replication and the persistence of the virus, and more social or aggressive interactions between the intact animals [52] .", "FCV vaccines have been shown to be efficacious in protecting cats from the development of severe disease; however, they do not induce sterilizing immunity [30, 31] . Moreover, most commercially available vaccines have been based on only a few FCV strains (i.e. FCV F9 and 255) for many decades. Therefore, the protective potential of FCV vaccines against different circulating FCV isolates has been controversially discussed in recent years [32] [33] [34] [35] . Efforts are made for the identification of new vaccine strains with broader cross-reactivity, the development of bi-or polyvalent vaccines and the inclusion of local FCV isolates [35] [36] [37] [38] . Along these lines, a vaccine containing two novel FCV strains has become commercially available in Switzerland (FCV G1 and 431) [35, 36] ." ] },{ "paper_id": "3ddbaa41fdf3c15e1677fd5cbc0a7d6c7f1e51fc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords Heat, inactivation, MERS-CoV. ", "The culture supernatants of the emerging Middle East respiratory syndrome coronavirus (MERS-CoV) were submitted to three temperatures over time and tested for infectivity by TCID 50 method on Vero E6 cells. At 56\u00b0C, almost 25 minutes were necessary to reduce the initial titre by 4 log 10 . Increasing temperature to 65\u00b0C had a strong negative effect on viral infectivity as virucidy dropped significantly to 1 minute. On the contrary, no significant decrease in titre was observed after 2 hours at 25\u00b0C. These data might be useful in establishing biosafety measures in laboratories against MERS-CoV." ] },{ "paper_id": "3ddc728885c89c86d141cc470752c9b740894e53", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Authors' contributions: SD and PC wrote and reviewed the manuscript together.", "The mechanisms by which diabetes confers altered susceptibility to infections are likely to be via multiple effects on the human immune system.", "It is generally recognised that people with diabetes are at increased risk of infection and worse outcomes, 10, 11 including diabetic foot infection, urinary tract infections (especially from ", "High-quality, large prospective epidemiology studies are needed to quantitate the problem, alongside randomised controlled trials of interventions to define optimal treatment strategies in diabetes. Raising awareness of the interaction of diabetes and infection with policy-makers, and ensuring the engagement of social scientists, health economists and the pharmaceutical industry in developing new strategies to fight this double burden in LMIC is vital." ] },{ "paper_id": "3dede13dfa857e159c3fd7830374e1dc76008f2e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Over the past decade, reverse genetics systems developed for the study of many of the positive-stranded RNA viruses can generate recombinant mutant viruses to study different aspects of virus biology. In particular, recombinant viruses expressing reporter proteins have been instrumental in tracking viral infection and spread in vivo, as well as in the development of novel antiviral drugs [17] [18] [19] [20] [21] [22] . In PRRSV, rescue systems to recover infectious viruses from full length complementary DNA (cDNA) clones have been established for type 1 and type 2 PRRSV to understand the viral life cycle, determine the function of viral protein, and study mutant virus pathogenesis [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] . Green fluorescent protein (GFP) and its variant enhanced GFP (EGFP) inserted into a number of viral genomes have become the widely used reporter genes to study viral entry mechanisms, observe the transport of viral nucleic acids in and out of the nucleus region, track the assembly and transport of newly synthesized viral components, and visualize the cell-tocell spread of newly synthesized viral particles [35] [36] [37] [38] [39] [40] .", "Previously, the drug CsA was demonstrated to inhibit the replication of a variety of RNA viruses using different pathways including herpes simplex virus, human immunodeficiency virus type 1, hepatitis C virus and influenza virus [53] [54] [55] [56] . In the present study, we demonstrate that CsA inhibited the HP-PRRSV replication in Marc-145 cells in a dose dependent manner ( Figure 5 ). These results were in accordance with a previous study showing that CsA inhibits arterivirus replication by interfering with viral RNA synthesis [57] .", "Cell to cell spread of rHP-PRRSV/SD16/TRS6-EGFP", "In conclusion, we report the rescue of a recombinant PRRSV carrying an EGFP reporter gene as a separate transcription unit. The PRRSV reverse genetics system used is highly flexible and may facilitate the engineering of recombinant multivalent vaccines by replacing the EGFP ORF sequences encoding immunogenic antigens from another virus. The generation of an EGFP-expressing HP-PRRSV could be a useful tool not only to monitor virus spread and screen for antiviral compounds and neutralising antibodies, but also for fundamental research on the biology of the virus." ] },{ "paper_id": "3df56c2e76799309cc7bdbc5ef8f968a1569a08c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In sum, our identification of a broad array of vertebrate-and marsupial-specific viruses in devils provides potential candidate viruses for future disease surveillance as part of the broader conservation management of devils once the pathogenic potential of these viruses has been elucidated.", "(ii) Random amplification. Extracted viral nucleic acids were pooled as for the total RNA preparations for metatranscriptomics described above. Pooled extractions were subjected to first-and secondstrand synthesis and random PCR amplification for 22 cycles using a complete whole-transcriptome amplification (WTA2) kit (Sigma-Aldrich) (17) . WTA2 PCR products were then purified using Agencourt AMPure XP beads (Beckman Coulter) prior to library preparation and sequencing.", "Fecal suspensions (10%) were homogenized for 1 min using the Bead Ruptor homogenizer (Omni International) at 5 m\u00b7s \u03ea1 and centrifuged at 15,000 \u03eb g for 3 min (Hitachi centrifuge, type CT15E; T15A62 fixed-angle rotor). Resulting supernatants were filtered through 0.45-m membrane filters (Corning), and filtrates were treated with a cocktail of nucleases at 37\u00b0C for 2 h. Viral DNA and RNA were then simultaneously extracted using the QIAamp viral RNA minikit (Qiagen) (17) ." ] },{ "paper_id": "3df8818685d06d65f93674101b8ca899731efc36", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A comparison of the incidence of rabies between four southern provinces (Guangdong, Guangxi, Hubei and Hunan) of China 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 Year", "Among the 244 cases with informative medical records, 67.2% (164/244) did not seek any medical service and the remaining 32.8% (80/244) received PEP. Table 1 " ] },{ "paper_id": "3e01904917aea1c46193a3e98307e95be703c7c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Acceleration of an initial stage in transferrin folding 10 Drosophila rhodopsin Folding and stability of R1-6 rhodopsin by the NinaA-encoded protein (an eye-specific CyP) 11, 12 Trafficking Apoptosis-inducing factor (AIF) Co-translocation to the neuronal nuclei to induce cell death after cerebral hypoxia-ischemia and ALS 13, 14 Heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2)", "CXCR4-mediated nuclear export of hnRNP A2, nuclear translocation of ERK1/2, and chemotactic cell migration 15 ", "The authors declare no conflict of interest.", "mediated, in part, through the activation of the ubiquitous Ig like CD147 cell receptor. 29 A growing body of evidence suggested its involvement in key processes underling human pathologies. The objective of this article is to review the current knowledge of CyPA regarding its potential role in several human diseases in order to offer novel therapeutic strategies." ] },{ "paper_id": "3e03474356ba4414f631c94959e3c22e8e239c49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No. of strains RealAmp", "Acinetobacter baumannii ATCC19606 a 1 + Pseudomonas aeruginosa ATCC27853 a 1 2", "Escherichia coli ATCC25922 a 1 2" ] },{ "paper_id": "3e035bd3c87d15ec4bca05cd13551c70d1bc5e78", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus-containing supernatants were centrifuged through 20% sucrose cushion. Concentrated viral sample was placed for 2 min onto a carbon-coated, UV-treated 200 mesh copper grid as described [58] . Sample-containing grids were rinsed 15 s in water, drained off water with filter paper, and stained for 1 min in filtered 1.3% uranyl acetate. Staining solution was drained off by applying filter paper to the edge of the grid. Grids were left to dry before viewing in a JOEL JEM-2000 EXII transmission electron microscope. Images were collected at 20,0006 and 60,0006.", "Compared to MoGag, which had significant amounts of Gag detected at lower sucrose density fractions (1 and 2), MoGagfsD molecules were mostly sedimented at fractions 3 to 5, a difference that may be explained in part by p6 pol -PR contributing to MoGagfsD multimerization via PR dimer interaction. Although GagfsD presented an efficient multimerization profile, it produced VLPs at a relatively lower level compared to WtGag (Figs. 4C and 4D). This may have been due to its lack of p6 gag , which is required for efficient virus budding [33, 34] .", "The Gag assembly-defective mutant MoGag was constructed by recombining the CA mutant M39A/W184A/M185A with NC mutant NC15A, which was kindly provided by P. Spearman [56] . NC15A has 15 NC-basic residues replaced with alanine. M39A/ W184A/M185A was created by overlapping PCR with the following mutagenic primers: for M39A, 59-CTGATAGCGCT-GAAAATGCGGGTATCA-39, and for W184A/M185A, 59-CAACAACGTTTCTGTAGCCGCATTTTTTAC-39. The Mo-Gag mutation was cloned into the indicated PR-leucine zipper constructs. As described previously, Gag/PR has deleted RT and IN coding sequences [23] . In D25, Arg is substituted for the PR catalytic residue Asp [20] . The backbone of all expression constructs is the HIV-1 proviral plasmid HIVgpt [57] ." ] },{ "paper_id": "3e168aef44683549563640db5ca32da62be4e27b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Western blotting. Ileum samples were lysed on ice in RIPA lysis buffer (Beyotime) supplemented with 1 mM phenylmethylsulfonyl fluoride (Beyotime). The protein concentration was measured using BCA Protine Assay Kit (Beyotime). Protein were separated by 8% SDS-PAGE and transferred to a polyvinylidene fluoride membrane (Millipore). Then, membrane was blocked with 5% non-fat milk and incubated with primary antibodies overnight at 4\u00b0C and secondary antibodies for 1.5 h at room temperature. Signals were detected with WESTAR NOVA 2.0 (Cyanagen). The antibodies used were: rabbit anti-APN (1:2000, a generous gift from YW Huang 11 ), mouse anti-\u03b2-actin (1:2000, Beyotime), HRP-conjugated anti-mouse IgG (1:10000, A0216; Beyotime) or HRP-conjugated anti-rabbit IgG (1:10000, A0208; Beyotime).", "Ethics approval. All experiments involving animals were performed based on the guidelines for the care and use of lab animals and approved by the Animal Ethics Committee of Jiangsu Academy of Agricultural Sciences (NKYVET 2014-063).", "To construct the targeting vector expressing Cas9n and one pair of sgRNA, each oligonucleotide encoding sgRNA was ligated with Bbs-digested PX461 plasmid (Gfp-containing) to construct PX461-sgRNA1 and PX461-sgRNA2, in which sgRNAs are driven by U6 promoters. U6-sgRNA2 was amplified by PCR, digested with Kpn I (New England Biolabs), and fused with Kpn I-treated PX461-sgRNA1 (New England Biolabs). The resultant plasmid was named PX-461-A213 + A258. The sequence of the four oligonucleotides encoding sgRNAs (Shanghai Sangon) were: sgRNA1 (A213-Fwd): caccgCAGGCAACAGCGTTGTGGGT; sgRNA2 (A213-Rev): aaacACCCACAACGCTGTTGCCTGc; sgRNA3 (A258-Fwd): caccgACCCTACCTCACTCCCAACG; sgRNA4 (A258-Rev): aaacCGTTGGGAGTGAGGTAGGGTc." ] },{ "paper_id": "3e18531b5a0a745c732d05de8eac8862a9b6a8e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition to the nsps mentioned above, other CoV nsps are involved in RNA binding (nsp9 and nsp10; [48, 49] ) or in evasion of the antiviral response of the host (nsp1 and nsp3; [50] [51] [52] [53] [54] [55] [56] [57] ). The function of nsp2 is not yet known, although this protein was shown not to be essential for virus replication [58, 59] . The reader is referred to several excellent reviews on this topic for more detailed insights [10, 60, 61] .", "The Coronaviridae are a family of evolutionary related, enveloped +RNA viruses that together with the Arteriviridae and the Roniviridae, belong to the order of the Nidovirales. Historically, CoVs have been recognized as important infectious agents for domestic livestock, poultry and companion animals. In contrast to the animal viruses, human CoVs (HCoVs) have been associated with relatively mild upper and lower respiratory tract infections, including ordinary common colds. However, in 2002-2003 the outbreak of a novel HCoV in China, causing severe fatal atypical pneumonia in infected individuals, demonstrated that HCoVs are also able to induce severe life-threatening disease in humans. This virus was called the SARS-CoV [6, 7] and emerged in the human population from an animal reservoir, probably originating from bats, with palm civet cats acting as intermediate hosts [8, 9] .", "Positive-strand RNA (+RNA) viruses are the most abundant viruses in nature. Many important pathogens belong to this category, including poliovirus (PV), hepatitis C virus (HCV) and the severe acute respiratory syndrome (SARS)-coronavirus (CoV). A distinctive common feature of +RNA viruses is the replication of their genomes in the cytoplasm of the host cell in association with rearranged cellular membranes that are remodeled into organelle-like membranous structures to which the viral replication-transcription complexes (RTCs) localize.", "The various membrane rearrangements observed in +RNA virus-infected cells range in size from 40 to 400 nm, contain lipids that are derived from various cellular compartments and demonstrate an impressively diverse plethora of morphologies that include, among others, clusters of vesicles for the Picorna-and Togaviridae, spherule-like invaginations for the Bromoviridae and Nodaviridae, and vesicle packets and membranous webs for the Flaviviridae (reviewed in [1] [2] [3] ). These membrane rearrangements seem to be beneficial for (i) sequestering and concentrating all viral and cellular components necessary for viral RNA synthesis and (ii) to provide a protective microenvironment against virus-elicited host defense mechanisms.", "The viral replicase is encoded by the two most 5' ORFs of the genomic RNA, ORF1a and ORF1b. Translation of ORF1a and ORF1b of the genomic RNA generates two very large replicase polyproteins (pp), pp1a and pp1ab. The latter is synthesized via a \u22121 ribosomal frameshift mechanism mediated by a pseudoknot structural element at the end of ORF1a [16, 17] . These replicase polyproteins are extensively processed by viral proteinases (reviewed in [18] ), resulting in the generation of sixteen nonstructural proteins (nsps). A schematic representation of the CoV replicase polyprotein is shown in Figure 1B ." ] },{ "paper_id": "3e276874c125f0c8c8490eb41e9ae26cf767447c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3e337761fbc884c46ccd834207c310a1b78f0e42", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords: tumor antigens; head and neck cancer; human papilloma virus-16 (HPV-16); luciferase immunoprecipitation systems (LIPS)", "The HV controls (n = 20) from the NIH Blood bank represented subjects with an average age of 57 years and were 80% male. For the subjects with HNSCC (n = 20), the average age of cancer diagnosis was 61 years and 75% were male. The clinical information on the CC (n = 20) was not available. The serum samples from SLE patients (n = 20) had an average age of 47.1 years and were 100% female.", "GraphPad Prism 6 software (San Diego, CA, USA) was employed for data plotting and statistical analysis. Non-parametric Mann-Whitney U tests were used to compare the antibody levels among groups and only statistically significant (p < 0.05) are shown in the figures. For calculations of sensitivity and specificity, cut-off limits for each antigen were derived from the mean value plus three standard deviations of the healthy blood donor controls [26] ." ] },{ "paper_id": "3e339ee119ba0065cad4c40897cd1bc9dd0f118a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples were lysed in 1\u00d7 loading buffer (0.08 M Tris, 2.0% (w/v) SDS, 10% (v/v) glycerol, 0.1 M dithiothreitol, 0.2% (w/v) bromophenol blue, pH 6.8). Samples were boiled for 10 min and resolved by one-dimensional SDS-PAGE. Proteins were transferred onto nitrocellulose membranes and the membranes were probed with the appropriate primary antibody. Secondary antibodies were alkaline phosphatase-conjugated anti-human, anti-rabbit, anti-mouse, or anti-goat IgG (Jackson Immunoresearch, Inc.). Gels were stained using 5-bromo-4-chloro-3-indolyl phosphate (BCIP) and nitro blue tetrazolium (NBT) solutions (Sigma).", "2BS cells were washed twice in cold 1\u00d7 PBS and harvested. Pellets were lysed in 700 \u03bcL lysis buffer (1% Nonidet P40 and 20 \u03bcL protease inhibitor cocktail set III (Calbiochem) in 1 mL HBS-EP Buffer (pH 7.4, BIAcore), followed by freezing at -70\u00b0C and thawing at room temperature three times. Cells were harvested by centrifugation (12,000 \u00d7 g, 20 min, 4\u00b0C). Supernatant was collected, aliquoted, and stored at -70\u00b0C.", "Protein bands of interest were cut out of the gel and rinsed twice in 50% (v/v) methanol (HPLC grade). In-gel digestion was performed using sequencing-grade modified trypsin (Promega). Extracted peptides were analyzed by matrix-assisted laser desorption ionization time-offlight (MALDI-TOF) mass spectrometry by the Life Science Academy of Beijing University, China using an Ultraflex\u2122 MALDI-TOF/TOF (Bruker) and Data Explorer (v. 4.0). Proteins were identified by comparison of their monoisotopic masses with those in the NCBI nonredundant or SwissProt databases using the MS-Fit search engine of ProteinProspector.", "The outbreak of severe acute respiratory syndrome (SARS), which began in the Guangdong Province of China, spread rapidly to more than 30 countries during 2003. SARS has an acute onset, is highly transmissible and has a high case-mortality rate (approximately 10%) [1, 2] . During SARS infection, three phases of viral replication result in respiratory tract pathological changes and an over-exuberant host immune response. This mediates immunopathological damage of the lungs and other organs, and pulmonary fibrosis. SARS mortality is caused primarily by extensive lung damage and severe lymphopenia [3] . Approximately 10% of individuals (6.8% of patients younger and 55% of patients older than 60 years of age) with clinical symptoms died as a consequence of immunopathological lung damage, caused by a hyperactive antiviral immune response [4] ." ] },{ "paper_id": "3e3925148a778080ac13f3f532ee63ae24a3d1e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The mode of CHIKV maintenance in nature is complex and appears to be region-specific. In Africa, CHIKV is maintained in enzootic cycles involving transmission between non-human primates and canopy-dwelling, primatophilic Aedes mosquitoes, primarily A. furcifer, A. taylori, A. africanus, A. luteocephalus and A. neoafricanus [15] [16] [17] [18] [19] . In contrast, CHIKV transmission in Asia is believed to rely on humans alone as reservoir/amplification hosts, with the domestic A. aegypti and to lesser extent the peridomestic A. albopictus serving as primary urban mosquito vectors [19, 20] . Recent evidence, however, suggests the possibility of additional sylvatic, zoonotic transmission cycles [21, 22] .", "A new lineage of Chikungunya virus (CHIKV) [arbovirus in family Alphavirus, genus Togaviridae] emerged in 2004 in Kenya and subsequently spread into many countries in the Indian Ocean basin [hence the name: Indian Ocean lineage (IOL)], causing devastating outbreaks of arthritic disease [9] . In India, IOL strains were first detected in December 2005 followed by extensive geographic expansion during 2006-2011 into 19 Indian states with a total number of human cases estimated in 2007 at between 1.4 and 6.5 million [10, 11] . During 2006, the states most affected by CHIKV were Karnataka and Maharashtra, with a subsequent shift to Kerala, Coastal Karnataka and West Bengal [12, 13] . Several hypothetical factors may have contributed to the CHIKV emergence/spread on the Indian subcontinent [14] , including: 1) the use of immunologically na\u00efve human populations for maintenance, amplification and virus dispersal among localities, 2) reliance on peridomestic and anthropophilic mosquitoes as vectors, and 3) the IOL-specific genetic predisposition for rapid adaptation to Aedes (A.) albopictus, which was previously considered only a secondary CHIKV vector [9] .", "The E2-L210Q substitution is responsible for increased CHIKV dissemination in A. albopictus" ] },{ "paper_id": "3e3dc81c5985a37a950e4f63ffa10f4d5f9581aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "TYLCV DNA cloned in pBluescript KS-at an XbaI site was purified from E. coli using NucleoSpin\u00ae Plasmid kit (Macherey-Nagel GmbH & Co, D\u00fcren, Germany). The concentration of DNA (39.74 ng/\u03bcl) was determined using a Nanodrop 2000 (Thermo Scientific, Wilmington DE) and calculating the mean of three repeats for each treatment.", "All primers (Table 1) were designed to function in both PCR and RPA. As recommended for RPA, primers were \u2265 29 bp long, were GC-rich in the 3'-end, contained a pyrimidine at the 5'-end, and amplified fragments smaller than 500 bp [12, 13] . Two primers were modified from existing primers TYC1F and TYC1R which had been used in PCR to amplify a portion of the C1 gene of TYLCV [32] . Primer TYC1F (underlined) was expanded to include more of the TYLCV genome sequence to create TYL828F: 5'-CCTAG AGACCTGGCCCACATTGTTTTGCCTGTTCTGC-3' , and similarly, TYC1R (underlined) was expanded to create primer TYL832R 5'-CCATCCGGTAATATT ATACGGA TGGCCGC-3'." ] },{ "paper_id": "3e418546d0b83c4b152b9e1200401bba25364427", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Whole-cell extracts were prepared by cell lysis, equivalent protein content boiled in SDS sample buffer, resolved by SDS/ PAGE, transferred to Immobilon-P membrane (Millipore), and probed with the indicated antibodies.", "The following antibodies were used in this study for either ", "Influenza A virus A/Puerto Rico/8/1934 (H1N1) (PR8, Charles River Labs) and A/WSN/33 (H1N1) (kind gift of Dr. Peter Palese, Microbiology Dept., Mt. Sinai School of Medicine, NY, NY) were propagated and assessed for viral infectivity as previously described [14] . Influenza A virus A/Vietnam/1203/ 2004 (H5N1) was propagated and characterized as previously described [61] .", "The 2009 H1N1 pandemic provided a strong reminder of the threat that influenza A virus poses to world health (http://www. cdc.gov/h1n1flu/cdcresponse.htm). The most effective means of protection against influenza is the seasonal vaccine. However, if the vaccine does not match the viral strains, its effectiveness can be reduced to 50% or less [1, 2] . Among small molecules, only two approved influenza drugs remain effective, zanamivir (Relenza) and oseltamivir (Tamiflu). Although resistance to zanamivir is rare, there has been an increase in oseltamivir-resistant flu strains [3] . Of concern, both drugs target viral neuraminidase (NA), precluding combinatorial therapy to minimize resistance [4, 5] . Thus, research to identify new anti-influenza strategies would be useful." ] },{ "paper_id": "3e4de1d7982eb2ce67d340a63175adfdab398686", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethical approval. All procedures and protocols for sample collection and processing were approved by the Administrative Committee on Animal Welfare of the Institute of Zhejiang and Fujian CDC Veterinary and the Ethics Committee of the CDC of Easten Theater. All methods were performed in accordance with the relevant guidelines and regulations (Approval number: 2015009). Table 1 . Each sample (approximately 1 g of intestine tissue) was immediately transferred into viral transport medium and stored in liquid nitrogen prior to transportation to the laboratory 35 . Samples were stored at \u221280 \u00b0C until analyzed.", "Adeno-associated viruses (AAVs) were discovered in 1965 as a small contaminant. AAVs are a group of small single-stranded DNA (ssDNA) viruses without envelopes that belong to the parvovirus family. The entire genome of AAV is approximately 4.7 kb and contains two major ORFs that encode for Rep and Cap proteins. Under normal circumstances, the AAV virus can coexist within the mammalian host for an extended period without apparent pathogenicity. However, productive infection only occurs in the presence of a helper virus, either adenovirus or herpesvirus [1] [2] [3] [4] [5] [6] [7] . Due to this, AAV has become an important gene therapy vector for its non-pathogenic and conditional infectious life cycle 8 .", "Nucleotide sequence accession numbers. All sequences obtained in this study were deposited in GenBank under accession numbers MK391482 for BtAAV-CXC1 complete genome, MK357907, MK394009-MK394021 and MK394023-MK394056 for the 48 partial rep sequences of AAVs, MK394057-MK394080 for the 24 partial cap sequences of AAVs 42 .", "In conclusion, our study of viruses in bat samples in southeast China identified novel AAVs and their distinct genetic diversity. This extends our knowledge of the diversity of bat AAVs and its evolution and emergence in humans and animals. However additional studies are warranted using larger samplings from different locations to further understand the global diversity of bat viruses." ] },{ "paper_id": "3e5668500c3bdc49bb0a1689019793b74c624407", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DMEM, fetal bovine serum, penicillin, streptomycin, PBS, and other tissue culture reagents were purchased from Gibco BRL (Grand Island, NY, USA). Quercetin, indomethacin, Griess reagent, and all other chemicals were purchased from Sigma-Aldrich (St. Louis, MO, USA).", "Viruses can induce tissue necrosis and inflammation and viral infections activate the immune response, trigger inflammatory diseases, and promote cancer growth [6] . dsRNA, which is recognized by Toll-like receptor-3, induces the production of inflammatory mediators, such as NO, interleukin (IL)-6, and tumor necrosis factor (TNF)-\u03b1, in macrophages; polyinosinic-polycytidylic acid (poly(I:C)) is considered a synthetic analog of dsRNA [7] . dsRNA activates nuclear factor kappa beta and the calcium signaling pathway [8] .", "NO is a membrane-permeable signaling molecule involved in a broad array of biologic processes through its ability to modify proteins, lipids, and DNA and alter their functions and immunogenicity [22] . Appropriate levels of NO assist in mounting an effective defense against invading microbes, whereas the inability to generate NO results in serious, even fatal, susceptibility to infections. Furthermore, dysregulation or overproduction of NO has been implicated in the pathogenesis of many disorders, including atherosclerosis, neurodegenerative diseases, inflammatory autoimmune diseases, and cancers; therefore, the potential exists for NO to behave like a \"double-edged\" biological sword depending on it level. Thus, it is crucial to understand regulation of NO [23] .", "Immunity is essential for life and innate immunity provides the first line of response to invading pathogens [1] . Inflammation is a primordial response that protects against infection and restores damaged tissue to its normal physiological functioning [2] . A recent study reported that it is becoming more important to maintain inflammatory homeostasis and to regulate the immune system [3] . Inflammation is an innate immune response by various immune cells, such as macrophages, to protect against harmful stimuli, such as viruses and bacteria [4] . During the inflammatory reaction, macrophages produce inflammatory mediators, such as nitric oxide (NO), cytokines, and growth factors. Calcium is released by macrophages during inflammatory processes. Therefore, modulating macrophage-mediated inflammatory responses is important for creating a new therapeutic approach against inflammatory diseases [5] ." ] },{ "paper_id": "3e572863713d0fbe8cf60ea9991dd5c9993e6c7d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Healthcare facilities were stratified into 8 categories: large, medium and small transfer volume teaching hospital; large, medium and small transfer volume community hospital; or medium and small transfer volume nursing home/long term care facility. Large transfer volume facilities referred to facilities that transferred more than 1,000 patients to another facility in a single year. Small transfer volume facilities referred to facilities that transferred less than 400 patients to another facility in a year and medium volume senders between 400 and 999 patient transfers (Table 1) .", "The highest overall error rate (8.4%) was for the last name variable and this was almost always due to spelling or typographical errors." ] },{ "paper_id": "3e5e8609bc2b23b770b037ee006b028a17f4a121", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One must be cautious when interpreting the literature on bat defenses. The order Chiroptera contains more than 1200 species [17] . Due to this diversity, the information obtained from one species may not apply to others. For instance, in the black flying fox (Pteropus alecto), the interferon gene locus is contracted, whereas in the Egyptian fruit bat (Rousettus aegyptiacus), this locus is expanded [18, 19] . Other examples are discussed later in this review.", "It has been observed that viruses which severely affect other mammals, including humans, are apparently nonpathogenic for bats [20] . This adaptability of bats to harbor many viruses without showing overt pathology suggests that bats have evolved immune mechanisms that allow for benign virus-host relationships.", "These studies suggest that in bats of several species, higher level of interferon and ISGs are always present in their cells, which makes them better prepared to control viruses. Overall, bats seem to possess either an \"always ON\" interferon strategy plus or a better antiviral ISG defense strategy." ] },{ "paper_id": "3e6c85e4e3409c135ec4d5525290a9908aac2b58", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After obtaining informed consent, peripheral blood mononuclear cells (PBMCs) from healthy adults were isolated using Lymphoprep and isolation of monocytes from the PBMC fraction was performed using an indirect negative selection magnetic labeling kit (Monocyte Isolation Kit II human; Miltenyi Biotec). Each 96-well plate was filled with 5 x 10 5 PBMC per well or 1x10 5 isolated monocytes per well. The study was approved by the committee on Research involved Human Subjects of the Radboudumc.", "The authors declare that they have no competing interests." ] },{ "paper_id": "3e6e8f31ed44595ef47bb2d50934901e5d681654", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bp: base pair; CGH: comparative genomic hybridization; chr: chromosome; CNV: copy number variation; SNP: single nucleotide polymorphism; WGA: whole genome amplification.", "Plasmodium falciparum is the intracellular parasite responsible for the majority of the world's malaria morbidity and mortality burden in humans, causing an estimated 243 million episodes of malaria and 863,000 deaths each year [1] . Efforts to control and eradicate malaria are hampered by the accelerated evolution of drug resistance in the parasite. To date, the parasite has developed resistance to all major antimalarial drugs, raising concerns about the spread of drug-resistant parasites and the ability to effectively treat malaria [2] . The development of new technologies aimed at understanding parasite genome variability provides hope in identifying new drug targets, implementing smarter treatment plans, and ultimately reducing or eliminating the burden of malaria.", "Microarrays provide a relatively fast and inexpensive way of examining genomic variation in P. falciparum [14] . Array comparative genomic hybridization (CGH) has been successfully used to look at structural variation and CNV in multiple P. falciparum strains [12, [15] [16] [17] , while large-scale sequencing efforts identifying SNPs [18] [19] [20] have spurred the development of SNP microarrays. Neafsey et al. [21] genotyped 1,638 out of 3,000 queried SNPs with 100% accuracy using an Affymextrix 3K SNP assay. Mu et al. [22] used Affymetrix molecular inversion probe technology to genotype 2,763 of 3,354 SNPs with >90% call rate. Multiple groups have successfully applied CGH for SNP detection with 80 to 90% sensitivity to approximately 3,000 SNPs [23, 24] and identified parameters influencing SNP detection [24, 25] . However, the reported detection rates are based on a core subset of SNPs (approximately 3,000) in a genome with more than 100,000 cataloged SNPs (PlasmoDB v5.5) [26] ." ] },{ "paper_id": "3e7042ac51bcdbd64db05d998292e8ed45ebfc07", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.ppat.1008314.g003 role in cell wall degradation. For consistency with what was previously proposed for \u03d511 [21] , we will refer to this protein as Tal, for \"tail-associated lysin,\" although its enzymatic activity has not yet been established.", "Our study provides a structural basis for understanding host specificity and the infection process in staphylococcal bacteriophages. Since bacteriophages are the primary mediators of horizontal gene transfer in staphylococci, this process is critical to the dissemination of virulence factors and the evolution of pathogenicity in S. aureus and other pathogens. The ability to infect a variety of strains and species will also be important for the development of effective therapeutic strategies utilizing phages." ] },{ "paper_id": "3e72fd7554ad263eefddd4a0c6ee06afea606a44", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The emergence of genetic tools to explore species differences has had a tremendous impact on our knowledge of global biodiversity and has in some instances provided greater insight into higher order taxonomic relationships [1] . In particular, due to the mitochondrial genome's limited intra-specific variation but significant inter-specific divergence, partial nucleotide sequencing (barcoding) of certain mitochondrial loci for the purpose of species discrimination has gained widespread acceptance [2, 3] . Two mitochondrial loci, cyt b (cytochrome b) and COI (cytochrome c oxidase subunit I), have gained particular prominence in this role [2, 4] . Based on the pioneering work of Hebert and colleagues [5, 6] , the international barcode of life (IBOL) consortium, which seeks to generate millions of DNA barcodes for thousands of species world-wide, has adopted COI barcodes as the standard for studies on biodiversity throughout the animal kingdom [7] .", "The reactivity and specificity of the 30 DIG-labelled probes on slot blots were first examined using COI PCR products generated from representative members of each of the initial 13 species. At a hybridization temperature of 37 \u00b0C, all probes exhibited strong binding to their targeted species and many showed either no or very weak cross reactivity with other species, as illustrated for selected probes in Figure 2 .", "Keywords: bats; microarray; rabies; Chiroptera; COI" ] },{ "paper_id": "3e7cfb0f2665388e6a1f1d8a92b16d16f65563ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study revealed a low AT rate in Taiwan than that in other countries. Pediatric AT incidence increased during 1997-2010. Although a rising prevalence of obstructive and PLOS ONE | https://doi.", "We conducted a retrospective, population-based cohort study using data from the National Health Insurance Research Database (NHIRD); the NHI commenced in 1995 and covers over 99% of the population in Taiwan [24] . The Longitudinal Health Insurance Database (LHID) contains the complete claims data from 2005 of 1 million beneficiaries. The authors used the registry files from 1997 to 2010 and all applications for reimbursements regarding the inpatient and outpatient healthcare services provided to each patient for analysis. The Institutional Review Board of Cardinal Tien Hospital approved this study (CTH-103-3-5-035) and waived informed consent because the datasets consisted of anonymized, de-identified nationwide data." ] },{ "paper_id": "3e8286a0531a46c267f34d20e60a4754c2391a09", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1) A Special Needs Preflight Checklist: 16 Things You Need to Do before Heading to the Airport (http:// www.friendshipcircle.org/blog/2012/01/09/a-specialneeds-pre-flight-checklist/). This website gives some tips about travelling with a ventilator.", "Ondine's curse, also called congenital central hypoventilation syndrome (CCHS) or primary alveolar hypoventilation, is a serious form of central nervous system failure, involving an inborn failure of autonomic control of breathing. Patients generally require tracheotomies and lifetime mechanical ventilator support. With advances of home ventilatory support, patients with central hypoventilation are no longer \"cursed.\" They can live a relative normal life at home, as reported by Hon et al., even in the remote countryside setting in one case report [5] [6] [7] .", "Websites of checklists for commercial air-travel preparation for ventilated children are as follows:" ] },{ "paper_id": "3e86a490327b0f473d776363d3f2e67ddd04d681", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Frontiers in Cellular and Infection Microbiology | www.frontiersin.org by shRNA were identified by sequencing and BLAST search.", "Y-LC and Y-LL designed research, analyzed data and wrote the paper. Y-LC performed research. C-LL provided critical reagents.", "This work was supported by grants awarded to Y-LL from Academia Sinica (106-2101-01-11-01) and Ministry of Science and Technology, Taiwan (MOST 106-0210-01-15-02)." ] },{ "paper_id": "3e8d0363f49f83917e0ddddf7b4322186da47dbc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical microbiology laboratories have been increasingly investing in next generation sequencing (NGS) in recent years. Clinical applications include, for example, outbreak investigation, viral typing and drug resistance analysis, pathogen (shotgun) metagenomics, and microbiome (amplicon-based) metagenomics.", "Clinical metagenomics is a complex workflow including several critical steps from sample preparation up to reporting of pathogens. In particular, it heavily relies on bioinformatics for data processing, analysis and interpretation. Efforts have been made to benchmark bioinformatics tools for the detection of bacteria from patient samples [10] , for internal laboratory validation of clinical metagenomics assays for pathogen detection in cerebrospinal fluid [1] and to establish guidelines for the validation of clinical metagenomics assays, also using spiked samples and artificial data [11] .", "Finally, a NIBSC negative control [14] was prepared by pooling the content of two vials of 4 mL, mixed and 1 mL aliquots were stored at \u221220 \u2022 C until shipment on dry ice.", "The common database, consisting of the training set, was provided in three versions: One with reference viral sequences only, one supplemented with non-target/contaminant sequences (bacteria, fungi, bacteriophages, etc.), and one supplemented with human sequences." ] },{ "paper_id": "3e8d47918fb2187af3e556eaf1d5e343f42b0c06", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HBoV (Human bocavirus); LTRI (Lower respiratory tract infection); Q-PCR (Quantitative polymerase chain reaction). ", "Finding" ] },{ "paper_id": "3e8d986f56b6afb805e70236871627835e68372c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Let L i (t) be a nonnegative continuous random variable that represents the duration of contact exposure, starting at time t, required for susceptible i to become infected. We assume that L i (t) is distributed exponentially with mean 1/\u03bb i (t), where \u03bb i (t) represents the instantaneous force of infection applied to susceptible i at time t [55] [56] [57] . The probability that susceptible i, whose contact exposure has started at time t, will develop infection at time t + \u0394t is then given as", "6", "where \u03b4 i \u00b7\u00b7 denotes the regression coefficient associated with resource i and \u03b4 im \u00b7\u00b7 is the regression coefficient for the interaction between resources i and m. Similar models are used for Y hk , D hk , and V hk .", "In Sections 2.1-2.3, we present the details of the simulation and optimization models. A testbed illustration and a comparison of our strategy to the myopic policy is given in Section 3.", "It is assumed that at any point of time, an individual belongs to one of the following compartments (see Figure 4 ): susceptible, contacted (by an infectious individual), infected (asymptomatic or symptomatic), and recovered/deceased. In what follows, we present the infection transmission and disease natural history model, which delineates the transitions between the above compartments." ] },{ "paper_id": "3e9d0220802e3e3fba0b25f1e2cd46b9412c4317", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 25 \u03bcg protein in each lane was separated by SDS-PAGE (8~12% gels) and then transferred to PVDF membranes (Millipore, Bedford, MA, USA). After blocking with 5% skimmed milk for 2 h at room temperature, PVDF membranes were incubated with primary antibodies at 4\u00b0C overnight. After washing the incubated membranes three times with TBST (0.05% M Tris-base, 0.5 M NaCl supplemented with 0.1% Tween-20), the membranes were incubated with horseradish peroxidase (HRP)conjugated secondary antibodies for 2 h at room temperature. After washing the membranes three times with TBST again, blots were visualized with the ECL plus ChemiDoc TM MP Imaging System (Bio-Rad, Hercules, CA, USA). Band intensities were determined using Image Lab software (version 5.1, Bio-Rad). The antibodies used were as follows: \u03b2-actin ", "Cisplatin binds to DNA and forms DNA adducts that will induce DNA damage and tumour cell apoptosis [19, 20] . Multiple mechanisms are responsible for cisplatin resistance; one of the most predominant mechanisms is defective apoptosis [6, 21] . It is clear that apoptosis defects not only promote carcinogenesis but also lead to chemoresistance [21] .", "Total RNA was extracted from cells using the TRIzol reagent and was reverse transcribed into cDNA with reverse transcription kits according to the manufacturer's protocols (Thermo Fisher Scientific, Waltham, MA, USA). Real-time quantitative PCR (RT-qPCR) was carried out by SYBR Green Master Mix (Bio-Rad, Hercules, CA) in the CFX96 Touch\u2122 Real-Time PCR Detection System (Bio-Rad, Hercules, CA). The cycle conditions were as follows: 40 cycles, denaturation at 95\u2103 for 5 seconds and amplification at 60\u2103 for 30 seconds. GAPDH was normalized as an internal control. Gene expression was calculated using the 2 -\u0394\u0394Ct method." ] },{ "paper_id": "3ea132bf32c7717caf9e57fd48e116eed79697b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The negative-positive cutoff value was set by the average OD ratio of 100 field negative samples and 100 positive samples by phage-based ELISA. A negative-positive threshold for each assay was determined using the Microsoft Excel spreadsheet which was generated.", "Receiver operating characteristic (ROC) analysis and Spearman test were run using SPSS 17.0 to analyze the correlation between GE in qPCR and corresponding OD values in the phage-based ELISA.", "Conceived and designed the experiments: XR. Performed the experiments: XW GL XR. Analyzed the data: XW YR XR. Contributed reagents/ materials/analysis tools: XR GL. Wrote the paper: XW XR. ", "Phage random peptide library is composed of a pool of billions of heterologous peptides expressed in the N terminus of the capsid protein of filamentous bacteriophages [8] . Phage random peptide library based phage display is well-developed technology to identify specific ligands of a target protein by a biopanning process. This technology can be applied in many fields such as antibody engineering [9] , drug discovery and manufacture [10] , pathogen diagnosis [11] and immunogen development [12] ." ] },{ "paper_id": "3eb1bcee33c1121bd5307cf9a0c91f2510f4f79f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3eb3c6212432888ecf0f2d3d2dc4a2fb6b4f17c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Programming language: Python 2.6 License: Free for academic use", "Where, N mat denotes the number of nucleotides matched between genomes A and B, L max is the max length of all genomes analyzed.", "Operating system(s): Linux for the distributed source code and operating system independent for the web servers" ] },{ "paper_id": "3ebb8d173e6297001673ec3ce3bb14e5c1cb9715", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The PCR products were analyzed by electrophoresis on a 2% TRIS-acetate-EDTA agarose gel.", "The vascular system was flushed via the ascending aorta with a rinsing solution containing heparin (2 ml/l; 10,000 U; Ratiopharm, Ulm, Germany), polyvinylpyrrolidone (25 g/l, MW 40.000; Roth, Karlsruhe, Germany) and procaine hydrochloride ( ", "The author(s) declare that they have no competing interests." ] },{ "paper_id": "3ebbe01c6f991fcc45a9b12f9421acd50d756503", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Methods: Prospective surveillance was conducted in a mixed medical and surgical ICU at a major teaching hospital from 2000 through 2008. Trend analysis was performed and logistic regression was used to assess prognostic factors of mortality.", "Surveillance of nosocomial infections (NIs) has become an integral part of infection control and quality assurance in many countries. Gastmeier et al. reported that effective surveillance could reduce the NI rate on average about 20-30% [1, 2] . Surveillance programs provide data on the microbes causing specific NIs and their resistance to antibiotics. Moreover, such programs can guide clinical practices and NI prevention efforts in different geographic regions and clinical settings.", "The rate of antibiotic resistance every year is presented in Table 3 (Figures 3 and 4) ." ] },{ "paper_id": "3ebbe746b0f09acf2bef30ee83a8fb7bb9cdc537", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the experiments were performed thrice with each sample in triplicate and results were graphed, with error bars indicating the standard deviation. Statistical significance was determined using Student's t-test.", "Our data may support the use of a vector containing amiRNAs against different targets in 3\u00a2UTR of JEV. These findings offer a proof of concept for the development of novel amiRNA-based therapeutics against emerging JEV.", "The JEV genome is a positive-sense, single-stranded RNA of *11 kb. The genome consists of a single open reading frame flanked by 5\u00a2 and 3\u00a2 noncoding regions. Several attempts were made earlier to target the viral proteins to inhibit JEV replication using different methods with varying success [11] [12] [13] [14] ." ] },{ "paper_id": "3ebd3fb346c40a654f1f9d8e48ef8daa1902d406", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "FIP occurs worldwide and is ubiquitous in virtually all cat populations [6] . The disease was reported as a major factor of kitten mortality in UK [9] and it is currently one of the leading infectious diseases causing death among young cats from shelters and catteries [6] .", "Multiple sequence alignment showed a few point mutations and single-nucleotide deletions in the sequences of local isolates ( Figure 2 ). These findings indicate single nucleotide polymorphisms (SNPs) in FCoVs as described previously [6, 20] . No particular pattern of mutation or deletion was found in this part of FCoVs genome.", "Phylogenetic tree constructed by cluster algorithm showed that the sequences were genetically separated in two distinct clusters; all local sequences fell into one main cluster and suggested they may derived from a common ancestor ( Figure 3 ). However, a whole genome sequence is needed to determine genetic pattern of Malaysian FCoVs. Phylogenetic tree constructed by neighbor-joining method showed the phylogenetic relations of the sequences in an unrooted-tree algorithm (Figure 4 )." ] },{ "paper_id": "3ec7aa1d4381bbaa7f5fa69fa8eb7cc1d90a39f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analyses were conducted with the SPSS 13.0 software for Windows (SPSS Inc, Chicago, IL, USA)." ] },{ "paper_id": "3ed1483725e4ea6abcdbf93585eeccde903202fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This report is an epidemiological study of the first patient (Patient #1) who initially brought MERS into Korea in 2015. From May 20, when a diagnosis of MERS was confirmed, the Division of Epidemic Intelligence Service, Korea Centers for Disease Control and Prevention (KCDC), in cooperation with a group of civilian volunteers in epidemiology, traced the infection route and performed preventive measures for the spread of additional infections." ] },{ "paper_id": "3ed3ca15292f7b5c1ace98e0cece9a60609d8138", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples were viewed with a TCS SP5 laser scanning confocal microscope (Leica Microsystems, Wetzlar, Germany) using a 63\u00d7, 1.3 NA Plan Neofluar oil-immersion objective. Fluorescence signals of triple-labelled specimens were serially recorded to avoid bleed-through. Images were digitally processed with NIH ImageJ and merged to yield pseudo-coloured pictures." ] },{ "paper_id": "3ed400293b6f0963dcffb081e94de5229fb42cc7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The four serotypes of dengue virus (DENV1-4) are responsible for approximately 50 to 100 million infections annually, and 2.5 billion people are at risk of infection, making DENV the most widespread arboviral disease [1, 2] . Most symptomatic DENV infections present as a debilitating, febrile disease known as dengue fever (DF), but serious cases can progress to dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). These can be fatal if patients do not receive fluid replacement. Currently, there are no approved therapies for DENV infections.", "Human embryonic kidney 293T cells and murine macrophage J774A.1 cells were grown in Dulbecco's minimal essential medium (DMEM; Invitrogen) and human myelogenous leukemia K562 cells were grown in Roswell Park Memorial Institute (RPMI) 1640 medium (Invitrogen). Media were supplemented with 10% fetal bovine serum, 100 U/ml penicillin and 100 mg/ml streptomycin.", "Cells were lysed with 1% NP-40 (Thermo Scientific) and Western blot analysis was performed as previously described [9] . C-myc-tagged IFITM proteins were detected by a murine monoclonal anti-c-myc antibody (9E10, Santa Cruz Biotechnol-ogy). Endogenous IFITM protein expression was detected by polyclonal rabbit anti-IFITM1 (FL-125, Santa Cruz Biotechnology) or rabbit anti-IFITM2 (12769-1-AP, Proteintech Group, cross reacts with IFITM3 protein). Anti-tubulin antibodies (Sigma) were used as a loading control." ] },{ "paper_id": "3ed4b5616c342d7185015a8553a8f8350511ca21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the literature review data published up to June, 2011, were obtained by searches of PubMed and Medline, and from review of the references listed in retrieved articles, using as search term \"Emergency Services, hospital\" as MeSH, coupled with general terms such as \"Civil Defense\", \"Bioterrorism\" and \"Hospital Preparedness\" and with the name of each HID included as MeSH term. No data restrictions were placed on our searches.", "stretcher isolator 8 (19, 5) special ambulance through an external pathway 3 (7, 3) different procedures depending on risk assessment 9 (21, 9) with a normal stretcher, without special procedures 5 (12,2)", "Author details" ] },{ "paper_id": "3edea664551396420ae233d6951c3a8a71c2870e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A retrospective study revealed 17 (3.1 %) out of 540 NPAs positive for HBoV, with 14 specimens tested negative for other viruses, giving the suggestion that HBoV is a causative agent of respiratory tract infections [1] .", "It remains unclear how far HBoV contributes to respiratory and/or gastrointestinal disease. More and more evidence supports the assumption that HBoV is indeed an infectious and contagious agent, but a chance remains that it solely synergistically increases the clinical severity of other infections. Consequently, well planned and designed clinical studies with sophisticated case controls need to be performed in order to finally rule out the role of bocavirus, unless animal or at least in vitro models demonstrate its pathogenicity. ", "The parvoviridae are small, non-enveloped viruses. The isometric nucleocapsids with diameters of 18 to 26 nm contain a single molecule of linear, negative-sense or positive-sense, single stranded DNA with an average genome size of 5,000 nucleotides.", "A study on the polarity of the packaged strand confirms that HBoV replication leads to packaging of single stranded DNA in the majority of cases. By using the NASBA methods, B\u00f6hmer et al. showed that negative strands were packaged in 87.5 % of the investigated samples [10] ." ] },{ "paper_id": "3ee0905adb62aaf5fc29019aac6add9ef862bb22", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The virus was pelleted by centrifugation at 35,000 rpm for 2 h at 4\u00b0C and was then resuspended with 100 \u03bcl Tris-NaCl buffer. The purified MHV viral particles were stored at 4\u00b0C.", "The tomographic data were processed with the software Protomo (Noble and Stagg, 2015) . The tilt series images were aligned for several iterations and then the aligned images were back-projected to generate the 3D reconstructions. The tomograms were denoised by band-pass filtering and virtualized using the software IMOD (Kremer et al., 1996) ." ] },{ "paper_id": "3ee10f61fbf042f0e6c1f90b5e26a1199c13f177", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author declares that he has no competing interests." ] },{ "paper_id": "3ef4a3e163427c45ff6d34808df3656167f6b855", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Frontiers in Microbiology | www.frontiersin.org", "All the data are available upon reasonable request at Dr. Rui Lin, pubmed1128@126.com.", "The project was supported by the National Natural Science Foundation of China (81600509)." ] },{ "paper_id": "3f00db51b8b2fa846179a56402bdb545643c14d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Interspecies transmission and infection have been reported in several viruses that infect humans [1, 2] . Likewise, aquatic animal viruses can also infect and cause disease in a wide range of aquatic animals [3, 4] . Specifically, the interspecies infection was reported following ranavirus infection [5, 6] . However, the basis for the broad ranavirus host range is not clear [7, 8] . Ranaviruses are large double-stranded DNA viruses within the family Iridoviridae [9] . Ranaviruses target aquatic animals globally and have been isolated from reptiles [10, 11] , amphibians [12] [13] [14] [15] , and bony fish [16, 17] . Among them, several isolates represent great threats to the development of the aquaculture industry and wild animal populations [18] . Aside from infecting several species within a given taxonomic class (e.g., frog virus 3 infects diverse amphibian species), ranaviruses may also infect members of different classes (e.g., frog virus 3-like agents have been isolated from both amphibians and fish) [19] .", "Viruses 2019, 11, 593 7 of 11" ] },{ "paper_id": "3f06c41154ff140670ba10f54eeaf640c39f29b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antibodies against APEX1, STUB1, and ATP5A1 were purchased from Santa Cruz Biotechnology (Santa Cruz, CA). GTPBP3 and HDAC1 antibodies were purchased from Abcam (Cambridge, UK), and anti-eIF4A1 was obtained from Cell Signaling Technology (Danvers, MA). Antibodies against ALDH2, ALDH6A1, MTRF1, NDUFS6, HNRPM, GLUD1, and PLG were purchased from Abnova (Taipei, Taiwan). Antibodies against COXI and COXIV were purchased from Invitrogen (Karlsruhe, Germany), and TFAM were prepared in our laboratory [51] . PARP1, HSPD1 (HSP60), NF-kB, SOD1, XRCC5 (Ku80), XRCC6 (Ku70), and b-actin were purchased from Santa Cruz Biotechnology.", "Citation: Jeon J, Jeong JH," ] },{ "paper_id": "3f1a7bb419c2658dfd71663cc87efd03a38f1716", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The MS data were analyzed using MaxQuant software (version 1.3.0.5). The peptides and related proteins were searched against the UniProt Anas platyrhynchos database (32,619 total entries, downloaded 02/09/15). The initial search was set at a precursor mass window of 6 ppm. The search followed an enzymatic cleavage rule of Trypsin/P and allowed a maximum of two missed cleavage sites and a mass tolerance of 20 ppm for fragment ions. Carbamidomethylation of cysteines was defined as fixed modification, while protein N-terminal acetylation and methionine oxidation were defined as variable modifications.", "Healthy 180-day-old shelducks were obtained from Siji Poultry Co., Ltd (Jintan, PR China). The ducks were maintained in special cages, and food and water were provided regularly. All animal experiments were conducted in accordance with the regulations and guidelines of animal experimentation outlined by the People's Government of Jiangsu Province. The ducks infected with Tembusu virus JS804 strain were maintained in our laboratory.", "KH and YL designed experiments; KH, DZ, YL, QL, and XH carried out experiments; JY and FA analyzed experimental results; KH wrote the manuscript." ] },{ "paper_id": "3f1d96625c0c358531ba0f8261c930dd6967bd79", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Besides RNA modifications affecting stimulation of TLRs, the same principle also holds true for other innate immune sensors. As a brief overview, the following findings have been made in the field. Polyadenylation in eukaryotic RNA limited induction of IL-12 from human monocyte-derived DCs, which was high upon activation by bacterial [68] . Confirming these findings, in-vitro transcribed mRNA lacking a poly(A) tail induced immune activation and this could be abolished by enzymatic 3'-polyadenylation.", "2'-O-methylation however is also naturally occurring at significantly higher abundance in eukaryotic as compared to prokaryotic (and mitochondrial) RNA [110, 111] and thus the findings were indicative of a concept of recognition of \"hypomethylated\" RNA to discriminate self/foreign origin.", "Limitation of endogenous DNA and RNA recognition by spatial restriction of NA-sensing TLRs to the endolysosome, degradation, and discrimination by sequence motifs and chemical modifications are secure strategies to impede self-recognition." ] },{ "paper_id": "3f1dd22fd366efca2448379f7becf69de113353a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ARMS-I is safe and well-tolerated, and it reduces influenza symptoms. This product has the potential to prevent viral upper respiratory tract infections. Further clinical development of this novel product is warranted. ", "Trial registration: ClinicalTrials.gov NCT02644135 (retrospectively registered)." ] },{ "paper_id": "3f21f365d6a8983fd6cf0406c66d2785d0c3a138", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IFITM1: Interferon-induced transmembrane protein 1 (IFITM1) is one of hundreds of IFN-stimulated genes. In hepatocytes, it was found to accumulate in tight junctions in HCV-infected patients undergoing IFN therapy. It bound to the tight junction proteins occludin, claudin-1, and ZO-1, and appeared to enhance the interaction between the HCV coreceptors occludin and CD81, yet inhibited virus entry. It is proposed that this disruption in entry results from the altered coordination of coreceptor interactions and complex formation, however this mechanism requires further investigation [146] .", "ADAP2: ADAP2 (ADP-ribosylation factor (Arf) GTPase-activating protein (GAP) with dual pleckstrin homology domains 2) is an IFN-inducible, GTPase-activating protein for Arf6. It associates with and can control actin dynamics, as well as induce membrane ruffling and macropinocytosis, leading to the formation of ADAP2-associated vesicles. These vesicles are also positive for Rab8a (recycling endosomes) and lysosomal-associated membrane protein 1 (LAMP1; lysosomes). ADAP2 expression shifts the endocytic association of Dengue virus and vesicular stomatitis virus (VSV) into these ADAP2-positive vesicles instead of Rab5 and Rab7 endosomes. This not only inhibits their entry into the cell but also likely delivers the viruses directly to degradative lysosomes [145] .", "PKR: PKR was found to interact with the actin-binding protein gelsolin, an enzyme that catalyzes actin cleavage and nucleation. Activation of PKR by dsRNA diminishes the interaction with gelsolin, as gelsolin is only capable of binding to PKR monomer and not the active dimeric form. In its latent state, PKR inhibits the ability of gelsolin to sever actin filaments to form lammelopodia. In fact, actin staining of PKR KO and WT MEFs indicate that KO cells contain less than one third of the amount of filamentous actin as WT cells. Given that knockdown of gelsolin inhibits virus uptake, the suppression of gelsolin activity by PKR represents a novel antiviral mechanism [143] ." ] },{ "paper_id": "3f23d2283c45fc77411d8b9cc748ddf8d1de15e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition to DPP4, MERS-CoV can bind to sialic acid via the S1 subunit of S protein, or utilize the membrane-associated 78 kDa glucose-regulated protein (GRP78) to attach to target cells, suggesting that these proteins may also have roles in virion attachment [82, 83] ." ] },{ "paper_id": "3f2d44465b679efa6237f96e001dcf8a9e9bd6ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human embryonic kidney 293 (HEK293; ATCC, www.atcc.org) cells were maintained in Dulbecco's modified Eagle's medium (D-MEM) supplemented with HEPES (MP Biomedicals, Santa Ana, CA, USA), and human hepatocellular carcinoma HuH7 cells [33] were maintained in minimum Eagle's medium-\u03b1 (Invitrogen, Carlsbad, CA, USA). Cell media were supplemented with 10% heat-inactivated fetal bovine or calf serum (Biowest, Nuaill\u00e9, France or Integro, Zaandam, The Netherlands), penicillin/streptomycin and D-MEM also with L-glutamine. Spodoptera frugiperda (Sf 9) cells, used for baculovirus expression, were maintained in TNM-FH medium (Sigma-Aldrich, St. Louis, MO, USA) as described previously [34] .", "Since there is no information on the function of the ZIKV 2K peptide, both NS4A and NS4B were expressed with and without p2K. The presence of p2K sequence directed both proteins to more membranous structures in Huh7 cells ( Figure 1 ). All proteins, except prM, NS2A, and NS2B, were detectable by immunoblotting in cell lysates from transfected HEK293 cells (Supplementary Materials Figure S1 ).", "For the luciferase assay data, the Student's t-test in SPSS (IBM, Armonk, NY, USA ) was used to determine the statistically significant differences between the observed levels of inhibition compared with the control following the transfection of different amounts of ZIKV plasmids.", "The Zika virus (ZIKV) is a flavivirus that was discovered in 1947 near Entebbe, Uganda. In humans, ZIKV infection has been associated with a mild disease characterized by fever, rash, arthritis, and conjunctivitis [1] . However, the recent epidemic in the Americas in 2013-2015 in an immunologically na\u00efve population revealed that ZIKV can also cause severe neurological symptoms, such as Guillain-Barr\u00e9 syndrome and microcephaly [2] . ZIKV is primarily spread by Aedes species mosquitoes, and vertical and sexual transmission among humans was confirmed during the last epidemic. Multiple infection routes of ZIKV are facilitated by its ability to productively infect several types of human cells, such as skin fibroblast and dendritic cells [3] , Sertoli cells [4] , trophoblast progenitor cells and cytotrophoblasts, as well as placental macrophages [5, 6] . ZIKV also replicates in human brains and cells of the neuronal origin [7, 8] ." ] },{ "paper_id": "3f36fd3fb1459eb47b0cd58e5b6fa52529f68695", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors searched the topic through the following steps a) Search in Google. b) Search in PubMed c) Evaluated the papers, divided them depending on the inclusion and exclusion criteria. d) Evaluated the articles and analyzed them.", "publications and the risk of bias of included studies, and extracted data (Table 1) .", "We searched through Google, Pub Med, Pub Med Central, CAS, Citebase, DOAJ, Embase, Embiology, MED-LINE, OAIster, SCImago, Scopus, SOCOLAR and Zetoc by using the keywords." ] },{ "paper_id": "3f3e46abb51fffc3d562bd26117eed795c3febe6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Directorate-General in 2008 [155] , concluded that no adverse effects of baculovirus on human health have been observed in safety tests, and they are not pathogenic, carcinogenic, or genotoxic in mammalian cells. However, environmental and ecological impacts of the baculovirus in invertebrates will be reduced by modification of baculovirus essential genes required for replication and budding, allowing the development of a baculovirus surface-displayed vaccine with an optimal safety profile in the future.", "Rabies virus (RABV) is highly infectious and poses a constant threat to humans and animals.", "Funding: This research received no external funding." ] },{ "paper_id": "3f551bf91d2b52cadac39dbd62e7ae0f51066446", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The protocol in this study was approved by the Committee on the Ethics of Animal Care and ", "Samples positive for coronavirus were cultured in Vero E6, BHK-21, MDCK, A549, HEp-2, CaCo-2 cells, as well as in an immortalized kidney cell line of Myotis Davidii. The cell lines were inoculated with positive samples and three blind passages were performed for each sample. The culture supernatant and cell pellet of each passage were harvested. The detection of viral replication was conducted using specific primers targeting the conserved region of RdRp.", "Conceptualization: LL GFG. ", "Coronaviruses are large, enveloped viruses with single-stranded, positive-sense, non-segmented RNA genomes [1] . Based on the current nomenclature of the International Committee of Taxonomy of Viruses (ICTV), coronaviruses of the family Coronaviridae are now classified into four genera: alpha-, beta-, gamma-and deltacoronavirus [2, 3] . Betacoronaviruses can be further subdivided into four phylogenetic groups [2] ." ] },{ "paper_id": "3f6a8fc2249ec3b9bc431c5eded7f6234c75c49d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All simulated epidemics were seeded with 10 index cases chosen at random, in order to avoid early stochastic extinction. Averages of 10 000 simulations are presented, consisting of 100 epidemic runs on each of 100 different network realizations. Proportions across all plots are relative to the total network size NZ10 000. The simulation time step used is DtZ0.04. Smaller time steps produced effectively identical results (not shown). The s.e. values of the averages of simulation outputs are at least three to four orders of magnitude smaller than the measurement itself and therefore are not discussed further.", "Contact-independent identification of infectious nodes I/T. Disease is detected at an infectious node (e.g. via clinical signs or screening) at rate a. This results in the isolation of the node and triggers the tracing of its contacts.", "The removal of triggering nodes T/R. Triggering nodes are removed at rate d." ] },{ "paper_id": "3f7b6af5cd76098945fd076e4fa43a541fb7a5a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We selected guidelines related to influenza, SARS and TB for this review. Given that influenza has the potential to cause both seasonal infections and pandemics; it was chosen as the primary infection of interest. TB was selected as an example of a chronic but highly infectious disease. In contrast to influenza, TB has a long incubation and infection period. Lastly, SARS was selected as an example of emerging infectious disease, which required a rapid response.", "Professor Raina MacIntyre receives funding from influenza vaccine manufacturers GSK and CSL Biotherapies for investigator-driven research. Dr Holly Seale holds an NHMRC Australian based Public Health Training Fellowship (1012631). Payment for presentations: Dr Seale has received funding from Sanofi Pasteur, GSK and CSL Biotherapies for investigator driven research and for conference presentations.", "Authors' contribution AAC, HS and CRM contributed to the design of the study. AAC undertook the search strategy and made the initial selections which were subsequently validated by HS and CRM. AAC developed the first draft of the manuscript and HS and CRM extensively reviewed the paper. All authors read and approved the final manuscript." ] },{ "paper_id": "3f7c34653f6fcd0675f13b47461b74cd0f0a51fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(MPI, Eugene, OR, USA). Terbium chloride hexahydrate (TbCl 3 ) and 2,6-pyridinedicarboxylic acid (DPA) were purchased from Acros Organics (Geel, Belgium). All reagents were used without further purification.", "ATR, attenuated total reflectance; DMPC, 1,2-dimyristoylsn-glycero-3-phosphocholine; DMPG, 1,2-dimyristoyl snglycero-3-phosphoglycerol; FP, fusion peptide; FRET, fluorescence resonance energy transfer; HA, hemagglutinin; HR, heptad repeat; lysoPC, 1-dodecyl-2-hydroxyphosphatidylcholine; NBD, 4-chloro-7-nitrobenz-2-oxa-1,3diazole; P/L, peptide to lipid ratio; POPC, 1-palmitoyl-2oleoyl-sn-glycero-3-phosphatidylcholine; Rho, Rhodamine; SDS PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis; TMD, transmembrane domain." ] },{ "paper_id": "3f842ddde61088937e203ddec6ace954e479499e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The use of CaMV 35S promoter sequence in LAMP has previously been reported as a screening method [16] ." ] },{ "paper_id": "3f8beb2781bb92d1e2fffd8361b1feec3fd834e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors have no conflicts of interest to declare.", "In this section, we summarize the most recent findings with respect to MERS-CoV vaccine development, particularly vector-and RBD-based vaccines.", "MyD88-dependent and TRIF-dependent signaling both use the TLR-4 pathway to activate downstream effectors [22] . However, mice lacking TLR-4 have more severe SARS-CoV infections than wild-type mice have. Thus, the protective signaling role through TLR-4/TRIF might be considered a distinctive feature in the pathogenesis of some coronaviruses [23] . We believe that using some special adjuvants as agonists for TLR-4 and TLR-3 plus the expressed MERS-CoV-S protein may help to improve the immunogenicity against MERS-CoV infection.", "It is known that coronaviruses express surface spike glycoproteins, which are considered predominant antigenic proteins that stimulate the antibody response [60] . These antibodies might be used for targeting spike proteins and blocking the entry of the virus into host cells [60] . Therefore, designing monoclonal antibodies directed against these proteins is preferable for protection in contrast with vaccine preparation, which is a time-consuming and laborious process. To date, no vaccine for either SARS-CoV or MERS-CoV is available in the market despite some laboratory clinical trials." ] },{ "paper_id": "3f8d3e900290496401f7a6557a64255fdb3ebf0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The total serum cholesterol and triglycerides from blood samples were determined using commercial colorimetric assay kits (Bioclin, Belo Horizonte, Brazil).", "ROS analysis was performed by flow cytometry using dihydroethidium (DHE) and dichlorofluorescein diacetate (DCF) to detect intracellular \u2022O 2 \u2212 and H 2 O 2 , respectively, as previously described [8, 16] . Briefly, DHE (160 mM) and DCF-DA (20 mM) were added to a cell suspension of 10 6 cells and incubated at 37\u00b0C for 30 min in the dark. The cells were kept on ice until flow cytometric acquisition (10,000 events; FACSCanto II, Becton Dickinson, San Juan, CA). The data were analyzed using FACSDiva software (Becton Dickinson) and were expressed as median fluorescence intensity (MFI).", "Hypercholesterolemia remains one of the most important risk factors for cardiovascular morbidity and mortality [1] [2] [3] [4] . High plasma cholesterol levels trigger a cascade of events, including inflammation [5] , oxidative stress [6] and cell damage [7, 8] , particularly in the cardiovascular system [3] . Additionally, we have previously shown that hypercholesterolemia increases oxidative stress in different cell types [6, 7, 9, 10] , including bone marrow mononuclear cells [8] ." ] },{ "paper_id": "3f962f74bcf72c06a4f0941b8da40742024dae3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Crystallization SUD core displayed .95% purity in SDS-PAGE, and monodispersity in Dynamic Light-Scattering. Initial crystallization screening was performed using the sitting-drop vapor-diffusion method in 96-well Intelli-Plates (Dunn Laboratories). Several commercial kits (Sigma, Jena Bioscience) were used for the screening. The protein concentration was 6 mg/ml. Using a Phoenix robotic system (Art Robbins), drops were made of 260 nl protein and 260 nl precipitant solution. The optimized crystallization condition consisted of 20% polyethylene glycol monomethyl ether 5000 and 0.2 M ammonium sulfate in 0.1 M morpholinoethane sulfonic acid (pH 6.5). Plate-like crystals grew in 3-5 days, to maximum dimensions of 0.0260.0260.01 mm 3 .", "The SUD core macrodomains fail to bind ADP-ribose", "The figures were made with PyMOL [76] .", "Since the refinements in BUSTER-TNT at that point showed some problematic low correlations between F o and F c at low resolution, the original images collected from the P2 1 crystal were reprocessed using XDS [73] and SCALA, applying different highresolution cutoffs for different segments of the collected images. Details for this dataset are given in Table 1 . Subsequent refinement of the P2 1 form with REFMAC, under application of weak NCS restraints, yielded a model with R = 0.211, R free = 0.264. The advanced handling of NCS restraints through LSSR in BUSTER-TNT gave a final model R = 0.211 and R free = 0.268. The final model in the P2 1 form comprises 513 residues (A389-A516; A524-A652; B393-B519; B526-B652)." ] },{ "paper_id": "3f9b24ea368416ce33708bb28327fb0b686b0ef0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "3fa2c03259615e7a062deaac928c626c0a1bfbf7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Supplementary Material for this article can be found online at http://journal.frontiersin.org/article/10.3389/fimmu.2016.00238 ", "The authors thank Dr. Veronique Dartois at PHRI for the PK/PD analysis and Dr. Erika Shor for critical review of this manuscript.", "This study was funded by NIH/NIAID grants to GK (AI054338) and SS (AI110335) and by a New Jersey Health Foundation award to SS. The funding agencies have no role in the study design, data collection, analysis, interpretation, or writing the manuscript." ] },{ "paper_id": "3fa90782b0cd99871663f5317bb69d255cfde50f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Western blotting. Proteins in sodium dodecyl sulfate (SDS) solubilizer (0.0625 M Tris\u00b7HCl [pH 6.8], 10% glycerol, 0.01% bromophenol blue, 2% [wt/vol] SDS, with 2% 2-mercaptoethanol] were heated at 95\u00b0C for 5 min, electrophoresed through 8% (wt/vol) polyacrylamide-SDS gels, transferred to nitrocellulose membranes (Bio-Rad), and incubated with mouse monoclonal anti-MHV-HR2 10G (obtained from Fumihiro Taguchi, Nippon Veterinary and Life Sciences, Tokyo, Japan), mouse anti-C9 (EMD Millipore), mouse monoclonal anti-MHV HE, clone 5A11, or goat anti-human IgG (sc-2453; Santa Cruz Biotechnologies). After incubation with appropriate horseradish peroxidase (HRP)-tagged secondary antibodies and chemiluminescent substrate (Thermo Fisher), the blots were imaged and processed with a FluorChem E (Protein Simple).", "Microscopy and image acquisition. Live-cell images were captured in a z series on an electronmultiplied charge-coupled-device digital camera (EMCCD Cascade 2; Photometrics) and deconvolved using SoftWoRx. Identical conditions were applied to all acquisitions. Deconvolved images were analyzed by an identical algorithm in Imaris 8.3.1 (Bitplane).", "Supplemental material is available online only. " ] },{ "paper_id": "3fae11ec9abada619c2f2ea754eba8d43e9924d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Targeting the specific gene prfA (GenBank Locus: AY512430.1) of L. monocytogenes, a set of LAMP primers were designed and selected with PrimerExplorer 4 and Oligo 7 according to the reported methodology [23] , and are listed in Table 5 .", "Isothermal Master Mix and Loopamp \u00ae Listeria monocytogenes Detection Kits were purchased from OptiGene Limited (West Sussex, UK) and Eiken Chemical Co., Ltd (Tochigi, Japan), respectively, and LAMP was carried out according to the manufacturers' instructions using a set of serially diluted DNA template of L. monocytogenes ranging from 1 to 1000 fg.", "In summary, non-specific amplification was a limiting factor in the applicability of the LAMP methodology. A few different options to eliminate this issue have been reported here to successfully selectively and sensitively detect L. monocytogenes. Designing ideal primers, additives such as DMSO, and method modifications such as Touchdown LAMP may be favorable alternatives for increased specificity and sensitivity in LAMP in other applications as well." ] },{ "paper_id": "3faebf3f78e4b42abd134372119fde0ed298fa4b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All of the expression plasmids were verified by sequencing.", "MicroRNAs (miRNAs) are a group of small noncoding RNAs about 22 nt in length that downregulate gene expression by either of the two posttranscriptional mechanisms: mRNA cleavage or translational repression [1] . miRNAs have been implicated in a vast array of cellular processes including cell differentiation, proliferation and apoptosis [2] . Links between miRNAs and To clone the plasmid expressing pre-miR122, cDNA library derived from HuH7 cells was used as template and forward and reverse PCR primers (5'GGAATTCGGAGTGTGA CAATGGTGTTTG 3' and 5'GCTCTAGATTTAGTGTGATAATGGCGTTTG 3') were used to amplify the gene fragment. After PCR, the DNA fragment was digested by restriction enzymes (EcoRI/XbaI) and cloned into the expression vector pcDNA3 (linearized by EcoRI/XbaI).", "Experiments were performed three times. Data were analyzed using student t test. P<0.05 was considered statistically significant (p<0.05, \u00c3 ; p<0.01, \u00c3\u00c3 ; p<0.001, \u00c3\u00c3\u00c3 )." ] },{ "paper_id": "3fb8269503a524e2257482ce479a05abd732ddfe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hypertension 10", "BALF samples were obtained from 181 individuals in whom a bronchoscopy was performed for different diagnostic or therapeutic purposes. All individuals underwent bronchoscopy following standard diagnostic procedures at the department of infectious diseases and pulmonary medicine at the Charit\u00e9 -Universit\u00e4tsmedizin Berlin with informed consents from the patients. The study was approved by the ethical committee of the Charit\u00e9 and all samples were available as residual material without any personal information or clinical data. BALF was centrifuged at 1,200 rpm and supernatants were then collected and stored in aliquots at \u221280\u00b0C until processing for ELISA." ] },{ "paper_id": "3fbbb5c2047570f4c33a88cb927a6f54e83de658", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Current whole-genome scanning technologies use array-based platforms (array-CGH and high-density SNP microarrays) to study CNVs. They are high throughput but lack resolution and sensitivity. Real-time PCR is a sequence-specific technique which is easy to perform, but is limited in its discriminating power beyond a 2-fold difference [11, 12] .", "Alternatively, consider M molecules randomly distributed in C chambers. The probability of any given molecule being in any given chamber is 1 C . So the probability p of a given chamber having at least one molecule is", "Define the estimator of l a\u015d l l~{ln 1{p p \u00f0 \u00de", "and its sampling distribution f(p) is approximately normal for large C. See Figure 3 for illustration of the above ideas." ] },{ "paper_id": "3fc9f794eaab19c5355f54fee069feaedf8d752a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since STAT proteins function as essential mediators of cytokine-or hormone-induced signaling to promote cell development, proliferation, and differentiation, activation of STATs is tightly regulated. Suppressive regulators of STAT activity include protein inhibitors of activated STAT (PIAS) family, suppressors of cytokine signaling (SOCS), and ubiquitin carboxy-terminal hydrolase 18 (USP18) [118, 119] .", "Although STAT4 plays important roles in driving differentiation of T helper cells, its molecular mechanism of action is largely unknown. By using chromatin immunoprecipitation and high-throughput sequencing to compare the transcriptional profiles of STAT4 and STAT6, STAT4 was found to bind over 4000 genes with distinct binding motifs [103] . Among those 4000 genes, more than 2300 genes are specific targets of STAT4 and these genes may be involved in Th1 differentiation [103] . Meanwhile, STAT4 plays a more dominant role in promoting active epigenetic marks [103] . Moreover, a recent study demonstrated that STAT4 deficiency in mice causes a failure to induce lung Th2 or Th17 immunity upon RSV challenge, but enhances the lung RSV-specific CD8+ T cell response to secondary RSV challenge [104] .", "Induction of IFNs typically results from activation of host PRRs during virus infection. PRRs mainly include RLRs and TLRs [1, 2] . After induction, IFNs stimulate cells via activation of specific signaling pathways, mainly the JAK/STAT (Janus kinase/signal transducer and activator of transcription) pathway [13] . Subsequent cascade events after the triggering of the pathway result in expression of IFN-stimulated genes (ISGs) [14] . Generally, hundreds to thousands ISGs can be upregulated by type I IFNs [15] ; ISGs include antiviral effectors that restrict virus replication." ] },{ "paper_id": "3fd4c59ae94e2ecc44c0c40d678dd18e31ddb7c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Influenza is a zoonotic disease that infects millions of people each year resulting in hundreds of thousands of deaths, and in turn devastating pandemics.", "Influenza A/Shanghai/2/2013 H7N9 that was not treated with a protease exhibited a titer of about 1 \u00d7 10 4 pfu/mL ( Figure 4 , Table 1B ).", "Our data demonstrate that human matriptase/ST 14 is a likely candidate protease to promote H7N9 infections in humans." ] },{ "paper_id": "3fd791accf9347c1e74f871c73b7d19c534059ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Ebola viruses cause viral hemorrhagic fever in humans and non-human primates and are endemic in Africa. Reston ebolavirus (REBOV) has caused several epizootics in cynomolgus monkeys (Macaca fascicularis) but is not associated with any human disease. In late 2008, REBOV infections were identified in swine for the first time in the Philippines.", "ZEBOV and Marburg virus were identified in African fruit bat species [19, 20] . More recently, Marburg virus was successfully isolated from a fruit bat, Rousettus aegyptiacus [21] , suggesting that fruit bats are reservoir animals of filoviruses. In the Philippines, we have recently demonstrated that an Asian fruit bat, Rousettus amplexicaudatus, has antibodies to REBOV [22] . Since the REBOV genome has not yet been detected in the bat, conclusive evidence that the bat species is a reservoir, or one of the reservoir animals, of REBOV is not available. Nevertheless, it is possible that REBOV was transmitted to swine from these bats since these bats inhabit many areas of the country, including the regions around the affected facilities both in Pangasinan and Bulacan." ] },{ "paper_id": "3fe17722a3541e556994dcad8f8d173be7f3ea88", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "AAY43180.1 (SmVAL1), AAY43181.1 (SmVAL2), AAZ04923.2 (SmVAL3), AAY43182.1 (SmVAL4), ABB88846.2 (SmVAL5), CCD74794.1 (SmVAL6), AAZ04924.1 (SmVAL7), ABW98681.1 (SmVAL8), ABB88845.1 (SmVAL9), ABO09814.2 (SmVAL10), ABA54555.1 (SmVAL11), ABB88844.1 (SmVAL12), ABB88843.1 (SmVAL13), ABO09815.1 (SmVAL14), CCD80670.1 (SmVAL15), CCD74792.1 (SmVAL16), CCD74934.1 (SmVAL17), CCD80318.1 (SmVAL18), CCD80317.1 (SmVAL19), CCD80812.1 (SmVAL20), CCD80564.1 (SmVAL21), CCD59744.1 (SmVAL22), CCD80666.1 (SmVAL24), CCD80667.1 (SmVAL25), CCD80638.1 (SmVAL26), CCD80648.1 (SmVAL27) and CCD80636.1 (SmVAL28)." ] },{ "paper_id": "3fe4e2a98af36485a9a4dc93c30eef62522af0e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Means for continuous variables were compared using independent-group Student's t tests when the data were normally distributed; otherwise, the Mann-Whitney test was used. Proportions for categorical variables were compared using the x 2 test, although Fisher's exact test was used when the data were sparse. Correlation was assessed using Pearson's test. Significance was set at p,0.05, using two-sided comparisons. Results were analyzed using SPSS for Windows version 17.0 (SPSS, Chicago, IL, USA).", "Duration of fever -d Mean 6.762.5" ] },{ "paper_id": "3fee471a12aa3fbfc3abab41a0f2604906c8acf0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses from Rhinolophidae bats, however, did not share this feature and appear to have undergone a number of host shifts.", "D. T. S. Hayman et al." ] },{ "paper_id": "3ff80f738629339b9e16ebe2a12a10dcbf325aa0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reporting summary. Further information on research design is available in the Nature Research Reporting Summary linked to this article.", "Statistical methods. To determine statistical significance in animal experiments, nonparametric analyses were used since the n is too low to determine normal distribution. We used a two-tailed Mann-Whitney test, exact p-values are displayed. For enumeration of GFP-LC3 punta and in vitro infection assays, we used one-way ANOVA followed by Tukey's test post hoc. The statistical methods for the proteomics analysis are discussed in the proteomics methods.", "Materials. We used an \u03b1-ISG15 antibody from Santa Cruz (F-9) at 1:200, an \u03b1-SQSTM1/p62 antibody from Abcam, UK (ab56416) at 1:1000. We used an \u03b1-LC3 NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-019-13393-x ARTICLE antibody from MBL, Japan (M152-3, clone 4E12) at 1:1000 and an \u03b1-ACTIN antibody from Sigma, Saint Louis, MO (AC-15, A5441) at 1:5000. We used an \u03b1-mTOR antibody from Sigma (PA5-34663) at 2 \u00b5g/sample for immunoprecipitation, an \u03b1-mTOR antibody from Cell Signaling (7C10) at 1:1000, an \u03b1-tubulin antibody from Sigma (T6074) at 1:5000, an \u03b1-ubiquitin antibody from Cell Signaling (P4D1) at 1:1000, and an \u03b1-NEDD8 antibody from Cell Signaling (19E3) at 1:1000. We used an \u03b1-HA antibody from Sigma (H6908) at 1:1000 for immunoblotting, and an \u03b1-GFP antibody from Santa Cruz Biotechnology (sc-81045) at 1:1000. We used an \u03b1-FLAG \u00ae M2 antibody from Sigma (F3165) at 1:10,000, an \u03b1-HA tag antibody-ChIP Grade from Abcam, UK (ab9110) at 1:5000, and an \u03b1alpha-tubulin antibody from Genetex (GT114) at 1:40,000. We used \u03b1-HA antibody magnetic beads from Pierce (88837), and anti-flag antibody magnetic beads from Sigma (M2 M8823 Millipore) for immunoprecipitation." ] },{ "paper_id": "3ffa62baea2f955470dff08e4d5e157ce0e28cc0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The governing model equations for the dimensionless intracellular signaling dynamics are then described by the following ordinary differential equations", "d\u00bdPlk1\ufffd dt \u00bc k 9 \u00bdmass s \ufffd\u00bdCycB\ufffd\u00f01 \u00c0 \u00bdPlk1\ufffd\u00de \u00c0 k 10 \u00bdPlk1\ufffd;", "The oxygen dynamics through HIF-1 \u03b1 is described as", "2. Assemble the LHS matrix L, wherein each row of L represents a unique combination of parameters sampled without replacement." ] },{ "paper_id": "4013a7e351c40d2bb7fdfe7f185d2ef9b1a872e6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NG, RR, SR, and MK contributed to the conception, writing, and final edits of this manuscript.", "This work was funded by the National Institutes of Health (NHLBI 5K08HL119359-02) to MK.", "Prevention of neonatal HSV infection is more elusive as neonatal HSV disease often occurs after transmission from asymptomatic women with primary HSV infection (162) . In cases of active maternal genital herpes, cesarean sections can decrease the incidence of neonatal HSV infection, especially when performed within 4 h of rupture of membranes (163) . A subunit HSV vaccine has shown promising results in prevention of genital herpes and is currently under Phase III trial (164) . Although not routinely recommended, antiviral prophylaxis with acyclovir in late pregnancy has been demonstrated to decrease viral shedding, leading to reduction in cesarean rates and recurrent herpes (165, 166) . Patients with severe neonatal HSV infection (those with disseminated disease and CNS infection) should be treated with intravenous acyclovir for 21 days (167) ." ] },{ "paper_id": "401ebad7d8d7416f0bf26c8192eb57bfb61f378b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It is therefore likely that MDA5 evolved first, perhaps from a common ancestor with the closely related LGP2 helicase family (184) , which is structural similar to RIG-I and MDA5 but lacks the CARD domains at its N terminus (185) .", "Frontiers in Immunology | www.frontiersin.org Frontiers in Immunology | www.frontiersin.org Frontiers in Immunology | www.frontiersin.org" ] },{ "paper_id": "402334dfcf4430553c3f99a5bbe869a3882c1d97", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data was analysed for statistical significance by SPSS W (SPSS Statistics Version 20.0, IBM Corp., Armonk, NY, USA). Datasets with two groups (PBMC) were analysed using paired two-tailed Student's T-test. For datasets containing more than two groups (spleen) one-way variance analysis with Bonferroni correction for paired sample means was applied. If sample size per group was < 4, no statistical evaluation was performed. Three different levels of significance were defined: p < 0.05 (indicated by *), p < 0.01 (indicated by **) and p < 0.001 (indicated by ***).", "Blood and spleens were obtained from 6-7 month-old healthy pigs from an abattoir. Animals were subjected to electric high voltage anaesthesia followed by exsanguination. This procedure is in accordance to the Austrian Animal Welfare Slaughter Regulation. Peripheral blood mononuclear cells (PBMC) were isolated using density gradient centrifugation (Lymphocyte Separation Medium, density: 1.077 g/mL, PAA, Pasching, Austria) as described previously [36] . Dissected spleen was cut into small pieces and mechanically dissociated by forcing through a sieve. After a washing step in phosphate buffered saline (PBS, PAA) cells were applied to density gradient centrifugation to isolate mononuclear cells. Isolated lymphocytes were finally resuspended in culture medium or PBS containing 10% (v/v) porcine plasma for analysis by flow cytometry (FCM).", "Data were analysed using the CFX manager software (Bio-Rad) in the linear regression mode. For the quantification we applied the method described elsewhere [45] . Target gene expression was displayed as 2^-\u0394\u0394Cq values representing the fold changes relative to IS." ] },{ "paper_id": "402fd2b6ffd34c3d1fb4aca45d84bd7079284d99", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Citation: Bobashev G, Morris RJ, Goedecke DM (2008) Sampling for Global Epidemic Models and the Topology of an International Airport Network. PLoS ONE 3(9): e3154.", "For each sample, we created an adjacency matrix A such that an element a ij is equal to 1 when a flight exists between cities i and j and is equal to 0 otherwise. We also created a weighted adjacency matrix W such that an element w ij is the average daily number of seats on flights between cities i and j.", "(Q1) How does sampling affect the main network characteristics of the entire network?" ] },{ "paper_id": "4032ba4bcf75cb306c06c5f2e9ba6b8580781a8f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data presented in the manuscript are readily available." ] },{ "paper_id": "403be352ce64603bdb313a00238d5b77b7305321", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The PCR amplification reaction was carried out in 50 \u00b5l containing 5 \u03bcl RNA template, 25 \u03bcl 2\u00d7 MyTaq one step mix (1\u00d7), 0.5 \u03bcl RT, 1 \u03bcl Ribosafe RNAse inhibitor, DEPC-H 2 O (MyTaq\u2122 OneStep RT-PCR Kit) up to 45 \u00b5l, and 4 \u03bcl primer (400 nM). Amplification reaction was carried out with thermal profile at 45\u00b0C, 20 min RT 95\u00b0C, 1 min polymerase activation, then 40 cycles (denaturation 94\u00b0C, 15 s; annealing 55\u00b0C, 30 s; and extension 72\u00b0C, 30 s) followed by final extension 72\u00b0C, 7 min.", "RS performed the work designed by RDS and ONP. All authors contributed in writing and revision of the manuscript. All authors read and approved the final manuscript." ] },{ "paper_id": "403d1861771bf1e5e3625b0f86247d7134c3873d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Participants were given a scenario in which they had been in contact with someone sick with influenza. In response, just over half (55%) would agree to take preventative medicine and avoid travelling to places with no signs of outbreak.", "The one area where our results matched those of Lau et al. [25] was in peoples' willingness to tell border officials if they were feeling ill. Nearly all participants from both studies agreed they would do so. We were unable to find any comparable literature related to other border measures, or about peoples' attitudes towards contact tracing.", "One to two days of data collection were observed in each province by one author (JH) to ensure quality and consistency of questionnaire administration. Additionally, each data collector's first three interviews were audiorecorded and reviewed for consistency. MCHWs were required to review completed questionnaires for missing or unclear responses and to resolve these before leaving the participant's home. Questionnaires were reviewed for completeness and logical data checks were made prior to computer data entry. Questions arising were resolved with the MCHW. The first 20 questionnaires from each province that were entered by the data-entry clerk were reentered by one author (JH) in their entirety to assess for errors. If errors were discovered, feedback was given to the data-entry clerk and/or MCHWs, the error corrected, and the next 20 records examined similarly. A 5% random sample of questionnaires was later re-entered to confirm data quality." ] },{ "paper_id": "403e103aa496e1a37de56fde51173fdee75854fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using Prism software (GraphPad). All statistical analyses were performed using an unpaired two-tailed Student's t-test or two-way ANOVA test as applicable. When applicable, data are displayed as mean + SD.", "Mice were sacrificed at the indicated times, and pulmonary homogenates were prepared. Supernatants were stored at -80\u00b0C. Cytokine and chemokine levels were measured using a Mouse Cytokine Magnetic 20-Plex Panel (Invitrogen) kit or a Mouse inflammation Panel Mix and Match Subpanel kit (BioLegend) according to the manufacturer's instructions and read on a Luminex 100 (Bio-Rad) or a FACS LSRFortessa flow cytometer (BD Biosciences).", "and D (http://www.cdc.gov/flu/about/ viruses/ types.htm) [11] . Type A and B viruses are important causes of diseases in human, in which the majority of cases are due to type A virus [12] . Worldwide, the IAV infections are estimated to result in about 3 to 5 million cases of severe illness, and about 250 000 to 500 000 deaths annually (http://www.who.int/mediacentre/ factsheets/fs211/en/). Influenza-associated morbidity and mortality disproportionately affect older adults [13] . It has been reported that \u226590% of annual influenza-related deaths occur in individuals \u226565 years of age [14, 15] .", "The B6-derived dendritic cell (DC) line DC2.4 [17] was a gift from Dr. K. Rock (University of Massachussetts Medical Center, Worcester, MA). Madin-Darby canine kidney (MDCK) cells (ATCC, CCL-34) were purchased from ATCC, and cultured with complete DMEM medium. As standard tissue culture medium, we used complete RPMI or DMEM which consisted of the indicated tissue culture medium supplemented with 10% FCS, 100 IU/ml penicillin, 100 \u03bcg/ml streptomycin, 10 mM HEPES buffer (all from Gibco), and 0.05 mM 2-ME (Amresco). All cells were grown at 37\u00b0C and 5% CO2." ] },{ "paper_id": "40400327bbd828910ba0e013d9de71c012b4d4e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "404bf0836c388f561f796369c26d0bbf6f37b407", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lentiviral vectors with shRNA expression cassette were produced by calcium phosphate-mediated, three-plasmid transfection of 293T cells [37] . Briefly, 293T cells (2.5610 6 ", "Table S1", "Found at: doi:10.1371/journal.pone.0005671.s001 (0.03 MB DOC)" ] },{ "paper_id": "40500cd7ae5b4e116e8b13e5408e7dfd96d43ab4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One additional procedure that we and other groups have used after screening the genomes of pathogens for putative binding peptides is to compare those candidate epitopes with known host protein sequences, and in some cases we have found peptides that are identical to host peptides. This is very important because several critical diseases are caused by pathogen molecular mimicry, that is, some diseases, such as diabetes, dengue hemorrhagic fever, and Guillian Barret syndrome, are hypothesized to be the result of infections that induce self-reactive pathogenic immune responses.", "In our discussion we have often compared and contrasted immunomics with genomics. Immunomics supervenes on genomics, in the epistemological sense, since immunology ultimately depends on the functioning of genes inside cells, but immunomics has its own independent character and properties. In the same manner that each cell has its own pattern of gene expression that defines its unique cellular properties, each reaction of the cognate immune system to an antigen has its own pattern of epitope-specific responses that define its final outcome.", "The growth ''boom'' of immunomics. While the growth boom in genomics took place in the 1990s and this field has now begun to enter a mature stage of development, a similar growth boom in immunomics is likely to take place over the remaining years of the current decade. We recently searched the PubMed database (with Sente 2.3) using the following query: ''immunomics OR immunomic OR immunome OR (antigen AND microarray AND functional) OR (epitope AND microarray).'' After removing nine irrelevant articles from the output list and adding five articles for the new journal Immunome Research, we obtained a list of 71 articles covering the years from 1999 to the present (please see Figure 1 ). It is clear that interest in this field has accelerated, supporting the expectation of a continuing boom in growth. It is expected that the number of publications will increase at an exponential pace as immunomic microarrays became commercially available for research use. As immunomic array technology evolves, we expect that immunomic arrays with a small number of features will eventually be designed for specific clinical diagnostic purposes and used regularly in medical practice. However, these clinical applications might still be in the distant future.", "Another great challenge is the polymorphism of HLA genes, in particular HLA class II, and the several combinations of different alpha and beta chains. Some approaches may be useful to limit the number of features, such as the selection of specific alleles most frequently found in a population to be used in broad screening arrays. A second such approach could be the use of supertype prototype HLA molecules compatible with a set of several HLA alleles. A third approach would be through customization of the arrays, by having many different arrays of single alleles and combining them according to the HLA types of the individuals being tested." ] },{ "paper_id": "40540b92cbf5d985e0648733de6f4a9062e1bbcf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral RNA was extracted from the EV71 isolates using EZ1 Virus Mini Kit v2.0 (QIAgen, Hilden, Germany). The RNA was eluted in 60 \u03bcl of AVE buffer and was used as the template for reverse transcription polymerase chain reaction (RT-PCR)." ] },{ "paper_id": "4055104522be7b53cb86035004c9406b118199f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The development of simple, rapid immunoassay approaches is of tremendous importance for on-site diagnostics and for monitoring highly infectious diseases [1] . Infectious diseases, such as the avian influenza virus, severe acute respiratory syndrome (SARS), hand-foot-and-mouth disease, influenza H1N1 and H7N9 are all threats to human health/life and collectively cause losses to social/economic development [2, 3] . Therefore, developing methods for the rapid on-site assay of these diseases at an early stage is extremely important. The enzyme-linked immunosorbent assay (ELISA) is one of the most widely used approaches in clinical diagnostics, food safety testing, and environmental monitoring [4, 5] . The technique is usually carried out in a 96-well microtiter plate and involves a series of tedious processes, including sample introduction, incubation and washing. Moreover, substantial amounts of sample are consumed and the method is time-consuming and sometimes suffers from low sensitivity [6] . In order to overcome these drawbacks, various efforts have been devoted to developing new methods for diagnostic immunoassays. For example, ELISAs have been integrated with a micro/nano system to increase the surface/volume ratio and improve reaction kinetics [7] [8] [9] . A variety of materials, such as quantum dots [10] , photonic crystals [11] , membranes [12] or papers [13] , have also been used in conjunction with immunoassays.", "The specificity and sensitivity of the assay can be influenced by the non-specific adsorption (NSA) of other proteins or biomolecules by occupying the active sites of the valid surface. Actually, various strategies have been employed to reduce NSA, in attempts to decrease the background signal, and enhance the sensitivity of an immunoassay. A simple strategy, involving surface blocking, is usually adopted to reduce the NSA. Therefore, we investigated the blocking conditions. Experimentally, bovine serum albumin (BSA), casein, and SuperBlock buffer were used to search for the best blocking option. Figure 4 illustrates the blocking efficiencies of the above blocking solutions. The BSA solution obviously showed best blocking efficiency. Thus, a 1% BSA solution was the most efficient, and was adopted in the following experiments. ", "After a 10 min incubation in the 97% RH cabinet at 37 \u00b0C, each microwell was washed 3 times with PBST buffer. The 2nd Ab solution was then introduced into microwells at a volume of 2 \u03bcL/well. After a 10 min incubation, the unabsorbed antibodies were removed by washing five times with PBST buffer. Finally, 2.5 \u03bcL/well of an Amplex \u00ae Red substrate solution (6.9 mmol/L Amplex \u00ae Red, 50 mmol/L H 2 O 2 , 100 mmol/L PBS) was pipetted into each well to generate Resorufin for fluorescence detection.", "A human IgA kit, including affinity purified goat anti-human IgA (1st Ab), a human reference serum solution and goat anti-human IgA HRP conjugated (2nd Ab), was obtained from Bethyl Laboratories (Montgomery, TX, USA). Bovine serum albumin (BSA) was obtained from Merck (Calbiochem, Darmstadt, Germany). 10-Acetyl-3,7-dihydroxyphenoxazine (Amplex \u00ae Red reagent) was purchased from Life Technologies (Invitrogen, Eugene, OR, USA). It was dissolved in dimethylsulfoxide (DMSO) to a concentration of 13.8 mmol/L for use as a storage solution and was stored in refrigerator at \u221220 \u00b0C prior to use. The working substrate solution of Amplex \u00ae Red was prepared by mixing with phosphate-buffered saline (PBS) buffer (pH = 7.4) and H 2 O 2 solution just before use. Na 2 HPO 4 , NaH 2 PO 4 and H 2 O 2 were purchased from Wako Pure Chemical Industries Ltd. (Osaka, Japan). Washing buffer (PBST) was prepared with 0.5% (w/v) BSA/0.1% (v/v) Tween-20 (Kanto Chemical Co., Inc., Tokyo, Japan) in 100 mmol/L PBS (pH = 7.4). 10 mmol/L NaOH (Kanto Chemical Co., Inc.) and 10 mmol/L HCl (Wako Pure Chemical Industries Ltd.) were prepared for the cleaning of the MCP. All solutions and buffers were prepared with deionized water purified by Milli-Q system from Nihon Millipore (Tokyo, Japan). All buffers used in the experiments were filtered through 0.45 \u03bcm membrane filter (Jhwpo 4700, Nihon Millipore). A neutral detergent (TCN-5) used for plate cleaning was obtained from Tomisc Company (Tokyo, Japan)", "We report herein on the development of a compact immunoassay utilizing microchannels within the MCP, which has a large surface area and high surface-to-volume. Thus, the MCP ratio could not only increase coating capacity, but also accelerate an assay. The method would be expected to decrease overall immunoassay time because of the short diffusion distance in the microchannels of the MCP. The compact immunoassay system shows considerable potential in terms of speed and high-sensitivity for on-site diagnosis and for rapidly monitoring a disease." ] },{ "paper_id": "405b2a0699c55c52df71d3a52c454486e2f3ad1c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "405e67def78a29e92a4de5e016d0334550153142", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We acknowledge the service provided by the central instrumentation facility of Sun Yat-sen University, Guangzhou, China.", "TABLE S1 | List of primers used for gene expression analysis in this study.", "Each experiment was performed in three technical replicates and three biological replicates. Mean significant values were determined by Student's t-test using SPSS package (SPSS V16.0, SPSS, Inc., Chicago, IL, United States). In each statistical data values are means \u00b1 SD from triplicate biological repeats. Significant differences were determined by analyzing the comparison between the control and the treated samples using the Post Hoc Test ( * p < 0.05 and * * p < 0.01)." ] },{ "paper_id": "40640676ca5aecdde3a40feb137cc3049c14faef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A. The basic reproduction number R 0 of system (1)", "and thus", "For an arbitrary function x(t) with non-negative components," ] },{ "paper_id": "406aad9b3f74f619a1aac3f29ad531b28fb7c37e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses that infect the respiratory system cause effects ranging from nuisance (i.e. common cold) to severe (i.e. severe acute respiratory syndrome (SARS), H5N1 influenza), with many viral infections being exacerbated by underlying medical conditions. The majority of respiratory viruses are RNA viruses that can be recognized by TLR7 (recognizes ssRNA), TLR3 (recognizes dsRNA in endosomes) and RIG-I/MDA5 (recognizes dsRNA in cytosol). RNA viruses have either a (+)sense (Group 4) or (-)sense (Group 5) ssRNA genome. Application of TLR3 agonists to treatment/ prophylaxis of two (+) and two (-)sense RNA viruses, each belonging to a different family, will be discussed.", "Double-stranded RNA is produced during the replication cycle of most viruses and triggers antiviral immune responses through TLR3 or retinoic acid-inducible gene I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5), the latter are helicases that bind the cytoplasmic dsRNA generated during viral replication [23, 24] , Fig. (1) . In mammals, dsRNA interaction with RIG-I/MDA5 triggers IFN regulatory factor-3 (IRF-3) activation followed by type I IFN induction through the mitochondrial antiviral signaling (MAVS)/ IFN-promoter stimulator 1 (IPS-1) adapter [24, 25] . RIG-I is essential for triggering innate immune defenses against respiratory syncytial virus (RSV) and influenza viruses [26] .", "Mitigation of cytokine-mediated adverse reactions by hydrocortisone treatment prior to or following i.v. poly (ICLC) administration reduced both the hypotensive responses and IFN induction in rabbits [115] . The IL-1R signalling pathway, stimulated by poly (ICLC) is implicated in increased plasma IL-6 concentrations. Male rats given IL-1 receptor agonist (IL-1ra) prior to poly (IC) administration had elevated plasma TNF-, but not IL-6, concentrations and a reduction of fever [139] .", "Coronavirus (Co-V) is a non-segmented (+)sense RNA virus of the Coronaviridae family. Coronaviruses are transmitted by aerosols of respiratory secretions, the fecaloral route and mechanical transmission. Most viral growth occurs in epithelial cells, however, organs such as the liver, kidneys, heart, eyes or other cell types (i.e. macrophages) may occasionally be infected. Most infections are localized to the epithelium of the upper respiratory tract causing a mild, self-limited disease (classical 'cold' or upset stomach), occasionally causing enteric infections (primarily in infants <12 months), and rarely causing neurological syndromes. Coronavirus infection is very common in children, less common in adults, occurs worldwide and exhibits a strongly seasonal incidence of infection. Re-infections recur throughout life, implying multiple serotypes (at least four are known) and/or antigenic variation, hence the prospects for immunization appear bleak." ] },{ "paper_id": "4070000cd4a0880ff387df1d1a42f5f45f34e015", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lungs were prepared and immersion-fixed for 24 hours in 4% buffered formaldehyde solution (pH 7.4), dehydrated in a series of graded ethanol and embedded in paraffin. Sections (0.5 mm) were cut from five evenly distributed levels of the paraffin blocks and stained with haematoxylin and eosin. For immunohistochemical studies, sections were stained with a polyclonal primary antibody (against influenza A H1N1 virions; Virostat) overnight at 4uC and subsequently tissue sections were incubated for 30 min with secondary antibody (rabbit anti-goat-biotin; KPL; Gaithersburg, Madison, USA) and counterstained with haematoxylin.", "Tmprss2 Knock-out Influenza Resistance PLOS Pathogens | www.plospathogens.org oligonucleotides swi09-HA-5Eco: GGGAATTCACCATGAAG-GCAATACTAGTAGTTCTGC and swi09-HA-3Xho: GGGC-TCGAGTTAAATACATATTCTACACTGTAGAG. The resulting PCR products were inserted into plasmid pCAGGS using EcoRI and XhoI.", "Tmprss2 Knock-out Influenza Resistance PLOS Pathogens | www.plospathogens.org site did not depend on TMPRSS2 expression [10] . Thus, murine Tmprss2, like its human homologue [11, 17] can activate HA." ] },{ "paper_id": "407207cc711d3067f35c04426fa4055ccb37ccfb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at http://www.mdpi.com/2414-6366/3/4/118/s1, Table S1 : Cross-correlation analysis (R 2 ) of Dengue incidence and Google Dengue Trends. ", "The National Epidemiology Centre (NEC) of the Department of Health in the Philippines has a reporting system for dengue in all its disease reporting units, such as hospitals and rural health facilities [11] . For the past decade, this traditional, health facility-based, and government-implemented surveillance system has undergone improvements, yet it still suffers from untimely reporting, aggregation, and publication of data. Due to these surveillance problems, the identification and efficiency of intervention that may prevent dengue epidemics could be limited. Many suggestions involving alternative approaches outside the virological and clinical domains (e.g., telephone triage calls, sales of over-the-counter drugs, and school/work absenteeism) have been proposed in parallel with traditional surveillance [12] [13] [14] . Among these non-traditional suggestions, online activity or Internet search tracking has shown the potential to complement current epidemiological methods because of its efficiency and the availability of real-time population trends [15] [16] [17] [18] [19] .", "Dengue is one of the leading and most important mosquito-borne viral diseases in the world where 2.5 billion people worldwide are estimated to be at risk of contracting the disease [1] . South-East Asia has been identified to be highly vulnerable to mosquito-borne diseases [2] where dengue is highly endemic in selected countries [3] [4] [5] [6] [7] [8] . Therefore, the significant health and economic burden [9] brought by dengue in the Philippines makes it a major public health concern and one of the national notifiable diseases since 1958 [10] ." ] },{ "paper_id": "407efcba93e1b021b6556011cf2f9997ee108a8f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "40825b0106c7d8664276f75be3df4a75fb046c44", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A cross-sectional study design will be employed to achieve this objective.", "Help of appropriately trained field investigators will be taken to aid in language related issues.", "A community-based cross-sectional study will be conducted to achieve the last objective of the research study." ] },{ "paper_id": "40847cd029d6f68acbb579f47f3635fee5c23b48", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Funding: This research was funded by the Incheon National University.", "DMF technology is also used as a tool to study the mechanism of viral infection, probing the viral fusion using influenza A to measure the kinetics of fusion of virions with target liposomes. Monitoring the kinetics of fusion was identified by analyzing pH-sensitive fluorescence intensity with the presented method in which virions and liposome were encapsulated within droplets and acidic conditions triggered fusion [110] .", "Limit of Detection" ] },{ "paper_id": "40886c8a1c173dab7ef1685c544a7554f63bd6ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Feelings of fatigue are also impacted with the Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-fatigue) scale, showing worsening of fatigue at exacerbation and worsening of scores with increasing exacerbation frequency [65] .", "There is a wide range reported of inpatient mortality from COPD exacerbations, which reflects comorbidity and admission practices. Risk factors for inpatient mortality include cor pulmonale, congestive heart failure, a low arterial pH, leg edema, age, oxygen saturations <86%, assisted ventilation and low body mass index [69, 70] . A UK audit showed that larger general hospitals and teaching hospitals also have better mortality rates than small district general hospitals [71] .", "Bronchodilator therapy, by improving small airway obstruction, has been shown to reduce lung hyperinflation in stable disease and therefore may partially 'reset' the threshold at which exacerbation occurs [23] . This provides a mechanism by which bronchodilator therapy may reduce exacerbation frequency even in the absence of any anti-inflammatory effects.", "By understanding the mechanisms of development of frequent exacerbations, and applying appropriate interventions, we will be at last able to impact on the health status of this high-risk patient group. Competing interests JAW has received honoraria for lectures and/or advisory boards from GSK, Boehringer, Bayer, Novartis, Vifor Pharma, Chiesi, Pfizer, Takeda and Almirall. JAW has also received research grant funding from Takeda, GSK, Novartis and Chiesi. SEB, JPA and GCD have no competing interests to declare.", "All the authors contributed to the writing of the review and performed the literature searches. All authors were involved at all stages of the editing process and have seen and approved the final manuscript.", "The impact of exacerbations as assessed by the SGRQ in a study also persists for some time after the event, as patients only approached baseline within the next 6 months [63] . Other assessment measures show faster rates of improvement, and in patients who did not relapse with another exacerbation, significant improvements were seen in the four domains of the Chronic Respiratory Questionnaire (CRQ) between presentation and 10 days later [64] ." ] },{ "paper_id": "408c98fbba5d5584cc7fda96ec9b307d1cbd73bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since genetically engineered vaccines composed of a single recombinant antigen are poorly immunogenic, it is important to increase their immunogenicity by combining with appropriate adjuvants. The E. coli heat-labile toxin B subunit (LTB) has been shown to be a potent mucosal adjuvant [29] [30] [31] [32] [33] with low potential of eliciting allergic responses [34, 35] .", "Statistical significance was determined using ANOVA, with a P value < 0.05 considered as significant.", "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "408e677725167e4c45863aab7d91de0a5dae6d22", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In recent years, Australians have been exposed to a range of large-scale news coverage and health promotion campaigns about communicable disease. These have included seasonal influenza advisories; campaigns promoting immunisation for vaccine-preventable diseases [1] ; traveller vaccination messages; sexuallytransmitted disease prevention campaigns [2] , including human papilloma virus vaccine to prevent cervical cancer [3] ; HIV/AIDS and hepatitis B and C prevention.", "With the exception of HIV/AIDS and sexually-transmitted diseases, each of these has a vaccine and clear directives about how to avoid infection, forming the central communicative focus of such campaigns.", "It was therefore unclear whether everyone was vulnerable to infection and poor outcomes, including those who were well and not part of the usual high-risk groups, or whether everyone was vulnerable to infection but only some groups vulnerable to poor outcomes. However, as time went on and more became known about the illness, health authority messages sought to clarify uncertainty (\"the important thing is to say that mostly people have the normal experience with the 'flu and will be fine... What we're looking for is people with underlying medical conditions that suddenly get worse, or ordinary people that've not got other conditions that start to deteriorate\")." ] },{ "paper_id": "408fb49191d282aa03d722d951eb500a1dde3b87", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Both trials were approved by Independent Ethics Committees of the participating centres and conducted according to the Declaration of Helsinki and applicable local regulations.", "All findings after the screening visit were documented as adverse effects (AEs) except for any symptoms attributed to common cold (sneezing, runny nose, nasal obstruction, sore throat, cough, headache, fatigue and chilliness). Nevertheless, if such symptoms were of marked intensity or deemed to be not related to the study disease, these were recorded as AEs." ] },{ "paper_id": "4091e78b118eed89910b5089f4303a51d7e4c4fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Collected culture supernatants were centrifuged to remove cell debris. Briefly, EECs cultivated in 96-well plates were inoculated with virus dilutions (100 \u00b5L/well) prepared by 10-fold serial dilutions. Cells were incubated at 37 \u2022 C with 5% CO 2 for about 120 h, and any cytopathic effect (CPE) was recorded. Virus titers were calculated using the Reed-Muench method, and recorded as the TCID 50 /mL. Each test was performed in triplicate.", "BY carried out the experiments, collected data, and wrote this manuscript. XQ checked and revised the manuscript. HG, PJ, SC, ZC, and TW participated in some of the experiments. JW and QX conceived the study and participated in its design and coordination. All authors discussed the results, commented on the manuscript, and approved the final version. ", "Pooled and validated siRNAs targeting caveolin-1 (Cav-1) were purchased from Santa Cruz Biotechnology. ShRNAs targeting clathrin heavy-chain (CHC) (shCHC) and scramble RNAs were kindly provided by Dr. Hung-Jen Liu (Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan)." ] },{ "paper_id": "4099867282145ec32ec26620f381a9251f160f3b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "e SVM models and supporting data are available at http://www.bclab.inha.ac.kr/VHPPI.", "1 S W W W W R 6 R S S S R R 11 R R R R R S 2 W W W W R S 7 S S S R R R 12 R R R R S S 3 W W W R S S 8 S S R R R R 13 R R R S S S 4 W W R S S S 9 S R R R R R 14 R R S S S W 5 W R S S S R 10 R R R R R R 15 R S S S W W", "In (3) " ] },{ "paper_id": "409c387fb844383d955d8a6d7aace1a4d9e40e63", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "409e8fa9c8b69d7982ac0ecc28437a2e8a246d2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1) Suspected or confirmed cases should be correctly identified. All suspected cases should be identified, even though they have not yet been confirmed.", "The authors have no conflicts of interest to declare for this study.", "Supplementary material (Korean version) is available at http: //www.e-epih.org/. " ] },{ "paper_id": "40a30eb6f76c29d52d4ee9c7619f9f8bbfef796a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Questionnaire. " ] },{ "paper_id": "40a57ffe8adda95a13b552b630b13d76344f666c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All environmental samples were collected using swabs (World Bio-Products LLC, Woodinville, WA) pre-wetted with sterile 1X phosphate buffered saline pH 7.4 (Life Technologies,", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "mixed for 5 minutes. The mixed feed was then discharged at a rate of approximately 4.5 kg per minute into the leg of the bucket elevator (Universal Industries, Cedar Falls, IA). The feed exited the bucket elevator through a downspout, collected, and then converted to pellets using a pilot-scale single pass conditioner and pellet mill (Model CL5, CPM, Waterloo, IA)." ] },{ "paper_id": "40ab93e7916aabc26190092d088a37d43b3240fc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "40ac6a37f332f47ff9e9c6a6f8b1d5d21752679e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported in part by the NIAID-funded Center of Excellence for Influenza Research and Surveillance-CEIRS (Contract HHSN272201400008C).", "Intravenous polyclonal immunoglobulin (IVIG) is a preparation of human serum that contains high titers of neutralizing antibodies against the virus. Usage of IVIG in severe RSV infections in high-risk children significantly reduced the rate of hospitalizations due to related respiratory infections (The PREVENT Study Group, 1997) . Currently, new recombinant mAbs against RSV are in different stages of development.", "AUTHOR CONTRIBUTIONS MB and VL-G wrote, reviewed, and approved the submitted manuscript." ] },{ "paper_id": "40ae6bae0a5f86ac9beb57de189ae3320875e22c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Many questions remain about ERAD components and how they identify and interact with different substrates. Similar to our analysis of other cellular and molecular biological processes through virology, studies of viruses that use ERAD are likely to prove insightful.", "www.frontiersin.org through its chaperone activity, whereas ERp57 or ERp72 expression leads to ERAD (Grubb et al., 2012) . Further, various cell types express different PDI proteins, allowing differential regulation of substrates (Benham, 2012; Pescatore et al., 2012) and, presumably, their ERAD targeting.", "The preceding experiments indicate that ERAD is used by viruses to allow trafficking events that promote replication. MMTV Rem trafficking through the ER allows access to signal peptidase and cleavage of Rem precursor into functional N-and C-terminal proteins. In contrast, the polyomaviruses use ERAD to partially uncoat virions on their path to the nucleus. Importantly, both types of viruses avoid proteasomal degradation during ERAD, although the mechanisms remain unclear.", "Although endoplasmic reticulum (ER)-associated degradation (ERAD) has been most thoroughly defined in yeast, recent studies in higher organisms have revealed the conservation of this process and its components. Multiple diseases, including Parkinson's, Alzheimer's, cancer, and infectious processes, result from failure of ERAD, confirming its significance for correct cell function. Predictably, viruses have exploited various aspects of this key cellular machinery to further their propagation. Nonetheless, the complexity of ERAD and the number of players involved necessitates a review of its features prior to a description of how viruses have manipulated ERAD to their advantage. In understanding how viruses exploit ERAD, we learn more about the cellular process, but also how we might alter the outcome of viral diseases." ] },{ "paper_id": "40afe56736a9733a103c22570b574165d7d38edd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ". ISG15 is one of the most abundantly-induced transcripts upon type I IFN treatment, as well as following TLR ligation and viral infection [3, 4] . It is synthesized as a 17 kDa precursor protein that is proteolytically processed into its mature 15 kDa form [3] . Following stimulation with type I IFN, ISG15 exists in three distinct states-free within the cell, released into the extracellular space, or conjugated to target proteins.", ". ISG15 conjugation cascade. Following exposure to IFN a cell will upregulate free intracellular ISG15 (1), conjugate ISG15 to target proteins (2), and release ISG15 into the extracellular space (3). Shown in red are the immune evasion strategies utilized by viruses to circumvent the ISG15 pathway." ] },{ "paper_id": "40b1e8bb31863fa9488fcbfc590edf4972fe4c0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was carried out in strict accordance with recommendations in the Guide for Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Institutional Animal care and Use Committee (Protocol Number: 140231307A) of the University of Minnesota.", "Virus RM461, a MCMV expressing Escherichia coli \u03b2galactosidase under the control of the human ie1/ie2 promoter/enhancer [24] , was kindly provided by Edward S. Mocarski. The virus was maintained by passage in weanling female Balb/c mice (Charles River, Wilmington, MA). Salivary gland-passed virus was then grown in NIH 3T3 cells for two passages, which minimized any carry-over of salivary gland tissue. Infected 3T3 cultures were harvested at 80 to 100 % cytopathic effect and subjected to three freeze-thaw cycles. Cellular debris was removed by centrifugation (1000\u00d7g) at 4\u00b0C, and the virus was pelleted through a 35 % sucrose cushion (in Tris-buffered saline (TBS), 50 mM Tris-HCl, 150 mM NaCl, pH 7.4) at 23,000\u00d7g for 2 h at 4\u00b0C. The pellet was suspended in TBS containing 10 % heatinactivated fetal bovine serum (FBS). Viral stock titers were determined on 3T3 cells as 50 % tissue culture infective doses (TCID 50 ) per milliliter.", "RNA from the brain tissue was extracted using TRIzol reagent (Invitrogen, Carlsbad, CA), respectively. cDNA was synthesized with 1.0 \u03bcg of total RNA using Superscript III reverse transcriptase (Invitrogen) and oligo d(T) [12] [13] [14] [15] [16] [17] [18] primers (Gene Link, Hawthorne, NY). PCR was performed with the SYBR Advantage qPCR master mix (ClonTech, Mountain View, CA). The PCR conditions for the Mx3000P QPCR System (Stratagene, now Agilent Technologies, La Jolla, CA) were as follows: 1 denaturation cycle at 95\u00b0C for 10 s; 40 amplification cycles of 95\u00b0C for 10 s, 60\u00b0C annealing for 10 s, and elongation at 72\u00b0C for 10 s, followed by 1 dissociation cycle. The relative product levels were quantified using the 2 \u2212\u0394\u0394Ct method [29] and were normalized to the housekeeping gene hypoxanthine phosphoribosyl transferase (HPRT)." ] },{ "paper_id": "40b7ed2533e026bb5323b85f9d81379ae0f17821", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "40bf10143cbee94371fb682e9bf1dbfe05884433", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For chimpanzee adenoviral-vectored vaccines, mice were vaccinated intramuscularly with a single dose of 1 \u00d7 10 8 infectious units (IU). For boosting, MVA vaccines were administered at a dose of 1 \u00d7 10 6 plaque-forming units (PFU) per mouse. All vaccines were diluted in endotoxin-free PBS.", "Female inbred BALB/c (H-2d), (6-8 weeks) were used for the assessment of immunogenicity (n = 6 mice per group). Mice were purchased from Envigo RMS Inc. (Bicester, G.B.). The experimental design took into account the 3R reduction (Replacement, Reduction, Refinement). No randomisation was used in this work.", "The authors declare that the data supporting the findings of this study are shown in the article.", "All animals and procedures were used in accordance with the terms of the UK Home Office Animals Act Project License. Procedures were approved by the University of Oxford Animal Care and Ethical Review Committee (PPL 30/2414)." ] },{ "paper_id": "40c15d7dfd277d6c181783e56c9c996664c2ba5b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Public health officials working with clinical experts must make rapid recommendations about appropriate personal protective equipment, and for novel threats, these recommendations must be updated as more information about the pandemic becomes available. Prepandemic simulations can play a vital role in preparing staff for these outbreaks-for infection prevention and control, for clinical care practices, and also to help staff prepare \"emotionally\" for stressful environments.", "Most large jurisdictions already have pre-approved tiered case report forms, with minimal or expanded versions, so they may serve as data collection tools for clinical trials [39] . Funding agencies must also provide shortened intervals from application to approval, ideally with prepositioned funds for immediate vetting and release. Finally, there should be coordinated communication of research interests and intent across global regions at the outset to promote complementary and generalizable results without unnecessary duplication in efforts [40] .", "Global hot spots for emerging infectious diseases and pandemic influenza are often in some of the regions with the least resources. Many countries where HPAI remains a major pandemic threat have limited participation (data generation, genetic analysis, data share, etc.) in avian influenza surveillance [62] . In addition, some countries may have political, economic, or scientific disincentives to share surveillance data gathered [63] ." ] },{ "paper_id": "40c1f536d2ba1ea36ff1f17881df3f1073e76586", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Functional interpretation of differentially expressed genes was computed using Ingenuity Pathway Analysis (IPA) software (Ingenuity Systems), as described previously [10] .", "A repeated measures analysis of variance (ANOVA) model was fit in Partek Genomics Suite 6.6 (www.", "Neutrophils were quantified as a component of the standard hematology panel. Absolute neutrophil counts were available at various time points for most patients." ] },{ "paper_id": "40c76ef7831f3e2df1619e05514849a67a07d5d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "40cdf2909c24827365de82a6a5d84a7c3aec0290", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We classified disease systems by pathogen taxon (bacteria, viruses, protozoa, fungi, oomycetes, or arthropods), geographic region (continent), and transmission type, which included one or more of: direct contact, vector-borne, trophic (including food-and water-borne transmission), or other indirect contact (such as contaminated surfaces). Systems with prion pathogens were excluded from this study.", "To classify pathogens depending on single versus multiple-species reservoirs, we created the \"community-dependent\" classification. Every disease system that included more than one species between the reservoir and required vectors was classified as community-dependent.", "Reservoirs were separately classified by the major animal taxa they included as one or more of amphibians, annelids, arthropods, birds, fish, helminths, mammals, mollusks, and reptiles. Further, we recorded the mammalian orders, as given by Wilson and Reeder [22] , associated with each reservoir when relevant." ] },{ "paper_id": "40cf1b3081095810f3ea2fe14764071d3c1c1c65", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Adenoviruses are species specific, making the study of hAd pathogenesis difficult in an animal model. MAV-1 represents a useful alternative to study adenovirus pathogenesis (41) (42) (43) (44) (45) . MAV-1 has molecular, genetic, and pathogenic similarities to and differences from hAd. Their genomic structures are similar at a gross level, and both contain early genes involved in pathogenesis and immune evasion. Pathogenically, their tropisms differ, with hAd infecting epithelial cells, leading to upper respiratory and GI tract infections and to conjunctivitis, while MAV-1 infects endothelial cells and monocytes, causing encephalitis and myocarditis. We and others have been investigating the adaptive and innate immune responses to MAV-1.", "Statistical analyses. Data were analyzed with GraphPad Prism 7.0 software. For qPCR and densitometry analyses, the data were analyzed by individual Mann-Whitney tests. A P value of \u03fd0.5 was considered significant.", "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .00668-19. " ] },{ "paper_id": "40d1dd0f992de32e06c688811ecc8445826cee20", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Anti-bacerial therapy [60] Bacterial membrane coated Gold NPs Antibacterial immunity [61] 2.1.1. Liposomes", "Maintaining the germinal center, and releasing neutralizing antibody for anti-HIV therapy [110] CSP-hepatitis B surface antigen and Abisco-100, Matrix-M Targeting infected erythrocytes and CD8 + T-cell responses in anti-malaria therapy [123] HER-2 antigen", "In this review, we discuss the recent advances in biomimetic nanovaccines and their applications in anti-bacterial therapy, anti-HIV therapy, anti-malarial therapy, anti-melittin therapy, and antitumor immunity.", "Liposome Hepa 1-6 cell lysate and Poly I:C High tumor specific CTL immune response [145] P5 peptide and Poly I:C CTL immune response and anti-cancer therapy [130] Tumor associated ESO-1 antigen and IL-1, MAP-IFN-\u03b3" ] },{ "paper_id": "40e94ea7aba6cfaed881217032da16d4a5c2fd1d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Frozen live cultures of human coronavirus OC43 and 229E were purchased from ATCC (Cat #VR-1558, VR-740) for use as positive controls. RNA was extracted from these cultures using RNA Mini Kit (Qiagen, Hilden, Germany) in accordance with the manufacturer's instructions. The samples were amplified using diagnostic primer pairs for pancoronavirus, OC43 and 229E as previously described [43] .", "MCM measures the number of consecutive bases that are exact matches, with high scores for similar sequences [17, 18] .", "Genome Biology 2007, Volume 8, Issue 5, Article R93 Wong et al. R93.3 comment reviews reports refereed research deposited research interactions information Genome Biology 2007, 8:R93 http://genomebiology.com/2007/8/5/R93 Genome Biology 2007, Volume 8, Issue 5, Article R93 Wong et al. R93.7 comment reviews reports refereed research deposited research interactions information Genome Biology 2007, 8:R93 http://genomebiology.com/2007/8/5/R93 Genome Biology 2007, Volume 8, Issue 5, Article R93 Wong et al. R93.11 comment reviews reports refereed research deposited research interactions information Genome Biology 2007, 8:R93" ] },{ "paper_id": "40f52a42602489ad329c93edf69e213267303c1f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Within high-income countries, influenza vaccination is readily accessible and many jurisdictions have implemented publicly funded programs to cover the cost [9] . However, public vaccination uptake has been variable [10, 11] , and perhaps more importantly, some HCWs continue to resist participation in vaccination programs.", "Not applicable.", "The datasets during and/or analysed during the current study available from the corresponding author on reasonable request." ] },{ "paper_id": "410252e2a079c3b04f48b19672baa63bc8e7ebe4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Valley fever, Ebola, Zika which either occur in sporadic outbreaks in neglected populations or that are new or re-appearing with increased incidence or geographical range [4] .", "The University of Nairobi, the first university to be established in the country, had 101 (60%) of the theses followed by Kenyatta University 32 (19%), Jomo Kenyatta University of Agriculture and Technology 26 (15%), Moi University 6 (4%) and Egerton University 3 (2%)." ] },{ "paper_id": "41109a7485f8648bc39545c38aa0dea1e8460f17", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical differences were analyzed using the Student's t-test for all analyses, except for the 3C and 3D dose-dependent test, for which the Pearson correlation coefficient was used. Data are presented as means and standard deviations (SD). * P-values of <0.05 were considered statistically significant.", "Cells were mock-infected or infected with CVA6 at an MOI of 1. After 2 h of virus absorption, cells were washed once with PBS, and cells were cultured with fresh culture medium.", "anti-cyclinE1 (Proteintech), anti-CDK2 (Cell Signal), anti-cyclinD (Cell Signal), anti-CDK6 (Cell Signal), anti-CDK4 (Cell Signal), anti-P53 (Cell Signal), anti-P21 (Proteintech), anti-P16 (Proteintech), anti-cyclinB1 (Santa Cruz), anti-CDK1 (Boster), anti-VP1 (Genetex) and anti-histone (GenScript). Secondary antibodies from mouse or rabbit were obtained from Jackson Immuno Research." ] },{ "paper_id": "412833ef524797198177f582425f82e45c0f7a06", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The PCR product was amplified with oligos #3629 (CCGAT-CATGACTCTAAAAGTTATTCTTGGAG) and #3716 (GG-AGCTCGAGTTACTTATCGTCATCGTC) followed by digestion with PagI and XhoI. It was cloned into NcoI and XhoI digested pCupHis92 [70] .", "To express recombinant FHV protein A in yeast, we generated plasmid pGAD/Cup/FHV/protein A/C-term/HA/FLAG. The following sequence was fused downstream to the full length FHV protein A coding region by repeated PCR and cloning steps:", "To obtain FHV replicase preparation, BY4741 yeast strain was transformed with plasmid pGAD/Cup/FHV/proteinA/C-term/ HA/FLAG and pESC-His-GAL1::FHVRNA1framshift. After selection of transformed yeast on SC-LH 2 plates, yeast were pre-grown overnight in selective media containing 2% glucose at 29uC. After centrifugation at 2,000 rpm for 3 min and washing pellet with selective media containing 2% galactose, yeast were grown 36 hours at 29uC in SC-LH 2 media containing 2% galactose and 50 mM CuSO 4 to induce FHV RNA replication. Affinity-purification was done similarly as for tombusvirus, except for using different buffers: homogenization buffer consisted of " ] },{ "paper_id": "412aab9232d9b674c8ba7519a3c85ae72c2f0b9e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human rhabdomyosarcoma cells (RD) and African green monkey kidney cells (Vero) were cultured in Dulbecco's modified Eagle's medium (DMEM, Gibco) supplemented with 10% fetal bovine serum (FBS) at 37\u00b0C under a 5% CO 2 atmosphere. EV71 (strain SK-EV006) with GFP (EV71-GFP) was kindly supplied by Prof. Bo ", "is the difference between the enzyme activity with quercetin concentration [I] and A(0), which is the enzyme activity without inhibitor.", "These results confirm that virus adsorption was quantitatively affected by quercetin.", "The data shown are the means \u00b1 standard deviations (SD) of three independent experiments. The levels of significance for the differences between the test and control groups were analyzed using Student t-test, and the differences were considered significant if P values were < 0.05." ] },{ "paper_id": "412e5e7d7abb90b1bbd1e91d1c89b937987e376e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The structure coordinate of the STI/A mutant was deposited in Protein Data Bank, with PDB ID code of 3EA8.", "In 2002, severe acute respiratory syndrome (SARS) suddenly broke out in China and then rapidly spread to 32 countries, resulting in ,8500 infections and over 900 deaths (http://www. who.int/csr/sars/en/). It is the first emerging infectious disease of the 21st century and was caused by a coronavirus termed SARS-CoV. Although now SARS appears to be contained, new coronaviruses have been detected, which may cause great threats to the human health. For example, since the appearance of a new coronavirus termed Middle East respiratory syndrome coronavirus (MERS-CoV) in April 2012, it has caused 207 confirmed cases, out of which 84 died (http://www.who.int/csr/disease/ coronavirus_infections/en/index.html). More importantly, so far neither a vaccine nor an efficacious therapy has been available for them. Therefore, it remains highly demanded to develop strategies to design potential therapeutic agents against SARS-and other CoVs.", "Experimentally, the His-tagged protease or mutants was expressed in E. coli strain BL21 (DE3) with induction by 0.4 mM isopropyl-1-thio-d-galactopyranoside (IPTG) under 20 degree overnight. The protease was obtained by in-gel cleavage with thrombin while the His-tag protein attached to the Nickel-NTA beads (QIAGEN), followed by a FPLC purification on a gel filtration column (HiLoad 16/60 Superdex 200). The pure protease was concentrated to 10 mg/ml and stored in the buffer (10 mM Tris-HCl, 10 mM DTT, pH 7.5). The molecular weight of the WT and N214A proteases were determined by a Voyager STR MALDI-TOF mass spectrometer (Applied Biosystems).", "The simulation cell is a periodic cubic box with a minimum distance of 10 \u00c5 between the protein and the box walls to ensure the protein would not directly interact with its own periodic images given the cutoff. The water molecules, described using the TIP3P model, were filled in the periodic cubic box for the all atom simulation, 6 Na + ions were randomly placed to neutralize the charge in MD system for STI/A and WT dimers, Each system contained approximately 75,000 atoms." ] },{ "paper_id": "413383034f00fe7c2c81688ac152dc102963d08b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Non-circular DNA was removed by exonuclease I and exonuclease III digestion. Specifically, the reaction was heated to 94 \u00b0C for 2 min and held at 37 \u00b0C while 10 units of exonuclease I and 50 units of exonuclease III were added. Samples were then incubated at 37 \u00b0C for 30 min followed by enzymatic inactivation at 94 \u00b0C for 15 min. Capture sequence was then amplified by the addition of Platinum taq (Thermo Fisher Scientific), 0.4\u03bc m forward 5\u2032 -CAGATGTTATGCTCGCAGGTC and reverse 5\u2032 -GGAACGATGAGCCTCCAAC primers, 1.0\u00d7 buffer with 50mm MgCl 2 , and 0.4 \u03bc M dNTPs. Reactions were amplified at 95 \u00b0C for 3 min, 40 cycles of 95 \u00b0C for 30 sec, 60 \u00b0C for 30 sec, 72 \u00b0C for 1 min, and a hold of 72 \u00b0C for 10 min. Following amplification samples were purified utilizing Agencourt AMPure XP beads (Beckman Coulter, Pasadena, Ca) per the manufactures protocol with the slight alteration to a 1:1 mixture of bead to sample volume.", "More than 2 million people in the United States succumb to antibiotic resistant (AR) infections annually adding significant fiscal burden to the healthcare system due to prolonged treatments, extended hospital stays, and increased mortality rates 1 . The emergence of organisms such as carbapenem-resistant enterobacteriaceae, vancomycin-resistant enterococcus, and drug-resistant Neisseria gonorrhoeae highlight the need for more efficient measures to diagnose and treat AR organisms 1 . These measures would help to stop transmission as well as evolution of future multidrug-resistant strains through better antibiotic stewardship. Further, better diagnostics are even more critical when addressing biothreat agents where inadvertent creation of resistant organisms through overuse of antibiotics could have dire consequences.", "Diagnostic tools identifying QRDR genetic variants are essential for both timely and appropriate therapeutic measures as well as managing the spread of drug-resistant bacteria. Ideal diagnostics should be rapid, sensitive, inexpensive, and provide information such as strain-type, virulence prediction, and AR profile. Compared to current molecular diagnostics such as real-time PCR, next-generation sequencing (NGS) will potentially better fulfill these requirements while providing information beyond the identity of the etiologic agent 9 including: species level identification, resistance profiling, genomic epidemiology, and microbial forensics [9] [10] [11] ." ] },{ "paper_id": "413d8c5b923d8572615bfb6d7199dad41f4ad370", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The neutralizing activities of pre-and post-nebulized C-8 and C-8-2-4B-10D IgG 1 were evaluated in PRNT 50 ", "The study that provided the human samples was approved by the Institutional Ethics Review Board of Seoul National University Hospital (IRB approval number: 1602-100-742), and written informed consent was obtained from all participants.", "The authors declare no conflict of interest. " ] },{ "paper_id": "4141cdba2be695f11c3f7278d72481ae521eebd9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4146f749b0883891603380e62be449df9a94a1a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "41472dcd6a621cee86ccbeedd2fc0f7ae93be71b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Of the participating slaughterhouse owners (see Table 2 ), 46.3% were male; 48.8% were 50-59 years old; 68.3% had completed primary school; 24.4% had been operating a slaughterhouse for 11-15 years; 82.9% slaughtered 1-50 birds/day; and 100.0% did not have a DLD license for slaughtering." ] },{ "paper_id": "4149c3d415d6963eb002ec43810b5b4a97838465", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Selenomethionine incorporation. Twenty hours following infection of an Sf21 suspension culture (27.8\u00b0C, with an agitation speed of 130 r.p.m./0.25g), cells were collected (70g, 10 min, 22\u00b0C) and resuspended in cysteine-and methionine-free SF900II medium (Gibco) supplemented with dialysed fetal bovine serum (Gibco; 7% v/v) and 150 mg l \u00c0 1 L-cysteine (Sigma). Following an additional 4 h at 27.8\u00b0C in the shaking incubator, 250 mg l \u00c0 1 selenomethionine (Sigma) was added. Protein expression was allowed to continue for another 48 h. Proteins were purified as above.", "Methylation of GTP was determined in the same buffer (minus the 3 H-SAM and RNA), using the EPIgeneous methyltransferase assay kit (Cisbio), which measures the generation of SAH, as it competes with d2-coupled SAH for binding to a Lumi4-Tb-labelled anti-SAH antibody, affecting the TR-FRET signal between these compounds. In practice, MTase reactions were stopped after 16 h by addition of the detection reagents, and 1 h later the TR-FRET signal was monitored using a PHERAstar Flashlamp plate reader.", "NATURE COMMUNICATIONS | DOI: 10.1038/ncomms9749 ARTICLE transfer takes place onto the pppG m GGACAAGU substrate where this atom is blocked (Fig. 2b , green bars). The 2 0 O-methylation of pppGGGACAAGU represents B50% of that observed with GpppGGGACAAGU (which has an extra methylation target in the GN7 atom; Fig. 2b , red bars).", "Synthesis of RNA substrates. RNA sequences were chemically synthesized on a solid support using an ABI 394 synthesizer. After RNA elongation with 2 0 O-pivaloyloxymethyl phosphoramidite monomers 34, 35 (Chemgenes, USA), the 5 0 -hydroxyl group was phosphorylated and the resulting H-phosphonate derivative 36 oxidized and activated into a phosphoroimidazolidate derivative to react with either phosphoric acid (for ppRNA synthesis), pyrophosphate (pppRNA) 36 or guanosine diphosphate (GpppRNA) 37, 38 . N7-methylation of the purified GpppRNA was performed enzymatically using N7-hMTase 37, 38 . To prepare monophosphate RNA (pRNA), the 5 0 -H-phosphonate RNA was treated with a mixture of N,O-bis-trimethylacetamide (0.4 ml), CH 3 CN (0.8 ml) and triethylamine (0.1 ml) at 35\u00b0C for 15 min, and then oxidized with a tert-butyl hydroperoxide solution (5-6 M in decane, 0.4 ml; 35\u00b0C, 15 min). After deprotection and release from the solid support, RNA sequences were purified by IEX-HPLC (495% pure) and their identity were confirmed by MALDI-TOF (Matrix-Assisted Laser Desorption/Ionization Time-of-Fight) spectrometry." ] },{ "paper_id": "4152ae12ac49d157a290281842bce9e9d16096a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fmoc deprotection was performed with a solution of piperidine in dimethylformamide in a 2/8 (v/v) ratio. Final deprotection of the peptides from the resin was performed in a mixture containing trifluoroacetic acid, phenol, water, triisprpylsilane in a 88/5/5/2 (v/v) ratio for 3.5 h. Peptides were then precipitated by addition of cold diethyl ether and dissolved in a mixture of 0.1% trifluoroacetic acid in water/acetonitrile and lyophilized. Purity of all peptides was checked by analytical high performance liquid chromatography on a Waters instrument using a C18 column (Novarpack, 5 \u03bcm, 300 \u00c5, 10.0 \u00d7 200 mm) and all were at least 70% pure (UV detection at 214 and 254 nm). They were characterized by electrospray mass spectrometry.", "T cell epitope prediction tools, ANN, SMM and ARB provided by IEDB are publicly available in a website (http://tools.immuneepitope.org/analyze/html/ mhc_binding.html) Version 2009-09-01B.", "Average Relative Binding (ARB) is a matrix method, which allows combination of searches involving different peptide sizes and alleles into a single global prediction [19] . ARB has achieved a favorable performance in predicting MHC I and MHC II molecules [20, 21] ." ] },{ "paper_id": "41546fbae5ea1a9c511d17fa9d9b583f944eda95", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by the institutional review boards (IRBs) of the Children's Hospital of Philadelphia (CHOP), the University of Pennsylvania School of Medicine, University of Washington, Harvard School of Public Health, Vanderbilt University, and the University of California at San Francisco.", "Genome-wide association studies (GWAS) are powerful, unbiased tools for the identification of common genetic variants, e.g., single nucleotide polymorphisms (SNPs), associated with complex traits [16] . Despite potential limitations [17] , GWAS have led to the identification of genetic susceptibility loci that reproducibly confer risk for complex diseases such as Crohn's disease, rheumatoid arthritis, and Type II diabetes [16, 18, 19] . To date, the GWAS approach has not been applied to the study of ALI.", "The exact function of the genetic regulation of rs471931 on the PPFIA1 gene is not known. It is approximately 280Kb downstream of PPFIA1 on 11q13.3 and there are intervening genes, including SHANK2. Future studies may focus on fine mapping the region to better understand the role of genetic regulation of liprin alpha expression in ALI risk.", "We report the first GWAS of ALI susceptibility, using a three stage approach, including a discovery phase, a replication phase, and a functional evaluation phase using gene expression screening in family trios. We hypothesized that a GWAS approach would identify common genetic variants associated with a reproducible differential risk of ALI." ] },{ "paper_id": "4156b347411e4071b10550a6acc2725c5e82df99", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Membrane fusogenicity is the result of an active virus-host cell interaction process that induces conformational changes within the viral envelope protein [1] .", "Ethics approval for this study was obtained from the Innsbruck Medical University, Austria.", "The T-lymphoblastoid cell line M8166 was cultivated in RPMI 1640 medium (Life Technologies) supplemented with 10% FCS, penicillin/streptomycin and 2 mM L-glutamine." ] },{ "paper_id": "415ccc587d634fc429ac080cf06694f78621ef73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ", "Additional file 1: Illness Visit Questionnaire." ] },{ "paper_id": "416266511be0451304064a125f0bcf108c56f375", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step 1. Problem Identification. Make clear the problem you want to study.", "Supporting information S1 File. PRISMA 2009 checklist. (PDF)", "Data curation: TX WL. Formal analysis: TX WL. Funding acquisition: TX. Investigation: TX WL. Methodology: TX WL. Project administration: XL GCG. Resources: TX WL. Software: TX. Supervision: XL GCG. Validation: XL GCG. Visualization: TX WL. Writing -original draft: TX." ] },{ "paper_id": "4169c478d00d20c1d3a2a3b5c1684ef749e32041", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bacterial species or specimen Number tested FI-nvCT positive FI-nvCT negative " ] },{ "paper_id": "417006f8744a4d8068ce146b06db09bbd48eaad2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Based on the sequence alignment ( Fig. 1 ) as well as the atomic coordinates of 1ko3, the 3D structure of NDM-1 was derived by using the I-TASSER algorithm, an extension of the previous TASSER (Threading/Assembly/Refinement) method [42, 43, 44] .", "(TIF) Figure S5 Per-residue error visualized by using a color gradient from blue (reliable region, estimated error below 1 \u00c5 ) to red (potentially unreliable regions, estimated error above 3.5 \u00c5 ).", "(TIF)", "In December 2009 a novel metallo-b-lactamase was identified in a patient hospitalized in New Delhi with an infection caused by klebsiella pneumonia [4] . This b-lactamase was later detected in bacteria in India, Pakistan, United Kingdom, United States, and Canada. The New Delhi metallo-b-lactamase (NDM-1) has the ability to make bacteria resistant to a wide range of b-lactam antibiotics, including the carbapenem family antibiotics that are a mainstay for the treatment of antibiotic-resistant bacterial infections [5, 6] . According to the report of the United Kingdom's Health Protection Agency, most isolates with NDM-1 are resistant to all standard intravenous antibiotics for the treatment of severe infections. The most common bacteria that make this enzyme are Gram negative such as Escherichia coli and Klebsiella pneumonia, but the gene for NDM-1 can spread from one strain of bacteria to another by horizontal gene transfer." ] },{ "paper_id": "417286ac22fc95bdfe96df0dc2a7c1e3eb5befe1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Description of measuring ambient CO 2 and O 2 concentrations during hypercarbic or atmospheric gas for in vitro Experiments 1 and 2b.", "Digital signals from the pressure transducer were recorded with a Powerlab 8/30 data acquisition system (ADInstruments, Inc., Colorado Springs, CO, USA) and the digital signals were transformed and analyzed using LabChart Pro software (ADInstruments, Inc., Colorado Springs, CO, USA).", "Thus, being exposed to high concentrations of CO 2 in the absence of any change in O 2 is clearly panicogenic." ] },{ "paper_id": "41734f9087773eafddb2a6907b4075a3cb661a85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The reliability results were visualized by constructing a map (Additional file 4 and Additional file 5)." ] },{ "paper_id": "41743a48f1acec724d627f76e02e85137debc076", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were fixed in 4% para-formaldehyde for 15 min, permeabilized with 0.1% Triton X-100 in PBS for 10 min, and counter-stained with antibodies against IRAK-M (4369, Cell signaling, USA) or IRAK4 (4363, Cell signaling, USA). The coverslips were mounted onto microscope slides in Anti-fade Mounting Medium (Beyotime, China). Fluorescent images were visualized and captured using Olympus BX51 upright fluorescent microscope (Olympus, Japan).", "All statistical analysis was performed using SPSS Graduate Pack 11.0 statistical software (SPSS). One-way ANOVA analysis or Student's t test was used to compare the mean of each treatment, with a P-value of less than 0.05 considered statistically significant.", "Six pairs of peripheral tissues from lung squamous cell carcinoma or lung adenocarcinoma, which were regarded as negative control, and tissues from human pulmonary tuberculosis were collected from surgical excision (Wuhan Institute for Tuberculosis Control, China). The formalin-fixed and paraffin-embedded tissues were respectively cut into 4-\u03bcm sections and then deparaffinized routinely. The slides were incubated with antibodies (Hif-1\u03b1, 2015-1, Epitomics, USA; IRAK-M, 4369, Cell signaling, USA), then washed with PBS and incubated with Envision\u2122 (DAKO, Shanghai, China; polyperoxidase-anti-mouse/ rabbit IgG). After washing, the slides were colored with 3,3-diaminobenzidine and counter-stained with haematoxylin." ] },{ "paper_id": "417754f2c930dac6e586d36eb8bfb07355f6e0ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "On more than one third of the days with information registered, children suffered from a runny nose (37.9 %). The second most frequent symptom was coughing (25.9 %), followed by wheezing (3.9 %) ( Table 2) .", "All analyses were performed with Stata for Windows, version 12 (StataCorp, College Station, TX)." ] },{ "paper_id": "417a6772d67e3b958d27a80ed09cabfea228d432", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 298 respondents participated in this study and the overall response rate was 87%. Table 1 summarizes the demographic characteristics of the 298 respondents. Majority of respondents (70.5%) were between the age of 18 to 29 years; 23.8% were married and only 7.3% had chronic medical illness. Majority of respondents (87.2%) were Chinese; 50.3% were students; 22.2% worked in an indoor setting and 27.5% worked in an outdoor setting." ] },{ "paper_id": "417fd2b2eba2473029f35d664f1bc72e03022eb1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This was a prospective observational study. The antibiotics provided were based on the guidelines of the Philippine Pediatric Society [18] . As supportive therapy, oxygen was provided using a nasal catheter or oxygen mask. Endotracheal intubation was done if necessary and hooked to a manual ambu bag as there was no mechanical ventilator in the pediatric ICU of EVRMC.", "Serotypes or genotypes of RSVs, HRVs, and AdVs were determined by sequencing the hypervariable region of the G protein gene for RSVs [27] , the VP4-VP2 region of HRVs [28] , and the hexon region of AdVs [29] . Sequencing was performed using ABI 3730xl with BigDye version 1.1 (Applied Biosystems, Carlsbad, CA), and sequence results were analyzed by MEGA ver. 4 [30] with reference strains from Genbank.", "Single virus positive " ] },{ "paper_id": "418826a231c08bed06a47bd7d0b96dcdf66bd3e6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistics. Statistical analyses were conducted using SPSS software (version 20 SPSS, Inc., Chicago, IL). For normally distributed variables, Student's t-test and one-way ANOVA were used for comparisons, and the data are presented as the mean \u00b1 SE. The Mann-Whitney U and Kruskal-Wallis tests were used for comparisons of variables that were not normally distributed. Correlations were assessed with Pearson's correlation coefficient for parametric distributions. Statistical significance was set at P < 0.05.", "Pentraxin-3 (PTX-3) ELIZA. The level of PTX-3 in plasma was measured using a Quantikine ELISA Human Pentraxin 3/TSG-13 kit (R&D Systems, Minneapolis) according to the manufacturer's protocol. The detection range was 0.31-20.00 ng/mL. Concentrations were determined using a standard curve generated from specific standards provided by the manufacturer. Each sample was measured in duplicate.", "Circulating cell-free DNA (circulating-cfDNA) is released from damaged cells and associated with various pathological conditions 3, 4 . Previous studies showed physical or emotional stress could augment circulating-cfDNA 5, 6 . Also, circulating-cfDNA was a predictor of mortality and showed a close association with chronic inflammation in HD patients 7, 8 . Pentraxin-3 (PTX-3) is a marker of systemic inflammation producing rapidly by various cells under the inflammation or stress conditions 9 . These three parameters are commonly used as stress parameters in pathologic status." ] },{ "paper_id": "418f1b85e589f3ac37ffc37075b6e558e510fa74", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Health departments consistently expressed uncertainty about how to effectively communicate with vulnerable or underrepresented population groups in their jurisdictions, and few had well established relationships with community leaders or organizations that could serve as messengers or communications channels to these groups.", "In several sites, law enforcement and EMS personnel present in exercises had greater familiarity with these groups and could help identify trusted community messengers. Further, in some communities, health departments had limited language capacities or were not sufficiently familiar with community leaders to communicate effectively with these groups.", "Even obtaining a census of available staff members turned out to be challenging as many health care participants noted that some staff would likely be double-counted, particularly nurses and security officers who might work in several institutions. Increasing staff capacity through the use of community volunteers, including retired medical personnel, while often recognized as one potential solution to staffing shortages, proved to be extremely difficult to actually implement. Public health participants universally recognized the importance of volunteers, but learned that their plans to recruit, train, and mobilize large numbers of volunteers were too vague and lacked concrete actionable steps for realistic application during a real emergency." ] },{ "paper_id": "41b659ac51b4f4596b414e93c5dd220b26386f34", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "41b92c19649c6e5cd6a4e883e7edf9a43589bcdd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Extinction coefficient_All Amount of light a protein absorbs at a certain wavelength (assuming ALL Cys residues appear as half cysteines) ", "Charged Physicochemical property 1 25", "Comparison of nine features used for classification of guanine nucleotide-releasing factor versus negative proteins Figure 2 Comparison of nine features used for classification of guanine nucleotide-releasing factor versus negative proteins." ] },{ "paper_id": "41baca2bc5af0758c336c9b56d09a5f95c7afcae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "gene knockdown in embryonal teratocarcinoma cell lines that are interferon defective [102] [103] [104] .", "97 Loqs-PD is required for endo-siRNA biogenesis, but dispensable for viral siRNA (vsiRNA) 98 biogenesis.", "99 Viruses 2019, 11, x FOR PEER REVIEW 4 of 32 100 Figure 2. Dicer proteins process double-stranded RNA (dsRNA) into small interfering RNA (siRNA).", "While the lack of CARD domains renders LGP2 signaling incompetent, it is important for fine tuning the immune response." ] },{ "paper_id": "41c7a01f11ed47591d99f45774e43e45aeba0619", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "tional analyses. If the glycosylation events are proven important for changes in immune responses, researchers can further examine CD3G-related PPIs to explore the underlying molecular mechanisms.", "Given the wide spectrum of biological functions in which PTMs are involved, variations in host protein PTM patterns should have major impacts on immune response and virus life cycle.", "CAPIH also provides a JAVA-based adjustable protein interaction viewer (The \"Protein Interactions\" section; Figure 4 ). The interaction view gives the user an idea of how HIV-1 proteins interact with the proteins of interest." ] },{ "paper_id": "41d0c75e25a257485a79211632b5c9ed93d4df14", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dynamic light scattering experiments were carried out on a Zetasizer Nano S Instrument (Malvern, Worcestershire, UK), with a 633 nm He-Ne laser. All measurements were carried out at 25\u00b0C in 20 mM Hepes pH 7.5, 150 mM NaCl, 5% glycerol.", "Samples were negatively stained with 1% uranyl acetate (SPI Supplies, Westchester, PA, USA) and observed with a FEI Tecnai T12 S/TEM at an accelerating voltage of 80 kV (FEI, Hillsboro, Oregon)." ] },{ "paper_id": "41dc0a864ad331ec921ed5411bfdd3030859ac6f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Isolation of suspected and confirmed MERS-CoV cases managed under airborne-infection control precautions [33, 34] has been shown to be effective in containing nosocomial outbreaks [14] [15] [16] 24] . Contact tracing and screening should be undertaken by relevant public health authorities [33, 34] .", "It remains an enigma that, while SARS-CoV spread rapidly globally and caused >8,000 cases and 775 deaths (10 % mortality) before disappearing within 8 months of discovery [10] , MERS-CoV continues to circulate 4 years after first identification [9] , causing intermittent community and hospital-associated outbreaks [19] . The exact mode of transmission to humans from camels and other possible animal sources remains undefined. Worryingly, the very high mortality and absence of specific MERS-CoV treatments or vaccines will seriously impact healthcare services of countries from which Hajj pilgrims originate if a Korealike outbreak [23-25] occurs from returning pilgrims.", "Between 8 and 14 September 2016, the cities of Jeddah, Makkah, and Madinah, Kingdom of Saudi Arabia (KSA), hosted the annual Hajj pilgrimage [3] . An estimated 2 million pilgrims attended from 184 countries, lived in crowded conditions, and performed religious rites in close proximity, exposing themselves and the local Saudi population to a range of infectious diseases. MERS-CoV was first isolated and identified in a 68year-old patient who died of pneumonia and multi-organ failure in Jeddah, KSA, in June 2012 [9] . This is the second time (after severe acute respiratory syndrome coronavirus, SARS-CoV) [10] in the 21st century that a coronavirus has emerged as a new lethal zoonotic pathogen of humans." ] },{ "paper_id": "41ed8edac17db0256c043cee4b27884395539746", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2)", "( 1 ) (0, , V) = 0, for all \u2265 0.", "where = * , = * + \u039b + * 2 + * 2 ,", "Generally, the basic process of viral infection and virus replication occurs in six main steps: attachment, penetration, uncoating, replication, assembly, and release [7] . After the whole replicative cycle, free viruses begin to diffuse and infect new host cell. Therefore, investigating the processes of viral growth and destruction of host cells so as to gain the insights into the evolutionary processes of virus and cell in body is very important. To this end, mathematical models and analysis are powerful tools." ] },{ "paper_id": "41f31582cb50c99b10a376f465107d82bacf135c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MERS is an epidemic that spread through contact with people, and as a result leads to the avoidance of contact in people of all ages, especially causing older individuals with a high mortality rate to avoid contact. Such fear grows with the increase in social distancing [10] , impacting the medical vulnerable group more significantly in social or economic aspects.", "The MERS break out started in Saudi Arabia in 2012 and expanded from the Arabian Peninsula. The World Health Organization [16] stated that 1599 people were infected, 574 people died and fatality reached 35.9%. A large outbreak later occurred in the Republic of Korea in 2015, resulting in the 2nd largest number of patients following Saudi Arabia [17] ." ] },{ "paper_id": "4208f9c98e378d4959debc3ba361e9cc6972e814", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "While alpine summering has a prominent role in cattle management in Switzerland, Austria, Liechtenstein and the alpine regions of France, Italy and Germany (Bavaria), the practice of bringing herds to higher summer pastures-often leading to a mixing of herds-exist in Table 1 Definition and sources of the network analysis terms used in this study Type / Name Definition Source", "The largest component in the network in which all pairs of holdings are linked via directed paths [43, 46] Giant weakly connected component (GWCC)", "Holding centrality metrics" ] },{ "paper_id": "4209267ef4da6a8206733929e58967faebf8a5b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Migration, including the seeking of political asylum, is also frequently characterised as having a purely social and \"economic\" causation [42] . Yet, economic factors are associated with elements that are both material (e.g. food, shelter) and social (e.g., freedom of association and speech, psychological security).", "The second category of greatest concern is of new strains of influenza A, arising either from intensively farmed birds, especially chickens with Highly Pathogenic Avian Influenza (HPAI) [49, 89] or pigs, or emerging from Asian \"wet markets\" where several species of bird have close contact [90] .", "If this theory is correct, then modern human conditions very rarely create the right circumstances for breeding a devastating human flu strain on the scale of Spanish flu. But this could change in future.", "From 1960 to about 1980 per capita production of the top 20 food crops (by tonnage) rose steeply, associated with a dramatic fall in global hunger (including as a proportion). In the last few years per capita production of these crops has again risen, yet global hunger has worsened. Raw data FAO (FAOSTAT), UN Population Division. events (especially resource scarcity, most often of land) and social factors [39, 40] . The tension between Israel and its Arab neighbours is very rarely analysed to have an environmental dimension, especially by Israelis [41] . Instead, the tensions are generally considered to have a purely social explanation, based on culture and religion." ] },{ "paper_id": "420944cb316179f6529d1d7a99d92910df8e49a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HS was supported by the China Scholarship Council; FP was supported by a post-doctoral fellowship from Academia Sinica. This work was funded by Grant No. BIO2016-80572-R and the FEDER program.", "BR drafted the manuscript with the collaboration of JAG. HS and FP contributed to the conception and design of the review and revised the manuscript. All the authors read, critiqued, and approved the final manuscript.", "The authors are grateful to Patricia Elhazaz Walsh for editorial assistance. They acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI). They would like to apologize to those colleagues whose relevant publications have not been cited because of space constraints or involuntary forgetfulness." ] },{ "paper_id": "42145eff1cc724f8e5ad1a8e04cc421512d8ec7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Gnotobiotic newborn piglets, which are highly susceptible to infectious agents, were obtained from four specific pathogen-free sows, following guidelines for the proper conduct of animal experiment at National Institute of Animal Health (17-061, 5 December, 2017, NIAH Animal experiment committee).", "Viruses 2018, 10, x 5 of 12", "Viruses 2018, 10, x 6 of 12" ] },{ "paper_id": "421bd6f23db8177832f8476dc64df824b7c2b017", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ACT : actin; UBC: ubiquitin-conjugating enzyme; \u03b1-TUB: alpha-tubulin; \u03b2-TUB: beta-tubulin; EF1-\u03b1: elongation factor 1-\u03b1; MUB: membrane-anchored ubiquitin-fold protein; CYP: cyclophilin; RPL: ribosomal protein L18; TIP41: TIP41-like family protein." ] },{ "paper_id": "421ee1f936a1714743c3cf06be01220009624a03", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1) BME integrates knowledge from epidemiology into Geographic Information System science by assimilating epidemic laws, empirical relations, and statistical calculations in SARS studies.", "(3) BME simulates SARS transmission and predicts diffusion tendency. The resultant study of these processes can reflect interesting underlying principles behind SARS spread." ] },{ "paper_id": "421f8341eae777852e0b4584e7221b39a0544518", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A combination of an ecosystem-focused perspective and a social-anthropological lens is vital Bbecause a pathogen requires a receptive population in order to cause disease ( Possas, 2016, p. 8) (Possas 2016) . Ultimately, the need for a cross-disciplinary response pathway cannot be understated (Possas 2016) .", "Funding Information LK's research is funded by the Canadian Institutes for Health Research. AR is a PhD candidate.", "The authors declare that they have no conflicts of interest.", "The paper is based on a review of the peer-reviewed published medical, social, and political literature, which was accessed using four electronic databases-PubMed, Sociological Abstracts, Scholars Portal, and Web of Science. The search was limited to full text articles published between 2002 and 2017." ] },{ "paper_id": "422cd9eb3c56e4f05ba9ced4ecbda48bdc043c16", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data analysis was performed using version 9.4 of SAS software package (SAS Institute Inc., Cary, NC, U.S.).", "Virus stock and MEM were mixed so that each piglet inoculum was a 5-mL volume containing 1 X 10 6 TCID50 of PEDV. This inoculum was administered to piglets via syringe and gavage needle immediately following dilution." ] },{ "paper_id": "423e1f15afb86012057acacc26d0766aa4bc582a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "XL and JW provided the concept and study information, revised the manuscript, and provided the final version. XX, JQ, XL, and JW drafted the manuscript. All authors approved the final version of the manuscript. ", "Enteroviruses are the members of Picornaviridae. International Virus Classification Committee classifies enteroviruses into 12 species according to their molecular structure and serotype analysis, including enterovirus A-J and Rhinovirus A-C. Five species (E-J) of enteroviruses infect only animals and the remaining seven species of enterovirus can cause various kinds of human diseases, such as infantile paralysis -caused by poliovirus (PV), myocarditis-caused by coxsackievirus B3 (CVB3), hand foot and mouth disease-caused by enterovirus 71 (EV71), coxsackievirus A16 (CVA16), CVA6 and other enteroviruses, respiratory disease-caused by enterovirus 68 (EV68), rhinovirus (Racaniello, 2013) . In particular, the outbreak of hand foot and mouth disease every year, which seriously threatens the health of infants and young children, has brought enormous burden to our public health (Huang et al., 1999; Chan et al., 2003; AbuBakar et al., 2009; Yang et al., 2011; Xing et al., 2014) . However, despite these risks, there are no effective antivirals for the treatment of enteroviruses (EVs) infection.", "Recent studies have shown that CVB3 infection results in the degradation of NLRP3 and its upstream RIP1/RIP3 protein by its proteinase 3C and leads to the inactivation of the NLRP3 inflammasome (Wang et al., 2018a) . Thus, enteroviruses may directly antagonize the function of NLRP3 inflammasome by inducing the cleavage of NLRP3." ] },{ "paper_id": "424061f2444cab0c4e972c7fcfc18a9dfbe7b4c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analysis was performed in SPSS version 18.0 software." ] },{ "paper_id": "4241f93b9e7128d98e8b1e81a410999283bc3599", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Y t *quasiPoisson(m t ,wm t ), log (m t )~b 0 zbFlu t zb 1 RSV t zs(t, df~11|k) zs(Temp t , df~3) zs(Hum t , df~3)zb 2 NO 2t zb 3 SO 2t zb 4 O 3t zb 5 PM 10t zb 6 SARS t :", "(TIF)" ] },{ "paper_id": "424606001b632c4148c73e7a2c288a08ff978842", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "424cd6cb670119aed604833cf1f107598f217574", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results were expressed as mean \u00b1 SEM for each treatment group in each experiment. Statistical analyses were performed using Statistical Analysis Systems statistical software package (SAS Institute, Cary, NC). Significance was determined by one-way analysis of variance, followed by Duncan range test for multiple comparisons. Differences were considered significant at P < 0.05.", "The present study was approved by the Hallym University Institutional Review Board and Committee on Animal Experimentation (hallym R2014-6). All experiments were performed in compliance with the University's Guidelines for the Care and Use of Laboratory Animals. No mice were dead and no apparent signs of exhaustion were observed during the experimental period.", "For the immunofluorescent histochemical analysis, paraffin-embedded lung tissue sections (5 \u03bcm thickness) were deparaffinized and hydrated. The sections were pre-incubated in a boiling sodium citrate buffer (10 mM sodium citrate, 0.05% Tween 20, pH 6.0) for antigen retrieval. The tissues were blocked with 5% BSA in PBS for 1 h. Specific primary antibody against mouse vimentin, mouse beclin-1, mouse LC3A/B or mouse \u03b1-smooth muscle actin (\u03b1-SMA) was incubated with the tissue sections overnight. Subsequently, the tissue sections were incubated for 1 h with FITC-conjugated anti-goat IgG or Cy3-conjugated anti-goat IgG. For identification of nuclei, the fluorescent nucleic acid dye DAPI was applied for 10 min. Stained tissues were mounted on slides using fluorescent mounting medium (Vector Laboratories, Burlingame, CA). Images of each slide were taken using an optical microscope Axioimager system (Zeiss, Gottingen, Germany)." ] },{ "paper_id": "424d6c622643d36a7f8d9a1d2714f4cef49387ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cancer is the second leading cause of death worldwide. While major advances have been made in design of chemotherapy agents, radiation, and surgical procedures, mortality rates remain high. Terminal cancer requires innovative therapeutic approaches, which are currently limited. Traditional use of herbs to treat diverse human illnesses dates back to thousands of years, but in today's society the use of natural product remedies is defined amongst others under the classification of \"complementary and alternative medicines\" (CAMs) [1] [2] [3] . The field of CAM is of global interest, in particular to augment traditional chemotherapies, prevent cancer remission, or serve as basic chemopreventive strategies [4] [5] [6] [7] .", "Materials used were Hanks Balanced Salt Solution, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), ethanol, 96-well plates, general reagents and supplies, and hLDH-A from Abcam (Cambridge, MA, USA). Rhus chinensis gallnut was purchased from Kalyx Natural Marketplace (Camden, NY), cell lines were purchased from ATCC (Manassas, VA, USA), and penta-1,2,3,4,6-O-galloyl--d-glucose, chemical reagents, and HPLC supplies and columns were purchased from Sigma Aldrich (St. Louis, MO, USA) and VWR International (Suwanee, GA, USA).", "The ethyl acetate fraction (20 g) was flash chromatographed over silica gel (200-400 mesh) and eluted at 10 mL/min with chloroform: methanol gradient (100 : 0, 10 : 90) solvent system. A total of 500 (15 mL) fractions were collected. Fractions were pooled according to their value on TLC and then combined to give 5 distinct fractions which were then evaporated to yield 0.5 g (1-166), 11.5 g (167-215), 4.2 g (216-267), 2.1 g (268-350), and 1.2 g (351-500). The resulting fractions were tested for activity at 0.7-0.0007 mg/mL. Fractions (167-215) showed significant hLDH-A inhibitory activity relative to other fractions. 1.5 g of the active fraction, 167-215, was further analyzed and separated into four major fractions by RP-HPLC with UV detection at 214 nm on PRP-15 um 15 \u00d7 2.1 mm column and eluted with a gradient system of acetonitrile: water consisting of 0.2% TFA." ] },{ "paper_id": "424ea1927a270902bd78e27db83dd9411b4ea9a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For arenaviruses, the attenuated Candid#1 JUNV is the only vaccine that is approved for use in humans in Argentina. The vaccine elicits strong and protective neutralizing antibody responses in those vaccinated and has been successful in controlling AHF within endemic regions [96] . A chimeric MACV expressing the GPC from Candid#1 JUNV is highly attenuated in a mouse model and protects animals from lethal MACV challenge [97] . This protection correlates with high titers of MACV-specific neutralizing antibody before challenge.", "Studies using a rodent model of LASV-induced hearing loss have provided further evidence that hearing loss may be caused by a cell-mediated immune response rather than through direct viral damage [105] . STAT1 knockout mice infected by clinical LASV isolates develop sensorineural hearing loss, though IFN\u03b1\u03b2/\u03b3 receptor knockout mice do not. Interestingly, while LASV antigen can be detected in the inner ears of both types of mice, tissue damage was only observed in the STAT1 knockout mice concomitant with profound CD3-positive lymphocytic infiltration [105] . It would be interesting to determine if depletion of T cells could prevent hearing loss in this model.", "In LASV infection, accumulating evidence has raised the possibility that the neurological sequelae are likely caused by virus-induced immunological injury. A recent study using NHPs as a model for LASV infection demonstrated that NHP survivors developed pathological findings consistent with autoimmune-associated vasculitis [104] . Two out of three NHP survivors also developed sensorineural hearing loss similar to that observed in human cases. Histopathological examination of the inner ear revealed inflammation of vessels and perivascular tissue at 45 days post-infection, long after the acute infection had subsided. Furthermore, serological analysis revealed that survivors developed elevated C-reactive protein and antineutrophil cytoplasmic antibodies, which are indicators of autoimmune disease [104] . These findings in NHPs indicate that hearing loss acquired after LF may be due to chronic inflammation." ] },{ "paper_id": "424f52f1d390c220aaaea5efa3e59696a2e903f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "During viral infection, viral proteins and viral nucleic acids are detected by pathogen recognition receptors (PRRs). These recognition patterns activate signaling transduction pathways that trigger production of type I interferon and other related cytokines [3, 25] . Type I interferon then elevates the expression of hundreds of genes, named interferon stimulated genes (ISGs), that weaken virus replication by a variety of mechanisms [3, 25] .", "Human DNA extraction", "Details of multivariable regression process are presented in Additional file 2." ] },{ "paper_id": "425007062aa63b14681dcf2414a0f5b77bca5ddd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "AUC \u2265 0.9 high accuracy 0.7 \u2264 AUC< 0.9 moderate accuracy 0.5 \u2264 AUC< 0.7 Low accuracy", ": Accuracy classification of AUC [2, 3, 4, 5, 6] ." ] },{ "paper_id": "425be277181521bab21a8e64d54657dfdcac6bde", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4261cfd373572b30e170171afce095e6eb5d806a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Electronic medical records were used to obtain information for the study population, including membership history, baseline characteristics, demographics, comorbidities, treatments, utilization, and outcomes. Each KPSC health plan member has a unique medical record number that is used as an identifier to retrieve and link all variables from different databases.", "Methods. Hospitalized adults aged \u226560 years who tested positive for RSV or influenza between 1 January 2011 and 30 June 2015 were identified from Kaiser Permanente Southern California electronic medical records. Baseline characteristics, comorbidities, utilization, and outcomes were compared." ] },{ "paper_id": "426d73371e7f29a3d046687525d416f68708f643", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mycobacterium tuberculosis and atypical mycobacteria (e.g. M. avium)", "McMaster technique and FLOTAC) [135, [137] [138] [139] .", "Schistosoma mansoni, S. mekongi, S. intercalatum and S. japonicum" ] },{ "paper_id": "4271774baf0182630ce43862b9e0b151eda34e8c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There has been a dramatic increase in the number of insect-specific flaviviruses (ISFs)", "Data on the ability of dISFs to suppress the replication of dual-host ISFs in mosquito cells are limited.", "In NOUV, a potential frameshift site (U UUU UUA with a 3'-adjacent predicted stem-loop structure) was identified in the NS2A-encoding region, and the sequence was shown to stimulate frameshifting in a reporter construct [87] . Frameshifting at this site would yield a truncated version of NS2A. The site is not conserved in BJV or NHUV, but a different potential frameshift site (again U UUU UUA with a 3'-adjacent predicted stem-loop structure) occurs in NHUV at a site around 25 codons upstream (again within NS2A). Between these two sites, BJV has a potentially slip-prone U CCU UUU sequence, but only a weak 3'-adjacent stem-loop structure was predicted. It remains unclear whether the NOUV, NHUV and BJV sites are chance features or functionally relevant -1 PRF sites." ] },{ "paper_id": "4277d45726b61850deb6a0a4b2cabe450127ec69", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two investigators (TS and KM) conducted independent English language literature searches and extracted data using standardised data extraction templates. One investigator (TS) whose first language is Chinese performed the search and data extraction from Chinese language databases (CNKI, Wanfang and CQVIP). Any discordance and/or uncertainties regarding relevance or inclusion were arbitrated by HN or HC.", "Regarding to sampling methodology, most studies used nasopharyngeal swab (NPS) (n=10), nasopharyngeal aspirate (NPA) (n=6) and nasopharyngeal wash (NPW) (n=1) as specimen. Five studies used mixed specimens including NPA, NPS, lung aspirate and oropharyngeal swab (OPS). All studies used PCR as diagnostic testing except one study from Gambia [16] , in which case indirect immunofluorescence (IIF) was applied.", "Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from TS). We declare that we have no conflicts of interest.", "Authorship declaration: HN and HC conceptualised the study. TS and KM conducted the literature review with oversight from HN and HC. All authors participated in data analysis and data interpretation. TS and KM prepared the initial draft of the manuscript. HN and HC contributed to report writing and critically reviewed the manuscript. All authors read and approved the final draft of the manuscript." ] },{ "paper_id": "4278a9b763f17829897dde88a49fcab6ab86b8c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Female BALB/c mice that weighed approximate 20 g were obtained from the Academy of Military Medical Sciences, Laboratory Animal Center (Peking, China). Mice were housed in the animal facilities of Nankai University with access to food and water. 4T1 murine breast carcinoma cells were obtained from the American Type Culture Collection (Manassas, VA) and cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (Invitrogen, Carlsbad, CA).", "The animal experiments were performed in accordance with institutional guidelines, and the study was approved by the ethics committee of Nankai University. Mice were anesthetized with a mixture of oxygen/isoflurane before each experiment to alleviate their suffering. For survival data, humane endpoints were chosen to terminate the distress of the experimental animal via carbone dioxide euthanasia. The animals were monitored twice per day and extreme anorexia (poor appetite and emaciated appearance) was determined as a humane endpoint.", "Statistical analysis was done with GraphPad Software (La Jolla, CA). Data were expressed as mean 6 SD of triplicate samples, from at least three independent experiments. Statistical significance was determined using Student's t-test or two-way ANOVA." ] },{ "paper_id": "427c25eb5418afb2f27b6f27b6c7c07b4ea7af08", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Other models used for the local display in the mice gut of therapeutic protein are Lactobacillus gasseri and L. casei both expressing superoxide dismutase (SOD) [39, 40] . As it happens with catalase, SOD action neutralizes ROS species and their derived inflammatory effect. ", "Cancer has a huge relevance in human health due to its growing incidence in developed countries. The strategies for effective cancer treatment under study are countless and the use of LAB has recently appeared in this field.", "Effective therapeutic approaches for autoimmune diseases like GIT related diseases and diabetes are urgently " ] },{ "paper_id": "428d1091cf63872ea81cb3c1632d76c4813748a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "42966e386536e2e45a30988e43e762c81e7ca6dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Generally speaking, PCV is not considered as an arbovirus. However, PCV2 has been often detected in M. domestica flies and culex mosquitoes in pig farms (50, 51) . Surprisingly, PCV3 was first identified in ticks (Ixodes ricinus) collected from wild roe deers that were negative for PCV3, making the source of PCV3 ambiguous (25) . PCV infection is postulated to occur when hosts get bitten by carrier flies, mosquitoes, and ticks.", "As we know, many viruses can spread through aerosols. Whether PCVs can spread via aerosol is little known. However, Canadian researchers found that high viral loads (up to 10 7 genomes per cubic meter of air) of PCV2 existed in swine confinement buildings (78) . Another study also identified the existence of PCV2 in bioaerosol samples from pig farms and abattoirs. In addition, PCV2 was detected in nasal washes of workers (4/78) from pig farms (65) . This revealed that PCV2 was a potential airborne virus.", "Intriguingly, PCV2 can be detected in various types of water samples from Brazil, including (a) water used for swine consumption, subjected to conventional treatment followed by chlorination; (b) tap water meant for human consumption, subjected to conventional treatment followed by chlorination; (c) surface water without treatment, used for swine consumption; (d) water from the Pinhal river, which crosses; (e) groundwater collected from a tap located at a school; and (f) water from the Jacutinga river, which is redirected and treated for domestic supply (79) . This indicated that PCV2 was widely prevalent in the environment.", "Bivalve shellfishes (such as oysters, clams, and mussels) intake nutrition by filtering up to 4.8 L/h of surrounding water and simultaneously concentrate microorganisms that are present (52) (53) (54) . Animal pathogens can contaminate the beds via runoff from fields fertilized using animal waste. One previous study reported high detection rate for PCV2 and E. coli (41%, 12/29 and 28%, 8/29) in blue mussels (Mytilus edulis) from Danish commercial harvesting areas, while common food-borne pathogens (such as hepatitis E virus, rotavirus, Salmonella) were absent. The geographic distribution of the PCV2-positive shellfish samples revealed that positive samples were localized to Limfjord in the northern part of Jutland and a bay area in the south-western part of Jutland, Denmark (55) . This suggested that these bay areas were contaminated by porcine waste, and PCV2 may be a specific indicator of porcine waste in shellfish." ] },{ "paper_id": "4296edbb527d1e55ad2079c76f619659e0b5720d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The threat of using orthopoxviruses, variola and monkeypox, as bioterror weapons has led to increases in vaccination particularly in military personnel as well as the investigation of countermeasures (antiviral treatments) for such infections [1] . A number of compounds have been identified that exhibit direct antiviral activity against these and related poxviruses in animal models [2, 3] . From these investigations, three compounds stand out as being clinical candidates, cidofovir [4] , CMX001 (an orally active prodrug of cidofovir) [5] , and ST-246 [6] . Cidofovir, CMX-001, and ST-246 have all been used in emergency settings to treat vaccination complications [7, 8] .", "The experiments were conducted in accordance with Protocol 552 approved by the Institutional Animal Care and Use Committee of Utah State University. The work was done in the AAALAC-accredited Laboratory Animal Research Center of Utah State University in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (Revision; 2010).", "Female BALB/c mice (Charles River Labs, Wilmington, MA) weighing approximately 13-15 g at the time of first treatment were used. After a 48-hour quarantine period the animals were randomly assigned to cages. All work with these animals was performed in the Biosafety Level 2 area of the AAALACaccredited Laboratory Animal Research Center at Utah State University." ] },{ "paper_id": "42a8d5fd943cd29a518ec9683f549f105aac92f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sample size was calculated using single proportion formula based on 95% confidence level, expected prevalence of 80% [2] , precision of 0.05, and design effect of 2. The recommended sample size was 492 children with one of their parents as a single unit.", "A structured self-administered parental questionnaire was developed by relying on previous studies [13] [14] [15] [16] [17] [18] [19] [20] and accounting for cultural sensitivities of the study population. The questionnaire was translated into Arabic and then back to English to ensure accuracy. Face validity, feasibility, and construct validity of the questionnaire was established prior to study." ] },{ "paper_id": "42b049c2b5b32c094dc8b10f967e43ac2169b890", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 fever (38\u00b0C)", "\u2022 and cough or sore throat", "\u2022 and onset less than five days prior to presentation" ] },{ "paper_id": "42bb18ca1f49d74b80f2bab85b3878cade647b08", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Weibull distribution function has been used to describe non-linear inactivation patterns of various microorganisms after different thermal and non-thermal processing [25] . Assuming that the temperature resistance of the virus is governed by a Weibull distribution, Mafart et al. developed the following Weibullian equation:", "Feed was suggested as a vehicle of transmission of PEDV when the first Canadian swine farm tested positive for the virus [9] . A follow-up epidemiological investigation suggested that a The shape parameter (n) indicates the shape of the curve with a value n > 1 forming shoulders and being convex, n < 1 forming tails and being concave, and n = 1 being linear.", "Inactivation kinetic data (log TCID 50 /mL) were analyzed by GInaFiT, a freeware Add-in for Microsoft Excel developed by Geeraerd et al. [23] . The traditional log-linear model that assumes a linear relationship between the virus concentration and processing time was developed by Bigelow and Esty [24] and used to characterize the survival curves of PEDV by using the following equation:", "Porcine Epidemic Diarrhea Virus (PEDV) is a pleomorphic, enveloped RNA virus, classified as a coronavirus under the family Coronaviridae [1] . The virus was first identified during an outbreak of diarrhea on a Belgian swine breeding farm in 1978 [2] . Upon infection with PEDV, suckling pigs experience diarrhea, vomiting, and high mortality [3] . Since the initial identification of PEDV, it has been reported in Canada, Korea, China, Thailand, Italy, Hungary, and Vietnam [4] . It is important to note that China and Vietnam are two of the top swine producing countries in Asia and that they were both impacted by PEDV [5] ." ] },{ "paper_id": "42c1d88111ece7fdf4a80dc8ddb30be44b211d80", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "THP-1 monocytic cells (ATCC, Manassas, VA) were grown and maintained in RPMI-1640 medium containing 10% fetal bovine serum and penicillin/streptomycin. Cells were harvested by centrifugation, washed with RPMI-1640 medium and suspended at 5610 5 cells/ml in fresh medium containing 5% human EDTA plasma.", "All values are expressed as mean +/2 S.E.M except in experiments where n = 2 (as indicated in figure legends) where data are expressed as standard deviation. Significance of peptide effects on cytokines was determined by Student's t test. Daily survival/death values were determined by x 2 test.", "RTD-1 is the most abundant of six h-defensin isoforms expressed in neutrophils and monocytes of rhesus monkeys [13] ." ] },{ "paper_id": "42c4f1b128cea03599c36e89eff62afa7e02caa2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Similar to the conserved proteins encoded by ORF1ab, the N gene is also another common target for phylogenetic analysis. Due to its immunogenicity, it is also a common target for cloning and generation of recombinant proteins for serological assays.", "Viruses 2010, 2 1805 coronavirus HKU1 (HCoV-HKU1). Codon usage bias in coronaviruses were observed, with HCoV-HKU1 showing the most extreme bias, and cytosine deamination and selection of CpG suppressed clones are the two major independent biological forces that shape such codon usage bias in coronaviruses.", "The E and M proteins are small transmembrane proteins associated with the envelope of all coronaviruses. In some coronaviruses, such as MHV and SDAV and possibly HCoV-HKU1, the translation of the E protein is cap-independent, via an internal ribosomal entry site. Although these two genes are conserved among all coronaviruses, they are not good targets for phylogenetic studies because of their short sequences." ] },{ "paper_id": "42d1823428c311725c7395123a3c2c276b7b5fd1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ZL and GB conceived the study and wrote the manuscript. CZ carried out the data analysis. JjS collected and detected the field samples using an antigen test kit. HS and JyS participated in manuscript preparation. ZL, GB, CZ, and JZ designed the experiments. All authors read and approved the final manuscript. ", "The datasets generated for this study can be found in NCBI, MK076889-MK076943, and MK460553-MK460560.", "The specificity of duplex FMCA was validated using DNA or cDNA (complementary DNA) samples from six CPV-2 variants and five other viruses (Supplementary Figure S2) . No specific melting peak was detected with the other non-targeted dog viruses such as CDV, CAV-2, CCV, CRV, and CPIV in either the FAM or HEX channels. These results suggested that the designed primer sets and probes were highly selective and specific for their target viruses, exhibiting no cross-reactivity with several other common canine viruses." ] },{ "paper_id": "42d750019224d03261c70185a1bae3afe5be8c3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The work described here was funded in part by the Wellcome Trust through core funding grant 098051 for the Sanger Institute Pathogen Variation Group.", "Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture. USDA is an equal opportunity provider and employer.", "b ; The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom c Bordetella bronchiseptica swine isolate KM22 has been used in experimental infections of swine as a model of clinical B. bronchiseptica infections within swine herds and to study host-to-host transmission. Here we report the draft genome sequence of KM22." ] },{ "paper_id": "42e321eedba25d380ae44d16cdf0bbdeab83d665", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data used for the statistical analyses is contained in S1 Table. Ethics Statement", "Finally, sapovirus transmission might depend on basic population parameters such as population density, principally represented by clan (group) size. If the chance of transmission increases with animal density, then individuals living in larger clans should be more likely to be infected than those in smaller clans. However, if an encounter reduction effect operates [48, 49] , then we expect the chance of susceptible individuals encountering an infected animal to decline with clan size.", "Supporting Information S1 ", "Phylogenetic relationships were reconstructed using Maximum Likelihood (ML) and Bayesian Markov chain Monte Carlo (MCMC) phylogenetic inferences. The ML analysis was performed in PAUP \u00c3 4.0b10 [55] using 1,000 bootstrap replicates to estimate the statistical support of the branches. The Bayesian analysis was carried out using MrBayes version 3.1 [56, 57] . The MCMC search was set to 10,000,000 iterations, with trees sampled every 1,000 th iteration. The nucleotide substitution model used in the ML analysis was obtained using ModelTest 3.7 [58] and for the Bayesian analysis using MrModeltest 2.3 [59] . For both cases the Akaike Information Criterion (AIC) was used to select the best-fitting model." ] },{ "paper_id": "42ef2bf3057aeedc9a51d599553ee98527e2bfb4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As the basic parameter of nanoparticles, size and morphology are firstly considered in many studies.", "Catalysis is an important process that associated with the chemical transformations, which is crucial for the development of modern industry [185] .", "In addition to the above techniques, the number of novel methods for the characterization of PMNPs, such as scanning tunneling microscopy (STM), atomic-force microscopy (AFM), Raman scattering and electron spin resonance (ESR) spectroscopy, is growing rapidly, providing more evidence for their applications [35] . " ] },{ "paper_id": "42f17b849628fb1db7c74cc15899bf9b9c59de93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In either case, having defined an appropriate populationlevel transmission rate, a stochastic susceptible-infectious model of transmission is defined through a Markov chain, in which a population with X susceptible individuals and Y infectious individuals transitions stochastically to a population with X \u2212 1 susceptible individuals and Y + 1 infectious individuals at rate \u03b2XY/(N \u2212 1). Then, the exact mean behaviour of such a system in the limit N \u2192 \u221e then has its transmission behaviour captured b\u1e8f", "Interdisciplinary Perspectives on Infectious Diseases", "Hence, we have a classic metapopulation model [43] , defined in terms of Poisson local and global connections and large local community sizes.", "where the sum of degrees is made over the neighbours (Nbrs) of i. One can then calculate the average of k nn over all nodes with degree k which is a direct measure of the conditional probability P(k | k), since", "This quantity corresponds to the standard verbal definition of the basic reproductive ratio, and correspondingly the invasion threshold is at R 0 = 1.", "While R 0 can be derived using expressions like (11), calculation of the asymptotic early growth rate r requires systems of ODEs like (14) . If we assume that transmission and recovery are Markovian processes with rates \u03c4 and \u03b3, respectively, two measures of early behaviour are" ] },{ "paper_id": "42f6f50759cb4c433e8c1ff0d695bdb32ae97df9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4300be597ccbea9acb374312063e2776b7f631c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total nucleic acids including DNA and RNA were extracted from 200 L of each specimen using a QIAamp MinElute Virus Spin Kit (Qiagen, Mississauga, ON, Canada) according to the manufacturer's instructions.", "The study followed the Declaration of Helsinki on medical protocol and ethics. The Ethics Committees of both Shandong Medicinal Biotechnology Centre and Qilu Children's Hospital of Shandong University approved the study. Written informed consent was obtained from the next of kin of the participants.", "Clinical and Developmental Immunology 7" ] },{ "paper_id": "430213ca4c52874f7082c2a1d1c3117187e41dae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Selection conditions can be manipulated to obtain aptamers stable in a wide range of environmental conditions Aptamers may be obtained against non-immunogenic proteins and toxins", "At present, the initial clinical testing for HIV in human is made with an antigen/antibody combination immunoassay that detects HIV-1 and HIV-2 antibodies and HIV-1 p24 antigen to screen for established infection with HIV-1 or HIV-2 and for acute HIV-1 infection [22] . Enzyme-linked immunosorbent assay (ELISA) and real time PCR are the methods used and accepted in clinical samples.", "HCV viral genome is a positive-strand RNA that contains approximately 9.6 kilobases and codified for a polyprotein of around 3000 amino acids. The HCV polyprotein maturation process mediated by proteases gives rise to 10 viral proteins, four structural (C, E1, E2 and p7) and six non-structural (NS2, NS3, NS4A, NS4B, NS5A and NS5B) [79] . To date, only three proteins (p7, NS4A and NS4B) have not been used as antiviral target for isolate specific aptamers.", "Non-translated 5\u2032 and 3\u2032 regions have highly conserved sequences and structured regions closely related with transcription and replication of the HCV virus. Specifically, 5\u2032 end contains the Internal ", "Human papillomavirus (HPV) is a DNA virus from the papillomavirus family. Most HPV infections cause no symptoms and resolve spontaneously, but some of them persist and result in warts or precancerous lesions which increase the risk of cancer of the cervix, vulva, vagina, penis, anus, mouth, or throat [119, 120] ." ] },{ "paper_id": "430903f42d10ae8f5729df9a61e75e2d6dc09f65", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Descriptive statistics, T-test and ANOVA were used to analyze data, when applicable.", "The data set(s) supporting the results of this article is included within the article.", "A summary of VI data is provided in " ] },{ "paper_id": "430e499fc7f67e711312d57680f20c15a235cb20", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "cDNA synthesis and library preparation for high-throughput sequencing", "Virome sequencing of R. solani isolate DC17", "The fungal strain DC17, originally isolated from sugar beet, was derived from the IRS (Institute of Sugar Beet Research, Netherlands) and identified as anastomosis group 2-2IV by sequencing of the internal transcribed spacer region [36] . The isolate showed unusual light pigmentation, slow growth on PDA and hypovirulence in a damping-off assay with sugar beet (data not shown). The strain was stored at -80\u00b0C on PDA. For extraction of DNA, RNA and dsRNA, mycelium was grown in PDB at 24\u00b0C." ] },{ "paper_id": "4315ae43f201739bb56193e328dfdbd8a6646b4b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Figure 2 summarizes the main targets of ADAM17induced shedding described in the text, the downstream events of their proteolytic cleavage and pathological and physiological processes influenced by ADAM17-dependent shedding.", "All authors: JX, SM, CS, AC, JC, CB, VB, EL, and MF, drafted the work, contributed to work design, revised it critically, approved the final version to be published and declare accountable for all aspects of the work.", "This study was supported by the Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq) and by the Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES), Brazil, Grant 88881.068184/2014-01 to MF, research grants from the American Heart Association (15POST25000010 to JX and 12EIA8030004 to EL) and the National Institutes of Health (HL093178 and GM106392) to EL." ] },{ "paper_id": "431b8b5c20edeb65055154ed5f93e8a9a49f4c97", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For a fuzzy measure \u03bc, let \u03bc(", "Furthermore, \u03bb can be obtained by solving following equation:", "In this case," ] },{ "paper_id": "4328e18bdf9b52875c87f3f5ddb1911636a192d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The exclusion criteria for this study were patients with: (1) any other kidney disease, (2) diabetes mellitus, (3) autoimmune disease, (4) hematological disease, (5) cardiovascular disease, (6) viral hepatitis (types A, B, C, D, or E), or (7) any other liver disease. In addition, no patients received corticosteroids or other immunomodulatory drugs during the study period (21) .", "All data were expressed as the mean \u00b1 SEM. Statistical analyses were performed using GraphPad Prism 5 (GraphPad Software, La Jolla, CA, USA). For association analysis of the rs12252 allele and genotype, Fisher's exact test was used. Independent samples t-tests were used for normally distributed data. Differences among groups were determined by one-way analysis of variance (ANOVA) with repeated measures, followed by Bonferroni's post hoc test. P < 0.05 was considered statistically significant.", "According to clinical symptoms and signs, such as fever, effusion, hemorrhage, edema, and renal function, the severity of HFRS can be classified as previously described (21): (1) mild patients were identified with mild renal failure without an obvious oliguric stage; (2) moderate patients were those with obvious symptoms of uremia, effusion (bulbar conjunctiva), hemorrhage (skin and mucous membrane), and renal failure with a typical oliguric stage; (3) severe patients had severe uremia, effusion (bulbar conjunctiva and either peritoneum or pleura), hemorrhage (skin and mucous membrane), and renal failure with oliguria (urine output, 50-500 ml/day) for \u22645 days or anuria (urine output, <50 ml/day) for \u22642 days; and (4) critical patients exhibited \u22651 of the following signs during the illness: refractory shock, visceral hemorrhage, heart failure, pulmonary edema, brain edema, severe secondary infection, and severe renal failure with oliguria (urine output, 50-500 ml/day) for >5 days, anuria (urine output, <50 ml/day) for >2 days, or a BUN level of >42.84 mmol/l. Due to the sample quantity required for SNP typing, the mild and moderate patients were assessed together in the mild group, and we combined severe and critical patients as severe group." ] },{ "paper_id": "4329714c2818a1caa58260ce4f82652106b535a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The raw data generated by MiSeq and HiSeq 2000 sequencers was processed to eliminate the adapter pollution and low quality to obtain clean reads. The qualified clean data was used for the further bioinformatics analysis. Firstly, paired-end reads with overlap were merged to tags by software FLASH (v1.2.11) 30 , and then tags were clustered to OTU at 97% sequence similarity using USEARCH (v7.0.1090) 31 . Secondly, Taxonomic ranks were assigned to OTU representative sequence using Ribosomal Database Project (RDP) Na, e Bayesian Classifier v.2.2 32 . At last, alpha diversity, beta diversity and the different species screening were analyzed based on OTU and taxonomic ranks by MOTHUR (v1.31.2) 33 .", "c N was the colony growth diameter, cm; t was the microbial growth culture time, h; A, A, k, x c as the model parameters.", "Measurement Method. The actual measurement is divided into two parts: the environment parameter measurement and air unit sampling. First, the temperature, humidity, and CO 2 concentration were automatically recorded by the temperature, humidity and CO 2 monitor (MCH-383SD, Japan)." ] },{ "paper_id": "432bff7a22efb0fd2d87b162ce6da91120d28cfe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "c Patients who did not receive any dose of vaccine were classified as non-vaccinated.", "https://doi.org/10.1371/journal.pone.0190507.t002 " ] },{ "paper_id": "433cb6b526e64343c82717d42daab33b2379f252", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All authors contributed to the collaborative writing of this project. " ] },{ "paper_id": "434ab543a48b7fb395d181ffb947814bd1b506c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consistent with such a scenario, the shielding from NMR relaxation agents of His549 and the fusion behavior His549 mutants somewhat resemble the respective observations that we made with the two conserved glutamates.", "Content release experiments were performed using a SpectraMaxM5 plate reader as described previously with slight modifications [25, 30] . Liposomes containing 12.5 mM 8-aminonapthalene-1,3,6 trisulfonic acid (ANTS) and 45 mM p-xylene-bis-pyridinium bromide (DPX) were prepared by extrusion method as described in lipid mixing section using HMA buffer without salt to match inside and outside osmolarity. The dye-loaded liposomes were separated from non-encapsulated dyes by size exclusion chromatography and lipid concentrations were determined by the modified phosphate assay [31] described in Kreutzberger et al. [32] .", "Mutagenesis, expression and purification of wild-type and mutant FLs was performed as previously described with slight modifications [15] . In brief, the EBOV FL wild-type construct (residues 507-560; derived from full-length DNA that was a gift of Dr. Paul Bates, University of Pennsylvania) was cloned into the pET41 vector (using Nde1 and Xho1 restriction sites), which contains a T7 promotor and a site conferring kanamycin resistance. Mutants were created by site-directed mutagenesis on wild-type EBOV FL using PfuUltra DNA polymerase. All constructs were grown in LB media supplemented with vitamins (Sigma product M6895 used at 1x concentration). These vitamin supplements add extra nutrients and reduce the burden on cells producing protein. This speeds up cell growth, but has a minimal effect on yield. Cell cultures grown at 37\u00b0C were induced at O.D. 600 of 0.6-0.8 with a final concentration of 0.5 mM IPTG. After introducing IPTG, cells were grown at 30\u00b0C for 4 hours and harvested. Cell pellets containing EBOV FLs were lysed by sonication for 10 min on ice and purification of FLs was performed by following the previous protocol [15] .", "The production of VLPs and the assay to measure their entry into cells were performed as described previously [33] . Briefly, HEK293T/17 cells (ATCC CRL-11268; obtained 8/7/13 from University of Virginia Cell Culture Core Facility) were co-transfected with plasmids encoding for VP40, \u03b2-lactamase-VP40, mCherry-VP40, and wild-type, H516A, or E540D/E545D GP with a C-terminal V5 tag (wild-type was a gift from Dr. Paul Bates, University of Pennsylvania) using the polyethylenimine method. After 48 hours incubation at 37\u00b0C, cells were centrifuged and clear media was taken and ultracentrifuged on a 20% sucrose cushion. The VLP pellets were resuspended in HM buffer (20 mM Hepes, 20 mM MES, 130 mM NaCl, pH7.4) overnight and were subsequently repelleted. All VLPs were analyzed by Western blotting for presence of EBOV GP and VP40. To measure cell entry, VLPs were allowed to enter 293AD cells (293AD cells: Stratagene #240085; obtained 10/2/14 from Stratagene) that were treated with the fluorescent CCF2-AM \u03b2-lactamase substrate for 3 hours at 37\u00b0C in the dark. Cells were washed and incubated overnight in the dark at room temperature. Cells were fixed and analyzed by flow cytometry with a FACSCalibur flow cytometer. The degree of the shift in fluorescence from green to blue was used to measure entry [34] . All data were analyzed using FlowJo software. Cells were typically passaged for not more than 30 passages before thawing and using fresh cells." ] },{ "paper_id": "434bd9335384207d750282844ad8ceb545e50462", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total genomic DNA was extracted from approximately 20 mg of spleen using Wizard TM Genomic DNA Purification Kit (PromegaH, Madison, WI, USA) following manufacturer's recommendations.", "The study protocol was approved by the Ethical Committee for the Use of Experimental Animals of the Universidade Federal de Ouro Preto, Ouro Preto -MG, Brazil.", "Unlabeled canine monoclonal antibodies (mAbs) anti-CD5 (rat-IgG2a: clone YKIX322.3), anti-CD4 (rat-IgG2a: clone YKIX302.9), anti-CD8 (rat-IgG1: clone YCATE55.9) and anti-MHC-II (rat-IgG2a: clone YKIX334.2), all purchased from Serotec, USA, were used in an indirect immunofluorescence procedure in which pooled normal rat serum (diluted 1:6000) was employed as the isotypic control and fluorescein isothiocyanate (FITC)-labelled IgG sheep anti-rat polyclonal antibody was used as the secondary antibody. FITC-labelled mouse anti-human-CD21 (mouse-IgG1: clone IOBla) and phycoerythrin-Cy5-conjugated mouse anti-human-CD14 (mouse-IgG2a: clone TUK4) mAbs were used in a direct immunofluorescence assay." ] },{ "paper_id": "4350c7bc82bb4dba102fe29a6b50ed632b28a920", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fungi mostly come from outdoors, while bacteria are mostly emitted indoors. This is mostly consistent with findings iii, v, vi, and viii above.", "Translation and/or comment (if applicable) \"In order to draw conclusions from an examination of air inside buildings, it is of course necessary to know the state of the outside air.\"", "\"Hence it is clear that a certain amount of physical disturbance in a room is a condition necessary to the presence of micro-organisms in the air.\"\"The skin and clothes of the persons present in a room at the time of an observation also occur naturally as a probable source of infection of air.\"" ] },{ "paper_id": "435b58b1b6b499274125be7c1b8d903fe6368959", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 7:46076 | DOI: 10.1038/srep46076", "0", "a new location or disease because of the amount of work associated with finding location specific data, tweaking parameters, and, often, reproducing code that is not freely available." ] },{ "paper_id": "435baf47b4f78fc06a8376f451993059407d2972", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One The following RT-PCR cycling conditions were used: 60uC for 5 min, 4uC for 10 min, 55uC for 45 min, 95uC for 10 min, followed by 8 cycles of 95uC for 30 seconds, 48uC for 30 seconds, and 72uC for 30 seconds, with the 48uC annealing temperature increasing 0.9uC each cycle. The PCR was then continued for 37 additional cycles of 95uC for 15 seconds, 56uC for 20 seconds, and 72uC for 20 seconds. The RT-PCR cycle ended with a final extension of 2 min at 72uC followed by a 4uC hold.", "Second, mixed viral populations in the same sample that differ only by a single mutation and is present in as low as 1-2% of the virus population can be identified, providing early insights into viral evolution as an integral component of surveillance. This information-rich result is provided with the same throughput and consumable costs as conventional, sequence-specific RT-PCR assays.", "The dynamic range for mixed RT-PCR/ESI-MS detections has previously been determined to be approximately 100:1 [20] , which allows for detection of viral variants with as low as 1% abundance in a mixed population. Figures 5C and 5D show results obtained with a clinical sample containing a mixture of viruses at the limit of detection for mixed populations. To demonstrate that these peaks truly represented mixed viral populations, the PCR amplicons were cloned and 450 independent colonies were sequenced. Nine (2%) of these 450 clones had the predicted mutations, correlating well with the measured amplitude of the low-abundance peaks.", "To measure the breadth of coverage and resolution offered by the panel of primers described in Methods (details in Table S1 ), we tested 92 well-characterized influenza virus isolates collected from human, avian, and animal species. Despite the extensive genetic diversity of this sample set, the broad-range primers generated amplicons from all isolates, and base composition signatures distinguished the isolates (Figure 1 ). Most isolates showed base compositions consistent with expected signatures for the corresponding H/N sub-types based on bioinformatic analysis of existing sequence data. Two of the isolates, however, showed previously unknown base compositions at several primer loci suggesting these might be novel influenza virus types; these are noted as ''Unknown'' in Figure 1 ." ] },{ "paper_id": "435c259a0b1c77cb1fab63dabf76fa1637d8e645", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest. " ] },{ "paper_id": "436164085d9fd52ea5d7ebed65465e0a41495c04", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The CPV genome is approximately 5.2 kb in length, and contains two open reading frames (ORF), which encode 2 nonstructural proteins (NS1 and NS2) and two structural proteins (VP1 and VP2) [4] [5] [6] .", "Canine parvovirus (CPV), genus Protoparvovirus, a member of the family Parvoviridae (subfamily Parvovirinae), is a small, highly contagious, nonenveloped, single-stranded DNA virus [1] . CPV is a major causative agent of acute gastroenteritis, leukopenia and myocarditis in dogs, and typical clinical signs include vomiting, fever, and diarrhea. Generally, puppies aged 6 weeks to 6 months have been found to be more susceptible to CPV infection [2, 3] .", "The CC 50 s and EC 50 s of drugs were determined by a best-fit Log(dose)-response curve-fitting in GraphPad Prism 7. One-way analysis of variance (ANOVA) and Dunnett's multiple comparisons test were used to analyze data. Statistical significances are denoted as follows; * p < 0.05; ** p < 0.01; *** p < 0.005; **** p < 0.001. " ] },{ "paper_id": "4363936c1edadc4d1a30103f0dba198354b16051", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting information S1 Text. Mathematical equations that parameterize the four investigated epidemiologic compartmental models. (PDF) S1 ", "Agricultural and geographic factors of the 2015 HPAI US outbreak PLOS Pathogens | https://doi.org/10." ] },{ "paper_id": "436e61a48e3f8612480cb7261040897dfa875524", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.", "Ethical statement. Euthanizing piglets was done in agreement with the European legislation on animal experiments. All experimental procedures were approved by the Local Ethical Committee of the Faculty of Veterinary Medicine, Ghent University, and all methods were carried out in accordance with the approved guidelines." ] },{ "paper_id": "43740caefa35d11ce1aa130cd8ca86b60442b046", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The inhibition of splicing due to ICP27 is naturally selective for host transcripts, as most HSV transcripts are intronless. However, recent results using 4sU labeling of nascent RNAs (reviewed more extensively in the next section, [111] ) have called into question how pervasive the effects of HSV-1 infection are on host mRNA splicing. Rutkowski et al. [111] did not detect widespread changes in splicing in cells infected with HSV-1. Nonetheless, the study did uncover that specific genes were spliced differently during HSV infection, suggesting that ICP27 has a key role in controlling alternative splicing.", "Herpesviruses are large enveloped double stranded DNA viruses that encode more than 80 genes per virus. They are classified into three subfamilies (\u03b1-, \u03b2-, and \u03b3-herpesviruses), based on differences in cell tropism. We will focus our discussion on \u03b1and \u03b3-herpesviruses because host shutoff has been extensively studied in these two subfamilies. \u03b1-Herpesviruses include the human viruses HSV-1 and -2, which cause oral and genital herpes. \u03b3-Herpesviruses include the human viruses KSHV and EBV, which cause tumors of endothelial cells (KSHV) and B cells (KSHV, EBV), and the rodent virus MHV68, often used as a pathogenesis model. Two genetic programs define herpesviral infections: latent infection and lytic replication. During lytic replication all viral genes are expressed through a highly regulated temporal cascade characterized by immediate-early, early, and late viral genes. Herpesviruses depend on cellular transcription and translation factors to efficiently express their genes and replicate. Multiple mechanisms to directly regulate host gene expression have been described in \u03b1and \u03b3-herpesviruses, with global effects on transcription, RNA stability, and RNA processing. A role for these mechanisms in both immune evasion and viral protein production has been established.", "Interestingly, evidence for conservation of the PA-X protein has been found in almost all IAV strains [172] . Stop codons in the +1 reading frame in the C-terminal region of overlap between PA and PA-X (the X-ORF reading frame) are found at two very specific locations in almost all IAV strains [172] . Additionally, the overall rate of synonimous mutations in the 0 reading frame (PA) is low, suggesting evolutionary pressure to maintain the PA-X protein sequence unchanged [172] . Maintaining two functional overlapping reading frames severely constrains the ability of the virus to mutate in this region. Therefore, if PA-X function was not actively retained one would expect to find stop codons at other locations within the X-ORF that do not cause changes to the PA amino acid sequence. This conservation suggests that PA-X-triggered RNA degradation may be a truly ubiquitous host shutoff mechanism for IAV." ] },{ "paper_id": "437a7f66e0cb7f9fdf9d6b3ff4da80939e9ac546", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MIA designed and planned the study. KJH and SDH did the collection of samples. KJH analyzed the samples. MIA and KJH interpreted the results. All authors read and approved the final manuscript. ", "Bovine respiratory syncytial virus (BRSV) is one of the main causes of severe pneumonia, interstitial edema, and emphysema in cattle [1] . BRSV is an RNA virus with a non-segmented, single-stranded, negative-sense 15.2 kb genome that belongs to the genus Pneumovirus and family Paramyxoviridae [2] . BRSV infection leads to sudden fever, rhinitis, cough, respiratory distress, abdominal breathing, and decreased appetite [3] ." ] },{ "paper_id": "437c2f5c3e920111eb679f26bde02cbb8a49ff49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza is a contagious disease that represents a serious health threat to humans and other animals worldwide. Influenza A viruses, in particular, can infect a variety of species. A global reservoir for these viruses exists in wild waterfowl and shorebirds, from which novel viruses can emerge to infect mammalian species. Influenza is therefore a potential threat to humans, pigs, horses, sea mammals, ferrets, mink as well as many terrestrial bird species [1] . In the past decades, several dramatic episodes of large-scale mortality have occurred in domestic birds, humans, and other species. To date, the main approach to control influenza epidemics and pandemics in human and other animal populations is through vaccination (reviewed in [2] ) and biosecurity, although other approaches may help prevent the transmission of highly pathogenic influenza in some species [3] .", "Average viral yields between different treatments were compared using 2-tailed Student's t-tests following checks for normality and variance homogeneity using Shapiro-Wilk and Levene tests, respectively. All tests were conducted as implemented in the R statistical program [33] .", "Viral yields in plaque forming units (p.f.u.) were titrated by plaque formation assay in Madin-Darby Canine Kidney (MDCK) cells using the Avicel method with media supplemented with trypsin [32] . The inoculum was also incubated with tryspin during the virus adsorption period.", "The simple modification described herein has the potential to improve the efficiency of the virus rescue process and expand the potential application for reverse genetic studies.", "Conclusion: The simple modification described here has the potential to improve the efficiency of the virus rescue process and expand the potential applications for reverse genetic studies." ] },{ "paper_id": "437df56a9488ff2c8be3754b2642fb688115a1b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Four additional cats were recruited from the western US. Two of them were 26-and 60-month old Burmese (388406 and 392312) from Paradise and Menlo Park, CA, respectively. The third was a 16month old Birman (388210) from San Jose, CA, and the fourth was a 2-year old Sphinx (Cat-T) from Mountlake Terrace, WA (courtesy Dr. Tracy Tomlinson). Full necropsies on all cats, except Cat-T were performed at the School of Veterinary Medicine Teaching Hospital (VMTH), University of California, Davis, CA. Cat-T was necropsied at a private veterinary diagnostic laboratory (Phoenix Central Laboratory, Everett, WA).", "Four Scottish Fold kittens were born into the same cattery in Sonoma, California; Red, Toby and Lucy were from the same litter of three, while Tux was born a week later in a litter of three to a sister queen and the same tom. Simba, an 11 year-old American curl, was born in an unrelated cattery and resided in another Sonoma household as a pet. Lucy was placed into this household with Simba when she was 17 weeks old, while Red went to live in another home with two other older cats when at 14 weeks of age. Tux and Toby remained in their home cattery with several other cats. Lucy, Tux, Red and Toby first showed signs of indicative FIP at 23, 33, 35 and 40, weeks of age, and were euthanatized with confirmed disease at 27, 37, 39 and 41 weeks of age, respectively. All other contact cats have remained healthy to this time.", "d The biotypes of the virus isolated from the feces of these cats were not determined due to an inability to amplify the 3c gene." ] },{ "paper_id": "437ea4d132e4263cc2841e01fb19da51c566d0a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2) C(t) = Ke \u2212e \u2212\u03b3 (t\u2212\u03c4 ) .", "(3)" ] },{ "paper_id": "438e817dea190348df99e09a8e519fc64101b899", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 21 available complete RNA sequences of HAV were obtained from GenBank randomly in October 2010. The serial number (SN), GenBank number, genotype and other detail information are listed in Table 5 .", "Where g ij is the observed number of the ith codon for jth amino acid which has n i type of synonymous codons. When the codon with RSCU values close to 1.0, it means that this codon is chosen equally and randomly.", "All statistical processes were carried out by with statistical software SPSS 11.5 for windows." ] },{ "paper_id": "43918c75d7b7d3f9402b1342dfea1e19eb2bd909", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The means, standard deviations, and statistics for the quantifiable data were calculated using Microsoft Office Excel 2003 (Microsoft, Redmond, WA, USA), SigmaPlot 10 (Systat Software, San Jose, CA, USA), and SPSS Statistics for Windows, Version 19.0 (IBM, Armonk, NY, USA). Significance of the data was examined using one-way ANOVA followed by the post hoc Bonferroni-corrected test. The probability of type 1 error \u03b1 = 0.05 was recognized to be the threshold of statistical significance.", "A serum-free and antibiotic-free cell culture medium (Dulbecco's modified Eagle's medium) was used in this analysis.", "Anthrax is a life-threatening infectious disease that spreads through contact with spores of the Gram-positive bacterium Bacillus anthracis through skin contact (generally with infected animal products), inhalation, or ingestion [1] . Approximately 2000 to 20,000 cases occur worldwide annually [2] , mostly in Africa and central and south Asia [3] . Anthrax spores have been developed as a biological weapon by several countries [4] [5] [6] . The 2001 US anthrax letter attacks further evidenced an emerging terrorist threat, leading to renewed attention to the importance of prophylaxis, prevention, and handling procedures for anthrax [7] . Agents commonly cited to inactivate anthrax spores include formaldehyde, hypochlorite solutions, chlorine dioxide, and radiation [8] . However, most of these agents are harmful to humans, limiting their use in public environments. Therefore, a safer disinfection technique that can exert a sustainable antimicrobial effect in human living environments is highly desirable." ] },{ "paper_id": "4393d1b0e0262247c9c6ace6ebda9dcd5395d6fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest.", "Author Contributions: C.-F.K.: investigation, methodology, data curation, writing-original draft preparation, formal analysis; H.-W.C.: project administration, conceptualization, methodology, resources, supervision, writing-review and editing, and approved the manuscript. All authors have read and agreed to the published version of the manuscript. " ] },{ "paper_id": "4395141eef1089f1c75a14912fade412fd694c19", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "son for the abnormal behaviour in SDS-PAGE remained unknown.", "To monitor viral replication, the viral polymerase gene was amplified using RT PCR [6] . Fluorescence signals were read by LightCycler \u00ae (Roche).", "Negative staining of purified viral particles was carried out as described elsewhere [22, 49] .", "Coronaviruses have a broad range of vertebrate hosts and usually cause mild respiratory diseases in humans and animals [1] [2] [3] . In March 2003 the world health organization issued a global alert about a severe partially fatal respiratory disease named severe acute respiratory syndrome (SARS). SARS originated in Southeast China, affected thousands and spread to many countries worldwide via international travel. Drastic quarantine measures and tight travel restrictions finally contained the SARS outbreak [4, 5] . In parallel, the etiologic agent of the outbreak was identified with unprecedented speed and turned out to be a novel coronavirus with several distinguishing features to known coronaviruses [6] [7] [8] . The SARS outbreak showed drastically that coronaviruses can develop into highly pathogenic agents with the potential to threaten public health and global economy severely [9, 10] ." ] },{ "paper_id": "439ddbbdb17f5ab18ac2e208e7df5c09a8dc9789", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thirdly, an unknown or unexpected virus might be causing diarrhoea.", "To isolate Salmonella and Shigella species, fresh stool specimens (within 4 hours after specimen collection) were plated on cystine lactose electrolyte-deficient medium (Brocalin agar; Merck, Darmstadt, Germany), Salmonella-Shigella agar (Merck), Hektoen enteric agar (Difco, Detroit), Rappaport medium (Difco), MacConkey agar (Becton Dickinson, Cock-eysville, MD) and gram-negative broth (Hajna; Difco) as enrichment. A selective cefsulodin-irgasan-novobiocin medium (Oxoid, Basingstoke, Hampshire, England) and a glucose broth enrichment medium were used to isolate Yersinia species. Isolates were further characterized by using conventional bacteriologic methods, as outlined [35] . A cell-culture assay was used to detect Clostridium difficile toxin [36] . The Campylobacter-selective medium (modified Butzler medium) consisted of a solid 7% hemolyzed sheep blood-based agar (nutrient broth no.", "2) with cefoperazone (30 mg/L), rifampin (10 mg/L) and seroamphotericin B (2 mg/L) [29] ." ] },{ "paper_id": "43b6759b989971eb0410fd45e7f97750183ed1bf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HIV could have evolved maintaining a similar sequence but different structures, as previously reported in literature (Rizvi and Panganiban, 1993) .", "The code is publicly available under an open source license compliant with Open Source Initiative at https://github.com/ armaos/algorithm-crossalign. The source code is deposited in a DOI-assigning repository https://doi.org/10.5281/zenodo. 1168294.", "GT designed the work, RD implemented the approach with SM. AA and RD developed the server. GT, RD and SM wrote the paper. All authors reviewed the manuscript." ] },{ "paper_id": "43c284998733a1d7cc474d14c378f08e4b509c63", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Phylogenetic analysis shows that CHIKV has three genotype variants; West African, East/Central/ South African (ECSA) and Asian 8 . Malaysia had its first outbreak in late 1998 at the suburb Klang in the state of Selangor and the CHIKV was identified as Asian genotype. Localized outbreaks and clustered cases were reported in Larut Matang, Lama, Perak. The ECSA genotype virus caused outbreaks after 2006. In early 2008, together with the neighboring Singapore, the epidemic in Johor began. This spread throughout states in Peninsular Malaysia and in 2009, many cases occurred in Selangor, Melaka, Negeri Sembilan and Pahang states and peaked in Kelantan, Kedah, Terengganu, Perlis and Sarawak 4, 9, 10 . From April 2008 until March 2010, over 10,000 cases were reported in these nationwide outbreaks, although there were no fatalities 11 .", "Flavonoids. Silymarin, quercetin and kaempferol were purchased from Sigma-Aldrich Corporation (Sigma-Aldrich, St. Louis, MO, USA) and stored in \u2212 20 \u00b0C for future use. Stock solution was diluted with EMEM and was filtered through a syringe filter with 0.2 \u03bc m pore size (Millipore, MA, USA) at the time of use; DMSO concentration in working solutions prepared on EMEM was kept at 0.1%.", "Silymarin inhibits early post-entry stages of CHIKV replication. From analyzed compounds only silymarin was able to suppress CHIKV mediated cytotoxicity. Therefore it was chosen for a time-of-addition assay performed with aim to determine which stage of virus infection cycle this compound affected.", "Silymarin, extracted from milk thistle (Silybum marianum), was shown to inhibit hepatitis C virus (HCV) in both in vitro and in vivo by inhibiting HCV entry, RNA synthesis, viral protein expression and infectious virus production; in addition it also acts by blocking of the virus cell-to-cell spread 18 . It becomes our concern to explain the definition for the nomenclature of 'milk thistle extract' , 'silymarin' and 'silibinin' since the findings that will be discussed further involve these three important terms. In brief, the initial extract of the crushed milk thistle seeds made up of 65-80% silymarin and 20-35% fatty acids, such as linoleic acid. Silymarin itself, is a complex of more than 7 flavonolignans (silybin A, silybin B, isosilybin A, isosilybin B, silychristin, isosilychristin and silydianin) and 1 flavonoid whereas silibinin is a semi-purified, commercially available fraction of silymarin, with an approximate 1:1 mixture of 2 diastereoisomeric compounds, silybin A and silybin B which are also referred to in the literature as silibinin A and B 19 ." ] },{ "paper_id": "43c296a219a62ac9f9a632490034b6fdfc7b871e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sweat test was performed according to Clinical and Laboratory Standards Institute guidelines [19] . For sweat stimulation and collection, the Macroduct\u00ae system (Wescor, Data are shown as ratios or the mean \u00b1 standard deviation incl. median (minmax). *p <0.001 (CF-all versus controls); **p = 0.003 (CF-PI versus CF-PS).", "We performed NPD and ICM measurement in CFpatients and healthy controls to determine (1) the ability of these measurements to differentiate CF patients from healthy controls, and (2) the influence of smoking on CFTR function in healthy controls.", "Smoking causes a decreased NPD response [17] , but although a decreased systemic CFTR function mediated by acrolein [18] . Raju et al. demonstrated a 65% decrease in the ICM CFTR response in healthy smokers compared with non-smokers [18] . Our results confirm these findings. In contrast to NPD, smoking did not influence the diagnostic cut-off for ICM in our cohort. Therefore, ICM seems to be a more robust diagnostic test than NPD to distinguish primary from secondary CFTR dysfunction. This is important for the interpretation of NPD as an adjunctive diagnostic test in patients with query-CF who are exposed to smoking." ] },{ "paper_id": "43c75c8c6a1fcb74ac151516e0cdd2a3a953d690", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virology laboratory. Virology work was performed in a biosafety level 2 enhanced laboratory at the UF.", "TEXT S1, DOCX file, 0.02 MB. ", "Supplemental material for this article may be found at https://doi.org/10.1128/ mSphere.00251-17." ] },{ "paper_id": "43d4ca7da86537799185698ae3463b736bc56fc1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tests of significance were performed using Duncan's multiple-range test after one-way ANOVA by SPSS 17.0 statistics software. Data were presented as means \u00b1 SD. A P-value less than 0.05 was considered statistically significant. ", "PCV2 capsid protein (Cap) was analyzed by western blot assay. The PK-15 cells were harvested, and the protein was separated on 12% SDS-PAGE gels and transferred onto nitrocellulose membranes. Non-specific binding was blocked with 1% BSA. The membrane was probed with monoclonal antibodies (mAbs) against the Cap or mouse anti-\u03b2-actin monoclonal (BIOSS, Beijing, China). The membrane was probed with a goat anti-mouse IgG antibody conjugated to horseradish peroxidase (HRP) (BIOSS, Beijing, China). Protein was detected using enhanced chemiluminescence (ECL) reagents (Vazyme, Nanjing, China).", "NO production was assessed by a colorimetric assay using the Griess reaction [29] . Briefly, at various time points during cell culture, the supernatants (100 \u03bcl/well) were harvested, and incubated with an equal volume of Griess solution (1% sulfanilamide, and 0.1% naphthyl ethylene diamine dihydrochloride in 5% phosphoric acid) (Sigma, USA) for 10 min at room temperature. The absorbance was read at 540 nm, and the concentrations of NO were determined from a least squares linear regression analysis of a standard curve for sodium nitrite." ] },{ "paper_id": "43d98a92044a0de6683fc54fb2b5694a828856d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were lysed in PBS containing 0.5% NP40, 140 mM NaCl, 30 mM Tris-HCl (pH 7.4), and an EDTA-free protease inhibitor cocktail (04693159001; Sigma Aldrich, MO, USA) for 30 min on ice before clarifying by centrifugation and retaining the supernatant. Cell lysates were resolved by SDS-PAGE and proteins were detected using antibodies as described above. Images were collected using a C-Digit digital scanner and Image Studio Digits software (Version 4; LiCor, NE, USA). When appropriate, immunoblots were incubated in stripping buffer (200 mM glycine, 3.5 mM SDS, 1% Tween 20, (pH 2.2)) and reprobed. Densitometry analysis was performed by measuring the intensity of each band using Image Studio Digits software. Relative density = normalized density target protein/normalized density loading control.", "Reoviruses, Type 1 Lang (T1L) and Type 3 Dearing (T3D), laboratory stocks originated from the T1/human/Ohio/Lang/1952 and T3/human/Ohio/Dearing/1955 isolates respectively and represent clonal isolates from the M.L. Nibert laboratory (Harvard Medical School) [23, 24] . The prototype reovirus serotype 3 strain Abney (T3A) was a kind gift from Dr. Barbary Sherry (North Carolina State University). Each virus was twice plaque-purified and passed two or three times on L929 cell monolayers before being subjected to three freeze-thaw cycles. Working L929 cell lysate virus stocks were titered on L cells, or by immunofluorescence staining for \u00b5NS as noted in the text, before use in experiments.", "The four cellular kinases known to phosphorylate eIF2\u03b1 are heme-regulated eIF2\u03b1 kinase (HRI), general control non-depressible 2 (GCN2), double-stranded RNA-dependent protein kinase (PKR), and PKR-like ER kinase (PERK) [4] . Both cell intrinsic and extrinsic stresses can activate these kinases: (i) HRI-heme-deprivation and oxidative stress; (ii) GCN2-amino acid starvation;", ". The ISR facilitates cellular survival and a return to homeostasis, or initiates cell death signaling under conditions of severe stress or when the initiating stressor is maintained [4] . Four distinct stress kinases can be activated in response to stress. Although these kinases may have a number of substrates, they all phosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2\u03b1) at serine position 51. When eIF2\u03b1 is phosphorylated, the GTP-exchange factor, eIF2B is unable to exchange GDP for GTP on eIF2. As a consequence eIF2B becomes sequestered and its effective levels drop, preventing efficient formation of the eIF2.GTP.Met-tRNAi ternary complex and thus inhibiting translation initiation [4] ." ] },{ "paper_id": "43e0f5f9add9380a45d39f55aab2ca96d589280c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The clinical manifestations of leishmaniasis can range from subclinical (inapparent), or a self-resolving cutaneous ulcer to a disseminated infection (cutaneous, mucosal, or visceral) and even to a lethal systemic illness [6] [7] [8] [9] [10] . Leishmania infects some of the poorest people in the world, and is linked to population displacement, malnutrition lack of financial resources, and poor housing [5] . Leishmaniasis is a public health problem and it is endemic in many parts of the tropics, subtropics and the Mediterranean [11, 12] . Middle Eastern countries including Arab world's countries are currently considered to be at risk from leishmaniasis because these countries are endemic for visceral and cutaneous leishmaniasis, and a huge deal of human migration from neighbouring countries is observed [13] [14] [15] [16] [17] .", "Similar to other studies [19, 33, [35] [36] [37] , some limitations of this bibliometric study should be addressed. Although Scopus is one of the most largest global database [84] , it might contain most publications in the field of leishmaniasis research. The main limitation relays to the citation and publications count applied for journals indexed by the Scopus. The citation and publication counts in these journals do not include citations and publications published in non-Scopus-indexed journals.", "The Statistical Package for Social Sciences (SPSS) software version 16 was applied for analysis, while graphical research output was also conducted in Microsoft Excel. Pearson correlation coefficient was used to analyze trends in publication between publication productivity related to leishmaniasis at global level and productivity related to leishmaniasis from Arab world." ] },{ "paper_id": "43ea5663d460f9bc3ec53ceea11e85b6265a1fef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Several cell surface molecules of the target cells have been identified to interact with HCV, including CD81, the LDL receptor, highly sulfated heparan sulfate (HS), SR-BI, and claudin-1 (CLDN1), occludin (OCLN).", "These factors include the viral envelope glycoproteins E1 and E2, CD81, scavenger receptor B1, and tight junction proteins claudin-1 and occluding. A clear understanding of the detailed mechanisms of HCV entry may shed light in the ways to prevent the liver graft from HCV recurrence.", "The current therapy against HCV infection, consisting of a combination of pegylated interferon (IFN) and ribavirin (RBV), is limited by resistance, adverse effects, and high costs. The absence of preventive regiment is a major limitation for patients undergoing LT for HCV-related liver failure. Moreover, accelerated progression to liver cirrhosis after graft reinfection and limited efficacy of IFN-based therapies for recurrent HCV are two major clinical issues leading to poor posttransplant outcome of the HCV recipients [80] . Thus, novel preventive and therapeutic antivirals are urgently needed. Viral entry is required for initiation, spread, and maintenance of infection. HCV entry is a multistep process orchestrated by a number of viral and host cell factors." ] },{ "paper_id": "43eaa4d7209e389a360aeab2b3b44e76fd89f5c2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations MOI: multiplicity of infection; CPE: cytopathic effect; PFU: Plaque forming unit; MEM: minimal essential medium; FBS: fetal bovine serum; RT-PCR: reverse transcription -polymerase chain reaction.", "For each assay, a standard curve for RTS11 and for CHSE-214 samples was generated by using 10-fold serial dilutions of pooled cDNA, generated from a mix of infected and control samples. Linear correlation coefficient (R 2 ) varying from 0.9910 to 0.9998 and efficiencies between 87% and 96% showed that these assays were suitable for quantitative purposes (see Additional file 1).", "The table contains information about primer sequences, product sizes, annealing temperatures (Ta), reaction efficiencies (E), Pearson's coefficients of determination (R 2 ) and melting temperatures of the amplicon (Tm) for each candidate reference gene in each cell line." ] },{ "paper_id": "43f0ed0ead4058d6f92c7390c15d0d9fe66af448", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These studies clearly demonstrate the existence of an avian reservoir of remarkably diverse bornaviruses and provide a compelling candidate in the search for an etiologic agent of PDD.", "Microarray analysis of specimens was carried out as previously described [18] . Briefly, 50-200 ng of DNAse-treated total RNA from each sample was amplified and labelled using a random-primed amplification protocol and hybridized to the Virochip. Microarrays (NCBI GEO platform GPL3429) were scanned with an Axon 4000B scanner (Axon Instruments). Virochip results were analyzed using E-Predict [28] and vTaxi (K. Fischer et al., in preparation)." ] },{ "paper_id": "43f0fd3b0c765c0dc92a49d8ac4a50a75a0135b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequencing STING from other primate species", "The following figure supplement is available for figure 3: in good agreement with what is known about the preferences of NS2B3, where glycine (G) often lies directly downstream of the peptide cleavage site, and an arginine (R) directly upstream (Li et al., 2005a) .", "Immunofluorescence 24 hr after plating, cells were fixed with 4% paraformaldehyde and permeabilized with 1% Tri-tonX100 in PBS. Blocking was performed with 3% BSA solution in PBS. Primary antibodies used were rabbit-anti-GRP78 (BiP) (Abcam ab21685) and mouse-anti-HA (clone 16B12 abcam ab130275). Secondary antibodies used were donkey-anti-rabbit conjugated to AlexaFluor594 (Invitrogen A21207) and donkey-anti-mouse conjugated to AlexaFluor488 (Invitrogen A21202). Cells were mounted using VECTASHIELD hardset mounting media (VectorLabs H-1400).", "To explore this idea, Stabell et al. looked at a protein called STING in humans and in three different primates: the chimpanzee, the rhesus macaque, and the common marmoset. STING plays an important role in the immune system and helps to fight infections caused by viruses and other microbes." ] },{ "paper_id": "43f3b3e2af86af484ab7aae55ad9b2354e4a14eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "e authors declare that there are no conflicts of interest with respect to the research, authorship, and publication of this article.", "e tools used in this study make reference to the above-mentioned literature.", "is study used a cross-sectional survey with convenience sampling, and behavioural observations were conducted from January to March in 2018. Before conducting this study, ethical approval was obtained from the research ethics committee of a local higher-education institute in Hong Kong. e ethical committee reference number is NUR/SRC/20171220/016." ] },{ "paper_id": "43fd9e9fa6ecb2ec700c15288e7e3c7ba38f26a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dogs with mild or moderate CanL produce IFN-\u03b3 and the lack of production is restricted to severe disease [10, 28] . Prospective clinical studies with cats with confirmed clinical leishmaniosis are needed to further evaluate if IFN-\u03b3 is as possible marker for staging the severity of disease and evaluating efficacy of therapy as documented in dogs [10, 28] .", "Leishmaniosis is a vector-borne disease of humans and animals caused in Europe by Leishmania infantum and transmitted by female sand flies of the genus Phlebotomus [1] [2] [3] . Dogs are considered the main reservoir of L. infantum but there is clear evidence that some wild and synanthropic mammals and domestic cats are able to infect sand flies and they play a variable role in a reservoir system according to local and ecological peculiarities [3] [4] [5] ." ] },{ "paper_id": "44001ef9803c7765b699fd7a95eb1edac878c840", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "length of stay, better antimicrobial stewardship, and better patient cohorting to prevent nosocomial infections (3, (5) (6) (7) (8) .", "Supplemental material for this article may be found at https://doi.org/10.1128/JCM .01945-17.", "SUPPLEMENTAL FILE 1, PDF file, 0.1 MB." ] },{ "paper_id": "4409a3d523a0e35a95671bb6d947c39763bd0bb0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NoD is currently the only predictor capable of providing and visualizing NoLS predictions for protein sequences.", "Cross-species testing shows NoD to perform best for mammalian and mammalian-infecting viral proteins but preliminary results suggest sequences from molluscs, amoebae, plants and their viruses are also wellpredicted.", "Additional file 1: NoD command line manual. The additional file describes the usage of the NoD batch predictor command line utility." ] },{ "paper_id": "440cc2be974b6cafe5ba948e02adbd679e1614a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "441421494c2a4ed45a8d6b711842ed8ee43ec038", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where is computed only once during the iterations. Moreover, Demons algorithm assumes that the displacement vector is reasonably small or local. In some cases, such an assumption might be violated, which can be mitigated through a multi-scale approach that reduces the magnitude of these ", "Image registration involves spatial alignment of images through transformations and can be formulated as a spatial transformation that defines correspondence between two images. Depending on the application, a registration algorithm can be decomposed into three components: a similarity metric [11] , a transformation model [12] [13] [14] , and an optimization method [14] [15] [16] .", "where" ] },{ "paper_id": "441656e0f7eea90edc2e3cb7e72d362b55e97ce3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sandfly fever Sicilian virus (SFSV) and SFNV were isolated from foreign soldiers stationed in Italy during 1943 and 1944. In spite of a full recovery after the so-called 'three-day' or 'Pappataci fever', the febrile illness provoked by SFSV and SFNV can be incapacitating due to headaches, myalgia, and general malaise [22] . The strongly neurotropic Toscana virus (TOSV) was also isolated in Italy first. It is the predominant cause of meningitis or meningoencephalitis during the summer season in countries" ] },{ "paper_id": "442464f84846ea95f2e99df37e18a512ea513ce2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4424d28032612c98a50bf8654f61badc6cd22c55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "which is equivalent to equation (7). We can use equation (7) as a likelihood function to obtain the maximum likelihood estimate of p t :", "An adjustment of the estimator b t by a factor of underestimation is achieved by rearranging equation (4):" ] },{ "paper_id": "442c4cc45848e962be501bd21f5484df9d547ce1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analyses were conducted using SPSS software.", "Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 SCiEntiFiC REPORTS | 7: 10658 |" ] },{ "paper_id": "4439e815dce011452a7edf3a68f737f1dc40fae1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dulbecco's Modified Eagle's Medium (DMEM), fetal bovine serum (FBS), penicillin and streptomycin, phosphate-buffered saline (PBS, pH 7.4 ) and other tissue culture reagents were purchased from Gibco (Thermo Fisher Scientific, UK). LPS, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) and Griess reagent were purchased from Promega, and all other chemicals were purchased from Sigma-Aldrich (UK). ", "deposited formazon. The optical density (OD) of each well was measured at 490 nm with a microplate reader (Dynex Technologies).", "Atmospheric solids analysis probe mass spectroscopy (ASAP-MS) experiments were performed on a Micromass ZMD mass spectrometer. Mass analysis was performed in positive ionization mode. Settings are the following: source temperature 400\u00b0C, sampling cone 14 V, corona 3.94 kV. UV-visible spectroscopy was carried out on a PerkinElmer Lambda 35 UV/visible spectrometer or an Agilent Cary 60 UV-visible spectrophotometer. Quartz cells with two polished sides were used." ] },{ "paper_id": "443aa07a6f57cab4c25fcdb0add50527028d6769", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Generally, DNA plasmids are delivered using a number of physical approaches including tattooing, Gene gun, Ultrasound, Laser and DNA electroporation [104] . Here we will particularly focus our attention on DNA electroporation.", "Several devices are available for in vivo DNA-EP. The most advanced technologies are those being developed by Inovio Pharmaceuticals [111] [113] .", "The authors declare that no conflict of interest." ] },{ "paper_id": "4465b8957219de75fb5b7f7ed57069405572cf00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Interviews and focus group discussions were digitally recorded and transcribed verbatim. Data were analysed using a thematic approach [29] to provide a flexible approach to identify, analyse and report themes or patterns within the data. Initially, two researchers (RB and BB) read three transcripts independently to generate initial codes and themes, which were then compared and refined until consensus was reached. A further three transcripts were coded using the schemata and this process was repeated, three transcripts at a time, to incorporate emerging themes, until all transcripts were coded. Data were managed using NVivo10. Study approval was obtained from Monash University Human Research Ethics Committee (CF14/1384-2,014,000,648).", "\"\u2026 every time I examine the patient\u2026\" GP11", "\"Not everyone, not if there's no skin contact\u2026\"GP12" ] },{ "paper_id": "44676dd185a852b134c04a333d31b7e081f419f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ubc9 [8, 9, 21, [24] [25] [26] . However, more recently it has become clear that there are SUMO-specific E3 ligases, and several types have been identified, including members of the PIAS protein family (Protein Inhibitors of Activated Stat) [27] [28] [29] ; RanBP2, a nuclear pore protein [30] ; the polycomb protein, Pc2 [31] ; TOPORS, topoisomerase I binding protein [32] , and members of the TRIM family [33] . Additional SUMO ligases are likely to be discovered and they undoubtedly will have important roles in regulating the functional biology of SUMO targets.", "There are two known examples of viral proteins targeting SUMO ligases, the human papillomavirus (HPV) E6 protein [86] and the Ebola virus VP35 protein [87] . The HPV E6 binds the PIASy SUMO ligase to inhibit sumoylation of PIASy substrates [86] . E6 did not induce degradation of PIASy so the inhibition of activity appears to be a direct result of binding. This binding and inhibitory activity was restricted to the high risk HPV 16 E6 protein and was absent in the low risk HPV11 E6 protein.", "Interestingly, the ability of E6 to overcome PIASy induced senescence was not dependent upon p53 so must be operating through other PIASy targets, such as pRB. The ability of the 16E6 protein to inhibit sumoylation-promoted induction of senescence through the pRB pathway would clearly be of value for viral infection and possibly transformation." ] },{ "paper_id": "446c633eb33c9168e597b53b0c93ead24aa9d43c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/JVI .00505-19.", "(Portions of this research were carried out as part of honors undergraduate thesis research by J. H. Girsch at the University of Iowa.)", "SUPPLEMENTAL FILE 1, PDF file, 0.6 MB." ] },{ "paper_id": "446f9b4e60a351d21b23f54b58628013aa8697d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethical approval. The study was approved by the ethical review committee of the School of Public Health at Fudan University, Shanghai, China (Ref: 2018-01-0659S). All methods were performed in accordance with relevant guidelines and regulations. Informed consent was obtained from all subjects (from a parent/guardian if participant was below 18 years of age)." ] },{ "paper_id": "44729b69ab4b60fc3e863c655d1dcc0bd02db6de", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Glycyrrhizin is 50 times sweeter than sucrose. It retains, when sapid, a singular liquorice flavour. The liquorice sweetness has a slower onset than sugar and lingers. Unlike artificial sweeteners like aspartame, saccharine, and cyclamates, it contains no sulfur molecule [3] , and retains its sweetness when heated [2] . On hydrolysis glycyrrhizin yields 2 mols of glucuronic acid and 1 of glycyrrhetenic acid, a pentacyclic, tri-terpene which structure partially resembles that common to steroids, with a moiety attached.", "Ingredient. The active chemical ingredients imparting the unique liquorice taste are glycyrrhizic acid and its glucoside, glycyrrhizin (C 42 H 62 O 16 ). These molecules are regarded as nearly synonymous, are powerful organoleptic flavorants, and impart characteristic liquorice taste and aroma to mixtures in small concentrations [2] .", "Liquorice concentrate-flavour is popular in alcoholic drinks too like Absinthe (thujole containing) and Pernod in France, Anise in Europe, and Ouzo in Greece. " ] },{ "paper_id": "447da2087b2d876e228b40eb8a29446bfd585499", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chi-square test was used to compare categorical data, Mann-Whitney U-tests for continuous data because of skewed distributions. Statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) version 19. This study is registered at clinicaltrials.gov (NCT01441466).", "None.", "None declared." ] },{ "paper_id": "4481ddf0d81e186b0be8ab48c20e8b206ec2879c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed using Prism 5 (GraphPad Software, Inc., CA, USA) and p values less than 0.05 were considered significant." ] },{ "paper_id": "4485f96496a208b7e77c9f53a8feb468483776db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "448c6dce11a897a8baa0815f46a77307b16049db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After both random amplification and dendrimer labeling [22, 23] were completed, the arrays were visualized with an Agilent slide scanner. SPSS version 16 http:// www.spss.com was used for statistical analysis and data plotting. ", "Additional File 1 Hybridization summary. Summary of viral and control hybridizations, corresponding GEO accession numbers and location of data presented in manuscript." ] },{ "paper_id": "4491bb88635bf0a02fd1e0475f98dcb23d9b5a2b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "449a30a14d55d5eb735468fac84e2dca5bcf75e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All diagnostic testing was conducted using protocols developed and validated by the South Dakota State University Animal Disease Research and Diagnostic Laboratory. ", "A " ] },{ "paper_id": "44a5bfa3f7ab0f7df199e81440995ab24b8e1c58", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The datasets generated for this study are available on request to the corresponding author.", "The studies involving human participants were reviewed and approved by Scientific Ethics Committee, Universidad Aut\u00f3noma de Chile. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin." ] },{ "paper_id": "44ab6aecdacb870226ce4ce36606e227f0a6ac00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Marburg virus (MARV) and Ebola virus, the two genera in the family Filoviridae, cause fulminant hemorrhagic disease in humans and nonhuman primates, resulting in high mortality rates [1, 2, 3] . Outbreaks of MARV disease in sub-Saharan Africa underline the emerging potential of this virus, which is classified as a highest-priority bioterrorism agent by the Centre for Disease Control [4, 5, 6, 7, 8] .", "The above characterisation indicates that production of fully infectious, filamentous virus is highest at 1-2 days p.i., when the cells still have intact membrane profiles. This was therefore selected as an appropriate time point for studying assembly and budding of filamentous particles.", "The filoviruses are members of the order Mononegavirales and contain a single-stranded negative-sense RNA genome, which is encapsidated by the nucleoprotein (NP). The MARV genome encodes seven structural proteins [9, 10] : the polymerase (L), VP35 and VP30 associate with NP to generate the helical nucleocapsid (NC) [11, 12, 13] . The viral glycoprotein (GP), which is inserted in the viral envelope, mediates cell entry [14, 15] . The major matrix protein VP40 plays a key role in virus assembly, and VP24, the second matrix protein, is suggested to support the template function of the NC [12, 16, 17, 18] ." ] },{ "paper_id": "44b6af6bcf205a0a6c91aee80d9b67e0f4e226ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The complete genome sequences of the BCoV isolates 4-17-03, 4-17-25, 4-17-08, and 7-16-23 have been deposited in GenBank under the accession numbers MH043952 to MH043955.", "We report four full-genome sequences of bovine coronavirus (BCoV) isolates from dairy calves in Pennsylvania obtained in 2016 and 2017. BCoV is a pathogen of great importance to cattle health, and this is the first report of fullgenome sequences of BCoV from PA cattle.", "B ovine coronavirus (BCoV), a member of the Betacoronavirus genus of the Coronaviridae family, is an enveloped virus with an approximately 31-kb single-stranded positive-sense RNA genome. Infection of cattle with bovine coronavirus is a major contributor to diarrhea in calves, is involved in the etiology of winter dysentery in adult cattle, and serves as a contributing pathogen in bovine respiratory disease complex (1, 2) ." ] },{ "paper_id": "44c4f131824378c773a3b2e006bed411214feec7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pathology. At the 14 months' time point, euthanasia was administered by CO 2 inhalation and blood collection by and exsanguination cardiocentesis, followed by a thoracotomy.", "Hematology examination (CBC) included red blood cell (RBC) count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell (WBC) count, differential blood cell count, and blood smear. Serum chemistry tests included glucose, urea nitrogen, creatinine, total protein, albumin, globulin (as calculation), total cholesterol, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, calcium, sodium, potassium, chloride, and phosphate.", "Michael Guarnieri owns a significant financial interest in Animalgesic Labs." ] },{ "paper_id": "44cbdded77107e8c97330deef77b1b761a9bb229", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Here, lncRNAs show repeated involvement in the interplay between virus and host and emphasize that these pathways deserve further investigation to clarify their exact contribution." ] },{ "paper_id": "44d9ad484dc917e82daa41c802c2157d3f20dda4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mice C57BL/6 mice (6-8 weeks old) were purchased from the National Cancer Institute (Frederick, MD). All animals were maintained under specific pathogen-free conditions at the Johns Hopkins Hospital (Baltimore, MD). All procedures were performed according to the Johns Hopkins Institutional Care and Use Committee approved protocols and in accordance with recommendations for the proper care of laboratory animals." ] },{ "paper_id": "44dd2bffc40a5e211d8a9c2b080b93570671d703", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "44e1e81a18b18799c1ab86e439050fff057897d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A national integrated emergency response system has also been developed and promoted. China's National Committee for Disaster Reduction (NCDR) was established in 2005 as the state inter-agency coordination body. It comprises 34 ministries and departments, as well as military agencies and social groups (10). The integrated system seeks to ensure the effective management of resources and rescue personnel from different facilities throughout China (16) .", "Two factors underpin this inadequacy. First, psychological problems have become common especially during natural disasters and infectious disease outbreaks and these affect both the victims and the rescuers (43). However, psychological problems have not received the same emphasis that physical illnesses and injuries receive.", "Several supporting systems were found to be wanting in terms of aiding the delivery of disaster relief emergency services, namely: the fragmentation of emergency health service systems, the lack of specific emergency legislation, the disparities in funding distribution, and inadequate cost-effective considerations. These systems are discussed below." ] },{ "paper_id": "44eb5c174b0fe94bde674772bebd4312af33b355", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The findings achieved herein are solely the responsibility of the authors.", "The data used to support the findings of this study are available from the corresponding author upon request.", "MERS-CoV-specific antibodies are widely found in dromedary camels (Camelus dromedarius) along with viral shedding of similar viruses detected in human. Accordingly, dromedaries are considered the primary source of MERS-CoV transmission to humans, although the original source for the virus is still unknown [2] [3] [4] ." ] },{ "paper_id": "44f34175ad29353c40276c6d19ee257e7511c8ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The differences in the level of antibodies between different groups were determined by One-way repeated measurement ANOVA and Least significance difference (LSD). Differences were considered statistically significant when p < 0.05. ", "Molecular graphics and analyses were performed with the UCSF Chimera package. Chimera is developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIGMS P41-GM103311).", "BHK21 cells infected with EMCV NJ08 strain in 96-well culture plate were rinsed with PBS and fixed with cold ethanol for 45 min at 4\u00b0C. The cells were washed, and " ] },{ "paper_id": "44f3796bf7bdaa361b977d350bc71190b31cf558", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These findings indicate that several predictive methods and experimental data should be combined when selecting candidates for the generation of protective immune responses.", "In order to estimate the generalization error, bootstrap validation was employed. Error estimates were acquired from out-of-bag validation -i.e. using those residues that are not part of the bootstrap sample as validation data. 50 replicates were calculated for the validation of each investigated model. ", "The BCIPEP data set is highly redundant with plenty of entries showing relation to more than one source protein." ] },{ "paper_id": "44f82307e441f32a4ddd4ea51a8f823c593e2151", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA isolated from BMDMs (RNAiso plus, TAKARA) was reversetranscribed using PrimeScript II 1st Strand cDNA Synthesis Kit (TAKARA). Real-time PCR was performed using SYBR Premix Ex Taq II (TAKARA) and the ABI 7500 real-time PCR system (Applied Biosystems). The following primers were used: TNF-forward 5 -CCCTCACACTCAGATCATCTT-CT-3 and reverse 5 -GCTACGACGTGGGCTACAG-3 ; IL-12p40 forward 5 -CCCATTCCTACTTCTCCCTCAA-3 and reverse 5 -CCTCCTCTGTCTCCTTCATCTT-3 ; IL-6 for- ", "Results are presented as mean \u00b1 SD of three independent experiments. Statistical analyses were performed using two-tailed Student's -test. Values of < 0.05 were considered significant.", "Nitrite accumulation in culture supernatant was measured by the Griess method [27] . Cell-free culture supernatants were mixed with 100 L of 1% sulfanilamide, 0.1% N-(1-naphthyl-) ethyl-enediamine dihydrochloride, and 2.5% phosphoric acid. The absorbency was read within 5 min at 550 nm and actual concentration calculated using a standard curve with serial dilutions of sodium nitrite." ] },{ "paper_id": "44f9f629bf4db860b1cbb1cce7f925d0f7d29b30", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results are reported as mean 6 s.e.m. The comparison of different groups was performed by two-tailed Student's t-test or one-way ANOVA with the Tukey post test for experiments with more than two groups. Differences were considered statistically significant at P,0.05.", "Cell proliferation was determined using an anti-Ki67 antibodyproliferation marker (Abcam), and cell death was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine tri-phosphate nick end-labeling (TUNEL) analysis using in situ Apoptosis Detection Kit (TaKaRa), according to the manufacturer's instructions. The sections were then viewed under 40X magnification, and the number of proliferative cells per palate was counted.", "Our fetal global gene discovery study on palatal fusion using microdissection and microarray analysis is the first of its kind. To the extent that epithelial adhesion is critical to palate formation, identification of new genes and pathways involved in this process will help efforts toward the development of novel strategies to protect and enhance palate fusion and improve treatments for cleft palate. " ] },{ "paper_id": "4501afb17c42f81f10cefa7c72ef331c15f61fb9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "siSTING -1:59-rGrGrCrArUrGrGrUrCrArUrArUrUrArCrAr-UrCrGrGrArUAT-39.", "siSTING-2:59-rArCrCrUrGrUrGrArArArUrGrGrGrArUrCr-ArUrArArUrCAC-39.", "siSTING-3:59-rGrGrArUrUrCrGrArArCrUrUrArCrArArUr-CrArGrCrArUTA-39.", "The University of Miami has an Animal Welfare Assurance on file with the Office of Laboratory Animal Welfare (OLAW), National Institutes of Health. The assurance number is #A-3224-01, effective July 11, 2007 . Additionally, as of July 20, 2010, the Council on Accreditation of the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC International) has continued the University of Miami's full accreditation." ] },{ "paper_id": "4509a768ab8962812dbdf4c610b6d741f84c8318", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "vaccination acceptance, it is essential for the government to understand the above factors", "A total of 250 questionnaires were distributed to parents of children studying in the selected kindergartens mentioned in section 2.1. Each eligible parent received one questionnaire, an information sheet, and a pre-addressed return envelope. Parents were told to return the completed questionnaires sealed in the envelopes provided before the designated deadline by submitting them to the class teacher. The researcher collected the completed questionnaires via class teachers at the kindergartens. The 118 questionnaires were collected at the end of July 2010 and the response rate was 47.2%.", "This study was approved by the Human Subjects Ethics Committees of the Hong Kong Polytechnic University." ] },{ "paper_id": "450b87fb527fca46dfc933e35d4de041bf170bd9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "450c84277f6e9475368ad36719ef5d7b6595b514", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Complete blood count was carried out on a HemaVet 950FS Hematology Analyzer (Drew Scientific group, Inc., Dallas, TX, USA) standardized for mouse blood. This instrument uses flow cytometric techniques to generate the following parameters in potassium-EDTA anticoagulated whole blood: red blood cells (RBC, 10 4 /\u00b5L), total and differential leukocyte count (neutrophils, lymphocytes, monocytes, eosinophils, and basophils as 10 3 /\u00b5L or %), hemoglobin concentration (HGB, g/dL), hematocrit (HCT, %), mean corpuscular volume (MCV, fl), mean cell hemoglobin (MCH, pg), mean cell hemoglobin concentration (MCHC, g/dL), red cell distribution width (RDW, %), platelets (PLT, 10 4 /\u00b5L), and mean platelet volume (MPV, fl).", "Biochemical analyses were performed using a VetTest 8008 Chemistry Analyzer (IDEXX Laboratories, Inc., Atlanta, GA, USA). The collected blood samples were used to assess the plasma levels of total protein (TP), globulin (GLOB), albumin (Alb), blood urea nitrogen (BUN), creatinine (CREAT), total cholesterol (Chol), aspartate-aminotransferase (AST), alanine-aminotransferase (ALT), alkaline phosphatase (ALP), amylase (AMS), total bilirubin (TBILI), blood glucose (BG), sodium (Na), potassium (K), calcium (Ca), and phosphorus (P), using reagents and methods provided by IDEXX Laboratories, Inc., Atlanta, GA, USA.", "Erythrocytes RBC M/\u00b5L 9.4 \u00b1 0.5 9.1 \u00b1 0.7 9.8 \u00b1 1. ", "Despite recent advances in the development of new antiretrovirals, human immunodeficiency virus (HIV) continues to spread worldwide with an astonishing rate of approximately 5500 new infections a day [1] . HIV is a highly mutable virus and, thus, a major limitation of existing antiretrovirals is the ability of HIV to develop resistance under selective pressure from these drugs. This has led drug designers to opt for complementary combinations with high manufacturing costs, which makes delivery in resource-poor areas (where the disease burden is often highest) unfeasible [2] . Therefore, new, more efficient, and inexpensive antiviral drugs are needed in order to better combat HIV/AIDS. A few years ago, an anti-HIV bioassay guided fractionation of aqueous extracts of the" ] },{ "paper_id": "4518da3d4fdddd13a397a1fd68ce915512615db2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceived and designed the experiments: CCK WBW. Performed the experiments: YTL HYK CCL CYL. Analyzed the data: YTL HYK CCL. Contributed reagents/materials/analysis tools: CLK WBW. Wrote the paper: YTL CCK WBW. Paper review and discussion: CY." ] },{ "paper_id": "45398efb94483b10fc0547f0784cf50d6b2c7b9a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Surveillance implementation", "Step 5: Information sharing", "Step 4: Surveillance implementation" ] },{ "paper_id": "4541100142ffce230655e3b7c3ee2f63173a147c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The key challenges and solutions that were highlighted can be found in the summary box below.", "Emerging and re-emerging infectious diseases", "\"A public health best buy\"" ] },{ "paper_id": "45413d24ce4a3a305bd77754c506c525d308396b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We consider a standard epidemic susceptible-infected (SIR) model", "Substituting expression [5] into [4] , we obtain:" ] },{ "paper_id": "454a87f362323152fc47fe4593afc755422f1e7b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A chi-squared test was performed to reveal the statistical difference using SPSS (version 16.0; SPSS Inc., Chicago, IL) software." ] },{ "paper_id": "454c099b504f30d078e4fff12a3212dcc5567e97", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Legionnaires' disease, campylobacteriosis and hepatitis B had a significantly lower burden compared to the The error bars indicate the 95% uncertainty intervals.", "However, as quantitative results alone might not fully encompass all unknowns, uncertainties and variability [58] other dimensions of health should be considered.", "The study promotes an evidence-based approach to describing population health and assessing surveillance data availability and quality, and provides information for the planning and prioritisation of limited resources in infectious disease prevention and control.", "To achieve these objectives, a methodology was developed [19, 20] that uses a composite health measure, the disability-adjusted life year (DALY) [21] , to express the disease burden of an infectious disease in a single metric and is therefore suitable for comparing their relative burden.", "four diseases discussed above. Invasive Haemophilus influenzae disease, invasive meningococcal disease, chlamydia, salmonellosis, pertussis and Shiga toxin/ verocytotoxin-producing Escherichia coli (STEC/VTEC) infection had an even lower burden. The remaining diseases were ranked with a significantly lower burden. YLL accounted for 71% of the total burden ( Figure 2 )." ] },{ "paper_id": "45510604115249ca0df4da68553498f079b7911f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Q2: What is the cellular function of membrane contact sites?", "The current findings likely represent only a narrow window into the roles of vMCSs during virus infections. Future experiments will address whether the co-opted vMCSs are involved in metabolite/phospholipid uptake by replication organelles, alteration of cellular signaling, ion homeostasis and pathogen defense signaling, and other cellular and viral processes. ", "MCSs are a general feature of compartmentalized cells. At MCSs, membranes of two organelles come in close apposition (membranes are typically~15-30 nm apart) to facilitate communication between various organelles. In particular, MCSs allow an efficient, nonvesicular exchange of lipids (e.g., cholesterol and phosphatidylinositol 4-phosphate [PI4P]) and ions (e.g., Ca 2+ ) between organelles [9]. As such, MCSs play pivotal roles in lipid and ion homeostasis, signaling, and organelle dynamics." ] },{ "paper_id": "4551a670ee8751ea93b9c5e01ea9ac30fde7ab03", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All monetary values are expressed in 2011 international dollars.", "Purchasing power parity exchange rates [19] were used to convert local currencies into international dollars. We conducted estima-tion of economic impacts building on a benefit-cost analysis approach [7] and included uncertainty distributions to account for the possible uncertainties in the estimation. Monte-Carlo simulation methods were selected to propagate the uncertainty from each component to our overall estimates using @Risk [20] .", "Losses from weeds, insects and pathogens were estimated as follows [7] :" ] },{ "paper_id": "4562513d3f2f9c259d9ce5a0eae9233dbf8b8f87", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Confluent monolayers of ST cells grown in 6-well tissue culture plates were infected with 250 \u03bcL of serial ", "Antibodies used in this study were: anti-LC3B ", "Data are presented as means \u00b1 SEM. Statistical analysis was performed using Statistical Program for Social Sciences (SPSS) 16.0. Significance was determined by Analysis of Variance (ANOVA). A P value less than 0.05 was considered to be significant, and less than 0.01 was considered to be highly significant." ] },{ "paper_id": "4564fff695ff930d022c77efecde703856943b7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It remains unclear whether only KoRV-B or also KoRV-A are involved in tumor induction [40, 42] . Like other retroviruses, including HIV-1 [45] , KoRV induces severe immunodeficiencies in the infected animals, leading to serious infections, such as severe chlamydial infections [46] . Since there are effective vaccines protecting cats from infections with the feline leukemia virus (FeLV) [47] , a virus related to KoRV, successful attempts have also been undertaken to generate an effective vaccine against KoRV infections [48] . Unfortunately, vaccination can be difficult in animals carrying an endogenous KoRV which produces a subsequent tolerance against the vaccine [49] .", "To increase the safety of xenotransplantation, additional measures can be undertaken, such as selection of PERV-C negative pigs, in order to prevent recombination with PERV-A which would result in highly replication-competent PERV-A/C, inhibition of PERV expression by RNA interference in vitro and in vivo in transgenic pigs expressing the corresponding siRNA, and vaccines based on the envelope proteins [63] . Recently, attempts were undertaken through genome editing to inactivate all PERVs in the genome, either using a zinc finger nuclease (ZFN) [69] , or clustered regularly interspaced short palindromic repeats (CRISPR) acting with CRISPR-associated nuclease 9 (Cas9) [70] . Using CRISPR/Cas, 62 proviruses were inactivated in immortalized pig cells and the question is, whether this strategy can be used to generate PERV-free animals suitable for xenotransplantation [71] .", "A closely related virus was isolated from a woolly monkey (Lagothrix lagotricha) with multiple fibrosarcomas, called first simian sarcoma-associated virus (SSAV), and then later woolly monkey virus (WMV) [23, 24] . WMV is a mixture of a replication-defective transforming virus and a replication-competent helper virus [24] , which has a high sequence homology and antigenic similarity with GaLV [19, 20, [25] [26] [27] . It was shown that the infected woolly monkey had close contact with an infected gibbon [22] . In addition to these strains, related GALV were isolated from a GALV-SSAV infected marmoset tumor cell line, designated GALV-MAR (Accession number U20589.1) and from an HIV-1-infected human cell line (GaLV-X) [28, 29] , revealing laboratory contaminations similar to the situation with the xenotropic murine leukaemia virus (MuLV)-related virus (XMRV) in human tissues [30] ." ] },{ "paper_id": "45654599b3a90fd3ecfb03ca55dee622a7565e94", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There is a method of regulation in place to ensure that the first three criteria are met.", "human nature being what it is, if the answer to you is \"no you don't get a bed\" than usually you're going to ask why and usually they try to give you a bit of a rationale as to why you didn't get the bed and \"Sid Viscious \" got the bed.", "there's this frustration of, you don't get a straight answer, \"well maybe we have a bed,\" \"well when will you know?\" \"Well, give us an hour.\"" ] },{ "paper_id": "45670b1f604c315c742a23956615cd8ef7745f3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "5. Institutional safety climate: Leadership's support and commitment was clearly visible at events and meetings. The Chief Executive Officer (CEO) led the hospitals staffs in November 2009 in a pledge of commitment to the Hand Hygiene Program (Figure 9 ).", "4. Reminders in the workplace: More than 150 posters were designed from March 2007 for display at lifts and walkways (Figures 2 and 3) . Giant posters on hand hygiene messaging were designed to convey the hospital's commitment to the public (Figures 4 and 5) . Shuttle Ling and How Antimicrobial Resistance and Infection Control 2012, 1:13 http://www.aricjournal.com/content/1/1/13 buses, floor surfaces and lift doors are used to display reminders to both staffs and public (Figures 6, 7 and 8) .", "They are encouraged to use it as often as possible to protect their hands." ] },{ "paper_id": "45673bc77a85f522c99ddfa23654813b570167bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ") and a 12-h light-dark cycle." ] },{ "paper_id": "4572a8588d9d97cf1aa46241f2cf9e4a4d52dab8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The World Health Organization (WHO) has started in 1948 the initiative to implement a worldwide identification of new influenza viruses [14] . Currently demand for vaccines and effective ways to quickly manage and fight a pandemic outbreak are enormous, which also motivated WHO to develop the Global Outbreak Alert and Response Network, enhancing the world's collaboration in containment of infectious diseases [47] .", "(1)", "(" ] },{ "paper_id": "4589d4013cf69c396e0fdb67131022fc11119654", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It was determined by the National Health and Family Planning Commission that the collection of data from A(H7N9) cases was part of a continuing public health investigation of a notifiable infectious disease and was exempt from institutional review board assessment. All patient records/information was anonymized and de-identified prior to analysis." ] },{ "paper_id": "458baa469db78afded4d1acdbc4b7d440a5f0a74", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following case definitions were used: Influenza-Like Illness. Influenza-like illness was defined as an axillary temperature $38uC and cough or sore throat in an outpatient of any age." ] },{ "paper_id": "458c9e598bc8757d58a592739384d70ae4560a50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following mAbs used for flow cytometric analysis and other experiments were obtained from eBioscience (San (Table 1) were synthesized at Bioneer Corp. (Daejeon, Korea) and used for PCR amplification of target genes." ] },{ "paper_id": "45a03a7fbd289f6da276b1c0bab12e09337b9ffd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Initial vital signs included BP: 110/55 mmHg, HR: 114 beats/minute, and SpO 2 : 95% in room air, while she was tachypneic at 20 breaths/min. Arterial blood gas analysis demonstrated pH: 7.44, PaO 2 : 90 mmHg, and PaCO 2 : 32 mmHg. Results of the initial laboratory analysis included WBC: 12,430 cells/\u03bcL, neutrophils: 88%, lymphocytes: 6%, CRP: 10.9 mg/dL, SGOT: 48 U/L, ALKP: 139 U/L, and \u03b3-GT: 201 U/L. Her physical examination was notable for decreased breath sounds, rhonchi, and wheezing in bilateral lung fields. The initial chest radiograph revealed bilateral alveolar infiltrates and a dense area of consolidation with a small pleural reaction in the left hilar region ( Figure 1 ).", "The patient was weaned from mechanical ventilation on day 15 and transferred to the obstetrical floor the following days. She continued to recover uneventfully and was discharged with her healthy newborn on day 20. The 4-month followup with chest CT continued to be abnormal with areas of pulmonary fibrosis while spirometry findings had features of restrictive syndrome.", "Due to the fact that community-acquired pneumonia was suspected, a broad-spectrum antibiotic coverage was initiated, with the support of oxygen therapy and bronchodilators. At the same time, urine sample was sent for possible detection of pneumoococcus and legionella antigens. A rapid influenza diagnostic antigen test (RIDT) was negative.", "Finally, consideration of the health of the fetus is an additional concern. Clinicians should attempt to maintain a minimum PaO 2 of 70 mm Hg to ensure adequate fetal oxygenation. The fetus is better supported in uterus up to 32-34 weeks of gestational age, if the mother can maintain adequate hemodynamics, oxygenation, and ventilation." ] },{ "paper_id": "45b4b6a49cc3373b0f67b014910073336dbca667", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the primers were designed with Primer Express 3.0 software (Applied Biosystems) and data were analyzed with the 2 -\u00c1\u00c1CT method (75) .", "All the primary and secondary antibodies were diluted in blocking buffer (3% goat serum, 0.1% Triton X-100 in 1\u00c2 PBS). The following primary antibodies were used: rat anti-HA (clone 3F10, 1:100 dilution, Roche), mouse anti-EBV nuclear antigen (EBNA-1, 1:100 dilution, Abcam) and rabbit anti-Myc (1:200 dilution, Cell Signaling Technology). Highly cross-absorbed Alexa Fluor Dyes linked to goat IgG (H+L) secondary antibodies were used at 1:1000 dilution, including Alexa Fluor 488 goat anti-mouse, Alexa Fluor 568 goat anti-mouse, Alexa Fluor 568 goat anti-rat and Alexa Fluor 647 goat antirabbit (Molecular Probes). Notably, the entire slide was examined and representative images of each sample slide were captured using a Leica TCS-SP confocal microscope with fluorescent filters.", "pMS2-GFP: was obtained from Addgene (plasmid 27121), and was originally deposited by Robert Singer (67) . It encodes a nuclear localized MS2-GFP fusion protein." ] },{ "paper_id": "45b5b1c24269b3ee4c2f74aba8872482c0a6a934", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MDL-1 is also essential in osteoclastogenesis and bone remodeling upon association with both DAP-12 and DAP-10 in bone marrow-derived osteoclasts [116] . Osteoclasts are multinucleated gianT cells that differentiate from macrophages and are involved in bone remodeling [116] . DV infection of osteoclasts was recently shown to upregulate osteolytic activity [117] . Attenuation of DV-induced osteolytic activity was observed in MDL-1 -/mice and, consistently, administration of a MDL-1 antagonist in wild-type mice also inhibited DV-activated osteolytic activity [117] .", "LSECtin was described to regulate intrahepatic T cell immunity and to limit liver injury in a model of induced experimental acute hepatitis [79, 80] . Using LSECtin-deficient mice in adenovirus infection and HBV replication as murine models for viral hepatitis, Liu et al. demonstrated that LSECtin facilitated the reduction of liver inflammation by delaying virus clearance and that this process could be hijacked by viruses as an immune evasion mechanism [81] .", "Since CLRs expressed by APCs represent attractive targets for novel antiviral therapies, glycan-based carrier systems have gained increased attention in the last years, particularly due to their tunability in terms of ligand density, rigidity of the scaffold, and immunogenicity [131] [132] [133] [134] ." ] },{ "paper_id": "45bb84571df3f2e42173366750302b2315783842", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Middle East respiratory syndrome coronavirus (MERS-CoV) first appeared in Saudi Arabia in 2012, and has since been reported in several neighboring countries in the Arabian Peninsula and on other continents [59] .", "The epidemic history reconstructed using both datasets was more accurate than when analyzing each type of data separately.", "Unraveling the complex evolutionary history of pandemic H1N1 influenza" ] },{ "paper_id": "45c54d1883027b09c51ea00cb13b1980569592a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that they have no competing interests.", "Authors' contributions BLC and HP designed and performed the experiments, analyzed the data, and wrote the paper. DGZ designed and performed the experiments, and analyzed the data. FZ analyzed the data. JF conceived and designed the experiments, and analyzed the data. FL analyzed the data, and facilitated the study. HRvD analyzed the data. BYW facilitated the study. WB-T designed the experiments, analyzed the data, and wrote the paper. All authors read and approved the final manuscript." ] },{ "paper_id": "45d2d838cb3d5ae2dabd7bb7c82329b398d1c65f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The amount of SARS-CoV in each cell fraction was measured by real-time quantitative PCR assay. 2 \u00b5l of RNA was reverse transcribed and amplified in 20 \u00b5l using 0.9 \u00b5M BMC Infectious Diseases 2004, 4:34", "The identification of human blood mononuclear cells as a direct target of SARS-CoV in the model system described here provides a new insight into disease pathology and a tool for investigating the host response and mechanisms of pathogenesis.", "Methods", "PBMCs were obtained by Ficoll-Hypaque separation of whole blood. 2 \u00d7 10 5 PBMCs were seeded into each well of a 24-well culture plate, 0.5 ml of complete RPMI-1640 (Life Technologies-Invitrogen, USA) added to each and cultured overnight at 37\u00b0C (5% CO 2 ). A seed stock of SARS-CoV (strain SIN 2774) passaged in Vero E6 cells was used for infection. Vero E6 culture supernatants were added to each well in 50 \u00b5l volume at a concentration of 0.1 or 0.01 MOI (based on plaque forming units) and a control plate (media only). Each culture was set up in duplicate. After 4 hours of incubation, one set of the duplicate wells of the control plate and a 4 hours incubation plate were harvested while the rest received 0.5 ml media top-up and incubated for a further 2, 4, 6 and 8 days." ] },{ "paper_id": "45d3b6128146d7df335e96fb8257644f0a5fca14", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were presented as the mean \u00b1 SEM. Statistical comparisons between the control and treated groups were performed using the Student's t-test. A value of p \u2264 0.05 was considered to be significant.", "Respiratory syncytial virus (RSV) belongs to the family Pneumoviridae and contains a negative-sense single-stranded RNA genome. RSV infection is a leading cause of severe acute lower respiratory tract disease and related hospitalization in children and the elderly [1, 2] . Despite the global burden from RSV infection, there are no available RSV-specific vaccines or effective therapeutic agents at present." ] },{ "paper_id": "45dd7b43349a7cd110254e46282dd4968dcdffbe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All mouse procedures were performed on protocols approved by the University of Pennsylvania's Institutional Animal Care and Use Committee (IACUC) (Reference Assurance # A3079-01). Intracranial inoculations were carried out under anesthesia with isoflurane and all efforts were made to minimize suffering. The University Of Pennsylvania School Of Medicine is fully accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC).", "Mouse oligodendrocyte cultures were derived from a mixed population of cells isolated from the forebrains of 1-to 3-dayold neonatal C57/BL6 mice and cultured in serum-free growth medium containing PDGF, FGF2, and NT-3, as previously described [37] . When confluent, the oligodendrocyte-lineage cells were purified using a modified wash down procedure to remove astrocytes and other contaminating cells [37] .", "Neurons were isolated from the hippocampi of E15.5-16.5 mouse embryos and plated on poly-L-lysine coated wells without astrocyte feeder layers as described previously [34, 35] . Hippocampal neuron cultures were typically >95% pure as assessed by immunostaining with an antibody recognizing MAP2 (1:2; AP14, kindly provided by Virginia Lee, University of Pennsylvania)." ] },{ "paper_id": "45edbd85cb93950fecbc8da86f684a9e45c1d8f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All calculations were performed with IBM SPSS 19. Data analysis for virus titers and NO release were performed by two factorial ANOVA followed by a post hoc test (Scheffe). Data analysis for cytokine expression was performed by paired, two tailed t-test. P values of ,0.05 were considered statistically significant. P values of ,0.01 were considered statistically very significant. All data are given as the mean 6 standard deviation.", "Swine influenza is an infectious disease caused by RNA viruses which are highly contagious. Multiple strains of this virus are common throughout pig populations worldwide and cause significant economic losses in industry. At least three SwIV subtypes H1N1, H1N2 and H3N2 are currently circulating in the swine population despite regular vaccinations, and exchange of influenza viruses between human and swine is common and not a one-way street [1, 2] . The traditional vaccine is less effective because it cannot possibly include all the strains actively infecting people in the world. Therefore, therapeutic alternatives for preventing infections and maintaining the health of livestock are highly warranted.", "Based on the in vitro data shown here for a porcine influenza virus, we hypothesize that the use of E. faecium as a probiotic feed (or food) additive has the potential of reducing influenza virus infections in mammalian tissues. SwIV challenge experiments with piglets which are fed E. faecium as a supplement are presently in progress in order to test this hypothesis.", "To investigate if virus could be trapped by probiotics, E. faecium (1.00E+06 CFU/ml) were mixed with 0.01 MOI SwIV in a total of 1 ml DMEM for 90 min co-incubation at 37uC in a CO 2 incubator for 1.5 h. The mixture was then centrifuged at 3,500 rpm for 10 min (compare Fig. 6 -Preincubation assay). Sediments were prepared for quantitative PCR and supernatants were used to infect cells. Total RNA was isolated from sediments and M protein of SwIV was amplified and compared to virus control. The virus titer and NO release assays mentioned above were carried out at 48 or 96 hpi.", "Probiotic microorganisms have been mainly studied in the context of bacterial infections of the gastrointestinal tract which is the natural target tissue of probiotics. However, there are a few reports which indicate that upon oral intake, probiotics can also affect infections of the respiratory tract [14] . There are also reports in the literature where probiotics induce antiviral activity in vitro and are even applied as a medical treatment against persistent virus infections in humans and animals." ] },{ "paper_id": "45f1fd0f1962aa8162216270b1a97e57e0708b18", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "45f6818a37c16f974f9be1d2e94e0ff5b9887c4d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Written informed consent was obtained from the patient for the publication of this report.", "Additional file 1: Questionnaire on investigation of attitudes, practices and information needs regarding novel influenza A (H7N9).", "Guangzhou is 7,434 square kilometers in size, situated at 22\u00b026\u2032N -23\u00b056\u2032N and 112\u00b057\u2032E -114\u00b03\u2032E. As of the 2010 census, the city had over 7.9 million registered inhabitants and a floating population (such as migrant workers) of 4.8 million. It is the largest trading city in southern China, and is about 120 km north-northwest of Hong Kong and north-northeast of Macau ( Figure 1 ).", "Pilot surveys were conducted prior to the study, to confirm that participants could understand the survey questions and to ensure the validity of the questionnaire content. Using the results of this pilot study, the survey questionnaire was amended to create a final version (Additional file 1). All questions were either closed-ended or multiple-choice." ] },{ "paper_id": "4600273935786871df51c3644a39d86c3ad2cc8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral genome sequences used in this study were taken from Genbank, accession numbers KF958252 (DRV), KF823814 (RFFRV), and KJ935003 (PNV).", "\u2020 These authors have contributed equally to this work." ] },{ "paper_id": "461e14fcd69e84dfcc444f0ab92632688997b40d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "462c15b07dd915107b852ace8f6c49eb53fc9a9a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral nucleic acids were extracted from nasal and throat swabs using RNA/DNA extraction kit \u00abRIBO-sorb\u00bb (Interlabservice, Russia) according to the manufacturer's instructions. The extracted viral nucleic acid was immediately used to perform the reaction of reverse transcription using commercial kit \"REVERTA-L\" (Interlabservice, Russia).", "The data were analyzed with regard to the seasonality. Overall, virus detection positive rate did not differ significantly between seasons, ranging from 71.3% to 73.3%. ", "All aspects of the study were approved by the Ethics Committee of the Federal State Budgetary Institution \"Research Center of Clinical and Experimental Medicine\" (2013-23). Accordingly, written informed consent was obtained from parents prior to sample taking." ] },{ "paper_id": "4630378a0db8bae16b58ac19b512f9fffb0fc98f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This was a retrospective study that did not require direct intervention, retrieval of clinical specimens or animal experiments. The pig owners provided written consent for data collection and publication. No specific permissions were required for the location of the data because the data were collected with swine management software.", "The objectives of the present study were to investigate the effects between a 1-year period before and after PEDV outbreak on a sow's reproductive traits on a commercial pig farm in Taiwan.", "Porcine epidemic diarrhea (PED) is an important swine disease that causes a significant impact in most pig-producing countries [1] . The causative agent, the PED virus (PEDV), belongs to the genus Alphacoronavirus, family Coronaviridae, and order Nidovirales [1] . Although PEDV was first observed in Europe in the early 1970s [2] , it has become an increasing problem worldwide, including in the Americas [3] [4] [5] , Asia [6] [7] [8] [9] [10] [11] and Europe [12, 13] . The devastating effect of PEDV infection is mainly due to the acute watery diarrhea and dehydration induced in infected pigs that not only leads to high (80-100%) mortality in neonatal piglets [3, 9] but also impairs the health and performance of the surviving pigs [14] ." ] },{ "paper_id": "4631d1a1d9384ce4aa9d96d6695417357855ce84", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1. Searching strategy.", "Workplaces, mostly civil services, were mentioned as study settings in a few surveys, but not in any interventions.", "Supplementary information accompanies this paper at https://doi.org/10. 1186/s12888-019-2307-0." ] },{ "paper_id": "46408d6638c45017e1dc70ef72bc0373c5514942", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Assign taxonomy (BLAST+)" ] },{ "paper_id": "46411996e57929617bbb462c3cbc429d3e70619d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "According to the viral genome sequence, a codonoptimized gene of capsid P2 was synthesized and cloned into pET-30a (Novagen). The recombinant capsid P2 protein was expressed in E.coli BLR (DE3) cells (Novagen) under the inducing of isopropyl-\u03b2-d-thiogalactopyranoside (Sangon Biotech) at concentrate of 1mmol/L and purified using Ni-NTA Agarose (Qiagen). After verified using convalescent goose sera by Westernblot, 200 \u03bcg purified recombinant protein was inoculated to 8-week old Balb/c mouse in abdomen at an interval of 10 days. 10 days after the 3rd immunization, the mouse blood was collected to prepare antisera.", "Fresh tissues collected from the diseased or experimental goslings were fixed with 10% neutral buffered formalin. Then paraffin sections were prepared and stained with haematoxylin and eosin (H&E) as described 16 . Histopathological changes in the tissues were observed under an optical microscope.", "In 2015, a gout disease emerged in 1-week-old goslings in Anhui province, which has spread to most provinces of China by 2017. The outbreak of the gosling gout disease has caused significant economic loss in goose industry.", "The clinical signs of the disease were characterized by white feces, leg joint enlargement with urate deposits and paralysis. At necropsy, kidney enlargement and intensive urate deposits were found in the gallbladder, knees, and ureters, and on the surfaces of cardiac, heart, liver, air sacs, trachea, and proventriculus ( Fig. 1a-f ). The disease lasted for 7-10 days with high morbidity and mortality. The survival goslings grew slowly and were susceptible to bacterial infection." ] },{ "paper_id": "4648b12f07c46586cff25b47a85a0f5b6167620e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "African green monkey kidney epithelial Vero (ATCC CCL-81) and human adenocarcinoma alveolar basal epithelial A549 (ATCC CCL-185) cells were maintained in Dulbecco's modified Eagle's medium (DMEM; Mediatech, Inc.) supplemented with 5% fetal bovine serum (FBS) and 1% PSG (100 U/ml penicillin, 100 \u00b5g/ml streptomycin, and 2 mM L-glutamine) at 37 \u2022 C in a 5% CO 2 atmosphere.", "Aurintricarboxylic acid (Catalog No. A1895) and Arbidol (ARB, Catalog No. SLM0860) were purchased from Sigma-Aldrich, MO, United States. Both compounds were prepared at 100 mM stock solution dissolved in dimethyl sulfoxide (DMSO) and kept at \u221220 \u2022 C until experimental use. Each drug was diluted into infectious media (DMEM 2% FBS, 1% PSG) for the described experiments, where the maximum DMSO concentration was 0.1%.", "Zika virus (ZIKV) belongs to the genus Flavivirus within the Flaviviridae family. ZIKV is an enveloped positive sense single-stranded RNA virus with a genome size of \u223c10.7 kb that encodes a single polyprotein, which is post-translationally processed by cellular and viral proteases into three structural (capsid, C; pre-membrane, prM; and envelope, E) and seven non-structural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins Avila-Perez et al., 2018) ." ] },{ "paper_id": "464e498ad4c25f88b02533864c5415900e53e412", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "List of abbreviations EbGP: Ebola virus glycoprotein; ER: endoplasmic reticulum; ERK2: mitogen responsive extracellular regulated kinase 2; GP1: surface subunit of GP; GP\u0394mucin: GP with the mucin-like region of GP1 deleted; MAPK: mitogen activated protein kinase; NP: nucleoprotein; NPC: nuclear pore complex; PERK: PRKR-like ER kinase; sGP: soluble glycoprotein; UPR: unfolded protein response; VLP: virus-like particle.", "alone [37] . While we did not detect NP in the VP40 filamentous structures here, previous studies suggest that NP interacts directly with VP40, and is present in VP40-containing VLPs when VP40 and NP are co-expressed [14] , [15] . Thus, perhaps NP is recruited to VP40-containing VLPs at a later stage during filament formation than the 24 hours experiment here, or another viral protein is required for VP40 and NP interaction.", "Previous studies suggest that Ebola GP is incorporated into VLPs along with the viral VP40 and NP proteins when co-expressed in cells [13] , [14] , [15] . VP40 is the major matrix protein of Ebola and can drive the formation of filamentous VLPs that resemble wildtype Ebola virus morphology [13] . VP40 plays an important role in viral replication, assembly and budding [16] . VP40 interacts with cellular factors such as the Nedd4 ubiquitin ligase, Tsg101 that comprises part of the ESCRT-I complex, and Sec24C that is a component of the COPII complex [17] , [18] , [19] . VP40 also has RNA binding and oligomerization properties [20] . The Ebola NP is the principal component of the ribonucleocapsid, which encloses the RNA [21] and is phosphorylated [22] ." ] },{ "paper_id": "465ce310d1edd953819b77c96fa57e62d8cbc042", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GO powders were dispersed in the silver-containing solution, which consisted of AgNO 3 (0.5 M, 35 mL) and ethylene glycol (EG, 70 mL). After the solution was mixed, pulse microwave-assisted (MA) synthesis was processed by placing the solution in the microwave oven (Tatung Co., Taipei City, Taiwan, 900 W, 2.45 GHz) at 160\u02ddC for 5 min to ensure the growth of silver seeds deposited on the GO surface. After GO-Ag solution was produced, it was dried in a vacuum oven at 60\u02ddC overnight.", "To understand the effects of GO and GO-Ag on the enveloped and non-enveloped viruses, FCoV and IBDV are chosen. Felis catus whole fetus-4 (fcwf-4) cells for FCoV [21] and DF-1 cells for IBDV were maintained in Dulbecco's Modified Eagle Medium (DMEM) with 10% fetal bovine serum (FBS), 100 IU/mL penicillin, and 100 IU/mL streptomycin solution in 5% CO 2 at 37\u02ddC. DF-1 cell is an immortalized cell line of chicken embryo fibroblasts (CEF), which can support the growth of several avian viruses including IBDV [22] .", "Graphene oxide (GO) sheets were prepared according to Hummers' method [23] . First, graphite powder and sodium nitrate were mixed with sulfuric acid in an ice bath with agitation for 4 h. Next, potassium manganate was added under stirring and the mixture was kept at 35\u02ddC for 2 h. Then, the mixture was diluted with distilled water and kept at 95\u02ddC for another 2 h before the further dilution with warm water. After the mixture turned yellow with stirring, the mixture was centrifuged to obtain GO powders. The GO powders were re-dispersed in water, and the solution was sonicated for 2 h to facilitate the exfoliation of stacked GO into monolayer or multilayered GO sheets about several micrometers in lateral size. The GO was further reduced using beta-mercaptoethanol, and the black powders of the final product were recovered after centrifugation." ] },{ "paper_id": "465fdc27c98bca041c61f4c5d85671ec92a3b53d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In order to show the real life usage and efficiency of our method, we annotated six proteomes namely Homo sapiens, Mus musculus, Saccharomyces cervisiae, Caenorhabditis elegans, Drosophila melanogaster and Arabidopsis thaliana. Their complete proteome set was downloaded from UniProt which had 68554, 45185, 5450, 26109, 22024 and 31527 proteins respectively.", "where Dipep(n) is the percentage of dipeptide 'n' in a given protein and (n) can be any dipeptides out of the all possible 400 dipeptides of a particular protein (p).", "Secretory proteins are known to contain signal to guide them outside of the cell. This feature also distinguishes them from the intracellular proteins (Wrzeszczynski & Rost, 2004) . Hence sequence encapsulation, which can highlight this difference, ought to be more informative." ] },{ "paper_id": "46605a285131acb104ba6ed5a7b15a23839bdb49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Estimate rate of waning immunity; identify contact structure and factors that change contact rates.", "**** assuming homogenous transmission dynamics." ] },{ "paper_id": "4660da2a8603d28150c9d3de1a17c0333094087c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical features. At week 7, the rats exhibited variable retardation in weight gain. By week 10, two rats showed moderate dyspnea and severe weight loss. None of the rats exhibited severe respiratory distress or marked changes in behavior during the experiments.", "Health monitoring of laboratory animals used in biomedical research is necessary due to the consequences of unwanted infections. Animals that appear normal and healthy may be unsuitable as research subjects due to unobservable, but significant local or systemic effects of viruses, bacteria, fungi and parasites with which they may be infected. There has been a steady increase in the awareness of the varied and generally unwanted effects of natural pathogens in laboratory animals, and there have been even greater efforts to exclude pathogens from these animals (1) . Valid experimental data can only be generated and interpreted when laboratory animals are free of pathogens that may alter the host physiology.", "It is well established that P. jirovecii infections cause severe pneumonia in immunocompromised humans and are a leading cause of mortality in patients with acquired immunodeficiency syndrome. However, evidence is starting to be amassed associating subclinical P. jirovecii infections in immunocompetent humans with several diseases in infants and adults, including sudden infant death syndrome, chronic obstructive pulmonary disease, asthma, bronchiolitis and other lung conditions (27) . The marked, predictable lung pathology in immunocompetent laboratory rats that are naturally infected with P. carinii may provide a possible animal model for P. jirovecii infection in immunocompetent humans." ] },{ "paper_id": "466c7e2cf0d7aae1c4595ce0bb752df2bbaeb033", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results indicate that testing of individual milk samples for antibodies against SBV by ELISA could be used to inform decisions in the management of dairy herds such as which, if any, animals to vaccinate.", "Two-sample and paired t-tests as appropriate (with statistical significance set at p < 0.05) were performed using Minitab version 16. Bland-Altman analysis (to evaluate the variability between the serum and milk antibody levels measured by ELISA over the full range of results) was performed using GraphPad Prism v6." ] },{ "paper_id": "467143e07e3d6ec8a0617a5bdee446ab2c63581c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "cleaved by signal peptidase thus separating Gn from Gc [96] [97] [98] [99] .", "After fusion of viral and endosomal membranes the three viral genomic segments (L, M, and S) which are associated with the viral polymerase are released into the cytoplasm and primary transcription of negative-sense genomic RNA (gRNA) into mRNA is initiated [94] . Transcription and translation are tightly coupled, i.e., the translation of the viral proteins starts before the transcription of the mRNA is completed [95] .", "The following abbreviations are used in this manuscript: " ] },{ "paper_id": "46795b2f533aa0d3e20b1df752cf6c18455ad862", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "467ab436fea0423f0621af047cd6e5c6dae5260e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses. Data were analyzed by unpaired t tests or ANOVA by Dunnett's multiple comparison tests using GraphPad Prism (GraphPad Software). The p values smaller than 0.05 were considered significant. Data availability. The datasets generated during the current study are available from the corresponding author on reasonable request." ] },{ "paper_id": "46833c3f5dcabbe5e696a5d76d61dec64422a433", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "S-palmitoylation also affects protein stability through its interplay with ubiquitination or phosphorylation, as found for the anthrax toxin receptor TEM8, antiviral interferon-induced transmembrane protein IFITM1, calnexin, and zDHHC6, one of palmitoyl acyltransferases described below (54) (55) (56) (57) .", "The work was supported by the National Science Centre, Poland, grant number DEC-2013/08/A/NZ3/00850 to KK.", "All authors contributed to writing and critically revised the paper." ] },{ "paper_id": "468c549a9b35a3f23be71f098c3ab910abadac8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Mitigation of injury risks more readily implemented by veterinarians than mitigation of infectious risks in equine practice;", "\u2022 Suboptimal HeV testing pathways ", "HeV infection in humans can be prevented by avoiding contact with infected horses or avoiding exposure to infected substances by implementing infection control (IC) measures such as using personal protective equipment (PPE) [13] . Administration of monoclonal antibodies during the incubation period has been shown to prevent experimentally induced HeV disease in ferrets and nonhuman primate models and this has also been used in humans exposed to HeV as an experimental prophylaxis [14] . A vaccine for horses became available in late 2012 and was promoted for the protection of horse populations from HeV and humans from secondary spillover [15, 16] ." ] },{ "paper_id": "468cd07dc546d39f95529846f303e76f02ae51b3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The matched protein was deemed as being positively identified when two or more peptides provided a mascot score greater than 22.", "SPR was performed on the Biacore T100 platform (GE Healthcare, Life Science, Milan, Italy). Purified human NCL was immobilized on Serie S sensor chip CM5 by amine coupling. Immobilization was performed in HEPES-NaCl running buffer (HEPES pH 7. ", "To identify the position of putative NCL binding sites onto the DNA G4 structures, we performed dimethylsulfate (DMS) footprinting. When a complex of NCL with the LTR-II+III+IV DNA was assessed ( Figure 4B ), the methylation pattern revealed that the 3 region of the LTR sequence was protected by protein binding with unique specificity for two G bases in G-tract 4, as highlighted in Figure 4C ." ] },{ "paper_id": "468d8047a0283ba355246ed938fac8434a589a26", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Diffraction data were collected at 100 K on beamlines 21-ID-G or 24-ID-C at the Advanced Photon Source. Data were integrated, indexed and scaled with XDS (34) and AIMLESS (35) . Initial phases were determined by molecular replacement using Phaser (36) with PDB ID: 5V1M (15) , and refinement accomplished by the iterative process of manual model building in Coot (37) and automated refinement in PHENIX (38, 39) and Refmac (40, 41) . All figures were generated with PyMOL (http://www.pymol.org/).", "5 -terminally cyanine (5 -Cy5) labeled U6 1-107 and U6 1-107+4U were produced by splinted ligation as previously described (43) . The transcripts corresponding to U6 12-107 and U6 12-107+4U were synthesized via in vitro transcription as described above. 5 -Cy5 labeled U6 1-11 and the splinted DNA oligonucleotides were purchased from Integrated DNA Technologies.", "To gain further insight into the enzymatic mechanism, multiple turnover kinetic parameters were determined for substrates ending in UU, UA and AA by monitoring initial rates of product formation as a function of substrate concentration ( Figure 2D and Table 1 ). These data reveal that Usb1 is most efficient at processing substrates terminating in UA. The k cat /K m value for UA is twenty-fold higher than UU ( Table 1) ." ] },{ "paper_id": "4691c6219bc10483f3291813a98d4145c1876827", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "46980d68b4e24f2abd5c94ce173c6f229cfb2162", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Biopanning and enrichment analysis of phage library using BEFV G 1 as target", "Each treated sample was run in triplicate. Statistical analysis was performed by one-way analysis of variance and values were considered significant when p < 0.05. ", "protein G consists of five major neutralisation sites (G 1 ,G 2 ,G 3a ,G 3b ,G 4 ) defined by BEFV G protein specific monoclonal antibodies (MAbs) in competition ELISAs, and among these sites, site G 1 composed of two minimal B cell epitopes is a linear neutralisation site involving in eliciting neutralizing antibodies. It is reported that site G 1 is predicted to face the viral membrane in both the pre-fusion and post-fusion forms of the trimer and may be approachable to antibodies [13] [14] [15] . Therefore, G 1 protein can be used as a potential target for antiviral drug screening." ] },{ "paper_id": "469ed0f00c09e2637351c9735c306f27acf3aace", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where, \u03b1 =number of expected cases at the baseline and \u03b2 = growth rate per day.", "The ultimate goal of this study is to attempt to provide some solutions to this paradox by providing early messages to inform control measures, to be optimistic and not panic, to ask right questions, and to take right actions.", "We used these estimated P i in this study in several ways." ] },{ "paper_id": "46ad7c3b64488b2ccb6556e31bc12a5ec9e8de0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(TIF)", "Supporting Information S1", "(DOC)", "None of the 419 samples from 257 M. Schreibersii bats screened by PCR was positive." ] },{ "paper_id": "46c2eb2186aa09c3963227ce0195a881ac26de7d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Peptide-nucleic acids or PNAs are oligonucleotide analogues in which the sugar-phosphate backbone has been replaced with peptide bonds [90] . They are resistant to both nucleases and proteases. They are used as antisense molecules to specifically bind to their complementary DNA or RNA sequences, creating a structural hindrance and inhibiting viral transcription, translation and replication processes.", "PPMO antiviral activity has mainly been exploited against a wide range of non-retroviral RNA viruses. In cell culture, PPMOs were tested against West Nile virus (WNV) [66, 67] , Japanese encephalitis virus [67] , St. Louis encephalitis virus [67] , dengue virus (DENV) [68] [69] [70] , severe acute respiratory syndrome coronavirus (SARS-CoV) [71] , MHV [59, 63] , equine arteritis virus [72] , porcine reproductive and respiratory syndrome virus [73] , foot-and-mouth disease virus [74] , poliovirus 1 (PV1) [75] , human rhinovirus 14 [75] , coxsackievirus B2 [75] , coxsackievirus B3 (CVB3) [76] , Sindbis virus [77] , Venezuelan equine encephalitis virus (VEEV) [77] , EBOV [64, 78] , respiratory syncytial virus (RSV) [79] , measles virus [80] , and influenza A virus (FLUAV) [81, 82] .", "Besides improving PMO cellular uptake, the CPP moiety was also shown to intensify PMO antisense activity against EBOV by 10-to 100-fold in cell-free translation assays [64] . These results are consistent with the findings of Nelson et a l. who showed that PPMOs exhibited antisense activity 3-to 25-fold higher than corresponding PMOs while bearing lower off-target effects [87] . The authors propose that the arginine-rich peptides enhance RNA-PMO binding affinity thereby increasing specific antisense activity.", "Upadhyay et a l. demonstrated that PNA TAR -penetratin conjugate is moderately immunogenic mainly due to its penetratin moiety [100] . Cytokine secretion profiles of the lymph node cells showed elevated levels of proinflammatory cytokines, such as IL-2 and IL-12, which are known to promote proliferation of T lymphocytes and slow down the death of CD4+ T cells. The authors emphasize that these immunogenic properties of the conjugate could prove to be beneficial to the host.", "There have been a few reports of PMO-mediated antiviral activity in animal models. How PMOs could successfully suppress viral replication in vivo without the help of CPPS is not understood. Warfield et al. reported the nearly complete protection of rhesus macaques against EBOV lethal infection using PMOs [88] ." ] },{ "paper_id": "46c464442591d7777212f7ee389bcbfa362ddc8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Phylogenetic trees were generated with MrBayes (version 3.2.7) (Huelsenbeck and Ronquist 2001) , using a mixed substitution model with sampling across fixed amino acid rate matrices (aamodelpr \u00bc mixed) and 5,000,000 generations. All other parameters were set as defaults.", "Data available in supplementary material and in GenBank accession numbers KF298275.2, KF298276.2, and KF298284.2.", "Supplementary data are available at Virus Evolution online." ] },{ "paper_id": "46da38c413e1fc657c3a7ea36435132d38a5e1b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Comparisons were performed using Kruskal-Wallis tests for continuous variables and Pearson's \u03c7 2 or Fisher's exact test for categorical variables. Statistical analysis was performed using R (v3.2.0, Vienna, Austria); significance was set at a p-value < 0.05.", "Close contact with ill travelers with respiratory symptoms during travel was found in 43 (46.7%) patients. Exposure to dromedary camels or contaminated camel milk or meat was found in five (5.4%) patients.", "Oseltamivir was given to 35 patients (37.6%) for a median duration of 120 h (24-120). It was discontinued after 48 h in 12/35 (34.3%) patients, between 48 h and 5 days in 4 (11%) patients and kept for the entire treatment duration in 19 (54.3%) patients.", "Oxygen therapy was required for 42 patients (45.6%), with a median maximal flow of 3 L/min (IQR = 2-4)." ] },{ "paper_id": "46db8b3db38acf771fe27031fee9445b99146308", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Autism spectrum disorders (ASDs) are complex, pervasive neurodevelopmental disorders that are characterized by dysfunctions in social interactions and communications and restricted/fixated interests or repetitive behavior that manifest in early childhood [1] . ASDs include classical autism, Asperger syndrome, and pervasive developmental disorder-not otherwise Specified [2, 3] .", "Prader-Willi syndrome (PWS) is a hallmark epigenetic disease; the causative epigenetic abnormality was identified more than 20 years ago. Approximately 70% patients have a chromosomal deletion at 15q11-q13, and the remaining patients have genomic imprinting errors. In PWS patients with maternal uniparental disomy, both paternal and maternal alleles of genes within the 15q11-q13 region are hypermethylated and thus expression from both alleles is suppressed ( Figure 1A ) [63] [64] [65] .", "The clinical features of PWS includes neurocognitive deficits, excessive daytime sleepiness, muscle hypotonia, short stature, small hands and feet, hypergonadism, hyperphagia starting from infancy, and subsequent obesity and type 2 diabetes [66] ." ] },{ "paper_id": "46e0a035e55b44ef196234e32b2c550b87db4fdc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We hope to make the method available to include ambiguous amino acid residues and nonstandard amino acids. We hope also to include the analyses of partial or gapped sequences.", "The results in Table 9 show that the magnitude (", "The authors declare that they have no conflicts of interest.", "Sequence comparison can be classified into alignmentbased methods and alignment-free methods [2, 3] . Alignment-based methods assign scores to different possible alignments, picking the alignment with the highest score. Some algorithms do global alignment or local alignment [4] [5] [6] . BLAST [7] and FASTA [8] are the most widely used applications. Alignment-based methods are computationally difficult with multiple sequence alignments at the same time. A wide range of scoring systems has been proposed such as amino acid substitution scoring matrices PAM and BLOSUM for protein alignment [9] ." ] },{ "paper_id": "46e2d24fe550946db723bc2af9e6d8cc043ce4ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pone.0181829.g007", "PLOS ONE | https://doi.org/10.1371/journal.pone." ] },{ "paper_id": "46e5064094ed75015cad5a226c704a0dc21b15c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since then, by implementing the diagnostic algorithms of gastroenteritis cases with NoV-specific molecular assays, canine NoVs have been repeatedly detected [42, [44] [45] [46] [47] , revealing a marked genetic diversity among the strains identified that allowed their classification into at least five genotypes from three distinct genogroups, i.e., GIV.2, GVI.1, GVI.2, GVI.3, and GVII [47] .", "The species Carnivore protoparvovirus 1 (genus Protoparvovirus) includes genetically and antigenically related viruses such as FPV, canine parvovirus (CPV-2), mink enteritis virus (MEV), and raccoon parvovirus (RaPV) [130] , causing all serious diseases, especially in young animals.", "The aim of this review is to provide an update on novel enteric viruses that have most recently been identified in association with enteritis signs in cats, focusing the main attention on feline norovirus, feline kobuvirus, and novel feline parvoviruses. ", "QT CCAGTGAGCAGAGTGACGAGGACTCGAGCTCAAGC (T 17 ) +/-3 /5 end [56] Except for the murine NoV [57], a reproducible system culture allowing the routine replication of in vitro NoVs is still not available. To date, there are two published systems (B cell line and stem cell-derived enteroids) [58, 59] supporting replication of human NoVs, but the levels of replication are not sufficient for the generation of highly purified virus stocks or the development of culture-based quantification assays [60] ." ] },{ "paper_id": "46e6c155f1b7e6d93735e45da3f93b0f1ae63113", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The SPSS software was used to analyze the data, which was presented as frequencies and number of participants in each category. Chi square test, Fisher Exact test and odd ratios with 95% confidence intervals were used to correlate demographic variables with needlestick and occupational infection. The P value of significance was set at 0.05 threshold.", "A total of 234 medical laboratory workers was recruited to participate in the study. The majority ( participants were vaccinated against HBV as this a requirement by health law in Saudi Arabia before employment in medical laboratories.", "In this cross-sectional study, we asked the participants if they have ever experienced needlestick injury or occupational infection. To have a better assessment of the current situation, conduction of a longitudinal study is strongly recommended where the incidence of such biohazards can be accurately measured. Inclusion of more questions in the assessment such as how often the participants perform phlebotomy and whether they use needlestick prevention devices are strongly recommended. Other limitations include the validity of key measures such as recall bias and social desirability related to recapping practices, selection bias and the data were not adjusted for confounder factors." ] },{ "paper_id": "46ebfbb3db79bab7f78361721e37e8b35a34037e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Values are presented as the mean \u00b1 standard deviation (SD) or standard error of the mean (SEM). Statistical differences between groups were assessed using one-way analysis of variance (ANOVA) post hoc tests and by Tukey's test using SPSS 17.0 (SPSS, Inc., Chicago, IL, USA). A probability (p) value of less than 0.05 was considered statistically significant.", "The experimental protocol was approved by the Institutional Animal Care and Use Committee of Taipei Medical University (IACUC approval no. LAC-100-0165). Male New Zealand rabbits purchased from Animal Health Research Institute, Council of Agriculture, Executive Yuan, Taiwan, weighing 2.5~3.5 kg with no signs of ocular inflammatory or gross abnormalities were used. The animals were housed in standard cages in a light-controlled room and were given food and water ad libitum. All examinations or surgical procedures on the rabbits were performed under general anesthesia administered via an intramuscular injection of a 1:2 mixture of Zoletil 50 (Virbac Anial Health, Nice, France) and 2% Rompun solution (Bayer, Kyonggido, Korea).", "The study design is summarized in Fig 1 and explained below." ] },{ "paper_id": "46ee8e5fc43eba4d4efe8979ba75a36991d9e283", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "46ffe37cdfe520a31dadf0a3308b1f7f98d4295d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The degree of hepatic injury was assessed by measurement of serum ALT. Serum ALT levels were analyzed using a serum multiple analyzer (Johnson & Johnson H , Ektachem DTSC II multianalyzer).", "Blood samples were collected at day1 post LCMV infection in heparinized tubes. Mouse serum IFNa measurements were performed using a VeriKine Mouse Interferon-a ELISA Kit according to the manufacturer's instructions (PBL Interferon-Source, Piscataway, NJ).", "Results are reported as mean6SEM unless otherwise specified. One-way or two-way analysis of variance (ANOVA) was used for group comparison. Differences with P,0.05 were considered significant." ] },{ "paper_id": "471239798c6ed87995720ee1a73092b8b79b9549", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The peptide solution was concentrated on a \u00b5-Precolumn Cartridge Acclaim PepMap 100 C18 (i.d. 5 mm, 5 \u00b5m, 100 \u00c5, DIONEX, LC Packings) at a flow rate of 20 \u00b5L/min and using solvent containing 98%/2%/0.04% H2O/ACN/TFA (v/v). Then, peptide separation was performed on a 75 \u00b5m i.d. \u00d7 150 mm (3 \u00b5m, 100 \u00c5) Acclaim PepMap 100 C18 column (DIONEX, LC Packings) at a flow rate of 200 nL/min and with detection at 214 nm. The solvent systems were: (A) 100% water, 0.05% TFA; (B) 100% ACN, 0.04% TFA. The following gradient was used t = 0 min 100% A; t = 3 min 100% A; t = 63 min, 80% B; t = 64 min, 100% B; t = 68 min 100% B (temperature was set at 30 \u00b0C).", "The unexpected pSP and hSP peptide patterns obtained by mass spectrometry are quite puzzling. Several hypotheses may explain these results." ] },{ "paper_id": "4716aa61386cb52b7aa834b557cb4e2ac7ec4cad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In this review, we summarize and critically discuss current knowledge about the interplay between the lung microbiome and IPF, with emphasis on its potential role in disease development, progression and acute exacerbation.", "A phase III double blind, randomised, placebo-controlled, multi-centre clinical trial of oral co-trimoxazole versus placebo in 330 patients with moderate and severe IPF is currently underway (EME-TIPAC-The Efficacy and Mechanism Evaluation of Treating Idiopathic Pulmonary Fibrosis with the Addition of Co-trimoxazole; EudraCT number 2014-004058-32) [49] . The primary outcome is the time to death (all causes), lung transplant or the first non-elective hospital admission.", "Acute exacerbations of IPF (AE-IPF) are episodes of acute respiratory worsening with a median survival following the event of approximately three to four months [38] . According to the recently revised definition and diagnostic criteria, they can be either idiopathic or triggered (for instance, by infection), but cardiac failure, fluid overload or extra-parenchymal causes, such as pulmonary embolism, pneumothorax or pleural effusion, need to be excluded [39] . Notably, because the original diagnostic criteria for AE-IPF required these events to be idiopathic [40] , studies published before the 2016 revised document have been conducted in patients without overt clinical infection." ] },{ "paper_id": "471711362b8adb4bda402d22aebd264f63f8e1b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Demyelination (N=14)", "Neuromyelitis optica (N = 2)", "Other Neurologic Disease (OND) (n=7)" ] },{ "paper_id": "471d089defc5afd2af77f05c43b8be4cdc103bab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "471d79fab1a95464be76c77dce4a2e263ca8b443", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The resulting products were submitted to bi-directional DNA sequencing using a BigDye Terminator v3.1 cycle sequencing kit following the manufacturer's directions (Applied Biosystems). Sequencing products were read on an ABI PRISM-3100 Genetic Analyzer (Applied Biosystems). The sense and antisense sequences obtained from each amplicon were assembled, and a consensus sequence for each gene was generated using the ChromasPro V1.5 program (Technelysium Pvt. Ltd., 2009). Nucleotide BLAST analysis (http://www.ncbi.nlm.nih.gov/ blast/Blast.cgi) was initially used to verify the identity of each fragment sequence obtained. The sequences were submitted to the GenBank Database under accession numbers (LK022327-LK022343)." ] },{ "paper_id": "472008db67b7b6037de590f4f25a12425ef181ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the experiments were performed in triplicate and the results are presented as mean \u00b1 SD. Student's t-test was used to determine significance of the obtained results. P values < 0.05 were considered significant." ] },{ "paper_id": "472602b70bca7504518686f34f5b1b15dbe21725", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Normalize the weights. Obtain the marginal model probabilities given by", "We also report the computational time required on a parallel implementation on an IntelCore i7-4770S 3.10 GHZ 8-core processors (Table 3) . ", "1/3" ] },{ "paper_id": "47266ea82145a11ad6e82db70a4d0fbd86a27cb2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "By some considerations, the ID-to-name conversion for viral sequences is both of particular relevance and of considerable complexity. First, a large body of results in virus research can be linked to underlying sequences, owing to relatively small number of known viruses and comparatively small sizes of their extensively characterized genomes. Second, the virus naming, at the species level and below, is not governed by either the binomial Latin name convention traditional for cellular organisms or another broadly accepted nomenclature [13] that complicates communication in virology. For species, naming viruses is under auspices of the International Committee of Virus Taxonomy (ICTV) [14] . At the isolate and strain level, it is left up to individuals or groups of researchers to decide how to proceed [15, 16] . Researchers studying few economically most important viruses developed nomenclatures restricted for these viruses [17] [18] [19] [20] [21] [22] . In contrast, each decision about naming that concerns a majority of viruses is an ad hoc and, often, lengthy process. Likewise, naming viruses with artificially designed genomes, which are not product of natural evolution [23] , is formally outside of the ICTV authority and completely unregulated.", "The SNAD web site has six pages including a detailed guide to SNAD with examples (\"Introduction\"), program execution page (\"Execution\"), guided access to Java and Perl APIs (\"APIs\"), frequently asked questions page (\"FAQs\"), list of the SNAD versions (\"History\"), and \"Reference\" page. SNAD execution page has three vertically arranged sections: \"Before unique ID (UID) conversion\" for uploading input, \"Names/format designer\" for choosing and refining pre-compiled name templates, and \"After UID conversion\" for accessing output (Figure 2 )." ] },{ "paper_id": "473207b36a728a21e7545bcde584d8618f714552", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following grant information was disclosed by the author: Taiwan ", "The author is grateful to the reviewers and the editor for their constructive comments. ", "In the context of infectious disease modeling (Hsieh, Lee & Chang, 2004; Hsieh & Cheng, 2006) , the analytic solution of the Richards model (Richards, 1959) is of the form" ] },{ "paper_id": "473b926e3266337d27883cca29c6186faf3d7ba2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virally encoded anti-IFN proteins, VP24 and VP35 play major roles in EBOV virulence [7, 8] . VP35 blocks type I IFN induction in dendritic cells (DCs) and macrophages, and acts as a virulence factor necessary for a recombinant virus to attain infectivity in the host [9] [10] [11] [12] . VP24, on the other hand, blocks IFN signaling by interfering with IFN activated JAK/STAT pathways [7] .", "Ebola viruses (EBOVs) are enveloped, negative-sense RNA filoviruses that can cause a severe hemorrhagic fever in humans and non-human primates (NHPs) [1, 2] . Mouse-adapted EBOV causes similar acute disease in mice, offering a useful animal model to study EBOV infection [3, 4] . EBOV infection is characterized by rapid viral replication and dysregulated innate and adaptive immune responses. The disease follows profound suppression of type I IFN signaling and a contrasting excess inflammation that leads to mucosal hemorrhages and multi-organ failure resembling septic shock syndrome [5, 6] .", "Total RNA from liver and spleen of EBOV infected mice were extracted by TRIzol method (Invitrogen) and cDNA was synthesized from 1 \u03bcg total RNA by Superscript II reverse transcriptase (Invitrogen). qPCR amplification was done with 3 ng cDNA in 5 \u03bcl SYBR Green PCR master mix (Applied Biosystems) with 3 \u03bcM of both reverse and forward primers used in the ABI prism 7500 Sequence Detection System (Applied Biosystems). mRNA of expression of indicated genes were analyzed as described in detail elsewhere [33] . The primer pairs were used for EBOV GP, 5'-TGGGCTGAAAACTGCTACAATC-3' and 5'-CTTTGTGCACATACCGGCAC-3'; NLRP3, 5'-TGCTCTTCACTGCTATCAAGCCCT-3' and 5'-ACAAGCCTTTGCTCCAGACCCTAT-3'. All other gene primer sequences were followed from the previous publications [10, 33] . Transcript levels were normalized with Hprt, and expressed as relative expression. Statistical analysis was carried out by Excel software using two-tail paired Student's t test. Data represent the mean of at least three independent assay \u00b1 SEM. A p value < 0.05 was considered significant.", "Ifnar -/-, Ifnar +/+ mice of BALB/c background and Irf8 -/and Irf8 +/+ mice of C57BL/6 background were bred in the NICHD animal facility and transferred to the facility of the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) for EBOV infection studies. Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the guide for the Care and Use of Laboratory Animals, National Research Council, 1996. The facility where this research was conducted is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International. The IACUC committee approving this protocol is the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) IACUC. Animals were monitored at least once daily and their status was evaluated according to an intervention score sheet approved by USAMRIID IACUC. Monitoring increased to three times daily if the animals were given a score of three or four. Euthanization was by CO 2 inhalation followed by confirmatory cervical dislocation. Analgesics and anesthetics were not used in this study and animals were euthanized for humane purposes if they reached a score of five or more, which would be indicated if the animals exhibited ruffled fur, weakness, unresponsiveness, and/or difficulty walking. Otherwise, animals were euthanized at the end of the study." ] },{ "paper_id": "474978e3a0f1a8064083d7ae5136b968d10184ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HeLa cells (human cervix carcinoma, obtained through American Type Culture Collection), and primary murine embryonic fibroblasts (MEF) were cultured in Dulbecco's modified Eagle's medium (DMEM, Gibco, Invitrogen, Karlsruhe, Germany), high glucose, supplemented with 10% fetal calf serum (FCS, Gibco), 100 U/ml Penicillin and 100 mg/ml Streptomycin (Sigma-Aldrich, Taufkirchen, Germany) at 8% CO 2 and 37uC. Cell culture medium for MEFs was additionally supplemented with 1% non-essential amino acids and 1 mM sodium pyruvate. MEFs were isolated from day E13.5 mouse embryos (strain C57BL6/J) using standard protocols (see http://www.molgen. mpg.de/,rodent/MEF_protocol.pdf).", "One third of each sample was incubated overnight with 3 mg of antibodies against RAR, RXR or with an isotype-matched immunoglobulin G (anti-HRS). For Egr1-ChIP, half of the sample was incubated with 5 ml of Egr1 antibody and the other half with 5 ml of an isotype-matched immunoglobulin G (anti-EGFR). Immunoprecipitation was performed by adding 30 ml of preblocked Pansorbin cells for 2 h at 4uC. Pansorbin beads were washed twice with ChIP-buffer and twice with PBS with centrifugation steps (2 min, 1500 g, 4uC) in between. Elution was done twice (15 min, room temperature) in 150 ml elution buffer (0.1 M NaHCO 3 , 1% SDS). Cross-linking was reversed by adding NaCl to a final concentration of 0.3 M and 20 mg of RNAse A and incubation at 65uC for 4 h. Proteinase K digestion was performed for 1 h at 55uC. Samples were purified by phenolchloroform extraction and ethanol precipitation. PCR was performed with primers Flot1-375 fwd, Flot1-rev and Flot2-ChIP fwd and rev, respectively. PCR products were separated on 1.5% agarose gels.", "Unless otherwise stated, all experiments were performed at least three times. Data are expressed as mean 6 SD. Statistical comparisons between groups were made using Student's t-tests, 1way or 2way ANOVA, as appropriate (GraphPad Prism 5, San Diego, CA, USA). Western blot bands were quantified by scanning densitometry using Quantity One Software (Bio-Rad) and normalized against GAPDH. Values of p,0.05 were considered significant (*) while values of p,0.01 were considered very significant (**) and p,0.001 extremely significant (***)." ] },{ "paper_id": "474a502696d79b407fb2ff9f85d1b974d0064bf6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by Spanish \"Ministerio de Econom\u00eda y Competitividad\" and European Regional Development Funds of the European Union (SAF2014-54840-R), \"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas, CIBERNED\" (Grant CB06/05/0064), and \"Fundaci\u00f3 La Marat\u00f3 de TV3\" (Grant 20140610).", "(2)", "EM, JC, EG, AC, and VC performed the experiments and analyzed the data. EM, JM, CL, AC, and VC designed the experiments. EM, EG, EC, AC, and VC wrote the manuscript." ] },{ "paper_id": "474dc8b54f9110f60b129220549c532355fe10b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "August 2015 | Volume 6 | Article 387" ] },{ "paper_id": "4753387619e93bba84ec49e59c52a5c8d32c6392", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analyses and graphics were implemented in the R computing environment; maps were created using QGIS software [17, 22] .", "\u2022 The presented approach is applicable for a wide range of infectious diseases in different settings, taking some practical considerations into account.", "The field teams obtained written informed consent from participants or their guardians (if <18 y of age) during community surveys. Healthcare utilization survey protocols were reviewed and approved by the Ethical Review Committee of the International Centre for Diarrhoeal Disease Research, Bangladesh.", "\u2022 Cases captured by surveillance differed from cases in communities by age and socioeconomic status." ] },{ "paper_id": "4753feb97a6db2b1172caa96791e23e96ac9d287", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "JS was responsible for conception of the study, data interpretation, supervision of data collection, statistical analysis, and drafting the manuscript. CM and GM were responsible for data collection and analysis, enrollee communication, review of relevant literature, and manuscript revision. GB was responsible for recruitment of patients and manuscript revision.", "The clinical trial was supported by a grant from Vital Planet, LLC which distributes the probiotic tested in this investigation.", "Forty percent of owners responded to requests for long-term follow-up (n = 24) following study completion. Diarrhea was reported in the follow-up period in 33.3% of dogs for which information was available (Table 1, n = 8).", "The linear regression identified a history of previous diarrhea episodes (\u03b2 = 1. Episode of diarrhea after study (n) 4 1 3 0.48 8 \u2020 numbers given are the n positive/n samples submitted. Not all dogs had sufficient sample for analysis. \u2020 \u2020 No results were statistically significant; ns indicates there were no significant differences for pairwise two-proportion z-tests which were assessed using Bonferroni correction (p < 0.017 considered significant). CPA, C. perfringens alpha toxin gene; CPE, Clostridium perfringens enterotoxin (CPE); CPnetEF, Clostridium perfringens netEF gene (CPnetEF)." ] },{ "paper_id": "475c8599530b970bbf476ee0e2798f5940dc1254", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "FAST CAT Assay kit (Molecular Probes) was used according the manufacturer's instructions and allowed accurate quantification of CAT enzyme levels over a wide linear range.", "The total protein concentration of the purified VLP preparations was measured by the BCA (Bicinchoninic Acid) method (Thermo Scientific Laboratories).", "VLP composition was determined by western blot analysis. Briefly, purified VLPs resuspended in endotoxin free PBS were lysed by resuspending them in equal amount of 2x SDS proteinloading buffer and loaded into a 12% SDS-polyacrylamide gel with a 4% stacking gel. 293T cell lysates processed similarly were run in parallel as negative cell control. Following electrophoresis to resolve the protein bands, and transfer to membrane, the blot was incubated with NiV-specific HMAF primary antibody at a dilution of 1:1000 dilution, overnight at 4uC, and HRP-conjugated antimouse secondary antibody (from GE Healthcare) at a 1: 20,000 dilution for one hour at room temperature. The proteins were revealed using western blot detection reagents according to instructions provided by the manufacturer (GE Healthcare)." ] },{ "paper_id": "475d4a59b08bc0524da46806dae55989e57dac4e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A retrospective single-center observational study was conducted from May 2015 to May 2019 in RuiJin Hospital, Shanghai, China. The study was approved by Ruijin Hospital Ethics Committee and written informed consent was obtained from all patients involved before enrolment.", "Multiple imputation of missing data was performed for: serum interleukins (28.9% missing); PaO2/FiO2 (25.3% missing); T lymphocyte subsets levels (27.4% missing); body mass index (BMI) and lymphocyte count (all < 1% missing)." ] },{ "paper_id": "47654cf27ea49e075f800ff503bbeecb4168e224", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition, the Receiver Operating Characteristic (ROC) curve was graphed for each algorithm and the area under the curve (AUC) was calculated as an additional assessment of model performance." ] },{ "paper_id": "476c677579fa461c4fbe5822f1df9a687a6d8928", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The betweenness centrality C B (i) of a node i is defined as", "calculate the value of Q for a given network, and the development of more accurate and efficient methods is still a very active research field. In particular, one has to be careful when comparing values of Q because some measures are normalized while others or not [51] . We have used the spin glass method introduced by Reichhardt and Bornholdt [52] to measure Q throughout this manuscript.", "where r 0 is the value of R 0 under the assumption of a homogenous network (i.e. no variance in the degree distribution) [1, 56] .", "Simulations with immunization strategies implement those strategies before the first infection occurs. Targeted nodes are chosen according to a given immunization algorithm (see below) until a desired immunization coverage of the population is achieved, and then their state is set to resistant." ] },{ "paper_id": "47826d4f9693f8859eff729ef432cc24d41cd896", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Population genomics analysis P. falciparum EBL-1 protein binds to the erythrocyte receptor glycophorin B, a highly polymorphic gene in malaria-endemic regions [50] Streptococcus Phage display 19 bacterial proteins identified as potential fibronectin-binding proteins [51] Fusobacterium nucleatum", "Haploid cell screens 46 cell host factors identified, including heparin sulfate proteoglycan biosynthesis and intracellular transport genes. The immunoglobulin domain-containing transmembrane protein KIAA0319L identified as AAV receptor [49] 4 Journal of Immunology Research ", "Transposon-based mutant libraries The bacterial protein Fap2 binds to the receptor TIGIT and downregulates NK-mediated killing of tumor cells [52] AVEXIS, Avidity-based extracellular interaction screen; NAPPA, nucleic-acid programmable protein array; MPA, microfluidic-based comprehensive protein array; CRISPR, clustered regularly interspaced short palindromic repeat; MS, mass spectrometry; PPI, protein-protein interaction." ] },{ "paper_id": "478eaa49054cba8f6ec4f2df3c6bfddd171e6ac5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ribavirin and sulforhodamine B (SRB) were purchased from Sigma-Aldrich (St. Louis, MO, USA). All other chemicals were a reagent grade. Q7R was isolated from aerial parts of Houttuynia cordata using a previously described method [15] ." ] },{ "paper_id": "47939863a50677044e74f69efc9b22a80d37562f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tamba Town (35 \u2022 9 42 N and 135 \u2022 26 31 E) is located in a hilly area 150-300 m above sea level, 50 km northwest of Kyoto City, Japan ( Figure 2 ", "Miyazaki" ] },{ "paper_id": "479ade65b7f5219559c4d8cc48c1c2f90bda977f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Entropies for predictors shown in Fig. 5 and location probabilities in Additional file 7 were calculated as", "For Fig. 2 mean absolute errors were computed as", "For Fig. 3 errors expressed in units of distance were calculated as" ] },{ "paper_id": "479b8abcecf4072618ebe266fb3d47b4b72ea91f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The NF-\u03baB pathways regulate the activities of a family of five transcription factors (RELA (p65), RELB, c-REL, NFKB1 (p105/p50) and NFKB2 (p100/p52)) that play numerous roles in physiological, but also pathophysiological, conditions [1] . The pivotal role of NF-\u03baB in promoting several of the ten hallmarks of cancer is well established and has been the subject of excellent reviews [2] [3] [4] .", "A considerable number of reports addressing the mechanisms of ER stress have used chemical compounds to induce the UPR, in particular tunicamycin, thapsigargin, dithiotreitol (DTT), proteasome inhibitors and brefeldin A [6] . Tunicamycin inhibits ER-associated glycoprotein synthesis [29, 30] , while thapsigargin, a sesquiterpene lactone isolated from the plant, Thapsia garganica L., has long been known to potently inhibit the sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA) [31] . Thereby, thapsigargin depletes Ca 2+ from the ER and is highly cytotoxic [32] . This has led to the testing of thapsigargin as an anti-cancer agent [31] . Another UPR-inducing compound is DTT, a reducing agent that disrupts disulfide bonds and thus, results in the accumulation of unfolded proteins [33] . In this review, we will specifically refer to mechanistic conclusions derived from such approaches using chemical effectors that allow exact and reproducible control of the experimental conditions, as opposed to alternative, more physiological settings", "A further inhibitor acting on the PERK-eIF2\u03b1 pathway is salubrinal. This compound suppressed eIF2\u03b1 dephosphorylation through the GADD34/PP1 and CReP/PP1 complexes [105] . Recently, salubrinal was shown to inhibit TNF\u03b1 (but not IL-1)-induced activation of NF-\u03baB and the expression of Ccl2/Mcp-1. This effect was not abrogated in cells with siRNA-mediated suppression of eIF2\u03b1, suggesting that the salubrinal effect occurred through PP1, independent from eIF2\u03b1. In support of this, the same effect was seen with guanabenz, another PP1 inhibitor [106] ." ] },{ "paper_id": "47aa21ec26143c3b7a9ff3fa57eb20634cc41940", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "[33]", "Sentrix MouseRef-8 cDNA array (Illumina)." ] },{ "paper_id": "47af8168767ac2a465a3744cffea615594a982fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recommendations:", "Here, I outline four potential objections and respond to them. These are:", "I respond to these in turn." ] },{ "paper_id": "47b84b720b0601da21090660ed223b7cfa1150cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study received exempt review status from the Human Subjects Division at the University of Washington. Analyses were performed with STATA statistical software (version 10.1; STATA Corporation; College Station, TX)." ] },{ "paper_id": "47c38815f36cc14e7160f1890cda9f39b7e1d778", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A similar approach has effectively estimated malaria activity in Thailand in the period 2005-2010 [14] .", "Please see Additional file 1 for translations of the abstract into the six official working languages of the United Nations.", "A systematic review published in 2014 by Nuti et al. highlighted that in recent years researchers have been increasingly utilising GT for a diversity of health topics with some successful applications in the field of infectious disease surveillance, especially in countries with high Internet penetration levels [7] . For instance, GT has been efficaciously used to develop a model, known as Google Flu Trends, which is able to provide early warning of increases in influenza-like illness (ILI) incidence one to two weeks before traditional influenza and ILI surveillance systems, but with some limitations [8, 9] ." ] },{ "paper_id": "47cf6a3f1e96d00834269394edef8c83f61ef1c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We divided monthly admission episodes by relevant population denominators to obtain admission rates, and stratified analyses by drug type, age group, and diagnosis codes. Our study received ethical approval from the Institutional Review Board of the University of Hong Kong.", "In conclusion, this study demonstrates the value of using electronic hospital records to analyze medication use, and identifies considerable oseltamivir use each year among inpatients in Hong Kong." ] },{ "paper_id": "47d93c4d0e435b2da5ebc11b4404ed209447f5a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PVDF membranes. Viral titer was evaluated by gradient dilution. The packaged lentiviruses were designated as Lv-ACE2 and Lv-ACE2-RNAi." ] },{ "paper_id": "47d9a4720ad71e2f3fa79c9b54ff23ababcec330", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consent for publication \"Not applicable\" see comment above", "The authors declare that they have no competing interests.", "Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations." ] },{ "paper_id": "47dbf69e1dd55cac224b406467542111d2124c06", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "During travel, travelers are often exposed to unfamiliar physical and environmental conditions or unknown risk factors. Travel medicine professionals must respond to travelers accurately and individually concerning the health risks associated with travel, and provide preventive measures that include information on recommended vaccines, malaria chemoprophylaxis, health education on water and food, measures to protect against insects or related to disease transmission through sexual contact, air or animal bites, or even self-treatment measures for diarrhea [4] .", "During the past six decades, international travel, especially tourism, has undergone unprecedented growth and diversification. Economically, tourism has become one of the most important and fastest growing sectors in the world.", "Analysis of descriptive statistics was performed with Microsoft Excel 2011 and IBM SPSS 22.0." ] },{ "paper_id": "47dfb70a9174ea549a6850eb64223361ff14e597", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "47dffc938eba5dd824d4f715af096791b0d2d04b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Opsonization of pathogens for phagocytosis; chemotaxis; modulation of virus-induced respiratory burst (84, 85, 135, (138) (139) (140) (141) Eosinophils Inhibition of eotaxin-triggered chemotaxis and eosinophilic cationic protein degranulation; increased apoptosis in activated cells; reduced TGF-\u03b21 production (142) (143) (144) Lymphocytes Inhibition of T cell proliferation and activation; repression of TLRs activation and TNF-\u03b1, IFN-\u03b3, Th17, and IL-6 expression; delayed apoptosis after short-term incubation; induction of apoptosis in activated lymphocytes after extended incubation (137, (145) (146) (147) (148) (149) (150) (151) (152) Basophils", "In situ hybridization IHC (40) IHC (10, 40) Seminal vesicle IHC (10)", "The main reported individual steps leading to SP-D-enhanced experimental outcomes relevant for atherosclerosis are illustrated in Figure 5 .", "The phenotype of GPR116 (Ig-Hepta) deficient mice is very similar to that of Sftpd \u2212/\u2212 mice, including accumulation of surfactant lipids, enlarged alveoli, hypertrophy of type II alveolar (AT-II) cells, decreased surfactant uptake by type II alveolar cells (AT-II cells), accumulation of enlarged foamy macrophages, and enhanced expression of the matrix metalloproteinase 12 (Mmp12) gene. Therefore, it was hypothesized that this adhesion class of G protein-coupled receptor may interact with SP-D. GPR116 is highly expressed in type II pneumocytes and immunoprecipitation of flag-tagged recombinant proteins supports SP-D as a likely ligand of this receptor (177) ." ] },{ "paper_id": "47ee3efc99d4ed2a08a7c8e677adfd98425dade6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At two days post-inoculation, infected pigs had an increased frequency of circulating CD4 + CD25 + Foxp3 + T regs , reduced frequency of CD4 -CD8 + and CD4 + CD8 + T cells, and enhanced IL-10, IL-4 and IL-12 secretion [57] .", "Viruses 2012, 4 834", "Inada and colleagues demonstrated that mice challenged with heat-inactivated or killed LDV induced a strong virus-specific delayed-type hypersensitivity (DTH) reaction, whereas a delayed hypersensitivity reaction was undetectable in young (1-3 month-old) mice challenged with live virus [63] . In these experiments pretreatment with cyclophosphamide partially restored the DTH response, which was attributed to cyclophosphamide mediated elimination of suppressor T cells [64, 65] . Live virus also elicited a DTH response in old mice (> 8 months) without cyclophosphamide treatment, which is not surprising in light of the fact that older mice have reduced suppressor T cell activity. The cumulative findings from this study suggest that inoculation with live LDV induces suppressor T cells, and that this dampens the virus-specific delayed hypersensitivity response [63] ." ] },{ "paper_id": "47fb645312a069e65bb7557c58204244c3c92953", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "APP virulent strain S259 was purchased from the Control Institute of Veterinary Bioproducts and Pharmaceuticals of China. The cells were cultured in Trypticase Soy Broth (TSB, Merck, Germany); nicotinamide adenine dinucleotide (NAD, Sinopharm, Shanghai, China) was added to the medium at a final concentration of 0.01%. One-hundred-milliliter cultures were shaken overnight at 37\u00b0C on a rotary incubation shaker running at 180 rpm until they reached the late stage of exponential phase. Cells were harvested by centrifugation at 10,000 \u00d7g for 10 min at 4\u00b0C and washed three times with phosphate buffered saline (PBS).", "Washed APP S259 cell pellets were re-suspended in 5-mL sample preparation solutions (7 M urea, 2 M thiourea, 4% w/v CHAPS, and 40 mM DTT) and sonicated in an ice bath for 50 cycles (5 s on, 10 s off) at a power setting of 200 W. The cell lysate was incubated for 30 min at 25\u00b0C to solubilize proteins (vortexing every 10 min) and centrifuged at 10,000 \u00d7g for 20 min at 25\u00b0C to pellet the insoluble components. To precipitate proteins, the cleared supernatants were treated with pre-chilled 100% trichloroacetic acid (TCA) to a final concentration of 10% and incubated in ice water for 30 min. Precipitated protein was collected by centrifugation at 10,000 \u00d7g for 10 min at 25\u00b0C and washed twice with pre-chilled acetone. The final pellet was air-dried." ] },{ "paper_id": "4800117f48b3a425e71f4271d450a1c07536765a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lipids. POPC was purchased from Avanti Polar Lipids (Alabaster, AL, USA), while cholesterol (Chol) was from Sigma." ] },{ "paper_id": "48106886ec5b19e6cc62abf552ff3529f1d8aca3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In all RCTs, fever was defined as having body temperature 538\u00b0C. Clinical respiratory illness (CRI) and ILI were in the primary outcomes in three clinical trials. CRI was defined as two or more respiratory symptoms or one respiratory symptom and a systemic symptom and ILI was defined as fever 538\u00b0C plus one respiratory symptom [21] [22] [23] .", "We analysed a dataset of laboratory-confirmed viral respiratory infections collected from three clinical trials of HCWs where active surveillance for respiratory viral illness was conducted in prospective follow up [21] [22] [23] . The same methods, data collection forms and outcome measures, were used across the three studies, allowing the data to be pooled [21] [22] [23] . Two studies were conducted in Beijing China: trial 1 (2008/2009) and trial 2 (2009/2010) and another study (trial 3) was conducted in Hanoi, Vietnam in 2010/2011 [21] [22] [23] . In all clinical trials, participants were asked to complete diary cards on a daily basis to collect information on number of working hours, patients seen, mask use hours, high-risk procedures performed and appearance of respiratory symptoms. Thermometers were given the participants to measure their temperature daily and at symptom onset. Symptomatic cases were asked to complete sick patient follow-up forms and detailed information was collected on the following symptoms: chill or fever, cough, congestion, runny nose, sore throat, sneezes, lethargy, loss of appetite, abdominal pain, muscle or joint aches. Swabs of both tonsils and the posterior pharyngeal wall were collected on the day of reporting.", "CRI symptoms were present in 84\u00b78% (137/158) of HCWs with laboratory-confirmed viral infections and 90\u00b79% (20/22) laboratory-confirmed influenza infections. The corresponding rates of ILI in the two groups were 9\u00b75% (15/158) and 13\u00b76% (3/22), respectively.", "The rate of fever also varies between influenza strains, being more common in influenza A strains than B, and higher in H3N2 [7] [8] [9] [10] 18] . Fever is a commonly reported symptom during influenza outbreaks and pandemics due to novel and more virulent nature of strains. In China 67\u00b74% of the patients infected by influenza A(H1N1)pdm09 had fever [19] . In another study in Beijing 465 suspected ILI cases were tested and of those 318 (68%) were positive for influenza virus (pandemic H1N1-165 and seasonal influenza H3N2-153) and all had history of fever [20] ." ] },{ "paper_id": "481c14a837af6dd6d5a5d8f3a26ae6cc51cca2f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Objectives The aim of this study was to compare the performance of 22 RAD tests in the diagnosis of EI.", "The study demonstrated the importance of choosing the right RAD tests as only three of 22 were fit for diagnosing EI. It was also indicated that even RAD tests with the highest sensitivity serve only as an adjunct to molecular tests because of the potential for false-negative results.", "Background Equine influenza (EI) is a highly contagious disease caused by viruses of the H3N8 subtype. The rapid diagnosis of EI is essential to reduce the disease spread. Many rapid antigen detection (RAD) tests for diagnosing human influenza are available, but their ability to diagnose EI has not been systematically evaluated." ] },{ "paper_id": "48215f45ce10b06c8f96b087cf1d72de2b40662a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "General Procedure for Preparation of N-[4-(1H(2H)-benzo[d][1,2,3]triazol-1(2)-yl) phenyl]p-R-arylcarboxamides (7a-h and 8a-h)", "General Procedure for Preparation of 1- [4-(5,6-dichloro-2H-benzo[d] [1,2,3] triazol-2-yl)phenyl]-3-alkyl and aryl-uree (10a-k)", "Vero ", "To a stirred solution of the 1-(4-aminophenyl)-5,6dichlorobenzotriazole (1a) and 2-(4-aminophenyl)-5,6dichlorobenzotriazole (1b) (1.4 mmol) in anhydrous dimethylformamide (DMFa) (10 mL) was added dropwise a solution in DMFa (2 mL) of appropriate R-benzoyl chloride (1.68 mmol) (ratio 1: 1+20%). The solution was then stirred at 80 \u2022 C for further 0.5 h (7a,d and 8d,f), 1h (7b, c, e, g and 8a), 1.5 h (8b), 2h (7f), 3 h (8e), 12 h (8c), 2 4h (7h), and 72 h (7g). After cooling, the obtained solids were filtered, and water was added to achieve quantitative precipitation. The resulting precipitates were collected by filtration, washed with water, and the crude products were purified by flash chromatography (7c, C/M = 95/5), (7d, C/M = 98/2), (7g, 7h, PE/EA = 7/3), (8b, C/M = 9/1), (8c, PE/DE = 3/7), (8d, PE/EA = 6/4), (8f, PE/DE = 75/25) or via recrystallization by ethanol (7a, 7b, 7e, 7f, 8a, 8e, 8g, 8h). C: chloroform, M: methanol, PE: petroleum ether, DE: diethyl ether, EA: ethyl acetate.", "Cell pretreatment with 10d failed to prevent viral infection, and time of drug addition assays confirmed that 10d effectively inhibited RSV activity in infected cells only when added during or immediately after infection. Both these results supported the hypothesis that 10d could inhibit viral infection by hampering the binding and penetration processes of the virus into the host cells." ] },{ "paper_id": "4826b9556f50d690979be891d770b33e25003440", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Probiotics use in the clinical practice", "Rotavirus [26] Candida albicans [27] Pseudomonas aeruginosa [28] A d e n o v i r u s [ 29] Candida glabrata [27] Klebsiella [30] Norovirus [31] Aspergillus fumigatus [32] Cronobacter sakazakii [33] A s t r o v i r u s [ 34] Shigella boydii [35] Echovirus [36] Coagulase-negative Staphylococcus [37] Cytomegalovirus [7] Clostridium spp. [38] C o x s a c k i e v i r u s [ 39] Campylobacter [40] Torovirus [41] Enterobacter cloacae [42] Coronavirus [43] Salmonella [44]" ] },{ "paper_id": "482ceb8b002b0c3f8ec6f26fc0093dd90cec2b0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The fresh plant parts of R. fairholmianus were collected from Marayoor Shola forest, Kerala, India, during the month of September 2010. The collected plant material was identified and authenticated by (Voucher specimen number BSI/SRC/5/23/2010-11/Tech. 1657) Botanical Survey of India, Southern Circle, Coimbatore, Tamil Nadu. The roots were extracted successively using acetone in a soxhlet apparatus for 72 hours. The extract was concentrated to dryness under reduced pressure in a rotary evaporator.", "The FTIR spectrum was recorded using a Nicolet 5700 (Thermo electron, Madison, WI, USA) spectrometer at room temperature. The bioactive compound was dissolved in dimethyl sulfoxide (DMSO) and scanned in the range of 4000-400 cm \u22121 .", "2.5.1. UV Spectroscopy. The UV-visible spectrum of the isolated compound in HPLC grade methanol was recorded using a Shimadzu 160 A UV-visible spectrophotometer at a range of 280-400 nm." ] },{ "paper_id": "48346dec8180ad8bc1f1bcab9fb95f52d13c920f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Significance was calculated with Mann-Whitney test using GraphPad Prism software.", "To measure the interferon concentration in the sera, blood was sampled from na\u00efve mice or four days after MHV infection or one hour after imiquimod treatment. Sera were separated by spinning the blood at 23006 g for 15 ", "Livers of MHV-infected mice were sampled, fixed in 4% neutral buffered formalin, and embedded in paraffin. Seven mm liver sections were stained with hematoxylin and eosin. Total liver sections were examined by light microscopy and foci of hepatocellular necrosis and inflammation were scored in a semiquantitative manner." ] },{ "paper_id": "4836e3bd00d59bf1af3b4f5000cf917c71655658", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "( _ x\u00f0t\u00de \u00bc g\u00f0t; x\u00f0t\u00de; y 0 \u00f0t\u00de; u\u00f0t\u00de\u00de y\u00f0t\u00dejx\u00f0t\u00de $ f \u00f0h\u00f0x\u00f0t\u00de\u00de; y 0 \u00f0t\u00de\u00de \u00f01\u00de", "Sinusoidal \u03b2", "for (j = 1:J) do 5." ] },{ "paper_id": "485b039c35ff2b0b0d592af3856fd9de63d47d01", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Respiratory viral infections are a major cause of morbidity and mortality worldwide. However, their characterization is incomplete because prevalence estimates are based on syndromic surveillance data. Here, we address this shortcoming through the analysis of infection rates among individuals tested regularly for respiratory viral infections, irrespective of their symptoms.", "Projects Agency contract W911NF-16-2-0035. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.", "We carried out longitudinal sampling and analysis among 214 individuals enrolled at multiple New York City locations from fall 2016 to spring 2018. We combined personal information with weekly nasal swab collection to investigate the prevalence of 18 respiratory viruses among different age groups and to assess risk factors associated with infection susceptibility." ] },{ "paper_id": "485b745f048cbac696175c1ca05eee8fb46ba026", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reed and Muench method was applied to determine infectious virus titration with a standard TCID 50 protocol by means of MA104 cells. 57 ", "All numerical results are expressed as Mean \u00a7 SEM. Statistical comparisons were analyzed by Mann-Whitney test for the data without normal distribution or t test for the data with normal distribution. P-values less than 0.05 were considered to be statistically significant. Analysis was performed using GraphPad Prism Version 5 (GraphPad Software Inc., La Jolla, CA). ", "No potential conflicts of interest were disclosed." ] },{ "paper_id": "4867e0d05f067189d610ca8e764d52dcc50a7b49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We next investigated EGFR phosphorylation during RSV infection. As described in ", "All animal studies were approved by the NIH Institutional Animal Care and Use Committee (IACUC) under the animal study protocol number LID 34E. The National Research Council's Guide for the care and use of laboratory animals and the Public Health Service Policy on humane care and use of laboratory animals served as the guidelines for the care and use of mice in this study." ] },{ "paper_id": "486ad1536fb8f8a3ac0f4a38ee97fc8af2435cc0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For fluorescence in situ hybridizations (FISH), tissues of jejunum were fixed overnight in 4% PFA, paraffin embedded, and sectioned at 10 \u03bcm. The probe sequences targeting Lgr5, Olfm4 and Lys (Lysome) was: Lgr5 probe (5\u2032-FAM-GACGACAGGCGGTTGGACGATAGGT-FA M-3\u2032), Olfm4 probe (5\u2032-FAM-CACTGACACCTCGCC ACCATTCCA-FAM-3\u2032) and Lys probe (5\u2032-CY3-GCA CCGATCATAGACCTTGGCCTGTA-3\u2032). The protocols used for in vitro transcription and in situ hybridization were previously described 44 . All images were acquired and processed with Zeiss Axio-Imager Z1 with apotome or Leica SP5 confocal microscope.", "Flow cytometry (FACS) experiments were performed with the following antibody: Alexa Fluor\u00ae647-Lgr5 (BD; 562912), FITC-CD24 (BD; 555427), PE-Cy7TM-CD24 (BD; 561646), PerCP-CyTM 5.5-CD13 (BD; 561361). FACS measurements were performed using a BD-FACS service device and analyzed with FlowJo software (FlowJo LLC). MFI is defined as the difference in the signal intensity between an unstained control and a stained sample. For sorting, a FACS Aria SORP device (Becton Dickinson) was used. ", "Immunoprecipitation (IP) and co-immunoprcipitation (CO-IP)" ] },{ "paper_id": "4873940c333a45e7913856b356309e2e4feffb7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4873db67f7f48325e1c63ccfa093d5077a9c9b50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All cell-lines were cultured in a 8% CO2 humidified atmosphere at 37uC and grown in Dulbecco's modified Eagle's medium (Invitrogen) with 10% fetal calf serum (Cambrex Corp.).", "Following database searching, only spectra that exceeded the corresponding MASCOT's threshold score for identify (set at the 95% confidence level) are here reported. The matching estimated false positive discovery rate is well acceptable and is only between 2 to 4% at the individual spectrum level as previously assessed [60] ." ] },{ "paper_id": "48764be42938595e40cb6c0bc73fc891a6e962e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Specialized TLRs for viral sensing are TLR-3 that recognizes dsRNA and localizes to the plasma membrane or endosome [25, 26] . The endosomal TLR-7 and TLR-8 recognize viral single-stranded RNA (ssRNA) [27, 28] . TLR-9 recognizes unmethylated CpG DNA of bacteria and viruses [29, 30] . Some evidence suggests that TLR-4, TLR-6 and TLR-2 play a role in recognition of RSV [31, 32] while MeV hemagglutinin is recognized by TLR-2 [33] (Figure 1 ).", "Viruses 2010, 2 2542", "The cytosolic mediators of viral sensing, the RLRs, include the RIG-I and melanoma differentiation-associated gene 5 (MDA5). RIG-I is activated by ssRNA or 5'-triphosphate double stranded RNA (dsRNA) and MDA5 by dsRNA [34] [35] [36] . Both MDA5 and RIGI signal through the mitochondrial-associated protein known as interferon beta promoter stimulator-1 (IPS-1) [36] [37] [38] [39] [40] ( Figure 1 ). The role of a third member of the RLR family, the RNA helicase Lgp2, is less understood. Lgp2 has been implicated both as a negative and positive regulator of MDA5 and RIG-I function [41] [42] [43] ." ] },{ "paper_id": "4878d966944fb0b66d96fec7b7dff3f79194f26d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Graphing and statistical analysis of data was performed using GraphPad Prism (GraphPad Software, San Diego, USA). An unpaired Student's t-test was used to compare two sets of data. When comparing three or more sets of values, the data were analysed by one-way analysis of variance (ANOVA; nonparameteric), followed by post-hoc analysis using Tukey's multiple comparison test. p values \u2264 0.05 were considered significant." ] },{ "paper_id": "488cfd5c8020cb081650f65c3cf7646ab9079654", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. The human coronavirus HKU1 strain reported here was deposited in GenBank under the accession number MH940245 and SRA accession number PRJNA509533.", "Human coronavirus HKU1 (HCoV-HKU1) was first detected in a patient with viral pneumonia from Hong Kong in 2004. Here, we report the first complete genome sequence of HCoV-HKU1 from Thailand, obtained from a nonill person who worked in a bat cave. Phylogenetic tree analysis revealed it as a group B HCoV-HKU1.", "Phylogenetic tree of HCoV-HKU1 using maximum likelihood method with 1,000 bootstrap replicates. The whole-genome sequence of HCoV-HKU1 (29,811 bp) from Thailand is colored in blue; it belonged to group B genotype and was closely related to HCoV-HKU1 from Hong Kong (GenBank accession number AY884001)." ] },{ "paper_id": "488e1294b604a8ea66aa4f21f431b52723dfc8de", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "489040d34aa5dc8e6eba3d4e9d3d48f0bcc6061f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A mysterious illness causing pneumonia in December 2019 in Wuhan, China is now growing into a potential pandemic. These pneumonia cases were eventually characterized to be caused by a novel coronavirus (2019-nCoV) 1 , of which Severe Acute Respiratory Syndrome (SARS) 2 and Middle East Respiratory Syndrome (MERS) 3 are members. SARS and MERS famously caused their own outbreak concerns when they were originally identified. SARS caused significant economic damage to Hong Kong and Southern China, before spreading to other countries. Ultimately, SARS infected up to 8,098 people and caused 774 deaths according to the World Health Organization (WHO) 4 .", "The simplest and most direct approach to combating 2019-nCoV during the outbreak would be one to neutralize the virus from entering cells, the function that antibodies normally perform in the body 39 . For the reasons mentioned above when discussing neutralizing antibodies, it will be difficult to validate a broadly neutralizing antibody quickly, and a challenge to make sure that the mutating RNA virus will not escape its neutralization. A cocktail antibody approach could be undertaken as was explored to treat the Ebola pandemic 40 , but would add complexity to the manufacturing process.", "Underlying data No data are associated with this article. " ] },{ "paper_id": "489581af56b842073e88412d6d28cf89c2e08d0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The stochastic variant was implemented as a continuoustime Markov process approximated via a multinomial modification of the t-leap algorithm [14] with a fixed time step Dt \u00bc 10 22 week.", "and N, the population size, assumed constant (electronic supplementary material, table B1).", "Subject Areas: health and disease and epidemiology, computational biology" ] },{ "paper_id": "4897212ecb3c7d659bda8a992f12f63d3abad13e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tannins are a complex group of polyphenolic compounds which are present in several plants as secondary metabolites against pathogens [12] . In ruminants, in vitro and in vivo trials have demonstrated that tannins can improve animal performance and reduce the impact of gastrointestinal parasitism, nitrogen pollution, and methane emission from rumen fermentation [13, 14] . Tannins may interfere with digestive processes by binding dietary protein, by modulating the activity of rumen micro-organisms, and by reducing the growth of the bacterial population [15] [16] [17] .", "This in vivo blinded study was approved by the Institutional Animal Care and Use Committee (OBA, Pisa, prot. n. 33,479/2016 of 29.06.2016) and was carried out at the University of Pisa's dairy farm, where nearly 100 animals are maintained in free-stall conditions.", "There were no alterations at the physical examination, and the hydration status was normal for all calves during the entire study period. No differences between groups were found for milk intake. Thus, no pharmacological treatments or fluid therapy were needed." ] },{ "paper_id": "48aba0f18c129840aeb900f176b1f40de0b598a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hemagglutination inhibition (HI) assay. HI assays were performed according to the standard method 41 .", "Scientific RepoRts | 6:37915 | DOI: 10.1038/srep37915", "Mouse study. Mice had free access to food and water and were maintained on a 12-h light/12-h dark cycle." ] },{ "paper_id": "48adda1d8bd8fc96174dc65e1d51bc16820387f5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In accordance with French ethical rules for epidemiological surveillance studies and the rules in place at APHP (Assistance Publique-H\u00f4pitaux de Paris) we obtained the non-opposition of the patient at hospital admission. [8, 9, 24] , as confirmed by our internal comparisons and method validations. Their reliability was also assessed throughout the study period by QCMD controls (Glasgow, UK).", "The results obtained for the 6532 (90.7%) samples for which the type of medical unit was recorded are depicted in Fig 2 and ", "intensive care units, emergency, infectious diseases, internal and general medicine departments, and the other two are geriatric hospitals. All nasopharyngeal swabs, bronchial aspirates and bronchoalveolar lavages were placed in Virocult MWE (Sigma, St Louis, MO, USA) transport medium for transport to the virology laboratory of Bichat-Claude Bernard Hospital. Repeat samples, defined as samples taken from the same part of the respiratory tract (upper or lower) of the same patient in the same month, were discarded." ] },{ "paper_id": "48bd5f768f3464ac253a120d2eddeb89c323f324", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We also describe a new paradigm in target nucleic acid quantification through the use of a chip-based amplification-diffusion channel. This method facilitates end point detection and enables the estimation of target (NA template) concentration from the lengths of emitting columns, akin to reading temperature in a mercury thermometer from the length of the mercury column.", "POC molecular diagnostics devices were first reported in the mid-1990s [45] , single-chamber PCR chips made in glass or silicon. In the last twenty years, these chips have evolved to more viable polymer materials, have integrated sample prep functions, included on-chip storage of reagents and buffers, and accommodate low-cost detection schemes, such as smartphone cameras, and as such now offer convenient, low-cost diagnostics suitable for use outside of traditional clinical laboratories, including resource-limited settings throughout the world.", "To date, most rapid tests for biomarkers are immunoassays [35] . The lateral flow strip test, or immunochromatographic assay, such as found in home pregnancy tests, is an elegantly simple implementation of immunoassays employed to detect antigens or antibodies in urine, blood, food, and water. Molecular assays for DNA and RNA targets offer many important advantages over immunoassays, including greater sensitivity (typically by a factor of 1000 or more) and higher specificity. The high sensitivity is due to the ~million fold amplification of the target sequence. The amplicons can be conveniently detected with intercalating dyes or reporters that specifically label the amplicons, allowing measurements with relatively simple fluorescence detectors such as CCD cameras or photodiodes, or less commonly with electrochemical sensors. Further, unlike immunoassays which rely on monoclonal antibodies and may require weeks or months of development time, NAATs utilize nucleic acid oligos for hybridization or as primers for enzymatic amplification, which can be designed, synthesized, and validated in a short timeframe-in some cases as short as one week-once the pathogen has been at least partially sequenced [36] ." ] },{ "paper_id": "48c0614e47f4de8d1d1f1edbf9c9663cd014926d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Furthermore, the late transcription elongation factor H3, the transcription termination protein A18 and the 2'-O-methyltransferase O1 possess conserved ubiquitination sites.", "Proteins with conserved ubiquitination sites assigned to morphogenesis comprise the protein F8, metalloendopeptidase H1, assembly protein H8, telomere-binding protein L1 and the virion protein S1.", "Besides subunits of the CPXV Pol itself, also viral transcription factors of all three classes contain ubiquitination sites. These include the A8 protein, a subunit of the early transcription factor, the A24 protein, an intermediate transcription factor subunit, and A1, a viral late transcription factor. Eukaryotic transcription factors seem to be activated and also tagged for degradation by ubiquitination 11,12 , but no mechanism has been described for OPV yet." ] },{ "paper_id": "48c1c1a52958c6fd6f18ff10121c1336b9eb1395", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Measuring the magnitude and impact of China's health assistance to Africa", "China's approach to aid: altruism or opportunism China's engagement in Africa health aid has differed from aid provided by traditional Western donors, particularly in the way China builds on its own prior experiences in building its own health system as a developing country, and in the manner in which it places special emphasis on the issue of the national sovereignty of recipient countries.", "The 2006 document \"China's African Policy\" granted the Forum on China-Africa Cooperation (FOCAC) a central role in shaping the China-Africa relationship. At each FOCAC summit since 2000, the Chinese government makes new assistance commitments, often including health-related aid. For example, at the Second Summit of the FOCAC in December 2015, Chinese President Xi Jinping announced a 60 billion USD package to support cooperation with Africa for the following three years, with public health being one of the areas to be covered [9] ." ] },{ "paper_id": "48c20fe82a21edeefb8e1966189db32213a446fc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Infections by herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2) are the most common opportunistic infections in HIV-1 infected patients. The risk of the onset of HSV infections in HIV positive patients has been related to the effect of HIV over the immune system. A recent study has also demonstrated that HIV proteins tat and gp120 are capable of disrupting TJs, facilitating the paracellular spread of both HSV-1 and HSV-2 [71] .", "The claudin family of proteins is another important component of the TJ. Claudins are tetraspaning proteins whose main function is to regulate the passage of ions across the paracellular space [14] [15] [16] . To date, 27 claudins are known in humans and their differential expression in different epithelia allows the paracellular transport of specific ions in each tissue.", "The role of several viral proteins with PBM domains has yet to be determined but there is clear evidence of the importance of TJs not only for virus cell entry but also for their spread inside their hosts." ] },{ "paper_id": "48cc713567a278caa4b15e0528e1babe71efe44c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "48d2cdd1975a60aa6d7ab15b51b523b10529b038", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vero cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM, GIBCO) supplemented with 10% fetal calf serum (FCS), 100 units/ml penicillin, and 0.1 mg/ml streptomycin.", "Oligopeptide comprising the amino acids 477-491 of preGP-C was chemically synthesized and covalently linked to keyhole limpet hemocyanin (KLH, Pierce) as a carrier protein by the cross-linker agent N-[\u03b1-maleimidoacetoxy] succinimide ester (AMAS) and used for repeated immunization of rabbits as described before [7] . The obtained antiserum Rb-\u03b1-GP2 was tested by peptide standard ELISA [18] and used for immunoblot analyses.", "Lassa virus belongs to the family of Arenaviridae which includes other important human pathogens like Machupo virus, Junin virus, Guanarito virus and Sabia virus as well as the prototype of this family, Lymphocytic Choriomeningitis virus (LCMV). Lassa virus is endemic in certain parts of West Africa and causes an estimated 150 000 clinical cases of a systemic viral illness per year, with a mortality rate of 10-15% [1] . Lassa fever is not only a public health concern in endemic areas, it is also sporadically exported to other parts of the world [2] ." ] },{ "paper_id": "48f553c843618f0cc189f9067685f551049a018f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The general term of the pseudo-likelihood for case i is:", "which is proportional to:", "Epidemiological pseudo-likelihood. The epidemiological pseudo-likelihood V 2 i is computed as:", "for this transmission to occur. Closer examination of the patterns of mutations between Sin2500, Sin2748 and Sin2679 bring further support to this scenario ( Fig. 6 ", "Moreover, carried pathogens are also more likely to cause multiple colonizations of the host, resulting in several lineages coexisting within the same patient. Our model assumes that a single pathogen genome exists within each host, and is therefore not designed to account for multiple infections. A simple workaround would consist in duplicating cases of multiple infections into single infections, assuming that multiple infections are made of independent, single colonization events. However, this would not allow for disentangling multiple infections from mere within-host evolution of a single lineage. A more satisfying approach would consist in modeling explicitly the evolution of isolates within host, but this will likely result in a much more complex model and is beyond the remit of our current approach." ] },{ "paper_id": "4903f4b49cff9b009f9413ae245ecb75bd97960c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(i) VSVpp infected cells were fixed 18 h p.i. and representative fluorescence microscopical pictures were taken (data not shown).", "Thus, in contrast to surface proteins of coronaviruses, the filovirus surface glycoprotein is able to infect bat cells in the context of a VSV pseudotype system.", "Apart from coronaviruses, bats (order Chiroptera) have been shown to host a variety of emerging viruses [34, 35] , comprising different viral families like Orthomyxoviridae [36] [37] [38] , Rhabdoviridae (especially the genus Lyssavirus) [39] [40] [41] , Paramyxoviridae [42] [43] [44] [45] [46] , Filoviridae [47] [48] [49] , and others (see [34] for more information)." ] },{ "paper_id": "4913c28e343a6cf2f8031799ff3b372e0e873bf5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cleavage Site" ] },{ "paper_id": "491a64ac4e81a8110aa76009bf9f6275712500bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where s is the GC content at the third codon position, namely the GC3s.", "P xy \u00bc f xy f y f x f x , f y represent the occurance of the nucleotide X, Y respectively, while f xy denotes the observed occurrence of dinucleotide XY. f x f y denote the expected occurance of dinucleotide XY. It is considered that P xy > 1.23 suggests over-represented while P xy <0.78 suggests underrepresented.", "Correlation analysis of nucleotide composition with A3s, T3s, G3s, C3s, GC3s, Aroma, Gravy, ENC, 1st axis and 2nd axis were calculated using Graph Pad Prism 6.0." ] },{ "paper_id": "491b2bd6232dd000fc79008d3d7044c2a1fece64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All computation was carried out using R version 3.4.0 25 .", "For each simulation, we proceed as follows:", "See Supplementary Material for detailed R-code." ] },{ "paper_id": "491f000353cbe2d030d16077ecb01f02d7c6bf3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Typically, 100 seeds were collected and crushed in Oster Blender (Model 4655; 600 watt, 3 speeds) with ice crushing blade (#4961 USA). One scoop (\u223c90 mg) of the seed powder was transferred to a tube containing 4 mL of lysis buffer (0.2 M NaOH). Each tube was shaken for approximately 5 seconds and incubated at room temperature (RT) for 1 minute to let the particulates settle down.", "The report also demonstrates the ease and reliability of the method starting from a laboratory sample such as purified DNA template or whole seed sample encountered in a field.", "The PCR products were mixed with 10x BlueJuice6 Gel Loading Dye (Invitrogen) and run in 8-well 1% precast agarose gel containing 1% ethidium bromide. Pictures of agarose gels were captured using the Molecular Imager5 Gel Doc6 XR.", "RPA has been successfully employed in a number of reports for both human IVD [23] [24] [25] [26] [27] and veterinary applications [28, 29] . Importantly, substrate templates suitable for RPA can be obtained from crudely treated sample material. For this reason, the simplicity of the nucleic acid amplification can be mirrored by uncomplicated and simple front-end sample preparation procedures." ] },{ "paper_id": "491f229f1a4bc9fb8f4c85097040666e5ad1c455", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sensitivity analysis: Impact of errors in reporting dates", "In this analysis, we choose a single imputed dataset and randomly jitter the onset dates of 10% of the sample within 30 days of their observed (or imputed) onset date.", "Our results are consistent with others in showing decreased transmission with age. We show that results can change markedly when we make the account for differential healthcare seeking behaviors by age." ] },{ "paper_id": "4922ec2dbaef5cf37c816d3b8bf8ef2003466949", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Participant age, sex, occupation and highest level of schooling were obtained by interview in fall 2000.", "Checklist S1 STROBE checklist. " ] },{ "paper_id": "49241d35c68b9ffeb0057758abdf00fc18cce2f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The HIV-1 Gag IRES mediates translation of both full length Pr55 Gag polyprotein and a N-truncated 40-kDa Gag (p40) isoform lacking the matrix domain [37, 49] . Despite the fact that p40 is produced at a much lower level than Pr55 Gag , this protein seems to be important in wild-type replication of HIV-1 in cultured cells [37] . Expression of p40 has also been observed in all HIV-1 clinical isolates from a large cohort of patients (n = 100) [18] .", "Optimal viral protein synthesis often occurs at the expense of cellular proteins and many viruses have evolved mechanisms that redirect and control the eukaryotic translational machinery. In these cases, viral factors can target the initiation, elongation and termination steps through interactions with key translation factors and mechanisms, which interfere with or disrupt the host translation machinery.", "In HIV-1-infected cells, viral proteins alter cell function by affecting different cellular pathways. HIV-1 viral protein R (Vpr) has been identified as a viral protein capable of arresting cells in the G2/M phase. Vpr mediates G2/M arrest via a complex signaling cascade involving activation of the ataxia telangiectasia mutated and Rad3-related kinase (ATR) [65] . Vpr-induced G2/M arrest also inhibits host protein translation by a process involving the regulation of eIF4E activity ( Figure 1C ) [66] ." ] },{ "paper_id": "4925de9bb1feab39f0ffda885f95b59fd0e10cc7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ancyclostoma spp. X Anisakidae spp. X Balantidium coli X Cryptosporidium spp. X X X X Enantomoeba histolytica X Giardia spp. X Gnathostoma spp. X Oesophagostomum spp. X Pentastomidia spp. X X X Sarcocystis spp. X X X Spirometra spp. X Strongyloides spp. X Taenia spp. Toxoplasma gondii X X Trichinella spp. X X X Trichuris spp. X", "CONFLICT OF INTEREST The authors declare that they have no conflict of interest." ] },{ "paper_id": "492ae848b7e2b20047ac406af1c7712ea6255461", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MeWo cells (1610 6 ) were inoculated with 100 plaque-forming units (pfu) of cell-associated virus. Infected cells were trypsinized at 24, 48, 72 or 96 h post infection (h.p.i.), titrated in 10-fold dilutions, and added to MeWo cell monolayers seeded 24 h before. The number of plaques was determined by indirect immunofluorescence using an anti-VZV antibody exactly as described earlier [89] .", "Metabolic parameters of infected and uninfected NHNP TLAs were measured every 24 h over the course of the experiments to monitor a cellular development profile and to monitor the metabolic status of the tissues. Glucose consumption was determined using the iStat clinical blood gas analyzer using an EC8 + cartridge (Abbott Laboratories, Abbott Park, IL) according to the manufacturer's instructions [60] .", "Human melanoma cells (MeWo, American Type Culture Collection, ATCC, Manassas, VA.) were propagated in Dulbecco's minimal essential medium supplemented with 10% fetal bovine serum, 100 U/ml penicillin and 0.1 mg/ml streptomycin (Sigma-Aldrich, St. Louis, MO) at 37uC under 5% CO 2 [71] . Wild-type and recombinant viruses were passaged on MeWo cells by co-cultivation of infected with uninfected cells at a ratio of 1/5 [72] . MeWo cells for the infection of NHNP cultures were adapted to GTSF-2 medium over two passages prior to harvest of VZV." ] },{ "paper_id": "4930fc9d9e3cb5bea0a97320187aca766f07493d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Construction of lentiviral vectors for wildtype, endodomain-truncated and chimeric forms of Fc\u03b3RII (hCD32)", "Results are shown as means \u00b1 SEM of the indicated number of observations. Statistical difference between groups was determined by the unpaired Students's t-test with a 0.05 significance level. ", "Because clinical observations have reported poor disease outcomes in early seroconverted SARS patients [25] [26] [27] , it would be of interest to test SARS patient sera collected at different time-points after SARS onset. However, we have been unable thus far to conduct conclusive assays on a well characterized serum library; moreover, we have to be cognizant of the possibility that ADE may only occur within a narrow window during the course of an infection and only in a subset of infected patients. The alternative possibility that internalization by macrophages may in fact represent an additional mechanism to control viral spread requires further investigation." ] },{ "paper_id": "49471df378964515ebc4e4f35f1248d84ac7d626", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Calu-3 2B4 cells were cultured in minimal essential media (MEM; Gibco) supplemented with 20% fetal bovine serum (HyClone) and 1% antibiotic antimycotic (Gibco [2] , where isolation of viruses from clinical samples is described. Virus stocks were tittered on VeroE6 cells using standard methods, as previously described [14] . SARS-CoV experiments were derived from the infectious clone of SARS-CoV (icSARS-CoV) as described in [18, 38] . ", "Raw microarray data have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO accession GSE33267 (icSARS-CoV), GSE45042 (MERS-CoV SA 1), GSE56677 (MERS-CoV Eng 1), GSE33264 (IFN-\u03b1, and IFN-\u03b3, Calu-3 treatments), and GSE56678 (IL-1\u03b1, and TNF Calu-3 treatments). All data sets and associated metadata have been submitted to Virus Pathogen Resource (ViPR, http://www.viprbrc.org). Study details can be accessed through the Systems Virology website (http:// www.systemsvirology.org)." ] },{ "paper_id": "495132370917fdb1762cd47fa73e9e6ff94a60b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Institutional Review Board of the University of North Carolina at Chapel Hill approved the protocol for recruiting and collecting blood samples from people. Written informed consent was obtained from all donors.", "Text S1 Supporting tables and figures. (DOCX)", "Vero E6 cells (ATCC CRL-1586) were maintained in MEM supplemented with 10% FCS (Gibco), non-essential amino acids (Gibco), L-glutamine (Gibco) and Anti-Anti antibiotic mix (Gibco) at 37uC in 5% CO 2 . C6/36 cells (ATCC CRL-1660) were maintained in MEM supplemented with 5% FCS, non-essential amino acids, L-glutamine and Anti-Anti at 28uC in 5% CO 2 ." ] },{ "paper_id": "4961ab3b26b0165a3f1b267fc776329d792fc5f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "x i , y i are the geographic coordinates of the centroid of each postal code of residence;", "x j , y j are the geographic coordinates of the Foothills hospital.", "Travel time calculations are then used as the dependent variable, while the independent variables remain unchanged. To this end, actual travel times are converted" ] },{ "paper_id": "4994fa72322bbf19120592304d92629226948d8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Circular dichroism (CD) spectra of peptides were recorded on a JASCO J-810 spectrometer (JASCO corporation, Tokyo, Japan) equipped with a temperature controller and a 0.1 cm path length cuvette. The measurements were made in water at pH 7.3 and 22uC and at a peptide concentration of 0.2 mg/ml.", "Human Plasmodium falciparum (Pf) infection is a dramatic public health problem. Today approximately forty percent of the world's population is at risk of malaria. Malaria causes more than 300 million acute clinical cases, and at least one million deaths annually. Ninety percent of malaria deaths occur in sub-Saharan African countries mostly among young children and pregnant women (http://rbm.who.int). Thus, there is an urgent need of a malaria vaccine. However, vaccine discovery, in general and particularly in malaria, is still a very empirical process. In fact, protective antigens do not bear any structural, physico-chemical or sequence-related characteristics that would allow their identification. For protective humoral responses, the only recognized characteristics of antigens are their antigenicity/immunogenicity and accessibility. In addition, the lack of surrogate markers of protection renders the vaccine discovery process difficult and time consuming. Hence, in spite of a constant and impressive progress in molecular biology techniques and antigen identification and expression [1, 2] , vaccine discovery is still labor-intensive, making the approach fastidious, costly and poorly adapted to highthroughput screening. Proper protein folding and solubility remain a limitation in numerous cases. Thus, overcoming the bottlenecks of manufacturing and identification of fragments/proteins, as possible targets of a protective immune response still constitute a scientific and technical challenge.", "The Uganda Palo Alto strain (FUP/C) was cultured in RPMI-1640 supplemented with 0.5% albumax I (GibcoBRL-Invitrogen, San Diego, CA). For ADCI assays, blood stage parasite cultures were synchronized by at least two successive sorbitol treatments followed, after maturation over 24 h, by floatation on 1% porcine skin gelatin type A (Sigma).", "CB6F1 mice were injected 3 times with 20 mg of the indicated peptide in Montanide ISA 720 at the base of the tail on day 1, 22 and 78. Bleeding was performed 10 days after the second and third immunization." ] },{ "paper_id": "4997e92b014bb26f8184eae26662a09ffcf4f733", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fmicb.", "(1) all accessible DENV nucleotide sequences were collected;", "We are grateful to Ms. Inamine from NIID for drawing the DGV icon. We thank Prof. Ikuta and Prof. Yasunaga from BIKEN for allowing us to use the original dataset \"dengue virus genotyping database.\"", "The above processes except for the original database construction are performed automatically every night to update the recent DENV database." ] },{ "paper_id": "49a40a6447a61f2a4a725095b19ac648419c09f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "dR dt~( 1{p)cI{mR:", "where", "Taking the log of both sides of equation (10) and performing linear regression (details in Supporting Information S1) on this equation, (Figure 1b gives an estimated value R 0~2 :15.", "At the end of the incubation period 1 s , the individual becomes infectious and moves to group I. At this point, they display signs and symptoms that include fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, jaundice, dark urine, clay-colored stool and joint pain [26] . The infected individual may recover at a rate c. These dynamics are given by dI dt~s E{(mzc)I:" ] },{ "paper_id": "49a9a8769ece770dba1c78176dfe4264e51fad4b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Macrodomains constitute a unique conserved 130-190 amino acids three-layered \u03b1/\u03b2/\u03b1 sandwich fold widely distributed throughout the phylogenetic scale. They exert a regulatory influence on cellular signalling, transcription, DNA repair, genomic stability, telomere dynamics, necrosis and apoptosis, in addition to cell differentiation and proliferation 1 . They are also involved in different aspects of posttranslational protein modification of the ADP-ribosylation signalling pathway, including reading, erasing, and modulating, in combination with two other important NAD + -using protein families, poly(ADP-ribose) polymerases (PARPs) and sirtuins 2-9 .", "Interestingly, the above-described human TARG1 (hTARG1) is the only known macrodomain able to hydrolyse OAADPr, MARylated proteins 10 , and the ribose-acceptor bond of PAR-modified PARP1, removing the entire PAR chain en bloc 12 . Its catalytic lysine residue forms a covalent intermediate with the ribose ring through an Amadori rearrangement mechanism, followed by aspartic acid-mediated hydrolysis 12 . Surprisingly, although this special class of macrodomain containing all three activities has been described in some bacteria as a possible alternative mechanism for reversing protein ADP-ribosylation 2 , they have not previously been characterized.", "Human TARG1 (Uniprot code Q9Y530) was also cloned using its corresponding synthetic gene, but inserted into pET28a vector (Merck, Spain), transformed into E. coli Rosetta2(DE3) and induced using 0.2 mM isopropyl-\u03b2-D-thiogalactoside (IPTG) for 16 h at 20 \u00b0C with constant shaking. In this case, the purification protocol was the same as above except for using a single Ni 2+ -chelating affinity chromatographic step. The protein concentration was determined using Bradford reagent (Bio-Rad, Spain) and BSA as standard." ] },{ "paper_id": "49af320db4eb8944ad055eff7bbd30d0dd3094b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For mOTNRT-PCR assay, the reaction mixture was prepared containing: 5 \u03bcL of 5 \u00d7 PCR buffer, 2\u03bcLof One", "Total RNA was extracted from 200 \u03bcL of clinical sample using the QIAamp Viral RNA Mini Kit (Qiagen, Hilden, Germany). The extracts were eluted into 50 \u03bcL RNase-free water and stored at \u2212 80\u00b0C." ] },{ "paper_id": "49b325fc505d265149ed0c2e9131662626c16939", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As with any occupational disease, the interventions available to health professionals can be considered as engineering or administrative controls. As well, pharmaceutical controls (prophylaxis) for avian influenza may provide an important role in prevention. However, there is limited clinical evidence for the effectiveness of currently available medications or vaccines.", "The first vaccine approved by the US food and Drug Administration for pandemic influenza is a reverse genetics vaccine and demonstrated low immunogenicity except for high doses with an adjuvant [18] . When this was approved by the FDA it was noted that the vaccine would not be marketed to the general public but rather stockpiled by governments [16] . It has previously been suggested that an appropriate vaccine will likely not be determined until the initial phase of a pandemic [19] . Furthermore, once a vaccine is developed a mechanism needs to be put in place that can provide an adequate supply at an affordable cost globally in lock step with the progression of the pandemic.", "There are many similarities between the SARS epidemic and the anticipated experience with avian influenza. Both have been associated with food and animals. In the early stages of SARS, more than a third of infected humans were food handlers [3] , and it was later inferred that the SARS coronavirus had originated in civet cats, and that the first transmission of infection to humans may have occurred in those workers handling civet cats [4] . However, the greatest impact of SARS was subsequently felt in health care workers where they were estimated to have accounted for over 20% of total SARS cases in Singapore and 40% in Canada [5] . Thus, not only are individuals working closely with infected animal hosts at risk for first line crossover transmission of an emerging virus but they are also at risk of acquiring the virus from coworkers, or in the case of health care professionals, from patients." ] },{ "paper_id": "49b957bb681c7cae440ef4241a9fc99f37028d78", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "49c210ede22653e57df63a78de1c116b79b518a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "49d38b24e73f9fc1e483f13ca5b9cbfc298fcd95", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HA and BA collected the samples and wrote the manuscript.", "No part of this work, including travel and sample collection, received support from grant funding.", "The hair texture of Mezayen camel coats comes into two varieties, straight and ringed ( Figure 7B) . These two varieties occur in all six breeds. Breeders select for curly hair that appear as rings, especially in the torso region, which are considered signs of beauty and health (personal observation). To achieve the most desirable coat for beauty competitions, breeders often select for a combination of short and ringed coat hairs (personal observation). The Crdom Archive currently contains 66 straight hair camels and 47 ringed hair camels, which we aim to use in genetic association studies-this relatively large sample size is optimal since a large number of genes are expected to be responsible for a curly coat (Figure 7B )." ] },{ "paper_id": "49e1868b232e6ec98ae7cbc0745613925205e056", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chemical reagents. Meropenem was purchased from TCI Chemicals (Shanghai). Kanamycin sulfate, Luria-Bertani (LB) Broth Powder, and LB agar were purchased from Affymetrix. All other chemicals were purchased from Sigma-Aldrich unless otherwise stated.", "where I stands for UV absorbance intensity; I max for maximal UV absorbance; C p and C m refers to the total concentrations of proteins and ligands, respectively; K d is the dissociation constant. For Bi 3+ , the dissociation constant from NDM-1 was derived by 66 Zn, and 34 S contents, which are used to quantify protein concentration.", "Data availability. The coordinates and structure factors for both zinc-bound native NDM-1 and Bi(III)-bound NDM-1 were deposited at Protein Data Bank with accessing code 5XP6 and 5XP9, respectively. Other data are available from the corresponding author upon reasonable request.", "At the end of MIC assay, 50 \u03bcL of aliquots of each well (containing a specified antimicrobial concentration) for each isolate tested were applied to a LB agar plate and incubated at 37\u00b0C overnight. Resulting growth (or lack of growth) was examined after overnight culturing and the lowest concentration that inhibits 99.9% of the original culture was taken as MBC." ] },{ "paper_id": "49e18956b9fad9e6114912a46567cdc6b9555c02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Major complex glycans were clearly characterized. And treatment of SARS infected Vero E6 cell with \u03b1-glucosidase inhibitor N -butyl-deoxynojirimycin (NB-DNJ) revealed that the suppression of glycosylation process could inhibit the virus infection by blocking the initial stage.", "Formaldehyde cross-linking could be applied to study the binding between nucleotides, e.g., DNA and RNA, and proteins (Petrotchenko and Borchers, 2010) . Formaldehyde is a reactive cross-linking agent that could bind nucleic acids, peptides, or proteins. Its carbon atom center is nucleophilic to bind cytosine and it could also react with side chains of lysine, arginine, histidine, and cysteine to form methylol groups, schiff-bases, or methylene ", "Invasive viruses are adaptively infectious and pathogenic. Although host cells evolve and occupy a network of multiple defensive measures, microbial pathogens could in turn manipulate cellular machinery to counteract those immune defenses in order to evade or neutralize them (Finlay and McFadden, 2006) . This might be in part attributed to the fact that viruses evolve and mutate much more quickly than their hosts, and result in emerging mutants with enhanced viral attacks. For instance, viral genomes of RNA viruses, e.g., influenza A virus, intrinsically exhibit hypervariations and continued mutations due to a lack of proofreading RNA dependent RNA polymerases (Holland et al., 1982) . This may also be derived from the diversity of virus families and a vast number of formidable viruses threatening mankind; for examples, the representatives are human immunodeficiency virus, influenza virus, respiratory syncytial virus (RSV), severe acute respiratory syndrome (SARS), dengue virus, and so on. Epidemic or even pandemic diseases occurred in recent years upon breakout of those infectious viruses." ] },{ "paper_id": "49e262acc674f6765222a7b46b8eb1c78aeda947", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SCIentIFIC RePoRts | (2018) 8:15177 | DOI: 10 .1038/s41598-018-33487-8", "All viruses generally replicated more efficiently in VeroFM cells than MA104 cells. However, relative differences between strains were very similar in both cell lines, suggesting that IFN beta gene induction that is only functional in MA104 cells may not play a significant role for the observed phenotypes (Fig. 2a) .", "Recombinant SCV was generated as previously described 25 ." ] },{ "paper_id": "49e38057aa849ee6e304090b6ee1d2633b76f274", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chikungunya virus (CHIKV) is one of the most important arboviruses and is primarily transmitted by Aedes mosquitoes 1 . Though CHIKV was isolated almost five decades ago, however the last decade witnessed numerous major outbreaks spanning different continents. It is now reported from both old and new world and is recognized as a global public health concern. The incursion of African genotype into Asia and Asian genotype into Americas led to massive unprecedented outbreaks in na\u00efve population 2,3 . CHIKV infection in human may last for 1-10 days and the clinical spectrum ranges from acute infection to severe complications 4-7 . The higher number of severe cases indicates an urgent need to develop safe and effective medical countermeasures against CHIKV. Currently there is no licensed vaccine or therapeutics available against CHIKV.", "CHIKV belongs to the family Togaviridae, genus Alphavirus 1,8 . CHIKV has a single-stranded positive-sense RNA genome which encodes two polyproteins viz non-structural and structural. During viral replication, non-structural polyprotein is processed into four nonstructural proteins (nsP1, nsP2, nsP3, and nsP4) responsible for viral replication and evasion from the host defence mechanisms. In addition structural polyprotein is processed into various proteins (C, E3, E2, 6K, E1) that are involved in viral particle assembly 9 . Currently, targeting viral enzymes that are crucial for viral replication is believed to be an attractive strategy for development of", "Though, virus-encoded proteases have emerged as an important target for antiviral intervention, but challenges do exist to develop potential lead molecules against viral protease. One of these challenges includes lack of an efficient assay system for screening inhibitors in HTS format. So far, few candidates were obtained through cell-based assays 14, 15 . The cell based assay has been low to medium throughput due to involvement of multiple steps. Moreover, their exact targets remain unknown and specificity is relatively low. Thus, development of a sensitive and robust HTS assay is very crucial for screening potent candidates against specific targets in the near future.", "Validation of FRET assay for HTS. The assay was validated statistically by determining the Z' factor. The Z' factor for the CHIKV nsP2pro was calculated to be 0.67 \u00b1 0.054 using the FRET-based peptide substrate based on signal and background controls evaluated on a given day. In addition, intra-plate, inter-plate and day-to-day variability calculated was CV < 10% and signal-to-background ratio (S/B) obtained was >5 as evaluated on a given day, together these statistical parameters confirm the high sensitivity, specificity and efficiency of the assay (Fig. 4) ." ] },{ "paper_id": "49ef14fbeee682057ed14674f623ca36c6d954cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, it was noted that clinical samples stored at 280uC prior extraction exhibited an IDP rate lower than 30%.", "Here, our objective was to develop and test on a large number of clinical samples a bacteriophage-based IC system suitable for a standard laboratory of medical virology. We present results obtained by using T4 and MS2 bacteriophages as ICs in a routine-based evaluation including ", "IDPs were significantly more frequently detected for MS2 (RNA) than T4 (DNA) in plasma, BAL and CSF samples (p,0.05, Khi2 test, Yates corrected). Conversely, IDPs were significantly more frequently detected for T4 than MS2 in stools (p,0.05, Khi2 test, Yates corrected).", "Simple protocols for preparing plasmid DNA or synthetic RNA quantified controls are described in Supporting Information S1 and schematised in figure 1. Such controls include specific sequences for the hybridisation of detection primers and probe, but also an exogenic ''Not I'' sequence (detectable by a specific probe or cleavable by the Not I restriction enzyme).", "The approval of the relevant Ethics Committee (IFR48, Marseilles, France) was obtained for investigating the benefit of using phage spiking, but individual consent from patients was not required since French national regulations under the term of Biomedical Research (Loi Huriet-S\u00e9rusclat (loi 881138)) indicate that the signature at the hospital entrance office warrants that all samples taken during hospitalization for diagnostic purposes are accessible for research (excluding human genetic research) without the specific consent of the patient." ] },{ "paper_id": "49f01042ee1df642748c8b65f2abde687b2750ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Male, Kunming mice (28-33 g, body weight, BW), 2-3 month-old, were kept in polyacrylic cages (38 cm \u00d7 23 cm \u00d7 10 cm) with ten animals per cage and housed in a room under controlled temperature (24-26 \u00b0C) , relative humidity (50-60%); with 12 h light-dark cycles. Mice had ad libitum access to food in form of dry pellets and water.", "The IFN-\u03b3 level was measured by immunoassay. IL-4 level was measured using IL-4 ELISA Kit from Diaclone Research, France." ] },{ "paper_id": "49f674332aef03ed0e231eaed321de8cb65b6644", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The trial was registered with the Australian and New Zealand Clinical Trials Register. Clinical trials number: ACTRN12608000150347.", "Assessment for viruses and atypical bacteria were described previously [30] [31] [32] . Nucleic acids were extracted from 0. ", "Checklist S1 CONSORT checklist." ] },{ "paper_id": "49fee1986467f0cff2bc3517dbc1570e52d069d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As previously described, 24 ", "1-4 times, SD: 0.64) with 19% requiring more than one visit (Table 2) .", "None." ] },{ "paper_id": "4a074382e2fd63f0f5e882c0014e1e07d61c286a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Salvia miltiorrhiza is a perennial herb in the mint family (Lamiaceae). Its dried root or rhizome is called Danshen in TCM and was recorded in first pharmaceutical monograph Shennong's Classic of Materia Medica (A.D. . S. miltiorrhiza has been cultivated throughout Eastern Asia and used to prevent and cure cardiovascular, cerebrovascular, hyperlipidemia and acute ischemic stroke diseases [64] . Both the hydrophilic and lipophilic components in S. miltiorrhiza are considered active ingredients. The hydrophilic compounds are mainly phenolic acids including rosmarinic acid, salvianolic acid B, lithospermic acid and dihydroxyphenyllactic acid or Danshensu, and they may also function as antioxidative, anti-bacterial and anti-viral reagents [65, 66] .", "A deep sequencing on the transcriptome of A. annua to identify genes and markers for fast-track breeding was performed, and a detailed genetic map with nine linkage groups was built. Replicated field trials resulted in a quantitative trait loci (QTL) map that accounts for a significant amount of the variation in key traits controlling artemisinin yield, and positive QTLs in parents of new high-yielding hybrids were enriched, which made it available to convert A. annua into a robust crop [82] . Ma et al. [83] recently reported an integrated approach combining metabolomics, transcriptomics and gene function analyses to characterize gene-to-terpene and terpene pathway scenarios in a self-pollinating variety of A. annua. Forty-seven genes that mapped to the terpenes biosynthesis pathway were identified by sequence mining, and such metabolites-transcriptome network associated with different tissues is fundamental to metabolic engineering to artemisinin. ", "Triterpenoids are cyclization product of squalene which is condensed by two molecules of FPP. In general, triterpenoids are formed from MVA pathway in cytoplasm, as sesquiterpenoids.", "However, multi-classes of natural products are generated by each plant species. In addition, geographic distributions, growth conditions and harvesting seasons could significantly affect chemical compositions of the plant. Whereas one component may act as the active ingredient, the effects of a mixture of many ingredients are often uncertain and this has caused increasing concerns [5] ; thus, the traditional practice of herbology has to face the challenges from modern medicine and the manufactures' requirement." ] },{ "paper_id": "4a077b9696d19b7d7fa3e71560b7fd5f414a4d19", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data used for this analysis has been translated from Chinese sources such as provincial centres of disease control, and made publicly available [8] . We took the data as available on 29 January 2020 (Supplementary Material S1).", "The analysis yields the probability of being infected (dark pink), i.e. the cumulative density function of the estimated infection moments, using the Weibull distribution.", "Since the epidemic was developing during that time period, it is more likely that travellers were infected towards the end rather than the beginning of their stay. This might produce a slight bias towards longer incubation periods, so the estimated upper limit of 11.1 days could be considered conservative." ] },{ "paper_id": "4a0df4a0f4d88046442f66ad84ba40b2c34e2493", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Collection (Manassas, VA). HK-2 cells were cultured in RPMI 1640 (Sigma-Aldrich, St. Louis, MO) supplemented with 10% fetal bovine serum (FBS) (Invitrogen, Grand Island, NY) and 1% penicillin and streptomycin (Invitrogen). PBMCs were obtained from three healthy donors, after obtaining informed consent, using Ficoll-gradient sedimentation. PBMCs were cultured with RPMI 1640 (Sigma-Aldrich) supplemented with 10% FBS (Invitrogen) and 1% penicillin and streptomycin (Invitrogen).", "TGF-b 1 increased the expression of chemokines that mediate LFA-1 activation of PBMCs on HK-2 cells", "Conceived and designed the experiments: YM. Performed the experiments: YM MW EN. Analyzed the data: YM. Contributed reagents/materials/ analysis tools: YM EK. Wrote the paper: YM KI EK." ] },{ "paper_id": "4a17cedf8c94b518c91dfa6719832894b5dd0417", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Arbitrarily primed PCR and virus genome sequencing were performed as described previously (van Boheemen et al., 2012) . GS Junior sequence reads were trimmed by 25 nt at both the 59 and 39 ends of the reads to remove primer sequences and aligned to the HMPV genome (GenBank accession no. AF371337) using CLC Genomics software v.4.6.1 (CLC bio). Using this software, singlenucleotide polymorphism analysis was conducted with a minimum of 2 % variation frequency and a minimal coverage of five reads per position.", "Given the cytoplasmic replication of HMPV, the editing motifs and the expression of ADAR mRNA, we suggest that ADAR1 is the most likely enzyme responsible for editing of HMPV DIs.", "Of note, the deep-sequencing analyses, Northern blots and RT-PCR assays performed using several independent P5 high stocks consistently revealed the presence of DIs and similar patterns of hypermutation. Our results indicated that different P5 high stocks contained various DIs.", "In theory, the detection of dsRNA structures could have been a result of the process of deep sequencing, as this method involves ligation of linkers to PCR products. However, no double-stranded structures were observed in P2 low , which was analysed using the same protocol. In addition, both RT-PCR and Northern blots were performed using RNA isolated directly from the virus stock." ] },{ "paper_id": "4a326f7b32461745b6e168b454a214839b704865", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Baby Hamster Kidney (BHK)-21 cells (clone 13) were obtained from the European Cell Culture Collection and maintained at 37uC, 5% CO 2 , in Glasgow Minimum Essential Medium (GMEM) (Sigma) containing 10% foetal bovine serum (FBS) (Autogen Bioclear), 2 mM glutamine, 100 U/ml penicillin, 100 mg/ml streptomycin and 5% tryptose phosphate broth solution (Sigma).", "Macropinocytosis is the major form of endocytosis responsible for the majority of fluid-phase uptake for a number of cell types [32] . Macropinocytosis is characterised by actin-dependent reorganisations of the plasma membrane to form macropinosomes, morphologically heterogenic vesicles that lack coat structures. Macropinocytosis is constitutive in many cell types but in others requires activation by growth factors [32, 33, 34] and contributes significantly to antigen presentation by specialised antigen presenting cells [32, 34, 35] . Macropinocytosis is also exploited by a wide range of important animal pathogens for cell invasion and possibly the avoidance of immune surveillance [36] .", "All data were collected sequentially to eliminate cross talk between fluorescent dyes on a Leica SP2 Confocal Scanning Laser Microscope. For experiments that involved dual labelling of virus and cellular compartments, the specificity of the secondary antibodies for the target primary antibody was confirmed by showing a lack of cross-reactivity with non-target primary antibodies. The data are shown as single optical sections through the middle of the cell." ] },{ "paper_id": "4a34c342ffd1ba52c4539dab0d2ccce00bfb8517", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Notably, only a few p90RSK inhibition studies are carried out in animals, future studies regarding this aspect, as well as development of more efficient and specific p90RSK inhibitors, are warranted.", "Author Contributions: L.L. and K.H. proposed and wrote the manuscript. S.A.W. wrote the manuscript.", "Funding: This research was funded by a National Institutes of Health (NIH) (grant number 1R01DK102624) and an American Heart Association (grant number 14GRNT20380289)." ] },{ "paper_id": "4a4829a678305f54711666d194597971627c7b48", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Parasites were collected during necropsies, preserved in 70% ethanol and identified microscopically after preparation in lactophenol [21] .", "Six 12-month-old purpose-bred female ferrets (Mustela putorius furo), seronegative for currently circulating influenza A (pH1N1 and H3N2) and B viruses and Aleutian disease virus, weighing 600-900 g., were obtained from a commercial breeder (Euroferret). Animals were housed and they received water and food ad libitum. The experiments were conducted in strict compliance with European guidelines (EU directive on animal testing 86/609/EEC) and Dutch legislation (Experiments on Animals Act, 1997). The protocol was approved by an independent animal experimental ethical review committee DCC in Driebergen, The Netherlands. Animal welfare was monitored on a daily basis. Virus inoculation of ferrets was performed under anesthesia with a mixture of ketamine/medetomidine (10 and 0.05 mg/kg resp.) antagonized by atipamezole (0.25 mg/kg). All animal handling (swabbing and weighing) was performed under light anesthesia using ketamine to minimize animal suffering. All experiments with ferrets were performed under animal biosafety level 3 conditions in class 3 isolator cages.", "Samples for microbiological investigations were taken under abacterial conditions from lung, pulmonary lymph node, liver, kidney, spleen, intestine and mesenteric lymph node. The samples were frozen at -25\u00b0C until further processing. For cultivation, samples were decontaminated superficially by heat after thawing and a new cut surface was streaked on blood agar containing 5% defibrinated sheep blood (E. Merck, Darmstadt, Germany) and water-blue metachrome-yellow lactose agar (acc. to Gassner, E. Merck). Plates were incubated at 37\u00b0C and analysed after 24 and 48 hours. Grown colonies were subcultured and pure cultures were identified using standard morphological and biochemical methods as well as MALDI-TOF mass spectrometry with the Microflex LT/SH instrument as instructed by the manufacturer Bruker Daltonics [15] . Additionally, thiosulfate-citrate-bile-sucrose agar (TCBS) (Vibrio selective) agar (E. Merck), Brucella agar base with Brucella selective supplement (Oxoid, Wesel, Germany), KIMMIG agar (E. Merck) for selective cultivation of fungi as well as a selective medium for the isolation of Erysipelothrix rhusiopathiae (mod. by B\u00f6hm 1971 [16] ) were incubated according to the respective methods necessary for cultivation of the different organisms (for example Brucella selective agar was incubated in a CO 2 -incubator with 10% C0 2 for at least five days; for isolation of fungi KIMMIG agar incubation occurred at 28-30\u00b0C for three to fourteen days) [15, [17] [18] [19] . For the detection of Mycoplasma spp. a genus-specific PCR targeting the 16S rDNA was designed according to Rawadi and Dussurget [20] ." ] },{ "paper_id": "4a57f2f528842aa5dc0fd95788f524bc9b4b03bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There is a lack of well-annotated, ferret genomic sequence infor- ", "This work was supported by NHMRC programme grant #1052979", "(SJK) and NHMRC project grant #1129099 (AKW). JW is supported by a Melbourne International Research Scholarship and Melbourne" ] },{ "paper_id": "4a5e7d2f1256d0aed03adae0c98c5bb522e28748", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Among members of the Flavivirus genus dengue virus (DENV) is responsible for the highest rate of disease and mortality and consists of a group of four serologically related viruses referred to as DENV types 1-4. Infection with these viruses results in a range of clinical diseases such as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome [1] [2] [3] . Global epidemics of DENV have occurred over the past few years. There were 390 million (95% credible interval 284-528 million infections) dengue infections per year, of which 96 million (67-136 million infections) apparently manifested some level of disease severity [4] . DENV are transmitted to humans by the bite of infective female mosquitoes of the genus Aedes.", "The novel compound inhibitors were tested for their IC 50 values and used for an enzyme kinetic study.", "Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/18/12/15600/s1." ] },{ "paper_id": "4a64ef9057367aec43ce6b8a40e9bb0c9587fdf4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data represent the mean \u00b1 one standard deviation (SD). Treatment groups were compared using the analysis of variance. Statistical significance was declared if the two-sided p-value was <0.05.", "Microscopy was performed using an IMT-2 Olympus microscope equipped with ultraviolet light (UV) and an OM-4 camera." ] },{ "paper_id": "4a698e56af8042a4c35a26127c4da5fc5ff7fa95", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Carnero have contributed equally to this work.", "Frontiers in Immunology | Molecular Innate Immunity" ] },{ "paper_id": "4a7c2c60763755a14783f728e9b4cde8bf899f09", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All analyses were performed in R, version 2.15.3 91 . Meta-analysis was performed with package meta 3.2-0 and metabin, forest and funnel functions 92 . Hardy-Weinberg equilibrium testing was performed in HardyWeinberg_1.5.2 package 93 , with HWExactMat or HWChisqMat functions, based on the cell expected frequencies.", "Protocol and registration. The review strategy and details were registered prospectively in PROSPERO as the record 2014:CRD42014009072. Eligibility criteria. We undertook an extensive and systematic search of all published studies related to host genetics implicated in development or outcome of respiratory tract infectious diseases. Instead of focusing on a single-disease approach, we aimed at delivering systematic evidence on all respiratory infections, including cases where a syndrome phenotype was reported, such as pneumonia, without the specific pathogen information.", "hypothesis-free approaches, like genome-wide association studies 15 , managed to spark a progress of the field, indicated as a lack of replication of results from such studies 10, [16] [17] [18] . Unfortunately, insights derived from the fields of clinical infectology, microbiology, immunology, epidemiology, as well as clinical, evolutionary and population genetics remained largely isolated from one another [19] [20] [21] , preventing systematic understanding of the entire field." ] },{ "paper_id": "4a80fc8045f1a85c35e038160bee95c2be0c2fd2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The pregnant sows acclimated using feces or intestinal contents from piglets with PED may induce mucosal immunity to PEDV. Feedback is expected to induce highlevel immunity by a booster effect when combined with vaccination. However, carries risks, including a tremendous increase in viral load of the farm and introduction of pathogens such as porcine reproductive and respiratory syndrome virus, porcine circovirus type 2, rotavirus, porcine parvovirus, porcine enterovirus, Salmonella spp., Lawsonia intracellularis, Escherichia coli, and Erysipelothrix rhusiopathiae, etc. via infective materials. PEDV included in infective materials cannot be stored for a long time in general home-use freezers. The use of sufficient virus level is not ensured in PED rebreak. Because it is challenging to control feedback and provide stable results completely, Japanese government published the PED prevention manual to guide farmers not to perform feedback unless veterinarians or applicable government agencies are involved [21] .", "Porcine epidemic diarrhea (PED) is a viral infection caused by oral infection with PED virus (PEDV) and causes symptoms including watery diarrhea and anorexia [1] . The mortality rate of PED is as high as 50 to 100% in piglets up to 1 to 2-week-old. Weaning pigs may have transient diarrhea or remain asymptomatic even if they have been orally administrated the virus.", "A genogroup 2 field strain was isolated in Vero cell culture, to be used as inoculum in the challenge test. The Jejunum from six piglets which show watery diarrhea were obtained from a PED affected farm. These specimens were used for generating a 10% (w/v) homogenate in Eagle's minimum essential medium (MEM; Life Technologies). The homogenate was centrifuged at 1,500\u00d7g for 15 min at 4\u00b0C. The supernatant was filtered through a 0.22 \u03bcm pore-size filter.", "Comparison of the mortality rate of suckling piglets among PED affected farms" ] },{ "paper_id": "4a82252b3b4f4f90c0c0bc98ab7d817798d48c98", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mutations were made using the QuikChange Lightning Kit according to the manufacturer's protocol (Agilent Technologies, Inc.). The PCR-generated plasmids were transformed into Escherichia coli NEB-5\u03b1 cells by heat shock. The mutant plasmids were confirmed by sequencing and transformed into T7 Express cells (New England Biolabs).", "Assays with K48 and K63 linked tri-Ub were run in the same manner except that tri-Ub was present at 20 \u03bcM.", "The vOTUS were constructed and expressed as previously described in published methods [32, 55] . Purification of QYBV, TAGV, and DGKV were carried out as previously described. For FARV, a slightly different approach altered from the previously described method was used to optimize the expression. E. coli strains with vOTUs from FARV were grown at 37\u02daC in 6 L of Luria-Bertani broth with 100 \u03bcg/ml ampicillin. Once the optical density reached 0.6-0.8, 0.8 mM isopropyl-\u03b2-D-thiogalactopyranoside (IPTG) was added to induce gene expression. The temperature was then dropped to 25\u02daC and expression continued overnight. The culture was subsequently centrifuged at 5000xg for 10 minutes and the pelleted cells stored at -80\u02daC." ] },{ "paper_id": "4a8a6f65da6c9eca4117de59c6377a0ff02a0d09", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Purpose Immune globulins for IgG supplementation have been produced for over 35 years with essentially no differentiating features regarding their specific antibody composition.", "Keywords Intravenous immunoglobulin (IVIG) . primary immunodeficiency (PIDD) . clinical trial . safety . efficacy . pharmacokinetics Introduction Immunoglobulin (IG) supplementation has been the standard treatment for patients with disorders of antibody production due to B cell or combined B and T cell abnormalities (PIDD) [1] [2] [3] [4] [5] . Regularly scheduled infusions of IG replace or supplement antibodies that decrease the risk of the serious bacterial and viral infections experienced by PIDD patients [6] [7] [8] . Although all available preparations of immune globulin provide sufficient antibodies to significantly decrease the frequency of infections in immunodeficient patients, infections continue to occur [2, 6] . Previous studies have suggested that some infections in antibody-deficient PIDD patients occur when the titer of protective antibody is inadequate [9] [10] [11] [12] . While many of these reports have focused on bacterial pathogens, additional evidence supports the proposition that high titer anti-viral antibody preparations may provide advantages over conventional IG [13, 14] .", "The two-sided 90 % confidence intervals were calculated using normal approximation with a continuity correction for proportion of infusions with \u2265 1 TAAEs." ] },{ "paper_id": "4a94f3fe57da5dad4c965d59faf0facc2039175a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BALB/c mice (4-5 weeks old) were obtained from the Jackson Laboratories, Bar Harbor, Maine. Mice received feed and water freely. The animal study protocol for the work described in this manuscript was approved by the Institutional Animal Care and Use Committee (IACUC) of the Center for Biologics Evaluation and Research, USFDA (CBER/FDA).", "Testing of antisera for the neutralization of influenza A virus rgA/Viet Nam/1203/2004 (H5N1), an attenuated vaccine strain generated by reverse genetics, was performed using a microneutralization assay as previously described [55] . The presence of virus was detected using biotin-conjugated antibody to influenza NP (clone A; Milipore, Billerica, MA, USA) followed by HRP-labeled Streptavidin (KPL, Gaithersburg, MD, USA).", "Unpaired, two-tailed Student's t-test for statistical comparison of antibody titers was performed using GraphPad Prism 6.02 software (GraphPad Software, Inc.). The Kaplan-Meier Survival LogRank test was performed using the SigmaPlot 13.0 software (Systat Software, Inc.), and was used to compare differences in the number of surviving animals in the various treatment groups after virus challenge. In all cases, a p value <0.05 indicates statistically significant differences between treatment groups." ] },{ "paper_id": "4a99bf8fae88d43868e5b8ec0fa4c1c375b951f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Participants' socio-demographic characteristics, including age, gender, education level and employment status, were obtained. Medical characteristics, including length of diagnosis, disease stage, and most recent CD4 count, were also obtained.", "Interview questions were open-ended and broad to elicit a detailed description of participants' experiences. ", "The interviews were audio-recorded and transcribed verbatim." ] },{ "paper_id": "4aa092956fea94f9487d129b4a05a8704b73d0fc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sequence was as f ol lo ws: C TG TGTACTAAATTTCTCTCCTGGAGAGTGCTATAGAATGGGCTGTCGCT GGCTCCGAGCCAGCAGAGTTGCCGGTACTTGGCCGTGGGC.", "The The 3-MA (M9281) was obtained from Sigma-Aldrich. All the chemical inhibitors were obtained from Selleck. The PMA (S1819) was purchased from Beyotime Biotechnology." ] },{ "paper_id": "4aa19640fd1b1a8fc71b31d32fe6009c992bd767", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Vero cells (African green monkey kidney cells) used in these studies were a modified line that expresses CD150 (aka Signaling Lymphocyte Activation Molecule (SLAM), as these were the Vero ", "Except where indicated, all DNA manipulation was done following standard methods. Plasmids were cloned and grown in Escherichia coli DH5a or SURE2 (Stratagene). Routinely plasmid DNA was purified on CsCl gradients. The plasmids pJAT-lacZ, pGAS-luc, and pIFNb-luc were the kind gifts of Prof Steve Goodbourn, St. George's Hospital Medical School, London, United Kingdom. The pGL3-Mx1P-luc was kindly provided by Prof Georg Kochs, Department of Virology, University of Freiburg, Germany. The following plasmids were used for the ISG15ylation and ubiquitination experiments: pCAGGS.MCS-6HismISG15, and plasmids expressing mHerc6, Ubcm8 and mUbE1L were provided by Prof Deborah J. Lenschow, Washington University School of Medicine, St. Louis, Missouri. Plasmid pHA-CCHFV-L1-354 is in pCAGGS-MCSII and was the gift of Dr Natalia Frias-Staheli, Mount Sinai School of Medicine, New York.", "Mouse monoclonal antibody against phosphotyrosine 701-STAT1 were purchased from BD Biosciences. Polyclonal antibodies against STAT1, STAT2, and phosphotyrosine 689-STAT2 were obtained from Upstate. Mouse monoclonal antibody against proliferating cell nuclear antigen (PCNA) was obtained from Santa Cruz Biotechnology. Mouse monoclonal anti-His antibody was purchased from Sigma Aldrich and HRP-tagged anti-HA antibody from Roche. The rabbit anti-N antiserum recognizing the amino terminus of the NSDV and GV N protein were previously made in our laboratory. Mouse monoclonal antibody against the V5 epitope tag was purchased from AbD Serotech. Mouse monoclonal antibody U85 recognising Newcastle disease virus was the kind gift of Ruth Manvell, AHVLA, Weybridge, UK." ] },{ "paper_id": "4abc50cfc81265083d4cb2aed0a493bb704d0b5b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Open reading frame virus (ORFV) belongs to the Parapoxvirus genus in the Poxviridae family. Due to its very restricted host range to sheep and goats, its skin tropism infection, and the absence of systemic virus spread, even in immunocompromised individuals or after intravenous injection of a high virus dose, a short-term vector specific immunity, and the robust and rapid stimulation of innate immune responses at the site of infection [57, 58] , ORFV has emerged as a novel virus vector system for expressing different foreign antigens and as vaccine candidates for other pathogenic viruses [32] .", "In contrast to the steady improvement in the availability and quality of cell culture-derived rabies vaccines and RIGs, there has been a consistent lack of interest in developing antiviral therapy for patients who have missed the deadline for valid vaccination or whose symptoms have already manifested. As of now, no effective antiviral therapy is available for these patients and death is inevitable, in most instances accompanied by agonizing pain. Fortunately, recent advances in rabies treatment have generated promising tools for preventing and eradicating rabies, at least in murine and non-human primate models. These developments provide hope for realizing the goal of curing patients who are suffering from rabies.", "Rabies is an ancient neurological disease caused mainly by the rabies virus (RABV) and is almost invariably fatal once clinical symptoms develop. Currently, rabies continues to pose a serious public health threat in most areas of the world, especially in the developing countries of Asia and Africa. It has been estimated by the World Health Organization (WHO) that more than 55,000 annual human deaths are caused by rabies, through bites of rabid animals, worldwide. After the virus has entered the periphery site after exposure, it subsequently spreads into the central nervous system (CNS), causing neuronal dysfunction, which is most likely the main cause of the fatal outcome of rabies." ] },{ "paper_id": "4acb83c4e07408c4c244a047ee85091c9e0a48ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4ace931a12cf4c36b131fcf16b49bf36eb15f8e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A. thaliana Ler seeds were obtained from Lehle Seeds (cat. # WT-04 18 01).", "Found at: doi:10.1371/journal.pone.0002397.s007 (0.07 MB XLS)", "Microarray raw data were deposited in the NCBI's GEO database under accession GSE11088." ] },{ "paper_id": "4ada63940f8817b1305316a9c44cfbb5bc39b762", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Classical reservoir systems fulfill all requirements proposed in this study.", "According to the accepted definition of a reservoir proposed by Haydon et al., 4 we discuss the requirements in two parts: the pathogen's maintenance in a potential population or community followed by a discussion on proof of a feasible transmission route. Although the two components are addressed separately, only together they demonstrate the existence of a functional reservoir.", "Neither laboratory experiments, nor intervention studies, nor epidemiological models alone can provide a full understanding of a natural reservoir of infection. Only the combination of methods that are based on established and validated species-specific assays and technically sound field investigations can provide confidence that the pathogen is maintained in a non-target population and that a feasible transmission route exists. This, however, requires the political will and financial support to conduct long-term One Health studies to explore diseases in their natural context." ] },{ "paper_id": "4ade9fb8ea22a3cc6328dd972c7401c4cefc0a0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data analyses and graphical maps were conducted by Origin Pro 8.0 and ArcMap 10.6 (version 10.6, ESRI Inc.); Cross-correlation and linear regression model were performed by SPSS version 25.0. (SPSS Inc.: Chicago, IL, USA). Regression tree and SARIMA model were conducted by R software version 3.4.3. Statistical significance was set at P < 0.05 (two-tailed test)." ] },{ "paper_id": "4ae32ac7470a95f95ccd2309bfb62a990c1e0e16", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional Supporting Information may be found in the online version of this article: Figure S1 . Supplimentary 1. Influenza A, influenza B and HCoV-OC43 Alignments." ] },{ "paper_id": "4ae484254680cec3d9d6f6d55bfd97bd90877445", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The human kidney cell line 293T [32] , the human fibrosarcoma cell line HT1080 [33] , and the PFV indicator cell line BHK/LTR(HFV)lacZ [34] were cultivated in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% heat-inactivated fetal calf serum and antibiotics. G418 was added at a final concentration of 1 mg/ml to BHK/LTR(HFV)lacZ cells.", "At 48 h post transfection, 293T cells were harvested and processed for electron microscopy analysis as described previously [45] ." ] },{ "paper_id": "4ae8479c3cef7cc97b7edb7cb3e9f86ec51d140e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Resolution of pneumonitis is delayed in some patients during SARS recovery and may be associated with delayed clearance of coronavirus, Complete resolution may occur by 90 days or later.", "Patients underwent HRCT and BAL on the 60 th and 90 th day after the onset of disease. HRCT was performed with 1-to 2-mm collimation sections reconstructed by the use of a high spatial frequency algorithm using a (General Electric Medical Systems, Milwaukee, WI). The HRCT protocol consisted of thin sections obtained at 10-mm through the chest in a supine position without using intravenous contrast medium." ] },{ "paper_id": "4afc459e347836f0f92a75ab0c6cbe2e02e6f3a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As described above, their current classification can incorporate phylogenetic data and any available information on neutralization properties in addition to VP1 distances. Combined, these may potentially resolve any remaining uncertainties over type assignments.", "1. An HRV type should be phylogenetically distinct from other HRV types.", "9. The 'prototype strain' of each new HRV type should be the first reported full-genome sequence or, if this is unavailable, the first reported full VP1 sequence.", "6. HRV variants divergent from all known VP4/VP2 sequences (i.e. above type-assignment thresholds for the identified species in this region) but without an available VP1 sequence may be designated a PAT." ] },{ "paper_id": "4b0552782eeeefd0e22a8f2c7ff55351ec6f0c3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "High School Contact Networks. The high school data [29] describes the cumulative time in close proximity between pairs of people over one day in a U.S. high school. Networks derived from this data provide examples of contact networks relevant to infections where close proximity, but not necessarily physical contact, is important. Such SIR-type infections include corona virus, influenza, norovirus, rhinovirus, varicella and measles. Pertussis (i.e., whooping cough) is an example of a bacterial SIR-type infection (at least in time scales up to years) for which close proximity is relevant.", "doi:10.1371/journal.pone.0142181.t004", "doi:10.1371/journal.pone.0142181.t007" ] },{ "paper_id": "4b130b88bd3514c7159a9c25c0f52e4a531950e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One nostril was closed off using an inflatable catheter as described previously [20] .", "Ecological intra-and inter-patient microbiota similarity was estimated using adonis, ANOSIM and MRPP methods included in QIIME 1.8.0. Briefly, these methods compare the ecological distance between samples (Unifrac distance) to test the null hypothesis that intragroup similarity is not significantly different than intergroup similarity [29] .", "Among the 5 most abundantly identified genera, three (Streptococcus, Prevotella and Rothia) showed very limited variation during HRV16 infection (less than 10 % of the baseline abundance), whereas Veillonella decreased by approximately 25 % and Haemophilus increased by 75 %." ] },{ "paper_id": "4b138ca6c96ce56fb2db1641847bd7686ca1cdff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In an ongoing pilot study at a university student health clinic (Student Health Services at Western University), a small cohort of undergraduate students, who were naturally-infected with influenza, are being referred by clinicians to the WeCoF aerosol study. Written informed consent is being obtained from all participants in this ongoing study. The HSREB reviewed and approved this study.", "The authors declare that they have no competing interests. " ] },{ "paper_id": "4b22861aa553b97e42e6a1b95b744e0ec2dcd6b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Notes" ] },{ "paper_id": "4b2607f3da8bf06c231145105ffd5ca24a07bbda", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was authorized by the Ethics Committee of the Federal University of S\u00e3o Carlos, note number 451,814. Participants received written and oral information regarding the research objectives and procedures and signed a written individual consent in accordance with Brazilian ethics regulation [21] .", "One study found an increased risk of Mycobacterium tuberculosis infection in health professionals, students, and CHAs, who are six times more likely to acquire the disease while caring for infected patients if they do not use specific protective measures [25] .", "\"N 1: I think it is not very clear to the team, I think we need to talk more about it. I know the theory, but in the practice, I have doubts.\" \"NA 3: What you are showing us here is something that we have to observe more and practice (...) no one gives any importance to this detail.\"", "As for sharps disposal at home, participants showed flawed knowledge of the guidelines on segregation and final disposal of the waste generated.", "The perception of low risk can be a major cause of shortcomings in adopting measures to prevent transmission of microorganisms.", "We do not intend our data to be fully transferable worldwide. Nevertheless, the results points to the need for guidance, training and adequate provision of supplies and structure to promote compliance with essential measures to prevent HAI across the entire health care system.", "The low perception of self-risk of infection was also discussed by a multinational study group highlighting the risk of extensively drug-resistant tuberculosis [24] ." ] },{ "paper_id": "4b2a69ec1289a04f3a94db719f855631f93f2d54", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceived and designed the experiments: TU. Performed the experiments: MT YT TK. Analyzed the data: MT TU. Contributed reagents/ materials/analysis tools: MT YT. Wrote the paper: TU. N/A.", "All incubations were performed in RPMI-1640 (Invitrogen Life Technologies) supplemented with 10% heat-inactivated FCS (HyClone), 100 U/ml penicillin, and 100 mg/ml streptomycin (Invitrogen).", "Student's t test was employed for the statistical analysis." ] },{ "paper_id": "4b2b67b0f48b99e75c190ad11bc215bb5f27503f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4b2ef217cb3fedccaffa0ecdd43344810630987b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Epidermal growth factor receptor pathway substrate 8 (Eps8) contains 822 amino acids and is located in chromosome 12p12-p13 in humans. The EPS8 gene encoded for the expression of proteins with molecular weights of 97 and 68 kDa, referred to as the two EPS8 isoforms. As a signaling adapter, EPS8 regulates actin cytoskeleton dynamics and architecture (3) and participates in transduction of signals from Ras to Rac by activating the Rac-specific guanine nucleotide exchange factor activity in the form of a trimeric complex together with SOS1 and ABI1 (4) . It involves in the regulation of processes including dendritic cell migration as well as cancer cell migration and invasion (5) .", "It is worth mentioning that certain CTL epitopes identified in vitro may be less immunogenic in vivo, which may be due to inadequate antigen processing and presentation by APC (58) . Therefore, a subsequent study by our group will test the immunogenicity of the epitopes in vivo using transgene mice.", "Concepts for treating hematologic malignancies by harnessing the immune system have been established due to defects of current treatment methods (27) . HSCT is the only potential method to cure hematological malignancies, but relapse rates remain high, particularly in patients transplanted during relapse or in second or subsequent remission (28) . Therefore, efforts are required to seek for novel avenues which are tumor-specific and have synergy with current treatment methods; from this viewpoint, therapeutic vaccines against LAAs are an optimal choice. Mounting evidence demonstrated the existence of LAAs (29) ; as most LAAs are not muted, their immunogenicity is often poor; however, at the same time, the immunity evoked by current therapeutic vaccines targeting LAAs is far from optimal. Accordingly, isolating specific components that have immunogenicity and can induce a strong immune response are rational choices for vaccines. Therefore, the most important task in the discovery of cancer vaccines is to identify novel TAAs and their CTL epitopes in order to make additional therapeutic targets available which are closely associated with tumor incidence and progression. Reverse immunology has been commonly used to identify epitopes of LAAs (30) .", "Strong evidence demonstrated that EPS8 had oncogenic potential, and its overexpression was reported in a range of human malignancies, including breast cancer (6) , pituitary tumors (7) , pancreatic cancer (8) , cervical cancer (9) , colon cancer (10), head and neck squamous cell carcinoma (11) , esophageal cancers (12) and human gliomas (13) , and its amplification is often associated with tumor progression, acquired drug resistance and poor prognosis (14) . EPS8 upregulation is thus expected to be involved in human carcinogenesis, implying that this gene may be used as a target in tumor immunotherapy. A previous study by our group demonstrated an elevated expression of EPS8 in patients with acute myeloid leukemia (AML), its overexpression was inversely correlated with overall survival of patients (15) , and EPS8 protein as a vaccine reagent induced a CTL response in a murine breast carcinoma model (16) . From the aforementioned facts, it was speculated that this gene may be a prognostic marker and could be a target for immunotherapy of hematological malignancies." ] },{ "paper_id": "4b382dd30271d1544237000616b02988687c4402", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GraphPad Prism 5 (Version 5.0, La Jolla, CA, USA) was used to graph data and perform statistical analyses. To compare blood cell count and cytokine expressed level between groups, the Mann-Whitney U test was used. Mean \u00b1 SEM (standard error of the mean) were graphed and * (p < 0.05) was considered to be statistically significant.", "Viruses 2017, 9, 104 5 of 13 mean 4.6% to 6.5%) when compared with the three days post-infection ferrets, but there is no change in the number of the lymphocytes and eosinophils ( Figure 1C ). ", "Viruses 2017, 9, 104 10 of 13" ] },{ "paper_id": "4b3ddd160ebda77b58843d167709d71a73a3bf4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Actin was detected by using rhodamine phalloidin (Invitrogen), and microtubule by using antitubulin \u03b1 mAb against sea urchin tubulin \u03b1 (clone B-5-1-2, Sigma-Aldrich, St Louis, MO, USA).", "Three lectins with different sugar binding specificities were investigated for anti-viral activity against human parainfluenza virus type 2 (", "Legume lectins are a family of carbohydrate-binding proteins, and are used as a model system for the study of protein-sugar interaction. Legume lectins can be divided into five groups according to the specificity of the sugar-binding site: fucose (fuc)-specific, N-acetyl glucosamine/glucosamine (GlcNAc/Glc) specific, Glucose/mannose (Glc/Man) specific, Galactose/N-acetylgalactosamine (Gal/GalNAc) specific, and those that do not bind to any mono-saccharides [12] . Plant lectins have been shown to inhibit the infection of human immunodeficiency virus (HIV) [13] [14] [15] and cytomegalovirus [13, 14] . Plant lectins were reported to inhibit HIV by the prevention of virus adsorption to the cells [16] . However, they also prevent fusion of HIV with their target cells [13, 14] . Against severe acute respiratory syndrome (SARS) coronavirus, the mannose binding lectins are the most effective [17] . Recently, Change et al. reported that recombinant chimeric lectins consisting of mannose-binding lectins and L-ficolin are potent inhibitors of influenza A virus [18] ." ] },{ "paper_id": "4b3de92b03457bddd57edad106262751d712c528", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest. " ] },{ "paper_id": "4b3e454f57edd89563485c04da1df5f95ebd2b5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following antibodies were used in the present study: monoclonal mouse Anti-V5 antibody (Invitrogen), dilution 1:1000; monoclonal mouse anti-HA Tag antibody (Upstate, Temecula, USA), dilution 1:5000; monoclonal mouse anti-\u03b2-actin (Sigma-Aldrich, Oakville, Canada), dilution 1:2000; and goat anti-mouse horseradish peroxidase conjugated IgG (BioRad, Mississauga, Canada), dilution 1:2000.", "Plasmid DNA was isolated from the positive yeast clones. The gene inserts were PCR amplified and then sequenced. Plasmid DNA from positively interacting clones was also re-transformed into the E. coli DH5\u03b1 strain.", "Accessory proteins are not necessary for viral replication in cell culture systems and in mice, but may be important for virus-host interactions and thus may contribute to viral strength and/or pathogenesis in vivo [4] [5] [6] ." ] },{ "paper_id": "4b43f61d164be997a34343c11c70c42edd91898b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our project receives support from the CDC, so we are required to comply with relevant CDC standards.", "The second disadvantage is the need to pre-specify the syndromes, age groups, and other data aggregation parameters in advance, since changing these requires the distribution of a new release of the aggregation software." ] },{ "paper_id": "4b4ac4cf566b08058a36a9ed00b7fb66f1623ae3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since its first reported isolation from a patient in Saudi Arabia in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) has posed a global threat to public health. A pandemic outbreak", ". MERS-CoV causes severe respiratory symptoms accompanied by high fever, cough, and severe pneumonia, and mortality rates can be as high as 35% [3] . The overall risk in areas outside Saudi Arabia, the country in which most of the cases have been reported, remains as significant as inside Saudi Arabia, and thus novel tools and reagents for therapy and diagnosis are urgently needed." ] },{ "paper_id": "4b6c86374fd6b66e8d0729a9d32d7cf6a11be71e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. These KOR/KNU14-04/2014 PDCoV sequence data have been deposited in GenBank under the accession no. KM820765.", "In April 2014, porcine deltacoronavirus (PDCoV) was first identified in feces from diarrheic piglets in South Korea and found to be closely related to other PDCoV strains. The complete genome of the Korean PDCoV strain, KOR/KNU14-04/2014, was sequenced and analyzed to characterize PDCoV circulating in South Korea.", "RNA viruses belonging to the family Coronaviridae of the order Nidovirales, which are further divided into 4 genera, Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus (1, 2) . Viruses of the Alphacoronavirus and Betacoronavirus genera have been detected in swine (3). The fifth porcine coronavirus was identified in 2012 in an investigation to discover new deltacoronaviruses in mammals and birds from China (2). In February 2014, the presence of porcine deltacoronavirus (PDCoV) was first announced in Ohio, United States, and since then, this novel coronavirus has been reported in 17 U.S. states (4) (5) (6) (7) ." ] },{ "paper_id": "4b6f64a80fb18cd5fa4b165916603d65bc6514e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceived and designed the experiments: F.P. performed the experiments: F.P., D.A.R.S.L. analyzed the data: F.P., D.A.R.S.L., S.P.G. Wrote the paper: F.P. critically reviewed the manuscript: F.P., D.A.R.S.L., S.P.G.", "Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/20/03/4748/s1. Marvin, Molecular Networks GmbH for access to CORINA. The authors thank W. Fenical for access to the AntiMarin707 database while S.P.G. was a postdoctoral researcher at the Scripps Institution of Oceanography, San Diego, CA, USA.", "Training set Test set I AntiMarin set Test se II Figure 1 . PCA score plot derived from CDK and PM6 descriptors, PC1 (t [1] ) versus PC2 (t [2] ). The bottom plot is the amplification of the cluster highlighted as 1." ] },{ "paper_id": "4b7667a10db8449042b2fa73329cdfac5358ad34", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Blood samples were collected to measure the concentration of C-reactive protein (CRP) in mg/L and white blood cell count x 10 9 /L." ] },{ "paper_id": "4b92357afea168410a305eca0e593b7955f08598", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Without loss of generality, the time step is assumed to be one day.", "Network models have been successfully used to describe the spread of many infectious diseases, ranging from human [1-8] through animal [6, [9] [10] [11] ] to plant diseases [12] . In these models, individuals are represented as nodes and potential contacts between individuals as edges of the underlying network. Much work has been devoted to studying how networks are assembled [13] [14] [15] and to analysing the effect of network topology on disease" ] },{ "paper_id": "4b9911544622c1028499e1db9cf9fb783c2ed863", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4ba9bd26567dc15bc9a0abf88342604d62e336ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Victor M Corman et al." ] },{ "paper_id": "4baa61e791ff5aa90affac055aee043503472aaa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Biodiversity loss diminishes the supplies of raw materials for drug discovery and biotechnology, causes a loss of medical models, affects the spread of human diseases, and threatens food production and water quality [10] . Its reduction has direct effects on the discovery of potential medicines.", "Human activities are known to be crucial to transmission of some diseases. Forest clearance eliminates species that breed in water in tree holes (e.g., the forest Aedes species that transmit yellow fever) but provides favorable conditions for those that prefer temporary ground pools exposed to full sunlight (e.g., many of the Anopheles species that transmit malaria). Drainage of wetlands eliminates the marshy pools exploited by many species but can provide the open channels preferred by others (e.g., some important European vectors of malaria, and Culex tarsalis, a vector of St. Louis encephalitis) [29] .", "Ingredients sourced from wild plants and animals are not only widely used in traditional medicines, but are also increasingly valued as raw materials in the preparation of modern medicines and herbal preparations. Greater demand and increased human populations are leading to increased and often unsustainable rates of exploitation of wild sourced ingredients, with some wild species already threatened with extinction [65] ." ] },{ "paper_id": "4bc632592ca471bbff7effd71f3a9f930913f3c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Table S1 . " ] },{ "paper_id": "4bc6d312effedb4dafb7bca22236c006ad1f7136", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and after the collective interventions it becomes", "Where the parameter set\u0177 is inferred by maximizing the total log-likelihood of the data L(\u03b8|t, v,w) [9] .", "where" ] },{ "paper_id": "4bc6ead9368ec84dba7c56b78624f681293e568b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pone.0220798.g002", "https://doi.org/10.1371/journal.pone.0220798.t003", "https://doi.org/10.1371/journal.pone.0220798.g003 however, it is clear that sufficient numbers of emergency medical personnel should be made available to attend to pediatric trauma cases during these busy periods." ] },{ "paper_id": "4bcd826716cefe4fbd8aecfda57a14ce69c4f7e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "e data used to support the findings of this study are included within the article.", "e list of tour group members and hospital records were evaluated, on-the-spot interviews were conducted, and epidemiological questionnaires were completed. We found that 7 people met the inclusion criteria.", "e authors declare that they have no conflicts of interest. Canadian Journal of Infectious Diseases and Medical Microbiology 5" ] },{ "paper_id": "4bcdac71c12d45032dfb8c6753e7d94643a11283", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using GraphPad Prism software (GraphPad Software, La Jolla, CA, USA). Significant differences between two means were determined by an unpaired Student's t-test. Data are presented as the mean \u00b1 standard error unless otherwise indicated. Statistical significance is indicated as * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001.", ". Excluding EBOV, SUDV has the highest mortality and outbreak rates among the species of ebolaviruses. SUDV has emerged at least six times with average mortality rates of up to 53.76% [6, 7] . Multiple vaccines and monoclonal antibodies against EBOV have been developed, but very few of them can effectively prevent and control SUDV infection [8] . Therefore, there is an urgent need to develop a safe and efficacious vaccine against SUDV." ] },{ "paper_id": "4bcf7c070cff74e01013527a1957c676487d98d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MT and JP conceived and wrote the manuscript. KW performed protein modeling for the figures and wrote the manuscript.", "Where virions are labeled, this can be done with direct labeling [including viral membrane labeling which would exclude detection of membrane-fused viruses (167) ], or internal labeling via co-transfection of genes encoding fluorescent non-structural proteins, resulting in their random incorporation into packaged virus particles (168) . Fluorescence labels can also be engineered to report internalization, either by the addition of a non-cellpermeable fluorescence quencher during the wash step (169) , or by using a pH-sensitive dye.", "This work was supported by NIH NIAID P01 grant AI120756, K01 grant OD024877, the Duke University Center for AIDS Research (CFAR; NIH 5P30 AI064518), and a fellowship from the Agency for Science, Technology and Research, Singapore (A * STAR)." ] },{ "paper_id": "4bd3a768f65bf203f8ac6e26fc5c82b373c868bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information is available from the Wiley Online Library or from the author.", "Virus Invagination" ] },{ "paper_id": "4bd41e4fe399ecfd7456792b11f51979999b4d1e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were processed for indirect immunofluorescent detection of viral proteins and cellular markers as previously described [3] . Images were acquired with an LSM710 confocal microscope (Zeiss) using a 636/1.4 numerical aperture oil immersion objective. Signals were sequentially collected by using single fluorescence excitation and acquisition settings to avoid crossover. Images were assembled using Adobe Photoshop software.", "Mouse anti-E1 MAb A4 [30] was produced in vitro by using a MiniPerm apparatus (Heraeus) as recommended by the manufacturer. Sheep anti-NS5A antiserum [31] was kindly provided by Dr M. Harris (University of Leeds). Mouse anti-CD71 (transferrin receptor) MAb was purchased from Santa Cruz Biotechnology. Sheep anti-TGN46 was from Serotec. Mouse anti-GBF1, anti-EEA1, and anti-GM130 MAbs were from Transduction Laboratories. Rabbit anti-BIG1 was from Bethyl Laboratories. Mouse anti-Arf1 MAb 1D9 was from Abcam. Mouse anti-b tubulin MAb (TUB 2.1) was from Sigma. Mouse anti-HSA (ZMHSA1) was from Invitrogen. Goat anti-HSA (507313) was from Calbiochem. Goat anti-ApoE was from Millipore. Alexa 555conjugated donkey anti-sheep IgG antibody was from Invitrogen. Peroxidase-conjugated goat anti-mouse, anti-rabbit, and antisheep IgG, and cyanine 3-conjugated goat anti-mouse IgG were from Jackson Immunoresearch.", "Dulbecco's modified Eagle's medium (DMEM), phosphatebuffered saline (PBS), trypsin-EDTA, OptiMEM, Oligofectamine, goat serum, and fetal calf serum (FCS) were purchased from Life Technologies. 49,6-diamidino-2-phenylindole (DAPI) was from Molecular Probes. Golgicide A and Mowiol 3-88 were from Calbiochem. Protease inhibitors cocktail Complete was from Roche. Other chemicals were from Sigma." ] },{ "paper_id": "4bdb53b23deb0bc56d0aa7b26551ab76b1fd082e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where \u03b4 was dealt with as" ] },{ "paper_id": "4be32977ea29039cf2fac3b4327ceea8f14d0af4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There are a number of EBV genes such as BHRF1 (encoding an Bcl-2-like anti-apoptotic protein) [107] , BXLF1 (encoding EBV thymidine kinase) [108] , BCRF1 (encoding viral IL-10) [109] , loss-of-function mutants of which exhibited no or only minor phenotypic alteration in in vitro studies. Examination of these EBV mutants in humanized mice may reveal critical roles for these genes in EBV life cycle and pathogenesis.", "154" ] },{ "paper_id": "4be572af41fbf94759bf8872ff257fa0f632dca0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza, a negative-sense RNA orthomyxovirus, is one of the few diseases that is truly global in scale. It is responsible for approximately three to five million cases of severe acute respiratory illness and 250,000 to 500,000 deaths each year throughout the world [1] . In 2009, the swift isolation of swineorigin H1N1 strain (S-OIV) from all continents within several weeks of onset reinforced the idea that influenza is a highly infectious agent circulating worldwide [2, 3] .", "Trains also stop at waypoint stations, which can be the junction of a large number of routes. Correspondingly, certain regions act as waypoint sources: important intermediate launch pads to other destinations. Others act as waypoint sinks: important points of convergence for multiple routes. Eigenvector centrality can gauge this property on the principle that connections to high-scoring nodes contribute more to the score of the node in question than equivalent connections to low-scoring nodes. We used a method akin to PageRank, Google's method of assigning importance to web pages [25] .", "of NA produced similar findings with the exception of North America being its own primary seeder ( Figure 3B ). No complete HA and NA isolates existed in the NCBI Influenza Virus Resource database [24] for Africa." ] },{ "paper_id": "4bf165f82a8648b69169a66114d29c690f0562e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Subjects were recruited from a specialized, orthopaedic tertiary care facility with high volumes of lower extremity arthroplasty. Inclusion criteria were as follows: a diagnosis of osteoarthritis (OA), scheduled for primary total joint arthroplasty, sufficient language skills to communicate in written and spoken English, and absence of neurological, cardiac, psychiatric disorders or other medical conditions that would significantly compromise physical function. Patients who underwent revision, bilateral or staged arthroplasties were excluded.", "To complete the 6 MWT, patients were instructed to cover as much distance as possible during the 6 minute time frame with opportunity to stop and rest if required. A premeasured 46 meter uncarpeted, rectangular circuit was marked off in meters and the distance each subject covered was measured to the nearest meter. Standardized encouragement was given at 60 second intervals as previous work has demonstrated that encouragement improves performance [35] .", "The TUG [36] was performed by having study participants rise from a standard armchair, walk at a safe and comfortable pace to a tape mark 3-meters away and then return to a sitting position in the chair. A standardized script was read to each patient and the test began on the word \"go\"." ] },{ "paper_id": "4bf4126bc494f791347e285c91b25bc2814beb4d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pulmonary edema is differentiated into two categories: cardiogenic and non-cardiogenic edema 8 .", "Keywords TNF; pulmonary edema; cytokine; sodium transport; hyperpermeability; reactive oxygen species" ] },{ "paper_id": "4bf5ba8fe5af1bf36c9f2f3af74541fbda3a2c89", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quantitative real-time PCR (qRT-PCR). Total RNA was isolated from cells by using either TRIzol or a Quick-RNA MicroPrep kit (Zymo Research). DENV RNA levels were estimated as described previously, using TaqMan one-step real-time PCR (Applied Biosystems) (10, 11) . The amount of DENV negative-strand RNA was measured by cDNA synthesis with a forward primer followed by real-time PCR using a PrimeScript RT reagent kit with a genomic DNA (gDNA) eraser (TaKaRa). A \u2424-actin primer-probe mix (Applied Biosystems) was used for normalization. Fold changes were calculated by the \u232c\u232cC T method.", "Immunofluorescence. Huh-7 cells grown on coverslips in a 24-well plate were infected and treated with 4 M inhibitors as described above. At 24 h p.i., cells were processed for immunofluorescence to visualize double-stranded RNA (dsRNA) as described previously (12) . For assessing the effect of inhibitors on endolysosomal markers, Huh-7 cells were treated with the inhibitors as described above for 4 h. Cells were fixed and stained with antibodies against early endosome antigen 1 (EEA1) (BD Biosciences), lysosome-associated membrane glycoprotein 1 (LAMP-1) (Developmental Studies Hybridoma Bank), and LC3b followed by secondary antibodies conjugated with Alexa 488. Images were acquired with a 60\u03eb or a 100\u03eb objective by using an Olympus FV1000 or IX 83 inverted fluorescence microscope. Images were processed by background correction using Olympus FluoView software, and z projection images are shown. Statistical analysis. GraphPad Prism software was used for all graphical representations and statistical analyses. All experiments were performed with two or three replicate samples, and results in each figure are a compilation of data from experiments performed at least two to three times. P values were estimated by a Mann-Whitney test or one-way analysis of variance (ANOVA).", "We postinfection (for a time of addition of 24 h). The addition of inhibitors was inhibitory up to 12 h postinfection, whereas at 24 h postinfection, it had no effect (Fig. 5a) . At 24 h postinfection, we expect later stages of the viral life cycle, namely, viral genome packaging, assembly, and egress, to be active compared to viral RNA replication; therefore, inhibitors that block viral RNA replication would have no effect at these stages of viral infection. Together, these data clearly suggest that all three inhibitors block early stages of the viral life cycle and are not able to prevent virus infection once the virus enters postreplicative stages of infection." ] },{ "paper_id": "4bf70dfd0cd0819f2eb424d977abedc85f5444d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical significance was calculated using SPSS version 22, using a Linear Mixed Model (LMM) (p < 0.05). Results were expressed as the mean \u00b1 SEM. Figures were generated using GraphPad Prism 7.0b software.", "All cells were cultured and maintained in Dulbecco's modified Eagle medium (DMEM) (Sigma Aldrich, St. Louis, MO, USA) supplemented with 10% fetal bovine serum (FBS) (GE Healthcare, Chicago, IL, USA) and 0.2% penicillin-streptomycin solution (Gibco/Invitrogen, Carlsbad, CA, USA) at 37 \u2022 C with 5% CO 2 .", "All peptides were based on the sequence AHX00731.1 (a camel isolate identical to a number of other deposited sequences) and were provided by Cambridge Research Biochemicals, UK. Peptides were provided as lyophilized products with a mean purity of \u226570%. Peptide stock solutions were prepared in a buffer consisting of 0.1 mM sucrose, 0.1 mM glucose, 10 mM DTT, 0.5% (v/v) DMSO." ] },{ "paper_id": "4c0a84d9d35e76db288afca33c1f63c27d436328", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Among the viruses evaluated, RSV was most prevalent and was documented in 9 (23%) of the 39 studies (see Table 1 ).", "EB, JZ, and JC conducted the literature review and wrote the manuscript. GG conceived of the idea of the review and helped revise the manuscript to add important scientific content. All authors reviewed the final version of the manuscript and agreed to its submission.", "This report was funded in part by Duke University discretionary funding (Gray PI)." ] },{ "paper_id": "4c16e6d3922d2b800f5f3e2dec0e51b9f7700898", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4c1e7d31ff353e605f4211eebae16eaea9defed6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protein structure accession number and statistical analysis. Coordinates and structure factors for PRRSV nsp11 were deposited in the RCSB Protein Data Bank under accession number 5DA1.", "IMPORTANCE" ] },{ "paper_id": "4c21ac102e96cf6a038edb3fd4fb7d7dd4471170", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(Beijing, China). Then, a sequence homology search was performed to identify the subgroup of adenovirus via the BLAST program at NCBI (http://blast.ncbi.nlm.nih. gov/Blast.cgi, 2015).", "Adv: Adenovirus; ARDs: Acute respiratory diseases; HAdv: Human adenovirus; ILI: Influenza like illness; RSV: Respiratory syncytial virus", "All data were entered into a database, and logical errors were detected and corrected using the Excel program (Microsoft Office EXCEL 2003, WA, USA). The corresponding frequency, constituent ratio, or incidence was calculated. Measurement data consistent with a normal distribution (tested by the Kolmogorov-Smirnov test) and expressed as x \u00c0 \u00b1 s (calculated by the Execl program).", "Background information was collected from the 800 recruits. There were 722 males and 78 females, who were aged 18.9 \u00b1 1.69 years. Most recruits came from Hebei (199, 24.9%), Shandong (102, 12.8%), Jiangsu (196, 24.5%), Shanxi (99, 12.4%) and Hunan (204, 25.5%). The ratio of recruits from urban areas to those from rural areas was 1:1.12 (378:422). Basic information, lifestyle, and medical history of the assessed recruits are summarized in Table 3 ." ] },{ "paper_id": "4c2205dd9943bdc4547fb999c6616269df83c685", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4c2d326a10d98f8f503f8df460291e059cc77a75", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Notably, the substitutions L18I and S31F occurred in the reported epitope NEP-D4 of the N protein." ] },{ "paper_id": "4c30f4001fb0068ba0b1444ea16b4d9cbe672996", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The experiments were repeated at least three times with consistent results. The significant difference between experimental groups and the control group was performed using the Student's t-test with the SPSS software (SPSS, Chicago, IL, United States). P < 0.05 was considered statistically significant. All data are expressed as the mean \u00b1 SEM.", "Please contact authors for data requests.", "YC and MZ designed the experiments. TG and YY performed the animal experiments. FH and XC performed the confocal microscopy experiments. JZ and YL verified the pathological results. YX and HW edited and revised the manuscript. TG and MZ drafted the paper.", "This study was approved by the Institutional Animal Care and Use Committee of the Nanjing Medical University." ] },{ "paper_id": "4c3ff586d4238ccd7324950db31a02037463f973", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All results are expressed as mean values \u00b1 standard deviations (SDs) (n = 3). The significance of difference was calculated by one-way analysis of variance, and values p < 0.01 were considered to be significant.", "(-)-\u03b1-Pinene, (-)-\u03b2-pinene and ribavirin were obtained from Sigma Chemical Co. (St. Louis, MO, USA) and was stored in glass vials with Teflon sealed caps at \u221220 \u00b1 0.5 \u00b0C in the absence of light.", "The IBV Gray strain was purchased from National Control Institute of Veterinatory Bioproducts and Pharmaceuticals (Beijing, P. R. China). Virus was routinely grown on Vero-E6 cells. IBV-Gray stock cultures were prepared from supernatants of infected cells and stored at \u221280 \u00b0C." ] },{ "paper_id": "4c4214329dbbf291d7c73b5afb2a145559f780e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Differences between groups were analyzed using a Student's t-test for continuous variables and a \u03c7 2 test or Fisher's exact test for proportions. The overall survival rate was estimated by the Kaplan-Meier method. Univariate analyses (Cox proportional hazard regression models) were also performed to assess the prognostic value of nucleolin expression and other clinicopathological features. We utilized SAS 9.2 software system for statistical analysis.", "Conclusions: eIF3f may play an important role in recurrence, thus representing a promising predictive marker for the prognosis of GC.", "From the 195 cases, 142 men and 53 women all accepted radical operation of GC, including 116 primary and 79 recurrent GC patients. Pathologically, all of the 195 cases were adenocarcinoma, which covered 12 well differentiated, 27 moderate differentiated, 156 low differentiated, and 4 signet-ring cell carcinoma. For all specimens, 31 cases were demonstrated as Her-2/neu-positive." ] },{ "paper_id": "4c452cc6bb3cb81575f11749b5fb5e5206d6836e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Diagnosis confirmation. RNA was extracted from the throat-swab samples using the QIAamp Viral RNA Mini kit (Qiagen, Hilden, Germany), according to the manufacturer's instructions. Specific RT-qPCR assays were performed to assess the presence of seasonal influenza viruses (H1, H3, or B), H5N1, severe acute respiratory syndrome coronavirus and novel coronavirus. RT-qPCR assays with self-designed specific primer and probe sets were subsequently performed for the detection of H1 to H16 and N1 to N9 subtypes, in order to verify the viral subtypes.", "Auxiliary examination. Hospital emergency blood gas analysis revealed a pH of 7.49, a PaCO 2 of 38.6 mmHg, a PaO 2 of 52.6 mmHg and a SaO 2 of 87% (without oxygen). An electrocardiogram (ECG) demonstrated sinus rhythm, atrial premature beats, poor R wave progression in the anterior wall and T wave changes.", "In the present study, the patient exhibited a rapid deterioration; however, a diagnosis of H7N9 avian influenza was only confirmed after five days of continuous fever. Thus, the treatment process has provided experience for dealing with cases of H7N9, particularly for community health centers." ] },{ "paper_id": "4c45bdd7e23c8ea6b0dfb04d48a5ceda8f022597", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where (x, y) is the spatial coordinates in the plane perpendicular to the propagation direction z, m and Q are the attenuation and phase shift induced by the object. They are given by" ] },{ "paper_id": "4c4dd391e165ce712cb8871ce3082927bbf21ec9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 File. Contains Fig A. Imaging ellipsometry. (a) Imaging principle [23] ; and (b) Laboratory prototype. Fig B. ", "This novel biosensor may be a valuable diagnostic tool for analysis of IgG antibody against CMV during CMV infection screening." ] },{ "paper_id": "4c5661848b054307106bd3b67311da7effd797a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The \u03b1-helical content was estimated from the Cotton effect at 222 nm by the equation previously reported 12 .", "S2" ] },{ "paper_id": "4c572b27658746d48b85b25fa8aa9c6d94a47bcf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4c59d82d87d20a5a5ab05c5c19895bda141167d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "d. Biotoxins. The analyses for hydrophilic and lipophilic biotoxins were negative.", "c. Analytical chemistry-lipid extraction. Blubber samples were freeze-dried and extracted with n-hexane in a Soxhlet apparatus. The lipid content of the extracted organic material was determined by gravimetry." ] },{ "paper_id": "4c5eab753837b6723778e80b1d37a32bee2b4375", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The avian influenza virus used in this study consisted of a sixth passage A/chicken/Italy/5093/99 H7N1, kindly provided by Dr Ana Moreno from the Istituto Zooprofilattico Sperimentale della Lombardia e dell' Emilia Romagna in Brescia, Italy. The intravenous pathogenicity index (IVPI) of this virus was 2.8, indicating that it is a highly pathogenic strain. This virus was propagated in 9 to 11-day-old specific pathogen free (SPF) embryonated chicken eggs. The fifty percent embryo lethal dose (ELD 50 ) was carried out in SPF embryonated eggs and was determined as described previously [15] .", "Although HPAIV neuroinvasiveness and neurovirulence are considered to be one of the main factors leading to the fatal course of infection in birds [22] , few detailed studies on viral neuropathogenesis have been conducted in chickens. Previous experimental studies carried out on different species have suggested that IAV could enter into the CNS through one or more of these three pathways: haematogenous [5, 23] , olfactory [24, 25] and neural routes [7, 26] .", "Positive controls consisted of sections of tissues where the distribution of AIV receptors has already been determined (human lungs, pig trachea, and duck lungs and intestines). Negative controls consisted of sequential tissue sections treated for 24 h with 12.5 U/\u03bcL of neuraminidase from Clostridium perfringes at 37\u00b0C (P0720L, New England Biolabs, MA, USA). Besides, an additional negative control consisted of substitution of the lectin by TNB buffer.", "The RT-qPCR technique used to quantify the viral RNA copies have been thoroughly described previously [20] . Briefly, viral RNA was extracted from each sample using QIAamp viral mini kit (Qiagen, Hilden, Germany). The RNA was eluted in 40 \u03bcL and amplified by one-step RT-qPCR for the detection of a highly conserved region of the matrix (M) gene of IAV using the previously described primers [21] . This procedure uses an internal positive control (IPC) to avoid false negative results due to RT-qPCR inhibitors." ] },{ "paper_id": "4c6a45d1e56660fa713b637825b96e287a0acef5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations SPF: Specific pathogen free. The dogs were free from infections with canine adenovirus (CAdV-2), canine coronavirus, canine distempervirus, canine parainfluenzavirus, canine parvovirus, leptospira and rabies virus.", "The mean values of all measured variables of each group were calculated. Statistical analyses were performed using SPSS software (version 13). The differences between the three groups at each time point were compared with P values of <0.05 considered to be significant.", "Infectious RD114 virus was not detected from TE671 (LacZ) cells co-cultured with buffy coat cells using the LacZ marker rescue assay. This finding was also confirmed by PCR assays using genomic DNA from the co-cultured cells as a template. Additionally, RD114 provirus was not detected in genomic DNA extracted from peripheral blood, lymph nodes, spleen and sternal bone marrow, using the one-step PCR assays ( Figure. 2)." ] },{ "paper_id": "4c6ceb1e0f1dd785f1f6859da440c64e49824fb6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sampled camels were classified into one of three distinct lifestyles (nomadic, sedentary or a mix of nomadic and sedentary). The mixed lifestyle is characterised by a seasonal spatial movement of less than 100 km for accessing new ressources while the nomadic lifestlyle was defined as travelling throughout the year over distances up to hundreds of kilometers.", "In total 1,500 camels were sampled, between February and March 2015, from 86 herds ( Figure 1B-D ", "Milk Transport" ] },{ "paper_id": "4c6efd303141e36db6479eda5dc5d2a379e6bcd9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The secondary structure of IL17A was predicted using PsiPred (http://bioinf.cs.ucl.ac.uk/psipred/) [42, 43] and DiAminoacid Neural Network Application (DiANNA) (http:// clavius.bc.edu/\u223cclotelab/DiANNA/) [44] . Both methods predict protein cysteines that create disulfide bonds, but while PsiPred uses Position Specific Iterated-BLAST (PSI-BLAST) to obtain evolutionary information used to predict the secondary structure of the query protein, DiANNA is a neural network that recognizes cysteines in an oxidized state (sulfur covalently bonded) distinguishing them from those in a reduced state.", "The number of nucleotide differences per site between sequences was estimated in MEGA6 [41] with the following options: bootstrap method (1000 replicates), p-distance as model, and pairwise deletion for gaps/missing data treatment. A Maximum Likelihood approach was used to estimate the phylogenetic relationships between the IL17A nucleotide sequences by using MEGA6; the best-fit nucleotide substitution model was predicted by the same software and 1000 bootstrap replicates were used.", "Haplotype phases of the sequences obtained were reconstructed with the program PHASE, built into the software DnaSP [38] . Multiple Sequence Comparison by Log-Expectation (MUSCLE; http://www.ebi.ac.uk/) [39] was used for sequence alignment. The putative N-glycosylation sites were predicted using NetNGlyc 1.0 (http://www.cbs.dtu.dk/ services/NetNGlyc/) [40] ." ] },{ "paper_id": "4c6fefd5a9ce1f7df6a863b7d91410d03bfc9139", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The cytotoxicity test for the different chemicals used was carried out by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay as described previously [34, 63] .", "FCV vaccines are available for cats [20] ; however, there is a limit on its efficacy because of low or no preventive effect against FCVs with different antigenicity and short-lived immunity [13, 20] . A lack of a robust and reproducible in vitro cultivation system for human noroviruses (HNoVs) has not been developed until recently, thereby hindering the development of effective interventions [21] . Therefore, our understanding of the HNoV life cycle was largely based on those surrogate viruses specifically the murine noroviruses (MNVs) [22] . Therapeutic candidates for FCV and MNV may be utilized for various FCV strains and HNoVs [13] .", "The Caliciviridae family is composed of small, non-enveloped, icosahedral viruses that possess a single-stranded, positive-sense RNA genome of 7-8 kb in size [1] . This family is comprised of five established genera, Lagovirus, Nebovirus, Norovirus, Sapovirus, and Vesivirus [2] , with six additional unclassified new genera tentatively named Recovirus [3] , Bavovirus [4, 5] Nacovirus [5] [6] [7] , Salovirus [8] , Sanovirus [9] , and Valovirus [10] . The members in this family are a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 important pathogens in both medical and veterinary fields [1] . For example, feline calicivirus (FCV) belonging to the genus Vesivirus causes acute, self-lining oral and upper respiratory tract disease in cats [11] . Moreover, virulent, systemic FCV mutant strains causing severe systemic diseases with edematous and ulcerative skin lesions, jaundice, and a high mortality of up to 67% have recently been found in the US and EU [12] [13] [14] . Porcine sapovirus (PSaV), and bovine norovirus and nebovirus cause widespread acute gastroenteritis in piglets and calves, respectively [15] [16] [17] . In the medical field, human norovirus and human sapovirus, especially the former, is the leading cause of gastroenteritis in humans, accounting for~200,000 deaths per annum in children <5 [18] [19] ." ] },{ "paper_id": "4c71e5b4d4b332ee8522373d949ceff2bed03718", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following primary antibodies were used: rabbit anti-mouse B 0 AT1 antibody ( [3] , 1:100 for IF, 1:2 000 for WB), goat anti-mouse ACE2 (R&D Systems, Minneapolis, MN, USA; dilution: 1:100 for IF, 1:1 000 for WB), rabbit anti-human CD13 (abcam, Cambridge, UK; dilution: 1:100 for IF, 1:2 000 for WB), and mouse anti-\u03b2-actin (Sigma Aldrich, Steinheim, Germany; dilution: 1:100 for IF and 1:5 000 for WB). Secondary antibodies were Anti-Rabbit IgG HRP Conjugate, Anti-Mouse IgG (H+L) AP Conjugate (Promega, D\u00fcbendorf, Switzerland) or donkey anti-goat IgG-HRP (Santa Cruz Biotechnology, Dallas, Texas, USA) for Western blot analysis (1:5 000 dilution) and Alexa Fluor 1 594 donkey anti-rabbit IgG (H+L) (life technologies, Carlsbad, California, USA) and Dnk pAb to Goat-IgG (DyLight 1 488) (abcam, Cambridge, UK) for immunofluorescence (1:2 000 dilution).", "Analysis of experimental data was performed with GraphPad Prism 5.0 and MS Office Excel. Statistical significance between mean values of groups was tested using paired two-tailed Student's t-test, one-way ANOVA or two-way ANOVA and a Bonferroni post test. Differences were considered significant at P < 0.05. Data are expressed as mean \u00b1 SEM.", "Taken together, our results did not support the hypothesis of an acute regulation of intestinal B 0 AT1 by dietary amino acids." ] },{ "paper_id": "4c76e1e9a4f5afc01accd2dbbd43f0463744e8d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The responsibility to communicate well can be derived from a number of sources; for our purposes, the central concern is the vulnerability of others to misunderstandings brought about by an improper communication of risk. Scientists, particularly in infectious disease, generate claims and evidence that are probabilistic in nature. Those scientists, presumably, have gained the skills to interpret scientific evidence and understand what the information doesand doesn't-tell us about the world. These skills, when applied to a broad public forum, generate a responsibility for scientists to do their part to prevent misinformation from spreading; unfortunately, they can do as much harm as good without responsible communication practices.", "\"Airborne\" Ebola: Potential Pandemic or Tempest in a Teacup?", "It is very likely that at least some degree of Ebola virus transmission currently occurs via infectious aerosols generated from the gastrointestinal tract, the respiratory tract, or medical procedures, although this has been difficult to definitively demonstrate or rule out, since those exposed to infectious aerosols also are most likely to be in close proximity to and in direct contact with an infected case [8] ." ] },{ "paper_id": "4c7ae8ea3cf737fe457b191ae7a7dc2fcaee44bf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the expression plasmids were verified by sequencing.", "RNAi experiments and establishment of cells with stably expressed exogenous proteins were performed using the lentiviral ", "Mouse anti-NS3 monoclonal antibody and Goat anti-cdN polyclonal antibody were used as the primary antibodies.", "The yeast two-hybrid system used for the screening was purchased from Clontech Laboratories (USA). The screening procedures were conducted following the manufacturer's instructions and our previous procedures [11, 12] . The cDNA library used for this screening was a human fetal liver library, HL4029AH (Clontech)." ] },{ "paper_id": "4c7cbcc5bec46c8c956a8f05adab670eb353cc30", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Email: Isaac Chun-Hai Fung cfung@georgiasouthern.edu -King-Wa Fu kwfu@hku.hk -Yuchen Ying yegle@uga.edu -Braydon Schaible bs05313@georgiasouthern.edu -Yi Hao yh00111@georgiasouthern.edu -Chung-Hong Chan chanchunghong@hku.hk -Zion Tsz-Ho Tse ziontse@uga.edu" ] },{ "paper_id": "4c84dbfd01f7b2009ebed54376da8afcbcf1ec64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protocol S1. Parameter Estimation", "Citation: Lim K, Lang T, Lam V, Yin J (2006) Model-based design of growth-attenuated viruses. PLoS Comput Biol 2(9): e116.", "Infections caused by viruses persistently threaten human health. For example, 40 million, 350 million, and 170 million people in the world are carrying human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV), and hepatitis C virus (HCV), respectively [1] [2] [3] . Annually 5% to 15% of the global population is infected with influenza, resulting in 250,000 to 500,000 deaths [4] . Protection against viral infections may be provided by inoculations with live-virus, killed-virus, or subunit vaccines. Live-virus vaccines offer advantages because they activate both humoral and cellmediated immunity, require only a single boosting, and generally provide longer immune protection than other forms of vaccines. However, they must be adequately attenuated in their growth to minimize the possibility of vaccine-induced pathogenic effects while retaining their immunogenicity. Attenuation of live viruses has traditionally been achieved by serially passaging viruses in tissue or cell culture and adapting them to grow well on new cell types or at elevated or reduced temperatures [5] , a process that tends to reduce their replicative ability and virulence in humans or animals [6] . Such attenuation has historically been a highly empirical process, where its mechanisms are often neither known nor elucidated.", "VSV is a prototype negative-sense single-stranded RNA (Mononegavirales, (-)ssRNA) virus and a member of the family Rhabdoviridae [18, 19] , which includes rabies virus. Each VSV particle has a single copy of an 11-kb genome carrying five genes that encode nucleocapsid (N), phospho (P), matrix (M), envelope (G), and polymerase (L) proteins. VSV is economically important because it can cause symptoms like those of foot-and-mouth disease in livestock [19] . It offers several advantages as a vaccine vector including low seropositivity in humans, a capacity to accommodate foreign genes up to 40% of its own genome size, and an established reverse genetics [18, 20] . Recombinant forms of VSV carrying foreign virus genes that encode immunogenic proteins have been proposed as potential vaccines against HIV, influenza, and respiratory syncytial virus [21] [22] [23] [24] [25] . Less pathogenic but more immunogenic VSV-based vaccines against infection by VSV or other viruses are being sought." ] },{ "paper_id": "4c874a97c374c6cd2375e7c5f0f690ee911dc3dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: In the spring of 1918, the \"War to End All Wars\", which would ultimately claim more than 37 million lives, had entered into its final year and would change the global political and economic landscape forever. At the same time, a new global threat was emerging and would become one of the most devastating global health crises in recorded history.", "Autopsies performed on preserved lung tissues in the modern era have revealed acute pulmonary hemorrhage and secondary bacterial infections associated with pulmonary lesions in nearly all the fatal cases examined [41, 43, 47] . Streptococcus pneumoniae was present in many cases; however, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pyogenes also appeared to complicate fatal cases [48, 49] . Neutrophilic pulmonary infiltration was seen in cases of pneumococcal pneumonia, while cases of staphylococcal pneumonia were marked by multiple microabscesses infiltrated by neutrophils [48] . However, alveolar cell damage was seen in each case along with pulmonary repair and remodelling [48] . Tissues from each of the fatal cases examined had similar pathologic presentation, independent of which pandemic wave they were associated with. Despite the difference in mortality rates, each wave showed similar cellular tropism, infecting both type I and type II pneumocytes, as well as the bronchiolar respiratory epithelium [48] ." ] },{ "paper_id": "4c9604ca5c3d30db29127225cc52ad90b50c1b13", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Measurement data are represented as the mean \u00b1 SD, and analyzed using the unpaired Student's t-test. Difference between rates was evaluated by Chi-square test and Fisher's exact test. P <0.05 were considered statistically significant. The cartogram was drawn using Excel software (Microsoft Co., USA). All statistical analyses were performed using the SPSS 13.0 software (SPSS Inc., USA).", "The research involving human participants was approved by the Medical Ethics Committee of Zhongshan School of Medicine, Sun Yat-sen University, in accordance with the guidelines for the protection of human subjects. Written informed consent was obtained from each participant or the guardian." ] },{ "paper_id": "4c9d7e3db46a6026e1554f2fa3df4f93645381e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA was extracted from lung tissue homogenate with the miRNeasy mini kit with on-column DNase I treatment (Qiagen). RNA concentration was quantified on an ND-2000c UV-Vis spectrophotometer (Nanodrop, Wilmington, DE) and controlled for integrity and purity on a capillary electrophoresis system (Agilent 2100 Bioanalyzer; Agilent Technologies, Santa Clara, CA).", "KEYWORDS" ] },{ "paper_id": "4c9f3df22b058cb0b95c53f12cdffd1c5fe1ce93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The overall surface analysis suggested that p4a did not possess any defined ligand-binding hydrophobic pocket, which could make this protein an unpromising drug target. However, understanding of the surface electrostatics can lead to the design of electrostatically active small molecules that could hinder p4a-dsRNA interaction." ] },{ "paper_id": "4ca552dd7e18609e57226f02001bf51bec3000bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4cb55c99b99ef1944a0b43b342a8bc9eda6ae227", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Because EV71 mRNA does not have 5' cap structure, translation is dependent on its IRES element. Numerous studies have shown that EV71 IRES-dependent translation is highly controlled by IRES-specific transacting factors (ITAFs) [48] .", "The authors declare that they have no competing interests.", "Authors' contributions RLK wrote the manuscript. SRS participated in its organization and coordination and helped to draft the manuscript. Both authors read and approved the final manuscript." ] },{ "paper_id": "4cb6f55ffe1a352419056feaae3bd4e164ce2119", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4cbd54dab5ad14f6d8c5ad9fb9bc223cb4431ba3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consequently, illness surveillance in recruits, which made up the largest proportion of our study population, can be beneficial in informing disease trends in the general public.", "Supporting Information S1 File. Tables S1 and S2. of Defense, or the US Government. Approved for public release; distribution is unlimited. U.S. Government Work (17 USC 105) . Not copyrighted in the U.S. This research was conducted in compliance with all applicable federal and international regulations governing the protection of human subjects in research (protocols NHRC 31230 and NHRC.1999.0002)." ] },{ "paper_id": "4cbde00704ec55e2d030ca4f8ecb73da6ba959ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "African green monkey kidney cells (Vero-CCL81), human hepatoma cells (Huh7), pig kidney epithelial cells (LLC-PK1), human embryonic kidney 293 cells stably expressing the SV40 large T antigen (HEK-293T) were maintained in Dulbecco modified Eagle medium (DMEM, Lonza, Basel, Switzerland) supplemented with 10% fetal bovine serum (FBS, Bodinco, Alkmaar, The Netherlands).", "FCoV Type1-S1", "FCoV Type2-S1" ] },{ "paper_id": "4cbebfa064d2b234ab25b2a1d0ffaf97739bcb04", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All samples were assayed for cytokines by multiplex, using MSD Proinflammatory II (Mesoscale Discovery) 4-plex plates in sputum and cell culture supernatants.", "Causally related AEs d 22 11 33 SAEs (fatal and non-fatal) 0 1 1", "Causally related SAEs (fatal and non-fatal) d 0 1 1" ] },{ "paper_id": "4cc161090a796945e7bda63489feb4f268bfeb3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: The spike proteins of coronaviruses associate with cellular molecules to mediate infection of their target cells. The characterization of cellular proteins required for virus infection is essential for understanding viral life cycles and may provide cellular targets for antiviral therapies.", "After five rounds of panning, the final enriched specific clones were plated and single pure plaques were isolated. The cDNA inserts in these plaques were amplified by PCR using primers (T7 Select Up primer: 5'-GGAGCTGTCGTATTCCAGTC-3'; T7 Select Down primer: 5'-AACCCCTCAAGACCCGTTTA-3') flanking the inserts. Each PCR consisted of 30 cycles of denaturation at 94\u00b0C for 1 min, annealing at 50\u00b0C for 1 min, and extension at 72\u00b0C for 1 min. The reaction also included an initial denaturation step at 94\u00b0C for 5 min and a final extension step at 72\u00b0C for 7 min. After PCR amplification, the products were purified by Qiaquick columns (Qiagen, Hilden, Germany) and were then sequenced.", "Approximately 100 clones were randomly picked from individual plaques, and the DNA sequences of clones were amplified by PCR and analyzed on an agarose gel to determine the insert size. Approximately 38% of the phage clones had an insert size of 830 bp, 25% had an insert size of 750 bp, 22% had an insert size of 400 bp and 15% had an insert size of 250 bp (Fig. 2) . The clones were then further sequenced." ] },{ "paper_id": "4cc3f3b34e4353ec33df7c231e22112232ae7218", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords: virus, metabolism, rhinovirus, host-pathogen interaction, metabolome", "KM and GG wrote the article. JS and GZ carefully revised the manuscript and provided critical intellectual input. All authors agreed to the final version of the article." ] },{ "paper_id": "4cc4711e7794e52f303fdd8557dd175e71989c7b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Invasive Pulmonary Aspergillosis (IPA) is a life-threatening infection caused mainly by Aspergillus fumigatus, an opportunistic fungal pathogen that frequently colonizes respiratory tracts and rapidly spreads to blood vessels and tissues [1] . The incidence of IPA infection has increased in the last years due to the use of immunosuppressive and immunomodulatory drugs and is still causing significant morbidity and mortality worldwide, especially in immunosuppressed and hematopoietic stem cell transplantation (HSCT) patients [2] .", "Whole blood samples from 21 healthy donors were collected into PAXGENE RNA tubes and stored at 280uC until use. Total RNAs were extracted using a PAXGENE Blood RNA Isolation Kit (PreAnalytiX) and reverse transcribed to cDNA using QuantiTect Reverse Transcription Kit (catalog number: 205311; Qiagen). Real-time quantitative PCR was carried out using an ABI PRISMH 7500 HT Sequence Detection System (Applied Biosystems) according to manufacturer's instructions. Briefly, 2 ml of the cDNA were loaded in a PCR reaction containing 12.5 ml of 26 QuantiTect SYBR Green PCR Master Mix with an appropriate concentration of MgCl 2 , 2.5 ml of primers (Hs_CLE-C7A_1_SG QuantiTect Primer Assay, catalog number: QT00024059; Geneglobe, Qiagen) and 8 ml of RNase-free water. PCR cycling conditions were as follows: 95uC for 15 minutes, followed by 40 cycles of denaturation at 95uC for 15 seconds combined with annealing at 60uC for 30 seconds and extension at 72uC for 30 seconds. All samples were run in duplicate. Relative quantification of Dectin-1 mRNA expression was calculated with the 2 2DDCt method. We obtained the fold changes in gene expression normalized to an internal control gene (GAPDH, Hs_GAPDH_2_SG QuantiTect Primer Assay, Catalog number: QT01192646; Qiagen) and relative to one calibrator (First- ", "The marked differences in susceptibility to IPA infection among hematological patients (with or without allo-HSCT) suggest that the effective immune response against Aspergillus is determined by both environmental and host genetic factors [44, 45] . Studies on genetic polymorphisms in genes coding for components of the innate immunity have supported this hypothesis [19, [23] [24] [25] [26] [27] [28] [29] [30] 46] ." ] },{ "paper_id": "4ccdf68a98517afb602bd6ab2eca8e77fac05830", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Primers. Large fragment Bst DNA polymerase (Invitrogen, Beijing, China) was used in amplification reaction.", "Ethics statement. The methods were carried out in accordance with Animal Epidemic Prevention Law of the People's Republic of China. Animal experiments in this study were approved by the animal care and use committee of the Institute of Special Economic Animal and Plant Sciences and the animal welfare committee of the Jilin Province, China." ] },{ "paper_id": "4cd3f43501d49e775838473a3edafb55e57d08df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mouse MAb 61-2-1 (m61), was generated according to standard procedures. Briefly, six-week-old female BALB/c mice (Japan SLC) were immunized intramuscularly two times with 100 mg of formalin-inactivated purified virions and boosted intraperitoneally [23] . Spleen cells harvested 3 days after boosting were fused to P3U1 myeloma cells according to standard procedures. Hybridomas were screened for secretion of HA-specific MAbs by enzymelinked immunosorbent assay (ELISA), and cloned by limiting dilution. The resulting cell clones were inoculated into BALB/c mice intraperitoneally to produce ascites. Antibodies were purified from ascites using the Affi-Gel Protein A MAPS II Kit (Bio-Rad). Mouse MAbs ZGP133 and ZGP226 used as control antibodies were generated as described previously [23] .", "Animal ID CP and CA MAb Peramivir Protective efficacy of passive immunization with MAbs m61 and ch61 in mice", "Correlation between disease severity and elevated levels of IL-6" ] },{ "paper_id": "4cd5e0a3e13b16bea2c7e595e6a77344fa3caebc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There are three documented detections of poxviruses in bat populations under distinct circumstances (summarized in Table 1 ). The viruses were detected in animals from both bat suborders on three different continents. They had varied clinical impacts on their hosts and were phylogenetically dissimilar. ", "Irrespective of their potential role as zoonotic agents however, the study of poxviruses in bats opens unique avenues of highly relevant research for multiple research fields beyond the individual host-pathogen relationships. Further field (in situ), in vitro and in silico studies could elucidate the possible coevolution, cross species infections and mechanisms of host range restriction of bat poxviruses, the implications of which are relevant for bat ecologists, virologists and emerging infectious disease specialists (including those with a specific interest in bats) alike.", "Between 2009 and 2011, a poxvirus associated with pathology (tenosynovitis and osteoarthritis) was detected in six adult big brown bats (Eptescicus fuscus, a microbat) sampled at a wildlife center in the North Western United States [35] . The clinical illness of the bats was progressive and ultimately led to their euthanasia. Histopathological examination of the joint lesions was indicative of poxvirus infection, which was confirmed by electron microscopy. The virus was successfully isolated on an African Green Monkey cell line (BSC40) and the genome was partially characterized (seven full protein coding sequences). Phylogenetic analysis revealed that the novel Eptesipox virus was most closely related with Cotia virus, a virus detected in sentinel suckling mice in Sao Paulo, Brazil in 1961 ( Figure 2 ) [36, 37] .", "Finally, a bat poxvirus was again detected in a clinical setting, in South Australia in 2009. The virus was identified as an incidental infection during investigation of an outbreak of parasitic skin disease in a population of Southern bentwing bats (Miniopterus schreibersii bassanii, a critically-endangered microbat species) [38] . Bats presented with white nodular skin lesions that contained encysted nematodes. However, in one of the twenty-one bats examined, an independent (non-nematode associated) lesion contained intracytoplasmic inclusion bodies indicative of poxvirus infection, which was confirmed with electron microscopy [38] . No further confirmation or characterization of the virus was reported, and both the epidemiology and consequent conservation implications of poxviral disease for this species remain unknown." ] },{ "paper_id": "4cd8e92fcab8da2c840ff39f14ca35bf5ba6e444", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author(s) declare that they have no competing interests." ] },{ "paper_id": "4cd92be2bf6b804588415da689ae6afa8ef97099", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4ce340ef89eb6535f11ace1d627d98e619e2d17b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mixtures were heated at 65uC for 5 min and cooled on ice for 2 min to denature the secondary structure. Then 4 ml 56firststrand buffer, 1 ml 0.1 M dithiothreitol (DTT), 1 ml 40 U RNase OUT, 1 ml 10 mM deoxynucleoside triphosphates (dNTPs) and 1 ml 200 U SuperScript III reverse transcriptase were added along with RNase-free H 2 O to bring the final volumes to 20 ml. The reactions were incubated at 25uC for 5 min followed by 50uC for 60 minutes, then inactivated at 75uC for 15 min.", "The significant data were aligned online against the nonredundant and viral reference databases of GenBank with BLASTx and BLASTn. The BLAST hits were defined as significant if E value #10e25 [10] . Contigs of bacteria and eukaryotes were eliminated and virus-like sequences were subjected to further analysis.", "The above viral nucleic acids were reverse transcribed with SuperScript III reverse transcriptase (Invitrogen, Carlsbad, CA) using a published method [36] . Briefly, four 20-nucleotide barcode DNAs were designed online (http://www.changbioscience.com/ primo/primor.html) and anchored to random hexamers to prepare barcode primers. Each of the four groups of nucleic acids was added separately to the four barcode primers (10 mM)." ] },{ "paper_id": "4ce5891928816eb6068228ce463b91ed70df44e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords: tuberculosis, co-infection, risk, immunology, children, pediatric, mycobacteria", "Vaccine cohorts \u2022 Do co-infections affect efficacy or immunogenicity of novel vaccine candidates", "EW and JS devised the manuscript. EW, EL-V, CB, and JS contributed to the manuscript. ", "The global burden of influenza disease in young children is high, with an estimated 90 million new cases of influenza and 20 million cases of influenza-associated acute LRTI in children <5 years old each year. Of the estimated annual 28,000-111,500 pediatric deaths attributable to influenza LRTIs, 99% occur in developing countries (122) .", "The composition of the gut bacterial microbiome changes with age (202) . Soon after birth the neonatal gut is dominated by Enterobacteriaceae. This is soon replaced by predominately Bifidobacteria which continue to be the most commonly represented class of bacteria until the child is weaned onto solids. Following weaning, the adult pattern is seen with Bacteroides, Prevotella, Ruminococcus, Clostridium, and Veillonella occupying the gut (203) .", "Innate immune responses play a pivotal role in early host defense against extracellular bacteria including S. pneumoniae and H. influenzae. Bacteria are initially recognized by pattern recognition receptors consisting of TLRs, the cytosolic NODlike receptors and DNA sensors. Recognition by these pattern recognition receptors triggers the release of pro-inflammatory mediators and stimulates the recruitment and activation of phagocytic cells. The resulting innate immune response involves complement (particularly C3), acute phase proteins (e.g., C-reactive protein, serum amyloid protein), neutrophils, macrophages, NK cells, and pro-inflammatory cytokines (TNF\u03b1, IL-1, -6, -12, -17, -18) (141) . Type I IFNs also appear to have an immunoregulatory role (142) . Adaptive immunity is also important, particularly the synthesis of IgM, IgA, and IgG antibodies by B cells activated by bacterial antigens (143) ." ] },{ "paper_id": "4ceca734c7185a61184a7e464e454b7f7d958dba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "See the Editorial Commentary by Graham on pages 686-7.)", "Disclaimer. The Bill & Melinda Gates Foundation had no role in drafting the manuscript or the decision to publish." ] },{ "paper_id": "4cfaea8e65d7e5f6884cffa4055f7f0b48ca164c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasmids containing full-length of individual Nsp gene including Nsp1\u03b1, Nsp1\u03b2, Nsp2-Nsp5, Nsp7, Nsp8-Nsp12 with a HA-tag were constructed and conserved in our laboratory [49] . The full sequence of each of the Nsp genes was amplified by PCR using the infectious clone pWSK-JXwn as a template [47] . The PCR fragments were cloned into the pCMV-HA (Clontech) mammalian expression vector. To construct lentiviral plasmids, individual Nsp gene was cloned into the pWPXL vector, separately. A C'-terminal GFP tag was fused to each DNA construct.", "The data represents the mean values and SDs from three independent experiments. All statistical analyses were performed using Graphpad Prism version 5.0 software. Statistical comparisons were performed using One-way ANOVA with Bonferroni correction. Significant differences (P < 0.05) are denoted in figures by asterisks.", "doi:10.1371/journal.pone.0156518.g003", "doi:10.1371/journal.pone.0156518.g004" ] },{ "paper_id": "4d0b62b91c66f47c6aff69dfa0ed2c25ffe064ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, viral genetic diversity can prevent the detection of viral variants. Use of degenerate consensus primers targeting conserved viral regions can improve detection of variants, but often at the cost of decreased sensitivity.", "Cellular debris and bacteria were removed from mouse tissue homogenates by filtration through 0.45 mM filter (Millipore). Filtered viral particles were then pelleted by centrifugation at 22,0006 g for 2 hrs at 8uC and resuspended in Hanks buffered saline solution (Gibco, BRL). Non-particle protected (naked) DNA and RNA was removed by digestion with a cocktail of DNase enzymes consisting of 14 U of turbo DNase (Ambion), 20U benzonase (Novagen) and 20U of RNase One (Promega) at 37uC for 90 minutes in 16 DNase buffer (Ambion). Remaining total nucleic acid was then isolated using Qiamp Viral RNA isolation kit (Qiagen) according to manufacturer's protocol. Purified viral RNA was protected from degradation by addition of 40U of RNase inhibitor (Invitrogen) and stored at 220uC.", "Enterovirus. According to California Department of Public Health records, sample VRDL2 produced flaccid paralysis in" ] },{ "paper_id": "4d0d82be6ba94422e252ff243a2cd89d13ea736a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "OCT4 (POU5F1) miR-146b-5p Octamer-binding transcription factor 4+ (Oct-4) is a stem cell marker protein. It acts as a master switch in differentiation by regulating cells that have pluripotent potential.", "CD34 let-7g let-7d let-7c", "Aquaporin5 miR-331-3p miR-497" ] },{ "paper_id": "4d10ef49bd91ac16d18f53f428f4ef3acc96469a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We first analyzed the data using RECCO (Maydt and Lengauer 2006) , which provides an initial suggestion of whether recombination might have occurred and approximates the location of breakpoints using cost optimization. Only those putative recombinant sequences that produced a cost saving greater than 20 (the mutation cost saved by each additional unit of recombination cost; (Maydt and Lengauer 2006) and which had a P value <0.001 were deemed, conservatively, to be worth investigating further.", "Supplementary materials S1-S7, figures S1-S4, and tables S1 and S2 are available at Genome Biology and Evolution online (http://www.gbe.oxfordjournals.org/).", "Many of the non-HPgV s were sampled in Africa and only the equine pegiviruses were isolated in Europe. As for the hepaciviruses, more closely related sequences tend to share the same continent of sampling, but there is little discernable pattern at the among-lineage level." ] },{ "paper_id": "4d1125dd2aac5fa05600973b570834950bbcbccc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For non-quantitative PCR applications, 100 ng of template was amplified using ReddyMix Complete master mix (Thermo Scientific) and products were visualized via ethidium bromide following agarose gel electrophoresis. Primer sequences and thermocycling conditions are listed in Supplementary Table 1 ." ] },{ "paper_id": "4d140ee8fb10afd86c19fc5ad4749771dc37d146", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "According to a phylogenetic analysis of their HEF genes the existing strains are divided into six genetic and antigenic lineages, Taylor/1233/47, Aichi/1/81, Sao Paulo/378/82, Kanagawa/1/76, Yamagata/26/81 and Mississippi/80 (Matsuzaki et al., 2003; Muraki and Hongo, 2010; Muraki et al., 1996; Speranskaia et al., 2012) . However, there is very little sequence variation (Table S1 ) and thus influenza C virus was considered to be monosubtypic and stable in evolution, but reassortment between strains within the influenza C genus occur frequently which leads to the appearance of new strains better adapted to their host (Matsuzaki et al., 2003; Peng et al., 1994) .", "The temperature sensitivity of HEF is probably an adaption of the virus to replicate only in the upper respiratory tract that has, due to contact with inhaled air before it is warmed up, a lower temperature than the lower respiratory tract. In the lab (cell culture and chicken embryos) influenza C virus is also amplified at 33\u00b0C where it grows to higher titers than at 37\u00b0C (Crescenzo-Chaigne and van der Werf, 2007; O'Callaghan et al., 1977; Pachler et al., 2010; Wagaman et al., 1989) . However, other proteins also influence the temperature preference for virus replication since the polymerase also exhibits a higher activity at 33\u00b0C than at 37\u00b0C (Nagele and Meier-Ewert, 1984 ).", "Several studies illuminated the essential role of palmitoylation for association of HA with rafts, cholesterol and sphingolipid-enriched nanodomains on the cellular plasma membrane that serves as the viral assembly and budding site (Engel et al., 2010; Levental et al., 2010; Melkonian et al., 1999; Veit and Thaa, 2011) (Fig. 6) . Interestingly, HEF is apparently not a component of rafts, at least it does not associate with detergent-resistant membranes, their controversial biochemical correlate indicating that virus particles buds from the bulk phase of the plasma membrane (Zhang et al., 2000) ." ] },{ "paper_id": "4d1696e014e57ca335e9fe116840afda273d2ba9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4d1c9efa716ac08a4527a14023fc714ef4e3d8ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors have no financial relationships relevant to this article to disclose.", "Acute cerebellar ataxia (ACA) is described as a clinical syndrome of acute onset of cerebellar dysfunction, with good long-term prognosis. However, it should be kept in mind that acute cerebellar ataxia and acute cerebellitis overlap considerably, there are no distinct boundaries, and occasionally the two entities can be used in a similar meaning [9, [14] [15] [16] . ACA must be differentiated from tumor, abscess, polyneuritis, intoxication, metabolic disease, hereditary degenerative disorders, meningitis, encephalitis, and acute disseminated encephalomyelitis.", "Regarding the systematic review of current literature for influenza associated cerebellitis, we searched for articles published up to 2016 in the following databases: Pubmed, Medline, Embase, Cochrane libraries, and CINAHL. We used search terms including \"cerebellitis,\" \"childhood,\" \"influenza\" to identify reports that presented data on influenza-associated cerebellitis. In Pubmed, when we researched the topics about \"cerebellitis and childhood\", 27 articles appeared. After excluding the articles which concerned studies of other viruses and radiological studies of AC, we found 10 articles which met our fundamental subject: cerebellitis and influenza infection." ] },{ "paper_id": "4d1f54f77265414c23216e284e9bdb257a8e7e26", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .02414-19. ", "Genomic DNA was extracted using a DNeasy Blood and Tissue kit (Qiagen). DNA fragments covering the region targeted by sgRNA were amplified by PCR using gene-specific primers (Table S3 ) mixed with GoTaq master mix (Promega), and the PCR products were sequenced. Cells with frameshift mutations (deletion or insertion) in targeted genes were selected for further experiments.", "The fragments were cloned into pMal (NEB) vectors between SalI and XbaI restriction sites. pMal-bOAS2-D2 and pMal-bOAS3-F2/3 were transformed into NEB-Express competent Escherichia coli, and IPTG was added to the bacterial cultures to induce expression of the proteins. The proteins were purified by elution from the protein bands cut from polyacrylamide gels with the Pierce zinc reversible stain kit (Thermo Fisher). The eluted proteins were concentrated and showed a single band on a polyacrylamide gel by staining. Rabbits were injected with 250 g protein each 4 times over about 2 months before bleeding. Mouse anti-GAPDH GA1R (1:1,000; Thermo Fisher) was used to detect bat GAPDH. Mouse anti-FLAG M2 antibodies (1:1,000; Sigma-Aldrich) were used to detect 3\u03ebFLAG-hOAS3. Secondary antibodies goat anti-mouse antibody (1:5,000; Santa Cruz) and goat anti-rabbit antibody (1:3,000; Cell Signaling), conjugated to horseradish peroxidase (HRP), were used to detect mouse-or rabbit-derived primary antibodies." ] },{ "paper_id": "4d1f8955a62f01fe7a4d7d19593bdbd6047f4f41", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflicts of interest and no competing financial interests.", "All animal work was conducted according to UK Home Office guidelines and approved by the Roslin Institute Animal Welfare and Ethical Review Body.", "Final results are shown as 40-Ct using the normalised value, or as fold-change from uninfected controls." ] },{ "paper_id": "4d2c66f3c30a2fd8f14f75c3f5405e2ba61b9345", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was run using Microsoft-Excel-2010 software, PASW Statistics 18 (Predictive Analysis Soft-Ware -SPSS Inc.) and R [28] ." ] },{ "paper_id": "4d2e434006533cb3bbb701dffb53169b40a9c315", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2015, 7 4 protein, or SUMO chain formation [19] . Additonally, there might be crosstalk between SUMOylation and phosphorylation [20] .", "AcMNPV (Autographa californica nuclear polyhedrosis virus) infects invertebrates and belongs to " ] },{ "paper_id": "4d392425fe3005f145fdfa835421ff0aa5fe0104", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and r i~rpop e g (i) r ;", "and", "." ] },{ "paper_id": "4d44402d0831ef5a86694ff70f9764a46fa06deb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were analyzed by analysis of variance (ANOVA) and post hoc Student-Newman-Keuls tests using SigmaStat software (Systat Software, San Jose, CA, USA). P-values less than 0.05 were considered significant.", "Needle-free vaccination via mucosal routes has drawn increasing recent attention as a vaccine delivery strategy. An ideal vaccine against an infectious pathogen should prime the host for induction of pathogen-specific memory immune responses at the appropriate mucosal compartment, thereby preventing the entry and/or replication of the invading pathogen at the site of infection [1] . Mucosal immunizations via nasal, buccal, or sublingual routes have recently emerged as alternatives to intramuscular (IM) vaccine administration. Non-parenteral, needlefree mucosal vaccination has several advantages, including reduced pain stresses, costs, and viral transmission associated with the injection [2, 3] .", "doi:10.1371/journal.pone.0119408.g001 diluted 3,000-fold and incubated on ice for 1 hour with 3-fold serial dilutions of serum. 293TT cells were infected by incubating with each PV-antibody mixture for 72 hours. The SEAP content in 10 \u03bcl of clarified cell supernatant was determined using the Great EscAPe SEAP Chemiluminescence Kit (Clontech, Mountain View, CA, USA). Neutralization titers were defined as the reciprocal of the highest serum dilution that caused at least a 50% reduction in SEAP activity." ] },{ "paper_id": "4d44adb48335ef12290b3584771b424aa28185e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4d4b94ef0c1fb8139c207f5cd7fe3037747fd551", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ELISA IFN-\u03bb1 protein was measured from culture supernatants by ELISA following the manufacturer's instructions (R&D Systems, MN, USA) with analysis using on a Fluorostar Optima microplate reader (BMG Labtech, Ortenberg, Germany)." ] },{ "paper_id": "4d4de01a6f9ad02ac0939d54713c209153fa66df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The virus strain used in this study was PHE-CoV-67 N (GenBank accession no. AY078417). The viruses were propagated and passaged in porcine kidney epithelial (PK)-15 cells [19] , and purified by sucrose density gradient centrifugation. The viruses were stored at \u221280\u00b0C until needed." ] },{ "paper_id": "4d5640c129096fd8a4da9d32030420def86285e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Non-specific antibody binding was blocked with a mix of mouse F c block (purified \u03b1-CD16/ 32, BD Biosciences) and normal mouse serum for at least 15 minutes. All antibodies (anti-CD45, anti-CD4, anti-CD8, anti-CD11b, anti-CD19 anti-Ly6G, anti-NK1.1 (BD Biosciences, San Jose, CA)); and anti-F4/80 (AbD Serotec, Raleigh, NC) were directly conjugated with one of the following fluorochromes: fluorescein isothiocyanate (FITC), phycoerythrin (PE), peridinin-chlorophyll proteins (PerCP), or alophycocyanin (APC). The cells were incubated with these antibodies for 20 min in FACS buffer (1% BSA in PBS), then washed with FACS buffer, fixed in 2% paraformaldehyde solution and acquired using a BD Fortessa flow cytometer (BD Biosciences, San Jose, CA). The flow cytometer was calibrated using beads (eBiosciences) conjugated with fluorescent antibodies for each channel in the assay. The resulting data from each samples was analysed using FlowJo (version 10) software (FlowJo, LLC, Ashland, OR).", "T cell Infiltration and Neurodegeneration in Zika Infected B6 Mice PLOS Pathogens |" ] },{ "paper_id": "4d601f59175ab8d983670ce69504c80be6fb38a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by The First Affiliated Hospital of Guangzhou Medical University Ethics Committee for research on human beings, and all participants or their guardians gave signed informed consent for participation in the study.", "ADV infection usually causes symptoms of low respiratory illness (LRI) in children, and can occur all year round. In Guangzhou, ADV was mainly found in summer and autumn, but was also present all year long (Figure 4 ).", "Statistical analysis was performed using SPSS statistical software (version 19.0; SPSS Inc., Chicago, IL, USA). For comparisons of categorical data, the x 2 test and Fisher's exact test were used as appropriate. All tests were two-tailed and p,0.05 was considered statistically significant.", "Pediatric patients (#14 years old) who presented with at least two of the following symptoms: cough, pharyngeal discomfort, nasal obstruction, snivel, sneeze, dyspnea or who were diagnosed with pneumonia by chest radiography during the previous week, were enrolled in this study. Chest radiography was conducted according to the clinical situation of the patient, and pneumonia was defined as an acute illness with radiographic pulmonary shadowing (at least segmental or in one lobe) by chest radiography." ] },{ "paper_id": "4d754b08444d19e6df8559afad357bb13be89bd8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed using GraphPad Prism version 5.0 for Windows (GraphPad Software, Calfornia, USA). Differences between groups were assessed using unpaired Students' t test or oneway ANOVA, with p 0.05 being regarded as significant." ] },{ "paper_id": "4d7ed140eb8fb2b02900f7ed3ad33e99dc438989", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pre-validated gene expression assays were purchased from Applied Biosystems. See Table 1 for the Assay and Gene", "Publish with Bio Med Central and every scientist can read your work free of charge ", "The pre-publication history for this paper can be accessed here:", "IDs. An aliquot of the cDNA from a subset of samples was TaqMan \u00ae analyzed with human GAPDH prior to profiling. TaqMan \u00ae analysis was done in duplicate reactions using the low density array format as described by Osman et al [24] . This was validated and processed through the Lucy Whittier Molecular and Diagnostic Core Facility (1). The samples were placed in a 384 well plate and amplified in an automated fluorometer (ABI PRISM 7900 HTA FAST, ABI). ABI's standard amplification conditions were used: 2 min at 50\u00b0C, 10 minutes at 95\u00b0C, 40 cycles of 15 seconds at 95\u00b0C and 60 seconds at 60\u00b0C. Fluorescent signals were obtained during the annealing temperature and Ct values exported with a threshold of 0.1 and a baseline of 3-10." ] },{ "paper_id": "4d94a96a67f554bab5caafc4501fb7fda538609f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Structures of the terpenyl-1,4-naphthoquinone (NQ) and 1,4-anthraquinone (AQ) derivatives tested. ", "Statistical analyses were performed using the statistical software GraphPad Prism\u00aev. 5.0 (GraphPad Software Inc., La Jolla, CA, USA). In all cases, p value < 0.05 was statistically significant.", "In recent years, the treatment and control of some viral agents has become a major challenge for the pharmaceutical industry due to their pathophysiological features and development of drug-resistance. Among these, Human Herpesviruses type 1 and 2 (HHV-1 and HHV-2), associated with cold sore and herpes genitalis respectively [1] , are neurotropic and neuro-invasive double-stranded DNA (dsDNA)", "Parametrization of ligands (NQ 4 and doxorubicin) and DENV-2 prefusion envelope protein (PDB:1OKE) was done using the AutoDock Tools suite [54] . Hydrogen atoms were added to the polar side chains and partial charges were calculated through the Gasteiger methodology. Then, a grid box was delimited in a binding site previously reported with some studied inhibitors [16] . Molecular docking was run with a modified version of AutoDock Vina that includes a scoring function parameterized also for halogen interactions [55] . We used an exhaustiveness (number of internal repetitions) of 20 for each protein-compound pair. The interactions (hydrogen bonds and hydrophobic interactions) and the predicted free energy scores in kcal/mol were obtained. Visualization of the docking results was generated using the Discovery Studio package." ] },{ "paper_id": "4d968bbfddfa8eb4f1cad1f00ed121ec2c4a4df6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4d9b9c94e5b2cd4016b42cdc8fbcb85fa908bc64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following themes emerged during the course of this workshop. On prioritizing animal and zoonotic disease research and related drug pipeline projects:", "On the regulatory aspects of drug and vaccine development for animals:", "Are the Existing Research Gaps that Impact Both Human and Animal Health? Is There Any Low-Hanging Fruit?" ] },{ "paper_id": "4db3931c4b24ae432d68b7e24f593b1272445523", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Labeled and used to hybridize chips", "For the SSH experiment, 1 \u03bcl subtractive PCR products were labeled with Cy3 and Cy 5-dCTP (NEN, Boston, MA) using random primers. Unincorporated fluorescent nucle-otides were removed using a Qiaquick PCR purification kit (Qiagen). The fluorescent-labeled DNAs were mixed with 30 \u03bcg of human cot-1 DNA (Invitrogen) and 100 \u03bcg yeast tRNA, precipitated and then resuspended in 30 \u03bcl of Microarray Hybridization Buffer Version 2 (Amersham Pharmacia). The hybridization solution was heated to 80\u00b0C for 10 min to denature the DNA and was then incubated for 30 min at 37\u00b0C, allowing cot-1DNA and yeast tRNA to block the repetitive sequences in genome probes. The probes were hybridized to a human cDNA microarray (GMRCL Human 15 K). We scanned the slides with a confocal scanner ChipReader (Virtek, Canada) and acquired" ] },{ "paper_id": "4dbe45a5961f17aaa90175a28dfec6fe5ab9094d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4dcde213ebf72aff0935b2714faf7fd691736c5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Acacetin (C 16 ", "The authors declare no conflict of interest.", "The following abbreviations are used in this manuscript: " ] },{ "paper_id": "4dd0f09aa22d567e9f5f9a0bebd8686be35da853", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The use of natural compounds has also been an alternative antiviral approach. For example, polyphenols, such as delphinidin and epigallocatechin gallate have exhibited potential antiviral activities against flaviviruses including ZIKV, DENV, and WNV [113] . A member of the largest family of polyphenols, the flavonoid isoquercitrin also demonstrated antiviral effect against ZIKV by acting on viral entry [114] . A bacterially derived nanchangmycin is another natural compound that inhibited ZIKV entry in human osteosarcoma cells (U2OS), human brain microvascular endothelial cells, and human trophoblast cell line Jeg-3, and was also active against DENV, WNV, and chikungunya virus [115] . Furthermore, berberine and emodin showed strong inhibitory effect on ZIKV infectivity in vitro [116] .", "Small non-coding RNAs are another potential restriction factor that can limit ZIKV replication. MicroRNA (miRNA) have been shown to have a role during ZIKV infection by regulating a broad spectrum of cellular processes [94] . Because a single miRNA has multiple targets within a specific cellular process, a change in expression level induced by a virus infection results in an amplified effect [95, 96] . In Smith et al., high content immunofluorescence screening identified miRNA34 to inhibit the replication of three flaviviruses (DENV, WNV, and JEV) through the Wnt/\u03b2-catenin signaling pathway, during which a dampened Wnt signaling leads to TBK1-induced phosphorylation of IRF3 and initiation of downstream IFN signaling [94] . It will be interesting to further study the antiviral role of differentially regulated small RNAs during ZIKV infection.", "Through active interference with viral replication in various ways, interferons (IFNs) orchestrate the primary response to viral infection [75] . Their origin and cellular targets distinguish the three types of IFNs (I, II, III), all of which engage with their respective receptors to initiate signaling through the JAK/STAT pathway, and induce activation of interferon-stimulated genes (ISGs) [76] . Upon activation, ISGs directly target factors of the virus life cycle to control the infection [77] . All three types of IFNs are implicated in mediating the antiviral state of the host immune response.", "Although remarkable progress in ZIKV research has created opportunities for the development of vaccines and therapeutics, some of which are currently advancing through clinical trials, the following key outstanding questions still remain to be addressed and should be the focus of future perspectives: 1) what is the mechanism by which ZIKV crosses the placenta and infects developing fetus? 2) What host and viral factors contribute to ZIKV persistence in the placenta and other immune-privileged sites? 3) What are the roles of noncoding RNAs during ZIKV infection?", "Flaviviruses carry out their life cycle by utilizing machinery and functions of the host cell [12] . Consequently, flavivirus-host cell interactions are essential for the pathogenesis. Many of these crucial interactions, however, remain elusive. In this Review, we focus on ZIKV, a member of the Flaviviridae family, and highlight the viral pathogenesis at the level of cellular mechanisms and interactions." ] },{ "paper_id": "4dd9d9ada59d79f3212e4451dd620f25cc84d86d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data are representative of at least three independent experiments. Data are presented as means \u00b1 standard deviations (SD). Statistical significance was calculated by GraphPad Prism 7 software using one-way ANOVA with Turkey's test, with P values < 0.05 considered significant." ] },{ "paper_id": "4dee76896810956dac4627041734652c1c953947", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We collected fecal samples from 72 individual bats representing four species from three bat families (Pteropodidae, Rhinopomatidae, and Emballonuridae) roosting in Bisha, KSA ( Table 2 ). Bat species were identified using external morphological features [28] by trained bat biologists and confirmed via molecular testing by cytochrome B gene PCR amplification and sequencing [11, 29] . Total nucleic acid was extracted from fecal samples prior to library preparation and sequencing on the HiSeq 2500 system (Illumina, San Diego, CA).", "Genbank accession numbers for reported viruses are summarized in Table 1 .", "Supporting information S1 ", "Bastrovirus shared homology to the capsid protein of Astroviridae and the putative non-structural protein was homologous to the non-structural protein encoded by members of the Hepeviridae family [34] ." ] },{ "paper_id": "4dfa5a3533ef3b79abb871f4b4132f8b654a52eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4dfc59a66e7a86f6a40c5fafad4c12f483ce40bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The multiple host-protective functions of PTX3 arise from the capacity for the recognition and binding to ligands. The reported PTX3 ligands are classified as follows: (1) complement components; (2) Fungi, bacteria, microbial components, and viruses;", "The release of neutrophil extracellular traps (NETs), first reported in 2004 (Brinkmann, 2004) , is one of the antimicrobial actions of neutrophils. NETs are mesh-like structures that contain DNA as a backbone, with anti-microbial proteins attached (Amulic and Hayes, 2011) . NETs trap microbes and form an anti-microbial-protein-rich microenvironment (Medina, 2009) .", "The mechanism by which PTX3 localizes in NETs has not yet been determined, but it is possible that PTX3 localization arises from an interaction with histones or the basic proteins AZU1, MPO, and defensin, along with a simultaneous association between these basic proteins and DNA (Figure 1) . It is not clear at present whether the PTX3-AZU1 and PTX3-MPO binding events in the bloodstream take place within or outside of NETs. Either or even both of these are possible, and these complexes may be active in pathogen recognition and also involved in clearance. In septic patients, the plasma levels of AZU1 are increased, but do not significantly correlate with mortality (Berkestedt et al., 2010) . As useful biomarkers of sepsis not yet available (Pierrakos and Vincent, 2010) , the binding levels of PTX3-AZU1 and PTX3-MPO in septic plasma have the important potential to fulfill this purpose.", "December 2012 | Volume 3 | Article 378 | 7 PTX3 and its complex component proteins were immunoprecipitated by anti-PTX3 antibody-crosslinked magnetic beads, and the isolated fractions were subjected to shotgun proteomics analysis for label-free relative quantitation via spectral counting (Daigo et al., 2012) . The identified proteins included the known PTX3 ligands such as C1q, ficolins, TSG-6, and I\u03b1I, as mentioned above. Additionally, the ficolin-binding proteins of mannan-binding lectin serine protease 1 and 2 (MASP1 and MASP2) (Ma et al., 2009) , and the TSG-6 binding proteins of the versican core protein (VCAN) and thrombospondin-1 (THBS1) (Salustri et al., 2004) were included in the proteins that were identified. As these proteins were identified in pooled normal human plasma with artificially spiked recombinant PTX3, these appear to be stable circulating PTX3 complexes. Nevertheless, the disease-specific dynamics of these binding levels need to be investigated further, as do the specific functions of these PTX3 complexes in sepsis." ] },{ "paper_id": "4e0851aa892c56090edbc47e9506313d2a1b20e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4e1119e030d3d053276c55c9220a388d743bb0e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition, RNAi studies identified antiviral defense genes in Drosophila, their impact on viruses replication in human cells has yet to be elucidated [51] .", "Global proteomic and metabolomics profiling study has also been used to identify the metabolic interplay occurring during infection with HCV [77] . Integrating computational modeling approaches revealed that mitochondrial fatty acid oxidation enzymes are differentially regulated both in culture and in HCV-infected patients. This study highlights the potential of complementary approaches to elucidate mechanisms by which viruses take over cellular resources for their own replicative advantage.", "Interestingly, 40% of a subset of these ncRNAs was similarly regulated in response to both influenza virus and interferon treatments suggesting a host response regulated by innate immunity [65] ." ] },{ "paper_id": "4e19f6204f9b71da1d578f07164ad58db49b8f92", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The microbial genomic DNA was extracted from the samples and purified using the QIAamp DNA Stool Mini Kit (Qiagen Ltd., Germany) following the manufacturer's instructions. Adequate quantity of high-quality genomic DNA was extracted, and the concentration of DNA was measured using a UV-Vis spectrophotometer (NanoDrop 2000c, USA).", "All animal experiments were reviewed and approved by the Institutional Animal Care and Use Committee of China Agricultural University and performed in accordance with the Guidelines for Experimental Animals of the Ministry of Science and Technology (Beijing, China). All the methods were in accordance with the guidelines approved by the Quality Supervision, Inspection, and Quarantine of the People's Republic of China (GB/T 17236-2008). The Animal Welfare Committee of China Agricultural University approved all experimental protocols (permit number: DK996).", "Several microorganisms, including Rotavirus, Coronavirus, Escherichia coli, Clostridium perfringens, Clostridium difficile, Cryptosporidium spp., Giardia spp., Cystoisospora suis, and Strongyloides ransomi, have been linked to enteritis and diarrhea in suckling pigs. Suckling piglets are the most sensitive to PED at the age of 3-7 days [3] , and the first week of birth is also a stage of gradual establishment of intestinal microorganisms [34] . The gut microbiota is relatively simple and susceptible to pathogenic bacteria [35] ." ] },{ "paper_id": "4e1a080ea558bba7654e05d59ed0b6c6e686b66e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4e2f13bbb7637dc94eba63f2170cbcbceafcc4c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 7:45473 | DOI: 10.1038/srep45473 in Fig. 1C . Typically, the reaction sets are operated in a 96-well format and either dynamic or endpoint reading of fluorescence excitation intensity is automated (details in Methods).", "The robustness and dynamic performance of the assay toward Ang II and apelin-13 substrates.", "To measure the dynamic formation of Ang-(1-7) from an in vitro reaction with kidney lysate, 20 \u03bc L reactions containing 0.5 \u03bc M Ang II and 10 \u03bc g lysates were incubated at 37 \u00b0C. Reactions were stopped at different time points by diluting 1000 times with ice-cold methanol. After further diluting the sample in EIA buffer (1/50), the quantity of Ang-(1-7) was determined using an EIA kit (Peninsula Laboratories LLC, San Carlos, CA, USA), as per manufacturer's instructions.", "We next evaluated the intra-assay and inter-assay precision and reproducibility. Samples that contain different rsACE2 amounts were measured in reactions with Ang II, and the results were subsequently calculated from the standard curves obtained above. Supplementary Table S1 shows the intra-assay coefficient of variation (CV) ranged from 2.12% to 7.4% and the inter-assay CV ranged from 6.23% to 10.1%. These low CV values indicate high reliability of the assay." ] },{ "paper_id": "4e30ead25a8574d9013af8ea6f6d5a1be19e41b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The questionnaire was accessible on line between January and May 2016, and we received 80 replies (11.7% of 685). Among the 80 respondents, 33 replied to all questions, 27 omitted between 1 and 3 questions, 8 did not reply to between 4 and 6 questions, and 12 did not reply to \u22657 questions (mean number of omitted questions \u00b1 SD = 4.687 \u00b1 9.832). This response rate was considered to be normal for this type of questionnaire, although not totally satisfactory for the category of interviewed professionals.", "Age and year of medical degree may interact with training components", "All analyses were performed using Systat ver. 13.1 (Systat Software Inc., CA) and S-Plus 4.5 (TIBCO Software Inc., CA).", "All the estimations were rated on a 10-point Likert scale [29] with 0 being the lowest and 10 the highest level. Reliability of the study instrument was determined using Cronbach's \u03b1. Because we have several questions that are heavily dependent on some core questions, we calculated Cronbach's \u03b1 by two different means. Cronbach's \u03b1 taking into account all questions yielded a value of 0.938 (number of items is 72) and Cronbach's \u03b1 using only main questions yielded a value of 0.789 (number of items is 58), suggesting that the items in our questionnaire have relatively high internal consistency." ] },{ "paper_id": "4e388424e65f63b5cc6b567b0980d430cb2d738c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virions are one kind of nanoscale pathogen and are able to infect living cells of animals, plants, and bacteria. The infection is an intrinsic property of the virions, and the biological process provides a good model for studying how these nanoparticles enter into cells. During the infection, the viruses employ different strategies to which the cells have developed respective responses. For this paper, we chose Bombyx mori cypovirus 1 (BmCPV-1) interactions with midgut cells from silkworm, and severe acute respiratory syndrome (SARS) associated coronavirus interactions with Vero E6 cells, as examples to demonstrate the response of eukaryotic cells to two different types of virus from our previous studies. The bacteriophage-bacteria interactions are also introduced to elucidate how the bacteriophage conquers the barrier of cell walls in the prokaryotic cells to transport genome into the host.", "A virus (including bacteriophages) is an infectious agent of small size and simple composition that can multiply only in living cells of animals, plants, or bacteria. The size of spherical virus usually ranges from ten nanometers to hundreds of nanometers in diameter. So they can be viewed as one kind of natural nanobiomaterial [1, 2] . A virus consists of single-or double-stranded nucleic acid and a protein shell, called a capsid. Some viruses also have an outer envelope composed of fatty materials (lipids) and proteins. The nucleic acid carries the virus's genome-its collection of genes-and may consist of either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). The protein capsid provides protection for the nucleic acid and may contain enzymes that enable the virus to enter its appropriate host cell. The host cells of viruses range from animals, plants, fungi, to bacteria and could be divided into two types: the eukaryotic cells and the prokaryotic cells.", "Transmission electron microscopy (TEM) is a powerful tool to investigate microorganisms and has long been used in the discovery and description of viruses [3] . With appropri-ate sample preparation and application on a grid, the visual look of virions can be directly obtained. Beside traditional electron microscopy techniques such as negative staining, ultrathin sectioning, and immunoelectron microscopy [4] , the relatively recently developed techniques such as cryoelectron microscopy (Cryo-EM) with single particle analysis that provides a new set of methods to investigate the 3D atomic resolution structures of macromolecules and cryoelectron tomography (CryoET) that allows the visualization of cellular structures under close-to-life conditions, are available to investigators [5] [6] [7] [8] [9] [10] . Thus, TEM has been and continues to be valuable in elucidating mechanisms of virus attachment and replication in cells. Such information can be useful in the understanding of cellular response to viruses. In this paper, we discuss our previous studies on Bombyx mori cypovirus 1 (BmCPV-1) interactions with midgut cells from silkworm, and severe acute respiratory syndrome (SARS) associated coronavirus interactions with Vero E6 cells as examples to demonstrate the response of eukaryotic cells to two different types of viruses [11, 12] . The bacteriophagebacteria interactions are also summarized to show how the bacteriophage conquers the barrier of cell walls in the prokaryotic cells to transport its genome into the host." ] },{ "paper_id": "4e3d9e4efadec3ac6b84928d59d18992b155d3ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two paired induced sputa and a nasopharyngeal (NP) swab specimens were collected from each child and transported to the laboratory within 2 h of collection. NP swabs were obtained before sputum induction using nylon flocked swabs (Copan Italia, Brescia, Italy) by trained study staff [11] . Each NP swab was immediately placed into 1.5 ml PrimeStore\u00ae transport and stabilization medium (PrimeStore\u00ae MTM, Longhorn Vaccines and Diagnostics, San Antonio, TX) and stored at \u221280\u00b0C within 2 h of collection until further batch processing. Samples were randomly selected from a convenience subset of 214 children, over a 1-year period for testing of NP specimens for other microbes.", "Results were interpreted according to manufacturer's instructions using the FTD resp33 Analyser, an in-house JAVA based program (available at http://www.gematics. com/analyser.html).", "Seasonal patterns were observed for hMPV, rhinovirus, enterovirus and influenza viruses with peak prevalence in late winter (August) and spring (November)." ] },{ "paper_id": "4e40f15493a3858973a18ef28a6f533926167e81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authorities (Lower Saxony State Office for Customer Protection and Food Safety) were notified when animals were specifically sacrificed for the purpose of organ collection. The sacrificing was conducted in accordance to the Animal Welfare Regulations of Lower Saxony. ", "Total RNA was isolated with peqGOLD TriFast TM following the instruction guide (PEQLAB Biotechnologie GmbH, Erlangen, Germany).", "The Supplementary Material for this article can be found online at:" ] },{ "paper_id": "4e45854eace4e5bb9255ad31f7425545f931f3fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The lynx was found dead on Dec 1, 2015 on private land consisting of a mixture of dense scrub and open pasture in an area known as \"Hornachos-Valle del Matachel\" located southwest of Badajoz (Extremadura), Spain (Latitude: 38\u00b027\u203210.98\u2033 N, Longitude: 5\u00b054\u203230\u2033W).", "The lynx that we studied was a wild~9-month-old male, born to a healthy 3-year-old dam. It belonged to the first two litters born in Extremadura (SW Spain) after Lynx pardinus was re-established in this region through the LIFE+ 10NAT/ES/ 000570 project. Using camera trapping, the estimated date of its birth was established to have been between March 8 and 12, 2015.", "Additional file 1: Table S1 . Primers used for SuHV1 amplification. " ] },{ "paper_id": "4e45a8379e00a6551b99dcb0c8ba91b7b358f853", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since user-friendly and publicly accessible web-servers represent the future direction for developing practically more useful models or predictors [91] , we shall make efforts in our future work to provide a web-server for the method presented in this study.", "Many studies have indicated that computational approaches, such as predicting drug-target interaction networks [21] , prediction of body fluids [22] , predicting HIV cleavage sites in proteins [23, 24] , predicting protein metabolic stability [25] , predicting signal peptides [26] , identification of DNA Binding Proteins [27] , predicting the network of substrate-enzyme-product triads [28] , predicting protein subcellular locations [29, 30] , predicting proteases and their types [31] , predicting antimicrobial peptides [32] , predicting membrane proteins and their types [33] , predicting GPCRs and their types [34] , identifying nuclear receptor subfamilies [35] , predicting gram-negative bacterial protein cellular locations [36] , and predicting transcriptional activity of multiple site p53 mutants [37] , can provide many useful insights and data for which it would be time-consuming and costly to obtain by experiments alone. Actually, these data, combined with the information derived from the structural bioinformatics tools (see, e.g., [38] ), can timely provide very useful insights for both basic research and drug development. In view of this, the present study attempts to develop a new computational modeling method in the hopes it may become a useful tool for the drug development.", "Chymase-dependent conversion of angiotensin I to angiotensin II and precursors of TGF-\u03b2 and MMP-9 to their active forms." ] },{ "paper_id": "4e550e034ccca6fa2a91e481ddba24db67bc9ae5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4e6709b68cb7312fda8a1c5a2b2505d21a38a1e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Committee for the Protection of Human Subjects at National Jewish Health has deemed the use of human lung donor cells as nonhuman subject research, since there is no risk to donors and all donors are de-identified. Use of the banked virus specimens and clinical data for this research was approved by the Colorado Multiple Institutional Review Board.", "At 72 hours post-infection, cells were harvested for RNA analysis using the RNeasy RNA extraction kit (Qiagen, Valencia, CA), cDNA synthesis using qScript cDNA SuperMix (Quanta BioSciences, Gaithersburg, MD). To quantitate mRNAs encoding interferons, cytokines and chemokines, we used Taqman ", "Viral RNA from pooled apical washes was extracted using Qiagen EZ1 Virus Mini Kits (Valencia, CA) on a BioRobot EZ1 Extractor (Qiagen, Valencia, CA) following the manufacturer's instructions. Virus yield was determined by a quantitative real time RT-PCR (qRT-PCR) which targeted the HCoV-HKU1 polymerase 1b gene with comparison to copy number from a plasmid encoding the region recognized by this assay. The RT-PCRs were performed using a 1-step reverse-transcription PCR master mix (RNA UltraSense One-Step Quantitative RT-PCR System, Invitrogen Life Technologies, Carlsbad, CA). Reaction mixtures were prepared using a 500-nM final concentration of the forward primer (59-TGGTGGCTGGGACGATATGT-39), 250 nM of the reverse primer (59-GGCATAGCACGATCA-CACTTAGG-39), and 100 nM of the probe (59-6FAM-ATAATCCCAACCCATRAG-minor groove binder nonfluorescent quencher-39). 10 ul of RNA was added to 10 ul of master mix containing an additional 1.3 mM MgCl. RT-PCR was performed using the following cycling conditions: 50uC for 15 minutes, 95uC for 2 minutes, and 40 cycles of 95uC for 15 seconds, 60uC for 30 seconds [12] ." ] },{ "paper_id": "4e687843401f339f6b5e8ae35626d0d0ef0b3e7e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As to outcome indicators for systematic care for children under 3 and maternal women, the mortality for children under 5 and maternal women decreased sharply in 2005-2014, especially in rural area, after 2009. The gaps between urban and rural areas have significantly narrowed since 2009, as shown in Fig. 4 .", "The narrowed gap of health outcomes between urban and rural area", "We recorded it, coded it and conducted qualitative content analyses." ] },{ "paper_id": "4e69eb0c40279678624a4085b3544199d0f5b712", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Zoonotic modes of MERS-CoV transmission have not yet been definitively determined. MERS-CoV in dromedary camels causes a mild upper respiratory infection with no documented viremia [10] , and therefore droplet or aerosol transmission by close camel contact is most likely. However, transmission through contaminated milk, meat, and urine is possible, although the contribution of camel products cannot currently be estimated due to a lack of scientific evidence.", "The World Health Organization (WHO) maintains a list of all human laboratory confirmed cases of MERS-CoV. Publicly available case data from January 2015-December 2017 were obtained. Case data prior to 2015 were excluded due to a lack of standardized data collection prior to 2015 [20] ." ] },{ "paper_id": "4e6b644a4ef4abd5283c18ec18237ca58e0d52e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ere is an urgent need for a major increase in funding for communicable disease control in the developing world and for more balanced allocation of the resources already provided [22] .", "New sequencing technology has enabled the identification of thousands of single nucleotide polymorphisms in the exome, and many computational and statistical approaches to identify disease association signals have emerged [59] .", "e authors declare that they have no conflicts of interest.", "us, a new exhilarating rapidly evolving scientific field, Bioinformatics (Biology meets computer programming), has recently emerged and uses novel computational approaches to help solve important biological problems. Bioinformatics is a set of activities: data acquisition, database development, data analysis, data integration, and analysis of integrated data. e majority of available bioinformatics software requires some knowledge of the text-based command line of the UNIX or Linux operating systems, allowing custom programming scripts and pipelines to automate data manipulation and analysis in a single step [65] . Although bioinformatics tools/software are both \"open sources\" and commercially available, clinicians have limited bioinformatics knowledge [66] [67] [68] [69] . It is clear that user-friendly bioinformatics pipelines are key to facilitating more widespread use of WGS, with more widespread bioinformatics expertise [65] ." ] },{ "paper_id": "4e6d4c7d205f8a78c8b6adf1e0a27a23254851d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells and virus. Hela and 293T cells were cultured in Dulbecco's Modified Eagle Medium (Invitrogen, Carlsbad, CA) supplemented with 10% fetal bovine serum (HyClone, Logan, UT), penicillin (100 U/ mL), streptomycin (100 g/mL), nonessential amino acids (0.1 mM), and L-glutamine (2 mM) (Invitrogen, Carlsbad, CA). SeV (Cantell strain) was propagated at 37 \u00b0C in 10-day-old embryonated chicken eggs.", "Plasmid constructs. Plasmids of pGL3-IFN\u03b2 -luc, pRL-SV40, pEGFP-IRF-3, and pCAGGS were previously described 15 . Plasmids expressing Flag-tagged MDA5C and MDA5H were constructed as previously reported 28 . Plasmids expressing GFP-tagged MAVS, Flag-tagged MDA5, RIG-I, TBK1, and IKK\u03b5 were previously described 60, 61 . The plasmid expressing HA-tagged IRF7 was a gift from Dong-Yan Jin (Department of Biochemistry and Microbiology, The University of Hong Kong)." ] },{ "paper_id": "4e6e76a1940fbfadea1d88bbcbfe4f1554f7719b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quantitative reverse-transcriptase PCR. RNA was purified by TRIZol extraction and diluted to 100 ng/uL. 200 ng was used in a Taqman probe-based one-step qRT-PCR according to previously-reported methods 57 . To quantify RNA, cycle threshold (Ct) values were converted to genome copies per 200ng of input RNA by comparison to a standard curve of serially-diluted pJFH-1 (10 2 to 10 9 copies).", "Modeling indicates that an ensemble of packaging signals with different degrees of affinity for capsid protein is required to promote efficient assembly 11, 22 . Lower-affinity motifs may not necessarily be easily identifiable through a SELEX screen, yet their presence at statistically significant numbers within the wild-type genome ", "Scientific RepoRts | 6:22952 | DOI: 10.1038/srep22952", "In vitro transcripts of the ~1.5 kb region encompassing SL5877 and SL6067 were synthesised from both JFH-1 and mutant templates. RNA was folded and subjected to structural analysis via SHAPE mapping. Following NMIA (+ ) or DMSO (\u2212 ) treatment and reverse transcription, a primer designed to bind approximately 20 nucleotides downstream of SL5877 was used for primer extension. Products were resolved on a 7% denaturing polyacrylamide gel (upper panel) and the relative reactivity was quantified using SAFA 58 . Sequencing ladders were included to identify individual nucleotides, based upon the wildtype genome sequence." ] },{ "paper_id": "4e70161128a045145f613dfd2029d383e4dde823", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where and represent the same parameters as before.", "By extending the covariate modeling approach for a particular evolutionary parameter to a matrix of transition rate parameters defining a CTMC process, Lemey et al. (2014) ", "Following the terminology of ANOVA and regression models, the specification of hierarchical priors can model random effects on the evolutionary response variable. In order to test the impact of patient groups defined by disease progression and host genetic status, Edo-Matas et al. (2011) further extend the HPM approach by incorporating fixed effects for N covariates, arriving at the following general form:" ] },{ "paper_id": "4e741d57fb2db417d3a82fae701233ed7d4c5b55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4e83f87fdf5b15fb7962c1b6235b520817924a9b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following viruses that had been stocked by one of the authors were examined: ", "Alternatively, the infected H292 cells were fixed with acetone and stained with amide black solution (0.5% amide black, 45% ethanol, 10% acetic acid). The stained cells in each well were pictured with greyscale, and the color intensity was quantitated by image processing program NIH image.", "The following lectins were purchased from Seikagaku Corporation (Tokyo, Japan). AAL: Aleuria aurantia, ConA: Canavalia ensiformis, MAM: Maackia amurensis, PNA: Arachis hypogaea, PWM: Phytolacca americana, SBA: Glycine max, WGA: Triticum vulgaris. The following lectins were purchased from Cosmo Bio (Tokyo, Japan). GNA: Galanthus nivalis, SNA: Sambucus nigra, UDA: Urtica dioica. The lectin AOL from Aspergillus oryzae was obtained from Tokyo Chemical Industry (Tokyo, Japan). ESA-2 from Eucheuma serra was prepared as described previously [13] and kept at 20 \u00b0C until used. Influenza virus vaccine for a mixture of A/California/7/09 (H1N1), A/Victoria/210/09 (H3N2), and B/Brisbane/60/08 was purchased from Denka-Seiken (Tokyo, Japan). " ] },{ "paper_id": "4e86bcd31bd05b5c131e397b7d3a74fe4020bb0b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Text S1 HALY formulae. (DOCX) " ] },{ "paper_id": "4e8f8ad6957ffac26673761935854e6c05b7768e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Proteins were produced in transiently transfected 293T or stably transfected CHO-Lec 3.2.8.1 (CHO-Lec) cells as described [27] , and concentration in cell supernatants determined by ELISA. Proteins prepared in CHO-Lec cells were used in crystallization experiments. Hybridoma cells secreting the TGEV S mAbs were grown in DMEM supplemented with 10% FCS in roller bottles. Proteins secreted to culture supernatants were initially purified by affinity chromatography. All protein samples were further purified by size exclusion chromatography in HEPES-saline buffer (20 mM HEPES, 150 mM NaCl) pH 7.5.", "Representative CoV species in each genus are Alphacoronavirus 1 (comprising transmissible gastroenteritis virus (TGEV), porcine respiratory CoV (PRCV) and related canine and feline CoVs), Human coronavirus (HCoV-229E and HCoV-NL63, genus Alphacoronavirus), Murine coronavirus (including mouse hepatitis virus (MHV), genus Betacoronavirus, cluster A), Severe acute respiratory syndrome-related coronavirus (SARS-related CoV, genus Betacoronavirus, cluster B), Avian coronavirus (including infectious bronchitis virus (IBV), genus Gammacoronavirus), and Bulbul-CoV (tentative genus Deltacoronavirus) [4] .", "RBDs [8, 11, 13] . The RBDs of the SARS and MHV Betacoronavirus adopt folds unrelated to the b-barrel shown for Alphacoronavirus." ] },{ "paper_id": "4e951550757b4a9f7b9b5167c9774a1113c787e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza infection represents a considerable global burden, affecting 5-15% of the adult population during annual influenza epidemics [1] . Each year, 3-5 million cases of severe illness and 250,000-500,000 deaths are thought to result from these epidemics worldwide [1, 2] ." ] },{ "paper_id": "4e9aa1aef7efca6b41b1503135145e0dd75a39ce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "high IFITM5 expression in liver, muscle and spleen, with lower levels in the ovary and brain. The expression patterns of IFITM5 in reptiles and amphibians are unknown.", "Additional file 1: Table S1 . Summary of IFITM orthologues and paralogues in animals from various classes. " ] },{ "paper_id": "4e9f9684ec67208f02fa5b822b18ccfa79ca6b6b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Worldwide, rabies causes approximately 55,000 deaths per year [1] . Rabies viruses are transmitted to humans via saliva from bites of carnivores and bats. Bats may be frugivorous, hematophagous or insectivorous. Vampire bats (3 main species Desmodus rotundus, Diphylla ecaudata and Diaemus youngi) feed on blood from warmblooded animals, e.g. horses and cattle [2] .", "The communications program had several levels (national and local) and targeted different types of people (general population," ] },{ "paper_id": "4ea1d124972eda4c488d6446f88964f60bed47fc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were seeded on coverslips and fixed with 4% paraformaldehyde in PBS, permeabilized with PBS containing 0.1% Triton-X-100, and blocked in PBS containing 0.1% bovine serum albumin (BSA) and 5% normal donkey serum for 2 h at room temperature. Coverslips were incubated with rabbit anti-phosphorylated histone H3 (Ser10) (Upstate Biotechnology; Lake Placid, NY, USA) diluted 1:500 in PBS containing 0.1% BSA overnight at room temperature. Following washes with PBS, coverslips were incubated with Alexa-Fluor Donkey 555 anti-Rabbit (Life Technologies; Carlsbad, CA, USA) diluted 1:500 in PBS 0.1% BSA for 1 h at room temperature protected from light. Coverslips were then washed, stained with DAPI, and mounted on slides with Vectashield fluorescence mounting medium (Vector Laboratories; Burlingame, CA, USA). Cells were visualized using an Olympus BX61 fluorescence microscope coupled with a Hamamatsu ORCA-ER camera and using SlideBook software (Intelligent Innovations, Inc., Denver, CO, USA). The percent of cells positive for phosphorylated histone H3 was quantified.", "regulation of cell motion, positive regulation of binding) and cytoskeleton (actin cytoskeleton organization) related genes were also previously seen to be upregulated in in vitro senescence of human dermal fibroblasts (Yoon et al., 2004) . The upregulation of inflammatory genes suggests a mechanism by which astrocyte senescence may be causing further damage in the brain.", "We confirmed an almost fourfold increase in p21 mRNA in senescent astrocytes compared with pre-senescent controls.", "The chromosomal coordinates of all promoter regions 1000 bp upstream of the transcription start site were obtained using the RefSeq genes track, refGene table and the hg19 human genome assembly on UCSC Genome Browser -Table Browser tool 2 . For all genes up-or downregulated 1.5 fold or more which enriched GO categories, promoter coordinates were submitted to the Cistrome Analysis Pipeline 3 SeqPos tool. Public motif databases Transfac and JASPAR were searched for motifs enriched in the promoter sequences. Additionally, a de novo motif analysis was performed to find motifs with no correlate in the public databases. Results were filtered by human and mouse speciesspecificity, using a 1000 bp scan length." ] },{ "paper_id": "4ea207323d2fedf5b4f5a4cbb8fd1acd100df8a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "4ea66e72fc7ed0902b973ab0fc9993aab3d4e4cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sequences were aligned using Clustal X and manually edited using BioEdit [30, 31] . Then the best fitting nucleotide substitution model was chosen via hierarchical likelihood ratio test with ModelTest implemented in PAUP*4.0 [32, 33] . ", "Three preliminary analyses were performed prior to Bayesian analysis: recombination, phylogenetic signal and temporal signal tests. First, identification of recombinant strains was done using Bootscan/Recscan method in RDP4 with default window size and parameters [34, 35] .", "Maximum clade credibility trees which had the largest product of posterior clade probabilities, were selected after 10% burn-in using Tree Annotator, part of the BEAST package [39] . Calculations of posterior probability were used to establish statistical support for monophyletic clades." ] },{ "paper_id": "4ea6973e872fb9116a21c6539d2aba2ea5c1337c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "cell-specific regulatory signals, or perhaps ambient glucose concentration.", "Data are presented as mean \u00b1 SE. Data were analyzed using SigmaStat (version 3.5; Systat Software, Inc., San Jose, CA, USA). For multiple comparisons, analysis was by one-way repeated analysis of variance followed by Bonferroni correction. For comparisons involving two groups, Student's t-test was used. A p < 0.05 was considered significant.", "Twenty-five micro liter of concentrated media (20-fold concentrate) was run on 7.5% SDS-polyacrylamide gels, and subjected to immunoblot analysis using commercially available goat anti-human ACE2 antibodies (1:500 dilution) (AF933, R&D Systems Inc., Minneapolis, MN, USA) as we previously described to characterize mouse shed ACE2 fragments by mass spectrometry . Mouse kidney cortex lysates were used as controls (1.5-10 \u00b5g protein). Densitometric analysis of the protein bands was performed using Kodak ID image analysis software (Eastman Kodak, Rochester, NY, USA)." ] },{ "paper_id": "4eb0645a5ab563b06ec101914438267b6552a95e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the chemicals and reagents were commercially available and used without further purification. Routine thin-layer chromatography (TLC) was performed on silica gel plates (silica gel GF254 from Qingdao Haiyang Chemical Co., Ltd., Qingdao, China), and visualization was performed using UV. 1 H-NMR and 13 C-NMR spectra were recorded on a Bruker-400 instrument (Bruker, Billerica, MA, USA) at room temperature with TMS as an internal standard and CDCl 3 or DMSO-d 6 as solvents. Chemical shifts are expressed in \u03b4 (ppm) and coupling constants (J) in Hz. Mass spectra were recorded with a MSQ Plus mass spectrometer (Thermo Scientific, Waltham, MA, USA). Melting points were measured by an SGWX-4 micro melting point apparatus (Shanghai Precision & Scientific Instrument Co. Ltd., Shanghai, China) and are uncorrected.", "Breast cancer is one of the most common diseases amongst women throughout the world. About 521,900 women lost their lives because of it in 2012, 197,600 of which were from developed countries and 324,300 from developing countries [1] . In 2016, 249,260 new breast cancer cases and 40,890 breast cancer deaths are projected to occur in the United States [2] . A current hot research topic is how to develop novel therapeutics with improved selectivity and higher anticancer activity by chemical modifications of natural sources. Up to now, a large number of chemotherapeutic agents derived from natural products and used for the treatment of cancer, have shown satisfactory therapeutic effects, like vinblastine, vincristine, the camptothecin derivatives, e.g., topotecan, irinotecan and etoposide, were derived from epipodophyllotoxin and paclitaxel [3] .", "Compounds 17-24 were obtained through the formation of an ester bond between compounds 5-12 and GA after stirring for 12 h at room temperature in dry dichloromethane (DCM) catalyzed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) and 4-dimethylamino-pyridine (DMAP). We applied the same method to introduce the N-Boc group to protect amino acids at position C-3 and obtained compounds 25-40. To get compounds 41-56, deprotection was performed by treating the compounds with dry HCl gas in DCM." ] },{ "paper_id": "4eb512e8b51929e92cae935e6355b1b571e9e7b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analyses were performed using SAS 9.4." ] },{ "paper_id": "4ebae5a999522c721177ba353fbd95a72439e060", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "AS and RP wrote the manuscript. AS supervised the process. MS wrote the part on Use of nanocarriers in vaccine delivery to dendritic cells. ", "In twenty-first Century, infectious diseases have emerged as a serious threat to the health of millions of people across the globe (1) . According to the World Health Organization (WHO) report for 2016, \u223c3.2 million deaths have occurred due to lower respiratory infections and 1.4 million from tuberculosis alone worldwide (2) . Over the past few decades, many new infectious diseases have emerged and few old diseases re-emerged, which were once considered to be no longer a threat to the human being (3) (4) (5) . Collectively, these diseases account for millions of deaths that cause enormous impact on the global socio-economical and health-care sectors. The major challenges to combat such diseases are that for many of them, there are no effective drugs available.", "Preclinical " ] },{ "paper_id": "4ebdb50f487a8f6c2421e3e3281b053990cb4fac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The complete genome sequence of PDCoV strain USA/IA/2014/8734 has been deposited in GenBank under the accession number KJ567050.", "The The PDCoV USA/IA/2014/8734 sequence data will facilitate future research on the epidemiology and evolutionary biology of PDCoVs in U.S. swine. Further study remains to be conducted to determine the clinical significance of PDCoV.", "Unexpectedly, all fecal samples tested positive for porcine deltacoronavirus (PDCoV) by a pan-Coronaviridae PCR (6) followed by sequencing confirmation of PCR amplicons, as well as by a PDCoV-specific real-time reverse transcription (RT)-PCR assay with cycle threshold (C T ) values ranging from 14 to 19." ] },{ "paper_id": "4ec1787f65505b0751777ff1f2cb40d13c0d2b96", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Frameshifting is a process whereby the ribosome is guided toward a triplet nucleotide that is either shifted one nucleotide position upstream (+1 frameshift) or one nucleotide position downstream (\u22121 frameshift). Such frameshifting occurs in all known organisms, from E. coli to mammals (Namy et al., 2004; Dinman, 2012a) .", "UGA stop codon and a 3 stem loop that forms a RNA pseudoknot. These RNA hallmarks are still the standard way to identify other +1 frameshifted proteins.", "An interesting approach for the identification of frame-shift peptides is de novo sequence analysis by MS. This is based solely on the analysis of MS and MS/MS spectra, without amino acid sequence information from databases. However, identification rates are typically lower than in classical database-based proteomics experiments." ] },{ "paper_id": "4ec19e6a2799bf2bebe635732de198d04ddedf64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The GenBank accession numbers for genes and proteins mentioned in the text are as follow: SARS coronavirus nsp3 unique domain (SUD), JN247391; SARS coronavirus nonstructural protein nsp5, JN247392; SARS coronavirus nonstructural protein nsp10, JN247393; SARS coronavirus nsp10-nsp11 fusion protein, JN247394; SARS coronavirus nsp12 N-terminal domain (nsp12N), JN247395; SARS coronavirus nonstructural protein nsp14, JN247396; SARS coronavirus nonstructural protein nsp16, JN247397. ", "25 mL reaction mixtures [40 mM Tris-HCl (pH 7.5), 2 mM MgCl 2 , 2 mM DTT] containing 1 mg of purified proteins and 1 mCi of S-adenosyl [methyl-3 H] methionine (67.3 Ci/mmol, 0.5 mCi/ml) were pipetted into wells of a microtiter plate. The reaction mixtures were incubated on ice and irradiated with 254nm UV light in a Hoefer UVC500 cross-linking oven for 30 min. The distance of samples from the UV tubes was 4 cm. The samples were then analyzed by 12% sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE). The gels were soaked in Enlightning Solution (PerkinElmer) and used for fluorography [68] .", "Coronaviruses are etiological agents of respiratory and enteric diseases in livestock, companion animals and humans, exemplified by severe acute respiratory syndrome coronavirus (SARS-CoV) which was responsible for a worldwide SARS outbreak in 2003 and caused over 8000 cases of infection with about 10% fatality rate. They are characterized by possessing the largest and most complex positive-stranded RNA genome (ranging from 27 to 31 kb) among RNA viruses. Fourteen open reading frames (ORFs) have been identified in the genome of SARS-CoV, of which 12 are located in the 39-one third of the genome, encoding the structural and accessory proteins translated through a nested set of subgenomic RNAs [1, 2] . The 59-proximal two thirds of the genome comprise 2 large overlapping ORFs (1a and 1b), which encode two large replicase polyproteins that are translated directly from the genome RNA, with 1b as the frameshifted extension of 1a. These two precursor polyproteins are cleaved into 16 mature replicase proteins, named as non-structural protein (nsp) 1-16, which form the replication-transcription complex (RTC) localized in endoplasmic reticulum-derived membranes [3, 4] . Strikingly, the coronavirus genome is predicted to encode several RNA processing enzymes that are not common to small RNA viruses [1] , including nsp14 as an exoribonuclease and guanine N7methyltransferase (N7-MTase) [5, 6, 7, 8] and nsp15 as a nidovirusspecific endonuclease [9, 10] ." ] },{ "paper_id": "4ec2396b81441bf6b11b19a271cbc96078a8f3ce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4eca3df95a8bf82f07ba51b6978bd4049f8df827", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Serology identified specific anti-MER-CoV IgM (titer 1/100) and IgG (titer 1/320) antibodies in the patient's serum sample.", "Since its discovery in Saudi Arabia in 2012, the Middle East respiratory syndrome coronavirus (MERSCoV) has been implicated in 1042 laboratory confirmed cases of human infection, including 419 deaths. Among these cases, 14 were reported by European countries, including 8 imported cases and 3 local person-to-person transmissions [1] .", "In addition to partial sequencing, full length ORFs of the S (4042 nt) and N (1242 nt) protein genes were obtained by the Centers for Disease Control and Prevention (CDC), Atlanta, GA, using Sanger sequencing methods and deposited into the GenBank database under accession numbers KJ782550 and KJ782549, respectively. Sequences were confirmed independently by two separate CDC laboratories.", "The MERS-CoV genome is comprised of at least 10 putative open reading frames, including 2 that encode the spike (S) and nucleocapsid (N) proteins [2] . The S and N protein genes have been used for coronavirus genotyping and phylogenetic analyses which have aided our understanding of the virus's temporal and geographic origins and evolution [3] . The S protein is involved in virus receptor binding and is known to be the main antigenic component to which significant neutralizing antibody responses are induced [4] . The N protein is a highly immunogenic phosphoprotein implicated in viral genome replication and modulation of cell signaling pathways [5] ." ] },{ "paper_id": "4ecd138ab31f520b06c5cf095657fab2685a8209", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To further optimize the amplification, we compared reaction temperatures ranging from 53 to 67 \u2022 C with 2 \u2022 C intervals. The most suitable reaction temperature range was shown to be (Figure 1B) , and 61 \u2022 C was ultimately chosen as the optimal reaction temperature.", "Twenty-six genomes of respiratory pathogens including artificial RNAs of Sudan EBOV (Subtype Sudan, strain Gulu), Zaire EBOV and MARV, SARS coronavirus, influenza A H7N9, H1N1, H2N3, human parainfluenza viruses (PIV) type 1/2/3 and 4, adenoviruses (ADV; serotype 3, serotype 5, and serotype 55), respiratory syncytial virus infection RSVA/RSVB, MERS RNA, human metapneumovirus HMPV, human coronavirus HCoV-229E/ HCoV-OC43/HCoV-NL63, and HCoV-HKU1, bocavirus BoV, as well as three respiratory bacterial pathogens such as Legionella pneumophila 9135, Mycobacterium tuberculosis 005, and Haemophilus influenza ATCC 49247 were used in this study. Total viral RNAs were extracted from 200 \u00b5l of each culture using a QIAamp viral RNA mini kit (Qiagen, Hilden, Germany). All infectious materials were handled in biosafety level 3 facilities.", "Ebola virus has extremely high morbidity and mortality levels in humans, it reemerged and caused an outbreak in Western Africa where 28,476 suspected, probable, and confirmed cases, and 11,298 deaths were reported in Sierra Leone up until Oct. 21 2015 according to Ebola Situation Report from WHO 3 ). Although several chemical agents, vaccines, and antibodies inhibit the spread of EBOV in humans and animals, effective therapies for clinical treatment are scarce." ] },{ "paper_id": "4ed134293562340d043a5e0b6f5d822df7cf7079", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In conclusion, our study shows that bioinformatics based analytical approaches using curated data can enhance the understanding of functional and disease implications of 3D domain swapping.", "Disease enrichment analysis of proteins in swapped conformation using disease ontology" ] },{ "paper_id": "4ed270652370f2ffd9aecd7288519c77d7b925ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional supporting information may be found in the online version of this article. ", "We used diverse techniques, including fluorescence microscopy, transmission electron microscopy, cryoelectron tomography, immunolabeling and biochemical methodologies to investigate the role of autophagy in host-virus interactions.", "854" ] },{ "paper_id": "4ed62784e978048e7494deb2f61a562c8140067e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For serum samples, RNA was extracted from Human Serum (BioIVT, Westbury, NY) and mixed with viral RNA.", "For quantitative reverse transcription PCR, SuperScrip-tIII RT/Platinum Taq Mix (Thermo Fisher Scientific; Waltham, MA), dNTP mix, MgSO 4 , ROX Reference Dye (Thermo Fisher Scientific; Waltham, MA), and the primers and probes listed in Table 2 were used to assay in the CFX Connect Real-Time PCR Detection System (Bio-Rad; Hercules, CA) using the following conditions: 50\u00b0C for 15 min, 95\u00b0C for two minutes, and 40 cycles of 95\u00b0C for 15 s and 60\u00b0C for one minute. Standard curves for DENV-1, DENV-2, CHIKV and ZIKV were generated from titrated viral RNA extract." ] },{ "paper_id": "4ed809f5b348f735454271411a4bef01bfad0734", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A group of aliphatic polymers, such as polyethylene, polytetrafluoroethylene, polypropylene, and also polyvinylidene fluoride, have selective affinity toward endotoxins (Davies, 1999) . Thus, they have the potential to facilitate the microenvironment for tissue regeneration by adsorbing the endotoxins. However, due to absence of hydrophilic ionizable groups, they cannot be used directly before further biocompatible functionalization. Charged polymers with effective functional groups can selectively bind and remove endotoxins from the systems. One such example is positively charged acrylic cellulose with DEAE or QAE functional groups that can significantly absorb endotoxins (Hou and Zaniewski, 1990) . This could be an important aspect while designing advanced biomaterials for clinical translations.", "Here, we review the biomaterials that are designed for use in compromised patients with inflammation or active infections. We present several examples of each of the groups of biomaterials, taken from our own research and cases that are documented within the literature.", "HP and MG conceptualize the area for this review. MI, JE, GP, and OB have contributed in their respective sections. " ] },{ "paper_id": "4ee2232fd9b2088955ad781243f135dc76edbaf1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Immunocytochemistry of activated Bax was performed using mouse monoclonal anti-Bax (clone 6A7, 1:400 dilution, Exalpha Biologicals, Watertown, MA) as previously described in detail [39] . Cells were imaged by confocal microscopy with excitation and emission wavelengths of 488 and 507 nm, respectively.", "A human gastric cancer cell line, AZ-521 (Culture Collection of Health Science Resource Bank, Japan Health Science Foundation, Tokyo, Japan), was used in the study. Cells were grown in Eagle's minimal essential medium (Sigma) containing 10% fetal calf serum (Invitrogen, Carlsbad, CA) under a 5% CO 2 atmosphere at 37uC.", "Whole cell lysates were directly lysed for 15 min. on ice using a commercially available cell lysis reagent from Thermo Scientific (Rockford, IL). For CHOP protein analysis, nuclear extracts from whole cell lysates were obtained using nuclear extraction reagent (Thermo Scientific, Rockford, IL) following manufacturer's instructions. Samples containing 50 mg of protein were resolved by 4-15% SDS-PAGE, transferred to nitrocellulose membranes, followed by incubation overnight with primary antibodies at a dilution of 1:1000. The primary antibodies used are as follows; Mouse anti-Bax (catalog # sc-7480), rabbit anti-Bad (catalog # sc-7869), rabbit anti-Bik (catalog # sc-10770), mouse anti-CHOP (catalog # sc-7351), and anti-Lamin B (catalog # sc-6216) antibodies were from Santa Cruz (Santa Cruz, CA). Goat anti-Bid antibodies were from R and D Systems (catalog # BAF860), rabbit anti-PUMA antibodies (catalog # 23404) were from Rockland (Gilbertsville, PA), and rabbit anti-Bak antibodies(catalog # 06-536) were from Upstate (Billerica, MA). Rabbit anti-Bim, rabbit anti-PERK (catalog # 3129S), rabbit anti-Cleaved PARP (catalog# 5625S) rabbit anti-eIF2-a (catalog # 9722), and rabbit anti-phospho-eIF2-a (catalog # 9721) antibodies were from Cell Signaling Technology (Beverly, MA). On the following day, membranes were incubated with appropriate horseradish peroxidase-conjugated secondary antibodies (Biosource International, Camarillo, CA) at a dilution of 1:3000 for 2 hr. Bound antibody was incubated with chemiluminescent substrate (SuperSignalH West Pico Chemiluminescent, Thermo Scientific, Rockford, IL) for 5 min and was visualized with a chemiluminescent imaging system (FluorChemH FC2, Alpha Innotech, San Leandro, CA). In selected experiments, density of bands was analyzed using Image J software (National Institutes of Health, Bethesda, MD) in order to quantify the results." ] },{ "paper_id": "4ee3d76ee71e4eac590b1b228fc72dc372cdc16f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GraphPad Prism version 7.0 was used for statistical analysis and statistical significance was accepted at P values of <0.05. ( \ufffd , P < 0.05; \ufffd\ufffd , P < 0.005; \ufffd\ufffd\ufffd , P < 0.0005; \ufffd\ufffd\ufffd\ufffd , P < 0.00005). Specific tests are indicated in figure legends. " ] },{ "paper_id": "4ee51bb838b0cdc2e59317a4b837f2997795b665", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 [11] were also included)." ] },{ "paper_id": "4ef4cb3ed4814b1afceebb92b410e53fd5646f4e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Target sequences were as follows: luciferase (acc.n\u00b0D " ] },{ "paper_id": "4ef6fc1277c3190055c77131bd2030f18ecb54ac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4ef86c928be12807b78ebc327eb41f0380cf0b75", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Compliance with ethical standards This article does not contain any studies with human participants or animals performed by any of the authors.", "Influenza A and B are among the most common causes of acute human respiratory illness and are associated with high morbidity and mortality rates in infants, the elderly, and immunocompromised individuals (Mallia and Johnston 2007; Simonsen et al. 2000) . Today, patients with influenza infection may be treated with antiviral drugs; however, these treatments are only effective when started within the first 2 days of the illness (Stiver 2003) . Thus, timely and accurate diagnosis of influenza plays an important role in targeting antiviral treatment and, furthermore, has a significant role in the prevention of the misuse of antibiotics, since the symptoms of influenza are often similar to those of other respiratory illnesses caused by bacterial infections (Low 2008) .", "Cons-B 5' TCCAGACTACAATAATACAAAAGGCCAAAAACACAATGGCAGAATTTAGTGAAGATCCTGAATTACAACCAGCAATGCT 3' IO-B 5' CCCCCCCCCCCCCCAAGGCCAAAAACACAATGGCAGAATTTAGUGAAGAUCCUGA 3' IFB-F 5' ACTACAATAATACAAAAG 3' IFB-R 3' GGACTTAATGTTGGTCGT 5'" ] },{ "paper_id": "4f0e7fc5e32e927fd76e1f5c156cb9caee8eda2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the second strategy, typically MS-based approaches are used in which proteins are digested into peptides, usually with trypsin whose cleavage sites are well known. Peptides are fractionated by chromatography, often in a multidimensional setup combining different separation principles (e.g. ion exchange-, reversed phase-, affinity columns). Quantitation in MS is based on isotopic or chemical labels that are introduced in a previous step into the organism, at the cellular level, by labelling the intact proteins or peptides, or performed in a label-free mode that requires high reproducibility of the analyses, besides the generally requested high mass accuracy and high-quality extensive databases (Nikolov et al., 2012) .", "There are multiple varieties of gel-based and gel-free approaches, depending on the question under investigation, and they are often combined with sample prefractionation methods to reduce the complexity of the original sample mixtures (Posch, 2008; Miller, 2011) . Studies have shown that both strategies provide complementary results (Anderson et al., 2004) . They also emphasized the importance of monitoring protein fine structure and modifications (e.g. glycosylation, phosphorylation), besides detecting protein concentration changes (Johnson and White, 2012; Ueda, 2013) .", "Quantification concatemers (QconCAT): an interesting approach for large-scale studies Because synthetic standard peptides are expensive and therefore a main scale-limiting factor, alternatives to commercially available peptides have been presented. An interesting approach is represented by the expression of QconCATs of tryptic standard peptides (Beynon et al., 2005) , which has proven useful and highly cost efficient when many biological replicates are to be studied. In this strategy, a chimeric protein is designed as a concatamer of tryptic standard peptides, which are metabolically labelled in Escherichia coli using stable isotopes. 13 C-labelled Arg and Lys are used, which adds a mass difference of + 6 Da to each peptide mass spiked into biological samples, to provide absolute quantities of the analysed peptides. As all isotopelabelled peptides are present in a single copy within the chimeric protein, they will inherently be present at the exact equimolar quantities within the analyte sample." ] },{ "paper_id": "4f2216e3b39b7303a9e4d7df96874542c853a3a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LC3R: CGGAATTCTCTCAGTTGGTAACATCCCTTT) that were designed based on the sequence of LC3B. The gene was then cloned into pEGFP-C1 to express LC3B fused with the EGFP protein at its N-terminus.", "To construct pEGFP-LC3B, the LC3B gene was amplified from PK-15 cells with primers (LC3F: GAA-GATCTGGGCTGAGGAGACACAAGAG;", "Rapamycin (R0935), rabbit polyclonal anti-LC3B antibody (L7543) and horseradish peroxidase (HRP)-conjugated goat anti-rabbit or -mouse secondary antibodies were purchased from Sigma-Aldrich (St. Louis, USA). Rabbit polyclonal anti-ATG5 antibody (sc-33210) and mouse monoclonal anti-\u03b2-actin antibody (sc-47778) were purchased from Santa Cruz Biotechnology (Santa Cruz, USA). Rabbit anti-p-AKT (Ser473) antibody (4060) and anti-p-mTOR antibody (Ser2448) (5536) were purchased from Cell signaling Technology (Beverly, USA). Rabbit anti-AKT antibody (ab32505) and anti-mTOR antibody (ab2732) were purchased from Abcam (Cambridge, UK). 4\u2032, 6-diamidino-2-phenylindole (DAPI) (C1005) and insulin (P3376) were purchased from Beyotime Biotechnology (Haimen, China)." ] },{ "paper_id": "4f25223579f443edc058800f30c4fe8847a6ab57", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step two: application of WHO guideline", "All hospitals were general hospitals and reported coverage of all age-groups and socio-economic population groups, although the hospitals in West Nusa Tenggara and Yogyakarta reported that more than 50% of their hospital admissions were for low socioeconomic population ( Table 2 ). All hospitals confirmed that surveillance could be conducted in all wards where SARI patients may be admitted.", "Based on the geographic location of the eight hospitals visited, there was representation of east (Maluku), west (North Sumatra), north (North Sulawesi), central (Yogyakarta, Kalimantan) and south Indonesia (West Nusa Tenggara)." ] },{ "paper_id": "4f2e6240097fc7f8699ec07c84d37bbc8a15310c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The guanine-containing phosphonates 25a-25d were prepared from the 6-chloropurine precursors 24a-24d by hydrolysis in acidic medium (Scheme 3) [34] .", "O H N X (EtO) 2 (O)P X = CH 2 , CH 2 CH 2 , CH 2 CH 2 CH 2 , CH 2 OCH 2 CH 2 B = natural or modified nuclebases", "Uracil (9)-, 5-fluorouracil (10)-, 5-bromouracil (11)-, thymine (12)-, and benzouracil (14) are also known compounds and they were synthesized by alkylation of the respective nucleobases by chloro-or bromoacetic acid [15] [16] [17] [18] [19] ." ] },{ "paper_id": "4f380911a4cf1b78dce1c016c1c0cc2f95a15f7b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Nosocomial infection of health-care workers (HCWs) during outbreaks of respiratory infections (e.g. Influenza A H1N1 (2009)) is a significant concern for public health policy makers. World Health Organization (WHO)-defined 'aerosol generating procedures' (AGPs) are thought to increase the risk of aerosol transmission to HCWs, but there are presently insufficient data to quantify risk accurately or establish a hierarchy of risk-prone procedures.", "In 2003, at least 284 healthcare workers (HCWs) were infected with SARS-Coronavirus during the severe acute respiratory syndrome epidemic [1] . Nosocomial infection was the primary accelerator of infection accounting for 72% of cases in Toronto and 55% of probable cases in Taiwan [2, 3] . Aerosol generating procedures (AGPs) performed on infected patients were implicated as the source of outbreaks among Health Care Workers (HCWs), however no direct evidence for this mode of transmission was demonstrated. [4] .", "WHO guidance states that standard and droplet precautions (i.e. SFMs) should be adopted when working in direct contact with infected patients and high level respiratory protective equipment (minimum of an FFP2/N95 class respirator) should be worn only in the vicinity of infected patients when AGPs are performed [5, 6] . As a result, this infection control strategy was adopted in all U.K. NHS organisations [14] ." ] },{ "paper_id": "4f3a25f455f5b0a76e0379e91f028a69de4be389", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our study was approved by the institutional review board of Peking Union Medical College Hospital.", "We described clinicians' characteristics as continuous (age) or categorical variables (sex, marital status, living status, status of influenza vaccination, and profession). All Likert-scale responses were dichotomized into complete agree/agree versus neither agree nor disagree/disagree/complete disagree, and expressed in proportions.", "There were more males among physicians (57.0%) compared to nurses (6.0%) and other professionals (24.0%). Significantly more nurses were single, living with their parents or living alone." ] },{ "paper_id": "4f47adf53fef07c0ca76beb4b100bbdfa54b2b0b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Electron microscopy. Cells were rinsed with PBS and fixed for 1 hr in 2% glutaraldehyde in PBS (pH 7.4) on ice. Cell pellets were collected and subjected to osmium post-fixation (1% OsO4 in PBS) for 1 hr (on ice), 2% uranyl acetate en bloc staining for 1 hr (on ice), followed by dehydration in an ascending ethanol series. The sample was infiltrated and embedded in Spurr's resin and then sectioned about 75 nm using an UCT ultratome (LEICA). Sections were collected on naked grids (100 mesh, copper) and stained with saturated aqueous uranyl acetate and lead citrate from both sides. TEM imaging was performed using an FEI Tecnai TF20.", "Total RNA from cultured cells was insolated using RNA Mini Kit (Invitrogen) and reverse transcribed into cDNA using qScript cDNA synthesis Kit (Quantas). Real-time PCR was performed using the specific primer sets (Table 1) . For XBP-1 splicing assays, the XBP-1 cDNA was PCR-amplified using the indicated primers and were then made subject to PstI digestion. Digestion of the unspliced XBP1 produces two DNA fragments (291 bp and 307 bp). The final DNA products were resolved on a 2.5% agrose gel, stained with ethidium bromide and visualized by UV. " ] },{ "paper_id": "4f4a156d0bc65afd5d8f5b80b4bb8436a590955a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "E. coli (ATCC 25922) from -80\u02daC glycerol stock was added to LB broth (Carl Roth, Karlsruhe, Germany) and incubated for 12 hours at 200 rpm and 37\u02daC with 5% CO 2 . Optical density of 0.03 was adjusted in LB broth followed by incubation until midlogarithmic phase for 1.5 hours at 200 rpm and 37\u02daC. After centrifugation, the pellet was resuspended in sterile 0.9% NaCl at 8 x 10 5 CFU E. coli / 200 \u03bcl and administered intraperitoneally (n = 10).", "- - - - - - + ++ + Vasculitis ++ - + - + + ++ - + Fibrinoid degeneration of vascular walls - - - - - - ++ - - Vascular thrombosis +/- - - ++ - ++ ++ - -" ] },{ "paper_id": "4f5a550869a4ff5f8c754a9aa89453486cab2985", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceived and designed the experiments: SDvH AW EH AtB ABM JV. Performed the experiments: SDvH AR EH ABM PHK. Analyzed the data: SDvH AW ABM JV. Wrote the manuscript: SDvH AW JV. Provided expertise for culturing and analyzing phenotypic characteristics of dendritic cells: AtB.", "Blood was drawn from HLA-typed healthy anonymous volunteers with informed, written consent in accordance with Dutch regulations and following approval from Sanquin Ethical Advisory Board in accordance with the Declaration of Helsinki. The volunteers nor those taking the samples know for what project specific samples were used. Moreover, allowed annual sample volume and frequency of donation were established after consultation with Sanquin Medical Secretary. Additional files, such as form signed by blood donors, are attached. The named institutional review board specifically approved this study.", "The HLA-content of each fraction was measured by ELISA." ] },{ "paper_id": "4f67438d123ec1a0d283496cba0ad18fdc5c8e31", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were entered using EpiData software (Version 3.1), converted into SPSS format, and analyzed using SPSS (v17.0, SPSS, Chicago, IL, USA). Descriptive statistics, including frequency analysis for categorical variables, and medians and interquartile ranges (IQRs) for continuous variables, were calculated. To further identify potential risk factors for severe SARI, we selected variables with p<0.05 on univariate analysis in addition to those we regarded as potential risk factors for severe SARI to include in a multiple logistic regression.", "of the authors and do not necessarily represent the policy of the China CDC or the U.S. Centers for Disease Control and Prevention." ] },{ "paper_id": "4f695bec496fb166d09c3377627d86cc587c2f27", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were compared by t-test, log-rank test (for survival data), or one-way ANOVA (with Bonferroni's test for pairs of groups). P < 0.05 was considered to be significant.", "Spleens excised from euthanized mice were placed into PBS. Splenocytes were extracted by passing spleens though wire mesh into wash media containing RPMI with 2% fetal calf serum, penicillin and streptomycin. The cells were then filtered through 70-micron nylon mesh (Elko, Miami Gardens, FL, USA) and transferred to FACS buffer, labeled with fluorescent probes and subjected to flow cytometry as described for cells obtained from BAL fluid.", "Individual wells of immunoassay plates were coated with influenza A H1N1 antigen (2 x 10 5 FFU/well in 50-mM carbonate buffer, pH 9.6) and incubated overnight at 4\u00b0C. Wells then were incubated for 2 h with 1% BSA/PBS to block non-specific binding. Serum from experimental animals was diluted 1:20 (to detect IgG1 and IgG2a) or 1:10 (to detect IgA, IgE and IgM) and then further diluted in serial fashion in PBS/0.05% Tween-20/0.5% BSA. 10-20 \u03bcl of diluted serum in each well were mixed with 50 \u03bcl of biotinylated anti-mouse IgG1, IgG2a, IgA, IgE or IgM solution (BD Pharmingen) and incubated overnight, followed by addition of 50 \u03bcl of alkaline phosphatase-conjugated streptavidin (1:3000; Jackson ImmunoResearch, West Grove, PA, USA). Alkaline phosphatase activity remaining bound after washing was detected using phosphatase substrate (4-nitrophenyl phosphate; Sigma-Aldrich) with spectrophotometric monitoring of cleaved substrate at 405 nm." ] },{ "paper_id": "4f7c1aeb6e5b1e35d6be98d478259a83a8dd6993", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In uenza A (H3N2)", "In uenza B/Victoria ", "The authors declare that they have no conflicts of interest.", "Nucleic acids were extracted from samples stored in 200 l of universal transport medium and eluted in 60 l of elution buffer using QiaAmp MinElute virus spin kits (Qiagen, France) according to the manufacturer's instructions. An internal control (T4 and MS2 phages) was added to each extraction tube to assess the quality of the extraction at the end of the amplification [13] ." ] },{ "paper_id": "4f9d106c41459601d3804f9db29621c92c321921", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The most common services provided were housing (52.5% of organisations handling dogs, 52.9% of organisations handling cats), rehoming (62.1% dogs, 54.2% cats) and financing veterinary care (46.9% dogs, 41.9% cats). Less common activities included trap-neuterreturn and providing financial assistance to other organisations. Other activities mentioned included providing pet care, rehoming and behavioural advice, social and community activities and education.", "Descriptive statistics were compiled using Microsoft Excel (2010). As the data were non-normally distributed, medians and inter-quartile ranges (IQR) were calculated.", "When asked about staffing levels, 445 respondents replied. A total of 19,302 staff members were employed by these respondents, of whom 2,758 (14.3%) were paid full-time, 1,125 (5.8%) paid part-time, 834 (4.3%) were voluntary fulltime and 14,585 (75.6%) voluntary part-time. ", "Financial records were obtained for 2009-2010 and 2010-2011 for all organisations registered with the Charity Commission (England and Wales) [25] , which fulfilled the criteria of housing or re-homing cats and/or dogs. Where their financial year did not run from January to December, records for the closest possible time period (e.g. March 2009 -February 2010) were obtained. Where organisations had several financially independent branches, all were included." ] },{ "paper_id": "4fa344b02899cb75cb81db82d2cee5f624343c54", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HBeAg in media was quantified using commercial kits of chemiluminescence immunoassay (USCNK Life Science Incorporation, Wuhan, China)." ] },{ "paper_id": "4fa871503ddbbaaead7a34fce89298a36648f662", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus plaque assays were performed as described previously [50] . Briefly, Vero cell monolayers were infected with dilutions of supernatants from infected cells, overlaid with soft agar, and allowed to form plaques for 72 h. Then the agar overlay was removed and cells were stained with a solution of 1% crystal violet, 3,6% formaldehyde, 1% methanol, and 20% ethanol.", "Cells were infected for the indicated times, total RNA was extracted and treated with DNase I. For reverse transcription (RT), 1 \u00b5g of RNA was incubated with 200 U of Superscript II reverse transcriptase (Invitrogen) and 100 ng random hexanucleotides in 20 \u00b5l of 1\u00d7RT buffer (Invitrogen) supplied with 1 mM each of the four deoxynucleotide triphosphates, 20 U of RNasin, and 10 mM dithiothreitol. The resulting cDNA was amplified by 35 cycles of PCR, with each cycle consisting of 30 sec at 94\u00b0C, 1 min at 58\u00b0C (using primer pairs specific for IP-10, IL-6, IL-8 and RANTES) or at 56\u00b0C (all other primer pairs), and 1 min at 72\u00b0C, followed by 10 min at 72\u00b0C. Primer sequences are available from the authors upon request. " ] },{ "paper_id": "4faaf584315206f342db3f18a118eae7ca702146", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The IBV Massachusetts (M)41 strain was purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA) and was used in all of the experiments. Nine day old SPF viable eggs were used to propagate M41 strain of IBV, and the allantoic fluid was harvested at 3 dpi by careful aspiration. The end point dilution assay was employed to assess the viral titers using ED 9 SPF eggs, and was expressed as a 50% embryo infectious dose (EID 50 ) [27] .", "The specific pathogen free (SPF) eggs from white leghorn layer hens were obtained from the Canadian Food Inspection Agency (CFIA), Ottawa, and were incubated according to the manufacturer's instructions in digital egg incubators (Kingsuromax 20 and Rcom MARU Deluxe max, Autoelex Co., Ltd., GimHae, GyeongNam, Korea), located at the Health Research Innovation Centre (HRIC) 53, University of Calgary. All of the animal care protocols as well as the use of live chickens, embryos, and SPF eggs in our experiments, have been reviewed and approved by the Health Science Animal Care Committee (HSACC, AC14-0013, 20 November 2014). At ED 11, the incubated eggs were candled in order to select viable eggs for further incubation, and the hatched birds were transported and housed in high containment poultry isolators at the Prion/virology animal facility, HRIC, University of Calgary, with access to ad libitum food, water, and necessary veterinary care.", "Further experiments elucidating the mechanisms of the CpG ODN-mediated adoptive response, such as cell-and antibody-mediated immune responses in chickens and the duration of protection provided by this ligand against IBV, would be greatly beneficial in order to better understand the protective effects of CpG ODNs, and may aid in the development of more effective IBV control measures." ] },{ "paper_id": "4facb7cbe620956211550e1a035b0281f2db5cfc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflicts of interest.", "Of the 91 respondents, 55% (50/91) worked in organizations based in Australia, 30% (27/91) in organizations in PICTs and 15% (14/91) worked in Malaysia or Indonesia. Table 1 shows the employment characteristics of survey respondents by region." ] },{ "paper_id": "4faf1ac964c605b384dda60bc37df300766401b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The K M and k cat values were calculated from the Lineweaver-Burk plot (1/v vs 1/s).", "The Pi released or a-NDP/dADP released was measured when [c-32 P] ATP/GTP or [a-32 P] NTP/dATP was used as tracer respectively.", "where Fc, Fractional Cleavag\u1ebd \u00bdIntensity of product released=Intensity of substrate zintensity of product released::", "We thank our colleagues for the valuable suggestions during the preparation of this manuscript. We thank K. Govind for providing the ssRNA transcripts to generate dsRNA, J.N.Kalyani for her help in determining the kinetic parameters and B.Chiranjivee for the kind gift of purified RecoP5I protein. " ] },{ "paper_id": "4faf34d795e5ff74a886528e46268af783fe712b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A mysterious pneumonia illness was first reported in late December 2019 in Wuhan, China, and has rapidly spread to a dozen of countries including the United States with thousands of infected individuals and hundreds of deaths within a month [1] . Scientists in China have isolated the virus from patients and determined its genetic code. The pathogen responsible for this epidemic is a new coronavirus designated 2019-nCoV by the World Health Organization. 2019-nCoV belongs to the same family of viruses as the well-known severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), which have killed hundreds of people in the past 17 years.", "The tissue expression pattern of ACE2 suggests other modes of virus transmission that may involve the functions of intestine, kidney, testis, and other tissues. Particular attention should be paid to the intestines which expressed the highest level of ACE2. Earlier studies have demonstrated that diarrhea was present in up to 70% of patients infected with SARS-CoV [19] . More importantly, a recent case report demonstrated the presence of 2019-nCoV in feces of a patient with an initial diarrhea episode [20] . While this finding has been noted in other reports, tests of feces and urine samples for the presence of 2019-nCoV is warranted, which may help to reveal alternative routes of virus transmission.", "By performing immunostaining, earlies studies have demonstrated the expression of ACE2 in lung alveolar epithelial cells as well as arterial and venous endothelial cells, arterial smooth muscle cells, renal tubular epithelium, and epithelia of the small intestine [15, 16] . The lung expression provides strong support for infection of SARS-CoV and 2019-nCoV through the airways of the lung. However, by searching the Human Protein Atlas database, we found that ACE2 mRNA is mainly detected in small intestine, colon, duodenum, kidney, testis, and gallbladder. Its expression level in the lung is minimal (Fig. 4) . Furthermore, by examining data from two single-cell RNA-seq studies [17, 18] , we only identified 2 out of 4599 and 13 out of 540 lung epithelial cells expressed a detectable level of ACE2 (www.ebi.ac.uk/gxa/sc). This confirms that the overall expression of ACE2 in the lung is low and may also suggest the presence of selected cells with upregulated ACE2 expression under certain conditions." ] },{ "paper_id": "4fbfedadab204c5165514312dd7cba7a907aaaba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "During an Ebola outbreak, real-time forecasting has the potential to support decision-making and allocation of resources, but highly accurate forecasts have proven difficult for Ebola [8, 9] as well as other diseases [10] [11] [12] [13] . Highly accurate forecasts of small, noisy outbreaks may be a fundamentally elusive ideal [14] . Previous work has found that probabilistic forecasts can have relatively high accuracy within a few weeks, though they become less useful as time horizons grow longer [15] . Thus, short-term forecasts may provide useful information for response organizations.", "These analyses were conducted using R 3.4.2 (R Foundation for Statistical Computing, Vienna, Austria)." ] },{ "paper_id": "4fc15d2af497369e0e7aa99dc78a403bdfa4790f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "were detected regarding appearance and disappearance of transcripts.", "cytometry experiments and helped to finalise the manuscript. All authors read and approved the final manuscript.", "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "4fc5e9665de47ef816e11dea365d068d1d1a77e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following euthanasia by cervical dislocation, the trachea was exposed and cannulated through the animal mouth with a 19 gauge tube. Lungs were lavaged three times with 400 ml of cold phosphate buffered saline (PBS). Samples were centrifuged for 10 minutes at 30006 g at 4uC to separate cellular content, and supernatants were collected to analyze their cytokine levels.", "To examine lung histopathology, left lungs of infected mice were incubated with 10% zinc formalin for 24 h at 4uC, embedded in paraffin, sectioned, and stained with hematoxylin and eosin.", "immune system activation has also been proven for other viroporins [53, [57] [58] [59] ." ] },{ "paper_id": "4fc79293e3efdfd44b408d923b2448ac6a5ddd0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In contrast, our SAPNs have been demonstrated as an innovative method in vaccine design. They repetitively display antigenic epitopes in their native conformation and have successfully been applied to construct vaccines that induce robust immune responses against numerous pathogens including malaria, influenza, SARS, toxoplasma and HIV [14, 16, 18, 19, 21, 23, 25] .", "SAPNs were analyzed as previously described [21] . The SAPN's hydrodynamic diameter was measured by DLS at 25\u02daC, and presented as the average of five runs. SAPNs were absorbed on a carbon coated grid, stained with 0.5% uranyl acetate, and imaged using a FEI Tecnai 12 G2 Spirit BioTWIN.", "Data was analyzed using one or two-way ANOVA with Bonferroni post-test in GraphPad prism 6.0. Statistical significance was achieved at levels of P values <0.05 ( \u00c3 ), <0.01 ( \u00c3\u00c3 ), and <0.001 ( \u00c3\u00c3\u00c3 ).", "The backbone of SAPN monomers were designed containing a pentameric and a trimeric coiled coil region held together by a linker and malaria (Plasmodium falciparum) epitope Cel-TOS (residues 24-83 and 84-182), amino acid residues were showed in S1 To render the nanoparticle more immunogenic, the two CD4+ epitopes AKFVAAWTLKAAA and HAAHAAHAAHAA-HAA were engineered into the scaffold of the SAPN. The sequences coding for both constructs were codon optimized, for expression in E. coli, synthesized and expressed by GenScript USA (Piscataway, NJ)." ] },{ "paper_id": "4fc7caae919d6b80f27561b9d034650a220affbb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(We refer to this network as 'adolescent sexual'.) -A high-resolution network of cattle movement between farms in the UK during the month of April 2004 [30] (N \u00bc 37 787", "-A contact network (for a sexually transmitted disease) based on surveys of romantic and sexual relationships between adolescents in a mid-size Midwestern US town [2] (N \u00bc 278,", "The three empirical outbreaks are results of respiratory, sexual and food-borne diseases, respectively." ] },{ "paper_id": "4fcb098e746e236ebc700fc79262c3263550b3d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Approximately 50 \u03bc g of purified NP protein was used for SEC-MALS experiments.", "Marburg viruses (MARV) that cause severe hemorrhagic fever with case fatality rates approaching 90% during some outbreaks are undoubtedly significant threats to global human health 1,2 . The recent largest filovirus epidemic in Western Africa caused by EBOV Makona variant, and the import of EBOV to non-African countries highlights the public health impact of these pathogens.", "Preparation of Chinese licorice extracts. The licorice powder (10 g) was macerated in 200 mL 70% (v/v) methanol aqueous solution and extracted by ultrasonication for 1 h. The extracted solution was filtered and concentrated to dryness using a combination of rotary evaporation under reduced pressure and lyophilization. The resulting powder of licorice extracts was stored at 4 \u00b0C ready for use." ] },{ "paper_id": "4fce2cc8270c75b0db8e7679d63b40abc5470f6b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MA104 monkey kidney epithelial cells (ATCC CRL2378) were maintained in Dulbecco's Modified Eagle's Medium (DMEM, Mediatech) supplemented with 5% fetal bovine serum (FBS, Atlanta Biologicals). Rhesus rotavirus strain RRV was propagated in MA104 cells and stock titers were determined by immunofluorescent focus assay (IFA, see below).", "Together, the data show GRA has a profound effect on the accumulation of rotavirus proteins in infected cells, consistent with the observed reduction in yields of infectious virus." ] },{ "paper_id": "4fcf6dedbf15427b8516654a5a24fbce54fb4b2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "4fd6ce6a0e0f551a80d019b4c9b6c25279605d91", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Diagnosis testing for EBOV was performed by China CDC Mobile Laboratory. Total RNA was extracted from patient peripheral blood samples or swab samples in Bio-safety Level 3 (BSL-3) facilities. Ebola viral RNA was then detected using Detection Kit for Ebola virus subtype Zaire RNA (Puruikang Biotech Co. Ltd, with PCR Fluorescence Probing) according to the manufacturer's recommendations [6] . For quantification purposes, the amplicon concentrations were converted to copies of EBOV per milliliter (method provided by China CDC Mobile Laboratory).", "Additional file 1: Multilingual abstracts in the six official working languages of the United Nations. (PDF 699 kb)", "EVD imposed a significant economic burden on the West African countries affected. Some studies suggest that due to EVD deaths, life expectancy may have declined in Liberia and Sierra Leone to a new low since 2001-2003 [4] . This dramatic healthcare crisis, coupled with human rights and global security concerns, underscored the urgent need for developing resilient healthcare systems, and called for the domestic and international aides and investments in these African countries [5] .", "Please see Additional file 1 for translations of the abstract into the six official working languages of the United Nations." ] },{ "paper_id": "4fe4eefd0cb0263c466d4e7895fcfec52b502a21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each interview took approximate 15-25 min to complete. The survey questionnaire was pilot tested in January 2014 (n = 50) to ensure practicability, validity, and interpretability of answers. The questionnaire was slightly refined for wording and format before distribution to the study sample based on the results of the pilot study. Results about vaccination practice and channels for disease surveillance have been reported elsewhere and not included in the analysis.", "Not applicable.", "The authors declare that they have no competing interests." ] },{ "paper_id": "4ff3cd099988eec4079249528fb8db645b3c9490", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hantaviruses (family Bunyaviridae, genus Hantavirus) are negative-stranded, trisegmented viruses that cause about 200,000 disease cases annually, with case fatality rates of 0.5%-40%, depending on the virus [1] . The viral gene segments encode four or five polypeptides. The large (L) segment encodes the RNA-dependent RNA polymerase (RdRp), the medium (M) segment encodes a precursor that is posttranslationally cleaved into Gn and Gc glycoproteins, and the small (S) segment encodes the nucleocapsid (N) protein. Some hantaviruses encode a second nonstructural polypeptide (NSs) downstream from the N start site in frame 2 [2, 3] . Little is known about the immunomodulatory abilities of these proteins; however, there is evidence the N, Gn and NSs may alter host cellular responses during infection.", "T.S. and J.P. reviewed the literature and wrote the manuscript.", "The authors declare no conflict of interest." ] },{ "paper_id": "4ff89a71126d2932544a8337ba28787fde5f02a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ",", "It follows from (1) and (2) that", "yields:" ] },{ "paper_id": "4ffacbedf65fc0a9fe529e94b43fc3e9018775f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data and information are available upon request." ] },{ "paper_id": "5009d7b5a27efb9b31d50a5266d077c4313c295a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "were sterilely minced into small pieces and cultured in 10% FBS/DMEM, 5% CO 2 at 37 \u00b0C on tissue culture plates. Fibroblasts at passage 4 (P4) were used for functional analysis or genomic DNA isolation for Southern blotting analysis. The P4 fibroblasts expressing mT were infected with recombinant adenovirus expressing Cre recombinase (Ad.CMV-Cre) or (Ad.CMV-LacZ) at a multiplicity of infection (MOI) of 100 particles/cell and were then cultured for an additional 14 days prior to analysis by fluorescent microscopy and FACS. The adenoviral vectors were generated by Viral Vector Core at the University of Iowa (Iowa City, IA, USA) (https://medicine.uiowa.edu/ vectorcore)." ] },{ "paper_id": "5016b361dce58077b3d647b0772425e079f98d8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Standard immunofluorescence was performed as described previously [29] . Briefly, neurons grown on glass coverslips were fixed for 20 min at room temperature with 4% paraformaldehyde, permeabilized using PBS + 0.1% Triton-X100 during 4 min, rinsed with PBS, and blocked overnight at 4uC with PBS + 2% normal goat serum. Incubation for 1 h at room temperature or overnight at 4uC with primary antibodies was followed, after several washes in PBS, by a 1-h incubation at room temperature with secondary antibodies. After extensive washing, coverslips were mounted using ProLong Gold (Molecular Probes).", "Quantitative cDNA amplification was performed according to manufacturer's instructions. The products of polymerase chain reaction (PCR) LightCycler amplification were detected with SYBR green I dye (Roche Diagnostics). PCR cycling conditions were 50uC for 2 minutes and 95uC for 10 minutes, followed by 40 cycles of 95uC for 15 seconds, 60uC for 1 minute, followed by the final melting curve program. The melting curve analysis of PCR products together with their analysis by electrophoresis revealed the presence of a single amplicon at the expected size. Each sample was run in duplicate and mean values were used for quantitation.", "The ", "Thus, BDV infects neuronal cultures efficiently and triggers significant neuronal MHC I expression. For all subsequent studies, we used neurons that had been infected for the same length of time (14 days) and verified for each experiment that infection was indeed complete prior to any subsequent analysis.", "Fluorescence measurements and imaging were performed on a Zeiss LSM-510 inverted confocal microscope with 10X, 20X or 40X objectives, whilst maintaining the cells at 37uC and 5% CO2. To minimize photobleaching, one frame was captured every 20 s on average. Single-cell-tracking analysis was performed automatically (intensity .130620; size <10 mm) with Imaris sotware and only tracks with durations of .120 s were included in the analysis. Image sequences of the time-lapse recordings were processed using Metamorph and Imaris softwares and 3-D images were generated with Imaris." ] },{ "paper_id": "502dd3d54b1d6ee5cf901fd441afdf5231cffa2b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusion: Young children living in a group context have a high risk of respiratory virus infections, especially rhinovirus. In some instances, viral genomes were detectable for about 1 month by PCR.", "Many studies have reported and identified respiratory viruses in sporadic cases of acute respiratory infection, but there have been few follow-up studies of individuals with multiple respiratory virus infections (Martin et al., 2013) ." ] },{ "paper_id": "502fc7e74c22bd0763542416c09589b5dca35b75", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and obtain a reduced version for (2):", "The application of the soft laser induces an intensity decay, which is reflected by the constant r p in (8) . Its value is determined by the signal decay in the (unbleached) control ROI C, assuming the following ODE:", "Our novel approach to introduce spatio-temporal resolved simulation techniques into computational virology paves a way for previously unexplored detailed biophysical understanding of virus replication dynamics, for example to unveil the relationship of form and function, as we have demonstrated already within our former paper [27] , or to reveal areas of the virus life cycle amenable to novel antiviral intervention that conventional biology may miss e.g., spatial dependence of virus-encoded factors within specfic intracellular regions. In the future, this avenue of research has the possibility of substantially impacting our understanding of complex biological systems." ] },{ "paper_id": "505d4036449010b44702841ae2564d6a55a3fbcd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were presented as means6SD for the immunized mice per group. The SPSS 13.0 software for windows was used for statistical analysis. The LSD t-test was used for between group comparisons. P values,0.05 were considered statistically significant.", "All participants gave written informed consent. This study was conducted in accordance with the Declaration of Hubei and approved by Health Department of Hubei Province and Wuhan Blood Center of Hubei Province, China.", "The spike (S) protein of SARS CoV is a key protein involved in viral entry and therefore the main target for vaccine design [32] .", "Analysis of the humoral immune response 6-8 wk-old female BALB/c mice were immunized intramuscularly with purified plasmid pcDNA-S or pcDNA-BS 3 times at a 2-wk interval. S-specific IgG and the subclasses (IgG1 and IgG2a) in serum were assessed by ELISA. Recombinant S2 protein expressed in E. Coli was purified and used as the detection antigen. Horseradish peroxidase (HRP)-conjugated goat anti-mouse IgG, IgG1 or IgG2a (sigma) was used as the secondary antibody. Optical density (OD) was read at 490 nm (A 490 )." ] },{ "paper_id": "505f56215f18a8d205927dd48898f22a336b5b4b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LY294002-only treatment of RK13 cells did not induce apoptosis as evidenced by the lack of caspase activity ( ", "Rubella virus (RV) is the sole member of the Rubivirus genus of the Togaviridae. It has a positive-sense single stranded RNA genome that is 9762 nucleotides (nt) in length and contains two non-overlapping open-reading frames (ORFs). The 5' proximal ORF encodes the p200 polyprotein precursor for the nonstructural proteins (NSPs) p150 and p90 [1, 2] . The 3' proximal ORF encodes the structural proteins: capsid (C), and glycoproteins E1 and E2 [3, 4] .", "Nucleic acids were precipitated using 3 M sodium acetate, 2-propanol, and ethanol. DNA pellets were dried and resuspended in 10 mM Tris pH 7.5, 1 mM EDTA. Ladder fragments were electrophoretically separated on 1.5% Tris-Acetate EDTA (TAE) agarose gels. Gels were stained in ethidium bromide solution (5 mg/ml) and fragmented DNA was visualized under UV light." ] },{ "paper_id": "506764ffd8140a103b330aa1dbb12d4b921ffda2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Comparison of xMAP assay with ELISA using clinical samples" ] },{ "paper_id": "5067fdcb872ccb895d1d4e5a856ad81aabe9b7b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human monocytic cells (THP-1) were purchased from the American Type Culture Collection (Manassas, VA, USA, ATCC Number: TIB-202) and cultured in RPMI 1640 medium supplemented with 10% heat-inactivated fetal bovine serum (FBS), 100 U/mL penicillin, 100 \u00b5g/mL streptomycin sulfate, 1\u00d7 Glutamax-I (L-glutamine alternate), and 0.05 mM 2-mercaptoethanol. THP-1 (differentiated) macrophages were obtained by exposing the cells to 60 nM phorbol-12-myristate-13-acetate (PMA) for 12 h, followed by culture for a further 24 h in complete growth medium without PMA.", "Mice were euthanized by overdose inhalation of carbon dioxide at different time points after infection with MERS-CoV. Lungs were harvested and total RNA was extracted and purified using an RNeasy Extraction Kit (Qiagen, Hilden, Germany).", "occurred, when compared to that in spleen.", "All animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of the Beijing Institute of Microbiology and Epidemiology (IACUC Permit No: BIME 2017-0011; Permit Date: 8 March 2017). Animal studies were carried out in strict accordance with the recommendations set out in the Guide for the Care and Use of Laboratory Animals." ] },{ "paper_id": "506b8507912862c6a87723c6a5babf2132748503", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5076cec908e9bc3ba685507e00ac19deab50b02e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "507796937879c600ac886d0aa7080e73bedb5044", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The recombinant 6\u00d7 His-tagged N protein was expressed in E. coli BL21 (DE3) cells after induction with 1 mM IPTG for 5 h in LB-medium at 37 \u00b0C . The recombinant protein was purified by a GravitrapTM affinity column (GE Healthcare, Bio-Sciences, Piscataway, NJ, USA) according to the manufacturer's instructions.", "BALB/c mice were immunized with 0.1~0.2 mg of purified recombinant N protein injected subcutaneously at multiple sites on the back. Booster injections were given two and four weeks later. Blood was drown from the mouse at the fifth week following the immunization, and the blood was allowed to clot at 4 \u00b0C and the antiserum was recovered by centrifugation at 5,000\u00d7 g for 10 min at 4 \u00b0C . A control serum was made by injecting normal saline under the same conditions. The animal experiment was approved by Harbin Veterinary Research Institute and performed in accordance with animal ethics guidelines and approved protocols. The animal Ethics Committee approval number is Heilongjiang-SYXK-2006-032.", "Vero E6 was grown and maintained in Dulbecco's modified Eagle's medium supplemented with 10% heat-inactivated fetal calf serum and penicillin-streptomycin, and incubated at 37 \u00b0C in 5% CO 2 . Vero E6 cells were infected with PEDV strain CV777 kindly provided by Pensaert M B at MOI = 1, and were seeded and after 24 h for both indirect immunofluorescence assay and Western blot analysis." ] },{ "paper_id": "5080b4cb5df826f641dc6602e27dcca510ccada8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Enzyme production. All methods were carried out in accordance with relevant guidelines and regulations.", "Amplified cDNAs were cloned into the pFastBac HTC vector (Invitrogen, Carlsbad, CA, USA), which was transformed into Escherichia coli DH5\u03b1 cells. The pFastBac HTC vector containing the target gene was transformed into E. coli DH10Bac cells and a baculovirus transfer vector was transfected into insect Sf9 cells. Recombinant enzymes were expressed by infection of Sf9 cells with a high-titre baculovirus." ] },{ "paper_id": "50897189565f10bfa3b4884058b5a51cf75c091e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The increasing incidence, severity and size of EBOD outbreaks highlight the importance of developing and standardizing diagnostic tools for EBOD rapid diagnosis and post-epidemic surveillance. The most devastating EBOD outbreak to date, the West African outbreak, prompted determining seroprevalence rates, infection risk population studies, and assessing occurrence of asymptomatic infections [35] ." ] },{ "paper_id": "509e9bda6a2f6b5525ba06641f8af156653a2aab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal procedures were performed in accordance with Flinders University Animal Welfare committee approval number 870/14 and Institutional Biosafety Committee approval NLRD 2011-10.", "Primers Sequence Accession No." ] },{ "paper_id": "50aa060bb87a548227b5b972c63920faef016f05", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The questionnaire comprised five categories of questions: (1) demographic and occupational characteristics;", "The study protocol as well as the questionnaire was approved by Ethical Committee of the Second University of Naples.", "Tables 4, 5, 6, 7 and 8. " ] },{ "paper_id": "50aa5eba3f398675c8f3c53a819aca7fb8b4af33", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data in this study were synthesized using Scopus database which has many important features that facilitate bibliometric analysis as in previous similar studies [10] [11] [12] [13] [14] [15] . Such features include citation analysis, country and author contribution as well as source titles and productivity per year. Scopus is produced by Elsevier and covers more than 20,000 journals that have 100 % Medline coverage. Scopus is larger than Web of Science and more accurate than Google Scholar [16] .", "The most research productive institution was Turun yliopisto (i.e., University of Turku) in Finland with 82 (2.91 %) publications and an h-index of 34. Furthermore, Turun yliopisto also ranked first in total citations 8095 (Table 9) .", "Abbreviations AAD, antibiotic-associated diarrhea; FDA, food and drug administration; GDP, gross domestic product; h-index, the Hirsch index; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome; IF, impact factor; IRB, institutional review board; NEC, necrotizing enterocolitis; SCR, standard competition ranking; USA The Unite States of America" ] },{ "paper_id": "50ad279de0a3f825b6280e07afc79439f59ecc3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All values were expressed as mean \u00b1 standard error of the mean (SEM). Statistical analyses were performed by using Student's t-test or analysis of variance (ANOVA) with Bonferroni test as post-hoc analyses. Data were analyzed and plotted with GraphPad Prism 5.0 (GraphPad, La Jolla, CA). P < 0.05 was considered to be statistically significant.", "The study protocol was approved by the Animal Use and Care Committee of the University Health Network. All animals were housed in a pathogen-free facility, with a 12-h light-dark cycle, and they were provided with free access to water and food, and received humane care in compliance with the Guide for the Care and Use of Experimental Animals formulated by the Canadian Council on Animal Care.", "Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are critical and leading cause of mortality in the Intensive Care Units. In United States, there were approximately 190,000 patients of ALI/ARDS each year with approximately 40% mortality [18] . ALI/ARDS can be caused by intrapulmonary insults (such as infection, acid aspiration, ventilator-induced lung injury, ischemia-reperfusion, and etc.), as well as by extrapulmonary insults (such as sepsis, hemorrhagic shock, trauma, burn, and etc.) [19] . Lipopolysaccharide (LPS) binds to Toll-like receptor 4, and induces the production of various pro-inflammatory cytokines and development of ALI [20] ." ] },{ "paper_id": "50adcf9bfee16b95201df9fdcc9dcf30c1f8ea6e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Natural VSV infection can cause disease in cattle, horses and swine, resulting in symptoms such as vesicular lesions around the mouth, hoofs, and teats [2, 12] . Natural infection of humans is rare and has only been reported in agricultural or veterinary contexts [13, 14] . There has also been a report of a laboratory worker infected after direct exposure to VSV [15] . Although human infection is typically subclinical or only results in mild flu-like symptoms [14, 16] , a single case of encephalitis in a Panamanian boy associated with VSV Indiana infection has been documented [17] . Neurotropism and neurovirulence have also been demonstrated in experimental VSV infection of rodents [18] [19] [20] .", "Survival data from the animal studies were analyzed with the log-rank test using GraphPad Prism 4 (GraphPad Software, USA). Statistical significance of the data was determined by Student's t-test.", "pUbEm, pCMV-\u0394R8.91 and pMD.G were kindly provided by Dr. Yasuhiro Ikeda (Mayo Clinic, USA) [25] and pVSV-XN2 by Dr. John Rose (Yale University, USA).", "Sera from immunized mice were 2-fold serially diluted in 96-well plates before being mixed with 100 TCID 50 of each influenza virus. The virus-antibody mixtures were incubated at 37\u00b0C for 1 h and added to monolayers of MDCK cells seeded in 96-well plates. Plates were incubated at 37\u00b0C for 1 h then washed, and media with 2 \u03bcg of TPCK-trypsin were added to each well. Plates were incubated at 37\u00b0C for another 72 h and supernatants were analyzed by the HA assay. Virus neutralization titer was defined as the reciprocal of the highest dilution of serum which showed completely no HA titer [30] .", "Sera were 2-fold serially diluted with PBS in U-bottom, 96-well microtiter plates (Thermo Scientific). Four HA units of influenza virus were added into each well and incubated at room temperature for 1 h followed by addition of 0.75% human type-O red blood cells. HAI titer was calculated as the reciprocal of the highest dilution of serum which completely inhibited the agglutination of red blood cells." ] },{ "paper_id": "50c268968326f133eeacd3745e43a4226d867ce8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Peptide constructs synthesis. For immunological assay (i.e., secretion of antibody, cytokine and Granzyme B), two peptide constructs (L1 and L2 peptides, Fig. 2) were synthesized by BioMatik Co. with more than 85% purity." ] },{ "paper_id": "50c5334ead9ce88189c0840243fb64fa9599bfdb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "50c63f3bfae37dbb495ef4d69b0d68c5c42b49ce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Kirchdoerfer et al.", " CoV nsp12 TCCGCCGATGCCTCTACCTTCCTGAATCGCGTGTGCGGCGTGAGCGCCGCAAGGCTGACACCATGTGGCACAGGCAC CTCCACAGATGTGGTGTACAGGGCCTTCGACATCTATAACGAGAAGGTGGCCGGCTTTGCCAAGTTCCTGAAGACCA ATTGCTGTCGCTTTCAGGAGAAGGATGAGGAGGGCAACCTGCTGGACTCTTACTTCGTGGTGAAGCGGCACACCATG AGCAACTACCAGCACGAGGAGACAATCTATAATCTGGTGAAGGATTGCCCAGCCGTGGCCGTGCACGACTTCTTTAA GTTTAGAGTGGATGGCGACATGGTGCCCCACATCAGCCGCCAGCGGCTGACCAAGTACACAATGGCCGACCTGGTGT ATGCCCTGAGGCACTTCGATGAGGGCAATTGTGACACCCTGAAGGAGATCCTGGTGACATACAACTGCTGTGACGAT GACTACTTCAACAAGAAGGATTGGTACGACTTCGTGGAGAACCCCGACATCCTGAGAGTGTATGCCAATCTGGGCGA GAGAGTGAGGCAGTCCCTGCTGAAGACCGTGCAGTTCTGCGATGCAATGAGGGACGCAGGAATCGTGGGCGTGCTGA CACTGGATAACCAGGACCTGAACGGCAATTGGTACGATTTTGGCGACTTCGTGCAGGTGGCCCCTGGCTGTGGCGTG CCAATCGTGGACTCCTACTATTCTCTGCTGATGCCCATCCTGACCCTGACACGCGCCCTGGCAGCAGAGAGCCACAT GGATGCCGACCTGGCCAAGCCTCTGATCAAGTGGGATCTGCTGAAGTATGACTTTACCGAGGAGCGCCTGTGCCTGT TTGATCGGTACTTCAAGTATTGGGACCAGACATACCACCCTAACTGCATCAATTGTCTGGATGACCGCTGCATCCTG CACTGTGCCAACTTTAATGTGCTGTTCTCTACCGTGTTTCCACCCACCAGCTTCGGCCCACTGGTGCGGAAGATCTT CGTGGACGGCGTGCCTTTTGTGGTGAGCACCGGCTATCACTTTAGAGAGCTGGGCGTGGTGCACAACCAGGATGTGA ATCTGCACTCCTCTAGGCTGTCCTTCAAGGAGCTGCTGGTGTACGCAGCCGATCCTGCAATGCACGCAGCATCTGGC AACCTGCTGCTGGACAAGCGGACAACCTGCTTCAGCGTGGCCGCCCTGACCAACAATGTGGCCTTTCAGACAGTGAA GCCAGGCAACTTCAATAAGGACTTCTACGACTTCGCCGTGTCTAAGGGCTTCTTTAAGGAGGGCAGCTCCGTGGAGC TGAAGCACTTCTTTTTCGCCCAGGACGGCAATGCCGCCATCAGCGATTACGACTACTATAGATATAACCTGCCCACC ATGTGCGACATCAGGCAGCTGCTGTTTGTGGTGGAGGTGGTGGACAAGTACTTCGATTGCTATGACGGCGGCTGTAT CAACGCCAATCAGGTCATCGTGAACAATCTGGACAAGTCTGCCGGCTTTCCATTCAATAAGTGGGGCAAGGCCAGAC TGTACTATGATAGCATGTCCTATGAGGATCAGGACGCCCTGTTCGCCTACACCAAGAGGAACGTGATCCCCACCATC ACACAGATGAATCTGAAGTACGCCATCTCCGCCAAGAACCGGGCCAGAACAGTGGCCGGCGTGAGCATCTGCTCCAC CATGACAAACCGCCAGTTTCACCAGAAGCTGCTGAAGTCCATCGCAGCAACCAGAGGCGCAACAGTGGTCATCGGCA CCTCTAAGTTCTATGGCGGCTGGCACAATATGCTGAAGACCGTGTACTCCGACGTGGAGACACCACACCTGATGGGC TGGGATTATCCTAAGTGTGACAGAGCCATGCCAAACATGCTGAGGATCATGGCCAGCCTGGTGCTGGCCAGAAAGCA CAACACCTGCTGTAATCTGTCCCACCGGTTCTACAGGCTGGCCAACGAGTGCGCCCAGGTGCTGAGCGAGATGGTCA TGTGCGGCGGCTCCCTGTATGTGAAGCCTGGCGGCACATCTAGCGGCGACGCAACAACCGCCTACGCCAACAGCGTG TTCAACATCTGCCAGGCCGTGACCGCCAACGTGAATGCCCTGCTGAGCACAGATGGCAATAAGATCGCCGACAAGTA CGTGCGCAACCTGCAGCACCGGCTGTACGAGTGTCTGTATAGAAATAGGGATGTGGACCACGAGTTCGTGGATGAGT TTTACGCCTATCTGAGGAAGCACTTTAGCATGATGATCCTGTCCGATGACGCCGTGGTGTGCTACAACTCCAATTAT GCCGCCCAGGGCCTGGTGGCCTCTATCAAGAACTTTAAGGCCGTGCTGTACTATCAGAACAACGTGTTCATGTCCGA GGCCAAGTGCTGGACCGAGACAGACCTGACCAAGGGCCCCCACGAGTTCTGTTCTCAGCACACAATGCTGGTGAAGC AGGGCGATGACTACGTGTATCTGCCTTATCCAGATCCCTCCCGCATCCTGGGAGCAGGATGTTTTGTGGATGACATC GTGAAGACCGATGGCACACTGATGATCGAGCGGTTCGTGTCTCTGGCCATCGACGCCTATCCCCTGACCAAGCACCC TAACCAGGAGTACGCCGACGTGTTCCACCTGTACCTGCAGTATATCAGAAAGCTGCACGATGAGCTGACCGGCCACA TGCTGGACATGTACAGCGTGATGCTGACAAACGACAATACCTCAAGATACTGGGAGCCCGAGTTTTATGAAGCAATG TACACCCCTCACACCGTCCTG >Codon " ] },{ "paper_id": "50c7a780f9115d0224ceeb6f2e29037d8e5703d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "During infection, many RNA viruses produce characteristic inclusion bodies that contain both viral and host components. These structures were first described over a century ago and originally termed \"X-bodies,\" as their function was not immediately appreciated. Whilst some inclusion bodies may represent cytopathic by-products of viral protein overaccumulation, X-bodies have emerged as virus \"factories,\" quasi-organelles that coordinate diverse viral infection processes such as replication, protein expression, evasion of host defenses, virion assembly, and intercellular transport. Accordingly, they are now generally referred to as viral replication complexes (VRCs). We previously used confocal fluorescence microscopy to unravel the complex structure of X-bodies produced by Potato virus X (PVX).", "Infectious PVX RNA was obtained by T7 in vitro transcription from plasmid constructs containing PVX.GFP-CP and PVX.mCherry-CP modified cDNA copies, as described in Santa . Combinations of agrobacteria carrying binary expression constructs were infiltrated into N. benthamiana leaves at an OD 600 of 0.15 or 0.25 each, as described previously . Microprojectile bombardments were carried out with a custom built gene gun according to the description in Gaba and Gal-On (2006) ." ] },{ "paper_id": "50d0f5fd4187d914ff40cacb3c436edc5b5bcc00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recruitment. How are participants recruited into the trial? Pragmatic Recruited from practice sites (emergency rooms, clinics).", "Setting. Where is the trial being done? Pragmatic Performed at the practice site.", "Organization. What expertise and resources are needed to deliver the intervention?" ] },{ "paper_id": "50e55ab8dd87f7523b7f25203ef10004c8d3b13e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A highly sensitive and specific ELISA was carried out by coating the wells with purified recombinant HA protein (expressed in baculovirus system) of p-H1N1-09 virus, sera at 1:100 dilution and anti-human-IgG-HRP conjugate as the detector antibody [7] . Isotyping was done as described earlier [8] .", "Analysis of gene expression profiles revealed significant findings; please see Table S1 :", "Comparison of controls with disease categories. " ] },{ "paper_id": "50e8d64761dddc0b7ce037734d813eca7cd63701", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Text S1 Influence of different sampling and analysis techniques on CoV RNA detection. (DOC)", "To minimize the possibility of contamination, all RT and PCR reactions were prepared in an enclosed acrylic nucleic acid workstation equipped with a UV light (Clone Zone, USA Scientific, Ocala, FL) in a room separate from the main laboratory. Water controls without template included in every RT and PCR experiment gave no false-positive results. Amplicons were analyzed by agarose gel electrophoresis and sequenced on an ABI 3730 DNA sequencer (Applied Biosystems Technologies, Carlsbad, CA) at the University of Colorado School of Medicine Cancer Center DNA Sequencing and Analysis Core. Samples were scored as positive if CoV RNA was detected on two PCR runs. Statistical significance was determined using Fisher's exact test. Phylogenetic analyses were conducted using MEGA version 4, and phylogenetic trees were constructed using the neighbor-joining method [34] . The nucleotide sequences from this study were deposited in GenBank under accession numbers HQ336973-HQ336976 and JF414933-JF414936. Table 1) .", "Capture, marking, and sampling of bats followed guidelines of the American Society of Mammalogists [25] and animal protocols were approved by the Institutional Animal Care and Use Committee of the U.S. Geological Survey, Fort Collins Science Center ('Standard Operating Procedure 01-01 for the Capture, Handling, Marking, Tagging, Biopsy Sampling, and Collection of Bats') and Colorado State University (CSU IACUC number 03-096A). Bats were captured under authority of a scientific collecting license (permit numbers: 07TR738A3, 08TR2010, and 09TR2010) issued by the Colorado Division of Wildlife." ] },{ "paper_id": "50ed67f9700cce235cfb173d78b22053243c1d38", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "50f42123b5035f840369d0ff88cc55263a1394b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Avian influenza: human\u00c1animal interfaces and global travel Specific subtypes of influenza A viruses that circulate in birds can infect humans. Influenza infections of avian origin occur through both direct and indirect exposure to infected animals, whether alive or dead. One important unique feature of influenza viruses is their ability to cause both annual epidemics (seasonal influenza) and, from time to time, more serious pandemics (93) . Each emerging strain has the potential to become seasonal.", "The consequences of further international spread are particularly acute today given the large number of polio-free but conflict-torn and fragile States which have severely compromised routine immunization services and are at high risk of re-infection. 14 Complicating the matter even further is the fact that alongside broader political issues that affect the possibility of implementing vaccination programmes, personal beliefs about the safety and benefits of vaccines are modulated by social ties, religious beliefs, and familial values. All of these factors affect vaccination uptake rates, as recent studies in both Pakistan and Nigeria have shown (112, 113) .", "The sustained transmission of a vector-borne disease requires the presence of a pathogen, a vector capable of transmitting that pathogen, and a susceptible human population (36) . The interconnections between multiple disease drivers and interdependencies created by a globalised world have enabled the global expansion of vector-borne diseases, of which recent examples include the arboviruses dengue (70) and Chikungunya (71, 72) .", "In another example, the E3 Network hosts a real-time model for the environmental suitability of Vibrio spp. in marine waters worldwide, taking into account temperature and salinity (125) . It uses daily-updated remotely sensed data to assess environmental suitability conditions for Vibrio spp. infections according to a model developed by Baker-Austin et al. (126) . Infections caused by Vibrio species (other than V. cholerae) can cause serious problems for immunocompromised persons, although the overall occurrence is generally low. Nonetheless, early information about the environmental suitability of Vibrio spp. infections will be of public health interest, and also demonstrates a proof-of-concept for predictive disease modelling more generally.", "Economic progress of the Roma population in Bulgaria has experienced a number of setbacks, ever since the political and economic transition of the late 80s (84, 85) . Discrimination, poor educational attainment, lack of occupational training, poor access to labour markets, and geographic isolation have all contributed to high unemployment rates (86) . The lack of job opportunities discourages further training and education, thereby perpetuating a vicious circle of poor education, poor working opportunities, and worsening living conditions (85) ." ] },{ "paper_id": "50f6c72d60ef3ae2d2235da9a307942a3f6685fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "k np is a macroscopic rate constant for conversion of nonproductive (E-DNA) np to productive Enzyme-DNA complexes (E-DNA) L The processivity in equation 1 is defined as", "This mechanism assumes that nsp13 unwinds total DNA in n number of steps of equal m-step size.", "Where k obs is the sum of the unwinding rate and dissociation constants k u and k d :" ] },{ "paper_id": "50f74fde0ed19bb067b5a48ae60a6d00354b1ba7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell lines used in this study were manufactured and thoroughly characterized under GMP conditions according to guidelines of the International Conference on Harmonization Topic Q5 (ICH Q5) [50] . The characterization of MRC-5 and Vero cells includes confirmation of cell line identity and the assessment of purity and freedom from fungi and bacteria (sterility), as well as mycoplasma and adventitious viruses testing.", "This study was partially funded by the UK Medical Research Council [(MC_UU_12014) and (MR/N017552/1)] (AK). 50 unit is the amount of virus required to result in infection of one-half of the cultures inoculated. Thus, for a virus stock at a concentration of 1 TCID 50 unit/ml, the probability that a well inoculated with 1 ml will be uninfected is 0.5 (and is the same as the probability that it will be infected; i.e. P=0.5 for both). Therefore, where a volume contains 1 TCID 50 unit, the number of infection units present is l=-ln (0.5) OR ln (2) . Thus, 1 TCID 50 unit is equivalent to ln (2) infectious units (or~0.69 infectious units).", "Statistical analysis for outliers were performed using Graph-Pad's Online Grubbs test (significance level 0.05, twotailed)." ] },{ "paper_id": "50f9ea2210efc3c98630da060b4254036f83c516", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Neosporosis is a disease caused by apicomplexan parasites such as Neospora caninum and Neospora hugheshi [1] . Considering its morphology, N. caninum is quite similar to Toxoplasma gondii, so neosporosis was misdiagnosed as T. gondii infection until 1988 [2] . Although the morphologies are quite similar, these parasites are biologically different and are considered as zoonotic compared with toxoplasmosis where it affects human, sheep and many other warm-blooded animals [3] . Neosporosis infection occurs from unsporulated oocysts in feces followed by ingestion by the cattle, transformation from the transformed into Escherichia coli BmDH10Bac, respectively, as described previously [15] . The white colonies were identified as positive transformants containing each recombinant BmNPV bacmid. ", "Two milliliters of crude hemolymph was mixed with 1 mL of PBS (pH 6.2). This mixture was centrifuged at 100,000\u00d7 g for 90 min at 4 \u2022 C, and the pellet was suspended in 1 mL of PBS (pH 6.2). This suspension was sonicated to dissolve the pellet, and the suspension was collected and subjected to western blotting.", "3.1. Expression of bx-PA-NcPROF-GP64TM, bx-PA-NcPROF, and PA-NcPROF in Silkworms" ] },{ "paper_id": "50fa3228f8067d61d3debffbe06c53deaf9dc863", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The filoviruses contain an RNA genome, approximately 19 Kb in length, which encodes seven proteins that are arranged from 39 to 59: nucleoprotein (NP); virion protein (VP)35; VP40; glycoprotein (GP); VP30; VP24; and the polymerase protein (L). The EBOV species express two extra nonstructural proteins from the GP gene referred to as soluble (s)GP [2] and small soluble (ss)GP [21] . Vaccine studies that have shown protection in animals from filovirus infections have primarily employed the GP protein as the immunogen with a few studies also using VP40 and/or NP [5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20] .", "Total white blood cell counts, white blood cell differentials, red blood cell counts, platelet counts, hematocrit values, mean cell volume, mean corpuscular volume, and mean corpuscular hemoglobin concentration were determined from blood samples collected in tubes containing EDTA, using a laser-based hematologic analyzer (Hemavet, Drew Scientific, Waterbury, CT). Concentrations of albumin, amylase, globulin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, lactate dehydrogenase, glucose, cholesterol, total protein, total bilirubin, direct bilirubin, urea nitrogen, creatinine, creatinine kinase, triglyceride, bicarbonate, calcium, phosphorus, chloride, potassium, and sodium were measured by IDEXX VetConnect (Westbrook, ME) using an Olympus AU5421 biochemistry analyzer (Olympus Americas, Center Valley, PA). ", "rVSV TaqMan PCR assay" ] },{ "paper_id": "50fc9068ff3d31f1caf01c012e7c08b3ea99d985", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hansen MH, Nielsen HV, Ditzel HJ. 2002. Translocation of an intracellular antigen to the surface of medullary breast cancer cells early in apoptosis allows for an antigen-driven antibody response elicited by tumor-infiltrating B cells.", "This work was supported by the High-Impact Research Ministry of Education Grant: UM.C/625/1/HIR/MOHE/SCI/18 and University of Malaya Research Grant; BKP/2013A. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." ] },{ "paper_id": "50ff548ec63f21fdb34fbdfe8fab41141c65fcb5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Herpes simplex virus-1 is a double stranded DNA virus associated with chronic infections in humans [1, 2] . HSV-1 infections may result in serious morbid, potentially mortal, conditions. HSV-1 corneal infections may cause herpes stromal keratitis (HSK), a condition that may advance to corneal opacity and blindness [1] [2] [3] . In fact, HSV-1 represents the leading infectious cause of corneal blindness worldwide [3, 4] . HSV-1 utilizes various pathways and strategies for entry into host tissues, including the cornea [3, 4] , from which it may disseminate into the nervous system causing a lethal condition, herpes encephalitis [1] [2] [3] [4] [5] . Additionally, HSV-1 may cause severe neonatal infections [1, 5] .", "Plasmids pEX-GFP-hLC3WT or pEX-HcRed-hLC3WT plasmid (simply referred to as GFP-LC3, or HcRed-LC3, respectively) previously described [49] were obtained from Addgene (plasmid numbers 24987, and 24991, respectively).", "Saponin was purchased from Sigma. The autophagy inducer MG132 was from Selleckchem (catalog number S2619), and was used at a final concentration of 1 \u03bcM.", "Experiments were replicated for three times. Quantification shown in figures shows mean values, and the error bars represent standard error of the mean. Student's t-test was performed to determine statistical significance. A minimum p-value for significance was considered 0.05." ] },{ "paper_id": "511ac6ac4422cee5357b1b6ff0b59acbfe2402c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "512ad31f56a7be38e686f3864431191b0b9f659e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2.3.1. Animals. Sixty-six nonfasted male outbred Swiss mice (20-30 g) were used. Mice were obtained from the animal facility of Universidade CEUMA (UNICEUMA) and were kept in a climatically controlled environment (room temperature of 22 \u00b1 2\u00b0C and humidity of around 60%) under 12 : 12 h light-dark cycle (lights on 07:00 a.m.). All procedures were approved by the Ethics Committee of UNICEUMA (April 24, 2014; #107/2014) and carried out in accordance with the Brazilian Society for Animal Welfare (SBCAL).", "Taken together, our data demonstrate that EAFPg may be used as food supplements, like tea, to prevent inflammatory disorders in which neutrophils play an essential role, such as ALI. However, further studies are necessary in order to address the effects of EAFPg in later time points of ALI.", "Samples. Total cell counts were performed in a Neubauer chamber and microscope (Zeiss Axio Imager Z2 upright microscope, Carl Zeiss, G\u00f6ttingen, Germany) after diluting an aliquot of the BALF with T\u00fcrk solution (1 : 20). Another aliquot (50 \u03bcl) was used for differential cell counts. For this, the slides were stained with May-Gr\u00fcnwald Giemsa and then analyzed by microscopy in an immersion objective. A minimum of 200 leukocytes was considered. Two independent researchers performed blinded analyses; if there was discordance, a third researcher performed the analysis." ] },{ "paper_id": "51340894a896316b58653a60c48da9c16b3ad0e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To support these findings a western blotting for HAdV E1A protein was run at 6 h post infection. Results obtained showed a significantly lower expression of E1A protein in samples treated with NIC and RAF compared with OXY (Fig. 4b) .", "Human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene was used as internal control. Primers, probes and conditions applied for GAPDH were those previously reported by Rivera et al. 52 . For quantification, gene fragments of hexon and GAPDH were cloned into the pGEM-T Easy vector (Promega), and known concentrations of those vectors were used to generate a standard curve for each experiment. All assays were performed in a C1000 thermal cycler apparatus (BioRad).", "For the evaluation of RNA expression, same conditions of infection applied for the DNA quantification were used. Six hours after infection, RNA was purified with the miRCURY RNA Isolation Kit (Exiqon Inc., MA) following the manufacturer's instructions. Quantification of RNA copy numbers was performed using primers in conditions previously reported for E1A 52 ." ] },{ "paper_id": "5136621ef7ae0c8d8b2dd396e432bedceb3f0331", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "While Alphacoronavirus transmission tends to be species-specific, experimental exposures have demonstrated that viral replication and seroconversion can occur across species [11] [12] [13] [14] [15] , theoretically providing evidence of the first step for adaptation to and emergence as a pathogen in a new host species.", "Most Alphacoronaviruses, including AcoV, utilize Aminopeptidase N of their natural host as a receptor, and host tropism differences of viruses are caused by the ability of their spike proteins to detect small species-specific amino acid differences in the aminopeptidase N [8, 13] . Despite the host specificity of this receptor, all of those viruses are known to bind and utilize feline Aminopeptidase N, suggestive of a common coronavirus ancestor infecting feline species [30] . This would explain the ability to grow ACoV on feline origin cell lines, such as Crandell-feline kidney cells (CRFK) [31] , and the failure to propagate virus on numerous other mammalian cell lines [1] .", "Among the RNA viruses, the coronaviruses possess the largest genomes, ranging from 26.4 to 31.7 kb. They are also among the most prone to homologous RNA recombination due to their unique use of random template switching during RNA replication, as well as the innate infidelity of RNA replication [6, 7] . These virus characteristics combine to generate significant diversity within genotypes of single CoV species, as well as allow coronaviruses to jump host-species and adapt to new ecological niches [7, 9, 10] ." ] },{ "paper_id": "513a25eb7a96ba7f7ae433498caf4791eb19e97c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "513bf780b2d2a5af6a194122cd3dd98c7b507fbe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "513cb067ae66876bca5e55d343cf196b8d5715e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quantification was performed using the open source image analysis framework CellProfiler Version 2 (www.cellprofiler.org). The raw fluorescence intensities were quantified in the perinuclear area. Raw fluorescence intensities were from lysotracker DND99. The ratios of green to red fluorescence (AO) or fluorescence intensities of compartments stained for early endosomal antigen 1 (EEA1, rabbit polyclonal antibody, Novus Biologicals, Cat# NB300-502) or LAMP1 (mouse H4A3 antibody, Santa Cruz Biotechnology) were measured relative to untreated cells.", "There are no vaccines or effective antivirals available against HRV, despite the fact that non-influenza related viral respiratory infections, predominantly by HRV, lead to an economic loss of USD 40 billion per year in the US alone and are among the top reasons for prescription of antibiotics [7] . Earlier developments of small compounds against HRV had targeted capsid or viral protease functions, for example pleconaril or rupintrivir [8, 9] . None of these antiviral molecules passed phase III clinical trials, or was approved by the FDA for broad human applications.", "BafA1 and ConcA were from Sigma-Aldrich & Enzo Life Sciences (Switzerland). Niclosamide was obtained from two sources, Prestwick (Illkirch, France) and Sigma. The batch from Sigma was 100% pure by thin layer chromatography (Batch 058K1597, see supplier homepage for certificate of analysis). All other TVB-compounds were supplied by 3-V Biosciences (Menlo Park, CA, USA). The original screening library of FDA approved compounds was from Prestwick.", "The discovery of antibiotics against microbes in the early 20 th century has had a major impact on society and saved countless lives [1] . Yet, broad range inhibitors against viral pathogens are presently not available. Classical antiviral strategies have targeted viral structural or enzymatic motifs with high specificity and potentially low side effects. These agents are, however, prone to viral evasion, and select for resistant strains [2] . To identify novel chemical inhibitors of virus infection we performed a high-content, image-based infection screen using a library of approximately 1200 known bioactive and food and drug administration (FDA) approved small compounds for their ability to inhibit human rhinovirus (HRV) 16 infection of HeLa cells.", "Viruses and cells where essentially prepared as described [21] . HeLa cervical carcinoma cells strain Ohio (from L. Kaiser, University Hospital Geneva, Switzerland), primary human embryonic lung Wi-38 cells (American Type Culture Collection) and human lung adenocarcinoma epithelial cells A549 (both from ATCC) were cultured in Dulbecco's Modified Eagle Medium (DMEM) supplemented with L-glutamine, non essential amino acids and 10% fetal bovine serum (all Sigma) at 37uC and 5% CO 2 in a humidified incubator and propagated sub-confluent twice a week. In all experiments passage numbers were kept at a maximum of 25 post thawing. For infection experiments in 96 well plates (Matrix, Thermo Scientific) 14000 cells were split in 100 ml the day before the experiment. HRV serotypes 1A and 16 were from W.M. Lee (University of Wisconsin, Madison, WI, USA), HRV 2 and 14 from L. Kaiser (University Hospital Geneva, Switzerland) and CVB3, B4 and A21 from T. Hyypi\u00e4 (University of Turku, Finland). Influenza strain A (Puerto Rico/8/34/H1N1) grown in MDCK cells was a kind gift from J. Pavlovic (University of Z\u00fcrich, Switzerland). HSV-1 expressing GFP from the major CMV promoter was a kind gift from C. Fraefel (University of Z\u00fcrich). The genetic nature of HRV serotypes used was verified by diagnostic sequencing [21] ." ] },{ "paper_id": "513d5ea4db4eb8e94c14c46b018c6041d78119cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cytokine/chemokine analysis WNV infected sera were analyzed for the presence and levels of TNF-a, IFN-c, CXCL10 (IP-10), and IL-6 by a mouse-specific cytokine/chemokine Milliplex ELISA (Millipore).", "For in vivo virus replication studies, infected mice were euthanized, bled, and perfused with 20 ml of phosphate-buffered saline (PBS). Whole brain, spinal cord, kidney, and spleen were removed, weighed, homogenized in 500ul of PBS, and titered by plaque assay.", "Cells were lysed in modified RIPA buffer (10mM Tris [pH 7.5], 150mM NaCl, 0.5% sodium deoxycholate, and 1% Triton X-100) supplemented with protease inhibitor cocktail (Sigma) and phosphatase inhibitor cocktail II (Calbiochem). Protein extracts (25 mg) were analyzed by immunoblotting as described previously [11] . The following primary antibodies were used to probe blots: mouse anti-WNV from the Center for Disease Control; rabbit anti-ISG56, rabbit anti-ISG54, rabbit anti-ISG49, kindly provided by Dr. G. Sen; mouse anti-PKR from Santa Cruz; rabbit anti-RIG-I and rabbit anti-MDA5 from IBL; mouse anti-tubulin from Sigma; and rabbit anti-STAT-1 from Cell signaling. Secondary antibodies included peroxidase-conjugated goat anti-rabbit, goat anti-mouse, donkey anti-rabbit, and donkey anti-mouse were from Jackson Immunoresearch." ] },{ "paper_id": "513f57a7efa430c143b840c17beb62c010429aac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\"When a country owns and is confident of their data\u2026. They are able to defend it\u2026 they are more willing to share\u2026 but when you don't build the capacity of a country to build and own an information system\u2026there is a problem\u2026 Vietnam data come monthly\u2026 they have Global Fund support but full data ownership, so they feel more confident\u2026\" (CAM-24).", "\"In my previous job, I often attended regional meetings (\u2026) I noticed that countries like Thailand and China speak confidently about their information system, but [representatives of] countries that have weaknesses in information systems say much less\u2026\" (CAM-20).", "\"We would like to invite partners from other countries [to attend meetings in Cambodia] but we no longer have budget for that. So, we are invited [by neighbouring countries] and cannot decide [the content and schedule of the meeting]\" (CAM-08)." ] },{ "paper_id": "5143bcbf109f693de355d2512a5810ed93a3072a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These differences indicate the need of regular review of surveillance-derived thresholds.", "The study was approved as a quality assurance project by the Melbourne Health Office of Research. GPSS and MMDS data in this study were collected, used and reported under the legislative authorization of the Victorian Public Health and Wellbeing Act 2008 and Public Health and Wellbeing Regulations 2009." ] },{ "paper_id": "51448d629c1d530b3001bc292c2d819a71ecdf23", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The underlined sequences were the universal Tag sequences.", "doi:10.1371/journal.pone.0162411.t001", "Conceptualization: LL GL. " ] },{ "paper_id": "5148320311832c95cb1c8b4fa32569e5a7945ff9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Received: 5 July 2019; Accepted: 26 September 2019;", "npj Vaccines (2019) 4:44" ] },{ "paper_id": "514a5ab6c1549c33d8acf502b929bc0699f5e21c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sequences from this study were deposited in GenBank under accession numbers KF524838 to KF524862.", "Despite the self-limiting aspect of interspecies transmission, the possibility of adaptation and generation of recombinant viruses may pose a threat for epidemics or pandemics. Moreover, continuous surveillance is further justified by the current emergence of a novel coronavirus strain in the Middle East (MERS CoV) [17] and by avian influenza infections occurring in the human population." ] },{ "paper_id": "514e24bfc28e0b5cf4b111d94604e7aa983500c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.ppat.1006838.g001" ] },{ "paper_id": "5159ab148faaafed700258c0a6278cb1fb5476e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Targeted sample concentration usually plays a crucial role in such experiments. To improve the final targeted fragments concentration, we added several steps to our modified workflow." ] },{ "paper_id": "515da9e83a07430922c9fe2a979c0698799aa56c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Astroviruses are non-enveloped, positive sense, single-stranded RNA viruses, with solid capsid shell~35 nm in diameter (~44 nm with spikes) [14] , classified into two genera: mammalian viruses (Mamastroviruses (MAstVs), 19 species recognized by the International Committee for Taxonomy of Viruses (ICTV)) and avian viruses (Avastroviruses (AAstVs), three species recognized by ICTV). The taxonomy does not take into account the species of origin anymore. The genome is 6.8 kb to 7.9 kb in length and harbors a 5 untranslated region (UTR), followed by three open reading frames (ORFs), namely ORF1a, ORF1b, and ORF2, a 3 UTR and a polyA tail [15] .", "HAstVs are a classic cause of viral diarrhea in children, along with rotavirus, norovirus, sapovirus and adenovirus. Seroprevalence studies indicate that most children in Europe encounter astrovirus before the age of two [2] . Astrovirus-associated diarrhea is not reported in immunocompetent adults, as infection in childhood is considered to confer protective immunity. Additionally, humoral immunity is considered to play a major protective role, along with cellular adaptive immunity [20] . Therefore, immunosuppressed patients and the elderly can also develop astrovirus-associated diarrhea.", "In non-immunocompromised individuals, after an incubation period of 4-5 days, an astrovirus infection will induce a mild disease, characterized by mild and short watery diarrhea for two to three days, followed by nausea, vomiting, and abdominal pain, which usually resolves spontaneously. These symptoms are most often milder than a rotavirus infection [21] . Recent seroprevalence studies have indicated that some infections can be asymptomatic as well [22] . As reported for rotavirus and norovirus, astrovirus has also been associated with intussusception in infants [23] . Although virological diagnosis of astrovirus-associated diarrhea is not routinely used in medical practice, it is sometimes used in epidemiological studies in the context of diarrheal outbreaks [24] and surveillance of diarrheal diseases [25, 26] .", "Finally, a more recent format of microarray was designed to detect about 100 viral species associated with gastrointestinal infections in vertebrates in order to expand the understanding of the etiology of the disease in humans and animals [119] . It is also interesting to note that, although microarrays are based on sequence homology with predefined known pathogens, the use of a Virochip allowed the identification of an astrovirus in a domestic rabbit with gastroenteritis after traditional diagnostic approaches, including virus isolation, failed to identify the pathogen [120] . Unfortunately, the somewhat complex and costly procedures of microarray experiments may limit their use in clinic." ] },{ "paper_id": "517aa0b6c174589d7183d73b1ce2f3787d86e369", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Both studies (5, 17) indicated several limitations about the epidemiological surveys on sepsis. Firstly, there was no population-level data available from low-income countries, which represent 87% of the world's population (17) and bear a huge burden of infectious diseases and sepsis (20) . Therefore, these figures were likely to be underestimates. Secondly, the lack of a universal and specific sepsis definition and severity criteria leads to substantial heterogeneity in case definitions among studies. Lastly, studies may use different denominators to calculate the incidence and mortality (e.g., person-years, specified populations, live births). These hurdles make meta-analysis more challenging and susceptible to bias.", "Licensed specific antiviral therapy is not available for HPeV or enterovirus infections, despite their relatively high incidence in neonatal encephalitis and systemic infections (58) . This presents a promising target for future research, and a tangible way to reduce the incidence of neonatal viral sepsis and associated infant mortality globally.", "Risk factors for neonatal enteroviral infection include exposure to maternal secretions or blood during delivery, maternal infection just before or at delivery, and a lack of previous maternal infection by the infecting serotype, resulting in low maternal antibody levels against that serotype of virus. The majority of severe neonatal enteroviral infections occur between days 3 and 5 of life, suggesting that the acquisition is generally in the perinatal period and is preceded by maternal infection (51) ." ] },{ "paper_id": "5187f0f3f45b0a1882a44001d193a24c97b0bb1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Six countries were affected with MERS during the period of this study. The majority of cases (approximately 93.9%) with highest mortality (98.6%) as well as 100% of female cases have been reported from Saudi Arabia ( Table 2 ).", "All statistical analyses were conducted using SPSS, version 21 (IBM Inc., Armonk, NY, USA). Quantitative measurement was expressed by medians and qualitative variables were presented as absolute frequency and percentage. Logistic regression was used to calculate the odds ratio (OR) with a 95% confidence interval in order to assess the probable relationship between risk factors and final outcome (dead/survived) of laboratory-confirmed MERS-CoV cases. P values of less than 0.05 were regarded as statistically significant.", "Our findings in Table 2 and Fig. 2 show that most cases are reported from Saudi Arabia after about 7 years since the start of MERS-CoV pandemic (June 2012 to January 17, 2018). So, it seems necessary that epidemiologic investigations are conducted by Ministry of Health in Saudi Arabia and international partners to better understand the transmission patterns of MERS-CoV." ] },{ "paper_id": "519b82201745afd08726b2c3e87cad65f8409da5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequence logos were generated from the web server WebLogo [55] .", "The electrostatic potential was mapped by averaging the last five frames of each MD trajectory using the APBS plugin [61] implemented in the VMD software.", "The DEFA/DEFT genes from the human, chimpanzee, orangutan, macaque and marmoset genomes were used for synteny analysis by mapping their loci onto chromosomes in scale." ] },{ "paper_id": "519bd743684c847c5a54c416f00c79c74068c6dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Three positive rodent samples representing different CoVs (JC30, \u03b2-CoV; JC34 and JC54, \u03b1-CoV) were used to perform viral isolation in Vero E6 cells (African green monkey kidney cells, ATCC: CRL-1586).", "Coronaviruses (CoVs) are enveloped viruses in the Coronaviridae family that contain a positive-sense and single-stranded RNA genome of approximately 30 kilobases [1] . CoVs consist of 4 genera and have been identified in a wide range of animals and in humans." ] },{ "paper_id": "519cc50b5527635a0a05f7efe73b2f30c62d9936", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Year 2012", "First name Name origin", "significance. This will improve our understanding of virus-host interactions in an ever-changing environment and enhance our preparedness for future outbreaks." ] },{ "paper_id": "519d5fa432c696fd94690fbffeb3d566a247019c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author ORCIDs. M. U. G. Kraemer http://orcid.org/0000-0001-8838-7147", "Here we describe the common applications and models used to predict acute viral diseases and discuss the current challenges and limitations. We then outline the advantages of integrating disparate data sources to advance our understanding of epidemic spread. We discuss how such research has been used in recent outbreaks and outline shortcomings that may be addressed in the future.", "During emerging infectious disease outbreaks, empirical information and mathematical modelling techniques are now commonly used to characterise and predict the spatio-temporal dynamics of the spread of pathogens. Such analyses may help policymakers to evaluate the threat to public health, determine the resources required to reduce disease burden, and guide disease surveillance efforts and the deployment of interventions." ] },{ "paper_id": "51a731857c1606428ec1eb47a97a290d2084c460", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following a large outbreak around 2010, porcine epidemic diarrhea virus (PEDV) has emerged as an eminent threat in the swine industry worldwide [1, 2] . Although PEDV can infect pigs of all ages, mortality in infected piglets aged below one week is especially high and could reach 100%. A few strategies have been employed to control PED outbreaks. For instance, feedback of PEDV infected materials to sows can induce lactogenic immunity for piglets [3, 4] . Despite being widely adopted in farms, this strategy poses serious safety concerns as contamination of other pathogens, dosage and virulence are often not well-controlled [3, 4] . Vero E6-N cells as an alternative system for enhancing propagation of PEDV vaccine strains and possibly other related viruses.", "Transfected or infected cells were harvested at indicated time points in RIPA buffer [50 mM Tris-HCl pH 7.4, 150 mM NaCl, 1% Triton-X 100, 0.5% Na-deoxycholate, 0.1% SDS] and separated in a 10% SDS-polyacrylamide gel. PEDV N was detected with a mouse monoclonal anti-PEDV N antibody (SD 6-29, Medgene Labs) or a mouse monoclonal anti-Myc antibody (Thermo Scientific). PEDV S was detected with a mouse monoclonal anti-S1 antibody (a kind gift from Q. He, Huazhong Agricultural University). IAV nucleoprotein was detected with a mouse monoclonal anti-NP antibody (Southern Biotechnology). PRRSV N protein was detected with a rabit polyclonal anti-ORF7 antibody (Median Diagnostics). Loading control, \u03b2-actin, was detected with a mouse monoclonal anti-\u03b2-actin antibody (Cell Signaling Technology).", "Data were prepared and analyzed with KaleidaGraph version 4.1.3 (Synergy Software). Statistical significance were determined for each pair of experimental and control groups by Student's t-test. Single and double asterisks represent p-values of < 0.05 and <0.01, respectively. No asterisk indicates p-values of > 0.05." ] },{ "paper_id": "51a7b35db673f0d7cb14a80b607192e3f44cc7f5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The likelihood that case i has been infected by a case observed up to year T can be approximated by", "This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001898. " ] },{ "paper_id": "51a9f0de2c657fd582c5ff023027833d48e4876b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Aedes albopictus C6/36 cells (ATCC) were maintained in Leibovitz L-15 media (GIBCO, Invitrogen) supplemented with 8% fetal bovine serum (FBS), at 28 o C, 5% CO 2 . BHK-21 cells (ATCC) and human erythroleukemic K562 cells (ATCC) were maintained in RPMI 1640 GlutaMAX medium (RPMI) (GIBCO, Invitrogen) containing 10% FBS, and incubated at 37 o C, 5% CO 2 . Vero cells (ATCC) were grown in 199 medium (M199) (GIBCO, Invitrogen) supplemented with 8% FBS, 1% sodium pyruvate and 1% NEAA. HEK293 T cells (ATCC) was cultured in Dulbecco's modified Eagle's medium (DMEM) (GIBCO, Invitrogen) supplemented with 10% FBS at 37 o C in 5% CO 2 .", "Mouse monoclonal antibodies 3H5 (m3H5), 4G2 (m4G2) and 2H2 (m2H2) are specific to EDIII of DENV2, EDII of flaviviruses and prM of DENV1-4 respectively. Chimeric humanized 3H5 (h3H5) and 4G2 (h4G2) were constructed by cloning the Fab portion (variable light and heavy chains) into an expression vector containing the human IgG1 framework for expression in HEK293 T cells [15] . Conjugation of HRP to antibodies-D29, -m3H5 and -m2H2, was performed using the Lightning-Link HRP Conjugation Kit (Innova Biosciences).", "The ADE assay was performed as described previously [20] . Briefly, pre-formed immune complexes were prepared by incubating serially diluted antibody with DENV2 or imDENV2 at a multiplicity of 25 GCP per cell (MOG 25) in RPMI MM at 37 o C for 1 hr before applying to 2610 4 K562 cells in 96-well U-bottom plate (Nunc). Supernatant was harvested 48 hr postinfection and virus titer was quantified by plaque assay.", "Dengue virus (DENV) is a flavivirus with four related but antigenically distinct serotypes (DENV1-4). It infects approximately 50-100 million people each year, of which 500,000 people exhibit the life-threatening form of severe dengue -dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) [1] . The current lack of treatment or licensed vaccine means dengue poses a serious public health threat [2] . Infection by one serotype of DENV confers lifelong immunity against the homologous serotype, but only limited crossprotection to the remaining three serotypes [3, 4] . The presence of cross-reactive, non-neutralizing antibodies generated during a primary infection has been suggested to enhance the pathogenicity of subsequent infections via the process of antibody-dependent enhancement (ADE) [5] . A successful and safe vaccine candidate must therefore elicit a protective long-lasting immune response to all four serotypes [4, [6] [7] [8] ." ] },{ "paper_id": "51b006f1087fca529dbda94f2ab41c71acc09654", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "51b2c04a95156d66aec99817f2dc769566cace9d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Disclaimers" ] },{ "paper_id": "51b8bdc5f732c68e830a09eb2ecd73191e6df2dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hibernation also may allow not only virus persistence in the bat, but trans-seasonal persistence as well, allowing virus to amplify and re-emerge when conditions are more amenable to transmission, such as seasonally for arthropod-borne viruses, colony formation and movement to maternity caves.", "Marburg and ebolavirus haemorrhagic fevers -Marburg and ebolaviruses -(Mononegavirales, Filoviridae), genera Marburgvirus and Ebolavirus, respectively, the 'filoviruses' -were discovered because they cause severe, often fatal, haemorrhagic diseases in humans and other primates.", "Finally, can we confidently link bats with emerging viruses? No, or not yet, is the qualified answer based on the evidence available. Only integrative and organised field and laboratory research, using ecological and epidemiological approaches conducted by bat biologists and medical researchers, will provide a useful and satisfactory solution.", "Epidemiologic and virologic investigations of an epidemic of haemorrhagic fever in humans in western Uganda in 2007 revealed the cause as being Bundibugyo ebolavirus, named for the district in Uganda where the epidemic occurred. This virus is more closely related to Ta\u00ef Forest ebolavirus than it is to other ebolaviruses, but is distinct from them all (Towner et al. 2008) .", "RNA of Cedar virus, another henipavirus, was detected in urine of pteropodid bats in Australia in 2009, but little is yet known about this virus . Challenge studies with Cedar virus in domestic ferrets [Mustela putorius furo (Carnivora, Mustelidae)] and domesticated guinea pigs [Cavia porcellus (Rodentia, Caviidae)], both susceptible to infection and disease with known henipaviruses, confirmed virus replication and production of neutralising antibodies, but no clinical disease. Also, the major genetic difference between Cedar virus and Hendra and Nipah viruses lies within the coding strategy of the P gene, known to play an important role in evading the host innate immune system. Preliminary studies indicated that Cedar virus infection of human cells induces a more robust interferon-\u03b2 response than does Hendra virus. Cedar virus is one that might be studied to develop a human and livestock vaccine." ] },{ "paper_id": "51c863bc37f993b3da543b91458e3ed5abd9aba9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Degenerative lesions. No degenerative lesions including amyloid deposition were identified in the pancreas.", "Inflammation. Focal ulcerative dermatitis located at the hindlimb (n = 2) or chronic lympho-histiocytic pododermatitis (n = 2) were present in 4 animals (11%).", "Supporting Information S1 " ] },{ "paper_id": "51d3450393a2a698cfe8ae3e94cb9d8f556e43ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analysed with GraphPad Prism and the indicated statistical tests. \ufffd P<0.05, \ufffd\ufffd P<0.01, \ufffd\ufffd\ufffd P<0.001.", "Perfused lung tissue, inflated with OCT were immediately embedded in OCT. Frozen sections (14 \u03bcm) were cut using a cryostat. Tissue sections were fixed in acetone, blocked in serum-free protein block and then stained for CD8 (53-6.7), CD45.1 (A20) and DAPI. Images were acquired on a Zeiss LSM700 microscope with a 20x objective. Acquired images were processed using ImageJ software.", "Total cell lysates were run on a 4-12% SDS/PAGE gel (Invitrogen) and transferred onto nitrocellulose membrane. Membranes were stained with antibodies against mouse IFITM3 (Abcam) and Actin (Sigma). Horseradish peroxidase (HRP)-conjugated anti-rabbit IgG antibody (Sigma) was used for protein detection." ] },{ "paper_id": "51dce3291fc7afaae1c28842c79dc9be97f90ae5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: K.M. designed study and collected data; K.J. gave an important advice on analyzing data; and K.M. and K.J. wrote the paper." ] },{ "paper_id": "51dd0bdd5680a978bf834d5b4cbfaa8dd84dea90", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Serum samples were analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/ MS), using compound spiked into control serum as a standard. Fecal MMV665917 was measured by homogenizing feces in PBS (0.1 g/mL) in a polypropylene tube and then further dilution prior to addition of an internal standard (enalapril) and acetonitrile protein precipitation. The supernatant was transferred to a fresh tube and dried using a speed vac. Samples were then resuspended and analyzed using LC/MS/MS.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "(EPS)" ] },{ "paper_id": "51dd595e1404da9a49935f1df61c163b6ad01a58", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "51e10bb6f0ef0363cab568d94c52db244ce7ad1f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The DEMETRA package (DEMETRA 2.0; Eurostat, the Statistical Office of the European Communities) was used for TRAMO-SEATS program; Microsoft Excel 2007 (Microsoft Corporation, Redmond, WA, USA) was used for data management; the SPSS 18.0 (SPSS Inc., Chicago, IL, USA) was used for statistical comparisons of seasonal indicators within subgroups." ] },{ "paper_id": "51e85d19c2cec68dfff68624118086ec2bb6de73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In 1993, a series of unexplained deaths in the American Southwest prompted an immediate response from scientists representing a variety of disciplines and institutions, who ultimately discovered critical linkages between the El Ni\u00f1o Southern Oscillation (ENSO), increased precipitation, vegetation primary productivity, deer mouse (Peromyscus maniculatus) populations, and Sin Nombre Virus (12) . This transdisciplinary group produced a wealth of outstanding science with immediate, high societal impact.", "The One Health initiative explicitly states that interdisciplinary and cross-sectional approaches are required for the prevention, surveillance, monitoring, control, and mitigation of EIDs. The terms multi-and interdisciplinary describe research efforts that incorporate a variety of disciplinary perspectives with varying degrees of integration across perspectives (11) . Collaboration between two researchers in different disciplines toward a more comprehensive understanding of a particular infectious disease is an example of multi-or interdisciplinary collaboration. In contrast, transdisciplinary collaboration extends beyond changing our understanding to invoke outcomes beyond the research arena, such as changing the way a disease is diagnosed or treated. Transdisciplinary collaboration explicitly seeks to have transformative outcomes for individuals, professions, or society as a whole, and accomplishes this by intentionally incorporating people and activities designed to convey research results beyond the research community. Hence, the One Health initiative call for interdisciplinary and cross-sectional approaches is an explicit call for transdisciplinary research that has transformative outcomes in all aspects of disease control. And most importantly, the need to support activities designed to foster transdisciplinary collaboration is clear if the collective effort to solve broad global health problems is to succeed.", "The need to develop a framework that captures the impact and benefit from scientific engagements is clear. Policymakers and Program Managers alike need to be able to evaluate when research and training activities are an efficient and effective use of federal dollars, and whether these activities help meet program objectives. But there are challenges to defining the appropriate metrics, including aligning long project timelines with shorter programmatic milestones. Traditionally, the focus has been on reporting research results rather than measuring broader benefits and the synergy of those metrics across different types of activities.", "In a study of 699 people working in groups from two to five in a wide variety of settings, Woolley et al. (21) found that the best predictors of creative outcomes were the degree of turn-taking in team interactions and team members' ability to read facial expressions. Intelligence of the team as a whole or of any individual on the team was less important. They proposed a new measure of collective intelligence as a predictor of the creativity of group outcomes (21) . A single workshop can begin to generate collective intelligence between participants that is difficult to obtain without the turn-taking and interpretation of facial expressions and body language that occurs in person." ] },{ "paper_id": "51f8792fd26cd2c094c1b2d0e5539902fb6221da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Overall ", "Supporting Information S1 " ] },{ "paper_id": "51f88d6a65a66742a19ec634400f8315fda5811e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusion: To end, the projected peptide gave us a solid stand to propose for vaccine consideration and that might be experimented for its potency in eliciting immunity through humoral and cell mediated immune responses in vitro and in vivo.", "Both NetCTL and CTLPred server were used to find epitopes for the activation of T-cell immunity with potential antigenicity. By examining the output it was predicted that FRYEFTAPF would be the best epitope candidate and was further subjected for binding proficiency analysis.", "Conservation analyses of the proposed epitopes were analyzed by the IEDB conservancy analysis tool that is shown in Table 4 . AllerHunter server predicted the " ] },{ "paper_id": "51f9ab9c7010dae7a662a33f0fd32e91a2001523", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Supporting information S1 " ] },{ "paper_id": "520074edb06a53db798395f49940fb5d24417b62", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasmids were transfected into cells using TurboFect\u2122 in vitro Transfection Reagent (ThermoScientific, USA). All transfections were performed following manufacturer's recommendations. ", "The forward primer of MID and C157 deletion mutants. 2 The reverse primer of N69 and MID deletion mutants. ", "forward primer 5'-ATACATATGCACCATCATCATCATCATCATTCATCAGGTGC TTTCAGAACTCAA-3', and reverse primer 5'-TTGCTCGAGTCATTCCAGTTCAGGTTTG-3'." ] },{ "paper_id": "5206b0be1000e6c8d75a827af94c1b8e61e297c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We also included an additional parameter e 0 determining the excess of distances observed within the lowest distance category, such that the probability of observing a distance in category i is given by", "Text S2 Additional Detail of the Analyses. (PDF) ", "Text S1 Questionnaires.", "The Institutional Review Board of China CDC granted ethical permission for the study. Oral informed consent was obtained from all adult participants and parental consent for minors at the time of interview.", "Increasing volumes of travel data for developed countries is becoming available, including origin-destination matrices for commuting obtained from census data, data from surveys and data from mobile phones [8] , but much less is known for other parts of the world. Here we analyse a unique dataset, collected in two very different areas of China that gives a snapshot of movement patterns in this rapidly developing country in the early 21 st century." ] },{ "paper_id": "52075e1e28bc2952fb7a2360fae88c76b36c722a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5208ab18e0b8b851eabda0c5c83c1d31156da8e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Genbank Accession Nos: AY733102-AY733566" ] },{ "paper_id": "52264dd990e495e82f511cfa80a14b52ec063722", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Asthma is chronic inflammatory disorder of the airways that induces a range of sub-clinical and clinical effects including but not limited to hyperresponsiveness, airflow limitation, and respiratory symptoms. Approximately 6.7% of adults and 8.5% of children in the United States are reported to suffer from asthma with the greatest prevalence among non-Hispanic black and Hispanic children under 18 years of age [1] . Triggers of asthma exacerbation are varied and include viral infections, certain animal allergens and criteria air pollutants, mites, environmental tobacco smoke (ETS), mold, chemical irritants, and exercise in cold air [2] . Reducing exposure to environmental agents shown to increase asthma symptoms or lead to asthma exacerbations is an important component of a strategy to manage asthma for individuals [3] .", "Our analysis included two residential building templates developed by NIST, a two story detached home and a single story detached home. Single family detached homes represent over 60% of the total housing stock in the U.S.", "ETS: Environmental tobacco smoke; PM 2.5: Particles less than 2.5 microns; HEPA: High efficiency particle arrestance; NIST: National Institute of Standards and Technology; AHU: Air-handling units; AER: Air exchange rates; SARS: Severe acute respiratory syndrome; CADR: Clean air delivery rate; qPCR: Quantitative polymerase chain reaction." ] },{ "paper_id": "522701df815e3cc124f0a2f55891879cde0ddffa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To determine whether there were any significant weather variations during the whelping season, daily environmental parameters were collected during the whelping season from Environment Canada (https://weather.gc.ca/ canada_e.html) for the four counties encompassing the study farms: minimum and maximum daily temperatures, total precipitation, and highest relative humidity." ] },{ "paper_id": "5227121ac5523e669cc04c9a8f2660080d995a34", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chinese Hamster Ovary (CHO) cells were grown at 37\u00b0C, 5% CO2 in Iscove's Modified Dulbecco's Medium (IMDM: Sigma, St. Louis, MO) and supplemented with 10% Fetal Calf Serum (FCS: Life Technologies, Grand Island, NY), 100 U/ml penicillin and 100 \u00b5g/ml gentamyin.", "CpG oligodeoxynucleotide (5'-TCCATGACGTTCCT-GACGTT-3') was provided by Coley (Ottawa, ON). Montanide ISA-51 mineral oil adjuvant was purchased from Seppic Inc. (Paris, France). The pcDNA3 construct expressing 1.5 kb XIAP gene encoding an anti-apoptotic gene product was a kind gift from Dr. R.G. Korneluk [24] .", "Results were expressed as mean \u00b1 S.D. In each experiment four animals were used per group. The t-test was applied for the statistical analysis of the data. The p value equal to or less than 0.05 was considered significant.", "XIAP: X-linked inhibitor of apoptosis." ] },{ "paper_id": "522970c3ab7dfd56f03358b19739d66ce7219097", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were analysed using GenStat \u00ae (version 16.2, VSN International Ltd.). All statistical models included sex as a fixed effect and birth weight as a covariate unless otherwise stated. A probability of p < 0.05 was selected as the level of significance, and where data was significant it was subjected to Fisher's protected least significant difference (PLSD) test." ] },{ "paper_id": "5229d13f7a121dfc9a455d2ec0807e3966da3e19", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dengue is the most prevalent mosquito-borne viral disease with over 500 million human infections annually and 2.5 billion people at risk, particularly in tropical and subtropical regions [1, 2] . The disease is caused by Dengue virus (DENV) belonging to the Flaviviridae family, which also includes several other human pathogens such as the West Nile virus, Japanese encephalitis virus, and yellow fever virus [1] [2] [3] [4] . So far, four antigenically distinct DENV serotypes have been identified: DENV-1 to -4, all of which cause dengue fever, dengue haemorrhagic fever and dengue shock syndrome. Despite intense studies, currently there are neither vaccines nor other treatments available to treat this disease [5, 6] .", "As the NS3pro contains no free Cys residue, three single-Cys mutants were prepared: Q27C, E86C, S158C by use of the QuikChange Site-Directed Mutagenesis Kit (Stratagene, La Jolla, CA, USA) as previously described [18] . The mutated plasmids were confirmed by DNA sequencing and their recombinant proteins were subsequently expressed and purified by the same procedures described above. 1 H-15 N heteronuclear single quantum coherence spectroscopy (HSQC) experiments were performed on each mutant to validate that these mutations did not significantly perturb the conformation of the native NS3pro sequence.", "was measured in the assay buffer containing 50 mM Tris-HCl (pH 7.5), 0.001% Triton X-100, 0.5 mM EGTA, or 100 mM sodium acetate (pH 4.0), 0.001% Triton X-100, 0.5 mM EGTA. Briefly, in the 100 \u03bcl reaction mixtures containing 0.3 \u03bcM protease, 20 \u03bcM protease specific fluorophore-tagged substrate benzoyl-Nle-Lys-Arg-Arg-aminomethylcoumarin (Bz-nKRR-AMC) was added and reaction mixtures were incubated at 37\u00b0C, and the liberated coumarin fluorophore was continuously monitored at \u03bb ex of 380 nm and \u03bb em of 450 nm on Infinite M200 PRO Tecan microplate reader. For steady state kinetics, 0.3 \u03bcM refolded NS3-NS2B protease was incubated with various concentrations of Bz-nKRR-AMC substrate in assay buffer containing 50 mM Tris-HCl (pH 7.5), 0.001% Triton X-100, 0.5 mM EGTA at 37\u00b0C. Progression of enzymatic reaction was monitored as an increase in fluorescence at \u03bb ex of 380 nm and \u03bb em of 450 nm. Initial fluorescence velocities (relative fluorescence units/sec) were calculated and curves were fitted to the Michaelis-Menten equation by nonlinear regression using Graph-Pad Prism. Steady-state kinetic constants were determined from triplicate measurements and reported as mean Standard Error.", "( 15 NH 4 ) 2 SO 4 , [ 13 C6]-glucose and D 2 O were purchased from Cambridge Isotope Laboratories (Andover, MA). The generation of the isotope-labeled proteins for NMR studies followed a similar procedure except that the bacteria were grown in M9 medium with the addition of ( 15 NH 4 ) 2 SO 4 for 15 N labeling and ( 15 NH 4 ) 2 SO 4 /[ 13 C]-glucose for 15 N-/ 13 C-double labelling as previously described [22] . The purity of the recombinant proteins was checked by SDS-PAGE gels and their molecular weights were verified by ESI-MS and Voyager STR matrix-assisted laser desorption ionization time-of-flight-mass spectrometer (Applied Biosystems). The concentration of protein samples was determined by the UV spectroscopic method in the presence of 8 M urea [23] ." ] },{ "paper_id": "5229e54b1866448ee22e138bb7c12ab67547ccac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The arenavirus envelope glycoprotein (GP), the sole protein found on the surface of virions, is processed into three associated subunits: the stable signal peptide (SSP), GP1, and GP2 [20, 21] . SSP is a unique component of the arenaviral fusion machinery and plays a role in the transport, maturation, and pH dependent membrane fusion activity of the GP complex [22] [23] [24] [25] . The GP1 subunit engages a cellular receptor(s), and GP2 mediates pHdependent membrane fusion after viral particles are internalized into acidified endosomes [21, [26] [27] [28] [29] .", "ClustalW was used to align the GP sequences of the NW arenaviruses and for phylogenetic calculations, and the cladogram was plotted using Drawtree [56, 57] . ", "The zoonotic reservoir of a given NW arenavirus has a unique geographical distribution, and each arenavirus prefers its own host [11] . Most of the natural hosts for NW arenaviruses belong to the subfamily Sigmodontinae in the family Cricetidae, which contains NW mice and rats [6, 12] . The host animals for MACV, JUNV and GTOV are Calomys callosus (large vesper mouse), Calomys musculinus (drylands vesper mouse), and Zygodontomys brevicauda (short-tailed cane mouse), respectively [13] [14] [15] [16] . The natural reservoirs of SABV and Chapare virus have not been identified. AMAV was isolated from Neacomys spinosus (bristly mouse) and Neacomys guianea (Guiana bristly mouse), and TCRV is suggested to have a non-rodent host, Artibeus species fruit bats in Trinidad and Tobago [12, [17] [18] [19] ." ] },{ "paper_id": "523d27d193f6bd636b6fae4da4af51ea66907772", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal procedures were reviewed and approved under the protocol number HUT100602MOU by the VA IACUC committee (Subcommittee on Animal Studies, NIH assurance number A3088-01) at the VA Palo Alto Health Care System and in accordance with the PHS Policy on Humane Care and Use of Laboratory Animals.", "Several immunochemical procedures are described below; antibodies used in this study are listed in Table 1 .", "(DOCX)", "HCV transgenic and non-transgenic mice were perfused through the left ventricle of the heart, first with 10 U/ml heparin in saline until the liver was cleared of blood (about 5 min), then with fixative (2% glutaraldehyde and 2% paraformaldehyde in 0.1M Na Cacodylate, pH 7.4) until the liver was completely fixed (about 6-8 min). Heparin and fixative solutions were delivered by a peristaltic pump (VWR, Westchester, PA, USA) with the flow rate set at 4.5 ml/min. One mm cubes were prepared from the fixed liver and were left to continue fixation at room temperature (RT) overnight. These specimens were processed and embedded in Eponate 12 resin as described above." ] },{ "paper_id": "524020333ab93c945ffd02838cb08672703724c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusions/Significance: This antibody display platform will complement existing technologies by virtue of providing properties unique to lentiviruses and antibody expression in human cells, which, in turn, may aid the discovery of novel therapeutic human mAbs.", "Monoclonal antibodies (mAbs) have been used with increasing frequency to treat a wide spectrum of human diseases, including heart disease, infections and immune disorders [1] [2] [3] [4] [5] . The mAb based immunotherapies are now standard of care in an increasing number of human cancers including Erb2+ breast cancer, Non-Hodgkin's Lymphoma, colon cancer and others [1, 6, 7] .", "Since 2001, human mAbs developed through recombinant DNA techniques have constituted the largest number entering clinical study [1] . This shift, toward de novo human mAb isolation and their clinical use, is in part due to new antibody display and other library screening techniques, which are now being exploited to isolate human antibodies with high affinity and specificity. The microbial surface display technologies for screening antibody libraries include phage, yeast and bacteria. Phage-display is widely used due to its simplicity, versatility and ability to be adapted to many specific conditions, including selection on whole cells and tissues [8] . Yeast and bacteria display platforms have several advantages over the phage system including use of flow-cytometry and sorting techniques to enable finer affinity discrimination of selected antibodies [9, 10] . Among the non-microbial systems is ribosomal display that has the capacity to screen libraries of greater size as well as facilitating diversity and efficient antibody maturation in vitro.", "Background: Isolation of human antibodies using current display technologies can be limited by constraints on protein expression, folding and post-translational modifications. Here we describe a discovery platform that utilizes self-inactivating (SIN) lentiviral vectors for the surface display of high-affinity single-chain variable region (scFv) antibody fragments on human cells and lentivirus particles." ] },{ "paper_id": "52431fafe4d5ccd27011d899aa54aa5aa3537e95", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "525511c3e146527c02bc25aed2833f0ef103d62a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Procalcitonin, Copeptin, pro-adrenomedullin (ADM), and atrial natriuretic polypeptide (ANP) were measured as previously described [32] .", "The study was an observational study without specific intervention. The IFNL3 genotypes and serum levels were retrospectively determined and had no impact on the treatment decisions. " ] },{ "paper_id": "525c07cc621b7185fb0d224710d883f523d08ba3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Walter Reed Army Institute of Research (WRAIR) Institutional Review Board (IRB) and the Kenya Medical Research Institute (KEMRI) Scientific and Ethics Review Unit (SERU) reviewed and approved this work under protocol numbers WRAIR# 2075 and KEMRI SSC#2673 respectively.", "Coronaviruses are enveloped viruses with a linear, nonsegmented, positive-sense, single-stranded RNA genome of about 27-32 kb [1] . They are round and sometimes pleiomorphic virions of approximately 80-120 nm in diameter. Their genome is the largest of all RNA viruses [2, 3] . Coronaviruses share features of genome organization and replication strategy, but have different virion morphology and genome lengths. The 20 kb polymerase (pol) gene, which covers the 5\u2032 two-thirds of the coronavirus genome, contains two large open reading frames (ORFs), ORF 1a and ORF 1b [1] . ORF 1b hosts the most highly conserved genomic sequences, encoding conserved functions such as polymerase and helicase activity [4] . These functions combined with similarities in replication and expression strategies, exhibit an evolutionary link among coronaviruses, arteriviruses, and toroviruses, thus forming the rationale for placing these viruses in the order Nidovirales [1] . Therefore, the highly conserved structure and function of viral polymerases make the pol a logical region for making phylogenetic comparisons.", "HCoVs have a global distribution and are endemic to many countries [5, 8, 23] . However, in Africa and especially sub-Saharan Africa, there is a dearth of information about these viruses in regard to their circulation dynamics, diversity, molecular characteristics and epidemiology [24] ." ] },{ "paper_id": "52659b7eb39ce3c761658f1f3e5df475cf495919", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using the GraphPad Prism software version 5.04. The non-parametric Wilcoxon signed-rank test was used to assess longitudinal differences in phenotype frequencies in vaccinated individuals. The non-parametric Mann-Whitney test was used to compare phenotype frequencies and cytokine concentrations between influenza-infected patients and subjects prior vaccination. P-values of ,0.05 were considered significant.", "The study was approved by the Massachusetts General Hospital Institutional Review Board and each subject gave written informed consent for participation in the study.", "Seasonal influenza epidemics result in an estimated 250,000-500,000 deaths per year worldwide [1] and in an average of 200,000 hospitalizations [2] and 36,000 deaths per year in the United States alone [3, 4] . Seasonal epidemics are instigated by the quick spread of influenza virus variants generated by antigenic drift, a process that facilitates the escape of the virus from the host immune system from one outbreak to another. As a result, influenza vaccines need to be reformulated before each annual epidemic, and while yearly immunization has been the most efficient way to prevent influenza so far, vaccines do not provide complete protection [5] ." ] },{ "paper_id": "52662ce54ce7eec49dce4d7c0592075227729f3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MiRNAs (small non-coding RNA molecules) have been documented to be widely expressed in both animal and plant species, and have key regulatory roles in a number of cellular pathways, including early development, cell differentiation and proliferation, apoptosis, signal transduction, and immunity [66] .", "Here we discuss some of the more promising results that include strategies spanning immune system activation, vaccinations, RNAi, and the application of herbal extracts.", "Animals suffering from WSD display various clinical signs including lethargy, reduced food consumption, reduced preening activities, a loosening of the cuticle, and a discoloration of the hepatopancreas [18, 19] . White calcified spots appearing on the exoskeleton are diagnostic of WSD in some [19] but not all host species (e.g., the Indian prawn (Penaeus indicus) [20] ). In farmed shrimp mortality is rapid and 3-10 days after infection cumulative mortality is generally between 90% and 100% [6, 21] .", "WSSV infection occurs in all tissues of mesodermal and ectodermal origin (e.g., gills, lymphoid organ, cuticular epithelium, sub-cuticular connective tissues). Infected nuclei become hypertrophied with marginalized chromatin, and contain inclusion bodies that stain intensely eosinophillic in early-stage infection and basophilic in more advanced infection ( Figure 1 ) [22] . Morphologically, WSSV virions are large and rod-shaped with dimensions in the range of 80-120\u02c6250-380 nm [13, 23, 24] . Structurally, they have a nucleocapsid surrounded by a trilaminar envelope [23] with a tail-like appendage, the function of which is unknown [13, 23] ." ] },{ "paper_id": "526919a3d53c54d8c3d0d6b3ba24c77f3a665e1a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two nearly identical rhabdovirus partial RDRP gene sequences (KY231 and KY330; 219 nucleotides) were identified in bats from two different species (M. africanus and Chaerephon sp.) in different locations. They were divergent from their near neighbors (about 60-65%% nucleotide identity by BLAST), for which relevant genetic information (L gene sequences overlapping our PCR product) is available in GenBank for comparison ( Figure 2) .", "Bats have long been known as natural hosts for lyssaviruses, and more recently, they have been recognized as potential reservoirs for emerging human pathogens, including henipaviruses, filoviruses, and severe acute respiratory syndrome (SARS) related coronaviruses. 3, 4 Novel viruses are documented in bats every year, which has drawn increasing attention to these mammalian reservoirs that are uniquely associated with a variety of known and potential zoonotic pathogens. In this study, we report the detection of nucleic acids of adenoviruses, rhabdoviruses, and paramyxoviruses in bats from Kenya.", "Our findings also show that Kenya bats maintain as much genetic diversity in paramyxoviruses as bats in other geographic locations. The concurrent detection of both RNA and DNA viruses in apparently healthy bats supports evidence that bats may be carriers of more than one virus. Of note, many bats that tested positive for adenovirus, paramyxovirus, and polyomavirus were O. martiensseni from Suswa Cave. Suswa Cave houses one of the largest known colonies of O. martiensseni and has an extensive history of guano mining and tourist visits. 23 Anthropogenic activities, including guano mining, cave tourism, hunting, and consumption of bats, likely increase the chance of zoonotic infection spillovers from these bats. 2 Studying viral diversity in bats and their biology will help understanding and response to novel emerging viruses." ] },{ "paper_id": "5278efe68b31540a1a68ecf36528c7dd4a5fa14d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Stoichiometry and composition of ribosomal stalk complexes.", "Monitoring intact ribosomes and their association with RNA.", "Received: 5 February 2018 Accepted: 28 May 2018" ] },{ "paper_id": "528641560911ad9dcdcd6f443f6d09885017b3f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "52879771bf3fb8b982308b90d70bebd2485ceaf1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "About 200 ng of total RNA extracted from insects was reverse transcribed into cDNA using MMLV reverse transcriptase. cDNA or DNA were subjected to polymerase chain reaction (PCR) reactions using specific primers. Oligonucleotide primers are listed in Supplementary Table S1 and were designed according to contig sequences obtained from our assembly pipeline. PCR products were subjected to direct Sanger sequencing.", "In Aedes mosquitoes we detected contigs that belong to a novel strain of Phasi Charoen Like-virus (PCLV), a bunyavirus previously identified in mosquitoes from Thailand (Supplementary Figure S3A) (42) . In addition, we also identified contigs from a novel virus related to Laem Singh virus (LSV) and two other recently described tick viruses, Ixodes scapularis associated virus 1 and 2 (Supplementary Figure S3B ) (7), all of which are taxonomically unclassified. This new virus was named Humaita-Tubiacanga virus (HTV) to reflect the origin of its host.", "Aedes aegypti mosquitoes used on the experiments were obtained from laboratory colonies established from eggs collected in three neighbourhoods of Rio de Janeiro (Humaita, Tubiacanga and Belford Roxo), in southeastern Brazil. Laboratory colonies of L. longipalpis sandflies were derived from wild-caught animals captured in the city of Teresina, in northeastern Brazil. Drosophila libraries were prepared from wild-type laboratory stocks that were infected with Vesicular stomatitis virus, Drosophila C virus or Sindbis virus as described previously (29) . Individual or pooled insects were anesthetized with carbon monoxide and directly ground in Trizol using glass beads. Ovaries were dissected from female mosquitoes and directly homogenized in Trizol reagent using a pipette. Total RNA or DNA was extracted using Trizol according to the manufacturer's protocol (Invitrogen)." ] },{ "paper_id": "5292c918c5d12afda175d53424b40633166081bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The KSHV transcriptome is extensively m 6 A-methylated in a cell typespecific manner", "Gene-annotation enrichment analysis were performed with The Database for Annotation, Visualisation and Integrated Discovery (DAVID) v6.8.", "All shRNA plasmids were purchased from either Sigma-Aldrich or Dharmacon. Scramble shRNA was a gift from Professor David Sabatini (Addgene plasmid # 1864)." ] },{ "paper_id": "52a61f0348480cb8c5b29d22307b8a1449e64f0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "7.83 \u00b1 6.50 (5/6) (p = 0.37)", "The animal study was reviewed and approved by Institutional Animal Care and Use Committee (IACUC) of S. Dakota State Universities (SDSU) (Protocol number-15-013A).", "GS, PS, and SD-L: data collection, analysis, and manuscript editing. AP, EN, and BW: data collection and manuscript editing. SR: conception, funding, and manuscript preparation and editing." ] },{ "paper_id": "52a8c303b6e299b80b20975105e7c9852beec5c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Synthetic ssRNA, resiquimod recruits macrophages posthatch in respiratory and gastrointestinal tracts when treated in ovo", "The innate immune system, which is known to elicit broader nonspecific protective host responses against invading pathogens, is equipped with a range of immune cells. One of the major immune cells involved in the recognition and the elimination of microbes such as viruses, bacteria, and fungi, are macrophages. Macrophages recognize these pathogens, through pattern recognition receptors (PRRs) including toll-like receptors (TLRs) [1] [2] [3] . These TLRs are able to detect the presence of specific molecular patterns, known as pathogen-associated molecular patterns (PAMPs) [4] [5] [6] [7] that are highly conserved amongst microbes." ] },{ "paper_id": "52babe7e5a33e5c40aab00ea9b3e0ff4a3dfa3ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information ", "The animal experiment, sampling, was approved by the Animal Care and Use Committee of the Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China. The sampling and data publication also were approved by animal's owners. The field study did not involve endangered or protected species. No specific permissions were required for locations of samples because the samples were collected from public areas or non-protection areas.", "After 1 mL of fecal samples was centrifuged at 1,500 \u00d7 g for 10 min at 4\u00b0C, the supernatant of each sample was transferred to a 1.5-ml Eppendorf tube. Viral RNA was extracted from each sample using the TIANamp Virus RNA Kit (Tiangen Biotech Co., Ltd., Beijing, China) according to the manufacturer's instructions. The extracted RNA were stored at -80\u00b0C." ] },{ "paper_id": "52bf83ff771d92f697a4ab0cfe70a99503940050", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lesions during DNA Replication", "In addition to the monoubiquitination of FANCD2, deubiquitination of FANCD2 by deubiquitination enzyme USP1 is known to be required for ICL repair. An USP1 knockout mouse showed an increased chromatin localization of monoubiquitinated FANCD2 without proper assembly of FANCD2 repair foci and subsequent defects in homologous recombination [49] . Deficiency of USP1 or FANCD2 promotes haematopoietic stem cells defects [50] , and siRNA knockdown experiments have shown that USP1 also deubiquitinates FANCI [48] , but whether this step is indispensable for ICL repair needs to be ascertained.", "Interstrand DNA crosslinks (ICLs) are extremely toxic DNA lesions and are particularly deleterious for the cell as they prevent the separation of DNA strands required for both replication and transcription. The repair of ICL is mediated by a group of factors that belong to the FA pathway. During DNA replication, monoubiquitination of two components of the FA pathway, FANCD2 and FANCI, triggers or activates ICL repair." ] },{ "paper_id": "52c813a9ed6582f44ae9b23fbb625e0f5a1b7365", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Except for the coronaviruses, numerous sequences were obtained from isolates that had not been assigned a specific taxonomic placement within their respective families in the NCBI Taxonomy database, but in general, all trees constructed were consistent with previously published reports on viral phylogeny.", "Additional file 1: List of s2m-containing sequences found in Genbank." ] },{ "paper_id": "52d222becd8912fcd1a81cf956a18f88b738c2ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The project leading to this work has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sk\u0142odowska-Curie grant agreement No 690984: DEMOSTAF project.", "The dataset containing ICD-9 codes and GBD cause categories needed to replicate this analysis are available upon request.", "http://orcid.org/0000-0002-9585-891X C. Jessica E. Metcalf http://orcid.org/0000-0003-3166-7521", "where y t are monthly counts of deaths, s\u00f0\u00de is a penalized spline, j \u2208 {Jan., Feb., \u2026, Dec.}, Year i 2 \u00c020; \u00c019; . . . 0; 1; . . . 19; 20 f gwhere 0 represents 1996, the middle of the analysis period and t \u2208 {1, 2, ..., 480} is a continuous variable reflecting the count of month.", "We evaluated goodness-of-fit by visual inspection of the deviance residuals, considering that a good fit was obtained if 95% of the deviance residuals were between \u22122 and 2 standard deviations and no large outliers were present. All analyses were conducted using R statistical software." ] },{ "paper_id": "52dfa9fbd6dcf7c51fac5cb85a88fb154506a722", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No potential conflict of interest was reported by the author(s).", "6th January 2020. Started mNGS sequencing on Miseq platform.", "8th January 2020. Performed genome comparisons and evolutionary analyses." ] },{ "paper_id": "52e083e335c8c29b8867ac67d5090b71348f2eac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Next the libraries were subject to final 20 cycles of PCR amplification.", "All processed array files were inspected for the quality metrics such as average signal present, signal intensity of species-specific housekeeping genes, relative signal intensities of labeling controls, absolute signal intensities of hybridization controls, and across-array signal distribution plots [22] . All hybridizations passed quality control according to indicated labeling and hybridization controls.", "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc= GSE121359", "Smoothelin Like 2" ] },{ "paper_id": "52e898e9b4110cbc6a8beac32cd86672f96489ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviation CRF: Climate Risk Factors", "The current study does not contain any individual persons data, thus ethics approval and consent to participate were not required.", "The datasets analyzed in the current study were publically available." ] },{ "paper_id": "52ee7bd3f076b9f68b8fcea6687db4327d99cf71", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Duodenal, mid-intestinal (jejunum) and aboral colon sections from each kit were fixed with needles on a piece of styrene foam and placed in 10% neutral buffered formalin in a CellStor Pot (CellPath, Newtown, Powys, UK). Two pieces from each of the three gut sections were embedded in paraffin and sections of 4-5 \u00b5m were prepared and stained with hematoxylin and eosin (HE). Selected sections were stained with Periodic acid-Schiff (PAS), Gram, and Warthin-Starry (WS). Each of the three sections was histologically examined and graded blindly according to the following manifestations (Table 1) ." ] },{ "paper_id": "52f1664a1d9fae42e3fbc1f19d936c711826a931", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical calculations were performed using GraphPad Prism v2.01 [40] . p values were determined with paired t test for RT-qPCR data.", "A DI RNA-free stock of the Mebus strain of BCoV [GenBank accession no. U00735] at 3 \u00d7 10 7 PFU/mL was used as a helper virus in the human rectal tumor (HRT)-18 cell line, as described previously [37, 38] ." ] },{ "paper_id": "53003a256222203353a3aec2be3ada210544775f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In situations where biologic samples or tissue specimens are unavailable, serology alone is the gold standard for diagnosis.", "The real potential of proteomic fingerprinting is in its use as a discovery tool for novel biomarkers that can then be incorporated into simple bedside diagnostics based on affordable technologies such as immunologically based antigen-detection tests that could be implemented in dipstick or cassette formats. ", "Most studies published about parasitic diseases have focused on SELDI. The SELDI, a derivation of MALDI, allows sample binding to chemically active ProteinChip surfaces. Several types of ProteinChip arrays are available with differing abilities to bind proteins with different chemical (anionic, cationic, hydrophobic, metallic, and normal phase) or biological (antibody, enzymes, receptors) properties, thereby allowing the direct analysis of proteins from complex biological samples without the need for prior separation by 2D gel electrophoresis. The output of the SELDI is a spectrum of mass-to-charge ratios (m:z values) with their corresponding relative intensities (approximating to relative abundance).", "The development of automated, high-throughput proteomic technologies such as MALDI-TOF and SELDI-TOF MS has enabled large numbers of clinical samples to be analyzed simultaneously in a short time. These platforms have made \"population-based proteomics\" feasible for the first time (reviewed in [184] ). All proteomics-based diagnostic efforts seek to identify biomarkers that, alone or in combination, can distinguish between \"case\" and \"control\" groups." ] },{ "paper_id": "5300635b9c02f28ee26a26ee5547b6bc16cd0139", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quantification " ] },{ "paper_id": "5303b7430b20a5e665f7cadd07ae77baa5687e73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Using Eq. (5) in Eq. (6) and performing the inner product gives", "which is a linear boundary.", "Including the LR interaction term gives" ] },{ "paper_id": "5306d1e54bdb040fea797ee3edbefe867ac400f5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "analyses. These findings indicated that CBJ113 arose from intratypic recombination events that have occurred among HAdV-C strains, including HAdV-1, and HAdV-2.", "The current classification of HAdV is based mainly on the marked nucleotide sequence divergence within the hexon and penton genes, which corresponds to serotype neutralisation 6 . The molecular typing by HAdV hexon sequences have been conducted in many countries to accelerate the discrimination of different types, resulting in timely improved patient care 5 .", "However, novel strains always arise from mutations or intratypic recombination among different types of HAdV 7, 8 . Recently, multiplex novel adenoviruses were detected in wild animals, such as the South Polar Skua (Stercorarius maccormicki) 9 , Chinstrap Penguin (Pygoscelis antarctica) 10 and gull 11 . Recombinant adenoviruses have also been sporadically identified in human, especially for HAdV-D and HAdV-B 8,12,13 species. However, few reports have been examined genetic recombinant of HAdV-C other than HAdV-C57 14 ." ] },{ "paper_id": "530fba50d0d6378e080e760093969b0b3b9c479d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The tests were conducted on a suitably prepared testing stand. The measuring stand was configured in a testing room equipped with air-supply/air-exhaust systems (Fig 1) . Both adjacent rooms, where the tests were conducted, had an area of 6x8 m and were 3 m high. They were connected by a single-wing swing door, 2x0.9 m in size.", "\u2022 a device for adjustment and measurement of supply/exhaust airflow rate, adjustment dampers, measuring area reducers and orifice plate, pressure transducers,", "The following relationship was obtained:" ] },{ "paper_id": "5314aaa04b14fdbb926bc8eeb0826eedee66dadc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although standardization of specialized breeds may be associated with lower pathogen diversity (Guernier et al. 2004 ) and thus reduced risk of new pathogen emergence, it can facilitate disease transmission due to homo geneity in genetic susceptibility. In addition, imported breeds may be more vulnerable to pathogens than indigenous breeds, which have unique adaptive traits selected by farmers in local environ ments over many generations, including resilience to local parasites and diseases (Shand 1997) .", "In this context, current trends in livestock production have received growing attention (Coker et al. 2011) . Although production in Europe and North America has gradually stabilized, in low-and middleincome countries (LIMCs) production is becoming more diverse, with continuing small-scale production-often on farms closely associated with natural habitats and wildlife-as well as highly intensified, industrial-style production units, often in peri-urban settings (Thornton 2010) .", "What are the effects of these economic changes on zoonotic risk? At each transitional stage in the value chain, from farm to final market, attempts to increase or maintain profit margins may create opportunities for risks to develop (Mcleod et al. 2009 ). As new large retail units seek to capture market shares, they must offer competitive prices by cutting costs. Pressure to survive in a highly competitive market with minimal government support and lack of adequate regulatory over sight may encourage retailers and producers to engage in risky practices, including disinvestment in animal health and biosecurity." ] },{ "paper_id": "5315d146c36ec79e45765ebf95759cfcad3a9f84", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Using the Ingenuity Pathway Analysis tool (www.ingenuity. com), inflammatory genes were mapped into multiple networks, each showing over-expressed and under-expressed ones.", "The relationship between cancer and inflammation was observed as early as the 19 th century, when Ronald Virchow described tumor-infiltrating leukocytes. However, it was not until the past two decades that the inflammatory microenvironment has been recognized as a key component in carcinogenesis, being involved in cancer initiation, promotion and metastasis [1] .", "Access to patient samples and anonymous analysis of data was approved by the Institutional Review Board for Human Research at the Medical University of South Carolina.", "Oncomine database (www.oncomine.org) was used to identify the clinical significance of the immune-related genes and their ability to predict patient survival and disease recurrence. X-tile software [21] was used to determine the optimal cut-off points for separating low risk from high risk patients.", "Background: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancerassociated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated." ] },{ "paper_id": "5323d48c2b2aa253087b13694b0e8b0bd0f8ccd7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "During their ICU stays, organ failure newly developed in 33 (64.7%) patients, which included shock requiring vasopressors in 30 patients and acute kidney injury requiring renal replacement therapy in 13 ( Table 3 ). The ICU mortality was 37.3% with a median stay of 15.0 (6.0-29.0) days. Ultimately, 23 (45.1%) patients died while hospitalized. The median hospital stay was 24.0 (15.5-32.5) days." ] },{ "paper_id": "5326626cf66eb61f7f001c6557c23058b57fb2e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Assay. S. pneumoniae adhesion was assayed using fluorescein-isothiocyanate-(FITC-) labeled S. pneumoniae as previously described [26] . Briefly, a bacterial suspension in 0.1 M NaCl-50 mM sodium carbonate buffer (pH9.5) at 1 \u00d7 10 8 CFU/mL was prepared. FITC isomer-I (Dojindo Laboratories, Kumamoto, Japan) was added at a concentration of 1 mg/mL, and the mixture was incubated at 4 \u2022 C for 1 h. The cells were washed three times with PBS (\u2212).", "These lines of evidence confirmed that the expression of the PAF receptor was induced by RSV infection and indicated that this induction, and subsequent RSV-induced S. pneumoniae adhesion, can be suppressed by CAM treatment.", "(RT-PCR). Semiquantitative RT-PCR was carried out as described previously [4, 30] ." ] },{ "paper_id": "532e417a66dbe4822a3f8f9b496c105ccc7dd412", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Highly virulent, mouse-adapted virus A/Fort Monmouth/1/ 47-ma (H1N1) [A/FM] has been previously described [35] and was kindly provided by Earl Brown, University of Ottawa, Canada. It was prepared as a pooled homogenate of lungs from BALB/c mice infected with the virus by the intranasal (i.n.) route 4 days earlier.", "Peptides NP 147-155 (TYQRTRALV) and SARS M 209-221 (HAGSNDNIALLVQ) were synthesized by the CBER core facility. An MHC-I restricted peptide of adenovirus DNA-binding protein (Dbp 419-427 : FALSNAEDL), present in PanAd3 [40] and recombinant M1 (rM1) protein from strain A/PR/8/34 (H1N1) were purchased from Genscript (Piscataway, NJ). Recombinant nucleoprotein (rNP) from strain A/PR/8/34 (H1N1) was purchased from Imgenex (San Diego, CA).", "Viral particle (vp) measurements of adenovirus stocks were made by measurement of absorbance at 260 nm as described [39] ." ] },{ "paper_id": "532f2c636fca1caae1f23885b9dc0e3302a0afd5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Why disorder?", "The authors declare that they have no competing interests.", "Similar to Tat proteins, lentiviral Rev auxiliary protein binds a structured RNA element (the Rev response element, RRE) present in partially-spliced and unspliced viral RNAs to facilitate nuclear export of viral RNA [94, 95] . The HIV Rev ARM was experimentally shown to be intrinsically disordered when unbound in physiological conditions [96] [97] [98] (Table 1, Fig. 1 )." ] },{ "paper_id": "53324ca7df9751947a7c1b54cf18c65af1c14df8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "TNF\u03b1 transcripts. Our results suggest bats may have a unique mechanism to suppress inflammatory pathology.", "To determine if the cells were capable of innate responses to viral ligands we treated the cells with poly(I:C), single-stranded RNA (ssRNA) and CpG ODNs. We used these surrogates instead of viruses capable of infecting both cells to prevent modulation of these pathways by viral proteins.", "Agarose Gel Electrophoresis. One percent agarose (Invitrogen, USA) gels were prepared using 0.5X TBE [Tris -1 M (VWR), Ethylenediaminetetraacetic acid disodium salt (EDTA) solution -0.02 M (Gibco) and Boric acid -1 M; pH 8.4]. One ul SYBR Safe DNA gel stain (Invitrogen) was added for every 1 ml of gel. Ten \u03bcl of PCR or qRTPCR products were run on the gel for 1 h at 105 volts and visualized under an ultraviolet gel imaging system (AlphaImager HP)." ] },{ "paper_id": "533809638564f3d5ce4a13acd1ec0eaadf5bd05d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This research was an experimental study of one group using multiple comparisons.", "All data were analysed with IBM SPSS Statistics 23. Descriptive statistics were used for all independent Tyvek, a brand of flash spun high-density polyethylene fibers, a synthetic material. Apparel with elasticated wrists and ankles.", "Zipper along the center front of the coverall, covered by a plastic apron. (Table 4 )." ] },{ "paper_id": "53408b1daf9132c89bebd23cdd7e417ad668b1ce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ELISA. Poultry sera were assayed for IBV antibodies using a commercially available blocking ELI-SA (Biocheck), and antibody titers obtained from samples were also evaluated. Laboratory results of IBV ELISA were entered and managed using Microsoft Excel (Windows 2010). Descriptive statistics for the ELISA antibody titers were performed using the same program.", "RNA extraction. Viral genomes were extracted from cecal tonsil samples (CinnaPure RNA, Sinaclone, Iran) according to manufacturer's instructions. The extracted viral RNA was contained in a 1.5 mL sterile RNase and DNase-free microtube and stored at -70\u00b0C until further use. cDNA synthesis. Viral RNA was reverse transcribed using Revert Aid First Strand cDNA Synthesis Kit (Thermo Scientific); cDNAs were stored at -20\u00b0C until use.", "Study area and sampling. Mazandaran province is one of the 31 provinces of Iran and is located along the Caspian Sea in Iran's Region 3, just east of Gilan province, west of Golestan province, and north of Tehran and Semnan provinces (36.5656\u00b0N 53.0588\u00b0E). Mazandaran is a major producer of poultry, and poultry farmers in this region provide an important economic addition to the traditional dominance of agriculture. For serology, we collected 460 sera from backyard chickens (9 cities, Table 1 ) during October to December 2014; and for molecular detection and characterization, we collected cecal tonsils from 75 chickens." ] },{ "paper_id": "5341fd2caa821b2616a8bc85763a608b29cb4947", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 41.", "SRW received funding from the National Institute of Allergy and Infectious Disease of the National Institutes of Health under award numbers R21AI114920 and R01AI104887.", "The authors declare that they have no competing interests." ] },{ "paper_id": "5349f364152c9a5e133f282cf5a1bd2449f8930b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The specimen was shaken vigorously for 5 minutes in phosphatebuffered saline solution, centrifuged at 9.6 g for 20 minutes, and the supernatant was aspirated. About 50 \u00b5L of RNA was extracted from 140 \u00b5L supernatant using the QIAamp Viral RNA extraction kit (QIAGEN, Hilden, Germany), according to the manufacture's instruction and was stored at \u221280\u00b0C. ", "The study was supported by the grants from the National Science " ] },{ "paper_id": "534a301ea6a76eb47c8d42e30981088ac5603418", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Polyamines are small, positively-charged molecules that are abundant in eukaryotic cells. Polyamines function in nucleotide metabolism, cell cycling, and cell signaling, among several other functions [16] [17] [18] . Several compounds have been developed that specifically target polyamine metabolism, either by reducing their synthesis or enhancing their breakdown, and these compounds have been tested clinically for the treatment of cancers and parasites [19] [20] [21] . Difluoromethylornithine (DFMO), which inhibits polyamine biosynthesis, has received attention as an anti-trypanosomal molecule and is well-tolerated in patients [22, 23] . Polyamines are also crucial for RNA virus infection, including CVB3 [24]. Polyamine depletion via DFMO restricts CVB3 infection, in vitro and in vivo [25]. We previously described how Chikungunya and Zika viruses rely on polyamines for viral translation and genome replication [26] ; however, whether similar processes are affected for other viruses and precisely how polyamines function during CVB3 replication remain to be completely understood.", "Polyamines play several roles in the eukaryotic cell and likely affect virus replication at several stages. By isolating DFMO escape mutants, we can glean insight into the mechanisms by which " ] },{ "paper_id": "534bc15ce844653ae863844b86d4ace2b98d42a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Distribution of Cryptosporidium spp. related to animal age and breed", "Cryptosporidium was most frequently detected in ALP, ANGL-NUB, and SAAN than in animals of the BARWNA USZL and MK breeds (F = 6.57, P = 0.001 < 0.05).", "Cryptosporidium infections were most frequently observed in WLKP in comparison to KAM and POG (F = 3.23, In the case of goats, more breed-related differences in parasite occurrence were found.", "Parasite genomic DNA was extracted from 0.1 g of feces using a previously described method (Rze\u017cutka and Kaupke 2013) . The correct performance of the method was monitored by a positive extraction control (feces of sheep contaminated with C. parvum oocysts (Iowa strain, Waterborne\u2122, Inc., New Orleans, LA, USA)) and a negative control (water instead of the analyzed template). These controls were included for each set of analyzed samples and simultaneously processed. The nucleic acids were subjected to further purification with the use of a GeneMATRIX PCR/DNA Clean-Up Purification Kit, (EURx, Ltd., Gda\u0144sk, Poland) as recommended by the manufacturer. The extracts containing parasite DNA were stored at \u221220\u00b0C until use." ] },{ "paper_id": "5350a5cc254f384ba7c7c0f36e0d2383c47d6f55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where \u03c8(s i ) represents the coordinate of the point corresponding to the i-th amino acid s i , and \u03c8(s 0 ) is set to be (0, 0)." ] },{ "paper_id": "535c73393b8f68ef2f9081e1e07d0d0aa0d44a8c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Blood samples were collected by using a standard aseptic technique. Native blood was incubated for 60 minutes at room temperature. Serum fractions were separated by centrifugation (1,500 g, 15 min) and kept in a freezer (220uC) until the measurements.", "The reaction buffer contained a protease inhibitor cocktail 10 mM Bestatin-hidrochloride, 10 mM Z-prolyl-prolinal (Enzo Life Science, Exeter, UK), 5 mM Amastatin-hidrochloride, 10 mM Captopril and 5 mM NaCI, 100 mM ZnCI 2 , 75 mM TRIS HCI, pH 6.5. All chemicals were from Sigma (St. Louis, MO, USA) if not stated otherwise." ] },{ "paper_id": "5367c37ddfee14aaa94c806703361f23e09caffd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bats were captured using harp traps and mist nets set up near water bodies or across forest tracks. Captured individuals were placed inside clean calico bags for at least ten minutes to allow time for defecation. Each individual was weighed and identified to species or genus level, using morphological features [33] .", "Reverse transcription PCR amplifications were performed using SuperScript III One-Step with Platinum Taq (Invitrogen, Thermofisher, Carlsbad, CA, USA). Additional PCRs were carried out with MyTaq PCR mix (Bioline, London, UK). Annealing temperatures are reported in Table 1 .", "Betacoronavirus Antigens Overall Summary A. australis" ] },{ "paper_id": "53847cf95615b651c07388b52222211db0b4d303", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bat-borne hantaviruses in China PLOS Pathogens | https://doi.org/10.", "To isolate infectious viruses, homogenized lung tissues of five XSV ARs and three XSV PRs were separately pooled. The two pooled samples, along with one LAIV BT33 positive lung tissue were thoroughly homogenized by grinding and their filtered supernatants were incubated with African green monkey kidney (Vero) and the E6 clone and baby hamster kidney (BHK-21) cell cultures. During five passages, no CPE was observed, and RT-PCR analyses of all passaged cultures were negative, with no HV isolated.", "Introduction Hantaviruses (HVs), members of the genus Orthohantavirus within the family Hantaviridae in the order Bunyavirales, are responsible for two major life-threatening diseases in humans: hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus cardiopulmonary syndrome (HCPS) in the Americas [1] . Every year around 100,000 HFRS cases and 1,000 HCPS cases are reported worldwide [2] . China suffers severely from epidemic HFRS; in 2017 alone, official statistics reported 11,262 cases with 64 deaths [3] ." ] },{ "paper_id": "53889c98bb5e342ae879f4e67c3b4c6368389716", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest." ] },{ "paper_id": "538d34ee99bf5a6c75bc18a2749e0aff5ce72d35", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Veterinarians do typically not plan their visits to farms days ahead, the pattern of their travel will generally be governed by chance and therefore difficult to predict. However, the data collected over time should give a realistic view of their travelling patterns.", "The reasons given for not participating included: timeconsuming (33%, n =4), too many farms visited (8%, n =1) and no longer in the business (8%, n =1). In addition, 50% (n =6) gave no reason for not participating.", "The time periods were chosen to be representative of all seasons and to avoid major holidays, as studies have demonstrated a deviation in e.g. recorded animal movements around major holidays such as Christmas [31, 32] . The geographical areas were chosen to be representative of different livestock densities and animal production types.", "ArcMap (GIS, ArcView, ESRI, Redlands, CA, USA) was used to plot the coordinates on to a map of Sweden. As the individual farm locations were not relevant for the study, polygons were used to illustrate the areas travelled by the visitor categories." ] },{ "paper_id": "5390aefc8bb1a06635a321c0cd82589e2b91c9ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "What is gene editing?", "At least six cellular molecules have been described so far as putative receptors for PRRSV, including CD163, the cysteine-rich scavenger receptor (SRCR; [17] ), sialoadhesin (CD169; siglec-1; [29] ), CD151 [106] , heparin sulfate [50] , vimentin [52] and CD209 [45] , reviewed by Zhang and Yoo [144] .", "Breeding for disease-resistant pigs might be the ultima ratio in combatting infectious diseases. Regardless of whether pigs would be resistant sensu stricto, (i.e., the absolute prevention of an infection, or just tolerating the infection) minimal amplification and shedding of the pathogen and minimal effects on health and performance could be achieved. Thus, the infectious pressure in and between herds could be efficiently reduced, followed by diminished disease incidence, improved performance and", "The facts outlined above for CD163 show that this protein has not evolved solely as a PRRSV receptor, but with a broad spectrum of tasks, including the elimination of pathogens other than PRRSV and the regulation of the immune system. CD163 awaits the discovery and evaluation of further involvements and mechanisms. Any knockout of CD163 as a whole or in part needs meticulous investigation of impacted pigs under field conditions, including the effects of other pathogens and adverse conditions. Work is currently in progress and results are expected in future." ] },{ "paper_id": "539ebc16737a7d43b43c582f3b625050c2bff9a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The mathematical formula of SVM regression model is provided below: a, a \u00c3 are Lagrangian operator. C is the upper bound of all variables, Q is a k by k positive semidefinite matrix, Q ij = y i y j K(x i , x j ), and K(x i , x j ) is the kernel. The expression of radial basis function is provided below:", "The statistical analysis and the construction of SVM regression model were performed using R statistical software version 3.4.2 with package e1071.", "(2)" ] },{ "paper_id": "53a126d28e3dee03d1bcda8154f4070e26212770", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A vaccine is a biological agent that provides active acquired immunity to a particular disease. A successful vaccine is one of the most cost-effective alternatives for controlling the incidence and mortality of diseases such as influenza [1] , cholera [2] , bubonic plague [3] , hepatitis A [4] , yellow fever [5] , measles [6] , mumps [7] , rubella [8] , tetanus [9] , diphtheria [10] , animal disease [11] , etc.", "The peptides have been seen as attractive as specific ligands because they can be easily synthesized by chemical methods on a large scale [50] , and peptide ligands and their cell receptors Figure 10 . Anti-BBD IgA levels in (A) nasal wash; (B) saliva (data are means \u00b1 standard deviations, n = 3). A significant difference between untreated and immunized groups was expressed as * p < 0.001, significant differences between untreated and immunized groups were expressed as * p < 0.001 and ** p < 0.05 and between BBD-CMs and BBD-MCMs groups as ## p < 0.05; (C) anti-BBD IgA levels in serum; (D) anti-BBD IgG levels in serum (data are means \u00b1 standard deviations, n = 3). Significant differences between untreated and immunized groups were expressed as * p < 0.001 and ** p < 0.05 and between BBD-CMs and BBD-MCMs groups as ## p < 0.05 [41] .", "The M cells dispersed among epithelial cells can be found in various mucosa-associated lymphoid tissues (MALT), such as nasal-associated lymphoid tissue (NALT), gut-associated lymphoid tissue (GALT) and bronchus-associated lymphoid tissue (BALT) [44] , although the M cells in the GALT are very important, because they play a key role in regulating gastrointestinal (GI) tract infection and immunity [45] ." ] },{ "paper_id": "53a61d8113ac61c3a987782564a2ee4f61c3e254", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The preferred approach to quantify the full disease burden of influenza in a population is indirect estimation using statistical modeling 5 . In this ecological approach, a time series of hospitalization or mortality rates is regressed against a variable indicating influenza virus activity over time in the same population. This statistical model can then be used to infer the proportion of hospitalizations or deaths associated with influenza 6 . Statistical models can be fitted for time series of hospitalizations or deaths from specific causes, or all causes.", "Published: xx xx xxxx OPEN www.nature.com/scientificreports/" ] },{ "paper_id": "53ac5d89055610d2b199e67d8438eba84dbfcf84", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusions: These data suggest the occurrence of active microevolutionary processes in S. aureus as well as the possibility of environmental propagation during a 14-month time span. Such findings are important to show that multiuser academic dental clinics can retain certain strains that are spreadable to different niches.", "Cluster IV: 3 highly related isolates 6.8% (isolates 5 ET20 -area B , 6 ET20 -area D , and 21 ET19 -area G ), or 2 highly " ] },{ "paper_id": "53c2f84a60048a66e83bd25c1521e7bc87efd5f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The current therapeutic strategy for managing the occurrence of arterial thrombosis generally relies on dual antiplatelet therapy (thienopyridines and aspirin). This approach is cost-effective and reduces thrombotic risk, but comes at a price, with a considerable number of patients experiencing bleeding complications. Genetic polymorphisms can also reduce the effectiveness of both aspirin [37] [38] [39] and the thienopyridines [40] resulting in drug 'resistance' in ,20-30% of patients [41] .", "Platelets (450 ml) were stimulated with agonist in a final volume of 500 ml at 37uC with continuous stirring (1200 rpm) in an optical aggregometer. For drug studies, platelets were incubated with losartan or cinanserin for 60 s after which time, agonist was added and aggregations monitored using AGRO/LINK8 software (Chrono-log Corp., Pennsylvania, U.S.A).", "A sensible place to identify new targets for the development of novel therapies is in the physiological processes that underlie the disease. Our most successful antiplatelet agents to date (aspirin and clopidogrel) work by directly inhibiting enzymes and receptors that mediate the secondary phase of platelet activation. However, as previously mentioned, undesirable side effects (inappropriate bleeding) is a major problem with current antiplatelet agents; new targets could yield better drugs with improved efficacy and reduced side effects." ] },{ "paper_id": "53c533539d95b75bb8f88fe08e4693f299fd116e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "newly formed virus and at MOI of 2 to determine the percentage of cell infection and cytokine release.", "Evidence of viral infection was established by a) assaying viral matrix RNA at 1, 3, 6 and 24 h post infection by quantitative RT-PCR, b) viral antigen expression by immunofluorescence staining with mouse anti-influenza nucleoprotein and matrix antibody conjugated with FITC (DAKO Imagen, Dako Diagnostics Ltd, Ely, UK) and c) assaying infectious virus in cell culture supernatant by TCID 50 assay to demonstrate complete virus replication." ] },{ "paper_id": "53c794c9dd0ae2b845a8be57742e1b74fa0f86d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "53d4dd6acd3501c47b364dbae1ba3dd2083b895a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using SPSS Statistics 19 for Windows (IBM Corp., Armonk, NY, USA). The Kolmogorov-Smirnov test was used to verify whether there were significant deviations from the normality assumption of continuous variables. Nonparametric tests of comparison were used for variables evaluated as not normally distributed. Difference testing between groups was performed using Student's t test, Mann-Whitney test, Chi-square test and Fisher's exact test, as appropriate. Friedman's test was used to assess the time course of organ function.", "Secondary respiratory infections occurred commonly in this cohort, predominantly with Gram-negative bacteria. Although Candida species were frequently isolated, these are probably not relevant as respiratory pathogens and the necessity of antifungal therapy is uncertain. Interestingly, Acinetobacter baumannii, which is an emerging fatal infection in ICU patients worldwide, was isolated from deep tracheal aspirates in one in four patients. This may explain, at least in part, the relatively high mortality rates in this cohort.", "Data are presented as mean \u00b1 standard deviation (SD), median value (25th-75th interquartile range [IQR]) or number (%), as appropriate. All statistics were two-tailed and a P < 0.05 was considered statistically significant." ] },{ "paper_id": "53da3d32d1193129d3366af8aee4bc9a4224aa46", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "3. In lines 189-190, the use of double negative is confusing and difficult to understand.", "We refer the reader to our response to Reviewer 1, Major Comment 1.", "None." ] },{ "paper_id": "53db274f4427f9f421959b5d0e6b5dc47c58612a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Significant differences were assessed via one or two way ANOVA with Sidak correction where appropriate, and results were considered significant if P<0.05 (Prism 7, Graphpad, San Diego, CA).", "All animal experiments were approved by The Scripps Research Institute (TSRI) Institutional Animal Care and Use Committee and were carried out in accordance with the National Institutes of Health's Guide for the Care and Use of Laboratory Animals." ] },{ "paper_id": "53eccda7977a31e3d0f565c884da036b1e85438e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "53ef9e00b8d6b8575d2e7dd68b840f487b24c5a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In 2016, as part of an ongoing IAV surveillance program, 2862 pigs at 102 exhibitions across six states were sampled by nasal swab or nasal wipe [17, 18] . All samples underwent nucleic acid extraction and were tested individually for IAV using real-time reverse transcription polymerase chain reaction (rRT-PCR) as previously described [19] . Five microliters of extracted nucleic acid of no more than seven individual pigs from the same exhibition were pooled and screened for PPIV1, PHEV, and IDV using rRT-PCR as previously described [14, 16, 20] and for PRRSv using the VetMAX PRRSv reagents and manufacturer's protocol (ThermoFisher Scientific, Waltham, MA, USA). Nucleic acid of samples within positive pools was subsequently tested individually using the same methods.", "During field sample collection, exhibitions with \u2265 1 pig showing clinical signs consistent with influenza like illness (ILI) were recorded as having pigs with ILI [1] . Five of the exhibitions were excluded from statistical analysis due to lack of clinical sign data. Logistic regression (Stata special edition 14.2, College Station, TX, USA) was performed to determine any association between ILI noted at the exhibition and the detection of a pathogen in the pigs.", "Focus on animal and public health at swine exhibitions is a priority, but the potential for introduction of infectious pathogens from exhibition swine into commercial swine facilities should also be considered. An estimated 39% of exhibition pigs are raised near commercial swine, with many of those returning home after attending an exhibition [12] . Detection of pathogens such as PHEV and PRRSv in exhibition swine raises concern for commercial swine due to the potential economic implications should they enter the production system. PRRSv alone causes an estimated $600 million in economic loses annually in the United States swine production system [23] . Detection of PPIV1 and IDV also raises concern, though they are more recently described in swine and their overall consequences to swine health are still unknown [15, 16] ." ] },{ "paper_id": "53fa60a93898a5901b87fe8ad651ac5f75611071", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ". Verifica*on of siRNA knockdown experiments using addi*onal siRNAs. (A) Knockdown efficiency of two different ISG15 siRNAs. A549 cells were transfected with 10nM of either control (ctrl) siRNA or the indicated ISG15 siRNA, followed by 24hour treatment with 1000IU/ml human IFN-\u03b2. Cell extracts were analyzed by immunoblots with the indicated Abs. ISG15 #1 siRNA is the siRNA used for the knockdown experiments described in the text. (B) ISG15 knockdown using ISG15 siRNA#2, like ISG15 siRNA#1, rescued the replica*on of 67 mutant virus (C) Knockdown efficiency of two different USP18 siRNAs as assayed by USP18 immunoblots of siRNA-transfected, IFN-treated A549 cells. USP18 siRNA #1 was used.in the experiments described in the text (D) USP18 siRNA #2, like USP18 siRNA#1, enhanced ISGyla*on and inhibited HA and NP protein produc*on in 67 mutant-infected cells. Related to Figures 1 and 4. ", "ISGyla'on occurs only when IFN-\u03b2 treatment precedes influenza B virus infec'on. (A) A549 cells were treated with1000IU/ml of human IFN\u03b2 for 12 hours or were not treated with IFN. Cells were then either mock infected, or infected with 5 pfu/cell of wt virus. Cell extracts isolated at 24 hours aPer infec'on or mock infec'on were analyzed by immunoblots probed with the indicated Abs. (B) Both wt and 67 mutant viruses inhibit IFN-induced synthesis of UbcH8. A549 cells were infected with 5 pfu/cell of wt or 67 mutant virus, or mock infected. At 6 hours aPer infec'on the cultural medium were replaced with fresh medium containing 1000IU/ml of human IFN-\u03b2. Cell extracts isolated at 24 hours aPer infec'on or mock infec'on were analyzed by immunoblots probed with the indicated Abs. Related to Figure 1 . A549 cells were transfected with USP18 siRNA for 24hrs, followed by 16 hours of treatment with 1000IU/ml human IFN-\u03b2 and subsequently infected with 5 pfu/cell of wt or 67 mutant virus. At 24 hours aOer infecPon, cells were collected, and the levels of NP mRNA, NS1B mRNA, NP vRNA, and NS vRNA were determined by RT-PCR, normalized to the level of \u03b2-acPn mRNA. The raPos of the levels of these RNAs in 67-infected cells to the levels in wt-infected cells are shown. Results shown are mean +/-standard deviaPon of three independent experiments, with each measurement performed in triplicate. P values were calculated using 2-way ANOVA test. *** P< 0.001, * P<0.05, ns P>0.05. A likely explanaPon for these results stems from the fact that NS1B mRNA, like the NS1A mRNA of influenza A virus, is synthesized predominantly at early Pmes of infecPon. Experiments with influenza A virus has established that the early synthesis of NS1A mRNA is coupled with the early synthesis of NS vRNA, the template for the transcripPon of NS1A mRNA 1,2 . It is likely that this is also the case for NS1B mRNA and NS vRNA of influenza B virus. Consequently, a substanPal amount of NS vRNA synthesis probably occurs prior to the Pme that ISGylaPon of NP results in the most effecPve inhibiPon of vRNA synthesis, resulPng in lible or no inhibiPon of NS1B mRNA. In human cells infected with wt influenza B virus, the NS1B protein does not block the ISGyla+on process per se. The viral NP protein is thus ISGylated. However, the ISGylated NP proteins are not func+onal as they are bound and sequestered by the NS1B protein in the cytoplasm. When NS1B sequestra+on is eliminated, as demonstrated in the case of the 67 mutant virus, the ISGyla+ed NP proteins are free to enter the nucleus, where they terminate the oligomeriza+on of NP molecules that lack ISG15 modifica+ons, resul+ng in incomplete NP oligomers containing ISGylated NP. As a result, ISGylated NP inhibits the forma+on of viral RNPs that catalyze viral RNA synthesis. " ] },{ "paper_id": "540308d13f057351fc824202d89629e4748e2814", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Despite the rapid growth of air travel, shipping and rail in many parts of the world, roads continue to be the dominant route on which humans move on sub-national, national and regional scales. They form a powerful force in shaping the development of areas, facilitating trade and economic growth, but also bringing with them the exchange of pathogens. Results here show that their connectivity is not equal however, with strong clusters of high connectivity separated by bridge regions of low network density. These structures can have a significant impact on how pathogens spread, and by mapping them, a valuable evidence base to guide disease surveillance as well as control and elimination planning can be built." ] },{ "paper_id": "5408b9cea3b1caf9f6cd026140d5414fab4c6e81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Regular-spreader:", "No ", "Author Contributions: Conceptualization, Y.K. and S.L.; Methodology, Y.K., H.R. and S.L.; Visualization, H.R. and S.L.; Writing-original draft, Y.K., H.R. and S.L.; Writing-review and editing, Y.K. and S.L." ] },{ "paper_id": "540a2a909e0ae17de908c236742379d073ab2d95", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 84 nasopharyngeal swabs (Universal Transport Medium, Copan Diagnostics, Murrieta, CA, USA) were collected from 20 adult and 64 pediatric patients with signs and/or symptoms of the respiratory infection between February and July, 2012. All specimens were stored at 2-8 \u2218 C for up to 72 hours prior to processing. The study was approved by the Institutional Review Boards of Gangnam Severance Hospital.", "Extraction Systems. Basic characteristics of the 3 automated nucleic acid extraction systems are summarized in Table 3 .", "Detection or characterization of the respiratory viruses by conventional diagnostic techniques such as cell culture, direct fluorescent antibody detection (DFA), and serological testing can be difficult and time-consuming [7] [8] [9] . Thus, rapid and highly accurate PCR methods have been numerously evaluated and multiplex real-time (RT)-PCR method is currently considered as the best technique for the detection and typing of comprehensive panel for many common respiratory viruses [7, 10, 11] ." ] },{ "paper_id": "540ccda8bb32d2b9192782b878cc2759da109212", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We purified both C proteins in two steps: Nickel Immobilized Affinity Chromatography (IMAC) followed by size-exclusion chromatography (SEC). Pellets were thawed and homogenized (Constant Systems homogenizer) at 25 kpi at 4uC. The lysate was cleared at 50,000 g for 30 minutes before batch incubation of the supernatant (i.e. the soluble fraction of bacteria) on Ni-NTA sepharose FF resin (Qiagen) for 2 hrs at 4uC. The material was collected in an Econo-Pac column (Biorad) and washed in 100 Column Volumes (CV) of lysis buffer. Elution was done in 0.5 CV fractions with lysis buffer containing 500 mM Imidazole. Fractions containing protein were pooled and loaded onto a preparative Superdex 75 (GE Healthcare Life Sciences) size exclusion column pre-equilibrated in 20 mM Tris 150 mM NaCl, 1 mM EDTA, pH 7.5. Peak fractions were pooled and concentrated using 15 ml spin concentrators (Millipore).", "Analytical size exclusion chromatography (SEC) was performed at a flow-rate of 0.5 ml/min using a Superdex 75 10/300 column (GE Healthcare Life Sciences) pre-equilibrated in 20 mM TrisCl, 150 mM NaCl, 1 mM EDTA pH = 7.9. The column was calibrated with a separate run of appropriate globular marker ", "i)", "Overlapping genes are an evolutionary paradox, because they simultaneously encode two proteins whose freedom to mutate is constrained by each other, which should severely reduce the ability of the virus to adapt [75] [76] [77] [78] [79] [80] [81] ." ] },{ "paper_id": "540f31cf68c580d6d3bf7f4bfd89e10767b89030", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "T20 is the \ue103rst peptidic HIV-1 fusion inhibitor approved for the treatment of HIV-1 infections. Although T20 possesses potent anti-HIV-1 potency, this peptidic drug suffers from short half-life in vivo due to its rapid degradation by proteolytic enzymes in the blood, which renders T20 to be s.c. injected twice daily at high dosage (90 mg), resulting painful injectionsite reactions. 24 Strikingly, (3HRN23) 3 exhibited much more resistant than T20 to proteolytic enzymes (Fig. 4) .", "Cell-cell fusion assays were performed as described previously. 26 HL2/3 cells, which stably express HIV Gag, Env, Tat, Rev, and Nef proteins, as well as TZM-bl cells, which stably express large amounts of CD4 and CCR5, were obtained from the NIH AIDS Reference and Reagent Program (contributed by Drs Barbara Felber and George Pavlakis and Drs John C. Kappes and Xiaoyun Wu, respectively). TZM-bl cells (2.5 \u00c2 10 4 per well) and HL2/3 cells (7.5 \u00c2 10 4 per well) were coincubated in 96-well plates (Corning Costar) at 37 C in 5% CO 2 in the presence of different concentrations of inhibitors. A\ue09der incubation for 6-8 h, the medium was aspirated, the cells were washed and lysed, and luciferase activity was measured using the Luciferase Assay System (Promega, Madison, WI) on a SpectraMax M5 plate reader (Molecular Devices, Sunnyvale, CA).", "To measure the inhibitory activity of the peptides on infection of HIV-1 IIIB and HIV-1 BaL , 1 \u00c2 10 4 MT-2 cells and TZM-b1 cells, respectively, were infected with 100 times the median tissue culture infective dose of a virus in the presence or absence of the peptides at graded concentrations. On the fourth day postinfection, the culture supernatants were collected for detection of p24 antigen using an enzyme-linked immunosorbent assay (ELISA). The percent inhibition by the peptides and EC 50 values was calculated using Calcusyn so\ue09dware. 27 " ] },{ "paper_id": "54125da57282e24d5bcc4c1b60fa54ba1ad784be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "541e4b9cc19cdef991c78ff39e6ad79c1f5ecb09", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human Papillomaviruses (HPVs) are non-enveloped DNA viruses that can infect the skin and mucous membranes. HPVs are known to cause cutaneous, cervical, and respiratory warts and lesions [5] [6] [7] . The capsid of HPVs is made of two virally encoded structural proteins L1 and L2 [8] [9] [10] . The major capsid protein L1 is primarily involved in attachment of the virus to the plasma membrane, while the minor capsid protein L2 functions in viral genome trafficking and encapsidation [11] [12] [13] [14] [15] ." ] },{ "paper_id": "5423004ce74c612a32c8ff24b3f161eb92a62979", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "54283f47537cca8cedd424a4097d258dc66a9e7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The rational and transparent setting of priorities for investment into health research is therefore becoming an essential part of research planning [2] [3] [4] . Usefulness of prioritization, irrespective of its methodology, has been demonstrated by several research groups [5] [6] [7] [8] [9] [10] [11] . Prioritization can provide directions for future resource allocation and strategic planning at different levels (institutional, regional, national or international) and act as a platform for inter-disciplinary debate involving decision-makers, researchers, clinicians and the general public [8, 12] .", "Each score was multiplied by the weight for the respective criterion. The sum of these weighted scores reflects the total weighted score of a pathogen. The total weighted scores were finally re-scaled to a range from 0 to 100 in order to facilitate final interpretation." ] },{ "paper_id": "543819a7a29de2c78dd6e147beed7be72466c610", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Through routine project management rather than at a designated time point, but at least one year after assessments were conducted, the uptake of recommendations by laboratories was assessed. For some laboratories this was accomplished during a repeat, on-site assessment of the laboratory as described above, for other laboratories it was completed through correspondence by telephone and/or email between CDC project officers and laboratory staff.", "This study did not constitute human subjects research; data about a human that cannot be linked back to the human is exempt [9] . Our data sources included 1) information collected during assessments of laboratories which was in a manner that subjects cannot be identified and 2) information from existing, publicly available data sets. Assessments are voluntary and are offered to countries supported by CDC or at the request of WHO. Laboratories are informed that all data collected through assessments is confidential and will only be used in aggregate unless permission is specifically requested to use individual country results.", "Countries participating in assessments included Angola, Argentina, Armenia, Brazil, Cambodia, Congo, C\u00f4te d'Ivoire, the Democratic Republic of Congo, Egypt, Ethiopia, Fiji, Georgia, Indonesia, Kenya, Laos, Mexico, Moldova, Mongolia, Morocco, Nepal, Nicaragua, Nigeria, Panama, Paraguay, Peru, Philippines, Rwanda, Sri Lanka, Tanzania, Thailand, Uganda, Ukraine, Vietnam and Zambia. Vietnam has two national influenza laboratories both of which were assessed and included in this analysis.", "Assessors are laboratory experts from U.S. public health laboratories (including CDC). At the time of the first assessments there was a pool of approximately 15 assessors. Some assessors went to several laboratories while others visited just one or two. All assessors were provided with group training prior to conducting their first assessment to help achieve standardization across the assessments. In addition, each new recruit was accompanied by an experienced assessor during their first on-site laboratory assessment. Lastly, inter-rater reliability exercises have since been added to trainings and a user guide with definitions for each question was developed to enhance standardization across reviews." ] },{ "paper_id": "543bb5a781a4069b7239c71dc88ccdadebd085bf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.ppat.1007296.t001", "https://doi.org/10.1371/journal.ppat.1007296.g002", "Papain-like protease varies among SARS-coronavirus species determined by Western blot using anti-myc antibodies. Each PLP was highly efficient in deconjugating ISG15 from the cellular proteins (Fig 2E) ." ] },{ "paper_id": "543eecd34daf0351160934011c8da277b883b56c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Eukaryotes are constantly exposed to a variety of pathogens, including viruses. As with other environmental signals, viral invasion triggers tightly regulated intracellular signaling cascades to optimally respond to infection. Mammals enact both an innate and an adaptive immune response to identify an infecting pathogen, to clear the foreign agent, and to protect against subsequent invasion. A primary mechanism for fine-tuning molecular pathways is utilization of post-translational modifications. Altering the functional proteome influences protein interactions, transcriptional programs, translation, secretion, and cytoskeletal arrangement. A variety of molecules, including phosphates, sugars, lipids, or proteins, can be attached or removed enzymatically to modulate protein function. Post-translational modifications thus enable rapid and reversible regulation. under positive selection [42] . This species-specific pattern of positive selection of closely related TRIMs suggests that individual TRIMs play specific antiviral roles.", "TRIMs have also been reported to mediate restriction against Flaviviruses ( Figure 5 ). The Flavivirus genus comprises more than 70 viruses including a number of important human pathogens such as Dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV), hepatitis C virus (HCV), and yellow fever virus (YFV) [216] . Flaviviruses are small enveloped viruses hosting a positive-sense single-stranded RNA genome. Several flaviviral proteins are associated with viral persistence, immune system evasion, or viral replication [217] . influenza viruses is currently unknown, although inhibition of translation through direct interaction between TRIM56 and the vRNAs has been proposed [215] .", "Vaccines 2017, 5, 23 2 of 38" ] },{ "paper_id": "54447606d747c1bb9865d1b344bdd8ad0e200bf0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Enhances osteoclast differentiation in murine macrophage osteoclast precursor cell line [41] Induces apoptosis via caspase-8 and -9 dependent pathways [29, [48] [49] [50] ; Bax, p53 and p38", "Induces apoptosis through mitochondria-dependent pathway [119] ORF8b Induces DNA synthesis [120] ORF9b", "Viruses 2012, 4 2903" ] },{ "paper_id": "54458ee775b72a18830ed116a31336638b909fa7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Amongst a multitude of other innate immune factors in this species, such as NACHT domain-LRRs and Scavenger receptors, sea urchin genomes encode for 222 TLRs. Among those, 211 TLRs belong to a greatly expanded set of genes with vertebrate like features, many of which seem to have duplicated recently. The high prevalence of pseudogenes (25% to 30%) among those might reflect a history of strong positive selective pressures.", "As obligate intracellular parasites, viruses have evolved an array of evasion mechanisms to escape their elimination by the host's immune system. Interestingly, viral antagonism is a general strategy and is not a peculiarity of animal viruses. Many bacteriophages, for instance, encode CRISPR-Cas inhibitors, termed anti-CRISPRs, to counter prokaryotic antiviral systems [173] . Plant viruses also encode viral suppressors of RNAi (VSRs) the main antiviral system in plant cells [20] .", "The emergence of somatic DNA recombination in vertebrate animals was considered an \"immunological Big Bang\" [28, 30] . Indeed, somatic DNA recombination in specialized B and T cell lineages provided jawed vertebrates with large repertoires of major histocompatibility complexes (MHC), T-cell receptors (TCRs) and immunoglobulins (Igs). Until relatively recently, adaptive immunity was believed to be exclusive to gnathostomes (jawed vertebrates). We now know that agnathans (jawless vertebrates), including lampreys and hagfish, have also evolved an equivalent adaptive immune system with specialized lymphocytes termed, VLRA, VLRB and VLRC cells, in which specific variable lymphocyte receptors (VLRs) are produced through somatic leucine-rich repeat (LRR) rearrangements [30] . In both gnathostomes and agnathans, somatic recombination events in specialized cells permitted a pathogen-tailored response and endowed vertebrate species with an immune memory.", "TLRs comprise an ancient family of membrane-spanning receptors that recognize ligands through their extracellular domains and initiate an intracellular response upon stimulation (see above). The Toll gene was first identified as a developmentally important gene in Drosophila in 1985 [124] . In the mid-1990s the discovery that this gene also plays an essential role in the ability of Drosophila to resist fungal infections connected for the first time Toll receptors to innate immunity [125, 126] . Although in flies Toll functions as a cytokine receptor, a human Toll receptor (TLR4) was rapidly identified [127, 128] and shown to induce an immune response in mice after induction by LPS [129] . We now know that there are ten TLRs in humans that can respond to many bacterial and viral PAMPs [130] ." ] },{ "paper_id": "544d61a716a23113ecb8bf04f412fbc6ba206942", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nanoparticles were prepared using standard double emulsion solvent evaporation technique [23, 24] . Briefly, 15% of PLGA 50/50 (750 mg) was dissolved in 5 mg of killed VR2332 proteins, homogenized at 6000 rpm for 90 seconds, then added to aqueous solution of 10% polyvinyl alcohol and homogenized. Finally, the preparation was stirred overnight and the washed nanoparticles were freeze-dried and stored at 4uC. The amount of entrapped PRRSV protein in the nanoparticles was determined as described previously [25] . The size and shape of nanoparticles was determined by scanning electron microscopy (Hitachi S-3500N).", "Nanoparticle mediated vaccine delivery has shown a great promise in mouse models against influenza, parainfluenza, hepatitis B, plasmodium, and venezuelan equine encephalitis pathogens [13, 32, 33] . However, the knowledge related to crossprotective efficacy of such vaccines in a suitable large animal model is limited. Our study has revealed the potency of nanoparticle-entrapped PRRSV vaccine in pigs.", "This study was carried out in strict accordance with the recommendations by Public Health Service Policy, United States Department of Agriculture Regulations, the National Research Council's Guide for the Care and Use of Laboratory Animals, and the Federation of Animal Science Societies' Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching, and all relevant institutional, state, and federal regulations and policies regarding animal care and use at The Ohio State University. The protocol was approved by the Committee on the Ethics of Animal Experiments of The Ohio State University (Protocol Number: 08-AG028). All the pigs were maintained, samples collected, and euthanized, and all efforts were made to minimize suffering of animals.", "Morphology of sham and PRRSV Ags entrapped PLGA nanoparticles was determined by scanning electron microscopy which revealed the size of particles as 200-600 nm (Figure 1, A) . The average protein content in nanoparticles or core-loading was 0.50-0.55% (w/w), which represents an encapsulation efficiency of 50-55%. Upon re-dispersion of the Nano-KAg in PBS, PRRSV proteins were released slowly in the first 48 hr, later a gradual release profile was observed over the next 5-weeks (data not shown).", "Among the swine diseases, porcine reproductive and respiratory syndrome (PRRS) is highly devastating, causing an estimated economic loss of $664 million annually in the US [5] . This translates into $1.8 million losses per day annually. PRRSV infects pigs of all ages and is caused by a highly mutating, positive sense, single stranded RNA virus belongs to the family Arteriviridae [6] . PRRS in growing pigs causes anorexia, fever, respiratory distress, and enhanced susceptibility to secondary microbial infections; while in pregnant sows it is characterized by reproductive dysfunction and abortions [7] . Primary PRRSV permissive cells are alveolar macrophages (Mws) [8] . PRRSV rapidly modulates the host innate immune response, such as dampens the NK cell cytotoxicity and reduces the IFN-a production, and upregulates immunosuppressive mediators from as early as two days postinfection [9] ; which lead to poor adaptive immune response and delayed/weak virus neutralizing antibody response, resulting in PRRSV persistence. Nevertheless, due to high degree of constant genetic and antigenic variations, control of PRRS remains a challenge to the swine industry worldwide." ] },{ "paper_id": "545def8771357b4cb2875f5795a0760e97534cc9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The collected data was analyzed by SPSS v.11.5. Frequencies and percentages were computed for descriptive purposes and X 2 test was administered to test significance. Significance was considered when p < 0.05." ] },{ "paper_id": "546de9ee7a4ee26a482af31e1b374ee85242e0c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The antibody-based therapeutic modalities have shown clinical success in the treatment of many diseases [1] [2] [3] [4] . In recent years, tremendous efforts have been made in the engineering of bispecific or multi-specific antibodies by combining two or more functional antigen-recognizing elements into a single construct [5, 6] . Such novel antibodies, or antibody-based fusion proteins, could be particularly beneficial for the treatment of viral infections, which typically require potent and multi-functional therapeutics to prevent the frequent incidence of viral escape mutants [7] . For instance, we previously engineered a bispecific and multivalent anti-HIV-1 fusion protein, by incorporating the HIV-1 neutralizing antibody and the engineered single-domain CD4 into a single antibody-like molecule,", "In conclusion, our study indicated that the bispecific inhibitors have increased the efficacy against MERS-CoV, compared to the neutralizing antibody or polypeptide alone. Such inhibitors with the advantage of multiple biologics have the potential to be further developed as effective prophylactic and therapeutic agents, and may find wide application in treating viral diseases.", "MERS-CoV neutralization assay was performed as previously described [43, 44] . Briefly, 293T cells in 10 cm 2 dishes were transiently co-transfected with a pcDNA3.1-MERS-CoV-S plasmid and a PNL4-3.luc.RE plasmid encoding an Env-defective luciferase-expressing HIV-1genome. After 48 h post-transfection, the produced pseudovirus was harvested from the supernatant, and filtered through 0.45 \u00b5m sterilized membrane. The MERS-CoV pseudovirus was incubated with four inhibitors at 37 \u2022 C for 30 min, and then pseudovirus and inhibitors were added to DPP4-expressing Huh-7 cells (10 4 /well) preplated in 96 well tissue culture plates for 6 h. After 12 h, fresh medium was added to the plates and incubated for another 48 h. Cells were lysed with lysis reagent (Promega, Madison, WI, USA) and lysates were transferred into 96-well Costar flat-bottom luminometer plates (Corning, Corning, NY, USA). Luciferase substrate was added and the readings were recorded with an Ultra 384 Microplate Reader (Tecan, M\u00e4nnedorf, Switzerland)." ] },{ "paper_id": "54774da1d5cb436f9bac63726a08b399b05c6992", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Given the serious nature of FTLS, it was decided to handle all clinical specimens and perform all experiments involving live virus in a biosafety level-3 (BSL-3) facility.", "Cells showing CPE and containing novel bunyavirus RNA were collected for thin-section electron microscopy. After discarding the culture supernatant, virus-infected cells (50 mL) were mixed 1:1 with 4% glutaraldehyde (paraformaldehyde), placed onto Formvar-carbon-coated grids, and stained with 1% methylamine tungstate. Specimens for thin-section electron microscopy were prepared by dehydrating washed cell pellets with serial dilutions of acetone and embedding in epoxy resin. Ultrathin sections were cut on an Ultracut LKBV ultramicrotome, stained with uranyl acetate and lead citrate, and examined under a transmission electron microscope (JEM-1400).", "IgG (Fc) was purchased from Sihuan Sci-Technics Company (Beijing, China)." ] },{ "paper_id": "5479a0b2eb8bb566074e933d9e398fbb7db09ab1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RT and AK conceived and designed the experiments. AR, NC, SP, TM, ST, and BT performed the experiments. CP, KY, and NK were the hospital staff involved in this study. RT, AK, and SD analyzed the data. RT, SD, and AK wrote the manuscript. ALR provided reagents and reviewed the manuscript. ", "Enzyme-linked immunosorbent assay for the detection of IgG class antibody against R. typhi and spotted fever group Rickettsia in human serum was performed using commercial kits (R. typhi EIA IgG Antibody Kit, Spotted Fever Rickettsia IgG EIA Antibody Kit, Fuller). The kits utilized a group-specific lipopolysaccharide (rLPS) antigen extracted from spotted fever group Rickettsia species and a species-specific protein (rOmpB) purified from R. typhi." ] },{ "paper_id": "5483fa35c312dcdefe0216e85fcbdafec45cf84e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The objective is now to synthesize current evidence regarding how space is taken into account in healthrelated accessibility studies.", "Unlike vectorial diseases that are not directly transmitted from human to human, interactions such as more or less close contact between healthy and infectious individuals are determining in infectious and contagious diseases [25] . A detailed follow-up of individual behaviors (their mobility in space-time, their exposure to the resulting risk factor) is made possible thanks to geolocation tools. Then the individuals themselves spread the diseases by means of their interactions in their space of activity, and thus create spaces with a more or less high risk of infection.", "The relation to space by different authors can range from space seen as a mere medium for the variables occurring there, to space acknowledged as a proper actor with specific attributes that will influence the phenomenon or the pathology under study either positively (amplification, facilitation\u2026) or on the contrary, negatively (barrier, constraint, attenuation\u2026).", "We decided to study the way space is considered via two areas which focus the energy of numerous researchers in Health Geographics, namely vectorial diseases and access to healthcare." ] },{ "paper_id": "5484795b90c22596ead5f0b9ccf08d95a3e6f5c2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MTase catalytic residues in SARS-CoV RNA replicon systems [17, 30] .", "The nsp14 D 331 residue is essential for N7-methylation whereas catalytic residues of the N-terminal exonuclease domain are not", "Short capped RNAs ( 7Me GpppAC 5 , GpppAC 5 , were synthesized in vitro using bacteriophage T7 DNA primase and were purified by high-performance liquid chromatography (HPLC) as previously described [69] ." ] },{ "paper_id": "54858134e5322fe2b97e39303e832f4b86d07a58", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The groups defined in this gene were clearly associated by host with lower support in some nodes and less resolution compared with the hexon partial gene analysed (Figure 3 ).", "Adenoviruses (AdVs) are subdivided in five genera, Mastadenovirus (mammals), Aviadenovirus (birds), Atadenovirus (mammals, birds and reptiles), Siadenovirus (birds and amphibians) and Ichtadenovirus (fish) [8] . In 2008, the first AdV from a bat, BtAdV1-FBV1, was isolated during attempts to establish a specific cell line from a Ryukyu flying fox (Pteropus dasymallus yayeyamae), in Japan [9] . Following a screening of 55 German free-ranging bats, family Vespertilionidae, a second, BtAdV-2 strain PPV1, was identified in 3 common pipistrelles (Pipistrellus pipistrellus) [10] , being the first AdV isolated from a microchiropteran bat and the second fully sequenced genome [11] . The first fully sequenced AdV genome from a bat was the BtAdV-3 strain TJM from a Rickett's big-footed bat (Myotis ricketti) [12] . According to ICTV, BtAdV-3 strain TJM and BtAdV-2 strain PPV1 were renamed as Bat mastadenovirus A and B. Several other studies have shown a large genetic viral diversity in bats from Brazil [13] , Japan [9] , Germany [4, 10, 11, 14] , China [12, 15] , Hungary [5, 14] , Ghana [16] , Zambia [17] , Kenya [7] , South Africa [18] and USA [19] .", "Bats are the second largest order of mammals, comprising more than 1200 different species [1] . Their high vagility and the organization typically in social groups predispose them to infection and viral dissemination [2] . Extensive surveys have shown their susceptibility to host a wide range of viruses and the possibility to be a source of emerging infectious in humans [3] . The Order Chiroptera plays a role as a reservoir for many significant virus families such as Rhabdoviridae, Coronaviridae, Herpesviridae, Filoviridae, Reoviridae, Paramyxoviridae and Astroviridae, among others. Several studies have shown bats to be a reservoir of Adenoviruses [4] [5] [6] [7] .", "Bat species studied, year of capture, type of sample and the corresponding GenBank accession numbers for the Iberian bat AdV sequences are listed in Table 1 . (Table 1 ). In 29 bats both partial genes were studied. In 41 bats only the hexon sequence were obtained. Finally, in 6 bats only the DNApol was studied." ] },{ "paper_id": "549ecd5271e2f5d8e14450001ff82f7c6a0f084d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "54a6d0d7afc568a29f625c33187e6800b0f72087", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "developed using an Amersham ECL Plus Western blot developing kit (GE Healthcare), and densitometric analysis was carried out using ImageJ software." ] },{ "paper_id": "54b5dbd04a27590d6b7d0e0e899cbec62c9f91c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Use common language across fields.", "Determine incentive structures that promote horizontal leaderships and shared identity.", "Create career advancement opportunities that recognize interdisciplinary and intersectoral experience." ] },{ "paper_id": "54b6c7145a0f7743409d5590780ef253152873dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To identify potential candidate compounds that can bind to GTases, the crystal structures of various GTases were retrieved from the Protein Data Bank (Chlorella virus: 1CKN and 1CKO; Candida albicans: 1P16; S. cerevisiae: 3KYH). The chemical databases used in our virtual screening included the Sigma-Aldrich, Ambinter, ASINEX, IS Chemical technology, MolPort, and Vitas M Laboratory catalogs. Collectively, these 6 databases offered a collection of 13,800,000 small-molecule compounds.", "The purified 59-triphosphorylated RNA was further processed to obtain a diphosphorylated 59 end using the S. cerevisiae RNA 59triphosphatase (Cet1) which was expressed and purified as described before [33] . The diphosphorylated RNA (ppRNA) was precipitated with ethanol, resuspended, quantitated by spectrophotometry, and stored at 220uC.", "In the current study, we used a combination of virtual database screening, homology modeling, and biochemical assays to search for novel GTase inhibitors. We demonstrate that mycophenolic acid, a compound which is currently used both in cancer and immunosuppressive chemotherapy, is an inhibitor of the GTase reaction. The biological implications of these findings for the MPA-mediated inhibition of RNA capping are discussed." ] },{ "paper_id": "54c8da2f34d0e830818e213cfa74e105e10dac38", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "STATA software version 14.2 (Copyright 1985-2015 StataCorp LLC, http://www.stata.com) was used for statistical analysis.", "Participants and study design ( Figure 1 )", "All participants provided their written informed consent.", "Nasopharyngeal swabs were obtained from each pilgrim, transferred to Sigma-Virocult\u00ae medium and stored at \u221280\u00b0C until processing. The sampling was done by the doctors accompanying the group, in a standardized way (3 cm in the nostril, 5 turns; post wall of the pharynx, 5 streaks)." ] },{ "paper_id": "54ca96205e785170fff9f439860d4f4fa4d95782", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Many pathogenic organisms synthesize proteases that resemble host proteases. Indeed, amino-acid sequences typical of pathogen proteases exist in key molecules involved in host immune response regulation including immunoglobulins (Ig), cytokines and chemokines. Here, I will discuss the functional role of proteinase and inhibitors from metazoan hosts and microbial pathogens, at the cross talk of host pathogen interactions and the contribution of these interactions to host protection and susceptibility to infections.", "Proteases play significant roles in innate as well as adaptive immune response. They are classified by their gene sequence homology and according to their catalytic mechanism as cysteine, serine, threonine, aspartate and metalloproteases, or unknown proteases [21] (http://www.merops. sanger.ac.uk). The activity of different proteases is tightly controlled at the level of expression, zymogene activation, localization in different cellular compartments, or by protease inhibitors.", "The author(s) confirm that this article content has no conflicts of interest." ] },{ "paper_id": "54cbbaf44335fdc1995cb19e5a08779929fd0966", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analyses were performed using Wilcoxon rank-sum test (two-tailed).", "HIV-1 gp120 Binding to CD4, CCR5, and CXCR4", "HIV-1 virions containing the BlaM-Vpr chimera were produced as previously described [33] . Briefly, 293T cells were cotransfected with pNL4-3 proviral DNA, pCMV-BlaM-Vpr, and pAdVAntage vectors. After 2 days of cultivation, the viruscontaining supernatant was centrifuged for 10 min at 3006g to remove cellular debris. The HIV-1 virion-containing supernatant was overlaid onto a 20% sucrose cushion and ultracentrifuged at 350006g at 4uC for 90 min. The resulting pellet was resuspended in medium and aliquots were frozen at 280uC until usage." ] },{ "paper_id": "54e56ec5b95cb23c2b682b181bcc66b7fae8aa07", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The mouse Bril and calmodulin 1 (Calm) coding sequences were cloned in the isopropyl \u03b2-D-1-thiogalactopyranoside (IPTG)-inducible pQE30 bacterial expression plasmid (QIAGEN).", "Data is expressed as mean \u00b1 standard deviation (SD) or SEM, as indicated. Significance was assessed utilizing ANOVA followed by Bonferroni post-hoc test, or a two-tailed unpaired ttest with a p-value 0.05 being considered statistically significant ( \u00c3 <0.05; \u00c3\u00c3 <0.01; \u00c3\u00c3\u00c3 <0.001). Statistical analyses were performed utilizing GraphPad Prism 5 (GraphPad Software).", "Citation: Patoine A, Husseini A, Kasaai B, Gaumond M-H, Moffatt P (2017) The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice. PLoS ONE 12(9): e0184568. https://doi.org/10.", "Two day old pups were processed for the whole skeleton staining with alizarin red (bone) and alcian blue (cartilage) according to standard procedures [24, 25] ." ] },{ "paper_id": "54ebc03fe88092d143f0758472adf54252d6c224", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Microfluorometry assay results, ISRE, ATF6 (activating transcription factor 6), and HCV (pJFH-\u0394V3-Rluc) luciferase activity, real time RT-PCR and FACS analysis were compared for significance using the Student's t test. P values less than 0.05 were considered significant." ] },{ "paper_id": "54fb720924d357327cedcc8da45b5e0ceb5a0006", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A buffer containing 150 mM NaCl, 50 mM Tris-HCl (pH 7.4), and 1% NP-40 was employed to encourage lysis of cells and to solubilize proteins. Protease and phosphatase are also added to prevent the digestion of the sample by its own enzymes. Prior to protein immobilization on a polyvinylidene difluoride membrane (Millipore), sample proteins were separated using SDS polyacrylamide gel electrophoresis (SDS-PAGE). After blocking, the membrane was incubated with a dilute solution of primary antibody and then with a horseradish peroxidase-linked secondary antibody under gentle agitation. Depending on incubation with a substrate, the images were captured using Alpha Innotech FlourChem-FC2 imaging system and developed manually.", "DNA was synthesized using reverse transcriptase MMLV (RNase H \u2212 ) from 500 ng total RNA with oligo-dT primer. cDNA was amplified by using gene-specific primers and Taq DNA Polymerase (TaKaRa, Tokyo, Japan).", "Primer sequences were as follows: IL-6: 5 -AACCTG AACCTTCCAAAGATGG and 5 -TCTGGCTTGTTCCTC ACTACT; GAPDH: 5 -ATGACATCAAGAAGGTGGTG and 5 -CATACCAGGAAATGAGCTTG." ] },{ "paper_id": "5503464f5c8ac4db987ce87b05f224a7aaafc1a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All datasets generated for this study are included in the article/supplementary material.", "All animal experiments were conducted in accordance with approved guidelines. One-month-old Peking ducklings were purchased from a DPV-free farm where vaccination against DPV was not implementation. All the ducks were housed in the animal facility at Sichuan Agricultural University, Chengdu, China. The study was approved by the Committee of Experiment Operational Guidelines and Animal Welfare of Sichuan Agricultural University (approved permit number XF2014-18).", "Data are expressed as the mean and standard error of the mean (SEM), and the significance of differences between groups was evaluated using the Student's t-test or one-way analysis of variance followed by Tukey's post-hoc test. Asterisks indicate the level of statistical significance ( * P < 0.05; * * P < 0.01; * * * P < 0.001; * * * * P < 0.00001). All experiments were repeated at least three times individually. Graphs were plotted and analyzed using GraphPad Prism software, version 6.0 (GraphPad Software, La Jolla, CA, USA)." ] },{ "paper_id": "550494d6d01569a05a8ca2d75f892486b01d1865", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A full necropsy was performed on each bat and all macroscopic findings including ectoparasite infestation were recorded. For histo-pathological examination, small slices of multiple organ tissues (i.e., lung, liver, heart, kidney, adrenal gland, spleen, intestine, pancreas, brain, tongue, larynx, salivary gland and pectoral muscle) and tissues conspicuous for pathological changes were fixed in buffered 4% formalin, processed using standard methods and embedded in liquid paraffin. Sections were cut at 2-5 mm and routinely stained with hematoxylin-eosin (HE). In addition, special histological staining methods were used depending on microscopic findings, i.e. for the detection of bacteria (Gram or Giemsa staining), fungi (periodic acid Schiff or Grocott's Gomori methenamine silver nitrate staining), iron (Prussian blue stain), mineralization (von Kossa staining), connective and collagen tissue (trichrome staining). Details on pathological results are published elsewhere [26] .", "Results of the diagnostic analyses follow the full data splitting into several subsets (see section 'Statistical analysis' in Material and Methods; Table 1 )." ] },{ "paper_id": "550568fe1bf0b6fc5b2fab39e4a3122f4bc5d0ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Major points:" ] },{ "paper_id": "551042ee7c8e1bd9f237a51c666376205c89bb3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This illustrates that sequence diversity in RNA sequences generated by genetic recombination can involve both gross changes and minor mutations. Genetic divergence within the alphacoronavirus is accounted for by linear evolution as well as by sudden dramatic shifts generated by RNA deletions or recombination [74] .", "In 2002, an epizootic outbreak of diarrhea occurred in a Beagle breeding colony in United Kingdom. A new CCoV, strain BGF10, was isolated and characterized. The virus revealed a highly divergent region at the amino-terminal domain of the M protein and a long nonstructural protein 3b of 250 amino acids associated with virulence in other CoVs [46] .", "A similar basic motif is present, approximately in the same position, in all betacoronaviruses and gammacoronaviruses identified and classified to date. Recently, Lorusso et al. [34] also has described an accessory gene, ORF3, 624 nts in length, unique to CCoV type 1 (Figure 1 ). The putative encoded protein, with a predicted molecular weight of about 24 kDaa, is 207 amino acids long, and the observation that no transmembrane region has been detected suggests that the protein is secreted from the infected cells." ] },{ "paper_id": "55123f88b470c8d819d169865c7fada386ee7821", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "551551b6447642735b59a49cbaa78a7b149b54d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "551c5105a50ea1d7d52d13424441d1788f67bc91", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quantitative data was collected using a dichotomous scale, with questionnaire data utilizing a five-level Likert scale [16] to measure each participant's hand hygiene reports and behavior.", "This hospital serves security force personnel and their families. It has 132 beds and some outpatient clinics and other departments created to manage infection and environmental controls.", "This clinic serves people who have insurance or pay for services out-of-pocket. It is a large facility with many outpatient clinics such as internal medicine, maternity, and otorhinolaryngology (ENT), but no hospitalization. Also, at the time of this study, it operated a 24-h emergency room in addition to its treatment room.", "Middle East respiratory syndrome (MERS) is a type of coronavirus first discovered in Saudi Arabia in 2012 [1, 2] . The virus causes a range of respiratory and gastrointestinal symptoms including fever, cough, shortness of breath, and diarrhea. Infections may progress to pneumonia and organ failure leading to approximately 35% reported mortality rate [3] .", "This hospital is one of the main public hospitals in the region, with a capacity of 500 beds. The facility has several other outpatient clinics, such as dermatologic, internal medicine, and orthopedics, and committees established to address infection control and organ transplants." ] },{ "paper_id": "55248fb2e12f9712b35a26e3fdb723baea0ac775", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine epidemic diarrhea virus (PEDV) is a positive-sense RNA virus that causes infectious gastroenteritis in pigs. Following a PED outbreak that occurred in China in", "Porcine epidemic diarrhea virus (PEDV), a member of the Coronaviridae family, and genus Alphacoronavirus, is an enveloped, single-stranded, positive-sense RNA virus, which causes infectious gastroenteritis in pigs [1] . The virus has a~28 kb genome containing a 5 0 untranslated region (UTR), a 3 0 UTR, and at least seven open reading frames (ORFs). The ORFs encode four structural proteins (spike (S), envelope (E), membrane (M), and nucleocapsid (N)), one hypothetical accessary protein (ORF3), and two polyproteins (1a and 1b), in the order of 5 0 UTR-ORF 1a/1b-S-ORF 3-E-M-N-3 0 UTR [2, 3] .", "All fecal samples of Japanese isolates were submitted from Livestock Hygiene Service Centers in each prefecture to National Institute of Animal Health during disease control activities of local official veterinarians during 2013-2014 epidemic [12] . Therefore, all fecal samples had been collected passively from pigs with clinical signs such as diarrhea, and no aggressive operation had been conducted against pigs for sampling purpose. All samples were included in our previous study [12] under sample specific permissions from the local government which provided the relevant sample. Submission of fecal samples was conducted under the supervision of Ministry of Agriculture, Forestry and Fisheries. Sequences of non-Japanese isolates were downloaded from the GenBank database." ] },{ "paper_id": "552ee0cc0a8266b6c22dbc287bd080513a3374fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pntd.0006257.g001" ] },{ "paper_id": "55322bfc591eeae6d68a9826baaebf6ec74234ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The datasets generated for this study are available on request to the corresponding author. ", "Crossbred, PRRSV-seronegative pigs were previously immunized with CSFV-modified live vaccine (MLV) (COGLAPEST R , Ceva Sant\u00e9 Animale, Libourne, France) at 4 and 7 weeks of age. At 16 weeks of age, porcine peripheral blood mononuclear cells (PBMC) were isolated from heparinized whole blood by density gradient centrifugation, using LymphoSep TM (MP Biomedicals, California, USA) according to the manufacturer's procedure. MoDC were generated as previously described (34) ." ] },{ "paper_id": "5534fcf5c7e7df182da3c253d2312cd5662259b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Some samples were treated with proteinase K after the assay. The incubation with proteinase K lasted for 10 min at 37uC using 0.5 ml of proteinase K from stock of 20 mg/ml (dissolved in 50 mM Tris-HCl pH 8.0, supplemented with 1.5 mM CaCl 2 ), followed by loading onto 5% nondenaturing polyacrylamide gel.", "Plant samples from infiltrated leaves were taken 60 hours after infection. RNA was isolated and Northern blot analysis was performed using previously described [14, 95] . For selected samples, proteins were isolated and total proteins level was adjusted based on Coomassie-blue staining. For Western blot analysis, anti-p33 antibody was used (a generous gift of Herman Scholthof, Texas AM University). Pictures of infected plants were taken 7 days after agroinfiltration.", "For in vitro pull-down assay, purified His 6 -tagged helicase proteins (200 mg) were loaded onto MBP columns, containing bound MBP-tagged p33C derivatives and incubated with mixing for 25 min at 4uC [30] . The columns were washed three times with cold column buffer and the bound protein complexes were eluted with MBP-elution buffer. The eluates were analyzed for the presence of His 6 -tagged proteins by SDS-PAGE, followed by Coomassie blue staining or Western blotting with an anti-His antibody.", "The split-ubiquitin assay was based on the Dualmembrane kit3 (Dualsystems). pGAD-BT2-N-His33, expressing the CNV p33 replication protein (bait construct), has been published earlier [26] . Yeast strain NMY51 was co-transformed with pGAD-BT2-N-His33 and one of the prey constructs carrying the cDNA for a given helicase or pPR-N-RE as a negative control or pPR-N-SSA1 as a positive control [26] . Yeasts were plated onto Trp2 2 /Leu2 2 synthetic minimal medium plates. After transformed colonies were picked with a loop and re-suspended in water, we streaked them onto TLH 2 (Trp2 2 /Leu2 2 /His2 2 ) plates to test for helicase protein-p33 interactions as described [26] ." ] },{ "paper_id": "5535ed240ab00c780ce2aa42f1fbe13ef24b9120", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Amongst pathogens, RNA viruses were a major source of emerging diseases during the last 30 years [1] . High mutation rate and in case of segmented genome, reassortment are responsible for genetic adaptability and variability of these viruses.", "Author Contributions: L.M., C.S. and F.D.P. conceived the review. L.M. wrote the review paper. C.S., F.D.P., K.D.C. and E.T. reviewed the article. Graff Sophie and K.D.C. improved the English. All authors read and approved the final manuscript.", "The authors declare that they have no competing interests.", "When it comes to arboviruses the choice of the route of inoculation can be driven by two main considerations:", "Since some data from other authors suggest a better reproduction of the diseases with intradermal inoculation, it could be further investigated, especially if more user-friendly devices would be available." ] },{ "paper_id": "5538bf904bcd32abf4ca1dbe9fc7e6c7514ebeda", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Information sources. H-index searches were undertaken in January 2012 using Web of Science (WoS) [18] . Previous work established that results of H-index searches for pathogens undertaken using different bibliographic sources (e.g. WoS, SCOPUS, Google Scholar) are not identical but are highly correlated [6] .", "Eligibility criteria. Searches were restricted to the years 1900 to 2010, inclusive. English is used in WoS, however searches also include foreign-language publication title translations. All literature in the WoS database has been published.", "Example of a search phrase. (''mycobacterium tuberculosis'' OR ''bacillus tuberculosis'' OR ''bacterium tuberculosis'' OR ''mycobacterium tuberculosis typus humanus'' OR ''mycobacterium tuberculosis var. hominis'')." ] },{ "paper_id": "554d4209692f1b384ec738f3c74b110ccf5e8dbb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mouse experiments. 9 week old C57BL/6J mice (Charles River, France) were injected i.p. with 5 mg/kg paroxetine in 5% DMSO in PBS or 5% DMSO in PBS (solvent) 24 h prior to infection. Mice were infected after ketamine (100 mg/kg)/ xylazine (5 mg/kg) anaesthesia (i.p.) with 10 PFU of A/Netherlands/602/2009 (pdmH1N1) (kindly provided by Dr. F. Krammer, Icahn School of Medicine at Mount Sinai, New York) or inoculated with PBS via the intranasal route. Paroxetine or solvent treatment was repeated on d0, d1 and d2 pi. The first group of mice was sacrificed on d2 and d4 pi by controlled CO 2 exposure and lungs and snout were removed aseptically. Organs were homogenized in 1 ml sterile PBS using sterile 1/4\" steel or ceramic beads in a 2 ml screw cap tube using a BeadBlaster 24 Position Homogenizer (Benchmark Scientific) at 6 m/s for two times 30 s with a 30 s break on ice. Homogenates were precipitated at 10,000 g for 10 min and clear supernatants were analyzed for infectious virus particles using standard plaque assay on MDCK. The second group of mice was monitored daily for weight loss and survival up to d7 when all infected mice reached humane endpoints. All animal procedures were in accordance with federal regulations (Schweizer Bundesamt f\u00fcr Veteren\u00e4rwesen BVET), controlled by institutional (Direction de l'exp\u00e9rimentation animale d'universite de Geneve) and cantonal authorities (Commission cantonale de Geneve pour les exp\u00e9riences sur les animaux) and approved under license no GE/159/17.", "The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium via the PRIDE60 partner repository [http://www.ebi.ac.uk/pride] with the data set identifier PXD009999. The authors declare that all other data supporting the findings of this study are available within the article and its Supplementary Information files, or are available from the authors upon request.", "Received: 30 November 2017 Accepted: 16 August 2018", "Western blot. Cell extracts were prepared using Laemmli buffer (62.5 mM Tris-HCl pH 6.8, 25% glycerol, 2% SDS, 350 mM DTT, 0.01% Bromophenol Blue). Samples were subjected to standard SDS-PAGE and proteins were transferred to nitrocellulose membranes (Hybond ECL, GE Healthcare). Indicated primary antibodies were used with fluorescent secondary antibodies from Li-Cor and images were acquired on a Odissey Fc imaging system. Zn 2+ -Phos-tag SDS PAGE gels. For sample preparation, cells were lysed using a pH neutral buffer (20 mM TrisHCl pH 8.1, 0.5% (v/v) NP-40, 200 mM NaCl, cOmplete EDTA-free protease inhibitor cocktail (Roche) and PhosSTOP (Roche)) before Laemmli buffer was added. Gels were cast according to manufacturer's protocol (wako-chem) using Phos-tag\u2122 AAL-107 (MW: 595, Wako Cat. No. 304-93525). Samples were run on the Zn 2+ -Phos-tag SDS PAGE gels for 4 h at 60 V and were blotted over night at 4\u00b0C onto nitrocellulose membranes (Hybond ECL, GE healthcare). Staining and analysis were done as described for standard SDS-PAGE. For the blots shown in Fig. 3d , e, the uncropped versions of the blots are provided in Supplementary Figure 8 ." ] },{ "paper_id": "554f6f5ca9031e8c6dd85eb32f3ad3e6c222c18f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The paper is organized as follows: in the next section we expose the model presented in its extended form. In Section 3, we present the simulation results and Section 4 is devoted to discussion and conclusions.", "In case that i is already in an extremist state (x i \u00b1 2) it remains extremist.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "555559ac51210f5ee896ad5d45a6790d52a3e4d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study protocol was reviewed and approved by the Research Ethics Committee of Harbin Medical University. All participants indicated their willingness to take part, both verbally and in consent forms signed before the commencement of interviews.", "Subsequently, the researchers visited these 17 agencies to conduct the face-to-face interviews. All the staff at each agency participated in the survey except those on leave. Finally, we obtained 309 completed questionnaires (response rate: 88.8 %) from health inspectors (with inspector licenses granted by China's Ministry of Health); data collection occurred during May to July 2010." ] },{ "paper_id": "555a36d1c3822baa8b6a2612b86ed5df5b1dbf7c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Lung tissue samples from all lobes were resected from formalin-fixed tissue. Tissue was embedded in paraffin, sectioned at 5-\u03bcm, and stained with hematoxylin and eosin (Histoserv, Germantown, Maryland). Sections were examined by light microscopy (LM) or fluorescence microscopy (FM), using an Olympus BX51 microscope, and photomicrographs were taken using an Olympus DP73 (LM) camera or DP80 camera (FM). All histopathology scoring of tissues was blinded.", "Mean viral titers are displayed with the standard error of the mean. Statistical significance was determined using one-way ANOVA with multiple comparisons tests in GraphPad Prism v7. " ] },{ "paper_id": "555bbbbd23da02c97c6a4238937e31b5781438a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author(s) declare that they have no competing interests. ", "At the start of the simulation, one infection is introduced into the fully susceptible population. To avoid bias between simulations, the initial infection is distributed over all age and risk classes." ] },{ "paper_id": "555c6d5dec99b8cf5c8c97415b127dbe30179721", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "B acterial secretion systems transport proteins and nucleic acids across the cell envelope. They serve essential roles in pathogenesis and in enabling communication between cells. Type VI secretion systems (T6SSs) are found in a broad range of Gram-negative bacteria and transport proteins directly into recipient cells 1, 2 . They can target either bacterial cells 3 , to provide a selective advantage enabling colonization of specific niches, or eukaryotic cells 4 , to modulate bacteria/host interactions and pathogenesis. As a result, the presence of one or several functional T6SSs correlates with the ability to induce host diseases or disorders for many pathogens 5 .", "Contraction of the TssB-TssC sheath is believed to propel the inner tube and VgrG-PAAR spike through the membrane complex of the donor cell, to puncture the envelope of a recipient cell and deliver effectors in the periplasm and/or the cytoplasm 9, 10 .", "The T6SS apparatus is assembled from at least 13 distinct types of proteins (Fig. 1a) encoded by a discrete gene cluster, so-called pathogenicity island, which generally also includes a subset of secreted effector and cognate immunity genes [6] [7] [8] . The T6SS needle oligomerizes in the bacterial cytoplasm and comprises an inner tube, made of Hcp hexameric rings arranged with helical symmetry, surrounded by TssB-TssC rings forming the sheath. Localization of the needle within a donor cell is mediated by a pre-assembled cytoplasmic baseplate comprising TssK, TssF, TssG, TssE, VgrG, and a PAAR-repeat protein. The baseplate docks to the bacterial envelope via interactions with a complex assembled from the inner membrane proteins TssL and TssM and the outer membrane lipoprotein TssJ." ] },{ "paper_id": "5566d234b7245b606a50f808fe09b5e3a4f04711", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As in previous studies [16, 28] , titres reported correspond to 100% neutralisation of pseudotype or virus input and are reported as IC 100 endpoint reciprocal dilutions. Mean neutralising titres were considered positive at the next dilution level above that at which there was no neutralisation against rabies (CVS-11) in previous studies: .1:40 for the pseudotype assay and .1:9 for the mFAVN [16, 28] .", "Linear regression models were implemented using the R package [30] to assess the comparative morphology of E. helvum annobonensis with E. helvum from continental populations and other islands (using data collected using the same methods by AJP, DTSH and KSB for other studies).", "Antibodies against LBV (LBV.NIG56-RV1) were detected using a modified Fluorescent Antibody Virus Neutralisation (mFAVN) test, with positive and negative controls, as previously described [16, 27] . Confirmatory testing was undertaken on a subset of 2 positive and 16 negative mFAVN samples using a lentivirus pseudovirus neutralisation assay which had been previously validated against the mFAVN for E. helvum plasma [28] . Details of viruses, pseudotype production methods and assays are described elsewhere [28, 29] . In this study, assays were multiplexed with two viruses per assay LBV (as above) + Mokola virus (MOKV.NIG68-RV4) and Duvenhage virus (DUVV.RV131) + West Caucasian Bat Virus (WCBV) [28] . All samples were analysed in duplicate in both assays." ] },{ "paper_id": "557a14f4857aab6fa0b5d3b980aa241b113977ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As a note of caution it must be mentioned that these calculations should of course not be mistaken as a prediction. It was for example not possible to validate the assumptions about the effectiveness of the interventions using real data.", "We used the following assumptions about the age distribution and size of the population of Germany: 71,000,000 adult population (. = 15 years of age), 11,000,000 children (,15 years of age)." ] },{ "paper_id": "5581ec03ebdca073e13b0df6329779940908f038", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, the presence of protective antibody epitopes in multiple spike domains, suggests that multi-domain approaches of spike-based vaccines may provide a broader repertoire of immune responses compared to RBD-focused vaccine antigen and reduce the risk of antigenic escape. This study also defines different correlates of humoral protection, which may need to be considered in the evaluation of vaccine-induced immune responses.", "This study was financed by a grant from the IMI-ZAPI (Zoonotic Anticipation and Preparedness Initiative (ZAPI) project; Innovative Medicines Initiative (IMI)) [grant agreement no. 115760], with the assistance and financial support of IMI and the European Commission, and in-kind contributions from European Federation of Pharmaceutical Industries and Associations partners. This study was also partially financed by grants from the Ministry of Science and Innovation of Spain (BIO2016-75549-R AEI/FEDER, UE) and NIH (2PO1AIO6O699). This work was supported by Center for Scientific Review, China Scholarship Council. ", "The half maximal inhibitory concentrations (IC 50 ) were determined using 4-parameter logistic regression (GraphPad Prism v7.0)." ] },{ "paper_id": "55844fc8a5cb75ffa1a249436ad30d6d93792df5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These simulations were designed to gauge the level of error associated with neglecting transmission from environmental or animal sources in our main Bayesian estimation approach, and also to assess the sensitivity of R estimates to prior distribution assumptions, under different epidemiological scenarios.", "Where \u03bb + is the dominant eigenvalue derived from linearization of the SEIR model around disease-free equilibrium, following [15] " ] },{ "paper_id": "558eec44990e2c8c43145a48bcae68219ae2ba52", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This analysis was exempt from ethical approval because ADHS' Human Subjects Review Board determined that SARI surveillance was part of public health practice.", "Nineteen percent (47/253) of SARI patients tested positive for influenza viruses in this analysis. We can make some comparisons to other studies with the caveat that varying populations, years studied and enrollment methods may affect the findings. The proportion of influenza-positive SARI cases in our study was higher than reported in Kenya (10%) [26] and China (16%) [21] , within range of eight African countries (5% in Tanzania to 26% in Madagascar) [19] and slightly lower than New Zealand (23%) [27] . In our surveillance system, the percent of SARI cases positive for an influenza virus varied by year from 5.6% to 20% and likely reflects the influenza activity of the dominant virus that year [11] .", "Overall, 207 (80%) patients had one or more underlying medical condition (27% had one, 23% had two, 18% had three and 11% had four or more). The most common underlying medical condition was hypertension (48%, n = 125) followed by chronic lung disease (33%, n = 84) and cardiovascular disease (26%, n = 69)." ] },{ "paper_id": "5599f83a71c2303da5ac9a56d85ed29bab998507", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Optical densities at 600 nm (OD 600 ) of all strains after 6 days fermentation were measured using a Shimadzu UV-2550 spectrophotometer.", "Yeast cells after 6 days fermentation were collected by centrifugation at 10,000g for 5 min and crushed using Bead Beater (BioSpec, USA) after which ultrasonic extraction with 2 mL extraction solutions (acetone:methanol = 1:1) occurred 2 times. The extracts were trimethylsilylated with N-methyl-N-trimethylsilyltrifluoroacetamide (Sigma-Aldrich) at 80 \u00b0C for 30 min.", "The MS transfer line and ion source temperatures were set to 300 \u00b0C and 280 \u00b0C, respectively. The Quadrupole temperature was Q1 = Q2 = 150 \u00b0C and solvent delay was 5 min." ] },{ "paper_id": "55a2b6184753d85b19f0425ac2d68868e73248b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "55b2f19377928da52d9826a5de0714e5c75ebd02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "doi:10.1371/journal.pone.0141423.g002", "Translation to short term epidemics", "Thus, E 0 is locally asymptotically stable if R 0 < 1 and unstable if R 0 > 1." ] },{ "paper_id": "55b3d85d69f463bf877361addcaba605014f2231", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After returning to Korea, he visited Asan Seoul Clinic on May 12, 14, and 15 for fever and coughing that started on May 11. " ] },{ "paper_id": "55b7d9b5320f9763edab4a3d32586bbf5dc2c487", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study describes a method to analyse microbial rRNA from vaginal samples that is applicable to variety of clinical sample types. It demonstrates how the data gained can provide valuable information for larger qPCR based screening studies." ] },{ "paper_id": "55bf861b16d4b28c89750602b96b3827bdaf0055", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 256 clinical samples from patients with febrile respiratory syndrome were collected at the Hunan Provincial Center for Disease Control and Prevention and the Children's Hospital of Hebei Province (China) from 2014 to 2017, including 196 nasopharyngeal aspirates and 60 throat swabs. They were stored at \u2212 80\u00b0C until extraction of nucleic acids. These specimens had previously been tested in a GeXP-based multiplex RT-PCR assay [29] for common respiratory viruses and 152 were found to be positive for HAdV. This study was conducted with the approval of the Institutional Review Boards of the National Institute for Viral Disease Control and Prevention, Center for Disease Control and Prevention of China. Written informed consent was obtained from children's caregivers.", "Total DNA was extracted from 200 \u03bcL of each clinical sample using a Viral RNA/DNA Isolation Kit (Tianlong, Suzhou, China) according to the manufacturer's protocol. The DNA was eluted in 50 \u03bcL of DNase-and RNase-free water and stored at \u2212 80\u00b0C until use. The plasmids were diluted 10-fold from 10 8 to 10 0 copies /\u03bcL, and stored at \u2212 20\u00b0C.", "Isothermal nucleic acid amplification assays including LAMP and RAA are increasingly used in virus detection [17, 19, 21, 27] , but few studies have reported the use of an IC in isothermal assays. ICs are required to distinguish between true negative results and reactions that simply failed. Detection is considered negative when there is amplification of the IC only. If neither the IC nor the sample is amplified, an invalid assay is indicated [22] . As LAMP requires multiple primers, potential interaction between primers may lead to a difficult and complex situation for introducing an IC [28] . The RAA A1 A2" ] },{ "paper_id": "55c55a0a490f47268c4690097420923bbb581956", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The open reading frames, in opposite orientations, are separated by a noncoding intergenic region predicted to fold into strong stem-loop structures [7] .", "GPC is expressed as a single precursor polypeptide that is cleaved twice by cellular proteases to generate a stable signal peptide (SSP), a receptor-binding subunit (GP1), and a trans-membrane fusion subunit (GP2). Both the peripheral GP1 and the SSP remain noncovalently associated with GP2, and assemble into the trimeric glycoprotein (GP) complex that mediates receptor recognition and fusion of the viral and host cell membranes [8] [9] [10] .", "Virus-Host Interactions Involved in LASV Entry" ] },{ "paper_id": "55cc676ae1d05bf9cacceacd765846abfeae92a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Alcohol dependence is defined in the Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) as the pres ence of three of a total of seven possi ble criteria within a 12-month period (figure 1A; American Psychiatric Association 1994). The diagnosis of alcohol abuse with DSM-IV criteria has helped standardize the classification of alcoholics, both across national and international research facilities and time (Harper et al. 2003b) .", "Sagittal human brain with cortical regions delineated.", "Human hypothalamic-pituitary-adrenal brain stress system. B) Human extrahypothalamic cortiocotropin-releasing factor (CRF) brain stress system. C) Rodent extrahypothalamic CRF brain stress system.", "The nonhuman pri mate is an especially appropriate model for studying disinhibition at the behavioral and frontal brain level because the size of the monkey's cere bral cortex is similar to that seen in humans (Grant and Bennett 2003) . Other animal models, however, do not correspond as well." ] },{ "paper_id": "55dc3ccae37d88301441558752efbc4700c116e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The coronavirus nsps have been shown to be involved mainly in viral RNA synthesis (123) (124) (125) (126) (127) . Nevertheless, nsp1, 3, 5, 7, 14, 15, and 16 have been observed to play additional roles in host immune modulatory functions (50, 60, (128) (129) (130) (131) (132) (133) (134) (135) (136) .", "Upon viral infection, infected host cells can sense the presence of both viruses and viral products by three main classes of host PRRs (77) . These are the endosomal toll-like receptors (TLRs), the cytoplasmic retinoic acid-inducible gene I (RIG-I)like receptors (RLRs), and the nucleo-oligomerization domain (NOD)-like receptors (NLRs).", "Both PEDV and PDCoV possess four structural proteins, namely spike (S), envelope (E), membrane (M), and nucleocapsid (N). Each virus has a unique set of accessory proteins, however. PEDV has only one accessory protein, ORF3 (29) , whereas the PDCoV genome encodes non-structural (NS)6, NS7, and NS7a accessory protein (30, 31) . Although distributed widely both within and between structural genes, the location and function of coronavirus accessory protein genes are species-specific (32) . In fact, coronavirus accessory proteins possess diverse functions, including modulating viral pathogenicity (33) , inducing cell death (34) , or antagonizing the IFN system (35) (36) (37) .", "SK, ST, and AJ contributed conception and design of the study. SK wrote the first draft of the manuscript. ST, PF, and TC wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approve the submitted version." ] },{ "paper_id": "55ef87ca0d0cdad3973a94294211e8e9ea8bcc87", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses are classified in four different genera, historically based on serological analysis and now on genetic studies: alpha-, beta-, gamma-, and delta-CoV (Table 1) . Coronaviruses belong to the Coronavirinae subfamily that together with Torovirinae form the Coronaviridae family in the Nidovirales order.", "Among alphacoronaviruses two human viruses (HCoV-229E and HCoV-NL63) can be found along with viruses that infect animals and can be responsible of severe illness: transmissible gastroenteritis CoV (TGEV) and canine CoV (CCoV) cause enteric disease in pigs and dogs respectively while feline coronaviruses cause enteric and systemic disease in cats.", "The difference in tropism mediated by S proteins results from different mechanisms linked to the two main functions of the protein: receptor binding and fusion, which will be further discussed." ] },{ "paper_id": "55f46f193444dd9f891aab9b4320f38d5161f8ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ribozymes and aptamers are RNA molecules identified in the 1980's that were also tested for therapeutic potential. Hammerhead ribozymes, a class of catalytic RNAs (~40 nts), are of particular interest because of their ability to recognize and cleave at specific RNA sequences [3, 4] . Aptamers are highly structured RNAs (25-40 nts) with a high affinity for their protein ligand making them useful as possible drug inhibitors. For example, the transactivation response (TAR) aptamer encoded by HIV-1 binds the viral transactivator of transcription protein (Tat), and when over-expressed in vitro, TAR renders cells resistant to HIV-1 replication [5] .", "earliest therapeutic nucleic acids explored were antisense oligonucleotides, typically short (13-25 nucleotides (nts)) single-stranded DNA or RNA molecules. Hybridization of an antisense molecule with its target RNA results in either degradation by RNase H or steric hindrance of the mRNA splicing or translational machinery [reviewed in 1] . In 1998, the United States Food and Drug Administration approved the first antisense DNA drug, fomivirsen by Isis Pharmaceuticals, to treat cytomegalovirus retinitis in immuno-compromised patients [2] , thus demonstrating that clinical application of therapeutic nucleic acids is an achievable goal.", "Lastly, the safety of a therapeutic for HCV that targets miR-122 is being analyzed in phase I clinical trials. SPC3649 (Santaris Pharma) is a LNA-modified phosphorothioate oligonucleotide that was published to effectively silence miR-122 in African green monkeys [102] and produce prolonged suppression of viremia without HCV resistance in chronically infected chimpanzees [103] with tolerated reduction in cholesterol levels. Phase I clinical trials of SPC3649 began this year, with a competing anti-miR-122 antiviral developed by GlaxoSmithKline and Regulus Therapeutics scheduled for phase I trial in 2011 [104] . These clinical studies pave the way to designing effective RNAi strategies in patients." ] },{ "paper_id": "55f72abf2de5e0b70b27e9ed512b9e456407b680", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material is available online only. SUPPLEMENTAL FILE 1, PDF file, 0.1 MB.", "The 5=-isopropyl ester prodrug of N 4 -hydroxycytidine, designated EIDD-2801 (26) , is currently under development for the treatment of a broad range of RNA virus infections. The initial focus will be on the treatment of encephalitic alphavirus infections and influenza. Although extensive work in animal models of both infections indicate the duration of treatment will be short, most likely between three to 5 days of dosing, every effort is being made to determine whether mitochondrial toxicity could still impact utility. To that end, the studies reported here were extended for up to 14 days using very high concentrations of NHC. The results strongly suggest that mitochondrial toxicity will not be a dose or duration of treatment limiting issue. Chronic-toxicity studies (28 days) are under way in rats and dogs, and every effort will be made to monitor for toxicities arising from mitochondrial dysfunction.", "N 4 -Hydroxycytidine (NHC) is a ribonucleoside analog currently in late-stage preclinical development. NHC has shown broad-spectrum antiviral activity against viruses in the Togaviridae, Flaviviridae, Coronaviridae, Pneumoviridae, and Orthomyxoviridae families (14) (15) (16) (17) (18) . It has been shown that the 5=-triphosphate of NHC can serve as a competitive alternative substrate and be incorporated into viral RNA (14) . Upon incorporation, NHC inhibits viral RNA genome replication, either by disrupting the secondary structure of the genome promoter regions and thus inhibiting replication of the virus (14) or by the introduction of mutations into the viral RNA genome that leads to error catastrophe (15, 19) . Given that this compound is a ribonucleoside analog with the potential for interfering with mitochondrial function, a series of experiments designed to evaluate the effect of prolonged exposure to NHC on mitochondrial death or mitochondrial dysfunction in vitro was conducted.", "polymerase (POLRMT) or by nuclear RNA polymerase (Pol) I, II, or III, resulting in undesired side effects (7, 8) . The development of several ribonucleoside analogs has been stopped as a result of toxicity observed during clinical trials. BMS-986094, a prodrug of 2=-C-methylguanosine being investigated for the treatment of HCV, was halted during phase II clinical trials due to cardiac and kidney toxicity (9) . Balapiravir, a prodrug of 4=-azidocytidine that was investigated for the treatment of HCV, was stopped in phase II clinical trials due to hematologic toxicity (10) . In both cases, later studies suggested the cause of the observed toxicity was mitochondrial dysfunction (8) . Zidovudine, the first approved antiretroviral for HIV treatment, was shown to have dose-limiting toxicity resulting from the depletion of mitochondrial DNA (mtDNA) (2) . To examine early in the drug development process the potential for nucleoside analogs to cause mitochondrial toxicity, a series of in vitro assays have been developed to characterize the effects of a compound on mitochondrial DNA copy number and mitochondrial function. Key among these are the measurement of mtDNA levels, lactate production, and mitochondrial protein expression (7, (11) (12) (13) ." ] },{ "paper_id": "55f79ab7db345d29089af0c330d95292350ba225", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "561bde3336a2cd2006251effb54e5428c4edf3b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data Mining Design Goals. In consultation with NIAID and PRCs within the project's Interoperability Working Group, we developed 3 goals for data mining. 1) All project data and other deliverables should be available via browsing and simple keyword searches.", "To provide a robust text search for the website, we used the PIR text indexing system [20] in which over 100 text fields and unique identifiers from the MPD database are indexed using Callable Personal Librarian (CPL) [21] which supports fast exact text search, substring & wildcard text search, range search and Boolean searches. Entry indexing and retrieval is supported by Oracle.", "II: Structured text search. The MPD database contains over 100 fields derived from iProClass and Proteomics Research Center's data. Currently 75 of these fields are available for individual searches and can be combined with Boolean operators as seen in some of the use case examples in this paper.", "The various Proteomics Research Centers all used different sources and identifiers for the nucleotide and protein sequences in their analysis pipelines and occasionally would change sources depending on the experiment. This is a common problem encountered when attempting to combine data across research laboratories unless identical sequence databases, processes, platforms and organism names are used. Examples of database identifiers used include Genbank/EMBL/DDBJ accessions and locus tags, UniGene accessions, RefSeq accessions, IPI accessions, NCBI gi numbers and IDs unique to a sequencing center or organism-specific database. The first step was to map all experimental results to a common representation of a protein. This was achieved by mapping all protein and gene IDs and names to iProClass proteins. The majority of the mapping using IDs from public resources was done using mapping services and tables provide on the Protein Information Resource (PIR) web site (http:// proteininformationresource.org/pirwww/search/idmapping.shtml) and FTP site (ftp://ftp.pir.georgetown.edu/databases/iproclass/). However, some mapping problems needed to be addressed either by automated rules, direct sequence comparisons or manual analysis and annotation." ] },{ "paper_id": "5620946d8f3bbeeed801a931baa135ee4dd65176", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Severe acute respiratory syndrome (SARS) coronavirus (SCoV) is the causative agent of SARS, which was first recognized in southern China in 2002 and spread to different areas of the world in a 2002-2003 epidemic [1] [2] [3] . It is believed that the bat-derived SCoV-like CoV [4, 5] underwent several mutations enabling the virus to cross the species barrier and replicate efficiently in humans [6] . Although it is uncertain whether SCoV-like CoV will reemerge in the human community and initiate another SARS epidemic, the previous SARS outbreak made it apparent that CoVs, which usually cause only mild or moderate self-limiting symptoms in healthy humans, can cause a severe epidemic disease in our communities.", "Vero E6 cells were infected with the Urbani strain SCoV or SCoV-mt [23] at a multiplicity of infection of 1. At 15 h postinfection, intracellular RNAs were extracted by using TRIzol reagent (Invitrogen). Total RNA was obtained from nucleaseuntreated rabbit reticulocyte lysates (Promega) by proteinase K digestion, phenol/chloroform extraction and ethanol precipitation. In both samples, poly A+ mRNAs were further prepared by using Oligotex poly A + RNA purification Kit (Qiagen).", "suggested. Finally, we discovered that SCoV mRNAs were resistant to the nsp1-induced RNA modification, a finding suggesting that SCoV has developed a strategy to selectively protect its own mRNAs from nsp1-induced RNA modifications to ensure efficient viral gene expression during infection.", "The present study was aimed at identifying the nature of the nsp1-induced host mRNA modification, exploring the basis of the RNA modification site selection, and further understanding template-dependent, nsp1-induced RNA modification by examining several different RNA templates, including SCoV mRNAs and their derivatives." ] },{ "paper_id": "562b04e742412e61bd4087a2a13734391a988a8f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One of the reasons why formoterol exhibits a rapid onset is because formoterol acts as a full agonist to beta-2 receptors compared to salbutamol that acts as a partial beta-2 agonist [6] . Furthermore, there are additional non-bronchodilatory beneficial effects of formoterol including the effect of reducing plasma exudation by closing the gaps between endothelial cells, stabilizing the mast cells and reducing neutrophilic recruitment, and thus reducing the release of reactive oxygen species through the activated neutrophils [9] .", "Formoterol is a long-acting \u03b2 2 -agonist (LABA) that has a rapid onset bronchodilatory effect within 1-3 min of inhalation [6] . Its rapid bronchodilatory effect is comparable with that of salbutamol, thus making it a suitable alternative for the treatment of acute asthma and to prevent exercise-induced bronchospasm [7] . In fact, formoterol has been shown to produce greater lung improvements than salbutamol up to 4 h after administration [8] .", "Defined as a chronic inflammatory airway disorder with bronchial hyper-responsiveness to a variety of stimuli, bronchial asthma is often punctuated with recurrent episodes of exacerbations with classical manifestations such as wheezing, breathlessness, chest tightness, and nocturnal or early morning cough. These episodes are usually associated with widespread but variable airflow obstruction within the lung that is often reversible either spontaneously or with treatment [1] ." ] },{ "paper_id": "5645bc52d703b021b132a5bb5ca1702809db4cb5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Internal controls for extraction, bead delivery, and movement within the cartridge are present, as well as those for amplification, digestion, and hybridization of DNA and RNA targets. For every specimen tested, a sample detection report was created, comprising the results for all targets and internal controls. Results of the targets are reported as positive or not detected. If an internal control fails, this will be noted on the detection report and samples should be retested with a new cartridge.", "The RP panel yielded a positive result in 17 specimens, where the laboratorydeveloped test (LDT) remained negative (PCR \u03ea /RP \u03e9 ), including 15 additional pathogens previously undetected by LDT in the 323 positive specimens and one influenza A H1N1 2009 virus that was detected as influenza A virus by LDT ( Table 1) . Seven of these 15 additional targets could be confirmed, including three of RV/enterovirus (EV) (all confirmed as RV), two of PIV4, and one each of hBoV and hCoV NL63.", "A single cartridge of the RP panel is able to detect 25 respiratory pathogens, including differentiation of subtypes of influenza A virus, parainfluenza virus, and respiratory syncytial virus (RSV) ( Table 1) ." ] },{ "paper_id": "5646a0eb649cd7e862225225aae1382f8de86f7d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Weibull prediction values showed much faster inactivation kinetics and thus characterized better the virus survival curves.", "The Weibull distribution function has been used to describe non-linear inactivation patterns of different microorganisms after thermal and non-thermal processing. Assuming that the temperature resistance of the virus is governed by a Weibull distribution, Mafart et al. [11] developed the following equation [12] :", "Serial 10-fold dilutions of all samples were prepared in maintenance medium followed by inoculation in monolayers of swine testicular cells contained in 96-well microtiter plates (Nunc, NY, USA) using 100 \u03bcL/well and 3 wells per dilution. Inoculated cells were incubated at 37\u00b0C under 5% CO 2 for up to 6 days and examined daily under an inverted microscope for the appearance of CPE. The highest dilution showing CPE was considered the end point. Virus titers were calculated as Tissue Culture Infectious Dose TCID 50 /mL by the Karber method [7] .", "There are three enteric coronaviruses that can cause gastrointestinal illness in young pigs e.g., transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine delta coronavirus (PDCoV) [1] . Transmissible gastroenteritis virus has been present in the United States since 1946, but PEDV and PDCoV were introduced more recently in 2013 and 2014, respectively. The spread of PEDV among swine herds was rapid; and strict biosecurity measures known to prevent transmission of other viruses such as porcine respiratory and reproductive syndrome virus were ineffective; later contaminated complete feed was demonstrated to be a route for PEDV transmission that has been overlooked in previous biosecurity protocols [2] . Therefore, for disease prevention purposes, it is essential to understand proper feed handling procedures that minimize risk of transmission, and to identify methods that can rapidly inactivate these viruses if present in feed." ] },{ "paper_id": "5669349639eae4f58b4fecca26fcc271094c70ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA was manually extracted from 638 rodent serum samples using QIAamp Viral RNA Mini Kit (Qiagen, Manchester, UK) and following instructions from the manufacturer.", "Viruses 2018, 10, x 5 of 12 ( Figure 1 ) was high in both liver tissue (median, 3.35 \u00d7 10 7 copies/gram; range, 0.9 \u00d7 10 5 -1.16 \u00d7 10 9 ) and sera (median, 5.7 \u00d7 10 6 copies/mL; range, 2.3 \u00d7 10 6 -2 \u00d7 10 7 ). ", "The following are available online at http://www.mdpi.com/1999-4915/10/3/102/ s1.", "Rodent and bat samples were collected within the VIZIONS (Vietnam Initiative on Zoonotic Infections) framework [25] for the screening of zoonotic microorganisms [21, [26] [27] [28] .", "The length of the sequenced screening fragments (excluding primer sequences) of homologues of HBV, HEV, HCV, and pegivirus was 257, 284 and 360 nucleotides, respectively." ] },{ "paper_id": "566bdd537595b38dc6ab764b13d6d9ae33f9c9af", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "San Jose, USA) were used. The conjugated secondary antibodies were purchased from Jackson Immunoresearch Laboratories.", "BFA is known to disturb membrane traffic in most cell types, resulting in a redistribution of Golgi proteins into the ER [17, 18] .", "Virus replication was quantified by determining either the virusdriven luciferase expression levels or the amount of genomic RNA.", "To validate the functional knockdown of the targeted genes, mRNA levels of each gene were determined after siRNA transfection using Taqman Gene Expression Assays (Applied Biosystems, CA, USA), according to the manufacturer's protocol." ] },{ "paper_id": "5676dd53889b4c43a772e163763ee7f1525f98da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In order to obtain the best chemical information and separation mechanism in chromatograms, different HPLC parameters including various mobile gases, detection wavelengths, and gradient Sample Availability: Not Available.", "Molecules 2018, 23, 1305 2 of 9 natural products of TCMs are chiral. Here, one isomer possesses a desired therapeutic effect, whereas its paired enantiomer could be inactive or even have undesirable effects [2] . For example, S-ibuprofen, the first chiral drugs of the non-steroidal anti-inflammatory drug approved in 1994, was over a 100-fold more potent as an inhibitor of cyclooxygenase 1 enzyme than R-ibuprofen [3] . Notably, 45 new drugs approved by the US food and Drug Administration in 2015 were single enantiomers, except for lesinurad [4] . For this reason, investigating the biological activities of specific enantiomers of chiral compounds in TCMs is becoming more important. Chiral analysis of the chemical constituents in TCMs is therefore urgent and desired.", "Results and Discussion" ] },{ "paper_id": "5678f2e8dc1710c96b5f4e5ae8d6ddae9c5e6580", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the ethics committee of All India Institute of Medical Sciences (AIIMS) New Delhi, and the written informed consent for research and publication of the data was obtained from all the participants." ] },{ "paper_id": "567be8096ec201b856ef35be5cc2c096f64e5fda", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MASP-1, MASP-3 and MAP-1 are alternative splice products of the MASP1 gene [8, 9] , while MASP-2 and sMAP are encoded by the MASP2 gene [10] . MASP-1 and MASP-2 cleave C3 and C4, respectively, while C2 is cleaved by both [11] . MASP-2 can produce the C3 convertase C4bC2a and thus activate complement [6] (Figure 1 ).", "MBL monomers are 32 kDa in molecular weight and possess a typical collectin structure: an N-terminal cysteine-rich domain, a collagen-like domain (CLD) of approximately 20 Gly-Xaa-Yaa tandem repeats, a neck region and a CRD responsible for ligand binding (Figure 2a ) [28] . These monomers form homotrimeric subunits that further oligomerise into trimeric to hexameric structures that can activate the complement cascade [29] . Trimeric and tetrameric MBL are the most common physiological configurations (Figure 3a ) [30] .", "When studying the association of polymorphisms with disease severity, the geographical population, ethnicity, disease severity, asymptomatic patients, age, route of transmission, study techniques and sample size must be taken into account. These confounding factors can, in part, explain discrepancies between studies.", "The FCN2 and FCN3 genes have three and two as yet undetected splicing variants, respectively [115, 151] . The FCN1 gene contains 45 SNPs, nine of which are exclusive to African populations and eight of which are non-synonymous. Gly43Asp, Arg93Gln and Trp279STOP likely affect M-ficolin structure and oligomerisation, whereas Gly303Ser may affect M-ficolin function. The FCN3 gene showed 15 low frequency SNPs, none of which were found globally. Only Leu117fs, Thr125Ala-corresponding to FCN2 Thr137Met-and Val287Ala are predicted to affect H-ficolin function." ] },{ "paper_id": "567cbbb719b238bcd46a7c4de309537911ea42a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All graphs presented in this work were created using GraphPad Prism 6 software. Significance was estimated using one-way ANOVA with multiple comparisons to virus control. Images obtained from the confocal microscope were deconvolved using AutoQuant X3 and processed in ImageJ Fiji [23] . Co-localization analyses were performed in ImageJ using JACoP plugin [24] where Pearson's and Manders' coefficient were calculated for 3D cell reconstructions. The bioinformatics analysis was conducted using arginine and lysine propeptide cleavage sites prediction algorithms ProP 1.0 server [25] using the following sequence data: AAO06124.1 (isolate 4182), ABG78748.1 (isolate 4182), ACX46840.1 (strain K9), AFW97360.1 (strain K37), ACX46860.1 (strain K39) and AQT26498.1 (strain BJ232).", "Coronaviruses are enveloped, single-stranded, positivesense RNA viruses belonging to the family Coronaviridae within the order Nidovirales [1] . Based on its properties, this family can be divided into four distinct genus: alpha, beta, delta, and gamma. Coronaviruses infect a wide variety of birds and mammals, including humans, livestock, and companion animals [1] [2] [3] . Human coronaviruses (HCoVs) are associated mainly with relatively mild upper and lower respiratory tract disease; however, emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in the winter of 2002-2003 in China, and more recently Middle East respiratory syndrome coronavirus (MERS-CoV) in the Middle East, demonstrates the potential threat posed by zoonotic coronaviruses [2] [3] [4] .", "Next, we used inhibitors of endocytosis to examine the endocytic pathway utilized by CRCoV to enter HRT-18G cell. All inhibitors were used at the highest non-toxic concentration (determined in an XTT assay; data not shown). The validity of the obtained data was verified using positive controls (transferrin, cholera toxin subunit B (CHT x B), and dextran), which enter the cell via clathrin-dependent pathway, caveolin-dependent pathway, and macropinocytosis, respectively [9, 32] .", "To determine whether CRCoV enters HRT-18G cells by clathrin-mediated endocytosis (CME), we treated cells with chlorpromazine, amantadine, or PitStop-2 [33, 34] . None of the compounds affected the virus entry to the cells (Figures 4A and B) ." ] },{ "paper_id": "5688011525aeb581afabe204b64d4da24257aff1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In conclusion, the present case report reveals that PEDV strains similar to S INDEL PEDV are currently circulating in different farm types in Southern Germany. Severe clinical signs and high mortality rates in suckling piglets observed in one farm might indicate that the potential of virulence can vary between S INDEL PEDV strains. However, experimental studies to confirm the potential of high virulence of S INDEL PEDV are lacking to date.", "Fairly little information on the current situation on PED is available from European countries. Recently, several outbreaks of acute PED occurred in Germany. In this case report we describe acute outbreaks of PED in one fattening farm and two sow farms in South-Western Germany between May and November 2014.", "In January 2014, a new variant strain of PEDV (OH 851), containing insertions and deletions in the S gene (S INDEL), was identified in Ohio causing mild clinical signs and lower mortality rates in suckling piglets compared to other currently circulating PEDV strains in the US [10] . At present, both S INDEL and highly virulent non S INDEL strains are co-circulating in the US, though S INDEL strains are less frequently diagnosed [11] ." ] },{ "paper_id": "5688f38645b50f19f5b36727b64e89bf73ad453c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ten patients developed IMI while receiving chemotherapy and 3 following hematopoietic stem cell transplantation (HSCT)." ] },{ "paper_id": "568917a765516d1397d8cb461644e755cd703c90", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Because of its role in proteolysis of extracellular matrix, targeting TMPRSS11D may prevent the development of metastasis in NSCLC.", "TMPRSS11D was originally purified and cloned from the sputum of patients with chronic airway disease [13, 14] . It is highly expressed in respiratory epithelium," ] },{ "paper_id": "568cf52b425ceaf8d1e9a14bbd088c493e8fd4fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analyses were carried out using the statistical analysis software SPSS Version 17.0.", "where s represents the given (G+C) 3 % value [21] ." ] },{ "paper_id": "568dd96f69f07844df6ac84d80188eaa94c7b4c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "-Doha Port (Mwani Ports), used by general cargo ships and container vessels;", "Qatar has six recognized points of entry that support international traffic and four seaports which are the followings:", "As comes to national field epidemiology and the workforce strategy, the Arab Board Community Medicine Residency Program (4 years) is the only locally available program to provide some field training in Qatar. Thus, establishing a dedicated surveillance and outbreak response training program is recommended; along with a human resource strategy to formulate a clear career pathway and in return allow for the engagement and retaining of homegrown as well as international experts." ] },{ "paper_id": "56948f3e281e7271f952181ed0c3bd83d1d70f8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "56964b8cbc98f8dd9a1a45190f0daceb59c62df9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was carried out in accordance with the recommenda- ", "inTrODUcTiOn Various types of viral vaccines have been developed over the last century with a wide spectrum of efficacy and safety (1, 2) . The manufacturing of most conventional vaccines-live attenuated, inactivated, or subunit vaccines-invariably require the culturing of infectious viruses in cell substrates (3) . Despite dedicated efforts, conventional cell culture often fails to produce sufficient amounts of virus for evaluating the immunogenicity, protective efficacy, and safety of viral vaccines. Moreover, some emerging viruses cause high-mortality rates, without options for treatment or prophylaxis, necessitating their manipulation, and manufacture under stringent bio-safety environment (4) . Not surprisingly, alternative technologies that circumvent these limitations are a high priority in the areas of vaccine development and production. Nanoparticles (NPs), virus-like particles (VLPs), and assembly of multimeric peptides each provide attractive platforms for vaccine design (5) .", "The hriD Facilitated the solubility of Mers-coV rBD-Fr", "In contrast to non-enveloped viruses, where virion assembly is exclusive to capsid proteins, enveloped viruses (e.g., coronavirus or flavivirus), require an additional membrane component for assembly into mature virions. Consequently, in enveloped VLPs, the assembly of matrix proteins provides a molecular scaffold, and viral antigens are embedded into lipid membranes. Different types of glycoproteins may be embedded in the lipid membrane as target antigens for generating immunological responses (12) . However, this process requires multiple proteins (surface antigens and matrix proteins), and the enveloped VLPs are not structurally uniform and are difficult to characterize. A promising alternative is to present the target antigens on the surfaces of self-assembled NPs, which, in lieu of lipid membranes, serve as the macromolecular scaffold for the presentation of the antigens of interest." ] },{ "paper_id": "569f5c13c3109817f6ce0882e4129f31e83cfd29", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide Change Amino Acid Substitution ", "-: silent mutation.", "Supplementary Materials: The following are available online at www.mdpi.com/1999-4915/9/5/121/s1, Table S1 : List of sequencing primers." ] },{ "paper_id": "56ac442721c9e0f335024cb4e414c9f00bc53aea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recent studies have Citation: Bailey-Elkin BA, van Kasteren PB, Snijder EJ, Kikkert M, Mark BL (2014) Viral OTU Deubiquitinases: A Structural and Functional Comparison. PLoS Pathog 10(3): e1003894.", "The proteasomal degradation pathway is an important cellular route to dispose of viral proteins, as exemplified by the turnover of the TYMV polymerase [45] . Moreover, the degradation of this protein is specifically counteracted by the deubiquitinase activity of TYMV PRO, which thus promotes virus replication [10] . The functional characterization of viral OTU DUBs remains incomplete and future studies will likely reveal additional roles in replication and virus-host interplay.", "A remarkable feature of EAV PLP2 is the incorporation within the OTU-fold of a zinc finger that is involved in the interaction with Ub ( Figures 1C, 2E) . The absence of similar internal zinc-finger motifs in other OTU superfamily members prompted us to propose that PLP2 prototypes a novel subclass of zinc-dependent OTU DUBs [26] ." ] },{ "paper_id": "56b2d409fd554bd2694eb7d938fd44fc282fd484", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HSV-1), pyridostatin (EBV) and Core-Extended Naphtalen Diimide compounds (c-exNDIs) (HIV-1) 5, 18, 19, 25, 26 . Since no definitive drugs have been found against most viral infections, there is an obvious need for new more active compounds." ] },{ "paper_id": "56bea8bc53d2703d7d33244508932aa26d1ad442", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The GenBank (http://www.ncbi.nlm.nih.gov/) accession numbers of organisms discussed in this paper are PMMV genome (NC_003630) and PBV prototype strains 4-GA-91 (AF246948) and 1-CHN-97 (AF246939). TaqI adaptor TaqI-F 59-AGG CAA CTG TGC TAT CCG AGG GAT-39 TaqI-R 59-CGA TCC CTC GG-39 Csp6I adaptor Csp6I-F 59-AGG CAA CTG TGC TAT CCG AGG GAG-39 Csp6I-R 59-TAC TCC CTC GG-39 TaqI amplification primer TaqI-F 59-AGG CAA CTG TGC TAT CCG AGG GAT-39 Csp6I amplification ", "Viral RNA shotgun library construction. Approximately 140-200 ng of purified viral RNA of each sample was utilized for cDNA synthesis using a random priming approach following the protocol from SuperScript Choice System (Invitrogen). Double-stranded cDNA was divided into two aliquots, which were digested separately with either TaqI (New England Biolabs, Beverly, Massachusetts, United States) or Csp6I (Fermentas, Burlington, Ontario, Canada) to generate short overlapping DNA fragments. TaqI-and Csp6Idigested cDNA fragments were ligated with TaqI and Csp6I adaptors (oligo sequences in Table 5 ) at 16 8C overnight, respectively. The TaqI and Csp6I adaptor-ligated DNA fragments were amplified by PCR using forward primers TaqI-F and Csp6I-F for 40 cycles, respectively. DNA fragments between 500 and 1,000 bp were fractionated and cloned into Zero Blunt TOPO PCR cloning vectors (Invitrogen) for sequencing.", "We further provide evidence that the fecal PMMV was viable and could cause infection to a host plant. PMMV viruses appeared to be stable through the human digestive system. This is consistent with the observation that members of Tobamovirus, including PMMV, are extremely robust viruses and can survive in challenging environments [29, 30] . The data presented here suggest that humans (and likely other animals) may play a significant role as transmission vectors for certain plant viruses through their digestive tracts. The discovery of this previously unknown transmission route for plant viruses is potentially important for a better understanding of certain agricultural practices, because in traditional agriculture and in developing countries, human and animal refuse are often used as fertilizers for crops.", "Infection of plants with fecally borne viruses. Two PMMV-positive fecal samples (10 g) were resuspended in 10 ml of SM buffer, centrifuged at 12,000 g for 15 min to pellet the bacteria and large debris, and the supernatants were mixed with ground glass. Two healthy Hungarian wax pepper (Capsicum annuum) plants were used for the test, and two leaves per plant were inoculated with 2 ll of the sample supernatant/ground glass mixture with gentle grinding followed by rinsing with sterile water. The inoculated leaves were then monitored visually over a period of 2 wk, and photos were taken with a digital camera to document viral infection symptoms. The leaves that developed viral symptoms were collected for RNA extraction and viral detection by RT-PCR and subsequent sequencing analysis. Negative controls of five plants were subjected to the same inoculation procedure, with the exception of the fecal supernatant addition." ] },{ "paper_id": "56deda06e91099aef48cd57fde743be79523f164", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since PERVs cannot be eliminated this way, they represent a special risk for xenotransplantation (see below).", "Xenotransplantation is being developed to overcome the shortage of human tissues and organs needed to treat organ failure by allotransplantation. Pigs are the preferred species to be used as donor animals for a number of reasons including the size of the animals, their similar physiology, and the ease with which they can be genetically modified and cloned.", "Although there are still some hurdles that have to be overcome, such as immunological rejection, physiological incompatibility and risk of transmission of porcine microorganisms, recent achievements in breeding genetically modified pigs, in the development of new immunosuppressive regimens and in approaches to safety suggest that xenotransplantation may soon be introduced in the clinic (for review see [1] [2] [3] )." ] },{ "paper_id": "56e7f3e210952c559633020f5910284c76111fde", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BToV, formerly called Breda virus, was originally isolated from diarrheic calves in Breda, Iowa, in 1979. Until today, BToV was described in diarrhoeic calves in various countries [4, 2, [22] [23] [24] [25] [26] 27] . The faecal prevalence of BToV in calf diarrhea ranges from 2.9 % in South Korea [25] to 36.4 % in southern Ontario, Canada [22] .", "This statement confirms that sampling for the purpose of this research was performed as non experimental clinical work with respecting the rules of veterinary profession. All samples were collected by veterinarian Nina Kre\u0161i\u0107, license number 2202. Sampling was performed strictly on the owner request. This statement is an annex to Ethical Committee permission of Veterinary Faculty University of Zagreb; number: 251-61-01/139-11-72.", "The (Table 2) . Samples were chosen to cover three-year period." ] },{ "paper_id": "56fb26305485a7d9c7844df6b25e30c8f1af4363", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since the first outbreak in Saudi Arabia in 2012, about 1,600 patients worldwide were infected with Middle East Respiratory Syndrome (MERS) through the beginning of 2015 [1, 2] . MERS is caused by infection with the MERS coronavirus (MERS-CoV). The virus can be transmitted between humans and animals and between humans. Transmission between humans mostly occurs in hospitals [3, 4] . Although MERS-CoV may be transmitted within households, the risk is reportedly low [5] [6] [7] .", "Chances of infection before May 31", "The Good Samaritan Bagae Hospital" ] },{ "paper_id": "56feb53034b99302ba30fa1c3e2042b2118fe6cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Generally, hepatitis E is a self-limiting disease with low mortality. However severe courses of the disease with acute liver failure have been reported during pregnancy [7] and in patients with liver cirrhosis [8] . So far prolonged courses have been registered only in organ transplant recipients [9] and patients suffering from leukemia [10] .", "The genotype 1 HEV genome synthesized by Geneart (Regensburg, Germany) served as template for subcloning Figure 2 ). Recombinatorial cloning of the HEV ORFs was performed as described recently [22] .", "Competing interests AO, MGVP, RH, HN, and AB declare that they have no competing interests. SJ, MS, and UM have received salaries from Mikrogen GmbH. MM is general director of Mikrogen GmbH." ] },{ "paper_id": "570259cab68c41a50bbfd4c998042c397bc8af33", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The incidence of respiratory troubles increased in winter and spring.", "Single infection " ] },{ "paper_id": "5706247afd9585354f3dae2f70d200a25f8e3f4c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "57175f1b43951c500b3fe6cb678824ea9e6d8ae2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step 4: Charting the data", "Steps 5 and 6: Collating, summarizing, reporting results and consultation", "Data charting by descriptive numerical summary was undertaken for the 300 articles that were selected after abstract screening. The types of disaster were: all hazards or disaster type unspecified (39%); infectious natural hazards (31%); and non-infectious natural hazards or natural disasters (24%) (Figure 2 ).", "Communicable disease control: A gap that was noted relating to SARS was the labour issues involved for front line health care workers in the setting of communicable disease outbreaks." ] },{ "paper_id": "57197f5ee8bd40e26cf5e08f825621755d2612d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Collection of field samples. Samples were collected from guinea fowls showing enteritis and concomitant high mortality (\u03fe10%) in flocks in five regions in France (Bretagne, Pays de Loire, Nouvelle-Aquitaine, Occitanie, and Auvergne-Rh\u00f4ne-Alpes) from February 2014 through November 2016. Gastrointestinal content was collected and stored at \u03ea80\u00b0C for viral RNA isolation. Tissues (duodenum, pancreas, air sac, lung, small intestine, large intestine, kidney, cloaca, trachea, and bursa) were collected during necropsy of euthanized or deceased animals in routine diagnostics by local veterinarians, fixed for 24 h in 4% (mass/vol) buffered formaldehyde, and stored in 70% ethanol.", "In conclusion, all tissues of the gastrointestinal tract, except cloaca, express GfCoV glycan receptors (Table 2) (15).", "Data availability. Contigs are available in GenBank under accession numbers MG765535 to MG765542 and accession numbers MK290733 and MK290734." ] },{ "paper_id": "5719934f2cd95ffe4bd1aec0b7b9a314481aab60", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nuclear extracts were prepared from OPCs using NE-PE Nuclear and Cytoplasmic Extraction Reagent Kit (Thermo Fisher, 78833, Pittsburgh, PA, USA). PPAR activity was assessed using the PPAR (\u03b1, \u03b4, \u03b3) Transcription Factor Assay Kit (Abcam, ab133113, Toronto, ON, Canada) or the PPAR\u03b3 Transcription Factor Assay Kit (Cayman Chemical, 10006855, Ann Arbor, MI, USA) following the manufacturers' instructions." ] },{ "paper_id": "5721c27ac5defb5f651b26e7f45324c848212c06", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza NP Non Coding Region Role in Translation", "Madin-Darby canine kidney cells (MDCK) cells, human embryonic kidney 293T cells and human skin melanoma cells (SK93/2) [46] were cultured in DMEM supplemented with 5%, 10% and 10% fetal calf serum (FCS), respectively. All cells were grown at 37uC with 5% CO 2 ." ] },{ "paper_id": "572e7221874d7e5d1c4ed293e60f021ba1d59367", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Searches 3 and 4 were carried out only when fatality or tropism data, respectively, were not already found from previous sources. Data collection and virus name search terms included the full species name, any synonyms or subspecies (excluding vaccine strains), and the standard virus abbreviation as given by ICTV Online Virus Taxonomy [49] .", "Taxonomic family being a highly informative predictor in the random forests implies that there is a broad phylogenetic signal to virulence, but it is also highly likely that the explanatory power represents a proxy for many other phylogenetically conserved viral traits that are challenging to implement in comparative analyses of this scale, such as variation at the proteomic, transcriptomic, or genomic level or further data beyond simple categorisations, e.g., specific arthropod vector species. Untangling these sources of variation from different scales of traits will be a critical next step in predictive modelling of viral virulence.", "The value of predictive modelling as an inexpensive and rapid tool for risk assessments during early emergence is increasingly recognised [16] . Instances in which machine learning model predictions do not match outcomes could indicate likely candidates for outcome class changes, e.g., future reservoir hosts for zoonotic disease [37] , and we note severe virulence was predicted for 12 viruses rated 'nonsevere' from literature protocols (S1 Table) ." ] },{ "paper_id": "5731445d010b69d663005de6dac188fe26b9c120", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5734e3b81e16fe1976a129c5a0872716f3dd50b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5739f33d00bed835fb29dd26757a04faf48905a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two types of membrane proteins in monolayer model membrane system will be briefly described below:", "The great advantage of using nanodiscs is keeping the membrane proteins in aqueous solution, in native-like phospholipid bilayer environment that is soluble, stable, monodisperse and detergent-free. Most important, it isolates proteins or complexes as individual particles in monomeric or oligomeric states for analysis by techniques that range from activity assays to electron microscopy. Since 2003, there have been more than 100 membrane proteins reconstituted into nanodiscs [54] , ranging from signaling receptors to transport machines. We will discuss the applications separately below.", "P-glycoprotein, the most extensively studied ATP-binding cassette transporter, has been implicated in the phenomenon of multidrug-resistance in tumor cells and has been suggested to play a significant role in drug absorption and deposition. How P-glycoprotein interacts with its substrates is still unknown. Functional studies are limited because of the difficulty of obtaining large quantities of stable P-glycoprotein. Besides that, no ATPase activity of P-glycoprotein solubilized in detergent could be detected. When P-glycoprotein is reconstituted into proteolipsomes, it has detectable ATPase activity; however, the whole complex is very unstable. Heikal et al. [75] have further found that P-glycoprotein reconstituted in the proteoliposomes has a half-life of less than one day." ] },{ "paper_id": "574285d317ef91b77f2dc770a3dbf2a9b514de21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Despite routine vaccination, the numbers of cats with URTD referred to veterinary clinics are increasing. To define effective prophylactic and management programs, precise information on the prevalence of FeLV and FIV and their role in respiratory disease progress is required.", "For detection of FIV/FeLV, a blood sample (0.5 to 1.5 mL) was collected from each cat by venipunctures containing EDTA. Tubes were centrifuged at 3,000 rpm for 10 min and buffy coat layers were collected.", "For better understanding the role of FIV and FeLV viruses in induction of FCV and FHV infections, the prevalence rates of these infections were investigated in healthy and diseased cats." ] },{ "paper_id": "574efe7771ff8495c4ace678a489b0a0869b0834", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Unlike short pentraxins, the PTX3 promoter does not contain a consensus site for hepatic nuclear factor-1 (HNF-1), which accounts for the absence of its induction in liver (Darnell et al., 1994) . Although human and murine PTX3 protein is homologous, the human promoter contains lesser transcriptional elements than does the murine promoter, an effect that needs to be studied using molecular and phylogenetic analysis.", "Altogether, more studies are required to determine the functional outcome of the role of PTX3 during differentiation and also in obese condition.", "The level of circulating PTX3 is low in healthy human condition (<2 ng/ml), but a rapid increase is observed in inflammatory conditions starting from very early stages. Due to its precocious appearance in various clinical conditions, research has focused on investigating whether PTX3 can be used as an index of systemic inflammatory activation. Another major reason suggestive of its suitability as a marker of severity of diseases like tuberculosis particularly in parasite endemic regions is the fact that its plasma level is unaffected by helminthic infections. There are several studies described in following sections, which demonstrate association between different diseased states and higher levels of PTX3." ] },{ "paper_id": "5752683f35a4f922c8a1a363c93dcae050b92b50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We should first address people's confidence about rabies knowledge, and then confirm how much knowledge they actually have.", "Vaccination is a health behavior that consists of a personal act to preserve or strengthen one's health [11] [12] [13] . Many methods have been employed to increase vaccination rates, for example, through increased knowledge and better attitudes, but these strategies have shown only limited success [14, 15] . Descriptions of vaccination determinants have been mainly from physician perspectives, and past studies have often ignored those who actually make the decisions [15] . Hence, the limited success of these interventions clearly indicates the need for a fresh approach and new methods.", "The geographic scope of this study is Taiwan and the Kimen district. We distributed the samples around Taipei, Taichung, Kaohsiung, Taitung, and Kinmen. To increase the response rate, each participant received a questionnaire accompanied by a gift valued at one US dollar. In total, 310 participants completed the questionnaire. The respondents were almost equally male (163; 52.6%) and female (147; 47.4%). Their age ranged from 16 to 73, with an average age of 37.6 years old (with a standard deviation of 12.33 years). As for the level of education completed, 12.9% (N = 42) had a junior/senior school degree, 72.6% (N = 225) had a bachelor's degree, 11.9% (N = 37) had a master's degree, and 1.9% (N = 6) had a doctorate degree." ] },{ "paper_id": "57599ec2644e90c8c79737ed565edb7d6b286fc5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NMR sample preparation followed procedures described previously using [methyl-13 C] Met-labeled PV RdRp [29, 30] . 1 H, 13 C HSQC (heteronuclear single quantum coherence) NMR spectra were collected on a Bruker Avance III 600 MHz spectrometer equipped with a 5-mm \"inverse detection\" triple-resonance ( 1 H, 13 " ] },{ "paper_id": "5759e5ac8b1cc3c13ba04aded6e588a059ad92a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Airborne biological particles drawn into the 1 mm diameter nozzle and down the capillary stem, then impacted and penetrated the liquid surface [32] . The adhesion properties involving liquid and airborne particles were exploited by this technology to capture the microorganisms [33] .", "Purified avian influenza virus (A/chicken/Jilin/9/2004 (H5N1), GenBank: AY653193~AY653200) was obtained from our laboratory stock, and diluted 10 -1 in phosphate buffered saline (PBS, 0.1 mol/L) supplemented with free calcium and magnesium. Aliquots of this stock solution were stored at \u221280\u00b0C until use. Prior to experimentation, virus was propagated by infection in chicken eggs, and yield was determined to be 6.7 log10 50% egg infection doses per milliliter (EID50/mL). All the experiments on animals were approved by the Ethics Committee " ] },{ "paper_id": "575aa2758f4a3c952d7cd9ab031eb42b25a87a96", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The third member of RLRs, LGP2, is able to bind dsRNA (63, 64) , however, its role in immune activation is poorly understood.", "Other viral RNA PAMPs can be produced during viral replication. David Baltimore has defined a classification of viruses based on the mechanism of mRNA production (13) . Viruses are clustered in seven groups depending on their genomes (DNA, RNA), strandedness (single or double), sense or antisense, and method of replication. The type of RNA ligands produced during viral replication will depend on the type of viral genome and the strategy used to generate mRNA. RNA ligands can be generated by DNA viruses and retroviruses via genome transcription, or by synthesis of mRNA and replication intermediates by RNA-dependent RNA polymerases (RdRps) of RNA viruses (8) .", "Infectious microorganisms have developed several strategies to evade cytosolic sensing. One of these strategies, which we only mention briefly here, is the direct targeting by microbial proteins www.frontiersin.org ", "Other host transcript specificities, like association to cellular components that prevent PRR binding, or specific tertiary structure such as the eukaryotic mRNA closed loop conformation (99) , could be determinants for the differentiation of host mRNAs from microbial RNAs. Identification of receptors able to recognize such features are lacking so far.", "Melanoma differentiation factor 5 ligand is less characterized than RIG-I. Using poly(I:C) as a synthetic dsRNA mimic, studies have shown that MDA5 binds long, but not short dsRNA (35, 40, 48) . Structural analyses have demonstrated that MDA5 specifically recognizes the internal duplex structure of dsRNA and uses it as a platform to stack along dsRNA in a head-to-tail arrangement. This mechanism promotes stochastic assembly of the tandem CARD oligomers that activates the signaling adaptor MAVS (49) .", "LGP2 was proposed to be a modulator of RLR signaling. Studies showed that LGP2 was required for RIG-I and MDA5 activity, in particular during picornaviral infection (65) (66) (67) . Another work proposed that LGP2 would inhibit RIG-I through competition with its ligand (64) . It is however unclear whether LGP2 binds microbial RNA in an infectious context, and what specific features of the RNA it would recognize. Further studies will be required to clarify the precise role of LGP2." ] },{ "paper_id": "575ce9765e914a2bdb2a02b265905f9e7e781c67", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the data generated or analysed during this study are included in this published article or available from the corresponding author on reasonable request.", "Published: xx xx xxxx opeN www.nature.com/scientificreports/" ] },{ "paper_id": "575faff450d20d0f359d000ebc8b66b638094613", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All images were obtained with an Olympus IX81 fluorescence microscope. Images were acquired using Image ProPlus software with a 40X objective and Hamamatsu monochrome cool charged couple device camera. Images were taken in green and red excitation filters for EGFP and TRITC, respectively for each region and then merged with the help of the software. ", "MN, MS, and JD performed all animal experiments and immunohistochemistry. KB participated animal experiments in India and did neuronal staining of MHV infected tissues. LK and JD participated in data analysis and data interpretation and drafted the manuscript. LK blindly read the pathological samples. KS, SH, and JG were involved in critical revisions of the manuscript. JD led all aspects of this work including experimental design, participated in or supervised all experimental procedures, analyzed, and interpreted data and critically revised the manuscript.", "For Olig2 staining, sections were specially post-fixed with icecold 95% ETOH at \u221220 \u2022 C for 20 min. These were subsequently washed with 1X ice-cold TBS (Tris Buffer Saline) at room temperature (RT) for 10 min. Post-fixed tissues were processed as previously described for washing, permeabilization, and blocking prior to the addition of the anti-Olig2 antibody. Biotinylated anti-Rabbit IgG was used as secondary antibody and sections were incubated for 30 min at RT. Further staining steps were followed as per the Tyramide signal amplification kit manual. Briefly, sections were washed with 1X blocking buffer (10 mg/ml Component D) for 15 min and labeled with Strep-HRP (provided with the kit; 1:200 dilutions in diluted component D) at RT for 30 min with three consecutive 1X TBS washes for 5 min each. Sections were then stained with Tyramide (1:200 dilution in amplification buffer) for 10 min at RT, washed three times with 1X TBS for 5 min each and then mounted in Vectashield (Vector laboratories Inc; Burlingame, CA) with DAPI." ] },{ "paper_id": "57694e4ef5e2af0338dc7ba54cf154b2b0cdda76", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "From a more formal perspective, our dataset (or corpus) is" ] },{ "paper_id": "576b829eeb6838282aa2ffdfa925301e2888bb9f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pntd.0007537.g007", "PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd." ] },{ "paper_id": "576bad43bf08b1a2d302695f5624a77fdbcaf6d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:25049 | DOI: 10.1038/srep25049" ] },{ "paper_id": "57739f7172bb6dd11a63147d6bd37a3c227c7bc2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed by Welch's t-test [58] for all transduction assays using Microsoft Excel 2013 and by Student's t-test using Graphpad Prism 6 for the colocalization studies. ", "https://doi.org/10.1371/journal.pone.0214968.g005", "Human embryonic kidney 293 T cells, African green monkey COS-7 kidney cells and African green monkey Vero 76 kidney cells were maintained in Dulbecco's modified Eagle's medium (DMEM; PAN Biotech) supplemented with 10% fetal bovine serum (FBS; Biochrome), 100 U/ ml penicillin and 100 \u03bcg/ml streptomycin (PAN Biotech), and 1% L-glutamine (PAN Biotech). The cells were grown in a humidified atmosphere at 37\u02daC and 5% CO 2 ." ] },{ "paper_id": "577c6a13f9ef70e9756890fc66e98f537c01ac0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus isolation. Tissue samples were homogenized in a TissueLyzer II (Qiagen) after addition of 1ml DMEM." ] },{ "paper_id": "578ad49441884c636eb9d6044237708eb6437afb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the procedures were carried out according to EC Directive 86/609/EEC for animal experiments.", "These authors contributed equally to this work." ] },{ "paper_id": "578d296ec1f6acc01c08cc5a9861bac6d47ddfda", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The NCBInr protein database was chosen over other genome specific databases to allow a wider search match found based on homology to other species. Parameters used for searching were partial methionine oxidation and acrylamide modified cysteine, a peptide tolerance of 60.6 Da, and a MS/MS fragment tolerance of 60.4 Da.", "abundance proteins and extremely small molecular weight proteins that are often lost during gel-separation or gel-extraction steps.", "All nine virus-encoded proteins previously described to be in the influenza virion were identified by both MS methods (Table 1) .", "Each of the QSTAR XL mass spectrometer spectra files was processed with MASCOT Distiller version 2.1 and the resulting peak lists were database searched using MASCOT Server 2.1. The search parameters included static carbamidomethyl modifications for cysteine and variable oxidation modifications for methionine amino acid residues. Data analysis on the resulting LC/MS and MS/MS datasets is accomplished using a dual processor Dell 650 Workstation. The search results for each fraction were analyzed using the NCBInr database. After MASCOT analysis, Peptide and ProteinProphet (Institute for Systems Biology) analysis was performed using the Trans-Proteomic Pipeline version 2.9 GALE rev.1, Build 200607201423. Peptide and Protein Prophet computes the probabilities for both individually searched peptides and the resulting proteins. The 95% Protein Prophet probability cutoff corresponds to a 0.6% false positive error rate. Finally, TPP identifications are submitted to Yale Proteomics Expression Database (YPED) web site [89] for further user analysis. All data are publicly available through http://yped.med.yale.edu/repository. " ] },{ "paper_id": "5794890e355a8abbec51b46d767b6ee67edcd274", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Supplementary Material for this article can be found online at:", "https://www.frontiersin.org/articles/10.3389/fmicb.2019. 00596/full#supplementary-material", "All datasets generated for this study are included in the manuscript and/or the Supplementary Files." ] },{ "paper_id": "579c99c1f830a59ff493ef9a08875f2e4ae2c405", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequence analysis for sites under positive selection revealed 1 site under positive selection in ORF1 and 13 sites under positive selection in ORF2 ( Non-bold percentages indicate nucleotide identities and bold percentages indicate amino acid identities. All sequence identities are based on the full-length sequences and calculated using MatGat [54] . GenBank accession numbers are as follows: porcine PtV HK1 -EU200671 [19] ; bovine PtV HK1 -EU200669 [19] ; bovine PtV HK5 -; ovine PtV-; human PtV PARV4 C51-4 -DQ873387 [55] ; bovine PV 2 -AF406966 [25] ; bovine PV 3 -AF406967 [25] ; minute virus of mice -DQ196317 [56] ; human PV B19 -AY044266 [57] ; bovine bocavirus -DQ335247 [58] ; human bocavirus -FJ858259 [59] ; Aleutian mink disease virus -NC_001662 [61] ; bovine adeno-associated virus (AAV) -AY388617 [60] . doi:10.1371/journal.pone.0025619.t002", "require further knowledge of the structure and function of the viral proteins for interpretation.", "DNA was extracted from all samples using QIAamp DNA Mini kit (Qiagen) according to manufacturer's instructions, and then subjected to PCR using 2 different sets of screening PCR primers. The primer sequences are: forward primer A 59-CCCGCKAS-TACWGGNAARAC -39 and reverse primer A 59-CCGTAAYT-CKRCCYTCKTCCCA -39 (targeting a 148 bp fragment); forward primer B 59-TCTGCTATTGTAATHAARGAYGT-39 and reverse primer B 59-AAACACTCTGCRTCRTGRTGYTC-39 (targeting a 293 bp fragment). The primers were designed from multiple alignments of the nucleotide sequences of VP2 regions of PARV4 and related parvoviruses using our previously described strategy [19] . The PCR mixture (25 ml) contained DNA extracted from samples, PCR buffer (10 mM Tris/HCl pH 8.3, 50 mM KCl, 2 mM MgCl 2 and 0.01% gelatin), 200 mM of each dNTP and 1.0 U AmpliTaq Gold polymerase (Applied Biosystems). PCR cycling conditions were as follows: hot start at 94uC for 7 min, followed by 50 cycles of 94uC for 1 min, 50uC for 1 min and 72uC for 1 min with a final extension at 72uC for 10 min in an automated thermal cycler (Applied Biosystems). Standard precautions were taken to avoid PCR contamination and no false positive results was observed in negative controls." ] },{ "paper_id": "57a145d6bea3653336fdd964a6d1e0494c32fcf4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was observational and non-invasive. Protocols were approved by Institutional Animal Care and Use Committees (IACUC) of Harvard University (protocol 96-03) and University of New Mexico (protocol 14-101186-MCC) and were exempt by Boston University's and the University of Michigan's IACUC. Protocols followed the Weatherall Report, NIH Guide for the Care and Use of Laboratory Animals, USDA Animal Welfare Act, Institute for Laboratory Animal Research Guide for the Care and Use of Laboratory Animals, US Public Health Service and National Academies of Sciences National Research Council, and US Centers for Disease Control and Prevention.", "Data Availability: Data are available in GenBank under accession numbers MH428626-MH428633.", "Polymerase chain reaction (PCR) and Sanger sequencing were used to complete viral genomes and to characterize viruses detected by Luminex assay in fecal samples (Table S1 ). To infer phylogenetic relationships among the two chimpanzee viruses and published viral sequences, we analysed full genome alignments of all available viruses in GenBank (alignment lengths 13,234 and 15,330 positions, respectively) using PhyML 3.0 [52] with 1000 bootstrap replicates of the data to assess statistical confidence in clades, and we displayed the resulting trees using FigTree 1.4.3 [53, 54] ." ] },{ "paper_id": "57a3e8ebd6f29c8e8126ff652f6f79b1b8fbffc6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ASEAN member states to facilitate the freer movement and employment of qualified and certified personnel such as doctors, nurses, and dentists (2) .", "Worldwide momentum for universal health coverage \u00c1 are migrants included?", "Reasons for such documentary requirements include concerns that the card will be rented out to other migrant workers (as had occurred in some cases) and a general unease among some providers about selling the card to undocumented migrants \u00c1 who themselves may not feel confident to approach the hospital and purchase the card (55) ." ] },{ "paper_id": "57a8f6955709acb05304154c9863ca79f6a5c1b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "57a9bfeac00b440a156ffa1f6ae21aca7152b22c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Critical questions include:", "A key challenge in doing this is to simultaneously protect wildlife and their habitats, thereby preserving vital ecosystem structures and functions that have local and broader implications for human wellbeing and environmental sustainability, and to prevent the spillover of pathogens from wild animals into human beings.", "New metagenomic studies of viral abundance and diversity in bats [21, 22] (Baker et al. 2012, unpublished data), as in other species [23] [24] [25] , have demonstrated the amazing breadth and diversity of microbial populations in different bat species. An unknown proportion of the detected infections will have the ability to cross the species barrier, with or without adaptation [26] . The spillover infection dynamics will, however, be very different between different species of bat and microbe, with additional and marked geographical variation influenced by environmental factors and human behaviours.", "There are a number of ways that specific research themes could be developed within our proposed conceptual framework. A thematic approach is critically important as it allows intra-disciplinary study, vital for ensuring impactful and relevant publications, each testing specific hypotheses. Such outputs are the building blocks for substantial interdisciplinary programmes and, while not every output will incorporate obvious interdisciplinary approaches, each should be informed by them. The same themes can cross geographical divides, providing integration on that scale. All these factors are critical for scientific inference as well as for evidence-based international and national policy development.", "The practices and health system factors that influence how prevalent spillover risks are, and how these are detected in different settings, need specific study in most developing world situations. Key questions here include:", "The dynamics of individual spillover events are based around the concept of the pyramid (triangle here) of pathogen emergence first proposed by Antia [26] and developed further by others, including Lloyd-Smith et al. [27] . It is proposed that humans are constantly challenged by animal-derived pathogens (the so-called pathogen, or viral, 'chatter'), but that only a small proportion manage to invade individual humans. Of those invading, most will be controlled by innate immunity and not replicate efficiently. Of those (proportionally) few that manage to replicate within the new host, most will not be able to transmit between individuals, or will do so only very poorly. As reviewed [27, 48] , the major determinant of whether these replicating pathogens will then invade human populations is the rate at which they can transmit between humans." ] },{ "paper_id": "57ae4e660730c4f3591f27a4058164362d6f5cb4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Authors' contributions COO conducted literature research and wrote the draft manuscript, JC provided editorial input and revision for the final version. Both authors read and approved the final manuscript.", "Agency for Science, Technology and Research-Singapore International Graduate Award (A*STAR-SINGA). Some of the work reviewed and cited in this paper was funded by different funding agencies.", "We would like to thank the authors' whose work has been reviewed and cited in this paper as well the funding organizations that funded the primary research." ] },{ "paper_id": "57b4aa7990ee59eb32397dc0dbb4af096a4e9aa8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "JY, X-fangY, and SH designed the experiments and wrote the paper, ZW and JY conducted the experiments, TZ and YW analyzed cell culture, FS, X-fengY and WZ prepared the virus, LX prepared the reagents.", "This study has obtained ethics approval from the ethics committee at the First Hospital of Jilin University.", "Statistical differences were analyzed using the Student's t-test for all analysis, except of 3C and 3D dose-dependent test in Figures 4B,D with Pearson correlation coefficient. Data are presented as means and standard deviations (SD). * P-values of < 0.05 were considered statistically significant. Frontiers in Cellular and Infection Microbiology | www.frontiersin.org" ] },{ "paper_id": "57b8e034f902f2883dbbafaeef554cb2deb64963", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Experiments were performed and repeated at least three times. All the data are presented as mean \u00b1 SD. The differences between two groups were analyzed by two-tailed Student's t test. Difference with P < 0.05(*) or P < 0.01(**) was considered statistically significant. Oneway analysis of variance was used in multiple group comparisons. These analyses were carried out using SPSS 13.0 for windows.", "HePG-2 cells were purchased from American Type Culture Collection (ATCC, Manassas, Virginia). Fetal bovine serum (FBS) and Dulbecco's modified Eagle's medium (DMEM) were purchased from Gibco. AKT, p53, PARP, and cleaved caspase-3 antibody were obtained from Cell Signaling Technology. Silver nitrate (AgNO 3 ) and vitamin C (VC) were obtained from Sigma. Thiazolyl blue tetrazolium bromide (MTT), 4\u20326-diamidino-2-phenyindole (DAPI), 2\u2032,7\u2032-dichlorofluorescein diacetate (DCF-DA), bicinchoninic acid (BCA), 6-coumarin, and propidium iodide (PI) were obtained from Sigma. LysoTracker Deep Red was obtained from Invitrogen. The water was supplied by Milli-Q water purification from Millipore in all experiments.", "As one of the most common type of liver cancer, hepatocellular carcinoma (HCC) is the third cause of malignant deaths from cancer-associated worldwide [1] [2] [3] . Unfortunately, the diagnosis of HCC is difficult in its earliest stages without screening tests available [4] . Meanwhile, owing to its poor sensitivity to chemotherapeutic agents, high metastatic potential, and resistance to traditional drugs, it is dismal to the overall prognosis of patients with HCC. Thus, it is imperative to develop efficient chemotherapy that has become the great challenge in clinical treatment [5, 6] . In addition, most of current anticancer agents usually have short half-life in the blood circulation and poor aqueous solubility, which hampers therapeutic efficacy of chemotherapy [7, 8] . Recently, nanomaterials have been widely used in biomedical field due to its unique physicochemical properties, including their size distribution, stability of dispersion, morphology, crystalline structure, and thermal properties, that might have the potential to overcome these problems [9] . The increased of application of nanomaterials resulted in raising hopes for employing nanoparticles as alternative anticancer agents [10, 11] ." ] },{ "paper_id": "57bac09c0563474a03a233b1e7f60ed8c82a9642", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "57cfa4c490208b9a56470ca156fd18ba8b813cc1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The complete genome sequences (DH1/2016 and DH2/2016) have been deposited to GenBank under the accession numbers KY354363 and KY354364.", "In conclusion, our study contributed to the collection of the complete genome sequences of PDCoVs, which might be useful for molecular analyses of the virus.", "Two porcine deltacoronavirus (PDCoV) strains, named DH1/2016 and DH2/ 2016, were isolated from feces of piglets which had severe watery diarrhea symptoms. A comparison of the complete genome sequences suggested that the DH1/2016 and DH2/2016 strains are highly homologous to each other and to PDCoVs isolated in early 2014 from the United States." ] },{ "paper_id": "57cffb9026a4e37031021f91832d48c79df0fd75", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This contrasting test allows us to specifically determine a standard p-value assessing the significance of treatment effects (e.g. viral pathogen, viral dose) significantly increases the fit (reduces the error estimate) of our statistical model that already accounts for daily and animalspecific effects.", "All statistical and data analysis were conducted within the R environment (cran.r-project.org). The package doBy was used for data manipulation, MASS was used for data transformations for normality, lme4 for the mixed-effect statistical analyses, and ggplot2 for data visualization.", "Supporting Information S1 ", "The present study was carried out in accordance with the recommendations for care and use of animals by the Office of Laboratory Animal Welfare, National Institutes of Health. The Institutional Animal Care and Use Committee (IACUC) of The University of North Carolina at Chapel Hill (UNC; permit A-3410-01) approved the animal study protocol (IACUC 13-026) followed here." ] },{ "paper_id": "57d2a2f022fc3ec32d1b92bb0a234c9f4ac8e1d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical Analyses All the graphs were made using GraphPad Prism Version 4.0a for Macintosh (GraphPad software, San Diego, CA, USA).", "Antibody responses Mouse serum was obtained from the tail vein 7 days after the second immunization. Serum IgG levels were measured by enzyme-linked immunosorbent assay (ELISA) as described previously [16] .", "Human 293 cells were plated in 6-well plates (2610 6 cells/well) and transfected with plasmid DNA (4 mg) using the FuGENE TM 6 (Roche Applied Science, Indianapolis, IN, USA) transfection reagents according to the manufacturer's instructions. The western blot analysis was done as previously described [15] .", "Immunization of mice Female BALB/c mice, 6-8 weeks of age, were obtained from Charles River (Kingston, NY, USA). Mice in groups of eight were each immunized twice (21 days apart), intramuscularly (i.m.), with 50 mg of the indicated plasmid and sacrificed 7 days later. For CD8 + experiments, the mice were challenged 21 days after the first immunization with a VDK-1 vaccinia virus plasmid containing the native Gag sequence (10 7 plaque-forming units; NIH AIDS Research and Reference Reagent Program, Rockville, MD, USA)." ] },{ "paper_id": "57d6bf2cc1fc387a33ba3ff4343e0bbd7a12dfaf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data analysis was performed using PASW (ver. 18; SPSS Inc., United States) and GraphPad Prism software (ver. 5.0; GraphPad Software, Inc., United States). Age, maximum body temperature, laboratory parameters, clinical features, and HRV prevalence were compared by \u03c7 2 -test or Fisher's exact test for categorical variables, and by two-tailed paired Student's t-test for continuous variables. A value of P < 0.05 was considered indicative of statistical significance.", "The seasonal distribution of HRV is shown in Figure 1 . ", "Of the 280 HRV-positive patients, 131 (46.8%) were co-infected-102 with one other virus, 21 with two other viruses, and 8 with three other viruses ( Table 3) . Most such co-infections involved AdV, HBoV, and RSV (39.7, 38.2, and 17.6%, respectively). The patients with co-infections did not have more serious disease (data not shown)." ] },{ "paper_id": "57d7804297acdd855f4f2e2a6903cf6ca04d323e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A " ] },{ "paper_id": "57da78ec8de4f8fd1761c46221d0e05872f14f1f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A P-value < 0.05 was considered statistically significant. All analyses were performed using SPSS 23.0.", "We thank the Institute of Microbiology and Immunology and the National Institute of Public Health who provided us with data necessary for statistical analysis.", "The authors have no competing interests." ] },{ "paper_id": "57debc6d188282301818dada90a7cee441c45379", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The intracellular GSH/GSSG ratio was determined by a fluorimetric assay kit (Biovision, Milpitas, CA). The GSH content was normalized for protein content and expressed as % of control." ] },{ "paper_id": "57df78198df2774be87635b81f850b6eeb2dd6f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Systematic review.", "cOnclusiOns 35 multimorbidity indices are available, with differing components and outcomes. Researchers and clinicians should examine existing indices for suitability before creating new ones.", "systematic review registratiOn PROSPERO CRD42017074211. cite this as: BMJ 2020;368:m127 http://dx." ] },{ "paper_id": "57e168131391d871fa93444a1741f3f2b4403d45", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Transmissible gastroenteritis coronavirus -TGEV (vaccine strain h-5; Nisseiken, Tokyo, Japan) was propagated in Vero cells; porcine reproductive and respiratory syndrome virus -PRRSV (live PRRS vaccine -Ingelvac PRRS\u00ae MLV-Boehringer Ingelheim company); Japanese Encephalitis virus -JEV and Getal virus -GV (live vaccine -Kyoto Biken company, Kyoto, Japan).", "The total RNAs were extracted from 250 \u03bcl cell culture supernatants of PEDV, TGEV, and PRRSV, JEV, GV using a RNA extraction kit (ReliaPrep\u2122 RNA Cell Miniprep System, Promega, USA), according to the manufacturer's instructions.", "The RtF-RT-LAMP reaction was conducted in a final reaction volume of 25 \u03bcl consisting of 2 \u03bcl RNA template, FIP and BIP primers (1.6 \u03bcM each), Loop F and Loop B primers (0.8 \u03bcM each), F3 and B3 primers (0.2 \u03bcM each), Isothermal Mastermixes (OptiGene, UK), 0.15 u of AMV reverse transcriptase (15 u/\u03bcl; Invitrogen, USA). Amplification reactions were performed at 63\u00b0C for 40 min (with fluorescence detection followed by melt curve analysis from 90 to 70\u00b0C at 0.05\u00b0C/s), and then heated at a start temperature of 98\u00b0C and end temperature of 80\u00b0C for 10 min with a ramp rate of 0.05\u00b0C/sec to terminate the reactions using Genie\u00ae III (OptiGene, UK). The fluorescence of the reaction was measured in real time, verifying the start of the amplification." ] },{ "paper_id": "57eb57853f082c4b343cb136c248c9b14f5e632c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Geometric mean fluorescence intensity (GMFI) was calculated using FlowJo 10 software (FlowJo, USA). Pearson correlation coefficients and P-values of differences between GMFI and IC 50 /IC 80 for each antibody were calculated using GraphPad Prism 7 (GraphPad Software, USA). " ] },{ "paper_id": "57ef6bf1ad8360243bf77eb91ed13430e42b35e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "57f469dc08da8f964d6c85c7d90ef62315f14e9d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Purpose of analysis Ensure that own food product is legally compliant and does not pose an unacceptable risk to consumer (can be perceived as safe)", "Interviews of patients/family : analytical detection targeting case specific markers from patient isolate(s) complemented with epidemiological analysis and sampling partly based on interviews. A pre-defined sample size is often applied, but a pre-defined LOD is usually not", "then only isolates G-I ( max = 2) might be considered isogenic (any other pair of isolates would yield min \u226511)." ] },{ "paper_id": "57f687e997bc7338adaefa13542e1f9ae7ddd7e6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, the Millennium Development Goals (MDGs), under revision, should include measurable objectives for good quality drugs. This will encourage national establishment of baseline status and achievable targets, particularly for essential drugs. Establishment of MDG targets and Sustainable Development Goals (SDGs) will help greatly to solve the poor quality drug epidemic by application of available technology and good pharmaceutical vigilance and governance. 41 One incentive that would transform the current system is applying a \"universal quality standard\" to drug products. For example, if India allows a substandard manufacturer to sell products in Africa, the FDA could ban import of products from India. Although difficult to develop and implement, a combination of incentives and penalties driven at the political and economic levels is needed.", "No independent agency has inventoried and performed comparative quality assessments of these packaging and drug-testing devices and made recommendations to countries for their use. Objective comparisons are needed of the diversity of field methods in terms of accuracy, reliability, costs of equipment and supplies, level of training needed, ease of use, spare part availability, and maintenance requirements. Simplified standard survey protocols and methods for sampling drugs at country entry points (seaports, airports, and roads); at major pharmacy depots; in health units (public and private hospitals and clinics); and at more peripheral distribution sites (district and village pharmacies and individual vendors) are also needed. 19 Low-cost, portable detection tools would empower pharmaceutical inspectors in numerous countries that have oversight of the medicine supply. Results would be available promptly rather than delayed when samples are sent to national or international laboratories as occurs now; lamentably, intervals of several years have occurred from the time specimens were collected to the time the results were available to those needing to take action. 1 Ideally, central reference laboratories vetted by WHO, FDA, or another agency would back up spot checks and random sampling of pharmaceuticals at the periphery.", "Good quality medicines by law. Falsified medicines are ultimately a problem that impacts public health. The solution needs to reflect various incentives, either via financial gain, avoidance of punishment or both. A multi-sectorial effort is essential for taking into account how this illegal market is interwoven with world trade agreements, business models, and associated legal ramifications. Globalization has enlarged the international trade in medicines. For example, India exports over US$15.5 billion in pharmaceuticals, which are among their most important exports. 26 As of 2011, 40% of drugs and 80% of APIs for drugs in the United States are imported from foreign countries. 27 An international law convention against substandard and falsified medicines would address both regulatory and criminal international governance challenges simultaneously through technical, legal, and financial mechanisms.", "How would the convention work and what national benefits would it bring? A convention would provide four legal underpinnings that do not exist, that together would advance patient safety and access to quality medicines. 12 First, a convention would define the various sorts of wrongful medicines accurately and thereby avoid misunderstandings caused by today's problematic or vague terminology (e.g., where countries seized good quality generic medicines as \"counterfeit\"). Second, a convention would promote the requirement that signatory countries enact national laws to designate wrongful actssuch as the intentional manufacture, trafficking, or selling of falsified medicines-as criminal offences, with attendant obligations to alert health-care workers and to prosecute or extradite the offenders to justice promptly. Third, a convention would provide the legal and institutional framework for participating countries to agree, implement, and evolve convergent standards of medicine regulation, so as to reduce poor quality medicines in international trade. Fourth, and for lower income countries particularly, a convention would contain mechanisms for financial and technical assistance, and, to join local and regional networks. These actions would help build national and regional medicine regulatory authorities (MRAs) to a point where patients' access to quality medicines is protected." ] },{ "paper_id": "57f7587c21f25f1d1542599749ad28af764cf8e6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Please see Additional file 1 for translations of the abstract into five official working languages of the United Nations." ] },{ "paper_id": "58072613e14774fd4f9bfc63ee4b2d6ef78811ac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Participating hospitals were selected based on four criteria: if the facility 1) admitted at least 200 patients per month with a discharge diagnosis of pneumonia during February through May 2013-2015; 2) used an electronic Hospital Information System; 3) demonstrated willingness and capacity to collaborate with both national and local CDCs and 4) was located within one of China's 21 of 31 provinces with previously identified H5N1 and/or H7N9 human cases.", "A PUE case is defined as an illness of unknown etiology with 1) axillary temperature > 38\u00b0C, 2) radiographic pneumonia, 3) low or normal leukocyte count or low lymphocyte count during the early stages of disease, and 4) no improvement or worsening symptoms after 3-5 days of antimicrobial treatment per clinical guidelines [1] .", "The patient was transferred to another hospital or ward 6 (4, 2-8) 0 (0, 0-2.4) 6 (2, 1-4)" ] },{ "paper_id": "58086bd6aa7a845eac58001de931144a3cebd644", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonotic pathogen that causes acute and severe respiratory illness with a high mortality rate 1 . Since 2012, more than 1,600 patients have been reported and the mortality rate approaches 35% 2 . Primary transmission of MERS-CoV might be mediated by close contact between humans and infected animal reservoirs such as camels 3,4 . However, in Middle Eastern countries, most MERS cases are associated with human-to-human spread starting in healthcare settings that then spark sporadic outbreaks 5 . An unexpected large outbreak in South Korea (186 confirmed cases with 38 deaths), initiated by an infected traveler from the Arabian peninsula, was also attributed to nosocomial infections 6 and highlights our limited knowledge of this emerging infectious disease 7 .", "The major symptoms of MERS cases are acute viral pneumonia often associated with extrapulmonary manifestations such as enteric illness 5 . Patients infected with MERS-CoV present with a wide range of clinical severity varying from asymptomatic to severe pneumonia with respiratory failure 5 . Mortality mainly results from acute respiratory distress syndrome (ARDS) 4, 5, 8 . Currently, the pathogenesis of the pulmonary and extrapulmonary manifestations of MERS remains poorly defined and knowledge of factors affecting disease severity is limited, although underlying illness, older age, and high viral loads are associated with poorer outcomes 5,8-10 .", "Study approval. Clinical data and specimens obtained from the MERS patients were used in this study after ethnical approval granted by the institutional review boards of Chungnam National University Hospital and Seoul National University Hospital. This study was performed in accordance with the ethical standards laid down in the 1964 declaration of Helsinki and all subsequent revisions. All surviving patients provided written, informed consent to participate. In fatal cases, we obtained an exemption of patients' consent from the institutional review boards for the retrospective analysis of clinical samples." ] },{ "paper_id": "5808eac43f4ee06a648815a400aab4b73ee2d6b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics statement. Institutional and national guidelines for the use and care of laboratory animals were closely followed. The use of animals in this study was approved by the South China Agricultural University Committee for Animal Experiments (approval ID: 201304152)." ] },{ "paper_id": "580ef02f408295bba21f0ad87b6eba6ba9676163", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Third, this study can be criticized for potential observer bias but is supported by other factors, such as both disease severity scores and cytokine values consistent with findings and outcomes.", "Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel coronavirus. It is believed that complicated pathogenesis and severity of SARS arise from complex host responses against infectious agents [10] . During the SARS outbreak in China, 40-60% of infected patients received standard modern medical treatment integrated with Chinese medicine treatment [11] . While facing the challenge to treat SARS patients, TCM Zheng differentiation enables physicians to prescribe medicine in accordance with the process and nature of the illness [12] . The positive effects of this integrative treatment were reported by WHO and other review articles [11, [13] [14] [15] [16] .", "Evidence-Based Complementary and Alternative Medicine 5 " ] },{ "paper_id": "5811a8c7d5d59061c11b2084dca1e307c49867b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mi et al. [43] 2010 IO Beijing", "Tian et al. [45] 1995-2007 SDA Beijing", "Shao et al. [48] 1994-2009 STIRPAT Shanghai" ] },{ "paper_id": "5813a786b66940f45bd1083081448cc53edcadd4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Duck embryo fibroblast (DEF) monolayer was incubated at 37\u00b0C with 5% CO 2 in tissue culture flasks with Minimal Essential Medium (MEM) that contained 10% fetal bovine serum (FBS), 100 U/mL penicillin, and 100 \u03bcg/mL streptomycin.", "All probes and primers were synthesized by Genecore Corporation (Shanghai, China) and purified by corresponding HPLC system." ] },{ "paper_id": "5819ca9f401da096d402b6d1956a4fe6ba1c74b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Competing interests Julian Gordon and Prasanthi Gandhi are co-founders and co-owners of Inspirotec LLC and plan to commercialize the Inspirotec Sampler.", "Following their standard isolation procedure, captured mold spores were determined by qPCR for the 23 most common mold species by EMLab P&K, Marlton, NJ. Primers and probes and amplification conditions used are in [41] . Electrodes were released into 15 ml Falcon tubes and shipped overnight for analysis. They were extracted by vortex mixing intermittently over 10 min with 0.05 % Tween 20, and spores were centrifuged down and extracted by bead-beating [46] . Results were computed as spore equivalents [46] [47] [48] [49] . These publications show that standard deviations of spore equivalent counts may be \u00b11 log or more.", "All sequence data will be made available through FigShare, http://dx.doi.org/10.6084/m9.figshare.1603492", "For the purpose of this study, three environments were selected for side-by-side comparison of the Inspirotec Sampler, with an air filter as a reference device. The environments were a clean bathroom, a basement room with an exposed sump drain, and a hay storage room in a large equestrian facility." ] },{ "paper_id": "58246d246bb1b2288dc58245c475fc314d34cc83", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Authors' contributions GW drafted the manuscript. HRS and GW outlined, edited and revised the manuscript and all authors read and approved the final manuscript.", "The authors declare that they have no competing interests.", "Oct4 is at the top of the pluripotency regulatory hierarchy in pluripotent cells [20, 21] . It forms a positive feedback loop [16] and is essential to maintaining pluripotency [14] , but is not required for initiating totipotency/pluripotency in embryos [37] [38] [39] . Therefore, understanding how early embryos activate Oct4 expression is key in clarifying the oocyte reprogramming mechanism." ] },{ "paper_id": "582d6fa298f66400e7059dae69cb5d3449144b0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rhizoma curcumae longae (Jiang huang)", "Regulates blood, moves blood, moves and regulates qi, descends the qi Curcumin", "Venenum bufonis (Chan su) Opens the orifices, detoxifies, relieves pain Bufalin", "These herbs are used to warm the interior organs, expel cold, tonify yang and rescue harmed yang qi and relieve pain. Interior cold of the human body can be caused by exogenous cold, or kidney yang deficiency which finally results in spleen and heart yang deficiency [115, 276] ." ] },{ "paper_id": "58383a13c8f80823bd6cf3516faf38c1687994a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "58432d2ad49266df441de364700684534498b777", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fecal swabs collected with Synthetic-Tipped Applicators (Thermo Fisher Scientific, Waltham, MA) were re-suspended by being swirled in 1 ml PBS (Thermo Fisher Scientific, Waltham, MA), followed by total genetic materials extraction using MagMAX\u2122 viral RNA isolation kit (Life Technologies, Carlsbad, CA) on a Kingfisher magnetic particle processor (Thermo Fisher Scientific, Waltham, MA) following the manufacturer's instructions with minor modification as described previously [2] . Specifically, extracted DNA/RNA was eluted into 50 \u03bcl elution buffer. Extracted nucleic acids were then treated by RNase-free DNase I (Qiagen, Hilden, Germany) for 15 min at ambient temperature to remove DNA, and was then purified by Agencourt\u00ae RNAclean\u00ae XP Beads (Beckman Coulter Life Sciences, Indianapolis, IN) following the manufacturer's instruction.", "Reverse transcription was performed on purified RNA using NEXTflex\u2122 Rapid RNA-Seq Kit (Bioo Scientific Corp, Austin, TX). Double-stranded cDNA was purified with Agencourt\u00ae AMPure\u00ae XP Beads (Beckman Coulter Life Sciences, Indianapolis, IN) per manufacturer's recommended procedure, and was re-suspended into 9 \u03bcl re-suspension buffer. The concentration of cDNA was determined by Qubit\u00ae 2.0 Fluorometer and Qubit\u00ae dsDNA HS Assay Kit (Thermo Fisher Scientific, Waltham, MA) and adjusted to 0.2 ng/\u03bcl for sequencing library preparation. Sequencing library was prepared using Nextera\u00ae XT library preparation kit (Illumina, San Diego, CA) with dual-indexing and sequencing was performed on an Illumina MiSeq\u00ae instrument (Illumina, San Diego, CA) according to user manual of \"MiSeq Sequencing System Guide\" for 2 \u00d7 150 base pair (bp) reads [9] . Each library composed of 24 pooled samples or fewer without negative control samples for cross contamination assessment.", "Sequence alignments were performed with \"muscle\" algorithm, and phylogenetic tree was built by \"neighbor-joining\" algorithm in MEGA 6 [15] ." ] },{ "paper_id": "585a9f7b2e41ffc6ead4df982ba9d0b0adb28f51", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "If at first the idea is not absurd, then there is no hope for it.", "Modern human activity fueled by economic development is profoundly altering our relationship with microorganisms. This altered interaction with microbes is believed to be the major driving force behind the increased rate of emerging infectious diseases from animals. The spate of recent infectious disease outbreaks, including Ebola virus disease and Middle East respiratory syndrome, emphasize the need for development of new innovative tools to manage these emerging diseases. Disseminating vaccines are one such novel approach to potentially interrupt animal to human (zoonotic) transmission of these pathogens.", "Microbial movement into humans from animals (zoonotic transmission) has always been responsible for the majority of EIDs, including at one time EIDs that form such present day matrix diseases as malaria falciparum, [11] measles and TB. [12] For modern EIDs, it is estimated that over 70% of zoonotic pathogens originate in wildlife, entering either directly from wildlife reservoirs, or indirectly via an intermediate domestic animal host. [4, 13] HIV, avian influenza, Hendra and Nipah viruses, SARS and MERS, and Ebola and Marburg filoviruses are all examples of zoonoses currently emerging from wildlife. All of these EIDs present a serious and increasing threat to health, biosecurity and economies worldwide. It is a sobering observation that most modern EIDs were entirely unknown before their entry into the human population. This pattern of emergence of new pathogens of global significance into humans from wildlife is expected to continue." ] },{ "paper_id": "585e27107bd360c6d5a6519bbafe7006a1ce7cce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For surface staining, splenocytes and isolated immune cells from spleen, muscle, and lymph node tissues were stained for 15 min at room temperature with antibodies against the following proteins: CD4 (clone GK1.5, 863 eBioscience; clone H129.19, BioLegend, CA, USA), CD8 (clone 53-6.7, BD Biosciences; clone 53-6.7, Invitrogen, CA, USA), CD44 (clone IM7, Invitrogen), CD62L (clone MEL 14, BD Biosciences), CD11b (clone M1/70, Bio Legend), F4/80 (clone BM8, Invitrogen), CD86 (clone GL1, BD Biosciences), and CD11c (clone N48, eBioscience). Cells were fixed with 1% paraformaldehyde, analyzed using a FACS Canto II flow cytometer (BD Biosciences, NJ, USA), and the data were analyzed using FlowJo software (TreeStar, OR, USA).", "HS68 cells, derived from human foreskin fibroblast were obtained from Korean Cell Line Bank (Seoul, Korea). HS68 cells were cultured in Dulbecco's modified Eagle medium (HyClone\u2122) with 10% fetal bovine serum (FBS, Corning, NY, USA) and 1% antibiotic-antimycotic (Anti-anti, Gibco, CA, USA). The cells were cultured in a humidified 37 \u2022 C incubator with 5% CO 2 .", "Pharmaceutics 2019, 11, x FOR PEER REVIEW 6 of 19" ] },{ "paper_id": "5864eb909b8a0b74359b9d4ae2ace23e41287159", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "58657873c0bc33b6cbd816292e2d239228cde3a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. Following the removal of human reads, our sequence data have been uploaded to the European Bioinformatics Institute (https://www.ebi.ac.uk/) under BioProject number PRJEB32861.", "Influenza virus phylogeny. We reconstructed the phylogeny using consensus sequences for the HA gene (Fig. 5) . This demonstrates closely related sequences, as expected within one geographic setting in a single influenza season.", "Supplemental material is available online only. SUPPLEMENTAL FILE 1, PDF file, 0.3 MB.", "Ferret study. We applied our sequencing approach to residual samples collected in a previous time course experiment undertaken in a controlled laboratory environment (43) . We tested ferret nasal saline wash samples from three independent animals over an 8-day time course, from 3 days prior to first exposure with influenza H1N1pdm09 virus and at days 1, 2, 3, and 5 postinfection. Sampling and plaque assays of the viral titer were described previously (43) ." ] },{ "paper_id": "586df9c5c975c38a6f646674374a1eb98d280f62", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was supported by a German-Egyptian Research Long Term Scholarship (GERLS), a joint program between the German Academic Exchange Service (DAAD) and the Egyptian Ministry of Higher Education and Scientific Research (grant ID: A/11/92510) to MS, and by iMed, the Helmholtz Association's Initiative on Personalized Medicine (to FP).", "MS did the literature search, wrote the initial draft of the manuscript, and prepared the figures and tables. FP oversaw the project, edited the manuscript including the final version, and takes responsibility for the integrity of the data.", "Many delivery systems, such as nanoparticles, cationic lipids, calcium phosphate, antibodies, cholesterol, and viral vectors, have been tested (107) . From another perspective, the use of a single RNAi silencing molecule with a low percent match with the target mRNA would lead to a poor target reduction. Possible solutions include either applying only one siRNA which is 100% identical to the sequences of interest or applying more than one siRNA sequence targeting different conserved regions of the target gene." ] },{ "paper_id": "5881e62ed1be0eec6603b49cf10c413d3c1e560f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Pearson product-moment correlation coefficient was generated to measure the correlation between viral titer and viral RNA copy number in CW sample using GraphPad Prism 5.0 (GraphPad Software, Inc.). Statistical significance for all other experiments was determined using Student's t test.", "Tissues for immunohistochemistry (IHC) were collected day 3 p.i with the viruses indicated. or from uninfected ferrets, fixed by submersion in 10% neutral buffered formalin for 3 days, routinely processed, and embedded in paraffin. Immunohistochemical detection of influenza A virus nucleoprotein was performed as described previously [59] .", "This study was carried out in strict accordance with recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All ferret procedures were approved by Institutional Animal Care and Use Committee (IACUC) of the Centers for Disease Control and Prevention and in an Association for Assessment and Accreditation of Laboratory Animal Care International-accredited facility. Animal studies were performed in accordance with the IACUC guidelines under protocol #2195TUMFERC-A3: ''Studies on the Pathogenesis and Transmission of Recombinant Influenza Viruses in Ferrets''." ] },{ "paper_id": "588631c5434bdc11922450678d5d65823f62e432", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The process of drug discovery from the bench to the market is long and expensive-more like 10 years and close to two billion dollars [7] . Since the viral epidemics die out within one year or two, such a process would be impossible for new viruses. Drugs are curatives; vaccines, as preventive means, have been a more attractive alternative, and development costs are relatively lower [8] , but the standard practice of utilizing inactivated or attenuated viruses for the purpose has been fraught with their own problems including allergenic reactions [9] .", "In this context, it may be worthwhile to consider whether the techniques of Quantitative Structure-Activity Relationship (QSAR) can be extended to the search for suitable peptides. Mathematical biodescriptors derived from toxicoproteomics maps, and chemodescriptors used to predict their toxicity [61] , could conceivably be extended to cover epitope binding. Integrated QSARs [62] , developed using chemodescriptors for ligands and biodescriptors covering transcriptional, translational, and post-translational modification processes, connect structural information of DNA/RNA sequences, RNA secondary structures, and protein tertiary structures, and may be used to predict parameters for new entities [63] . It has been found that using numerical indices derived from protein-2-dimensional molecular graphics for QSAR studies is simpler than having to work with the 3D protein structures [64, 65] , and could be extended to optimize the search for surface antigens.", "A primary requirement for the analysis of viral proteins to select segments suitable as vaccine targets is adequate data of the molecular sequences. The data needed are, for the purposes of this review, nucleotide sequence data, protein sequence data, and 3D structures of the associated proteins; other data useful for furthering analysis would comprise MHC binding data, epitope data, etc.", "A third type of vaccine manufactured from the original virus is the viral-like particle (VLP) vaccine. VLPs are constructed out of surface proteins that can self-assemble to a virus-like structure, which mimics the original virus structure and can elicit strong immune response with adjuvants. The first VLP vaccine license was granted by the US Food and Drug Administration for the hepatitis B virus in 1986 [11] ; since then, two more licenses have been granted-for the human papillomavirus, and hepatitis E virus.", "With the growth of web accessibility and expanding entries in biological databases, numerous servers have been developed for various purposes. In silico screening of genomic information has reduced the workload of experimentalists with more focused goals. A number of server-based tools are available for prediction of probable antigenic sites, and their success is dependent on the accuracy of their predictions. While most approaches use sequence alignment to identify antigens, this approach has its limitations since some proteins may have additions, deletions and/or substitutions, but similar functions within the overall structure of the sequence, and these methods obviously cannot predict new and hitherto unrecognized antigens. This has given rise to alignment-free approaches, as in VaxiJen [46] , which is based on auto cross-covariance, allowing for antigen classification solely based on the physicochemical properties of proteins collected from bacterial, viral, and tumor protein datasets." ] },{ "paper_id": "588ad9cd788e0631c93e4164f98489d9b3f30811", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell-surface receptors such as DPP4 play a key role in facilitating viral invasion and tropism. As a consequence, the long-term co-evolutionary dynamics between hosts and viruses often leave evolutionary footprints in both receptor-encoding genes of hosts and the receptor-binding domains (RBDs) of viruses in the form of positively selected amino acid residues (i.e. adaptive evolution). For example, signatures of recurrent positive selection have been observed in ACE2 genes in bats [9] , supporting the past circulation of SARS related CoVs in bats. To better understand the origins of MERS-CoV, as well as their potentially long-term (compared to short-term which lacks virus-host interaction) evolutionary dynamics with bat hosts [5, 10] , we studied the molecular evolution of DPP4 across the mammalian phylogeny.", "MERS-CoV may parallel that of the related SARS-CoV [22] . Although one bat species, Taphozous erforatus, in Saudi Arabia has been found to harbour a small RdRp (RNA-Dependent RNA Polymerase) fragment of MERS-CoV [17] , a larger viral sampling of bats and other animals with close exposure to humans, including dromedary camels were serological evidence for MERS-CoV has been identified [23] , are clearly needed to better understand the viral transmission route. Alternatively, it is possible that the adaptive evolution present on the bat DPP4 was due to viruses other than MERS-CoVs, and which will need to be better assessed when a larger number of viruses are available for analysis. Overall, our study provides evidence that a long-term evolutionary arms race likely occurred between MERS related CoVs and bats. ", "Background: The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) that first appeared in Saudi Arabia during the summer of 2012 has to date (20th September 2013) caused 58 human deaths. MERS-CoV utilizes the dipeptidyl peptidase 4 (DPP4) host cell receptor, and analysis of the long-term interaction between virus and receptor provides key information on the evolutionary events that lead to the viral emergence. Findings: We show that bat DPP4 genes have been subject to significant adaptive evolution, suggestive of a long-term arms-race between bats and MERS related CoVs. In particular, we identify three positively selected residues in DPP4 that directly interact with the viral surface glycoprotein. Conclusions: Our study suggests that the evolutionary lineage leading to MERS-CoV may have circulated in bats for a substantial time period." ] },{ "paper_id": "588bebe109353fc242f41c7655aa3bf906cecc3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "589045646462acd78b115142b5464cca998f26d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "589bb887a113e04b714724a7ec3589037449dc39", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Students' t-Test with equal variance was used to compare RL 2/2 and wt C57BL/6 mice. Significant differences between groups are noted by: *, = P#0.05.", "One-half brains and whole spinal cords were snap frozen in liquid nitrogen and stored at 280uC. Frozen brain or spinal cord tissue was homogenized in 2 mL and 1 mL Trizol reagent (Invitrogen, Carlsbad, CA), respectively, in RNase-free Tenbroeck glass grinders. RNA was purified according to the manufacturer's protocol (Invitrogen, Carlsbad, CA). Briefly, 0.2 mL chloroform/ 1 mL trizol (Sigma-Aldrich, St. Louis, MO) was added to homogenate, mixed and centrifuged at 12,0006g for 15 minutes at 4uC. RNA was precipitated from the aqueous phase by addition of isopropyl alcohol and centrifugation at 12,0006g for 10 min at 4uC washed in RNase-free 75% ethanol and resuspended in Ultrapure DNase/RNase-free water (Invitrogen, Carlsbad, CA). Cells isolated by FACS were immediately resuspended in 400 mL of Trizol reagent (Invitrogen, Carlsbad, CA) and treated as above.", "Isolated total RNA was treated with DNase1, using the DNA-free kit (Applied Biosystems, Foster City, CA) following the manufacturer's protocol. The concentration and purity of RNA was measured by spectrophotometry at 260/280 nm. RNA integrity was confirmed by 1.2% formaldehyde-agarose gel electrophoresis." ] },{ "paper_id": "589fe7dd846e7bbab5e7d6dacf7fab2ca6c4f340", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study has been approved by the Clinical Research and Ethical Review Board of the Royal Veterinary College (project number 3597).", "During the field activities, the data was recorded on paper questionnaire forms and subsequently entered and checked by the primary investigator into a Microsoft Access database. Data analysis was performed using the R software version 3.3.0 [29] and the MASS package [30] . Spatial data analysis was performed using ArcGIS Desktop version 10.1 [31] .", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "58a0105289bbee3214a3fe6494ba86fce867df3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Adenoviruses (Ad) are commonly used as vectors for gene therapy and/or vaccine delivery.", "DNA was purified from Ad, rAd-core, rAd-NS3, rAd-NS4, rAd-NS5a and rAd-NS5b vector stocks. Briefly, 1x10 8 pfu of each vector was taken in individual tubes and DNA was prepared by using High-Pure Viral Nucleic Acid KitR (cat.# 11 858 874 001, Roche Applied Bio). PCR reaction was set up with 10 \u03bcl template DNA obtained from the above preparation using 50 \u03bcl total reaction volume consisting of 1x PCR buffer, 10 \u03bcM dNTP, 25 \u03bcM of each primer (forward and reverse, listed in S2 Table) and 1.25 unit of Taq polymerase. PCR tubes containing reaction mixtures were incubated in a thermo-cycler with initial denaturation at 92\u00b0C and 40 amplification cycles (92\u00b0C: 30 Sec, 50-55\u00b0C: 30 Sec, 68\u00b0C: 60 Sec). PCR amplification products were run on 1% agarose gel at 80 volts to resolve amplification products along with 1 KB sized Quick Load DNA Ladder (Cat.# N0468S, NEB Biolab, Germany).", "Data were analyzed by Graph-pad Prism software (Graph-pad Software Inc., CA, USA). Two tailed student t-test was used to determine the significant difference between two groups, and P-values less than 0.05 (<0.05) were considered to be statistically significant." ] },{ "paper_id": "58a21f91c8d3c79e8be084088092f29dec2fc4d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It is known that the same TFs can repress or activate transcription depending on cell type and specific promoter sequence. There can be different coexisting modes of TF action: direct activation or repression, indirect activation or repression via interaction with cofactors, induction or suppression by disruption of binding sites and other 55 . Given complex and optional interactions of TFs with TFBS, our in silico analysis was not either definitive or exhaustive but rather tentative and suggestive with an intension to test the approach for further more detailed investigations supported by experimental data.", "variations being performed for the genes of TNFa 4 , MBL2 5 , IL6 6,7 , IL10 7 , and FCGR2A 6 with no association effect and for the loci ACE 8 and TLR4 9 found to be associated with pneumonia. Several studies showed that genetic associations of sepsis in pneumonia differ from those in other infections [10] [11] [12] and may in particular depend on a specific pathogen 13 .", "CAP and HAP case-control studies. The study protocol was approved by the Ethics Committee of the V. A. Negovsky Research Institute of General Reanimatology (with IRB approval number 2/6/2012), and adhered to the tenets of the Declaration of Helsinki. Informed consent was obtained from all subjects." ] },{ "paper_id": "58a9c23ad5702fdc007f682342e3a77fe5516a8f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were expressed as mean \u00b1 SD from at least three independent experiments. Statistical analysis was performed by Student's t-test or Newman-Keuls Multiple Comparison Test, using SPSS 11.5 statistical software. All statistical tests were two-sided and p values < 0.05 were considered statistically significant." ] },{ "paper_id": "58b271e61f06e148dd80d5dbf0c037118dcc9963", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HIV-GminA, HIV-GminB, and HIV-GminC were also highly attenuated in MT-4 cells (p < 0.001) ( Figure 4 ).", "All of the synthetic HIV-1 variants used in this study are based on the HXB2 strain (http://www.hiv.lanl.gov)." ] },{ "paper_id": "58bb44f68691a167fdfb89c3a90f8fe520e37d06", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "58bb89f7722922bd9a47cd49e172c498d5cd73cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following grant information was disclosed by the author: King Abdul-Aziz City for Science and Technology (KACST). MERS-CoV research grant program: 20-0004. Targeted Research Program (TRP).", "This work was funded by a grant from the King Abdul-Aziz City for Science and Technology (KACST), through the MERS-CoV research grant program (number 20-0004), which is part of the Targeted Research Program (TRP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.", "MERS-CoV may infect a wide group of people ranging from very young ages, even infants less than one year of age, to 109 years of age (CDC, 2016) . However, children are less likely to be infected with MERS-CoV when compared to adults and, if infected, they tend to have asymptomatic or mild disease (Arwady et al., 2016) . The reason for this is still not entirely clear and requires further study.", "The case fatality rate is always very high in case of the immunocompromised infected patients especially those who are suffering from chronic diseases such as cancer, diabetes, blood pressure, kidney problems, etc. (Arwady et al., 2016) ." ] },{ "paper_id": "58d1eab77cf8a541864220d8b3130336881891b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A written informed consent was obtained from the owners of each patient for publication.", "Hematology, biochemistry, fasting bile acids, thyroxine levels, and urinalysis were unremarkable. Feline leukemia virus antigen and feline immunodeficiency virus antibody tests were negative (SNAP FIV/FeLV Combo test; IDEXX, Maine). Systolic blood pressure measured upon admission using Doppler sphygmomanometry was considered within normal limits for a hospital environment (mean reading = 151 mmHg).", "A standardized MRI protocol was used in all cats to assess the brain including the following sequences: fast-spin T2, T2 fluid attenuated inversion recovery (FLAIR), T2 * gradient-echo, spin echo T1, spin echo T1 post-contrast in transverse planes and fast-spin echo T2 in sagittal plane." ] },{ "paper_id": "58d91841094c91e8269b22337c66dfa16e04b965", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Continued research into what differentiates murine and human noroviruses and how norovirus infection affects the host cell is therefore of upmost importance to both fields of research.", "The following 28 full length genomic sequences were downloaded from GenBank and used for bioinformatic prediction of open reading frames: DQ223042, EU854589, EU004665, FJ446720, FJ446719, AB435514, EU004660, EU004672, EU004679, EU004681, EU004682, EU004674, EF531291, EU004673, EF531290, DQ911368, EU004683, EU004670, EU004668, EU004663, EU004671, EU004664, EU004677, EU004676, DQ223041, DQ223043, EU004678 and EU004680. Sequences were selected based on showing .1% sequence divergence from all other sequences and thus representing different MNV isolates.", "In vitro translation of the MNV-1 subgenomic RNA produces three proteins, VP1, VP2 and VF1" ] },{ "paper_id": "58ebd3ddb3543355def684c9762e4e24388c61bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusion: Some measures, particularly good air ventilation in SARS wards, may be effective in minimizing or preventing SARS transmission among HCWs in hospitals.", "In summary, good air ventilation in wards and a series of simple control and preventive measures might decrease or prevent SARS transmission among HCWs in hospitals." ] },{ "paper_id": "58f68e82f134cf3549778fca86251ee61975b596", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quantification of band intensities in Western blots of figure 2B was carried out using the Image J software [31] ." ] },{ "paper_id": "58f93bf42d2c4e21ed8effe492719d992849eff6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using the GraphPad Prism version 4.0 software (GraphPad Software Inc., La Jolla, CA, USA). The Student t test was used to investigate significant differences between groups. Values of P,0.05 were considered statistically significant. ", "Conclusions/Significance: Due to its cost-effectiveness, high production yield and varied range of possible applications, polyclonal IgY antibodies are useful tools for studies involving T. gondii." ] },{ "paper_id": "58f9cce5d568b8cc7c7eb62a3b03b476a5ced52d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Katherine T. Jones offered valuable comments during the writing of this manuscript and her contributions are greatly appreciated. This work was supported in part by NIH grant 2 G12 RR003061-2.", "Viruses can induce cancer in species outside their natural hosts (80) (81) (82) . However, not all viruses, especially those of avian origin, easily transmit directly to humans in nature (79) . Canadian wildlife personnel, who handle wild ducks when they are shedding high levels of virus, consistently have negative viral and serologic assays (83) . Volunteers inoculated with high doses of avian subtypes H4N8, H6N1, and H10N7 failed to produce a detectable antibody response, even though~25% shed virus and had mild clinical symptoms (83) . Only 2 of 27 persons in a sample of chicken farm laborers and residents regularly in contact with infected chickens and wildfowl tested positive for antibodies to Rous sarcoma virus-Bryan (RSV-B) (84) . On the other hand, pigs have receptors for both avian and human viral strains and likely serve as a \"mixing vessel\" for genetic reassortment and subsequent introduction of genes into humans (85, 86) .", "While few epidemiologic studies alone provide convincing evidence of an animal microbial basis for cancer, the data nevertheless are suggestive of a possible effect when examined as a whole. Perhaps the excess risk observed for some cancers, but not necessarily the same cancers across studies, may reflect a random cancer susceptibility to infection and inflammation rather than a specific microbe-cancer relationship. By analogy, animal viruses and bacteria may represent a chambermaid's master key, capable of opening all hotel doors, but only if left unlocked by the guests.", "Avian viruses can directly infect humans without passing through pigs as evidenced by the recent outbreaks of influenza A strains H5N1 (87, 88) and H9N2 (89) in Asia, and H7N7 (90) in Netherlands (78, 91) . The history of human infection closely parallels the domestication of the duck, which introduced respiratory-type influenza A viruses into the \"farmyard (91) .\" H5 subtype infection initially was detected in human sera from rural China, a region known for poultry farming (87, 92) . Approximately 30% of poultry workers sampled around the time of the 1999 H9N2 flu outbreak in Hong Kong were found to be seropositive for antibodies to the virus (89) . H9N2 viruses are prevalent in domestic poultry such as chickens, ducks, geese, quail, and pigeons throughout Asia (89) . In Netherlands outbreak, investigators reported a high infection rate of H7N7 among people directly involved in handling infected poultry and noted evidence for person-to-person transmission (90) .", "The transmission route for over 200 (~14%) human pathogens remains unknown and zoonotic transfer or species jumping cannot be ruled out as a potential source of infection (1). Among known routes, infected feces and urine remain one of the most prominent modes of transmission whether by primary or secondary sources. Animals that are not susceptible to infection may still spread disease to other animals and humans if they become contaminated and share water or food sources (103) . However, for domestic poultry, secondary transmission often is associated with human involvement in the agriculture setting through personnel and/or animal movement, food delivery, and the use of fomites (103) . Because poultry often do not display clinical signs of infection they may not be quarantined from other animals or their human caretakers (103) . Furthermore, the increasing global demand for poultry and meat products coupled with improvements in transportation, have propagated closer contact between humans and farm animals (104) ." ] },{ "paper_id": "5900930fcaa79a701a7a31a05c3fb85232f31fc6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mice were anaesthetized and perfused transcardially with ice cold PBS and 10% formalin. Perfused kidneys were dehydrated, embedded in paraffin, sectioned at 4 mm thickness and mounted on glass slides. Paraffin sections were stained with periodic acid-Schiff (PAS) and Masson's trichrome and examined under light microscopy.", "After treatment, mice were euthanized by decapitation and trunk blood was collected in ice-chilled heparinized tubes. Blood was centrifuged at 10,0006g for 10 minutes at 4uC. Plasma was separated, aliquoted and stored at 280uC. Tissues were removed from mice, frozen in liquid nitrogen, and stored at 280uC. All experimental procedures were approved by the Wright State University Animal Care and Use Committee.", "Mice were placed individually in metabolic cages for 24-hour urine collection with free access to food and water. Urine specimens were collected every 12 hour and kept at 4uC until the 24-hour collection period was completed. To prevent protein degradation, a total of 10 ml of protease inhibitor (Roche Diagnostics, IN, USA) was added to the collection tubes during the 24-hour collection period. Urine samples were centrifuged at 10,0006g for 5 min at 4uC to remove debris and supernatants were aliquoted and stored at 280uC for later use." ] },{ "paper_id": "5908982f4dbbfde0faabcfadc0988b8a19223411", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Poly(I:C) and 2-5A transfections Cells plated in 24 well-plates were transfected with 2.5 mg poly(I:C) per ml (Amersham-Pharmacia) or 5 mM unfractionated 2-5A (prepared as described in [19, 60] ) using 2 ml Lipofectamine 2000 transfection reagent according to the manufacturer's protocol (Invitrogen).", "L* ectopic expression prevents poly(I:C) and 2-5Amediated rRNA degradation", "Poly ", "To test FS96 persistence, female 3-week-old FVB/N (Charles River Laboratories) were anesthetized and infected intracranially by injection of 40 ml of serum-free medium containing 10 5 PFU of the virus. Control mice were injected with 40 ml of serum-free culture medium. At 45 days post-infection, total RNA was extracted from the spinal cords of infected mice as previously described [59] ." ] },{ "paper_id": "5909957e376b289b8aa76f7c40ac4db57084ac52", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As a swine enteric coronavirus, PEDV is an enveloped, positive-sense, single-stranded RNA (ssRNA) virus [8] . e PEDV genome of 28.5 kb is polycistronic and consists of ORF1a, ORF1b, ORF3, spike protein, envelope protein, membrane protein, and nucleocapsid protein [9] . PEDV", "e authors declare that there are no conflicts of interest." ] },{ "paper_id": "590dc551804c7579ac9623ee64f81d1186261faa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Text S1 Stable cell line generation. (DOCX)", "For superior membrane preservation, samples were processed by high pressure freezing-freeze substitution (HPF-FS). Cells were grown in glass-bottom dishes (MaTek Corp.) on top of sapphire discs with a carbon finder-grid mask and coated with poly-L-lysine. At appropriate time post infection with MOI of 100, the dishes were processed directly for HPF as follows: Discs were removed from media, placed between hexadecane-treated aluminum specimen carriers with a 0.1 mm cavity and immediately transferred to LEICA HP010 holder and processed by HPF. Discs were then transferred from liquid nitrogen to the cryovials containing freeze-substitution medium (1% OsO 4 and 0.2% uranyl acetate in Acetone) and then to FS device (LEICA AFS1) for FS processing with final embedding in EPON.", "Movie S12 Volume rendering and color annotations for SIF. SIF inner membrane (yellow), SIF outer membrane (orange), and Salmonella (green) corresponding to Movie S11 and Figure 10B ." ] },{ "paper_id": "5912189e6ca5053f8e7a2de341c90341f737aa7e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were entered in duplicate for quality control. Analysis was performed using existing software (SPSS, version 19.0; SPSS). Continuous variables were analyzed by Student's t-test or Mann-Whitney U test for parametric and nonparametric data, respectively. Categorical variables were evaluated by chi-squared, Fisher's exact test, or Spearman correlation. Multiple nonparametric groups of continuous variables were analyzed by Kruskal-Wallis testing. All p-values are two-tailed and statistical significance at p ,0.05. Table 2 , and seasonal variation presented in Figure 1 .", "Primers and probes used have been reported for adenovirus by Heim et al. [19] All qPCR was conducted using Applied Biosystems 7900 and 7500 real-time PCR instruments (Applied Biosystems, CA).", "For adenovirus testing, cycling was conducted with 500 nM concentrations of both forward and reverse primers and 300 nM concentration of probe. Reaction conditions included an initial 10 min denaturation at 95uC, followed by 45 cycles of 95uC for 15 sec and 60uC for 1 min. A specimen was considered positive if its cycle of threshold (Ct value) was equal to or less than 40, as described previously. [19, 20] ." ] },{ "paper_id": "5926e0775494fcad788d2e93e3a5ddac4d5aeb0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Objective: This paper describes the physical structure and environmental contamination in selected hospital wards in three government hospitals in Bangladesh.", "The study protocol was approved by the Ethical Review Committee of the International Centre for Diarrhoeal Disease Research, Bangladesh (FWA # 00001468, Human Welfare Assurance # 00001822). The team obtained informed consent from hospital authorities for data collection and secured written consent from participants before conducting discussions. They observed public behavior and individuals were not identified.", "Since the hospitals were also teaching facilities, medical students accompanied senior physicians on their rounds. On one ward, 37 students accompanied two doctors for almost an hour. Students stood nearby or sat on patient beds. Below is the description of a pediatric ward from the observation notes." ] },{ "paper_id": "592c1efd20dcb1ff5644f5d20e76f2c28a2b8da0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HPV, most often HPV16, is the primary etiological agent responsible for cervical cancer [12] . While cervical cancer rates in more developed regions have dropped due to implementation of screening programs, it ranks as the second leading cause of cancer death in less-developed regions where such programs are not available [13] . In addition to cervical cancer, HPV has also been associated with head and neck cancer as well as several other ano-genital cancers [14] . Despite the recent advent of commercial prophylactic HPV L1 VLP-based vaccines targeting the major high-risk cancer-causing types, the high cost of production and requirement for refrigeration make these vaccines inaccessible to most of the individuals in low resource settings, who demonstrate the greatest need for vaccination [15] .", "Presence of L2 and encapsidated DNA do not interfere with HPV immunogenicity when HPV PsVs are applied by microneedles", "doi:10.1371/journal.pone.0120797.g003 recently developed technology such as patches and hollow microneedles [2] . Also, dissolvable microneedle patches composed of water-soluble excipients represent perhaps the most promising alternative technology and should be examined in future studies [37, 46] ." ] },{ "paper_id": "593333395be3bd94387b4e273cc8ed13b398d5c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PCR products were resolved on 2% agarose gels in 1xTAE buffer as indicated, and the images captured using the Vilber Lourmat Fusion FX gel documentation system.", "The myogenic cells were transfected, 3 days after the initiation of myogenic differentiation, with the 23mer AO complexed with Lipofectamine 2000 1 (1:1 w/w) in Opti-MEM media (Gibco) as per the manufacturer's instructions. AO concentrations of 2.5, 5, 10, 25, 50 and 100 nM were used and the cells were then incubated at 37\u00b0C for 3 days before RNA extraction.", "doi:10.1371/journal.pone.0145620.g004", "All experiments performed on animals were approved by the University of Western Australia Animal Experimentation Committee (approval number RA4/100/702) and carried out in strict accordance with the recommendations in the National Health and Medical Research Council Australian code for the care and use of animals for scientific purposes 8th edition (2013)." ] },{ "paper_id": "5934262a2b502aa5c1312dca72507395da00ccbe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Waiting for the results of susceptibility tests to select an effective antituberculosis drug regimen often causes a delay in effective treatment which can be disastrous, especially in children.", "Neopterin for which high quality ELISA systems to measure urine and blood levels are commercially available is an underused marker in clinical practice and is suitable for introduction into the routine clinical laboratory practice.", "The author declares that there is no conflict of interests regarding the publication of this paper.", "Because the X-ray changes tend to resolve very slowly and may get even worse after starting therapy because of a paradoxical reaction due to immune-reconstitution even in otherwise immune-competent patients, other than clinical status there is no reliable parameter to reflect success or failure of the drug regimen [77] ." ] },{ "paper_id": "5938b0be5d7696d37c227bc647bcbc3f7f3ae18b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recombinant NTCP-GFP and GFP proteins were incubated with different concentrations of compounds in 50 mM potassium phosphate buffer (pH 7.0) containing 100 mM NaCl, 0.2% BSA, and 0.005% DDM (n-Dodecyl\u03b2-D-maltopyranoside) for one hour at room temperature. Samples were loaded on Monolith NT.115 Standard Treated Capillaries (Nano Temper Technologies) and analyzed with a Monolith NT.115 Blue Red microscale thermophoresis instrument.", "All graphs represent means and standard deviations. The statistical significance of differences between two groups was tested using a two-tailed unpaired t test with Prism 6 software (GraphPad). ", "KM designed and performed research, analyzed data, and wrote the manuscript; SM, YY, MD, and KF performed research and analyzed data; HK and TC analyzed data; HN, KW, KS, and TW contributed reagents and analyzed data; and AR designed and supervised the research, analyzed the data, and wrote the manuscript." ] },{ "paper_id": "593d2241563c6bf2e57327ce40e7e83dacbd80fc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MAb-based immunotherapy is becoming important in infectious diseases because of widespread resistance to drugs among pathogens, immunocompromised hosts, and the emergence of new pathogens. For controlling pathogens such as acute cytopathic viruses that can cause fatal damage in infected tissues, the best way is to prevent the disease.", "search for sequence against nonredundant database (NCBI) (Note 4).", "(iii) Spin briefly and mix Opti-Mem with plasmid and Lipofectamine together into the same tube. Incubate for 20 minutes at RT." ] },{ "paper_id": "595019b82939f4fc62cda92fe6eedd34f6933c35", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lung airways are perpetually exposed to inhaled particulate materials that include pollens, viruses, bacterial and fungal spores [1] . While many of these particles are innocuous, some spores have the potential to germinate and cause invasive lung diseases [1] . A recent theory suggests that infections could also trigger lung cancerogenesis [2] . This hypothesis has been formulated mainly for viruses, although it has been not excluded that also bacteria and fungi could be involved.", "Aspergillus colonies were subcultured for subsequent identification to species level. Species names were determined by following the taxonomic keys of Klich [18] . Culture were incubated for 7 days on CYA (Czapek Yeast Extract Agar) at 25\u00b0C and 37\u00b0C, CZ (CzapekDox Agar) and MEA (Malt Extract Agar) at 25\u00b0C to enable morphological features exploited as diagnostic characters. Penicillium colonies were identified only at genus level.", "A p value of < 0.05 was considered statistically significant.", "Lung cancer is also characterized by airways inflammation, that usually follows cigarette smoking which is likely to play a role in cancer transformation [4, 5] . The inflammatory status also further compromises host lungs, promoting tissue invasion and systemic dissemination of the infection [4, 5] ." ] },{ "paper_id": "59532e3fbb23c6bca0ad86898cdf50817b38633f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Review. Emerging and endemic zoonoses surveillance J. Halliday et al. 2875", "Zoonoses are often underreported, and it is important to understand and tackle the reasons for this [5] . Many factors contribute to underreporting, arising from both an inability and an unwillingness to report (figures 1 and 2). The relative importance of these factors varies in different situations, but they often act in combination to stifle the collection and distribution of accurate and comprehensive data, particularly in resource-poor settings." ] },{ "paper_id": "595582a254c921f28d7c5cb9cb42e1dcabff7108", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bacterial Strains, Antimicrobial Susceptibility Testing, and Pulsed-Field Gel Electrophoresis (PFGE)", "Reaction temperatures ranging from 55 to 69 \u2022 C at a 2 \u2022 C intervals were compared to determine optimal amplification conditions. The amplification efficiency was highest at 65 \u2022 C ( Figure 2) and was, therefore, used in subsequent experiments.", "Frontiers in Microbiology | www.frontiersin.org " ] },{ "paper_id": "595f2518368eb7c7c56b8669bcf66978ac636ad1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5977507d38a03786e12e8e48cda0b431871af042", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conducting animal studies in BSL-4 severely restricts the number of animal subjects, the volume of biological samples that can be obtained and the ability to repeat assays independently and thus limit statistical analysis. Consequently, data are presented as the mean calculated from replicate samples, not replicate assays, and error bars represent the standard deviation across replicates.", "PRNTs were determined using a conventional serum neutralization assay. Briefly, sera were serially diluted twofold, and incubated with~100 pfu of NiV for 1 hour at 37\u00b0C. Virus and antibodies were then added to individual wells of 6-well plates of confluent Vero cell monolayers. Plates were stained with neutral red 2 days after infection and plaques were counted 24 hours after staining. The 50% neutralization titer (PRNT 50 ) was determined as the serum dilution at which there was a 50% reduction in plaque counts versus control wells.", "Animal studies were performed in BSL-4 biocontainment at the GNL at the UTMB at Galveston and were approved by the UTMB Institutional Animal Care and Use Committee (IACUC). Animal research was conducted in compliance with the Animal Welfare Act and other Federal statutes and regulations relating to animals and experiments involving animals and adheres to the principles stated in the eighth edition of the Guide for the Care and Use of Laboratory Animals, National Research Council, 2013. The facility where this research was conducted is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International." ] },{ "paper_id": "598afbc9be3b81a14195c3a45e3a4ca580e4958f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA viruses have developed numerous strategies to block or avoid PRR initiated host responses. For example, both HCV and DENV proteases cleave critical molecules involved in the early stages of RLR signalling pathways, resulting in the abrogation of downstream signalling and immune activation [34, 35] . Additionally, tick-borne encephalitis virus has been proposed to evade RLR activation through the formation of intracellular membrane structures that sequester viral dsRNA away from the cellular recognition factors [36] . Immune evasion by hiding viral PAMPs from PRRs has also been postulated for a number of other viruses, but this has not yet been experimentally confirmed [24] .", "For analysis of intracellular RNA transcript levels, total RNA was extracted from cells using Trizol (Invitrogen, 15596018) and cDNA was synthesized using random primers (Invitrogen, 48190-011) and superscript II (Invitrogen, 18064014) according to the manufacturers specifications. Primers for qPCR were designed using Primer3 software and primer sequences are supplied in S1 Table. PCR efficiency for each primer was determined using the slope of a standard curve derived from qPCR analysis of cDNA serial dilutions. qPCR was done using a SYBR green super mix (Quanta, 95070-500) on a Stratagene Mx3005p real time PCR machine. To obtain the relative abundance of specific RNAs from each sample, cycle threshold (ct) values were corrected for the specific PCR efficiency of the primer, and normalized to hypoxanthine phosphoribosyltransferase 1 (HPRT) transcript levels. For analysis of HCV RNA levels in subcellular fractions, RNA was isolated from 200 \u03bcl of the media obtained from infected cells using a High Pure Viral Nucleic Acid Kit (Roche, 11858874001). The cDNA was synthesized using superscript III (Invitrogen, 18080044) and an HCV specific primer (see HCV reverse primer sequence S1 Table) . qPCR was done using TaqMan Master Mix with HCV primers and labeled probe (S1 Table) .", "Subcellular fractionation was performed as previously described [37, 83, 84] . For details, see extended Materials and Methods (S1 Text)." ] },{ "paper_id": "598cb2d5c28e701d3f3533d2690dcc2202f10a8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors thank Joy Winzerling for her critical reading and editing of the manuscript.", "Author Contributions: All authors compiled the information, wrote the review, read and approved the final manuscript.", "The authors declare no conflict of interest. " ] },{ "paper_id": "59914aa651a598b95b58825690eeb4477c7777ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was financially supported in part by Yuhan Co. " ] },{ "paper_id": "5993ed074d10970cc93e82fc038ae239f61a16e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the generation of CRISPR-Cas9(D10A) knock-out constructs oligonucleotides defining the gRNA sequences were annealed in pairs and cloned into a modified pX335 vector (Addgene 42335) containing a GFP-puromycin selection cassette [70] [71] [72] and verified by sequencing: (1) forward: caccccaattacagcatgtgtaaa, reverse: aaactttacacatgctgtaattgg (2) foward: cacccagattggaggaaggggtg, reverse: aaacgcaccccttcctccaatctg (3) foward: caccgctctctgctaagcaggctg, reverse: aaaccagcctgcttagcagagagc (4) forward: caccagcaccctctgcttgaagct, reverse: aaacagcttcaagcagagggtgc.", "Plasmids and oligonucleotides. The OARD1 coding sequence was amplified from human cDNA using Gateway (Invitrogen)-compatible primers and cloned into pDONR/Zeo (Invitrogen). GW-p-N-TAP-C6orf130 was generated by Gateway recombination between pDONR/Zeo-C6orf130 and a Gateway-compatible pcDNA5/ FRT/TO-N-TAP vector 20 ." ] },{ "paper_id": "5999e5bdbde2e8bfb3389bfe0ea96e229245cf67", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nosocomial infections, such as methicillin-resistant Staphylococcus aureus (MRSA), pose a major challenge to clinical management and health policy [87] . Recent whole-genome sequencing (WGS) of MRSA clones made it possible to trace the origin, evolution and global spread of EMRSA-15, currently the most rapidly spreading and tenacious healthcare-associated clone in Europe [88] .", "Acute viral infections such as influenza also have profound impacts on global health [58] . In contrast to the yearly epidemics caused by seasonal influenza, a pandemic can occur when a new virus emerges in a naive population and is readily transmitted from person to person [59] . The US Centers for Disease Control (CDC) estimates that the H1N1 2009 pandemic resulted in 41 to 84 million infections, 183,000 to 378,000 hospitalizations, and nearly 285,000 deaths worldwide [60] . Although the morbidity and mortality of that pandemic were lower than feared, public health professionals continuously monitor for the emergence of more virulent strains [61] .", "In addition to influencing the actual behavior of highrisk individuals, genetic information could affect attitudes and beliefs about the individuals who engage in risky behavior. The knowledge that a genetic variant increases the risk of spreading a sexually transmitted disease might lead to negative judgments about, and marginalization of, individuals who carry that variant. Discrimination against entire subgroups could also occur if, for example, genetic variants were found to correlate with a more favorable vaccine or treatment response, but only in certain ethnic groups; also, drug development might focus on these 'more responsive' subgroups.", "These are just a few examples of other types of infectious diseases for which genomic advances may play a role in prevention and control, with corresponding ELSI issues.", "In addition to diseases that are transmitted from human to human by air, blood or other bodily fluids, there are entire classes of globally burdensome infectious diseases that have different modes of transmission but exhibit similar variability in degrees of preventability, infectivity, transmission risk, treatability and chronicity." ] },{ "paper_id": "599be9828fd5c11926e88c8474f37f67f1fe4ebc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A comprehensive study on these questions will certainly shed new lights in the UPR pathways, and assist in a better understanding of host-virus interactions and, in the long run, developing novel antiviral strategies.", "December 2012 | Volume 3 | Article 293 | 9", "December 2012 | Volume 3 | Article 293 | 11" ] },{ "paper_id": "599f44a88bfd9fcd7cc5b03f3b0bf01c9b3c5ba8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Comparison of log-normal, gamma, Weibull, and Ehrling distributions." ] },{ "paper_id": "59a11e8976b666ba112da942d7ba7c698d06a9e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The chicken embryo fibroblast cell line (DF1), human epidermoid carcinoma cell line (HEp-2), and African green monkey kidney cell line (Vero) (ATCC, Manassas, VA, USA) were grown in Dulbecco's minimal essential medium (DMEM) with 10% fetal bovine serum (FBS) and maintained in DMEM with 5% FBS. Primary chicken neuronal cells were grown in Neurobasal medium with B-27 supplement (Invitrogen, Carlsbad, CA).", "The APMVs are frequently isolated from a wide variety of avian species worldwide. APMV-1 has been isolated from most species of birds and, as noted, can be highly pathogenic and has a major agricultural impact. APMV-2 and -3 also have been reported to cause significant disease in poultry [17] [18] , whereas the pathogenic potential of serotypes 4-9 is generally unknown [19] . APMV-4 strains have been isolated predominantly from feral birds of the order Anseriformes [20] and from domestic ducks, chickens, and geese [21] [22] [23] . APMV-4 has been reported to cause an increase in white-shelled eggs but did not affect the egg production in laying hens [2] . The genome of the prototype APMV-4 strain duck/Hong Kong/D3/75 consists of 15,054 nt [10] , which follows the ''rule of six'' common to other members of subfamily Paramyxovirinae. APMV-4 encodes a nucleocapsid protein (N), a phosphoprotein (P), a matrix protein (M), a fusion glycoprotein (F), a hemagglutinin-neuraminidase glycoprotein (HN), and a large polymerase protein (L). The genes are flanked on either side by highly conserved transcription start and stop signals and have intergenic sequences varying in length from 9 to 42 nt. The genome contains a 55 nt leader region at the 39 end. The 59 trailer region is 17 nt, which is the shortest in the family Paramyxoviridae.", "The various tissue samples harvested from infected 2-week-old chickens and 3-week-old ducks were fixed in phosphate-buffered formalin (10%), embedded in paraffin, and sectioned (Histoserv, Inc., Germantown, MD). Sections from mock-infected birds were used as controls. The tissues were deparaffinized, rehydrated, and subsequently, immunostained to detect viral N protein [36] ." ] },{ "paper_id": "59a34f8561b8a70870682450d318e81fc0820676", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The total white blood cell count, lymphocyte, platelet, reticulocyte and red blood cell counts, hemoglobin, hematocrit values, mean cell volume, mean corpuscular volume, and mean corpuscular hemoglobin concentrations were determined from EDTA blood with the HemaVet 950FS+ laser-based hematology analyzer (Drew Scientific, Waterbury, CT). Serum biochemistry was analyzed using the Piccolo Xpress Chemistry Analyzer and Piccolo General Chemistry 13 Panel discs (Abaxis, Union City, CA).", "All data were analyzed by Prism software (GraphPad, version 5.0 d). Statistical analysis was performed using unpaired t-test with Welch's correction to compare two groups and represented as twotailed p-value with a confidence interval of 95%. Presented results show the mean of measurements within a group. For all statistics, the following notations are used to indicate significance between two groups: *p,0.05, **p,0.01, ***p,0.001. ", "Levels of viral RNA were determined using quantitative RT-PCR (qRT-PCR) as described previously [12] . For determination of virus titers in NHP blood and tissue samples, Vero E6 cells were seeded in 48-well plates the day before titration. Blood samples were thawed and serial dilutions were prepared. Tissues were homogenized in 1 ml plain DMEM and, as with the blood, serial dilutions were prepared. Media was removed from cells and triplicates were inoculated with each dilution. After one hour, DMEM supplemented with 2% FBS, penicillin/streptomycin and L-glutamine was added and incubated at 37uC. Cells were monitored for cytopathic effect (CPE) and 50% tissue culture infectious dose (TCID 50 ) was calculated for each sample employing the Reed and Muench method." ] },{ "paper_id": "59ac4eae51d6084c2346ebd27125a3b56e25d72e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Both infections are chronic in nature and develop through different disease stages. Characteristically for both infections, there is a long asymptomatic phase, in which cats do not show clinical signs.", "Clinical signs in both retrovirus infections are variable. After a long asymptomatic phase, cats can develop tumors, hematopoietic disorders, neurologic disorders, immunodeficiency, immune-mediated diseases, and stomatitis. The pathomechanism of these disorders is different in both retrovirus infections (Table 2) .", "Myelosupression and other hematopoietic disorders can occur in both, FeLV and FIV infection. It is, however, much more common and more severe in FeLV-infected cats." ] },{ "paper_id": "59acd41ff6a97e730a76fd661b5e10d8cf5290b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "WoS: Web of Science; KSA: Kingdom of Saudi Arabia; USA: United States of America; JCR: Journal citation report; SCR: Standard competition ranking; IFs: Impact factors.", "Of the 2,408 documents considered for the h-index, 64 had been cited at least 64 times at the time of the data analysis. Analysis of citation revealed that the Arab country with the highest h-index was Egypt (h-index = ", "Additional file 1: Multilingual abstracts in the six official working languages of the United Nations.", "Please see Additional file 1 for translation of the abstract into the six official working languages of the United Nations." ] },{ "paper_id": "59ae1705d9fe9d34f1d7996bea46a83eacf92f47", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(3) (4) ", "where n is the number of reflections and p is the total number of parameters refined.", "Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/20/04/5771/s1." ] },{ "paper_id": "59b6229ca07d737a197ae0708282a1f6ed4fa435", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Methods were performed in accordance with relevant guidelines and regulations.", "npj Vaccines (2017) 2:15 ;" ] },{ "paper_id": "59c41eef8e1d079fc6d1de1cf07cd989c8456d1c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Furthermore, performing now the following non-dimensionalization", "from the dimensional Eqs (1)-(4) we obtain the associated dimensionless equations with a smaller set of essential control parameters, namely:", "The analysis was carried out using the method of [11] with sample size 10000." ] },{ "paper_id": "59c761eaa72007b50d08705d896c18b2802e2cbb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This case highlights the complicated nature of treating the PRS airway. Treatment continues to be highly individualized and dependent on a variety of factors, including severity of the airway, provider experience, and associated syndromes.", "Four months later, per dentistry the patient's mandibular alveolus was better aligned but the teeth remained crowded and calculus was present. Repeat sleep study 5 months after surgery was essentially normal. At last follow-up, the patient has continued to do very well for the last 2.5 years (Fig. 3 ).", "Conceptualization: Brooke French. Data curation: Robyn Randall, Aaron Kian. Formal analysis: Robyn Randall." ] },{ "paper_id": "59cbbd255acc779e36311d1c4f5be34bdc904888", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusions: Overall, HMPV genetic diversity and viral load did not impact symptom severity in adults with acute respiratory tract infections. Differences in viral load dynamics over time between genotypes may have important implications on viral transmission.", "Human metapneumovirus (HMPV) is a negative-stranded RNA virus classified in the Pneumoviridae family [1] . HMPV infections are commonly associated with mild respiratory symptoms, but severe cough, bronchiolitis and pneumonia have also been reported, sometimes accompanied by high fever, myalgia and vomiting [2] . Several risk factors associated with more severe disease due to HMPV infection in adults have been identified, which include patients with pulmonary disease or congestive heart disease, healthy elderly patients with age over 65 years old, long term stay in hospital care facilities and immunocompromised patients [3] .", "Although HMPV genetic diversity continues to be described and linked with disease severity in hospitalized children [6] , pediatrics [13] , elderly adults [10] and immunocompromised patients [3] , reports that address this association have been limited in the adult outpatient settings. A recent study which showed that HMPV can also cause respiratory outbreaks in adults [14] highlights the fact that adults may play a role in the transmission and evolutionary dynamics of the virus, and more severe disease could occur in adults during an outbreak." ] },{ "paper_id": "59cd9fecfcd1ef7eb2bbe427809ef0fd01e894b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For RNA stability assay, RNAs were incubated with wheat germ extract supplemented with all amino acids. At various time points of post incubation, viral RNAs were isolated and analyzed by Northern blotting.", "All the PCR products were cloned into the pGEM\u00ae -T Easy vector (Promega, Madison, WI, USA) and verified by DNA sequencing. The SapI 6207 -to-SacI (located 3\u2032 to the insert) fragment was then subcloned into pBS2-8 to replace the corresponding SapI-to-SacI region. Because pBS2-8 has two SapI sites, mutant constructs were done by three-fragment ligation and confirmed by DNA sequencing. These mutant plasmids were designated as pBaMV-S/P, -/ABCP, -/ABCDP, -/PABCDE, -/PDE, -/PE, and -/ABCPE, respectively (Figure 1) ." ] },{ "paper_id": "59cdfbf3b9e99d780b3ad6cf2985e34ec61e8f5a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "59cee2c2d1c8e2b5c732523f10682153c278395c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A 20 \u00b5L cell-free translation reaction containing 200 ng -FLAG-CUUUGA-mPK reporter plasmid was incubated at 37 \u2022 C for 4 h. The reaction was then mixed with phosphate buffered saline (PBS) buffer (137 mM NaCl, 2.7 mM KCl, 10 mM Na 2 HPO 4 , 1.8 mM KH 2 PO 4 , pH7.4) containing 1:100 dilution of anti-FLAG M2 (Sigma) in a final volume of 400 \u00b5L, and rotated overnight at 4 \u2022 C. The sample was then incubated with 160 \u00b5L Protein G Magnetic Sepharose Xtra (GE Healthcare) at 25 \u2022 C for 2 h with gentle shaking. Following incubation, the beads were washed three times with 320 \u00b5L PBS buffer, and boiled in 20 \u00b5L 5 \u00d7 SDS-gel loading buffer at 95 \u2022 C for 5 minutes to elute FLAG-tagged polypeptides. The elution fractions were resolved by 10% SDS-PAGE, and then stained with Coomassie Brilliant Blue R-250 (PanReac). After the gel was destained with destaining buffer (20% methanol, 10% glacial acetate acid), the target band was sliced for mass spectrometry (MS) analysis.", "The gel slice containing translation products excised from the resolved gels was cut into pieces for in-gel trypsin digestion. Briefly, the gel pieces were first washed with 25 mM triethylammonium bicarbonate buffer (TEABC) / 50% (v/v) acetonitrile (ACN). The washed samples were then reduced with 10 mM DTT at 65 \u2022 C for 1 h and alkylated with 55 mM iodoacetamide (IAM) at room temperature for another 1 h in the dark. Trypsin buffer (protein:trypsin = 40:1, w/w) was added to cover the gel pieces, and incubated at 37 \u2022 C for more than 16 h. Tryptic peptides were extracted by incubating with 5% formic acid (FA)/ 50% acetonitrile (ACN) for 15 min, and vacuum dried. The sample was dissolved in 12 \u00b5L 0.1% (v/v) formic acid (FA) and 4 \u00b5L used in LC-MS/MS analysis. The synthetic peptide standard was purchased from Kelowna International Scientific Inc. (Taiwan).", "As the first U of the E-site UAU codon juxtaposing the CUUUGA +1 frameshifting site in wildtype RF2 was reported to involve E-site invasion through base-pairing with anti-SD in 16S rRNA [24] , we performed E-site sequence mutagenesis to explore the mechanism of non-canonical -1 frameshifting. Interestingly, replacing E-site sequence from CGC to CGU dramatically diminished the -1 frameshifting product with the restoration of +1 frame product (compare lanes 4 and 5 in Figure " ] },{ "paper_id": "59d3750e2fc06cf47e64fbe18dd09649750e05cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Marked decline in cardiac function correlates with increased fibrotic deposition, impeding normal heart contraction. Fibrotic involvement is prevalent from a young age (17% of patients under 10 years), and escalates with age (34% between 10-15 years and 59% older than 15 years of age) [16] .", "Patients with DMD suffer from severe cardiomyopathy. Although the degree of cardiac involvement varies between patients, cardiomyopathy generally manifests at about 10 years of age and is prevalent in most patients by 20 years of age [6] . These patients first exhibit left ventricle (LV) dilation and hypertrophy, which progresses to a stage known as dilated cardiomyopathy (DCM). Additional cardiomyopathic features include decreased fractional shortening and electrocardiogram (ECG) abnormalities [7] [8] [9] [10] . Approximately 26% of patients also display tachycardia, and 51% exhibit an increase in pathological heart rate variability [7] . These ECG abnormalities are associated with morphological changes to cardiac muscle (thin and thick filaments of heart) [11] , myocardial fibrosis and conduction defects [12] . Indeed, deep Q wave abnormalities have been associated with lateral wall scarring [13] .", "No heart data. [142] [143] [144] " ] },{ "paper_id": "59d3f98d78f2ff993174b173807435e75df8bc3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Also the height of IIFT titers observed in our study, up to 1:1,280, corresponds to CCHFV-specific titers in experimentally infected wild mammals that reached endpoint titers of 128-1,024 by IIFT 47 . We conclude that African bat species have been infected with CCHFV or a closely related nairovirus in the same serogroup and probably the same species.", "As several cave-dwelling bat species migrate over various distances, bats might contribute to the geographic dispersal of CCHFV in similar ways as hypothesized for birds [9] [10] [11] . Future studies should aim to clarify whether the CCHFV strains carried by bats or bat ticks are identical or distinct from strains associated with birds or bird ticks.", "As shown by Ishii et al. the bat-related nairovirus LPHV was primarily detected in lung samples 15 . Therefore, destructive sampling involving the collection of organ tissue of designated bat species may be more promising for nairovirus detection as virus might persist for prolonged periods in parenchymatous organs such as the lung or liver 14, 15 . In the context of this retrospective study we did not test different organs from bats because most species are protected and were sampled without destruction or samples were exhausted from previous experiments 40, 41 .", "The identification of high neutralizing antibody titers (up to 1:160 based on full virus neutralization) indicates that bats experience infections followed by seroconversion, which in case of humans is correlated with clearance of the virus and survival of infection 48 . CCHFV might thus exemplify another highly pathogenic agent that is effectively controlled in bats." ] },{ "paper_id": "59d6529a7cd680c358b3caf56b8517ad61b82aca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The complete genome sequence of PEDV strain K14JB01 was deposited in Gen-Bank under accession no. KJ623926.", "A novel variant strain of porcine epidemic diarrhea virus (PEDV) emerged on pig farms in South Korea during late 2013. Genomic DNA isolated from a K14JB01 strain identified in a diarrheal pig showed high sequence similarity to PEDV strains prevailing in the United States in 2013. This is the first study to identify the complete genome sequence of a novel variant PEDV in South Korea.", "tion in the United States, and the viral genome showed a close relationship with that of variant strains identified in China (8) . Frequent outbreaks of PED have occurred in South Korea since the early 1990s; however, piglets infected with PEDV from November 2013 suffered from several enteric diseases, resulting in a high mortality. Here, the complete sequence of a novel variant PEDV strain, K14JB01 (isolated from an infected pig in South Korea), was sequenced and analyzed." ] },{ "paper_id": "59d9705d1665532f12f9014317352297b8a834e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Descriptive analyses were conducted to summarize the differences in ARI costs across the respiratory and nonrespiratory viral seasons. Poisson regression was used to assess the difference in cost per resident-day for influenza versus non-influenza seasons. Statistical significance was set a priori to 0\u00c105.", "A respiratory illness algorithm is used to guide diagnostic testing at this facility. For residents who present with signs and/or symptoms of ARI for greater than 48 hours, direct DOI:10.1111/irv.12350 www.influenzajournal.com Short Article 34 fluorescent antigen (DFA) testing is performed. If DFA is negative and symptoms persist, a viral culture is performed. If the resident remains symptomatic and both the DFA and viral culture are negative, the reverse transcriptase polymerase chain reaction (RT-PCR) testing is completed. All testing is performed at a referral laboratory.", "We conducted a retrospective cohort study from October 2012 to September 2013 at a 137-bed pLTCF in the New York metropolitan area. The cost of illness study was conducted from the facilities perspective. Residents ranged in age from 2 months to 21 years (mean = 9\u00c17 years) and length of stay ranged from 1 day to 21 years (mean = 4\u00c14 years). Approximately 85% of residents had a gastrostomy, 51% had a tracheostomy, and 12% were on mechanical ventilation. Residents have the following comorbidities: 90% neurologic disorder (e.g., intraventricular hemorrhage, hypoxic ischemic encephalopathy, agenesis of corpus callosum), 64% pulmonary disorder (e.g., chronic lung disease, congenital respiratory failure, bronchopulmonary dysplasia), 25% cardiac disorder (e.g., congenital heart disease), 26% premature (i.e., <37 weeks gestational age), and 10% genetic disorders (e.g., trisomy 18, trisomy 21). All eligible residents receive seasonal influenza vaccination. This study was approved by our institutional review boards." ] },{ "paper_id": "59e339e8a09eb0b00c603cbd5867d8edabc2151d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Currently available diagnostic tests used for dengue diagnosis in most dengue-endemic countries include commercially available IgM-and IgG-based ELISAs. These assays use dengue-specific antigens from all 4 serotypes (DENV [1] [2] [3] [4] and are designed to capture anti-dengue specific antibodies present in serum. However, serology tests are usually inconsistent since detection of antibodies requires appropriate collection times and test results may be confused with false-positive reactions due to the presence of antibodies from previous infections.", "The dramatic global spread and increased frequency and magnitude of epidemic dengue/dengue hemorrhagic fever (DEN/DHF) over the past 40 years underscores the critical need for more effective surveillance, prevention, and control measures. Most countries where DEN/ DHF is endemic do not conduct adequate surveillance as a means of assessing disease burden, nor do they possess adequate mosquito control or vaccine prevention programs. The lack of available, affordable, sensitive, and specific diagnostic tests represents the primary hurdle affecting DEN/DHF surveillance in resource limited countries. Early diagnosis of dengue patients is also critical to patient management since it prevents the administration of expensive (and ineffective) antibiotics, expedites the triage of febrile patients to appropriate clinics, and reduces health care costs. With the prospect of specific antiviral therapy in the near future, early diagnosis will be crucial in the identification of patients with dengue, allowing them to receive the proper care. Prompt diagnosis of index cases would also facilitate vector control activities in the community thereby mitigating further transmission.", "The genomic viral RNA was extracted from 140 \u03bcl of patient serum samples by using the QIAamp viral RNA mini kit (QIAGEN, Hilden, Germany). The RNA was eluted from the QIAspin columns in a final volume of 60 \u03bcl of elution buffer and was stored at -70\u00b0C until it was used.", "Virus isolation from acute-phase serum or plasma samples cultured in the presence of the C6/36 mosquito cell line remains the \"gold standard\", although the disadvantage of this approach is that results are not available for >7 days. Furthermore, isolation of dengue virus from clinical samples using the cell culture approach has generally been unsuccessful due to the fastidious nature of the virus and the low level of transient viremia associated with the disease process [1] ." ] },{ "paper_id": "59e3592ad1516fe1b4f4a1ea5a8cae320af5cf7d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(v) If any of these criteria is not observed, the sequence region homologous to reference sequences will be identified as a non-functional gene region, and will be marked as a possible sequence mutation.", "(i) Coding sequences must have both start and stop codons, or span the 5' or 3'-end of the input sequences for partial genomic sequences.", "\u2022 Project name: VIGOR \u2022 Project home page: http://www.jcvi.org/vigor \u2022 Operating System(s): Platform-independent \u2022 Programming Language: Perl and PHP \u2022 Any restrictions to use by non-academics: None.", "Arcturus is responsible for invoking the appropriate gene prediction program in the VIGOR package for the specified virus type. Currently, all jobs are executed on a single, dedicated server. The backend service is implemented to support scalability. The entire backend service was implemented in Perl." ] },{ "paper_id": "59e5392ae9728ae529623e00c6d2e411a931fffc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Questionnaire items regarding having a USC in the KHP survey were asked of adults aged 18 years and over.", "Statistical analyses were performed with SAS version 9.4 (SAS Institute, Cary, North Carolina, USA) software, with P = 0.05 or less regarded as a significant difference.", "Regarding longitudinality, the median duration \u00b1 interquartile range of a doctor-patient relationship was 5.0 \u00b1 7.0 years, and there were no significant differences between the types of institutions the regular physicians worked for (P = 0.077; Table 4 )." ] },{ "paper_id": "59f0dcb0a9c96b60a795162ec2230238896a96e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "293 (human embryonic kidney cells expressing HAd5 E1 gene products; obtained from ATCC) and 293Cre (293 cells that constitutively expresses Cre-recombinase enzyme (a gift from Merck Inc., Whitehouse Station, NJ) [35] were grown as monolayer cultures in Eagle's minimum essential medium (MEM) (Life Technologies, Gaithersburg, MD) and supplemented with 10% reconstituted bovine serum (Fetal Clone III; Hyclone, Logan, VT) and 50 mg/ml gentamycin. All constructs were purified by cesium chloride densitygradient centrifugation and titrated by plaque assays on a hybrid cell line using MDBK and 293 cell lines (BHH2C) [36] as described previously [37] . The construction and propagation of replication defective HAd-DE1E3 (HAd5 vector having deletions in the E1 and E3 regions) has been previously described [11] . HAd5-WT virus was purified by cesium chloride density-gradient centrifugation and titrated by plaque assay on BHH2C cells.", "suggesting that the level of preexisting vector-neutralizing antibody titer could serve as an indicator for predicting the efficacy of Adbased vaccines.", "The " ] },{ "paper_id": "59f96c4166966aa929450a859c3d3fb2b6058c50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses. Pearson's Chi square tests or Fisher's exact tests were used for categorical variables and Mann-Whitney U tests was used to compare continuous variables by using R version 2.15.3 (R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria). P < 0.05 was considered statistically significant.", "Metagenomic analysis has been widely used for viral identification, sequencing, characterization, and origin tracing 23 . The implementation of such methodologies has greatly improved the identification of pathogens, especially for mutant strains and novel viruses. For example, deep sequencing data has been used as direct evidence to identify an H10N8 influenza virus infection in a single human case 24 . Optimization and implementation of the protocols suitable for clinical samples will no doubt improve the microbial diagnosis in clinical practice.", "The study was approved by the Medical Ethics Review Board of the Institute of Pathogen Biology, Chinese Academy of Medical Sciences. All the methods were carried out in accordance with relevant guidelines and regulations, including any relevant details. Written informed consent for scientific assessment was obtained from each patient as part of the clinical treatment contract." ] },{ "paper_id": "5a054a570f409d5c2006369f19addc98d024b6c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "H\u00f0i, 0\u00de \u00bc 0, 0 i n H\u00f00, j\u00de \u00bc 0, 0 j m H\u00f0i, j\u00de \u00bc max 0 H\u00f0i \u00c0 1, j\u00de H\u00f0i \u00c0 1, j \u00c0 1\u00de \u00fe sim\u00bds i \u00f0x\u00de, s j \u00f0y\u00de H\u00f0i, j \u00c0 1\u00de" ] },{ "paper_id": "5a073b51c60bf4d599c2e5bfe236bd11abf07daa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Simultaneous in situ hybridization and antibody labelling.", "Cells were viewed using a Leica SP2 laser-scanning confocal microscope and optical sections recorded using either the \u00c263 or \u00c240 oil-immersion objective with a numerical aperture of 1.4 and 1.25, respectively. The data are shown as single optical sections through the middle of the cell with the exception of Fig. 4(b) , which shows maximum projections of z-stacks (spacing 0.3 \u00b5m). All data were collected sequentially to minimize cross-talk between fluorescent signals. Images were processed using Adobe Photoshop software.", "Murine mAbs against dsRNA (mAb J2), PI4KIIIb and PI4P were purchased from English and Scientific Consulting, BD Transduction Laboratories, and Echelon biosciences, respectively. Rabbit antibody against PI4KIIIa for Western blotting was obtained from Cell Signalling Technology. The murine mAb against actin was from Sigma." ] },{ "paper_id": "5a0d8474822c0a07e6a8cd805f0fbf2e17a38680", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the sample of 65,534 Danish unrelated individuals born after 1981, a total of 28,472 individuals had infections during the study period from birth to end of followup. Among the 45,889 individuals with mental disorders, the number was 21,728, and, among the 19,645 individuals with no psychiatric diagnosis, it was 6744.", "Samples were genotyped on the Illumina Psych chip. Before QC, there were 78,050 samples genotyped in 23 of the original 25 waves. A full description of the procedure of the sample and SNP QC is provided elsewhere 24 .", "Genetic markers, quality control for markers and samples, and imputation", "A subset of the iPSYCH sample was exome-sequenced (with an average depth of 20\u00d7). Sequencing libraries were produced using a custom adaptation of the Illumina Rapid Target Kit (Illumina ICE Broad Exome) and sequenced on Illumina Hiseqs. The raw reads were mapped using bwa aln (v5.9) 27 with the parameters -q 5 -l 32 -k 2 to GRCh37, including unplaced and unlocalized contigs and Epstein \u2212Barr (NC_007605.1). PCR duplicates were removed using picard MarkDuplicates, combined per sample, and realigned across indels using GATK IndelRealigner 28 . Variant-calling was performed using GATK's Haplotype-Caller. Variant filtration was performed using GATK's variant quality score recalibration modules and the variant annotation was performed using SnpEff 29 . For the analyses that used the exome-sequencing data only, given that we looked only at mutations that may alter the protein coding sequence, we utilized samples even if they were excluded earlier based on relatedness and ancestry, if they passed the other QC measures (N = 18,819)." ] },{ "paper_id": "5a17ed3e4abf295f5820c65f56398266c1baae98", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A mysterious illness causing pneumonia in December 2019 in Wuhan, China is now growing into a potential pandemic. These pneumonia cases were eventually characterized to be caused by a novel coronavirus (2019-nCoV) 1 , of which Severe Acute Respiratory Syndrome (SARS) 2 and Middle East Respiratory Syndrome (MERS) 3 are members. SARS and MERS famously caused their own outbreak concerns when they were originally identified. SARS caused significant economic damage to Hong Kong and Southern China, before spreading to other countries. Ultimately, SARS infected up to 8,098 people and caused 774 deaths according to the World Health Organization (WHO) 4 .", "The simplest and most direct approach to combating 2019-nCoV during the outbreak would be one to neutralize the virus from entering cells, the function that antibodies normally perform in the body 39 . For the reasons mentioned above when discussing neutralizing antibodies, it will be difficult to validate a broadly neutralizing antibody quickly, and a challenge to make sure that the mutating RNA virus will not escape its neutralization. A cocktail antibody approach could be undertaken as was explored to treat the Ebola pandemic 40 , but would add complexity to the manufacturing process.", "Underlying data No data are associated with this article. " ] },{ "paper_id": "5a1a67485f8d803e18aeb66383d616ceac659b47", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Twelve, 3 month-old, domestic cats (Felis catus) of the Chinese Li Hua breed were purchased from a local breeder and were housed in a controlled environment. The cats belonged to two litters, six cats per litter. These 12 cats were randomly allocated to four groups (two infected and two control) with three cats per group. Before the experiment, all cats were confirmed to be free from T. gondii using the modified agglutination test and free of major viral infections (e.g. feline calicivirus and coronavirus, feline immunodeficiency virus, feline leukemia virus, and feline parvovirus) based on serological examination. Cats were maintained on commercial cat diets (Royal Canine Inc., St. Charles, MO, USA) and water ad libitum during the 3 weeks prior to experimentation in order to allow cats to acclimate and to minimize any potential dietary influence on the study results. During the experiment cats were individually fed once daily based on daily energy requirements and water was available ad libitum.", "This study was performed in strict accordance with the recommendations set forth in the Animal Ethics Procedures and Guidelines of the People's Republic of China. All animal experiments were reviewed and approved by the Animal Ethics Committee of Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (Approval No. LVRIAEC2014-009). Liver tissue collection was performed as a terminal procedure under isoflurane anesthesia and all efforts were made to minimize suffering.", "Under the conditions we used positive PCR results were obtained, providing laboratory confirmation of T. gondii infection in the livers of infected cats. RFLP analysis of the positive PCR amplicons of T. gondii B1 gene revealed a restriction fragment pattern characteristic to T. gondii genotype II. The livers of control cats and negative PCR control yielded negative PCR results." ] },{ "paper_id": "5a1ae510c59da66b27b5a5a8adf78b252303f9f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was conducted at Hospital das Clinicas, University of S\u00e3o Paulo School of Medical Sciences (HC-FMUSP) from May to October 2006. The Hospital das Clinicas is a 2,000-bed tertiary teaching hospital consisting of 5 buildings attached to the University of S\u00e3o Paulo. The main building has approximately 900 beds and contains most of the surgical and clinical wards and 12 intensive care units. Hospital das Clinicas has an estimated 15,000 HCWs, including permanent and casual staff, employees, students, and volunteers.", "During the 4-month period following influenza vaccination, respiratory symptoms were evaluated in 337 HCWs. A total of 4,182 follow-up visits were performed (median 12 per HCW, ranging from one to 25 visits).", "Misconceptions about influenza vaccine, be it about its safety or its effectiveness, have been identified in all studies included in a recent review of attitudes and predictors of influenza vaccination among HCWs, highlighting the importance of education efforts [5] .", "Interestingly, we observed that some sectors showed significantly higher rates of AE than others, supporting the subjectivity of the information. Also, this data may suggest a mouth to mouth effect among sector coworkers influencing the self-report of AE. Among HCWs, the belief that coworkers take influenza vaccine influences the vaccine uptake. Thus, it is possible that the same occurs concerning to adverse events." ] },{ "paper_id": "5a2360e93ec038502133c97cf78a114c012e5df4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Overall we included 72 female samples and 38 male samples of Bulgarian ancestry.", "It is well known that environmental factors can influence genome function without changing the DNA sequence itself -the concept of epigenetics. The epigenetic characteristics are maintained by specific mechanisms that firstly ensure the epigenetic profile through cell generations and secondly allow the cell to perform specific functions (differentiation) and to adapt according to different stimuli [17] . The major epigenetic modifications include DNA methylation, histone modifications, miRNA interference [18] . The dynamics of epigenetic processes allow the cells to respond reversibly and in a precise way to environmental stimuli, but also preserve cell type specific gene programmes. When alteration of epigenetic pattern occurs, diseases such as cancer could occur through pathological gene expression. Epigenetic changes over time display familial clustering [19] . This could explain the clustering of some common diseases in families and actually the epigenetic pattern could be implicated in transmitting a \"predisposition\" over generations.", "The third sample cohort -49 cases, were collected from Serbian endemic regions. DNA was extracted by DNA extraction kit and stored at \u221280\u00b0C. 19 female samples and 30 male samples of Serbian ancestry were enrolled in our study.", "200 \u03bcl of the fragmented DNA pool sample were subjected to methylation DNA immunoprecipitation (MeDiP) for extraction of the methylated fraction from whole genome DNA according to Agilent protocol (v1.1, 2010). For immunoprecipitation we used Dynabeads\u00ae Pan Mouse IgG (Invitrogentm) and Anti-5-Methylcytidine Monoclonal Antibody (Eurogentec).", "In conclusion, our results suggest that methylation alterations in genes related to dysregulation of immune response can contribute to BEN development. It is worth further investigation of their expression levels in kidney samples from BEN patients in order to verify the pathogenic consequences of their hypomethylated status." ] },{ "paper_id": "5a2b335f389f88025ca1994a95e220479646d581", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "FCoV replication, like replication of all RNA viruses, is prone to error [165] . Multiple individual mutations occur during each cycle of viral replication [12, 58, 166, 167] . It is hypothesized that specific mutations or a combination of mutations then lead to the development of the virulent pathotype FIPV and trigger the tropism switch from enterocytes to macrophages as a key event in FIP pathogenesis [4, 153, 168] ." ] },{ "paper_id": "5a2d0804fc8a4c5d6c661deca4e3150e5cbc77d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Comparison of the transcription and replication strategies of marburg virus and Ebola virus by using artificial replication systems.", "Ebola haemorrhagic fever causes deadly disease in humans and non-human primates resulting from infection with the Ebola virus (EBOV) genus of the family", "This work was supported by grants from the Major Program of National Natural Science Foundation of China (#81590763), and the Science & Technology Key Program of Zhejiang China (#2014C03001-2/3)." ] },{ "paper_id": "5a2e46bae8ee2f620f032cf40f4057963ac7ab03", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5a3f46d6fe292e51aa8ad833905cd913ade65caa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Most frequently, ADEM is heralded clearly by discernible febrile illness or immunizations. While ADEM is a monophasic disease, more often affecting pre-pubertal children (10-18yrs) , MS is a chronic relapsing and remitting disease that attacks young adults. The demarcating lines between these different acute demyelinating diseases are blurred, except that the CSF results are less pronounced in ADEM. A clinical continuum is the more typical characteristic in the closely connected acute demyelinating conditions, including optic neuritis, hemiparesis with facial nerve palsy, transverse myelitis, meningoencephalitis, Guillain-Barr\u00e9 syndrome and vasculitis implicating the central nervous system. However, the primary pathophysiological processes involved continue to remain ambiguous [5] . In this study, the report of a 46year-old male Saudi is included, who initially presented with a prodromal respiratory condition and only later on exhibited neurological signs and symptoms.", "Normally, cerebrospinal fluid (CSF) is unremarkable; however, sometimes it might reveal heightened protein and low glucose levels resembling bacterial meningitis but without any cellular constituents as supporting evidence for bacterial infection and negative cultures. This was the case for the patient in this study, who showed PCR (poly-chain reaction) on CSF as being negative for Mycobacterium tuberculosis. The IgG and IgM subtypes in the CSF at times are linked to ADEM and MS, although they are not diagnostic. Electroencephalograms (EEG) are non-specific, while the visual evoked potentials may show abnormality and delay. When specific biomarkers for ADEM diagnosis are completely absent, they are very often delayed and are based on the one hand on the exclusion of the likelihood of the other demyelinating and meningoencephalitis disorders and on the other hand on abnormal clinical reports and characteristics that are obvious on radio imaging [9] .", "Acute disseminated encephalomyelitis (ADEM), an immunemediated inflammatory demyelinating disorder, primarily affects the white matter of the brain and spinal cord [1, 2] . Acute onset encephalopathy expresses itself as distinctively self-limiting multifocal neurological deficits. This disorder is very similar to other acute demyelinating syndromes, like multiple sclerosis (MS), from the clinical and pathophysiological symptoms presented. However, ADEM is clearly detectable from other demyelinating disorders from its radio imaging MRI characteristics and laboratory reports. However, in the absence of any distinctive biomarker, definite diagnosis becomes challenging. Therefore, it is essential that such patients are followed up long term, as a few patients initially diagnosed with ADEM finally had MS [3, 4] ." ] },{ "paper_id": "5a4760a109394f2d59a82a5831c23ab7ac259eb2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At elite levels, such as the National Hockey League (NHL), aggression (i.e., a purposeful physical act driven by intent to cause physiological or psychological harm) is valued and has been considered to be an effective success strategy [14, 15] . Aggressive players are quickly recognized for their style of play by coaches, management, other players, and fans [16] . Moreover there still exists, among the sports community, a widespread attitude that concussions are ''a part of the game'' and resiliency to medical council is considered a sign of ''toughness'' [17] . These issues hinder prevention and treatment efforts and call for research to address these concerns.", "To investigate specific trends over time, [1998] [1999] [2000] . We compared these time periods by means of a thematic and content analysis to explore the nature of and frequency distribution of MUs between time periods and geographical regions (i.e., Canada and America). Three members of the team reviewed the articles, and collaboratively discussed any discrepancies in the classifications of MUs. We assessed coder agreement by means of inter-rater reliability (Cronbach's alpha for coding of MUs was 0.91)." ] },{ "paper_id": "5a4a0f630530c7225fd23178fbdfedd2dccf535c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To investigate the effect on amino acid requirement, we used CDM containing 18 amino acids necessary for S. aureus growth. The amino acids used in this experiment and their concentrations have been previously described [33] . The CDM was prepared using 2-fold serial dilutions with CDM depleted of all amino acids. Then, 10 \u03bcl of the bacterial culture (1x10 5 cells) was applied to each well. After incubation for 24 h at 37\u00b0C, the minimum dilution rate that showed visible bacterial growth was determined.", "Staphylococcus aureus is a commensal bacterium in humans that can also be pathogenic primarily as an opportunistic infectious agent. S. aureus causes various suppurative diseases, food", "doi:10.1371/journal.pone.0165831.t001" ] },{ "paper_id": "5a4fe515ba7441d9da4fd72539d9c525b8c7b0b3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: M.D. and E.P. conceived the idea of this study, collected the data, drafted the manuscript, and approved the final version to be published. N.A., H.K., A.M., and A.K. analysed data, revised critically the manuscript, and approved the final version to be published.", "Chronic mucopurulent secretion should also raise suspicion for adenoidal hypertrophy, chronic rhinosinusitis, anatomical abnormalities, primary ciliary dyskinesia, cystic fibrosis, and other clinical entities [10] .", "Children with AR, as well as chronic mouth breathers, may present with characteristic facial feature changes, such as narrowing of the hard palate, gothic arch, discoloration of frontal incisors, dental malocclusion (crooked teeth), everted upper lip, and loss of nasolabial fold, which all lead to a narrow, long face [10, 18, 22] . However, we should be careful interpreting these changes, as they may appear in every condition with chronic nasal obstruction and mouth breathing, like adenoid hypertrophy, and nasal tumours." ] },{ "paper_id": "5a55cfceb7365142481967c11c4f70b359a1e4b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5a575cf8c90efa9e40cfbf87f2a202bb39d68951", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The CoPanFlu-France cohort protocol was approved by the French ethics committee (\"Comit\u00e9 de Protection des Personnes Ile-de-France I\") on 8 September 2009. All study participants provided written informed consent [18] .", "The patients' age ranged from 1 month to 79 years (median: 31.2yo).", "(DOCX) S1 " ] },{ "paper_id": "5a57a6330daa19227fb5011f690e68accf1c4b1d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Little is known about the longevity of antibody titres after infection from longitudinal studies. A study following camels on a closed farm found that neutralizing antibodies remained consistent during a year [30] , while other studies found that antibody titres rapidly drop by 1-4-fold within a period often as short as 2 weeks [24, 27] .", "Author ORCIDs.", "R. S. Sikkema, 0000-0001-7331-6274" ] },{ "paper_id": "5a5a25d733b227ba661f3ba8f69af5886999f02c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analysed by two-tailed t test, using Prism (version 5, GraphPad 339 Inc.). Data are mean \u00b1 SEM for 3 experiments. P-values are denoted as follows: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.", "HCMV is the largest member of the herpesvirus family and consists of a linear double-stranded DNA genome of ~240 kb that encodes from 170 [14] to 750 proteins [15] . Only about 50 of those proteins are believed to be essential for virus replication and production of new viral progeny. Instead, the vast majority of proteins aid the virus to interfere with cellular and immunological functions to enable it to coexist with its host [16] . HCMV also utilizes multiple strategies to exploit host functions for efficient virus production and its own spread and survival. Many of these are believed to confer oncomodulatory functions.", "For the siRNA study, HSS119452 stealth siRNA POLR1A 20nmol (Thermofisher Scientific, Invitrogen) and Lipofectamine RNAiMAX protocol (Invitrogen) following the manufacturer's instructions, were used. AllStars Negative Control siRNA (Qiagen) served as negative control. In brief, cells at 80-90% confluency in 12-well plate were transfected with siRNA 24h before infection with HCMV at an MOI of 1. The cells were harvested for quantitative TaqMan PCR analysis 6h, 24h and 48hpi." ] },{ "paper_id": "5a5dde5900813ecf3b68e226c3976cb2226ccf5b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step a3 to a6) were remaining same as discussed for above two searching methods.", "Several web-based antigen/epitope databases are available the content of which is freely available to the users. A brief description of MimicDB along with comparison with miPepBase is as follows:", "Pepstats was used to calculate physicochemical properties of amino acids (such as molecular weight, number of residues) present in mimicry protein.", "An important aspect of any database is to keep it up to date by adding new data. We would constantly add information about newly discovered peptides, which exhibit molecular mimicry and cause autoimmune diseases." ] },{ "paper_id": "5a5e5fb3101062ab42831dae0bf504fd3e3a41f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All potential linear epitopes of a protein are short peptides that can be synthesized and arrayed on solid supports, e.g. glass slides [4] . By incubating these peptide arrays with antibody mixtures, such as human serum or plasma, it is possible to determine specific interactions between antibodies and peptides." ] },{ "paper_id": "5a616c081f34c8ead17742a91a121ae167d77e17", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ISG15, a ubiquitin-like interferon-stimulated protein, is stimulated by interferon or viral infection [34, 35] . ISG15 is cytokine-like protein that promotes antiviral immune response. On mice, ", "The viral protein precursor is cleaved by cellular proteases (e.g., matriptase or furin) into active protein form.", "Supplementary Materials: The following is available online at www.mdpi.com/2227-7382/4/1/3/s1. Table S1 : IAP and nuclear trafficking motifs." ] },{ "paper_id": "5a63186e3d015f0bb7378218ebd26b96f7bae63e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, it is not true that NFSA has substantially associated with CDI. What NEMA learned from its agencies' American and British counterparts was only their physical location. Thus, NFSA has to actively exchange related training information and materials with CDI to improve its EMT and vice versa.", "Via a comparative perspective, NEMA, which has a relatively short history in modern EMT, can adopt the same strategies applied by the United States and the United Kingdom toward effective EMT. Without this comparative perspective, it would be not easy for Korea to learn such an important lesson within such a short time.", "If NEMA considered the viewpoint of other local stakeholders, it would decide to set up CDI's local academies in local communities, like the case of NFSA's local fire academies. To this point, the supply side of NEMA's public policy on EMT continues to prevail." ] },{ "paper_id": "5a6330a739f18fd6bc502bd9b59de55e8c081d4e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5a63d131a9fdbdb837c56458c72d6e29942c1fb9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chemokines, a group of small (8-12 kd) proteins, are key regulators of leukocyte migration and play important roles in many physiological and pathological immune and inflammatory contexts. Chemokines are characterized by the presence of 3 to 4 conserved cysteine residues and can be subdivided into 4 families based on the positioning of the N-terminal cysteine residues [44] .", "Macrophages, NK cells, dendritic cells, and fibroblasts were reported to produce IFN-I (\u03b1 and \u03b2) in response to viral infection or exposure to microbial pathogens. The early induction and action of IFN-I result in cellular resistance to viral infection, inhibition of viral replication, and impediment of viral dissemination [38] . Liu and coworkers showed that polyriboinosinic: polyribocytidylic acid (poly(I : C)), a potent IFN inducer, improved the survival rate and decreased the tissue viral titers after EV71 challenge, which correlated with an increase in serum IFN-\u03b1 concentration, the percentage of dendritic cells, the expression of major histocompatibility complex class II molecule and IFN-\u03b1 in spleen of mice [39] .Type I IFNs represent an essential innate defense mechanism for controlling EV71 infection in mice.", "Humoral mediators including cytokines are the molecular proteins of the innate and immune response and play key roles in the pathophysiology of viral infection [1] . Systemic inflammatory response syndrome (SIRS) caused by infection is a typical condition within which proinflammatory mediators released from infected cells and persistent hypercytokinemia may result in progression to multiple organ failure [2] . It is known that activation of cytokine networks increases levels of various cytokines in blood. The burst of cytokine release that follows sepsis, toxin-mediated shock syndrome (e.g., Streptococcus pyogenes and Staphylococcus aureus) [3, 4] , some virus infections such as severe acute respiratory syndrome (SARS) [5] , influenza [6] , dengue virus [7] , and Epstein-Barre virus [8] induce an overwhelming stimulation of innate and/or immune responses that storm the physiology of the body." ] },{ "paper_id": "5a6e220c6796a02e36a272103dd39dd62c9311eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Widespread applications include splicing of peptides and deoxyribonucleic acids, dissolution of blood clots, and killing of viruses.", "Frontiers in Microbiology | www.frontiersin.org", "AS, RW, SL, and SW designed the study. AS and SW wrote the paper and all the authors approved its submission. " ] },{ "paper_id": "5a7988cd92e05a8bca504b5f1a467e2c8d3976d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2)", "(4)", "Substituting (A2) into the fifth equation in (6) yields" ] },{ "paper_id": "5a7eaaf283f1005f17f029f26a9ec33eebe566bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animals were cared in compliance with the French directive on animal experimentation, and they were killed in compliance with national regulations and according to procedures approved by the French Veterinary Services at INRA experimental facilities. The study was submitted to and approved by our institutional ethics committee (Comit\u00e9 Rennais d'Ethique en mati\u00e8re d'Exp\u00e9rimentation Animale, CREEA, Rennes, France) and authorized by the French Ministry of National Education, Higher Education and Research." ] },{ "paper_id": "5a85b1a03f6d5cebc70bad6027c941a2224f0df0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In June 2013, an outbreak of acute gastroenteritis occurred in a client-owned litter of dachshunds in Apulia, Southern Italy. The six 5-6-months old animals had completed the first-year vaccination protocol against CPV, CDV, CAdVs and Leptospira spp. The clinical signs in the dogs were severe, with hemorrhagic diarrhoea, vomiting and death of 2 animals after one week of illness. The other dogs completely recovered within 12-15 days after the onset of clinical signs. One dog carcass was frozen at 220uC after three days of storage at +4uC and sent to our Department for necropsy and laboratory investigations only after three months. Samples from the other dead dog and from the surviving animals were not available for additional analyses, as they were not collected timely.", "At post-mortem examination, the dog displayed hepatitis and haemorrhagic enteritis with involvement of the mesenteric lymph nodes that appeared congested and haemorrhagic.", "Citation: Decaro N," ] },{ "paper_id": "5a85cf34eee367f1a73ac62a05779d4c815dc767", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two-tailed Student's T-tests were performed with two sample equal variance using Microsoft Excel software. Values of p < 0.01 were used as statistically significant.", "Growth of F. tularensis in Airway Epithelial Cells and Murine Lungs", "doi:10.1371/journal.pone.0127458.g008" ] },{ "paper_id": "5a89b93e5c8c6fb1352d9881f6ca6b592ef4af30", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "FRET MAPKKide LF activity. For drug testing in 96-well plates, the reaction volume was 250 \u03bc l per well, containing 20 mM HEPES pH 7.2, 5 \u03bc M MAPKKide conjugated with DABYL and FITC (List Biological Laboratories, Inc), and 3.3 \u03bc M of JHCCL compound. The reaction was initiated by adding LF to a final concentration of 6 \u03bc g/ml. Kinetic measurements were obtained at 37 \u00baC every 40 sec for 40 min using a fluorescent plate reader. Excitation and emission wavelengths were 490 nm and 523 nm, respectively, with a cutoff wavelength of 495 nm.", "Whereas medical treatments generally target specific cellular functions of patients to cure or mitigate the effects of diseases, the strategy underlying treatment of infectious disease treatment is to target the infecting pathogen 1 . Inevitably, and not surprisingly, the targeting of pathogens has led to the emergence and spread among pathogens of mutational resistance to countermeasures. Such resistance, together with a desire to expand the utility of countermeasures by increasing their range of therapeutic efficacy, has in recent years sparked interest in agents aimed at host functions that pathogens exploit to enter or be released from host cells 1 . Not infrequently, multiple pathogens or toxins that affect hosts by different mechanisms use the same host pathways 2 , raising the prospect that multiplex strategies that concurrently or sequentially screen for host functions exploited by multiple pathogenic agents may lead to the discovery of broadly active and host-oriented infectious disease countermeasures.", "Activation of caspase-1 by LF is a late step in pyroptosis and depends on LF catalytic activity 19 . To determine whether AQ blocks proteolysis of cellular MAPKKs by LF, we assessed the cleavage of MEK2 by immunobloting. While MEK2 was cleaved in LF-PA treated RAW264.7 cells, treatment with AQ completely prevented this effect (Fig. 3b) . These results show that AQ inhibits either cytotoxicity upstream of MAPKK cleavage or blocks LF directly." ] },{ "paper_id": "5a9b4ede657bcb4bd1e154dfc2b6ef0f274af4a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5aa7bb757f909abc71347a4add89dcdde3f9b7b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There is currently no immunoprophylactic strategy to generate broad spectrum protection against diverse respiratory viral pathogens. Conventional strategies to protection against respiratory pathogens have relied on vaccination against individual virus strains or the use of drug based therapies. However, the efficacy of these immunoprophylactic strategies is often significantly limited by either difficulty in engineering effective vaccines to some respiratory viruses such as respiratory syncytial virus, or because of evasion of acquired immunity as a result of antigenic variation of circulating respiratory viral pathogens (H1N1 swine influenza pandemic, 2009). In addition, conventional strategies are generally not applicable to newly emerging viruses (SARS outbreak, 2003) since their sudden appearance does not allow for time to develop a vaccine." ] },{ "paper_id": "5ab2ff8df3b1bc8a71ab66025f5dcee729242583", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In recent years, RNAi has emerged as a powerful tool for gene silencing with a potential for therapeutic use in viral infections such as Human immunodeficiency virus (HIV) [13] Influenza [14] , Respiratory syncytial virus (RSV) [15] , SARS coronavirus [16] and Ebola virus [17] .", "(http://www1.qiagen.com/Products/GeneSilencing/SiRnaDuplexes/ HPGuaranteed.aspx).", "For flowcytometry acquisitions were done using FACScalibur (BD Bioscience) and analyses were performed using cell quest software (BD Bioscience)." ] },{ "paper_id": "5ab81ec18627585be0e852bdd61472e98f531701", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All chemicals were of analytical grade and were purchased from Sigma-Aldrich (St. Louis, MO, USA) unless otherwise indicated. All enzymes and related buffers were purchased from New England Biolabs (NEB, Ipswich, MA, USA) unless otherwise indicated. All oligonucleotides and gene blocks (summarized in Supplementary Tables S1-S4) were obtained from Integrated DNA Technologies (IDT, Coralville, IA, USA). Virus genomic RNA and inactivated virions (Supplementary Table S5) were obtained from BEI Resources (Manassas, VA, USA).", "For performing in vitro run-off transcription, ZIKV gene segments cloned in a pCR2.1-TOPO vector were amplified from sequenced plasmids by PCR using Phusion DNA polymerase. The PCR products were verified by agarose gel electrophoresis and then purified using the Wizard SV gel and PCR clean-up system (Promega, Madison, WI, USA), according to the manufacturer's instructions.", "Complementarity is denoted by a single prime symbol." ] },{ "paper_id": "5abea4a5497c9cfa476bf766b8360f73c12e8122", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were cultured in complete Dulbecco's modified Eagle's medium (DMEM) supplemented with 5% newborn calf serum (Sterile) and 1% penicillin/streptomycin (Invitrogen), and maintained at 37uC in humidified 5% CO 2 .", "In vitro transcription of luciferase RNA was preformed using T7 RNA polymerase (Promega). After extraction with phenol/ chloroform, the in vitro transcribed RNA was precipitated with ethanol and dissolved in RNase-free water.", "Plasmids pGEX-5X1, pGEX-SDC and pGEX-3f were expressed in bacteria by induction with 0.4 mM IPTG at 37uC for 3 hours. GST and GST fusion protein were purified using the GST purification module (Amersham)." ] },{ "paper_id": "5ac10a9b15162482ce6936829201e0f6d08fb441", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Statistics (Mann-Whitney Rank, Wilcoxon signed rank or t-tests) were calculated using R, Sig-maPlot11, GraphPadPrism6.0 and MS EXCEL2010.", "Complete experimental procedures including reagents, buffers, nucleotide sequences, additional methods and software used are described in detail in S1 Supporting Experimental Procedures." ] },{ "paper_id": "5ac2943caeef1105169bfa7240df08281b7c2733", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5ac39b49492fe7a6f53ad50d840e4ce8ed579e77", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To allow comparisons with other studies and identification of orthologues, a standardized systematic nomenclature of NKR genes (Schwartz et al., 2017) was used. However, when referring to original reports on human or mouse genes, both the original and standard gene names and symbols were used.", "JF made NKC annotation, designed primers, carried out PCR for NKR genes, and analyzed data. JO made all NGS mappings. AJ made LRC annotation and carried out PCR for LILRB1. JE provided CamDro2 whole genome sequence and annotation. JW made microsatellite definition and analysis. AK designed the microsatellite project. PB designed the project. PH designed the", "Type of repetition C. dromedarius amplicon size Forward primer Reverse primer", "The predicted proteins of the NCR1, NCR2, and NCR3 genes were studied as potentially activating immunoglobulin-like receptors for various ligands different from MHC class I." ] },{ "paper_id": "5ac423d77382c035d9ba1f51ed94d524d1a9ec7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Individuals may experience a co-infection or sequential infections of multiple viruses or bacteria which can complicate both disease diagnosis and drug prescription decisions. Furthermore, patients infected by multiple pathogens may have further complications due to drug-drug interactions, cumulative drug toxicities and immune system suppression, as observed during HIV and Mycobacterium tuberculosis co-infections [18, 19] . Indeed, a study in children under five years showed pervasive clinical occurrences of co-infections involving combinations of RSV, HRV, Paramyxoviridae Parainfluenza Virus, FLU, Coronaviridae SARS-Coronavirus (CORON), Paramyxoviridae Metapneumonia virus (MPNEU), Parvoviridae Human Bocavirus and ADENO [4] . Therefore, in addition to minimizing drug resistance, there is a need for new therapeutic approaches to safely and effectively treat co-infections by multiple viral and/or bacterial pathogens, particularly where strain-specific diagnostics or treatments are unavailable.", "As mentioned above, CASP1 is a component of the NLRP3 inflammasome, activating the precursor to IL1B [69] . Therefore, a CASP1 inhibitor would have an antagonist relationship with IL1B, hence the inflammasome. Further, CASP1 inhibitors would be agonists for PARK2, thereby reducing accumulation of SNCA. In this regard, CASP1 inhibitors may not only prevent unnecessary NLRP3 inflammasome activation via ILB1, but may also reduce accumulation of neurotoxic Lewy bodies through activation of PARK2." ] },{ "paper_id": "5adc4dd51a8d7dfe7e252c55e8bac9bcc108143a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Medium was changed every 3-4 days and polarization was monitored by determining trans-epithelial electrical resistance (TEER) of each Transwell culture, using an EVOM voltohmmeter (World Precision Instruments, Sarasota, FL, USA) and STX2 electrodes [47] .", "Sequence", "Respiratory syncytial virus (RSV) causes serious lower respiratory tract illness in the young and the elderly leading to substantial morbidity and hospitalizations [1] [2] [3] [4] [5] [6] . There is no safe and effective vaccine to prevent RSV. Previous vaccination approaches using formalin-inactivated RSV (FI-RSV) were associated with an increased risk of serious RSV illness upon subsequent natural infection [7, 8] . Vaccine strategies have focused on using either live-attenuated viruses, inactivated whole virus vaccines [9] or subunit vaccines targeting the two major surface viral proteins, RSV fusion (F) and/or attachment (G) proteins [10] [11] [12] . Insufficient or over-attenuation, induction of enhanced disease with natural infection, or inadequate protection against infection [13] [14] [15] [16] have blocked moving these vaccines to licensure and challenged the understanding of events at the host-virus interface." ] },{ "paper_id": "5adc6c6cf5b6d7306ed52327e9ccec7a1512f1e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chromatogram files and trace data were read and assembled using SeqMan Pro, and genome annotation was conducted with SeqBuilder (DNASTAR, Inc., Madison, WI, USA). Each sequence was aligned to a representative genome; Mass/Mass41/41 (GenBank accession #AY851295), or CAL99/CAL99/99 (GenBank accession #AY514485) as a backbone for genome assembly.", "Whole genome analyses were generated and phylogenetic trees constructed with the Neighbor-Joining method with 1000 bootstrap replicates as well as with Minimum Evolution, Maximum Parsimony and UPGMA methods [17] .", "The PCR products were agarose gel purified using the QIAquick gel extraction kit (Qiagen, Valencia, CA, USA) according to the manufacturer's protocol. The PCR products were cloned into the TOPOXL vector using the TOPOXL cloning kit (Invitrogen, Carlsbad, CA, USA) according to manufacturer's protocol to prepare cDNA libraries for sequencing.", "Primers for one-step RT-PCR were specifically designed for each virus (Supplemental Table 2 ). Viral RNA was amplified using the Titan One Tube RT-PCR kit (Roche Diagnostics, Indianapolis, IN, USA) following manufacturer's instructions. A DNA Engine Peltier Thermocycler (Bio-Rad Laboratories, Inc., Hercules, CA, USA) was used for the RT-PCR reaction, which had the following steps: one cycle of 42 \u00b0C for 60 min and 95 \u00b0C for 5 min, followed by 10 cycles of 94 \u00b0C for 30 s, 50 \u00b0C for 30 s, and 68 \u00b0C for 1 min 30 s, and then 25 cycles of 94 \u00b0C for 30 s, 50 \u00b0C for 30 s, 68 \u00b0C for 1 min and 30 s adding 5 s with each cycle." ] },{ "paper_id": "5adf1ce218579cf9f0f919c778c05bf0f864c1a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5ae438eff01ac41a451ff26064c3346805d1c1dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was conducted according to the principles expressed in the Declaration of Helsinki and was approved by the Ethics Review Committee of the Hospital das Cl\u00ednicas de Ribeir\u00e3o Preto (Number 10466/2008) and a written informed consent was obtained from all parents and guardians prior to enrollment.", "HBoV is in the family Parvoviridae, which includes agents capable of causing persistence, like parvovirus B19, which can persist in both immunocompromised [16] and immunocompetent individuals [3] . A previous study by this group has shown that hypertrophic adenoids commonly harbor HBoV, albeit only 20% of them were actively replicating [17] . That was suggestive that HBoV genomes detected in tonsils were most likely latent as episomal genomes, or as viral DNA concatemers [18, 19] . Consistent with that, HBoV DNA was not detected in any of the 83 individuals after adenotonsillectomy.", "Supporting information S1 ", "Asymptomatic respiratory shedding of HAdV and HBoV is significantly reduced by tonsillectomy, which agrees with persistence of respiratory DNA viruses in human tonsils." ] },{ "paper_id": "5ae7223cc6ab3437ba262bb2bb47768948e01d59", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For immunoblotting, total cell or pre-IP extracts were lysed in sample buffer containing SDS and protease and phosphatase inhibitors. Proteins were resolved on a SDS polyacrylamide gel, transferred to a polyvinylidene difluoride (PVDF) membrane, hybridized with a primary antibody, reacted with the horseradish peroxidase-conjugated secondary antibody, and visualized using chemiluminescent substrate (Thermo Scientific).", "For immunoprecipitation, frozen cell pellets were lysed in lysis buffer (0.5% NP-40, 50 mM Tris-Cl pH 8.0, 125 mM NaCl, supplemented with protease and phosphatase inhibitors) using an end-over-end rotator at 4uC for 30 minutes. Cell extracts were cleared by centrifugation at 16,0006 g for 15 minutes. Supernatants were incubated with protein A-coated Dynabeads that were coupled to 1 mg anti-HA (HA.11, Covance), 1 mg anti-GFP (3E6, Invitrogen) or 2 mg anti-APC3 (AF3.1, Santa Cruz) mouse monoclonal antibodies at 4uC for 1-2 hours. Beads were washed with PBS and immunoprecipitated protein complexes were eluted by boiling beads in reducing sample buffer for 5 minutes. Cell extracts (pre-IP) were also collected and boiled in reducing sample buffer. For mass spectrometry analysis, protein complexes were resolved by SDS-polyacrylamide gel electrophoresis (Invitrogen) followed by staining with a silver stain kit (Sigma-Aldrich). Protein bands specific to immunoprecipitated pUL21a complex were excised for identification by MS/MS mass spectrometry [47] .", "Total RNA was extracted with TRIzol (Invitrogen) and treated with Turbo DNA-free reagent (Ambion) to remove genomic DNA contaminants. cDNA was reverse transcribed from total RNA with random hexamer primers using the High Capacity cDNA reverse transcription kit (Applied Biosystems). cDNA was quantified using SYBR Advantage qPCR Premix (Clontech) and primers for the cellular genes geminin, APC4, APC5, and GAPDH (glyceraldehyde-3-phosphate dehydrogenase) as an internal control (see below). cDNA from infected cells was used to generate a standard curve for each gene examined. The standard curve was then used to calculate the relative amount of specific RNA present in a sample.", "Primers used for RT-qPCR are as follows: geminin, forward 59GCCTTCTGCATCTGGATCTCTT39 and reverse 59CGAT GTTTCCTTTTGGACAAGC39 [24] ; APC4, forward 59ATT CTCGTCCTTGGAGGAAGCTCT39 and reverse 59TTCTG GCCATCCGAGTTACTTCAG39 [24] ; APC5, forward 59GTG CCATGTTCTTAGTGGCCAAGT39 and reverse 59GATGCG CTCTTTGCAGTCAACCTT-39 [24] ; GAPDH, forward 59CT GTTGCTGTAGCCAAATTCGT39 and reverse 59ACCCACT CCTCCACCTTTGAC39 [30] ." ] },{ "paper_id": "5ae9d09818e63828c80da0e37f6a5c1a1ccc22e6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "5. Setting a broad remit allowed a wide range of ideas to be proposed, but the 6 finalists naturally did not fully represent the breadth of ideas proposed. Consider establishing different categories-best new tool, best cross-cutting application, etc.-rather than having a single winner. Alternatively, consider refining the OSP funding model to create future global initiatives focused in particular areas (e.g., gene-by-environment research, rare diseases, immunization, obesity).", "4. Proposals at differing stages of development were received. Define clearly whether applications have to focus on a completely new concept (or tool) or whether an existing tool/service-which wishes to add additional new functionality-is also eligible. If both are eligible, it is important to consider how to tension the 2 types of applications against one another in the fairest and most transparent way.", "analyses of viral genome sequences can be used by public health officials for epidemiological insights within days of genome sequences having been obtained from viral pathogen samples taken from patients. Nextstrain.org expanded upon the submitters' prior work on influenza tracking (nextflu.org) to include many other viral pathogens. Using OSP funds, the team developed detailed phylogeographic analyses of viral movement, created a platform for rapid (realtime) data sharing of pathogen genome data with open source code, and constructed a database and associated parsing scripts to quickly consolidate emerging data from multiple sources." ] },{ "paper_id": "5aebac2302d94acc406291d65cc7c538ab71dae1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "F1000 Faculty Reviews are written by members of the prestigious . They are F1000 Faculty commissioned and are peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. The reviewers who approved the final version are listed with their names and affiliations.", "In this review, we summarize the main therapeutic approaches that target different stages of viral entry (Figure 1 ), either by inhibiting virus-specific interactions or by blocking conserved cellular mechanisms that viruses exploit to enter cells. This latter tactic is indicative of a change of focus for viral therapeutics, combining more traditional approaches directed at specific viruses with novel cell-targeted strategies with broad-spectrum potential." ] },{ "paper_id": "5af166022c0575cefcd0f2107b4fd1a657b6391b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5afa333a59a3d818c758dbc752463b90436a1c57", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although ISG56/IFIT1 is the major ISG that inhibits PIV5, other ISGs also contribute to the antiviral activity of IFN", "Cells, viruses and IFN. Vero, Huh7, A549 and Hep2 cells and their respective derivatives were grown as monolayers in 25 or 75 cm 2 tissue-culture flasks in Dulbecco's modified Eagle's medium supplemented with 10 % fetal calf serum at 37 uC. When needed, cells were treated with human recombinant IFN (Roferon-A; Roche) at 1000 U ml 21 . The CPI2 isolate was grown and titrated in Vero cells.", "qPCR. Total cellular RNA was extracted from infected cells using TRIzol (Invitrogen). Two micrograms of RNA was subsequently used for RT-PCR. Fragments of~200 bp were amplified with primers for NP, P, M, HN and L. b-Actin was used as a reference gene. Primer sequences were: NP: 59-AGGGTAGAGATCGATGGCT-39 (forward) and 59-GTCTGACCACCATTCCCTT-39 (reverse); P: 59-AATACCA-CCAGGGGTCACAG-39 (forward) and 59-CGAGCACCCAAACTG-TGCTT-39 (reverse); M: 59-TCATGAGCCACTGGTGACAT-39 (forward) and 59-TGGAATTCCCTCAGTTGTCC-39 (reverse); HN: 59-AACTCTGCAGTCGCTCTACC-39 (forward) and 59-GCAATCTG-ACACTTGGCCCA-39 (reverse); L: 59-TCCAAGTGATGACTTTG-AATT-39 (forward) and 59-CCATACTCATTACTCGTGTGCC-39 (reverse); and b-actin: 59-ACCAACTGGGACGACATGGAG-39 (forward) and 59-TAGCACAGCCTGGATAGCAAC-39 (reverse). The plotted values of mRNA were expressed as the quantity of the gene of interest relative to the quantity of the reference gene, to obtain normalized and relative expression values. Each sample was performed in duplicate on the same qPCR plate in two separate experiments. A non-template sample and a non-reverse transcriptase sample were analysed routinely as negative controls. Data were collected using a 7300 Real-time PCR System (Applied Biosystems)." ] },{ "paper_id": "5afe948e33645324e3fb0fe4e4d27b1bba317364", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Patients were eligible if they had an admission diagnosis of (probable) bronchiolitis, (probable) pneumonia, or respiratory failure. Exclusion criteria were a primary cardiac or central origin of respiratory failure, and overt sepsis at the time of admission. The study described here was conducted as part of normal patient care; therefore, according to the Medical Ethical Research Council of our institution, there was no need for patient consent/ethical approval.", "For the analysis of continuous variables, an unpaired t test was used to compare means. Categorical variables were analyzed using a two-tailed Fisher's exact test.", "Briefly, samples were assayed in duplicate in a 25 \u00b5l reaction mixture containing 10 \u00b5l (c)DNA, 12.5 \u00b5l 2 \u00d7 TaqMan Universal PCR Master Mix (Applied Biosystems), 300-900 nmol/l of the forward and reverse primers and 75-200 nmol/l of each of the probes. All samples had been spiked before extraction with an internal control virus (murine encephalomyocarditis virus [RNA virus] and phocine herpes virus [DNA virus]) to monitor for efficient extraction and amplification, essentially as described previously [15] ." ] },{ "paper_id": "5b029e946adb1adaf73c953ca02413da64fc6c53", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The stock insulin solution was filtered through 0.2 mm disk membrane and then diluted to a final concentration of 2.0 mg/ml. The experiments were performed at pre-adjusted temperature of ", "Steady-state anisotropy was recorded with a Hitachi model F-4500 spectrofluorometer equipped with a polarization accessory. Excitation of FITC labeled NK9 was done at 453 nm. The fluorescence anisotropy (A) values were obtained using the expression as of Equation 2. ", "O:D of treated cells=O:D of untreated control cells|100 \u00f05\u00de", "where, I VV and I VH are the vertically and horizontally polarized components of probe (emission wavelength 526 nm) with excitation by vertically polarized light at 453 nm. G is the sensitivity factor of the instrument. The excitation and emission slits were set to 5 nm. The FITC tagged NK9 concentration was 10 mM, whereas insulin concentration was varied between 0.5 to 8 mM. The curve data were fitted using one site binding model of SigmaPlot software v.10.0. according to the Equation 3 ." ] },{ "paper_id": "5b13c9552c2cf5956633dff2463ab0f274d93708", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since the early 2000s, the South Korean government has legislated a special act to improve air quality in the SMA 11 , with emphasis on the reduction of fugitive dust (street wash-out and control of industrial and construction site sources), mobile fuel type change (diesel to compressed natural gas for buses and trucks), and residential heating source change (coal to liquefied natural gas). However, the efficiency of this act is sometimes questioned by the public, since they still experience severe high pollutant episodes. One intriguing question for the SMA Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 4710 |", "Surface monitoring data. Hourly observations of surface PM concentrations and wind speed were obtained from NIER and KMA, respectively. PM measurements, based on the beta-ray absorption method 54 , were collected from 247 urban air monitoring network sites, and wind data were collected from 79 meteorological monitoring sites. Locations of monitors are shown in the supplementary material.", "In addition to the changes in the amount of released emissions of pollutants and their precursors, meteorological conditions are also primary contributors to regional haze and air pollutions 15, 16 . Wind, in its velocity and transport pattern, is one of the major meteorological components that affects surface air pollution 17, 18 . Winds can control vertical mixing and regional ventilation 19 . Persistent stagnant conditions (i.e. calm wind) provide critical conditions that lead to the development of local pollution episodes. Wind direction controls the source-receptor relationship 20 , and it also directly initiates local emissions such as dust storms or sea salt emissions 21, 22 . Large scale transport, both regional or inter-continental, can affect the atmospheric composition by altering their lifetime (e.g. longer lifetime at higher altitudes), and influences global meteorology and climate 23, 24 ." ] },{ "paper_id": "5b13e81ee4495ff3eccaeea21f955ebc5e5cbde1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "5b15c62ee761d6eefeb7d2ef023f804bfdc41edc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS) and avian influenza are three newly emerged serious infections with pandemic potential [1, 2] . These pandemic infections and diseases usually cause considerable loss of lives, resulting in increased social trepidation [1, 3, 4] . The role of a hospital is basically to be a line of defense against the spread of these infections and diseases. However, hospitals with inadequate building facilities have unexpectedly become the most hazardous areas, zones of defenselessness that undermines the entire medical and healthcare system.", "Combined with declining birth rates, societies around the world are now facing the challenges of declining birth rates combined with rapidly aging population [54] . In Taiwan, the birth rate in 2010 was the world's lowest [55] . As a result of this declining, the number of students there has also been decreasing each year. In fact, it is estimated that 30% of middle school spaces will be unoccupied by the end of 2028 [56] . The aging population in Asia is increasing, from 10% in 2009 to 30% in 2050. While healthcare service is essential for the well-being of elderly people in terms of ", "subject to:" ] },{ "paper_id": "5b1c9c575d37e7026b0c2c0fdfe309b7a06a528a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analyses were performed using SAS\u00ae (Enterprise Guide 5.1; SAS Institute, Cary, NC, USA). A Fisher's Exact Test was used to evaluate pairwise differences in the proportion of pigs positive by bioassay between all 10 treatment groups. Ct values were analyzed using two way analyses of variance (ANOVA) models with treatment, time (pre versus post) and their interaction. Pre-treatment Ct values were compared between groups using an F-test. Differences in Ct values between pre-and post-treatment were assessed for each study group using a two-sided T-Test. A p value <0.05 was considered statistically significant." ] },{ "paper_id": "5b1ff90bfb94f984a838fe6f3a806cdedc3aa182", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5b263e22abc98f73d06f4d7baa292027c941f3c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Significance was set at p < 0.05 (*), p < 0.01 (**), p < 0.05 (***).", "Data are presented as the mean \u00b1 standard deviation. Differences between the test and control groups were analyzed by the Student's t test using the Prism software. Significance was set at p < 0.05 (*), p < 0.01 (**) and p < 0.05 (***).", "Some viral proteins regulating autophagic activity have been reported. Overexpression of the hepatitis B virus X gene (HBx) enhances starvation-induced autophagy through the upregulation of Beclin 1 expression [47] . Poliovirus 2BC and 3A proteins regulate LC3 modification and membrane induction [30, 48] . Furthermore, DV2 NS4A protein induces LC3 cleavage and translocation in epithelial cells [35] . However, whether DV2 NS4A alone in vivo is capable of inducing autophagy requires further investigation." ] },{ "paper_id": "5b31a92b9c0bbc361c12fb2c00bcb17ff3fab61c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All PCR-amplified sequences were subjected to automated sequence analysis (Microsynth SeqLab) to verify their integrity. Sequences of primers used for cloning of the different constructs are available upon request.", "One-way or two-way analysis of variance (ANOVA) with Dunnett's posttest was used to test for statistical significance. Only p values of 0.05 or lower were con- ", "The DPP4 protein structure (4PV7) [43] and the structure of the complex formed by the MERS-CoV S receptor binding domain bound to DPP4 (4L72) [16] were retrieved from the Research Collaboratory for Structural Bioinformatics Protein Database (RSCB PDB, https://www.rcsb.org/). Structure visualization and colorization was performed using the YASARA software (http://www.yasara.org/index.html) [44] and UCSF Chimera version 1.14 (developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco) [45] .", "Soluble S comprising the S1 subdomain of MERS-CoV S (aa residues: 1-747) fused to a human IgG Fc tag was generated by inserting the PCR-amplified S1 sequences into the pCG1Fc vector [39] (kindly provided by Georg Herrler, University of Veterinary Medicine Hannover) making use of the BamHI/SalI restriction sites. In addition, we generated an expression vector for the enhanced green fluorescent protein (eGFP) by inserting the eGFP coding sequence, which was PCR-amplified from the pEGFP-C1 vector (Clontech), into the pCAGGS plasmid using the EcoRI/XhoI restriction sites." ] },{ "paper_id": "5b34ff95646a7d1127a291315068bf8907e0d301", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sample reads were cleaned with Trimmomatic software [31] and aligned to the PEDV CV777 (Accession no. AF353511) complete genome using tmap (Torrent Suit 4.0.2, https:// github.com/iontorrent/TMAP) to evaluate coverage depth for each sample, Mira assembly [32] was ran on uncleaned, downsampled reads to a mean coverage depth of 80 after best kmer size estimation by kmergenie [33] . Spades assemblies [34] were performed after Trimmomatic cleaning.", "https://doi.org/10.1371/journal.pone.0193682.g002 ", "Supporting information S1 ", "The secondary structure of the 5\u00b4-terminal region of the viral RNA was predicted using Mfold [40]." ] },{ "paper_id": "5b36690d168ab53e08482ce4b4b956d9ad3c1a10", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analysis. Data were analyzed with SPSS 18.0, and the statistically significant differences were checked by test.", "HEK293T cells were performed using modified calcium phosphate transfection method as previously described [21] .", "Canine parvovirus (CPV) was first identified in 1978 as a pathogen that is responsible for serious gastroenteritis and myocarditis in dogs [1] . Currently, there are mainly three antigenic types of CPV (CPV-2a, CPV-2b, and CPV-2c) that are prevalent in different countries and cause major infectious disease threatening dog-raising industry. CPV is a small nonenveloped, single-stranded DNA virus [2] [3] [4] . The linear single-strand DNA genome, about 5 kb long, contains two open reading frames (ORFs). One ORF encodes two nonstructural proteins (NS1 and NS2), while the other encodes two structural proteins (VP1 and VP2). VP2 (426 amino acid residues) is the main component in CPV capsid which possesses strong antigenic properties. The canine transferrin receptor (TfR) has been identified as a receptor for CPV infection mediated by VP2-TfR interaction [5] [6] [7] .", "CPV was amplified in F81 cells and the virus titers determined by TCID 50 ." ] },{ "paper_id": "5b3e895eea9402eca728dbe11b00431d4bacbc7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5b454b34b6611cd015799280a78b9fed001068cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2) case containment measures: voluntary case isolation, voluntary quarantine of members of households with ill persons; and (3) infection control measures: hand hygiene, cough etiquette, and mask/respirator usage [1, 7] .", "x(0) = (s (0), i(0), r(0), d(0)) initial disease state of a community ", "where the switching curve \u03c8 (s, i) is the coefficient of u in Eq. (5), defined as:", "proportion of the control space" ] },{ "paper_id": "5b470094ead1416c283ca042644ac1061103b101", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The main objectives of this study were:", "For each location and each month, the variability in Cx. pipiens favorability (i.e. suitability) was calculated as:", "b. Connectivity: If animals traded in the market originated within the same district, the score for connectivity was 1. If animals originated from the same governorate, the score was 2, and if animals originated from different governorates, the score was 3.", "1. To understand the structure and patterns of the legal trade of live animals into Egypt, and then how those animals are distributed throughout the country." ] },{ "paper_id": "5b7e79c51c0788a3bb6e9c3a67e37d2dfedf9541", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Over the last 15 years, our planet has faced more than 15 deadly zoonotic or vector-borne global outbreaks, both viral (e.g., Hanta, Ebola, highly pathogenic avian influenza [H5N1 and recently H7N9], West Nile, Rift Valley fever, norovirus, severe acute respiratory syndrome [SARS] , Marburg, influenza A [H1N1]) and bacterial (e.g., Escherichia coli O157:H7, Yersinia pestis, and Bacillus anthracis, the causes of hemolytic uremic syndrome, plague, and anthrax, respectively). Since 1980, more than 87 new zoonotic and/or vector-borne EIDs have been discovered.", "N The Global One Health paradigm requires working across discipline and administrative barriers; this is a crucial component for effectively tackling complex One Health issues. ", "While zoonotic EIDs are a major concern globally, their impact in less developed countries is disproportionately high because of the occurrence of risk factors such as a high rate of population growth, lack of infrastructure and skilled-manpower capacity to tackle disease outbreaks, a high proportion of people with compromised immunity due to comorbidities such as HIV/AIDS or parasitic diseases, and lifestyles in which daily life depends on animals." ] },{ "paper_id": "5b80e43b1261e5998412a0976e64cabb01c8b121", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One microliter of ITS amplicon was mixed with 2 U pfu DNA ligase (Epicentre Biotechnologies, Madison, WI, U.S.A.) and 0.1 lmol l -1 padlock probe in 20 mmol l -1 Tris-HCl (pH 7.5), 20 mmol l -1 Cl, 10 mmol l -1 MgCl 2 , 0.1% Igepal, 0.01 mmol l -1 rATP and 1 mmol l -1 DTT, with an overall total reaction volume of 10 ll. Padlock probe ligation reaction was performed as described by [34] by one denaturation cycle for 5 min at 94\u00b0C, followed by five cycles of 30 s. at 94\u00b0C and 4 min ligation at 63\u00b0C.", "Exonucleolysis is needed to eliminate unligated padlock probe and template PCR product and therefore minimize subsequent ligation-independent amplification events. It had been done in a 20-ll vol by addition of 10 U every one of exonuclease I and III (New England Biolabs, Hitchin, UK) to the ligation mixture and incubation at 37\u00b0C for 30 min, followed by 94\u00b0C for 3 min to inactive the exonuclease reaction.", "Some species can be classified by physiological characteristics, for example, temperature tolerance and nitrate assimilation, however, for many taxa molecular characterization are needed. [17] . Sequencing of the rRNA ITS location is generally adequate for routine species distinction in the genus Exophiala [18] . This method is relatively costly and timeconsuming and less suitable for large numbers of strains in case of monitoring of epizootics." ] },{ "paper_id": "5b87c5054e29782b51940d6ab29ce3ca2b27d54b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where BRW i denotes the list of indices of the groups encountered by group i as it travels to and from the hotspot.", "We model infectious disease dynamics using a simple stochastic susceptible-infectious-removed (SIR) epidemic model, with oneday time steps. Each individual moves independently through the three states: Susceptible (at risk of contracting the disease), Infectious (capable of transmitting the disease), or Removed (recovered or dead). Susceptible individuals can be infected by infected individuals from either its own group or other groups. The latter can occur during neighbour-neighbour contacts or travelerresident contacts." ] },{ "paper_id": "5b8bd7273e2cd3875283e705102b12ddf38d25c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A new era of surveillance research is attempting to address these issues while taking advantage of available data. Electronic data captured at the point of care provides an efficient means for the conversion of clinical data to surveillance information. This has resulted in a new area of research called syndromic surveillance.", "3) urgent (contact family physician within 24 hours); 4) referral 72 (contact family physician with 72 hours);" ] },{ "paper_id": "5b8be7d97df4b06c42eedda3d997677d60100828", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tech (New York, NY, USA). Anti-GFP and Alexa Fluor 555-conjugated secondary antibodies and 4,6-diamidino-2-phenylindole (DAPI) were purchased from Beyotime (Haimen, China). Longchain dialkylcarbocyanines (DiD) were procured from Life Technologies (Grand Island, NY, USA).", "The siRNA oligonucleotides targeting IFITM3 and universal negative control siRNA were designed and synthesized from Ribobio (Guangzhou, China), their sequences are: ", "Data were calculated as the mean \u00b1 SD. Student's t-tests were performed for all analyses using GraphPad Prism 6 software (GraphPad Software Inc., CA, USA). Differences among groups were determined by one-way ANOVA with repeated test. Statistical significance was determined by two-tailed P values: *P < 0.05, **P < 0.01, and ***P < 0.001." ] },{ "paper_id": "5b965255f0dc3c8ef81a95673bcbfe57d902010f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mechanisms of immunological escape can explain why total antibody titers are not always protective. Many infectious organisms, including viruses, can constantly mutate surface proteins and exploit glycans to shield important epitopes, diverting the antibody response away from functionally important epitopes in favor of immunogenic irrelevant epitopes [4] .", "An IV form of PRO 140 tested as monotherapy in HIV-1 subjects with only R5 virus detectable [96] demonstrated potent and prolonged antiviral activity, with a 1.83 log10 mean reduction in HIV-1 RNA and safety relative to placebo. The successive randomized, double-blind, placebo-controlled IIa trial examined the antiviral activity, tolerability and pharmacokinetics of single intravenous infusions of up to 10-mg/kg of mAbs. All PRO 140-treated subjects treated with 10 mg/kg experienced a 1-log10-unit reduction in HIV-1 RNA level, there being just one exception; a post-study analysis using the enhanced-sensitivity Trofile assay determined that this subject had dual/mixed virus at screening. There was no change in co-receptor tropism or emergence of PRO 140-resistant virus during the course of this study, supporting the view that PRO 140 broadly inhibits R5 HIV-1 with a high barrier to resistance. The maximum tolerated dose of IV PRO 140 has not been determined, suggesting a sizeable margin of safety for PRO 140 SC administration study [97] .", "The innate immune response is the first-line defense in determining the outcome of an infection. Infectious agents contain conserved motifs on their surface that react with conserved pattern recognition Toll-like receptors of the host. This interaction initiates a powerful innate immune response. Moreover, the infectious agent's surface proteins and carbohydrates come into contact with B-cell receptors, membrane-bound immunoglobulin of isotype M (IgM) or D (IgD), and often induce potent antibody responses, which take some weeks to fully develop [1] .", "system is the exhaustion of virus-specific T cells. Exhaustion consists of a progressive dysfunction characterized by the inability to proliferate and to produce key antiviral and immune stimulating cytokines (for example, interleukin (IL)-2, tumor necrosis factor (TNF)-a, interferon (IFN)-\u03b3), or to lyse infected cells [29] ." ] },{ "paper_id": "5b97940d7cbe82e8c8b2482f6d6ab6fd45ecdbb1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5b9c63d5acc2fe8fde000803aca5a7e6a0d6df75", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "+ R 2 R 1 R 4 R 3 H O (for R 1 -R 4 see Figure 1a) i O O O OH -H 2 O [R 1 -R 4 , c.f. Figure 1a] [R 5 -R 8 , c.f. Figure 1b] O OH O O OH O R 3 R 4 R 2 R 1 1-15 (c.f. Figure 1a) O OH O O O R 6 R 7 R 5 16-20 (c.f. Figure1b) O R 8 CR R 1 R 2 R 3 R 4 AL O O O R 1 R 2 R 3 R 4", "Tables S1 with hydrogen-bonded geometries, Figures S1-S4 presenting hydrogen bonds for compounds 7, 9, 16 and 18." ] },{ "paper_id": "5ba627a0ae4eae9a35185493fbfb080849d1ce5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell total protein extraction was performed, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transmembrane antibody incubation, and color development.", "Cancers still remain the second leading cause of death worldwide after cardiovascular diseases [1] . Many classes of antitumor agents, especially tyrosine kinase (TK) inhibitors, have been introduced to the market during the last decade, and more candidates are now under development [2] . However, given the emergence of drug resistance and the low success rate in clinical development, the discovery of novel chemical compounds with a completely new mode of action is clearly needed.", "The Annexin V-APC/7-AAD Apoptosis Detection kit, Cell cycle detection kit, Mitochondrial membrane potential detection kit, SDS-PAGE gel preparation kit and the enhanced chemiluminescence (ECL) kit were purchased from Nanjing KeyGen Biotech Co., Ltd. (Nanjing, China). DMSO and MTT were purchased from Sigma-Aldrich (Merck Millipore, Darmstadt, Germany). Other reagents were purchased from Beyotime Institute of Biotechnology (Jiangsu, China)." ] },{ "paper_id": "5ba8056230c17ec133169d79aacf61ed7d4b458b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Population mobility to other cities from Wuhan was restricted on January 23, 2020, and all the inhabitants have been affected to either go out or come back to the city ever since. Vehicle transportations in Wuhan such as city buses and subways were banned and outbound transportations have been canceled (airlines, trains, and long-distance buses). In many places, the Chinese Lunar New Year Festival celebration and other gatherings were cancelled to reduce population concentration. Besides, Wuhan not only imposed a ban on overseas travels for tour purposes, but also suspended selling flight tickets and hotel-booking.", "Many kinds of guidelines have been developed, and useful information about risk factors and preventive measures are recommended to the public by various means [4] . It is found that the COVID-19 can be transmitted through droplets, contact, aerosol, etc. [5] . A person will not be infected if he washes his hands before touching the conjunctiva. Accordingly, measures such as washing hands, wearing masks and goggles are very effective to prevent potential infections. Further, Wuhan has implemented closed management of communities. Inhabitants are not allowed to go out of their communities and they are very supportive to this regulation.", "Since December 2019, a new type of coronavirus called novel coronavirus (2019-nCoV, or COVID-19) was identified in Wuhan, China. The COVID-19 has then rapidly spread to all over China and the world. It can cause symptoms including fever, difficulty in breathing, cough, and invasive lesions on both lungs of the patients [1] . It can spread to the lower respiratory tract and cause viral pneumonia. In severe cases, patients suffer from dyspnea and respiratory distress syndrome." ] },{ "paper_id": "5bae3e47050469780ae94d2f254ab80221178ebf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Occasionally, thyroid stimulating hormone (TSH) receptor blocking antibodies can be responsible of an atrophic form of AT; more rarely, anti-TSH receptor stimulating antibodies can cause a transient form of hyperthyroidism (hashitoxicosis) [20] .", "(d) Selenium: a selenium deficit is linked to a higher AT prevalence [28] .", "(e) Irradiation: AT occurs more frequently after the exposure to low doses of radiations [26] ." ] },{ "paper_id": "5bb2fe58be63844d5b13a6b0cacd3ec2c80d3cb3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Expression systems have been engineered for RNA viruses as described below. All ssRNA viruses share the feature of high level of RNA replication in the cytoplasm, which provides the basis for extreme transient expression of heterologous genes. However, the different polarities of the ssRNA genomes of self-replicating RNA viruses have required the design of vectors with specific features. Moreover, the viral vectors can be utilized in different forms as indicated for the individual types of viruses below.", "An interesting approach comprises the introduction of micro RNA-124 (miR-124) into an SFV4 vector [90] . As IFN-1 tolerance has been associated with the SFV nsP3-nsP4 genes, conditionally replicating SFV4-miR-124 virus was able to replicate in neurons and allowed targeting of gliomas otherwise sensitive to IFN-1. Evaluation of CT-2A mouse astrocytoma cells and IFN-1 pretreated human glioblastoma cells showed increased oncolytic potency. Moreover, a single intraperitoneal injection of SFV4-miR-124 into mice with implanted CT-2A orthotopic gliomas showed significant inhibition of tumor growth and improved survival rates." ] },{ "paper_id": "5bb362d1be223686ad4467e317cf5abb8383ab3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Despite substantial decline in global child mortality over the past two decades, over six million children die annually due to preventable or treatable illnesses approximately 50% of them in resource-limited settings in Africa [1] .", "Supporting Information S1 Strobe Checklist. (DOCX) S1 Appendix. (DOCX) S1 File. " ] },{ "paper_id": "5bb58fba5bb25b55cc4bcb4e229ba2d196b4bc99", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.ppat.1007875.g005" ] },{ "paper_id": "5bb8f28608aad3bde8b470c81025ce3c9e3a5fc3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where y denotes an n \u00d7 1 vector of response variable observations collected at n cities; X is an n \u00d7 k matrix representing explanatory variables; \u03b5 is an n \u00d7 1 vector of normally distributed (with constant ", "Data Accessibility: The data and analysis code for this study have been made publicly available under the MIT license at the GitHub repository, https://github.com/BoXu123/H1N1RoadSocioeco. ", "SD i = min {D ij , i = all cities, j = center cities}," ] },{ "paper_id": "5bbf8689ab8b16eeb47592fc469a390f63fa232e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: All authors contributed significantly to the work presented, the preparation of the manuscript, and have read and approved the final version.", "The number and capabilities of HLCC units throughout the world have increased in recent years; nonetheless these assets remain a relative rarity due to the significant cost and resources needed to build and maintain them. We advocate that funding for biopreparedness efforts, including outbreak investigation and response efforts; building of infrastructure; development of novel diagnostics, therapeutics and vaccines; and maintenance of this preparedness against HHCDs remain a high priority. We believe that this is critical if we are to effectively investigate, clinically manage, and ultimately prevent the transmission of HHCDs.", "A similar argument might be made with many other infectious diseases, including brucellosis, wherein the causative pathogens (Brucella sp) are included as Centers for Disease Control and Prevention (CDC) Category B agents of bioterrorism. Practically speaking, infectivity may be the least important of the three properties in determining the need for HLCC care. This derives from the fact that an exposure (via sneeze or cough) typically involves an inoculum order of magnitude greater than the ID 50 . Conversely, infectious dose is an important consideration when evaluating the efficacy of masks and respirators in preventing nosocomial transmission." ] },{ "paper_id": "5bc5b2f9dee2ff454efe226384070d467112e25d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the 64 codons illustrated in Table 1 , their corresponding triplets of DNA are illustrated in Table 2 .", "For example, from Table 3 , we will have \u03a8 (GCT) = 1.1, \u03a8 (GCC) = 1.2, \u03a8 (ATG) = 20.1, etc., and in addition, we can propose a novel 2D graphical representation of DNA sequences as follows:", "In the recent years, an exponential growth of sequence data in DNA databases has been observed by biologists; the importance of understanding genetic sequences coupled with the difficulty of working with such immense volumes of DNA sequence data underscores the urgent need for supportive visual tools. Recently, graphical representation is well regarded which can offer visual inspection of data and provide a simple way to facilitate the similarity analysis and comparison of DNA sequences [1] [2] [3] [4] [5] . Because of its convenience and excellent maneuverability, currently, all kinds of methods based on graphical representation have been extensively applied in relevant realms of bioinformatics." ] },{ "paper_id": "5bc8dd515058e0fe94c6fc4a2c3cb85572030fec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This multicenter prospective study, approved by the regional investigational review board (Comit\u00e9 de protection des personnes Nord Ouest, ref.: 08/07) involved the Pediatrics Departments of Lille University Hospital (Lille, France) and Roubaix Hospital (Roubaix, France). Parental written informed consents were obtained for all children.", "Rhinovirus A9 was propagated on MRC5 cells and supernatant was quantified in TCID50/mL. RNA of culture supernatant was extracted and serial 10-fold dilutions submitted to the quantitative RT PCR in order to establish a standard curve for quantification. Results of quantification are expressed as TCID50/mL equivalents.", "Statistical analyses were performed by SAS 9.3 software (SAS Institute Inc., Cary, NC 25513). Qualitative variables are reported as the number or the percentage and compared via the chi-square test or Fisher's exact test. Continuous variables, reported as median [interquartile range (IQR)], were compared via the Mann-Whitney test. Normality was assessed via the Shapiro-Wilk test. A p-value <0.05 was considered to be statistically significant. To evaluate the magnitude of differences between groups, we calculated the absolute standardized differences; a standardized difference between 20 and 50, 50 and 80 and higher than 80% denotes low, medium and large imbalance, respectively [26] ." ] },{ "paper_id": "5bc94c9cd8e4bcae0c56a4343f6f60cdc0effa9c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession numbers. The complete genome sequences of VN/KCHY-310113, VAP1113_1 and JFP1013_1 isolates have been deposited in GenBank under accession numbers KJ960178 through KJ960180.", "Porcine epidemic diarrhea virus (PEDV) has emerged in Vietnam since 2009. Herein, full-length genome sequences are reported for three PEDV isolates from pigs displaying severe diarrhea from farms located in northern and southern provinces of Vietnam. The results provide more understanding of the molecular characteristics of PEDV in Vietnam.", "stranded positive-sense RNA virus in the genus Alphacoronavirus, family Coronaviridae, order Nidovirales, is a causative agent of porcine epidemic diarrhea (PED) (1), a disease characterized by severe watery diarrhea with high mortality in young pigs (2) . PED is endemic in Asia (3) (4) (5) (6) (7) (8) , has been reported in Europe (2, 9) , and its recent emergence in North America suggests a threat to the swine industry worldwide (10) . PED has been observed in Vietnam since 2009, but no Vietnamese strains have previously been sequenced." ] },{ "paper_id": "5bcd3c424887a848429ff1027ac2aacf50944fbf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "I thank Ms. Noriko Tokushige for secretarial assistance. This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS), by a Grant-in-Aid for Research on Hepatitis from the Ministry of Health, Labor, and Welfare of Japan, and by Takeda Science Foundation.", "Hepatitis B virus is also the causative agent of chronic hepatitis, which progresses to liver cirrhosis and HCC worldwide. HBV belongs to hepadnavirus family and contains a small partially double-stranded circular DNA genome of 3.2 kb. Even though HBV is a DNA virus, HBV replicates its DNA genome via reverse transcription. Upon HBV infection, the HBV DNA is converted into covalently closed circular DNA (cccDNA) as the template for the viral transcription. Pregenomic RNA (pgRNA) of 3.5 kb is selectively packaged into nucleocapsid together with HBV Pol. The pgRNA is reverse transcribed by HBV Pol to generate relaxed circular (RC) DNA. The HBV reverse transcription occurs entirely within nucleocapsid following encapsidation.", "In conclusion, DDX3 participates in anti-viral innate immune signaling pathway leading to type I IFN induction. In contrast, viruses must target DDX3 and evolve mechanisms to overcome this host immune system. Indeed, several RNA viruses sequester and utilize DDX3 for their viral replication and prevent IFN induction.", "of HuH-7 cells by HCV (JFH1) was not affected by expression of the GFP fusion protein. These results suggest that the role of DDX3 in HCV infection involves aspects of the viral life cycle that vary in importance between HCV genotypes. Therefore, the exact contribution of HCV core-DDX3 interaction remains to be determined." ] },{ "paper_id": "5bcfcf89e794c73c8d079ddacc6eb7849501b927", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In summary, the emerging picture of allergic asthma suggests that the disease can be mediated or exacerbated in genetically predisposed individuals by infection. In some cases these infections may induce an inflammatory state that protects against asthma, while in others the infection may elicit an acute allergic response or bias the host towards a subsequent Th2 response (figure 1).", "The potent stimulatory responses mediated by TLR signaling must be tightly regulated at numerous levels in order to prevent the deleterious consequences of excessive innate immune activation [25] . For example, soluble forms of TLR4 and TLR2 may function as decoy receptors to terminate ligand interactions with membrane bound TLRs [26] . Furthermore, IRAK-M has 30-40% homology to the other IRAK-family members and stabilizes the TLR-MyD88-IRAK4 complex, leading to a unique negative regulatory influence on TLR signaling [27, 28] . TLR signaling is also inhibited by transmembrane receptors like ST2, SIGIRR, and TRAILR while proteins such as Tollip [29] , SARM [21] , an inducible splice variant of MyD88 (MyD88s) [30] , and the suppressor of cytokine signaling 1 (SOCS1) [31] are responsible for modulation of intracellular TLR signaling.", "Constant interactions between the respiratory tract and the environment pose a major challenge to host immunity and necessitate robust surveillance mechanisms to distinguish innocuous from pathogenic exposures. One strategy that is used by TLRs for selective induction of a host response is recognition of unique microbial structures termed pathogen-associated molecular patterns (PAMPs) [5] [6] [7] [8] . Eleven functional TLR genes that play diverse roles in host defense, inflammation, autoimmunity, and neoplasia have been discovered in mouse and man (mouse TLR10 is a pseudogene and human TLR11 encodes a truncated protein) [5] . Prototypic examples of PAMPs include lipopolysaccharide (LPS), a outer membrane component of Gram-negative bacteria that stimulates TLR4 [8, 9] , bacterial lipoproteins that stimulate TLR2 in conjunction with either TLR1 or TLR6 [10] , and flagellin, the protein monomer of bacterial flagella that activates TLR5 [11] . Nucleic acids are recognized by endosomal TLRs; double-stranded DNA with unmethylated CpG motifs activates TLR9 in a host species-specific manner while TLR3 and TLR7/8 are activated by dsRNA including synthetic poly (I:C) [12] and ssRNA, respectively [13, 14] ." ] },{ "paper_id": "5bd0d5db60f72689e429b6f1e98678d789930366", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "C. leptum preparation C. leptum was purchased from Jilin Baoxin Biological Technology (Changchun, China). We isolated the strain from a human fecal sample and stored it at \u221280\u00b0C. A single C. leptum colony was grown in chopped meat broth (before use, 500 \u03bcg/mL cycloserine and 15 \u03bcg/mL cefoxitin) for 24 h, harvested by centrifugation, and washed with phosphate-buffered saline (PBS). The freshly prepared bacteria in PBS were used for oral feeding.", "All data are presented as the mean \u00b1 standard deviation (SD). We assessed differences between control and experimental groups by analysis of variance. We considered p < 0.05 to indicate statistical significance." ] },{ "paper_id": "5bd910b6b8b82e7b70c97ebe2c34ad638236c67d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "C.R.R., A.M.A., and T.C.H. wrote this review. C.R.R. provided the illustration for Figure 1 . ", "The Flaviviridae family includes many significant global pathogens including Hepatitis C virus (HCV), West Nile virus (WNV), and Dengue virus (DENV). This family is comprised of four genera, with the human pathogens belonging to the genera Flavivirus and Hepacivirus. The Hepacivirus genus contains HCV, a prominent blood-borne human pathogen that causes chronic hepatitis and is estimated to have infected 170 million people worldwide. The Flavivirus genus includes DENV, WNV, Yellow Fever virus (YFV) and other viruses causing either haemorrhagic or encephalitic disease. Except for YFV and Japanese Encephalitis virus (JEV), vaccines for use in humans are not available against members of this family. Current treatment options are very limited and supportive care is often the only option. Arthropod vectors, mainly mosquitos and ticks are used by most flaviviruses to infect their hosts.", "Togavirus virions are enveloped, spherical particles (50-70 nm in diameter) that contain a single-strand +RNA with a 5-cap and 3 1 poly A-tail [124] . The family includes the genera Rubivirus and Alphavirus. Rubella virus (RUBV) is the sole member in the Rubivirus genus and is the causative agent of Rubella (also known as German Measles). The Alphavirus genus contains at least 30 members that are separated into New World and Old World viruses. The New World viruses include Venezuelan equine encephalitis (VEEV), Western equine encephalitis (WEEV) and Eastern equine encephalitis virus (EEEV). Old World alphaviruses evolved separately [125] and members include Semliki Forest virus (SFV), Sindbis virus (SINV), Chikungunya virus (CHIKV) and O'nyong'nyong virus. Transmission occurs mainly through mosquito vectors and human infections are often associated with fever, rash, severe joint pain (arthralgia) and stiffness that can last weeks to months in duration. Some pathogens in this group can cause much more severe illnesses including encephalitis in humans and animals." ] },{ "paper_id": "5be812ecd3a63e7b5e718f17d9ca3a0d0fdb4a70", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.ppat.1006721.g002", "https://doi.org/10.1371/journal.ppat.1006721.g005", "https://doi.org/10.1371/journal.ppat.1006721.g007" ] },{ "paper_id": "5bf2ab79a25fdb03f50dafb0d08de60acbd50af0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To generate sialic acid-knockout cells, we used the CRISPR-Cas9 gene-editing tool to delete the GNE gene.", "Zika virus (ZIKV) is an arthropod-borne RNA virus in the genus Flavivirus with other vector-borne viruses significant to human health, such as dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), and Japanese encephalitis virus (JEV) [1] . ZIKV was first isolated from a febrile sentinel rhesus macaque in 1947 and from an Aedes africanus mosquito in 1948 in Zika Forest, Uganda [2] . ZIKV infection has been associated with mild symptoms such as fever, rash, arthralgia, and conjunctivitis. Sporadic cases of ZIKV infections were reported over the next half century before ZIKV emerged in major outbreaks in Yap Island in 2007 [3] , French Polynesia in 2013 [4] , and Brazil in 2015 [5] . These ZIKV outbreaks have been associated with Guillian-Barr\u00e9 syndrome and congenital microcephaly [6, 7] .", "ZIKV and H1N1 genomic RNA and housekeeping (small nuclear ribonucleoprotein D3, SNRPD3) mRNA levels were determined by real-time PCR. In brief, cDNA was synthesized using the Quantitect Reverse Transcription kit (Qiagen) and real-time PCR was performed with CFX96 real-time PCR detection system (Bio-Rad) using SensiFast SYBR No-ROX kit (Bioline)." ] },{ "paper_id": "5bf6b6685fadbbc4899faa052321c697190bbade", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Numerous reports have shown that some clinical anticancer drugs could be obtained from natural products, thus, finding novel anticancer agents from natural plants has been recognized as one of the best strategies for the development of chemotherapeutic agents. Glycyrrhetinic acid (GE) can occupy ", "These observations indicate that cytochrome c and AIF were released from the mitochondria into the cytoplasm compared to the control group. ", "Values were presented as mean\u02d8standard deviation (SD) from triplicate experiments. Statistical analysis of all data was conducted by Student's t test. The p < 0.05 was considered statistically significant.", "Leukemia is a heterogeneous group of hematopoietic malignancies [1] and the sixth leading cause of cancer-associated death, causing 7.1 deaths per 100,000 persons per year in the USA [2] . In Taiwan, where 4.2 per 100,000 persons die annually from the disease based on the 2012 report from the Department of Health, Executive Yuan, Taiwan [3] leukemia is the 13th leading cause of cancer-associated death. Acute leukemia are clonal disorders of hematopoietic stem cells that can be divided into acute myeloid leukemia (AML) which can occur at all ages and acute lymphoid leukemia (ALL) which most often occurs in children and adolescents, with approximately 60% of patients being younger than 20 years [4] [5] [6] . It was reported that about 50% of the young adult patients and approximately 90% of older patients with AML or ALL die from those diseases [5, 6] . Currently, the cure-rate for patients with AML remains at approximately 25% [7] , mainly due to the side effects which still are the major limit to treatment success. Thus, finding new compounds derived from natural products for leukemia is needed." ] },{ "paper_id": "5bff4ea8641b22fa07590fce75e19dccf9f75548", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The neonatal period represents a critical stage in the development of physiological functions. During this phase, the newborn has to face several adjustments to adapt the body systems to extrauterine life [1] . Newborns are in metabolically unstable conditions, which make these subjects particularly sensitive to perinatal diseases resulting in high mortality rates [1, 2] ." ] },{ "paper_id": "5c0beb565af7a9bcad425207e8b5141540ff3778", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "New England Journal of Medicine 379 8th", "Lancet 400 5th", "Clinical Pharmacology and Therapeutics 371 9th", "Journal of the American College of Cardiology 381 5th" ] },{ "paper_id": "5c10b401cc688e4f966e2ab5f41ab3a056685a3d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As control, a one step qRT-PCR targeting the GAPDH sequences was performed [24] .", "Viral genomic RNA was extracted using QIAamp Viral RNA Mini kit (Qiagen) according to the manufacturer's recommendations and cDNA, PCR and sequencing were performed as previously described [10] . All primer sequences are available from the authors upon request.", "Cells were solubilised in LDS sample buffer (Invitrogen) complemented with \u03b2 mercaptoethanol, and proteins were separated by polyacrylamide gel electrophoresis (NUPAGE Invitrogen) followed by western blotting. Rabbit polyclonal anti-NS antibody was a kind gift from D. Marc (INRA, Tours, France). The rabbit anti-PR8, used to detect NP, was produced in house [25] . Anti beta-actin (Abcam, Cambridge, UK) antibody was used for loading controls." ] },{ "paper_id": "5c21db27b83fa2b5d4c1b0739b99e53c83e0430c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tissues were obtained from either non-diseased lung tissue obtained from patients undergoing lung resection for lung metastasis cancer therapy (Thoracic Surgery, University Hospital Basel, Basel, Switzerland).", "Polymerase chain reaction was performed with the following primers: RVqR447f: 5'-GGC CCC TGA ATG YGG CTA A-3' qR561r: 5'-GAA ACA CGG ACA CCC AAA GTA G-3', following the protocol described by others [36] . The PCR products were analysed by gel electrophoresis.", "Asthma patients were classified as Mild-sever according to GINA guidelines (Pneumology Clinics, University Hospital Basel, Basel, Switzerland)." ] },{ "paper_id": "5c29db6b02088e3b38e416bf32f6a02dbcf9cdf8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Small, custom arrays can be designed for many more species as long as genomic sequences are available for a particular organism or family of organisms [2, 9, 11] .", "Common steps employed to ensure quality and validity of microarray results", "Researchers identified clusters of genes as being representative of each type (i.e. being present in one group, but not in another) with functional implications [45] .", "Whatever synchronization method is used should be applied to all of the biological samples to ensure a valid comparison is being made." ] },{ "paper_id": "5c313555924b8f0f82f082673f42b56ef736c20a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Regularly removing unintentional standing water both inside and outside the house and in communal areas.", "Seeking antenatal care to monitor pregnancy and discuss Zika risk and prevention.", "Seeking counseling from a trained provider on modern family planning methods if not planning on getting pregnant." ] },{ "paper_id": "5c364a85b8e920e9b4ad2fa201589fc319bc174b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Neurons and astrocytes are generated from common neural precursors, yet neurogenesis precedes astrocyte formation during embryogenesis. The mechanisms of neural development underlying suppression and de-suppression of differentiation-related genes for cell fate specifications are not well understood.", "Preparation of Protein Extracts: Cell pellets were first washed three times with PBS and lysed in lysis buffer (0.25 M Tris-HCl at pH 6.8, 1% SDS). Protein concentration was obtained by BCA TM protein assay. Cell lysate was then dried and stored in 230uC." ] },{ "paper_id": "5c3f5dde0537e3072d046990501a4e71471d9ddc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the authors declare that there are no competing interests.", "The parent study and this genetic sub-study conformed to the procedures for informed consent (parental permission) approved by institutional review boards at all sponsoring organizations and to human-experimentation guidelines set forth by the United States Department of Health and Human Services.", "Authors' contributions MAP and SS conceived, designed and led the study. AS assisted with the SNP genotyping and managed the genetic data. MS managed the clinical data and assisted with recruitment of patients. HWW performed the analysis and both AS and HWW assisted with the interpretation of the genetic analysis results. MAP and SS wrote the manuscript, and all authors participated in drafting the manuscript to the final version. All authors read and approved the final manuscript." ] },{ "paper_id": "5c4dfdf8ee6230324845b917be55c47d1e991f2c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HCLE is a Shuttling Protein whose Import Depends on Active Transcription", "The videos were analyzed with Leica Microsystems LAS AF software (version 2.3.0).", "In-gel protein digestion and sample preparation for MALDI-TOF/TOF analysis. Bands of interest from silverstained gels were excised manually and processed automatically in a Proteineer DP (Bruker Daltonics, Bremen, Germany). The digestion protocol used was as reported [19] ." ] },{ "paper_id": "5c4e986c0995292d3e3839bb20c20b95039ae9d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It will be important to analyze the effects of selectively ablating CXCR2 on oligodendroglia during JHMV-induced demyelination, while simultaneously manipulating the cellular sources of ELR-positive chemokines in the CNS that may promote neuroprotection during chronic JHMV-induced disease.", "The JHMV-induced model of viral-induced encephalomyelitis provides an important tool in defining molecular and cellular mechanisms that regulate neuroinflammation during both host defense and disease progression. Our research on chemokines and chemokine receptors has revealed important roles for these molecules in orchestrating CNS inflammation in response to JHMV infection. We and others have found unique and pleiotropic roles for ELR+ chemokine signaling via CXCR2 in moderating neutrophil infiltration and protecting oligodendroglia from apoptosis in response to exposure to virus and proinflammatory cytokines. Ongoing research in our laboratory continues to focus on the role of ELR(+) chemokine signaling on oligodendroglia during JHMV-induced neuroinflammation.", "Intracranial infection of susceptible mice with the JHM strain of mouse hepatitis virus (JHMV) causes an acute encephalomyelitis followed by a chronic demyelinating disease. JHMV, after initially infecting ependymal cells lining the ventricles, rapidly disseminates to astrocytes, oligodendroglia, and microglia throughout the brain and spinal cord (Wang et al., 1992) . Although inflammatory virus-specific T cells are efficient in controlling viral replication through the secretion of IFN-\u03b3 and cytolytic activity, sterile immunity is not achieved. Viral protein and/or RNA persist within oligodendroglia and drive continual T cell and macrophage infiltration, leading to chronic neuroinflammation and demyelination. Histological features associated with viral persistence include the development of an immune-mediated demyelinating disease similar to the human demyelinating disease MS; both T cells and macrophages are critical mediators of disease severity, contributing to myelin damage (Cheever et al., 1949; Perlman et al., 1999) ." ] },{ "paper_id": "5c5088ded6a49170c4ee50c8a9bfc5422cc31668", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The life cycle of enveloped viruses is initiated after binding to a specific receptor(s) on the host cell surface, followed by membrane fusion, which is mediated through one or more viral glycoproteins [6] [7] [8] . In general, the viral attachment proteins (G, H, or HN, depending on the virus) of paramyxoviruses, ", "Scientific RepoRts | 5:15584 | DOi: 10.1038/srep15584 (Fig. 8) . The mechanism underlying the effect of position 294 on the fusogenicity of aMPV and hMPV F proteins requires further study.", "Avian metapneumovirus (aMPV) belongs to the genus Metapneumovirus in the subfamily Pneumovirinae of the family Paramyxoviridae 1 . aMPV causes acute rhinotracheitis in turkeys of all ages and swollen head syndrome in chickens, resulting in a major economic burden for poultry farmers 2 . Since aMPV was first detected in South Africa in 1978, aMPV has been reported in many countries 3 . Phylogenetic analyses have categorized the aMPV strains into four subtypes, termed A, B, C, and D, which are sometimes designated as aMPV/A, aMPV/B, aMPV/C, and aMPV/D, respectively 4 . Metapneumoviruses have recently been subclassified into two types based on phylogenetic analysis: type I metapneumoviruses, including aMPV/A, B, and D, and type II metapneumoviruses, including aMPV/C and human metapneumovirus (hMPV) 5 ." ] },{ "paper_id": "5c5236506e7dfce0f35caf94d9eec62c5b815d0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Acknowledgments This manuscript was greatly improved by thorough and constructive criticism from the anonymous reviewers.", "Keywords Epidemic model \u00b7 Metapopulation \u00b7 Host-vector \u00b7 Control \u00b7 Demography", "dt = \u03b3 I W MC i \u2212 \u03c1 MC R W MC i + \u03c4 MC R H i d R Y dS Y V dt = \u03ba N 5 \u03bc \u2212 \u03b2 S Y V I Y \u03a3 N Y \u03a3 \u2212 \u03bcS Y V (36) dE Y V dt = \u03b2 S Y V I Y \u03a3 N Y \u03a3 \u2212 \u03b5 V E Y V \u2212 \u03bcE Y V (37) dI Y V dt = \u03b5 V E Y V \u2212 \u03bcI Y V (38) where Y = H 1 , H 2 , S 1 , S 2 or W, N Y \u03a3 = N Y N M 1 + N Y N M 2 + N Y NC 1 + N Y NC 2 + N Y MC 1 + N Y MC 2 + N Y H M ." ] },{ "paper_id": "5c533a06c3dc5afefab5dd138ec4de394b537261", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Here we used lentivirus pseudovirions with MERS-CoV spike protein to study S-mediated cell entry at Biosafety Level 2.", "Codon-optimized cDNA encoding the spike glycoprotein of MERS-CoV [15] was synthesized with the c-terminal 16 amino acids replaced with a GGGGS linker and a FLAG tag (GenScript, Piscataway, NJ), and for eukaryotic expression was cloned into pcDNA3.1(+) (Invitrogen) between the BamHI and NotI sites. To make constructs for expression of truncated soluble MERS S aa1-351, S aa1-384, and S aa1-748 proteins, PCR reactions were performed using the same forward primer AATGAAAAGCTTCACCATGATTCACTCCGTGTTCCTC pairing with the following reverse primers, for S aa1-351: TAGTTTTCTAGAACTTCCGCCTCCACCATAA CTACAGTGGAGCTGGCT; for S aa1-384: TAGTTTTCTAGAACTTCCGCCTCCAC CGTCGCACTCCACGCCTTCTGCC; or for S aa1-748 TAGTTTTCTAGAACTTC CGCCTCCACCTGGGGTCAGTGTGCTGGGGGT, and cloned into p3xFLAG-CMV 14 (Sigma, St Louis, MO) between HindIII and XbaI sites for expression. The VSV-g plasmid and lentiviral packaging plasmid, psPAX2, were obtained from Addgene (Cambridge, MA). The lentiviral reporter plasmid, pLenti-GFP-Luc, which expresses green fluorescent protein (GFP) and luciferase, was kindly provided by Fang Li, Duke University [68] ", "Pseudotyped lentiviruses were produced as described previously [71] with minor modifications. Briefly, plasmids that encode viral spike glycoproteins MERS-CoV S\u220616, SARS S\u220619, or VSV-g were co-transfected into 293T cells with psPAX2 and pLenti-GFP-Luc using polyetherimide (PEI) (Polyscience Inc, Warrington, PA). Forty to 60 hr later the supernatant media containing pseudovirions were centrifuged at 800g for 5min to remove debris, and passed through a 0.45\u00b5m filter. To quantitate entry of pseudovirions into different cell types, 250\u00b5l of pseudovirions with 8 \u00b5g/ml of polybrene (Sigma) was inoculated onto cells in 24-well plates, incubated overnight at 37\u00b0C, and cells were fed with fresh medium. At 40hr post inoculation (pi) cells were lysed at room temperature with 120\u00b5l of medium with an equal volume of Steady-glo (Promega, Madison, WI). Transduction efficiency was monitored by quantitation of luciferase activity. Living cells transduced by pseudovirions were detected by GFP expression. For all experiments triplicate samples were analyzed, data are representative of two or more experiments, and the standard error is shown.", "Although the novel group c betacoronavirus MERS-CoV is highly virulent in humans and can infect cells from several different species, including humans, monkeys, pigs, and some species of bats [10, 16, 34] , little is known about the biology of this virus. Because the spike glycoprotein is essential for coronavirus entry, elucidating the functions of the MERS-CoV spike can provide valuable insight into the pathogenesis of MERS-CoV, and suggest potential therapeutic interventions." ] },{ "paper_id": "5c5491d07d2c4e996988e591b870ed272d2f944e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A sample of 5 ml of peripheral blood was obtained from each participant and placed in a test tube containing EDTA. We then isolated genomic DNA from the collected whole blood samples using a genomic DNA purification kit, in accordance with the manufacturer's instructions (Axygen Scientific Inc., Union City, CA, USA). Genotyping was conducted using PCR and the improved multiple ligase detection reaction (iMLDR). Five percent of samples were re-genotyped to verify the initial results." ] },{ "paper_id": "5c6b707c8cbd087e87e1a1c1f2e809cffc96a9dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The key events in CRY/PHR evolution and major changes in the global light regime", "Conceived and designed the experiments: VD. Performed the experiments: QM. Analyzed the data: QM. Contributed reagents/materials/analysis tools: VD QM. Wrote the paper: VD QM.", "Photolyases and cryptochromes are evolutionarily related flavoproteins, which however perform distinct physiological functions. Photolyases (PHR) are evolutionarily ancient enzymes. They are activated by light and repair DNA damage caused by UV radiation. Although cryptochromes share structural similarity with DNA photolyases, they lack DNA repair activity. Cryptochrome (CRY) is one of the key elements of the circadian system in animals. In plants, CRY acts as a blue light receptor to entrain circadian rhythms, and mediates a variety of light responses, such as the regulation of flowering and seedling growth." ] },{ "paper_id": "5c78286b1684b83d68551054909958005fc2529a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Detection of proteins by Western blotting was performed as described previously ( [44] ) using the following antibodies: antitubulin (1:5000; clone B512, Sigma), anti-BUNN (1:5000; ( [35] )), anti-BUNNSs (1:500; ([8])), anti-NEDD8 (1:1000; Epitomics), anti-rabbit IgG-HRP conjugate (1:5000; Cell Signalling), antimouse IgG peroxidase conjugate (1:5000; Sigma). Typically, exposures for N protein and tubulin were very short (5-15 sec), whereas detection of NSs required much longer exposures ranging from 2 to 30 min.", "In the experiments described above the inhibitors MG132, epoxomicin and PYR-41 were added at 5-8 hpi, to allow N protein synthesis to commence before treatment. When added from the start of infection, the proteasome inhibitor MG132 and the E1 inhibitor PYR-41 significantly delayed onset of N protein production (by more than 12 h; data not shown). This is an indication that, like many other viruses, BUNV requires an active UPS during the early stages of infection.", "Analysis of DNA fragmentation, as a measure of apoptosis, followed the method detailed by Kohl et al. ([9] ).", "Where indicated drugs were used as follows: to block the proteasome the medium on the cells was replaced at 5-6 hpi by medium containing 10 mM MG132 (Calbiochem) or 200 nM Epoxomicin (Sigma), which was left on until harvest. The inhibitor of the E1 ubiquitylation enzyme, PYR-41 (Merck), was used at 50 mM and added at 8 hpi. The NEDD8 E1 activating enzyme inhibitor MLN4924 (kindly provided by Prof. R.T. Hay) was used at 1 mM, and added at 5-6 hpi." ] },{ "paper_id": "5c8323be8a418f5df5d877da4a51720e9aa60425", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vaccination would have to be given in early infancy because of the very young age of primary infection, and those vaccinated would have to be followed for six or seven decades thereafteran unrealistic possibility. This leaves antiviral treatment as a desirable, safe and potentially effective alternative.", "An interesting overlap of HAD proteins and AD proteins was discovered by Zhou et al. (2010) , who analyzed total proteins from frontal cortices of HAD and HIV non-demented patients: 90% of the proteins they identified had been reported previously for several neurological diseases including AD (referred to by the authors as a \"non-viral\" disease for comparison with HIV, despite their citing several studies on AD viral aetiology!). Indeed, as they pointed out, their data might help to elucidate the involvement of any pathogen in \"non-viral\" neurodegeneration.", "Reactivation of HSV1 in brain obviously does not lead to overt herpes simplex encephalitis (HSE), as that outcome would be probably be fatal unless diagnosed rapidly and treated immediately with antivirals. Therefore reactivation events must presumably be very localized or mild; in fact such limited and asymptomatic reactivations have been described in a number of cases of recurrent HSE (see below)." ] },{ "paper_id": "5c8dd07d1f935b762960eff3a7cf7c6f1233ccd3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As IFN signaling and stress granules are important for a variety of viral pathogens, answers to these questions may provide broadly relevant insight into host-pathogen interactions.", "EF was supported by a David Delo Research Grant. MD was supported by Action de Recherches Concert\u00e9e (ARC). Research in the TM lab was supported by the Belgian Fund for Medical Research (FRSM, PDR # T.0185.14) and by EOS joint program of Fonds de la Recherche Scientifique -FNRS and Fonds wetenschapelijk onderzoek -Vlaanderen -FWO (EOS ID: 30981113).", "EF, MD, and TM wrote the manuscript and approved its final version.", "Interferon secreted by infected cells binds to its receptor on surrounding cells, activating a signaling cascade that leads to expression of hundreds of interferon-stimulated genes (ISGs). Two of these ISGs, PKR and oligoadenylate synthetases (OAS) are part of the best-characterized interferon effector pathways." ] },{ "paper_id": "5c8e391286fba644689754596eaf50c7f32b5a99", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 Table. Reference strain used for phylogenic analysis. " ] },{ "paper_id": "5ca36a454b447db9cb215c7bbb13f8cd1d6ff3e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The procedures employed for this study were approved by the Plum Island Animal Disease Center (PIADC) Institutional Animal Care and Use Committee (IACUC) under protocols: 209-12-R and 209-15-R." ] },{ "paper_id": "5ca68ac4cbda643bc9b11a04d5fdb30cd57b3c4d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5ca920dabf09c2c2dd2c62f8ef5917e3bd72f087", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The recombination predictions of the concatenated genome sequences were conducted with a suite of programs within the RDP3 package [39, 40] . The individual programs RDP [39] , GENECONV [73] , Bootscan [40] , Maximum Chi [74] , Chimaera [75] , SiScan [76] and 3Seq [77] , were implemented for the analysis. Since no single program provided optimal performance under all conditions, any event supported by five or more methods with p-values #10 25 was the criteria used for positive recombination breakpoints identification. The breakpoint position and the putative parental sequences were also determined.", "NDV, a single-stranded, non-segmented, negative-sense RNA virus of the genus Avulavirus, family Paramyxoviridae, infects a wide range of domestic and wild bird species worldwide, and causes a significant economic burden to the poultry industry [1] . The first outbreaks of NDV were reported during the mid 1920s in Java, Indonesia and Newcastle-upon-Tyne, England [2] , and within a few years were occurring throughout the world [3] . The name ND is reserved exclusively for the disease that results from infection with strains of aPMV-1 that are pathogenic for domestic chickens [4] . aPMV-1 has been grouped by virulence phenotype, with lentogenic, mesogenic, and velogenic strains representing increasing levels of virulence, ranging from subclinical infections with moderate respiratory involvement to extensive hemorrhagic lesions and neurological signs [5] . Inactivated vaccines were first made commercially available to the poultry industry in 1946, but because they provided incomplete protection against ND [6] , they were replaced with live lentogenic NDV vaccines. Although these vaccines reduce disease, they do not always prevent infection and birds can shed both vaccine and challenge strains of the virus [7, 8, 9] .", "RNA viruses typically have a high mutation rate due to low fidelity and processivity of their polymerase [25] , which coupled with a high replication rate and short generation time [26] lead to high evolutionary rates. In addition, evidence is accumulating that recombination is an important process driving genotype diversity for many RNA viruses [27, 28, 29] . Although recombination was not thought to contribute to aPMV-1 evolution [30, 31] , evidence of recombination in NDV has recently been reported [32, 33, 34] . This debate may be due, in part, to the reliance on a single gene for determining virus diversity and phylogeny. Because recombination can lead to the emergence of novel virus strains of unknown virulence [35, 36, 37, 38] , a better understanding of the role of recombination in circulating aPMV-1 is warranted." ] },{ "paper_id": "5caced13bcb8a42cca41369c5a71ae7df5381ca8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were obtained as the means + \u2212 S.E.M. of three replicates per test in a single experiment. GraphPad Prism V6.0 (San Diego, CA, U.S.A.) used to perform statistical analyses. Tukey's multiple comparison tests and one-way ANOVA were used to analyze the significance of the difference between means. P-values less than 0.05 (P<0.05) were considered significant and P-values less than 0.01 (P<0.01) as highly significant.", "The immunohistochemistry detection was performed with the SABC kit (Boster Bioscience). Hydrogen peroxide was used to deactivate intrinsic peroxidase. Antigen retrieval was performed in a water bath using citrate-EDTA buffer (10 mM citric acid, 2 mM EDTA, 0.05% Tween 20, pH 6.2). Sections were incubated with diluted anti-IgA antibody (1:100; Abcam) overnight at 4 \u2022 C. As negative controls, immunostaining performed by incubating samples with control antiserum instead of primary antibody. The addition of biotin-labeled secondary antibody to the slides was followed by adding HRP-labeled streptavidin. After staining with DAB, the slides were recorded using a digital camera (Leica-DM4000B) [25] .", "Amidst the PEDV outbreak, various vaccines have been developed to control diseases and the effects are unsatisfactory. Oral vaccines can induce more robust mucosal immunity than injectable counterparts [32] . Therefore, oral immunization has appeared as an effective strategy for controlling PEDV outbreak [33] .", "Specimen collection was then performed every 7 days post boost immunization ( Figure 1C ). Blood samples were collected weekly from all piglets after the boost immunization and allowed to clot overnight at room temperature to collect serum. Blood samples were separated by centrifugation and stored at \u221220 \u2022 C in order to detect the levels of specific IgG and IgA. Three swabs were collected every week lasting for 1 month, including nasal, oral, and feces swabs for the ELISA. The piglets were sacrificed in 33 days. The same location of the small intestine and ileum tissues from each piglet were fixed with Bonn's liquid and 4% paraformaldehyde." ] },{ "paper_id": "5cb67b8103fed813182562e341dd55edb81c4998", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Respiratory syncytial virus (RSV), an enveloped, singlestranded, negative-sense RNA pneumovirus, is a member of the Orthopneumovirus genus and Pneumoviridae family. Inflicting high morbidity and mortality rates in infants and young children, RSV is the most important pathogen responsible for lower respiratory tract infections in infants worldwide [1] ." ] },{ "paper_id": "5cc7d19d8c064e59978daa0699ca18d5b139b0db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using Prism 7 (GraphPad, San Diego, CA, USA). Data are presented as means \u00b1 standard deviations (SDs). The statistical significance of numerical data was analyzed using two-way analysis of variance (ANOVA), and p < 0.05 was considered statistically significant.", "Six-to eight-week-old female C57BL/6 mice were purchased from the Koatech Laboratory Animal Center (Pyeongtaek, Korea) and housed under specific pathogen-free conditions with water and food provided ad libitum. Animal experiments were approved by the Institutional Animal Care and Use Committee of Chonbuk National University (Approval No. CBNU 2017-0055) and followed the guidelines suggested by the committee." ] },{ "paper_id": "5cd3d3edd1b68bce986c6b9e6bfa9720efd041e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ", .", "(", "Then we have" ] },{ "paper_id": "5d04b1e66045a858dd72847b88dcc6a280da3165", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study protocol was in accordance with the Declaration of Helsinki and was approved by the ethics committees of the 12 ", "A single throat swab, using Sterile Rayon Swabs (167KS01, Guangzhou, China), was collected from each study patient before receiving antivirals or antibiotic drugs. The swab was immediately placed in a virus transport media tube (167KS01, Guangzhou, China). Each sample was frozen at \u221280\u00b0C within 24 h until analyzed.", "The authors' declare that they have no competing interests." ] },{ "paper_id": "5d1257333598094fd630f16f989336a2c5d223a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Until there is a greater understanding of why NP occasionally complicates pneumonia, its prevention will depend upon reducing CAP and its severity. Efforts should focus upon children aged <5 years who have the highest incidence of CAP [108] . Indeed, since the year 2000, deaths from CAP in this age group have declined >50% globally, falling below one million in 2015 [109] . Decreases in CAP are attributed to a combination of improved housing, water supply and hygiene, better indoor air quality, reduced parental tobacco smoking, increased education, breastfeeding rates and nutrition, and greater healthcare access and vaccine uptake [110] . Vaccines contributing to this success globally are pertussis, measles, Hib, and pneumococcal conjugate vaccines [111] .", "The second aim of surgery is managing progressive lung parenchymal necrosis. This involves segmental or lobar resection or pneumonectomy and is rarely required in children. Indications for surgery include massive hemoptysis, large or multiple tension pneumatoceles, and pulmonary gangrene where cavities or subsequent abscesses exceed 50% of the involved lobe [2, 5, 106] .", "Children with NP usually have a prolonged hospital stay. The median length of stay in cases listed in Table 1 ranged from 12 to 30 days. Not surprisingly, those undergoing surgery had a longer stay in hospital than those managed conservatively [36, 106] ." ] },{ "paper_id": "5d1e7636378e32ba1d2228d2ec7b3f82ac2661e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by grants to AM from the Spanish Ministry of Economy and Competitiveness (projects SAF2012-31187, SAF2013-49788-EXP, SAF2015-65878-R), Carlos III Institute of Health (projects PIE14/00045 and AC15/00022), Generalitat Valenciana (project Promete-oII/2014/065 and Prometeo/2018/A/133), Asociaci\u00f3n Espa\u00f1ola contra el Cancer (project AECC 2017-1485) and cofinanced by the European Regional Development Fund (ERDF).", "2) Surveying the whole virome requires the use of two entirely different protocols for RNA and DNA viruses. Whereas the methods for processing DNA viruses fall closer to regular WGS methodology, RNA viruses comprise a significant fraction of the virome that is often ignored as it specifically requires retrotranscription of the RNA to cDNA, often using SISPA or similar protocols that complicate the downstream laboratory procedures and bioinformatic analyses. It is important to note that most limitations and issues inherent to metatranscriptomics also apply to viromic RNA workflows [105] .", "In summary, viromics was the last successor in a long lineage of culture-independent approaches arising in the latter half of the 20 th century, and as such, inherited many of the advantages and the scope of metagenomic analyses. However, the field faces several unique methodological, ecological and conceptual challenges that represent key limitations to this day (Figure 1 ):" ] },{ "paper_id": "5d254ed178c092d3639ce70ae9653593acc471f9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This response is one of the swiftest, coordinated global responses to an emerging infectious disease the world has seen in modern times, but is it the appropriate response, will it be effective and is it sustainable?", "Key to that approach, however, is confidence that decisions will not be criticised based on information that was not available at the time. It is also important to be ready to change decisions when the available information changessomething that both scientists and politicians can find difficult.", "Working with journalists and the media to help them understand the science and epidemiology, particularly in a fast moving event, will improve risk communication to the public and reduce inappropriate concerns and panic.", "In that context, China should not be judged for implementing what might appear to be extreme measures but China should also be prepared to discontinue the measures quickly if evidence suggests they are not the best way to solve the problem. By closing airports the international spread from Wuhan may be decreased, but success will depend on how effective the measures really are at stopping people moving out of the affected area as well as on the behaviour of the virus. As always, only time will tellbut time is scarce." ] },{ "paper_id": "5d295bdf0e26bc9492f3fb1580833419f26b4e7c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.pcbi.1006876.g003", "whose Jacobian matrix is" ] },{ "paper_id": "5d2bf5e0b24d87dd18a0dba2ef76131efc31fb2c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Digital epidemiology -from expert knowledge to 'knowledge without truth'", "Thus, the politics of preemption in the present era of elevated pandemic threat are intimately intertwined with expanding recourses to apprehending Big Data sources and employing algorithmic processing techniques to produce advanced alerts, indications and insights of potential pathogenic uncertainties.", "For sure these points need further critical examination. Thus I am looking forward to future interdisciplinary exchange and discussion. ", "Thus, these continued shifts towards employing advanced algorithms to make sense of unprecedented amounts of information (Leese 2014) , across practices of contemporary disease surveillance must be continually matched with equally robust interrogations of the unforeseen or unprecedented implications of securitization by algorithms in the realms of ethics, law, politics and society." ] },{ "paper_id": "5d2c1aaad487ae9b76099721947c8948a57ebba3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nasal, oral and rectal swabs were collected and stored in 1 ml DMEM and vortexed for 30 seconds. Tissue samples were weighed and homogenized in 10 equivalent volumes of DMEM to generate a 10% solution. The solution was centrifuged at 10,000 rpm under aerosol containment in a table top centrifuge for 5 min. Supernatants from swabs and tissue homogenates were serially diluted in DMEM, and 200 ml volumes of each dilution were placed onto monolayers of Vero-E6 cells in six-well plates. Following 1 hour of incubation at 37uC, the cells were overlaid with 0.8% agarose-containing medium. Two days later, the plates were stained with crystal violet and the plaques were counted. Titers were calculated as plaque forming unit (pfu) per ml or gr for swabs and tissues respectively. Titers were graphed using GraphPad Prism.", "All tissues were inactivated and fixed in 10% phosphate-buffered formalin for at least 7 days prior to being processed by conventional methods, embedded in paraffin, sectioning at 5 mm thickness and hematoxylin and eosin staining. Slides were evaluated by a veterinary pathologist (D.G.). Tissues for immunohistochemistry were stained on the Discovery XT automated stainer (Ventana Medical Systems) using the anti-SARS-nucleoprotein antibody (Imgenex) and the DAB map detection kit (Ventana Medical Systems). Non-immune rabbit IgG was used as a negative staining control.", "A mobile digital radiography unit with a flat panel digital detector (Sound Technologies tru/Dr) and a portable x-ray generator (Poskom model PXP-HF) was used to acquire chest radiographs. The system operates on veterinary specific software system (Vetpacs). Animals were positioned for ventrodorsal radiography by using a Lexan v-shaped thoracic positioner. Radiographic views acquired included ventrodorsal, right lateral, and left lateral thoracic images while under anesthesia. The digital images were interpreted and assigned a numeric score by a veterinary radiologist who was blinded to the study design (JM). A score on a scale of 0-3 based on severity of radiographic changes were assigned to each set of radiographs (ventrodorsal, right lateral and left lateral) at each time point. Radiographs were evaluated and scored using the following criteria: Grade 0, normal examination; Grade 1, mild interstitial pulmonary infiltrates; Grade 2, moderate interstitial infiltrates, this may include partial cardiac border effacement and small areas of pulmonary consolidation (alveolar patterns and air bronchograms); and Grade 3, pulmonary consolidation as the primary lung pathology, seen as a progression from Grade 2 lung pathology." ] },{ "paper_id": "5d36857d0cdaff4320e21e718bdc2e12599ef124", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Characterization and production of S protein of G1b PEDV", "Evaluation of cross reactivity of serological assays using G1b PEDV S-hyperimmune serum", "(Continued on next page)", "The purity and quality of the S 1-501 protein were confirmed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) (Additional file 1: Figure S1 ).", "The procedures involving animals were approved and permitted by the Institutional Animal Care and Use Committee (IACUC) of National Taiwan University (NTU; Taiwan, Republic of China) and carried out under the regulations of the IACUC protocol at NTU with the approval number of 106-EL-00054." ] },{ "paper_id": "5d3e915d8571f298da4ff2e929d8475d68dc559f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Another well-characterized viral entry strategy is seen in the Herpes simplex virus-1 (HSV-1), a member of the Herpesviridae enveloped DNA virus family that can cause either lytic or latent infections. While HSV-1 entry shares similarities to HIV-1, there is also a clear difference. Upon interaction with the TNF superfamily receptor, HSV-1 envelope glycoprotein gD undergoes conformational changes to promote endocytosis (Fig 1B, step i) [7]. The low PLOS Pathogens |", "Viral genomes are protected within a proteinaceous shell called \"capsid\" and, for enveloped viruses, an additional lipid coat. The capsids are generally constructed from a few capsid proteins into helical or icosahedral structures that are, in turn, stabilized by numerous covalent and noncovalent interactions [1] . However, during infection, viruses must uncoat in order to release their genomes into the host. This process is highly dependent on host elements called \"cues\" [2], which have been previously broadly categorized as (1) receptor-and/or enzymebased cues, (2) chemical cues, or (3) mechanical cues [3] . In this brief article, we systematically analyze the available information on how 30 different enveloped and nonenveloped viruses exploit these host cues during infection and tabulate the observations in Table 1 . By categorizing these cues, a general pattern can be deduced. Specifically, we find that these viruses use a distinct order and combination of the host cues during entry. To illustrate this principle, the mechanism by which four viruses hijack these cues will be highlighted (in Fig 1) . We envision such analysis will provide an opportunity for investigators to evaluate whether viruses within the same family-for which the uncoating mechanism is unknown-employ a similar uncoating strategy.", "One virus whose entry mechanism has been intensely studied is HIV-1, a Retroviridae enveloped RNA virus that causes the devastating acquired immune deficiency syndrome (AIDS). Viral entry commences when the viral envelope glycoprotein GP120 binds to the host surface glycoprotein receptor CD4 and coreceptor CCR5/CXCR4. This causes GP120 to undergo structural alterations that promote membrane fusion (Fig 1A, step i) [4]. After fusion, the HIV-1 capsid core is released into the cytosol, where reverse transcription of its RNA genome is initiated. This is followed by a two-stage viral disassembly process: a loss of core integrity followed by viral genome release. In the first stage, the cytosolic peptidyl-prolyl isomerase (cyclophilin A) catalyzes isomerization of peptide bonds between the capsid proteins, inducing a conformational change that causes capsid disintegration (step ii) [5] . Mechanical disruption by motor proteins (dynein and kinesin) near the nuclear pore ensues [6], thereby liberating the newly reverse-transcribed DNA into the nucleus (step iii). Thus, HIV-1 multistep uncoating requires the coordinated use of host receptor, enzyme, and mechanical cues leading to genome release." ] },{ "paper_id": "5d445fbd8aa18aca2c2f7c947b25ddd62533f96b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "METHODS 3 4 High throughput screening: Huh-7 cells were seeded into 96-well plate (2000 5 cells/well) and infected with 5 MOI of DENV-2. One hour post-infection (h pi) cells 6 were washed twice with PBS and further cultured in DMEM with 2% FBS 7 containing DMSO (vehicle control) or 10 \u00b5M inhibitors from LOPAC 1280 (Sigma-8 Aldrich). 24 h pi cells were placed on ice and washed twice with ice-cold PBS 9", "and fixed with ice-cold methanol at -20\u00b0 C for 30 min. Cells were washed twice 10 with PBS followed by blocking and washing with PBS containing 0.2% BSA and 11 stained with DENV-E primary antibody (4G2-Merck Millipore) for one hour 12 followed by donkey anti-mouse Alexa-488 secondary antibody (Thermo 13", "procured from American Type Culture Collection (ATCC-VR-26). Human 25 rotavirus (Wa strain) and MA-104 cells were a kind gift from Dr. Gagandeep 26" ] },{ "paper_id": "5d46c99fa67d9b839724a7349e6ffb22ba71cf1d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Other than the country-specific surveillance systems, certain global, region-specific, and non-governmental organizations which provide information related to zoonoses in general are:", "(1) diagnostic tests to accurately classify the health status of individuals (2) the most effective preventative and therapeutic interventions (3) any emerging antimicrobial resistance and counter measures (4) public health strategies for population-based interventions", "The focus of this commentary is on resources for evidence updates to counter emerging zoonoses, for example, Severe Acquired Respiratory Syndrome (SARS), West Nile, Avian Influenza, new variant Creutzfeldt \u00c1 Jakob Disease, Nipah, and the most recent Middle East Respiratory Syndrome. There is no certainty when and where the next zoonosis will emerge. Miscalculating an emerging zoonosis and poor risk communication between veterinary and medical sectors could have dire consequences for public health and cause considerable economic loss." ] },{ "paper_id": "5d5edffd3b3213b480c77b6a06949a8a88618b69", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5d62acbb74aea7559783bcf556ce7352b55ca03a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After slow thawing, each individual swab (of 10 swabs sampled from flock) was hydrated in phosphate-buffered saline supplemented with antibiotics (100 U of penicillin with 100 mg of streptomycin/ml), incubated for 1 h at room temperature and clarified by centrifugation at 1500 g for 20 min. Five such obtained supernatants were combined into one pool so that two pooled samples were then tested per flock. Total RNA and DNA were then extracted from 250 \u03bcl of each two pools into 50 \u03bcl RNase-free water using commercial kits (RNeasy and DNeasy Mini Kits, respectively, Qiagen, Germany) according to manufacturer's instruction. Extracted nucleic acids were stored in -70\u00b0C for further molecular analysis.", "Sampling was conducted under the permission of the owners or other responsible persons. The birds in the farms were under the supervision of veterinarians, who took different samples as part of their routine work (i.e. as screening flocks for efficacy evaluation of applied vaccines or presence of any infections) and thus part of them were used in this study. For this reason, sampling did not require the approval of the Ethics Committee. Table 2 .", "AstV: Astrovirus; CoV: Coronavirus; PV: Parvovirus; RoV: Rotavirus" ] },{ "paper_id": "5d6c145129db8973b797726818f229dfaa997f11", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "General data are presented as a percentage (P), logarithm of the percentage [LN(P)], or mean \u00b1 SD. Statistical analyses was performed using Statistics Analysis System (SAS) version 9.0, Statistical Product and Service Solutions (SPSS) version 13.0, and Microsoft Excel 2007. Differences in categorical variables between groups were compared by the \u03c7 2 test. A single-tailed Pvalue of <0.05 was considered to be statistically significant.", "Of the enrolled patients, 26,747 (67.3%) were male and 13,009 (32.7%) were female ( Table 2 ). The percentage who tested positive was significantly higher for females compared with males for both single infections (\u03c7 2 = 188.7, P<0.001) and co-infections (\u03c7 2 = 81.4, P<0.001).", "Blood samples were collected from each child who was given a case definition. Specimens were obtained from children before clinical treatment (within 24 h after hospital admission to avoid inclusion of hospital-acquired infections and antibiotic interference). Blood samples were collected in vacuum blood tubes without the addition of anticoagulants and were further clarified after clotting. Serum was stored at \u221220\u00b0C on ice until analysis. Specimens were stored at \u221270\u00b0C if analysis was not possible within 24 h after collection." ] },{ "paper_id": "5d7698a990270f5ebfa2c879d56187116acc7646", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A) Healthy volunteers aged 30 to 70 years B) Ability to give informed consent", "The exclusion criteria for the study were:", "Trial Registration: NCT01478009." ] },{ "paper_id": "5d76f48664d2e90c67768d51a2efda3e12c316ce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The project consists of 9 objectives as detailed in Table 1 . They can be divided into five main streams:", "(2) influenza risk that considers organism, host and environmental factors; (3) the impact of viral-viral and viral-bacteria co-infections on clinical disease and severity; and (4) the nature of responding adaptive immune responses in determining individual's risk of acquiring influenza virus infection.", "Keywords disease burden, epidemiology, immunology, influenza, risk factors, vaccine effectiveness. " ] },{ "paper_id": "5d7ef1b6d6d20f3a2d0c1cad4daa1496ef8a195b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical comparisons were performed with the Prism program, version 4.03 (GraphPad Software, Inc., San Diego, CA) using an ANOVA 1 or an unpaired 2 ttest with p,0.05 indicative of significance. ", "In silico docking study " ] },{ "paper_id": "5d89d3273a8590afe87b37195d47f7e0c00d777c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Castor oil was applied as the parallel solvent control.). This indicates that the dose of 100 mg/kg by oral administration in mice had little acute toxicity.", "Influenza A virus (IAV) is extremely prone to cause periodic epidemics and pandemics in the world through evolution by point mutations or swapping of gene segments, correspondingly [1] [2] [3] .", "As exhibited in Tables 3 and 4 , N30 showed antiviral activities against different strains of EV71 (reference drug pirodavir) or CVB (reference drug RBV). In addition, N30 suppressed CVB3 structural protein 1 (VP1) mRNA and protein expressions in a dose dependent manner (Fig. 4a) ." ] },{ "paper_id": "5d9c87ae912ec13a723b6d75bd0ab59618a39164", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sample group: 140 \u03bcL PBS buffer solution (0.1M\uff0cpH = 8.0), 20 \u03bcL sample solution and 20 \u03bcL AChE solution (0.28 U/mL) were introduced into the enzyme label plate in turn. The solution was preserved at 4\u00b0C for 20 min after mixing. Then 10 \u03bcL dithiobis nitrobenzoic acid (DTNB, 7.5 mM) and 10 \u03bcL acetylthiocholine (ATCI, 10 mM) were added. After 20 minutes, the absorbance was measured at \u03bb = 405 nm.", "Sample-out group: 20 \u03bcL enzyme solution was replaced by 20 \u03bcL PBS buffer solution (pH = 8.0), ceteris paribus.", "Blank group: 20 \u03bcL sample solution was replaced by 20 \u03bcL PBS buffer solution (pH = 8.0), ceteris paribus." ] },{ "paper_id": "5d9de14dd116027eb2325fc91534d038f8eac88b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5d9e52011787ca962e5391dd027c6641a37f9cba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The dataset supporting the conclusions of this article is included within the article (and its additional file).", "Additional file 1: Instructions for Using Survival Functions to Generate LTFU Cut-Offs. (DOC 26 kb)", "Not applicable." ] },{ "paper_id": "5da136317f5b97ed8371d5121d8828f1c9a5372d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The symptoms of congenital malaria vary significantly between cases, so clear and early diagnosis is difficult. We suggest that active surveillance might be necessary for neonates born to mothers with a history of malaria.", "N In China, many clinicians involved lacked sufficient understanding of the mechanism of congenital malaria and ignored the potential risk of side effects due to primaquine treatment." ] },{ "paper_id": "5da7956e10ac1b78cc0fda6f4043ea034227459e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lower respiratory tract infections, including pneumonia, are a group of diseases that constitute a leading worldwide cause of pediatric morbidity, requiring hospitalization, and mortality [1, 2] . Childhood pneumonia causes diverse long-term sequelae, such as restrictive or obstructive lung disease, as well as bronchiectasis, particularly in a considerable proportion of children hospitalized due to community-acquired pneumonia (CAP) [3] .", "Pneumonia was diagnosed by pediatricians based on both physical examinations and radiologic assessments. MP pneumonia was defined as meeting at least one of the following criteria: (1) positive results in both RT-PCR analysis of nasopharyngeal samples and the specific IgM against MP at the time of hospitalization due to CAP, (2) seroconversion of the specific IgM against MP, or (3) four-fold or greater increase in the specific IgG against MP in the acute and convalescent stages [8, 12] .", "RT-PCR was performed to identify the causative respiratory viruses using an Anyplex II RV 16 Detection kit (Seegene, Seoul, Korea) [8] . The identified respiratory viruses were as follows: adenovirus (AdV), human rhinovirus (HRV), influenza virus (FLU), parainfluenza virus (PIV), human metapneumovirus (HMPV), respiratory syncytial virus (RSV), bocavirus (BoV), and human coronavirus (HCoV). RT-PCR was performed to identify MP using an ABI 7500 (Applied Biosystems, Foster City, CA, USA) with an EuDxTM-PN MLC Detection Kit (EUDIPIA) and an Any-plexTM II RB5 Detection Kit (Seegene). The results of RT-PCR analyses and serologic titers for MP infections were obtained from comprehensive reviews of laboratory records." ] },{ "paper_id": "5db737c9e3b8b52dd6c4778e9ade92d2ff9fadbe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by the Animal Use Committee of Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences (No. OKU-2014502) and was conducted in accordance with National Institutes of Health Guidelines.", "Eight-week-old male C57BL/6 mice (21-24 g body weight) were purchased from Charles River Laboratories (Yokohama, Japan). They were housed in a specificpathogen-free animal facility at 25\u00b0C with a 12-hr light/ dark cycle and fed a standard pellet diet (Oriental MF; Oriental Yeast Ltd., Tokyo, Japan).", "Data are expressed as the mean \u00b1 SEM. Comparisons were performed with the Mann-Whitney U test using Prism 6.0 software (GraphPad Software, San Diego, CA, USA). The p value of the difference in survival was determined by the log-rank (Mantel-Cox) test. P <0.05 was considered statistically significant." ] },{ "paper_id": "5dc0b8b662824323881c3a1ae3a1bae2a821484d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5dc0c03f8620c881a56b6b17db77b6ffe430ca28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To co-exist with their hosts viruses have evolved diverse mechanisms to exploit cellular processes and to evade from host defenses. One such central cell pathway is an ancient degradative process, designated autophagy. In contrast to proteasomal degradation that specifically targets ubiquitinated proteins, autophagy is mediated by the lysosome, which serves as an end point degradative organelle.", "Autophagy is thus a catabolic process that maintains cellular homeostasis by degradative removal of damaged or excess cellular organelles and protein aggregates from the cytoplasm, thereby enabling cell survival. Both cell culture and in vivo studies revealed the fundamental roles of autophagy in numerous diseases, including cancer or neurodegeneration, in aging, but also in innate and adaptive immunity to pathogen infection.", "As an organelle gathering cytosolic content into a double-membrane vesicle that fuses with endosomal compartments, the autophagosome can specifically deliver intracellular pathogen-associated molecular patterns (PAMPs) to endosomal pattern recognition receptors (PRRs) and MHC-loading compartments to initiate innate and adaptive immune responses (Figure 3) . Moreover, the autophagosome can selectively target virions and virus components for degradation via the autolysosome. Both aspects will be discussed in the following paragraphs. " ] },{ "paper_id": "5dc1559b4274012d8152b7c5f4ca0d637e8b62fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The importance of patient-centred research during epidemics Improving patient outcomes", "It is clear that there is significant room for improvement in the systematic collection of data and biological samples from patients with the explicit aim of improving the evidence-base for public health decision-making." ] },{ "paper_id": "5de6f9a65ba8f1857af0057539ff471a4427a157", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5deb9073195a49301f2eb72bc7d327ea2e9393e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quantitative results are represented as mean +/\u2212 SEM. Statistical comparisons were performed with Prism 7 software (GraphPad) using the indicated tests. The following P-values were considered significant: P < 0.05 (*), P < 0.01 (**), P < 0.001 (***) or P < 0.0001 (****)." ] },{ "paper_id": "5dee0488f20951e191da1c58d425a28eda883f49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Objective: Human pluripotent stem cells are self-renewing cells with the ability to dif", "Due to this, it has been suggested that the citations to an article within each individual year should be used instead (24) . Almost all articles in figure 3 had high annual citation growth rates and thus great vitality, as evidenced by Takahashi and Yamanaka (28) ", "The eight leading Web of Science categories which published at least 10% of all the articles were: cell biology with 835 articles (29% of 2,844 articles), followed by cell and tissue engineering with 594 (21%) articles, hematology with 475 (17%) articles, biotechnology and applied microbiology with 414 (15%) articles, multidisciplinary sciences with 393 (14%) articles, biochemistry and molecular biology with 252 (12%) articles, research and experimental medicine with 344 (12%) articles and oncology 294 (10%) articles." ] },{ "paper_id": "5df25b46c3f42c20960c6e6e0caeb981b2f7759d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No potential conflict of interest was reported by the author. ", "ARTICLE HISTORY" ] },{ "paper_id": "5df3884ac512e1ad4cedd33f5e83b09a9cfa5668", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the local research ethics committee of the University Hospital and the Eberhard-Karls University T\u00fcbingen, Germany." ] },{ "paper_id": "5df6b1ce03de2b78801de3d8e20a50b3563a2cf4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ability of E4ORF1 to activate PI3K in a DLG1 dependent fashion was found to be a conserved function between human Ad subgroups A through to D, including those members used as E4ORF1-encoding vectors in human gene therapy and vaccination, raising possible safety concerns of their use in humans [93] .", "The HBVc can also bind via its PBM to the non-receptor protein tyrosine phosphatase PTPN3; however the precise role of this association in HBV pathogenesis is not known. PTPN3 has been shown to have a suppressive role on HBV gene expression, but this control is independent of the PBM activity of the HBVc [27] .", "as yet there is no experimental evidence that supports interaction between NS4B and PDZ proteins [52] . Nevertheless, propagation of other RNA viruses within Flaviviridae (tick borne encephalitis virus, West-Nile virus and dengue virus) is dependent upon PBMs within the non-structural NS5 proteins, and have been shown to bind to various PDZ proteins, including those involved in polarity control and tight junction assembly and maintenance; and mutations in these PBM negatively affect viral replication [53, 54] . " ] },{ "paper_id": "5e00a4c6f4faed178e0f2c24b7c2678c9404f84c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence phylogenetic trees were reconstructed using Markov chain Monte Carlo analysis implemented in the BEAST software package (version 1.8.4; http://beast.bio.ed.ac.uk/). The analysis was performed using the generalized time reversible substitution model with gamma distributed rate variation among sites and using default priors. The Markov chains were run for 10 million generations, with the first 10% of samples discarded as burn-in. Convergence of parameters was verified using Tracer v1.4 and indicated as effective sample size (ESS > 200). A maximum clade credibility tree was summarized using TreeAnnotator, which annotates all nodes with posterior probability support values [16] .", "Baby hamster kidney (BHK-21) cells were stored in the laboratory. The cells were cultured in minimal essential medium (MEM; Gibco, Grand Island, NY, USA) containing 10% fetal bovine serum (FBS; Invitrogen, Carlsbad, CA, USA), 1% penicillin-streptomycin combination, 1% glutamine, and 2% NaHCO 3 (pH 7.4) at 37\u00b0C in a 5% CO 2 atmosphere. African green monkey kidney cells (Vero E6) were cultured in a similar manner [10] [11] [12] .", "The bat specimens were collected in Xiangyun County of Dali Prefecture, Yunnan Province (100.32\u00b0E, 25.28\u00b0N). Sticky nets were placed at the outlet of the cave in the evening. Once trapped, the bats were classified according to the morphological characteristics. The bats were released after the blood samples were collected. The blood samples were kept in \u2212 80\u00b0 [10] ." ] },{ "paper_id": "5e01fabcf9b38073be541d0ac1c9f147c99a7af7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For performing feature selection, we used AttributeSelection class in Weka toolkit. We used wrapper subset evaluator in combination with Random Forest classifier and best first search method.", "We computed the following statistics, as described in Baldi et al. [50] , to measure the performance of the classifiers. The F-Measure is a composite indicator of performance that attempts to \"balance\" precision and recall. F-Measure values range from 0 to 1, with values close to 1 indicating better performance. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was also computed. AUC values also range from 0 to 1: the AUC = 1 for a perfect classifier and for a random classifier = 0.5." ] },{ "paper_id": "5e022a5ce7ca2c5463c52d20ed1a1e63259c17a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5e0504a1c581c36bbf2c2c97439b87b9834b108b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Buffy coats or apheresis cones, obtained from the National Health Service Blood and Transplant service (NHSBT) in Birmingham, were used as the source of peripheral blood for this study. Healthy blood donors were recruited according to NHSBT standard procedures, which included obtaining full consent to allow use of donations for our experiments.", "EBV transformation assays were carried out as described elsewhere [26] , using 96-well plates with a fixed number of 10 3 B cells/well and a range of virus doses (0.2-100 m.o.i.). Wells were examined for transformed colonies after 6 weeks culture.", "(DOCX)" ] },{ "paper_id": "5e0c586f047ff909c8ed3fe171c8975a90608d08", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PEDV is an enveloped single-strand RNA coronavirus with a 28 kb genome, which includes 4 open reading frames encoding spike (S), envelope (E), membrane (M), nucleocapsid (N), as well as 3 open reading frames encoding replicase 1a, 1b and ORF3 [10] . As known for other coronaviruses, the three PEDV S glycoproteins form a club-shaped functional S trimer, which is localized on the surface of the virion and mediates essential biological functions, such as membrane fusion and receptor binding. The S protein is also responsible for the induction of nAbs and protective immunity, making it an appropriate candidate for developing an effective vaccine and diagnostic reagents [1, 11, 12] . In addition, variation in the S gene leads to antigenic diversity, and thus the S protein is useful in evaluating genetic diversity [13] .", "Porcine epidemic diarrhea virus (PEDV), which belongs to the Alphacoronavirus genus of the Coronaviridae family, is an etiological agent of porcine epidemic diarrhea (PED) and causes an enteric disease that affects all ages of swine [1, 2] . The clinical presentations and complications of infection are characterized by acute vomiting, dehydration, watery diarrhea, and high mortality in sucking piglets [3] and are indistinguishable from those of infection by either transmissible gastroenteritis virus (TGEV) or porcine enteric alphacoronavirus (PEAV) [4, 5] .", "First detected in the UK in 1971, PEDV resulted in mass epidemics within Europe in the 1970s and 1980s [6] . Before 2013, PED was prevalent in Asia and Europe [1] . After spring 2013, however, PED outbreaks reached North America, which was due to variant PEDV strains that researchers revealed might derive from Chinese variants [7, 8] . In spite of widespread immunization with the currently marketed vaccine, PED still persists in swine raising countries and resulted in devastating damage to the pork producers [9] ." ] },{ "paper_id": "5e0e39574ffd7d5f3dcdc97d0301507de50e5c54", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We measured binding of antibodies either to virus directly coated on ELISA-plate wells or to solubilized Env. For the direct virus binding assay, plates were coated with HIV-1 JR-FL (20 ng p24/well) for 2 hours at 37uC, washed with PBS and blocked with 4% non-fat dry milk in PBS. After 1 hour at 37uC, plates were washed, antibodies were added in serial dilutions and incubated for 1 hour at 37uC. Detector antibody (horse radish peroxidaselabeled goat anti-human Fc) was added to the washed plate and incubated for 45 min at 37uC. Finally, plates were washed, developed (TMB solution, Life Technologies), and read at 450 nm using a plate reader (BioTek).", "Fc mutants designed to enhance (M428L) or reduce (I253A) mAb b12 binding to FcRn were constructed as follows: briefly, the b12 variable regions were PCR-amplified from pDR12 and cloned into the pc1HC and pkLC vectors [68, 69] . Amino acid substitutions were introduced by QuikChange site-directed mutagenesis (Stratagene, La Jolla, CA). Constructs were verified by sequence analysis before transiently expressed in FreeStyle 293 cells (Invitrogen, Carlsbad, CA) and purified by protein A affinity chromatography (GE Healthcare, United Kingdom).", "Antibodies were tested for neutralizing activity against indicated HIV-1 strains using TZM-bl cells." ] },{ "paper_id": "5e0efb6f40dc7f8e441d0569c8b7a86f2bfbc13a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5e11e3105842cf7cedf10e26bff170a52c23cf00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In order to quantitatively assess the membrane order, a ratiometric method known as generalized polarization (GP) was developed [52] . The GP function or value characterizing the spectral properties of Laurdan is calculated through the following expression:", "The interferon (IFN) system is the first line of host defenses against pathogen invasion, including viral infections. It protects by producing hundreds of IFN-stimulated genes (ISGs) that modulate diverse biological functions. A number of ISGs (such as PKR, RNase L, ISG 15, etc.) have been characterized and shown to suppress viral replication, the mechanisms of which are still poorly defined (reviewed in reference [1] ). One exciting development in the last few years has been the discovery of some novel ISGs, also known as cellular restriction factors (such as APOBEC3G, Trim5a and Tetherin, etc.), which intrinsically block different steps of retroviral replication [2, 3, 4, 5, 6] . It is notable that many viruses, including retroviruses, have evolved to acquire a variety of strategies that evade IFN-mediated restrictions [7, 8, 9] . This type of intrinsic immunity is believed to play crucial roles in virus-host co-evolution and viral pathogenesis [7, 10] .", "Generalized Polarization~I blue {I green I blue zI green \u00f01\u00de" ] },{ "paper_id": "5e1989bee9ae95c79dea0e12d9f455cb1d2b61d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Authors' contributions LS, MSG, MDO, DAO, FB, AH, SR, VR, JB participated in patient recruitment and assisted in the analysis, interpretation of data, and writing the report. RA developed the bioinformatics analysis. LR performed the gene expression profiling works. IML and JFBM assisted in the design of the study, coordinated patient recruitment, analyzed and interpreted the data, and assisted in writing the paper. CASAJ introduced the clinical data and helped with data interpretation. MCG, VF performed the microbiology diagnosis and assisted in writing the paper. ROL and CD assisted in writing the paper. All authors read and approved the final manuscript.", "The authors declare that they have no competing interests" ] },{ "paper_id": "5e1e254fc92ef00d3a23ebaab664289a8a58c88a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The VSV *G-VSV\u0394 G is a recombinant virus that harbors a genome in which the glycoprotein gene is replaced by the green fluorescence protein (GFP) reporter gene, and is a generous gift from Michael Whitt from University of Tennessee.", "with the lipophilic fluorophores: octadecylrhodamine B chloride (R18), a red-emitting fluorophore, at a sufficient concentration and sonicated 30 min to quench fluorescence.", "To produce biomimetic planar supported lipid bilayer, various methods have been developed [37] [38] [39] . Here, self-assembling of lipid vesicles was performed to form a host cell-mimetic membrane bilayer, and the procedure is described as follows. Glass microscope coverslips (25 mm \u00d7 25 mm; No. 1.5) from VWR were cleaned in piranha solution (45 mL 50% hydrogen peroxide and 105 mL 70% sulfuric acid) for 10 min then rinsed 30 min with deionized water with a minimum resistance of 18.2 M\u03a9 cm (Siemens Purelab Ultra water purification system). Glass slides were flushed with deionized water again and dried by a stream of ultra-pure nitrogen gas prior to plasma cleaning." ] },{ "paper_id": "5e2457559eab2f9b131de9084d5dfc66bd875aee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "served elements such as the 2C helicase motifs GXXGXGK(S/T) and DDLXQ, the 3C protease active-site motif GXCG, and the 3D RNA-dependent RNA polymerase motifs YGDD, KDELR, PSG, and FLKR were all confirmed.", "Phylogenetic analyses were conducted in MEGA4 [42] . RNA secondary structure was predicted by Mfold, version 3.2 (Zucker, 2003. Similarity plots and Bootscan analyses were done with Simplot software [43] )." ] },{ "paper_id": "5e2dc7663e6a6b53d6b8f37f5ccd4e6dc0c71a57", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2012, 4 3453 information regarding the epidemiology and molecular epidemiology of BRSV worldwide, and it highlights the importance of viral evolution in virus transmission.", "The bovine respiratory syncytial virus (BRSV) has been recognized as a pathogen in cattle responsible of an acute respiratory disease syndrome in beef and dairy calves since the early 1970s [1, 2] . The impact of BRSV infection on the cattle industry results in economic losses due to the morbidity, mortality, treatment and prevention costs that eventually lead to loss of production and reduced carcass value [3] .", "BRSV outbreaks can become epidemics affecting animals in all age groups. However, the age distribution of BRSV infection seems to be a function of exposure. In other words, herds that have been previously exposed to the virus tend to experience infections that are limited to younger, more susceptible animals. In consequence, morbidity is commonly high during the occurrence of outbreaks [21] . Importantly, natural infection affects both beef and dairy cattle, although management practices can significantly impact the infectivity rates [22] . Climate also favors the dissemination of the virus during winter, after the sudden drop in temperature [11] , although infection can occur throughout the year." ] },{ "paper_id": "5e3580584a2340a7db087f4115d14f6782e22a36", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5e3a5143a77a6faeb480c65a23137616c14e7bad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In summary, the limited proteolysis assays suggest that TBHQ inhibits H7 HA-mediated entry by stabilizing the neutral pH conformation and thereby disallows the conformational change necessary for membrane fusion.", "In the limited proteolysis experiments, ,10 mM H7 HA was pre-incubated in the presence of ,330 mM TBHQ for 15 min at 37uC (control experiments were performed in 0.7% DMSO). Phosphate-Citrate buffer stock solutions at the appropriate pH were added to result in final buffer and TBHQ concentrations of 50 mM and 250 mM, respectively. The buffered solution was then incubated for 30 min at 37uC. Next, the solutions were neutralized to pH 8.0 and incubated with 2 mg of trypsin for 30 min at 37uC. The proteolysis was stopped by adding 11 mL of 5X SDS running buffer and heating the samples at 95uC for 10 min. After SDS PAGE and Coomassie staining, the HA bands were quantified using Bio-Rad Image Lab 2.0.1. Subsequently, the HA band intensities were fit to % Native = 100/(1+ (I obs /[H+] mp ) n ), where I obs is the observed intensity at a particular pH, [H + ] mp is the midpoint [H+] concentration, and n = Hill Coefficient, using Kaleidagraph 4.1.3.", "The membrane glycoproteins hemagglutinin (HA) and neuraminidase (NA) play critical roles in influenza infection [1] . Antigenic properties are used to classify HA and NA of influenza strains into subtypes (HA: H1-17 and NA: N1-9) with some strains posing enormous threats to human health. For example, the pandemic H1N1 influenza outbreak of 1918 resulted in over 50 million deaths worldwide with a fatality rate of 3% and, despite improved vaccination efforts and better treatments, seasonal influenza is still responsible for greater than 250,000 deaths per year worldwide [2] , [3] . Of very high concern is the recent outbreak of H7N9 influenza in China, which has exhibited a mortality rate of .20% [4] , [5] , [6] . Current treatments for influenza include Tamiflu (oseltamivir) and Relenza (zanamivir), which target NA, and Symmetrel (amantadine) and Flumadine (rimantidine), which target the M2 channel [7] . Unfortunately, resistance is increasing in circulating influenza strains. For example, the 2008-2009 H1N1 strain exhibited ,100% resistance against Tamiflu [8] . Moreover, the recent H7N9 strain contains a sequence rendering it insensitive to the M2 channel blockers [9] and some H7N9 strains are also showing resistance to Tamiflu and Relenza [10] . As a consequence, novel antiviral treatments against new targets are highly desirable." ] },{ "paper_id": "5e3b24f55fdc84cfc263d4784c6ad6349d212866", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The main component profile of KIOM 198 was analyzed using HPLC. As shown in Figure 6 , among marker compounds of Epimedium Koreanum Nakai, quercetin and icariin were representatively identified at 270 nm based on comparison to the standard compounds. Several unidentified peaks were detected.", "Vero cells (African green monkey kidney cell line; ATCC CCR-81) and ST-cells (pig testis cell line; ATCC CRL-1746) were purchased from KCLB, Korean Cell Line Bank (Seoul, Republic of Korea) and maintained in alpha-minimum essential medium (Hyclone, Logan, UT) with 5% fetal bovine serum and 100 U/mL of Penicillin and Streptomycin at 37 \u2022 C with 5% CO 2 . Two strains of PED, KPEDV-9 and sm98 and other subtype TGE viruses were obtained from National Veterinary Research and Quarantine Service in Korea. Plaque assay was performed as below. The supernatants harvested were serially diluted up to 10 6 and added to Vero cells seeded in 6 well (1 \u00d7 10 6 cell/well). After 1 h incubation, media were removed from infected cells and over-layered with 0.5% agar-containing alpha-MEM media, and incubated for 4-5 days at 37 \u2022 C. Plaques were fixed with 7% formalin, stained with crystal violet, and counted.", "Virus-containing supernatants were collected from the cells infected with virus (0.01 or 0.1 MOI) with or without KIOM 198 or KIOM 124 at 0, 24 h, 40 h, and 48 h postinfection. Total RNA was isolated using viral Gene-spin Viral DNA/RNA Extraction Kit (European Biotech Network, Belgium) and used for cDNA synthesis using iScript Reverse transcriptase (iNtRON Biotech, Daejeon, Korea) according to manufacturer's instruction. Real-time PCR using Bio-Rad iQ5 (Bio-Rad Laboratories, Inc., Hercules, CA, USA) was performed by subjecting the reaction mixtures to initial denaturation at 94 \u2022 C for 3 min, followed by 40 cycles of 94 \u2022 C for 20 sec, 65 \u2022 C for 20 sec, and 72 \u2022 C for 30 sec. The primer sequences specific for Nucleocapsid gene of PED virus are used for PCR and as follows: 5 -CGCAAAGACTGAACCCACTAATTT-3 for forward, 5 -TTGCCTCTGTTGTTACTTGGAGAT-3 for reverse [37] ." ] },{ "paper_id": "5e3f2dabebc87da9fd1323d941ef57df3e7f913b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hsp27 WT -11.86 \u00b1 0.24 -Hsp27 N1 -3.06 \u00b1 0.27 -8.80", "Hsp27 N2 -6.05 \u00b1 0.23 -5.81", "Hsp27 C1 -9.99 \u00b1 0.25 -1.87" ] },{ "paper_id": "5e545b25250d9239c3096fa6925fad84c88199cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5e58ef2fc3058da627802377e2b2441149d29c19", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SA conducted the project across four countries while she was in Canada, analyzed the data, and wrote the paper. L-JJ was a postdoc mentor of SA; shaped the project and contributed to writing the paper. MM conducted the project in the US, and contributed to writing the project. ZZ collected data from China.", "Lastly, we relied on a self-report based methodology. In other future research, it would be interesting to investigate the topic using other approaches, such as behavioral and neuroscience approaches, in order to get a more comprehensive picture of the processes involved in the present findings.", "This research was approved by the Queen's University Institutional Review Board where the study was designed (and also each institution in each country where the studies were conducted), in accordance with APA ethical standards. Written informed consent from each respective country's participants was given.", "There are some limitations to the present research. First, participants were all students. While the mean sample age and occupations were consistent across all four countries, we did not sample the general population. As mentioned, the American sample had a higher percentage of Hispanics compared to Caucasians; although the difference between them was not statistically significant, this test may have been underpowered given the amount of participants in the two groups. Thus, it is possible this could have impacted the mixed findings for the Americans." ] },{ "paper_id": "5e69bc12b5603039722d86b5b9b770dcb5470a98", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5e6b537332182bd3c8f642accc5eae577055a4c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since the beginning of the 21st century, a number of infectious disease threats have emerged that demand a global response. Among them, severe acute respiratory syndrome virus, avian influenza in humans, pandemic influenza A (H1N1), Middle East respiratory syndrome coronavirus, chikungunya virus, and Ebola virus have been the most threatening ones. Nonetheless, the emergency of a vector-borne virus, Zika virus (ZIKV), which is responsible for congenital malformations and other neurological and ophthalmological disorders, was hard to predict.", "ZIKV is a mosquito-borne virus belonging to the Spondweni serocomplex in the genus Flavivirus of the family Flaviviridae [1] . The virus has been isolated from various mosquito species, although it seems that the natural transmission vectors are mosquitoes of the genus Aedes [2, 3] . Besides mosquito bites, viral direct human-to-human transmission can occur perinatally, sexually, and through breastfeeding and blood transfusion [4] . The ZIKV genome is a single-stranded RNA molecule (\u224810.7 kb) of positive polarity encoding a single open reading frame (ORF) flanked by two untranslated regions at the 5 and 3 ends [5] .", "Current search for ZIKV antivirals is being conducted with different approaches: by screening of compounds libraries; by the repurposing of drugs of known active efficacy against other diseases now in use in clinical practice, many of which display broad-spectrum activity; and by testing natural products. Two different strategies can be applied when pursuing for antivirals, those searching for compounds directed to viral targets (direct-acting antivirals) and those aimed to target cellular components needed for the viral life cycle (host-directed antivirals).", "ZIKV replication and particle morphogenesis take place associated with a virus-induced organelle-like structure derived from the membrane of the endoplasmic reticulum (ER) (Figure 1 ) [4] . De novo synthesized positive strand-RNA, once packaged, form enveloped immature virions in the ER, enter the secretory pathway and, then, in the trans-Golgi network, the prM is cleaved before the virus is released from the infected cell ( Figure 1 ) [89, 90] ." ] },{ "paper_id": "5e77269850b7b4bf57514e226ea66cd48ac31db5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Many members of the Parvoviridae family, single-stranded DNA containing non-enveloped icosahedral viruses, utilize glycans for attachment or/and cellular entry. Bovine adeno-associated virus and human parvovirus B19 use gangliosides, adeno-associated virus serotype 1 (AAV1), AAV4, AAV5, AAV6, bovine parvovirus, H-1 parvovirus, porcine parvovirus, and minute virus of mice (MVM) use SIA, AAV2 and AAV3b use heparan sulfate proteoglycan, and AAV9 utilizes terminal galactose as a receptor [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] . Sialic acid commonly occurs at the non-reducing termini of glycans linked within glycoconjugates and comprises a family of structurally diverse monosaccharides derived from neuraminic acid, a nine-carbon sugar. More than 50 natural analogues result from modifications to the SIA backbone [21] . In general, the C-5 position is either N-acetylated (N-acetylneuraminic acid; Neu5Ac), N-glycolylated (N-glycolylneuraminic acid; Neu5Gc) or hydroxylated (deaminoneuraminic acid; KDN). The hydroxyl groups on SIA can be free, esterified (acetylated, lactoylated, sulfated, phosphorylated), or etherified (methylated), leading to increased chemical diversity [22] .", "A9 ouab r 11 cells were grown in spinner culture in DMEM containing 5% fetal bovine serum and antibiotics to a density of ,6610 5 cells/ml. The cultures were infected with predetermined titers of transfection-derived parvovirus MVMp stocks and expanded until cell counts indicated a progressive rise in numbers of dead cells. The cells were harvested by centrifugation, washed in PBS without Ca 2+ or Mg 2+ , pelleted, and resuspended in 10 ml of TE8.7 (50 mM Tris-HCl pH 8.7, 0.5 mM EDTA) per liter of infected cells. Following three cycles of freeze-thaw at 37uC the samples were centrifuged repeatedly at 8006g to clarify the supernatant and were stored at 220uC.", "Abbreviations:" ] },{ "paper_id": "5e80e58924fd2feae8218fc7c2c066e75cec0149", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Most cancers arise from as a result of a complex interaction between genetic and environmental factors. The risk factors for CRC also includes increasing age, positive family history, low dietary fibre, high saturated fat intake, red meat consumption, excess alcohol, lack of physical activity and having diabetes mellitus [5] [6] [7] [8] [9] [10] [11] .", "The survey recruited a population-representative sample using multistage sampling. The five districts of the Perak state (Kampar, Kuala Kangsar, Taiping, Parit Buntar and Gerik) were selected. At the second stage, four villages were chosen per district. Both districts and villages were chosen purposively with discussion with state and district health offices. Finally, households were selected from villages with simple proportionate random sampling. From the village maps, the sampling frames were constructed by tagging every household with a serial number. Selection of households was done by using a computer generated random number table. A total number of 1250 households were included in the study (Figure 1) .", "The remaining questions covered self-rated confidence level of noticing bowel cancer (4 Likert score: \"not at all confident: 1\" to \"very confident: 4\"), health seeking behaviour and opinion on age related bowel cancer incidence. The socio-demographic information and having of any cancer for self, partner, family and friend were asked." ] },{ "paper_id": "5e85184d2ba432306c3c21f22113aa590b09fe89", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Terminally anesthetized mice (isoflurane overdose) were perfused with 50 mL of 4% paraformaldehyde (PFA) via intracardiac puncture, and tissues were postfixed in 4% PFA for 24 h. Brain tissue was macrosectioned using a brain matrix, making cuts through the optic chiasm and infundibulum. The resulting tissue block containing the dorsal hippocampus was embedded in 4% agarose gel and sectioned at 70-\u03bcm thickness by vibratome. Freefloating sections were blocked in PBS containing 1% BSA, 10% normal donkey serum, 1% FBS, and 0.1% Triton-X 100 for 1 h, incubated overnight at 4\u00b0C with primary antibody (anti-MCP-1/CCL2: Cell Sciences, CPM001, 1:400 in block), incubated with secondary antibody for 1 h (donkey anti-rabbit Cy3: Jackson Immu-noResearch, 711-166-152, 1:1000 in block), washed, and mounted in DAPI-containing mountant on charged slides. CCL2 immunoreactivity was imaged with the Zeiss AxioObserver.Z1 and ApoTome.2 structured illumination system (Carl Zeiss Microscopy GmbH, Jena, Germany) using a \u00d720 objective (LD Plan-Neofluar 20x/ 0.4 Korr Ph 2 M27, 0.55 NA), 538-562-nm bandpass excitation, 570-640-nm bandpass emission, 7-\u03bcm optical thickness, and 300-ms exposure time. For detection of the mCherry fluorophore in CCL2:RFP animals, freefloating 70-\u03bcm sections were mounted on charged slides in DAPI-containing mountant. Fluorescence images were captured with a laser scanning confocal microscope (LSM780, Carl Zeiss Microscopy GmbH, Jena, Germany) using a \u00d740 objective (C-Apochromat 40x/1.20 W Korr FCS M27, 1.2 NA) with water as the refractive medium. Validation of mCherry-specific emission and exclusion of autofluorescence was obtained with spectral imaging using a lambda scan at 488, 561, and 594 nm excitation and 8-nm-stepped emission spectra. Forty-micrometer z-stacks were acquired with a step thickness of 2 \u03bcm, pixel dwell time of 0.39 \u03bcs, and pinhole equivalent to 1 airy unit across all samples. Uncompressed TIFF-images were exported from Zen software (Zen Black 2012 64-bit, Carl Zeiss Microscopy GmbH, Jena, Germany) and post-processed in ImageJ (ImageJ v1.50b, Wayne Rasband, National Institutes of Health, USA) and Photoshop (Adobe Photoshop CC, 2014 Release, 64-bit). Levels were normalized, when appropriate, equally across images and groups; gamma values were not changed." ] },{ "paper_id": "5e8669392733113d4bbaeebd9347764807872fa2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fully human \u03b31 heavy chain and \u03ba light chain coding regions were generated by total gene synthesis (GeneArt AG, Regensburg, Germany) and combined into the EBNAbased expression vector pCB15 essentially as described [33] .", "Recently, the M2-specific human antibody Z3G1 has been reported to show therapeutic activity in mice [22] . However, multiple injections of Z3G1 starting as early as 5 h after infection were required for full protection. Antibody D005 compares favorably to this, since it was fully protective with a single injection at day 1 and still showed some protection when administered 3 days after challenge. Taken together, these data indicate that treatment with antibody D005, in addition to its potential as pre-exposure prophylaxis, may also be used therapeutically at the early stages of infection.", "sistently yields antibodies that are highly expressed in mammalian cells." ] },{ "paper_id": "5e8f40e1096456d1b5b0c24b57104bf15f45d37e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Standard SDS-PAGE was performed with DTT in 15% Tris-Glycine gel with TGS running buffer or in NuPAGE under nonreducing conditions (4-12% Bis-Tris gel with MES-SDS running buffer) according to the manufacturer's protocol (Invitrogen). The sample, 5 mg, (final concentration of 2 mg/ml) was mixed with sample buffer for 1 min followed by heating at 95uC for 5 min before loading into the gel. The gel was run at constant voltage of 200 V for 50 min at room temperature. The standard SDS-PAGE gels were stained with Coomassie blue while the NuPAGE gels were stained with SimplyBlue SafeStain (Invitrogen) or silver stain (Bio-Rad).", "Effect of reconstitution protocol on p7 secondary structure", "Conceived and designed the experiments: SWG JT WS. Performed the experiments: SWG WS AV. Analyzed the data: SWG WS JT AV. Contributed reagents/materials/analysis tools: JT. Wrote the paper: JT WS.", "These residues also appear between two helical segments in a recent structure of p7 in DPC micelles [20] , where TM1 is proposed to line the lumen of the channel." ] },{ "paper_id": "5e93750f999d2d9a74e43f51d61de527957e8502", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study has been approved by the ethics committee of Nanjing University of Traditional Chinese Medicine and written informed consent was obtained from all subjects.", "The exclusion criteria were:" ] },{ "paper_id": "5e9ccecdd40825f5c30da3a900fc5cf1b063b47d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MTW, co-first author, carried out the molecular genetic studies and drafted the manuscript." ] },{ "paper_id": "5ea003777403bda990fe5a2471273b477e529751", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animals. The male C57BL/6 mice (8-10-wk-old; 20 \u00b1 2 g) were purchased from Charles River (Beijing, China). Mice were kept in a temperature (21 \u00b1 2 \u00b0C) and humidity (60 \u00b1 5%) controlled room on a 12-hour light/dark cycle. They were fed a standard mice chow and water ad liblitum. All experiments were performed in accordance with the Declaration of Helsinki and were approved by the Institutional Animal Ethical Committee of the Peking Union Medical College Hospital.", "Acute lung injury (ALI) is a critically severe, life-threatening condition in ICU, characterized by high mortality of approximately 40% 1 . ALI, along with its more severe form, acute respiratory distress syndrome, often results from a massive insult to the lung, whether be the direct alveolar infiltration or the indirect effects of systemic inflammatory response syndrome or multiple organ dysfunction syndromes 2 . An effective treatment of this life-threatening disorder calls for a better understanding of the molecular pathophysiology of ALI.", "The SPSS program (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Data were expressed with means \u00b1 SD or percentage. The distribution analysis was conducted by Shapiro-Wilk test. If the data were conforming to the normal distribution, then the comparison of multiple groups was performed Scientific RepoRts | 6:22044 | DOI: 10.1038/srep22044 using ANOVA with LSD to compare differences between individual groups; if the data were not conforming to the normal distribution, then the comparison of multiple groups was carried out by Kruskal-Wallis test, and difference between individual groups were compared by Mann-Whitney U test. The survival rate was analyzed using the Kaplan-Meier log-rank test. Statistical significance was set at a 2-tailed P value < 0.05." ] },{ "paper_id": "5eb1e53fb44c8a997713bd4fc55d65b904df3ce8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The magnitude of gynaecological and obstetrical consequences of vaginal infections, particularly severe in pregnant women [17, 18] recently fostered the development of newly emerging therapies, including either novel vaginal delivery systems aimed to prolong the residence time of drugs into the vaginal cavity, or novel antimicrobial agents. Nifuratel [19, 20] , plant-derived essential oils [21, 22] , glycerol monolaurate [23] and silver [11] are just a few examples of emerging strategies with a good safety profile.", "Pathogens responsible for vaginal infections include bacteria, fungi and protozoa. Bacterial vaginosis (BV), aerobic vaginitis (AV) and candidiasis are the most common infections in women of childbearing age, characterised by an imbalanced vaginal microbiota population and vaginal discharge. Whereas BV, often asymptomatic and characterised by a discharge of typical fishy odour, is a polymicrobial syndrome with a variety of opportunistic pathogenic bacteria such as Gardnerella vaginalis, replacing the resident Lactobacillus species [2, 3, 4] , in AV the resident lactobacilli are replaced by intestinally-derived aerobic microorganisms, such as Escherichia coli, Streptococcus agalactiae, Staphylococcus aureus and Enterococcus faecalis [5, 6] . An highly symptomatic inflammatory state, AV typically presents with a yellow, smelly vaginal discharge. BV and AV are generally accompanied with a vaginal pH increase above 4.5, beyond the healthy vaginal pH of 3.8-4.5 [5, 7] .", "Candidiasis is the most frequent symptomatic mycotic infection caused by the yeast Candida albicans and a few other pathogenic Candida species. During their lifetime, 75% of all women are expected to experience at least one episode of Candida-induced vaginitis [8, 9] . Acute pruritus and smelly vaginal discharge are usual complains in vaginal candidiasis, associated with vaginal discomfort, irritation, vulvar burning, dyspareunia and dysuria. Differently from BV and AV, the vaginal pH usually remains in the normal range [9] ." ] },{ "paper_id": "5eb20deb48c231973cf0a796ca1c6898cbf2d07d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animal procedures were approved by the Institutional Animal Care Committee of Universit\u00e9 Laval according to the guidelines of the Canadian Council on Animal Care (protocol 2015031).", "200 L/min-no separator 0% \u00b1 9% 200 L/min-160 orifices 11% \u00b1 5% 400 L/min-no separator 12% \u00b1 19% 400 L/min-160 orifices 6% \u00b1 5% 400 L/min-40 orifices 11% \u00b1 5%" ] },{ "paper_id": "5eb34e4b386106962c368bb7c32db8995190e5c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics Statement: The Emory University Institutional Review Board (IRB) granted waiver of all elements of informed consent and waiver of HIPAA authorization.", "This is a prospective study.", "Staff. RFID tags were issued to assenting ED staff members to wear." ] },{ "paper_id": "5eb39003823f5339573f8f9ed82eaf7763feda68", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The identity of all generated transfer vectors was verified by sequencing.", "A targeted recombination system was established for PEDV in a two-stage process as outlined in Fig. 1B .", "VERO cell monolayers were infected as described above with the PEDV-Rluc and PEDV-DORF3/Rluc viruses at indicated MOI's. At indicated times post infection, cell lysate samples were assayed for luciferase activity using the Renilla Luciferase Assay system (Promega) according to the manufacturer's instructions, and the relative light units (RLU) were determined with a Berthold Centro LB 960 plate luminometer.", "Porcine epidemic diarrhea virus (PEDV) causes diarrhea and dehydration in newborn piglets. The virus infects the epithelial cells of the small intestine resulting in severe mucosal atrophy and consequent malabsorption. PEDV is common and the cause of serious problems, particularly in pigs in Asia. The disease usually appears in winter during which it can cause high fatalities in suckling piglets (see for a recent review [1] ). From 2010, an outbreak of PEDV has swept China with over 1 million fatalities among newborn piglets causing substantial economic losses in the swine industry [2] . The characteristics of the infection and its epidemiology were quite dramatic with morbidity and fatality approaching 100% in one-week old piglets, despite the use of commercial, inactivated vaccines. Virus transmission occurs via the fecal-oral route and possibly also by vertical transmission through lactation [2] . Currently there is no efficient way of treatment of the disease. Prevention of the infection usually relies on vaccination with cell culture adapted live-attenuated or inactivated viruses although the efficacy of current vaccines has been questioned [2, 3] ." ] },{ "paper_id": "5eb90019b82d03c01d91fd62ca9ba89d60814f82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Several respiratory viruses cause Influenza-Like Illnesses (ILIs) in humans, including Influenza A (InfA) and B (InfB) viruses, Adenoviruses (ADV), Respiratory Syncytial virus (hRSV), Enteroviruses (EV), Rhinoviruses (hRV), human Metapneumovirus (hMPV), human Bocavirus (hBoV), human Coronaviruses (hCoV) and human Parainfluenza virus (hPIV) [1] [2] [3] . These human respiratory pathogens may express prominent seasonality and cause overlapping epidemics [4] [5] [6] , so deciphering their dynamics requires extensive virological investigation, facilitated nowadays by molecular kits." ] },{ "paper_id": "5eba29203084de16f501b71b64873f5c96ce55f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analysis of single nucleotide polymorphisms (SNPs) in the complete gene sequences of TLR7 between goat breeds did not show any differences that could account for this.", "Following eradication of rinderpest, focus has shifted to PPRV as a potential virus for eradication efforts. The single serotype of PPRV, availability of an efficacious live attenuated vaccine, sensitive diagnostic tests and the economic impact of this disease, coupled with its ability to spread into new geographical regions, render it an attractive target [30] . PPR was first reported in India in sheep with a lineage IV virus in 1989 [31] , with no further reports until 1996, when a massive outbreak occurred in goats throughout northern India with a lineage IV virus [32] . Three live attenuated vaccines, specific to lineage IV PPRV strains have so far been tested in India [33] .", "Cytokine gene expression levels were compared by SyBr Green qRT-PCR using gene specific primers (Applied Biosystems, Carlsbad, CA) (primer sequences available upon request). Unstimulated PBMC were used as control. Corrected Ct was calculated as:" ] },{ "paper_id": "5ec99e67f23c0c2795fad1ad551ab1abe4406841", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scheme 1. Illustration of the mechanism of test paper for colorimetric inspection of FAs according to the color changes of TMB induced by Ag + oxidation." ] },{ "paper_id": "5ecad9a5929549f90a9aa621ea0548c62d1385ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We thank the reviewer for their positive comments." ] },{ "paper_id": "5eccf590cffbe86092abe652fa471515e9f37249", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For maximum precision, descriptive analyses include all sampled individuals." ] },{ "paper_id": "5ed3b0cd33b9af56879a3b5f10d6b7399ae86785", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Steric block oligomers such as of 2'O-methyl (2'OMe) and phosphorodiamidate morpholino (PMO) oligonucleotides possess high affinity for their complementary pre-mRNA targets and can modulate alternative splicing, correct aberrant splicing, and induce skipping or inclusion of specific exons (for reviews see [1, 2] ). These splice modulating oligonucleotides (SMOs) represent a powerful class of compounds with broad utility for basic and translational research and are poised to show rapid growth as pharmaceuticals. However, for many in vivo applications, SMOs administered alone show an inadequate delivery profile for reaching target cell nuclei, necessitating the use of carriers. Indeed, inefficient delivery of SMOs remains the foremost limitation to their usefulness as pharmaceuticals.", "Male mdx mice (C57BL/10ScSn-Dmd mdx /J) and agematched 6-9 wk old normal mice (C57BL/10SnJ) were obtained from Jackson Laboratories (Bar Harbor, ME). All animals were housed according to NIH and University guidelines (Drexel University College of Medicine, ULAR facility, Philadelphia, PA)." ] },{ "paper_id": "5edd56f96660760a5f8ae69efd7d9e976a00c4ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Baculoviruses have a cloning capacity as large as 38 kb, allowing them to accommodate a single large insert or multiple genes encompassing regulatory elements [17] . These attributes have fueled interest in exploring baculoviruses as vectors for recombinant protein expression systems and gene therapy [18] [19] [20] . In spite of the advantages of baculovirus, overcoming their lower efficacy relative to that of conventional vaccines remains a challenge [21] . We previously reported that a non-replicable baculovirus vector containing antigen-encoding DNA could serve as a nano-delivery system, and improve exogenous gene delivery into human cells by incorporating the envelope glycoprotein of human endogenous retrovirus (HERV-W) on recombinant baculovirus [21] [22] [23] .", "Virus-like particles (VLPs) represent an advanced vaccine platform with enhanced immunogenicity [24] . VLPs are formed by structural viral proteins, which have an inherent tendency to self-assemble and mimic the morphology of the pathogen [25] . In contrast to live viruses, VLPs are non-infective and non-replicating, since they are essentially devoid of pahogenetic material [24] . Moreover, VLPs have been known to enhance immunogenicity by presenting antigenic epitopes in correct conformation, resulting in strong humoral and cellular immune responses [24, 26, 27] . Given these advantages, VLPs have been widely used for vaccine development and other biomedical applications [28] .", "A recombinant baculoviral vector expressing HERV env (pFastBac1-HERV) was previously constructed by inserting a synthetic, codon-optimized envelope gene of HERV type W (Gen-Bank accession number NM014590; GenScript, USA) into pFastBac1 (Invitrogen) [29] .", "Recent trends in influenza vaccine development have followed two general paths: a universal vaccine approach using the stalk domain to induce a broad-spectrum neutralizing antibody, and a specific approach using VLPs [33, 34] . In addition to their advantages of improved safety and strong immune response, VLP vaccines can readily substitute HA or NA genes to allow rapid, dynamic responses to a new influenza outbreak [14, 35, 36] . However, efficient construction and production of VLPs are major obstacles to commercialization [37] ." ] },{ "paper_id": "5ee02e510d7fb0b2523b669dacadf4f56ee6b55f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5eeeb39d1eda252e3ba5fff3596679b8e3376f8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It has also been noted that autoantigens have a tendency to relate to proteins known to bind to dermatan sulphate, a component of dead cells [259] and a constituent of glycosaminoglycan receptors for many bacteria and viruses [260] .", "No other immediately apparent relationships with betaamyloid could be found by literature survey for CD2AP, CD33, and EPHA1 or for MS4A-related proteins, although such are not precluded.", "The principles discussed here may apply to many other, if not most, human diseases." ] },{ "paper_id": "5ef330551dd1c93b532c49305501f9a5abd3d799", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It becomes evident that both mechanical and biological prosthetic heart valves are associated with tissue reactions developing against implanted foreign materials. Upon that, macrophages, neutrophils, and T cells are the major players of cellular immunity in this process. However, dynamic changes of their quantities in systemic blood flow, participation in pathogenesis of responses against foreign materials, and potential diagnostic importance were poorly investigated.", "All persons enrolled to the study were properly notified and signed an informed consent.", "Statistical analysis of the data was done by using Statistica 7.0 and GraphPad Prism software. The data are presented as median (VA) values and interquartile range (25; 75%). Significance of differences between data was evaluated by applying nonparametric Mann-Whitney test and -Wilcoxon test. A correlation analysis was done by using Spearman -test. Significance level was set at < 0.05." ] },{ "paper_id": "5ef424a39823c1e6a0fc472b7ed744121356f11d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Some potential methods for avoiding OAS have been described [37] . These include masking gp120 epitopes [80, 81] , using cytokines [82] , and suppressing dominant B and T cell clones [80, 83] .", "Similar experiments in humanized mice and humans where multiple mAbs were evaluated for therapeutic efficacy against established infections did not reveal a significant benefit to the combination bnMAb approach [101] [102] [103] . In those experiments, the broadly neutralizing antibodies (b12, 1 Membrane-proximal external region of gp41. 2 EBV transformation of B cells. 3 V1V2 site on gp120. 4 Glycan V3 site on gp120. 5 CD4 binding site on GP120. 6 Neutralization assays of B cells from infected donors. 7 Resurfaced stabilized core 3 probe. 8 Somatic mutation primers, gp120 and gp140 probes. 9 454 pyrosequencing to characterize additional VRC01-like antibodies from HIV-1-infected individuals. 10 Efficient B cell immortalization and high throughput screening.", "Since intracellular virus would be better protected than free virus from adverse effects of antiviral factors in the genital environment such as antiviral antibodies [108] , and cell-cell transmission enables HIV-1 to evade inhibition by potent CD4bs directed antibodies [109] , anti-cell mAbs [110, 111] will be an important component of a multi-mAb microbicide.", "Clinical and Developmental Immunology 3 OAS therefore is a complex immune response that can result in production of effective neutralizing Abs in some cases." ] },{ "paper_id": "5efa53c00c644015671a7f0827caa63032940442", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "White powder, yield 59%, m. p. ", "These authors contributed equally to this work" ] },{ "paper_id": "5efae4eb4c986da7483e7628d420be2a29df90d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments were performed a minimum of three times unless otherwise stated. For comparisons between the control and treated groups, unpaired Student's t-test was employed. For comparisons of multiple groups, a one-way analysis of variance (ANOVA) followed by post-hoc analysis using the Bonferroni t-test was conducted using GraphPad Prism 5.0 software (GraphPad, San Diego, CA). A p value of ,0.05 was considered significant.", "All animal experiments were performed in accordance with, and with the approval of, protocols sanctioned by the IACUC committees at the University of California, San Francisco and the San Francisco VA Medical Center (approval #10-075-01).", "Cell culture supernatants were assayed using ELISA for TNF-a, IL-6 (BD Biosciences, San Jose, CA) or IL-1b (R&D Systems, Minneapolis, MN) per manufacturer's instructions." ] },{ "paper_id": "5f1066c0868ef0e9c5325de77d1ebbf40d6208ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nasopharyngeal aspirations (NPAs) of all subjects were obtained within 24 h after admission. About 1-2 ml NPAs were drawn using a disposable sterile suction tube which was inserted 7~8 cm into the throat via the nose and under the pharyngeal. NPAs samples were then transferred to sterile collection tube after normal saline was added. Then 2 ml of virus protection solution containing 200 U/ml penicillin, 200 U/ml streptomycin, 200 U/ml amphotericin B, and 0.125% BSA was added into NPAs samples. After mixing, the samples were immediately placed in \u2212 80\u00b0C refrigerator for future examination.", "Other microbiological including typical bacteria were detected by Gram staining of sputum specimens and blood culture. Atypical bacteria, chlamydophila pneumoniae and mycoplasma pneumoniae, were detected by blood antigen. All specimens were stored in dry ice at low temperature and transported to the China Center for Disease Control and Prevention for respiratory virus identification.", "The study was approved by the Ethics Committee of Hunan Provincial People's Hospital." ] },{ "paper_id": "5f1378b1fa0165baf6bd31d9e4d0d66d818a37c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Notably though, summer URTI incidence is roughly half of winter for all groups; also, the least protected group (10 ng/ml of 25-hD) in summer had approximately 25% lower URTI incidence than the protected group (30 ng/ml of 25-hD) had in winter. Additionally, influenza spikes can occur in October and November when 25-hD levels are reported relatively high [45] . Thus, 25-hD is a probable influence but whether it is sufficient in itself to explain seasonality is at most an open question. Vitamin A (present in cod liver oil with 25-hD for some studies) may also be a significant factor since vitamin A shows a strong influence on measles [46] , which is another enveloped virus spread by aerosol. Such factors need continued study in order to include them properly in our understanding and epidemiological models." ] },{ "paper_id": "5f14950df2d6d428b1dff4d58e7775f92da020d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protein chips were read using the PBS-IIC ProteinChip Reader (Biorad Laboratories). Data were collected between 0 and 200 kDa. An average of 105 laser shots per spectrum at laser intensity 140 and detector sensitivity 6 was collected. The focus mass was set to 3000 Da. Settings for tissue analysis were optimised independently, resulting in an average of 105 laser shots per spectrum at intensity 165 and detector sensitivity 6 and a focus mass at 6000 Da. Mass-to-charge (m/z) values were calibrated externally with the all-in-one peptide mixture (Biorad Laboratories).", "Pre-and post-surgery serum samples were available from 24 CRC patients (marked in Table 3 ", "Snap frozen tissue sections were disintegrated in deep frozen state by pulverisation with a Microdismembranator II (Sartorius AG, G\u00f6ttingen, Germany) (14) . First, tissues were cut into smaller blocks, placed into a pre-cooled shaking fl ask with a stainless steel ball and then pulverised in three rounds of shaking (55s) and cooling in liquid nitrogen (3 min). Ten mg of the resulting frozen tissue powder was then added to 100 \u03bcl of denaturation buffer consisting of 9 M urea, 2% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) and 1% dithiotreitol (DTT) and stored at \u221270 \u00b0C until analysis. For measurement of the protein concentration lysates were thawed on ice, centrifuged at 15000 rpm for 5 min and the supernatant collected for protein profi ling. Protein concentration in the supernatants was determined using the 2D-Quant Kit (GE Healthcare, Diegem, Belgium) according to the manufacturer's instructions." ] },{ "paper_id": "5f1578a62c27bf79646c2ef894cc185b322c8b4f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Middle East respiratory syndrome (MERS) is a viral respiratory disease caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). MERS cases continue to occur and are often associated with respiratory and multiorgan failure [1] . There is no antiviral treatment with proven efficacy at present [1, 2] .", "Recruitment started in November 2016 and is currently ongoing.", "Supplementary information accompanies this paper at https://doi.org/10. 1186/s13063-019-3846-x." ] },{ "paper_id": "5f1e08abe8648487cc1738dac17cb2adb25cffe7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The prediction of motifs for posttranslational modifications suggested a protein kinase C phosphorylation motif and one or two casein kinase II phosphorylation site(s) [139, 141] . Additionally, Wang et al. proposed the existence of a zinc finger structure [140] . However, to our knowledge, a crystal structure is not yet available.", "Recently, it has become evident that IFN\u03b3 also represses the expression of numerous genes termed IFN-repressed genes (IRepGs) [43, 45, 46] . In combination, the IFN-induced alterations of ISGs and IRepGs elicit antiviral activity [45, 46] .", "Based on their potent antiviral activity, IFNs have been approved and are successfully used as antiviral drugs, e.g., against hepatitis viruses. However, with the development of effective direct acting antiviral (DAA) drugs, e.g., against hepatitis C virus (HCV), the use of IFNs is declining." ] },{ "paper_id": "5f28070e492b933fa2cfd460fd67b9f6731c4345", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5f36e6c3da64e8d95c81d9c63ad4909144f9191c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interests.", "One could speculate about increasing number of contacts by age in the community, but we did not collect information enabling further analysis of this possibility.", "Double or triple infections were detected in 16% of the virus-positive children, which is comparable to that observed by others [31, 34] . We do not have any explanation for the observed relatively higher frequency in the older children." ] },{ "paper_id": "5f3a91dcea8198642e968d058fdb0c42cc1730d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5f3f613be264f8b10318dfe8e92777fe7a95848e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell culture of influenza-negative specimens ", "Sequences for pH1N1 and H3N2 sequence datasets respectively were combined with references available from the Influenza Viral Resource at Genbank [17] and the GISAID EpiFlu database [18] representing global diversity of pH1N1 from 2009-2013. Sequences were aligned using MUSCLE version 3.8.31 [19] implemented in Seaview version 4.4.2 [20] and manually inspected for accuracy. Best models were determined from alignments using jmodeltest2 version 2.1.4 [21] . Maximum likelihood (ML) phylogenetic trees were generated using PhyML version 3.0 as implemented in Seaview version 4.4.2 [22] . See Table 1 for a detailed description of datasets and models used in analysis. ML phylogenies were annotated using MEGA version 5 and FigTree version 1.4.0 [23] . All influenza sequences used in analysis have been deposited into Genbank under accessions KU299790-KU299957.", "Descriptive statistics of demographic and clinical data including frequencies and cross-tabulations were entered in a study database by double data-entry using Microsoft Excel 2013 and analyzed using IBM SPSS Statistics 21.0 (SPSS, IBM Inc.)", "Influenza A H3N2 (H3N2). All sequences were highly related with no more than 1.77% divergence between the samples and the furthest related respective vaccine (S9 Table, Fig 6) for any of the segment. The majority of segments were more closely related to the A/Victoria/361/ " ] },{ "paper_id": "5f50a65482a507e61c9a7cd9a9b80a0017494dcb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The multidimensional richness of human experience generates considerable intragroup variation [36, 37] . Thus, migrants from a common sending place rarely share the same socio-economic and political backgrounds and mobility experiences [38, 39] . Recipes of cultural characteristics miss the complexity of perspectives and behaviors that exist within ethnic groups due to varied social origins and behavioral inclinations, exposure to different experiences, mixed and emerging identities, and uneven transborder ties and involvements [40] . As Marjorie Kagawa-Singer and Shaheen Kassim-Lakha illustrate:", "The TC framework explicitly encompasses five discrete, but mutually reinforcing, skill domains. Transnational competence involves mastery of analytic, emotional, creative/imaginative, communicative, and functional skills. Each skill domain encompasses multiple dimensions.", "Publish with Bio Med Central and every scientist can read your work free of charge ", "TC's second core principle holds that patient advocacy is an indispensable physician activity. A TC education aims to move learners beyond patient sensitivity into responsiveness to patient needs. Across its five skill domains, the TC framework remains focused on two interconnected objectives: improved short-and long-term health outcomes for patients in spatial transition and reduced health inequities for dislocated populations and disadvantaged communities. Both objectives lie at the core of the People's Charter for Health that emerged from the People's Health Assembly held at Savar, Bangladesh, in 2000 [76] .", "The capacity to engage in meaningful dialogue and to facilitate mutual self-disclosure via questioning is particularly important in transnational health-care situations characterized by vast social distance [168] . Similarly, a prerequisite for negotiating appropriate treatment plans and commitment to agreements is that participantsespecially migrant patients -are comfortable expressing serious doubts and constructive challenges [168, 63, 58] ." ] },{ "paper_id": "5f6cbbe720247466895b4469f21b0967b35feb5a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Biological factors Team members suffered from fatigue after their long, physically, emotionally and mentally draining mission in Liberia. This fatigue lowered their resistance to disease.", "Interview participants thought their lack diplomatic skills partly contributed to the delayed delivery of supplies from China, and their inability to efficiently apply for supplies from other organizations or local governments.", "Lack of readily prepared medical teams, and inadequate equipment were other major challenges", "Please see Additional file 1 for translations of the abstract into the five official working languages of the United Nations." ] },{ "paper_id": "5f7b5b1f4748ede29130df5606fd51f4820edc20", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The first outbreak of severe acute respiratory syndrome (SARS) occurred over 10 years ago in 2003. This outbreak has led to significant attention and intensive study of the treatment and prevention of coronaviruses over the past decade. Recently, a new coronavirus called the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has emerged. MERS-CoV first appeared in Saudi Arabia in 2012 and quickly spread into Europe. To date, approximately 3-4 out of every 10 patients who have been diagnosed with MERS have died 1 . Although significant advances in the understanding of coronaviruses have been made over the past decade through the study of SARS-CoV, more research is needed to develop effective countermeasures, such as drugs or vaccines, to control the new pathogen.", "Inhibition assay. The isatin derivative, 1-(2-naphthlmethyl) isatin-5-carboxamide (5f) 26 , is known to inhibit SARS-3CLpro. 5f was dissolved in dimethyl sulfoxide (DMSO) to test inhibition efficiency towards GLRQ. GLRQ (18.5 \u03bc M) and 5f (160 \u03bc M ) or control 2% DMSO were pre-incubated in 40 mM of phosphate buffer (pH 7.3) at 37 \u00b0C for 5 min, and then 200 \u03bc M of the substrate (Thr-Ser-Ala-Val-Leu-Gln-pNA) was added to the mixture and allowed to react for 750 s.", "Oligomeric state of GLRQ. Analytical gel filtration and sedimentation velocity methods were used to check whether both the GRQ and GLRQ mutants maintain monomer structure. The same concentration of wild-type 3CLpro served as a control." ] },{ "paper_id": "5f81496a02673e6967f71dfbc8d4112a29d3d1b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Minimal essential medium (MEM) was purchased from Gibco TM (Thermo Fisher Scientific, Seoul, Korea). Monoclonal antibody (3B19) to AI virus nucleoprotein prepared using H9N2 strain as immunogen was purchased from Median Life Science (South Korea). Anti-mouse -FITC secondary antibody was purchased from (Thermo Fisher Scientific, Seoul, Korea).", "Immunofluorescence protocol. After 2-4 days of incubation for CPE study, the supernatant was removed.", "Compounds. Sodium salt of 3\u2032-sialyllactose (3\u2032-SL; Neu5Ac\u03b12-3Gal\u03b21-4Glc\u03b2; empirical formula: " ] },{ "paper_id": "5f88f46f2e2fe48b05a5cfefcfbe74f4bc90f574", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This paper describes the process and the resulting framework, starting with a formulation of the key research questions based upon the need to have a more refined and user friendly means of classifying risk and vulnerability for MMPs. The research questions were formulated as follows:" ] },{ "paper_id": "5f8c204d73feaf62ba6caa3be033d007e3134d5a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thirty occlusion cycles were performed over thirty minutes, once daily. Data from the first week of testing were discarded as training; remaining data were averaged within animal, within day, and then within week before group comparisons were made.", "Circulating Angiotensin II (and III). Trunk blood was collected at sacrifice into tubes coated with EDTA, and plasma was isolated and frozen at \u2212 80 \u00b0C after centrifugation for 5 minutes at 5,000 \u00d7 g. Plasma was subsequently thawed and then extracted using a commercially-available C18 SEP-Column kit per manufacturer's instructions (Peninsula Laboratories International, Inc.; Catalog Number S-5000). 100 uL of plasma was extracted, lyophilized, and stored at \u2212 80 \u00b0C. The dried extract was then reconstituted in 150 uL of EIA buffer and analyzed using a commercially-available EIA kit per manufacturer's instructions (Peninsula Laboratories International, Inc.; Catalog Number S-1133).", "Statistics. Throughout, ANOVA-based analyses (with repeated measures as appropriate) and independent t-test were utilized. Tukey multiple-comparisons procedures were used for post-hoc analyses. Differences were considered significant at P < 0.05. Data are reported as mean \u00b1 1 sem, throughout." ] },{ "paper_id": "5f8d96a8606eb6c9a89a1160f8b498c6c0efecba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There have been considerable advances in mechanistic models of how several viral envelope glycoproteins function in driving the membrane fusion reaction (reviewed in [76] [77] [78] ). A key component of many of these fusion glycoproteins is two -helical domains referred to as heptad repeats (HR) that are involved in the formation of a trimer-ofhairpins structure [79, 80] . HR-1 is located proximal to the amino (N)-terminal fusion peptide and HR-2 precedes the transmembrane domain near the carboxyl (C)-terminus [79, [81] [82] [83] . For many viral fusion glycoproteins the N-terminal HR-1 forms an interior, trimeric coiled-coil surrounded by three anti-parallel helices formed from HR-2 and the formation of this structure mediates and provides the necessary energy to drive viral-host cell membrane merger (reviewed in [84] ).", "NiV and HeV are classified as zoonotic biosafety level 4 (BSL-4) viruses and infectious virus can only be studied at a handful of laboratories worldwide. Both viruses have also been included among the various pathogenic agents of biodefense concern and each are classified as priority pathogens in category C by the Centers for Disease Control and Prevention (CDC) and the National Institute of Allergy and Infectious Diseases (NIAID). The category C agents include high emerging pathogens with the potential for causing morbidity and mortality with major economic and health impacts. Henipaviruses in particular, could be engineered for mass dissemination because of their availability from natural sources and their relative ease of propagation and dissemina-tion. Currently there are no specific antiviral therapies or vaccines available for treating or preventing NiV or HeV infection resulting from a natural outbreak, laboratory accident or deliberate misuse.", "Experimental NiV infection in Pteropid bats has been attempted [39] . All bats that were challenged with 50,000 TCID 50 NiV remained clinically well throughout the study period and no febrile responses were recorded following NiV inoculation via a parenteral route. Challenged bats developed a sub-clinical infection characterized by episodic viral shedding in urine, limited presence of virus within selected viscera and seroconversion. No gross abnormalities were identified on post-mortem examination of animals at various times post exposure; all bat tissues were negative upon immunohistochemical labeling for NiV antigen." ] },{ "paper_id": "5f938778c47463eaa1e15fd63c0656cf830220e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Color Key and Histogram", "Row Z-Score" ] },{ "paper_id": "5f96f9d0f4775e4803ec0d9c0b3c181a40ea27ce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thus, e q,a = log", "Then", "(S11)" ] },{ "paper_id": "5f9daea45653f753380db839c7320be13dd2cbc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviation: HLH = hemophagocytic lymphohistiocytosis.", "A cardiac ultrasound was performed and revealed no suggestive images of infectious endocarditis or valvular heart disease. Initially, the chest radiography revealed no changes, but in evolution, it showed bilateral alveolar condensation and left pleural effusion." ] },{ "paper_id": "5fa442d7a4a81f82d7c5f0ecc72ab708ac2a7266", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5fa62370245d4ad73220d6f42f8cb66064627aaa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The architecture of biological membranes is defined by the composition and distribution of lipids and proteins in the bilayer.", "Liquid chromatography/mass spectrometry for targeted sphingolipid analysis. The method was slightly modified from [65] . Briefly, each sample was extracted according to published protocol then dried and reconstituted in 100 mL of methanol : water : formic acid (74:25:1) containing 5 mM ammonium formate. An Agilent 6400 QQQ (Agilent Technologies, Santa Clara, CA) was used for analysis coupled to an 1100 Series LC equipped with HPLC Chip interface (Agilent Technologies Santa Clara, CA). Solvent A consisted of methanol : water : formic acid [65] with the following source conditions: gas temperature 300uC, gas flow 4 L/minute, capillary voltage 1900 V. The fragmentor voltage was set to 180 V in all cases. Data were processed with Agilent Mass Hunter software version B03.01.", "As a second messenger, CER can also induce apoptosis and autophagy [34] . However in mosquito cells, DENV maintains a persistent infection and antagonizes apoptotic pathways [19, 43] ." ] },{ "paper_id": "5fa7de71e210e3f7884579d7da079c77fa0d5d6d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, while this research can give a broad picture of associations, many nuances of relationships are missed. One example is the cholera outbreak in Haiti after the 2010 earthquake. The epidemic was actually traced back to Nepalese UN Peacekeepers who brought the disease after the earthquake [25] . One could argue that the epidemic would not have occurred if the earthquake had not happened. However, the opposite could be argued as UN Peacekeepers had been in Haiti long before the earthquake occurred. The complexity of causality in these circumstances is not always clear.", "In terms of type of outbreak, 42% were acute respiratory illnesses (influenza, MERS-CoV) followed by the VPDs (39%): yellow fever (10.0%), poliomyelitis (9.1%), meningococcal disease (8.7%), and cholera (7.8%). This proportion was similar for all regions, except Africa where 70% of the outbreaks were vaccine preventable.", "A ND is a phenomenon caused by rapid or slow onset of geophysical, hydrological, climatological, or meteorological events [8] . People have long associated NDs with a high risk for outbreaks. While this belief persists, evidence is lacking, except for specific cases such as Ebola or when NDs lead to similar circumstances as CEs [9, 10] ." ] },{ "paper_id": "5fa8a1eb8fab8c225ab28402700a6c3aa950f2d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Citation details: Chen,L., Liu,B., Yang,J. et al. DBatVir: the database of bat-associated viruses.", "Emerging infectious diseases have remained a major threat to public health during the past decades (1) . Zoonotic diseases, or zoonoses, are diseases that are transmissible from animals to humans under natural conditions. Because 60% of all emerging infectious disease agents in humans are of zoonotic origin (1, 2) , the study of animal diseases and their emerging potential has become increasingly important.", "Usually, searching the database would be a more efficient way to find the required information than browsing the database. DBatVir provides a powerful search engine for users to extract information from the database quickly through three different ways: (i) text search (for viruses), (ii) BLAST sequence similarity search and (iii) bat-related information search." ] },{ "paper_id": "5faef288fa2cd3e02a6d12b9e09912decde1032c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5fb0184e30b9a7107983d9316b1c925508b75834", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "conclusion: Microbial NA induces a moderate and transient myelin vacuolation that is not caused either by neuroinflammation or complement system activation.", "Animals were anesthetized with 2,2,2-tribromoethanol and transcardially perfused with saline followed by Bouin's fixative (45) . Brains were removed and immersed in the same fixative for 24 h, and later embedded in paraffin wax. Seven-micrometer sections were obtained from each brain and mounted on poly-l-lysinetreated slides. Series of sections along the brain region of interest (from Bregma \u22120.3 to \u22121.2 mm approximately) were obtained. Hematoxylin-eosin staining was applied to counterstain the sections.", "immunohistochemistry Immunohistochemistry was carried out on deparaffinized tissue sections using the immunoperoxidase technique. The primary antibodies used were as follows: rabbit anti-rat C5b-9 (1:200, Abcam, ab55811); rabbit anti-rat C9 (1:100, provided by Prof. B. P. Morgan, Cardiff University); rabbit anti-myelin basic protein (MBP) (1:500, Zymed, 18-0038); goat anti-Olig2 (1:100, RyD System, AF2418); and mouse anti-caspase-3 (1:100, Thermo, MS1123R7). The secondary antibodies used were as follows: biotinylated goat anti-rabbit IgG (H + L) (1:1,000, Pierce, 31820); biotinylated horse anti-goat IgG (H + L) (1:1,000, Vector, BA9500). For the mouse antibody against caspase-3, the Ultravision Quanto HRP system (Thermo Fisher Scientific, TL060QHD) was used. All antibodies were diluted with PBT buffer (0.3% bovine serum albumin, 0.3% Triton X-100 in PBS pH 7.3). Primary antibodies were incubated overnight at room temperature (RT). Secondary antibodies were incubated for 60 min at RT. Negative controls for the immunostaining consisted of equivalent sections subjected to the same protocol but omitting the primary antibody.", "None of the antibodies against MAC (anti-C5b9 and anti C9) revealed a positive labeling in any of the vacuolated axonal bundles studied (Figures 7A,C) , thus suggesting the absence of MAC deposition on vacuolated tracts. Swollen lymph nodes were used as a positive control for anti-C5b9 (inset in Figure 7B )." ] },{ "paper_id": "5fb9518f07541bb5ee6f8f9ef9d374416ffeecc7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Arterial blood pressure was measured in concious mice prewarmed to 30 \u2022 C, using a tail-cuff sphyngomanometer (LE 5001; Letica scientific instruments). To prevent stress animals were trained for 5 consecutive days before measurements.", "Signal to noise ratio (SNR), of a particular region of interest (ROI) was defined as follows:", "NER (%) = SNRca SNRt Post injection \u2212 SNRca SNRt Pre injection SNRca SNRt Pre injection" ] },{ "paper_id": "5fbed89aaeda377c284ad02fc944fc80571e0cab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HIV-1 continues to be a major public health problem, and new safer and more effective therapies are needed. Therapeutics approved for clinical use have varying degrees of side effects and none can eradicate the HIV-1. Protein therapeutics are typically cell target-specific and relatively safe 1 . Currently, antibody therapeutics are dominant protein therapeutics with more than 50 monoclonal antibodies (mAbs) approved for clinical use 2 . However, there are no mAbs approved for therapy against any viral diseases. The humanized mAb Synagis is the only one approved by the FDA against a viral disease, however, it is only for prevention and not for therapy 3 .", "non-reducing SDS-PAGE gels with molecular weight (MW) corresponding to the calculated ones of approximately 28 kDa (Fig. 1b) . They were soluble, did not precipitate even at concentrations higher than 30 mg/ml and ran as monomers in size exclusion chromatography (Fig. 1c) ." ] },{ "paper_id": "5fc3eedb09f3b7624fec7d2b9afedfffbab47a21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As for JNK, activated JNK phosphorylates c-Jun and other downstream substrates, enhancing their transcription activity [58] . Activated c-Jun dimerizes with other proteins such as cellular FBJ murine osteosarcoma (c-Fos) to form the activator protein 1 complex, thereby inducing genes harboring the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element [59] .", "Taken together, current evidence demonstrates that coronavirus infection induces ER stress and triggers UPR in general. It is apparent that coronavirus might subvert or utilize certain aspects of the UPR to benefit its own replication and pathogenesis." ] },{ "paper_id": "5fe161cec1e62818c325d515ec8a2a93af178cfd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Target gene segments of ASFV, CB and BB were synthesized by Beijing Genomics Institute (BGI), Beijing, China. Then, 3 plasmids, containing above 3 target segments, were constructed as a positive control for further works." ] },{ "paper_id": "5fe3454a5e41a3e84b93a71a60d5aad0d81ce840", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "5feab9a11d87a3bcb88dedd98948063b7d259ae2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Intact MS2 PLP were verified by transmission electron microscopy (TEM; electron microscope Philips EM 208; FEI, Czech Republic) at 18,000 \u00d7 magnification and an accelerating voltage of 80 kV.", "A two-step, duplex, RT-qPCR was optimized for MS2 PLP and internal amplification control (IAC) detection and quantification.", "RT-qPCR quantification method was chosen as the most accurate method because it was the only method capable of identifying a specific control RNA encapsulated inside the MS2 PLP.", "Conception and design of the work: PM, PV, and PeK; Acquisition of data: PM, RT, HM, PK, and TV; Interpretation of data: PM, PV, and PeK; Drafting the work: PM; Revision of the manuscript: PV and PeK; All authors approved the version to be published in Frontiers in Microbiology and agreed to be accountable for all aspects of the work." ] },{ "paper_id": "5ff6f535016d7b46687474786efd07db9c19ce8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each LTQ-Orbitrap raw file was analysed using the Proteome Discoverer 1.0 (Thermo Fisher Scientific). Protein identifications were performed with the SEQUEST algorithm searching against even toed ungulate database available at NCBI with trypsin as digestion enzyme, and allowing for maximum two missed cleavage sites. Carbamidomethyl (C) was set as a static modification, and oxidation (M) as a dynamic modification. Precursor ion and fragment ion mass tolerances were set to 10 ppm and 0.8 Da, respectively. Results were filtered for minimum 2 peptides and using a high and medium significance XCorr Score adjusted for peptide charges (z), Table 7 .", "Prion diseases, like scrapie in sheep, are often called Transmissible Spongiform Encephalopathies (TSEs). These are fatal neurodegenerative diseases in a variety of host species, including humans. They are all associated with the conversion of the normal host cellular prion protein, PrP C , into the abnormal protease-resistant isoform, PrP Sc . The PrP genotype influences susceptibility, incubation period and clinical presentation, the V 136 R 154 Q 171 allele being most highly associated with classical scrapie in sheep. To control and prevent spread of scrapie, genetic screening and breeding for resistance are widely used, and was implemented in the EU through Decision 2003/100/EC [1, 2] . The PrP genotype is, however, neither a marker for definitive disease, nor the only genetic factor influencing prion diseases [3, 4] . Despite the effort of reducing susceptibility, and monitoring and culling of ruminants, scrapie still exists [5, 6] ." ] },{ "paper_id": "5ff8a6df6aa6e3ec16db9ff91702f691c18541df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2.1. Bacteria. B. bronchiseptica 0301 was isolated from rabbits having clinical symptoms of rhinitis or pneumonia; the animals originated from commercial farms located on the flat plain near Bogot\u00e1, Colombia (2,600 m.a.s.l.). Samples were collected from nares or trachea, cultured on brain heart infusion agar (BHI), and were stored in 10% glycerol at \u221270 \u2218 C until use.", "Experimental error was controlled for as follows: random application of treatments, blind evaluation of tissue, independence with the Durbin-Watson test and normality with Shapiro-Wilk's test. A test for comparing means was used for the proposed hypotheses, which proved to be significant.", "Large-scale virulent B. bronchiseptica cultures were collected in BHI agar and its biomass was harvested. The bacterium was suspended in distilled water (DW) with 0.1% thimerosal at 4 \u2218 C for inactivation and conservation. The cells were centrifuged at 2,500 g for 50 min in sterile DW." ] },{ "paper_id": "5ffaf1c1d5f763636ec3334c1b1547d4a8b8abb9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human bocaviruses (HBoV) contain 3 open reading frames (ORFs) encoding a nonstructural protein (NS1, NP1) and two capsid proteins VP1 and VP2, respectively [2] . The genomic organization of HBoV closely resembles that of bovine parvovirus type 1 [1] .", "S\u00f6derlund-Venermo et al., [23] reported that the unique region in VP1 is less immunogenic than the major virus capsid protein VP2, Also he expressed HBoV VP2 viral like particles (VLPs) in insect cells for use in IgM and IgG ELISA that are superior to immunoblots in diagnostic performance.", "A plasmid containing the PCR product cloned in the vector PCR 2.1-TOPO (Invitrogen) was used as positive control.", "DNA was extracted from 200 \u03bcl of the NPA samples using the High Pure Viral Nucleic Acid Kit (Roche, Mannheim, Germany) according to the instructions of the manufacturer.", "Attempts to culture this virus on conventional cell lines had failed but, Dijkman et al., [19] had investigated whether the virus can replicate on pseudostratified human airway epithelium. The cells were inoculated with human bocavirus-positive nasopharyngeal washes from children, and virus replication was monitored by measuring apical release of the virus via real-time PCR." ] },{ "paper_id": "6003e4441a559c056ce473a86dca5db1e2a9bf8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PCR for herpesvirus detection [40] and RT-PCR for enterovirus detection [41] were performed as previously described. Rotavirus, enteric adenovirus, norovirus and astrovirus were detected using a multiplex RT-PCR kit (Seeplex\u00ae Diarrhea-V ACE detection, Seegene) according to the manufacturer's instructions.", "Background: The pteropine orthoreovirus (PRV) was isolated from monkey (Macaca fascicularis) faecal samples collected from human-inhabited areas in Lopburi Province, Thailand. These samples were initially obtained to survey for the presence of hepatitis E virus (HEV)." ] },{ "paper_id": "60081af7cc91d270d05e6cb45285578f86c918fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The recombinant virus had normal plaque sizes and grew like wildtype virus in Vero cells after infection at a MOI of 0.1 PFU/ cell ( Figure 3B ). Thus, deletion of ORF9b is not lethal.", "Recombinant SARS-CoV technology was done as described by Yount et al. [16] . The sequence of the mutated SARS-CoV ORF9b knockout (icSARSDORF9b) was confirmed by sequencing cDNA isolated from recombinant virus.", "PCR conditions were 20 mM of dNTPs, 0,2-0,4 mM forward and revers primers, 20 ng of template and 1 U of Long Expand Taq Polymerase Enzyme (Roche Diagnostics GmbH). Depending on size and nucleotide composition of the amplificates two standard conditions were used for amplification. PCR fragments were separated by Agarose gel electrophoresis and purified utilizing Nucleospin Extraction Kits (Macherey& Nagel). The resulting PCR-fragments, flanked by complete attB1 and attB2 sites, were cloned by GatewayH recombinatorial cloning into the entry vectors pDONR207 or pDONR221 (Invitrogen) via the BP Clonase reaction as described by the manufacturer (Invitrogen). The overlaps of the vector and SARS-CoV-ORF sequences were confirmed by DNA sequencing using the Big Dye Terminator kit (Perkin Elmer) on a 377 DNA Sequencer, a 310 Genetic Analyser (both Applied Biosystems) or the Genome Lab DTCS-Quick Start Kit on the CEQ TM 8800 Sequencer (Beckman Coulter).", "For the elucidation of molecular mechanisms during the course of viral growth and propagation there is a need to systematically examine possible interactions of all viral proteins. We therefore cloned the SARS-CoV ORFeome by recombinatorial cloning (GATEWAY technology) and performed a genome-wide analysis for viral protein interactions by yeast-two-hybrid (Y2H) matrix screen." ] },{ "paper_id": "600daeb2ed49a45c29ca225659768556fcee30d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All contrasts performed using the mixed-effects models were corrected for the multiple comparisons using stepwise correction, to achieve a family wise error rate of 5% within each measure. The hypothesis tests of correlations were corrected using the false discovery rate method of Benjamini-Hochberg, to the 5% level. These analyses were performed in R v3.2.0 (10) statistical software with libraries lme4 (11) and multcomp (12) .", "The authors thank John Burr, Joe Digennaro, Laurie Gunderson, and Jennifer Taylor for their contributions in the design and execution of this study.", "This study was carried out in accordance with the P&G Pet Care Animal Research Policy, and the protocol was approved by the P&G Pet Care Institutional Animal Care and Use Committee. All cat owners provided written consent to participate in the study." ] },{ "paper_id": "600e8fba699669f496224f1ab80caa3df030a77a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Now, if we consider two models H 1 and H 2 , the two models are compared using the maximum likelihood ratio statistics defined by:", "The field work has been made by qualified people according to current French legislation. Accreditation has been granted to the UMR-CNRS 5558 (accreditation number 692660703) for the program.", "For 0#m#M and 0#f#F we have:" ] },{ "paper_id": "601a2a29ef252c46e3a3b19f35d1d6fb591b0af6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Oxidation of metal amines to imines by 2-bromoanisole.", "Conversion of \u03b1-amino acids into imines.", "silylamines; (b) from \u03b1-cyano silylamines." ] },{ "paper_id": "602e006ebff0a1b81a8d922ce9504421f218bfb7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Grey literature or other documents not peer-reviewed were excluded because only rigorous research was sought.", "Cost-effective in conjunction with early warning systems", "Laboratory-based, enhanced dengue surveillance system (EDSS)" ] },{ "paper_id": "602fbb4e85804b8ca5c0842b46afd343981181e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The raw data of the RNA-Seq datasets was deposited in Sequence Read Archive (SRA) under the accession number SRP104704. ", "A total amount of 3 \u03bcg RNA per sample was used as input material for the RNA sample preparations. Sequencing libraries were generated using NEBNext\u00ae Ultra\u2122 RNA Library Prep Kit for Illumina\u00ae (NEB, USA) following the manufacturer's recommendations, and index codes were added to attribute sequences to each sample.", "The index of the chicken reference genome (Ensembl, Galgal4, updated 11-2015) was built using Bowtie v2.2.3 [31] and paired-end clean reads were aligned to the reference genome using TopHat v2.0.12 [32] . And HTSeq v0.6.1 was used to count the number of reads mapped to each gene [33] . Then, the expression level of each gene was calculated by the expected Fragments Per Kilobase of transcript per Million fragments mapped (FPKM) [34] ." ] },{ "paper_id": "603e11d248463c9b79a1030663946c5640810536", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results are expressed as means + \u2212 S.D. or S.E.M.. One-way ANOVA and Student's t test were employed to determine statistical differences among multiple groups. A P value of <0.05 was considered to be significant (*P<0.05, **P<0.01)." ] },{ "paper_id": "604397da653890b54d4af23b45adab3365e1f042", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "VeroE6 cells (ATCC CRL-1586), 293 cells (ATCC CRL-1573) and A549 cells (ATCC CCL-185) were maintained in Dulbecco's modified minimum essential medium (DMEM) containing 10% fetal calf serum (FCS). BHK/T7-9 cells that stably express T7 RNA polymerase [79] were maintained in MEM-alpha containing 10% FCS. Penicilin (100 U/ml) and streptomycin (100 g/ml) were added to the culture media.", "Unpaired Student's t-test was performed by using the Graphpad Prism 5.03 program (Graphpad Software Inc.) for the comparison of two groups,", "RVFV has a tripartite negative-stranded RNA genome, referred to as Small (S)-, Medium (M)-and Large (L)-segment. The Ssegment encodes for N and NSs genes in an ambi-sense manner, M-segments encodes for NSm, 78-kD protein, NSm-Gn, Gn, and Gc proteins, and L-segment encodes for RNA-dependent RNA polymerase [20, 21, 22, 23] . NSs is a major virulence factor of RVFV and inhibits host general transcription through sequestration of TFIIH p44 [24] or promotion of TFIIH p62 subunits degradation [19] . NSs also inhibits host antiviral response by inhibiting the activation of interferon (IFN)-b promoter through interaction with Sin3A-associated protein (SAP30) at aa.210-230 [25, 26] , and promotion of dsRNA-dependent protein kinase (PKR) degradation [17, 27, 28] ." ] },{ "paper_id": "604491e627b3cb8661ee7f8747623eb4c61f0315", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The degree of collaboration in Kazakhstan is emphasized especially in teamwork to develop strategies and cooperate effectively. Leveraging existing resources while reinforcing networks and maintaining relationships should be frequent and encouraged. The ability to link consecutive projects through effective collaboration and funding pursuits builds greater capability and avoids one-off studies.", "Leveraging existing resources including knowledge of in-country organizational structure, workflow, related networks, and current studies are important to establish buy-in from a top administrative level to the working research level which further reinforces multi-sectoral approach and encourages communication.", "CBR has served as a foundation for incorporating standard operating procedures into working practice under multiple research studies, especially related to BS&S to ensure that the work is performed in a safe and secure environment while supporting tasks to enhance infectious disease surveillance for human and animal health. More importantly, growing a quality research program especially in terms of capability maturity, that is the state \"as is\" and \"to be\", requires a strategic vision. The evolution and progression of the Kazakhstan CBR program are linked and illustrated in an iterative fashion (Figure 1 )." ] },{ "paper_id": "6044c9d0aae3d02db03c409496ca81f8f83ebeab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sample handling and DNA purification. On arrival the samples were handled as outlined in Figure S1 .", "Sequence data for the flight samples are available for download through ENA.", "Current international disease surveillance system is mainly based on reports made by doctors after treatment of infected patients 7 . It has been attempted to establish regional and global networks, for the", "Ethics. This study was conducted in accordance with the Danish Act on scientific ethical treatment of health research, as administrated and confirmed by the Research Ethics Committees of the Capital Region of Denmark (www.regionh.dk), Journal nr.: H-14013582." ] },{ "paper_id": "60498316646f729173d57cac8d9c2cf9a701a2c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 454 sequencing data supporting this article are available in the GenBank repository, SUB435282. The genome data of M. nonliquefacience is under submission to the DDBJ/EMBL/GenBank databases under accession No. PRJNA232737.", "The draft genome sequence of Moraxella nonliquefaciens DSM 6327 T was determined through paired-end shotgun sequencing performed by using the MiSeq system (Illumina) with 300\u00d7 coverage. The sequencing reads were assembled using CLC genomics wb5 (CLCbio). Annotation, comparative genomic analyses and average nucleotide identity (ANI) calculation were performed as described [25] ." ] },{ "paper_id": "6049f1c151fa95bc40deaf050225dd7a00880171", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since H5N1 HPAI viruses was first identified in 1996, diverse subtypes of H5 HPAI were classified. Global and domestic spread of these virus caused huge losses to the poultry industry [18] . Novel H5Nx HPAI viruses appeared due to reassortment of the HA gene with different NA genes. According to the WHO report [22] , H5Nx [24] , Vietnam [25] , and Laos [26] between 2013 and 2016.", "In this study, we tested our one-step multiplex method using clinical poultry samples to simultaneously detect pan-HPAI and two H5 clades. Thus, our one-step multiplex RT-qPCR assay can be used for the screening of virus-infected field samples.", "To detect the pan-H5 HPAI-specific and HPAI clade-specific probes, H5Nx HA gene sequences of 1018 low pathogenic and 4301 highly pathogenic avian influenza viruses from the GenBank database of the National Center for Biotechnology Information or Influenza Research Database (IRD, www.fludb.org) were analyzed, and complementary sequences were designed using ClustalW in BioEdit software (7.2 version) to identify conserved regions. The All amplicons obtained using one set of HA primers were 201 base pairs in length." ] },{ "paper_id": "605669a3876e7ff3961f0cca4c58a7059144d0ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "rsif.royalsocietypublishing.org J. R. Soc. Interface 13: 20160540", "Data accessibility. Simulation data have been archived at the Dryad Digital Repository doi:10.5061/dryad.dp4kb [40] .", "\u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022" ] },{ "paper_id": "60643032cb50195802cf9a11f268e7301d4ad61a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This was performed with NCSS statistical program. Normality of distributions for quantitative data was tested with the Shapiro-Wilk test. For normally ", "Coronary artery disease SA:", "Stable angina UA:" ] },{ "paper_id": "60666795212b915f165db9762a95445be1fb2bad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Physical inactivity has been linked to obesity, coronary hearth disease, hypertension, strokes, diabetes, colon cancer, breast cancer and osteoporotic fractures [49] .", "Global environmental threats to ecosystems include global climate change, loss of biodiversity, global ozone depletion and the global decline in natural areas.", "Globalising cultural flows result in interactions between global and local cultural elements.", "Tobacco is predicted to be the leading health risk factor by 2030 [50] . It causes, for example, cancer of the trachea, bronchus and lung [49] , and cardiovascular diseases. Alcohol use", "Excess energy intake results, together with physical activity, in obesity. Obesity is an increasing health problem and has several co-morbidities such as non-insulin dependent diabetes and cardiovascular diseases [49] . The nutritional quality of the diet (e.g. fruit and vegetable intake, saturated versus unsaturated fats) is also very important for good health. Inactivity" ] },{ "paper_id": "60721983c03cfb1fd6e277fb6cc20bd117a3df80", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The complete genome of the ChinaGD01 strain was deposited at GenBank under the accession number KT006149.", "On 26 May 2015, an imported Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in Guangdong Province, China, and found to be closely related to the MERS-CoV strain prevalent in South Korea. The full genome of the Chi-naGD01 strain was sequenced and analyzed to investigate the epidemiology and evolution of MERS-CoV circulating in South Korea and China.", "In this study, viral RNA was extracted from the nasopharyngeal swabs using the QIAamp viral RNA minikit. Overlapping reverse transcription-PCR special primers were conducted by 44 sets of special primers designed according to all available published complete genomes of MERS-CoV. The 5= and 3= ends of the genome of ChinaGD01 were determined by rapid amplification of cDNA ends. Meanwhile, the original respiratory sample was also processed for deep sequencing using the Ion Torrent PGM sequencer system." ] },{ "paper_id": "60758e874c80de9dcab280027279347b055b945a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using GraphPrism version 5.02 applying the appropriate statistical test (associations between mNGS and viral real-time PCR assay were determined by applying the Pearson's correlation coefficient and differences between median and distributions were evaluated by the Mann-Whitney U test). A p-value less than 0.05 was considered to be statistically significant.", "The objective of this study was to implement QCs in a single metagenomic protocol and to evaluate it for the detection of a broad panel of DNA and RNA viruses in clinical respiratory samples.", "The potential of mNGS is very promising but several factors such as inhibition, competition, and contamination can lead to a dramatic misinterpretation in the clinical setting. Herein, we provide an efficient and easy to use mNGS workflow including quality controls successfully evaluated for the comprehensive characterization of a broad and representative panel of DNA and RNA viruses in various types of clinical respiratory samples. " ] },{ "paper_id": "607d648e224430e7c79b94f6c2d770272616c5bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This cross-sectional study was conducted at the Illovo Sugar Limited Estate Hospital (K1) and Clinic (K2). K1 Hospital is a private 80-bed hospital, serving Illovo employees and dependents as well community members from nine surrounding villages, including: Nyandeo, Msolwa Ujamaa, Mkula, Mangula, Kiberege, Msolwa Station, Ruaha, Kidogobasi and Luhembe. K2 Clinic is operational five days a week (Monday-Friday) and is only available to Illovo employees and dependents. Employees and dependents are offered medical care free-ofcharge; other community members who are not affiliated with the Illovo Company are offered care however must pay a fee for service, which is partially subsidized by the Illovo Company.", "With gains in vector control across sub-Saharan Africa and a significant decrease in overall malaria incidence rates, a better understanding of the prevalence of both malarial and nonmalarial agents potentiating fever syndrome is needed for several reasons including efforts to more rapidly detect and control diseases at their source to ensure global health security [1] [2] [3] [4] [5] .", "Kilombero (population >321,000) is situated at an elevation of 300m above mean sea level, in the Morogoro Region (population >2 million) of South-Central Tanzania. The climate is characterized by a long rainy period (March-May) and a short rainy period (October-December). Malaria transmission intensity in this region is considered high, with 13% prevalence in community-based surveying of children (6-59 months) testing positive for malaria by rapid diagnostic testing [16] [17] .", "This body of work served as part of the dissertation for Christine Hercik in pursuit of a PhD in the Global Infectious Disease Program at Georgetown University. We would like to thank her committee members for their constant advisement and unwavering support of her work, including: Joel Montgomery, PhD, Christopher Loffredo, PhD, Seble Kassaye, MD, and Daniel Lucey, MD." ] },{ "paper_id": "6080abc37c89429748cd5984f1d76f234f83eccf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The challenge emerging from the need to assemble datasets from multiple, disparate sources is not new within epidemiology. Analysis of such data is complicated in that data are often aggregated at different spatial and temporal scales, and datasets must be aggregated or disaggregated to harmonize the spatiotemporal scale of the consolidated dataset. Even when combining a single type of data (i.e., diagnostic records) from various institutions, inconsistencies in data structure and vocabulary must be mapped to make the data interoperable.", "Finally, data relevant to disease dynamics are representative of processes that operate at different spatial and temporal scales. Epidemiological modeling provides a means to connect processes across multiple scales and account for the inherent dynamic elements of disease systems. For stochastic disease models, thousands or even hundreds of thousands of simulations are performed to understand the behavior of the system and optimize parameter values, thus requiring extensive computational resources and generating big data. Machine learning techniques, such as random forests and genetic algorithms, are used to optimize parameter values so that the model simulates epidemiological dynamics that closely resemble real-world data. Computational modeling provides an effective means to link data to processes, and understand mechanistically how disparate data may interact to influence the occurrence of disease.", "July 2017 | Volume 4 | Article 110" ] },{ "paper_id": "6081206484e5e671f9a73195a8b1fac39e456a3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6085ea96b3a7c381215ba90b26f8664ae7c63178", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. The CH/FJWT/2018 sequence data have been deposited in GenBank under the accession number MH615810.", "The full-length genome sequence of a novel swine acute diarrhea syndrome coronavirus (SADS-CoV), CH/FJWT/2018, was determined, which was genetically most closely related to CN/GDWT/2017, recently discovered in Fujian, China. The indel sites of the spike (S) gene of CH/FJWT/2018 were most similar to those of bat-origin SADS-related coronaviruses.", "Alphacoronavirus in the family Coronaviridae and is an enveloped, positive-sense, single-stranded RNA virus (1) . In January 2017, SADS-CoV was first discovered in suckling piglets with severe enteritis in South China after ruling out the presence of porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and other known pathogens associated with piglet diarrhea (2) (3) (4) (5) (6) (7) (8) . SADS-CoV had 95% nucleotide (nt) identity at the full-genome level with the previously reported bat-HKU2 strains (3, 4) ." ] },{ "paper_id": "6086be90c6e06e3fcbef307a61c0563e029ee24d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All infants' parents were asked to participate in the study and gave written informed consent. The study was approved by the Policlinico Umberto I institutional review board (Reference n\u00b02377/09.02.2012).", "Background: Preliminary results suggest that pertussis infection might be considered in infants during a seasonal respiratory syncytial virus (RSV) outbreak." ] },{ "paper_id": "608a7194b225bedf27e124dfbe8f2acecbca587f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, exosomes and many viruses share size, shape, and molecular characteristics. Technical improvements in methods to separate and obtain pure exosomal fractions will facilitate the understanding of their role in infection, namely in immune activation, viral spread, and persistence.", "In 1996, Raposo et al. demonstrated that B lymphocytes infected with Epstein-Barr virus (EBV), a human gammaherpesvirus associated with a variety of lymphoblastoid and epithelial cancers, released exosomes containing MHC II molecules, and that these vesicles were capable of activating specific CD4 + T cell clones in vitro [122] . Two years later, Zitvogel et al. published a study showing that exosomes released by dendritic cells had the ability to suppress the growth of tumors in vivo. This led to the interpretation that exosomes could be used as therapeutic agents modulating immune responses [123] .", "Second, little is known about the biological processes sorting material to ILVs of MVBs. The inclusion of viral proteins and RNAs in exosomes offers a unique system to identify signals and sorting mechanisms into ILVs.", "Viral infection is thought to be responsible for 10% to 15% of all human cancers, which makes the understanding of how pathogens modulate host cell functions during their transformation program seminal, both from a scientific and a clinical perspective [133] . Seven human tumor viruses have been identified, human papillomavirus (HPV), Merkel cell polyomavirus (MCV), HCV and hepatitis B virus (HBV), the members of the herpes family EBV and Kaposi's sarcoma associated herpesvirus (KSHV), and the Retrovirus human T-lymphotropic virus-1. HIV is also tumorigenic, although indirectly, since the decrease of host immunity it provokes allows cell transformation, mostly by other viruses such as KSHV." ] },{ "paper_id": "6091444b4f7495b1b4cb0c72b6f30da73ccf867d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Li et al. eLife 2019;8:e51230.", "https://elifesciences.org/articles/51230#video1" ] },{ "paper_id": "609c3b3465c19726b4777d17e3e2b19ca9de990b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ten percent fecal suspensions were homogenized for 1 min at 3000 rpm with a MINILYS homogenizer (Bertin Technologies) and filtered consecutively through 100 \u03bcm, 10 \u03bcm and 0.8 \u03bcm membrane filters (Millipore) for 30 s at 1250 g. ", "Identification of five novel gemycircularviruses in the fecal samples from the badger and mongoose", "Identification a partial RNA-dependent RNA polymerase of a nodavirus in the fecal material of the otter" ] },{ "paper_id": "60a7721ab454f05f6622087ecde3b186b505779f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Checklist one contained three major sections: Infrastructure; technical equipment; and personnel management. A fourth section on Emergency Departments was not obligatory [14] . All checklists can be downloaded after free registration from: www.EUNID.eu.", "The checklists underwent a pilot application to identify structural gaps and sources of misinterpretation [13] . The facilities of the Steering Committee members and one external facility applied the checklists and cross-checked all itmes for their applicability, but no external validation process was conducted. Following minor changes, the checklists were disseminated to all eligible facilities until December 2009 and expected to be resubmitted within three months. Data provided were cross-checked by personal on-site visits by a coordination team member in all but four centres enrolled. Investigator (the National Project Representative) and observer (the Coordination Team member) bias may be ruled out, as all data recorded were cross-checked on-site and agreed with the facilities operational manager or director.", "Three checklists were developed and based on projectmember's experience, available literature, national preparedness plans, and guidelines of international authorities for the management of HIDs [13] . Each checklist contained questions addressing specific items of interest, and answers were structured as openended, closed, semi-open or free text options. Overall, the checklists included 44 items and 148 specific questions." ] },{ "paper_id": "60abca9911a64805e51aa8deb70bb238c2f3d414", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "60b69719c85b64d84bb0b4621ed53108914aebe8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The first highly pathogenic avian influenza (HPAI) H5N1 virus outbreak in poultry in Asia occurred at a goose farm in China in 1996 [1] . Serious H5N1 outbreaks in poultry accompanied by human casualties soon followed in Hong Kong in 1997 [2] . In 2002, outbreaks reemerged in both terrestrial poultry and wild waterfowl [3] . In late 2003, an outbreak of HPAI H5N1 in poultry was confirmed for the first time in South Korea. This was followed by eruptions in Vietnam, Japan, Thailand, Cambodia, China, Laos, and Indonesia at the beginning of 2004 [4] . By 2006, H5N1 HPAIV, the so-called Qinghai strain, had spread throughout Central and Southeast Asia, Europe, and Africa [5] .", "All the chickens were monitored daily for clinical signs and survival until 10 days post-infection. The main expected clinical signs were face edema, swelling in the leg or face, and discoloration of the comb or leg cyanosis, weakness, anorexia, depression, ruffled feathers, twitch or convulsion, diarrhea, and death. A humane endpoint was applied when severe clinical signs were observed for more than 24 h, and they were euthanized by intraperitoneal injection of pentobarbital. The chickens that survived until 10 days after infection were also euthanized by pentobarbital injection (30-40 mg/kg).", "Supporting Information S1 " ] },{ "paper_id": "60bb4454a34fb7642d6805ff6261abc91809a135", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Wastewater as a source of infection Developing countries", "In food industry, food safety is essential and regulated." ] },{ "paper_id": "60bc864d9515f3919e673bf5eeadfbd60ef84770", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thus it raises the question whether IBV infection of the proventriculus is a classic feature of IBV and occurs in association with an old IBV strain. A recently isolated M41 strain [26] resulted in an increased proventriculus index 7-28 days after experimental infection of 1-day-old chickens [Mohamed AA: Studies on infectious proventricultis in broiler chicken. Master thesis, In progress]." ] },{ "paper_id": "60c8949b06f825932f883b28f0be1251cefd2525", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "60cd26dae93a4048b5aceb66c68bec325392fdf0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The BioTorrents web server along with the source code is available freely under the GNU General Public License at http:// www.biotorrents.net.", "The most basic requirement of any torrent server software is the actual ''tracker'' that individual torrent clients interact with to obtain information about where to download pieces of data for a particular torrent. In order to minimize any possible transfer disruptions arising from the BioTorrents tracker not being accessible, a secondary tracker is added automatically to all new torrents uploaded to BioTorrents. Currently this backup tracker is set to use the Open BitTorrent Tracker (http://openbittorrent. com/). Also, many BitTorrent clients support a distributed hash table (DHT) for peer discovery, which often allows data transfer to continue in the absence of a tracker, further enhancing the reliability over traditional client-server file transfers.", "The source code for BioTorrents.net was derived from the TBDev.net (http://tbdev.net) GNU General Public Licensed (GPL) project. The dynamic web pages are coded in PHP with some features being implemented with JavaScript. All information, including information about users, torrents, and discussion forums are stored in a MySQL database. The original source code was altered in various ways to allow easier use of BioTorrents by scientists; the most significant being, that anyone can download torrents without signing up for an account. In addition, torrents can be classified by various categories and license types, and grouped with other alternative versions of torrents." ] },{ "paper_id": "60cd8a2169f79423f22c91678fc76cf5bb216ef5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All error bars denote \u00b1 SEM. Student t tests were used to ascribe statistical significance. For all figures, * = p value \u2264 0.05 and ** = p value \u2264 0.01.", "All mice used in this study were on the C57BL/6 J strain background. Oct1 (Pou2f1) conditional mice crossed to CD4-Cre have been previously described [4] . All animal experiments were approved by the University of Utah Institutional Animal Care and Use Committee (17-05008).", "Samples were analyzed using a BD LSR Fortessa X-20 flow cytometer and FlowJo software." ] },{ "paper_id": "60cfb43ca9b8d54f5b8cb4ab264d8d628c7c227b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "60d5290b70e9b780174187da93ecf4392b97539d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting information S1 Table. Nine primer pairs used to amplify the EV-D68 genomes.", "To analyze the 5 0 UTR sequences of the EV-D68 strains, sequences at nucleotide positions 501-1000 were aligned in MEGA 7.0 and visualized using Genetyx ver. 13 (Genetyx Corp., Tokyo, Japan).", "(XLSX)" ] },{ "paper_id": "60d68e4052a397966e72c6eda0895ca7d27afb68", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RF and RHD produce a significant burden of disease in New Zealand (NZ) [4, 5] . RF is associated with social deprivation and household crowding. It almost exclusively affects Maori and Pacific children [5, 6] .", "These systems perform poorly in several important areas. Gaps in control-focused surveillance include the inability to effectively track highly mobile cases, lack of consistency in patient management and data collection across District Health Boards (responsible for health care delivery and public health services at local and regional levels). A limited ability to monitor compliance with secondary prophylaxis was also noted. An absence of systems to monitor general practitioner's delivery of secondary prophylaxis was considered a gap.", "Although RHD in cases younger than 20 years is notifiable, [22, 23] many KIs were unaware of this and described confusion surrounding which conditions were notifiable. Around half of all patients hospitalised for RHD had not been previously hospitalised with RF, so are likely to have missed out on the benefits of antibiotic prophylaxis [24] . Clarifying that RHD in younger cases is notifiable could help improve RF control." ] },{ "paper_id": "60da5c83bb867ca0f2f6eb9471d2bfc15c2b8d3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tissue remodeling Fertility Hyaluronic acid/TSG-6/inter-\u03b1trypsin inhibitor", "High resolution models are urgently needed to disentangle the structural complexity of this long pentraxin and shed light on its structure/function relationships, some of which are remarkably different to those classically described for the short pentraxins.", "These data are in line with recent studies showing that the anaphylatoxins C3a and C5a may contribute to cancer-related inflammation, recruit myeloid suppressor cells, and promote IL-1\u03b2 and IL-17 response in neutrophils thus promoting colon carcinogenesis (104) (105) (106) (107) .", "PTX3 expression and production is regulated by different signaling pathways, mainly depending on the cell type and/ or stimuli. The NF-\u03baB pathway controls PTX3 expression in conditions of IL-1 receptor-or TLR-dependent inflammation (13) (14) (15) , while induction of the protein by TNF\u03b1 in lung epithelial cells involves the c-Jun N-terminal kinase (JNK) pathway (16) . HDL-induced PTX3 production in endothelial cells requires the activation of the PI3K/Akt pathway through G-coupled lysosphingolipid receptors (7) ." ] },{ "paper_id": "60e49bb744eb678ae1ac1fb9bb920a5b01954041", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1) cardiovascular disease;", "(2) injury (including road traffic, child, and occupational injuries); (3) cancers; and (4) respiratory disorders", "The following method was used to obtain secondary data from existing peer-reviewed journal articles and reports of government agencies and related health organisations:" ] },{ "paper_id": "60f0773c8eeace01dd0364c5c63febbfe9dd3a62", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments were performed according to the instructions of R&D Systems using 96-well plates (Corning Incorporated, COSTAR 1 , Washington, DC, USA). The microplate automatic reader (EL800; Biotek, Winosski, VT, USA) was employed at a wavelength of 450nm.", "The spleen specimens (5mm) were collected during necropsy and stored at -80\u00b0C until use for DNA extraction. The Wizard\u2122 Genomic DNA Purification Kit (Promega, Madison, WI, USA) was used to extract total genomic DNA in 20mg of spleen following manufacturer's recommendations.", "doi:10.1371/journal.pone.0161169.t001", "All research involving dogs was carried out according to the regulations of the Brazilian Society of Science in Animal Research, adopted by the Federal University of Ouro Preto Ethics Committee in Animal Experimentation, that approved the technical procedures using dogs under protocol number 2010/71." ] },{ "paper_id": "60f1445b5e867f960e1a6cd99db51a965a2e9006", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "60f1a9fff7e34e6a528a2a06dedb23700c87e114", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus stocks of A/Panama/2007/1999 (H3N2) were propagated in the allantoic cavity of 10 day old embryonated hens' eggs while A/Indiana/8/2011 (H3N2v) was grown in Madin-Darby canine kidney cells (MDCK) as previously described [20] . Titers of virus stocks were determined by standard plaque assay using MDCK cells and are reported as plaque-forming units (pfu)/mL.", "All ferret procedures were approved by Institutional Animal Care and Use Committee (IACUC) of the Centers for Disease Control and Prevention and in an Association for Assessment and Accreditation of Laboratory Animal Care International-accredited facility. Animal studies were performed in accordance with the IACUC guidelines under protocol #2234MAI-FERC: \"Transmissibility of influenza viruses with pandemic potential\".", "There are three generally accepted modes of influenza virus transmission [11] . Aerosol transmission occurs via respirable particles (<5 \u03bcm) that may remain suspended in the air for prolonged periods of time thus increasing the opportunity for them to be inhaled. Droplet transmission occurs when larger droplets (>5 \u03bcm), typically expelled during coughing or sneezing, encounter the upper respiratory tract or ocular mucosa of a susceptible individual. Lastly, contact transmission involves directly touching an infected host or contaminated surface. The relative contribution of these modes of transmission to the overall spread of influenza viruses and the role of environmental conditions is not completely understood. However, recent studies in human volunteers support a role for aerosols in influenza virus transmission [12, 13] .", "Male Fitch ferrets 5-11 months of age (Triple F Farms), serologically negative by hemagglutination-inhibition (HI) assay for currently circulating influenza viruses, were housed during each experiment in cages placed inside a custom environmental chamber (Bahnson Environmental Specialties, Raleigh, NC) with HEPA filtration operating at 20 air changes per hour. Experiments were conducted at four environmental settings with consideration for the comfort of the animals: 5\u00b0C/70%RH (4.8 g/m 3 AH); 23\u00b0C/30%RH (6.2 g/m 3 AH); 23\u00b0C/50%RH (10.3 g/ m 3 AH) and 23\u00b0C/70%RH (14.4 g/m 3 AH). Prior to inoculation, ferrets were allowed to acclimatize inside the chamber for at least four days. Baseline temperatures were measured using an implantable subcutaneous temperature transponder (BioMedic Data Systems, Seaford, DE) and baseline serum, weight and minute volume (MV) of respiration measurements were collected as described [20, 21] .", "For each virus and each condition, three ferrets were sedated with a ketamine/zylazine/atropine hydrochloride cocktail injection and were presented with 10 3.8 to 10 5.5 pfu of aerosolized virus as described [21] using an aerosol exposure system with an AeroMP management platform (Biaera Technologies, Hagerstown, MD). Inoculations were performed at ambient laboratory temperatures (21\u00b11\u00b0C) and at the corresponding experimental RH. Aerosol presented dose (PD) refers to the amount of virus inhaled by the animal, not necessarily the amount that is deposited within the respiratory tract. PD is based on the time of exposure, baseline MV of respiration of the animal and the aerosolized virus concentrations achieved during the exposure session." ] },{ "paper_id": "61022af06d0f830787f610e94f66ca49343c3de2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "610adc2e0b9fea5bdaa4ea21b46e4bd6b02d558d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Longitudinal relaxation of 1 H N spins enhanced by the proximity to a paramagnetic probe can be used to map the orientation of helices respect to the lipid phase [1] . Due to the compact arrangement of the six 15 N-labeled amino acids near the center of the transmembrane helices, the paramagnetic relaxation enhancement (PRE) should reflect the distance of the corresponding 1 H N to the surface of the pentameric assembly, provided the employed paramagnetic probe is primarily localized at the center of a micelle. We selected a 16-DSA, which typically induces PRE near the center of DPC micelles carrying a membrane protein [2] . Following the theoretical guidelines outlined by Zangger and co-workers[1], we derive below an analytical expression for the dependence of PRE on the shortest distance of 1 H N to the lipid-exposed outer surface of the ETM channel. For paramagnetic probes where the unpaired electron has a short longitudinal relaxation time, the influence of the unpaired electron on nuclear relaxation (both longitudinal and transverse) can be described by the \"outer sphere\" relaxation approach [3]. In order to obtain an expression for PRE as a function of geometric parameters, we performed a volume integration shown in Equation (1). In this equation, the probability of finding a paramagnetic center in a particular volume element of the system formed by ETM, detergent and 16-DSA, is multiplied by the inverse of the 6 th power of the proton-electron distance, r, and integrated[1].", "To ETM in DPC, we added the lipid analogue 16-DSA, bearing a doxyl paramagnetic radical (spin electron) at position 16 of the alkyl chain. This resulted in a measurable PRE effect that was linearly proportional to the concentration of 16-DSA in the range 1 mM to 5 mM. In this calculation, the ETM system can be described as a pentameric \u03b1-helical bundle (Fig. S3 , A), represented by a cylinder with radius R b , aligned with the z-direction of the laboratory coordinate frame. This cylinder is embedded in a spherical micelle of radius R, and integration should be limited to the volume of the micelle accessible to the probe, V. This volume comprises the core and inner layers of the micelle, i.e., a fraction a of the total micelle volume. The nuclear spin is localized at the immersion depth d (Fig. S3, B) from the surface of the bundle accessible to the paramagnetic probe. For the sake of simplicity, Eq. (1) can be approximated as PRE = a/d 3 , where a is a collection of various fundamental constants. R b is defined by a rolling-sphere approach, with sphere radius of 3 \u00c5, corresponding to the size of the doxyl radical (Fig. S3, D) . Alternatively, PRE can be calculated using a distance from the amide proton to the axis of the pentamer (Fig. S3, C) . The position of this axis can be defined with greater precision than the immersion depth from the surface of the pentamer. In this case the equation can be simplified to PRE = a/(D/2-l) 3 , where a is a collection of various fundamental constants, D is the diameter of the cylinder representing the pentamer and l is the distance from the C 5 symmetry axis to the amide proton. " ] },{ "paper_id": "610cdf0a90ee7272f51c5531375a7355768f865a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Enhancers Located in the 3 \u2032 -UTR", "The -1 PRS usually requires two signals in the mRNA, a slippery sequence of the type X_XXY_YYZ, where X normally represents any nucleotide, Y represents A or U and Z represents A, C or U (gaps delimit codons in the original 0 frame); and a downstream secondary structure element separated from the slippery sequence by a spacer region of 5-9 nt (Dinman, 2012) . In plant viruses these structural elements, acting as stimulators of frameshifting, fall into three structural classes: an apical loop with a bulge, a compact hairpin-type pseudoknot or a stem-loop (Figure 3 ) (reviewed by Miller and Giedroc, 2010) .", "Optimization of Viral mRNA Coding Capacity, WM, VT, and MA edited and added specific information to all sections, MA supervised MM writing and wrote Sections Introduction and Perspectives.", "Given the unstructured and sequence non-specific nature of the IRES RNA in the examples above, which is unlike the much longer, highly structured and powerful mammalian viral and dicistrovirus IRESes, we think these observations should be interpreted with caution. It may be possible that, due to lack of structure, the RNA is sensitive to nuclease cleavage providing a 5 \u2032 end, which, being unstructured, may be a very efficient leader to allow detectable translation of CP (or Rap1) ORF from undetectable amounts of degraded RNA. This alternative mechanism of expression may still be biologically relevant, or simply an artifact of the assays, but would not result from an IRES." ] },{ "paper_id": "610f76ebccfa38957d15943fab5eb37c13ee6040", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A small piece of each tissue sample was removed using sterile scalpel blades and forceps, placed in a sterile Petri-dish, weighed, immediately submerged in buffer ATL (Qiagen, Manchester, UK) (360 \u03bcl per 50 mg tissue) and homogenised using a hand-held homogeniser (PRO 200, Bio-Gen Series; PRO Scientific Inc. Oxford, USA). Following homogenisation, 205 \u03bcl homogenised tissue was transferred to a 1.5 ml microcentrifuge tube (sterile) and 20 \u03bcl proteinase K was added. The microcentrifuge tube was placed in a shaking incubator overnight (300 rpm, 56\u00b0C)." ] },{ "paper_id": "611159c87e69ac113f1652442897b3cf96878939", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A Kaplan-Meier estimate of the two main outcome measures, i.e., the need for ICU admission and for mechanical ventilation, was performed using tertiles of serum CRP levels (i.e., <28, 28-69, and \u226570 mg/L).", "The median time from symptom onset until presentation to the ED was 72 hours (IQR 48-120). The median time from admission until first serum CRP level determination was 1 hour and 17 minutes. One hundred sixty eight (88%) patients were hospitalized and 23 (12%) were discharged to their homes after the initial evaluation in the ED. The median length of hospitalization was 3 days [2] [3] [4] [5] .", "Seventeen (9%) patients were admitted to the ICU, of whom eight (4%) required mechanical ventilation and three died (2%). All 185 (98%) of the 188 surviving patients contacted through a follow-up telephone survey described an unremarkable clinical course of the disease in the thirty days since they presented at the ED." ] },{ "paper_id": "61143198570c983e9975d2c20a361749d92396df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and K(D, A) is defined as:", "Author contributions" ] },{ "paper_id": "6129997a5fe45179b0acf89be52fe803bf5719dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "During a 26 month period (January 2008 to February 2010), adult patients with haematological disorders at the Karolinska University Hospital, Stockholm were, after informed consent, included in a cross sectional study where the inclusion criterion was chemotherapy-induced neutropenia (absolute neutrophil count #500/mm 3 ). Patients that developed fever (auricular temperature .38.0uC twice within an hour or $38.5uC at one occasion) were sampled within 72 hours from fever onset, whereas patients without fever were sampled upon routine medical appointments during the neutropenia episode. Whole blood was collected in EDTA-tubes and plasma was prepared by centrifugation before storage at 280uC until use. Additional blood and nasal pharyngeal aspirates (NPA) samples were collected for microbiological testing. Medical records were retrospectively acquired for all included patients. The study was approved by The Regional Ethical Review Board in Stockholm, permit numbers 2007/1213-31/4 and 2008/1300-32.", "Statistical analyses were made with the Prism suite (Graphpad Inc., CA, USA). Fisher's exact test and Mann-Whitney test were used for investigating the patients' general characteristics. Mann-Whitney test was further used for analyses involving continuous data for two groups and Kruskal-Wallis test was used for all other analyses where comparison of continuous data for 3 groups or more were required. Correlations were calculated by using Spearman's rank test. A p-value ,0.05 was considered statistically significant.", "LPS was detected in patient plasma by the endpoint chromogenic Limulus Amebocyte Lysate (LAL) method using the QCL-1000 kit (Lonza group ltd., Switzerland) with modifications in the visualisation of the cleaved substrate. [24] All reagents and consumables were endotoxin -free (Lonza)." ] },{ "paper_id": "612fc352956cba3b9e5e74179125dc5d9aadba23", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusion: This raises the possibility that mismatched AOs could still be therapeutically applicable in some cases, negating the necessity to produce patient-specific compounds.", "Total RNA was harvested 96 h after transfection from duplicate wells using TRIzol \u00ae (Invitrogen) according to the manufacturer's instructions, and resuspended in 30 \u03bcl of sterile water (Baxter Healthcare, Sydney, Australia). Approximately 100 ng of total RNA was used as Table 2 ." ] },{ "paper_id": "6135c4bb442a034b18ef4e9b3fc5701507225f0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal studies were reviewed and approved by the Duke University Institutional Animal Care and Use Committee.", "Vesicular stomatitis virus (Indiana strain) was originally obtained from Dr. John Rose (Yale University). Virus was propagated on BHK-21 cells (ATCC CCL-10) and titered using a standard plaque assay.", "To obtain peripheral blood lymphocytes blood was collected into serum free medium (DMEM) containing heparin. Blood was layered onto a Ficoll gradient and spun, after which lymphocytes were collected from the interface. Cells were washed and resuspended in DMEM containing 5% FCS." ] },{ "paper_id": "61472699f26e3bedce001d84f6e4791ac50652f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background \"An urgent appeal for adopting\u2026some uniform system of publishing the statistical records of hospitals. If they could be obtained\u2026they would show subscribers how their money was being spent, what amount of good was really being done with it, or whether the money was doing mischief rather than good.\" (Attributed to Florence Nightingale, 1863)", "Competing interests KEMRI-Wellcome Trust Research Programme team members receive research funding for work on improvement of health services.", "Ethics approval and consent to participate Not appropriate for this debate manuscript.", "Authors' contributions ME and RS conceived of the idea for this debate article and all authors contributed to data collation and analyses and reviewed early and final drafts of this manuscript." ] },{ "paper_id": "615071c8c959f24857b1bad521cc432b59719bfb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u03ea\" and \"\u03e9\" denote the absence and presence of GFP-expressing E. coli, respectively.", "Dispersion measured using fluorescent microspheres. Fluoresbrite YO carboxylate microspheres (Polysciences, Inc.) which had a 1-m diameter and maximum excitation and emission of 529 nm and 546 nm, respectively, were used as a tracer in the preliminary experiments to understand droplet dispersion from the hand-wash sinks.", "D espite early reports (1) (2) (3) (4) (5) , the premise that hand-wash sink traps can act as reservoirs of bacteria that cause nosocomial infections has been frequently overlooked. There has recently been an alarming increase in sink-related outbreaks worldwide, with many reports establishing an observational link (6) (7) (8) (9) (10) (11) (12) (13) . A sink often operates as an open conduit to wastewater in a patient care area that is often in the same room as the patient." ] },{ "paper_id": "61573a5ebe4f84a5b5738bc12a3c18d2bf69651c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations: DC, dendritic cells; Fc\u03b3R, Fc gamma receptors; FGL2, fibrinogen-like protein 2; FRED, fibrinogen-related domain; HBV, hepatitis B virus; HCV, hepatitis C virus; IL, interleukin; MHC, major histocompatibility complex; MHV-3, murine hepatitis virus strain 3; SVR, sustained virological response; Treg cells, Foxp3 + CD4 + CD25 + regulatory T cells.", "Treatment of acute infection with PegIFN results in high rates of virus clearance, in part by an efficient early stimulation of anti-HCV CD4 + Th1 responses. 21, 22 It has been recently demonstrated that chronic HCV-infected patients with mild or absent disease had circulating memory CD4 + T cells that recognized NS3 and HCV core antigens in contrast to those with severe disease. 23 Similarly, chronic HCV patients who responded to treatment with IFN also demonstrate an increased Th1 cytokine profile and persistent viral-specific CD4 + responses, responses which are weak or absent in non-responders. 24 " ] },{ "paper_id": "615c4a00d39f88f880ce3677ed76771c499ff652", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "616eb9a60a8da572b0a60b6d33f4618c91c7b55c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2015, 7 2359 and tMRCA estimation, provides important information for understanding the dynamics of the evolution of these epidemic coronaviruses.", "Total nucleic acids of 300 \u03bcL of clinical specimens and VR759 cultures supernatant were extracted using the QiAsymphony automate and the QIAsynphony virus/bacteria kit (Qiagen, Holden, Germany), following instructions of manufacturer." ] },{ "paper_id": "61722c462b054f36461375e96e502cbf22648c04", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Niclosamide is a well-established drug that has been safely used for antihelmintic therapy against tapeworm infection for approximately 50 years 33 . Its antiparasitic activity is attributed to its ability to inhibit mitochondrial oxidative phosphorylation and anaerobic ATP production, which affect the pH homeostasis of parasites 42, 43 .", "All data generated or analyzed during this study are included in this article (and its Supplementary Information file) .", "Scientific RepoRts | (2019) 9:8682 | https://doi." ] },{ "paper_id": "6177fd107242a0dbf2cfdd0d617e6a384dba6eaa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The open-source statistical package, R (http://www.rproject.org/), was used to analyze data. Statistical methods used include MANOVA (Multivariate Analysis of Variance).", "Journal of Pathogens", "Clues to Viral Behavior" ] },{ "paper_id": "617ec397b4376957e6d055f1989e66b158b93f1a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Before it was realized that IFITM proteins perform broad-spectrum antiviral activities, they were implicated in pathways important to embryonic development and cancer (exhaustively reviewed in [73] ). A crucial contribution to developmental processes seems unlikely, since transgenic mice in which the murine ifitm locus is knocked out exhibit no obvious abnormalities apart from being fat, suggesting a metabolic irregularity [74] . There is ample evidence, on the other hand, for both positive and negative regulation of IFITM expression during tumorigenesis. While detailed descriptions were previously lacking, recent developments have provided a mechanistic grounding to many observations linking IFITM proteins to cell proliferation, adhesion, and migration.", "A recent and comprehensive study now links an additional variant in the IFITM3 locus to severe influenzaassociated illness in three independent cohorts, albeit the SNP identified is distinct from rs12252-C. Known as rs34481144-A, it is found in the 5' untranslated region and is linked to lower IFITM3 protein levels in cells [72] . Experimental evidence showed that the SNP controls gene promoter activity via decreased binding of transcription factor IRF3 and increased binding of CTCF, which promote and repress IFITM3 transcription, respectively. In agreement with the previous finding that IFITM3 preserves antiviral CD8 + T cells [65] , individuals harboring rs34481144-A contained reduced numbers of these cells in lung airways during infection [72] . The evolutionary pressures responsible for the maintenance of this 'defective' allele in humans are unclear, but its existence may allude to the involvement of IFITM3 in cellular processes requiring fine-tuned protein expression.", "The IFITM protein family is encoded by five genes in humans, including the immune-related IFITM1, IFITM2, and IFITM3, as well as IFITM5 and IFITM10 which have no characterized roles in immunity [1] . Today, IFITM genes are present in many vertebrate animal species yet they likely emerged in early unicellular eukaryotes via horizontal gene transmission from a bacterium [2] . Since then, species-specific gene expansions have given rise to unique IFITM gene repertoires that vary at the level of sequence and copy number [3] [4] [5] . In addition to the canonical IFITM gene locus on chromosome 11 in humans, there are a number of IFITM-like genes dispersed throughout our genome for which a functional understanding is lacking [2] . Despite what their name implies, only the immune-related IFITM genes are interferon-inducible, and furthermore, moderate to high levels of expression may be seen in several tissue types even in the absence of interferon." ] },{ "paper_id": "6180801d741a7b821bf100e3040773f298ba4deb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These results demonstrate the power of complementary structure-and sequence-based approaches in drawing evolutionary links between diverse viruses.", "Calculated evolutionary distances derived from this analysis are indicated next to each branch.", "As the repertoire of the PDB continues to expand, SBPA has been proven to be an increasingly useful method for rationalizing differences in protein functionality. Here, with a particular emphasis on viral receptor-binding proteins (RBPs), we demonstrate how SBPA provides insights into the means by which a common protein fold architecture can be adapted, modified, and elaborated to achieve differential functionality." ] },{ "paper_id": "61810c29377a4573810dc313f4f5d526e7451c0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PCR fragments from each sample were pooled and labeled with CY3 (Nimbelgen Onecolor DNA Labeling Kit, REF 05 223 555 001) independently and 800 ng of the labeled reaction were used for array hybridization, following the manufacturer\u00b4s instructions (NimbleGen Hybridization Kit, REF 05 583 683 001).", "Microarrays were scanned using a GenePix 4000B scanner and processed with the Nimble-Scan and EvolStar softwares to translate the fluorescence intensity into nucleotides and obtain a sequence FASTA file.", "Data are means \u00b1 standard deviation (SD), or number and percentage. *2 patients had asthma and 1 COPD." ] },{ "paper_id": "61843499666ad3d4f0ea75554cd06a745e9a7f8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Isolate designations and GenBank accession numbers are shown in S1 ", "https://doi.org/10.1371/journal.pone.0176709.g005", "https://doi.org/10.1371/journal.pone.0176709.g007" ] },{ "paper_id": "6191082ec9ddfe582a3ba67622a638c0ed353bde", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "61a3e6188ff0e2fcbb6667aea8550b2bf0318d35", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 7:41559 | DOI: 10.1038/srep41559" ] },{ "paper_id": "61aa22d85170a908912fd1f0c0f86ea251b4e311", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting information S1 Table. Cytokine/Chemokine primer sequences for qRT-PCR analysis. (TIF) S1 Fig. Mortality (A, C) " ] },{ "paper_id": "61ab8b92a20e33291536d1b0ef49ca4657cd4b43", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It stems out from several lines of evidence that a tight bidirectional regulation between the autophagic machinery and mitochondria morphodynamics exists.", "The authors declare no conflict of interest. " ] },{ "paper_id": "61b90922be286db0340b0543233488c3764c611d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In a 2C 9 N 2 O 6 H 14 \u00b7H 2 O unit cell of a D crystal, one D molecule adopts a gauche-trans conformation around its C4'-C5' bond, while the other preferentially adopts a trans-gauche conformation over a gauche-gauche conformation [89] . Conversely, unmodified uridine strongly favors the gauche-gauche conformation over the trans-gauche and gauche-trans conformations [90] . Although the D residue is asymmetric, both the gauche-trans and the trans-gauche conformations allow for the formation of loop structures within tRNA, while the gauche-gauche conformation of uridine is typically found within double helical structures [89] . D has the potential to destabilize double-stranded, helical RNA due to its ribose conformation. When substituted into 21-nucleoside RNA duplexes, D disrupted the A-type helical structure and decreased the melting temperature of the duplexes [91] ." ] },{ "paper_id": "61baa9b1ae842b28e3e7aa90a3e8034d96ba9aa9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An anti-HA antibody and an anti-actin antibody were purchased from Vazyme (Vazyme, China). An SR-30 FITC-conjugated mAb was purchased from Rural Technologies (Brookings, SD). Antibodies against Nsp12 were kindly provided by Professor Changjiang Weng at Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences [21] .", "The deduced amino acid sequences of the different Nsp12 strains were examined using the ClustalW method in Lasergene software (version 7.1) (DNAS-TAR Inc., Madison, WI, USA). Multiple sequence alignments were conducted using GeneDoc software.", "MARC-145, BHK and HEK293 T cells were maintained in Dulbecco's Modified Eagle's Medium containing 10% FBS. The PRRSV HuN4-F5 strain is a highly pathogenic (HP-PRRSV) strain isolated from a farm in 2006 (GenBank accession no. EF635006) [19, 20] ." ] },{ "paper_id": "61be2db10d752ec61e879d76e6328b6d676a0f55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All authors contributed to the assembly and revision of this review manuscript. (4) ", "2 Louis et al." ] },{ "paper_id": "61c8af64ef0a95e3f6dfc71ced3f94c2768e23d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Histopathological staining. Lung tissues collected from the challenged mice were immediately fixed in 10% buffered formalin, applied to dehydration and embedded in paraffin wax. Sections of 5 \u03bc m thickness were mounted on slides. Histopathological changes were examined by hematoxylin and eosin (H&E) staining under a light microscope as described previously 32 .", "Scientific RepoRts | 6:22008 | DOI: 10.1038/srep22008" ] },{ "paper_id": "61cd0ce1029799eed2e471e0017fcac99e09fb20", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "61d48e2dee3bd05595403b3e5115d88d4e1dad5d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The availability of effective antiviral therapy for most clinically significant myxovirus infections is limited. Licensed neuraminidase inhibitors for influenza therapy, Zanamivir and Oseltamivir, show efficacy when administered within a 48-hour window after the onset of symptoms, but are increasingly compromised by preexisting or emerging viral resistance [6, 7, 8] . Ribavirin, although approved for RSV treatment, shows limited utility due to efficacy and toxicity issues [9] . The polyclonal immunoglobulin RSV-IVIG [10] and the humanized monoclonal antibody Synagis [11] provide RSV prophylaxis, but use is limited to high-risk pediatric patients. Considering the high mutation rates seen in particular with RNA viruses [12, 13] , the development of novel types of myxovirus inhibitors that circumvent the rapid development of resistance is highly desirable.", "Myxoviruses are enveloped, negative-strand RNA viruses that are transmitted through the respiratory route. The orthomyxovirus family comprises five different genera of which the influenza viruses are clinically most relevant. Of the paramyxoviridae, respiratory syncytial virus (RSV), measles virus (MeV), mumps virus (MuV), human parainfluenzaviruses (HPIV) and the recently emerged, highly pathogenic zoonotic henipaviruses constitute major human pathogens [1] . Although clinical complications associated with some myxoviruses involve persistent infections, the viruses predominantly induce acute respiratory or systemic disease.", "Chemical synthesis of compounds AS-48, AS-136A and RDEA-806 was achieved as previously described [24, 34, 36] . Synthesis of JMN3-003, N-(4-methoxyphenyl)-2-nitroaniline (substance (3) in figure S1), and analogs JMN5-165 and JMN5-166 was achieved as outlined schematically in figure S1. To prepare inhibitor stocks, compounds were dissolved at 75 mM in DMSO.", "After a 60-minute exposure, approximately 80% of the input material remained intact, corresponding to an extrapolated halflife of approximately 200 minutes (figure 3A). Unstable analogs of JMN3-003, JMN5-165 and JMN5-166 (figure S1), returned half lives of 38 and 5 minutes in this assay, respectively, confirming metabolic competency of the S9 fractions used." ] },{ "paper_id": "61dbde818b21b253a6656b32d30b0dfa2bf0e234", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations WHO: World Health Organization; PHEIC: Public health emergency of international concern; SARS: Severe acute respiratory syndrome; MERS: Middle East respiratory syndrome; China CDC: Chinese Center for Disease Control and Prevention; ARDS: Acute respiratory distress syndrome; AI: Artificial Intelligence; ECMO: Extracorporeal membrane oxygenation; TCM: Traditional Chinese medicine.", "In addition, some traditional Chinese medicine (TCM), such as Snow Lotus (Saussuea involucrata), LianHua-QingWen [36] , LiuShenWan [37] might be beneficial for coronavirus infection treatment through immunity enhancement. Further evidence is needed to assess the effect of TCM treatment for patients infected with 2019-nCoV.", "Coronaviruses are enveloped, positive-sense, single stranded RNA viruses that are distributed broadly among humans, other mammals, and birds, which cause respiratory, enteric, hepatic, and neurologic diseases [5] . Six coronavirus species are known to cause human disease. Four viruses including hCoV-229E, OC43, NL63, and HKU1 are prevalent and typically cause mild respiratory diseases [6] . The two novel fatal coronaviruses emerge periodically in different Open Access Given the high prevalence and wide distribution of coronaviruses, the genetic diversity and frequent recombination of genomes, and increasing human and animal activities, novel coronaviruses are likely to emerge periodically in humans owing to frequent cross-species infections and occasional spillover events [7, 8] .", "The blood cell counts of patients showed total white blood cells, lymphocyte, and platelet were lower than the average with extended activated thromboplastin time, increased C-reactive protein and muscle enzyme level. D-dimer level were higher and lymphocyte decrease progressively, if the disease had aggravation. The cytokine storm such as IL1B, IL1RA, IL7, IL8 could be associated with disease severity [2, 21] ." ] },{ "paper_id": "61e9b0e59092872671011d724f22401d3c2f8288", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Values were presented as mean with SD. Statistical significance among different vaccination groups was calculated by Student's t test using Stata statistical software. P values less than 0.05 were considered significant.", "Fc fragment of human IgG has been previously used as a fusion compartment to improve immunogenicity of the proposed proteins [20, 21, 23] . The underlying mechanism of Fc fusion protein-based vaccines may be partially due to that proteins with Fc could bind to cells with FcR, while the latter plays important roles in the clearance of virus infections and protection against virus challenge via FcR-mediated phagocytosis [37] .", "The lung tissues of challenged mice were immediately fixed in 10% formalin and embedded in paraffin wax. Sections 4-6 mm in thickness were made and mounted on slides. Histopathological changes caused by H5N1 virus infection were examined by H&E staining and viewed under light microscope as previously described [39, 47] .", "Influenza epidemics and pandemics caused by influenza A virus (IAV) occur frequently. The first influenza pandemic of the 21 st century emerged in 2009, with a novel swine-origin influenza virus (S-OIV) H1N1 as the causative agent. Originating in Mexico, it rapidly spread to North America and then globally [1] [2] [3] [4] . Of more concern, however, is the continual outbreak of highly pathogenic avian influenza (HPAI) H5N1, an influenza A subtype virus circulating in poultry, which has caused hundreds of human diseases with severe morbidity and high mortality since its re-emergence in 2003 (http://www.who.int/csr/disease/avian_influenza/country/ cases_table_2010_12_09/en/index.html). Although genetic analysis of H5N1 isolated from humans revealed that all genes were of avian origin, limited person-to-person transmission of H5N1 viruses was identified [5] . Now the concern is that future influenza epidemics may be caused by new virus strains derived from mutations and/or reassortments of existing influenza viruses, particularly HPAI H5N1. Therefore, the development of effective preventive and therapeutic measures against IAV, particularly avian H5N1, is urgently needed." ] },{ "paper_id": "61f7459a82d39c89e72c2c8068dbb87f7652dba9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Multiple-sequence alignments were performed using the T-Coffee algorithm [54] [55] [56] . Phylogenetic trees were constructed using the neighbor-joining algorithm [57] and a bootstrap analysis with 100 replicates." ] },{ "paper_id": "61f80012b6b8ea03a65fe97eefc30480990b11be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.", "To score immunohistochemical staining, the same method described above was used to score the entire cardiac lobe surface, except that a scoring system of 0-3 was used with 0 as ''none,'' 1 as ''infrequent,'' 2 as ''common,'' and 3 as ''widespread.''" ] },{ "paper_id": "61fabfc758361c0d84c86c3d735de857d9537b94", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6204b15a79e3551e09c29cd4865fae0497462ec3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mice were euthanized by CO 2 inhalation. Tissues were collected and fixed in 4% paraformaldehyde overnight. Immunohistochemical staining was performed on 5 mm thick sections prepared from formalin fixed, paraffin-embedded blocks. Sections were deparaffinized in xylene and rehydrated in a graded alcohol series. Slides were quenched in 3% hydrogen peroxide, steamed for antigen retrieval in DIVA/citrate buffer (pH 6. media. Blood smears on positive charged glass slides (Surgipath, Richmond, IL), fixed in methanol for 15 sec and stained as above. Mouse anti-human IgG1 (eBioscience, San Diego, CA) was used as an isotype control." ] },{ "paper_id": "62067c9aa24d6b8cbd2a02101c4d4e34681fab97", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "620831ad78fde11d52ab3119bb3a524a8e74628d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In order to thrive, viruses have evolved to manipulate host cell machinery for their own benefit. One major obstacle faced by pathogens is the immunological synapse.", "This study has received funding from the Wellcome Trust Seedcorn Fund Grant/Code AC11900001 and the Department of Medicine University of Toronto." ] },{ "paper_id": "620c2d071dd49eb5bcc31f378eb219310e4b1ebc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments followed the institutional guidelines for animal research, and approval was obtained from the Ethics Committee of the Jinan Maternity and Child Care Hospital.", "The data are presented as the mean AE standard deviation. Two-tailed Student's t-test was employed for comparison.", "Values of P < 0.05 were considered statistically significant: *P < 0.05; **P < 0.01; and ***P < 0.001." ] },{ "paper_id": "620df0595486589bbc677f72cc78f2d158b9810c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Multiple sequence alignment using NCBI showed that isoforms 2 and 3 are identical with PLP except region 117 to 152 which have been eliminated in DM20, and the region 1-55 which is lost in isoform 3.", "Using Prosite, it was found that PLP has two motifs at positions 28-37 (PS00575) and 228-247 (PS01004) that don't have any defi ned function.", "The antigenic criteria proposed for the selection of these sequences were:", "Applying the consensus approach results obtained for PLP interactions with the T-Cell epitopes (MHC I & MHC II binder peptides) are arranged in Table 2 . This table includes peptides with higher affi nities (low ranks) for the corresponding alleles while peptides with lower affi nities were ignored.", "After prediction of the consensus epitopes, three high ranked selected epitopes were directed to protein similarity BLAST search (BLASTp) (http://blast.ncbi.nlm. nih.gov/Blastp.cgi ) for the evaluation of similar peptides reported in diff erent bacteria, viruses, and protozoa species. The selected algorithm was blastp (protein-protein BLAST), with expecting threshold of 10, word size 3, and blosum62 matrix. Then we selected the closest hits and summarized them in an informative table." ] },{ "paper_id": "621648da481a06d1a2bb80c56e998f7373215be6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The T = 4 capsids were analysed, and class averages were calculated for the twofold, threefold and fivefold axes of symmetry. A preliminary icosahedral 3D model was visually inspected using the Chimera software package [15] . Data were then analysed using projection matching [14, 16] . Between each refinement cycle the software package SITUS [17] was used in parallel to select the contiguous mass which corresponded to a single T = 4 HBV/G capsid.", "Cryo-EM and specimen preparation was performed as previously described [11, 12] . Briefly, specimens on glowdischarged Quantifoil grids (Quantifoil MicroTools GmbH, Jena, Germany) were plunge cooled in liquid ethane using a Vitribot Mark IV (FEI Company). Specimens were imaged at 200 kV in a FEI Tecnai 20G 2 electron microscope equipped with a 4K CCD camera (FEI Company, Hillsboro, Oregon, USA). Images were recorded at a magnification of 80 000\u00b7, (corresponding to 108 240\u00b7 at the CCD detector, or 1.353 \u00c5 /pixel) using a total dose of 10 electrons/\u00c5 2 and a defocus of 3.5-6 l. A total of 13 455 particles were analysed. Correction was made for the contrast transfer function using EMAN [13] . T = 3 or T = 4 capsids were separated in SPIDER [14] (Fig. 1b,c) . Two populations of 1887, and 11 568 images of T = 3 and T = 4 capsids, respectively, were analysed.", "Preparation and purification of core protein from HBV Genotype G HBV/G-infected individuals were identified through routine diagnostic testing and strain surveillance at the National Microbiology Laboratory (NML) using sequencing and phylogenetic analysis [10] . The gene coding for the HBV/G core protein was PCR amplified, cloned into the pET28b vector (Novagen, EMD Biosciences, Gibbstown, NJ, USA) and expressed in Escherichia coli strain BL21 (DE3). Clarified culture lysates were centrifuged on a 20-60% sucrose gradient at 30 000 rpm in a Beckman SW4OTi rotor for 14 h. Fractions were analysed by SDS-PAGE and Western blotting with anti-HBc antibody (MA1-21697; Pierce Antibody, Rockford, IL, USA). Cores were dialysed against PBS pH 7.4 using a 10 K MW cut off Pierce Slide-A-Lyzer cassette (Thermo Scientific, Waltham, Massachusetts, USA). The HBV/G core sequence was submitted to the National Center for Biotechnology Information GenBank database under accession number GU325783." ] },{ "paper_id": "621832d547930a8c23859fa443c2c9c38ff07e42", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analysis in this study was performed using the software GraphPad Prism 7.0 (2016 3 ), with P < 0.05 considered as statistically significant.", "Differentially Expressed in C. parvum", "G-HZ conceived and designed the experiments. T-LL and X-CF performed the experiments and drafted the manuscript. T-LL, X-CF, Y-HL, Y-JY, and Y-LY analyzed the data. X-TW and L-XZ contributed to reagents and materials. All authors read and approved the final manuscript. " ] },{ "paper_id": "62189c3e0d5823002bc5785f7acc61d89fb85666", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protein purity was verified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (15 % gel). Following purification, the denatured monomeric peptides were refolded using one of the following three methods: (1) dialysis performed in a stepwise manner (stepwise refolding) (2) one step dialysis against a buffer with no urea (direct refolding) or (3) concentrated (Amicon Ultra centrifugal filter devices, Millipore, Billerica, MA, USA) and diluted to a buffer with no urea (quick refolding). The proteins were filtered with a 0.1 \u03bcm polyvinylidene fluoride membrane filter before and after dialysis (Millipore, Billerica, MA, USA, #SLVV 033 RS).", "The hydrodynamic diameter was obtained with a Malvern Zetasizer Nano S equipped with a 633 nm laser using a 3 mm path length quartz suprasil cell. The measurements were done at 25 \u00b0C and for each protein five scans were collected.", "Transmission Electron Microscopy samples were negatively stained with 1 % uranyl acetate (SPI) at a peptide concentration of 50 \u03bcg/ml. Electron micrographs were taken with a Philips EM 300 transmission electron microscope at an accelerating voltage of 80 kV. The micrographs were scanned at 600 dpi." ] },{ "paper_id": "621c17ebf69617fe8e330f6c9818880902ee6a97", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mia: Before swine flu came along, MRSA and C-Diff was in the news like an awful lot, and nowadays you hear like nothing about it, and it is still aroundand people like still do need to know about how that can like affect you as well. Katy: No, it shouldn't just be dropped just because something new and big has come along... (FG 5).", "It's kind of they're damned if they do, and damned if they don't. I think if they didn't come up with a vaccine for swine flu, we'd all be like, 'well what are they playing at? Come on -get it sorted.' And now they have, it's like, 'oh, that was a bit fast, that was too fast for my liking' (Sophie, FG 1).", "Once target groups were identified, individualised posters, leaflets and adverts were developed to recruit participants. These recruitment materials were placed in a range of community settings including universities, community groups run in leisure/sport and community facilities, and shops. Adverts were run in local newspapers and on websites inviting interested parties to contact the researcher. A small number of participants who fitted our sampling frame were also recruited via snowballing.", "Ethical approval for the study was obtained from the research ethics committee of the University of Glasgow's Law, Business and Social Sciences Faculty." ] },{ "paper_id": "621c8306765f418717c3de4497c2dace5f8a9c73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human cytomegalovirus (HCMV) is a highly prevalent herpesvirus, infecting 30 to 100% of the global population depending on the socio-economic status. Although normally asymptomatic in healthy individuals, HCMV infection is a significant cause of morbidity and mortality in immunocompromised populations, individuals with heart disease and recipients of solid organ and bone marrow transplant. HCMV is also the leading cause of infectious congenital birth defects [1] [2] [3] [4] [5] [6] [7] [8] [9] .", "Laboratory adapted HCMV strain AD169 infected cells were fixed and permeabilized in Methanol:Acetone solution (1:1) for 7 minutes, and then blocked with 5% human serum in PBS for 30 minutes. Primary and secondary antibodies were diluted with 5% human serum in PBS. Cells were washed with PBS after primary and after secondary antibody incubations. Primary antibodies used in this paper are mouse anti-CMV IE2 monoclonal antibody (12E2, Santa Cruz Biotechnology), rabbit anti-VCP polyclonal antibody (H-120, Santa Cruz Biotechnology) at 1:500. Alexa-fluor-647 conjugated goat anti-mouse or Alexa-fluor-488 conjugated goatanti-rabbit IgG secondary antibodies were diluted 1:1000. All images were acquired with Zeiss LSM 710 confocal microscope fitted with 63X/1.4 oil-immersion objective lens.", "Normal Human Dermal Fibroblasts (NHDF; Gibco) were maintained in Dulbecco's modified high glucose media (DMEM; Sigma) supplemented with 10% fetal bovine serum (FBS; Gibco) and 1% penicillin-streptomycin (Invitrogen). A low passage HCMV strain TB40E, which expresses GFP from an SV40 promoter was used for siRNA library screening, western blot analysis, and northern blot analysis. Laboratory adapted HCMV strain AD169 was used for immunofluorescence experiments." ] },{ "paper_id": "621fb61c827a3f1f0c6c69849319ed45f6dc1f5b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Isolation of viral nucleic acid from control material and patient specimens was performed using an EasyMag automated extractor (bioMerieux, Durham, NC) as previously described [5] . Previously published, virus-specific primer and probe nucleotide sequences were used for detection of influenza A and B virus RNA [5] using the ABI 7500 Real-Time PCR Instrument (Applied Biosystems, Foster City, CA).", "Among the 935 ARI patients sampled over the 17-week study period, all completed the enrollment questionnaire and 83.3% completed a follow-up survey." ] },{ "paper_id": "621fc53e298c0a2dc4e8c6c871fcd8cca0e707e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Observations arguing against an RNAi-like function would be that the stem region of s2m is a bit short compared to standard processed RNAi molecules (albeit mRNA binding regions as short as 17 base pairs have been reported [22] ). We were also unable to find any good candidate target genes using sequence similarity searches to look for potential microRNA binding sites, and even when looking at viruses infecting relatively closely related species (such as bats, see Figure 2 ), there was significant variability in the s2m stem regions that could be predicted to be involved in mRNA binding. These observations make it less likely that s2m is involved in conventional RNAi-based gene silencing.", "The presence of s2m near the 3 1 end of some coronavirus genomes has been documented previously [6, 11] , but due to the exponential growth of gene sequence data available through public Diseases 2016, 4, 27 2 of 8 databases, this review is an update on the current status of s2m in this virus family. The evolutionary history is discussed and different hypotheses for the possible function of s2m are presented in light of recent progress in virus genomics.", "For some positive-strand ssRNA viruses, genome circularization has been shown to be essential for virus replication [28] . RNA circularization would require s2m to bind either directly or indirectly (mediated by RNA binding proteins) to the 5 1 end of the genome. The primary binding 5 1 site could either be a five-prime cap (5 1 cap) or an RNA structure (see discussion in [29] ). It is possible that there are conserved structural RNA elements with such a binding affinity near the 5 1 end in all s2m viruses, but it seems unlikely given the complete lack of sequence similarity when comparing data from the 5 1 flank of these genomes. The direct involvement of a 5 1 cap also seems implausible, as, for instance, s2m-containing picornaviruses lack 5 1 capping." ] },{ "paper_id": "6223b84467e6bdc875ce49a403acf34055e4d141", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Modified Vaccinia virus Ankara (MVA) was derived from Chorioallantois Vaccinia virus Ankara (CVA) through serial passaging in chicken embryo fibroblasts (CEF) [69, 70] . From 1968-1985, the Bavarian State Vaccine Institute produced MVA as a human smallpox vaccine. The application of this MVA vaccine was successful to increase the safety of the conventional smallpox vaccination as documented by the absence of any serious adverse event in large field trials involving more than 120,000 individuals in Germany [71] .", "Respiratory viruses, such as seasonal and pandemic influenza viruses, human parainfluenza virus (hPIV), respiratory syncytial virus (RSV) and coronaviruses, cause substantial burden of disease globally. These pathogens cause respiratory tract infections, mainly in young children, the elderly and immunocompromised individuals. In contrast to seasonal influenza, currently no licensed RSV and hPIV vaccines are available.", "The serial passage of MVA in primary and secondary CEF cultures resulted in major deletions in the viral genome and many mutations that affected most known vaccinia virus (VACV) virulence and immune evasion factors [72] [73] [74] . Consequently, MVA replication is highly restricted to avian cells and the virus is unable to produce infectious progeny in most cells of mammalian origin [75] [76] [77] ." ] },{ "paper_id": "6224ce8bb65afbb10b08238d5ecde8991d7ab0e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In another study, a nanoparticulate system based on the cationic poly(b-amino ester)polymer, C32 [375] , was used as a DNA delivery system of a suicide gene encoding for a diphtheria toxin A chain (DT-A) under the transcriptional regulation of a prostate-specific modified human PSA promoter, PSE-BC [371] . The genetic material/cationic polymer complex was locally delivered into normal prostate and prostate tumors in mice, causing massive apoptotic prostate cell death, without damaging surrounding tissue [341] .", "Ovarian cancer is a common malignancy in women, and causes more deaths than any other type of female reproductive tract cancer [379] . Lidor et al [342] have demonstrated specific protein synthesis inhibition in malignant ovarian cell lines transfected with plasmids encoding transcriptionally regulated diphtheria DT-A. The toxic gene transcription was regulated by elements of the human chorionic gonadotropin (hCG) promoter, a heterodimeric glycoprotein placental hormone involved in different pregnancy-promoting processes. Although principally produced by trophoblasts, hCG is also expressed in some malignant tumors of the ovary, uterus, testis, colon, liver, pancreas lung, and stomach [380] [381] [382] .", "The half-lives of proteins in a living cell range from a few seconds to many days. Features of proteins that confer metabolic instability are called degradation signals, or degrons. The N-end rule degron (N-degron), which was the first to be discovered, relates the in vivo half-life of a protein to the identity of its amino-terminal residue. In eukaryotes, the N-degron comprises at least two determinants: a destabilizing N-terminal residue and internal lysine/s that function as acceptor site/s for the formation of a multi-ubiquitin chain that \"marks\" the ubiquitin-protein conjugates as a substrate for proteosomal degradation. Destabilizing residues in mammalian cells can be hierarchically divided into three classes: Primary (type 1 (Arg, Lys or His) or type 2 (Ile, Leu, Phe, Tyr or Trp)), secondary (Asp, Glu or oxidized Cys) and tertiary (Asn, Gln or Cys) (reviewed in [506] [507] [508] [509] [510] [511] )." ] },{ "paper_id": "62406757c331d6c939bf09fa005bb565b3fac0b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "On 18 June 2015, the Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Thailand, hospitalized a laboratory-confirmed case of MERS-CoV infection. The patient was a 74-year-old man from Oman who had been admitted to a private hospital 3 days earlier.", "Paired sera of HCWs were investigated for the MERS-CoV antibody by an indirect enzyme-linked immunosorbent assay (EUROIMMUN Medizinische Labordiagnostika AG, Germany) at Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand. The assay protocol of the manufacturer was followed. In brief, a 100 \u03bcl volume of the test serum at dilution of 1: 101 was added onto the wells coated with purified S1 antigen of MERS coronavirus in duplicate. Peroxidase labeled rabbit anti-human IgG was used as the secondary antibody and tetramethylbenzidine was used as the substrate. The reaction plate was measured for optical density by a spectrophotometer using the wavelengths of 450 and 630 nm. Positive control, negative control and calibrator human IgG were included in every reaction plate to determine the cut-off value for defining positive, negative or borderline result. Informed consent was obtained from HCWs. The study was reviewed and approved by the Bamrasnaradura Institution Review Board. Results were analyzed by SPSS version 15.0.", "All materials involved in the case were carefully managed. The waste from the patient and soiled linen were collected in leak-resistant, triple-layered bags. All the exteriors of the bags were disinfected with 70 % alcohol spray. They were destroyed by incineration. The clean linen was collected with triple bagging. They were washed with bleach in a temperature of 70\u00b0c for 45 min. Food utensils and dishware were disposable and managed as infectious waste. For the patient's room, a 0.05 % sodium hypochlorite solution was used to disinfect the room floor daily. The patient's bed, high-touch surfaces, and room equipment were cleaned by 70 % alcohol twice a day. Contaminated sharps were collected in punctureresistant containers and incinerated. Clinical specimens were destroyed by incineration." ] },{ "paper_id": "62426ec5038825e2c7928b6ac82a66ff1c2a578e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Computational approaches have been widely applied to molecular biology and medicine [41] [42] [43] [44] [45] [46] [47] [48] [49] [50] . Structure-based methods, including docking and MD simulation, are invaluable tools in", "TamifluH was used as the control for N1, and its N1 docking score was set as the minimum requirement. The top TCM compounds that passed the filtering were selected for de novo evolution.", "Virtual screening, de novo derivative generation, and molecular dynamics (MD) simulation were performed using Discovery Studio Client v2.5.0.9164 (DS2.5; Accelrys Inc., San Diego, CA). The two-dimensional and three-dimensional structures of TCM compounds were generated using ChemBioOffice 2008 (Perki-nElmer Inc., Cambridge, MA). Comparative molecular field analysis (CoMFA) and comparative molecular similarities indices analysis (CoMSIA) models were constructed using SYBYL\u00df 8.3 package (Tripos Inc., St. Louis, MO).", "H-Bond network during MD simulation. The H-bond occupancy of each compound in N1 is summarized in Table 3 Figure 7 . The distance between Xylopine_2 and Glu228 was maintained between 2-3 \u00c5 ( Figure 7A ). The distance of Rosmaricine_14 and Glu119 and Glu 228 also remained between 2-3 \u00c5 ( Figure 7B ). From Table 3 , Rosmarcine_15 and TamifluH did not form high occupancy H-bonds with Tyr402. Intriguingly, bond distance profiles indicate that Tyr402 was one of the key amino acids for H-bond formation ( Figure 7C , 7D). Tyr402 bond distance generally exceeded 2.5 \u00c5 in Rosmaricine_15, thus explaining the low occupancy rate in Table 3 . For TamifluH, the distance in the first ns was between 3-4 \u00c5 and then decreased to 2-3 \u00c5 from 1-20 ns, thus accounting for the low occupancy rate as well. Despite the low occupancy rates, the bond distance profiles suggest that Tyr402 is an important N1 binding site for Rosmaricine_15 and TamifluH.", "The first global pandemic of the 21st century was announced by the World Health Organization (WHO) in 2009 due to the worldwide spread of influenza A subtype H1N1 (H1N1/09) [1] . More than 214 countries have reported laboratory confirmed cases, and more than 18,449 deaths have been recorded [2] . Currently, the neuraminidase inhibitor TamifluH (oseltamivir) remains the primary drug prescribed to patients infected with H1N1/09 [3] . However, the emergence of drug resistant viral strains [4] and limited drug administration window [5] exemplifies the need for additional therapies." ] },{ "paper_id": "624840869f8c5f365a639a67cae53f56c740749f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Average duration of asymptomatic phase of infection (\u0394s) (days).", "Early real time estimation of R0", "Average duration of the symptomatic phase of infection (\u0394i)." ] },{ "paper_id": "624d182cc7495a9fd996eb51663e8774a42d2cca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An example of parameters in each of the categories is presented in Table 1 .", "Correlation coefficients were defined as follows: rho = 0.25-0.44weak correlation; rho = 0.45-0.60moderate correlation; rho 0.61-0.80strong correlation, and 0.81-1.00 very strong correlation. Each level of correlation is regarded as statistically meaningful if p < 0.05." ] },{ "paper_id": "625afb5a588fd265e15b652a437ef9f521682aee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All datasets generated for this study are included in the article/Supplementary Material.", "The animal study was reviewed and approved by the Shanghai Public Health Clinical Center Laboratory Animal Welfare & Ethics Committee.", "PZ conceived and designed the experiments. YC, YL, and XW performed the experiments. YC and YL analyzed the data. YC, YL, and PZ wrote the manuscript. " ] },{ "paper_id": "625c0fb8bd8fe9121b9139f318397b074208d5e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed using SigmaPlot version 11.0 (Systat Software, Inc., San Jose, CA). One-way Repeated Measures ANOVAs were used to compare three or more groups, and square-root-transformed data was used to analyze data from PneumaCult\u2122-differentiated cultures.", "Highly ciliated cultures are more susceptible to C15 infection" ] },{ "paper_id": "626267a319f0390205d0e2c5fa2c93e7402f274b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In principle, there is no \"universal\" production system which can guarantee high yields of recombinant antibody, particularly as every antibody-based molecule itself will cause its own issues in terms of expression. ", "The Fab format requires expression, periplasmic transport, correct folding, and assembly of two different polypeptide chains. Among the different vector formats and arrangements, bicistronic vectors with the first cistron encoding the light chain and the Frontiers in Immunology | B Cell Biology second cistron encoding the Fd fragment are optimal (56). Even aglycosylated full-size IgGs were successfully produced in E. coli (72, 73). In our view, the raison d'\u00eatre of complete IgG production in E. coli is doubtful.", "Overexpression of the ER resident chaperone binding protein (BiP) significantly enhanced levels of soluble and secreted IgGs in T. ni cells (143). Enhanced secretion of IgGs was also achieved by coexpression of protein disulfide isomerase (PDI) or the human cytosolic chaperone hsp70 in T. ni cells (138).", "Expression of IgGs in insect cells under control of the strong Polyhedron promoter resulted in an extensive aggregation, probably caused by overloading the cellular folding and post-translational processing apparatus (142)." ] },{ "paper_id": "626347808e0ebaed5176f6a00206c35e48aeb90d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The cDNA used for sequencing and probe construction was made by MMLV-RT on viral RNA with 1 \u00b5g of random hexamer DNA primers in 10 mM Tris pH 8.3, 50 mM KCl, 0.1% Triton-X100, 6 mM of MgCl 2 and 50 \u00b5M of each dNTPs at 37\u00b0C for 1 hour. The single stranded cDNA product was made into double-stranded DNA in a standard PCR reaction with 1.25 U of Taq polymerase (Perkin-Elmer) per reaction with appropriate primers (see below)." ] },{ "paper_id": "62641fdbeeff7b487788b42b59a3d1ca66bdb978", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All ITC experiments were carried out at 25 \u00b0C on an iTC200 instrument (MicroCal, US). The sample cell contained NPC1 domain A or C (30 \u03bc M), and tamoxifen/clomiphene/ U18666a (300 \u03bc M of each compound) was added in 20 injections with 2 \u03bc L of each. Data were processed using Origin software (MicroCal, US). Each experiment was duplicated three times.", "Statistical analysis. The data were analyzed for statistical significance with the SPSS 12.0.1 Package (SPSS Inc., US). Data for all groups were first tested for normality with the Shapiro-Wilk test. If the group's data were normally distributed, they were compared using a one-way analysis of variance. P values < 0.05 were regarded as statistically significant. All values are presented as the means \u00b1 SEM (standard error of mean). All of the graphs were generated with GraphPad Prism 5.0 (GraphPad Software Inc., US)." ] },{ "paper_id": "626e2623bbb406b7fc1bd5b1da3ff4eb30e3888c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our studies suggest that the frameshifting mRNA pseudoknot structures stabilized by highly cooperative secondary and tertiary interactions may serve as kinetic barriers against the forward translocation of ribosome and reduce the speed of translation, and thus increase the probability of \u2212 1 frameshifting. The minor-groove stem 1-loop 2 base triples in mRNA pseudoknots may be generally employed for stimulating translational recoding in other viruses and cells 8, 9, 15, 59 . Our studies provide detailed insights into the determinants of a pseudoknot structure affecting frameshifting efficiency, which may help us understand and manipulate the \u2212 1 frameshifting process by designing pseudoknot-binding ligands 12, 13, 60 .", "Recent advances in the discovery and understanding of complex RNA structures, dynamics, and functions have dramatically changed our view of RNA's role in biology. RNA has been found to play increasingly important and diverse regulatory and catalytic roles in many biological processes ranging from replication, transcription, splicing, to translation 1 . In this study, we focus on understanding how the translation reading frame can be regulated by cis-acting mRNA structures. The translation process is highly regulated and remarkably accurate. Normally, the reading frame needs to be maintained at a constant frame (0 frame) because shifting of the reading frame results in the generation of completely different protein products. Minus-one ribosomal frameshifting is a translational regulatory mechanism programmed by cis-acting mRNA structures and widely utilized by viruses and cells 2-13 . During \u2212 1 ribosomal frameshifting, a ribosome is positioned at a certain sequence of mRNA called slippery sequence, and has a certain probability to move one nucleotide backward, before continuing translation in the new reading frame (\u2212 1 frame) 11, 14, 15 . Minus-one frameshifting is important for (i) maintaining a fixed ratio of certain gene products through the translation of a fusion protein by bypassing the original 0 frame stop codon, and (ii) regulating the half-lives of mRNAs by employing mRNA degradation pathways through premature translation termination at a \u2212 1 frame stop codon 11, 13 ." ] },{ "paper_id": "6275144a4a4a08d1c72f3c52109ac757c72e6424", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Research waste: hidden data, irreproducible research", "Individual incentives were grouped into research fields. A qualitative description of each incentive was presented.", "(2015) conducted a survey to investigate the differences in experiences with and perceptions about sharing data, as well as barriers to sharing among clinical and basic science researchers [16] ." ] },{ "paper_id": "6276adaeca8fcd42c9565718ac6bbdc4f97aa10f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NiV is a re-emerging infectious disease which causes outbreaks with a high case-fatality rate.", "Nipah virus was discovered in 1998 after an outbreak in Malaysia. Since then, several outbreaks have been reported in Bangladesh and India. Although most outbreaks are relatively small, a very high case-fatality rate is reported (75%). Furthermore, human-to-PLOS Neglected Tropical Diseases | https://doi." ] },{ "paper_id": "627ada5c21fb8d0e43b37999fa66bf41ca36c353", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For all selected and analysed sequences, short (<300bp of the corresponding gene) and abnormal sequences were removed from the datasets, and only six viral genes were studied because the short length and insufficient codon usage diversity of the other genes might have biased the results. The six genes analysed were the E, M, N, S, ORF1ab and ORF3, and all these genes were classified according to their viral isolation date and location." ] },{ "paper_id": "6283f1857cb5e2a448314edd73d5ff5d2203c566", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6285a0930a05dfe14ae9f09101a789e070435b3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and their glycosides (Table 3) . Table 3 . Hydrogenation derivatives of amentoflavone. ", "The IC 50 ", "In recent years, pharmacokinetic studies of extracts and bioactive compounds from traditional Chinese medicine and natural medicine have become research highlights. As a representative biflavonoid with several pharmacological functions, amentoflavone was not an exception." ] },{ "paper_id": "628b63978a499c7cdecbccf06dd60980da895fb0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Renalase protein was obtained using prokaryotic expression system. After being purified and measured for concentration, it then was stored at 220uC [5] .", "Renalase is a newly discovered monoamine oxidase enzyme originating from renal tissues [1] . It degrades circulating catecholamines, regulates blood pressure and cardiac function, and is closely associated with cardiovascular diseases and chronic kidney disease (CKD) [2] [3] [4] . Renalase is a protein made of 342 amino acids with a molecular weight of 37.8 KDa approximately. The N-terminate of renalase contains one signal peptide, one flavin adenine dinucleotide binding site and one monoamine oxidase domain, and 13.2% of its amino acid sequence is similar to the monoamine oxidase A.", "Primer for renalase gene was designed as Sp 59-ATAA-GAATGCGGCCGCATGGCGCAGGT GCTGATC -39, As 59-GGAAGATCTCTAAATATAATTCTTTAAAGCTT -39, and then renalase gene was replicated using RT-PCR technique. Renalase gene was then inserted in pBudCE4.1 (Invitrogen, Carlsbad, CA, USA) vector plasmid, after which the immunization plasmid was completed." ] },{ "paper_id": "62918573a167d69a0056aa9462d5cc1d9ae351fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. Sequencing data have been deposited in ArrayExpress (http://www.ebi.ac.uk/arrayexpress) under the accession number E-MTAB-5206. The data that support the findings of this study are available from the corresponding author upon request.", "Immunoblotting. Infected cell lysates or purified proteins were separated on 15% acrylamide/bisacrylamide gels (BioRad mini-protean tetra cell apparatus) and transferred to nitrocellulose membranes for 120 min using a mini-protean transblot cell and Tris glycine transfer buffer. Following blocking with 5% non-fat milk, primary antibody incubations were carried out overnight at 4\u00b0C using 1:1,000 diluted anti-2A (rabbit polyclonal raised against the C-terminal 14 aa of 2A by GenScript) or anti-tubulin (rat monoclonal; Abcam, ab6160) antibodies. Secondary antibody was the appropriate IRDye-conjugate (Li-Cor) used at 1:10,000 dilution. All washes employed PBS containing 0.1% Tween 20. Blots were scanned on a Licor Odyssey infrared scanner.", "Proteins were resolved by 12% SDS-PAGE and dried gels were exposed to X-ray film or to a Cyclone Plus Storage Phosphor Screen (PerkinElmer). The screen was scanned using a Typhoon TRIO Variable Mode Imager (GE Healthcare) in storage phosphor autoradiography mode and bands were quantified using ImageQuantTL software (GE Healthcare). PRF efficiencies were calculated as [IFS/MetFS]/[IS/MetS \u00fe IFS/MetFS], where the number of methionines in the stop and frameshift products are denoted by MetS and MetFS, respectively, and the densitometry values for the same products are denoted by IS and IFS, respectively. All frameshifting assays were performed at least three times.", "Ribosome profiling data analysis. Adaptor sequences were trimmed using the FASTX-Toolkit (Hannon lab) and reads shorter than 25 nt were discarded. Trimmed reads were first mapped to Mus musculus databases of rRNA, ncRNA (Ensembl, GRCm38.70, ncRNA) and mRNA (NCBI RefSeq mRNAs) using bowtie version 1 with seed length 23 and default parameters 37 . Remaining reads were mapped to the relevant virus genome (EMCV or mutants thereof). To ascertain that prior mapping to host sequences did not remove viral reads, we also tested mapping reads to the virus genome first, and found that the same set of reads were identified. Supplementary Table 1 shows the composition statistics for each library." ] },{ "paper_id": "629a7c48e6c7c91265533e47a8e7f3afe54cbc4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The online Rho calculator https://www.socscistatistics.com/tests/spearman/Default.aspx was used for the Spearman correlations. This software has been audited by established statistics packages. ", "The DNA viruses in the study take an intermediary position.", "The collective results above served the compilation of the predictive framework for animal virus evolution shown in Figure 4 , Discussion section." ] },{ "paper_id": "62a1f28a0ad0c2c37252351ad64fd7d8b0efdcc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Frontiers in Microbiology | www.frontiersin.org ", "The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fmicb. 2016.00089" ] },{ "paper_id": "62a1f5bb2940b4c4c29338c8f9fc47fd431aed28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The identification of transmission clusters is irrelevant in flu as the virus is transmitted so rapidly and so frequently that it is highly unlikely that transmission pairs will be sampled. Instead, we have used the CP to down sample a dataset of sequences while maintaining its full genetic diversity. This might be useful for downstream analyses in BEAST [3] , or to investigate the effects of sampling. In the present analysis, the CP was run with the aim of downsizing the dataset from 2989 sequences to ~150. All PB2 avian influenza A sequences were downloaded from NCBI Influenza Virus Resource [4] , duplicate sequences were removed, and a phylogenetic tree reconstructed in FastTree. The CP was run with a series of thresholds (using the command line version) until we found a threshold which maximized inclusion of sequences in ~150 clusters. 70% bootstrap and 6% genetic distance thresholds yielded 158 clusters containing 98% of sequences. A single sequence from each cluster was selected for further analysis (L. Lu, manuscript in preparation).", "Previous phylogenetic analyses of Hepatitis C virus (HCV) have used different regions of the genome, including E1, E2 and the HCV core region. We selected the core region because it is longest (~500 nucleotides). Core sequences (>200 nucl.) were downloaded from the Los Alamos National Laboratories repository (http://hcv.lanl.gov). Sequences were sorted by subtype, and as HCV subtype 1b was the most frequent, it was chosen for analysis. After deletion of duplicates, 3786 sequences remained, with a mean sequence length of 505 nucleotides (accession numbers listed in Additional File 5). Accompanying information was downloaded in parallel, including country of origin for 88% of sequences. Sequences originated from 46 different countries. A phylogenetic tree with 100 bootstrap replicates was reconstructed using RaxML [1] . Based on previous work, a cluster threshold of 70% bootstrap and 2% genetic distance was used to identify clusters [2] . The Cluster Picker (CP) completed in <6 seconds, and identified 144 clusters. When the bootstrap was increased to 90%, only 50 clusters were identified. Using the Cluster Matcher (CM), we determined that at both thresholds, sequences from the same country clustered together 100% of the time, suggesting that they represent epidemiologically-relevant clusters. Note that multiple sequences may originate from the same patient and that the tree is fully bifurcating.", "We used the CP in a BEAST Maximum Clade Credibility (MCC) [3] tree comprising 492 full genome H1N1 human pandemic sequences (segments concatenated, excluding PB1), mostly from the Spring and Fall waves of the pandemic (2009-2010). Details of the sequences and BEAST tree models can be found in the original publication [5] . The BEAST MCC tree was generated with Tree Annotator (distributed with BEAST) in the extended nexus format, and was converted into a newick format with the posterior probabilities encoded as support values at the nodes using an R script MCC_to_NWK.R (see the Tutorial files). Initial and main support thresholds of 0.7 were used together with a genetic distance threshold of 2%. These resulted in three large clusters, broadly corresponding to the initial clades present in the USA at the start of the pandemic as determined by hand on a maximum likelihood tree on USA only data [6] . The largest of these clusters (Cluster3, purple) corresponds to \"Global Clade 7\", which became dominant in Wave 2 of the pandemic. A data set comprising 1027 H3N2 human seasonal influenza full length haemagglutinin sequences, from 2004 -2012 was obtained from the NCBI Influenza Virus Resource [4] . Sequences from each isolate were classified by global region (North, Tropical and South), continent and year, similar to the H3N2 Global Migration Dynamics study by Bedford et al [7] . Time resolved trees were generated using BEAST with the SRD06 nucleotide model, the relaxed lognormal uncorrelated clock and constant population size. Two independent runs of 500,000,000 MCMC samples (step 10,000) were combined, and the final MCC tree was converted to newick format (using MCC_to_NWK.R). The CP was used with initial and main support thresholds of 0.7, and genetic distance threshold of 2% to reveal 93 clusters, including 76% of the sequences. The composition of the clusters was analyzed with the CM. We found that on average 76% of the sequences in a large cluster (>= 20 sequences) were isolated in the same year, 72% of them were isolated in the same global region (North, Tropical, South) but only 66% in the same continent. " ] },{ "paper_id": "62a510dfb56136e79dbfcb424fae13b47c476635", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA extraction and quantitative real-time polymerase chain reaction (RT-PCR)", "Gene name Primer name Primer sequence (5\u2032-3\u2032) Position (bp)", "All experiments were repeated at least three times. The experimental data were statistically analyzed with two-way repeated measure analysis of variance (RM-ANOVA) using GraphPad Prism software (version 5.0). P-values less than 0.05 were considered statistically significant, and those less than 0.01 were considered highly significant." ] },{ "paper_id": "62a67d1f86138972ae0d79681ddd2a4a75f6dec0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were analyzed using software package SPSS version 16.0.1. The protocol-defined objectives were as follows (Text S1):" ] },{ "paper_id": "62a87de16c26fdb905173879c56ec19a2879921f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cow vaccinations. All beef and dairy cows were immunised against the inactivated antigen strain of BoHV-1 (gE-) with a primary vaccine and a secondary booster vaccine at day (d)-84 and d-56 relative to the expected calving date (d 0), with 2 ml (S/C) of a commercial vaccine, Bovilis IBR marker inactivated (MSD Animal Health, Buckinghamshire, UK). All cows received a combined rotavirus, coronavirus and E. coli F5 (K99) vaccine (inactivated) (Rotavec Corona) by intra-muscular injection between 4 and 12 weeks prior to calving date." ] },{ "paper_id": "62af9e71368a90bd8fce0347e90527e3e4da3800", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As a further measure of lytic infection, we stained PLN sections for the MCMV IE1 antigen (Fig 4a) .", "Organs were fixed in 1% formaldehyde-10mM sodium periodate-75mM L-lysine (24h, 4\u02daC), equilibrated in 30% sucrose (18h 4\u02daC), then frozen in OCT. Sections (6\u03bcM) were air dried (1h, 23\u02daC), washed 3x in PBS, blocked with 0.3% Triton X-100-5% normal goat serum (1h, 23\u02daC), then incubated (18h, 4\u02daC) with antibodies to B220 (rat mAb RA3-6B2, Santa Cruz Biotechnology), CD68 (rat mAb FA-11), ER-TR7 (rat mAb), CD11c (hamster mAb N418), SiglecH (rat mAb 440c), \u03b2-galactosidase (chicken pAb), Caspase 3, Lyve-1 (both rabbit pAb, AbCam), CD206 (rat mAb MR5D3), CD169 (rat mAb 3D6.112, Serotec); NKp46 (Rat Mab 29A1.4, Biolegend), MCMV IE1 pp89 (mouse mAb Croma101) [55] and MCMV virion antigens (rabbit pAb, raised in house by subcutaneous inoculation with MCMV K181 propagated in NIH 3T3 cells). After incubation with primary antibodies, sections were washed x3 in PBS, incubated (1h, 23\u02daC) with combinations of Alexa 568-or Alexa 647-conjugated goat anti rat IgG pAb, Alexa 647-conjugated goat anti-mouse IgG1 pAb, (Life Technologies), and Alexa 488-goat anti-chicken pAb (Abcam), then washed x3 in PBS, stained with Hoechst 33342 and mounted in ProLong Gold (Life Technologies). Fluorescence was visualised with a Zeiss LSM510 confocal microscope and analysed with Zen imaging software. " ] },{ "paper_id": "62b348dd9761ec78af4d53ad162a747cd300edce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HPV-16 E6 and E7-expressing TC-1 tumor cells were generated as previously described [13] and was grown in RPMI 1640 medium containing 10% fetal bovine serum, 2 mM glutamine, 1 mM sodium pyruvate, 100 IU/ml penicillin, 100 \u03bcg/ml streptomycin, 100 \u03bcM non-essential amino acids and 0.4 mg/ml of G418.", "Mouse tumor challenge model C57BL/6 mice (five per group) were injected with 1 \u00d7 10 5 TC-1 tumor cells subcutaneously at the flank site in 100 \u03bcL PBS. Tumors were measured twice a week. Tumor volume was estimated using the formula 3.14 \u00d7 [largest diameter \u00d7 (perpendicular diameter) 2 ]/6.", "Data expressed as means \u00b1 standard deviations (SD) are representative of at least two different experiments. Comparisons between individual data points were made by 2-tailed Student's t test. A p value of less than 0.05 was considered significant." ] },{ "paper_id": "62bd8c44c827603bc80a41b75fa8ba219969d48a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BCoV are widespread around the world and cause enteric or respiratory infections among cattle [9, 10] . These viruses are associated with different syndromes in cattle, ranging from neonatal calf diarrhea, winter dysentery in adult cattle, to respiratory infection in cattle of different age groups [11] .", "Coronaviruses belong to the family Coronaviridae and are the largest enveloped single-strand RNA viruses, ranging from 26 to 31 kilobases in genome size [1, 2] . These viruses infect a wide range of avian and mammalian species, and are responsible for enteric or respiratory infections [3] . There is a rising concern about the emergence of two human coronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle-East respiratory syndrome coronavirus (MERS-CoV), who emerged in 2002 and 2012, respectively [4, 5] . Both SARS-CoV and MERS-CoV have a zoonotic origin, revealing the importance of the control of coronaviruses associated with domestic animals in close contact with human populations [6] ." ] },{ "paper_id": "62c1b83631e0a74cb6f73b5c46460769271c21b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2.1.1. Antibodies or Recombinant Proteins Targeting gp120 CD4bs", "The gp120 CD4bs-Targeting Proteins", "The gp41 MPER-Targeting Antibodies" ] },{ "paper_id": "62d7719c3402b89f11ccb6a158dc2812f10bc234", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Female C3H/HeJCr and C3H/HeNCr mice were purchased from the National Cancer Institute (NCI, Fredrick, MD) and were used at 5 to 8 weeks of age. All animals were maintained in accredited facilities at the University of Iowa (Iowa City, IA).", "Single-cell suspensions of the various tissues were plated into 96well round bottom plates at 1.5610 6 to 2610 6 cells/well. Cells were washed with staining buffer (PBS containing, 2% FCS and 0.02% sodium azide), blocked with anti-FccRII/III monoclonal antibody (mAb; clone: 24G.2) and stained with fluorochromeconjugated antibodies. The following antibodies were used: CD4peridinin-chlorophyll proteins (PerCP; clone: RM4-5, Biolegend), CD49d-Alexa Fluor 647 (clone: R1-2, Biolegend), CD8-PerCP-Cy5.5 (clone: 53-6.7, Biolegend), CD11a-phycoerythrin (PE; clone: M17/4, eBioscience) and CD90.2-fluorescein isothiocyanate (FITC; clone: 53-2.1, eBioscience). Samples were acquired on a FACSCanto flow cytometer (Becton Dickinson, San Jose, CA) and analyzed using FlowJo software (Tree Star, Inc., Ashland, OR).", "All statistical analyses were performed using Prism software (GraphPad Software, Inc., San Diego, CA). Statistical significance was determined by using an unpaired t test. A value of p,0.05 was considered significant. Asterisks indicating significance were defined as follows: *, p,0.05; **, p,0.01; ***, p,0.001." ] },{ "paper_id": "62dd39338a12f7b81ae4e79e030c238c9ddaedfe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza is a highly contagious, respiratory disease that causes high morbidity and mortality worldwide. Typical symptoms of influenza infections range from fever, malaise, sore throat and muscular pain, to fatal pulmonary or cardiac complications [1] . The recent 2009 H1N1 pandemic caused a moderate death toll compared to previous pandemic events but the threat of an emerging pandemic virus remains high with human cases of highly pathogenic avian A/California/7/2009 A(H1N1)pdm09, A/Victoria/361/2011 (H3N2), B/Wisconsin/1/2010 (B/Yamagata-lineage) and B/Brisbane/60/2008 (B/Victoria-lineage) to ensure seronegativity against currently circulating influenza subtypes and lineages.", "The use of ferrets as an in vivo model of infection is not limited to influenza virus alone and includes other viruses of public health concern such as Hendra virus [27] , Nipah virus [28] and severe acute respiratory syndrome-coronavirus (SARS-CoV) [29] . With additional testing to validate its applicability to infections with other viruses, this improved method for monitoring ferret activity has the potential to assist in measuring both the pathogenesis and the impact of therapeutic interventions such as vaccines and antiviral drugs using the ferret model of infection. ", "To check these findings, we repeated the experiment using a higher dose of virus inoculum [10 5 TCID 50 influenza A(H1N1)pdm09 virus] and obtained similar results, with untreated ferrets experiencing 4 to 6 days of significantly lower activity, distance covered or velocity following infection, whereas oseltamivir-treated ferrets displayed no significant change in any of these parameters (S4 Fig.) . Comparison of video activity with manual scoring for assessing ferret activity" ] },{ "paper_id": "62df738127972a011de37d5c27776c48442889a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The models that were tested during the model structure selection procedure performed better than random. The AUC ratios of partitions were 1.84 (SD = 0.069, P = 0) and 1.85 (SD = 0.053, P = 0) with the same 20% omission rate.", "Parameter priors:" ] },{ "paper_id": "62e4e3bb07c0d49b928f9cfb46d2efedc04991dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The isolated plasmids were diluted to 100, 600, and 1,200 \u00b5g/ml with sterile PBS (137 mM NaCl, 2.7 mM KCl, 10 mM Na 2 HPO 4 , and 1.5 mM KH 2 PO 4 , pH 7.2), respectively, a day before use. Dilutions were prepared under aseptic conditions, in sterile serum glass bottles, closed with inert silicone stoppers and sealed with a tear away center aluminum cap (Sigma-Aldrich).", "The chicks were quarantined for 28 days after relocation and random testing was performed for avian influenza. This is required by avian influenza control measure before ostriches can be released and allowed to mix with other populations on any farm to which they have been transported.", "Fractions (1 ml) were collected and their protein concentration determined using a modified Bradford assay (40) . Expression and isolation products were analyzed using SDS-PAGE (40) and Western blot analysis (41) ." ] },{ "paper_id": "62f01258c5feeb75f8e3e3d628f5094b4b20b8c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Percent of inhibition (%) = (OD compound treated group \u2212 OD virus control )/(OD normal control \u2212 OD virus control ) \u00d7 100%.", "The EC 50 was calculated by regression analysis of the dose-inhibition relationship using SPSS 13.0. The selectivity index (SI) was evaluated with the following formula: SI = CC 50 /EC 50 .", "HEp-2 (human laryngeal carcinoma) cells were routinely grown in DMEM (Dulbecco's modified Eagle's medium) supplemented with 10% fetal calf serum (Gibco, Langley, OK, USA), penicillin (100 IU/mL), streptomycin (100 \u03bcg/mL) and 0.1% L-glutamine. Coxsackie virus B 4 strain was maintained in our laboratory and propagated in HEp-2 cells. The virus titer was estimated from cytopathogenicity of cells induced by viral infection and expressed as 50% tissue culture infectious doses (TCID 50 ) [20] ." ] },{ "paper_id": "62f5729ba9ae176c206cafd0221804a80772ea37", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "J774A.1 murine macrophages (ATTC, TIB-67) were cultured in Dulbecco's modification of Eagle's medium (DMEM) (cellgro, Mediatech, Manassas, VA, USA) supplemented with 10% v/v heat-inactivated fetal bovine serum (hiFBS) (Hyclone, Thermo Scientific, Rockford, IL, USA), 100 U/mL penicillin (cellgro), 100 \u03bcg/mL streptomycin (cellgro), 1.5 g/L sodium bicarbonate (BioWhittaker, Lonza, Walkersville, MD, USA) and 4 mM glutamine (cellgro). Cells were incubated in a humidified atmosphere at 37 \uf0b0C with 5% CO 2 .", "GFP expression was analyzed in live or 4% paraformaldehyde fixed cells. Cells were incubated with 300 nM DAPI (4',6'-diamidino-2-phenylindole dilactate; Invitrogen, Molecular Probes, Eugene, OR, USA) for nuclei stain for 3 min at RT. Images were obtained with an Olympus 1X81 motorized inverted fluorescence microscope (Center Valley, PA, USA) using Digital Microscopy software (Slidebook\u2122 5.0 software, Intelligent Imaging Innovations, Denver, CO)." ] },{ "paper_id": "63008713691bdb1d8eed016dbc54332f11d43739", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dengue E-protein was assessed in suspension HepG2 cells by intracellular staining and fluorescence activated cell sorter (Becton Dickinson, USA) and an Alexa-647 conjugated (AlexaFluor conjugation kit, Invitrogen, USA) monoclonal antibody (4G2, ATCC). Cells were scraped and permeabilized using BD FACS Perm/Wash solution (Becton Dickinson, USA) and acquisition and analysis was performed using CellQuest software (Becton Dickinson, USA)." ] },{ "paper_id": "6302e80258b85ac4f27c6db06bcf9e245e981ba9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by the institutional review boards (IRBs) of the Institute of Tropical Medicine, Nagasaki University, Ebetsu City Hospital, Kameda Medical Center, Chikamori Hospital, and Juzenkai Hospital. The requirement for obtaining written consent from all participants was waived by all IRBs because of the study's observational nature without any deviation from the current medical practice. Anonymized data were used for the analyses.", "Diagnosis of viral infection was made according to PCR results. Bacterial infection was diagnosed when any of the following criteria were fulfilled: 1) culture yielded pathogenic bacteria from microscopically purulent sputum samples (i.e., Geckler's classification groups 4 and 5) or normally sterile site samples; 2) PCR assays were positive for bacterial DNA in microscopically purulent sputum samples; or 3) urinary antigen tests showed a positive result." ] },{ "paper_id": "6308a19784dd34b796ecd3a981e32c01e866ee03", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A.", "B.", "B. " ] },{ "paper_id": "630a27f09c2caab65471e97cf1d538d364a2498a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Methods: Sera from 277 peafowls, including 272 blue peafowls (Pavo cristatus) and 5 green peafowls (Pavo muticus) originated from two geographic areas in Yunnan Province were assayed for T. gondii antibodies using the modified agglutination test (MAT).", "The present study was approved by the Animal Ethics Committee of Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (Approval No: LVRIAEC2011-006). All birds were handled in strict accordance with good animal practice according to the Animal Ethics Procedures and Guidelines of the People's Republic of China." ] },{ "paper_id": "630a94063d188ceeb2302472ac2e1a0da2e31216", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(TIF)", "PLOS Pathogens |" ] },{ "paper_id": "6312f554c8e95f9c8f3b5c0b150d88d35d657ae2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For all children, their legal guardians provided written informed consent for sample donation and allowed diagnostic tests to be performed. All participants assented to participate in the study.", "The Science and Bioethics Committee of the INER revised and approved the protocol (B-2613) and the consent procedure." ] },{ "paper_id": "63205fe99a388f19fde06f422c9ce6c1ddfc52f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Glioblastoma is the most frequent and most malignant primary brain tumor. Despite advances in neurosurgery, radiation and chemotherapy, the prognosis of patients remains poor with a median survival of 14 months [1] .", "Rats bearing glioblastoma xenografts were treated by daily i.p. injections of 50 mg/kg ganciclovir (GCV, Roche, Basel, Switzerland).", "For analysis of transduction efficacy, consecutive sections (every 20.-30.) throughout the tumors were examined under a fluorescence microscope (Nikon) with an automated stage using 106magnification. The transduction volume was calculated using Nikon Lucia imaging software." ] },{ "paper_id": "633715b2acfa849d613285b7a01531072c2b3422", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The NP-specific IgG-ELISA, which is similar to the GP 1,2 -specific ELISA except for the purified recombinant RESTV NP with a histidine tag at the C-terminus, has been previously reported [6, 16] .", "Conclusions: These results imply that both the antibody response to GP 1,2 and the proinflammatory innate responses play significant roles in the recovery from RESTV infection in cynomolgus macaques." ] },{ "paper_id": "634b79269e0f00d35bcea1a2dc7643884b8c6b3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sf9 (Spodoptera frugiperda) insect cells were maintained at 27\u00b0C while being supplied with Sf-900IISFM medium (Gibco). Vero E6 cells (African green monkey kidney epithelial cells) were maintained at 37\u00b0C with 5 % CO 2 in Dulbecco's modified Eagle's medium (Gibco), supplemented with heat-inactivated fetal bovine serum (8 %), penicillin (100 units/ml), and streptomycin (100 \u03bcg/ml)." ] },{ "paper_id": "634b8c282afdd06201cb2531fb70985d92270271", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/ mBio.02320-16.", "TABLE S1, DOCX file, 0.1 MB.", "Statistics. Student's unpaired t test or Mann-Whitney U test was used to analyze differences in mean values between groups. All results are expressed as means \u03ee range or standard error of the mean. P values of \u05450.05 were considered statistically significant." ] },{ "paper_id": "634d9f6010d3e4f1586f4382b5c5c89e316d58bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A " ] },{ "paper_id": "635bc39e204a9e098961ccaef51d67e83226b07e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cyst burden or neuropathology has been reported in some strains of mice infected for a month or two [15, 36, 53] . However, one to two months following infection would still be considered an acute or subacute infection in humans [1, 54] .", "All measures were determined for the pilot and initial cohort. Illness behavior, general appearance, activity, gait, exploratory behavior, and sensorimotor function were assessed in the additional, kinetic studies.", "Illness behavior Sick rodents often show characteristic hunched posture, ruffled fur and a reluctance to move. Illness related behaviors and general appearance were assessed using the following scales:" ] },{ "paper_id": "635ceee37108f92116fe91230b8d14b7ec5373be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DENV is transmitted to humans by mosquitoes (Aedes aegypti and A. albopictus). A. aegypti can pick up DENV from people showing no symptoms or oligosymptom, resulting in silent transmission [11] . A positive association was established between DENV infection in humans and mosquitoes at very fine spatiotemporal scales in the natural setting; specifically, human cases were reported at about one week after positive A. aegypti in one study [12, 13] .", "The degree of agreement between two assays was assessed by calculating Cohen's kappa values." ] },{ "paper_id": "6360e58e9bb14d3e03b5c78025509ea6f9482bec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal experiments were done in accordance with institutional and national ethical guidelines. The protocol was approved by the Ethical Committee for animal experiments of Southwest University for Nationalities.", "Primary cultures of chicken embryo fibroblasts (CEF) were prepared from 10-day-old specific-pathogen-free (SPF) chicken embryos (Yebio Bioengineering Co. Ltd, Qindao, China) as described previously [12] , and maintained in DMEM supplemented with 10% fetal bovine serum (FBS). The cells were seeded (approximately 5 \u00d7 10 6 cells/well) in 24-well culture plates. Then the cells were infected with 100 TCID 50 (50% tissue culture infective dose) ALV-J strain NX0101, obtained from the China Animal Health and Epidemiology Centre in Qindao, China. After 1 h incubation, the cells were washed and further incubated in media with 2% FBS. Host-virus interactions were tested in triplicate wells, which were harvested at 0, 24, 120 and 192 hours after infection for RNA extraction.", "Total RNA was extracted from each sample using commercial RNAiso Reagent (TaKaRa, Japan) and purified with RNase-free DNase (TakaRa, Japan) following the manufacturer's instructions. Complementary DNA (cDNA) was synthesized using the PrimeScript W RT reagent (TaKaRa, Japan) with random primers following the product instructions. cDNA products were treated with RNase H to remove remnants of RNA, and stored at\u221220\u00b0C until the time of real-time PCR testing." ] },{ "paper_id": "636fb28e842b058bff497388c5444fc1f53cb61c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The separation and preservation of the DHAV H strain were performed at the Institute of Preventive Veterinary Medicine of Sichuan Agricultural University. Duck embryo fibroblast (DEF) cells were cultured in modified Eagle's medium (MEM; Gibco) containing 10% newborn bovine serum (NBS; Gibco) and cultured in a humidified 37\u00b0C, 5% CO 2 incubator.", "(Continued on next page)" ] },{ "paper_id": "63771fc756683bf14c7f7e169990c7268b35d8ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Timely knowledge of the etiology of inflammatory conditions is crucial. Not only does it facilitate appropriate treatment, but also unnecessary interventions may be avoided. In light of the critical shortage of new antibiotics, reduction in antibiotic prescription is warranted.", "Peripheral blood mononuclear cells (PBMCs) were isolated from buffy coats of healthy individuals after informed consent. Briefly, PBMCs were isolated by density gradient centrifugation using Ficoll-Paque PLUS (GE Healthcare, Zeist, The Netherlands) and collecting the white interphase. Cells were washed twice in cold PBS and concentrations were adjusted to 5 \u00d7 10 6 cells/ml in RPMI-1640, supplemented 2 mM L-glutamine, 1 mM pyruvate and 50 \u03bcg/ml gentamicin (GIBCO Invitrogen, Carlsbad, CA). Mononuclear cells (5 \u00d7 10 5 ) in a 100-\u03bcl volume were added to round-bottom 96-well plates (Greiner, Nurnberg, Germany) and incubated with either 100 \u03bcl of culture medium (negative control), or LPS from E. coli O55:B5 (10 \u03bcg/ml; Sigma-Aldrich, St Louis, MO), Pam3Cys (10 \u03bcg/ml) or heat-killed E. coli ATCC 35218 (10 7 micro-organisms/ml). After 24 hour incubation at 37\u00b0C, the supernatants were stored at -80\u00b0C until measurement of sTLR2, sTLR4 and IL-6." ] },{ "paper_id": "637c82c1bb56fb9d7ff5a5a2b1c9645a80180065", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 7:17501 | https://doi.org/10.1038/s41598-017-17951-5" ] },{ "paper_id": "6387603fb5f8eda220411438a86234c475aa728e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using Prism 7.0 (La Jolla, CA, USA) with unpaired (Student's) t-test. ", "Total RNA was extracted from primary, LCMV-infected cells using TRI reagent (Molecular Research Center Inc.). RT reaction was carried out using RT master mix with reagents obtained from Froggabio (North York, ON, Canada). PCR was performed using Taq 5X Master Mix (Froggabio) and the following primers (Forward and Reverse) obtained from Integrated DNA Technologies (Coraville, IA, USA) for LCMV Nucleoprotein (F: 5\u2032-TCC ATG AGA GCA CAG TGC GGG GTG AT-3\u2032, R: 5\u2032-GCA TGG GAG AAC ACG ACA ATT GAC C-3\u2032) and 18S control (F:5\u2032-AAACGGCTACCACATCCAAG-3\u2032, R: 5\u2032-CCTCCAATGGATCCTCGTTA-3\u2032).", "In contrast, M(IL-4) induced the lowest proliferation (20%) by antigen-specific CD8 + T cells (Figures 5A,B) .", "inTrODUcTiOn Tissue macrophages (M\u03a6) comprise an important member of the mononuclear phagocyte system where they regulate inflammation, cancer, and autoimmunity (1) . They are involved in innate and adaptive immune responses to invading pathogens (2) , and adapt their phenotype and function in accordance with their environment through a process termed M\u03a6 polarization (3) (4) (5) . It is now understood that both tissue M\u03a6 and bone marrow (BM)-M\u03a6 can develop into pro-inflammatory (M1) or anti-inflammatory (M2) (6) (7) (8) ." ] },{ "paper_id": "638c36249e56a71ae71edd5391b1ca7fafd82daf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The topology of the BI tree was identical to that of the ML tree, except for a few branches with low support values. Thus, only the ML trees are presented here and used for further cophylogenetic analyses. Phylogenies tend to be well supported for more recent divergence events, but not deeper nodes. Nodes with bootstrap values $50 are labeled on all tanglegrams (Figures 1-6 ). " ] },{ "paper_id": "638c6b2e4772152a6cba52184c98dec9ca288c16", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In summary, this case suggests that macrolides are a potential treatment option in HIV-infected patients with mild BOOP. In cases that are otherwise unexplained or unresponsive to treatment, BOOP should be taken into consideration and surgical biopsy performed to confirm a diagnosis of BOOP.", "The limitations of this case report are as follows. The patient's CD4 T-cell count improved significantly (from 5 to 181 cells/mm 3 ) from the time of diagnosis of BOOP until the end of macrolide treatment. This improvement in immune status may have provided protection from other opportunistic infections. Empirical treatment with ceftriaxone may have improved the clinical course, and there is also the chance that the BOOP resolved spontaneously. Our evaluation of the patient's response to clarithromycin treatment may not have been accurate for the above reasons.", "Bronchiolitis obliterans organizing pneumonia (BOOP) is a type of diffuse interstitial lung disease characterized by the pathology of fibroblastic plugs in the lumens of the respiratory bronchioles, alveolar ducts, and alveoli [1] . Various lung diseases have been reported in patients infected with human immunodeficiency virus (HIV), but there are few reports of the occurrence of BOOP in HIV patients and prior to this study, there was no clinical case report in Korea [2] . Here, we describe a unique case of BOOP in a HIV-infected patient diagnosed by surgical lung biopsy and successfully treated with clarithromycin." ] },{ "paper_id": "638ee8a365b38f69e411c8d92bb90c2b6c4fb405", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The datasets generated during the current study are available from the corresponding author on reasonable request." ] },{ "paper_id": "639215bc06ff8518135073d907b7bf6a9089c1fc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Controlling the epidemic of HIV infection worldwide remains a major challenge. Indeed, even though significant success in controlling the disease has been achieved by understanding the virus biology and by developing targeted drugs, vaccine-based preventive measures are still needed. Major challenges toward this goal are the antigenic variability and multitude of virus strains (54) . Several viral vectors have been tested as vaccines against HIV, most notably poxviruses and Ad, but have met little success in protective efficacy and even adverse effects in terms of protection against HIV infection (1). This was, in particular, the case of the STEP human trial which used Ad vectors encoding HIV proteins (55) .", "Nipah virus (NiV) and Hendra virus (HeV) are closely related, recently emerged paramyxoviruses, belonging to the henipavirus genus. Both viruses are capable of causing considerable morbidity and mortality in a number of mammalian species, including humans (45) . Infection of humans is characterized by a rapid and extensive spread of the virus in several organs with symptoms including respiratory distress and encephalitis (46) . These symptoms can be reproduced by experimental infection of several animal models including hamsters (47) . Because of their high pathogenicity in humans, their broad tropism and the absence of any vaccine or treatment, henipaviruses are presently classified as biosafety level 4 (BSL4) agents and considered as potential biothreats (48) .", "Both of these strategies illustrate the potential of capsid modification for manipulating the immune response and it is likely that, in a very near future, new AAV vectors specifically selected for their ability to induce strong transgene-specific immune responses will continue to emerge.", "The currently available vaccines are insufficient to keep in check the seasonal influenza outbreaks that affect people of all ages and claim at least one millions of lives in children up to 5 years of age worldwide (61) . The reason vaccines are relatively less successful is the high variability of the virus and highly type-specific nature of the vaccines that need to be designed for the actual emerging virus strain. The unavoidable delay between the identification of a new variant and availability of the appropriate vaccine -particularly owing to the laborious manufacturing process of virus replication in chicken eggs -leaves the population unprotected at least against the first wave of a new epidemic." ] },{ "paper_id": "63a0d9767212d4316c91660dc4eedc8cb3fe527f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data are expressed as mean AE S.E.M in quantitative experiments. Statistical analyses of the differences between groups were performed with ANOVA. A P-value of less than 0.05 was considered statistically significant.", "Berberis is a traditional Chinese medicine. Berberine is an alkaloid that is isolated from Berberis having biological and pharmacological activities, including antibacterial, anti-inflammatory, and anticancer activities, and has been widely used in human health care [16] .", ". (E AB : the inhibition rate of drug A plus drug B; E A : the inhibition rate of drug A; E B : the inhibition rate of drug B).", "All animal experiments were carried out according to the guidelines and approval of the Institutional Animal Care and Use Committee of Xi'an Jiaotong University." ] },{ "paper_id": "63a206dc7356041e3054110691cbd8146278cee1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dromedary camels (Camelus dromedarius Linnaeus, 1758) are multi-purpose livestock, domesticated for their adaptations to survive, reproduce, and produce (e.g. milk and meat) in hot-arid environments [1] . The two main hot-desert adaptations in dromedary camels are both extreme thermal tolerance and their high level of water conservation [2] . a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 nature of room-temperature storage prior to DNA extraction (unlike blood, which needs refrigeration).", "Nine unrelated research camels housed at the Camel Research Center in King Faisal University in Saudi Arabia were used for the study. The camels represent three widely recognized camel breeds in the Arabian Peninsula ('Majaheem', 'Sofor', 'Waddah') [31] ." ] },{ "paper_id": "63a98dbb196b0ceacae4a16715ca8540b857cd22", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results are shown as mean\u02d8standard deviation (S.D). ANOVA was used to test statistical significance between groups. In all cases, p < 0.05 was regarded as statistically significant and p < 0.05 was marked with **.", "(A) ", "HA-Forward 5 1 -TTCCCAAGATCCATCCGGCAA-3 1 HA-Reverse 5 1 -CCTGCTCGAAGACAGCCACAACG-3 1 GAPDH-Forward 5 1 -AGGGCAATGCCAGCCCCAGCG-3 1 GAPDH-Reverse 5 1 -AGGCGTCGGAGGGCCCCCTC-3 1" ] },{ "paper_id": "63aeb2ae0cf9c92c1d5b86516efc0bc748e805e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ". . 0 15, 0 35, 0 5), alternative to a non-infectious state followed by permanent immunity (panel b). Model 3 is a variation of model 2 that considers temporary immunity of average duration \u03c9 \u22121 (panel c).", "1 , to account for reduced mixing between different species (\u03b1 = 0 refers to non-mixing conditions).", "Bats are natural reservoirs of the largest proportion of viral zoonoses among mammals, thus understanding the conditions for pathogen persistence in bats is essential to reduce human risk.", "The uncovered strong spatial component to transmission dynamics may help understanding the observed spatial diffusion of the virus at a larger scale on the continent and across a diverse range of host species, through long-range migration and seeding of local populations. Given the primary role of bats in carrying the largest proportion of zoonotic pathogens across mammals, determining how hosts enable persistence and which host species are critical in a multi-host infectious disease setting is essential for disease prevention and control. Our framework can readily be extended also to other zoonotic viral pathogens of public health concern circulating in spatially dispersed bat populations." ] },{ "paper_id": "63af0d8b639b0abe14d9be9eaa3a135bb9a9eaf1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "63b21e59e43206a09eaa36fdc5233f22af7515e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A deleterious consequence of excessive telomere shortening is the premature induction of replicative senescence of CD8+ T cells [21] . While senescent cells are unable to expand, they can survive for extended periods of time, occupying immunological space where functional immune cells could exist [22] . The accumulation of senescent CD8+ T cells has been proposed to play a role in failed immune surveillance and in facilitating the development of metastasis of certain cancer types [23] . Interestingly, some studies proposed that it may be possible to reverse this phenotype by reactivating telomerase expression [23, 24] .", "T-cell exhaustion is a state whereby normal T-cell functions are impaired as a consequence of chronic antigen stimulation. The details of T-cell exhaustion are still being defined, but include: 1-impaired memory T cells; 2-impaired CD8+ T-cell effector responses; 3-impaired CD4+ T-cell responses; 4-resistance to apoptosis; and 5-accelerated immune senescence ( Figure 3 ).", "Like HIV, hepatitis B and C (HBV and HCV) viruses are productive, chronic viruses and display T-cell exhaustion from telomere shortening. HBV and HCV are the major causes of acute liver infection; however, only HBV and HCV are responsible for a large proportion of global, chronic liver disease. Anywhere from 60-90% of HBV and HCV infections reroute to chronic infection. A delayed immune response to the ever-changing viral mutational landscape allows the virus to adapt and persist, especially in HCV infections. In fact, chronic viral liver disease is nearly completely due to the adaptive immune response where immunopathology, consisting of a low-level CTL response, destroys hepatocytes and leads to liver cirrhosis and hepatocellular carcinoma (HCC) [69] .", "One target that could prove promising is P-Selectin Glycoprotein Ligand 1, PSGL-1. Knockdown of PSGL-1 led to improved anti-viral response and down-regulation of not only PD-1, but several inhibitory receptors, including CD160, BTLA, TIM-3, and LAG-3 [152] . Blockade of PSGL-1 could therefore be a more effective therapeutic target against T-cell exhaustion than targeting individual inhibitory markers alone. Since telomere attrition appears linked with long-term T-cell exhaustion, another concern to address is whether telomerase therapy needs to be added in addition to anti-exhaustion therapy. Rebounding exhausted T cells would still have critically shortened telomeres that are unable to up-regulate telomerase. Telomerase may be required to restore the proliferative capacity of the newly effective T cells." ] },{ "paper_id": "63c22b2cf82f4e4e9942d252fc33975a6db4d0d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Matchmaker GAL4 Two-Hybrid System 3 (Clontech) was used for the screening of a human fetal brain cDNA library (Clontech) with pGBKT7-HBc as bait. Co-transformants were selected on synthetic dropout (SD), media lacking leucine, and tryptophan (SD/-Leu/-Trp) and were validated by growth on SD, media lacking leucine, tryptophan, adenine, and histidine (SD/-Leu/-Trp/-Ade/-His) and containing 5-bromo-4-chloro-3-indolyl-\u03b1-D-galactoside (X-\u03b1-gal). Then, positive colonies were sequenced (Invitrogen, Carlsbad, CA, USA).", "5'-CGTCGCCAACCATCTTCCTGTCCCTAG-3'; IFITM2, forward: 5'-CATCATCATCCCAGTGTTGG-3', reverse: 5'-GATAAAGGGCTGATGCAGGA-3'; IFITM3, forward: 5'-CAAGGAGGAGCACGAGG-3', reverse: 5'-TTGAACAGGGACCAGACG-3'; \u03b2-actin, forward: 5'-CTCTTCCAGCCTTCCTTCCT-3', reverse: 5'-AGCACTGTGTTGGCGTACAG-3'; GAPDH, forward: 5'-GATGGCAAGATCTTCTGCGTG-3', reverse: 5'-CCGTCGACTCACAGGAAATAGTCGGC-3'.", "The siRNAs were designed using Oligo 6.0 software, and synthesized by GenScript Co. Ltd. (Nanjing, China) as follows: siIFITM1: siRNA1: 5'-AAACCUUCACUCAACACUUCCUU-3', siRNA2:", "5'-AAACUUAAGAGAAAUACACACUU-3'; siHBc: siRNA1: 5'-AAACUUUACUGGGCUUUAUUCUU-3', siRNA2: 5'-AAGAGAAACUGUCCUUGAGUAUU-3';" ] },{ "paper_id": "63c2fc6a6f91490370687f314718221c70e0f9b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "China re-oriented its malaria programme from control to elimination in July 2010. In order to look for infections and to interrupt transmission, the focus was shifted from high levels of coverage of interventions to an emphasis on completeness and timeliness of activities. Methodology of reactive case detection (RACD) was used in eliminating malaria. Fig. 3 ).", "The study was carried out in Hekou County (103\u00b023\u2032-104\u00b017\u2032E, 22\u00b030\u2032-23\u00b002\u2032S; altitude from 76.4 to 2354.1 m), which is located at Red River Valley, southeast of Yunnan Province, China, and shares a border of 193 km with Vietnam (Fig. 1) . The county has a population of 104,609 people (2010) living in an area of 1332 km 2 , with a tropical monsoon rainforest climate and an annual mean temperature of 23.0 \u00b0C [14] . Anopheles minimus is the primary malaria vector [15, 16] . Indigenous malaria transmission was interrupted at Hekou County in 2011, and it passed the provincial elimination assessment in 4 November, 2015.", "The study design was an ecological study. Malaria burden before 1951 and the 64-year dynamics from malaria hyperendemicity to elimination are described. Association between malaria incidence and socio-economic development and environmental change are analysed by single and bilinear regression." ] },{ "paper_id": "63c5c1f61a3aadefcb0e9c01bc4e67cc0a99d8f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Table 3 ). " ] },{ "paper_id": "63c9d5537c05b45dde4b7584c66a95e839b582ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA was extracted from the supernatants of cultured viruses or from clinical specimens by RNeasy Mini kit (Qiagen, Hilden, Germany) according to the manufacture's instruction. Virus RNA extractions were conducted in Biosafety Level 3 (BSL-3) facilities.", "The specificity of the duplex real time RT-PCR assay was validated by using human genomes and a panel of respiratory tract viruses including human seasonal H3N2 influenza viruses, seasonal H1N1 virus, human respiratory syncytial virus A and B, human coronavirus 229E, human coronavirus OC43, influenza B virus, human parainfluenza virus and human adenovirus. All samples were tested negative (data not shown).", "In March and April 2009, a novel swine-origin pandemic H1N1 influenza virus appeared and spread worldwide. The pandemic of H1N1 2009 influenza virus poses a public health threat. According to the World Health Organization (WHO), as of 30 April 2010, worldwide at least 17919 death cases have been reported [1] . Compared with influenza A H1N1 virus, the highly pathogenic avian influenza virus H5N1 has a much higher mortality rate: H5N1 has a mortality rate of more than 50% while novel pandemic H1N1 has only about 1% [2] . Nevertheless, pandemic H1N1 and highly pathogenic H5N1 manifest similar clinical symptoms at the early stage of infection [3] . Early detection of these two pathogens is an essential prerequisite for effective control and prevention of the pandemic." ] },{ "paper_id": "63cb88b9fee3f16bcf3666b4665e445325addf9d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition to encephalopathy and orofacial infection, HSV-1 also infects the eyes leading to 8 cases of herpetic keratitis per 100,000 population every year [6] . Keratitis refers to inflammation of corneal epithelium due to a number of irritants such as infections by viruses, bacteria, and fungi. Herpetic keratitis is the major cause of corneal blindness, with unilateral visual impairment occurring in at least one-third of patients with recurrent disease [7] .", "Protein extract was subjected to 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis and transferred onto nitrocellulose membranes. The blots were blocked using PBS with 5% (wt/vol) non-fat dry milk and washed in PBS. Rabbit anti-Egr-1 polyclonal antibody (Santa Cruz SC-110x) or cAMP response element binding (CREB) Ser-133 phosphorylation (Abca-m#ab32096) was used at a dilution of 1:1,000. Anti-a-Tubulin mouse antibody (Calbiochem, Cat#: CP06, San Diego, CA) was added at a dilution of 1:10,000. The chemiluminiscent signal from the membranes was detected by Syngene GeneGnome HR Bioimaging system (Frederick, MD). The protocol was performed essentially as described by the manufacturer.", "Cells, viruses and culture conditions VERO (derived from kidney epithelial cells of the African Green Monkey) cells and HEK293 cells were grown in DMEM supplemented with 10% FBS. SIRC (Rabbit cornea) cells obtained from ATCC (Cat#: CCL-60) were grown in MEM supplemented with 10% FBS. The RE-EGFP strain of HSV-1 was used throughout the study [18] . Unless otherwise indicated, all viral infections were carried with a MOI of 5 for 1 hour." ] },{ "paper_id": "63cbd57061c1709dc5aca57716a3ab95f6ba6446", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Table S1 Data used in our analysis. This comma separated file (CSV) has 5566 lines and 38 columns. The first line is a header specifying the contents of the columns. (CSV)", "with l~1:99+0:07 (99% confidence interval; R 2~0 :995). For sure, Equation (2) can be associated from Equation (1) with the assumption that accumulating a discrete time series is a good approach for an integration process over a continuous variable. In particular, the numerical solution to the continuous approach", "First we considered Y t , the total annual absolute frequency at each year t, obtained by summing y i,t over the total of N Brazilian cities, Y t~P N i~1 y i,t . Figure 2A shows the temporal evolution of Y t and compares it with the curve Y (n; t)~b a" ] },{ "paper_id": "63cfe8fa64e33300471ac1e2a5b87cb52be553d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Based on data generated by illumina sequencing, we constructed three libraries that yielded a total of 23 331 ", "Extraction of total RNA was carried out using the RNeasy mini Kit with on-column DNase treatment according to the manufacturer's instructions (Qiagen, Hilden, Germany). The concentration and quality of RNA was analyzed using a Nanodrop ND1000 (Nanodrop Technologies, Wilmington, USA) and Agilent 2100 Bioanalyzer (Agilent Technologies, USA), respectively." ] },{ "paper_id": "63cfec0de40f78765303a3fd6f853c672a193320", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For analysis of peripheral blood lymphocyte populations, patients' PBMCs were stained with CD3, CD4, CD8 and CD25 (all from BD Biosciences, San Jose, CA). Flow cytometric analysis was performed using a LSR II (BD Biosciences). The data were analyzed using FlowJo software (Tree Star, San Carlos, CA)." ] },{ "paper_id": "63d069bab41ecd46a0c6462f46f27844322cad61", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "from this it follows that dN/dk = 0 when \u2212(A + 2Bk)x = Byk 2 or that," ] },{ "paper_id": "63dda1b262c68b84a8058a50480f0d5ae1b4f2ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Schwartz. CHIKV-118-GFP, previously rescued by transfecting the recombinant viral genomic RNA and passaging thrice in BHK21, was passaged twice in C6/36 following the method described elsewhere [35] .", "where m(%viability) DMSO and 4s (%viability) DMSO are the mean and 4 standard deviations of the DMSO vehicle control, respectively.", "Cluster analysis was done using a molecule-clustering module from Pipeline Pilot (Accelrys Software Inc., San Diego, CA, USA). Structural relationship among the primary hit compounds was analyzed using the Tanimoto coefficient structural similarity [41] . The core scaffolds of hit compounds that exhibited anti-CHIKV activity were selected for structural analysis." ] },{ "paper_id": "63e680dd648bb477a87f55d53d3f0ff3f2c18e0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "but could pose high impact on public health and global economic activities.", "where R comm = \u03b2 0 /(\u03b3 a0 + \u03b3 I ) and", "R hosp = \u03b2 0 l 0 (1/\u03b3 r )(\u03b3 a0 /(\u03b3 a0 + \u03b3 I ))." ] },{ "paper_id": "63f04bb7051a4d43795615877a0a351ca5d79740", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For those syndrome groups with severe symptoms, including skin rash, neurological symptoms and death/ coma that might be related to bioterrorism attacks, there was no significantly cyclic or seasonal patterns ( Figure 4J , 4K and 4L). One spike of syndrome cases with clinical severity (severe syndrome) appeared in mid-May, but that occurred as a result of one hospital sending duplicate data that escaped from our check algorithm ( Figure 4L ).", "The author(s) declare that they have no competing interests.", "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "63f58030dbe7e46d82ccf7794885cac6a912351f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "63f776d8ae5084cc5a3aa5e09aa55f1a302b1b1f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The phylogenetic tree ( Figure 4) The mean of genetic distance among the clades is 0.4897 (SD = 0.0381). The mean of genetic distance among the subclades is 0.1773 (SD = 0.0147). The mean of genetic distance within the clades is 0.0929 (SD = 0.0095). The mean of genetic distance within the subclades is 0.0732 (SD = 0.0073).", "This study suggested that subclade 1.1 was worldwide predominant and subclade 1.4 was predominant in China. Their predominance may result from that they were of greater transmission ability than others. Vaccines targeting these predominant subclades may be better than those targeting other subclades in the relevant regions.", "Taken together, this study shed new insight into the diversity, distribution and evolution of avian CoVs. It also provided important information for the relevant vaccine research." ] },{ "paper_id": "63f9ef8701b8b68aab585d81fa58bd567ade8e4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data were presented as mean \u00b1 standard deviations (SD) of three independent experiments. The differences between groups were assessed by Student's t test. A P value < 0.05 was considered statistical significant. All statistical analyses were performed using GraphPad Prism." ] },{ "paper_id": "63fb289aa51f77907321626b838ccae5e0939dc1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "with c virus as the total virus concentration in virions/mL. The relative standard deviation of the method was \u00b1 0.09 log (HA units/0.1 \u03bcL) (Kalbfuss et al. 2008 ).", "The implementation of the hybrid strategy in benchtop bioreactors showed a similar performance compared to analogous experiments in shake flasks and led to a clear improvement of virus yields towards perfusion (for HCD) and batch (for conventional cell densities). Next, broader benefits in relation to reported production strategies with different cell substrates and its advantages for a potential industrial application were analyzed.", "The hybrid cultivation yielded a maximum HA titer of 3.3 log HAU/100 \u03bcL (3.8 \u00d7 10 10 virions/mL) at 60 hpi (Fig. 4) . This represented a fivefold increase compared to the reference perfusion cultivation (Fig. 4) . Compared to a conventional batch process (Table 2) , the increase was sevenfold." ] },{ "paper_id": "63fcbf2d0f0015b1b4ab01e20349ca7ee4c82dd4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "5\u2032 Race and sanger sequencing. 5\u2032 RACE was used to obtain the missing leader sequence (52 bp).", "Bioinformatics. Read quality was assessed using FastQC and trimmed using Trimmamatic 27 (Version 0.36)." ] },{ "paper_id": "64053a0785373722d802b6a2fac9db7489b1474e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data S1 State-of-origin of the animal shelters.", "Text S1 Details of the epidemic model. (PDF)", "which is bounded above by d/(c+d) as R 0 becomes large (see Supporting Information, Text S1, Section 1.6).", "We compiled all available CIV HA1, NP and M gene segment sequences from GenBank and the Influenza Research Database (www.fludb.org) and by sequencing samples provided by the Animal Health Diagnostic Center (AHDC) at Cornell University. For the sequencing of the virus samples obtained from AHDC we extracted viral RNA using Qiagen viral RNA mini kit and synthesized cDNA using Avian Myeloblastosis Virus (AMV) reverse transcriptase and influenza universal primer Uni12. Three gene segments, HA1, NP and M, were then amplified by PCR with gene specific primers (primer sequences are available upon request) for all samples. The PCR products were purified using EZNA Cycle-Pure Kit and sequenced by the Sanger method. All sequences derived here have been submitted to GenBank and assigned accession numbers KM359803-KM359864." ] },{ "paper_id": "6413beddc3f8af0a526e84316ae46e44dab8ee7e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "of all ages suffer from a serious fungal infection each year globally [11] . Notably, over 1.5 million of these individuals are estimated to die from their fungal disease [12] .", "The fact that there are no licensed antifungal vaccines underscores another clear failure in science. Similarly, reliable diagnostic methods are available for a very limited number of mycoses [23] , and therapeutic options are restricted to a few classes of drugs that too frequently are associated to both intrinsic and acquired resistance [24] , toxic, and expensive [25] . In fact, innovative tools to combat invasive mycoses are rare and of slow development. For illustration, the most recently developed antifungals (echinocandins) were approved for clinical use in 2002 [26] , reinforcing a major science failure in the area. It is noteworthy that this class of drugs is ineffective against various high-mortality mycoses [25] .", "On the basis of currently available therapeutic and diagnostic tools, short-and mediumterm impact actions also need to be implemented. For example, in 2019, WHO reinforced the need to use the Histoplasma capsulatum antigen detection test to diagnose histoplasmosis [47] . This test allows the diagnosis of the disease in more than 85% of patients within 48 hours, which would hasten the implementation of lifesaving antifungal therapy. Without proper diagnosis, patients are usually treated for tuberculosis, which has similar clinical symptoms. Under these conditions, patients usually die within 1 to 3 weeks. It is estimated that 48,000 lives could be saved over 5 years if appropriate diagnosis and treatment approaches are implemented for histoplasmosis." ] },{ "paper_id": "642113801b5c8906fb7eb9bf989d0c4fabd712e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study highlights the need for integrated One Health approaches to model zoonoses more effectively in order to betterinform disease control and prevention. Zoonoses remain a neglected group of diseases, under-prioritised in national and international health systems. " ] },{ "paper_id": "642e03f3b71051b01c77af78f51bb4ef5d00ad08", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The other types (n = 54) p value *WBC, \u00d7 10 9 cells/L, n = 68 11.69 6.85 (1. substitution (C to T) in hexon assembly-associated protein of isolates IP02_2011. Isolate IP03_2011 had one more non-synonymous substitution located in 34 kDa protein (G to T).", "CAP is a common and serious infection that afflicts children throughout the world 36 . It is the world's most important cause of child death 37 . In the United States, the annual incidence of pneumonia was 15.7 cases per 10,000 children, with the highest rate among children younger than 2 years of age (62.2 cases per 10,000 children) 38 .", "Scientific RepoRts | 6:37216 | DOI: 10.1038/srep37216" ] },{ "paper_id": "643ce1300f0c4056a709e1b13269a51924960a3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An unpaired t-test was used for statistical analysis of the drugs' effects." ] },{ "paper_id": "644979755526ea0ca2ce4990c87f0dd9342aaf89", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Collectively, these data indicate that there is a statistically strong correlation between PBNA and RFFIT in qualitative and quantitative analyses of clinical samples whereas the former is at least 25 times more sensitive.", "The current assays for immunogenicity determination of rabies vaccines and immunoglobulin have several inherent limitations. Specifically, vaccine-induced or natural infection-elicited antibody responses against rabies virus are determined using serological assays including the rapid fluorescent focus inhibition test (RFFIT) 8 , fluorescent antibody virus neutralization (FAVN) test 9 and enzyme linked immunosorbant assay (ELISA) 10 . Currently, the \"gold standard\" for in vitro assays are RFFIT and FAVN, both of which are routinely used in WHO reference laboratories; however, both assays require the use of live rabies viruses which must be handled in biosafety level 2 (BSL-2) containment facilities 8, 9, 11 . Although inactivated viruses are used as coating antigens in", "In vivo bioluminescence imaging analysis. Bioluminescence analyses was conducted using IVIS-Lumina III imaging system (Xenogen, Baltimore, MD) as described previously 45, 46 . Briefly, mice were anesthetized by intraperitoneal (i.p.) injection of pentobarbital sodium (40 mg/kg body weight), followed by an i.p. injection of the substrate D-luciferin (150\u03bc g/g body weight, Xenogen-Caliper Corp., Alameda, CA). Seven minutes later, bioluminescence was detected for each mouse in the imaging chamber with an acquisition time of 1 min. The relative bioluminescence was calculated using a photon-per-second mode with normalization for the imaging area (photons/s/ cm 2 /sr) (total flux) as previously described 47 .", "In the neutralization assay, although the addition of DEAE-dextran could reduce the virus volume to yield similar levels of SNR, this had little effect on the final results. Based on these observations, 10 \u03bc g/ml of DEAE-dextran was chosen to enhance the infectiousness of the pseudovirus without causing cytotoxicity." ] },{ "paper_id": "644b4c7ff157be28bf0c216d2d6cb9edef3e1d4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "64504909cf5e7b5249b8c617c2d1973a3c301e85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Zika: A talk showed that dengue 2 antibody levels appear to determine susceptibility to ZIKV infection with high dengue 2 titers being protective, while lower titers enhance infection.", "I.", "The last plenary session included three presentations that addressed new approaches to define protective immunity and drug discovery." ] },{ "paper_id": "64536ef4a2d1df35305df73397d745ae55be8d47", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical data were prospectively collected with use of a standardized form by the treating physician. Tables 1, 2 and 3 summarize the data collected. Missing information, laboratory results and, when available, radiology reports were retrieved from the patient's medical electronic record.", "Wheezing, n(%) 95(47. ", "The characteristics per virus group are presented in Tables 1, 2 and 3 and are highlighted per virus group below." ] },{ "paper_id": "6460342e18e6d3fea8f62630e12b083d46a6eb99", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "clicks. Because questions are labelled with keywords and linked to papers in which they were initially mentioned, suggested associations of potential appropriate questions can be easily accessed.", "List of the published papers analysed that used the question (full article references, links to PubMed and Google Scholar, journal impact factors [IF]).", "To maximise the likelihood of compatibility among questionnaires, we paralleled the e-commerce approach, according to which shoppers know when they buy, for example, a book, what other books other customers also bought. Here, we implemented the function 'users who selected this question also selected . . . Bnames of the other questions '. " ] },{ "paper_id": "646484c8081b3f1bf336bae89411c2aa86885788", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The regulatory environment includes accreditation of retired medical practitioners and allied health professionals, laws and regulations which support or hinder the flow of qualified personnel across a jurisdiction's health facilities [48] , and ensuring an appropriate medicolegal framework to support clinical decisions on prioritising medical care during a pandemic, for example, modifying clinical standards, deferring treatment, and restricting access to certain treatments." ] },{ "paper_id": "646b9174e7fbba65d545caf0347e94f6d63e7ad3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "646d3092d14896e26c741391f0b5fe5b724f4a39", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In vitro gp120-binding assay", "Additional Supporting information may be found in the online version of this article: ", "HIV infections cannot currently be cured, but there is a window of opportunity lasting 30-60 min between exposure and infection during which pre-exposure prophylaxis can block the uptake of the virus (Shattock and Rosenberg, 2012) . When the virus interacts with mucosal tissue, an infection is established within 16-72 h (Haase, 2011) . Topical microbicides represent a subset of pre-exposure prophylaxis strategies and are classified according to their target and mechanism of action. Surfactants kill the pathogen, replication inhibitors prevent virus replication, buffers enhance the vaginal milieu of protectors, and entry/ fusion inhibitors block virus entry into host cells (McGowan, 2006) ." ] },{ "paper_id": "647652b31779d67fcdecf1848f7492b2ab10a4ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Because MERS is a healthcare-associated infection, it is interesting that digital surveillance using Google search and Twitter, which operate via input from the general public, may also work well for surveillance. In fact, most digital surveillance has been used to detect community-based transmitted diseases 10, [16] [17] [18] [19] [20] . It may be related to the fact that MERS also infects the general population, such as patient family members and caregivers.", "\" (\"MERS symptoms (in Korean)\"), and \" \" (\"MERS hospital (in Korean)\"). Additionally, we found high correlations between the Google search and Twitter results and the number of quarantined cases using the above keywords. This study demonstrates the possibility of using a digital surveillance system to monitor the outbreak of MERS." ] },{ "paper_id": "648043eabf0ac87a2bd28909cd4a739f8b2c4a35", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We separated the analyzed organs into three categories in relation to their shedding potential:", "Several transmission routes have been demonstrated for brucellosis in domestic animals: horizontal direct or indirect transmission through genital secretions, aborted fetuses or products of live births (placenta, fetal fluids and vaginal exudate) from infected mothers, vertical transmission in utero or during birth, pseudo-vertical transmission through the consumption of colostrum or milk, and venereal transmission (D\u00edaz-Aparicio, 2013) .", "On the final model, we verified that random effects were normally distributed, and checked adequacy of the model with residual plots. The amounts of variability explained by the fixed and random effects of generalized linear mixed models were respectively estimated using marginal and conditional R\u00b2 of Nakagawa and Schielzeth (2013) .", "BG-B, YG, JH, SR, CP, and MJ designed the study. PF, EP, and CT collected the data during the field work, and YG, GR, and M-NB performed laboratory analyses. SL and PF filtered, entered and prepared the data for the analysis. SL, PF, and EG-F performed the analysis. SL, PF, SR, AT, EG-F, and CT interpreted the data. SL wrote the manuscript. SR and JH supervised the monitoring program conducted by the French Hunting and Wildlife Agency. All authors participated in drafting the manuscript or revising it critically for important intellectual content. All the authors approved the submitted version of the manuscript.", "The strong variability of bacteriological results among seropositive individuals illustrates the heterogeneity of the hostpathogen relationship, and underlines the limits of serological investigations to infer the transmission dynamics of pathogens (Gonz\u00e1lez-Barrio et al., 2015) ." ] },{ "paper_id": "648e9c790e9707c35271988c3f86aa147a9eda05", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results indicate that CVT-E002 can be safely used by similar groups and may prevent symptoms of URIs; larger sample size is warranted.", "During an URI, subjects completed a daily log of the severity of their URI-related symptoms on a scale of 0-3 (0 = no symptom, 1 = mild symptom-no change in daily activities, 2 = moderate symptom-some decrease in ability to carry out daily activities, and 3 = severe symptom-confined to home or bed). The following symptoms were evaluated: sore throat, runny nose, nasal congestion, cough, myalgia, sneezing, ear aches, headache, fever, chills, and fatigue. Subjects completed their daily logs at approximately the same time each day. Daily symptom scores for all days in which a score exceeding 4 were reported were summed to calculate the total symptom score (TSS) [7, 9, 10] .", "Adequacy of blinding was assessed by completion of a study medication perception questionnaire which subjects completed during their last visit to the center. Compliance was assessed by counting the capsules returned and was verified by checking the subjects' daily logs." ] },{ "paper_id": "6493fb02dfb851e5f1ca0d5f196b381a67dba56d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Internet-based participatory surveillance systems, such as the German GrippeWeb, monitor the frequency of acute respiratory illnesses on population level.", "year-round and generates representative data in all age groups.", "Individual laboratory results of their swabs were fed back to each participant through their personal GrippeWeb diary webpage that can be individually accessed at any time using the login of the participant." ] },{ "paper_id": "649b2f2aba88c512775160f197a250e51ac8bc14", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: All these authors wrote the manuscript." ] },{ "paper_id": "64a0b8711c7e7553c8025dc56a843ce601fc029b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Checklist S1 STROBE checklist for cohort studies. (DOC)" ] },{ "paper_id": "64a2b883a0ce91110c5cd56722520d862476ba3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 44,782 medical records of canine patients were analyzed from 11 selected primary-care veterinary clinics, for the period from January 1, 2016 to December 31, 2016.", "This study was supported by the 2018 RDA Fellowship Program of the National Institute of Animal Science, Rural Development Administration and it was carried out with the support of \"Cooperative Research Program for Agriculture Science & Technology Development (Research for prevalence of common disorders by life cycle and hematological phenomenon in companion dog, PJ01284303),\" Rural Development Administration, Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.", "We observed that, for Shih Tzu, orbital problems, including conjunctivitis, disorder of the orbit (unspecified), and keratitis were more frequent than in other breeds; we suspect that this is because of persistent irritation of the cornea or conjunctiva by eyelashes or facial hair, similar to congenital malformations of hair (e.g., trichiasis, median canthus, or aberrant cilia). Additionally, conformation character, such as median entropion, tends to be more common in brachycephalic breeds with prominent nasal folds, including Shih Tzu, Pekingese, English Bulldog, and Pug (Christmas, 1992) .", "A total of 44,782 EMRs of dog patients were analyzed from veterinary clinics who shared medical data for the period from January 1, 2016 to December 31, 2016. When records for non-medical services and repeat visits (29,251, 65.3%) were excluded, a total of 15,531 EMRs and 11,085 individual dogs were analyzed. The proportion of dogs with more than one disease was 4,446, 28.6%." ] },{ "paper_id": "64ada09043be47208d892a974b842d4ccb4df356", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Is AMR an epidemic?", "Abbreviations AIDS: Acquired immunodeficiency syndrome; AMR: Antimicrobial resistance; CRISPR: Clustered regularly interspaced short palindromic repeats; CRISPR-cas9: CRISPR-associated protein-9 nuclease; DURC: Dual-use research of concern; HIV: ", "Severe acute respiratory syndrome (SARS) was an epidemic infection, in contrast to Middle East Respiratory Syndrome (MERS), which has displayed a more sporadic pattern with occasional outbreaks. For most emerging viruses which have spread globally (such as SARS, MERS, Ebola, dengue, encephalitis), there are no commercially available anti-virals, and thus AMR is not relevant. However, drugs are in development for some of these, such as Ebola, which has epidemic potential.", "These factors are influenced by inherent characteristics of the pathogens themselves in addition to external contextual factors. For example, the ability of the microbe to spread is determined by epidemiological parameters including R 0 , incubation period and transmission rates. The burden of AMR during a pandemic will also vary for different regionsfor example, low income regions will likely suffer a higher burden due to poorer health care standards in hospitals, greater crowding, limited access to laboratories, widespread purchasing of antimicrobials without prescription and poor regulatory frameworks for antibiotic use." ] },{ "paper_id": "64adce98190f9491944dc9d5141e0cccb6360519", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reverse transcription was performed using 1.2 \u00b5l M-MLV-RT and 8 \u00b5l M-MLV-RT 5\u00d7 buffer (Promega), 4 \u00b5l 5 mM dNTPs, 4 \u00b5l Random Primers at 100 ng/\u00b5l, 2 \u00b5l DTT 0.1 M, and 1 \u00b5g RNA in a final volume of 40 \u00b5l. The reaction was run in the C1000 Touch Thermal Cycler from Bio-Rad. The samples were incubated at 37\u00b0C for 60 min, then at 95\u00b0C for 60 s, and next immediately placed at 4\u00b0C.", "Microarray data normalization was performed using the quantile algorithm. After quality assessment, a filtering process was carried out to eliminate low expression probe sets. Applying the criterion of an expression value >64 in the three samples of at least one of the experimental conditions, 45322 probe sets were selected for statistical analysis. LIMMA (Linear Models for Microarray Data) (62) was used to identify the probe sets with significant differential expression between experimental conditions. Genes were selected as significant using a B statistic cut-off of B > 1.5. Data processing and statistical analyses were performed with R and Bioconductor (63) .", "Elena Carnero and Marina Barriocanal have contributed equally to this work.", "Elena Carnero and Marina Barriocanal designed and performed the experiments, analyzed and interpreted the data, and contributed to the writing of the manuscript; Celia Prior performed some of the experiments; Victor Segura and Elizabeth Guruceaga were in charge of all the bioinformatics analyses; Kathleen B\u00f6rner and Dirk Grimm prepared and provided the RNA samples from HIV-infected patients; and Puri Fortes conceived the project and the required experiments, provided the budget, interpreted the data, and wrote the manuscript." ] },{ "paper_id": "64b4ec9158c8f378000f3d15492f317f19baeafb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by the Swiss Science Research Foundation (grant 3100-156806 and grant 310030_175686 to BC).", "BC and GB planned the manuscript and wrote sections of the manuscript. Both authors read and approved the submitted version of the manuscript.", "Virosomes are a special category of liposomes, where part of the lipid content is derived from viral components that self-assemble into an organized three-dimensional structure that mimics the antigenic structure of the original virus (170) . Interestingly, they have been demonstrated to be immunogenic without further addition of adjuvants (171) , although addition of immunopotentiating agents further improves their vaccine efficiency (172) ." ] },{ "paper_id": "64b95b0bd76c83bc56ae6e150c4aad0dd36437a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Initial laboratory investigations at JMC included dengue (IgM antibody and NS1 antigen), malaria (blood film), leptospirosis (IgM antibody and IgG antibody), and influenza A and B (virus A and virus B antigens). All tests were negative. A multiplex PCR for 33 respiratory viruses and bacteria (FTD respiratory pathogens 33; Fast-Track Diagnostics) was positive for rhinovirus and also for influenza (A-F). An added tropical fever panel multiplex PCR (FTD Tropical Fever Core; Fast-Track Diagnostics) that included seven viral and bacterial families including Rickettsia spp. (targeting the citrate synthase gene, gltA) gave negative results for all pathogens. The multiplex PCRs were outsourced by JMC to a laboratory in West Malaysia. Additional throat, nasal, and rectal swabs, and urine were collected for PCRs, at the Sabah Wildlife Department's Wildlife Health, Genetic and Forensic Laboratory, on pooled cDNAs, screening for coronavirus [19, 20] , filovirus [21] , influenza [22] , paramyxovirus [23] , enterovirus ( [24] , unpublished; VP4/2 and 5 UTR genes, Centre for Infection and Immunity, Columbia University, 2013), flavivirus [25] , and hantavirus [26, 27] using the PREDICT Universal Control. A PCR product was obtained from the enterovirus protocol [24] and confirmed by sequencing to be a 98.6% match to human rhinovirus A30 HRV30/DJ0692/11 (KC414928, 513 bp), which did not explain the patient's symptoms.", "Rickettsiosis was suspected due to the patients' response to doxycycline and azithromycin therapy. Samples were tested retrospectively for genetic and serological evidence of rickettsial infection. Unfortunately, there was only a limited number of samples available for testing as the admission blood and serum samples were destroyed on D7. Additional samples were collected on D15 for PCR and serology testing. amongst the SFGR species. IFA results were confirmed by western blot (WB) [28] that demonstrated specific OmpA (130-160 kDa) and OmpB (115-150 kDa) bands for R. honei, R. australis and R. conorii, when reacted with the patient's serum using IgM and IgG conjugates (Figure 2 ). (Figure 2 ). ", "To conclude, there should be an emphasis on clinicians in Sabah to closely monitor patients with acute febrile illness given the historical and current prevalence of rickettsioses and the rapid and Trop. Med. Infect. Dis. 2018, 3, 29 6 of 8 unpredictable fatal course of spotted typhus. Special attention must be given to those patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, a condition present in five to ten percent of all ethnic races in Sabah [34, 35] , since rapid fulminant courses of SFGR is known to occur in patients with this condition [36] . Therefore, typhus and typhus-like diseases must be included in the early differential diagnosis of nonspecific fevers in Sabah. In addition, a culture of preserving acute and convalescent samples for repetition of tests to confirm diagnoses must also be encouraged. Finally, without a rapid and reliable diagnostic test for confirming or excluding the disease at an early stage, the prompt administration of empirical antibiotic therapy to patients presenting symptoms related to rickettsioses is recommended in a closely-supervised manner to prevent antibiotic resistance, which will be detrimental at the individual and community level [8, 37] ." ] },{ "paper_id": "64bfeb561f0664d74a04ee30a24a48159261d4fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We would then have", "and thus", "The Jacobian matrix at the disease-free equilibrium is", "For the SI model (32) , under the assumption that every infection is uniquely assigned as a secondary infection for either a removed or an infected individual," ] },{ "paper_id": "64c22236bc20680680fffab70eedef1f21641bd0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Concentrations of IP-10 (CXCL10) were measured in BAL sample supernatants using paired Abs and standards (Platinum ELISA, eBioscience). All assays were carried out according to the manufacturer's instructions, and 100 ml from each sample was assayed in duplicate. The lower limit of detection for these assays was 7.8 pg/mL.", "This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by The Institutional Animal Care and Use Committee at the Research Institute at Nationwide Children's Hospital (AR09-00012). All animal experiments were performed using 2,2,2-tribromoethanol anesthesia, and all efforts were made to minimize suffering.", "An ideal adjuvant serves to enhance the action of vaccines (thus reducing the dosage of vaccine that needs to be delivered) without inducing strong direct effects on its own. The most commonly used adjuvant, aluminum hydroxide, primarily induces a Th2 type antibody response. Yet, for infections such as tuberculosis, human immunodeficiency virus and respiratory syncytial virus (RSV) increasing evidence indicates that there exists a need for adjuvants that can additionally bolster cellular immunity. Thus, it is coming to light that adjuvants that can induce both cellular and humoral immunity are optimal. As such, agonists that trigger PRRs are currently viewed as attractive candidates for vaccine strategies [1, 2] ." ] },{ "paper_id": "64c3ee477952b5dd96e786d2c9695e76953b03b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "64c59c6ee1a8693c4bc296bf844047426f046e1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA was extracted and reverse transcribed and analyzed by quantitative real-time PCR as published [25] . Reactions were performed in a total of 20 \u00b5L containing 10 \u00b5L GoTaq qPCR (2\u00a2) Master Mix (Promega, Mannheim, Germany) and 1 \u00b5g BSA. According to reference sequence NM_005038 primer sequences were selected for Cyp40, 5 I tgaaaggtgaaaaacctgctaaa 3 I for the sense primer CyP40.s, and 5 I cagagccatcttttgggaata 3 I for the antisense primer CyP40.as. An amplicon of 96 bp was generated. The p21 primer sequences are as published [25] .", "Results", "The cyclosporine A analog NIM811 is a non-immunosuppressive cyclophilin inhibitor." ] },{ "paper_id": "64e2d8f1f9eccda51fa3b8398c20e040c7fbcd06", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "any obvious side effects in the mice at the tested doses (data not shown).", "Lycorine is one of the most abundant alkaloids of Amaryllidaceae [18] , and has a wide range of biological effects including apoptotic effects on tumor cells [19] , antimalarial effects [20] , anti-inflammatory effects [21] and induction of nausea and emesis [22] . Importantly, lycorine also has been shown to have antiviral effects on human immunodeficiency virus (HIV-1), severe acute respiratory syndrome-associated coronavirus (SARS-CoV), poliovirus, coxsackie virus, measles virus, and herpes simplex virus type 1 [23] [24] [25] .", "All data are expressed as the mean \u00b1 SD. The statistical significance of differences in mean values was assessed by Duncan's multiple-range test following a one-way analysis of variance (ANOVA), and survival rates were analysed by Kaplan-Meier analysis. A P value of < 0.05 was considered to be significant." ] },{ "paper_id": "64ee665b9ca47283ff31e1789655e70838efc849", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "64f5af205494b75764762ed86fd202387c77b0b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Supplementary Material for this article can be found online at http://journal.frontiersin.org/article/10.3389/fvets.2016.00019 reFerences", "are quite common in ME countries including countries of the Arabian Peninsula, where severe LSDV outbreaks were recently reported (24, 45) . This could be attributed to multiple risk factors including: favorable climatic conditions for vectors, low biosecurity measures, introduction of new animals and mixing of different livestock species, as suggested elsewhere (5, 13, 20, 26) . In addition, cattle farms with close proximity to urban areas are under intensive human surveillance, and thus the number of detected outbreaks is expected to be higher than non-urban production systems.", "aUThOr cOnTriBUTiOns MA formulated the spatial and temporal models and was primarily responsible for report and manuscript preparation; KV provided interpretation on the use of epidemiological models, collaborated in the design of the analytical model, and assisted in manuscript preparation.", "Our data covered 36 months of outbreaks for the currently circulating LSDV (Figure 2B) . We converted the epidemic curve into the time course of effective R-TDs. No seasonal patterns were observed in our epidemic curve. Instead, LSDV outbreaks followed were erratic in ME countries ( Figure 2B) . Our estimates indicate that the average monthly effective R-TD was 2.2, indicating a " ] },{ "paper_id": "64f8cf1eb3fcbf713912d805032e3c95d4dda259", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Gold nanoparticles (GNPs) have attracted signi\ue103cant interest as a novel platform in nanobiotechnology and biomedicine because of their convenient surface bioconjugation with molecular probes 1 and their remarkable optical 2 and immunological 3 ", "Professor Nikolai G. Khlebtsov is head of the Nanobiotechnology Laboratory at the Russian Academy of Sciences' Institute of Biochemistry and Physiology of Plants and Microorganisms. He also is Professor at the Faculty of Nano-and Biomedical Technologies at the Saratov State University. He has published over 400 scienti\ue103c works, including 12 monographs and book chapters. His current research interests are in biophotonics and nanobiotechnology of plasmon-resonant particles, biomedical applications of metal nanoparticles, static and dynamic light scattering by small particles and clusters, and programming and computer simulation of light scattering and absorption by various metal and dielectric nanostructures. Professor Khlebtsov also serves as associate editor for the Journal of Quantitative Spectroscopy and Radiative Transfer.", "In summary, the experimental results give grounds to state that:" ] },{ "paper_id": "64fbda4f1a32fd2610ce90ef77b775ec4676bec8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Specific information on coronavirus and paramyxovirus positivity by sampling site, time and species is indicated in Tables S1-S3. " ] },{ "paper_id": "64fe1b9afa90e2e1ea0c1c10e2ae5ada566e270a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Whole genome sequencing, phylogenetic analysis and genetic analysis of the viruses were performed. This study highlights the first LPAI subtypes H4N6 and H4N9 ever reported in poultry from Thailand.", "other hand, all other samples were negative for influenza A virus. Interestingly, two influenza A subtypes, H4N6 (CU-LM1983) and H4N9 (CU-LM1984), were isolated from oropharyngeal (CU-LM1983) and cloacal (CU-LM1984) swabs of the same duck. Both H4 subtypes have never been reported in Thailand.", "Live-bird markets (LBMs) are the places where wild birds, pet birds, meat birds and domestic poultry are sold to households. In Asia including Thailand, due to the cultural preference of consuming freshly slaughtered poultry, LBMs are located in both suburban areas and center of the communities. In the markets, thousands of birds from different sources are sold in wire stacked cages containing densely packed and mixed bird populations. These conditions provide excellent environments for animal to animal and animal to human influenza virus transmissions and may result in an outbreak of influenza A virus in both animals [1, 2] and humans [3, 4] . Therefore, LBMs are considered a major source of influenza A virus dissemination and potential influenza A virus reassortment [5, 6] ." ] },{ "paper_id": "6507acff69dc9963ee7fdffc4a7f4edae0b5f609", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All calves remained healthy throughout the study period and maintained a normal appetite, normal rectal temperature, were alert and responsive, and had a normal growth curve (data not shown)." ] },{ "paper_id": "650c105dc3718ea36a7abffa0de7f9068390045f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lungs were dissected and incubated with collagenase type IV (1 mg/ml; Sigma) and DNAse (100 U/ml; Roche) at 37uC for PerCP (53-6.7), IFNc Alexa 647 (XMG1.2) and CD16/32 (2.4G2) from BD Pharmingen. Samples were acquired on a LSRII Cytometer and analyzed using FACSDiva software (BD Biosciences). Propidium iodide was used to discriminate between live and dead cells.", "Results are expressed as the mean 6 SEM. Statistical significance between groups was assessed using two-way ANOVA. The differences for in vivo experiments (at least 5 mice per group) were calculated using the Mann-Whitney U-test for unpaired data. Statistical significance of differences between survival rates was analyzed by comparing Kaplan-Meier curves using the log-rank test (GraphPad Prism version 5, GraphPad, San Diego, CA).", "All experiments on mice were conducted according to the national (Belgian Law 14/08/1986 and 22/12/2003, Belgian Royal Decree 06/04/2010) and European (EU Directives 2010/ 63/EU, 86/609/EEG) animal regulations. Animal protocols were approved by the ethics committee of Ghent University (permit number LA1400091, approval ID 2010/001). All efforts were made to ameliorate suffering of animals. Mice were anesthetized by intraperitoneal (i.p.) injection of a mixture of ketamine (12 mg/ kg) and xylazine (60 mg/kg)." ] },{ "paper_id": "6518eb44df3244c513ccb0ceea5b7f3eb3dd9b52", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Multiplex PCR. Multiplex PCR primers were designed using BioEdit Sequence Alignment Editor (Version 7.1.11).", "Scientific RepoRts | 6:26017 | DOI: 10 .1038/srep26017 ultra-low copy and frequent variation of viral genomes obtained from specimens. However, the characterization of viral genomic sequences by NGS provides broad and deep insights into preventive and therapeutic strategies for the virus infections 11 ." ] },{ "paper_id": "6522e893e7f5739f96db413b61932c949e5fad2d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: The highly pathogenic avian influenza (HPAI) virus H5N1 causes multi-organ disease and death in poultry, resulting in significant economic losses in the poultry industry. In addition, it poses a major public health threat as it can be transmitted directly from infected poultry to humans with very high (60%) mortality rate. Effective vaccination against HPAI H5N1 would protect commercial poultry and would thus provide an important control measure by reducing the likelihood of bird-to-bird and bird-to-human transmission.", "The OD values of the 250-fold diluted samples, which were in the logarithmic phase of the curve, were plotted." ] },{ "paper_id": "6525c7e5a16bc1ecd8fcdfda2cc6c82fe89c85c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal experimental procedures were approved by the National Institute of Biomedical Innovation Committee on Animal Resources as the Institutional Animal Care and Use Committee.", "Procedures for cell culture, tumourigenicity test, RNA-seq, phylogenetic analysis, and genomic PCR are described in Supplementary data.", "Metaphase chromosomes from Vero cells and AGM peripheral blood mononuclear cells (PBMC) were analysed by conventional Giemsa-banding (G-banding) 26 and multi-colour fluorescence in situ hybridization (M-FISH) with 24 differentially labelled human chromosome-specific painting probes (24xCyte kit MetaSystems, Altlussheim, Germany). For detailed information, see Supplementary data." ] },{ "paper_id": "652fdea5cc6137511f2de628166875707670b10b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data described in this paper is available via anonymous ftp as reads, BAM format alignments, consensus sequence, nucleotide frequency profiles at: ftp:// gdo144.ucllnl.org/pub/orpdat/.", "Average of 5 samples" ] },{ "paper_id": "6531f45674dda196c08f5a81a18eeea88ee6bb55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Toll-like receptors (TLRs) are pattern recognition receptors playing a fundamental role in sensing microbial invasion and initiating innate and adaptive immune responses. TLRs are also triggered by danger signals released by injured or stressed cells during sepsis.", "Experimental animal models and human clinical studies support a crucial role for TLRs in infectious diseases. The first evidence came from the observation that TLR4 defective C3H/HeJ and C57BL/10ScCr mice are hyporesponsive to LPS and susceptible to otherwise non-lethal infection with Escherichia coli and Salmonella typhimurium. Subsequent studies with mice knockout in TLRs or TLR adaptor molecules have demonstrated the importance of the TLR pathway in host defenses. For example, TLR2 knockout mice are highly susceptible to infections by Staphylococcus aureus and Streptococcus pneumoniae (32) . More recently, human association studies have linked polymorphisms affecting TLR expression or TLR structure with an augmented propensity to develop infections (32) (33) (34) (35) .", "Imiquimod (Aldara, originally developed by 3M Pharmaceuticals, Maplewood, MN, USA) is the only TLR7 agonist marketed for anti-viral treatment, i.e., external ano-genital warts caused by human papilloma virus. Numerous TLR7/8 agonists are in clinical development, like CL097, isatoribine, ANA975, ANA773, PF-04878691 (852A), R-848 (resiquimod), and GS-9620." ] },{ "paper_id": "6534f8468fbb6dbdaf078a9a59d92dc686a2c4b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A cell-based, quantitative and isoform-specific assay for exchange proteins directly activated by cAMP Yingmin " ] },{ "paper_id": "653c1744be45d5e3ba3e9fb48edf6c6997976324", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Most research has focused on replication-defective poxvirus vectors (which have better safety profiles) as vehicles for delivering antigens derived from human pathogens. For example avipox- [73] , MVA-and NYVAC-based vectors expressing components of human pathogens, such as HIV-1 and tuberculosis, have been developed and evaluated in monkeys [74, 75] and humans [76] [77] [78] [79] . However, although promising in animal models, these vaccines did not induce sufficiently strong immune responses in humans, nor did they protect humans from infection [79, 80] . Therefore, more effective vehicles are needed for human vaccine development.", "Thus, a replication-competent VV that has been proven to be safe for human vaccination against smallpox could be a good candidate. The safety profile and strong antigenicity of LC16m8\u2206, a genetically-stable variant of LC16m8, make it a promising vehicle for a vaccine against HIV or other human diseases.", "VV has been widely used as a vector for expressing foreign genes, because it has many excellent properties: high expression efficiency, a broad host range, a very large capacity for accepting foreign genes, heat stability and inexpensive vaccine production [71] . Therefore, VV vectors have been examined for use as live vaccines against both human and veterinary infectious diseases and cancers [6] [7] [8] . However, concerns about the safety profile of VVs are a major barrier to developing recombinant VV vaccines for use in humans [72] ." ] },{ "paper_id": "65438bb97d2ff9725a706241b92f3be6f695f368", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study has been submitted for approval and the results reviewed by the Scientific Council of the Tour du Valat Foundation. Birds were handled, ringed and sampled under the supervision of a veterinarian (Michel Gauthier-Clerc) and a registered duck ringer of the \u00ab Museum National d'Histoire Naturelle \u00bb of Paris (Matthieu Guillemain). All procedures were carried out in accordance with the permit delivered by the prefect of Paris to the \u00ab Office National de la Chasse et de la Faune Sauvage \u00bb (permit n 2009\u00b1014). (Table 1) . Samples were stored in 3 ml of universal transport medium (Biolys kit) and frozen at 280uC until molecular analysis was performed.", "During the last decade, awareness concerning the intimate links between human and animal health has rapidly increased in the context of disease emergence [1] . Indeed, approximately 80% of the infectious diseases that recently emerged were zoonotic [2] . The role of wildlife in emerging pathogen transmission to humans and domestic animals has in many cases been pointed out [3\u00b15] . Conversely, pathogen transmission from domestic animals to wildlife has received far less attention, although the importance of this issue was often mentioned [6, 7] . Indeed, contacts between wildlife and livestock or their environment sometimes result in wildlife diseases with conservation issues [8, 9] . Besides, handreared animal releases into the wild for either conservation or exploitation purposes represent a particular case in which handreared individuals eventually share natural habitats with their wild congeners. In both cases such releases can dramatically influence disease dynamics in the surrounding wild animal populations [ 10\u00b1 14] .", "For this reason, avian influenza viruses (AIV) have been studied since 2004 in the area. These negative-sense single stranded RNA viruses belonging to the Orthomyxoviridae family are commonly characterized by the combination of their surface proteins: hemagglutinin (HA) and neuraminidase (NA) [22, 23] . AIVs are highly variable and undergo continuous genetic evolution via two mechanisms: i) accumulation of point mutations at each replication cycle, ii) reassortment involving gene segment exchanges that occur when a cell is co-infected by different viruses [24] . These mechanisms contribute to the emergence of new variants with the ability to transmit to new hosts and/or with epidemic or even pandemic potential. Aquatic birds, particularly Anseriforms (ducks, geese and swans) and Charadriiforms (gulls, terns and shorebirds) constitute their major natural reservoir [23, 25] . The AIV circulating in wild birds are usually low pathogenic ones (LPAIV). LPAIV generally have little impact on their host [26, 27] , although some studies have reported a possible influence on migration capacities [28] . Besides, when LPAIV of H5 or H7 subtypes are transmitted from wild birds to domestic ones reared in artificial environments, their virulence can evolve to high pathogenicity [29, 30] . Highly pathogenic avian influenza viruses (HPAIV), such as HP H5N1 strains currently circulating in Asia and Africa, are still of great economic concern, notably due to the cost of preventive actions including vaccination and massive birds culling [31] . Moreover, HPAIV infections represent a threat for human health since 603 HPAIV H5N1 human infections including 356 fatal cases have been reported worldwide since 2003 [32] ." ] },{ "paper_id": "6548b941beede8bb57cde83a928e4383b54697ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The test concentrations and contact periods were chosen in order to observe the point at which each test preparation produced efficient virus inactivation.", "In December 2013, the Ebola virus (EBOV) epidemic began in Guinea, and on March 23, 2014, the Ebola virus outbreak was officially communicated by the World Health Organization (WHO). This outbreak in West Africa (mostly affecting Guinea, Sierra Leone and Liberia) has been the largest and most complex outbreak since the virus was discovered.", "Povidone iodine (PVP-I) has been known for a long time as a broad spectrum microbicide against bacteria, fungi, protozoans and viruses [13] . In a water-soluble complex, the elemental iodine is bound to the carrier polyvinylpyrrolidone. In an aqueous medium, a chemical equilibrium develops to release the active antimicrobial agent iodine, while the complex-linked iodine builds a reservoir for delivery [14] . Thereby, its microbicidal activity is maintained but the cytotoxic effects of high concentrations of iodine are reduced [14] . The oxidative potency of PVP-I enables the iodine released to react rapidly with functional groups of amino acids and nucleotides, as well as with double bonds of fatty acids, resulting in a manifold destruction of various structures and enzymes of microbes and viruses. The development of resistance mechanisms against the very broad oxidative attack appears almost impossible [13, 15] .", "The most probable average number of TCID 50 can be calculated by the use of the following formula, which is derived from the Taylor series:" ] },{ "paper_id": "655537fc8cc52bccf43cf7189ab060d3097caa7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thus, prior to 2018, bats collected in some areas of China have been shown to carry CoVs capable of directly infecting humans.", "Bats have an ability to migrate more than 1000 kilometers and tend to fly to insect-rich areas [48] . Abundant insects are often found in wildlife market areas due to their selling of various animals. Animal carcasses also make these places suitable habitats for bats. Bats are also attracted to artificial green lights and tend to gather around green light areas [49] .", "Funding: This work is supported in part by the National Natural Science Foundation of China under grant no. 71964020." ] },{ "paper_id": "6567692317d79659efda807e54ced960c8588ffb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments were reproducible and were carried out in triplicate or quadruplicate. Each set of experiments was repeated at least three times with similar results, and a representative one is shown. The results are presented at the means6s.d. Student's t test for paired samples was used to determine statistical significance. Differences were considered statistically significant at a value of P#0.05." ] },{ "paper_id": "656d6bf0f5b0f360d55d5321e0c305eb6a12cbab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical differences were calculated using the twotailed unpaired Student's t-test. P values <0.05 were considered significant. *p < 0.05, **p < 0.01, ***p < 0.001." ] },{ "paper_id": "65731cfe4b5e1d05aa7c85d3b088346832c35315", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Linear amplification of circular plasmid DNA was between copy numbers of 4 x 10 0 and 4 x 10 6 , and generated a standard curve with calculated efficiency of 86% from y-slope (-3.72) with correlation coefficient (R 2 ) of 0.9993.", "Positive control virus was isolated from swine vesicular lesion tissue obtained in 2007. A 10% homogenate (w/v) was made in Minimum Essential Medium Eagle containing 4% fetal bovine serum (Lonza) in a Retsch Mixer Mill 400 using a 25 ml stainless steel grinding jar and a single 20mm stainless steel grinding ball (Retsch). The homogenate was clarified by low speed centrifugation and passed through a sterile 0.45 micron filter (GE Healthcare). The filtered homogenate was used to inoculate a confluent monolayer of swine kidney (SK-6) and or Instituto Biologico Rim Suino-2 (IBRS-2) cell cultures [18] [19] . Once cytopathic effects (CPE) were observed, the cell lysate was clarified by low speed centrifugation, and the supernatant was reserved as virus stock.", "Sequence data were obtained from the MiSeq instrument as raw, paired end reads in fastq format. Subsequent sequence assembly was produced through a reference guided assembly using BWAMEM from the Burrows-Wheeler alignment (BWA) software [21] . Assembled SV-A sequences were aligned using MUSCLE [22] , and visualized with BioEdit (7.2.5) software [23] for comparison of the primer binding regions of the completed genomes (Fig 7) ." ] },{ "paper_id": "659220e080e623e34f3efe2ce84e63fb2cefdd8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For example, in the era of global health, translational genomics, and personalized medicine, the accumulating availability of genetic and clinical data provides the unique opportunity to apply this approach to studies of, e.g., tumor metastasis and chronic infections, which comprise complex transmission dynamics among tissues and/or cell types, not unlike the geographical spread of infectious diseases. ", "Globalization has dramatically changed the way in which pathogens spread among human populations and enter new ecosystems [1, 2] . Through migration, travel, trade, and various other channels, humans have and will continue to intentionally or unintentionally introduce new organisms into virgin ecosystems with potentially catastrophic consequences [3] . Humans are not the only culprits, however; global climate pattern changes can alter local ecosystems, creating favorable conditions for the rapid spread of previously overlooked or even undiscovered organisms among humans, giving rise to unexpected epidemics [4, 5] . Recent years have been marked by global epidemics of Ebola, dengue, and Zika, derived from pathogens previously restricted to local outbreaks [6] . According to the World Health Organization, more than one and a half billion people are currently awaiting treatment for neglected tropical diseases with similar potential for global spread, for which we have limited knowledge of etiology and treatment options [7] . This lack of knowledge further limits our ability to investigate the putative role of these pathogens in future epidemics or even pandemics.", "Traditional phylodynamic analysis applied to nosocomial outbreaks has been successfully used in the past to identify the likely source; however, the inclusion of extensive patient data, such as treatment regimens, admission and discharge dates, and length of stay, can improve not only phylogenetic estimates but also the translation of the interpretation to public health policy. Epidemiological and genomic data on Methicillin-resistant Staphylococcus aureus (MRSA) infections were recently utilized by Azarian and colleagues to reconstruct MRSA transmission and to estimate possible community and hospital acquisitions [94] . Findings from this study revealed that as high as 70% of the MRSA colonization within the hospital's neonatal intensive care unit (NICU) was acquired within the NICU itself. These findings indicated that current, standard prevention efforts were insufficient in preventing an outbreak, calling for the improvement of current care or alternative implementation strategies." ] },{ "paper_id": "65942c10db7359edef15f156cecccf3deee45b72", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6598644894c24fccef62e4df45e859f023bea4c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Contact distributions. We consider the following contact distributions, each with mean l (see also appendix B.1).", "-Deterministic. Every individual has exactly l contacts. -Mixed deterministic. There are n types of individuals, where the kth type occurs in proportion p k and has exactly l k contacts. -Poisson.", "Linear mutational schemes represent single directions through strain space, where strains 2, . . . , m 2 1 are intermediates between strains 1 and m. We consider the following possibilities.", "Thus, extending the notation of \u00a72.1, the PGF for number of infections transmitted by an initial infective of type i is and for a later generation infective, the PGF is" ] },{ "paper_id": "65a49f91fda031c7e95543c2d73082b090d08ffc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "strains may cause nephritis or facilitate secondary bacterial infections, increasing mortality up to 50% (2) . In addition, some serotypes demonstrate tropism for the oviduct, directly causing decreased egg quality and production (3) . Poultry is an important food source worldwide, with an estimated 55 billion chickens produced worldwide per annum, including 5 billion for egg production. It has been estimated that every 10% reduction in IBV would be worth around \u00a3654 million to the global poultry industry (4) .", "Detection of viral RNA. Trachea stored in RNAlater was freeze-thawed and homogenized using the TissueLyser II (Qiagen) for 2 min at 25 Hz. Total RNA was isolated using an RNeasy minikit (Qiagen) by following the manufacturer's animal tissue protocol with on-column DNase treatment.", "Data availability. The sequence was deposited in GenBank under accession number MK728875.", "Overall across all four passages, 43 (70.5%) of the identified consensus SNPs were nonsynonymous (NS), 11 (18.0%) were synonymous, and 7 (11.5%) occurred in untranslated regions (Fig. 4E) .", "Conversely, through our mutational analysis we have identified regions across the viral genome that undergo a high level of genetic change as the result of passaging and may contribute to attenuation. This has additionally identified areas of the genome where mutation does not occur and may not be evolutionarily tolerated, a feature which will equally assist future vaccine development." ] },{ "paper_id": "65aa725092d0b73054cce187137a0c22afb92d10", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "65aad42469b115f496dac7fe5b1a74ee5bbbf93e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. Survival curves were generated by the Kaplan-Meier method and statistical analyses were performed using the log-rank test. The statistical significance was assessed by Student's t-tests. A P value < 0.05 was considered significant.", "Immunoblotting. Nuclear and cytoplasmic extracts were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, transferred to membrane filters, and analysed by immunoblotting with a rabbit anti-NF-\u03ba Bp65 antibody (clone D14E12), a mouse anti-IKK\u03b1 antibody (clone 3G12), a rabbit anti-IKK\u03b2 antibody (clone D30C6), a rabbit anti-phospho-IKK\u03b1 /\u03b2 (Ser176/180) antibody (clone 16A6), a mouse anti-I\u03ba B\u03b1 antibody (clone L35A5), a rabbit anti-phospho-I\u03ba B\u03b1 (Ser32) antibody (clone 14D4), a rabbit anti-AMPK\u03b1 antibody (clone D63G4), a rabbit anti-phospho-AMPK\u03b1 (Thr172) antibody (clone 40H9) (all obtained from Cell Signaling Technology), a mouse anti-lamin A/C antibody (clone 3A6-4C11, Active Motif), or a mouse anti-\u03b2 -actin antibody (Merck Millipore).", "Scientific RepoRts | 6:37815 | DOI: 10.1038/srep37815" ] },{ "paper_id": "65c5b049ad6a45d3533e0fee55018ba631d338b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Leishmania genome plasticity allows swift adaptation to new antiparasitic drugs.", "Top five papers " ] },{ "paper_id": "65c8138a4905491ab3bcd6aa58320408abecc9e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Using available rosavirus B and C genome sequences for analysis, the Ka/Ks ratios for various coding regions were estimated ( Table 5 ). The Ka/Ks ratios for most coding regions were low, supporting purifying selection.", "Roof rat" ] },{ "paper_id": "65ca70396d041072aeab57a007cffef0870897cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu. 2019.02186/full#supplementary-material", "Our analyses pointed out that viral evasion mechanism observed in one virus could also be relevant for other viruses. To test this, we obtained known drug-gene interactions from DGIdb (77).", "All datasets used for this study are accessible as stated in the Materials and Methods section 2.1. " ] },{ "paper_id": "65cc7496f21429d81b3ae129d9c39764e2a1f568", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There is a growing demand from many quarters for a new international policy framework [3] . A new international treaty on essential health R&D could provide a binding framework to redirect today's knowledge and scientifi c expertise to priority health needs. The treaty could help to cement new political commitments and coordinate complementary partnerships aimed at generating and rewarding health innovation as a global public good.", "Prioritization for neglected diseases: to ensure that immediate efforts are made toward fi nding new tools for lethal diseases that are currently diffi cult or impossible to diagnose and treat.", "Citation: Dentico N, Ford N (2005) The courage to change the rules: A proposal for an essential health R&D treaty. PLoS Med 2(2): e14.", "The recent epidemic of severe acute respiratory syndrome-SARS-clearly shows that biomedical knowledge and the pharmaceutical sciences can be mobilized to achieve rapid advances relevant to social needs if suffi cient resources and political will can be mustered. The SARS virus was completely sequenced in just six days, and a diagnostic test was developed in only three months. The public-sector funded, collaborative \"public-goods model\" used for the Human Genome Project shows that public collaborative research can be more effi cient than the closed, monopolistic, private sector approach.", "The patent system is also promoting new inequalities in high-income countries. Americans now spend a staggering $200 billion a year on prescription drugs. This fi gure is growing at a rate of about 12% per year [7] . The average price of the fi fty drugs most used by senior citizens in America was nearly $1,500 for a year's supply in 2002. Prescription drugs have become inaccessible even to many people in the rich world.", "Patents, with their focus on maximizing profi ts, have at least three negative consequences. First, it has been argued that the patent system causes substantial welfare losses because consumers who would buy the product if it were priced at somewhere nearer production cost do not buy it at the monopoly price [8] . Second, the system encourages counterfeiting-counterfeit drugs may represent up to 10% of the global market for pharmaceuticals [9] . Third, patented drugs are promoted through excessive marketing-on average, twice as much is spent on marketing a drug as on its R&D [10] . Across industries, it is becoming increasingly apparent that the patent system isn't working well [11] , leading some in industry to express public concern that the blockbuster business model is \"irreparably broken\" [12] . A new approach is needed, for all our sakes." ] },{ "paper_id": "65dad274ae49f213826f7cb5c43415778e053ce0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Immunostaining was performed on formalin-fixed, paraffin-embedded lung tissue. Paraffin sections (4 mm thick) were deparaffinized and then rehydrated through series of xylene and graded ethanol. Antigen retrieval was performed by heating in citrate buffer (10 mM Citric acid, 0.05% Tween 20, pH 6.0). Primary antibody was incubated overnight at 4uC with rabbit anti-CCSP polyclonal antibody (Seven Hills Bioreagents, Cincinnati, OH) and mouse anti a-smooth muscle actin (Abcam, Cambridge, MA) antibodies 32, 74, 76, 79 . Appropriate fluorescently labeled secondary antibodies (FITC-or Texas red-conjugated 2u antibodies) were used to detect the immune complexes before tissues sections were counterstained with 4',d-diamidino-2-phenylindole (dapi)." ] },{ "paper_id": "65e06f3980bdecbbbfc2f5018f79ec9ae44f3d04", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Working with pathogenic microorganisms requires good laboratory practices, risk assessments, and biosafety/biosecurity measures to ensure the safety of personnel, community, and the environment from accidental or deliberate infection. An occupationally-acquired infection of laboratory personnel is referred to as a laboratory-acquired infection (LAI) and these have been reported in scientific literature since 1897 [1] . Accidents or exposure events leading to LAIs may include inhalation of infectious aerosols, contact with mucous membranes by splash, touch, or spill, or infection via the percutaneous route (bites, cuts, accidental self-inoculation). However, in many LAI cases, the actual cause often remains unknown or uncertain [2] [3] [4] .", "Rabies has been estimated to infect as many as 31,000 humans annually in Asia [37] . In India alone, there were approximately 20,000 cases annually, which was one-third of the rabies cases reported worldwide [38] . Even though laboratory-acquired rabies is rare, the mortality rate of the infected cases is 100% in the case of an untreated exposure [39] . High disease prevalence combined with increased exposure risk through diagnostic activities with poor biosafety practices could increase the potential of LAIs to laboratory personnel. Pre-exposure vaccination, good laboratory practices, effective biosafety measures, and post-exposure prophylaxis (PEP) treatment are key to protecting those who work with the rabies virus.", "In conclusion, clinical and diagnostic laboratories are on the front line for detecting outbreaks of EIDs and zoonotic diseases. Laboratories require strong biosafety measures to protect staff health and prevent environmental contamination with pathogens. The fundamentals of a biosafety program include staff education and awareness to ensure good understanding and implementation of biosafety measures, including risk assessment and control measures [56] . The international community has an important and continuing role to play in supporting laboratories in UMIC and LMIC to ensure that they maintain a safe working environment for the staff, their families, and the wider community.", "Regions such as South and Southeast Asia are considered hotspots for emerging infectious diseases (EIDs). This is due to a combination of high-density human and animal populations, basic sanitation problems and inadequate health-related capacities [17] . The risk of infection is greatly increased by necropsy procedures, sample collection, clinical treatment, sample processing, and in vitro propagation. Specific control measures including personal protective equipment, and primary and secondary containment measures involving engineering controls are requires to mitigate risk of infection. Examples of emerging and zoonotic infectious diseases of high risk potential in Asia-Pacific region are presented in Table 2 . [20] and Cambodia, Japan, Korea, and Taiwan during January 2018 [21] . Animal disease surveillance and monitoring activities have been routinely performed throughout Asia with a focus on HPAI virus and other transboundary diseases that affect international trade [22] . Processing samples originating from animal sources in a limited biosafety environment could pose a significant risk of LAI and could lead to unintentional release of the pathogen into environment by aerosol transmission when performing laboratory procedures [23] ." ] },{ "paper_id": "6606f7964096d15ffdcb9772acbe40ae415dcb97", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The prevalence of RHD in children aged 5-14 years is higher in sub-Saharan Africa (5.7 per 1000), in Indigenous populations of Australia and New Zealand (3.5 per 1000), and southcentral Asia (2.2 per 1000), and lower in developed countries (usually 0.5 per 1000) [7] .", "Therapeutic options with doses and duration recommended by American Academy of Pediatrics are illustrated in table 4 [3] .", "Not suppurative, immune-mediated sequelae are acute rheumatic fever (ARF), acute post-streptococcal glomerulonephritis, Sydenham chorea, reactive arthritis and Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus pyogenes." ] },{ "paper_id": "6620e8406c8ad908234205ff102d7bd2cc0dce72", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples were adsorbed to polyvinyl formal-carbon-coated grids (EMS) for 2 min, fixed with 1% gluteraldehyde for 1 min, washed twice with PBS and twice with water, and then negatively stained with 0.5% phosphotungstic acid for 20 s. All grids were viewed in a FEI Tecnai12 BioTwinG 2 electron microscope at 80 kV accelerating voltage, and images were obtained using a Hamamatsu ORCA HR camera and compiled using ImageJ software (NIH) [47] .", "(DOCX) assistance with mass spectroscopy services. All opinions expressed in this paper are the author's and do not necessarily reflect the policies and views of USDA, ARS DOE, or ORAU/ORISE. Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U. S. Department of Agriculture. USDA is an equal opportunity provider and employer.", "Whole cell lysates of Nagasaki and D74 were generated by growth in liquid supplemented BHI media to OD 600 of 0.5-0.6. One ml of culture was centrifuged (Eppendorf 5424R centrifuge, FA-45-24-11 rotor, 7,500 \u00d7 g, 5 minutes, 4\u00b0C) to pellet bacteria and supernatant was discarded. Bacterial pellets were suspended in 0.1 ml 6M Urea and boiled at 100\u00b0C for 10 min. Lysates were aliquoted and stored at -20\u00b0C until SDS-PAGE analysis was performed." ] },{ "paper_id": "662d865c6858d8e9f3b7f583719579ee0aeabdfb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Terence W. K. Chung designed the study, collected the data, and wrote the first draft of the manuscript. Alice Y. Loke contributed in the finalization of the data analysis and presentation of the results. John W. M. Yuen provided guidance throughout Mr. Chung's study and wrote the final manuscript based on the first draft.", "A field experimental study was designed to assess the degree of staphylococcal contamination on the bedside surfaces of a medical ward, and the effects of JUC polymer on reducing such contamination. Routine operations continued to be carried out in the ward to reflect the most natural environment for assessment.", "In hospitals, surfaces with which patients have close contact or that are highly accessible to patients are more likely to become contaminated. Environmental MRSA contamination has been extensively reported in different areas of a hospital, including in intensive care units [6] [7] [8] [9] , burn units [10] , isolation rooms [11, 12] , and general wards [13] . In acute hospital wards, MRSA can be recovered from 1%-27% of surfaces in MRSA-positive patient rooms [14] . However, the incidence of MRSA contamination varies among different hospital ward surfaces, as contamination is influenced by various factors such as the condition of the patient, the ward setting, crowding, and even the sampling method [15, 16] . It has been well documented that high-touch surfaces are major reservoirs for MRSA in hospital environments. Of all hospital surfaces, bedside rails in wards occupied by MRSA patients have been identified as the site most frequently contaminated with MRSA [14] . Other frequently contaminated surfaces include bed cranks, overbed tables, bed linens, bedside lockers, bedside trays, pressure cuffs, intravenous pumps, curtains, door handles, keyboards, and floors [6, 9, 11, 13] ." ] },{ "paper_id": "66309c65612bed65732f79f347693a170e10e1f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell culture. Isolation and culture of pulmonary microvascular endothelial cells (PMVECs) were performed as described previously 3 . Briefly, the rats were euthanized after intraperitoneal injection of pentobarbital sodium. Thoracotomy was performed and the lung circulatory system was perfused by injection of 50 mL ice-cold phosphate buffered saline (PBS) via the right ventricle. The lungs were removed and washed with 30 mL ice-cold serum-free Dulbecco's modified Eagle's medium (DMEM, Sigma-Aldrich, St. Louis, MO, USA).", "Apoptosis assay. Apoptosis was determined using an annexin V-FITC apoptosis detection kit (BD, Franklin Lakes, NJ, USA) in accordance with the manufacturer's protocol. In brief, the cells were harvested, washed 3 times with PBS, centrifuged at 2000 3 g for 5 min, and resuspended in 500 mL of binding buffer (0.1 M Hepes/ NaOH, 1.4 M NaCl, 25 mM CaCl 2 , pH 7.4) to a final concentration of 1 3 10 6 cells/ mL. After incubation with 5 mL of annexin V-FITC for 10 min and 5 mL of propidium iodide for 5 min at room temperature, the cell suspension was subjected to flow cytometry on a FACSCalibur (BD, Franklin Lakes, NJ, USA) and detected at excitation wavelength 488 nm. Data were analyzed using CellQuest Pro software (BD, Franklin Lakes, NJ, USA).", "Statistical analyses. All data are presented as mean 6 standard deviation (SD). Statistical analyses were performed with the Prism software package (GraphPad v5, San Diego, CA, USA). Data were analyzed using one-way ANOVA and then the Newman-Keuls test for multiple comparisons. A P-value less than 0.05 was accepted as statistically significant.", "A cute respiratory distress syndrome (ARDS) is an inflammatory response to both pulmonary and extrapulmonary stimuli, characterized by acute onset of new or worsening respiratory dysfunction. Despite improvements in intensive care with optimal ventilation support and fluid balance, the mortality of patients with ARDS remains above 30% 1,2 . Diffuse pulmonary endothelial cell injury that results in impairment of the alveolar-capillary barrier, and increase in microvascular endothelial permeability, are considered central to the pathogenesis of ARDS 3 .", "For the present study, we investigated whether upregulation of ACE2 expression may prevent LPS-induced pulmonary inflammation and cytotoxicity by way of the MAPK/NF-kB signal pathway." ] },{ "paper_id": "6652151e876145926c6b4c6d683346811588bdfa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "C6/36 mosquito cell line derived from Aedes albopictus and Vero (African green monkey kidney) cell line were used in this study. Both cell lines were maintained and propagated in Eagle's Minimum Essential Medium (EMEM) (Gibco, NY, USA) containing 10% fetal bovine serum (Gibco, NY, USA). Cultured C6/36 and Vero cells were incubated at 28 C and 37 C, respectively in 5% CO 2 humidified chamber. At the time of virus propagation, serum concentration was reduced to 2%. Dengue virus type-2 (DENV-2) New Guinea C strain (NGC) was propagated using C6/36 cell line and harvested after CPE presentation on day seven post-infection. After titration, viral stock was stored at -70 C. Cell lines and virus were provided by Virology laboratory of the Tropical Infectious Disease Research and Education Center, Faculty of Medicine, University of Malaya (Kuala Lumpur, Malaysia).", "Dengue virus (DENV) is a member of the genus flavivirus of the Flaviviridae family. It is a significant human pathogen which causes a wide spectrum of clinical illnesses ranging from a silent or mild febrile infection, self-limited dengue fever (DF) to the severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). There are four dengue virus genotypes, DENV-1, DENV-2, DENV-3 and DENV-4 which are transmitted to humans mainly by two species of mosquitoes, Aedes agypti and Aedes Albopictus [1] . All four DENV can cause dengue. To date there are no effective vaccine or antiviral treatment for dengue. Dengue patients are usually supportively-treated until they recover without any specific treatment measures. Several studies have shown that the level of viremia correlates with the severity of disease with high viremia often seen in severe dengue. Hence, antivirals that can reduce the level of viremia or the viremic phase could possibly reduce the severity of dengue." ] },{ "paper_id": "665337fda98a7d10a291ae640001a65017960049", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "XRD was used to estimate the crystalline structure of AuNPs synthesized under optimal conditions. Measurements were performed in the symmetric \u0398/2\u0398 Bragg-Brentano geometry, using a X-Pert Pro MPD diffractometer (Malvern Panalytical, Malvern, UK) equipped with a CuK \u03b1 radiation source (\u03bb = 0.15406 nm). They were carried out after placing resultant NFs onto a poly(methylmetacrylate) holder and left to dry in ambient air." ] },{ "paper_id": "6653fce31fb0a8080aa11dde06f1c32032b28950", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lactoferrin displays high resistance to proteolytic degradation by trypsin-like enzymes, though its digestion is proportional to the degree of iron saturation. This resistance to proteolysis results in only partial digestion in the gut [28, 29] , and iron-saturated lactoferrin (i.e., halolactoferrin) is more resistant than the iron-depleted form (apolactoferrin) [29] . Abnormal N-glycan composition decreases the resistance of lactoferrins to proteolysis, and alters their immunogenicity [30] .", "Mass analysis by MS is now so accurate and sensitive that experiments can provide qualitative (structure) and quantitative (relative abundance) information on molecules after their conversion to ions [67, 68] . Although several MS techniques exist, the underlying principle is the same. Methods for separation and analysis of N-glycans by high-pressure liquid chromatography coupled to MS (HPLC-MS) and tandem MS (MS/MS)-are discussed below.", "Interestingly, lactoferrin acts as a selective anti-microbial by killing pathogens, and stimulating the growth of beneficial microorganism such as Lactobacillus and Bifidobacteium. Petschow et al. [40] demonstrated that blF specifically promotes the growth of B. infantis and B. breve, whereas human lactoferrin (hLF) stimulates greater growth of B. infantis in vitro. Karav et al. have also shown that glycans consisting of the five monosaccharides-hexose (Hex), N-acetylglucosamines (GlcNAc), fucose (Fuc), sialic acid (NeuAC), and N-glycolylneuraminic acid (NeuGc)-released from cheese whey, or lactoferrin-rich colostrum, selectively stimulated the growth of B. infantis [41] . Especially, the glycan compositions 4Hex-3HexNAc-1Fuc, 3Hex-5HexNAc, 5Hex-2HexNAc-1NeuAc, 5Hex-4HexNAc-1NeuAc, and 5Hex-3HexNAc-1NeuAc, potentially originating from lactoferrin, were preferentially utilized as substrates by B. infantis. Lactoferrin also plays important roles in immune host defense by supporting the proliferation, differentiation, and activation of immune system cells [14] . " ] },{ "paper_id": "667001630cb051990f577e069785590fce4b4d14", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Phthalides are a class of structurally very diverse secondary metabolites with more than 180 naturally occurring compounds described [1] . They are produced by a wide range of organisms, i.e., by marine and terrestrial fungi belonging to genera such as Ascochyta [2] , Aspergillus [3] [4] [5] , Alternaria [6] , Penicillium [7] , Hericium [8] or Talaromyces [9] , but also by plants and liverworts [1] .", "[http://www.beilstein-journals.org/bjoc/content/ supplementary/1860-5397-7-192-S1.pdf]", "1636" ] },{ "paper_id": "6673835e81ea115480bd68bc4e2d90c742bb77c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chicken intestinal tissues and other major organs (lung, liver, heart, kidney, and spleen) were examined grossly and histologically, and routinely fixed in 10% (vol/vol) phosphate-buffered formalin for 48 h at room temperature [29] . They were then embedded, sectioned, and stained with hematoxylin and eosin (H&E). Slides were examined for light microscopy examination by conventional light microscopy.", "Fresh and formalin-fixed samples, including the heart, liver, spleen, lung, kidney, duodenum, jejunum, ileum, cecum, rectum, and pancreas, were collected during the chicken necropsy. The fresh samples were used for viral distribution assay and the formalin-fixed tissues served as the pathologic examination.", "Coronaviruses (CoVs) are enveloped, single-stranded, positive-sense RNA viruses that can infect and cause diseases in avian and mammal species, including humans [1, 2] . CoVs contain the largest known RNA genomes and can be genetically divided into four genera; namely, Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus [3] . Deltacoronavirus (DCoV) genus was mainly discovered in a variety of avian species and pigs [4, 5] . Porcine DCoV (PDCoV) was first detected in pigs during a molecular surveillance of CoVs in mammals and birds in Hong Kong in 2012 [5] , while the first PDCoV outbreak in swine herds was reported in 2014 in the United States [6] [7] [8] . Thereafter, PDCoV was rapidly identified in many countries, including China, Canada, South Korea, Lao People's Democratic Republic, Thailand, and Vietnam [9] [10] [11] [12] [13] . PDCoV can cause severe diarrhoea, vomiting, and dehydration in suckling and nursing piglets, and the clinical symptoms are indistinguishable" ] },{ "paper_id": "668aeb98c355caf8edcbbcb808215f26e7c388ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were detergent-lysed and performed as previously described 62 ." ] },{ "paper_id": "6694490cc1353addf66465e4d06419ff0b0af753", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our published protocol was followed with slight modification [9] . Briefly, homogenized brain material was centrifuged through a 30% Percoll gradient at 7,800 g ave for 30 minutes without braking. The washed and strained cell suspension was then centrifuged on a 1.100 g/mL Percoll layer for 20 minutes at 800 g ave . The interface containing neutrophils and inflammatory monocytes was collected, washed, and used for flow cytometry.", "Cognitive performance was assessed beginning at 14 days postinfection using our previously published methodology [1] ." ] },{ "paper_id": "669511bfee375dd73d141c494f53d027c903f734", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6695dd7f637481312d8589cbc32aa3bef1c816a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Another possibility is that G3BP1 recruits a larger fraction of the cell mRNPs than other SG-nucleating proteins. G3BP1 binds mRNA through its RRM domain, however, the number of binding targets is unknown, but may be numerous, and includes c-myc and tau mRNAs [72] [73] [74] . Unfortunately, no RNAseq data are available to determine to what extent G3BP1, G3BP2, Tia1, TDP-43 or other SG nucleating proteins are bound to unique or overlapping sets of mRNAs in the cell.", "Acknowledgments: This work was funded by NIH Public Health Service grants AI50237 (Richard E. Lloyd) and CA168872 and supported by the Integrated Microscopy Core at Baylor College of Medicine with funding from the NIH (HD007495, DK56338, and CA125123), the Dan L. Duncan Cancer Center, and the John S. Dunn Gulf Coast Consortium for Chemical Genomics.", "The author declares no conflict of interest." ] },{ "paper_id": "66a137256be1759200f9fc27164e526287470c8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ": Summary of the minimum sampling threshold S min after 12 weeks for random movement sampling (RMS), snowball node sampling (SBS) and targeted node sampling (TNS) without markets and S min after one infectious period with markets for epidemics seeded in Cumbria, Devon and Aberdeen. Parameters were \u03b2 = 1 and T = 21 days. For TNS the number of movements a farm needs in order top be sampled is given in parentheses.", "Cumbria Devon Aberdeen RMS without markets 50% 40% 60% SBS without markets 30% 20% 30% TNS without markets 9% (50) 3% (80) 8% (60) RMS with markets 20% 10% 10% SBS with markets 50% 40% 50% TNS with markets 30% (20) 25% (25) 30% (20) Table 1: Summary of the minimum sampling threshold S min after 12 weeks for random movement sampling (RMS), snowball node sampling (SBS) and targeted node sampling (TNS) without markets and S min after one infectious period with markets for epidemics seeded in Cumbria, Devon and Aberdeen. Parameters were \u03b2 = 1 and T = 21 days. For TNS the number of movements a farm needs in order top be sampled is given in parentheses.", "Supplementary figures for Cumbria \u03b2 = 1, T = 21 days Figure SI 8: Epidemic measurements for outbreaks seeded in Cumbria using the RMS method with \u03b2 = 1 and T = 21 days. Plot a) shows the mean epidemic size in weekly intervals with ascending contours representing the epidemic size progression through time in weeks, the size after 6 (red) and 12 (blue) weeks are highlighted for reference. Plot b) shows the mean epidemic duration in weeks with 95% confidence intervals. Plot c) shows the mean peak size of the epidemic with 95% confidence intervals. Figure SI 9: Epidemic measurements for outbreaks seeded in Cumbria using the RNS method with \u03b2 = 1 and T = 21 days. Plot a) shows the mean epidemic size in weekly intervals with ascending contours representing the epidemic size progression through time in weeks, the size after 6 (red) and 12 (blue) weeks are highlighted for reference. Plot b) shows the mean epidemic duration in weeks with 95% confidence intervals. Plot c) shows the mean peak size of the epidemic with 95% confidence intervals. Figure SI 10: Epidemic measurements for outbreaks seeded in Cumbria using the SBS method with \u03b2 = 1 and T = 21 days. Plot a) shows the mean epidemic size in weekly intervals with ascending contours representing the epidemic size progression through time in weeks, the size after 6 (red) and 12 (blue) weeks are highlighted for reference. Plot b) shows the mean epidemic duration in weeks with 95% confidence intervals. Plot c) shows the mean peak size of the epidemic with 95% confidence intervals. Figure SI 11: Epidemic measurements for outbreaks seeded in Cumbria using the TNS method with \u03b2 = 1 and T = 21 days. Plot a) shows the mean epidemic size in weekly intervals with ascending contours representing the epidemic size progression through time in weeks, the size after 6 (red) and 12 (blue) weeks are highlighted for reference. Plot b) shows the mean epidemic duration in weeks with 95% confidence intervals. Plot c) shows the mean peak size of the epidemic with 95% confidence intervals. " ] },{ "paper_id": "66a1d5898c1fb5c8e8554f92e446d262abb10fdb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "66a3eded4d7bae681a0079a333c4acb75fe05828", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.", "To investigate the prevalence of human bocavirus (hBoV), human coronaviruses (hCoV), and human polyomaviruses (hPyV) among patients with severe acute respiratory illness (SARI), in South Africa.", "The study included 680 South African patients randomly selected in agedefined categories from hospitalised patients enrolled through SARI surveillance during 2012 to 2013. A multiplex reverse transcription real-time polymerase chain reaction assay was used to detect hBoV; hCoV-OC43, hCoV-229E, hCoV-NL63, and hCoV-HKU1; and Washington University hPyV (hPyV-WU) and Karolinska Insitute hPyV (hPyV-KI), in respiratory tract specimens collected from patients with SARI. All respiratory specimens from patients enrolled through SARI surveillance were also routinely tested by multiplex reverse transcription real-time polymerase chain reaction for adenovirus; enterovirus; human metapneumovirus; parainfluenza virus types 1, 2, and 3; respiratory syncytial virus; rhinovirus; influenza A, and influenza B." ] },{ "paper_id": "66a6a5cb7b41fb6edd030629be7c455c079f47bf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA was extracted from each sample using TRIzol \u00ae reagent (Ambion: ThermoFisher, Waltham, MA, USA) and cleaned with RNA Clean and Concentrator-5 \u2122 (Zymoresearch, Irvine, CA, USA). After DNaseI (New England Biolabs, Ipswich, MA, USA) treatment, RNA was again cleaned with RNA Clean and Concentrator-5 and the quality of RNA was checked with an Agilent Bionalyzer 2100 using RNA nano chip (Agilent Technology, Santa Clara, CA, USA). RNA samples with RNA integrity numbers > 7 were subjected to library contraction.", "TUNEL staining was performed using in situ Apoptosis Detection Kit according to the manufacturer's instruction (Abcam, Cambridge, UK). Formalin-fixed paraffin embedded sections from diseased tissues were permeabilized with protease K, and labeled with HRP-conjugated dUTP. Labeled cells were visualized with DAB colorimetric detection.", "DC-SIGN (CD209) showed significant down-regulation, while known receptor molecules for other coronavirus species of people and animals were either marginally down-regulated (DDP4) or their RNAs not detected (ND) (L-Sign, ACE2, APN) (Table 8 ).", "scenario, more immature and less virus-laden peritoneal monocyte/macrophages fail to undergo programmed cell death, while older virus laden cells are specifically targeted for destruction by a mechanism distinct from classic apoptosis [35] . Such a process assures persistence of infected cells, while allowing for efficient dissemination of the pathogen [36] ." ] },{ "paper_id": "66adc3747695647a2654d4c3bad5d90a3acafbd1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The siRNA was designed by and obtained from GenePharma (Shanghai, China). Beclin1 siRNA sequence: 5'-CCCAGUGUUCCCGUAGAAUTTAUUCUACGGGAACACUGGGTT-3'; ATG5 siRNA sequence: 5'-GCAACUCUGGAUGGGAUUATTUAAUCCCAUCCAGAGUUGCTT-3'.", "All experiments were performed independently three times, and variables are expressed as the means with SEM. Statistical analyses were performed using student's t-test. A p-value < 0.05 was considered as statistically significant." ] },{ "paper_id": "66bffe926972c130c5b6239868ae422a8c7d7229", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Survey questions with missing values for key analytical variables were excluded using a pairwise method.", "Not applicable.", "The National Research Foundation of Korea was the study sponsor. The researcher was independent of the study sponsor." ] },{ "paper_id": "66cda0b3d87b530e2659f8ac93a74ed963e9645e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Silanization of the PWA chip to avoid cross-contamination", "Recently, a number of reports have proposed RPA-based strategies for pathogen detection. The detection formats include fluorescence detection in real time or endpoint detection via a lateral flow strip [52] [53] [54] [55] . Reverse transcription RPA can be also used to detect RNA targets from foot-and-mouth disease virus or Middle East respiratory syndrome coronavirus [56, 57] . Additionally, RPA is highly sensitive for the detection of HIV proviral DNA and Mycobacterium tuberculosis DNA [52, 55, 58] . Instrument-free and electricity-free RPA can be performed using body heat or heating achieved using sodium acetate trihydrate for nucleic acid diagnostic tests in low-resource settings that lack expensive thermal cycling PCR equipment or even electric power [59, 60] ." ] },{ "paper_id": "66d172659a7156097bd453af7028c06632c231a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A representative sample of New South Wales (NSW) residents aged 16 years and older were interviewed during May and June 2011 using a computer assisted telephone interview (CATI) method. NSW is Australia's most populous state with a population of 7.2 million in 2010. The sample consisted of people who had been randomly selected in 2010 for a population health survey using an electronic telephone directory and geo-coded to ensure satisfactory NSW representation [Hunter New England Area Health Service: Good For Kids: good for life. Data Dictionary. Baseline Random Household CATI, Section 1.3 page 1 (unpublished). Newcastle: Hunter New England Area Health Service; 2010]. This group had indicated their willingness to participate in future surveys. The database (containing names and telephone numbers only) formed the sampling frame.", "Ethics approval was obtained from the Hunter New England Human Research Ethics Committee (approval number 11/04/20/5.12).", "Respondents reported a range of reasons for handling bats ( (Table 3) ." ] },{ "paper_id": "66daba9fe4360f00714bd778402b6ac3489b2ec6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "G-quadruplex (G4) structures formed by guanine (G)-rich nucleic acid sequences are characterized by their fourstranded G-tracts in combination with multiple stacked G-quartets. As opposed to typical Watson-Crick base pair forming duplexes, G-quartets are constituted by noncanonical Hoogsteen hydrogen bonds between these G bases. Although both RNA and DNA can adopt G4s, structural analysis demonstrates that RNA G4s fold into parallel-stranded conformations independent of nucleotide sequences, the species of cations and the concentration of RNA molecules (1) . DNA G4s show structural polymorphism according to various factors (2, 3) . These polymorphic structures have been shown to correlate with biological functions (4, 5) .", "Supplementary Data are available at NAR Online.", "Funding for open access charge: Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands", "Selected G4 constructs were tested in HEK293T cells using the dual luciferases reporter, pDUAL-HIV(0), as described earlier (29) . In short, pDUAL-HIV(0) was digested by KpnI/BamHI, followed by insertion of complementary oligonucleotides. HEK293T cells were cultured in Dulbecco's modified Eagle's medium/high glucose/stable glutamine (PAA Laboratories) supplemented with 10% fetal calf serum and 100 U/ml penicillin and 100 mg/ml streptomycin. Cells were kept in a humidified atmosphere containing 5% CO 2 at 37 C on a regular subculturing regime. Cells were transfected with 300 ng of plasmid by 1 ml of Lipofectamine 2000 (Invitrogen) in a 24-well culture plate. Cells were lysed 20-24 h after transfection and luciferase activities were measured by GLOMAX multidetector (Promega) using Dual-Luciferase Reporter Assay Kit (Promega). Frameshifting efficiency was obtained by dividing the ratio Renilla luciferase (RL) over Firefly luciferase (FL) activity of the mutant by the RL/FL ratio of the in-frame control and multiplied by 100." ] },{ "paper_id": "66e863b67f8ef14a8a953841b6ddf7a2cefaf696", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For", "where (p t i ) : (d i j ) is a vector by matrix multiplication.", "The parameter values after the next EM iteration are given by" ] },{ "paper_id": "66f31952c8b998f8c9de4d34c17a7c2e0d2e35fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Newcastle disease virus (NDV) is a member of the genus Avulavirus within the subfamily Paramyxovirinae of the Paramyxoviridae family [10] . NDV has a negativesense, non-segmented, single-stranded RNA genome of at least three sizes of 15,186, 15,192, and 15, 198 nucleotides (nt) [11] . Six transcriptional units encode two surface glycoproteins, the fusion protein hemagglutininneuraminidase, the matrix protein, and the ribonucleoprotein complex, composed of the nucleocapsid protein (NP), a phosphoprotein, and large polymerase, which is necessary for viral transcription and replication. As is often the case, for its genomic replication, NDV first generates a full-length positive-strand antigenomic RNA and then, in turn, serves as a template for the synthesis of new negative-stranded RNA genome, which forms a dsRNA intermediate [12] .", "Data were expressed as means \u00b1 standard deviations. Significance was determined with the two-tailed independent Student's t test (p < 0.05) between two groups. One-way ANOVA followed by Tukey's test was used to compare multiple groups (>2).", "HeLa cells were lysed in lysis buffer (50 mM Tris-HCl, pH 8.0, 150 mM NaCl, 20 mM NaF, 1 mM ethylenediaminetetraacetic acid, 1% Triton, 1 mM phenylmethylsulfonyl fluoride, 1 mM ethylene glycol tetra-acetic acid, 20 mM Na 4 P 2 O 7 , 1 mM Na 3 VO 4 ) containing the protease inhibitors leupeptin (0.5 \u03bcg/mL), aprotinin (0.5 \u03bcg/mL), and pepstatin (0.7 \u03bcg/mL). Cells were sonicated for 1 second using a Vibra Cell VCX130 sonicator (Sonics Vibra cell; Sonics & Material, Newtown, CT, USA), boiled for 5 min, and then cleared by centrifugation for 10 min at 12,000 g at 4\u00b0C. The lysates were further denatured by incubation for 5 min at 95\u00b0C in SDS-PAGE sample loading buffer (Beyotime, Nantong, China). The samples were further separated on 10% polyacrylamide gel (Bio-Rad Laboratories, Inc., Hercules, CA, USA), and transferred to a nitrocellulose membrane at 250 mA for 90 min, and then blocked using Tris buffered saline (TBS) solution containing 0.1% Tween 20 and 5% non-fat milk for 2 h. The membrane was incubated overnight at 4\u00b0C with the indicated antibodies. After washing three times with TBS/0.1% Tween 20, the membrane was exposed to horseradish peroxidase-conjugated anti-rabbit or anti-mouse IgG antibody (Sigma-Aldrich) at a dilution of 1:10000 for 2 h at room temperature. The protein bands were visualized with an enhanced chemiluminescent reagent (Pierce Biotechnology, Rockford, IL, USA) and quantified using Image J software." ] },{ "paper_id": "66f3b61dee5fb0898bad0667c35c210bdd020b9f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In summary, suicide prevention is an everyday battle and requires close cooperation of suicide prevention professionals, media professionals, and policy makers. Improving the social economic environment is important for protecting the population from suicide risk, whereas strategically and constructively changing media reporting practices is certainly a powerful weapon in defending lives against suicide. ", "The shape parameters of the above self-or mutual-excitation effects around or smaller than 1, which indicates that those effects mainly took place in the following one or two days and then quickly diminished." ] },{ "paper_id": "66f425e847bc112e32f81cac4c2c57b1b6d0f284", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The SJL/J mouse is an interesting model for a number of diseases and it remains possible that with further study, significant information may be forthcoming on the inflammatory environment within the liver and salivary glands. However, it appears that such responses are antigen non-specific.", "A mitochondrial fraction isolated from bovine heart tissue was prepared as described previously (Fregeau et al., 1990) ; native PDC-E2 was thence purified (Stanley and Perham, 1980) . As a negative control, a-casein, was purchased from Sigma Inc. (St Louis, MO). A lipoated, huPDC-E2 peptide (p163) spanning amino acids 163-176 (GDLLAEIETDKATI), previously shown to be a major T cell epitope (6 -8), was synthesized by Alpha Diagnostic International (San Antonio, TX). Peptide purity was confirmed by reversed phase HPLC.", "Interestingly, focally globular amyloid depositions developed along the walls of hepatic vessels in mice immunized with bovine PDC-E2 regardless of IFN-g treatment (Fig. 3d) . These amyloid depositions were characterized as AA type as the amyloid was sensitive to KMnO 4 treatment. In contrast, amyloid deposition was not detected in mice injected with the a-casein and there was no significant difference in histology between a-casein groups treated with or without IFN-g administration (data not shown)." ] },{ "paper_id": "66fb607e8ee0e7b13f1abaedf0ed42451c8924a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A standardized questionnaire was used to gather demographic and hospitalization data such as signs, symptoms, underlying medical conditions, and laboratory test results, radiographic findings, and disease outcome. Laboratory tests included sputum culture and an array of serological assays including IgG and IgM enzyme-linked immunosorbent assays (ELISAs) for previous infection with cytomegalovirus (CMV), Epstein-Barr virus (EBV), Chlamydia pneumoniae (CP), and Mycoplasma pneumoniae (MP)." ] },{ "paper_id": "66ffa4cc6c425005054eea58142f7b23307025ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analysis of similarities (ANOSIM) is a nonparametric test that shows whether the difference between groups is greater than that within groups. The analyses were performed in vegan or QIIME in R (version3.2.2) by using the Bray-Curtis algorithm [31] .", "We ran a regression analysis between bacterial microbiome diversity and virome richness with the stats package and plotted the results using the ggplot2 package." ] },{ "paper_id": "670ade9d86b2fb507104d011a048323450e21b59", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The highly conserved species of B. anthracis exhibits near perfect probe reuse. Almost every B. anthracis probe" ] },{ "paper_id": "670f2388055a866aa6706a2c1130d68c2f37d15d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Adenovirus harboring different dominant-negative (DN) PKC isoforms and DR6 was titrated and added to cell culture at the 50x MOI (multiplicity of infection) for 24 hrs.", "Northern blot was performed as described previously [23] . Total RNA was extracted using TRIzol reagent (Invitrogen) and subjected to formaldehydeagarose gel electrophoresis. RNA was transferred to nylon membranes (Amersham Biosciences), UV-crosslinked and hybridized with dCTP-labeled 444-bp fragment (see Supplemental Figure 2 , in Supplementary Material available online at https://doi.org/10.1155/2017/2754756) of human DR6 cDNA. 18S and 28S rRNA were used as internal controls. Intensities of hybridized bands were quantified using Image J software.", "All experiments were repeated for at least three times. Image bands from Western blot, Northern blot, and PCR/qPCRs were quantified using Image J software (NIH website). Data was presented as mean \u00b1 SD. Statistical analysis was performed using Prism software for comparison by either Student's -test (two groups) or one-way ANOVA (\u2265three groups). A value of less than 0.05 was considered a significant difference." ] },{ "paper_id": "671f1c2956296e84da394af512513ea165882eba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Measurements are mean \u00b1 standard error of the mean (SEM ", "Data from six consecutive cardiac cycles were used to determine heart rate (HR) and a marker of left ventricular contractility, peak velocity (PV). Values of SV and HR were used to calculate cardiac output (CO). Respiration rate was determined from movement of the diaphragm using time-motion (M)-model. At the end of the study rats were euthanized by intravenous pentobarbitone and exsanguination.", "Human tissues samples were obtained with informed consent (Papworth Hospital Research Tissue Bank REC08/H0304/56) and local ethical approval (REC05/Q0104/142)." ] },{ "paper_id": "67282d82fcba34faf696a510ca4d54b8804289cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DNA sequencing. The positive clones from the monoclonal ELISA were cultured at 37 \u00b0C and 200 rpm for 15 h. The cell pellets were collected and plasmid extraction was performed using QIAprep Spin Miniprep Kit (Qiagen, Germany). The purified plasmids were sent for sequencing (FIRST Base Laboratories Sdn Bhd, Malaysia). The sequencing results were then analysed by IMGT/V-QUEST bioinformatics tool available at IMGT \u00ae , the International ImMunoGeneTics information system \u00ae 62,63 ." ] },{ "paper_id": "672ae4f77f6a2cc3358bfe1e492c268e2dbe3d7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This system, which can produce .0.4 million clones per run within a half-day, could also be very useful for the rapid identification of important mutation(s) by direct comparison with wild and mutant viruses, including ''pandemic Flu'' [35] and more virulent noroviruses [36, 37] .", "Viral RNA was extracted from nasopharyngeal and fecal specimens with a QIAamp Viral RNA Mini Kit (QIAGEN), and cDNA was synthesized using SuperScript TM III reverse transcriptase (Invitrogen) with a random hexamer, as described previously [21] . The generated cDNA was subjected to PCR using the Expand High Fidelity PLUS PCR System (Roche) with primer sets specific to viruses, such as human coronaviruses [38] , WU polyomavirus [24] , and PMMV [31] .", "As shown in Table 3 , 3,039-23,955 (11.9-83.1%) reads were estimated to be bacterial genes. Of those, more than half (54.7-69.9%) were rRNA-derived (Table 5 ) and a BLAST searching predicted the existence of commensal bacteria in the human intestine (data not shown)." ] },{ "paper_id": "6737b541bf9d5d5bbb80cc1dd06456f93dbcda72", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "were recently hypothesized to occur on a haplotype associated with an increased risk for Johne's disease [46] . Consequently, we used PHASE 2.1 [31] to test the hypothesis that haplotype frequencies for bacterial-sensing TLRs differ between cases and controls. However, none of the investigated loci possessed significantly different haplotype distributions between cases and controls (P.0.05; 1,000 permutations).", "Bovine DNA samples (n = 96) representing B. t. taurus, B. t. indicus, and their hybrids were isolated from spermatozoa as previously described [23, 25, 30] Bovine TLR Sequencing and SNP Detection", "At each polymorphism we estimated the effective number of alleles as E i = 1/(1 -2p i (1-p i )) = 1/(p i 2 + (1 -p i ) 2 ) = 1/(expected HWE frequency of homozygotes) where p i is allele frequency at the i th locus. Thus a measure of polymorphism diversity is log 2 (E i ) which also represents the information content of each SNP [30] . For monomorphic SNPs log 2 (E i ) = 0 and for SNPs with p i = 0.5, log 2 (E i ) = 1. Thus by summing across the N j polymorphisms within the j th gene we obtain the diversity index I j = . We used regression analysis to examine the relationship between I j and N j for these genes and to test for outliers using 95% confidence estimates for the fitted regression." ] },{ "paper_id": "67448222647675616fa788dcf9426cefa3fd9575", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "To date, four MPXV small animal models have been used for the testing of antiviral drugs Cidofovir, CMX001 and ST246 (tecovirimat). Herein we will summarize those studies, efficacy data, and discuss the advantages, and limitations, of the animal models used." ] },{ "paper_id": "67466fd44aa1843c57174386e917578f0d83d71a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In order to facilitate research and make our model more reasonable, some assumptions are made:", "6. Avoiding close contact with people who are sick;", "7. Covering your mouth and nose with a tissue or your sleeve when coughing or sneezing." ] },{ "paper_id": "67727dc7bb076ef6ddeb55c754af98e672ee60e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors contributed equally to this work. bacteria to mammalian cells. ", "In the future tailor-made vaccines might be the solution for individuals with a genetic profile prone to autoimmunity.", "Active vaccination using recombinant L. johnsonii to treat allergy has been suggested [32]. IgE epitopes was fused to proteinase PrtB and cell wall-anchored. Subcutaneous and intranasal immunization of mice induced a systemic IgG response against human IgE. As such, allergy-inducing IgE may be cleared by IgG antibodies induced by the recombinant L. johnsonii. However, it remains to be proven if these antibodies are protective in human patients.", "In conclusion, LAB has been successfully used for active vaccination of animals like rodents (Table 2) . Whether LAB will be effective as a mucosal vaccine in humans can only be answered by clinical trials. Furthermore, as the dose of recombinant LAB needed to elicit immune Lactobacillus johnsonii TTFC mimotope Mouse [116] responses in animals is high it is unknown if the necessary dose for use in humans will be feasible and cost effective.", "It can be concluded that immune polarization towards either a Th2 or a Th1 response can be obtained using different LAB. As such the intrinsic immune modulatory capacity of the LAB must be evaluated and selected to fit the purpose of vaccination." ] },{ "paper_id": "67773f5f18353fa2783c550d6c7fc52a2e10d0bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Let \uf04c be the set of 4 bases, i.e., = A C G T { , , , } \uf04c and Q = (s 1 , s 2 , ..., s n ) be a DNA sequence of length n, that is,", "Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 12226 |" ] },{ "paper_id": "6777d788e99e108bf3439ed5a79ac921ee60d06e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "678116d4f14c2470ef9dbde987d11b2e9b679865", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All studies were carried out in strict accordance with the recommendations in the National Guide for the Care and Use of Laboratory Animals. The protocol (VMRI-AP140516) was approved by the Review Board of National Research Center of Engineering and Technology for Veterinary Biologicals, Jiangsu Academy of Agricultural Sciences.", "The inactivated IB monovalent vaccine (M41 strain) was prepared according to the criteria of multivalent vaccine, which contains the component of M41 strain, 10 6.5 mean egg infective dose (EID 50 ) per dose, and the live IB commercial vaccine (H120 strain) was derived from Tianbang.", "Results were presented as means \u00b1 the standard errors (SEM). Prism software (GraphPad Software, Inc., San Diego, CA, United States) was used for data analysis with unpaired two-tailed Student t-test or a one-way analysis of variance (ANOVA). Comparisons used to generate P-values are indicated by horizontal lines ( * P < 0.05, * * P < 0.01, * * * P < 0.001)." ] },{ "paper_id": "6783ff6a7398428f7a6bb894d39c44746b85cf73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusions Although the quality of association studies seems to have improved over the years, more and better designed studies, including the replication of previous findings, with larger sample sizes extended to population groups other than those of European descent, are needed for identifying firm genetic modifiers of ALI.", "Our search identified a total of 29 studies reporting positive findings for 16 genes involved mainly in the response to external stimulus and cell signal transduction. The genes encoding for interleukin-6, mannose-binding lectin, surfactant protein B, and angiotensin-converting enzyme were the most replicated across the studies. On average, the studies had an intermediate quality score (median of 4.62 and interquartile range of 3.33 to 6.15).", "Positive genetic association studies with acute lung injury/acute respiratory distress syndrome susceptibility and/or outcome (by year of publication)" ] },{ "paper_id": "6799e37b5fda2d18292b86b6a6c7ba1eb185d018", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "might offer targets to develop novel strategies of treatment. Comprehensive knowledge about the underlying mechanisms of pathogen-host interaction and the induction of the antiviral host innate immune response is crucial.", "Transient transfection of plasmids and siRNA. A549 and A431 cell lines were transfected with plasmid using Lipofectamine 2000 (Invitrogen) according to the manufacturer's protocol. pCMV-myc-hIFITM3 was kindly provided by Jacob Yount (Addgene plasmid number 58461). Human AnxA6 was expressed from the plasmid pEGFP-N1 (41), and murine NPC1 was expressed from the plasmid pEYFP-N2 (42) . pEGFP-N3 served as a control.", "Acidic bypass. The applied assay was established previously by Stauffer et al. (23) . Prior to infection, cells were preincubated with bafilomycin A1 (Cayman catalog no. cay-11038) (250 nM). Virus (PR8M) was primed for 1 h at 37\u00b0C with DMEM adjusted to pH 5.8 with MES (morpholineethanesulfonic acid) (30 mM). Cells were infected at an MOI of 50 with primed virus for 1 h on ice and subsequently washed twice with" ] },{ "paper_id": "67a33cdb3341a7385fe74d41f0ba2b9e22f68300", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Swine are an important models for human anatomy, nutrition, metabolism and immunology [1] [2] [3] . Their organs are anatomically and histologically similar to humans as are their sensory innervation and blood supply [4] . Pigs are naturally susceptible to infection with organisms that are closely related or identical to those species infecting humans including helminths (Ascaris, Taenia, Trichuris, Trichinella, Shistosoma, Strongyloides), bacteria (Campylobacter, Chlamydia, Eschericia coli, Helicobacter, Neisseria, Mycoplasma, Salmonella), protozoans (Toxoplasma) and viri (Coronavirus, Hepatitis E, Influenza, Nipah, Reovirus, Rotavirus) [2, 5, 6] . The last 10 years has seen a boon in the development of genetically modified pig as models for human cardiovascular and lung disease, neurodegenerative and musculoskeletal disorders [7, 8] and cancer [9] . There is also a robust effort to develop pigs as sources for organs and tissues for human xenotransplantation [10] .", "We have discovered several sources of systematic errors in the Ensmbl and NCBI gene/protein prediction or annotation pipelines. For example all selenoproteins in Ensembl are truncated because the codon (UGA) for selenocysteine is mistranslated or translated as a stop codon. We and others have identified a systematic error in the identification of another gene family, the Taste receptor, type 2 (TAS2R) Superfamily. Despite being intronless and mostly devoid of 5\u2032 and 3\u2032 UTR regions, Ensembl consistently fails to recognize them as genes [3] . These data illustrate the critical importance of the manual-curation process to reduce errors.", "The state of the current genome build (mis-annotations, duplication artifacts, and missing sequences) effectively prohibits its use for aligning RNAseq reads. We have used these sequences to compare gene expression separately from Ensembl 10.2 and have also compared the number of reads obtained from the corresponding templates in Ensembl 10.2. For the great majority of transcripts compared, as expected, our full-length sequences provided a higher level of sensitivity than the corresponding Ensembl sequences (H. Dawson unpublished) . The full 5\u2032 and 3\u2032 representation of each gene will also allow for characterization of regulatory regions and miRNA target sites. In our estimation, >40% of transcripts in Ensembl or NCBI genomes do not represent the fulllength gene. Our efforts will also allow for further consolidation of porcine Unigene numbers. Currently, each gene is represented by from 0 to >10 Unigene assignments, and >10% of genes have more than one." ] },{ "paper_id": "67a72161f9ca2ec9aa5649980667e7fef2125539", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Acute myositis accompanied by rhabdomyolysis may rarely happen, most commonly in children who present with extreme tenderness of lower extremities, and the laboratory investigation shows marked elevation of serum creatinine phosphokinase and myoglobinuria [82] . Myocarditis and pericarditis have also been rarely described in clinical cases, but demonstrated in autopsy studies [83, 84] . Central nervous system complications associated with influenza include encephalitis, acute disseminated encephalomyelitis, transverse myelitis, aseptic meningitis, and Guillain-Barre syndrome [85] [86] [87] (Table 2 ).", "More recently, a large cohort from Australia and New Zealand reported that during the winter of 2017, the predominant H3N2 virus strain was associated with unprecedented high levels of ICU admission due to viral and bacterial pneumonias, even higher than 2009 H1N1 pandemic [38] .", "The ferret has traditionally been used as a model of influenza transmission as most human influenza viruses do not need any adaptation to infect and transmit among ferrets. Studies in ferrets have identified the soft palate as a major source of influenza viruses that are transmitted between individuals. Notably, the soft palate is enriched in \u03b12,6-linked sialic acids, which are preferred by the hemagglutinin proteins currently found in circulating human influenza viruses [2] . This enrichment also occurs in the soft palate of humans [3] ." ] },{ "paper_id": "67ad221f50d67a02b89b0ea67da2a74d6d463d16", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:36197 | DOI: 10.1038/srep36197", "Results obtained with time-series word count are easily understandable even for those unfamiliar with evolutionary biology. When social importance of time-series word count of oligonucleotides becomes clear, experts in various fields will participate actively. Huge numbers of genome sequences, including those from disease-causing microbial strains, have accumulated rapidly because of revolutionary development in sequencing technologies and of social importance. In this era of big data accumulation, participation of experts in big data analysis becomes increasingly important for interdisciplinary efforts against big threats presented by infectious microorganisms.", "Viruses have always posed significant threats to public health, as highlighted by the recent ebolavirus outbreak in West Africa [1] [2] [3] [4] and the emerging and re-emerging nature of influenza viruses 5 . To face the world-wide threats caused by zoonotic RNA viruses, which suddenly cause serious outbreaks by invasion from nonhuman hosts and mutate rapidly, we must understand the molecular evolutionary changes in their genome sequences extensively by innovating various technologies, including those used in big data analyses, e.g., large-scale word count. Time-series word count of oligonucleotides in genome sequences can be conducted without specialized assumptions and prior knowledge and is useful for unsupervised data mining. Importantly the obtained results are easily understandable, even for those unfamiliar with molecular evolutionary studies.", "Averaged mono-and dinucleotide compositions (a,b), for strains in each month are plotted according to the elapsed months from April 2012. Camel-derived strains are specified by small brown symbols, and regression lines (blue) were calculated only for human-derived strains. The null hypothesis was rejected for all data (8 cases) at the significance level of 0.01, except for A% and G%, with or without camel-derived strains; this was rejected for the G% at the significance level of 0.1." ] },{ "paper_id": "67b6aa7293bbb9a8fed752ae0e96553f4f5c44aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To extend the molecular characterization of quantitative differences and only-one-exists groups, UniProt and GO databases were used to characterize information about biological processes (BPs), molecular functions (MF), and cellular components (CC).", "The MS data were analyzed using MaxQuant software version 1.3.0.5. MS data were searched against the uniprot Sus scrofa sequence database (including 34 253 sequences downloaded on 12/27/2014). An initial search was set at a precursor mass window of 6 ppm. The search followed an enzymatic cleavage rule of Trypsin/P and allowed maximal two missed cleavage sites and a mass tolerance of 20 ppm for fragment ions. Carbamidomethylation of cysteines was defined as fixed modification, while protein N-terminal acetylation and methionine oxidation were defined as variable modifications for database searching. The cutoff of global false discovery rate for peptide and protein identification was set to 0.01. Label-free quantification was carried out in MaxQuant as previously described. Protein abundance was calculated on the basis of the normalized spectral protein intensity (LFQ intensity).", "The animal study protocols were approved by the Animal Care and Use Committee of Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences." ] },{ "paper_id": "67bd507b6486d95e40e4f1435d45efd6421267c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The full-length genome sequence of the PDCoV strain CH/SDX1/2015 has been deposited at GenBank with the accession number KT021234.", "A porcine deltacoronavirus (PDCoV) was identified in the Chinese mainland and found to be closely related to Hong Kong strain HKU15-155 but differed from PDCoV strains in the United States and South Korea. The complete genome of PDCoV strain CH/SXD1/201 was sequenced and analyzed to further characterize PDCoV in Chinese swine.", "The genome of CH/SXD1/2015 was identified as 25,419 nucleotides (nt) in length excluding the 3= poly(A) tail, three nucleotides shorter than the other U.S. and South Korean strains deposited in GenBank. The genomic structure of PDCoV, except the 3= pol(A) tail, was 5=-UTR-ORF1-S-E-M-NSP6-N-NSP7-3=UTR, and the nucleotides numbers of these parts were 539, 18,803, 3,480, 252, 654, 285, 1,029, 603, and 392, respectively." ] },{ "paper_id": "67c9acbf8204919fe540d58d7db296b9210f1e90", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "From September 2011 through March 2013, we recruited students presenting to McMaster University's campus health clinic who were at least 17 years old, reported a sore throat, presented within three days of symptom onset (to maximize viral detection) [7] , and did not have concurrent serious illness, as judged by their health-care provider. After providing consent, patients completed a questionnaire regarding onset of illness and severity of signs and symptoms, adapted from a previously validated survey [8] . Trained study staff then sampled the patient's left side of their throat and tonsils with a rayon throat swab (Copan Italia); the left nostril was subsequently sampled using a flocked mid-turbinate nasal swab (FLOQSwabs; Copan Italia). Both swabs were placed into universal transport medium (UTM; Copan Italia) and frozen at \u221280\u00b0C until analysis. Seven days later, patients were e-mailed a follow-up survey regarding the impact of their illness on their day-to-day lives.", "Specimens were batch extracted using the NucliSENS easyMAG assay (bioM\u00e9rieux Canada; St. Laurent, Qu\u00e9bec) and tested for respiratory viruses using the xTAG respiratory virus panel (RVP) version 1 (RVPv1, Luminex; Austin, TX), which detects 16 virus types and subtypes [9] ; two laboratory-developed multiplex real-time polymerase chain reaction (PCR) assays for adenovirus [10] , metapneumovirus [11] , respiratory syncytial virus [12] , and influenza A and B and parainfluenza 1-3 [13] used by the Hamilton Regional Laboratory Medicine Program for routine respiratory virus diagnosis; and a reverse-transcriptase PCR for enterovirus and rhinovirus [14] . In addition, information regarding detection of betahemolytic streptococcal species (group A, C and G)-as diagnosed by the treating clinician during routine care-was also gathered per patient from the clinic, which did not use any of the specimens gathered from our study. As per standard of care, the clinic used rapid antigen detection tests for GABHS (Rapid Response Strep-A, BTNX; Markham, Ontario) and/or anaerobic culture on 5 % sheep-blood agar plates followed by Lancefield grouping (PathoDx Strep Grouping, Oxoid; Nepean, Ontario). Furthermore, S. pyogenes was detected using the throat swabs collected in our study with PCR, using primers that have shown high sensitivity and specificity [15] .", "Eighty-three patients participated, of whom 60 (72 %) had a respiratory virus and/or beta-hemolytic streptococci detected in at least one sample. As shown in Table 1 , 48 patients had virus-positive samples and 20 had betahemolytic streptococci-positive samples (17 GABHS and three group C); there were eight viral-streptococcal co-infections and one dual viral co-infection. The most common viruses detected were rhinovirus/enterovirus (22 patients, of whom 18 were confirmed as rhinovirus, and the remainder could not be resolved and were assumed to be rhinovirus), coronavirus (10 patients), and influenza A (8 patients). There were no salient differences regarding clinical presentation and one-week follow-up between patients detected with beta-hemolytic streptococci and various viruses ( Table 2) ." ] },{ "paper_id": "67d137d0496d7339e302c18d693c7ec960ddf733", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There were five notable external provincial level factors that facilitated implementation.", "This imbalance was frustrating for staff and managers who had to do more with less." ] },{ "paper_id": "67d23e2a0388959fbee3dfa60b7097acaebfe4dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where \u03b1 is the weight parameter.", "p is the final similarity between receptors p j and p l ." ] },{ "paper_id": "67e43e9157face441254689d2bab22b781f6b989", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Numerous viruses have developed strategies to modulate TGF-\u03b2 signaling using viral proteins. Examples include hepatitis B virus pX; hepatitis C virus core protein, NS3 and NS5; Kaposi sarcoma-associated herpesvirus K-bZIP; and Epstein-Barr virus LMP1 [76] [77] [78] [79] . Like HBZ, the HBV pX and severe acute respiratory syndrome N protein enhance the transcriptional responses of TGF-\u03b2. Curiously, these viruses seem to employ a common strategy to nullify the TGF-\u03b2 signaling by having their viral proteins bind to Smad proteins [76] [77] [78] .", "Regulatory and accessory genes encoded by HTLV-1. p12, p13, p30, Rex, p21, and Tax are transcribed from the 5' long terminal repeat (LTR). HBZ is located on the complementary proviral strand and transcribed from the 3' LTR. Spliced (s) and unspliced (us) HBZ are shown. Shaded boxes represent their coding regions.", "Polakowski et al. reported that HBZ activates expression of neurotrophin BDNF. Moreover, HBZ promotes a BDNF/TrkB autocrine/paracrine signaling loop in HTLV-1-infected T cells, leading to the survival of these cells (Figure 2 ) [52] ." ] },{ "paper_id": "67e55038298b84f9d71e2e300abcead42e725783", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Computational modeling suggests a mechanism for persistent directional mobility", "To model diffusion of the virus, we use expressions derived for dilute suspensions of cylindrical rods (Brenner, 1974) :", "For quantification and localization of blinking events, we use the ImageJ plugin Thunderstorm (Ovesn\u00fd et al., 2014) , combined with custom Matlab scripts for additional drift correction and removal of fluorophores that remain in the 'on' state for more than one frame. This analysis results in a list of coordinates for each localization that we then use to reconstruct images of virus at varying resolutions. Reconstructed STORM images (e.g. Figure 1C & D) are displayed by representing each localization as a gaussian with a standard deviation of 30 nm." ] },{ "paper_id": "67e7efbd1d4c301ca5e676c366dbaf31f3bf3949", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At each study visit (both routine clinic visits and exacerbation visits), subjects underwent a history, physical, medication history, height/weight, vital signs including pulse oximetry and an oropharyngeal (OP) swab. OP swabs were processed for comprehensive microbiology following Cystic Fibrosis Foundation consensus guidelines [13] . Cough severity was assessed at each visit by parent and physician report using an ordinal cough score ranging from 0 (no cough) to 3 (frequent) for parent report of day and nighttime symptoms and from 0 (no cough) to 4 (frequent) for cough during physician exam (Wisconsin Cough Score), with a maximum possible score of 10 [14] . Antibiotic data was retrospectively captured at each quarterly visit to assess for antibiotics prescribed by primary care providers, at urgent care visits or through telephone triage.", "Ramsey and colleagues noted that patients who received prophylactic antibiotics in the first 2 years of life had higher FEV 0.75 and FVC compared to those who did not receive them [26] .", "The association observed between FEV 1 and exacerbation frequency was used to estimate a sample size needed to detect this correlation in a future study. A sample size of 193 would be required to detect a correlation of 0.20 between the number of pre-school exacerbations and FEV 1 at age 7 with 80% power using a two-sided hypothesis test with a 0.05 significance level.", "This pilot study was powered to detect an effect size of 0.55 standard deviations or larger for the change in chest radiograph scores over 2 years; a sample size of 30 patients is needed to achieve 80% power using a two-tailed 0.05 significance level paired t-test. Descriptive statistics were used to define the baseline demographic characteristics of this cohort. We determined the relationship between factors using Spearman correlation coefficients and corresponding 95% confidence intervals; correlations with " ] },{ "paper_id": "67ef4b8a1eaaf14328ad66f28e0f103c608e73d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analysed using a Student's t-test for independent means or two-way analysis of variance (ANOVA) as appropriate. When analysis by ANOVA indicated significance (P,0.05), the post hoc Student Newman-Keuls test was used. Data are expressed as means 6 standard errors of the mean (SEM)." ] },{ "paper_id": "67f2ba141bcc1bffbd19f77b1aedde25a0f0022b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The SPSS 17 (IBM, New York, USA) was used for data analysis.", "Hospitals with both basic and advanced courses had a higher level of performance (89.2 \u00b1 15.5) as compared to hospitals with only the basic course (77.1 \u00b1 13.3), although the difference was not significant (P = 0.07).", "There was no significant difference between small and medium hospitals (P = 0.09). No large hospitals participated in the study.", "The range for the total HICS score was 1-192 (see additional file 1), and was divided into at three categories: Fair: 1-76; Intermediate: 77-134; High: 135-192. These cut-off values are based on expert consensus.", "Public affiliation was the only independent predictor of the HICS performance (P = 0.04) in a regression model including medium size, public affiliation, advanced course, and earthquake scenario." ] },{ "paper_id": "67f9fc7574738473d4155929c1637f1e7c36afb2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Amino acids ", "Restriction endonuclease sites: BamHI (underlined) and XhoI (italic)." ] },{ "paper_id": "68011fab7fc7a4d29797a161cb32d21ffd2a2ea7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All computations were conducted using the Discovery Studio 2.5 (DS2.5) program developed by Accelrys Software Inc and the SYBYL 8.1 program developed by Tripos Inc on an SGI Fuel workstation running Red Hat Enterprise 5.3 and a Dell server running the Red Hat Enterprise 5.2 Linux operating system.", "SPF chickens were housed in HEPA-filtered isolators.", "Results were expressed as mean 6 S.E.M. for two replicates. Statistical analyses were performed using SPSS 16.0 for Windows. Significant differences (P,0.05) between means were tested by one-way ANOVA, followed by Tukey's Honestly Significant Difference test.", "The structures of the octapeptides and nonapeptides were modelled using DS2.5. In total, seventy-five peptide structures were prepared for docking analysis." ] },{ "paper_id": "68050f9429a9f9fe023c51014f830e9d2572d2d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations: ARCO = Association Research Circulation Osseous, MRI = magnetic resonance imaging, NEX = number of excitations, ONFH = osteonecrosis of the femoral head, SLE = systemic lupus erythematosus, STIR = short t inversion recovery.", "MRI performed 2 to 3 months after steroid therapy may present normal images. Another MRI examination is necessary to make a definite diagnosis.", "To explore the clinical characteristics of steroid-associated osteonecrosis of the femoral head (ONFH) presenting initially normal magnetic resonance imaging (MRI) results." ] },{ "paper_id": "6807bdafe0aadb07814a155a43e4205e0246a2e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "68081e6d2768743855003f159baf5cb7ab59087d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA secondary structure analysis RNA secondary structure were predicted using the MFold web server version 2.3 [29] , while the VIENNA RNAFOLD program and RNASTRUCTURE 5.0 were also used to compare the predictions. All predictions were conducted under default conditions of the software. The predicted secondary structure was modified by RNAviz 2.0 (http://rnaviz.sourceforge.net/).", "MARC-145 cells in six-well plates were infected with WT and rescued viruses (P1) at 0.01 multiplicity of infection (MOI). After 1 hour adsorption at 37\u00b0C, the cell monolayer was washed and replaced with 5 ml of equal volume of mixture of MEM containing 2% FBS and 1% low melting agarose (Cambrex). After the gel overlay solidified, the plate was reversely (top side down) placed into an incubator at 37\u00b0C with 5% CO 2 . At 4 days post infection (dpi), the plaque was visualized by crystal violet staining. The plaque size was determined with a millimeter ruler.", "PRRSV 5'UTR displays inter-genotypically conserved high order structure, despite with distantly related primary sequences" ] },{ "paper_id": "680c8cd646f4f78d97eddff21292668beba44d09", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To distinguish between live and necrotic cells 10 mg/ml Hoechst 33342 and 1 mg/ml propidium iodide (both from Sigma Chemicals Inc., St. Louis, MO) were used for a double staining. Three hundred cells were analyzed in each of three independent experiments [30] .", "One-way ANOVA by GraphPad Prism 4 was used to evaluate statistical differences among experimental groups. A Dunnett's test was applied and a value of p < 0.05 was considered significant. Data are shown here as the mean \u00b1 SEM from three independent experiments." ] },{ "paper_id": "68139e318bd8880a6b11f4dee8779ff0bd3a83a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments in mice were approved by an external committee according to the national guidelines of the animal welfare law in Germany (BGBl. I S. 1206 , 1313 and BGBl. I S. 1934 ). The protocol used in these experiments has been reviewed by an ethics committee and approved by the relevant authority, the 'Nieders\u00e4chsisches Landesamt f\u00fcr Verbraucherschutz und Lebensmittelsicherheit, Oldenburg, Germany' (Permit Numbers: 33.9.42502-04-051/09 and 3392 42502-04-13/1234).", "Functional analysis of gene groups was performed with the R package clusterProfiler (Yu et al. 2012 ).", "A/Hong Kong/01/68 (H3N2) was originally obtained from Otto Haller, University of Freiburg (Haller et al. 1979) . All viruses were propagated in the chorio-allantoic cavity of 10-day-old SPF (specific pathogen-free) embryonated chicken eggs (Charles River Laboratories, Germany) for 48 h at 37 \u00b0C, as described previously , aliquoted, and stored at \u2212 80 \u00b0C. The titer of the stock viruses was determined by focus forming unit assay (FFU/ml) in Madin-Darby Canine Kidney II (MDCK) cells (ATCC) as described previously . Viral RNA was extracted using the QIAamp Viral RNA Extraction Kit (Qiagen) according to the manufacturer's instructions and submitted for sequencing by Next-Generation Sequencing (Illumina) to validate identity of virus stocks." ] },{ "paper_id": "681a8e1fb48060f3b784fb224d80d6ed43510bda", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All analyses were performed using Stata SE 13.1 software (Stata Corp, College Station, TX). Patient demographic and clinical characteristics were compared by rhinovirus status, using Mann-Whitney, Chi Square, or Fisher exact tests, as appropriate. Table 1 summarizes demographic and clinical characteristics of the 110 enrolled infants. Overall, the median age was 3.8 months (IQR 2.0-5.1 months), 56 % were male, 51 % were non-Hispanic white, and 90 % were born >37 weeks." ] },{ "paper_id": "6825e9b1b3377b18ec3725a954b15d2760603a28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To quantify the amount of infectious virus in tissues, lung, liver, kidney, spleen, and brain tissue were weighed, placed in 0.5 ml DPBS, homogenized, and titered via plaque assay on Vero E6 cells as previously described [53] . Whole blood was harvested via cardiac puncture and collected in BD microtainer tubes for serum separation. Serum was titered via plaque assay as described above.", "Lungs from mock-or rMA15-infected mice were removed and homogenized directly in 1 ml of Trizol reagent (Invitrogen) and total RNA was isolated following the manufacturer's instructions. Complementary DNA was generated from 0.25-1 ug of total RNA using 250 ng random primers (Invitrogen) and superscript III reverse transcriptase (Invitrogen). Real-time PCR experiments were performed using Taqman\u00df gene expression assays and an AB Prism 7300 (Applied Biosystems). 18S rRNA was used as an endogenous control to normalize for input amounts of cDNA. The relative fold induction of amplified mRNA were determined by using the Ct method.", "Percent starting weights, viral titers and inflammatory cell numbers were evaluated for statistically significant differences by the non-parametric Mann-Whitney test within GraphPad Prism or unpaired t-tests using GraphPad InStat3 software. P values of #0.05 were considered significant." ] },{ "paper_id": "682a9c91d32a70c08413f3c3f0daba54239c0af0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceived and designed the experiments: DNF. Performed the experiments: CHC ART DNF. Analyzed the data: CHC ART DNF. Wrote the paper: CHC ART DNF. Contributed to composition of figures: CHC ART.", "Even though there is much uncertainty about the reliability of Brigham's data, the R 0 values produced in this study are for the most part remarkably similar to R 0 estimates from studies using more detailed transmission models and greater number of parameters. King et al. estimated an R 0 of 1.660.3 for endemic cholera in the Bengal region when taking into consideration environment-human transmissions and human-human transmissions [9] . Postulating the existence of a ''hyperinfective'' stage for cholera, Hartley et al. estimated an R 0 of 18 for the disease in this stage [11] . Our estimated unrecognized to recognized case ratios are also consistent with those generated using contemporary data (which are also highly variable) [9] .", "Cholera is an infectious diarrhoeal disease caused by Vibrio cholerae. The earliest western record of cholera dates back to at least 16 th century, when cases were observed in India [1] , but global pandemics of ''asiatic cholera'' were first documented in 1817. Cholera can be endemic or epidemic, and is a disease with pandemic potential, with pandemics occurring as a result of genetic reassortment microbial strains [2] ; the seventh recorded cholera pandemic occurred in the 1960s and cholera remains endemic in many countries [3] . Cholera is treatable with oral rehydration therapy and preventable with adequate sanitation and water treatment, and cholera epidemics have not been seen in high income countries since the early 20 th century [3] ; however, the disease remains a major global threat, with an estimated 3-5 million cases and 100000-120000 deaths annually [4] . In recent years, Africa has accounted for over 90% of cases reported to the World Health Organization (WHO) globally, with majority of the remaining cases reported from low and middle income countries in Asia and South America [5, 6] ." ] },{ "paper_id": "68405384d530f6beb4fd8cce0841878a72640d28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Microscopic imaging was performed with a fluorescence microscope (Axioplan, Carl Zeiss GmbH), equipped with an AxioCam MR3 camera (excitation/emission filters 500/535 nm for green fluorescence, 546/590 or 565/620 nm for red fluorescence, Carl Zeiss GmbH). Image processing and editing was done with Axiovision (Carl Zeiss GmbH), GIMP (GNU Image Manipulation Program, version 2.8.20; www.gimp.org) and Microsoft Power Point (Microsoft Corp.)." ] },{ "paper_id": "68422d2849ca1b297e561f73160f9a74a7077797", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Studies with the RNA viruses lymphocytic choriomeningitis virus (LCMV), foot-and-mouth disease virus (FMDV) and vesicular stomatitis virus (VSV) have demonstrated that 5-FU is incorporated as 5-fluorouridine monophosphate (FUMP) into replicating viral RNA, thus increasing genomic mutations [60] [61] [62] .", "Viral RNA from SARS-ExoN+ or ExoN2 infected Vero monolayers was harvested using TRIzol reagent, and was reverse transcribed (RT) using SuperScript III as described above except with 5 mL of random hexamers (50 mM stock), 5 mg of total RNA, and in a final volume of 100 mL for each reaction. Four microliters of RT product was then used to generate 12 overlapping ,3 kb amplicons for each virus treated with either 0 or 400 mM 5-FU by PCR. The high-fidelity polymerase Easy A (Agilent) was used to ensure that errors were minimal during PCR. All primer sets generated single bands which were then purified using the Wizard SV Gel and PCR Clean-Up System (Promega).", "Statistical tests were applied where noted within the figure legends and were determined using GraphPad Prism (La Jolla, CA) software. Statistical significance is denoted (*P,0.05, **P,0.01, ***P,0.0001) and was determined using an unpaired, two-tailed Student's t test compared to either untreated samples or to the corresponding ExoN+ sample. For the cell viability studies, treated samples were compared to the DMEM sample containing DMSO." ] },{ "paper_id": "6844a1c61fe924441532dad545f96e1d6a6d677c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: A.K. conceived the idea and both S.S. and A.K. wrote and revise the manuscript to final form. All authors read and approved the manuscript.", "Funding: Research in our laboratory is supported in parts by National Institute of Health (NIH) Grants (R21AI135583, R01EY026964, and R01 EY027381 to A.K.), NIH Core Grant P30EY004068 (to Linda D. Hazlett), and an unrestricted grant from Research to Prevent Blindness Inc. (to Kresge Eye Institute, Wayne State University).", "The authors declare no conflict of interest.", "A prospective case study in India revealed that 70% of positive cases with WNV infection reported additional ocular complications apart from what was initially reported. The fundus examination revealed discrete superficial white retinitis, arteritis, phlebitis, and retinal hemorrhages with or without a macular star [5] . Moreover, areas of retinal inflammation with unclear borders, vascular and optic disc leakage, vessel wall staining, or capillary non-perfusion were also observed. One of the patients with diabetes exhibited choroidal inflammation.", "The authors would like to thank other members of the lab for their helpful discussions." ] },{ "paper_id": "6848f444e963e825730c6fbcf63b78b65d0efd3d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Dengue virus (DENV) is a significant public health threat in tropical and subtropical regions of the world. A therapeutic antibody against the viral envelope (E) protein represents a promising immunotherapy for disease control.", "Dengue is the most important arthropod-borne viral disease in humans and an increasing public health concern in tropical and subtropical regions of the world. Approximately 50-100 million cases of dengue fever (DF) and 500,000 cases of dengue hemorrhagic fever (DHF) occur every year, and 2.5 billion people are at risk of dengue infection globally [1, 2] . Dengue infection may lead to fever, headache and joint pain in milder cases but may also lead to the more severe life-threatening DHF/dengue shock syndrome (DSS) has plasma leakage, thrombocytopenia, and hemorrhagic manifestations, possibly leading to shock [3, 4] ." ] },{ "paper_id": "68493ffac48a4fdbc15314a0a2bf5cabd087f853", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "doi:10.1371/journal.pone.0152134.g006" ] },{ "paper_id": "684a0a1db464c0c6e1571a6ca9ea5d2003f62456", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To prepare the samples for microarray profiling, total RNA was isolated from the CTEPH patient and normal tissue samples using TRIzol\u2122 reagent (Invitrogen Life Technologies, Inc., Burlington, ON, Canada) and purified using an RNeasy Mini kit (Qiagen, Hilden, German), including a DNase digestion treatment. RNA concentrations were determined by measuring the sample absorbance at 260 nm with a NanoDrop 2000 spectrophotometer (Thermo Fisher Scientific, Inc., Waltham, MA, USA). A260/A280 ratio values of 1.8-2.1 were set as the quality control standard.", "When conducting a network analysis, the simplest and most important measure of gene centrality within a network is degree centrality. Degree centrality is defined as the number of links a particular node has to other nodes in the network (23) . Furthermore, k-cores were introduced using graph theory in order to simplify the graph topology analysis and investigate various network properties. A k-core of a network consists of a subnetwork where all the nodes are connected to at least k other genes. A k-core of a protein-protein interaction network usually contains cohesive groups of proteins with similar functions (23, 24) .", "Network structure analysis aims to locate core regulatory factors (genes). Within a network, core regulatory factors connect the majority of nearby genes and have the highest degree centralities. When evaluating different networks, core regulatory factors are determined by the degree differences between the CTEPH and normal tissue samples (25) , since they show the highest degree differences. The network was constructed using Cytoscape software version 2.8.3 (Cytoscape Consortium, San Diego, CA, USA)." ] },{ "paper_id": "684dc6fccb8e9d754f09076c6a122bc0eead903f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. The p-values for rodent studies were determined using the Log-rank (Mantel-Cox) test.", "Calculated values of less than 0.05 were considered statistically significant. All in vivo studies were performed once." ] },{ "paper_id": "6858a81e65c28599c9e674b9b8aa77ab11b79fad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sequence of hs\u03b2ADR1 (AC No: P08588) was retrieved from UniProt KB [30]. This target sequence comprises of 477 amino acid residues was submitted to NCBI-Protein BLAST [31] to Fig 1. Schematics of strategy implemented towards successful homology modeling of hs\u03b2ADR1 and its docking studies. *Y00 = Dobutamine, P32 = Cyanopindolol, P0G = Nanobody (Nb35), CAU = Carazolol, ERC = FAUC50. RET = Retinal, P32 = Cyanopindolol, CAU = Carazolol, Y00 = Dobutamine, WHJ = Carmoterol, 5FW = Isoprenaline, 68H = Salbutamol, TIM = Timolol, JRZ = ICI 118,551.", "For cross-docking, 11 complexes were extracted from PDB in which eight proteins are homodimers (chain A and chain B) while the rest of three are monomers (chain A). For those proteins that are present as homodimers, ligands were docked into both chains. Overall, 19 complexes were evaluated for cross-docking. The results were quantified as Best (1-3 position), Moderate (4-5 position) and Worst when the cognate ligand ranks position lowers than 5 within its cognate protein, respectively.", "Salt bridges play important roles in protein structure and function. Disruption and the introduction of a salt bridge reduce and increase the stability of the protein, respectively [47] . In membrane proteins, one expects salt bridges to be particularly important because of a smaller dehydration penalty (loss of favorable contacts with water) on salt bridge formation [48] . Charged groups become largely dehydrated when inserted into membranes, and therefore, experience a smaller change in hydration between non-salt-bridging and salt-bridging states. There should also be a smaller effect because of solvent screening, strengthening salt-bridge interactions [48] . Multiple salt bridges are observed in the homology model of hs\u03b2ADR1; Asp154:Arg157, Asp209:Arg213, Asp332:Lys335, Glu155:Arg158, Glu200:Lys203 and Glu212: Arg213. In addition, salt bridges can also serve as key interactions in much the same way as disulfide bonds (S6 Fig) ." ] },{ "paper_id": "685dca5083db2a2e85ca216e930a246108c07986", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "FABP1-F 5\u2032-TATCAAGGGGGTGTCGGAAATCGTG-3\u2032 FABP1-R 5\u2032-ACTGGGCCTGGGAGAACCTGAGACT-3\u2032 EIF2AK3-F 5\u2032-AGGTGCTGCTGGGTGGTCAAGT-3' EIF2AK3-R 5\u2032-GCTCCTGCAAATGTCTCCTGTCA-3\u2032 RPIA-F 5\u2032-CTTACCCAGGCTCCAGGCTCTATT-3' RPIA-R 5\u2032-CTCTACCTCCCTACCCCATCATCAC-3\u2032 IGKC-F 5\u2032-TGGAAGGTGGATAACGCCCT-3' IGKC-R 5\u2032-TGGAAGGTGGATAACGCCCT-3\u2032 IGKV-F 5\u2032-AGTCAGGGCATTAGCAGTGC-3' IGKV-R 5\u2032-GCTGCTGATGGTGAGAGTGA-3\u2032 PGK2 5\u2032-TGTTCTCCTCTTCCTCATCTCC-3\u2032 GFP2 5\u2032-TGAAGGTAGTGACCAGTGTTGG-3\u2032 GFP-F5 5\u2032-TGGAACTGGATGGCGATGTGAATGG-3\u2032 GFP-R5 5\u2032-GGTAATGGTTGTCTGGGAGGAGCAC-3\u2032 CreCAGzeo-F3 5\u2032-GCCCTCACCTTGCAGACCACCTCCATCAT-3' CreCAGzeo-R3 5\u2032-CCTCTCCTGCTCAGTCCCCTTCCTTCCATC-3' CH1 5\u2032-F 5\u2032-CCGACAGGCAGGGCACGAGGAG-3' CH1 5\u2032-R 5\u2032-TGCGAGGCGGGACAAAGACAC-3\u2032 14CENKO-F3 5\u2032-ACTGAAATATTTTAAATGTTTGCCCTTCCCACTCC-3' 14CENKO-R3 5\u2032-AGACCTCCGCGCCCCGCAACCTCCCCTTCTAC-3' CAGpuro-F3 5\u2032-GCGGCGCCGGCAGGAAGGAAATG-3' CAGpuro-R3 5\u2032-CGAGGCGCACCGTGGGCTTGTA-3' SC355F3R3KO-F2 5\u2032-GCCATTGTCGAGCAGGTAGT-3' SC355F3R3KO-R2 5\u2032-TCCCTCATCAGCCATCCTAA-3\u2032 MTA1-F3 5\u2032-AGCACTTTACGCATCCCAGCATGT-3\u2032 MTA1-R3 5\u2032-CCAAGAGAGTAGTCGTGCCCCTCA-3\u2032 ELK2P2-F 5\u2032-CCCACTTTACCGTGCTCATT-3\u2032 ELK2P2-R 5\u2032-ATGAAGGTCCGTGACTTTGG-3\u2032 g1(g2)-F 5\u2032-ACCCCAAAGGCCAAACTCTCCACTC-3\u2032 g1(g2)-R 5\u2032-CACTTGTACTCCTTGCCATTCAGC-3\u2032 VH3-F 5\u2032-AGTGAGATAAGCAGTGGATG-3\u2032 VH3-R 5\u2032-CTTGTGCTACTCCCATCACT-3\u2032", "All animal procedures were approved by and conducted according to the guidelines of the Utah State University Animal Care and Use Committee. All chemicals were purchased from Sigma-Aldrich (St. Louis, MO, USA) unless otherwise specified.", "Published: xx xx xxxx OPEN www.nature.com/scientificreports/" ] },{ "paper_id": "685efeb0ad4c214b8295dc4f723c3269464772d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bats have been increasingly associated with emerging and re-emerging viruses. The likelihood of possible transmission of these pathogens to humans is ever increasing as a result of human encroachment on animal habitats, climate change and change of human behaviour. Pathogens of particular public health importance are filoviruses [1, 2] , coronaviruses [3, 4] , paramyxoviruses [5, 6] and lyssaviruses [7, 8] . Other viruses, without a known human disease link, have also been detected recently [9] [10] [11] . Some human pathogens, such as Rift Valley fever virus, that have been detected in bats were likely a result of coincidental infection and do not constitute proof that bats play a role as reservoirs [12] .", "Stock virus titres were determined by standard tissue culture infectious dose 50 (TCID50) titrations on 96-well microtitre plates as described previously [36] . ", "Stock virus titres were determined by standard tissue culture infectious dose 50 (TCID 50 ) titrations on 96-well microtitre plates as described previously [36] ." ] },{ "paper_id": "686258462f76bc196e1b056ebbbb93a6f53c982e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The biological antiviral activity of E. coli-derived recombinant porcine IFN-lambda 3 was prepared in our laboratory and evaluated in MDBK cells using a recombinant vesicular stomatitis virus (VSV) with a GFP reporter as described previously (22, 24) . The weight-activity unit (U/ml) of samples was calculated using porcine prokaryotic-derived IFN-\u03b1 (4.0 \u00d7 10 8 U/mg) (Prosit Sole Biotechnology, Co., Ltd., Beijing, China) as a reference.", "The intestinal porcine epithelial cell line J2 (IPEC-J2; kindly provided by Dr. Anthony Blikslager, North Carolina State University, Raleigh, NC, USA) was maintained in Dulbecco's Modified Eagle's Medium Nutrient Mixture F-12 (DMEM/F12) supplemented with antibiotics (100 units/ml penicillin and 100 \u00b5g/ml streptomycin), 0.1 mM HEPES (Gibco, USA), and 10% heat-inactivated fetal bovine serum (FBS) (Gibco). African green monkey kidney cells (Vero E6) were grown and maintained in DMEM supplemented with antibiotics (100 units/ml penicillin and 100 \u00b5g/ml streptomycin) and 10% heat-inactivated FBS (Gibco). PEDV strain CV777 of genotype 1 (GenBank Accession No. KT323979) was maintained at the Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin.", "Expanded 3D enteroids were recovered from the Matrigel after 7-11 days of growth by the addition of ice-cold DMEM/F12 medium, transferred into 15-ml tubes, and centrifuged at 250 \u00d7 g at 4 \u2022 C for 5 min. The pellet of enteroids was incubated in 0.25% Trypsin (Gibco) for 5 min at 37 \u2022 C and dissociated by repeated pipetting to obtain a single-cell suspension. DMEM-F12 with 10% (v/v) FBS was added into the single-cell suspension, and the mixture was centrifuged at 800 \u00d7 g for 5 min. The cell pellets were resuspended in complete IntestiCult Organoid Growth Medium at RT and seeded at 50 enteroids per well in a Matrigel-precoated 96-well plate. After differentiation for about 3-4 days, planar monolayers of 2D enteroids were ready for use in experiments." ] },{ "paper_id": "6865c538b9045fd64c560c10a4f1855300a221a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "687da34d9c50dd79ad55b5067ffdbb7282c03d35", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following primers were used for cloning reactions (purchased from Integrated DNA Technologies, Inc. ", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "The " ] },{ "paper_id": "687dd2bd2a0f74f0ef9383f75fb1147e28dfe1d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Seropositive rates were evaluated using x 2 tests. A P value #0.05 was considered significant." ] },{ "paper_id": "6885e0e09ec18e5a9ec6e40efb3645824f25fe79", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and then deriving from that an estimated reproduction number Rj for each case:", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "to each outbreak's R and d values (S1 Fig) ." ] },{ "paper_id": "68a4cb26f4d7448117bfcb2d2794211c04605765", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "reported in the state. (1), (2) and the cumulative number of deaths are shown in Table A2 . [1] , \u2020United States Census [2] .", "cumulative H1N1 cases in the state; (2) cumulative H1N1 cases per million population; and (3) a dichonomous variable to indicate if one or more deaths were" ] },{ "paper_id": "68aa709cc13d459268d903c0a505c56dda9bcc81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The respondent 8.6%", "The opinions expressed by authors contributing to this journal do not necessarily reflect the opinions of the Centre for Health Behaviours Research or the institutions with which the authors are affiliated." ] },{ "paper_id": "68ac410cd36c5699f58d2b76b0eeb84956573f77", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lung tissues were fixed in PBS/4% para-formaldehyde, pH 7.3, embedded in paraffin, and 5 mm sections were prepared by the UNC histopathology core facility. To determine the extent of inflammation, sections were stained with hematoxylin and eosin (H & E) and scored in a blinded manner.", "Percent starting weights, viral titers and inflammatory cell numbers were evaluated for statistically significant differences by the non-parametric Mann-Whitney test within GraphPad Prism or unpaired t-tests using GraphPad InStat3 software. P values of #0.05 were considered significant. ", "This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose." ] },{ "paper_id": "68b617740b5abe48673b58026457150cf7fc5985", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\"At first, we are going to each and every household. . .but this time it's not often.\" HSA, #RU03", "The facility level HCWs identify cases based on their clinical judgements and epidemiological history. These identified cases were recorded in various paper registers or computer system for surveillance purposes.", "\"There are guidelines for malaria. . . and guidelines for ARI. . .. So it depends on the presentation of the patient, as you are going for assessment, and then you compare which guideline tallies the presenting symptoms.\" HCW, #RDH03" ] },{ "paper_id": "68b8a4f644c4195bd6a89ea7e70cd45072ea979e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The baseline hazard function, h 0 (t), was chosen between exponential and Weibull distribution according to the Deviance information criterion (DIC) of each model; the same is true for deciding whether to include random effect parameters. The smaller the DIC value is, the better the model performance.", "Possession of comorbidities increased the mortality rate of MERS patients in this study. This is in line with previous studies of other diseases: for example, influenza patients with chronic cardiovascular disease 30 , or SARS patients with diabetes mellitus, end-stage renal disease 15 . The relationship between comorbidities and emerging infectious diseases or gene association has been studied in SARS [31] [32] [33] , and found that some comorbidities are strongly associated with SARS, such as immunological, neurological, metabolic and dermatologic disease 31 . The mechanisms underlying such mortality enhancing interactions are not always clear, but an already weakened host may have fewer options available to counteract the new infection 34 .", "We also found no significant differences in outcome based on sex once we had accounted for both age and underlying comorbidities. This may indicate that the higher fatality rates for males detected in the univariate analysis, could be because males are more likely to have these underlying comorbidities, or because elderly males with underlying comorbidities are more likely to exposed to infection than equivalent females.", "The full conditional posterior distribution was derived by using directed acyclic graphic (DAG) model using WinBUGS environment. In addition, the non-informative prior distribution of N(0, 10 4 ) for the regression coefficients, non-informative prior distribution of gamma (0.01, 0.01) for the shape parameter (v) of Weibull distribution and the inverse of variance parameters of random intercept and random slope (\u03c3 2 \u03b2 ). The evaluation of parameters was based on 15000 samples with the thinning interval of 3 after a burn-in period of 5000, which gives 5000 posterior samples. The analysis was carried out using WinBUGS 44 .", "The collected data consisted of a disease cohort of MERS cases with follow up till the occurrence of fatal outcome or discharge, thus a prospective cohort design. In some cases, information on infection outcome is unavailable (censored) either because the case is too recent or because no publically available update was reported. For reported cases with missing onset date, the date of symptom onset was calculated by subtraction the reported date by the median of the time period between onset date and reported date at each country 12 ." ] },{ "paper_id": "68b905ee32b8aad54ae9006fc7aab007c63e9895", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This software excludes degenerate bases (e.g. R = G or A, Y = T or C, etc.) indicated within a given genome from consideration as SNPs. Degenerate bases may be due to polymorphic populations within a given strain or to low quality sequencing, and thus do not deliver a confident characterization of differences between strains.", "Background: Microbial forensics is important in tracking the source of a pathogen, whether the disease is a naturally occurring outbreak or part of a criminal investigation.", "If a less restrictive definition of a SNP is required, it is possible to set either (but not both) min_len_downstream or min_len_upstream equal to 0, and thus pick up more regions, including those that may be the beginning of insertion/deletion variations among genotypes. This might be a desired approach for the Single Base Extension assay, since only conservation immediately 5' of the variable position matters [9] .", "Microbial forensics and epidemiology is important in tracking the source of a pathogen, whether the disease is a naturally occurring outbreak or part of a criminal investigation. Polymorphisms among isolates or strains provide information as to the origin, phylogenetic relationships, or transmission patterns of those isolates [1] . The 2001 anthrax attacks highlight the importance of rapid forensic identification of the source of an agent used in a bioterrorism event. Sequencing HIV fragments indicated that a Florida dentist probably infected at least six of his patients with HIV [2] . A series of court cases in Scotland center on accusations that hospital staff are transmitting methicillin resistant staphylococcus aureus to patients [3] . The Centers for Disease Control and Prevention has also developed a network for molecular subtyping, or fingerprinting, of foodborne pathogens [4] . Because SNPs, insertion/deletion mutations, or sequence repeats may affect or be linked with phenotypic traits such virulence or antibiotic resistance, analysis of variance in polymorphic markers may also contribute to improvements in the diagnosis and treatment of infectious diseases [5] .", "Highly heterogeneous viruses like many of the singlestranded RNA viruses (e.g. human immunodeficiency virus, hepatitis virus species, poliovirus, etc.) must be subdivided into clades or other sub-groupings of genetically similar strains even before this software can be applied." ] },{ "paper_id": "68c13cb464cbe2b35102008464c5c196f7c122c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our power calculations are based on three main processes:", "phenotypes such as gene expression for which the genetic architecture is relatively simple.", "(2)", "These are described in detail below, after a description of the genomic data that serves as the basis for the simulations." ] },{ "paper_id": "68c511101e72f75c7c7146306567114789e25be4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A. Computational sitewise assessment of changes in stability (\u0394\u0394G, kcal/mol) ", "Library design can be guided by information regarding each position's mutational tolerance and naturally evolved sequence to reduce the prevalence of overly destabilizing mutations as well as identifying structurally stabilizing mutations. Additionally, the chemical diversity found at the interfaces of well characterized natural binders, such as the complementarity determining regions (CDR) of antibodies, can be applied to protein scaffolds to accommodate for strong binding interactions. Here, a model for library design was built based on a linear combination of (A) computational stability, (B) natural homolog sequence frequency, and (C) CDR diversity input matrices. These three elements were weighted based on the (D) target exposure (i.e. proximity to the binding interface) and solvent exposed surface area (i.e. orientation and packing) of each site. !" ] },{ "paper_id": "68c82e3e364e4f32d14a480538ccc8d0b5d5802c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To verify the absence of contaminants that can cause the inhibition of qPCR assays after the RNA extraction procedure, the extracted RNAs of 10 specimens were diluted 1:10 (v/v) in water and subjected to qRT-PCR. Inhibition was evaluated by calculating the differences in mean Cq values between diluted and undiluted samples.", "The study was exempt of ethical approval procedures because animal samplings were performed during the routinely diagnostic procedures in naturally infected farms. ", "The limit of detection (LOD) and limit of quantification (LOQ) were determined by testing 10 replicates of a 10-fold serial dilution of ssRNA transcript, from an initial concentration of Inhibition assay 3.15 cycles R 2 , linear correlation index; LOD, limit of detection; LOQ, limit of quantification.", "To ascertain the specificity of the qPCR used in this study, we tested eight samples that were negative for PEDV and positive for different viral agents, including " ] },{ "paper_id": "68c9e356d0a2c9f60cd7a48356df0670d99b59d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral pathogens cause devastating economic losses in poultry industries worldwide.", "For FADV Gp1, two distinct clinical conditions exist, the first known as inclusion body hepatitis (IBH), causes characteristic pale livers with pinpoint hemorrhages. The second condition, caused primarily by infection with serotype 4, is known as hydropericardium syndrome (HPS). Disease is characterized by an accumulation of fluid in the pericardial sac and results in higher levels of mortality than for IBH [54] . FADV Gp1 is found widely in both sick and healthy chickens and, like IBDV, it suppresses the immune system making infected birds susceptible to other infections [55] . EDSV is an avian adenovirus from Group 3. It causes a drop in egg production, as well as the production of defective eggs [56, 57] . These clinical signs, though not exclusive to EDSV [41, 58] , can lead to severe economic losses for poultry farmers.", "NDV is a member of the Paramyxoviridae family that affects both poultry and wild birds. The disease can range in severity depending on the infecting virus strain [30] . Newcastle disease (ND) is considered endemic in many countries worldwide and has been identified as a major cause of disease in poultry as far back as the early 19th century [31] , particularly in backyard type farms [32] . Countries with large poultry industries generally vaccinate their intensively produced layer and broiler poultry against NDV, but backyard flocks are often left unvaccinated." ] },{ "paper_id": "68ca53b6414e682661c4decd41eb9ff00574d862", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Generation of porcine NEC. NEC were generated as previously described (68), with improvements. Briefly, nasal epithelial tissues were harvested from pigs at a local slaughterhouse, and tissues were transported on ice in phosphate-buffered saline (PBS) lacking Na 2", "Porcine macrophages preparation and infection. MDM were generated from monocytes as previously described (70) . To this end, blood from 6-to 24-month-old specific-pathogen-free (SPF) Swiss Large White pigs from our own breeding facilities was taken, and peripheral blood mononuclear cells (PBMCs) were isolated using density centrifugation (1.077 g/liter; Amersham Pharmacia Biotech). Then monocytes were isolated by magnetic cell sorting with an LS column (Miltenyi Biotec, Bergisch Gladbach, Germany) as CD172a \u03e9 cells using monoclonal antibody (MAb) clone 74-22-15 (ATCC). Sorted monocytes were seeded at 5 \u03eb 10 5 /ml in DMEM-10% FBS and porcine macrophage colony-stimulating factor (M-CSF; 20 U/ml, produced in-house [70, 71] ) and cultured for 3 days at 39\u00b0C and 5% CO 2 . After MDM differentiation, medium was replaced with fresh MDM (for nonpolarized MDM) or with medium supplemented with IL-4 (100 U/ml, produced in-house; for IL-4-polarized MDM) (72, 73) and incubated for another 24 h.", "RNA extraction and RT-qPCR. RNA was extracted using NucleoSpin RNA II filtered columns (Macherey-Nagel). cDNA was generated with the Omniscript reverse transcription (RT) kit (Qiagen) using random hexamers (Thermo Fisher). RT-quantitative PCR (qPCR) was performed using TaqMan Fast Universal PCR master mix (Applied Biosystems). The primer and probe sequences used in this work are listed in Table 1 . Fold change of gene expression was calculated using the threshold cycle (2 \u03ea\u0394\u0394CT ) method (69) , and the 18S housekeeping gene was used for normalization. Relative gene expression results are presented on a base 2 logarithmic scale.", "Statistics. Figures and data collection analysis were done using GraphPad Prism 7 software (Graph-Pad Software, San Diego, CA). For viral titrations, differences between groups were assessed by Kruskal-Wallis analysis, and for individual differences the Mann-Whitney U test with Bonferroni correction as post hoc was employed. For the rest of the comparisons, such as differences between groups in the percentage of infected cells or gene expression levels, we employed a two-way analysis of variance (ANOVA). A P value lower than 0.05 was considered statistically significant." ] },{ "paper_id": "68d01d19a8c579cd8c528e8e24cd0720216ba700", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "68daf58b8957645121d653fcecec61447d573bb5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "In this paper, we describe an alternative method for calibrating a general class of stochastic compartmental models using the types of data that would be available during the early period of epidemic spread. Unlike deterministic models, stochastic models capture chance events, a feature that proves essential for the accuracy of model-based parameter estimation and prediction during pathogen emergence.", "x\u00f0t; x 0 ; y\u00de \u00bc GL\u00f0x\u00f0t; x 0 ; y\u00de; y\u00de;" ] },{ "paper_id": "69003af6f71b1554fa58853d5d29d1dffd9afc24", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Duck virus hepatitis (DVH), which was first described in Long Island in 1949 [1] , is commonly recognized as an acute and fatal disease of ducklings. DVH is caused by duck hepatitis virus (DHV) types 1, 2 and 3, and no antigenic relationships have been found among them [2] [3] [4] [5] .", "The animal experiments were carried out in accordance with the guidelines issued by Shandong Agricultural University Animal Care and Use Committee (SDAUA-2014-014)." ] },{ "paper_id": "6907124581ac28f6712e3676396cfc4a3b8a9502", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data are presented as a mean \u00b1 standard deviation (SD). Data were analyzed using the analysis of variance Tukey-Kramer multi-comparisons test to compare the means between study groups and their controls. A p value of < 0.05 was considered as a statistically significant difference between mean values." ] },{ "paper_id": "6908a089fea0a7345e066dfd10462507601d88eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The complete genome sequence of PEDV strain SD2014 has been deposited in GenBank under the accession no. KX064280.", "In conclusion, the whole genome of a PEDV strain isolated from a vaccinated farm was characterized and showed highest genetic similarity with early strains isolated in 2011. This finding indicates the variant strains that are less closely related to the vaccine strain are still circulating in the fields of China.", "Porcine epidemic diarrhea virus, a member of the family Coronaviridae, is an economically important pathogen that causes severe enteritis, vomiting, dehydration, and a high mortality rate, especially among suckling piglets. Here, we report the complete genome sequence (28,036 nucleotides [nt]) of a porcine epidemic diarrhea virus (PEDV) strain isolated in a novel outbreak in" ] },{ "paper_id": "690ab99a21dca381b585a6a7d32f1e5c01f1e52c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Experiments were performed with female C57BL/6 N mice (Charles River, Sulzfeld, Germany) aged 8 to 12 weeks, weighing 20 " ] },{ "paper_id": "69129d8f3e4a1c80f2437d16f044e37e43c03f37", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "691856452de91727b7b9b7644f82b4bc5876f32f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, a few open-ended questions on factors that may increase or decrease transmission and were posed to experts.", "The questionnaire was designed to take about 30-40 min, and be filled in by experts individually using a link to online software (see Image S1 in Supplementary Material). It consisted of expertise questions, relative importance of risk factor questions, transmission risk estimations, and open-ended responses, in that order, all of which will be described in more detail below.", "MVK and FR designed the study, contributed to the analyses, and drafted the manuscript. AF and FG designed the data collection instrument, analyzed the data, and drafted the manuscript. MP, EM, MB, VC, and BF reviewed the results and drafted the manuscript. All authors agree with the conclusions of the paper. " ] },{ "paper_id": "692088c942db684cd4e1ec03c927eb3ae6f6caf6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was reviewed and approved by the Ethic Committee/Institutional Review Board (HIRB) of Huashan Hospital, Fudan University, and informed written consent was obtained from each participant." ] },{ "paper_id": "692fedb674101b505fb28fe7b96e552ed224c07d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "69360aaa87b55456c581620207955ad5fe24223b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability statement. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request." ] },{ "paper_id": "693a04c2c05485c6f19c6fc281ebf65dc4fe06dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The genotypes that infect humans include 1, 2, 3, 4, and 7 ( Table 1 ; Smith et al., 2016) .", "World Health Organization estimates that there are 20 million HEV infections annually across the world. Among these cases, there are over 3 million symptomatic cases and 56,600 deaths (WHO, 2015) . Hepatitis E is highly endemic in East and South Asia. Data indicates over 50% of global hepatitis E deaths occur in this region. In East Asia, large outbreaks of hepatitis E have only been described in China. Hepatitis E accounts for 20-50% of acute hepatitis cases in this region. The seroprevalence of anti-HEV antibodies in the region varies from 10 to 50%, indicating that hepatitis E is hyperendemic in this region. In South Asia, outbreaks of hepatitis E have been reported in most countries in this region, but variable in scale (WHO, 2015) . HEV accounts for 20-60% of sporadic acute hepatitis and fulminant liver failure in this region. In particular, the rates of fulminant liver failure are usually higher in pregnant patients. A recent paper reported that HEV infection causes 49% acute viral hepatitis and 75% fulminant hepatic failure in pregnant women in one area in India . However, the seroprevalence rates of prior exposure to HEV are relatively low, ranging from 10 to 40% in most studies.", "Hepatitis E was initially designated as enterically transmitted non-A, non-B hepatitis (ET-NANBH) due to similar clinical presentations to hepatitis A and B in patients, but the prospective causative agent was initially unknown (Balayan et al., 1983) . Early research implied that an RNA virus was the potential pathogen for the ET-NANBH. By analysis of a cDNA library from infectious bile sample, a portion of a highly conserved RNAdependent RNA-polymerase (RdRp) motif, commonly found in RNA viruses, was identified (Reyes et al., 1990 ). This new virus was designated as HEV, which was responsible for the outbreak of ET-NANBH.", "Hepatitis E virus was initially classified as a member of the Caliciviridae family. However, sequence analysis of HEV ORF1 indicated no similarity to Caliciviruses, or other picorna-like viruses. On the other hand, there is limited but significant similarity to the alphavirus-like superfamily of RNA viruses, specifically, the rubella virus (Berke and Matson, 2000) . Consequently, HEV was classified into the family Hepeviridae (Berke and Matson, 2000; Emerson and Purcell, 2003) ." ] },{ "paper_id": "693a08804a5da83a38bff8f67201eb50817e557e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Half of the lung (or liver, spleen, kidney, heart) of each mouse was fixed in formalin, embedded in paraffin and then stained with haematoxylin and eosin (H&E) for histological analysis. Slides were randomized, read blindly and examined for tissue damage and inflammatory cellular infiltration. The lung pathology was scored in a range of 0-4 as previous report [32] .", "Human lung carcinoma A549 cells, human embryonic kidney 293T cells and the Madin-Darby canine kidney (MDCK) cells were maintained in Dulbecco's modified Eagle's medium (DMEM; Gibco, Los Angeles, CA, USA) supplemented with 10% foetal bovine serum (FBS; Gibco), and 1% penicillin-streptomycin at 37\u00b0C with 5% CO 2 .", "The chemical library of 20,000 structurally diverse small molecule compounds (Chemdiv) was purchased from J&K Chemical Company (Shanghai, China). ZBDM-1 (\u226595% purity) was synthesized by Institute of Medicinal Chemistry (SYSU) and stocked in dimethyl sulphoxide (DMSO). Oseltamivir phosphate (Os) was purchased from Selleck Company (Shanghai, China), and a stock solution was prepared in DMSO. Leptomycin B (LMB) was purchased from Cell Signaling Technology (Beverly, MA, USA) and dissolved in ethanol (EtOH). Lipopolysaccharides (LPS) were purchased from Sigma-Aldrich (St. Louis, MO, USA), and a stock solution was prepared in water." ] },{ "paper_id": "693b013cbc9a762c6116b82a671e2eb24b1731b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The recent Ebola outbreak that began in West Africa in December 2013 [1] has revealed how poorly prepared the medical world is to effectively face this disease [2] . As of March 19th 2015, more than 24,600 cases have been documented in West Africa [3] . This implies a great economic and logistic burden.", "doi:10.1371/journal.pone.0135859.g006" ] },{ "paper_id": "693d0f533004851d03a1f38a336f6aa943ea2733", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ten-day-old embryonated, pathogen-free chicken eggs (Lim Chu Kang Veterinary Station, Singapore) were inoculated with IBV as described previously [29] . The allantoic fluid and different organs were harvested after the embryos were chilled at 4uC overnight. Total RNA was extracted from the homogenized tissues and used for RT-PCR with oligo(dT) 18.", "PCR digoxigenin (DIG)-labeled DNA was used as probes for Bak and Mcl-1 mRNAs. The DNA probe for the pXJ40-myc-Mcl-1 plasmid corresponding to 251-715 nucleotides (nt) within the open reading frame (ORF) was labeled by incorporation of DIG-11-dUTP (Roche, Basel, Switzerland) during PCR. Likewise, the DNA probe for the pXJ40-myc-Bak plasmid corresponding to 332-615 nt within the ORF was similarly labeled. As loading control, glyceraldehyde-3-phosphate dehydrogenase (GAPDH)specific probes were also synthesized. The oligonucleotides for GAPDH-specific probe amplification are: (59R39) sense GTC-AGTGGTGGACCTGACCT and anti-sense TGCTGCAGC-CAAATTCGTTG.", "Anti-IBV-S and anti-IBV-N polyclonal antibodies were raised in rabbits as described previously [28] ; anti-Bak monoclonal antibody was purchased from Calbiochem (EMD Biosciences, California, USA); anti-actin polyclonal, anti-Bax and anti-Mcl-1 monoclonal antibodies from Santa Cruz (Santa Cruz Biotechnology, California, USA); anti-tubulin monoclonal and anti-myc polyclonal antibody from Sigma; anti-PARP monoclonal antibody, anti-CHOP/GADD153 monoclonal antibody and anti-Bcl-2 monoclonal antibody from Cell Signaling Technology (Cell Signaling Technology, Inc., Massachusetts, USA). Polyclonal goat anti-mouse IgG, polyclonal rabbit anti-goat IgG and polyclonal mouse anti-rabbit IgG secondary antibodies, all conjugated with horseradish peroxidase (HRP), were purchased from Dako (Dako, Glostrup, Denmark)." ] },{ "paper_id": "69422fc5757c3c88a574d830594a4dc1a06337b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We developed a probabilistic model and used parameters from a published model (i.e., InfluSim) and travel data from Pacific Island Countries and Territories (PICTs).", "Background: Some island nations have explicit components of their influenza pandemic plans for providing travel warnings and restricting incoming travellers. But the potential value of such restrictions has not been quantified.", "For this pandemic scenario, we developed a probabilistic mathematical model that is described in detail in the Technical Appendix (Additional file 1) along with a numerical example for one island nation. An interactive software application that was based on this model was also developed and is freely available online http:// www.influsim.info/software/escaval [7] ." ] },{ "paper_id": "695f0e7afa181c640a015a3b43d1ae401435107a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Issues and suggested improvements with coordination comprised the following subthemes:" ] },{ "paper_id": "696ae2cd59982a2cb456ed723adb98586ebdf7f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses and cells TGEV strain (GenBank No. HQ462571), PCV2 strain (GenBank No. EU366323), PPV YL strain (GenBank No. JN860197), PEDV strain (GenBank No. AF353511) and PRRSV Shaanxi strain (GenBank No. HQ401282) used in this study were isolated and purified previously by our team and stocked in our laboratory [22] [23] [24] [25] [26] . The CSFV Shimen Strain (GenBank No. AY775178) was provided kindly by Professor Yanming Zhang [27] . These virus strains were maintained at -80\u00b0C and used as standard viruses for this study. TGEV, PCV2 and PPV were propagated in PK-15 cells. CSFV was propagated in ST cells. PEDV was propagated in Vero cells. PRRSV was propagated in Marc-145 cells. Four types of cells (PK-15, ST, Vero, and Marc-145) were maintained in Dulbecco's modified eagle medium (DMEM) (Gibco, Gaithersburg, MD, USA) supplemented with 10% heat inactivated fetal calf serum (Gibco).", "Purification of viral DNA or RNA Viral RNA/DNA Kit (OMEGA, USA) was used to extract and purify viral genomic DNA or RNA from virus-infected cell cultures or serum samples according to the manufacture's protocol. Then the extracted viral RNA was reverse transcribed into the complementary DNA (cDNA) using the reverse transcriptase kit (Takara Corp., Japan) according to manufacturer's instructions.", "Along with the development of large-scale and intensive swine production, mixed infections of multiple pathogens are increasingly becoming common in swine farms. Porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2 (PCV2), classical swine fever virus (CSFV), porcine pseudorabies virus (PRV), transmissible gastroenteritis virus (TGEV), porcine parvovirus (PPV) and porcine epidemic diarrhea virus (PEDV) are major pathogens causing heavy economic losses in swine industry [1] [2] [3] [4] [5] [6] [7] [8] . On the basis of clinical signs, it is difficult to determine whether sick pigs are infected by single or multiple viruses [9] . Therefore, it is imperative to establish an effective and rapid method to detect multiple DNA and RNA viruses simultaneously in single sample." ] },{ "paper_id": "69718b1722e6fb921fa5c56b5135454ddbdf7457", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using GraphPad Prism 6 (GraphPad, San Diego, CA, USA). Two groups were analyzed using the unpaired two-tailed Student's t-test and more than two groups were analyzed with one-way ANOVA. P-values lower than or equal to 0.05 were considered statistically significant (* = p < 0.05, ** = p < 0.01, *** = p < 0.001). The data represent the mean \u00b1 SD of at least three independent experiments.", "The attenuated vaccine strain MV-Edmonston and the recombinant Edmonston-based MV strain rMV-eGFP expressing eGFP [20] were propagated using Vero cells. To assess the effect of individual genes on viral replication, Vero cells transduced with respective vectors were seeded in 6-well plates and infected at a MOI of 0.1. The virus was harvested after the indicated times by freezing and thawing the complete culture, thus the cell associated and supernatant virus was harvested together.", "For shRNA expression, we used the vector F6gW-DsRed also expressing DsRed2 as a control for transduction efficiency as described in [21] . To clone the shRNA expressing vectors, we selected siRNA sequences from published mRNA sequences by the program provided by Block-iT RNAi designer (Invitrogen, Carlsbad, CA, USA) and used DNA oligonucleotides for cloning into pF6gW-DsRed (all shRNA sequences can be provided on request). The oligonucleotides were aligned and cloned into the HpaI and XhoI sites of F6gW-DsRed. The sequences of the clones were confirmed by sequencing. The selected KDELR2-specific shRNA expression construct 2 (KDELR2sh2) most efficiently silenced the expression of KDELR2 and was used for further experiments. Lentiviral expression vectors for KDELR-Flag were generated using the BamH1-SacII fragment of KDELR2-expression plasmid RC200007 (OriGene) and cloned into the BamH1-EcoR1 sites of F6gW. The sequences of the cloned plasmids were confirmed by sequencing." ] },{ "paper_id": "6973170d4c8d9576b0e3bfd8391e907d779ee355", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step 3 consists of construction of interaction networks based on RPI-Pred interaction predictions. More detailed descriptions for each step are given below.", "The sequence and structural features of protein and RNA used in this work were represented as follows. The protein sequence of 20 amino acids were classified into 7 groups ", "RNA-protein interactions (RPI) play a crucial role in fundamental cellular processes, such as human diseases (1), viral replication and transcription (2, 3) and pathogen resistance in plants (4) (5) (6) . Recent high-throughput techniques produce remarkable evidences to prove that protein can interact with RNA to mediate different kinds of cellular functions. During the post-transcriptional regulation pro-cess, RPI complex interacts with targeted mRNAs and/or non-coding RNAs (ncRNAs) to regulate cellular functions, such as RNA splicing, RNA transport, RNA stability and RNA translation (7) (8) (9) . Experimental studies on RPI reveal that many functional ncRNAs play pivotal roles in gene expression and regulation (10) (11) (12) (13) (14) (15) (16) . Although a few individual ncRNAs have been well studied, e.g. HOTAIR (17) , MALAT-1 (18) and Xist (19) , the majority are still not well understood. Over 30 000 ncRNAs have been identified and this number is expected to increase every year (14, 15, 20) . Currently, NPInter (21) is the only database, which provides the functional information for all the experimentally validated ncRNA-protein interactions (ncRPI). The experimental techniques are generally time-consuming and expensive. Our understanding of function of individual ncRNAs is far outpaced by the sheer volume and diversity of the available data. Furthermore, our understanding of ncRPI in gene regulatory networks is very limited, especially when compared to the regulatory roles of proteinprotein and DNA-protein complexes. This is because the advances in genomics and proteomics techniques have resulted in tremendous amounts of data on protein-protein and protein-DNA interactions (22) (23) (24) ; however, much less information is available on ncRPI." ] },{ "paper_id": "69735aa238c755d99f12f259ae3d7ac5a6210978", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza A or B virus 1 (6.3%) 0 (0%) 0 (0%) 1.0 0 (0%) 0 (0%) 0 (0%) -Metapneumovirus 0 (0%) 0 (0%) 0 (0%) -1 (6.3%) 0 (0%) 0 (0%) 1.0", "Parainfluenza virus types 1-3 2 (13%) 0 (0%) 0 (0%) 0.32 2 (13%) 0 (0%) 1 (7.1%) 0.77", "Supplementary information accompanies this paper at https ://doi. org/10.1186/s1360 1-019-0302-7." ] },{ "paper_id": "697b9d764f13648fa38faa8d93fefde6049d6517", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Luciferase reading of mock treated virus{ Luciferase reading of Ab treated virus| 100=Luciferase reading of mock treated virus{", "The antibody mediated inhibitions of different mutant pseudoviruses were then normalized to HIV/Urbani-S inhibitions.", "Information S1" ] },{ "paper_id": "697cf5b78c388d6e79a7a87ac9b82e4911de135a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "High-titer virus stocks were produced by ultracentrifugation using a 20% sucrose cushion. Centrifugation was done on an SW 32 Ti rotor (Beckman Coulter, Brea, CA, USA) at 32,000 rpm for 4 h in vacuum and at 4 \u2022 C. The virus pellet was resuspended in 1 mL 1\u00d7 phosphate buffered saline (PBS) and kept at 4 \u2022 C for 24 h to enable the pellet dissolve fully.", "The ultracentrifuge-purified virus was inactivated in a 6-well tissue culture plate with 0.1% beta-Propiolactone (ACROS Organics TM , Thermo Fisher, US). This was done overnight at 4 \u2022 C and further incubated at 37 \u2022 C in a cell culture incubator to hydrolyze the beta-Propiolactone. The virus was then grown on LLC-MK2 cells and checked by quantitative real-time PCR for virus growth.", "The amount of protein in the virus stock was quantified using the Bradford assay as previously described [29] . Briefly, the viral protein and a two-fold serial dilution of a protein standard (bovine serum albumin, Carl Roth, Karlsruhe, Germany) in Sodium carbonate (NaCO 3 ) buffer were mixed with Bradford solution (Coomassie Plus TM , Thermo Fischer, US) and incubated at room temperature for 10 min. Protein quantity was subsequently measured on a spectrophotometer (Eppendorf, Hamburg, Germany) at 595 nm." ] },{ "paper_id": "698174035746c185ce55489b4a345026d82dcc42", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For monocyte isolation, pig blood from four different animals was collected in 10 ml EDTAcoated vacutainers and independently processed (BD Bioscience, Mississauga, ON, Canada). The vacutainers were centrifuged for 30 min at 400 x g and the buffy coat resuspended in 7.5% PBS-EDTA and layered on a 60% FICOLL-PAQUE1 Plus gradient (GE Healthcare Bio-Sciences, AB, Uppsala, Sweden) to isolate peripheral blood mononuclear cells (PBMCs). Monocytes were further isolated as described elsewhere [37] . Briefly, PBMCs were incubated for 20 min with anti-human CD14 microbeads (Miltenyi Biotec Inc., Auburn, CA), and CD14 + monocytes were positively selected using the Magnetic Activated Cell Sorting system (MACS1; Miltenyi) and plated in 24-well plates (Fisher Scientific, Pittsburgh, PA).", "All raw microarray data are available and have been deposited on the Gene Omnibus Expression database under accession numbers GSE75687.", "(DOCX) " ] },{ "paper_id": "6986e55cd9e5fd76339b6a6825b2c3069126555e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step RT-PCR Kit ver. 2 from Takara.", "The genome of this genus consists of a single-stranded positive-sense RNA, ranging from 8.2 to 8.4 kb, including the poly(A) tail [8] . All kobuviruses share essentially the same genomic organization. Nonstructural protein L (leader) is encoded at the N-terminus of the polyprotein and is followed by three structural capsid proteins, VP0, VP3, and VP1 and seven nonstructural proteins, 2A, 2B, 2C, 3A, 3B, 3C, and 3D [9] (Figure 1 ).", "Kobuviruses have been detected in a variety of animals, including sheep [16] , bats [17] , dogs [18] , goats [19] , and cats [20] . However, the full spectrum of kobuvirus hosts must be determined to establish the possibility of cross-species infections among animals and humans and the genomic similarities and homologies between different regions and different hosts." ] },{ "paper_id": "699369c8d371b09fca7aeb53e54b3b569e1653d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, it appears that inoculation via the skin or nasal mucosa tended to produce modified disease. If true, this would indicate that natural transmission did not occur via direct skin or mucosal contact. Figure 1 shows graphically a how these different routes of exposure may have produced altered patterns of viral replication within the host and resulted in different risks of extensive viremia and severe disease.", "Overall, the air sampling studies suggest that animals and people infected with poxviruses generated respirable aerosols, but that air concentrations may have been low, or airborne virus was present in submicrometer particles that could not be collected the instruments available. Because detection of virus aerosols is subject to potentially large losses in sampling equipment, especially when sampling dilute natural aerosols over extended periods, and because plaque assays may not accurately represent the infectivity of virus deposited in human airways at 100% relative humidity, (Spendlove and Fannin, 1982; Ijaz, 1987, 2002) the available data can be considered a lower limit on concentration of infectious natural poxvirus aerosols.", "The animal data show that artificial respirable aerosols were effective means of producing poxvirus infections, that the infectious dose by the airborne route could be very low, and that animal-to-animal airborne transmission of rabbitpox and variola was observed. They also suggest that inoculation of mucus membranes was less effective at producing a generalized rash than was exposure of the lower respiratory tract.", "These considerations suggest that models of a potential smallpox attack should incorporate an aerobiological perspective to predict how the infection might propagate in the modern environment. It is particularly important to examine smallpox transmission in hospitals because hospitals have previously been identified as the major site of transmission in developed countries and ill patients will inevitably gravitate to hospitals, at least early in the outbreak before alternatives exist (Mack, 1972 (Mack, , 2003 . Additional attention to prevention of airborne transmission in hospitals from unrecognized cases may not only be an important aspect of public health preparedness for smallpox, but may also benefit society by reduced morbidity and disruption from SARS and other emergent airborne infections.", "Air sampling for viruses is a difficult undertaking and the literature on the subject remains sparse in comparison with that for bacteria and fungi (Sattar and Ijaz, 2002) . Only three attempts to detect airborne variola were published. The earliest attempt used highly inefficient methods and was negative (Meiklejohn et al., 1961) . In a subsequent study, Downie and colleagues used short duration, low volume air sampling with liquid impingers and obtained 5 positive samples out of 47 attempts to sample exhaled breath of patients (Downie et al., 1965) . Assuming that each positive sample represented a single infectious particle, the concentration of airborne infectious particles was 0.85/m 3 ; higher concentrations were observed close to shaken bed sheets. Concentrations were likely to have been underestimated because of several frequently encountered problems with air sampling for viruses including failure of impingers to retain particles less than 1 \u00b5m in diameter that represent the majority of particles in exhaled breath, culture of only a portion of the impinger fluid, uncertain suitability of sampling fluid for virus survival, and loss of infectivity due to sampling trauma (Spendlove and Fannin, 1982) ." ] },{ "paper_id": "699ffcdbc72afc6d6243a7d0dbd50cc055d03aeb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data Availability. All data generated during the current study are available in GenBank (accession numbers or are included in this published article and its Supplementary Information files.", "Scientific RepoRts | 7: 5287 | DOI:10.1038/s41598-017-05236-w but are vectored by arthropods, had levels of CpG depletion comparable to those of the mammal-specific lyssaviruses, if not somewhat higher. KYAV and Oita virus genomes stand out among ledantevirus genomes by having very high CpG frequencies, similar to insect-specific sigmaviruses. We again caution that dinucleotide composition appears to be shaped more by virus taxon than by host species 36 ; however, this metric remains useful for comparing similar viruses that infect very different hosts (e.g., mammals versus arthropods) 16, 39, 40 .", "DNA was reconstituted, and libraries were prepared for NGS as previously described 48, 49 ; this method is approximately as sensitive as real-time quantitative PCR for detecting viruses 11 . Briefly, DNA was purified using Agencourt Ampure XP beads (Beckman Coulter, Brea, CA, USA). Approximately 1 ng of DNA was prepared for sequencing on a MiSeq instrument (Illumina, San Diego, CA, USA) using the Nextera XT DNA sample preparation kit (Illumina). Sequence data were analyzed using CLC Genomics Workbench version 8.5 (CLC bio, Aarhus, Denmark). Low-quality bases were trimmed (phred quality score < 30), short reads (<75 bp) were discarded, and the remaining reads were subjected to de novo assembly. Assembled contiguous sequences (contigs) were analyzed for nucleotide-(blastn) and protein-level (blastx) similarity to known viruses in GenBank. All sequences generated in this study were deposited into GenBank. All sequences used for analyses and their accession numbers are listed in Supplementary Table S1 .", "Based on coding-complete virus genome sequences detected in the course of bioinformatics analysis (see Results), PCR primers KYAV-10368 (5\u2032-GCGAACCCGACGATCATAGT-3\u2032) and KYAV-10695 (5\u2032-GCTGTGCATTCCAGTCTCCT-3\u2032) were designed to amplify a 327-bp region of the KYAV RNA-dependent RNA polymerase (L) gene. PCR conditions were optimized using bat fly cDNA samples known to be positive and negative for KYAV infection by NGS. The optimized PCR was used to test cDNA extracted from swab samples. PCRs were conducted using the HiFi kit (Kappa Biosystems, Wilmington, MA, USA), with 40 cycles at 94 \u00b0C for 15 sec, 56 \u00b0C for 15 sec, and 72 \u00b0C for 15 sec. Amplicons were visualized on 2% agarose electrophoretic gels stained with ethidium bromide." ] },{ "paper_id": "69a50ad03d5fb9a5129663062a9b718217b62665", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using GraphPad Prism version 5.02 for Windows (GraphPad Software). Data were subjected to two-tailed unpaired Student t test analysis. The obtained p values were considered significant when p,0.05." ] },{ "paper_id": "69b4d83503fda10464dc830c82e76af9b8fbf73f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Positive test results were identified quicker in samples with high viral load (C T value of \u03fd25), although the absolute differences are small and probably of minor importance in routine care (Fig. 2) .", "Citation Peters RM, Schnee SV, Tabatabai J, Schnitzler P, Pfeil J. 2017. Evaluation of Alere i RSV for rapid detection of respiratory syncytial virus in children hospitalized with acute respiratory tract infection. J Clin" ] },{ "paper_id": "69b7df3f6f4dd18c96e2d6b064e7ee3190cd54d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Technology Type(s) data item extraction from journal article", "Sample Characteristic(s)", "Design Type(s) data integration objective \u2022 epidemiological study" ] },{ "paper_id": "69bce356ec4ad3fcc2a0d7ba9ecfaf0d90d8e423", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where d(x A a ,x B a ) is the distance between two atoms in a superimposed coordinate system and the cutoff distance d c is set to 2.5 \u00c5 .", "To the contrary, we can only infer high function similarities for high sequence or binding site similarities.", "We have confirmed that selecting different random sets of representatives in all the above cases did not alter the results significantly." ] },{ "paper_id": "69c94e49590a47b77cd12156e6d8e3bd318997b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "69cf21ea0c191cb1ea580856df13fea7b1608b00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Trial registration: HATRIC was registered on the ISRCTN registry (ISRCTN17672884) on 16 August 2018.", "Some potential candidates for symptom relief such as steam inhalation have not been shown to be helpful [12] whilst ibuprofen had no significant benefit [13] and may cause harm [12] . Other potential symptomatic treatments in adults (the expectorant guaifenesin, mucolytics, and antihistamine-decongestant combinations) have not been shown to have consistent benefit in a recently updated Cochrane systematic review [14] .", "To improve the return rate of completed diaries, patients who return a fully completed diary or complete a diary by recall will receive a \u00a35 shopping voucher to thank them." ] },{ "paper_id": "69d2e69e949dab8909be8c7b764a0d5469546b31", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u0394\u0394C" ] },{ "paper_id": "69d3400351b1b4dbce54ecdec3d4c897dc76b9a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "M. tuberculosis after intravenous challenge, which was determined in a related study.", "Supplemental material for this article may be found at http://mbio.asm.org/ lookup/suppl/doi:10.1128/mBio.01516-16/-/DCSupplemental. Figure S1 , TIF file, 10.4 MB. Figure S2 , PDF file, 1 MB.", "C3HeB/FeJ substrain forms caseating lung lesions upon M. tuberculosis infection (70) , which closely resemble those of humans. Determining whether any mouse lines in the CC panel recapitulate this phenotype will require additional infections studies in parallel with C3HeB/FeJ animals." ] },{ "paper_id": "69ddca48a5d1e593fbd057160b100afb374276c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since their identification in 1972, toroviruses have been poorly studied, and many issues regarding torovirus infections remain unexplored. Significantly, little is known about the morphological, physiological and biochemical changes that occur in torovirus infected cells. Investigating the complex virus-host interactions is important to understand the basis of torovirus-induced disease.", "Statistical analyses were performed using Student's two tailed t test. Means 6 standard deviation for each sample are shown.", "Equine dermal (E. Derm) cells (NBL-6, ATCC CCL-57), and human fetal lung fibroblasts (MRC-5, ATTC CCL-171), kindly provided by R. de Groot (Utrecht University, Utrecht, The Netherlands) and R. E. Randall (University of St. Andrews, Scotland, UK) respectively, were cultured at 37uC, 5% CO 2 and 98% humidity, in Dulbecco's modified Eagle's medium (DMEM; Invitrogen, corp) supplemented with 15% and 10% fetal calf serum (FCS) respectively, non-essential aminoacids (1%), gentamicin (50 mg/ml), penicillin (100 U/ml), streptomycin (100 mg/ ml) and fungizone (0.5 mg/ml).", "The torovirus genome consists of a single RNA molecule of about 25-30 kb. The 59 two thirds contain two large and overlapping open reading frames, ORF1a and ORF1b, that code for the replication machinery. The last third of the genome contains four open reading frames, ORFs 2-5, coding for the spike (S), membrane (M), hemagglutinin-esterase (HE) and nucleocapsid (N) structural proteins [6] . In BEV the HE gene is partially deleted when compared with other torovirus strains, though the corresponding mRNA is produced [7] ." ] },{ "paper_id": "69dfbde6c5ed2f0c93261cf763e206f0f3d63132", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ities, neutralization mechanisms, cross-neutralizing activity against divergent MERS-CoV strains, half-life, and protective efficacy against lethal MERS-CoV infection in an established hDPP4-Tg mouse model (38) . This study reveals that efficacious, robust, and broad-spectrum Nbs can be produced to target MERS-CoV S protein RBD and that they hold great promise as potential anti-MERS-CoV therapeutics.", "NbMS10 and NbMS10-Fc present superior characteristics common to other Nbs. They target the MERS-CoV RBD, which plays an essential role in cell entry of MERS-CoV by binding to its receptor hDPP4. Both Nbs can be expressed in yeast cells with high purity and yields and are soluble in solutions. All of these properties suggest costeffective production, easy storage, and convenient transportation of these Nbs in potential commercial applications.", "To detect the binding between Nbs and denatured MERS-CoV RBD protein, ELISA plates were coated with RBD-Fd protein (2 g/ml) overnight at 4\u00b0C and then sequentially incubated with DTT (10 mM) and iodoacetamide (50 mM) (Sigma) for 1 h at 37\u00b0C (28) . After three washes using PBST, ELISA was performed as described above." ] },{ "paper_id": "69e7ecb2ece358ef53df31c8ba497a183b007cc1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal experiments were conducted in accordance with the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) guidelines.", "About 0.5-1 ml of blood was collected directly through cardiac puncture immediately after euthanasia. Blood collected was transferred to a 1.5 ml centrifuge tube which was later centrifuged at 5000 rpm for 5 min, and serum was subsequently stored for further analysis." ] },{ "paper_id": "69e95489dff0da006349ceb3a46a1f215cb1b910", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The samples were stained as described above and examined with a Leica TCS SP2 or SPE laser scanning spectral confocal system (Leica Microsystems GmbH, Wetzlar, Germany) linked to a DM IRB inverted microscope (Leica Microsystems). Argon and Helium/Neon laser lights were used to excite FITC (488 nm line) and Texas Red (543 nm line) fluorochromes, the violet diode laser was used to excite Alexa Fluor 405 (405 nm line). The images were obtained with Leica confocal software and processed with the GIMP.", "Two genetically highly similar biotypes of coronaviruses are described in cats: feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV). These coronaviruses can infect both cats and other members of the Felidae family. An infection with FECV is usually sub-clinical, except in young kittens where it may cause mild to severe diarrhoea [1] . In contrast, FIPV infection causes a chronic and very often fatal pleuritis/peritonitis. In fact, it is the most important cause of death of infectious origin in cats. Cats with clinical FIP often have very high titers of FIPV-specific antibodies. Yet, these antibodies are not able to block infection, which suggests that antibodies and antibody-driven immune effectors are not able to efficiently clear the body from virus and/or virus-infected cells.", "Triplicate assays were compared using a Mann-Withney U test with SPSS 11.0 (SPSS Inc., Chicago, WA). P values < 0.05 were considered significantly different." ] },{ "paper_id": "69ed0332751ba504d01cf6d6c266c9ae499ceb38", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No specific posture was requested of the volunteers. They were asked to just perform their coughs in their usual manner.", "This airflow dynamical data in combination with data from other researchers investigating exhaled or expelled droplet characteristics from human volunteers will be useful to understand the risk that coughing may pose for the transmission of airborne infectious agents, and therefore to improve aerosol infection control interventions in healthcare and community environments.", "(WMV)", "The raw images from the Photron high-speed camera were recorded as individual TIFF files. For the video montages, these were saved using the proprietary camera/image analysis software PFV (Photron Fastcam Viewer) then converted to smaller and more manageable JPEG files for editing. Final presentations were further edited and annotated using Corel VideoStudio Pro X3 (Corel Corp., Ottawa, Canada) and Windows Movie Maker v.5.1 (Microsoft Corp., Redmond, WA, USA).", "Twenty healthy human volunteers with no acute or chronic respiratory illness were recruited for the cough study. All volunteers were over 21 years of age and mostly were either staff or graduate students of the National University Hospital or the National University of Singapore respectively. Recruited volunteers received a small cash reimbursement for their time and inconvenience. Each volunteer was asked for their height and weight in order to calculate their body-mass index (BMI), as well as their smoking status." ] },{ "paper_id": "69ef51ebe3e2ce0b8d6fc292b06b293ba2942bd7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where the weighting scheme is typically the Indicator", "with tolerance parameter t { k v0vt z k or the Exponential", "dG ik dt~(", "ABC relates evolutionary and epidemiological data mechanistically through an evolving dynamic system and thereby allows us to investigate empirical phylodynamic hypotheses more directly than is possible with other statistical data synthesis approaches [44, 45] . Whenever the evolution and ecology of the virus are inseparably linked [1] , case report and phylogenetic summaries are co-dependent. In general, this reduces the degrees of freedom Figure 5L )." ] },{ "paper_id": "69f5726e6b53f93b94630c1388479879f49f456e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Descriptive analysis of infant demographic, clinical and biological measurements will be performed using means and standard deviations or medians and inter-quartile ranges for continuous variables, and proportions for categorical variables.", "Primary Hypothesis 2, Nested Case-Control Study: Preliminary data from previous studies provide estimates of selected biomarkers, including leukotrienes, CC-16, KL-6, IL-18, TNF-\u03b1, and HNE. Estimates of minimal detectable differences (two sided \u03b1 = 0.05) are given in Table 4 , for different numbers of asthma cases identified [46] [47] [48] [49] [50] ." ] },{ "paper_id": "6a0c165fd5c40909228209e01112875b6d968dea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sizes of parasites found in blood smear and histologic specimens were measured by a manual micrometer and light microscope.", "Detection of antibodies for FIV in cat sera was performed using the Feline Immunodeficiency Virus Immuno Run Antibody Detection assay W (Biogal Galed Labs, Israel)." ] },{ "paper_id": "6a0f0170d5ad8bb5c0f2af642c0fc37e48dbd3a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Different canine tissue samples were collected from healthy mix-bread dogs and flash-frozen in liquid nitrogen. Peripheral blood mononuclear cells (PBMCs) and granulocytes were isolated from blood of healthy mixbread or beagle dogs by density-gradient centrifugation through Ficoll-Paque (GE Healthcare, Freiburg, Germany). Granulocytes located on top of erythrocytes were harvested and remaining erythrocytes were lysed (ammonium chloride buffer).", "For surface staining, cells were suspended in PBS/0.3% (w/v) BSA supplemented with 0.1% (w/v) sodium azide. Cells were incubated with 0.5 \u00b5g/10 6 cells of the relevant mAb for 30 min at 4\u00b0C. Cells were washed twice and analyzed with a FACScan (BD Biosciences, Mountain View, CA). Dead cells were excluded by propidium iodide staining. The following reagents and mAbs from Serotec were used: FITC-conjugated anti-CD3, FITC-conjugated anti-CD4 and PE-conjugated anti-CD8\u03b1." ] },{ "paper_id": "6a0f2ecf39a72ca6067517375a485d98b308e2aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "China's improvements in research funding and technical capabilities have led to a series of important findings. For example, Chinese researchers have revealed the crystal structures of key viral proteins (e.g., SARS-Cov protease, H1N1 neuraminidase N1, and H5N1 polymerase PA C -PB1 N complex) [36] [37] [38] , which is useful for drug design, and discovered an oseltamivir-resistance mechanism in H7N9 [39] . A traditional Chinese medicine (TCM) herbal formula was confirmed to reduce H1N1 influenza-associated fever safely and with efficacy similar to that of oseltamivir in a randomized clinical trial [40] .", "Worldwide cooperation is necessary to combat the current Ebola epidemic. As of June 2015, nine countries have been affected by Ebola (27,273 cases/11,173 deaths) [42] . Based on its recent experiences with epidemics, China has provided comprehensive support to West African nations battling BioMed Research International 5 Ebola, including provision of capital, anti-Ebola materials, testing and treatment support, tactical rapid-response training, and collaborative research. China placed approximately 1000 medical experts in West Africa, helped build an Ebola diagnosis and treatment center and a biosafety laboratory, and trained more than 13,000 local medical care and community workers [43] .", "In December 2014, Chinese-made Ebola diagnostic kits were made available [44] . In March 2015, China's first Ebola vaccine (the first to be based on the 2014 Zaire strain instead of the 1976 Zaire strain) passed its first phase I clinical trial and is being produced in a lyophilized form that is more stable than prior aqueous-form vaccines [45] . China is producing a therapeutic chimeric antibody agent, MIL-77, which is amenable to large-scale production via mammalian cell expression. It was reported that a 25-year-old British nurse infected with the Ebola virus was treated successfully with MIL-77 without adverse effects [46] ." ] },{ "paper_id": "6a0f4aac2dfa46df489b653a06df4b5036e452ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. ", "Normal cellular function including signal transduction and metabolic processes is often mediated through protein-protein interactions, and are routinely targeted by viruses. The host cell cycle is no exception, as illustrated below.", "Cell cycle, or cell-division cycle, is a highly regulated process during which a cell undergoes duplication and division leading to the generation of two daughter cells. The eukaryotic cell cycle is generally divided into four stages: gap 1 phase (G1), synthesis phase (S), gap 2 phase (G2), and mitotic phase (M). In between M and G1, a cell may enter a quiescent state called gap 0 phase (G0), during which cells are neither dividing nor preparing to divide." ] },{ "paper_id": "6a0f7cfb9306380e01f35d7f8c0e75c0f91dcbc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were analyzed with the GraphPad Prism 5 software. A P-value < 0.05 was considered as significant, and labeled with an asterisk in the figures (*).", "Vero cells were cultured in Dulbecco modified Eagle medium (DMEM; Hyclone, USA) with 10% fetal bovine serum (FBS; TCB, USA) and maintained at 37 \u00b0C with 5% CO 2 . Cyclosporin A (CsA), Z-VAD-FMK (caspase inhibitor), Dimethyl sulfoxide (DMSO), and Cy3-labeled Goat Anti-Mouse IgG (H+L) were purchased from Beyotime (Shanghai, China). The PEDV specific monoclonal antibody 5E2-C4 was made in our laboratory.", "The mock or PEDV-infected Vero cells were collected gently with a rubber policeman, washed twice with cold PBS (with centrifugation at 2500 \u00d7 g for 5 min between washing), and then fixed in 2.5% glutaraldehyde overnight at 4 \u00b0C. The cell pellet was used to prepare thin sections for observation under TEM, as described previously [28] . The final samples were visualized using a Hitachi-7650 transmission electron microscope (Hitachi Ltd., Japan)." ] },{ "paper_id": "6a1b5c9d6a0e52a6e0c3bdf192b5acb5bc9fed40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Owing to the overwhelming quantity of literature available on isothermal DNA amplification devices, we will describe the strategies of five major isothermal techniques. Because several reviews have previously focused on isothermal methods in bioanalysis applications [3] [4] [5] , we focus mainly on recent advances in the rational design and fabrication of integrated DNA microchips. The measurements of amplified DNA using different approaches will also be reviewed. Finally, future challenges and perspectives on diagnostic device construction are described.", "In addition to single-target detection, RCA is also desirable for multiple-analyte sensing assays because amplified products are considered to be localized at the array spot [62] . An array of real-time RCA in combination with the parallelism of arrays was developed by Yang et al. for protein quantitation down to the low nanomolar range [53] . Konry et al. constructed a two-layer sandwich assay on microbead surfaces for the combined detection of DNA and protein molecules in a single approach [63] . This array chip achieved detection limits of 1 pM and 10 fM for target DNA and proteins, respectively.", "Isothermal approaches can facilitate rapid target amplification through single-temperature incubation, reducing system complexity compared to PCR-based methods. Established isothermal amplification methods differ in terms of complexity (multiple enzymes or primers), attainable sensitivity, and specificity. In this section, we introduce the main isothermal methods used in diagnostic systems, including nucleic acid sequence-based amplification, strand displacement from the molecular beacon, and the fluorescence provides a real-time monitoring of NASBA progress [5, 14, 15] . Recent effort has shown that an automated NASBA system, NucliSENS EasyQ, can perform simultaneous amplification and detection using fluorescence quantification. The detection of amplification products takes place in a single closed tube to significantly reduce contamination risks. This platform also helps decrease the hands-on time and provides rapid results (within 4 h), thus becoming a potentially suitable device for diagnostic applications [16] [17] [18] [19] .", "To date, the development of chip-based isothermal assay systems has received great attention, whereas achieving a higher degree of portability remains a challenge. No device reported thus far is clearly superior, resulting in the possibility that sensing platforms based on different isothermal amplifications may find their way to market. Commercialization requires further improvement in on-chip sample pretreatment, miniaturization of detectors, decrease in power consumption, and the establishment of quality control. We can expect the full integration of all components on disposable credit-card-sized systems for isothermal nucleic acid amplification and detection in the near future. Given the great effort being invested in isothermal DNA microchip systems, there is no doubt that they will provide significant contributions to point-of-care diagnostics and decentralized testing." ] },{ "paper_id": "6a1fd48435dc54d1682a0bafd6cdf7142b6b5bc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These equalities imply that", "rsif.royalsocietypublishing.org J. R. Soc. Interface 13: 20160288" ] },{ "paper_id": "6a2386de99a966c8755732f196ba4c2cc0dda2f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The cartilage endplate specimens were separated from disc and bone tissues immediately after they were harvested from the intervertebral space. They were then snap-frozen in liquid nitrogen and stored at 280uC until the extraction of total RNA.", "Total RNA (200 ng) was reversed-transcribed to first-strand cDNA using a Reverse Transcription System (Promega) in a total volume of 20 ml, according to the manufacturer's instructions. ", "The concentration and purity of the isolated RNA were estimated in triplicate using a NanoDrop 2000 spectrophotometer (Thermo Scientific). Samples with concentrations $50 ng/ml and optical density absorption A 260 /A 280 between 1.8 and 2.1 were taken for cDNA synthesis. The integrity of RNA samples was confirmed by electrophoresis on 2% Sybr Green agarose gel (Invitrogen) as indicated in the MIQE (Minimum Information for Publication of Quantitative Real-Time PCR Experiments) guidelines [19] ." ] },{ "paper_id": "6a246d3621609eba5e7fb36c483280aa9cacd166", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CD and SX designed the study. MZ performed the experiments. MZ, CD, and SX interpreted the data. MZ, CD, and SX wrote the manuscript. All authors approved the final version of the paper.", "Cytotoxicity (%) = [(effector and target cell mixture \u2212 effector cell control) \u2212 low control]/ (high control \u2212 low control) \u00d7 100%;", "Statistical analyses were performed with GraphPad Prism. Data were from three separate experiments and given as mean and standard deviation. The data were statistically analyzed by twotailed independent Student's t-test through SPSS 12.0. The level of statistical significance was set to P < 0.05." ] },{ "paper_id": "6a2d0c94c7467bc93eab84eb348c458e85738aa3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tf-EE (code number: PBC-194AS) was obtained from the Plant Extract Bank in the Plant Diversity Research Center (Daejeon, Korea). Torilidis fructus was extracted using ethyl alcohol 95 & GR grade.", "Male BALB/c, 7-week-old mice weighing 19-22 g, were obtained from Daehan Biolink (Eumseong, Korea) and maintained in plastic cages under conventional conditions. Water and a pelleted diet (Samyang, Daejeon, Korea) were supplied ad libitum. All animal studies followed the guidelines established by the Sungkyunkwan University Institutional Animal Care and Use Committee. Peritoneal exudates were obtained from 6-week-old male ICR mice via lavage for 4 d after 1 mL sterilized 4% thioglycollate broth (Difco Laboratories, Detroit, MI) was injected intraperitoneally .", "ARTICLE HISTORY" ] },{ "paper_id": "6a3acbb2d3cf75b9cb9221b0d8acc32559ec4cf8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results are expressed as means \u00b1 SD. Statistical analysis was performed with GraphPad 5 software. The statistical significance from control values was determined by Student's t-test. Values were considered to be significant at P 0.05." ] },{ "paper_id": "6a3fa8ed278df0d05c5e009521de11c72308f60b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A detailed written protocol was prepared and reviewed in advance (complete protocol can be obtained from the corresponding author)." ] },{ "paper_id": "6a45607f711714e68936b74d1af18df649a96b07", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceived and designed the study: CE, POH, BL, CAG, and EB. Sample collection: CE, POH, BL, CAG. Laboratory work: HF, AGH. Data analysis: CE, ST, EB. Wrote the paper: CE, BL, ST and EB. All authors contributed in revising the paper, and read and approved the final manuscript.", "Apart from BD and ADFI that are continuous predictors, the following are categorical predictors:", "The authors declare that they have no competing interests.", "\u03b2 is a vector of coefficients for predictors and their interactions, and X [i,j,k] is the vector of explanatory variables for the ith observation of the jth pig and kth herd." ] },{ "paper_id": "6a45821b7c9010079cc6021326c1fc2f5cb05e13", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6a54a1fdb5e1476e36b632b0fb061da5b3b69b5c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The amplicons of positive for PIC were gel-purified for DNA sequencing using a QIAquick Gel Extraction (Qiagen, Germany), according to the manufacturer's instructions. DNA sequencing was performed with specific primers using an ABI PRISM BigDye Terminator Cycle Sequencing Reaction kit (version 3.1) on an ABI PRISM 3130 DNA sequencer (Applied Biosystems, Foster City, CA), following the manufacturer's instructions. Enteroviruses (EV) or rhinoviruses were identified based on sequence alignment of amplicons." ] },{ "paper_id": "6a5d030ebc7695f82f5dd6e738f9aee0d24633b3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations AMP: Antimicrobial peptide; PRV: pseudorabies virus; TCID 50 : Tissue Culture Infective Dose", "All of the animal experimental protocols were approved by the Ethics Committee of Huazhong Agricultural University according to Hubei province Laboratory Animal Management Regulations (HZAUMO2015-0015). During the experiments, mice were offered ad libitum access to water and food in a controlled environment of a 12 h light/dark cycle. All efforts have been made to reduce suffering of animals.", "On day 6, three mice from control group and noncontrol groups were euthanized and brain tissues were collected and transferred to 4% paraformaldehyde. The tissues were dehydrated in ascending grades of ethyl alcohol i.e. 70, 90 and 100% ethanol. Afterwards, the tissues were cleared with xylene. Slides were stained with Haematoxylin and Eosin (H&E) stain and analyzed through a light microscope.", "PRV, a large enveloped DNA virus, is a swine neurotropic herpesvirus [17] . Although the pigs are the natural reservoir for the virus, most mammals and some avian species are also susceptible to PRV. PRV infected animals may die from central nervous system disorders [18] . PRV infection poses a severe threat to pig industry and either attenuated live or inactivated vaccines are usually used to control the disease [19] . Although vaccination can suppress development of the disease, vaccines cannot eliminate virus infection. Mutant isolates emerged and caused Pseudorabies outbreak in 2012 [7] . Thus, novel antiviral agents should be developed as a complementary to vaccination." ] },{ "paper_id": "6a5ec0f5b18ea19bc152ad79a1b72043385a8f3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thus, we have", "kI t m j otherwise:", "Statistical estimation and assessment" ] },{ "paper_id": "6a6032614741732c373d0a939ce85785519c3fa6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition, the C-terminal region (a \"tail\" including amino acids [aa] 180 to 198) is required for NSP5 decamerization in vitro (27) and VLS formation in vivo (7) .", "(This article was submitted to an online preprint archive [30] .)", "Signals were detected using the enhanced chemiluminescence system (Pierce ECL Western blotting substrate; Thermo Scientific)." ] },{ "paper_id": "6a6327ac7ce00c6d5b2bffd0ff65c8476d94760b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Table S1 . Oligonucleotide sequences used for constructing synthetic viral genomes and the sequences of the assembled DNA constructs of the synthetic viral genomes. ", "RNA was extracted from 1 cm 2 leaf disks from plants showing viral symptoms using the RNeasy Plant Mini Kit (Qiagen, Germantown, MD, USA). RNA (10 \u03bcl) was annealed to Ampoligo 30 R and reverse transcribed using SuperScript III (Life Technologies, Carlsbad, CA, USA). cDNAs of viral genomes were amplified using Ampoligos and were sequenced by Genewiz using the Sanger method.", "Each long-oligonucleotide (0.5 \u03bcl) of two consecutive sets of long-oligonucleotides (Figure 1 ) was annealed in 16 to 18 \u03bcl TE buffer by heating to 95\u00b0C for 1 minute and cooling to 30\u00b0C at 0.1\u00b0C/s. Annealed long-oligonucleotides (0.5 \u03bcl) were reacted with 4.5 \u03bcl synthesis reaction mix (1 \u03bcl 5\u00d7 isothermal reaction buffer [48] , 0.1 unit Phusion DNA polymerase (Thermo Scientific, Waltham, MA, USA), 16 units Taq DNA ligase (New England Biolabs, Ipswich, MA, USA), and water) at 50\u00b0C for 1 h. The assembly (0.5 \u03bcl) was amplified by PCR for 20 cycles using amplification oligonucleotides and Phusion Hot Start II DNA polymerase (Thermo Fisher Scientific). DNA was separated by agarose-gel electrophoresis. DNA fragments were purified using UltraClean 15 (MO BIO Laboratories, Carlsbad, CA, USA).", "Background: Synthetic biology is a discipline that includes making life forms artificially from chemicals. Here, a DNA molecule was enzymatically synthesized in vitro from DNA templates made from oligonucleotides representing the text of the first Tobacco mosaic virus (TMV) sequence elucidated in 1982. No infectious DNA molecule of that seminal reference sequence exists, so the goal was to synthesize it and then build viral chimeras." ] },{ "paper_id": "6a68e3a345d7da33f2fcb9456aca1998647cb69e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Submit your manuscript here: http://www.dovepress.com/therapeutics-and-clinical-risk-management-journal Therapeutics and Clinical Risk Management is an international, peerreviewed journal of clinical therapeutics and risk management, focusing on concise rapid reporting of clinical studies in all therapeutic areas, outcomes, safety, and programs for the effective, safe, and sustained use of medicines. This journal is indexed on PubMed Central, CAS, EMBase, Scopus and the Elsevier Bibliographic databases. The manuscript management system is completely online and includes a very quick and fair peer-review system, which is all easy to use. Visit http://www.dovepress.com/testimonials.php to read real quotes from published authors. ", "A hospital-based retrospective study was performed on the study subjects with chronic diseases who presented to the adult ED at KAMC-RD, which is the largest university hospital in Saudi Arabia.", "Unadjusted analysis of negative binomial ( ", "The study received ethical approval from the Ethical Review Committee at the Ministry of National Guard -Health Affairs, approval #RC17/081/R. Due to the retrospective design of the study, consent from patients to review their medical records was not required by the Ethical Review Committee at the Ministry of National Guard -Health Affairs. Data were de-identified to protect the privacy and confidentiality of patient information." ] },{ "paper_id": "6a776cdff97d90eae72e7f8be666aef3a14224e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The anti-FLAG monoclonal antibody, the EZview Red anti-FLAG affinity gel, and anti-mouse immunoglobulin G (IgG) coupled to phycoerythrin (PE) were purchased from Sigma (St. ", "Immunostaining CHO or CHO/XPR1 cells were fixed using 4% paraformaldehyde in PBS, permeabilized using 0.5% Triton X-100 and stained using anti-XPR1 and anti-rabbit IgG coupled to FITC. Before mounting the slides, cells were counterstained with the nuclear stain DAPI. Pictures were taken using a fluorescence microscope (Carl Zeiss, Goettingen, Germany) and images were processed using the ImageJ software (U.S., National Institutes of Health).", "The HTX (a subclone of HT1080), 293T, 293, 293T/GFP (293T cell line stably expressing GFP) and 293/GP-LAPSN (293 cells stably expressing MoMLV Gag-Pol and alkaline phosphatase or AP) cell lines have been previously described [19, 65] . The 293/ XPR1, HTX/XPR1 and CHO/XPR1 cell lines were generated by transducing the 293, HTX or CHO cells using a retroviral vector, LXSN, encoding the XPR1 receptor (LhXPR1SN, kind gift of Dusty Miller) [33] and bearing VSV-G. Infected cells were selected using G418 (Invitrogen, Carlsbad, CA) for ,10 days. All cell lines were cultured in DMEM (Invitrogen) supplemented with 10% fetal bovine serum (FBS) at 37uC at 10% CO 2 -air atmosphere at 100% relative humidity." ] },{ "paper_id": "6a7cec5919100b5ee95c8c84b99455a7611bc79c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6a80b22e84d2692545c6f11d7cb4c96602a25c39", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The intestinal epithelial barrier forms a selectively permeable immunologically tolerant but alert barrier between the sterile inside and microbe-laden lumen.", "Endemic and emerging viral infections cause profound morbidity and mortality, with over 13 500 hospitalisations and more than 3000 deaths per year in Australia due to influenza alone. 83 Pathology in susceptible individuals is likely to involve either an inability to control the viral replication and dissemination, or the development of a local 'cytokine storm' damaging the mucosal epithelium.", "UPR activation plays important role in mucosal homeostasis. Of note, the UPR is involved in cell differentiation and can also be manipulated to accommodate a change in protein load within cells. 21, 22 This is important at the mucosal surfaces where secretory cells must produce large amounts of large, complex proteins to maintain the secreted mucus barrier and provide defence against microbes." ] },{ "paper_id": "6a8270cbdb7222a8a18248627314bdd6c9823cd4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Learning points for our case includes:", "Appropriate written informed consent was obtained for publication of this case report and accompanying images.", "Survival is likely, and treatment involves ventilation if necessary and steroids with uncertain utility. The rate of mortality is directly associated with the large volumes of silicone and high-pressure injection [2] .", "A previously healthy 30-year-old woman presented with three days history of cough with dyspnoea and fever. She had a history of breast augmentation with silicone implant two years ago and had received bilateral gluteal silicone injections from an unlicensed provider one week before the current presentation. The injected volume was approximately 500 mL for each gluteal." ] },{ "paper_id": "6a8d67876f9d695b2ad3251846bb303a9cc46ba1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following the verification process, 15 " ] },{ "paper_id": "6a93283b499ae5bc6aaf29f14e701dc8f25138ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6aa27afc427161cdd39fe7f702b00f85bf04c5b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Healthcare-acquired infections (HAIs) such as nosocomial influenza outbreak are major problems in medicine, which have yet to be resolved 1-4 . The simplest and most effective means of preventing HAI is maintaining good hand hygiene 5 .", "The use of alcohol-based hand rubs (ABHRs) has spread around the world since the Guideline for Hand Hygiene in Health-Care Settings was released by the Center for Disease Control and Prevention in 2002 6 . Based on this and the 2009 World Health Organization Guideline on Hand Hygiene in Health Care 7 , most clinical settings have adopted the practice of keeping hands, which are not visibly contaminated, clean using ABHRs. However, HAI in medical facilities has not been completely prevented, which is partly due to lack of compliance among medical staff; indeed, a reduction in HAI incidence has been linked to greater compliance 5,8-11 . However, some studies suggest that there may be room for improvement in standard hand hygiene practices 12,13 .", "Mucus (viscous body fluids such as sputum or nasal discharge) contain large amounts of mucin, which has a central protein core with multiple polysaccharide chains. Epithelial mucins are high-molecular weight glycoproteins that provide viscosity and gel-forming ability to mucus 18 . The thick epithelial mucus layer has a barrier function that is attributed to its high viscosity and protects the mucosal epithelium from gastric acid, digestive", "CMC is a cellulose derivative with carboxymethyl groups bound to some of the hydroxyl groups of the glucopyranose monomers that make up the cellulose backbone. GG is a polysaccharide composed of the sugars galactose and mannose." ] },{ "paper_id": "6aa72847e6c019bbc18254ec5cca30db62200120", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Commentary \u00ae T cells were the principal mediators of inflammation and damage in this model. Notably, survival of infected, CD4 \u03e9 T cell-depleted mice was improved despite an inability to induce fungal clearance and markedly elevated fungal burdens compared to mice with sufficient CD4 \u03e9 T cells.", "The data generated by Neal et al. (2) demonstrate that CD4 \u03e9 T cells can play dichotomous roles in C. neoformans infection. On one hand, they can mediate fungal clearance in the CNS, but on the other hand, they can induce inflammation that leads to neurological deterioration and death. This suggests a possible explanation for why inflammation is often a prominent feature of cryptococcal meningitis in HIV-uninfected, but not HIV-infected patients, and raises the intriguing possibility that the profound CD4 \u03e9 T cell deficiency, which portends risk for cryptococcosis, may actually limit inflammatory pathology in HIV-infected persons not on ART. This dichotomy may also provide insight into the failure of adjunctive steroid therapy to reduce mortality or improve morbidity in HIV-associated cryptococcosis (19) and the fact that cryptococcosis may have a better prognosis in immunosuppressed patients than in nonimmunosuppressed patients (20) (21) (22) . The detrimental effect of activated CD4 \u03e9 T cells in mice also suggests the possibility that antifungal therapy-induced fungal clearance and reduced levels of glucuronoxylomannan (GXM) (an immune suppressing molecule [23] [24] [25] ), could enhance CD4 \u03e9 T cell activation and damage. This may help explain paradoxical worsening of cryptococcosis in certain patients after initiation of antifungal therapy (26) .", "Neal and colleagues (2) describe another mouse model in which CD4 \u03e9 T cells mediate inflammation and host damage in the setting of C. neoformans infection. Their study was undertaken to gain insight into the role that CD4 \u03e9 T cells may play in the pathogenesis of IRIS-and postinfectious inflammatory syndromes (PIIRS) in HIVinfected and HIV-uninfected patients with cryptococcosis. Mice infected intravenously with 10 6 CFU of C. neoformans were monitored clinically or analyzed to determine their central nervous system (CNS) fungal burden (CFU), inflammatory pathology, and cellular and cytokine responses. The number of C. neoformans CFU in the brains of mice increased from 1 to 3 weeks after infection and then decreased from 3 to 5 weeks thereafter. Interestingly, the mice developed symptomatic disease and neurological deterioration 3 to 4 weeks after infection, corresponding to fungal clearance and surprisingly, mortality. CNS pathology revealed cellular inflammation marked by leukocytes beginning 3 weeks after infection that subsequently increased due to infiltration of CD4 \u03e9 and CD8 \u03e9 T cells, with CD4 \u03e9 T cells being the predominant population and both populations being antigen experienced. Infiltrating CD4 \u03e9 and CD8 \u03e9 T cells exhibited a Th1-type bias, producing IFN-\u2425. Depletion of CD4 \u03e9 T cells resulted in reduced mortality and inflammatory pathology, providing proof of concept that CD4 \u03e9" ] },{ "paper_id": "6aa7ff7bbaba12fef375a84c5ba297d9f848541f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bulgarian samples were collected by preliminary clinical screening in Vratza endemic regions in Bulgaria in 2003 [16] . All subjects were born of Bulgarian ancestry, born and living in the endemic region. DNA was extracted by standard phenol-chloroform extraction procedure and stored at \u221280 \u2218 C. All samples were checked for DNA consistency by 1% gel electrophoresis.", "Serbian samples were collected from Serbian endemic regions. DNA was extracted by DNA extraction kit and stored at \u221280 \u2218 C. All samples were checked for DNA consistency by 1% gel electrophoresis.", "MiSeq System using the MiSeq Reagent Kit v2 and a 500cycle 14-tile flow cell. Only Pool 9 was sequenced using a 300cycle MiSeq Reagent Micro Kit v2 and a micro 4-tile flow " ] },{ "paper_id": "6aaa4563100d784e74766eac29f4b2718ad7d256", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6aae752380943069e39342f1d86741124211c312", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Oropharyngeal and cloacal swabs were pooled in viral transport media (brain heart infusion [BHI] broth based medium [Oxoid] with 0.3 mg/ml penicillin, 5 mg/ml streptomycin, 0.1 mg/ml gentamicin, and 2.5 g/ml amphotericin B). Swabs were placed in viral transport media at the collection sites, transported at 4 \u00b0C to the laboratory and stored at \u221280 \u00b0C until the nucleic acid extraction was performed." ] },{ "paper_id": "6ab55fd404dc1987435bb3fd1b1a7d02c0951f08", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Respiratory syncytial virus (RSV) is one of the leading causes of lower respiratory tract infections in children, with a high morbidity and mortality, especially in developing countries [1] [2] [3] . Most children are infected during their first year of life, and infants under six months of age are at highest risk for severe disease, especially those with bronchopulmonary dysplasia or cyanotic heart disease [4, 5] .", "The RSV strains A2 (VR-1540: ATCC), Line19 and rA2-F19 (kindly provided by ML Moore, Emory University, Atlanta, GA, USA) were propagated in Hep-2 cells, purified and quantified as described previously [16] .", "Vaccines 2018, 6, x 6 of 10" ] },{ "paper_id": "6ab7d80bb6dc14cac7fe9c7d5a6060af434bef0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6abb30ae61aa5e41f16a28b9437940d5d76d745b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "R software (version 3.6.2) was applied for all the calculations and estimates in the current study.", "Our model predicted 2323-3381 deaths in Wuhan, China when we assumed R t as 0.9 and the percent of deaths as 4%; 2235-3256 deaths when we assumed R t as 0.5 at the fourth phase. An average of 2279-3318 deaths were also estimated ( Table 1) .", "We assumed no new transmissions from animals, no differences in individual immunity, the time-scale of the epidemic is much faster than characteristic times for demographic processes (natural birth and death), and no differences in natural births and deaths. In this model, individuals are classified into four types: susceptible (S; at risk of contracting the disease), exposed (E; infected but not yet infectious), infectious (I; capable of transmitting the disease), and removed (R; those who recover or die from the disease). The total population size (N) is given by N = S + E + I + R. It is assumed that susceptible individuals who have been infected first enter a latent (exposed) stage, during which they may have a low level of infectivity. The differential equations of the SEIR model are given as: 32, 33 dS=dt \u00bc \u00c0\u03b2 S I=N;" ] },{ "paper_id": "6ac37ecc83bd4e2f6a28476954dd962e10b1b69c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Radiolabeled antibodies were prepared as detailed above, and injectate was assayed using a well counter with a calibration factor of 517, as determined previously. 29 In a volume of 150 \u00b5L, 225 \u00b5Ci of radiolabeled antibody (approximately 100 \u00b5g) was administered intravenously via the retro-orbital sinus. Mice were serially scanned (10-20 min acquisitions, 350-750 keV energy window) on days 1, 3, 5, and 7 on a microPET R4 system (Concorde Microsystems Inc., Knoxville, TN) followed by Faxitron MX-20-DC12 digital X-ray imaging system (Faxitron Bioptics, LLC, Tucson, AZ).", "Bone Research (2018) 6:13 ; https://doi." ] },{ "paper_id": "6ac46cebdca71f2e25d8a884c5d3ce11fcaf16e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Patients were instructed to self-administer 1 puff (0.14 mL) of trial medication to each nostril 4 times per day. Trial medication was either I-C nasal spray (1.20 g iotacarrageenan/L in 0.5 % NaCl) or placebo (0.5 % NaCl). Both patients and investigators were blinded to treatment allocation. Treatment was to be mandatory for 4 days, and depending on patient preference, could be continued for up to 6 additional days, resulting in a maximum treatment duration of 10 days.", "Although not addressed in the ICICC trial, I-C's antiviral properties lead to speculation that its use might decrease cold transmission to patients' family members and other social contacts.", "Trial registration: NCT01944631 (clinicaltrials.gov)", "For the secondary endpoints SSS 2-4 , LSS 2-4 , and AUC-TSS 1-10 , there were no statistically significant differences between I-C and placebo (Table 3) ." ] },{ "paper_id": "6acfca277c3e484c1dead20fc58db53b179c33ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All procedures were performed in compliance with protocols approved by the Cleveland Clinic Institutional Animal Care and Use Committee. aUThOr cOnTriBUTiOns CS designed and performed experiments, collected and interpreted the data, and wrote the manuscript. RD analyzed data and edited manuscript. CB designed the research, provided materials, interpreted the data, and wrote the manuscript. All authors approved the final manuscript.", "The authors would like to thank Natasha Towne for her exceptional technical assistance, as well as Jennifer Powers for performing FACS purification.", "The Supplementary Material for this article can be found online at https://www.frontiersin.org/articles/10.3389/fimmu.2018.01325/ full#supplementary-material." ] },{ "paper_id": "6ad08282a281d311d1a9e87b8085a6f0c968ad50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The pigeon fecal sample from Hungary was analyzed using 6,818 unique reads from 454 pyrosequencing and showed viral hits to picornaviruses, astroviruses, and tobamoviruses.", "We received 36.5 million 250-bp paired-end reads generated on the Illumina Mi-Seq platform. Short reads were debarcoded using vendor software from Illumina. A total of 6,818 reads from 454 pyrosequencing were trimmed of their primer sequence and adjacent eight nucleotides corresponding to the randomized part of the primer. In-house analysis pipelines were developed to process both datasets. Adaptors were trimmed by in-house code. The cleaned reads were de-novo assembled using SOAPdenovo2 (38) . The assembled contigs, along with singlets, were aligned to an in-house viral protein database using NCBI BLASTx. The significant hits to viral sequences were then aligned to an inhouse non-virus-non-redundant (NVNR) universal protein database using BLASTx. Hits with more significant adjusted E-value to NVNR than to virus were removed.", "Rotaviruses consist of at least eight groups or species (A through H) with multiple P and G genotypes which together comprise a genus in the family Reoviridae. Rotavirus has a non-enveloped, triple-layered icosahedral capsid containing eleven segments of double-stranded RNA, encoding for six structural and five nonstructural proteins [78] [79] [80] . We successfully acquired 17,827 nucleotides of this highly divergent rotavirus (HK18), encoding the complete proteins of all 11 genome segments (GenBank KC876005-KC876015)." ] },{ "paper_id": "6ad4ebbfb6b68ed621ad2d67db85fac7ab6dc3cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Emitted dose (ED)-the amount of drug exiting the delivery device. Fine particle fraction (FPF)-the mass of particles below a cut-off diameter [31] .", "Significance-Uncertain benefits requiring further studies to demonstrate effects of surfactant.", "Because of a variety of proposed mechanisms, patient sputum is thought to cause aminoglycoside inactivation resulting in 'sputum antagonism' [78] ." ] },{ "paper_id": "6ae480b7554d3210fa26f2410a6ed06ade025eec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells. Madin-Darby canine kidney (MDCK) cells were maintained in Eagle's minimal essential medium (MEM) containing 5% newborn calf serum. The genetic origin of the MDCK cells was confirmed by DNA fingerprinting (using random amplified polymorphic DNA) conducted by Takara Bio Japan. MDCK cells were used for plaque assays to titrate viruses.", "Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 ScIentIfIc REpoRTS | (2018) 8:4801 |", "Pathologic examination. Animal tissues were fixed in 10% phosphate-buffered formalin for pathologic examination. They were then processed for paraffin embedding and cut into 3-\u00b5m-thick serial sections. One section from each tissue sample was subjected to standard hematoxylin-and-eosin staining, while another was processed for immunohistochemistry with a mouse monoclonal antibody for type A influenza virus NP antigen that reacts comparably with all of the test viruses. This antibody was produced in our laboratory and used for immunohistochemistry at 1:1000 dilution. Specific antigen-antibody reactions were visualized by use of 3,3\u2032-diaminobenzidine tetrahydrochloride staining and a Dako EnVision system (Dako Co. Ltd., Tokyo, Japan)." ] },{ "paper_id": "6aea0cd2aa64321c5528944e105c69a167350dbd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at http://www.mdpi.com/1999-4915/11/1/73/s1, Table S1 : Gradient elution program applied for UPLC-MS analysis, Figure S1 : OPLS-DA model validation and permutation test. The funding sources had no role in study design, data collection, analysis or interpretation or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.", "High performance liquid chromatography (HPLC)-grade methanol, acetonitrile, chloroform and 2-propanol were purchased from Merck (Darmstadt, Germany). HPLC-grade water was prepared using a Milli-Q water purification system (Millipore, Burlington, MA, USA). Analytical grade acetic Viruses 2019, 11, 73 3 of 16 acid and commercial standards used for biomarker identification were purchased from Sigma-Aldrich (St. Louis, MO, USA). Internal standards (IS) including Arachidonic acid-d8, 15(S)-HETE-d8, Leukotriene-B4-d4 and Platelet-activating factor C-16-d4 (PAF C-16-d4) were purchased from Cayman Chemical (Ann Arbor, MI, USA) [18] .", "Coronavirus replication is associated with intracellular membrane rearrangement and depends on the formation of double membrane vesicles (DMVs) and other membranous structures as replicative organelles [16] . The cell membrane components consist mainly of glycerophospholipid components such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylcholine (lysoPC), and lysophosphatidylethanolamine (lysoPE). A specific phospholipids composition is required by different viruses to form the optimal replicative organelles best suited for their replication [43] . Moreover, the lysoPC/PE was produced from PC/PE by cPLA2 activation, which simultaneously generated corresponding fatty acid moiety. In this regard, cPLA2 activation is commonly believed to be beneficial for virus replication [16, 17] ." ] },{ "paper_id": "6aea4f0b8aaacfac3d0d3b49bd7558481da9b03f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6af02873a430f5f75dc56a917f26feaea89b8e79", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Suppose a test is available to determine the infection status of traced contactees. We can then continue tracing iteratively before infected contactees are detected due to symptoms, until no further infecteds are found ( Figure 1B) .", "In this paper we consider detection and isolation as an autonomous process most likely governed by detection via clinical symptoms. This allows us to concentrate on contact tracing and quarantine, which are initiated by this autonomous process. Also we only regard transmission prior to control: we will consider tracing effective if R pre ,1.", "Control of epidemics of (emerging) infectious diseases, such as SARS, pandemic influenza, or foot-and-mouth disease, always faces the difficulty that some infectives are not yet observed. By concentrating control measures only on observed cases (treatment, isolation, culling), resources are used efficiently but control is often not effective enough. On the other hand, by directing control to the whole population (mass vaccination, prophylactic treatment, preventive culling), epidemics are most likely contained, but at high cost." ] },{ "paper_id": "6af49373c566eac05d2609e3474e847157cafb3b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The same amount protein of each sample were applied to a parallel SDS-PAGE gel and stained with Coomassie brilliant blue ( Figure 5B )." ] },{ "paper_id": "6b05be390f36231b7e3a06bc30979536eda0ee6e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was published with the permission of the Director of KEMRI.", "This work was funded by the Wellcome Trust (grants 093724 and 102975).", "Nucleotide sequence accession numbers. The complete genome sequences of the rhinovirus genomes are available at GenBank under the accession numbers KX348029 to KX348032." ] },{ "paper_id": "6b0f17a81d8f9849d4937aafbdbf74ec71820811", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All procedures involving animals were approved by the Laboratory Animal Center, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology IACUCs (Permit number: BIME 2017-0011). Animal studies were carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals. All experimental operations on mice were performed under sodium pentobarbital anesthesia, and mice were euthanized by overdose inhalation of carbon dioxide.", "Lungs and spleens were collected and sampled in accordance with standard procedures. Sections 4 \u03bcm in thickness were stained with hematoxylin and eosin and examined by light microscopy. Lung tissue lesions were assessed according to the extent of denatured epithelial tissue, degeneration or necrosis of alveoli pneumocytes, infiltration of inflammatory cells, and expansion of parenchymal wall, hemorrhage, and interstitial edema 28 .", "To detect the expression of C5aR in lung tissue, lung samples were harvested and total RNA was extracted and purified using an RNeasy Extraction Kit (Qiagen, Germany). For each sample, 2 \u03bcg of total RNA was used as template for first-strand cDNA synthesis. The resulting cDNA was subjected to quantitative PCR using Power SYBR \u00ae Green PCR Master Mix (Life Technologies, Carlsbad, CA, USA) to determine the relative abundance of C5aR in the tissues. The forward and reverse primers used for C5aR were previously described 26 . The relative amount of C5aR was determined by normalizing mRNA expression to that of the endogenous control gene GAPDH." ] },{ "paper_id": "6b1560c20661e5dea1c1d2c391c1fa68f6cf83ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Calves born to dams vaccinated against E. coli, rotavirus and coronavirus also shed less C. parvum oocysts [6] . This lower shedding of C. parvum oocyst is most likely a reflection of a generally higher standard of herd management in these herds, rather than a direct protective effect. A vaccine against C. parvum has not been developed yet.", "The functional importance of colostral leukocytes is not yet fully understood. Some studies show that they enhance lymphocyte responses to nonspecific mitogens and specific antigens and increase antigen-presenting capacity [41] [42] [43] [44] , while others suggest that the role of fresh colostral leukocytes may not be as important as once thought [45] . As protection against C. parvum is mainly cell-mediated, further research into the importance of colostral leukocytes is warranted.", "The authors declare that they have no competing interests. " ] },{ "paper_id": "6b1684f4f6c7966725627602b6771c2f1224df89", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We ", "Therefore, we should provide pre-pregnancy education to avoid gestational hypertension and diabetes and improve prenatal diagnosis rate to adopt measures in advance." ] },{ "paper_id": "6b18559c0c4de907cce17857d77321b52375ea36", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protein identification and relative quantitation was performed using ProteinPilot 2.0.1 software (AB Sciex). Data files from both technical replicates of an iTRAQ sample set were processed together. The search database was a self-built combination of Uniprot human protein sequences and Uniprot ssRNA negativestrand viruses sequences (both form the release 55.0, 02/08). The search criteria were: cysteine alkylation with MMTS, trypsin digestion, biological modifications allowed, thorough search and detected protein threshold of 95% confidence (Unused ProtScore .1,3) . Additionally, automatic bias correction was used for intracellular fractions to correct for uneven protein loading. ProteinPilot identification and quantitation results were also manually checked: for each identified protein at least two unique peptides with good quality MS/MS data were required, and MS/ MS spectra with all reporter ion peak heights below 10 counts were manually removed from quantitation results. False discovery rates were calculated using a concatenated normal and reversed sequence database and a previously reported method [54] .", "The percentage of apoptotic cells was assayed with APOPercentage Apoptosis Assay according to manufacturer's instructions (Biocolor Life Science Assays). Photographs were taken with an Olympus DP70 Digital microscope camera connected to an Olympus IX71 light microscope using DP Controller (version 2.2.1.227) and DP Manager (version 2.2.1.195) softwares. The stained (apoptotic) and unstained cells were manually counted, and the percentage of apoptotic cells was calculated. ", "The cells grown in complete Macrophage-SFM medium were washed tree times with PBS and the media was changed to RPMI growth media supplemented with 1 mM HEPES, L-Glutamine and antibiotics. The RPMI media has lower content of initial media proteins than Macrophage-SFM medium. The cathepsin B inhibitors, Ca-074 Me (Calbiochem) and z-FA-fmk (Calbiochem) were added 0.5 h before influenza A virus infection and used at final concentration of 40 mM and 50 mM, respectively." ] },{ "paper_id": "6b18741fd5c6ab895acb11a559286c68b43eb9d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6b18c718ecf5fb496443591ba267b2ccae0c2863", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\"I declare that my institution holds or has applied for several United Stated and International patents based on technology developed in my laboratory. These patents or patent applications cover a range of technologies including diagnostic assays, human A-type retroviruses and a Btype retrovirus (betaretrovirus), and peptides that inhibit viral infectivity. Tulane University has licensed some of these technologies to private companies for commercial development (list available on request), and I receive royalties from these licenses. I have also served on several study sections for the National Institutes of Health and currently served as the Chair of a biodefense study section (SSS-Z). I receive a per diem and reimbursement from the NIH for service on the study sections. Except for mutual funds in a retirement account managed through Tulane University, I own no stocks or other commercial instruments.\"", "It is also a BioMed Central policy that Editors should declare their competing interests. Several years ago, I suggested that it would be a useful policy for the Editors of scientific and medical journals to declare their competing interests on a yearly basis [12] . Few editors have accepted this suggestion, but by way of example I shall declare my own here:", "There are several outstanding virology journals covering all aspects of this dynamic field, but none of the general virology journals are exclusively published on-line or are Open Access. With the launch of Virology Journal, we hope to catalyse a fuller utilization of the Internet for scientific communication in virology drawing on our long experience with the ATV website. We welcome any advice and input." ] },{ "paper_id": "6b20f25b48785e488fb280a76ec8f1da3bf8e2a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We used egr-1/pCDNA3.1(+) and gL/pCDNA3.1(+) vectors in this study. Both these vectors have been described elsewhere [6] . ", "IVT of egr-1/pCDNA3.1(+) and gL/pCDNA3.1(+) was conducted as per earlier studies [45] using the TNT-coupled rabbit reticulocyte lysate system (Promega).", "Equal amounts (20 mg) of protein was used in Western blotting experiments as per earlier studies [47] ." ] },{ "paper_id": "6b377682a1b0f72ead6fe21eb275ab3bd1308f21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal experiments were approved by the Institutional Animal Care and Use Committee of National Defense Medical Center (IACUC-10-005). Female BALB/c mice at 4-5 weeks of age were purchased from National Laboratory Animal Center (Taipei, Taiwan), and housed under specific pathogen-free conditions until virus challenge at 6 weeks of age. Four to seven mice per group were anesthetized by intraperitoneal injection of 0.5 mg zolazepam chlorhydrate (Virbac, Carros, France) before intranasal inoculation with 50 \u03bcL virus solution containing 200 PFU or serum free DMEM/HG (control). Mice were observed for illness or death for 14 days. Illness was recorded as lethal if mice lost 25% body weight, and euthanization was performed humanely by CO 2 asphyxiation. For lung titer determination, three to five mice per group were euthanized at 72 h post-infection, and the lungs were homogenized in 1 mL DMEM/HG supplemented with antibiotics and 2.5 \u03bcg/mL TPCK-treated trypsin. Homogenates were then centrifuged at 2000\u00d7g for 5 min. Supernatants were aliquoted, and stored at \u2212 80\u00b0C for viral titrations. The lung viral titers were determined by plaque assay as described previously [24] .", "Amino acid position 216 in PB1 of influenza A/H1N1 is a species-associated position that distinguishes between human and avian influenza viruses after the emergence of pdmH1N1" ] },{ "paper_id": "6b3ebb32594707253e29179e7616236fdff6f362", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Robert Heinrich Hermann Koch (1843-1910), the founder of modern bacteriology, identified the specific causative agents of tuberculosis, cholera, and anthrax and provided experimental support for the concept of infectious diseases, which included experiments on humans [16] .", "The 1860s-1870s marked the development of the germ theory. In France, Louis Pasteur (1822-1895) discovered the principles of vaccination, microbial fermentation, and pasteurization [15] .", "Pasteur, Virchow and Osler were the forerunners of the next macrocycle around One Health-which is still ongoing. Another step forward in knowledge about the interconnection between animal and human health was when zoonotic diseases were discovered and understood in their complexity. These were just part of a much bigger picture; evidence that an animal virus such as rinderpest could give origin to a devastating human virus such as measles was a true revelation [17] ." ] },{ "paper_id": "6b3f7521b0b4ed6a0230e0ce6ab2f4c02892a287", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Curiously, after initiation of treatment with intravenous steroid, both the virus-positive and -negative groups had no significant difference in duration of respiratory failure, wheezing, days in hospital, and even in the time required for steroid treatment.", "No established treatment for prevention of HRV-induced asthma is available, and we describe the exploratory interventions as follows.", "In this regard, Bartlett et al. (2008) generated a transgenic BALB/c mouse expressing a mouse-human ICAM-1 chimeric receptor for HRV-16 infection. This study also showed asthma exacerbation model by intraperitoneally sensitized with ovalbumin with aluminum hydroxide followed by intranasal inoculation of HRV-1B or UV-inactivated HRV-1B." ] },{ "paper_id": "6b40e3b543867aa91f5d01345cf3ed074300159c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The CAI is used as a quantitative method of predicting the expression level of a gene based on its codon sequence. The CAI value ranges from 0 to 1. The most frequent codons simply have the highest relative adaptiveness values, and sequences with higher CAIs are preferred over those with lower CAIs [32] .", "ENC expected~2 zsz 29 s 2 z(1{s 2 )", "where s represents the given GC 3 % value [30] ." ] },{ "paper_id": "6b47bb3bca780af716c9e986d983f1d2364136c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To determine the specificities, our assays were tested on other different viruses and they turn out negative.", "Bacterial isolates were identified using conventional biochemical methods including urease and indole production, citrate utilization, hydrogen sulphide, gas production and fermentation of sugars. The biochemical media used included Simon's Citrate medium, Urea and Triple Sugar Iron agar (TSI). Coagulase tests were performed for all staphylococci organisms." ] },{ "paper_id": "6b51562f63de5739f2b7ebf5f9c34365ac6ee545", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Alternative strategies are needed to combat the constant threats posed by influenza. One of such strategies may come from passive immunoprophylaxis with monoclonal antibodies (mAbs) recognizing broadly conserved influenza epitopes and endowed with broad-range neutralizing activity [18] .", "APR834_fw:CACCATGAAGGCAAACC-TACTGGTCCTGTTATGTG.", "APR834_rev:TCAGATGCATATTCTGCACTGCAAA-GATCCATTAGA." ] },{ "paper_id": "6b58f76c98afb6435969ef4d9f9a063058265b98", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Saimiriine and Ateline Herpesviruses ", "To date, the best evidence for gammaherpesvirus infections of bats is based upon ", "Supplemental material for this article may be found at http://dx.doi.org/10.1128/ mSphere.00070-15. Figure S1 , EPS file, 1.6 MB." ] },{ "paper_id": "6b5de60d9f674c951315c0c7549fe9e9987e239f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. Prolonged fever continuing at 37.5\u00b0C -40\u00b0C. 2. Iconographic pneumonia with apparent respiratory symptoms.", "3. Normal or lower total WBC. 4. No apparent improvement or became more severe after 3-day treatment with antibiotics." ] },{ "paper_id": "6b5fd83b8ea551e2637d8291e2f74ed9113b92ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Patterned solid wax on a paper substrate is heated to diffuse deeply into the paper and to form hydrophobic walls to prepare micro channels. The heating and drying processes are optimized by comparing the six different heating and drying processes: two different heating temperatures (90 and 130 \u2022 C) and three different drying times (6, 12, and 30 min), producing six different conditions ( Figure S3 )." ] },{ "paper_id": "6b60cd0bf36070ca9ee5a9fa65ac9ddd3b61bcd4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6b67761a8689f2744b4046161187a0d128a5d7d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virions were purified in a 15-50% sucrose density gradient using an SW32Ti rotor (Beckman Coulter, Inc., Fullerton,CA) at 20,000 rpm for 12-16 h at 4uC. Gradient fractions were analyzed by 16% SDS-polyacrylamide gel electrophoresis and Coomassie Brilliant Blue G staining (Fig. 2B) . Protein bands were excised and either directly sequenced by automated Edman degradation (Applied Biosystems model 491cLC) or digested with lysylendopeptidase prior to HPLC purification and sequencing.", "The acquisition of ExoN by an ancestral nidovirus must have produced viable progeny but it remains unknown whether, besides ExoN, any additional properties of the ancestral nidovirus were critical for genome expansion, as was speculated elsewhere [15] .", "For electron microscopy, virus was concentrated from ICF by centrifugation at 12,000 g for 30 min at 4 C, after which 6.6% polyethylene glycol 6000 and 2.2% NaCl were added to the supernatant. After stirring for 1 h at 4 C and centrifugation at 12,000 g for 1 h, the supernatant was discarded. The viruscontaining pellet was dissolved in saline-Tris-EDTA buffer, sedimented at 250,000 g for 1 h and resuspended a second time. The concentrated virus was negatively stained with 1% sodium phosphotungstic acid, pH 6.0, and examined at 100 KV using a transmission electron microscope (JEM-100CX, JEOL, Japan) [79] .", "(RTF)", "To sequence the genomic region upstream of the index clone, the following amplification strategy was used, involving two DNA fragments called double-stranded (ds) cDNA and anchor DNA. To produce ds cDNA, viral genomic RNA was mixed with 10 mM dNTP mix and 2 pmol of 15-mer gene-specific primers (NDiV-RACE492-477RP, NDiV-RACE302-288RPB and NDiV-RACE435-420RPC) (Fig. S1A, Table S2 )." ] },{ "paper_id": "6b749617eb4a9f2760720a1b2a061cd0d45f9e3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Prediction of H2-Kd binding epitopes from CEA-SRAS-CoV fusion polypeptides", "Results are expressed as mean \u00b1 SE. Student's t test was applied to compare the effects of treatment in the different groups, and the Mantel-Cox significance test was employed to analyze the survival rate. A value of p < 0.05 was considered significant." ] },{ "paper_id": "6b74be7b5e6870fb9f10027347b2ad067aa8b4d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed with Graph-Pad Prism, version 6.2 (Graph Pad Software, la Jolla, CA).", "Cifaldi et al.", "and canonical splice site variants were considered potentially pathogenic (6) . In silico prediction of functional consequences of novel SNV was performed using Mutation taster, LTR, Polyphen2, SIFT, and CADD score >15 (26-30) and literature available data. Supplementary Figure 1A summarizes all steps of the process." ] },{ "paper_id": "6b76a747ec773a8604c95aa082bbb51fd95af353", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In all post hoc multiple pairwise comparisons with the Kolmogorov-Smirnov test, a Bonferroni adjustment was applied by testing individual hypotheses at the level \u03b1 * = 0.05/21 (where 21 is the number of tests).", "higher percentage of risk tolerant. Alternatively, the current baseline model could be correct and the observed data could represent a rare case that happened to be actualized in reality. Only independent data on risk attitude collected from a sample of producers can help answer this question.", "GB, SW, EC, and SCM assisted with design and conceptualization of the agent-based model. EC helped with data collection. GB, SCM, EC, and SMM worked on data analysis. Project funding was generated with the help of JS, SCM, CK, and AZ. Experiments were conducted by GB and EC. Software development was primarily led by GB, SW, and EC. Initial manuscript drafts were created by GB. Subsequent manuscript editing was completed by all authors. " ] },{ "paper_id": "6b810552f81fc62a9f69f64033011fd5c627c8ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The R. ferrumequinum transcriptome was assembled using the Brujin graph and SOAPdenovo software packages as described previously [37] .", "There are presently no known extra copies of MlERV-\u03b2E within the M. lucifugus genome.", "All nucleotide and protein alignments were conducted using the Create Alignment function of the CLC Main Workbench except where stated otherwise." ] },{ "paper_id": "6b83ccbaff4b9d9f4ac38fcfbbb2bdde5b3c53aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PLOS Neglected Tropical Diseases | https://doi.", "Field procedures were approved by the University of Georgia Animal Care and Use Committee (A2014 04-016-Y3-A5) and the University of Glasgow School of Medical Veterinary and Life Sciences Research Ethics Committee (Ref08a/15); all procedures were conducted in accordance with accepted guidelines for humane wildlife research as outlined by the American Society of Mammalogists [50] . Bat capture, sample collection, and exportation were authorized by the Belize Forest Department under permits CD/60/3/15 (21) and WL/1/1/16 (17) ", "Bartonella was detected by PCR in all nine sites in each year, with prevalence ranging from 30-100% (Fig 4) . " ] },{ "paper_id": "6ba9d2be64380669690c2e8a8a614100a7a5a50a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pone.0193131.g001", "Peptides representing murine mesothelin coding sequence, GVYGFQVSEADVRALGGLAC and CPPGKEPYKVDEDLIFYQN, were synthesized and conjugated to KLH carrier proteins via the terminal cysteine residues (underlined, Genemed Synthesis), and used for immunization of two rabbits [7] . Sera were confirmed for reactivity with the immunizing peptides by ELISA.", "Experiments were repeated at least three times, and representative data are shown. A twotailed Student's t test was used to compare groups. P values < 0.05 were considered significant." ] },{ "paper_id": "6bb112bc662ab0ff3a6f44b4f28873c12228c641", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fluorescence signal HIV-1 p24 <0.1 pg/mL [146] AgNPs-G gold electrode coated with AuNPs-G, whose is modified with H7-monoclonal antibodies Electrochemical immunosensor Aviar Influenza Virus H7 1.6 pg/mL [147] FSNPs highly fluorescent bioconjugated nanoparticles probe Fluorescence signal L. monocitogenes 50 CFU/mL [148] Fluorescence Si-MNPs high specificity for dsDNA and bright fluorescence upon intercalation into dsDNA.", "Nucleic-acid dye SYBR Green I signal (Intensity) S. aureus 50 CFU/mL [149] AgNPs ", "The authors declare no competing financial interest. " ] },{ "paper_id": "6bba4b00882498efa69f66a1a92b1c240acfd2a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "App is the causative agent of porcine pleuropneumonia, a severe and highly contagious respiratory disease responsible for major economic losses in the swine industry worldwide [14] . The disease, transmitted by aerosol or by direct contact with infected pigs, may result in rapid death or in severe pathology characterized by hemorrhagic, fibrinous, and necrotic lung lesions. Exposure to the organism may lead to chronic infection such that animals fail to thrive; alternatively, they survive as asymptomatic carriers that transmit the disease to healthy herds. Many virulence factors of this microorganism have been well characterized [14] [15] [16] . To date, fifteen serotypes of App based on capsular antigens have been described [17, 18] . The prevalence of specific serotypes varies with geographic region [17] .", "App Cell Culture Supernatant Antiviral Activity Against other DNA and RNA Viruses", "PRRSV can lead to persistent infections [36, 37] and current PRRSV vaccines are not yet optimal, since they lack the ability to induce a strong immune response and since they do not provide complete immunity against homologous PRRSV infections (for review see [38, 39] ). Moreover, most PRRSV vaccines are live attenuated virus and thus present a safety issue; some vaccinated pigs were shown to produce shedding of virulent PRRSV particles [40] . Thus, it is important to further investigate new possible ways to control PRRSV infections. In that regards, an antiviral molecule or metabolite might be a good alternative to the currently used vaccines. Recently published studies showed few compounds that can inhibits PRRSV as glycosides, terpenoids, coumarins, isoflavones, peptolides, alkaloids, flavones, macrolides [41] , N-acetylpenicillamine [42] , cyclosporine A [43] , sodium tanshinone IIA sulfonate [44] , flavaspidic acid AB [45] , Ribavirin [46] , and morpholino oligomer [47] , or compounds derived from plant as a polysaccharide isolated from Achyranthes bidentata [48] or a mushroom extract from Cryptoporus volvatus [49] . However, there is no commercially available antiviral drug against PRRSV on the market.", "Porcine reproductive and respiratory syndrome (PRRS) is the most economically devastating viral disease affecting the swine industry worldwide [8] . The etiological agent, PRRSV, possesses a RNA viral genome with ten open reading frames [8] [9] [10] . PRRSV virulence is multigenic and resides in both the non-structural and structural viral proteins. The molecular characteristics, biological and immunological functions of the PRRSV structural and nonstructural proteins and their involvement in the virus pathogenesis were recently reviewed [8] . The disease induced by PRRSV has many clinical manifestations but the two most prevalent are severe reproductive failure in sows and gilts (characterized by late-term abortions, an increased number of stillborn, mummified and weakborn pigs) [11, 12] and respiratory problems in pigs of all ages associated with a non-specific lymphomononuclear interstitial pneumonitis [11] [12] [13] ." ] },{ "paper_id": "6bc785e1a4016681657922ea713cb52b1c30e655", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In contrast, it has been seldom reported in other SOT settings such as renal transplantation [9] .", "This is the second hMPV pneumonia in a kidneytransplanted recipient described in the literature. The first reported case was a severe LRI requiring transient intensive care unit stay [9] . It occurred three years after kidney transplantation, while receiving immunosuppressive regimen consisting of ciclosporine (125 mg b.i.d), azathioprine (75 mg/d), and prednisone (10 mg/d). Compared to this case, our patient had mild symptoms, mainly cough and upper respiratory symptoms. He was also less immunosuppressed without corticosteroids regimen.", "In conclusion, hMPV has to be considered as a potential cause of LRI in kidney transplant recipients and may mimic Pneumocystis pneumonia. A prompt recognition would have avoided antibiotic use and further diagnostic studies such as bronchoscopy. Its early detection using immunofluorescence and/or RT-PCR must be proposed routinely in transplantation settings. In addition, early recognition could improve the implementation of appropriate infection control practices to prevent viral spread of this potential lifethreatening infection in immunocompromised patients." ] },{ "paper_id": "6bcf5a5f877be9a08113db6aec4a409f8d111895", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our first case is a 69-year-old Caucasian man with a past medical history of coronary artery disease, chronic renal insufficiency, hypertension and type 1 diabetes. Two weeks earlier, he had been exposed to a child with an upper respiratory infection. He lived in a rural area. He had no history of insect bites, but was exposed to farm animals and pond water.", "On admission main laboratory examations were as follows: white blood cell count (WBC) was 9.8 K/mL (87% neutrophils, 4% lymphocytes); C-reactive protein 205 mg/L; serum sodium 132 mEq/L; serum phosphorus 2.3 mg/dL; serum glutamate pyruvate transaminase (SGPT) 175 IU/L; serum oxaloacetate transaminase (SGOT) 184 IU/L; serum ferritin 4100 ng/mL; creatinine phosphokinase (CPK) 241 IU/L. Winthrop scale score was > 15." ] },{ "paper_id": "6bd542932368c6d6a32847714e3327136f3c4bd8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6bd5e8bc7dfa11b9f9d98c97a7e7b1e8ba0e5909", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A constructive solution will reflect the legitimate priorities-and depend on the engagement-of several groups. We propose a framework of three broad categories: transparency in reporting; clarity about the role of a preprint versus a peer-reviewed journal article; and responsibility for safety.", "These practices will clarify relationships between preprint and published versions and discourage unwarranted or uncritical application of information contained in preprints." ] },{ "paper_id": "6be52161b7c2d20ad15f376399586a3ab395206d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The next question we might ask is why the old belief can be passed on from generation to generation. In particular, why is \"Chikui\" a choice people want to make? Could it be real gold or fool's gold?", "Accordingly, we searched for Chinese and foreign anecdotes of celebrities (successful people) in history, culture, literature, politics, science, and business." ] },{ "paper_id": "6be6ca48112c227ce80a36601ea8b464edbf1367", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza B, unlike influenza A, viruses have no animal reservoir and predominantly infect humans. Influenza B can be divided into two phylogenetic lineages: Yamagata-like and Victoria-like [1] . These viruses have lower mutation rates [2] , but also contribute to seasonal influenza activity considerably. Influenza C viruses are rarely isolated and disease caused by these viruses is usually limited to mild symptoms in children [3, 4] .", "Lidewij C. M. Wiersma, Guus F. Rimmelzwaan and Rory D. de Vries wrote the manuscript.", "The authors declare no conflict of interest.", "In order to induce antibodies that recognize conserved epitopes in the stem region various vaccination strategies have been employed, including the use of so-called \"headless HAs\". These immunogens are essentially an HA molecule that lacks the globular head domain while maintaining the structural integrity of the stem. Mice were vaccinated with DNA encoding headless HA, followed by a boost with VLP containing headless HA protein and challenged with PR8. This headless HA vaccination strategy resulted in production of immune sera with broader reactivity than when full-length HA was used. Although sterile protection was not achieved, mice challenged with homologous virus showed no mortality and were partially protected against weight loss [60] ." ] },{ "paper_id": "6bf7eb57bcb46ac71e49305ef93f2acafc869e9b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Most RVF patients suffer from a self-limiting, febrile illness. However, some patients develop neurological disorders, vision loss, hemorrhagic fever, or thrombosis as shown in Figure 1 .", "Although the genetic diversity of RVFV strains is relatively low (approximately 5% in primary sequences [131] ), the susceptibilities to rat IFN-\uf061/\uf062 differed among RVFV strains. Most of the sub-Saharan RVFV strains are very sensitive to rat IFN-\uf061/\uf062 (ED 50 : 0.3-0.7 units), whereas Egyptian strains, including ZH501 and ZH548, and a Zimbabwean isolate (2269/74) are relatively resistant to rat IFN-\uf061/\uf062 (ED 50 : 50-200 units) [132] . All of those RVFV isolates show a similar sensitivity to human IFN-\uf061 (ED 50 : 70-880 units).", "RVFV encodes several virulence factors, and the major virulence factor NSs plays an important role in evading host innate immune responses. In the next chapter, we discuss how humans or host animals develop protective immune responses against highly virulent wt RVFV.", "Another case with encephalitis and retinitis was described by Alrajhi et al. [30] . The patient had a fever, ataxic gait, and bilateral retinal hemorrhage. She could not count fingers, and the CSF contained many leukocytes, including lymphocytes. Her consciousness level was decreased. She was discharged on day 30 of the illness to her home, at which time she was awake, blind, quadreparetic, and incontinent. Moreover, her neurologic conditions did not improve for the next year.", "In summary, RVFV NSs induces the shut-down of host transcription, including transcription of both type-I IFN and ISGs mRNAs, to prevent antiviral responses. NSs also induces the degradation of PKR to prevent eIF2\uf061-mediated host and viral translational shut-off and promote an efficient viral protein synthesis." ] },{ "paper_id": "6bfa66e7befc8ca735ef61dc392a32d1c56ea01e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Authors' contributions JD and ES contributed equally to writing this review. RDH provided substantive intellectual input. All authors read and approved the final manuscript. ", "rDNA promoter methylation has been detected in the parietal cortex of Alzheimer's disease patients [157] .", "The authors declare that they have no competing interests." ] },{ "paper_id": "6bfd7a2e092c039e792bae569c8406f2a47c2759", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We assessed transmission reduction potential provided by personal respirators, surgical masks and homemade masks when worn during a variety of activities by healthy volunteers and a simulated patient.", "In these short term experiments, adjusting for covariates, face mask type had a strongly significant independent effect on protection (p,0.001). Children were significantly less protected than adults (p,0.001). There was no significant impact of activity on protection.", "All volunteers received written information prior to the experiments and gave oral informed consent. For the children also a parent gave oral informed consent, and a parent remained present during the experiments. The Dutch Central Committee on Research Involving Human Subjects (CCMO) informed us in writing that this project did not need to be assessed by an Ethics committee." ] },{ "paper_id": "6bffaf7e11f81818a630ae32f752c963664bdc71", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sodium periodate (NaIO4), Sodium azide, Sepharose and Cyanoborohydride coupling buffer were obtained from Sigma-Aldrich. Poly I:C and EnzChek pyrophosphate Kit were purchased from Invitrogen, Cell lysis buffer M-PER were obtained from Pierce.", "Poly I:C Coupling to Activated Sepharose Beads", "All the cell lines were purchased from ATCC. The normal prostate epithelial cell line RWPE1 (ATCC) was cultured in K-SFM (keratinocyte serum free medium) supplemented with BPE (Bovine pituitary extract) and EGF (Epidermal growth factor) as per the supplier's recommendation. The 293T were cultured in high glucose DMEM media. The prostate cancer cell lines LNCaP were culture in RPMI, DU145 in F12 medium. The cells were incubated at 37\u00b0C and 5 % CO2 under sterile conditions." ] },{ "paper_id": "6c0431081c9d7d41d0efddd87fb0244b401ef67c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6c04f5f55db4cef127e6799e220f5cb86b9ffa18", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We obtained ethical approval from the Medical Ethical Committee of the University Medical Center Utrecht, The Netherlands (13-664/C). Informed consent was obtained before survey participation." ] },{ "paper_id": "6c18f2bf81bf9b00f2a628d540151912b2dfe980", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6c26acf9ba8059cbd9caa58acb1a64538cfb7df9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed using the SPSS Statistics software and results were expressed as means \u00b1 standard deviation (SD).", "The statistical significance of differences was determined by an independent-sample t-test.", "YiL and QL conceived and designed this research; QL, YuL, JY, and XH performed this experiments; DZ and KH analyzed the data; KB contributed reagents/analytic tools; QL and YuL wrote the paper. All authors read and approved the paper." ] },{ "paper_id": "6c3d20fd2c5c86c813cddcaef028a3c5f6d7cf34", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "all \"", "Ppdummyq \"", "According to [12] , PseAAC can be generally formulated as:" ] },{ "paper_id": "6c3e1a43f0e199876d4bd9ff787e1911fd5cfaa6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6c3e8d0fde7d37c97f68675d4d8012c9445be551", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Compounds and formulation for in vitro studies. Remdesivir (RDV), lopinavir (LPV), and ritonavir (RTV) were solubilized in 100% DMSO and provided by Gilead Sciences, Inc. Recombinant human interferon beta (IFNb) protein was purchased from R&D Systems (8499IF010/CF, 2.8 \u00d7 10 8 IU/mg compared with WHO standard) and solubilized in sterile water as recommended.", "Prophylactic in vivo efficacy studies. For all drug studies, mice that lost >20% of their starting weight were weighed twice and subjected to an additional visual check each day for clinical signs (hunching, ease of mobility, lethargy, etc.). Mice that fell <70% of their starting weight were immediately euthanized. Mortality was defined as unexpectedly finding mice dead in the cage.", "Acute lung injury histological assessment tools. We used two different and complementary quantitative histologic tools to determine if antiviral treatments diminished the histopathologic features associated with lung injury. Both analyses and scoring were performed by a Board Certified Veterinary Pathologist who was blinded to the treatment groups." ] },{ "paper_id": "6c4acd1676d614bf6b2e4fdf9d17337e237d440d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study procedure and study protocol were approved by the Regional Ethical Review Board in Uppsala, Sweden. All participants gave their informed consent. An information letter sent together with the questionnaire stated that if the subjects answered and returned the questionnaire, it meant they had given their informed consent.", "All statistical calculations were done by SPSS version 21, and a p-value <0.05 was considered statistically significant. Odds ratio (OR) with a 95% confidence interval (CI) was calculated for the logistic regression models. Associations for age in the logistic regression was expressed for an escalation of 10 years.", "Nonparticipants were 3 years older (p = 0.001) and had worked 3 years longer at SAS (p = 0.02)." ] },{ "paper_id": "6c4f3eeb65df5c4294024c37835fa5097dd604e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6c4fd19f82c72d0d52f0de8c0290f522646c6da7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the only study on dromedaries, Group 6 genotype \"Macaque1\" and a novel genotype named \"Camel-2\" (related to members of the group 8 E. bieneusi genotypes \"Macaque1\", \"KB5\" and \"Horse2\") were identified [16] . The zoonotic potential of E. bieneusi genotypes from camels, their frequency and distribution still need to be investigated.", "heat tolerance, etc. enable them to survive almost one week with little or no food and water [6] , making them suitable also for trade and trafficking over longer distances in arid areas. Indeed, they are utilized since ancient times for transportation of people, goods, warfare and as draft animals including in agriculture and in local industry. Furthermore, they provide food (meat and dairy products) with great nutritional value, wool and leather in regions of the globe where the common ruminant livestock species (cattle, sheep and goat) cannot be used for this purpose. In the year 2017, camels produced 2,852,213 tons of milk and 630,210 tons of meat [1] . In this article \"camel\" refers only to \"dromedary camel\".", "Schistosomiasis is an infectious disease that affects more than 230 million people worldwide [101] . Four Schistosoma species, Schistosoma bovis, Schistosoma mattheei, Schistosoma indicum and Schistosoma turkestanica (syn. Orientobilharzia turkestanicum, Ornithobilharzia turkestanicum), have been reported in camels [102] [103] [104] . Schistosoma bovis and S. mattheei have also been described in humans [105] , as well as human cercarial dermatitis caused by S. turkestanica has been reported [106] .", "Microsporidia are diverse emerging opportunistic pathogens with 200 genera and 1500 species, 17 of which infect humans [35] . Of these, Enterocytozoon bieneusi, a ubiquitous protozoan that infects the gastrointestinal tract of a large number of mammals, is frequently recognized in humans [36] . Currently 474 distinctive E. bieneusi genotypes from 11 groups have been differentiated out of which Group 1 members are mainly identified in humans whereas others have been suspected [35] .", "Due to its exceptionally wide range of warm-and coldblooded hosts, T. gondii is one of the most successful zoonotic parasites on earth [37] . Indeed, approximately 30% of the world's human population are infected with this cosmopolitan food-and water-borne parasite [38] ." ] },{ "paper_id": "6c5521b73b11d4e229b4ca98f116bc32aa4052c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mutation mapping microarrays were designed with NimbleGen algorithms that select a 29-mer oligonucleotide every seven bases on each strand of the reference genome sequence (GenBank Accession NC_009442). All probes were synthesized in parallel on a two-array set using a Digital Light Processor \u2122 (Texas Instruments, Plano Texas) and photoprotected phosphoramidite chemistry (i.e., maskless array synthesis) (NimbleGen Systems, Madison WI) in a random probe layout [38, 39] .", "Labeled genomic DNA was hybridized to arrays in Nim-bleGen hybridization buffer for 16 h at 42\u00b0C using a MAUI hybridization system (BioMicro Systems, Inc. Salt Lake City, Utah). Labeled genomic DNA (~5 \u03bcg) from the 05ZYH33 reference strain and from each tested strain were co-hybridized to each array. Arrays were washed with NimbleGen wash buffer, spun dry in a high-speed microarray centrifuge (TeleChem International, Inc., Sunnyvale, CA), and stored until they were scanned.", "Analysis of mapping array data and design and hybridization of re-sequencing microarrays Microarrays were scanned at 5-\u03bcm resolution using a Genepix \u00ae 4000B scanner (Axon Instruments, Union City CA), and pixel intensities were extracted using NimbleScan\u2122 v2.4 software (NimbleGen). Probes that spanned potential mutations were identified by Nimble-Gen software. Probe sequences corresponding to all possible candidate mutation sites were selected for resequencing. The strategy used to automatically generate the sequencing arrays was similar to that described previously [9] . Briefly, eight probes were designed per base position analyzed, i.e., four per genome strand. These probes contain all possible alleles at a centrally located position. The length, melting temperature, and mismatch position of each probe were optimized. When target DNA is hybridized to these arrays, the perfectly matched probe will hybridize more strongly than the three corresponding mismatch probes for each strand. This differential signal intensity between the perfect match probe and mismatch probes allows the base to be determined precisely. These re-sequencing arrays were synthesized, hybridized with labeled genomic DNA from each tested SS2 strain, and scanned as above. Sequence base assignments were made using a machine-learning algorithm [40] . Putative mutation-containing DNA segments were PCR amplified and verified by capillary sequencing. The microarray data was deposited in the National Center for Biotechnology Information Gene Expression Omnibus Database (GEO; http://www.ncbi. nlm.nih.gov/geo/), with the accession number of GSE17868." ] },{ "paper_id": "6c6622a7955d513c961a57d13a287300a8ec5c87", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.", "Funding for this research was provided through Centers of Excellence for Influenza Research and Surveillance (HHSN272201400004C).", "Research into the specific mechanisms of H1N1 influenza A virus binding, entry, RNA replication, transmission, and induction of the host immune system has been extensive since the 1918 Spanish influenza pandemic; however, investigations into how these mechanisms manifest in disease in immunologically unique populations, such as infants, the elderly, HIV + or asthmatic patients, and pregnant women have been limited." ] },{ "paper_id": "6c6ac6629c8a603c01953ae37469014700102ed8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Because the NHIRD prohibited any break of confidentiality, we did not continue the analysis hierarchically from geographic location to accreditation level. Instead, we displayed the aggregate data in location and level separately. However, hierarchical modelling could be used to examine the factors associated with reduced utilization and would help construct a real-time and on-line analytical processing system for nationwide surveillance during an outbreak of an infectious disease.", "The aim of the current study was to describe the changes in hospice inpatient utilization during and after the SARS epidemic within the NHI program in Taiwan. Such quantitative analyses might provide evidence for discussion in health policy-making and help with effective planning in the future." ] },{ "paper_id": "6c6e27a1a325b80e4b57ab890da40aca90737d7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Introduction Standard patient care requires sterilizing or disinfecting surgical equipment and reclaimed medical devices that are contaminated by infectious agents [1] . Those items do not include masks, which should not be reused under normal circumstances. Healthcare workers (HCWs) often use disposable masks following outbreaks of SARS [2] [3] [4] , H1N1 [5, 6] MERS and influenza. In hospitals, HCWs use these masks as the front-line defense against airborne droplets and bioaerosols; however, in public, most people use the masks as a precaution or from a sense of panic.", "Ethanol * 10 min submersion in 70% ethanol solution.", "Set the temperature at 121\u02daC with 1.06 kg cm \u22122 for 15 minutes.", "Experimental data were analyzed using SPSS software, version 17.0 (SPSS Inc., Chicago, IL). After linear regression between the \u0394p and flow rate was performed, the assumption of homogeneity of the regression slopes was carried out to confirm the effects of decontamination using analysis of covariance (ANACOVA) [16] . The statistics were considered significant at p<0.05." ] },{ "paper_id": "6c7ee2062b49226bfee08114f12cb1cd07509d9d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "[ 80] f. N-phenylureas AG-26 [76] FPR2 > FPR1 [78, 79] e.", "Pyridazin-3(2H)-one derivative 1 ", "[76] " ] },{ "paper_id": "6c982280e9ca5251ee74d0f2b84489a63a68c5bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. Survival curves were generated by the Kaplan-Meier method, and statistical analyses were performed using the log-rank test. The statistical significance was assessed by Student's t-tests. A P value < 0.05 was considered significant.", ". BAL was carried out as described previously 25, 49 . In Brief, tracheas of mice were cannulated with 1.2-mm diameter polyethylene catheters. Lungs were instilled with 1 mL of pre-warmed PBS containing 5 mM EDTA, followed by the retrieval of lavage fluid aliquots. Cells in the BAL fluid (BALF) were counted after red blood cell lysis and subjected to flow cytometric analysis. The supernatants of the BALF were subjected to multi cytokine/chemokine expression analysis and cytokine ELISA.", "Antigen-specific B cell responses. B cell-mediated humoral responses were measured as virion-specific immunoglobulin production by ELISA, as previously described 32 . Briefly, 96-well ELISA plates (Corning) were coated with ultrasonicated influenza virion (A/PR/8/34 strain) at 5 \u00d7 10 6 PFU/ mL in a carbonate buffer (pH 9.6), and incubated overnight at 4 \u00b0C. Plates were then washed with PBS containing 0.05% Tween 20 (Wako Pure Chemical Industries). Serum and BALF collected from mice at day 14 after the secondary infection were serially diluted with PBS/Tween 20 containing 5% skim milk, applied onto the virion-coated plates, and incubated for 2 h at room temperature. After washing, goat anti-mouse total IgG or IgA conjugated to horseradish peroxidase (Jackson Immunoresearch, Baltimore Pike, PA) was applied and incubated for 2 h at room temperature. After washing, the plates were stained with a TMB Substrate Set (Biolegend). The reaction was terminated with 1 M H 2 SO 4 (Wako Pure Chemical Industries) and the absorbance was measured." ] },{ "paper_id": "6c99164301444faa6eacb7f37d4e00944fbd167b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To prevent epidemics, it is needed to markedly improve public infrastructures, sanitation, and the health systems. For instance, the public and animal health surveillance systems must transform, so interventions occur within acceptable response times [1, 3, 4] .", "In Africa, 47 of the 54 countries (87%) have reported ErEIDs to the WHO since 1997 ( Table 1) . While several initiatives have been implemented globally to accelerate progress toward a safer world [4] , it is yet not clear whether African countries are ready and capable of handling the magnitude and threats associated with ErEIDs [4] . Here, we reviewed plausible reasons and drivers for the upsurge of ErEIDs in Africa and proffer some mitigating measures.", "Emerging and reemerging infectious diseases (ErEIDs) and antimicrobial resistant pathogens will continue to challenge global public and animal health and will need concerted efforts to combat.", "The creation of interdisciplinary educational programs aimed at local and regional decision-makers involved in disease diagnosis, dissemination, and control, is recommended. Such programs could develop and integrate: (i) local data on antimicrobial resistance, (ii) high-resolution, local geo-referenced data, and (iii) site-specific control measures that can be implemented within biologically valid critical response times." ] },{ "paper_id": "6c9c09c364d2fbd8d8f319029e60693060b6c756", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The software R (version 2.8.1) was employed to perform all tests. A p value less than 0.05 was considered significant.", "The difference between log 2 serum anti-CpHV-1 IgG1 and IgG2 titers (within the same vaccine group) was analyzed by the Students' t-test.", "The experiments were approved by the Italian Ministry of Health (Prot. n. 2174/07) and were carried out at the University of Bari according to the National Guide for Care and Use of Experimental Animals." ] },{ "paper_id": "6c9ce983d25f6c0727c9e4fedc01e84b046673a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Children enrolled in this investigation were part of a large prospective cohort assessing the causes of fever and respiratory disease in Tanzanian children [18] . Participants aged from two months to 10 years of age and presenting with an axillary temperature \u011b38\u02ddC were recruited in 1 urban and 1 rural hospital in Tanzania. Exclusion criteria were severe malnutrition and emergency signs according to World Health Organization criteria [19] .", "The procedures followed were in accordance with the ethical standards set by the Tanzanian and Swiss ethics committees and the Declaration of Helsinki as previously described [18] . The protocol was approved by the regional ethics committee in Basel, Switzerland, and by the national ethics committee in Tanzania. Written informed consent was obtained from the parents or guardians of each participant.", "Statistics were performed using SPSS software (IBM SPSS Statistics for Macintosh, Version 22.0., IBM Corp, Armonk, NY, USA). For continuous variables, Student's t-test or Mann-Whitney U-test were used to compare means or medians, depending on variable distribution. For categorical variables, chi-square test was used to compare groups." ] },{ "paper_id": "6c9d5c49fd907d0380d25e4df6cac63b00bce66b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Based on similarity to other alphaviruses, E2 mediates receptor attachment, while E1 is a class II viral fusion protein. A third glycoprotein, E3, is associated with mature virions in some alphaviruses [10] , but not others [11] , while 6K protein, a membrane-associated peptide created by cleavage of the poly-protein to release E2 and E1, is incorporated into particles at a low level [12, 13] .", "CHIKV mAb C9 variable chains were sequenced by MC Labs (South San Francisco, CA). For mammalian expression, C9 variable heavy (VH) and light (VL) chain cDNAs were synthesized by Genscript (Piscataway, NJ). The closest human germline signal sequences (ss), VH5 5a and VKIII A27, were used to ensure efficient processing and secretion. SS-VH cassettes were cloned into a pCAGGS mammalian expression vector as EcoRI-NheI fragments, upstream of the human IgG1 heavy chain constant region. SS-VL cassettes were cloned as EcoRI-BsiWI fragments upstream of the human kappa light chain constant region. CHIKV FAb CAP101A.E8 variable heavy and light chain cDNAs bearing human IL-2 signal sequences were synthesized by Genscript. IL-2ss-VH and IL-2ss-VL cassettes were cloned as MfeI-NheI and MfeI-BsiWI fragments upstream of their respective constant regions, as described above.", "Text S1 Supporting methods. (DOCX)" ] },{ "paper_id": "6ca67d203ed9f4870c85f2289d62ee3c498b5a13", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human metapneumovirus (HMPV) is a new member of the Paramyxoviridae that was first identified in children with respiratory diseases in Netherlands [1] . The clinical symptoms that are caused by HMPV infections in children are similar to those observed with respiratory syncytial virus (RSV) infection, ranging from upper respiratory tract infection to bronchiolitis and pneumonia. HMPV has become recognised as a major cause of lower respiratory infection in children [2, 3] ." ] },{ "paper_id": "6cabb3c8d1e85384320c6d9f7c927f4abc93fd93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Heterotopic cardiac transplantation was performed as previously described [50] . In this study, transplant surgery involved the transfer of fully MHC-mismatched hearts from BALB/c (H-2 d ) donors to C57BL/6 (H-2 b ) recipients. Heart beat of the grafts was monitored and evaluated daily by direct abdominal palpation to detect the state of cardiac health/rejection.", "Allograft samples were fixed in 4% paraformaldehyde. Serial sections (5 mm in thickness) were prepared using a microtome and stained with hematoxylin/eosin for the analysis of pathological changes.", "After deparaffin and rehydration, the paraffin-embedded heart sections (5 mm) were treated with 3% H 2 O 2 for 5 min. The nonspecific proteins were blocked with 5-10% goat serum for 10 min. For Beclin-1 staining, specimens were incubated with a rabbit antimouse Bcelin-1 Monoclonal antibody (1:200) at 4uC overnight, followed by incubation with a HRP conjugated goat anti-rabbit secondary antibody. The sections were finally incubated with DAB chromogenic substrate and counterstained with hematoxylin." ] },{ "paper_id": "6cabb9dc94d381013cd38885a5f0af29490c74f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6cad43bc914661354dc70f971c5517021eb3a823", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "General data are shown as percentages or means with 95% confidence intervals (CI). Fisher's exact test was used to study the association between the viruses and PICU admission. " ] },{ "paper_id": "6cbe44ed557bcc33f3373f4901da645d23e37901", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "including organizational command, emergency maneuver, injury and treatment, medicinal materials protection, classified and sent, epidemic prevention and anti-health preservation.", "Repeat published studies.", "Yearbooks, patents, conference abstracts, personal comments, letters, newspaper articles, work plans, and summaries. 3 .", "Evaluation results fall within the scope of low quality research after using the Ekman quality assessment tool [1] ." ] },{ "paper_id": "6cc00d24747f80a0e94f4dbdebcd9cc84b7e086f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleic acid was purified from clinical sample using the MagMAX Express-96 platform (Applied Biosystems) as previously described [19] . Respiratory samples underwent tandem multiplex real-time polymerase chain reaction (PCR) testing for respiratory viruses including Human Adenovirus species B-E; Human Bocavirus (HBoV); Human Coronaviruses OC43, 229E, HKU1 and NL63; Influenza viruses A and B; Parainfluenzaviruses 1-4;", "Additional requested diagnostic investigations included urine culture (36/151; 24%), blood culture (44/ 151; 29%) and cerebrospinal fluid (CSF) analysis (9/151; 6%). Urine and CSF cultures were negative in every case. Of four cases with positive blood cultures, three were considered contaminants; one was positive for Streptococcus pneumoniae. This case also had multiple viruses identified on per-nasal sample (Adenovirus, HBoV, HHV6, HMPV, Enterovirus A-16, Rhinovirus A).", "Neurological sequelae rarely result from either simple or complex febrile seizures [1, 2] ." ] },{ "paper_id": "6cc30d377f0bd9004378ef98ef2b7c145a79711e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Genomic DNA was prepared from live bacteria on agar slants to maximize the yield of extremely high-molecular weight DNA. Optical maps were generated by digestion with NcoI of DNA arrayed linearly on glass slides and the resulting maps were aligned and compared with the MapSolver software package (OpGen, Inc., Gaithersburg MD).", "Catalase activitywas assayed by spotting drops of hydrogen peroxide (3%) onto isolated colonies on LB agar plates. Colonies were monitored for bubble formation, signifying the release of water and oxygen. A colony was considered to be catalase positive by observation of bubbles.", "Spores were germinated by plating on LB media at 37uC. Plates were examined by stereomicroscopy using indirect lighting and imaged usinga Nikon SMZ1500 with a total magnification of 166. Colonies exhibiting distinct morphologies were repeatedly streaked to confirm stability of the phenotype." ] },{ "paper_id": "6cc5fe5c208412e13970cc93efbd1e68d1fe6459", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical data, including the demographic data (age and sex), and the vital symptoms and signs at admission, were considered. Statistical comparisons were made with Fisher's two-tailed exact test and the Mann-Whitney U test. All analyses were performed with SPSS 19.0 software.", "The sequences determined in this study were submitted to GenBank under accession numbers KY774318, KY774319, KY774320 and KY774321." ] },{ "paper_id": "6ccce7b6fb9a213959f56ae465bb75ad130d6c9a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In summary, in this systematic review and meta-analysis, MRI as a diagnostic method is associated with higher accuracy for detecting ANFH. More studies and randomized controlled trails with high-quality and large samples are warranted for further evaluation. Ethics approval and consent to participate Not applicable.", "The studies that met the following criteria were excluded in our review: (1) repeat publications, or shared content and results; (2) case report, theoretical research, conference report, systematic review, meta-analysis, expert comment, and economic analysis; (3) the outcomes were not relevant; and (4) two or more results of the TP, FP, FN, and TN were zero.", "A total of 2092 articles were searched by the indexes. After screening the titles and abstracts, 1986 articles were excluded, leaving 106 articles for further selection. During full-text screening, 63 articles were excluded due to the following criteria: unqualified outcomes [7] , theoretical research or review [8] , and has non clinical outcome [9] . At last, 43 studies with 3133 hips were involved in the final meta-analysis. The selection process was presented in Fig. 1 . The main characteristics of the included studies were summarized in Table 1 . The basic information included number of hips, age, and gender." ] },{ "paper_id": "6cd8cfb4dd10db30a8bbd630da2e8c15ee4e4956", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Porcine cytomegalovirus (PCMV) is an immunosuppressive virus that mainly inhibits T-lymphocyte and macrophage immune functions; it has significantly damaged the farming industry. Although recent studies have shown that miRNAs play important roles in immune responses, the regulatory mechanisms of miRNAs during immunosuppressive virus infection remain unclear.", "Porcine cytomegalovirus (PCMV) belongs to the genus Cytomegalovirus, subfamily Betaherpesvirinae and family Herpesvirus. It has a 128,367-base-pair (bp) doublestranded DNA genome containing 79 open reading frames. This virus is distributed all over the world, and it mainly spreads through the respiratory tract or placenta [1] ." ] },{ "paper_id": "6ce3549c42e7ee6246de3eac9ac764f65393ecf8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6ce5b9aac3338153eaf845252d28c3f06a0fb014", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 Dataset. FASTA file. DNA sequence alignment of herpesvirus glycoprotein B sequences used for phylogenetic analysis in ", "Nucleotide sequences were trimmed and aligned against each other and with available sequences in GenBank (GenBank, National Center for Biotechnology Information. http://www. ncbi.nlm.nih.gov) using the Geneious alignment tool (Geneious Pro 5.1.7 software; Biomatters LTD. Auckland, NZ) and Bayesian analysis was performed (MrBayes 3.1 plugin in Geneious Pro using gamma distributed rate variation using a general HKY85 substitution model [21] )." ] },{ "paper_id": "6cef5ad67e84f17e96de7c2d9af64487a4637cb9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two viruses known to also cause febrile illness or skin rash illness were tested for analytical specificity. Zika virus (MR766, PRVABC59 strain) were from the American Type Culture Collection, Manassas, VA, USA. Chikungunya virus (CK9500004 strain) was from the Taiwan Center of Disease Control, Taipei, Taiwan.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "6cfa11e4308af9ef83f7800b45f011139915cd43", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Only in 2016, in the framework of COST Action FA1207, a coherent and common IBV genotype classification was proposed [6], grouping the identified strains in 6 genotypes and 32 lineages.", "The final HVR12 dataset included 76 sequences collected from 12 countries (S1 Table) . Tem-pEst analysis demonstrated the presence of a significant temporal structure, being the correlation between genetic distances and sampling dates equal to 0.52 (R 2 = 0.27; slope 2.70x10 -4 ).", "tMRCA of GI-16 genotype, averaged over all runs, was estimated in 1905. 23 (1860 23 ( .76-1934 , and the results were proven highly consistent among the different tested datasets (Fig 1) . Similarly, repeatable results were obtained for the substitution rate analysis (Fig 1) , which was estimated to be 1.89x10 -3 (1.42x10 -3 -2.45x10 -3 ).", "The periodic emergence of new genotypes has been characterizing the epidemiology of IBV, continuously raising the bar for the implementation of effective control strategies. Although it has been accepted that the high evolutionary and recombination rates are the main drivers of IBV variability [3] , the actual genesis of new genotypes remains elusive. In fact, these emerging variants are typically peculiar from a genetic perspective, which is incompatible with the recent differentiation from already known genotypes. Actually, the estimates of tMRCA of circulating lineages often largely backdate their first identification [23] . These evidences allow to speculate that many of the so called \"emerging\" genotypes could actually be quite ancient genetic groups that have not been correctly identified or classified yet." ] },{ "paper_id": "6cfcbd2a102a3666d0d168f9bdaba0b2107fc8bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In June 2002 we conducted a Round-Robin test in analogy to the established quality control procedure of laboratories and other testing units [17] . Round-Robin tests are mainly used in proficiency tests in order to determine laboratory performance by means of comparing tests on identical items by two or more laboratories in accordance with predetermined conditions [18] .", "\u2022 Epidemiological link to another laboratory-diagnosed human infection through \u274d Person-to-person transmission OR \u274d Same source of exposure (e.g. animal contact*, food*) \u2022 Consumption of food (including drinking water), for which Salmonella spp. was laboratory-detected in non-consumed food.", "\u2022 In some case definitions detection of the pathogen is only accepted if the detection was done in specific materials (normally sterile material such as blood for detecting N. meningitidis). This limitation was frequently neglected.", "\u2022 We rephrased the definitions in a way that for serologic confirmation the necessity for two samples is clearly apparent at the beginning of the phrase." ] },{ "paper_id": "6d002db4a643cb5525e9a3b80954b75973706d6b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GT \"Do you agree or disagree with local leaders?\"", "(1) Strongly disagree, (2) Disagree, (3) It does not matter, (4) Agree, (5) Strongly agree \"Do you agree or disagree that local government works well?\"", "(1) Strongly disagree, (2) Disagree, (1) Strongly disagree, (2) Disagree, " ] },{ "paper_id": "6d021f582f338ea0a0e9a61e6a4e76df73287b1d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bronchoalveolar lavage (BAL) fluid samples were obtained after intratracheal injection of 3 \u00d7 1 ml of PBS supplemented with 5% fetal calf serum (FCS). Lungs were perfused with PBS, excised and finely minced then digested in a solution of RPMI 1640 medium (Gibco) containing 1 mg/ml collagenase VIII (Sigma-Aldrich) and 80 \u00b5g/ml DNase I (Sigma-Aldrich) for 20 min at 37 \u2022 C. After washes, red blood cells were removed using a lysis solution (Pharmlyse, BD Bioscience). Lung cell homogenates were then suspended in a 20% percoll gradient and centrifuged at 2,000 rpm without brake at room temperature for 10 min. The cell pellets were washed with PBS supplemented with 2% FCS and cells were filtrated before antibody labeling. BAL and lung cells were stained with anti-CD45-allophycocyanin-cyanine 7 (clone 30F11), anti-CD11b-Brilliant Violet 785 (clone M1.70), anti-SiglecF-AlexaFluor 647 (clone E50-2440), anti-Ly6C-peridinin chlorophyll protein-cyanine 5.5 (clone HK1.4), anti-Ly6Gphycoerythrin (clone 1A8), anti-CD11c-phycoerythrin-cyanine 7 (clone HL3), and CCR2-Brillant Violet 421 (clone SA203G11) antibodies. Dead cells were excluded from the analysis using propidium iodide. The antibodies were purchased from BD Biosciences (San Jose, CA) or BioLegend (San Diego, CA). Data ", "were collected on a BD LSR Fortessa and analyzed with the BD FACSDiva software.", "The results were described as the mean \u00b1 standard error of the mean (SEM) or the median (range), as indicated. Intergroup differences were analyzed using the Mann-Whitney test and the log rank test. All analyses were performed with Prism software (version 5.0, GraphPad Software, La Jolla, CA). The threshold for statistical significance was set to p < 0.05." ] },{ "paper_id": "6d06153cd1a8bff48ea762c95c01acc5a53453f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Integration of systemic immune signals by CNS-resident cells may occur via coordinated signaling through the autonomic nervous system and the hypothalamicpituitary-adrenal (HPA) axis [13] , trafficking and effector functions of immune cells within the meninges [14] , and gut microbe-mediated mechanisms [15] . Each of these systems undergoes overlapping periods of development and refinement during the first few weeks following birth. Therefore, immune activation during these critical periods of development can have broad implications on neurodevelopment and neural function later in life.", "On P12 or P15, animals were deeply anesthetized with 4% isoflurane in oxygen. Blood samples were then collected via cardiac puncture followed immediately by transcardial perfusion with sterile phosphate-buffered saline (PBS). Blood was centrifuged (12,000\u00d7g, 4\u00b0C, 10 min) to obtain serum, which was then stored at \u2212 80\u00b0C. Whole brains of animals randomly chosen for cytokine measurement analyses were quickly removed following transcardial PBS perfusion and, using a dissection scope and sterile surgical equipment, microdissected in PBS on ice to isolate the hippocampi, cortices, and cerebella. All tissues were snap-frozen in liquid nitrogen and stored at \u2212 80\u00b0C until further assayed. Animals randomly chosen for immunohistochemical analyses were anesthetized with 4% isoflurane in oxygen and subsequently perfused transcardially with 100-ml cold PBS at a rate of 15 ml/ min using a Masterflex peristaltic pump (Cole Parmer, Vernon Hills, IL) followed by 100 ml of cold 4% paraformaldehyde (PFA) in PBS. Fixed tissues were removed, post-fixed in 4% PFA overnight, and then stored in 30% sucrose in PBS at 4\u00b0C for 48 h. Fixed brains were snapfrozen in O.C.T. Compound (Sakura Finetek, Torrance, CA) and then sectioned into 10-\u03bcm-thick sagittal sections. Sections were stored at \u2212 80\u00b0C until further processed for immunohistochemical analyses." ] },{ "paper_id": "6d073fc71e9b58f7d85ab4ae64aaeadf10d56ae4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following immunoprecipitation, the combined samples were subjected to SDS-PAGE electrophoresis on a precast gel, and extracted as a single band for in-gel trypsinisation. The resulting peptides were fractionated using an Ultimate 3000 nanoHPLC system in line with an Orbitrap Fusion Tribrid mass spectrometer (Thermo Scientific). In brief, peptides in 1% (vol/vol) formic acid were injected onto an Acclaim PepMap C18 nano-trap column (Thermo Scientific). After washing with 0.5% (vol/vol) acetonitrile 0.1% (vol/vol) formic acid, peptides were resolved on a 250 mm \u00d7 75 m Acclaim PepMap C18 reverse phase analytical column (Thermo Scientific) over a 150 min organic gradient, using seven gradient segments (1-6% solvent B over 1 min, 6-15% B over 58 min, 15-32% B over 58 min, 32-40% B over 5 min, 40-90% B over 1 min, held at 90% B for 6 min and then reduced to 1% B over 1 min) with a flow rate of 300 nl min \u22121 . Solvent A was 0.1% formic acid and Solvent B was aqueous 80% acetonitrile in 0.1% formic acid. Peptides were ionized by nano-electrospray ionization at 2.0 kV using a stainless steel emitter with an internal diameter of 30 m (Thermo Scientific) and a capillary temperature of 275 \u2022 C.", "All complexes were assembled in SEC buffer.", "All spectra were acquired using an Orbitrap Fusion Tribrid mass spectrometer controlled by Xcalibur 2.1 software (Thermo Scientific) and operated in data-dependent acquisition mode. FTMS1 spectra were collected at a resolution of 120 000 over a scan range (m/z) of 350-1550, with an automatic gain control (AGC) target of 300 000 and a max injection time of 100 ms. Precursors were filtered using an Intensity Range of 1E4 to 1E20 and according to charge state (to include charge states 2-6) and with monoisotopic precursor selection. Previously interrogated precursors were excluded using a dynamic window (40 s \u00b110 ppm). The MS2 precursors were isolated with a quadrupole mass filter set to a width of 1.4 m/z. ITMS2 spectra were collected with an AGC target of 20 000, max injection time of 40 ms and CID collision energy of 35%.", "The host innate immune response provides a first line defence against invading pathogens. Following infection, pathogen recognition receptors (PRRs) sense non-self, pathogen-associated molecular patterns (PAMPs) trigger-ing signaling pathways that activate an immune response (reviewed in 1). Detection of viral signatures by PRRs, such as RIG I-like receptor sensing of double stranded RNA, induces production of Type I and Type III interferon (IFN). Through binding of cell surface IFN receptors and subsequent activation of the JAK-STAT pathway, IFN activates the transcription of hundreds of IFN-stimulated genes (ISGs) (2), many with known antiviral properties, priming neighbouring cells to restrict viral spread." ] },{ "paper_id": "6d077aec25d3730a6037bf89f1fb73286846fb64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6d08d5d8add16122735dcfa90a4c36f8d2a348ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Defensins' bactericidal effect can be limited by high salt concentration of local environment where they encounter with the pathogens [18, 19] . Also, the antimicrobial action appears to be regulated by the redox response, as -defensin-1 become more potent after reduction of disulfide bridges by thioredoxin or a reducing environment [20, 21] .", "The classic mechanism of defensins' bactericidal effect is the \"pore formation\" theory. These positively charged antimicrobial peptides target negatively charged bacterial membrane components, such as lipopolysaccharides, teichoic acids, or phospholipids. Then they form transmembrane pores, disrupt cell integrity, and lead to bacteria lysis [10, 11] . Recently, another mechanism has been reported that defensins kill bacteria by inhibiting the synthesis of bacterial cell wall through interaction with certain precursors such as lipid II [17] .", "Defensins are also reported to have modulating effects on both innate and adaptive immune response. It is well known that HNP1-3 participate in the host immune defense via multiple mechanisms, including enhancing macrophage phagocytosis, facilitating neutrophil recruitment, modulating complement activation, and chemoattracting immature T cells and dendritic cells [12, 22] .", "The -defensins, which have a unique macrocyclic structure, are isolated from leukocytes from some species of monkey and have not been detected in humans [14] . They are also reported to have antimicrobial activity against a spectrum of pathogens including E. coli, S. aureus, and C. albicans [15] . Also, they are found to have protective effect in a mouse model from a lethal pulmonary infection by a mouse adapted strain of SARS-coronavirus [16] ." ] },{ "paper_id": "6d12d0dd222c803e8a4e4f3e516d5feecd103358", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the MD simulations (NAMD_2.8b1_Linux-x86_64-CUDA) were performed on an ubuntu 10.04-based workstation, and the benchmark maintained 1 ns/day with the maximal system.", "Glycosylation exerts a significant influence on envelope glycoproteins. To perform the MD simulation for glycoprotein, the complete coordinate file is necessary. Unfortunately, complete larger glycans are too flexible to yield sufficient electron density; consequently, their 3D structures cannot be derived using X-ray crystallography. Many oligosaccharide NOEs (Nuclear Overhouser Effects) also cannot be resolved and are difficult to assign by NMR. Additionally, there are often too few inter-residue NOEs to render an unambiguous 3D structure determination possible [51] . Given this situation, glycosylated HAs must be reconstructed manually.", "Author Contributions", "A dataset of the protein sequences for H5N1 HA was retrieved from the National Center for Biotechnology Information (NCBI) flu database (http://www.ncbi.nlm.nih.gov/genomes/FLU) accessed in Sep. 2011 [28] , containing approximately 330 human reports in 3602 sequences. An alignment of whole sequences was performed by ClustalW 2.0 (File S1) [29] . [30] . The internal branching probabilities were determined by bootstrap analysis with 1,000 replicates." ] },{ "paper_id": "6d1a2055895ffdcdf57aabcaf436f176b1650c50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral RNA was extracted from 200 ml of sample using QIAamp MinElute Virus Spin kits (Qiagen, Germany). cDNA was synthesized with AMV reverse transcriptase and random hexamer primers (Promega, USA) as described previously [19, 23, 25] .", "Statistical analysis was performed using the predictive analysis software (PASW) statistics 18 package with X 2 -test and Fisher's exact test.", "All aspects of the study were performed in accordance with the national ethics regulations and approved by the Institutional Review Boards of the Centre for Disease Control and Prevention of China, as well as the Ethics Committee of Peking Union Medical College Hospital. Participants were received \"Written Informed Consent\" on the study's purpose and of their right to keep information confidential. Written consent was obtained from all participants or their guardians." ] },{ "paper_id": "6d1b4e1200c1da4dff5048bdff36805e28511154", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Are there differences in regulation by the canine and feline microbiome?", "Are there differences between the canine and feline immune systems?", "Primary inherited immunodeficiency diseases markedly differ between dogs and cats. In the dog, there is a spectrum of some 30 distinct breed-related putative immunodeficiency disorders, although only four of these have been characterized as to the genetic mutation responsible for the disease (i.e. the canine leucocyte adhesion deficiency, canine severe combined immunodeficiency [X-linked and not], the trapped neutrophil syndrome and the grey collie syndrome) [39, 59] . In distinct contrast, only three primary immunodeficiency diseases are reported in the cat: Pelger-Huet anomaly, Chediak-Higashi syndrome and a genetic mutation resulting in athymic and hairless Birman kittens [39, 60] ." ] },{ "paper_id": "6d20ab75d7394461e9acd16899bd55902177d8fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The HAstV1 isolate was provided by Dr. Mitsuaki Oseto (Ehime Hygiene Environmental Institute, Japan). Caco-2 cells (from Dr. Naomi Sakon, Osaka Prefectural Institute of Public Health, originally given by Dr. Albert Z. Kapikian) were maintained in a culture medium (EMEM+) consisting of minimum essential medium with Eagle's modification (EMEM) (catalog no. M4655; Sigma-Aldrich, St. Louis, MO, USA) supplemented with 1 mM sodium pyruvate, non-essential amino acids (Invitrogen, Green Island, NY, USA), and 10% fetal bovine serum.", "Genistein, U0126, JNK inhibitor II, H-89, Akt inhibitor V (triciribine), and Y-27632 were purchased from Merck (Whitehouse Station, NJ, USA). Wortmannin and staurosporine were from Sigma-Aldrich. SB203580 and LY294002 were obtained from Promega (Fitchburg, WI, USA). NSC23766 and MK-2206 were from Santa Cruz Biotechnology (Santa Cruz, CA, USA) and Selleckchem (Houston, TX, USA), respectively. All drugs were solubilized in dimethyl sulfoxide (DMSO). Initial drug concentrations were selected after consulting the following references: staurosporine [41] , genistein [42] , U0126 [19, 43] , SB205830 [19] , JNK inhibitor II [44] , LY294003 [43] , wortmannin [45] , triciribine [46] , MK-2206 [47] , NSC23766", "Another important group of cellular signaling pathways are those of the mitogen-activated protein kinases (MAPKs), which include extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38, and c-Jun N-terminal kinases (JNK). In the ERK1/2 pathway, signal is transduced by activated receptor tyrosine kinases, the small G protein Ras, Raf, and MAPK/ERK kinase1/2 (MEK1/2), which then activate ERK1/2 through phosphorylation. Activated ERK1/2 is known to regulate cell survival, proliferation, and differentiation [18] ." ] },{ "paper_id": "6d2f0e8c7dd69338395c49a3e3aab7c4239766c2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Co-administration of a NEI enhances serum IgG1 and IgG2b responses to a sublingual vaccine.", "Animals. Female C57BL/6J mice were obtained from The Jackson Laboratory (Bar Harbor, ME). Mice were maintained in a specific pathogen-free environment and used at 10 \u00b1 2wks of age. All the experiments were approved by and performed in accordance with the guidelines of NIH and The Ohio State University IACUC.", "Published: xx xx xxxx OPEN www.nature.com/scientificreports/" ] },{ "paper_id": "6d304a9fd7873449676f289294df478dcbc7b53d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reads were quality-trimmed with trimmomatic (Version 0.36) and mapped to their respective host genomes (alpaca: BioProject PRJNA30567, assembly Vicugna_pacos-2.0.1, deer: BioProject PRJNA324173, assembly CerEla1.0, goat: BioProject PRJNA340281, assembly ARS1, sheep: BioProject PRJNA179263, assembly Oar_v4.0) using STAR (Version 2.5.3a). Quality-trimmed and unmapped reads were assembled via SPAdes (Version 3.11.1).", "Note:", "Data are available at NCBI Genbank under accession numbers MK404645. ", "Simea Werder performed the experiments, contributed reagents/materials/analysis tools, approved the final draft. C\u00e9line L. Boujon performed the experiments, contributed reagents/materials/analysis tools, authored or reviewed drafts of the paper, approved the final draft. Torsten Seuberlich conceived and designed the experiments, contributed reagents/ materials/analysis tools, prepared figures and/or tables, authored or reviewed drafts of the paper, approved the final draft." ] },{ "paper_id": "6d3e2a9b44f902aba943050ec1dbd4cd0b85309c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Authors' contributions SR performed DNA extraction. MK performed qPCR and pyrosequencing. MK, EP, JKJ and JM performed pyrosequencing data analysis. SG, MK and SV performed the respiratory virus multiplex PCR. MK, JM and GBu performed statistical analysis. GHA and GR contributed to data collection. GHA conceived and designed the study. JM, GR, SV, EC and GBa contributed to design. MK, GHA and JM wrote the manuscript. All authors read and approved the final manuscript. ", "One sample (A1) was not included in this screening as having not enough DNA. From the remaining 19 samples, viral RNA and DNA were extracted using the automated NUCLISENS \u00ae easyMAG \u2122 (bioM\u00e9rieux, Marcy l'Etoile, France) after a treatment with 25 \u00b5l of proteinase K (10 mg/ml) during 2 h at 56 \u00b0C. The nucleic acids were eluted in 50 \u00b5l and conserved at \u221280 \u00b0C. The Res-piFinder \u00ae SMART 22 FAST (PathoFinder, Maastricht, The Netherlands) was used according to the manufacturer's instructions and then, qPCR was performed in a GeneAmp \u00ae PCR System 9700 (Applied Biosystems, Courtaboeuf, France ", "In the light of these new findings, the present study investigated whether early P. aeruginosa colonization in CF patients was accompanied by significant changes in respiratory microbiota in terms of community structure and relative abundance, with the challenge of identifying potential biomarkers or predictive factors of P. aeruginosa implantation.", "The present study allowed identifying bacterial species, including anaerobic bacteria, the role of which may be underestimated and which may be indirectly implicated in P. aeruginosa lung infection pathogenesis. In addition, this study demonstrated the impact of P. aeruginosa status on the composition of the CF lung microbiota. It was confirmed that core OTUs including anaerobes, were a common denominator in CF patients." ] },{ "paper_id": "6d480c492ee63a4f78a6f6aa78260d79d3e281bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Asian lineage Z16006 (GenBank no. KU955589.1) was obtained from the Institute of Microbiology in the Center for Disease Control and Prevention of Guangdong Province, China. It was isolated on 16 February 2016 in China from the serum of a patient who travelled to Fiji and Samoa where it happened to be the epidemic country of ZIKV, and its related articles were published in Chinese journals [47, 48] . ZIKV strain Z16006 with a single round of amplification on mouse brain cells and three rounds of amplification on C6/36 cells, was grown to 5 \u00d7 10 6 TCID50/mL (50% tissue culture infective dose).", "Following infection with 20 \u00b5L of the inoculum, various organs were harvested, including the brains, livers, spleens, kidneys, and testes, during the clinical course. Blood was collected every day post-infection for viremia detection. Organ samples were washed with PBS thrice, and collected in 1.5-mL Eppendorf tubes. Tubes were weighed and organ weights were determined by subtracting the tube weight. After the organ was ground into homogenate by an electric blender, viral RNA was extracted from 140 \u00b5L of tissue homogenate using the QIAamp \u00ae (Qiagen, Hilden, Germany) Viral RNA Mini Kit and was quantified by real-time RT-PCR using the LightCycler480 \u00ae Instrument (Roche Diagnostics, Roche Instrument Center AG, Rotkreuz, Switzerland). Primers ZIKV/F (5 -CVGACATGGCTTCGGACAGY-3 ), ZIKV/R (5 -CCCARCCTCTGTCCACYAAYG-3 ) and probe (5 -FAM-AGGTGAAGCCTACCTTGACAAGCARTCA-BHQ1-3 ) were designed in our own laboratory.", "Averages of daily weight data were analysed by independent sample t-tests with \u03b1 = 0.05 each day and each group." ] },{ "paper_id": "6d4c934e5babea34af1b80d784ce9422735c9dc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It is time to shake up public health surveillance. New technologies for sequencing, aided by friction-free approaches to data sharing, could have an impact on public health efforts.", "Such rapid results are crucial if the intention is to intervene in an outbreak rather than simply document it in retrospect. For such applications, the useful halflife of genomic information for epidemiology, while there is a chance to influence control practices, can be measured in days or weeks.", "Controlling potentially lethal pathogens requires timely, comprehensive surveillance systems. These systems currently rely on case counting and simple genotyping techniques, but surveillance could be markedly improved through genomics. Pathogen sequencing has commonly * Correspondence: n.j.loman@bham.ac.uk 2 Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, UK Full list of author information is available at the end of the article been used for the identification of isolates and their classification into 'genotypes' (genetic lineages) that can be associated with host species or geographical regions. More recently, however, genome sequencing has emerged as a crucial tool in our real-time response to outbreaks of infectious disease." ] },{ "paper_id": "6d5600b0c8725f08c005efaaf90fe3668aef1c65", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mann-Whitney U-test was applied to statistically analyze clinical scores. The difference in arthritis incidence between experimental groups was checked with Fisher's exact probability test. One-way ANOVA was performed to analyze ELISA and flow cytometry results. Data were considered statistically significant, if p-value was < 0.05.", "To measure inflammatory cells in the arthritic joints, isolated limb joints were digested with 2 mg/ml collagenase (Clostridium histolyticum,Type IV; Sigma-Aldrich, St. Louis, MO) for 30 min at 37 \u2022 C, and cell suspensions passed through a 70 \u00b5m cell strainer similar to that previously described (40, 62) . Leukocytes were stained and analyzed by forward and side-scatter plots for Ly-6G + Ly-6C + CD11b + neutrophils.", "RA is a chronic, systemic autoimmune disorder affecting millions of patients in the US. Treatment of this progressive, degenerative disease demands constant use of anti-inflammatory drugs and often immunosuppressive treatments that increase susceptibility to infections and neoplasia (4, 15, 16) . Instead, intervention strategies that focus on redirecting or reeducating T cell responses to produce tolerance instead of inflammation have the potential of being a superior treatment for RA.", "MM, IK, and DP: conceptualization. MM, IK, CH, and DP: formal analysis, investigation, methodology, validation, visualization, and writing. DP: funding acquisition. All authors approved the final version to be published and agreed to the content and all aspects of the work ensuring the accuracy or integrity of the work are appropriately investigated and presented." ] },{ "paper_id": "6d5c9139359f0be11be696bec88268a4f1cf7131", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Significance was assessed for each phenotype using 500 permutations. QTL regions were denoted using a 1.5 LOD-drop method.", "Significance in these situations was assessed using a total of 250 permutations.", "KEYWORDS", "This work was funded in part by National Institutes of Health grants U19 AI 100625 (R.S.B.), K99AG049092 (V.D.M.), and F30 MH 103925 (A.P.M.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." ] },{ "paper_id": "6d6e142b8ccce1104fecb15ccc6b62433552a013", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Loop-mediated isothermal amplification (LAMP) is a DNA amplification technique with high specificity, efficiency, and speed, performed under isothermal conditions [1] . We are using LAMP to perform highly sensitive and specific detection of blood-borne pathogens with a new point-of-care instrument that is in development, targeting pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pneumoniae. This approach has the potential to operate at significantly lower cost than TaqMan PCR detection because it can be performed with less expensive materials and equipment [2, 3] .", "We suggest using the LAVA wrapper SLAVA (Serial-LAVA) for individual sequences and highly conserved MSAs over 10 kbp. SLAVA splits the MSA into sections, executes LAVA for each individual section, and combines the results into a single set of non-identical signatures. Running a series of smaller chunks through SLAVA is likely to result in more optimal signature combinations, because each sub-analysis can identify more primer candidate regions.", "When designing LAMP signatures, we found there is a general pattern we fell into of relaxing design parameters to identify signatures for difficult to target sequences. On average, the order which we adjusted parameters were to increase melting temperature range, decrease primer minimum length, and finally to increase signature max length." ] },{ "paper_id": "6d7084462a7462edc93ce2d350bf6dd08c232ef4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Peptide cytotoxicity was measured using the TACS\u2122 MTT cell proliferation assay (R&D systems, Minneapolis, MN) according to the manufacturer's instructions.", "Enveloped viruses utilize membrane-bound fusion proteins to mediate attachment and entry into specific target host cells. During the virion assembly process, newly synthesized envelope proteins are targeted to the endoplasmic reticulum and golgi apparatus where initial folding and post-transcriptional processing occurs, including multimerization, glycosylation, and proteolysis. This initial folding and processing is required to achieve a confor-mation where the proteins are held in a metastable state prior to virion release. Post virion release, the multimeric envelope proteins are poised to undergo structural rearrangement leading to fusion of the virion and the new target cell lipid bilayer membranes. Depending on the virus system, the rearrangement trigger can take the form of specific receptor binding, multiple receptor binding, decreased pH following receptor mediated endocytosis, or a combination of triggers.", "Dose-response curves for WN53, WN83 and DN59 peptides " ] },{ "paper_id": "6d756b7df1778be58daa0e30caefc968807d6a80", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Evolution of chromosome structures in Brassicaceae has been traced and established through comparative chromosome painting techniques using BAC probes of the A. thaliana genome 4, 30 . Using these techniques, Lysak and (Fig. 1a) . Six tribes (Calepineae, Coluteocarpeae, Conringieae, Eutremeae, Isatideae, and Sisymbrieae) of expanded lineage II were found to derive from a common ancestor with the Proto-Calepineae Karyotype (PCK; n = 7). Among these tribes, three (Eutremeae, Isatideae, and Sisymbrieae) displayed an additional whole-arm translocation in the second and seventh chromosomes (translocation PCK, tPCK; n = 7) 32-34 (Fig. 1a) . ACK and PCK shared five similar chromosomes. Thus, they might descend from a common ancestor; alternatively, PCK may have evolved from ACK.", "The PacBio long reads and Illumina short reads were uploaded to the NCBI SRA database under BioProject PRJNA549758. The final chromosome-scale genome assembly was submitted to the NCBI with accession number VHIU00000000. The genome fasta and gff3 files were uploaded to Figshare." ] },{ "paper_id": "6d76fbc0763d467e9109feefe43e4e52113b78f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the Medical Ethics Committee of the Instituto de Salud Carlos III (CEI PI 15_2012) and informed written consent was obtained from all participants.", "Virus identification by target-agnostic highthroughput sequencing analysis", "Several specimens among the \"Case\" group contained more than one virus (Table 4 ). Among these co-infections, HRSV was detected with either HPIV, EV or HRV, and HCoV was detected along with HRV (Table 4) . No co-infections were detected in the \"Control\" group." ] },{ "paper_id": "6d86f444589890a4657acab7888a38806287387e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data analysis was conducted as described in a previously published methodology article [19] : Raw Cq values were exported from 'Fluidigm Real-Time PCR Analysis' software version 3.0.2 to Microsoft Excel. To even out possible variation between the AA48.48 runs, all Cq values were normalized to an Interplate Calibrator. Next, Cq values from each sample were normalized to their respective \"Domain Bacteria B V4-V5\" primer set, thereby calculating the relative quantification.", "The models were validated through graphical procedures. A p-value of less than 0.05 was considered significant. Statistical analyses were performed in R [22] .", "Phylum Firmicutes, class Bacilli, genus Lactobacillus, and genus Streptococcus" ] },{ "paper_id": "6d8c165aff79de76522a52da6616f6595fbc1976", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BCoV belongs to the order Nidovirales, family Coronaviridae, sub-family Coronavirinae within the genus Betacoronavirus. BCoV consists of a non-segmented, single-stranded, positive-sense RNA (ssRNA) (Wentworth & Holmes 2007) .", "The Kakegawa (Akashi et al. 1980 ) strain of coronavirus which propagates in HmLu-1 (hamster lung) cells with a hemagglutination titre of 256 and DEPCtreated water was used as positive and negative controls respectively.", "Microsoft \u00e2 Office Excel 2010 was used for identity mean and standard deviation calculations.", "These results emphasise the importance of molecular characterisation of BCoV, enabling a more detailed understanding of the dynamics and pattern of developmentelements which are fundamental when planning epidemiological action." ] },{ "paper_id": "6da13d90743ba52bded6ed06e214541ba19d5078", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bats harbour a plethora of CoV species, some of which are thought to be the initial source of recent spillover events such as SARS, MERS and PEDV [3, 4] . However, the recent discovery of new", "The novel UKRn1-5, UKMa1, UKMa2&UKMg1, UKSa1/UKMa3 and PLMg1 sequences were 97.6%, 83.8%, 84.6%, 78.4% and 81.8% similar and 98.6%, 96.2%, 96.2%, 91.9% and 94.3% similar to the corresponding region of the Lucheng Rn CoV, at the nucleotide and amino acid level, respectively ( Table 2) .", "This study has shown the first evidence of alphacoronaviruses present in European rodents and shrews demonstrating that rodent and shrew coronaviruses sampled to date, from worldwide locations, form a discreet clade within this genus. CoV infection of rodents and shrews appears both geographically and temporally widespread and therefore these mammals may pose a threat for cross-species transmission to humans and/or other animals. Further characterization is required for better understanding of their genetic diversity, host range and cellular receptors." ] },{ "paper_id": "6da3f66c681b4b60ce1f6f246340517b79b67137", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Differential expression of chIFITMs in chicken tissues. We assessed the tissue-specific gene expression pattern in chickens using a panel of RNA extracted from tissues from 3-week-old A549s transfected with huIFITM proteins 1 to 3 (D, E, and F) in the absence of infection. Panels show nuclei stained with DAPI (4=,6-diamidino-2-phenylindole) (blue), endosomes marked with an antibody against Lamp1 (green), IFITM protein marked by an antibody against the HA tag (red), and a merged image.", "Expression of IFITM proteins in different chicken tissues. Tissues were removed from 3-week-old specific pathogen-free (SPF) Rhode Island Red (RIR) chickens, specifically thymus, spleen, bursa of Fabricius, cecal tonsil, gastrointestinal tract, trachea, bone marrow, brain, muscle, heart, liver, kidney, lung, and skin. RNA was DNase treated, and reverse transcription was carried out (SuperScript III reverse transcriptase; Life Technologies). The cDNA from each tissue was amplified by PCR using the following primer sets: chIFITM1 (F=-AGCACACCAGCATCAACA TGC, R=-CTACGAAGTCCTTGGCGATGA), chIFITM2 (F=-AGGTGAG CATCCCGCTGCAC, R=-ACCGCCGAGCACCTTCCAGG), chIFITM3 (F=-GGAGTCCCACCGTATGAAC, R=-GGCGTCTCCACCGTCACCA), and chicken_GAPDH (glyceraldehyde-3-phosphate dehydrogenase) (F=-ACTGTCAAGGCTGAGAACGG, R=-GCTGAGGGAGCTGAGATGA)." ] },{ "paper_id": "6dab259f3cac146d0cadf07d4085a8ecc4069bed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6dab7c67db93625257a0e3aa8a8d88f22573d1fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "were examined microscopically (400\u00d7 magnification) for Eimeria species.", "All statistical analyses (normality test and Wilcoxon signed-rank test) were performed using SPSS Statistics 25 for Windows (IBM, Armonk, NY, USA). All graphical procedures were performed using GraphPad Prism 6 (GraphPad, Software, San Diego, CA, USA).", "Fecal samples were analyzed for the presence of oocysts using the flotation method with Sheather's solution (saturated sugar solution; specific gravity = 1.28) and" ] },{ "paper_id": "6daca390ad9b7e330f843410f2218f0b27915cd0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where p are the probabilities of events.", ". 10 21", "The regulatory information is calculated as encoding the order of all protein molecules in a cell, which includes timing and volume of expression. If you know the first 10 molecules produced are protein A, the next 100 molecules are protein B, the next 50 molecules are protein A again, the last 200 molecules are protein Z, you know the timing and volume of expression." ] },{ "paper_id": "6dbc1181175c5ce84c649469fc4e9a4c7b6b8f32", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Infection source (6) Near-field dispersion Drying (4) Receptor exposure (6) Inhalation deposition", "Environmental and engineering controls", "(1) Type of ventilation system (2) Airflow distribution structure (3) Air exchange rate ", "Diseases can spread wherever people have direct or indirect contact, but this paper focuses on infections that occur in health care facilities, because they often contain a large proportion of infectious or vulnerable people, and because gov-ernments and other health care providers have a clear responsibility to mitigate infections that occur within their walls." ] },{ "paper_id": "6dbe5c842f58c1846c7659a0fb4f0da62d137c73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6dc7f0acaa45433001b3b0586094e88c0d400911", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The leaves were shade dried at room temperature for 8 days. The dried leaves (50 g) were ground to fine powder using mortarpestle and extracted with 500 mL of 70% ethanol (Merck) for 24 h with intermittent shaking. The extraction process was repeated two times with fresh solvent. Then, extracts were pooled, filtered (Whatmann filter paper No. 1) and dried under reduced pressure using rotary evaporator (R-210, BUCHI).", "ARTICLE HISTORY" ] },{ "paper_id": "6de6302336946d92dfdf1e1ec1c573a2299f195c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Veterinarians were advised to taper corticosteroid treatments if started before the study, but they were allowed to continue corticosteroid therapy at the lowest effective dose to maintain appetite and well-being.", "No toxicity or adverse events due to the administration of PI were reported by the veterinarians or owners.", "Skewness and kurtosis statistics found non-normal distributions for all temporal variables associated with survival. Therefore, nonparametric statistics were employed to yield inferences based on the respective research questions. Between-subjects comparisons for age groups and disease groups were conducted using Kruskal-Wallis and Mann-Whitney U-tests. In addition to means and SD, medians and interquartile ranges were reported to give context to non-parametric statistical findings. Kaplan-Meier survival curves were used to display the cumulative survival of cats across " ] },{ "paper_id": "6df7585dc7616c55baf0dd0df0a8a283f8805acd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following abbreviations are used in this manuscript: " ] },{ "paper_id": "6e0759e9f0c620a14bac6b9939d66bf18847de9c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Significance was calculated by means of the two-tailed Student t test, and a P value of \u05450.05 (*) was regarded as statistically significant.", "Negative-stain electron microscopy. Both uncleaved and FPC HPV16-PsVs at a final concentration of 0.1 g/l were prepared for electron microscopy by washing in HSB buffer (25 mM HEPES [pH 5.7], 0.5 M NaCl, 0.02% Brij 58, 1 mM MgCl 2 , 100 M EDTA, 0.5% ethanol) and purification through an Amicon Ultra-4 filter device (100,000-kDa molecular mass cutoff). A 3-l drop of sample solution was then adsorbed to a glow-discharged carbon-coated copper grid (Agar Scientific) for 30 s, washed with 2 drops of deionized water, and stained with 2 drops of 2% aqueous uranyl acetate (SPI Supplies). The air-dried grid was then viewed with a Philips Tecnai F20 transmission electron microscope equipped with a field emission gun operating at 200 kV. Imaging was done with a Gatan US 4000 4kX4k charge-coupled-device (CCD) camera using the Digital Micrograph software suite.", "Here we report the identification of surface-expressed vimentin for binding of both furin-precleaved and uncleaved HPV16-PsVs modulating infectious internalization of the incoming virions." ] },{ "paper_id": "6e0b5bbe1af91b80c9ac2fa22fea4d845c6230c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Laboratory service consolidations have to answer the following: \"How can the consolidation make the laboratory operations more advantageous both financially and clinically, given available resources?\"", "In addition, the ability of networked CMLs to access multiple different partners, geographies, and clinical specialties can enhance their capabilities to provide advanced disease surveillance and early outbreak recognition. For example, in the Brussels region, the LHUB-ULB laboratory structure provided 68% of all infection notifications reported in 2016 to the Belgian sentinel laboratory network (Vandenberg O, unpublished data).", "It is conceivable that consolidated CMLs and their regional health-care networks would pave the way to new public health information and cooperation models. Examples of such developments include regional health-care hospital networks with interactive surveillance for AMR control in EU cross-border regions (47) . Due to their 24/7 working scheme and advanced automation, consolidated laboratories are also able to provide surge capacity for the analysis of a large influx of samples in the context of an outbreak investigation.", "All authors contributed constructively in the conception, drafting, and final approval of the manuscript and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The views and opinions expressed herein are the authors' own and do not necessarily state or reflect those of ECDC. ECDC is not responsible for the data and information collation and analysis and cannot be held liable for conclusions or opinions drawn. " ] },{ "paper_id": "6e0d5cb338ea8a2916c74b3b06789d3b21ac36a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The substrate 30-mer oligos 5'-TAG AAA GGG AGA CCC AAA GAG GAA AGG TGA-3', 5'-TAG AAA GGG AGA CCC GAA GAG GAA AGG TGA-3', and 5'-TAG AAA GGG AGA CCC TAA GAG GAA AGG TGA-3' (IDT, Coralville, IA) were radiolabeled at the 5' terminus with [\u03b3-32 P] ATP (Perkin Elmer, Waltham, MA) using T4 polynucleotide kinase (New England Biolabs, Ipswich, MA), as described previously [35, 52] . Radiolabeled oligos were desalted using a Bio-Spin 6 column (Bio-Rad Laboratories, Hercules, CA).", "HEK293T, TZM-bl, and CEM-SS cell lines were obtained from the American Type Culture Collection. HEK293T and TZM-bl cell lines were maintained in Dulbecco's modified Eagle's medium and CEM-SS cell line was maintained in RPMI 1640 medium (Corning Cellgro). Both media were supplemented to contain 10% fetal calf serum (Hyclone), 100 IU/ml penicillin and 100 \u03bcg/ml streptomycin (GIBCO).", "Virus p24 CA amounts were determined using enzyme-linked immunosorbent assay (Xpress-Bio). TZM-bl indicator cells [59] were infected using equivalent p24 CA amounts of viruses, and infectivity was determined by measuring luciferase enzyme activity using Britelite luciferase solution (PerkinElmer) and a LUMIstar Galaxy luminometer (PerkinElmer).", "Together, this study provides a deeper understanding of A3G anti-viral activity and expands our knowledge of the deamination mechanism of related cytidine deaminases." ] },{ "paper_id": "6e1a04ccbbb614c9a28dd37899d7537f907028a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6e1e3f91f3642424e7328ee1fafc4151b7ba826c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition to Aspergillus, Candida spp. represents another fungal genus of potential importance, one routinely cultured from airway samples. Importantly, Candida spp. are abundant in the oral cavity even of healthy individuals and hence whether they represent genuine respiratory colonisers and/or pathogens in bronchiectasis remains uncertain [120] .", "A PUBMED review of all articles mentioning the keyword \"bronchiectasis\" in combination with \"epidemiology\" or \"microbiology\" published between 1997 and 2017 was performed. As bronchiectasis in Cystic Fibrosis (CF) represents a separate disease entity in its own right, retrieved articles dealing exclusively with CF-associated bronchiectasis were excluded, as were original articles without radiological confirmation of bronchiectasis. Studies of both adult and paediatric populations were considered and appropriately included.", "In the Asian subcontinent, considerable gaps in our understanding of bronchiectasis epidemiology continue to exist. No comprehensive prevalence datasets for either China or India are currently available however work is currently ongoing to address this. There are sporadic regional reports available that provide some insight into bronchiectasis in this highly affected region.", "Bronchiectasis is a major chronic pulmonary disease characterised by infection, inflammation and a permanent, irreversible dilatation of the bronchial wall. The interaction of chronic infection, exacerbations and inflammation drive a vicious cycle resulting in lung injury to the bronchi and lung parenchyma. This model proposed by Cole is not well understood in terms of the underlying biology but includes deficits in mucociliary clearance and innate and adaptive immunity (Fig. 1 ). There is amplification of injury processes following anatomical damage to the bronchi leading to progressive worsening of pulmonary physiology and symptoms with associated increase in exacerbations [1] . The host immune response to infection is primarily neutrophilic and neutrophil derived proteases are deleterious and result in further pulmonary damage amplifying a recurrent cycle [2] (Fig. 1) ." ] },{ "paper_id": "6e25ab9800baa443a7f103bd9e4940cac7db05f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The respondents were asked, 'How old are the employees at this institutional facility?' Respondents provided each staff member's age on a spreadsheet.", "The directors of the finance departments answered the questions regarding their institutional facilities' sources of income between 2007 and 2012.", "The region in which an HIA was located was indicated using a categorical variable based on administrative divisions, geographical locations, and economic factors. There are three regions. The eastern region included the provinces or municipalities with high GDP ( ", "The respondents were asked, 'How many staff members are currently working at this institutional facility?' Answers were numerical and open-ended at the end of the question." ] },{ "paper_id": "6e2b123ad273e69afefb875594ac0fac7c785c74", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each assay well had a 20 \u03bcL reaction volume consisting of 10 \u03bcL 2 \u00d7 PCR master mix with uracil N-glycosylase (Applied Biosystems), 3.8 \u03bcL of sterile distilled water, and 0.4 \u03bcL each of 20 \u03bcM forward and reverse primers, 0.4 \u03bcL of 20 \u03bcM probe (Exiqon, Vedbaek, Denmark) and 5 \u03bcL of sample cDNA (templates) or water (negative controls).", "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "6e2c37e888f6266374356b4dded392359a4695db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The datasets generated for this study are available on request to the corresponding author.", "Data were presented as the mean \u00b1 standard deviation (mean \u00b1 SD) and analyzed with the GraphPad Prism software v.5 (GraphPad Software Inc., La Jolla, CA). Statistic differences between groups were determined by one-way analysis of variance (one-way ANOVA) with Bonferroni's multiple comparison tests. The probability of the mouse survival was estimated using Log-rank test. A value of p < 0.05 was considered significant.", "This study was carried out in accordance with the recommendations of the Chinese Animal Protection Act and the National Research Council criteria. The protocol was approved by the Ethics Committee of Wuhan University School of Medicine. " ] },{ "paper_id": "6e30b6ac327ca9f75d9f409d2c0884144569e414", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6e4a162ab67f96a6b889e1f09d5531770fb1996d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The full-length gene encoding the receptor-binding domain of hemagglutinin (HA1) from influenza virus strain A/wild-duck/ Korea/ES/2004 (H5N2) was obtained, as previously described [14] . The HA1 gene was amplified by PCR and digested with XhoI and HindIII and then subcloned into the pBAC6 baculovirus transfer vector (Novagen, Darmstadt, Germany), which contained 6 His-tag at the N-terminal and signal peptides for protein secretion in insect cells.", "The purified protein was separated by SDS-PAGE and identified by immunoblotting analysis. As shown in Fig. 1A , the gHA1 protein fused to His-tag revealed a single band with a molecular weight of 50 kDa in SDS-PAGE. Although the molecular weight of gHA1 is estimated to be about 46 kDa, including 10 kDa of signal sequence plus the His-tag, a slightly higher molecular weight of 50 kDa appeared in SDS-PAGE, probably due to glycosylation.", "The glycosylation status of the recombinant gHA1 protein was determined with Peptide-N-Glycosidase F (PNGase F) that cleaves the complex oligosaccharides at N-linked glycosylations. Briefly, purified gHA1 (3 mg) was denatured in buffer (0.5% SDS and 4 mM DTT), heated at 100uC for 10 min, and subsequently incubated with PNGase F (New England Biolabs, Beverly, MA) according to the manufacturer's protocol. The reaction products were resolved by 12% SDS-PAGE, and the presence of HA1 was subsequently determined by immunoblotting, as described above." ] },{ "paper_id": "6e568297d56de743ad08b1b3c4ef6dc8dc50fb89", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fiber-optic microsphere-based antibody array [41] IL-8, IL-8mRNA Oral Cancer Electrochemical magneto biosensors [42] (NO 2 \u2212 and uric acid), and pulmonary inflammation biomarkers ", "This article gives an overview of research in molecular diagnostics, microbiology, and immunology. Routine laboratory testing includes the majority of haematology testing, clinical chemistry, and immunochemistry by using high-throughput instrumentation. Therefore, salivary PoCT diagnostics is replacing the central laboratory and offers efficient, fast, quick and easy automation. Since the emphasis is switching more towards prevention and early detection of a variety of diseases, development of small wireless devices has made a dramatic impact on healthcare services. The next decade will bring breakthroughs in terms of precision, efficiency, and bedside monitoring instead of hospital setups.", "Salivary anti-Ro60 and anti-Ro52 Antibody Profiles Sj\u00f6gren's Syndrome Luciferase Immunoprecipitation Systems (LIPS) [45] Salivary glucose Diabetes Glucose monitoring using saliva nanostructured biosensor [46, 47] cRP, MPo, ctnl, Myo, cK-MB, d-dimer, apoa1, apoB, BnP, nt-proBnP, scd40l, McP-1, adiponectin Cardiovascular disease (CVD) Programmable bio-nanochip (P-BNC) system [48] cea, ca125, Her2-neu, Psa (free and complexed) Cancer Programmable bio-nanochip (P-BNC) system, 2D nanomaterials [48, 49] " ] },{ "paper_id": "6e67417fbe15bbfa1dc530ceb8a41c796074aa9b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were resuspended in a 1.4% methylcellulose solution in growth medium, plated on a layer of 0.9% agarose and incubated at 37\u02daC, 5% CO 2 . After nine days, images were taken from 6-10 random fields (10x magnification) and colonies were counted.", "Antibodies, inhibitors and DNA constructs ", "The following dataset was generated: " ] },{ "paper_id": "6e6c7a4e78fe8ffc7ca59f523fd6fcdef4333758", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6e6fb58bc0253b1c8326599159f321be8a37736f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This article did not receive any funding support.", "The authors declare that they have no competing interests.", "Ethics approval and consent to participate Not applicable for this manuscript. ", "Please see Additional file 1 for translations of the abstracts into the five official working languages of the United Nations." ] },{ "paper_id": "6e7a017e7e61ae4634cd4be5ad5646470e43054d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\"I think most people just don't look at posters now. Probably because people have phones, right? When they're in [an exam room] by them self, they don't look around, they just look at their phone.\"", "Another general practice veterinarian said:", "The veterinary technician was asked to respond in reference to both herself and what she observed in her interactions with veterinarians in her clinic. Responses were transcribed and analyzed using conventional content analysis (20) ." ] },{ "paper_id": "6e8e102a4453c1bf7d9d4886d32d6aa1bebb3e53", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rotavirus (RV) is an enteric pathogen of humans and other vertebrates. Symptoms of RV infection include gastroenteritis, leading to dehydrating diarrhea and death in some cases (for reviews see [1, 2] ). More than an estimated 700,000 children under the age of five died of diarrhea in 2011. Importantly, 28% of these fatal diarrhea cases were associated with RV [3] .", "Next, the subcellular distribution of the different RV structural proteins in HSV-1 vector transduced Vero2-2 cells was examined by confocal laser scanning microscopy and specific antibodies ( Figure 1D ).", "Meier performed the experiments; Mark Suter, Kurt Tobler, Andrea S. Laimbacher and Anita F. Meier analyzed the data; all authors contributed reagents/materials/analysis tools; and Mark Suter, Mathias Ackermann, Andrea S. Laimbacher and Anita F. Meier wrote the paper." ] },{ "paper_id": "6e94aa9c37dd7be5b553090717c59992005d114b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal research was carried out in adherence with protocols approved by the National Institutes of Health Rocky Mountain Laboratories Animal Care and Use Committee, animal protocols 2012-47 and 2012-46. The method of euthanasia for neonatal mice used for generation of primary glial cell cultures was hypothermia, followed by decapitation following the NIH guidelines since neonatal mice are not sensitive to inhalant anesthetics.", "doi:10.1371/journal.pone.0127336.g002" ] },{ "paper_id": "6ea0187c80591fcbe19d37343f9957859753b129", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis were performed using the non-parametric Mann-Whitney test with Prism GraphPad software; p values less than 0.05 were considered to be significant.", "onto poly-L-lysine-coated slides, fixed and permeabilized with acetone and were stained with mAbs against anti-IE and -E antigens (Argene Biosoft, France). Four distinct fields were digitalized and analyzed with ImageJ software to determine the percentage of I.E.A./E.A.+ MDDCs. n = 6 independent experiments with eight different donors in total. doi:10.1371/journal.pone.0034795.g001", "Protein contents of subcellular fraction were quantified by BCA assay (Sigma) according to the manufacturer's instructions. In the absence of a conserved reference protein in all subcellular fractions obtained after cell fractionation equal amounts of total protein were loaded on a 10% SDS/PAGE gel (Pierce Biotechnology, " ] },{ "paper_id": "6ea1978890ab099e90e61ddf078b6d983e60b07f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In summary, our study reveals that the respiratory microbiota is more complex than expected.", "Another interesting observation was that mixed infection was observed in many BAL fluids from pneumonia patients. Interestingly, recent works report that probable interactions between parasitic species can occur in their host, and these reports also show that infection with a given microorganism may increase or decrease susceptibility to infection by another one or can create a cross-immunity response [21] [22] [23] [24] [25] [26] [27] . Such interaction remains to be investigated.", "Bacterial and fungal nucleic acid sequences obtained from broad-range primer PCR were aligned with BioEdit program (http://www.mbio.ncsu.edu/BioEdit/bioedit.html) and phylogenetic trees were create with MEGA software version 4.1 using the neighbor-joining method and the Kimura-2 parameter [48] . Species having sequence similarities ,98% with those available in GenBank databases were also blasted and classified in silico using ''Classifier'' program in the Ribosomal Database Project (http:// rdp.cme.msu.edu/) [49] . Statistical analyses were performed using Chi square test, Fisher's exact test, students t-test or Mantel-Haenszel's Chi square test when appropriate. P values that were less than or equal to 0.05 were considered significant." ] },{ "paper_id": "6eb0faeda9396efaf96674c33b40395012a01e0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Singlestranded DNA MREs targeting bacteria can be classified into two general categories, (1) targeting whole cells with known or unknown molecular targets and (2) targeting predefined bacteria cell surface targets or bacteria spores (Table 1) .", "Dengue virus is a member of family Flaviviridae, genus flavivirus. It is a mosquito-borne RNA virus that can cause gangue fever, dengue hemorrhagic fever, and dengue shock syndrome [101] . Gandham (Table 4) .", "In order to identify nucleic acid MREs, the SELEX process generally begins from a very large random library consisting of 10 13 to 10 15 different molecules. An individual nucleic acid MRE is composed of two constant regions for primer attachment during polymerase chain reaction (PCR) amplification flanked by 20-80 bases of random region [3] ." ] },{ "paper_id": "6eb145a990b1132457f78c4e1521ab827b715ad0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After incubation with 10 mM Dio dye at room temperature, followed by elution in a Sepharose G-50 column, the labeled and unlabeled SIV were analyzed for different characteristics. The results show that the hemagglutination activity and infectivity were not altered by labeling. The neuraminidase activity of Dio-labeled SIV was 91% of that of unlabeled SIV. Measured by dynamic light scattering and laser Doppler anemometry, the size and surface charge of the labeled virions were not significantly altered (Table 1) .", "Madin Darby Canine Kidney (MDCK) cells were maintained in Minimum Essential Medium (MEM, Gibco) supplemented with 10% fetal calf serum (Gibco), 100 mg/ml of streptomycin and 100 units/ml of penicillin (Invitrogen). The avian-like H1N1 swine influenza virus Sw/Belgium/1/98 was used at the third passage on MDCK cells. The virus was propagated in MDCK cells in MEM supplemented with 5 mg/ml trypsin (Gibco), 100 mg/ml of streptomycin and 100 units/ml of penicillin (Gibco).", "Five sections were examined for each mucus sample for the semi-quantification of a2,3and a2,6-SA coverage in the mucus.", "Confluent MDCK cells were inoculated with SIV at a multiplicity of infection (m.o.i) of 0.01 in MEM. Twenty hours post inoculation, the supernatant was harvested. The cellular debris was removed by ultracentrifugation at 7 000 6g for 20 min at 4uC in a Type 35 rotor (Beckman, Fullerton, CA, USA) and the suspension was clarified by filtration with a 0.45 mm filter (Millipore). Afterwards, the virus was pelleted at 75 000 6g for 2 h at 4uC in a type 35 rotor. Following resuspension in PBS (1/ 100 of the original volume), the virus suspension was brought on a discontinuous OptiPrep (Sigma) gradient containing 10-30% (w/ v) of iodixanol and centrifuged at 100 000 6g for 3 h at 4uC in an SW41Ti rotor (Beckman, Fullerton, CA, USA). The visible opalescent virus bands at the interfaces were harvested separately. The buffer was exchanged with HNE (5 mM HEPES, 150 mM NaCl, 0.1 mM EDTA, pH 7.4) buffer by the use of a 50 kDa filter device (Millipore)." ] },{ "paper_id": "6eb282b0887ed1a7ab59123919bbadbf9ce6ed55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 With broader adoption by scientists, journals, and funding agencies, preprints can complement peer-reviewed publication and ensure the early, open, and transparent dissemination of science relevant to the prevention and control of disease outbreaks.", "\u2022 Preprints posted during the Ebola and Zika outbreaks included novel analyses and new data, and most of those that were matched to peer-reviewed publications were available more than 100 days before publication." ] },{ "paper_id": "6ebb0d128a1f03635f662f5419927c90c61855e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the patients provided informed consents, which was approved by the Ethics Committee of the Third Affiliated Hospital of Suzhou University.", "All data were presented as the mean \u00b1 SE and statistically analyzed using GraphPad Prism software (San Diego, CA). P values less than 0.05 were considered statistically significant." ] },{ "paper_id": "6ebbce608cb316b579ed926190d068a6fa90534a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It is believed that microaspiration, which occurs in healthy individuals but has a higher prevalence in asthmatics, could in part explain the presence of oral microbiota in the lower lung [15] . However this does not fully explain why some individuals have a higher relative abundance of certain bacteria originating from the upper respiratory tract [15, 75] .", "The \"disappearing microbiota\" hypothesis contends that as we become less colonised by ancient commensal microorganisms, which aid in a multitude of processes such as vitamin uptake and immunity, we become more susceptible to attack by potential pathogenic microorganisms. A shift in an individual's microbial balance may have detrimental consequences. The \"disappearing microbiota\" hypothesis has been studied in relation to the increased and decreased prevalence of several diseases in developed nations. While the hygiene hypothesis highlights our susceptibility to infection caused by our decreased sampling of microorganisms from the environment the disappearing microbiota hypothesis suggests that our susceptibility is due to a decrease in ancestral microorganisms which offered protection [77] .", "It has been reported by Black et al., in 37 patients admitted to the ICU for an acute asthma attack, that 54% tested positive in a skin test for fungal spores which included Alternaria tenuis, Cladosporium cladosporides, Epicoccum nigrum and Helminthosporium maydis [98] . O' Driscoll et al., recruited 181 patients, aged between 16 and 60 years of age and divided them into three groups; severe, moderate and mild, dependent on their number of lifetime hospital admissions. 76% of patients with severe asthma tested positive in a skin test toone or more moulds including Aspergillus fumigatus, Penicillium notatum, Cladosporium herbarum, Alternaria alternata or the yeast Candida albicans in comparison to lower rates of positivity in patients with moderate or mild asthma (16-19%) [99] .", "Asthma is a heterogenous disease, with airway inflammation induced by epithelial exposure to allergens, pollutants and microbes which further stimulate the underlying APC (antigen presenting cells) cells inducing an immune response [83] . This epithelial exposure can result in a predominantly eosinophilic or neutrophilic cell influx into the airway. The allergic subtype, which responds to environmetal allergens, is characterised by increased eosinophil, basophils, and mast cells along with expansion of the T helper 2 cell (T H 2 cell) subtype. As the epithelial or mucosal barrier is where the allergen presents itself, a breakdown in these physical barriers, the site of allergen presentation, can further propagate allergic, inflammatory response [8] . Indeed fungal spores, which are potent allergens, are postulated to damage the epithelial barrier by inducing cell shrinkage and subsequent inflammation and barrier breakdown [84] .", "The so-called 'hygiene hypothesis' contends that exposure to soil, dust, microbes, antibiotics, vaccinations, farm animals and family size in addition to factors such as caesarean section birth versus vaginal birth and exclusive formula feeding versus breastfeeding can all in some part determine asthma risk [52] [53] [54] . In one meta-analysis study there was a 20% increase in the subsequent risk of asthma development in children born by caesarean section [55] ." ] },{ "paper_id": "6ec1c2c2244a8d8f5959fad54ba3b7923e72e971", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coping appraisal is also represented in its three dimensions:", "The area under the ROC curve (AUC) was used as model performance indicator and Nagelkerke R 2 to estimate the determination level for each model. The limits for interpreting the AUC (or c-statistic) were set to 0.90, 0.80, and 0.70, denoting very strong (outstanding), strong (excellent), and acceptable discriminatory performance, respectively [26] . All tests were twosided and P,0.05 was regarded as statistically significant. All calculations were done using SPSS version 18 or higher.", "Text S1 Interview guideline for collection of data on perceptions associated with precautionary behaviors. (DOCX)" ] },{ "paper_id": "6ec5ee2681be3633672ac2d32249110514289a5c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6ed0c79fde1a2d37093e6a97ee3ffb2d8c4410eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "None.", "Published by Elsevier B.V. This is an open access article under the CC BY license" ] },{ "paper_id": "6ed1c5f102cce4bbcbd9d5438b6b8be3d4746484", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.", "Statistical significance of differences between experimental groups was determined through the use of the unpaired, nonparametric Student's t test. Values of p,0.05 were considered significant." ] },{ "paper_id": "6ed77e5ebba3c0f0b10c6e0af3e8df28b57335e6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After amplification, 2\u03bcl of each reaction was run on a 1% agarose gel for 1 hour to visualize bands and confirm amplification. Unincorporated dNTPs were dephosphorylated and excess primers were removed from products using a SAP/Exo I reaction containing 0.5 units of shrimp alkaline phosphatase (USB Corporation), 1.0 unit of exonuclease I (USB Corporation) and molecular biology grade water. The cycling program was: 1 cycle of 37\u00b0C (60 min) and 1 cycle of 72\u00b0C (15 min).", "Project name: JCVI Primer Designer. Project home page: http://sourceforge.net/projects/ primerdesigner/. Operating system: Tested and in production on Linux. Programming language: Perl. License: GNU GPL. Any restrictions to use by non-academics: none." ] },{ "paper_id": "6ed9a8fa706f8553d2111e38145c95990b26ba9b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6ee9f517e7b70ca8149459475ea4de6095c46f26", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Alnus genus has abundant diarylheptanoids containing the 1,7-diphenylheptane frame [21] . Diarylheptanoids have drawn attention due to their physiological activities, especially their anticancer activity [11] . A total of 99 diarylheptanoids have been reported from Alnus species. They are categorized into three major groups: linear-type (compounds 1-89), cyclic diphenyl ether-type (compounds 90-93) and cyclic diphenyl-type (compounds 94-99).", "Free radical damage is linked to the occurrence of many degenerative diseases, including cancer, cardiovascular disease, cataracts, and aging. Antioxidants can attenuate the damaging effects of reactive oxygen species (ROS) in vitro and have attracted major interest, not only for health care and cosmetics, but also in the food industry [118] .", "Diarylheptanoids and phenolic glycosides isolated from A. japonica, A. hirsuta, A. firma, A. formosana, A. nitida, A. nepalensis and A. acuminata showed significant anti-inflammatory effect [33, 41, 57, 70, 99, 121, 122] ." ] },{ "paper_id": "6ef3cd7a4e284ef443c3d10514760c0c446866e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethical declaration. This study was approved by the CCS-UFPE Ethical Committee (CAAE: 61603316.7.0000.5208) and all patients gave informed consent. Whole blood and urine samples were collected as part of an education and follow-up campaign for arboviruses and cardiovascular diseases conducted by LIKA in the states of Para\u00edba and Pernambuco, Brazil in February-July 2016. All experiments were performed in accordance with relevant guidelines and regulations." ] },{ "paper_id": "6efcaa639a97ba506cf341230c166208d1312a11", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The protein sample was dialyzed into 20 mM Potassium phosphate pH 7.4, and the concentration was adjusted to 0.5 mg/mL. Circular dichroism signal was measured using a J-815 Circular Dichroism Spectropolarimeter (Jasco Analytical Instruments). The wavelength range was set from 200 nm to 280 nm with a step size of 0.2 nm. The results were analyzed using BeStSel [32] .", "doi:10.1371/journal.ppat.1006231.g006" ] },{ "paper_id": "6efd9d7ed926ebe9979cc13990888257507e2e19", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that they have no conflict of interest.", "The gene encoding the F protein of human respiratory syncytial virus (RSV)-F was constitutively expressed in apple leaves using the CaMV35S promoter. Protein expression was considered stable and corresponded to 20 mg/g of plant tissue [137] .", "B subunit expression studies of E. coli thermolabile toxin were conducted in the soybean (Glycine max) endoplasmic reticulum, in which a total antigen level of up to 2.4% of the soy seeds' total protein was obtained without producing any instability during seed drying for further processing treatment; moreover, oral consumption by rats led to increases in systemic IgA and IgG levels [82] .", "Lines of transgenic cherry tomatillos were developed for the HBsAg gene of hepatitis B. Gene expression was observed throughout the plant but was highest in the leaves, reaching 300 ng/g fresh weight, with 10 ng/g fresh weight in fresh fruit. Significant immune system activation was observed in rodents [138] ." ] },{ "paper_id": "6efde6b65a96f7b14d75d637f5dd77f8e6e1c51c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. Home confinement of symptomatic school children." ] },{ "paper_id": "6efeb37a50a81c7769a49bcf030e54b148bd1fbd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The pCTCON-2 yeast display vector was kindly provided by Prof. Dane Wittrup [23] . The DNA fragments coding the HA1 and HA2 proteins were amplified from plasmid CMV-R-Cali Two Xcm I restriction sites (CCANNNNN/NNNNTGG) were introduced between Nhe I and BamH I sites of pCTCON-2 to create pCTCON-T. Digestion of pCTCON-T by Xcm I restriction nuclease and gel extraction yielded the T-vector with two 39 T overhangs. Random fragments with 39 A tails were inserted between the two Xcm I sites by T-A ligation.", "HA is the key viral antigen in determining host specificity and inducing neutralizing antibody since it plays a major role in binding to host cell receptors and fusing with host cell membranes [3] . For many challenging diseases caused by viruses, the recognition of certain neutralizing epitopes by the immune system can indeed provide broad and potent protection [4, 5] . The antigenic structure of HA and the corresponding antibody response are not fully understood, complicating rational design of vaccines aimed at modulating antibody responses for targeting key epitopes.", "Cruz, USA). Oligonucleotides were synthesized by Invitrogen or Takara. The kits for DNA purification, gel recovery, plasmid miniprep and A-Tailing modification were obtained from Tiangen (Beijing, China) or Takara (Dalian, China). The kit for yeast plasmid DNA isolation was from Omega Biotech (Victoria BC, Canada). Sequencing was performed by Invitrogen or by SinoGenoMax (Beijing, China). Escherichia. coli DH5a was obtained from Takara. Yeast strain Saccharomyces cerevisiae EBY100 was obtained from Invitrogen." ] },{ "paper_id": "6f048749badc8f1c756857ceb24421f5e6c05e62", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Strongly agree", "[4] [4] [5]" ] },{ "paper_id": "6f0572cc1fa39ecc775cf576db694638a7fb9bc1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis and graphing was conducted with GraphPad Prism software (GraphPad Software Inc., La Jolla CA). Significance values for Figures 2, 3, 4 , 5, and 6 utilized repeated measures of ANOVA with the Bonferroni post-test to explore differences between groups (SVV BAC and WT SVV) at each time-point." ] },{ "paper_id": "6f06d1fd7c4ae1397b0a8f5192e9f0c7dc5e62df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The experimental protocol for the pig studies was approved by the Iowa State University Institutional Animal Care and Use Committee (IACUC, Approval No. 4-14-7777-S; approved on 24 th of April 2014).", "*All pigs PCR positive on rectal swabs were necropsied on day 4 due to the severity of clinical signs doi:10.1371/journal.pone.0139266.t003", "The villus height, crypt depth, and villus/crypt ratio were compared with a generalized linear mixed (GLIMMIX) model. IHC scores were compared using a Kruskal-Wallis Test. All tests were performed using JMP software (SAS Institute, Cary, North Carolina, USA), with P<0.05 considered significant." ] },{ "paper_id": "6f07f87e8ef78f0416556e69c88247e588f9192c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dataset S1. Molecular Genetic Analyses of Stems 2 and 3", "The GenBank (http://www.ncbi.nlm.nih.gov/Genbank/) accession numbers for the sequences discussed in this paper are AIBV (NC_001451), BCoV (NC_003045), HCoV-229E (NC_002645) , HCoV-HKU1 (NC_006577), HCoV-NL63 (NC_005831), HCoV-OC43 (NC_005147), MHV (NC_001846), PEDV (NC_003436), SARS-CoV (NC_004718), and TGV (NC_002306)." ] },{ "paper_id": "6f08b893f2190ac79dbeb85302703bf519037b7b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6f0c490d80ef3e7032010a057baa96d4d45ababc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We searched PubMed and Web of Science (WoS) for records published between January 2010 and December 2015. After discussing and defining the inclusion and exclusion criteria, we obtained our final search query which we used in PubMed on 12 January 2016 and in WoS on 13 January 2016: '(behavio* OR decision*) AND (change* OR influence* OR dynamic* OR adapta* OR adapt OR adaptive OR strategic*) AND (infect* OR epidemic OR epidemics OR epidemiology OR epidemiological OR epidemiologic OR pandem* OR outbreak*) AND (disease* OR vaccin*) AND (model OR models OR modelling OR modeling OR simulat* OR transmission*)'.", "The popularity of emergence-driven research has many drivers: often new research funding and data collection opportunities arise as an emergence unfolds for the development and parametrization of new models to inform health policy.", "In a second step, the remaining articles' full texts were screened to confirm eligibility, independently by F.V. and L.W. Whenever there was doubt about eligibility, agreement was sought through discussion.", "In a first step, F.V. screened the results of the search query based on title and abstract in accordance with the following pre-specified eligibility criteria:" ] },{ "paper_id": "6f1a0067a1612a8293e7cb64c89bf2e92b674fae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "AA, SD, and SK-A have all contributed to literature review and writing this manuscript. AA and SK-A contributed to the production of figures. All authors have approved the final version of the manuscript.", "In conclusion, while existing animal models do not recapitulate all clinical aspects of human SCI, the compression and contusion models are considered to be the most relevant and commonly employed methods for understanding the secondary injury mechanisms and therapeutic development for SCI.", "This work was supported by grants from the Canadian Institute of Health Research to SK-A. AA and SD were supported by studentships from Research Manitoba, the Children's Hospital Research Institute of Manitoba, the University of Manitoba GETS program, and the Manitoba Paraplegic Foundation.", "Balloon Compression model has been also utilized extensively in primates and larger animals such as dogs and cats (84) (85) (86) . In this model, a catheter with an inflatable balloon is inserted in the epidural or subdural space. The inflation of the balloon with air or saline for a specific duration of time provides the force for induction of SCI (51) . Generally, all compression models (clip, forceps, and balloon) have the same limitation as the velocity and amount of force are unmeasurable (51) ." ] },{ "paper_id": "6f1f4714674c1dbe218971f0fcb9cd986e6f6a4f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Three types of autophagy [macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA)] are depicted in Figure 1 . ", "To alleviate autophagy-associated diseases, a variety of drugs, biomolecules, chemicals, and epigenetic strategies have been developed to either promote or inhibit autophagy.", "The apparent dual role of autophagy may be due to our poor understanding of this ubiquitous cellular recycling system. Understanding the differences between physiological and pathological autophagy may help us design therapeutic strategies to target pathological autophagy without hindering its physiological effects." ] },{ "paper_id": "6f251e71a441068ffe96970bf5d857713ec30163", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "hMPV infection causes a wide spectrum of diseases from mild upper respiratory tract infections (RTI) to severe lower RTI such as bronchiolitis or pneumonia and can result in hospitalization of both children and adults [49] . HMPV is one of the most prominent respiratory pathogens in children, accounting for 5-15% of pediatric hospitalizations for respiratory tract infections [49, 50] . A recent study estimated the hospitalization rate for hMPV in older adults to be 9.8 per 10000 residents, a rate similar to those of hRSV and influenza [51] .", "An aliquot of 250 \u00b5l of lung homogenates was added to 250 \u00b5l of 50 mM KPO 4 , pH 6.0 buffer containing 0.2% CHAPS (Sigma, St. Louis, MO) and 0.2% protease inhibitor cocktail (Sigma, St. Louis, MO) and then stored at -20\u00b0C. On the day of the experiment, samples were centrifuged at 13,800 \u00d7 g for 10 min at 4\u00b0C and then 50 \u03bcl of the supernatant were used for cytokine quantification. Levels of interleukin (IL)-4, IL-6, IL-12(p40), IL-12(p70), IFN-\u03b3, KC, MCP-1, MIP-1\u03b1, RANTES were determined using 9-plex mouse bead kits (Millipore, Billerica, MA) according to the manufacturers' instructions. Experiments were performed in a 96-well filter plate and results were analyzed with the Luminex system (Qiagen, Germantown, MD).", "PAR1 agonist (TFLLR-NH 2 ) (Genscript, Piscataway, NJ) was reconstituted in H 2 O at a concentration of 10 mM, aliquoted and stored at -20\u00b0C. Immediately before intranasal administration, the compound was diluted to 50 \u00b5M or 500 \u00b5M in OptiMEM. As a control, H 2 O was diluted 1/20 in OptiMEM before administration. PAR1 antagonists (SCH79797 and SCH530348 (Vorapaxar)) (Axon MedChem, Groningen, The Netherlands) were reconstituted at a stock concentration of 22 mM in DMSO and stored at -20\u00b0C. Immediately before intranasal administration, these compounds were diluted to 50 \u00b5M or 500 \u00b5M in OptiMEM. As a control, DMSO was diluted 1/44 in OptiMEM before administration.", "Hospitalized patients are currently treated symptomatically, since no specific prophylactic or therapeutic modality is available. Although not approved for this indication, ribavirin has been administered as an antiviral agent in a few severe cases of hMPV pneumonia with variable outcomes [20] [21] [22] . Several hMPV vaccines have been investigated in animal models, including live-attenuated and subunit vaccines; however, vaccine-induced immunity was often partially protective and/or waned rapidly [52] . Importantly, hMPVinactivated vaccines have been shown to induce an enhanced disease upon infection reminiscent of hRSV-inactivated vaccines [52] [53] [54] . Clearly, alternative approaches for the management of hMPV infections are needed." ] },{ "paper_id": "6f3c5be389b060803e0eaa4727b6180637168dad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Understanding the mechanisms by which viruses develop resistance is a vital component of the fight against viral diseases, and can lengthen the lifespan of existing antivirals. Potentially any antivirus molecule could be transformed into an activity-based or affinity-based probe, allowing isolation and characterization of enzymes that detoxify the antiviral drug.", "Natural products represent an important treasure box of biologically active molecules, from which many drug candidates have been developed (Newman and Cragg, 2007) . Since a large number of the proteome remains functionally uncharacterized and is therefore difficult to assemble into larger biochemical networks, competitive ABPP will inevitably accelerate the development of novel inhibitors from natural products.", "ABPP with live cell imaging may provide additional insight into understanding the pathogenesis due to viral infection (Furman et al., 2009) . Identification and functional characterization of serine hydrolases involved in pathogenesis and virulence of viruses would be a novel approach to uncover molecular processes at the basis of viral diseases." ] },{ "paper_id": "6f402164832578c18fec0cc33d29c944acf81a26", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CH25H has been described as being able to negatively regulate immunity in return for its induction by IFN.", "First, in na\u00efve B cells, treatment with 25-HC suppresses B cell proliferation in response to IL-2stimulation and blocks class switch recombination, leading to markedly decreased IgA production [210] . Secondly, in monkey-derived macrophages and PBMC cells, SIV infection induces CH25H expression via IFN which inhibits SIV replication but, in return, 25-HC produced by CH25H restrict mitogen-stimulated proliferation of cells and inhibit inflammation [288] .", "While the SPRY-PRY domain of TRIM5\u03b1 is responsible for the recognition of viral capsid, the E3 ubiquitin ligase RING domain is important for effector function probably through the recruitment of the proteasomal machinery [100] . Indeed, inhibition of proteasome prevents the premature disassembly of the capsid and restores HIV-1 reverse transcription [101] [102] [103] ." ] },{ "paper_id": "6f62efb20f820241aeb1a8e16af68502fedc9b43", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(Responsive-to-Dessication protein 29A), and RD20 (Responsive-to-Dessication protein 20), when they were activated under drought stress conditions [2] . Besides, the protein profile analysis of salt-responsive proteins suggests that salinity tolerance could be partially controlled by glutathione S-transferase which plays a key role in antioxidant defense mechanisms [3] . However, the detailed molecular mechanisms in these processes remain elusive.", "ChIP-PCR reactions were set up as follows: 4 ul template (~< 0.1 nmol) was mixed with 0.4 ul dNTP (10 mM), 0.4 ul forward primer (10 uM), 0.4 ul reverse primer (10 uM), 2 ul 10 \u00d7 PCR buffer, 0.25 ul Taq polymerase (Promega, Wisconsin, USA), and 1 ul MgCl 2 (25 mM). The final volume was adjusted to 20 ul by distilled milli-Q water. Information on primers and PCR settings were summarized in Additional File 8, Table S2 . The PCR products were resolved on a 2% agarose gel.", "Background: Accumulated evidence suggest that specific patterns of histone posttranslational modifications (PTMs) and their crosstalks may determine transcriptional outcomes. However, the regulatory mechanisms of these \"histone codes\" in plants remain largely unknown.", "The presence of the acetyltransferase domain in the GmGNAT1 suggested that it might transfer the acetyl group to its substrates from acetyl-CoA. However, its substrates remained elusive.", "Recombinant plasmids containing the target clones were transformed into the bacteria strain DE3. The transformed bacteria were inoculated into Luria-Bertani (LB) broth supplemented with 100 \u03bcg/ml of ampicillin and incubated at 37\u00b0C for 2.5-3 h until the optical density at 600 nm reached about 0.6-0.8. IPTG was then added to reach a final concentration of 1 mmol/L to induce the expression of the recombinant proteins at 25\u00b0C. After overnight expression, the bacteria were collected, suspended in phosphate buffered saline (PBS) and lysed with 1 mg/ml lysosome on ice for at least 1 h. The supernatant was collected after centrifuged at 4\u00b0C for 15 min at 21,500 g and stored at -80\u00b0C until use." ] },{ "paper_id": "6f647c734a4bdf8adc7a70f380483ad7f02ba772", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that there are no conflicts of interest regarding the publication of this article.", "UPR is an important modulator in the induction of inflammatory cytokines, and UPR activation was shown to be sensitive to inflammation [21] . It has been well established that NF-kappaB activation is required for the induction of proinflammatory cytokines and has been linked to UPR [8, [22] [23] [24] .", "The inflammatory response due to ER stress is frequently observed in the development of nonmalignant immunological disorders, such as rheumatoid arthritis and neurodegenerative diseases [12] . Evidences have shown that ER stress enhances TLR-induced intracellular cascades to produce proinflammatory cytokines (Table 1) . However, more research is needed to understand the role of ER stress in host immune responses and to exploit this knowledge to design new drugs for patients with various inflammatory and metabolic diseases. Overall, this review emphasizes that the ER stress-induced inflammatory cytokine productions are shared with TLR-mediated signaling pathways and taking advantage of ER stress may be used as therapeutic option to prevent inflammatory diseases and protect secondary infection in septic patients through recovery of immune responses." ] },{ "paper_id": "6f66ba164fba7cd9449ae02d511e2ae8c32b53e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Comparison of the partial replicase nucleotide sequences revealed 97.9 % and 82.1-93.7 % homology within the analyzed local DogCV isolates and between the local DogCV and reference strains, respectively ( Table 4 ). The same nucleotide sequences for local DogCV strains also exhibited 91.6-93.7 % homology with those for Italian DogCV strain Bari/411-13 (Table 4 ).", "The study did not involve any animal experiment. The Institutional Animal Care and Use Committee (IACUC) of National Pingtung University of Science and Technology did not deem it necessary for this research group to obtain formal approval to conduct this study. The dog owners gave his/her written consent for sample collection and data publication. Besides, according to Dr. Baneux' recommendations \"Privately owned animals that are recruited for clinical studies (not Public Health Service funded) do not need to be subjected to IACUC oversight as long as their involvement includes only procedures that are consistent with the standard of care provided to patients with the same diagnosis that are not included in the clinical study\" [7] .", "PCV2 causes clinical conditions including systemic, lung, enteric, reproductive and skin diseases [5] . In recent years, a possible association between DogCV and canine enteritis has been suggested [3, 4] . DogCV has also been reported to cause necrotizing lymphadenitis [4] and vasculitis, which are also caused by porcine circovirus type 2 infections in pigs [5] . Previous studies have shown that DogCV is associated with hemorrhagic enteritis in dogs [3, 4] , however, limited information is available to determine the direct correlation between the severity of diarrhea and DogCV infections.", "SYBR Green-based real-time PCR assays were performed using a LightCycler Nano (Roche Diagnostics, Mannheim, Germany). Each 10-\u03bcl reaction mixture contained 0.2 \u03bcM of forward and reverse primers, 5 \u03bcl of Master buffer (Roche Diagnostics, Mannheim, Germany) and 3 \u03bcl of DNA extract. The thermocycling conditions consisted of 10 min at 95\u00b0C, 45 cycles of 10 s each at 95\u00b0C, 10 s at 51\u00b0C and 10 s at 72\u00b0C. Each run included serial 10-fold dilutions of the standard plasmid DNA as a positive control and for the construction of a standard curve. A negative control without the DNA template was included to detect possible cross-contamination." ] },{ "paper_id": "6f67e5b5e61f9ce94ddc8aaae34799a81c4c213d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed with GraphPad Prism 5 (GraphPad Software, La Jolla, CA, USA) using unpaired one-tailed Student's t-test and shown as mean \u00b1 SD. *P < .05, **P < .01, ***P < .001, ****P < .0001." ] },{ "paper_id": "6f6da38ab5fa77f94deb29bfa51504be4ebd018b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Effect estimates ", "Written informed consent was obtained from the patient for the publication of this report and any accompanying images. results and conclusions: WC, BL, LQW, JR, JPL. Wrote the first draft of the paper: WC. All authors read and approved the final manuscript." ] },{ "paper_id": "6f779376c8f76658fa6ab19c24748a56ee00aa49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Text S1 Supplementary protocols and figures. Protocols S1-S2 and figures S1-S7. (PDF)", "Subsequently V was also determined at higher substrate concentrations ranging from 1 mM to 20 mM for PRO wild type (10 nM) and Pro I847A (100 nM). Results were fitted to Michaelis-Menten kinetics by nonlinear curve fitting using Graphpad Prism (Graphpad Software inc., la Jolla, CA).", "Data were expressed as the means and standard deviations of these independent experiments. All experiments were performed at least in triplicates for K app values and at least in duplicates for the higher substrate concentrations experiments.", "Details of the structure determination are given elsewhere [11] . Briefly, the structure was solved by MIRAS from three poor derivatives thanks to the high (69%) solvent content of the crystals. Heavy atom derivatives (HgAc 2 , NaI and CsCl) were obtained by soaking. Data were processed with the XDS package [31] . Initial heavy atom sites were located with SHELXD [32] . This first heavy atom model was refined, completed and pruned and initial phases were computed and improved with autoSHARP [33] . The resulting map was interpretable and a first model was built with phenix.autobuild [34] . The model was manually rebuilt with COOT [35] and refined with phenix.refine [34] . Data processing and refinement statistics are collated in table 1." ] },{ "paper_id": "6f9149e2caa1229df655448839a15cafab5a03e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In some countries, mainly young males up to two years old (named hachi in Arabian countries) are slaughtered for meat, whereas in other regions adults are preferred (Faye 2013 ). These preferences have led to different fattening systems: (i) extensive, pastoral fattening mainly used for adults, e.g. in Somalia and Ethiopia; and (ii) intensive fattening with feedlots for young camels as practised, for example, in Saudi Arabia, United Arab Emirates and Tunisia.", "In the long term, the challenge remains to harmonise and standardise the collection of phenomic and genomic data und to utilise them in a way that is beneficial for human and animal needs. This includes not only the improvement of desirable production traits but also the conservation of genomic diversity and of the evolutionarily significant physiological adaptations in camels.", "Meat performances and composition according to camel type were investigated in four Saudi Arabian dromedary Table 2 Examples of high-, medium-and low-producing milk camel ecotypes/breeds." ] },{ "paper_id": "6f94dde3cf8c2776d869b8490fb491d7416088f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by the Survey and Behavioural Research Ethics Committee, the Chinese University of Hong Kong.", "Tai Po (147.84 km 2 ) is a district in the Hong Kong Special Administrative Region of China and it has a population of about 300,000 residents. Most of the residents in this district are living in apartment buildings with multiple (3 to over 30) storeys, a typical floor of which contains 4 to 8 flats that measure 40 to 90 m 2 in size.", "We attempted to study the spatiotemporal associations of emergency department visits that presented with fever and hospitalized, and identified clustering of cases to predict occurrence of outbreaks." ] },{ "paper_id": "6f95128d6a8899b5c90dc234a613d4b08415a9e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations CFI: Comparative fit index; HCCQ: Health Care Climate Questionnaire; RMSEA: Root-mean-square error of approximation; SDT: Self-determination theory; TPB: Theory of planned behavior; TSRQ: Treatment Self-Regulation Questionnaire; WLSMV: Variance-adjusted weighted-least squares; WRMR: Weighted root mean square residual", "The six-item autonomous motivation subscale from the Treatment Self-Regulation Questionnaire (TSRQ) [33] was used to measure autonomous motivation. The stem of TSRQ items was modified to refer the specific behavior of interest (i.e., \"I want to wear a facemask in an enclosed public place because \u2026\"). Participants responded to items on 7-point Likert scales with 1 (\"not at all true\") and7 (\"very true\") as scale anchors. The Chinese version of TSRQ has demonstrated sufficient validity and reliability [20] .", "Facemask-wearing behavior was assessed at Time 2 during the face-to-face interview. The interviewer disclosed in an offhand manner that they had caught influenza and feigned influenza symptoms. Participants were made fully aware of the availability of facemasks and that they were free to use. The interviewer was trained to observe and record the correct use of the facemasks according to World Health Organization guidelines (i.e., complete coverage of mouth and nose) [5] . The interviewers recorded a 1 (\"yes\") when participants took and used the facemasks correctly and otherwise recorded a 0 (\"no\")." ] },{ "paper_id": "6f9a39f53149621828b62fd7d65513ee915ac30c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "with a boundary condition", "The datasets are reported in a discrete time interval (i.e., year); thus, here I discretized models Eqs. (5) and (6) as", "and" ] },{ "paper_id": "6fa76790be17b5874ff6402f20c43a89e5caaf43", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ref.", "Well tolerated. Increase in spleen and liver mass. [44]", "Rhesus macaques Intravaginal 0.1% gels No change in rental proteome or microbiome [42] " ] },{ "paper_id": "6fa9d1fe1938a48f36f837cec479925de3a69b64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are expressed as mean \u00b1 standard deviation (SD) of at least three replicates, unless stated otherwise. Differences between groups were examined for statistical significance by Student's t-test. A P-value less than 0.05 was considered statistically significant.", "Total RNA from A549 cells was isolated using an RNeasy Mini Kit (QIAGEN, Hilden, Germany) using the protocol supplied by the manufacturer. The cDNAs were synthesized using oligonucleotide primers and SuperScript III RT The following primers were used in this study: b-actin, 5'-GCCGGGACCTGACTGACTACCTC-3' (forward) and 5'-CTAGAAGCATTTGCGGTGGACGAT-3 (reverse); PRSS1, 5'-ATCCAGGTGAGACTGGGAGAGCACA-3' (forward) and 5'-GTAGACCTTGGTGTAGACTCCAGG C-3' (reverse); PRSS2, 5'-CCCCTTTGATGATGATGAC-3' (forward) and 5'-AACTGTTCATTCCCCTCC-3' (reverse); PRSS3, 5'-AGCGAACAGTGGGTGGTATC-3' (forward) and 5'-GGCAGGTGAGGAGAGTTTGA -3' (reverse); IL-1b, 5'-AAATACCTGTGGCCTTGGGC-3' (forward) and 5'-TTTGGGATCTACACTCTCCAGCT-3' (reverse); IL-6, 5'-GTAGCCGCCCCACACAGA-3' (forward) and 5'-CATGTCTCCTTTCTCAGGGCTG-3' (reverse); TNF-a, 5'-CCCAGGGACCTCTCTCTAATCA-3' (forward) and 5'-GCTTGAGGTTTGCTACAACATG-3' (reverse).", "A SYBR Green PCR kit (Roche Diagnostics, Mannheim, Germany) and an ABI 7300 system (Applied Biosystems, Foster City, CA) were used to quantify these genes. The reaction conditions were set at 95\u00b0C for 10 minutes, followed by 40 cycles of 30-second denaturation at 95\u00b0C, 30-second annealing at 58\u00b0C (for b-actin, PRSS1 and PRSS3), 55\u00b0C (for PRSS2) or 60\u00b0C (for IL-1b, IL-6, and TNF-a) and 50-second extension at 72\u00b0C. The relative units were calculated from a standard curve and normalized to that of human b-actin." ] },{ "paper_id": "6fad5703e838cae052bc9cd18b32ea812b942fb4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Poly(rI):poly(rC)-Sepharose pull-downs, SDS-PAGE and western blot Poly(rI):poly(rC) (pI:C) Sepharose pull-downs were performed as described [15] , albeit using transiently-expressed (293T) PR8 NS1-V5 proteins as bait. Nucleo-cytoplasmic extracts were prepared using commercial nuclear and cytoplasmic extraction reagents (NE-PERH, Thermo Scientific, IL, USA). For western blot analysis, lysates were prepared in disruption buffer (6 M urea, 2 M b-mercaptoethanol, 4% SDS), sonicated to shear nucleic acids, and boiled for 5 min prior to polypeptide separation by SDS-PAGE on 4-15% Tris-HCl gradient gels (Bio-Rad Laboratories, CA, USA). Proteins were detected by standard western blot techniques following transfer to polyvinylidene difluoride (PVDF) membranes.", "Stocks of Sendai virus (SeV; Cantell strain) propagated in 10day old embryonated chicken eggs were kindly provided by Silke Stertz (Mount Sinai School of Medicine, USA). Recombinant rPR8 (wild-type, WT) was rescued according to a previously reported protocol [15] , albeit using PR8 RNA expression plasmids. The plaque-purified rescued virus was propagated and titrated in MDCK cells, and the genotype confirmed by RT-PCR and sequencing of the entire NS segment.", "Crystallization, data collection and structure solution/ refinement Data were collected on an in-house rotating anode (RA Micro7 HFM) and a Saturn944 CCD at 100K and processed with HKL2000 [47] . Structures were solved by molecular replacement using PHASER [48] and refined using Refmac5 [49] and PHENIX [50] with manual model building using O [51] and Coot [52] . Figures were created using PyMol [53] ." ] },{ "paper_id": "6fb5ec70b6d25243856c076c05809c2ed9d49bf1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "N-terminally hexahistidine-tagged proteins expressed in pQE30 or pET21a were purified from Escherichia coli TG1 or BL21/DE3/pLysS cells. Single colonies were picked into Luria-Bertani broth and grown at 37 \u2022 C to an OD 600 of 0.6. Protein expression was induced by addition of isopropyl \u2424-D-1-thiogalactopyranoside (to 0.1 mM) and continued for 2 h at 37 \u2022 C (or overnight at 22 \u2022 C) after which cells were pelleted and resuspended in lysis buffer (20 mM Tris, pH 7.5, 20 mM imidazole, 0.5 mM MgCl 2 , 1.4 mM 2-mercaptoethanol, 0.05% Tween 20, 500 mM NaCl, 0.1 mg/ml lysozyme). Cells were incubated on ice for 30 min and sonicated to complete lysis. Protein purification was performed using Ni-nitrilotriacetic acid (Ni-NTA; Qiagen) according to standard procedures (29) . Nterminally glutathione-S-transferase (GST)-tagged nsp1\u2424 was expressed in BL21/DE3/pLysS cells as above and purified using glutathione agarose resin (ThermoFisher Scientific) according to standard procedures (30) . Proteins were dialysed against 50 mM Tris, pH 7.5, 100 mM KCl, 1 mM dithiothreitol (DTT), 0.05 mM ethylenediaminetetraacetic acid (EDTA) and 5% glycerol, quantified by bicinchoninic acid assay (Pierce) and stored at \u221280 \u2022 C until required.", "Details are provided in Supplementary Data.", "Supplementary Data are available at NAR Online.", "In programmed \u22121 ribosomal frameshifting (\u22121 PRF), mRNA signals induce a proportion of translating ribosomes to slip back by 1 nucleotide (nt) into an overlapping open reading frame (ORF) and to continue translation, al-lowing the coordinated expression of two or more proteins from a single mRNA (1) (2) (3) . First described as the mechanism by which the Gag-Pol polyprotein of the retrovirus Rous sarcoma virus (RSV) is expressed from overlapping gag and pol ORFs (4), related \u22121 PRF signals have been documented in many other viruses of clinical, veterinary and agricultural importance (reviewed in Ref. 5 ). PRF has also been increasingly recognized in conventional cellular genes of both prokaryotes and eukaryotes as well as in other replicating elements, such as insertion sequences and transposons (6, 7) ." ] },{ "paper_id": "6fb63e6ddb93b95e451c44a18ca67e506e126c3d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Appendix S1 Detailed syndrome definition for hospitalizations with lower-respiratory infection syndrome. ", "See Appendix S2 for further details on use and settings of the scan-statistics." ] },{ "paper_id": "6fb874a7dee1d36545f8ea3c9714b288dca736e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The association rates (ka), dissociation rates (kd), and affinity constants (K D ) were evaluated using BIACORE 3000 evaluation software using a 1:1 Langmuir binding with a mass transfer model." ] },{ "paper_id": "6fc6b211d30d357b07a3d6de138a6964363ef154", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Second, retroviruses allow passive incorporation of host membrane proteins into virus particles [85] [86] [87] . Most cellular proteins are incorporated into the retrovirus envelope without significant sorting [88, 89] .", "Prenylated Rab acceptor 1 (PRA1), which was identified as a Rab regulatory protein, was reported to be a binding partner for the SIV gp41 CT in a mammalian yeast twohybrid (Y2H) assay [122] . Although colocalization of PRA1 and SIV Env was observed, changes in the endogenous levels of PRA1 did not affect virus production, Env incorporation, or infectivity of SIV or HIV-1 [123] .", "[ ", "First, viral pseudotyping with a foreign glycoprotein can occur easily in many cases although there are some exceptions, one of which is the exclusion of HIV-1 or SIV Env with the long CT from most retrovirus cores [70] . With respect to HIV-1, the virus can be pseudotyped with Env glycoproteins not only from several other retroviruses but also with those from other virus families such as ortho (para) myxoviruses and flaviviruses [71] [72] [73] [74] [75] [76] [77] [78] [79] [80] [81] [82] [83] [84] ." ] },{ "paper_id": "6fc8c1b4cfbd790cbe02c825fd6f9181b1fc6645", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The National Research Ethics Service advised us to treat this study as a service evaluation, exempt from research ethics approval.", "Appendix 2 summarises the sub-themes that emerged within each of our main themes.", "\u2022 Did you find that reassuring or useful?" ] },{ "paper_id": "6fcc000ecf39dd1da69d94d8cd764790ce96aaba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Six to eight week old female Swiss-Webster and C57BL/6 mice were obtained at the Rene Rachou Research Center (FIOCRUZ) in Belo Horizonte, Brazil.", "Animal housing and experimentation were strictly performed according to guidelines set forth by the Institutional Ethics Committee from the Oswaldo Cruz Foundation (FIOCRUZ), Brazil. The protocol of this study (registration number P-4/09-2) was approved by the Institutional Ethics Committee from FIOCRUZ.", "Author Contributions" ] },{ "paper_id": "6fd5ec9e4ec79f24c0bf011e388410d8ec35fe0f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Introduction Allogeneic stem cell transplantation (alloSCT) has been established as an important treatment modality for patients with hematological malignancies, aplastic anemia, and inborn errors of hematopoietic progenitor cells. Nevertheless, major lethal and non-lethal complications still prohibit a broader application of alloSCT." ] },{ "paper_id": "6fdb54d00b9abc340c37abe6fe840458a8eab54b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Here we report the presentation and clinical course of a UTI in a dog due to P. acnes infection.", "Our case was diagnosed as emphysematous cystitis (EC), a rare type of UTI, based on several diagnostic imaging techniques. EC occasionally occurs in diabetic dogs [12] but is relatively rare in nondiabetic dogs [13] . EC results from an infection by gas-producing bacteria, including E. coli, Proteus spp., Aerobacter aerogenes, and Clostridium spp. [14] . While P. acnes has not been reported to cause EC in dogs previously, gas production was noted in a human with P. acnes infection [15] . Thus, P. acnes should be regarded as a gas-producing bacterium and a potential cause for EC in dogs.", "Urinary tract infections (UTIs) are either temporary or permanent breaches in host defense mechanisms that allow microbes, mainly bacteria, to adhere, multiply, and persist within the urinary tract [5] . The main clinical features of UTI are dysuria, pollakiuria, and hematuria. These are most commonly caused by Escherichia coli; other uropathogens include Gram-positive cocci, Proteus spp. Klebsiella spp., Pasteurella spp., Mycoplasma spp., Enterobacter spp. and Pseudomonas spp. [6] . However, P. acnes has not been previously reported as a causative agent of UTI in dogs.", "A 6-year-old female Japanese Shiba Inu was hospitalized in November 2014 for polyuria, polydipsia, severe hematuria, loss of appetite, weight loss, and lethargy. She had a recent history of hospital visits for cholestasis and hemorrhagic diarrhea due to severe whipworm infection. The owners granted permission for the publishing of this case report." ] },{ "paper_id": "6fe01cb9f2b36418bd0f5a17bc665e2e02fd2460", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additionally, Ang-(1-7) was found to inhibit neuronal activity in BP regulatory centers [62] through preventing norepinephrine release [63] , inhibiting activity and expression of tyrosine hydroxylase [64] and activating hyperpolarizing I Kv in catecholaminergic neurons in a NO-dependent manner [65] , which may also contribute to its antihypertensive effect.", "Atherosclerosis represents the most common cause of ischemic stroke [66] . It is now widely agreed that endothelial dysfunction and proliferation of VSMC are involved in the development of atherosclerotic plaques, and rupture of atherosclerotic plaque usually triggers plaque thrombosis, blocking the cerebral arteries and leading to the ischemic stroke [67] .", "The author(s) confirm that this article content has no conflict of interest." ] },{ "paper_id": "6fe5d96d6e7a93c94a8788af735bdc919cd8d71d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasmid ADAMTS13 containing human full-length cDNA sequence was generously provided by Dr. Jingfei Dong (Baylor College of Medicine, Houston, TX, USA) [24] . Recombinant ADAMTS13 (rADAMTS13) with the C-terminal His-tag was expressed in a stably transfected HeLa cell line. Expression medium was concentrated and purified using a Ni-NTA agarose column (QIAGEN GmbH, Hilden, Germany).", "Plasma-derived human VWF (pVWF) was purified from commercial VWF/FVIII concentrate by gel filtration with a Sepharose 4B-CL column (Amersham Pharmacia Biotech AB, Uppsala, Sweden) and heparin-Sepharose 6FF (Pharmacia) affinity chromatography, as reported [22] . VWF antigen (VWF:Ag) concentration was determined by an enzyme-linked immunosorbent assay (ELISA) kit from Dako (Glostrup, Denmark) and VWF multimers analysis was performed as reported [23] .", "Heat treatment and denaturization treatment with guanidine-HCl were used to unfold recombinant VWF fragments and pVWF. Purified pVWF was denatured by heating at 80uC for 20 min in a thermo-block heater (ThermoStat Plus, Eppendorf) as reported [32] .", "The cleavage reactions were measured by the distribution of proteolytic fragments (350 kDa) on a 5% SDS-PAGE under nonreducing condition or by VWF multimeric size distribution on a 1.5% agarose gel electrophoresis, and then analyzed by Western blotting with HRP-conjugated anti-VWF IgG (Dako) and visualized by chemiluminescence as reported [23, 30] . The intensity of the bands was analyzed using Image J software. Plasmids encoding different VWF fragments were all generated from pSVHVWF1 [29] ." ] },{ "paper_id": "6fe7dbbe77090cf3a1ac5ce68b0aca877c08dd71", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "6fea71c8f426d1dd72886aeca6e4f7c1c98f21fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Substituting the expressions for P i ( m) and \u03be( m + d m i ) in Eq. (1), the extinction coefficient becomes:", "If the rate of the i th reaction is defined as a i such that", "." ] },{ "paper_id": "6fecfe80a5c76339823ebe9f93f69eb8388cc882", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleic acid was extracted from the samples using QIAamp MiniElute Virus Spin kits (Qiagen, Mississauga, Ontario, Canada) following the manufacturer's protocol. cDNA was synthesized from 10 \u03bcL RNA eluted using the Promega Reverse Transcription System with random hexamer primers and avian myeloblastosis virus reverse transcriptase (Promega, Madison, WI, USA) as described previously [15, 16] .", "Statistical differences were determined using the Chisquare test using SAS software (version 9.2). P-values < 0.05 were considered to indicate statistical significance." ] },{ "paper_id": "6ff089187feaca34bce964cc052bd1fa0f016d40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These events can become chronic if the proinflammatory environment is not regulated. If not regulated, the response would involve the participation of other immune cells, other signaling pathways, and other patterns of gene expression. The persistent influx of immune cells from the systemic circulation as neutrophils, macrophages, lymphocytes, basophils, and eosinophils is correlated with additional elevation of proinflammatory cytokine levels and neural tissue destruction that would unavoidably make tissue recovery more difficult [108, 160, 161 ].", "The mechanical reduction of the superoxide anion mediated by NAD(P)H oxidases causes the anion to react with NO and form a neurotoxic compound known as peroxynitrite [73] . At physiologic pH, peroxynitrite first reacts with proteins and phospholipids and then breaks down into other cytotoxic products such as NO \u2022 , nitrogen dioxide (NO 2 ), and OH \u2212 radicals.", "Cord Injury", "One of the degradation products of peroxynitrite, NO \u2022 , alters the mitochondrial electron transport chain and induces the production of FR. These molecules have direct deleterious effect on enzymes with iron-sulfur clusters in their catalytic core, such as ubiquinone succinate [82] ." ] },{ "paper_id": "6ff529e1f29ef13037ef1117086082db53d12691", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sensitivity \u00bc TP TP \u00fe FN \u00f04\u00de" ] },{ "paper_id": "70068338c7b42c6afe98139eadbf9b150a0d1af1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "702157bbe24c5eca7ab92f90cd717c3e56aa6ccf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Below we illustrate the detailed implementation methods for building an indoor contact network.", "Distribution of domestic household size, assuming a maximum of seven household members", "Mechanical ventilation 1" ] },{ "paper_id": "7025d7269f1bc09bfb96f51de30e2e0309a3fadc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Overall our data supports a potential role for viruses in AOM, particularly HAdV, encouraging prospective studies and clinical trials to better understand the role viruses might have in endemic OM." ] },{ "paper_id": "702d0144bdeae0782bbebcbe41d432fa7ae41415", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Jena Virus (JV), a bovine Norovirus, causes enteric disease in cattle and represents a potential model for the study of enteric norovirus infection and pathogenesis. The positive sense RNA genome of JV is organised into ORF1 (nonstructural proteins), ORF2 (major capsid protein) and ORF3 (minor capsid protein). The lack of a cell culture system for studying JV replication has meant that work to date has relied upon in vitro systems to study non-structural protein synthesis and processing.", "In vitro coupled transcription and translation was performed using the TNTH Coupled Reticulocyte Lysate System (Promega) as per the manufacturer's instructions. Reactions were incubated at 30uC for 1-2 hr. For non-radiolabelled reactions the 35 S-Methionine was replaced with 1 mM unlabelled Methionine (2 ml). Reaction products (1-2 ml) were analysed by SDS-PAGE. Gels were stained and prepared for autoradiography by incubating for 30 min in a solution containing 32 g sodium salicylate, 100 ml methanol and 100 ml dH 2 O. Gels were dried under vacuum and the reaction products were detected by exposure to Kodak X-Omat scientific imaging film (Sigma) at 270uC for 16 hr followed by developing using a Kodak automated developer.", "A comprehensive study of polyprotein processing within the murine norovirus (MNV) suggests likely identities for the equivalent proteins in the similar profile for JV [12] . Using region specific antisera the authors were able to identify p110 as the 3ABCD uncleaved precursor, p90 as the 3BCD, p57.5 as the 3D-like polymerase, p52 as a 3ABC precursor and p40 as the 2Clike NTPase, which was determined by mutagenesis and microsequencing experiments. The 19 kDa protein was identified as the 3C-like protease. The antisera used to detect the MNV Nterm protein recognised 3 products; one was the predicted molecular weight at 39 kDa and the other two bands migrated as a 45 kDa doublet.", "Human norovirus infection has been shown to be the leading cause of non-bacterial gastroenteritis [31] , however there is currently no cell culture system available to facilitate viral replication and ethical considerations have hindered progress in establishing a permissive human organ culture system. The study of Jena virus offers a potential animal model of enteric noroviral infection. However, until a permissive bovine cell and/or organ culture systems is established analysis of the molecular mechanisms underpinning viral replication and pathogenesis rely upon in vitro systems, most notably polyprotein synthesis and processing." ] },{ "paper_id": "703744c49c4908516297844dee0ba03affc36a74", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Determination of protein concentration. The protein content was determined via tryptophan fluorescence measured with a microplate reader (Tecan Infinite \u00ae M1000 PRO) 17, 52 . Briefly, 3 \u03bcL of lysate were mixed with 197 \u03bcL of 8 M urea in 50 mM Tris pH 8.5 (UA) and the fluorescence was measured at 350 nm with 295 nm excitation in a white opaque 96-well plate. The tryptophan content was determined by measuring a tryptophan standard curve ranging from 0.1 to 0.9 \u03bcg of tryptophan. Calculation of protein content was performed by assuming a tryptophan weight content of 1.3% for virus 17 ", "Determination of viral GE. Viral DNA was isolated from 5 \u03bcL of purified virus suspension or from 200 \u00b5l of HeLa supernatant using the PureLink \u00ae Viral RNA/DNA Mini Kit (Life Technologies) according to manufacturer's instructions. DNA was eluted in 50 \u00b5l of RNase-free water and viral GE were quantified using an OPV real-time PCR assay 51 . By measuring plasmid standards in the range of 10 1 to 10 6 copies per reaction the amount of GE was calculated." ] },{ "paper_id": "703b5f4019a1c215901309bcabddba33738c506a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Limit of detection 95% (LoD 95% ) was determined by probit analysis with a 95% confidence interval (95% CI) by using the SPSS v14 (SPSS, Chicago, IL, USA). Kappa analyses was used to assess interrater agreement. ", "Nucleic acid was extracted from the cell culture supernatants for specificity testing." ] },{ "paper_id": "70419bf8c8f69f99d3127967e958ead655296b3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Authors' contributions RJW, LXZ conceived and designed the experiments; ZHC, JYH, and JQL performed the experiments; HYW, JFZ, ZJZ, and NNL analyzed the data; ZHC, RJW, and LXZ wrote the manuscript. All the authors have read and approved the final version of the manuscript.", "Cryptosporidium-positive samples were determined by microscopy and stored in 2.5% potassium dichromate at 4\u00b0C prior to DNA extraction.", "The authors declare that they have no competing interests.", "During specimen collection, all animal experiments were conducted in accordance with the Chinese Laboratory Animal Administration Act 1988.Prior to experiment, the protocol of the current study wasreviewed and approved by the Research Ethics Committee of Henan Agricultural University (License no. 2014-018)." ] },{ "paper_id": "7045ec55df870b7d611154081ae7e469883f64c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Aurintricarboxylic acid (ATA), amantadine hydrochloride (AH), and N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (NAA) were from Sigma (St. Louis, MO, USA). Stock solutions of each drug were prepared immediately before use in dimethyl sulfoxide (DMSO) and filtered using a 0.22 nm filter." ] },{ "paper_id": "704a894ab79031263de39fc49d954f7d13aa1bf2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Anti-FCoV antibody titers in feline serum samples were determined by IFA using porcine kidney-15 (PK-15) cells and porcine transmissible gastroenteritis virus (TGEV) [19] . In brief, PK-15 cells were inoculated with TGEV at a multiplicity of infection of 10 plaque forming units (PFU)/cell and incubated for 8 h at 37\u00b0C. PK-15 cells were trypsinized, mixed approximately half-andhalf with uninfected cells, and seeded into wells of eight-well glass plates (Nutacon, Amsterdam, The Netherlands). Cells were incubated for 60 min at 37\u00b0C with serial two-fold dilutions of serum samples in phosphate buffered saline (PBS), washed three times for 5 minutes, and incubated for 1 hour with fluorescein isothiocyanate-conjugated goat anti-feline immunoglobulin G (KPL, Gaithersburg, MD).", "Korean FCoV sequences from this study and 30 sequences from global FCoV isolates obtained from GenBank were aligned using the Clustal X 1.83 sequence alignment program [21] . Nucleotide and amino acid sequence identities among the Korean FCoV isolates were calculated using BIOEDIT 7.053 [22] . The phylogenetic tree was created by a neighbor-joining method using MEGA 4.0 software [23] .", "Feline serum and fecal swab samples were collected from 212 cats consisting of 107 samples from six local animal hospitals (four in Seoul and two in Kyunggi) and 105 samples from two animal shelters (Incheon and Daejeon) in 2009. Of the 212 samples, 129 were from clinically healthy cats and 83 were from cats displaying symptoms of illness that included inappetence, anorexia, weight loss, lethargy, icterus, fever, diarrhea, and thoracic effusion." ] },{ "paper_id": "704daa0a70b4f0c0ba3c8f723b27396877dca38b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Blood cells were subjected to DNA extraction by treating them first with 0.5% SDS lysis buffer and then protease K (1 mg/mL) for digestion of nuclear protein for 4 h at 60 \u2022 C. Using the Gentra extraction kit followed by 70% alcohol precipitation, total DNA was harvested.", "KD: Kawasaki disease IVIG: Intravenous immunoglobulin CAL: Coronary artery lesions.", "Analysis. JMP 9.0 for Windows was used for analysis. The statistical differences between case and control in genotype and allele frequency were assessed by the \u03c7 2 -test. Statistical differences in genotype and allele frequency of KD patients with/without CAL formation were assessed using the \u03c7 2 test. Linkage disequilibrium (LD) was assessed for one pair of SNPs, and haplotype blocks were defined using the default setting of the Haploview software 4.1 (Broad Institute, Cambridge, MA, USA)." ] },{ "paper_id": "704eebd9653b61d2dfbe1483d1a616e6836eeec8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords: sputum, homogenization, nucleic acid, purity, concentration, influenza A virus", "Each included specimen was collected into three EP tubes separately (500 \u00b5l per tube) by using a disposable pipette after vortex. Each tube of specimens was preprocessed with NS, DTT (Sputasol Liquid, France), and PK ( Figure 1) . Then, 200 \u00b5l of specimens was taken to extract nucleic acids.", "Data were statistically analyzed with Excel 2007 and SPSS 18.0. The Ct values among the three groups were compared through one-way ANOVA. Comparison between two groups was tested by LSD. The measurement data of abnormal distribution were described by median (M) and quartile (P25-P75) and subsequently evaluated through nonparametric Kruskal-Wallis test. P < 0.05 indicated significant differences." ] },{ "paper_id": "70542f1f1a2ced1e26658f62372e882da4c2b366", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "7072f43043b3cbcaffc357902409ece63bc6f828", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We are also using next-generation-sequencing technologies, such as transcriptome sequencing (RNAseq) and selective 2=hydroxyl acylation analyzed by primer extension (SHAPE) analysis of RNA, to investigate RNA structure-function correlations. Paired with these analyses, we are investigating the RNA transcriptome to correlate conserved and unique RNA structure elements with pathogen virulence factors, identify previously uncharacterized and/or rare translation initiation sites, and associate protein structure elements with virus biology, pathogenesis, and host range.", "As described above, we have used a multipronged investigation strategy to directly evaluate unknown and hypothetical genes from a diverse array of pathogens to characterize the biological functions encoded by these genes (Table 1) . A particular strength of this approach is that this systematic workflow, which can be adapted to all pathogens with sequenced genomes, can ensure rational, directed, and rapid response times for vaccine and therapeutic design in answer to emerging and reemerging epidemics. The work of this program is defining a future blueprint to perform functional analysis of new pathogens as they emerge and to more rapidly respond to the need for knowledge of emerging organisms. ", "Genetic approaches: identifying phenotypes. We are using multiple strategies to identify phenotypes that are associated with the deletion or overexpression of target genes of unknown function. For bacterial pathogens, we have initially focused on genes that, when disrupted, produce measurable growth phenotypes or alterations in cellular barrier function under specified conditions, including antibiotic treatment. These assays are facilitated by wholegenome-mutant defined mutant libraries that allow more efficient high-throughput screening for specific phenotypes (10) ." ] },{ "paper_id": "70748788b2a175a08f02878c528efbd024a45064", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The differences among different treatment groups were analyzed and compared by one-way analysis of variance (ANOVA), followed by a least-significant difference test, using the statistical package SPSS ver. 17.0 for Windows. A value of P < 0.05 was considered statistically significant." ] },{ "paper_id": "707a1297b8ac950819a217102e5f4847a67b48c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Within viral families, both positive and negative correlations are seen with genome size", "Weak overall tendency for smaller viral genomes to be more disordered", "where " ] },{ "paper_id": "7080c264017e67e26a1e222507314d891b13e3f9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "7081473cf95db2a82c1960a38625593cab0dc0f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In this commentary, we elaborate on the main points that Karamouzian and colleagues have made about HIV data scarcity in Middle Eastern and North African (MENA) countries. Without accessible and reliable data, no epidemic can be managed effectively or efficiently. Clearly, increased investments are needed to bolster capabilities to capture and interpret HIV surveillance data. We believe that this enhanced capacity can be achieved, in part, by leveraging and repurposing existing data platforms, technologies and patient cohorts. An immediate modest investment that capitalizes on available infrastructure can generate data on the HIV burden and spread that can be persuasive for MENA policy-makers to intensify efforts to track and contain the growing HIV epidemic in this region. A focus on key populations will yield the most valuable data, including among men who have sex with men (MSM), transgender women and men, persons who inject drugs (PWIDs), female partners of high risk men and female sex workers.", "Throughout the history of the HIV/AIDS pandemic, key populations-including PWIDs, MSM, transgender populations, and female sex workers-have been subject to discrimination, stigmatization and criminalization. These policies drive away stigmatized subgroups and make it harder to engage them in the vital therapeutic and prevention alliances that enable implementation of successful health programs. Just as some health ministries outside the MENA region have adopted best practices from countries like Iran and Morocco, 5 the MENA region could also learn lessons from countries with similar cultural conditions on how to best engage and reduce high-risk behaviors among key populations within their borders. One notable example comes from Nigeria, where homosexuality remains criminalized, 19 yet also has well-established programs that collect data from and provides services to MSM populations. 20 Given the cultural climate and standing laws in Nigeria, it is not surprising that this group has been difficult to contact, trace and recruit into research and treatment cohorts. Hence, researchers and public health practitioners have recruited key community leaders to lead the outreach efforts to members of their communities. It is likely that, in MENA countries, high-risk social and sexual networks are also best accessed and followed with the help of community leaders and/or peers already integrated into these networks; and that these efforts can be best operationalized with respondent-driven sampling, snowball sampling strategies or post-testing counseling of newly diagnosed persons.", "MENA investigators have shown that both key HIVuninfected, vulnerable populations and HIV-infected persons can be studied with modern field and clinical methods. Prospective follow-up is feasible, molecular phylogeny is obtainable and interpretable for understanding transmission dynamics and surveillance can guide improved policies. [21] [22] [23] [24] [25] [26] History teaches time and time again that epidemics ignored are epidemics unleashed. A dearth of relevant data will simply misrepresent the true epidemic profile, misleading public health and clinical practitioners and policy-makers. Europe and North America, with decades of HIV successes and failures, can be allies, given their imperative to support global health for both humanitarian and self-serving interests. 27 It has become clear that no region, no culture, and no population is immune to the emergence and expansion of an HIV epidemic. Despite bold claims in the past that HIV/AIDS is not a problem for predominantly Muslim nations, all indicators have pointed to rising HIV incidence and mortality, both in absolute numbers and in relation to the rest of the world. In the current commentary, we have elaborated on the argument made by Karamouzian et al that a key measure for preventing a concentrated epidemic from becoming a disseminated one is to intensively and consistently collect population-based data. 2 Although recognition and characterization of a problem is the first step toward its resolution, it is meaningless if that knowledge does not translate into action. Action starts with active surveillance efforts and meaningful investments into regional networks and national programs, such as those that have been outlined in the course of this commentary. Efficiencies can evolve from repurposing existing tools, using translatable data-collection platforms and partnerships and adopting best surveillance practices. The story of HIV can be traced along a convoluted path of both maladaptive decisions and farsighted strategies. MENA countries have the opportunity now to move from the former to the latter, turning the tide of a potentially worsening public health crisis." ] },{ "paper_id": "708330752dfbcdd2731c67c7ed3263d1a911241e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tissues were scored using the following scale: 0 = no apparent pathology/change, 1 = minimal change (minimally increased numbers of small lymphocytes, plasma cells, macrophages, and/or mast cells), 2 = mild change (mild inflammation, edema, and/or parafollicular expansion, secondary follicle formation, and presence of tingible body macrophages within lymph nodes), 3 = moderate change (as previously described, but more extensive), 4 = marked changes (as previously described, but with severe inflammation, edema, and/or lymphoid reactivity).", "Tissue N4 FFV1 FFV2 FFV3 FFV4 FFV5 Total Cats Salivary gland - - - - - - 0 Tongue - - - - - - 0 Oral Mucosa - - - 2.4 Ileum - - - - - - 0 Bone marrow - - - 6.10 \u00d7 10 2 - - 1 Kidney - - - - - - 0 Muscle - - - - - - 0", "Supplementary Materials: The following are available online at http://www.mdpi.com/1999-4915/11/7/662/s1, Table S1 : Antibody marker combinations used for PBMC phenotype analysis through flow cytometry. Table S2 : FFV prevalence and chi-square analysis data for CKD studies. " ] },{ "paper_id": "70943b05f17f2b7620ca6cc063b95ba2d7e8aab3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chicken embryo fibroblast (DF-1) and African green monkey kidney (Vero) cell lines, obtained from the American Type Culture Collection (ATCC, Manassas, VA), were grown in Dulbecco's modified Eagle medium (DMEM) containing 10% fetal bovine serum (FBS) and maintained in DMEM with 5% FBS.", "All the experiments where 9-day old embryonated chicken eggs were used ended on or before day 13. Before collecting allantoic fluid from the eggs, the embryos were sacrificed by incubating the eggs at 4uC in a refrigerator for 2 hour.", "Nine APMV strains were used in this study (see Table 1 ), all of which had been constructed in previous work: (i) biologicallyderived wt APMV-2 strain chicken/Yucaipa/California/56 [8] ;" ] },{ "paper_id": "70945e1b77b2dd46582a7d73d30746432f209f0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 If schools/nurseries were closed or other childcare services were disrupted.", "\u2022 If your spouse/partner fell ill." ] },{ "paper_id": "70948646d2777b7a433c7558b5c3488bdb77e526", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although it is an unusual chymotrypsin-like cysteine protease, 3C pro adopts a fold similar to that of the serine protease chymotrypsin; indeed, 3C pro combines features of both serine and cysteine enzymes. Structural studies on picornaviral 3C pro may identify unique features, providing useful information on protease inhibitors." ] },{ "paper_id": "70adc25ffcec7b3d1871ea866658c3cd01080f49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical calculations were performed with STATIS-TICA ver. 10 (StatSoft, part of Dell Software, USA). For correlation analysis, Spearman r correlation coefficients and P-values were determined, since these values were not distributed normally.", "Porcine reproductive and respiratory syndrome (PRRS) is a viral disease of significant economic impact on a swine industry worldwide. Clinically the disease manifests by reproductive disorders in sows and respiratory lesions and poor growth performance in growing pigs. The etiological agent of the disease, PRRS virus (PRRSV) is an enveloped, positive-sense single-strand RNA virus classified in the order Nidovirales, family Arteriviridae. Two genotypes, Type 1 and Type 2, sharing approximately 60% of genetic similarity were described [1] . A newly proposed classification denotes both types as different species within Arteriviridae family (https ://talk.ictvo nline .org/taxon omy/). Type 1 can be further divided into at least four genetic subtypes, namely Pan-European subtype 1 and subtypes 2, 3 and 4 represented by strains circulating in Eastern European countries [2] . Gathering evidences suggest the existence of additional 1 3 subtypes. However, the genetic subtyping based on a small genomic fragment of ORF5 and ORF7 can be affected by genetic recombination [3] [4] [5] .", "PRRSV shows a remarkably high degree of genetic variation translating into high antigenic and pathogenic variability. High frequency of recombinations also contributes to occasional changes of biological properties and virulence level [6, 7] . The most striking example is a highly pathogenic Type 2 PRRSV variant with 30 aa discontinuous deletion within nsp2 protein that emerged in 2006 in China devastating swine industry in several Asian countries [8, 9] . Recent animal infection studies indicated that some East European strains of PRRSV Type 1 have been characterized by higher pathogenicity compared to the mild syndrome produced by infection with subtype 1 [10] [11] [12] .", "Comparison of the pathways associated with up-or downregulated genes between groups of animals infected with particular PRRSV strains revealed some difference indicating that particular strains may utilize variable mechanism to interact with the host." ] },{ "paper_id": "70afb22f932f20c402dd57e6b09ea9c658a1b3a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Over half (58.6%; 174/297) of the 297 interviewed cohort members reported recent occupational injuries that induced bleeding while working with the animals ( ", "Raw animal blood is commonly consumed in Vietnam as a dish named ''tiet canh.'' Almost a quarter (24.6%; 73/297) of interviewed cohort members reported the consumption of raw blood, and over a third (37%; 110/297) had consumed raw mammal or bird meat within the year prior to interview ( ", "The ethics boards of Dong Thap Hospital, Dak Lak Hospital, the Sub-Departments of Animal Health in Dong Thap and Dak Lak, and the Hospital of Tropical Diseases in Ho Chi Minh City provided ethical approval for this study. The protocol associated with HRSC study was additionally approved by the Oxford Tropical Research Ethics Committee (OxTREC) in the UK." ] },{ "paper_id": "70b27df77b5f3ef4c9be9028cc34110d4dd7d22b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clarified PRV3M virus-containing supernatant was overlaid on 2 ml of 20% sucrose in an ultra-clear centrifuge tube (Beckman coulter) and was centrifuged at 125,000 \u00d7 g for 90 min (SW41 rotor in Opitma XPN-100 ultracentrifuge). After centrifugation, the supernatant was gently removed and the pellet was resuspended with DPBS (Invitrogen) and stored in \u221280\u00b0C.", "Pteropine orthoreoviruses (PRVs) are a group of emerging bat-borne viruses, belonging to the genus Orthoreovirus within the family Reoviridae. PRV virions are non-enveloped, fusogenic, and contain doublestranded RNA genomes with ten segments (S1, S2, S3, S4, M1, M2, M3, L1, L2 and L3).", "Quantitative PCR (qPCR) was performed using Quan-tiTect Probe RT-PCR Kit (Qiagen) reagents and with the CFX96 Real-Time System (Bio-Rad). Each 25 \u00b5L PCR reaction contained 12.5 \u00b5L 2X QuantiTect PCR master mix, 1 \u00b5L of each 10 mM primer, 0.5 \u03bcL 0.2 mM probe, 0.5 \u03bcL reverse transcriptase, 3 \u00b5L RNA template and 6.5 \u00b5L H 2 O. Every PCR was performed as follows: reverse transcription at 50\u00b0C for 10 min, initial PCR activation at 95\u00b0C for 5 min and 45 amplification cycles consisting of a 95\u00b0C denaturation for 10 sec and a 60\u00b0C annealing/extension for 30 s. Sequences of primers and probes are as follows; PRV3M-S4-F: 5 \u2032 -CAT TGT CAC TCC GAT TAT GG -3 \u2032 , PRV3M-S4-R; 5 \u2032 -TGG GAG GGT GCA GAG CAT AG -3 \u2032 , PRV3M-S4-probe5 \u2032 -/56-FAM/ GTA GGC ATG CCG CTC GTG GAA TCC A /3BHQ_1/ -3 \u2032 . Each PCR was performed in duplicate to obtain an average Ct for each sample. Amplicons were quantified by plotting the Ct values against standard curves made using 10-fold dilutions of cDNA " ] },{ "paper_id": "70b6d8307a4bba54b599dc35cec46f521fe6f2ac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "70bae0f6fbce9a54e7574b4309c5a3ebd1be7133", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 5:14753 | DOi: 10.1038/srep14753 technique is very simple and highly sensitive; hence provides a tool for HTS of antivirals. Moreover, the in vitro assay is very convenient and does not need BSL2 or BSL3 containment.", "SCIEnTIfIC REPORTS | 5:14753 | DOI: 10.1038/srep14753 3D model generation. Homology modeling was performed for active CVCP in the following steps:", "Preparation of CHIKV stocks. An Indian isolate of Chikungunya virus, DRDE-06 (Genbank accession no: EF-210157.2) belonging to East Central and South African (ECSA) genotype maintained at Virology Division, DRDE, Gwalior was used in the present study. The C6/36 cells (Aedes albopictus larval cell line) was obtained from National Center for Cell Science (NCCS), Pune. The cells were cultured in Eagle's minimum essential medium (EMEM) supplemented with 10% tryptose phosphate broth (TPB), 10% fetal bovine serum (FBS), 80 U gentamicin, 2 mM L-glutamine and 1.1 g/L sodium bicarbonate (NaHCO 3 ). Briefly, monolayer of cells were grown at 90% confluency and washed with plain medium prior to infection. The virus was allowed to adsorb to the cells for 1 h at 37 \u00b0C in serum-free medium. Following adsorption, the inoculum was removed by washing once with Dulbecco's phosphate-buffered saline (D-PBS) and replenished with maintenance medium (EMEM-TPB with 2% FBS). The culture medium was harvested on appearance of cytopathic effects after 48 h post infection. Aliquots were stored in a \u2212 80 \u00b0C freezer. RNA extraction. Viral RNA was isolated from 140 \u03bc l of the clarified infected culture supernatant using QIAamp viral RNA mini kit (Qiagen, Germany) according to manufacturer's protocol. The viral RNA was quantified, aliquoted and stored at \u2212 80 \u00b0C up to use. Molecular cloning and construction of expression plasmid. The obtained RNA was denatured at 70 \u00b0C for 5 min and chilled on ice. The first strand cDNA was synthesized using oligo(dT) 30 primer with M-MulV reverse transcriptase at 37 \u00b0C for 1 h. The primers for recombinant DNA cloning were designed according to the sequence provided in NCBI (National Center for Biotechnology Information) ( Table 1) ." ] },{ "paper_id": "70bf84100e6157f3815acca7b5120131c0f8cf4e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The aged mice showed higher clinical severity which is coincident with attenuated production of virus-specific antibody and IFN-\u03b3 and increased IL-4 expression [251] .", "The cotton rat has recently been used to model HRV infection. In the cotton rats, major group strains HRV-A16 and HRV-B14 infect and replicate better than minor group HRV-A1B [6, 7] . The receptor employed by these major group HRVs has not yet determined. Of note, currently, there is no available animal model for HRV C strains.", "In addition to acute respiratory infection, cases of AFM were reported coincident with the 2014 EVD-68 outbreak [146, 147] . The paralysis occurred primarily in children and many of them experienced respiratory illness before the onset of the limb weakness. A case-control study from the 2014 AFM cases in Colorado suggested an association of EV-D68 [148] ." ] },{ "paper_id": "70c53ce121228fdd6ba78b20f143736b56f71984", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Twenty five EAE mice and five na\u00efve control littermates underwent in vivo DTI with isoflurane/oxygen anesthesia (5% induction and 1% maintenance) delivered by a custom nose cone that also allowed respiratory-gated acquisition. The mice were placed in a custom holder designed to immobilize the spine and isolate respiratory motion. An actively detuned radiofrequency transmit coil (6 cm internal diameter \u00d7 10 cm length) was used with a receiver coil (16 mm internal diameter \u00d7 9 mm length) designed to fit around the spine of the mouse. The entire preparation was placed in an Oxford Instruments 200/330 magnet (4.7 T, 40 cm clear bore) equipped with a 20 cm innerdiameter, actively shielded Magnex gradient coil (up to 60 G/cm, 280 \u03bcs rise time). Core temperature was maintained at 37\u00b0C with circulating warm water. The magnet, gradient coil, and gradient power supply were interfaced with a INOVA console (Varian NMR Systems, Palo Alto, CA) controlled by a Sun Blade 1500 workstation (Sun Microsystems, Santa Clara, CA)." ] },{ "paper_id": "70c7a787bebc60a3c5e63f7f8409b8be92960964", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All research chemicals and solvents were purchased from Sigma-Aldrich (Sigma-Aldrich, Saint-Quentin-Fallavier, France) and were used as such for the reactions. The progress of all the reactions was monitored by thin-layer chromatography (TLC) using glass plates precoated with silica gel-60 F254 to a thickness of 0.5 mm. The melting points were taken in an open capillary tube using an Electrothermal melting point apparatus (Electrotermal, Rochford, Great Britain). The values are reported in \u2022 C and are uncorrected. NMR spectra were recorded with a Bruker Avance 300 spectrometer (300 MHz ( 1 H) and 75 MHz ( 13 C)) (Bruker Biospin GmbH, Rheinstetten, Germany). Chemical shifts are expressed in parts per million (ppm) downfield from using tetramethylsilane (TMS). Data are reported as follows: chemical shift (multiplicity (s: singlet, d: doublet, dd: double doublet, ddd: double double doublet, dm: double multiplet, dt: double triplet, t: triplet, td triple doublet, tm, triple multiplet, tt: triple triplet, q: quartet, quint: quintuplet, m: multiplet, br: broad), coupling constants (J) in Hertz, integration). All the compounds gave satisfactory elemental analysis within \u00b1 0.4% of theoretical values.", "Pure heteropolyacids H n XM 12 O 40 (PM 12 ) were prepared by the standard method involving the synthesis of the corresponding sodium salt and the extraction of acid by diethyl ether and its purification by crystallization in water at 4 \u2022 C [38] .", "The POMs, particularly the heteropolyacids (HPAs), having the Keggin structure, have received much attention for organic synthesis. They are soluble in all the solvents, which allows for the recovery of the synthesized product by simple filtration [28] . Thus, HPAs offer a strong option for efficient and cleaner processes compared to polluting and corrosive liquid acid catalysts, such as mineral acids. Effectively, in previous works, HPAs showed excellent catalytic activities in several reactions as the synthesis of substituted 1,4-diazepines and 1,5-benzodiazepines [29] , 4(3H)-quinazolinones [30] , calix [4] resorcinarenes [31] , and 3,4-dihydropyrimidinones [32] ." ] },{ "paper_id": "70d09fb4f3c4d083724543f4d885d904ea69a5d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Depending upon the clinical manifestations and epidemiological link, 81 cases were included in the study (S1 Data). Of them 45 were male and 36 were female, with age ranging from 14 months to 81 years (mean age: 49 \u00b1 14 years) ( Table 1) .", "To conclude, despite the lack of nasal carriage and lower transmission rate of this virus; higher incidence of morbidity and mortality and recent outbreak in South Korea with devastating outcome demands continuous monitoring and further investigations to ensure public health security. ", "OPEN ACCESS" ] },{ "paper_id": "70da3ee5739197acb1879c1d23606681aaac2e1c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical comparisons were performed using GraphPad Prism 5 (GraphPad Software Inc., San Diego, CA, USA). The results are presented as the mean \u00b1 SEM. Two-way ANOVA analysis was used to analyze the statistical significance among multiple groups and unpaired Student's t-test between two groups. Statistical significance is indicated by p values of > 0.05 (non-significant, ns), < 0.05 (*), 0.01 (**) or 0.001(***).", "A total of 12 six-week-old specific-pathogen-free (SPF) White Leghorn chickens, half females and half males, were purchased from Guangdong DaHuaNong Animal Health Products Co., Ltd (Guangzhou, China) and housed under pathogen free conditions. Laboratory ALV-J strain SCAU-HN06 was kindly provided by Prof. Weisheng Cao, South China Agricultural University. All animal experiments were performed with approval and guidance from South China Agricultural University Institutional Animal Care and Use Committee." ] },{ "paper_id": "70f03de789f72ae5b9709cb6bef62c10ab8dcdef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After giving written informed consent the patients were enrolled. The study was approved by The Regional Ethical Review Board in Stockholm that handles applications for research at Karolinska University Hospital.", "Positivity by either method was used as gold standard for presence of viruses. Cohen's kappa was calculated as a measure of agreement of the results obtained from either method [17] . Wilcoxon signed-rank test and Pearson's correlation coefficient were used when appropriate. Age is presented as means \u00b1 SD, whereas neutrophil count is presented as median followed by range. A p-value < 0.05 was considered significant. InStat 3.05 and Prism 5.00 for Windows were used." ] },{ "paper_id": "70f3c90a651224f9292378da905af4ec635d5f43", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Please see Additional file 1 for translations of the abstract into the six official working languages of the United Nations.", "The growing public health concern and the burden of Ebola outbreaks", "Hence, accelerating the response through provision of minimum essential information on risk communication for behavioural impact, developmental communication and health promotion/education personnel and community, working in multidisciplinary to respond to the disease outbreak, will be very useful for adequate and appropriate national staff and other national resources to the field operational epidemiologists, clinicians, and public health officers in fostering positive behavioural changes while respecting cultural practices, and impact on local contexts and outbreak dynamics, prevention and control interventions and scaling up outbreak containment measures, especially effective contact tracing." ] },{ "paper_id": "70fe1da70b714ba14f71d217ecf93da18e291aa7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses depend on host cell ribosomes to produce their proteins, and sometime use host cell DNA and RNA polymerases for replication and transcription, respectively. Many viruses encode proteins that modify the host transcription or translation apparatus to favor the synthesis of viral proteins over those of the host cell. Among", "SLC14A2, also is known Urea transporter 2 (HUT2), is important gene involved in urea transport and play role in physiology. In mammals, two types of urea transporter (SLC14A1 and SLC14A2) has been reported 71 and were regulated by vasopressin hormone 72 . The kidney uses urea to maintain the appropriate concentration and volume of blood. Without control of these proteins, organism would result in extreme damage in urinary system. Besides, a previous study has reported that genetic variation including nucleotide change is known to significantly influence blood pressure (BP) and metabolism syndrome 73, 74 .", "BGLAP, also known as Osteocalcin, is a noncollagenous protein, mainly found in bone, which needs vitamin K for its synthesis. This protein was thought to play a role in calcium ion homeostasis and used as biological marker for bone formation 55 . In addition, it concerns in endocrine regulation, especially in digestive system, by stimulating release of insulin hormone from \u03b2-cell of the pancreas and adiponectin hormone from fat cells, respectively 56 . As well as these function, it has been reported to take a role in promotion of energy availability and sexual maturation of male by stimulation of testosterone biosynthesis 57, 58 ." ] },{ "paper_id": "70fefc54856d09f01cb983932a860dc4dacb9f46", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. Data were expressed as the mean \u00b1 SE. Statistical evaluation was carried out by one-way ANOVA followed by Dunn's test. All statistics were calculated using SigmaStat version 3.5 (Systat Software). P<0.05 was considered to indicate a statistically significant difference.", "Curcumin is known to be an anticancer chemical at high doses. To avoid the obvious cytotocicity in the subsequent experiments, the MTT assay was applied for cytotoxicity analysis. The results show that curcumin dose-dependently decreased cell viability (Fig. 1) . The dose <20 \u00b5M was selected for subsequent analysis, given that the viability of 25 \u00b5M curcumin treatment is <80%.", "HO-1 knockdown by siRNA. Cells (3x10 6 ) were seeded in 10-cm dishes for 6 h, then negative control small interfering (siRNA) (10 nM) or HO-1 siRNA (10 nM) (Invitrogen) was transfected into cells using the RNAiMAX Transfection Reagent (Invitrogen), according to the manufacturer's instructions. Subsequent to adding siRNA for 6 h, the medium was changed to fresh condition medium for 18 h. Then the transfected cells were then analyzed by western blotting." ] },{ "paper_id": "7107f088cbed45d8a06a026276ccf4d602d50f10", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Use of animals and all experimental procedures were reviewed and approved by the Institutional Animal Care and Use Committee at the Indian Institute of Science Education and Research Kolkata and Indian Institute of Science, Bangalore India. Animal protocols adhered to the guidelines of the CPCSEA, India.", "MS is best studied in some experimental models such as experimental autoimmune encephalitis (EAE), Theiler's murine encephalomyelitis (TMEV), and mouse hepatitis virus-(MHV-) induced neuroinflammation. Virtually, all types of adaptive immune response have been proposed to play important roles in the pathogenesis of EAE [4, 12] , TMEV [13] , and a neurotropic strain of mouse hepatitis virus (MHV); MHV-JHM [14, 15] , mimicking the pathogenesis of the MS.", "On day 2 after seeding, neonatal microglial cultures were infected at a multiplicity of infection (MOI) of 2 : 1 with RSA59 or mock-infected with noninfected cell lysate. After allowing viral adsorption for 1 hr, cells were washed and placed in fresh media without virus. At 6, 12, and 24 hrs after infection, cultures were examined by microscopy for EGFP fluorescence.", "In order to replace gene 4 with the EGFP gene, pMH54 was modified by the introduction of a SalI site 42 nucleotides downstream of the intergenic sequence for gene 4a and a NotI site 102 bp upstream of the stop codon for gene 4b, using the Quick Change site-directed mutagenesis kit (Stratagene, La Jolla, CA, USA). (These are coding-silent nucleotide changes.) The coding sequence of EGFP was cleaved from the pEGFP-N1 vector (Clontech, Palo Alto, CA, USA) using SalI and NotI and inserted in the place of the SalI/NotI fragment of pMH54. The resulting plasmid contains 760 bp of non-MHV sequence, including the 722-bp EGFP open-reading frame, replacing the entire gene 4a and the rest 213 bp of gene 4b." ] },{ "paper_id": "710a40e33a20fe517c78c06748005fea78f21105", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The effect of chloroquine on pDC activation (see Figure ", "Chloroquine and hydroxychloroquine have so far been tested in several HIV clinical trials. The results summarized in Figure 3 support the hypothesis that the chloroquine/hydroxychloroquine dosage may be an important driver of at least partial clinical success.", "pDCs decrease in peripheral blood during progression to AIDS, because, upon activation, they migrate to the lymphoid tissue [30] . As a huge number of cells reside in the gut-associated lymphoid tissue (GALT), according to the microbial translocation theory, the intestinal mucosa damaged by the consequent inflammation may become permeable to products of the gut microbiome which further enhance HIV-related immune hyperactivation [31, 32] .", "AS and ILS contributed to the ideas and to the interpretation of the data presented in the manuscript. AS and ILS contributed to manuscript drafting and preparation of the figures. Both authors read and approved the final manuscript." ] },{ "paper_id": "710bf21a0b14c7512f2680ba1413c518432d7278", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Until a quantitative assay is available, the viral load in both cases and controls cannot be assessed. However, a limited sample dilution analysis with current assays, for which the sensitivity has not been quantitatively assessed, have indicated viral loads range from 100 to at least 10 11 DNA copies per gram of feces (data not shown).", "Although our original isolation of HBoV2 was from a sample taken in the summer of 2001, screening of the 2001 sample set indicated HBoV2 was detected throughout the year from summer to early spring (Southern Hemisphere) with no obvious peak incidence. It is interesting to note that most AGE infections in Adelaide occur after this period, from late winter to early summer (predominantly rotavirus and NoVII). Additional screening is proceeding to assess if this distribution recurs annually.", "Although we originally targeted a 'summer' peak of AGE cases to screen for the presence of novel viruses, HBoV2 was detected throughout 2001, predominantly between January and mid-September (in the Southern Hemisphere, mid-summer to early spring).", "The family Parvoviridae are among the smallest viruses measuring 18 to 26 nm, unenveloped, with an icosahedral capsid. Their genomes are single, mostly negative-stranded linear DNA between 2 and 6 kb in length [36] . Other parvoviruses, such as canine parvovirus and feline panleukopenia virus, are associated with gastroenteritis or enteric disease of their natural host [36] and it was perhaps anomalous that to date there had not been a parvovirus with a similar association in humans. In addition, other parvoviruses are known to replicate only when the host cell is in S phase, and results in the death of the host cell [36] . This would suggest that virus shedding may peak later in the course of an infection as any damaged and dead cells are replaced." ] },{ "paper_id": "710d63d02151ad5a6ed5eb93dd30d7a531445402", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.pone.0204605.g008", "Supporting information S1 File. Synthetic chemistry procedures. (DOCX) S1 ", "In an effort to validate this phenotypic assay and to better understand the clinical relevance of the DNL assay, we tested niclosamide, Metformin-the classic anti-diabetic drug, and Triacsin C-a potent inhibitor of long fatty acyl CoA synthetase for their ability to attenuate the steatosis phenotype in this platform. Triacsin C and niclosamide both inhibited the steatotic phenotype in PH5CH8 in a concentration dependent manner, albeit with different potencies (Fig 1G and 1H ). Triacsin C and niclosamide reduced steatosis by 92 \u00b1 19% and 77 \u00b112% respectively." ] },{ "paper_id": "710dd69c07a692bbdcd7261bb4508cd9935556c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Six cDNA clones representing the full length of the BCoV-Mebus genome, and pNrep1 which encodes the entire subgenomic mRNA 7 [17] were kindly provided by David Brian (University of Tennessee, Knoxville, TN).", "Construction of pDrep1 and pDI RNA-M (formerly called pDI RNA-2) [6] which encodes BCoV DI RNA and DI RNA-M, respectively, and were kindly provided by David Brian (University of Tennessee, Knoxville, TN), has been described [6, 17] . In brief, pDI RNA-M was made by replacing the 288-nt 3' UTR of BCoV-Mebus in pDrep1 with the 301-nt 3' UTR of MHV-A59 (GenBank accession no. NC_001846) from fragment G DNA [33] .", "To construct pHisBM-25A, p\u039450HisBM-25A, p\u039450HisBM-45A and p\u039450HisBM-65A, an overlap PCR mutagenesis procedure was used as described [34] , but with the appropriate sets of oligonucleotides for poly(A) tail lengths of 25, 45, or 65 As. The overlapping PCR product was cloned into TOPO-XL vector (Invitrogen) and digested with XbaI and MluI. The digested fragment was cloned into XbaI-and MluIlinearized pDrepI to make pHisBM-25A or pD50 to make p\u039450HisBM-25A, p\u039450HisBM-45A and p\u039450HisBM-65A [17] ." ] },{ "paper_id": "7110b46076a08c546102c3501ab5220f96e78708", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Potential function", "This work was supported by grants from AHA (15SDG25700381 and 13POST17210033) and Mid-Atlantic Nutrition Obesity Research Center (NORC Pilot & Feasibility Program) to Dr. Zhong." ] },{ "paper_id": "7115c4bf2dfc029be764f0cd2e13de0bf8ec1312", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ".", "(1)", "Therefore 0 = = ( + ) ( + ) . ", "The corresponding characteristic equation of the Jacobian matrix is" ] },{ "paper_id": "711a2350fec569de818a1bd51ab4a3a8b793918c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The procedural values of transparency and inclusiveness are widely accepted and crucial for ethical decision-making. \u2022", "Recognizing that cultural perspectives may shape the ethical context of an emergency response, the Centers for Disease Control and Prevention (CDC) funded four regional meetings to explore cultural perspectives relevant to pandemic influenza preparedness and response. Although regional cultural differences were observed, these differences will not prevent countries from coming together to collectively address a shared existential health threat. Pandemics create a global predicament that can unite countries around the shared value of health, rather than divide on the basis of cultural differences.", "No \"one size fits all\" approach to allocating resources can cover the variety of economic, cultural and other contextual factors that must be taken into account, but engaging with communities can help both to discover these factors and to get buy in. \u2022 Although meeting participants acknowledged the importance of social distancing as a tool to limit disease transmission, they also recognized the difficulties associated with this measure. \u2022 Healthcare workers often have competing obligations that can compromise their ability to fulfill public health duties during an emergency response. Government has a responsibility to assist them in doing their job by providing appropriate training and equipment. \u2022 Although international collaboration can be difficult, focusing on shared values and fair procedures (procedural ethics) can bring countries together to combat the common health threat that global pandemics pose." ] },{ "paper_id": "711a278ba27cfbfa11c5585a117f63a464560de4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "qa (M.A.); eabdfarag@moph.gov.qa (E.A.B.A.F.); halromaihi@moph.gov.qa (H.E.A.-R.); malthani@moph.gov.qa (M.A.-T.); dralmarri@moph.gov.qa (S.A.-M.)", "SCH launches an awareness campaign including helpline services", "Reports on personal story of the second Qatari case" ] },{ "paper_id": "7120211f7eda128e441ed22e3e4d8d3eda07b771", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sera from all nine patients were evaluated for white blood cell counts (WBC), red blood cell counts (RBC), hemoglobin (Hb) and platelets (PLT) and the following liver function tests were carried out: aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (\u03b3-GTP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), albumin (Alb), total bilirubin (T.Bil), and creatinine. The blood levels of hemoglobin A1c (HbA1c) and fasting blood glucose (FBS) were measured. Ultrasonographic examination was performed for all patients in order to investigate the shape of the liver and lesions occupying the liver. Computed tomography and liver biopsy were performed in some patients.", "This study included nine Japanese patients (4 males and 5 females) with OLP who were positive for HCV antibody (anti-HCV) and who visited our clinic at the Kurume University Hospital in Japan from November 2, 2011 to November 16, 2011. The patients ranged in age from 55 to 76 years, with an average age of 67.9 \u00b1 7.6 years.", "We used a simple and low-cost test for detection of xerostomia and this required chewing on a piece of gauze for 2 min. A salivary flow rate \u2264 2 g/2 min was judged as decreased salivary secretion." ] },{ "paper_id": "712c86986815982dc6d918b660f70f5e05616643", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cytoplasmic DNA sensors (CDSs), such as Z-DNA binding protein 1 (ZBP1) and cyclic GMP-AMP synthase (cGAS), are well known to induce innate immune responses upon recognition of pathogen-derived double-stranded DNA (dsDNA) or even RNA [20] [21] [22] . A contribution of CDSs in innate sensing of RSV replication has not yet been reported.", "The capacity of RSV to suppress the anti-inflammatory effect of glucocorticoids through NS1 and NS2 are in line with the ineffectiveness of glucocorticoid treatments off severely ill RSV patients.", "https://doi.org/10.1371/journal.ppat.1007984.g002", "A third class of PRRs, the nucleotide-binding oligomerization domain-like receptors (NLRs), is also important for the recognition of RSV. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) can be activated by intact genomic single-stranded RNA (ssRNA) and is involved in the induction of IFN-\u03b2 in mice in a MAVS-dependent way (Fig 1) [19]." ] },{ "paper_id": "7139441855f3ac67f104fb9e067b1359c5582fd6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses are particularly adept at adapting to new hosts due in part to their amazing capacity for genome recombination. Coronaviruses have the largest genome of RNA viruses, consisting of 27-30 kb positive sense single-stranded RNA. Although recombination can lead to an interspecies transmission event, as was believed to be the case with SARS-CoV, accumulation of point mutations may also enable the coronaviruses to adapt to new host species [5] [6] [7] .", "A 500 ml sample was homogenized with 500 ml TRIzol reagent (Invitrogen) following manufacturer's protocol except that incubations were performed at 30uC instead of room temperature.", "(DOCX) " ] },{ "paper_id": "713f2cff38e6555558825cb304f67eb31c35687f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were lysed in RIPA buffer (50 mM Tris-HCl (pH 7.4), 150 mM NaCl, 1% NP-40) containing a protease inhibitor cocktail (Yhermo Science). The protein concentration was determined. Equal amounts of protein were separated by SDS-PAGE and electrophoretically transferred onto a polyvinylidene difluoride (PVDF) membrane (Millipore, Shanghai, China). After blocking with 5% nonfat milk in Tris-buffered saline containing 0.1% Tween 20, the membrane was incubated with specific primary antibodies (1:1000), followed by incubation with appropriate horseradish peroxidase-conjugated secondary antibodies. Signals were detected using SuperSignal WestPico kit (Thermo Scientific) and subjected to Image Reader LAS-4000 imaging system (FUJIFLIM, Japan).", "Intestinal epithelial cells, which were originally called \"mitochondria-rich\" cells, are important for absorbing nutrition and mediating the immune response (Brown and Breton, 1996) . Moreover, mitochondria play an important role with regard to reactive oxygen species (ROS), inducing programmed cell death and transducing stress and metabolic signals (Albers and Beal, 2000; Galluzzi et al., 2012) . Therefore, mitochondrial biogenesis is tightly regulated to maintain overall cellular homeostasis (Wai and Langer, 2016) . A variety of pathogens and chemicals can affect the mitochondrial dynamics of intestinal epithelial cells and destroy cell homeostasis (Novak and Mollen, 2015) .", "This work was supported by a National Science Grant of PR China (No. 31372465) and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).", "YX: study conception and design, performance of the experiments, data analysis and interpretation, manuscript writing; ZL: performance of the experiments, data analysis and interpretation; LJ and YuQ: data analysis and revise this manuscript; YaQ: study conception and design, financial support, administrative support, manuscript writing, final approval of the manuscript." ] },{ "paper_id": "714370d75af9d91c8812733f732d98ddfff8074a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Single chamber, phase transition, blood-compatible RT-qPCR with no pre-processing", "accessing viral nucleic acids for this form of viral particle disruption, even for the highly robust MS2 coliphage virions.", "The authors declare no competing \ue103nancial interests." ] },{ "paper_id": "7146a5eb303bef6ef7c4bc2588a0305fc7b58cd3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells. HeLa R19, BGM (buffalo green monkey), and COS-1 cells were grown in Dulbecco's minimal essential medium (DMEM; Lonza) supplemented with 10% fetal bovine serum and penicillin and streptomycin at 37\u00b0C and 5% CO 2 .", "-Microbe Biology crossmark Volume 1 Issue 4 e00104-16 msphere.asm.org 1 van der Schaar et al. Volume 1 Issue 4 e00104-16 msphere.asm.org 2 Live Imaging of Enterovirus Replication Organelles Volume 1 Issue 4 e00104-16 msphere.asm.org 3 van der Schaar et al. Volume 1 Issue 4 e00104-16 msphere.asm.org 4 van der Schaar et al. Volume 1 Issue 4 e00104-16 msphere.asm.org 6" ] },{ "paper_id": "714e40f88f6e629f0f63574ec52ea967aeee4065", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The human kidney cell line 293T [64] was cultivated in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% heat-inactivated fetal calf serum and antibiotics. Cell culture supernatants containing recombinant viral particles were generated by transfection of 293T cells with the corresponding plasmids using polyethyleneimine (PEI) as described previously [7, 8] . For subsequent Western blot analysis the supernatant generated by transient transfection was harvested, passed through a 0.45-\u03bcm filter and centrifuged at 4\u00b0C and 25,000 rpm for 3 h in a SW32Ti rotor (Beckman) through a 20% sucrose cushion. The particulate material was resuspended in phosphate-buffered saline (PBS). For cryo-EM analysis, viral particles were produced in serum-free medium and a further concentration step using Amicon Ultra 0.5 ml 100K concentrators was included following the first concentration by ultracentrifugation through 20% sucrose similar as described recently [20] .", "Cells from a single transfected 100-mm cell culture dish were lysed in detergent-containing buffer and the lysates were subsequently centrifuged through a QIAshredder column (QIA-GEN). Protein samples from cellular lysates or purified particulate material were separated by SDS-PAGE on a 10% polyacrylamide gel and analyzed by immunoblotting as described previously [9] . Hybridoma supernatants specific for PFV Env LP (Env LP, clone P3B8-B7), PFV Env SU (Env SU, clone P3E10) or PFV Gag (Gag, clone SGG-1) were employed [13, 15, 61] . After incubation with a horseradish peroxidase (HRP)-conjugated secondary antibody, the blots were developed with Immobilon Western HRP substrate. The chemiluminescence signal was digitally recorded using a LAS-3000 (Fujifilm) imager and quantified using ImageGauge (Fujifilm).", "Data Availability Statement: The PFV glycoprotein structures from subtomogram averaging (EMD-4006, EMD-4007 and EMD-4008 for PFV wt, iFuse and iNAB respectively) and cryo-EM (EMD-4010 and EMD-4011 for iNAB hexagonal assembly and single spike reconstructions respectively and EMD-4012 and EMD-4013 for iFuse hexagonal assembly and single spike reconstructions respectively) have been deposited in the Electron Microscopy Data Bank. All relevant data are within the paper and its Supporting Information files.", "Among the various morphology of PFV viruses, one large population (Class C in Fig 2) representing 57% of the spherical particles has no sign of regular internal ordering and it is also the most variable class in terms of dimensions. The smallest members of this class cannot accommodate the 30 nm capsid of the mature particles and may constitute Env-only virus-like particles consistent with the role of Env in budding [23] ." ] },{ "paper_id": "715063d01372186739566d9c343b16ebb45f32eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "7150b10d52da822055fd899a9df210131bf8104e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HBoV invasion and replication by undermining host immune responses resulting in high levels of HBoV replication facilitating its spread to the blood circulation to cause systemic disease; however this remains to be proven.", "1.5 ml sterile saline (0.9%) was added into each tube of NPA and tubes centrifuged at 13000 rpm for 2 minutes; the supernatant was removed and pellet resuspended in 200 mL of Eagle's Minimum Essential Medium. Blood samples were centrifuged at 3000 rpm for 5 minutes; plasma was isolated and kept at 270uC. 3 ml sterile saline (0.9%) was added into each tube with stool samples, the mixture was vigorously vortexed for 5 minutes, and centrifuged at 13000 rpm for 5 minutes. The supernatant was aspirated and stored at 270uC.", "Statistical analysis was performed using the Epi Info software (version 3.5, CDC, USA), and graphs were prepared using Prism Graphpad v5. Mentel-Haenszel, Kruskal-Wallis x 2 or Fisher's exact x 2 test were used to assess the significance; p value #0.05 was considered statistically significant for all tests.", "HBoV1 was detected in patient NPAs throughout the course of the study with peak detection in autumn and winter. It was noticeable that HBoV appeared to co-circulate with RSVA ( Figure 1) , which was the most frequently co-detected virus; however, an extended study with a larger dataset would be required to confirm such a correlation." ] },{ "paper_id": "7151947d17c83f7764b115d4e21a982738bb12f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest.", "Funding: This work was supported by the Canadian International Development Research Centre (IDRC-108410-001) and Foundation for Science and Technology of Pernambuco (FACEPE-APQ-0154-2.12/16). The funders had no role in study design, decision to publish, or preparation of the manuscript." ] },{ "paper_id": "715ec0aac4ad78092007345159945afa560b3f05", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A more modern approach to global public health should de-emphasize the a priori criterion of international spread. Modeling studies have demonstrated that, for pathogens with relatively short generation times, early cross-border coordination between nations is crucial when epidemic diseases arise in border regions [8] . But even for diseases with relatively long generation times, as with the current EVD epidemic, waiting for cases to cross borders can result in disastrous delays. As such, removing the requirement that an outbreak be an \"international threat\"-or at minimum interpreting that criterion liberally-will decrease delays between reporting and response and allow much needed support to at-risk countries before epidemics have reached a tipping point.", "Additionally, a PHEIC declaration may inadvertently trigger harmful measures, such as border closings and travel bans, which can hinder the response to an epidemic. However, the current epidemic has taught us that delaying an announcement imperils lives and health systems and, in the long run, may do more economic harm [9] , cost more response dollars, and undermine domestic political legitimacy much more than an early, errant PHEIC declaration.", "\u2022 Strategies to consider include development of a more precise system to risk stratify geographic settings susceptible to disease outbreaks, reconsideration of the 2005 International Health Regulations Criteria to allow for earlier responses to localized epidemics before they reach epidemic proportions, increasing the flexibility of the World Health Organization director general to characterize epidemics with more granularity, development of guidelines for best practices to promote partnership with local stakeholders and identify locally acceptable response strategies, and, most importantly, making good on international commitments to establish a fund for public health emergency preparedness and response.", "Overwhelmed and under-resourced, the affected countries have implemented drastic measures to control the epidemic, including hospital and school closures, local and national quarantines, and border closures [13] . Not surprisingly, these measures have engendered widespread public distrust of health authorities [14] . In contrast, prior successful responses to Ebola [15, 16] and other epidemics [17] have prioritized early partnerships with local authorities, anthropologists, and civil society to establish buy-in from multiple stakeholders. This strategy helps ensure that the design and implementation of control measures are culturally appropriate. In hindsight, some of the negative fallout from decisions to use extraordinary measures might have been avoided had WHO, in partnership with local community leaders and public health experts, more assertively used their legitimacy to caution against the use of coercive measures without an evidence base." ] },{ "paper_id": "716bf47d34e36f3c165ee3c84a70d93bf6f0bf5d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine bone marrow MSC were grown and expanded as described above. When MSC reached at about 80% confluence, medium was aspirated and cells were washed three times with phosphate-buffered saline. Cells were cultured in serum-free medium for 24 h. CM was removed and centrifuged to remove cellular debris and used in epithelial differentiation assays.", "During the culture of BMCs for the isolation of mesenchymal stromal cells (MSC), we observed colonies of epithelial cells surrounded by mesenchymal cells. The colony cells exhibited cuboidal morphology typical of epithelial cells (Fig. 1A) .", "Influenza viruses belong to the family Orthomyxoviridae and cause highly contagious respiratory infections in humans and animals. These viruses cause seasonal epidemics and infrequent pandemics in humans. Seasonal influenza epidemics are responsible for between 200,000 and 500,000 influenza-related deaths each year [15] . Avian influenza viruses caused three human pandemics during the last century. The 2009 pandemic, the first pandemic of 21 st century, was caused by a triple reassortant H1N1 influenza virus of swine lineage [16] . In addition to seasonal and pandemic viruses, highly pathogenic avian influenza (HPAI) H5N1 virus has crossed species barrier to infect humans. As of August 9, 2011, more than 500 human cases with over 300 deaths have been reported worldwide [17] . H5N1 viruses replicate to higher titers in lungs and extra-pulmonary tissues leading to acute respiratory distress syndrome, multiple-organ dysfunction, lymphopenia, and hemophagocytosis [18, 19, 20] . Influenza viruses, therefore, pose a constant public health threat, and it is important to understand its pathogenesis to devise effective control measures." ] },{ "paper_id": "717168e782bf72b65add057c1cebe8d1bfdffbda", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "doi:10.1371/journal.ppat.1005274.g007", "doi:10.1371/journal.ppat.1005274.g010", "doi:10.1371/journal.ppat.1005274.g011" ] },{ "paper_id": "7173c0b2dec6dea33c883abf933ebc5fecccc320", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Serum samples were tested for PEDV antibodies using a commercial ELISA test, ID Screen \u00ae PEDV Indirect (ID Vet, Grabels, France). The ELISA test is validated if the mean value of the positive control optical density (OD) is greater than 0.350 and if the ratio of the mean values of the positive and negative controls is greater than 3. A sample-to-positive (S/P) ratio was calculated. Samples with an S/P ratio equal to or greater than 60% were considered positive for PEDV antibodies.", "A homogenate of each tissue was prepared at 20% (w/v) in PBS (phosphate buffer saline) using a bead mill (Retsch, Haan, Germany). Subsequently, the suspensions were centrifuged at 10 000 \u00d7 g for 10 min at 4 \u00b0C and the supernatants were stored at -80 \u00b0C.", "Fecal homogenates were prepared with 1 mL or 1 g of feces homogenized with 9 mL of Dulbecco's phosphatebuffered saline (Sigma-Aldrich, Saint Louis, MO, USA). The homogenates were then centrifuged at 15 000 \u00d7 g for 10 min at 4 \u00b0C, and the supernatants were stored at -80 \u00b0C." ] },{ "paper_id": "717582da95cea3e8b268b404e9f1ecc486fff6c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors also showed that others cardiac glycosides such as digoxin, ouabain, and G-strophanthin have comparable anti-HSV activity [19] . Finally, adenoviruses, which are common human pathogens, are also susceptible to cardiac glycosides such as digitoxin and digoxin, which are able to impair adenovirus genome replication by altering the host pre-RNA splicing machinery [39] .", "In this review, we analyze both the effects that viral infection have on the Na,K-ATPase function and the effect of Na,K-ATPase ligands cardiac glycosides on viral biology. We will also review the mechanisms by which these drugs impair the replication of different types of viruses (Table 1) . ", "Since first described by Skou more than 60 years ago [1] , Na,K-ATPase has been extensively studied, and novel concepts about structure, physiology, and biological roles continue to appear. The classical role of Na,K-ATPase is to maintain the electrolyte homeostasis of the cells by pumping cations in and out of the cell using the energy obtained from the hydrolysis of (Adenosine triphosphate) ATP. However, Na,K-ATPase is also a key scaffolding protein that is able to interact with signaling proteins such as protein kinase C (PKC) and phosphoinositide 3-kinase (PI3K) [2] [3] [4] [5] . It also works as a classical receptor in which the binding of cardiac glycosides induces activation of the tyrosine kinase Src and down-stream signaling cascades, independent of changes in intracellular ions [6] [7] [8] ." ] },{ "paper_id": "71788152b25d71db652985de1cc4fb0513873969", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After acute infection, which is mainly asymptomatic, HCV establishes a lifelong, persistent intrahepatic infection in approximately 80% of the patients. Development of chronic hepatitis C (CHC) leads to progressing liver fibrosis and eventually cirrhosis (15-30% of CHC patients), which can cause liver failure or the development of hepatocellular carcinoma (2-4% of CHC induced cirrhosis patients per year) [70] . Consequently, HCV causes app. 700,000 deaths per year [70] .", "Besides the cytosol, HCV dsRNA can also be present in extracellular, ER, or endosomal compartments. Extracellular dsRNA, maybe released from dying cells, can be taken up into uninfected neighboring cells by class A scavenger receptors [77] . After endocytosis, dsRNA is brought to the endosome, where it is bound by Toll-like receptor 3 (TLR3). Alternatively, TLR3 might engage HCV in autophagic vesicles, as HCV replicating cells display an enhanced amount of them [78] . Recognition of dsRNA by TLR3 activates TIR domain-containing adapter-inducing IFN-(TRIF; also called TICAM-1) signaling.", "hepatocytes [88, 91] . Type III IFNs and ISGs are similarly inducted upon HCV infection of primary human fetal liver cells [98, 99] . Here the magnitude of induction differs from donor to donor but correlates with virus replication.", "Worldwide 92-149 million people, representing approximately 2% of the world's population, are chronically infected with HCV [66] , one of the causative agents of viral hepatitis. HCV is a blood borne virus and transmission occurs parenterally, mainly by reusing injection material, insufficient sterilization of medical tools, or by transfusion of unscreened blood or blood products. As screening of blood products is a standard procedure nowadays in most countries, people who inject drugs have the highest risk of contracting hepatitis C. In fact, over 60% of injecting drug users are positive for HCVantibodies [67] .", "Although IFNL2 and IFNL3 have high sequence homology, they differ in their antiviral activity with IFNL3 displaying the strongest antiviral activity in a HepG2 challenge experiment with encephalomyocarditis virus [62] . This finding is in line with a strong ISG (MX1 and IRF9) induction by IFNL3 in hepatocytes [55] . IFNL4, in turn, displays antiviral activities which are comparable to IFNL3 as shown in reporter cells expressing the IFNLR and a luciferase gene under the control of the IFI6 promoter [3] . In conclusion, IFNLs signal through the JAK1/STAT pathway for ISG induction and the set of ISGs largely overlaps with that induced by type I IFNs." ] },{ "paper_id": "719011222a3dd0642fb565e5f80fa03a184835eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at www.mdpi.com/1999-4915/9/8/214/s1, Figure S1 : Geographic origin of samples, Figure S2 : Natural disease symptoms, Table S1 : RT-qPCR assay details, Table S2 : Accessions of related viruses.", "as sub-optimal as can be and inferior to either of the possible ORF-2 start codons (UAA 8266 AUGCGC; AAU 8473 AUGACU), neither of which are particular optimal themselves. Therefore, unless ORF-3 is translated through a dedicated IRES hidden in the CP gene (e.g., [27] ), it may well be produced as a read-through product of ORF-2, through a leaky UAG stop codon. Such a strategy has plenty of precedence elsewhere in the virus world, particularly for coat proteins that thus acquire extensions with potentially useful functions for cell entry, infectivity, and host-range [26] .", "Viruses 2017, 9, 214 3 of 11 chain reaction (RT-qPCR) fragments from the prevalence survey was also confirmed through sequencing. These PCR products were sequenced by Macrogen (Seoul, South Korea)." ] },{ "paper_id": "71a82ecd1070ef91422c1ed772c73ad189ea4c0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All in-vivo procedures were conducted in accordance with the Animal Welfare Act and the CDC-NIH Biosafety in Microbiological and Biomedical Laboratories and were approved by the Southern Research Institutional Biosafety Committee and Institutional Animal Care and Use Committee (ACUP protocol #08-05-031B). The Animal experiments were performed in the AAALAC-accredited ABSL-2 facilities at Southern Research Institute, Birmingham, AL. Four ferrets, two males and two females were intranasaly infected with 10 4 TCID50/ml influenza H1N1 A/California/07/2009. Viral titers in nasal swabs were analyzed by establishing the median tissue culture infective dose in Madin-Darby canine kidney cells according to our previously published protocols [32] . Analysis of nasal swabs is a straight forward method to analyze presence of replicating virus during influenza infection ( [33] and our unpublished results). One male and one female were euthanized on days three and six postinfection to increase chance of identifying transcripts with specific temporal expression patterns. Tissues were collected and snap frozen in liquid nitrogen. We collected cranial and caudal lung, heart, bone marrow from the femur, lymph node, spleen and blood.", "Five thousand thirty nine of the 19'342 transcripts were aligned to genes staring with LOC followed by the geneID. For such transcripts, no published gene symbol is available nor has an ortholog been determined yet. Gene annotation processes are continuing at the NCBI, and the actual number of individual genes identified in this data set may be altered. Investigating the best hit for each contig from the Refseq protein blast analysis showed that most hits were gene orthologs of the giant panda (A. melanoleuca, 14'816 contigs) and the domestic dog (C. familiaris, 8038 contigs) (Fig. 1 ). Both of these species, as well as the ferret, are part of Caniformia, a suborder within the order Carnivora. More than 7000 contigs showed high similarity to LINE-1 reverse transcriptase and were removed from functional analysis.", "Using the human protein and RNA databases for the blast analysis resulted in 52'510 contigs being aligned to human proteins or RNAs (corresponding to 13'697 different human transcripts or proteins). As we expected these genes to represent the a large amount of the expressed ferret genes, it was not surprising that the most overrepresented gene-annotation categories from the enrichment analysis were of a more general type, such as ''cellular process'', ''metabolic process'', ''macromolecule biosynthetic process'' and ''protein localization''. When investigating the overlap with the genes associated the GO-term representing the immune system process (GO:002376), we found that the combined sequence assembly contained full or partial transcripts corresponding to almost 80% (1078 of 1390 genes) of the human gene orthologs associated with this GO-term (Table S3 )." ] },{ "paper_id": "71afb4cf84163bef90c7ea2f8d816aef07582d85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "International standards for animal welfare were used for all animal samples collected, following the regulations for animal sampling of the article number 134 of Animal Welfare Law included into the National Constitution of the Republic of Ecuador.", "In this study, a rigorous measurement of the global phylogeographic approach for PEDV strains was performed based on complete S gene sequences. The present work is the first study providing evidences that PEDV strains are circulating into Ecuador swine herds and revealing the molecular characteristic of the PEDV isolate in the South American region. The spatial analyses suggested that these strains were introduced to Ecuador by an importation from US.", "After the PEDV outbreak in the United States in 2013, followed by the fast spreading of the virus to Canada, Mexico, Korea, and Taiwan, an important turn in PED research has taken place [1] . Thus, a relevant increase of studies about the epidemiology, genetic structure, and characteristics of PEDV has occurred to get a better understanding of this disease, which is currently the most fatal in pigs and one of the economic concerns for the pig industry [4] ." ] },{ "paper_id": "71b9d32718c8ba343468da22dc28314f84b852ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "N Age-Classes.", "N Balance between random nature of contacts and assortativity.", "N The neighbors of infected individuals can move without any restriction.", "The estimation of the reproductive number, R, and the generation time interval, v, leads to some interesting results." ] },{ "paper_id": "71c95bd39c649d3ba3fee28d11be98cd4019de7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PSG N domains are more closely related with each other than with N domains of membrane anchored CEACAMs in M. lucifugus", "We next analyzed CEA families in additional microbat species belonging to different families of Yangochiroptera (Fig. 6) ." ] },{ "paper_id": "71d047965ff6d3d2dc68d07cb90770fce84edcb8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LAB (Lactococcus, Streptococcus, and Lactobacillus) are nonsporulating, have low G + C content and are nonpathogenic food-grade bacteria. They are an excellent candidate for functioning as adjuvants, immunostimulators and live antigen carriers to deliver antigens and cytokines at the mucosal level [69] . Dieye et al. characterized L. lactis as a potential vehicle for protein delivery (VP2 and VP3), serving as a live mucosal vaccine against IBDV in chickens [70] .", "Nevertheless, there is no single vaccine that has all the above characteristics. The use of vaccines to control disease is based on assessing the risks and evaluating the benefits following vaccination. Generally, genetic vaccines are composed of either DNA (as plasmids) or RNA (as mRNA) that is taken up and translated into proteins by cells of the vaccinated animals. Since there are limited reports on RNA vaccines compared to the extensive literature on DNA vaccines, genetic vaccines are generally referred to as plasmid DNA antigen-expression systems. Genetic immunization, also termed DNA immunization, is a recent vaccine technology utilizing eukaryotic expression vectors encoding antigens [1] .", "Vaccines have been effective against infectious diseases in animals and have successfully controlled and/or eradicated major animal pathogens. Based on the guidelines proposed by the Royal Society's report on infectious diseases of livestock in 2002, UK, the characteristics of an ideal vaccine are:" ] },{ "paper_id": "71d134916c750fb6f875d3936a957b27a5df72bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1) Genetic diagnosis: genes known to cause the syndrome (PRF1, UNC13D, STX11, STXBP2, RAB27A) (2) Signs and symptoms (at least five of the following criteria): a) Fever b) Splenomegaly c) cytopenias (minimum 2 cell lines reduced) d) hypertriglyceridemia (\u2265 265 mg/dL) and/or hypofibrinogenemia (\u2264 150 g/dL) e) hemophagocytosis in any involved organ f ) very little or no NK cell activity g) increased ferritin \u2265 500 mg/L h) increased soluble CD25 (serum interleukin-2 receptor alpha) \u2265 2.400 U/mL", "( (7) Serum cryptococcal antigen and serum galactomannans", "The authors declare that they have no competing interests." ] },{ "paper_id": "71d2ad06792c5adb2c8fb934e9bedc53659b1dfe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Significance was set at p \u2264 0.05 for all tests. This was lowered to p \u2264 0.017 for Mann-Whitney test whereby it was used for post-hoc analyses, in order to reduce the family-wise error rate in multiple comparisons. Analyses were performed using a commercial software package (SPSS v20.0 for Windows, Chicago, IL). ", "Overall, 31 cats had non-ICGN renal disease, including 11 (35.5%) end-stage CKD, 9 (29%) focal segmental glomerulosclerosis, 6 (19.4%) global and multifocal glomerulosclerosis, 2 each of glomerular atrophy (6.5%) and renal dysplasia (6.5%), and 1 amyloidosis (3.1%).", "With regards to kidney samples, formalin-fixed and paraffin-embedded renal tissues were stained with haematoxylin and eosin (HE), periodic acid-Schiff (PAS), Masson's trichrome, and periodic acid-Schiff methenamine silver (PASM) or Jones Methenamine silver. Renal tissues for TEM were always fixed in glutaraldehyde and analysis was performed using standard procedures as previously described [18] . To achieve a final diagnosis of ICGN, glomerular immune-deposits had to be identified with TEM and, according to their location, ICGNs were further classified in MPGN, MGN and MeGN, following the WSAVA-RSSG classification scheme used in dogs [1] ." ] },{ "paper_id": "71d8abeec95c4d64d23aebfb95379158d85253e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "71e40892b5ee0084f5953a80dcae63e68df725d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The generation of Ebola VLPs in insect cells (eVLP) has been described previously [26] . Briefly, recombinant baculoviruses co-expressing Ebola VP40 and GP (rBV-GP-VP40) proteins or only expressing Ebola VP40 (rBVVP40) proteins infect Spodoptera frugiperda Sf9 insect cells at an MOI of 1. After 48h, the supernants were collected and VP40 and eVLPs proteins were purified in a discontinuous sucrose gradient (10-50%). A visible band between the 30% and 50% sucrose layers was harvested, concentrated by ultracentrifugation and then resuspended in PBS.", "A Student t test was used for statistical analysis. Results with a P value of less than 0.05 were considered as statistically significant. ", "RNA was isolated with RNAeasy Mini Kit (Qiagen, Valencia, CA) and cDNA was synthesized with First Strand cDNA Synthesis Kit (Fermentas). Quantitative PCR was performed with a SYBR Green PCR kit (Roche, Laval, Canada) in an iQ5 (Bio-Rad) detection system. The sequences of the primer pairs of TNF-\u03b1, IL-6, CARD9 and TLR4 were described before [40] [41] [42] [43] . LSECtin primer pairs were purchased from Qiagen." ] },{ "paper_id": "71e571db52c00a9c67fffc6f075580fe0732cde1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: L.D. and C.S. initiated and designed the study. X.W., W.T., and X.Z. performed the experiments and analyzed the data. Y.Z., L.D., and C.S. wrote, edited, and approved the manuscript.", "The authors declare no conflict of interest.", "Vaccines 2019, 7, 161 2 of 16 with microcephaly, fetal demise, and other congenital disorders [4] [5] [6] . Thus, ZIKV has emerged as a global health threat and there is an urgent requirement for an effective vaccine to combat ZIKV-associated diseases." ] },{ "paper_id": "71e8fcabcecb3f5ce3a699f95a618bd21a68bd76", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All lipopeptides were synthesized by Synpeptide Co., Ltd (Shanghai, China). Mass spectrometry was used to determination molecular weight and to confirm product sequences. The purity of all synthetic lipopeptide samples was over 90% by HPLC. Ten synthetic lipopeptide samples were named SLP1 to SLP10. And their sequences as Table 1 .", "Cercopithecus aethiops kidney epithelial cells (Vero, ATCC, CCL-81) were cultured in high glucose DMEM (Gibco, US), supplemented with 10% fetal bovine serum (FBS, GIBCO), at 37 C in a 5% CO 2 humidified atmosphere. Cells were routinely seeded at a density of 2\u00d710 5 /mL ", "https://doi.org/10.1371/journal.pone.0215227.g006", "where OD S , OD B , and OD P represent the optical density of the SLP-treated samples, negative control and positive control, respectively. 1% Triton X-100 was used for the positive control. Each sample was run in triplicate." ] },{ "paper_id": "71f2f3ffaa761b9d7e50b3d22eb0aacb78728bd9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Manipulations were carried out in a BSL2 facility with BSL3 practices. SARS-CoV isolation was not attempted on clinical samples during the outbreak due to safety concerns and time constraints.", "The author(s) declare that they have no competing interests. The study was funded by the Beijing Ditan Hospital. " ] },{ "paper_id": "71f40deaea2448ea82b36aea4b91149e588c39c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The nucleotides of restriction sites are underlined and mutants are bolded." ] },{ "paper_id": "71f45bcdac8e83e02ee1d8b5eab8ce5c425f5cce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/20/03/4610/s1.", "Immediately before use, the printed microarrays were rinsed with PBS, pH 7.4, with 0.05% (v/v) Tween 20 and then blocked by incubating the slides in 1% (w/v) bovine serum albumin (BSA) in PBS containing 0.05% (w/v) NaN3 at room temperature (RT) for 30 min. They were then incubated at RT with 2G12 (NIH AIDS Reagent Program, Germantown, MD, USA), biotinylated PHA-L (PHA-L BI ), or GNA BI (EY Laboratories, Inc., San Mateo, CA, USA) at an indicated titration in 1% (w/v) BSA in PBS containing 0.05% (w/v) NaN3 and 0.05% (v/v) Tween 20. The secondary antibodies or streptavidin conjugates applied for microarray staining are specified in the figure legends. The stained slides were rinsed five times with PBS with 0.05% (v/v) Tween 20, air-dried at room temperature, and then scanned for fluorescent signals using a ScanArray5000A Microarray Scanner (PerkinElmer Life Science, Boston, MA, USA) following the manufacturer's manual." ] },{ "paper_id": "71f9800bec3740702f01d4658029642ad7e801f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coagulation parameters (n = 2 SPF animals; n = 2 conventional animals). Rotational thromboelastometry (ROTEM \u00ae , Tem International, Munich, Germany) analysis was conducted on citrated whole blood samples according to manufacturer's instructions to measure clotting time (CT; sec), maximum clot firmness (MCF; mm), actual clot firmness 60 min after clot initiation (ACF; mm), and maximum clot lysis (ML; %) 29,30 . Assays included EXTEM (extrinsically-activated test using tissue factor) and APTEM (activation as for EXTEM with aprotonin). Aprotinin at low levels (10-50 KIU/mL) inhibits plasmin activation of fibrinolysis and plasmin-induced platelet activation 31 . Hyperfibrinolysis is defined as ML \u2265 15% 32,33 and confirmed with APTEM test.", "Animal pathogen status availability. A list of infectious agents in animals supporting the conclusions of this study are available by contacting the author(s) and/or institutional data hub (with an appropriate URL)." ] },{ "paper_id": "71fd4bd89b7dc7a87a4cc7bdcb25be3e444becc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequences were aligned using Geneious Pro v5 [56] and presented in a neighbourjoining tree prepared in MEGA 5 [57] . Nucleotide sequences deposited into GenBank as a result of this study include JQ732182-JQ732203.", "Nucleotide sequencing reactions were performed using 2 \u03bcL of amplicon with the ABI PRISM\u2122 BigDye cycle sequencing kit (Perkin Elmer Applied Biosystems Division, USA). Sequences were determined using an Applied Biosystems 3130xl capillary electrophoresis genetic analyser.", "The study comprised 888 respiratory specimens from individuals who had presented to Queensland hospitals with signs and symptoms of ARI during May to September 2004. This included 324 previously described specimens [43] . Specimens were predominantly nasopharyngeal aspirates (NPA; 97.9%) collected either from outpatients or admitted patients. Specimens were selected by season, without prior knowledge of patient details or viral diagnostic status. The subjects ranged in age from three days to 92.4 years (mean = 7.9 years, median = 1.1 years, mode = 0.2 years), with infants (one to twelve months old) comprising 41.1% of the study population." ] },{ "paper_id": "71ff6abe3023a4c48fd6e6c54265bce395b88397", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "7203ff6238ce039aad6fbcbceab04051a59ae0e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In pediatric HIV-1 infections, LF enhanced responses to antiretroviral therapy by decreasing plasma viral load and modulating the immune system [107, 108] . LF treatment alone increased CD4+ cell counts, but a more significant increase was observed when LF was combined with antiretroviral therapy [107] . Result suggested that no HIV-1-related symptoms were evident for the duration of the experiments. However, large-scale studies are required in order to further assess LF's therapeutic potential against HIV.", "Eosinophils contain large cytoplasmic granules that play a critical role in innate immune responses. These granules are storage hotspots for major cationic antimicrobial proteins including eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP). Both EDN and ECP are human antimicrobial proteins that are active ribonucleases and members of the human RNase A superfamily [119, 120] . The antimicrobial properties of RNases were mapped to the N-terminal domain that is conserved among ribonucleases [3] . While both proteins contain characteristic RNase A superfamily structures and catalytic residues, they exhibit antimicrobial activity against both bacteria and viruses (Table 1) .", "The authors declare no conflicts of interest.", "Defensins are defined by the presence of a conserved spacing pattern comprised of cysteine residues, which is critical for the efficacy of their cationic antimicrobial properties [9, 12] . Human \u03b1-defensins are composed of 29 to 34 amino acids with an overall positive charge [9, 12, 13] . Defensins exhibit a characteristic \u03b2-sheet structure with a distinctive six-cysteine motif for which stabilization is a consequence of the presence of three intramolecular disulfide bonds. The \u03b1-defensins are synthesized as pre-propeptides consisting of a N-terminal signal sequence, an anionic pro-peptide, and a C-terminal mature peptide comprised of approximately 30 amino acids. HNP1, HNP2, and HNP3 are synthesized by promyelocytes and stored in primary neutrophil granules as mature peptides [10] . In contrast, \u03b2-defensins have a short N-terminal pro-region and can retain antimicrobial activity in full-length form, and; therefore, do not require N-terminal processing to be fully active [14] . They are synthesized in epithelial compartments and can range from 38 to 42 amino acids in length." ] },{ "paper_id": "720d81cbf900cfce68db61398f8c41f92f798314", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "there is no data supporting whether this effect of IFN-\u03b1 on ion transport is a generalized response during pulmonary infections.", "In this review, we will highlight advances in the understanding of how inflammatory responses in pulmonary infection affect ion transport, including common patterns and unique pathways activated by different respiratory pathogens, and how these mechanisms might be modulated to improve the outcomes of ARDS patients.", "Pathogen-induced lung injury but also sepsis can lead to widespread respiratory inflammation that favors accumulation of lung edema leading to multiorgan dysfunction and poor outcomes. Recent advances in the development of novel treatment strategies targeting respiratory ion homeostasis show encouraging results, identifying them as promising candidates to improve AFC in ALI which could potentially improve the survival of patients with ARDS. " ] },{ "paper_id": "7212e4cdbb493aa171b9d07c3946114d715f1e5b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The bacterial strains and plasmids used in this study are listed in Table S1 . S. suis strains were grown in Todd-Hewitt broth (THB) (Difco Laboratories, Detroit, MI, USA) supplemented with 2% yeast extract (THY), and E. coli strains were cultured in Luria-Bertani (LB) medium. Agar (1.5%) was included when solid medium was desired. If required, antibiotics were added at the following concentrations: spectinomycin, 100 mg ml -1 for both S. suis and E. coli; chloramphenicol, 5 mg ml -1 for S. suis and 10 mg ml -1 for E. coli; erythromycin, 1 mg ml -1 for S. suis and 250 mg ml -1 for E. coli; ampicillin, 100 mg ml -1 for E. coli; kanamycin, 50 mg ml -1 for E. coli.", "SS2-NDrecA 8.7 \u00a5 10 -8 CDxis SS2-NDrecA 2.9 \u00a5 10 -6 05ZYH33Dhlc SS2-NDrecA < 10 -8 CDhlc SS2-NDrecA 6.5 \u00a5 10 -6 05ZYH33 (pVA838-oriT) SS2-NDrecA 6.1 \u00a5 10 -4 DmobA89K (pVA838-oriT) SS2-NDrecA < 10 -8", "*These values are the means of three independent experiments.", "Where appropriate, the data were analysed using Student's t-test, and a value of P < 0.05 was considered significant. G.F.G. is a leading principal investigator of the Innovative Research Group of the NSFC (81021003)." ] },{ "paper_id": "721f194d7cd4953a229e067f3e1b79ec2cf22aca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The term ''focused ethnography'' describes a qualitative research approach employed when what is sought is an explication of behaviour or beliefs pertaining to a specific area so that their meaning among a defined group of individuals might be understood [23] . In focused ethnography, research is not directed towards a culture but rather a particular subculture or group of participants that share some feature or features [23] . This method is used when research questions are best responded to through descriptive analysis and interpretation [23] .", "I support my family by doing a lot of technical stuff\u2026 pulling calves, pushing prolapses, preg[nancy] testing cows.", "One participant described how much the veterinary profession had changed during their career.", "Study participants were located in a variety of practice settings in all areas of the province of Alberta. Each participant came from a different veterinary practice; two participants were female (20%). Veterinarians had from two to 38 years (median, 24 years; mean, 22) of clinical experience. Nine (90%) veterinarians were in mixedanimal practices, while one was exclusively in beef cattle practice. Further details on the study participants are not provided to protect their identities." ] },{ "paper_id": "722a5ed90b663c564f0ea7e7efd9eefc369f19be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request." ] },{ "paper_id": "7234aab6f4e46d4349fee1e8b38412a5eaebbe3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen, which is distributed in sub-Saharan Africa [1] and has also caused large outbreaks in Madagascar [2] , Egypt [3, 4, 5] , Saudi Arabia [6] , and Yemen [6] . In endemic areas, RVFV naturally circulates among mosquitoes and ruminants, such as sheep, goat and cattle [7] . RVFV infection in adult ruminants causes febrile illness and a high rate of abortions, while some newborn animals less than 1-2 weeks of age develop an acute infection which results in higher mortality rates than those in adults [8] . Humans infected with RVFV usually develop an acute febrile myalgic syndrome; however, a small percentage of patients have a lethal illness that results in hepatic damage, hemorrhagic fever-like illness, encephalitis and/or retinal vasculitis [8] .", "The luciferase assay was performed on a Renilla Luciferase Assay System (E2810, Promega Corporation) according to the manufacturer's instructions.", "Cells were lysed in sample buffer and boiled for 10 min. Equal amounts of samples were subjected to sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE). Proteins were electroblotted onto polyvinylidene difluoride membranes (immobilon P; Millipore). Western blot was performed as described previously [27] . The following primary antibodies were used: anti-RVFV [27] ; anti-NSs [48] " ] },{ "paper_id": "724974cf3a9e24f32408a976803e16254a9803c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All models were applied using backward removal of variables with a p-value of \u22640.2, with this higher p-value chosen to avoid early exclusion of variables that might influence the model [24] . Manual backward step-down selection was then applied at a p-value of \u22640.05. Confounding was controlled for by including omitted variables that changed the estimate of the other variables by more than 20%. Two-way interactions between all explanatory factors were investigated. The statistical significance level was defined as a two-tailed p-value \u22640.05. QGIS 2.0.1 software was used to map the distribution of villages in \u00a9 OpenStreetMap contributors (openstreetmap.org).", "The study involved three out of Cambodia's four agroecological regions, to cover possible differences in climate, farming traditions and culture. These regions were: Kampong Cham province, a lowland area characterised by fertile cultivated plains close to the Mekong river; Battambang province, characterised by immense wetlands resulting from flooding which have substantial biological diversity and border Lake Tonle Sap [17] ; and Kampot province, a coastal area dependent on fish and containing the wildlife-rich Preah Monivong Bokor National Park ( Figure 1 )." ] },{ "paper_id": "724fa0c1969874d0051c6f86795971aab0054c05", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Significance of the data was determined by a two-tailed Mann Whitney U test for non-parametric independent samples using IBM SPSS (Version 21).", "Supplementary Materials: The following are available online at http://www.mdpi.com/1999-4915/11/2/152/s1, Figure S1 : Full size blots for Figure 3C , Figure S2 : Full size blots for Figure 4A ,B, Figure S3 : Full size blots for Figure 4D , Figure S4 : Full size blots for Figure 5A . ", "One percent agarose (Invitrogen, USA) gels were prepared using 0.5\u00d7 TBE (Tris-1M (VWR), Ethylenediaminetetraacetic acid disodium salt (EDTA) solution-0.02 M (Gibco), and Boric acid-1M; pH 8.4). A 1 \u00b5L SYBR Safe DNA gel stain (Invitrogen, Camarillo, CA, USA) was added for every 1 mL of gel. In total, 10 \u00b5L of PCR or qRT-PCR products were electrophoresed on the gel for 1 h at 105 volts and visualized under an ultraviolet gel imaging system (AlphaImager HP)." ] },{ "paper_id": "725984c84bc703a34bc290f897e9f411ba3a67ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Increasingly, bioaerosol sampling has been proposed and implemented in outbreak investigations and pathogen surveillance using ad hoc approaches. The development of best practices in these areas is essential to generating valid and actionable data.", "Keywords: bioaerosols, microbes, virus, infections, viral dissemination, network, CANIBAN, collaborations", "SM framed the manuscript and contributed content. NG contributed content and generated the figure. ES contributed content and supported manuscript organization. TC, ST, JS, CR, NT, EB, GA, SK, MG, GK, and CZ contributed content and expertise and CD helped to frame and contributed content." ] },{ "paper_id": "725b175750813a29f16faee9a389ed706eba5ae4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Apoptosis. Immunoblot analysis of cells driven apoptotic by Clinical and Developmental Immunology ", "To compare individual experiments, optical density (OD) of cells that were not exposed to the apoptogenic protein was set to 1. All other OD values within an experiment were divided by the OD of untreated control cells to provide a relative apoptosis value in arbitrary units. Data obtained from independent experiments are presented as the mean \u00b1 SE, and the differences between conditions were analyzed using Student's t-test and Student's paired t-test. Differences at P < 0.05 and P < 0.01 were considered significant.", "A few mycobacterial molecules involved in macrophage apoptosis have been identified; among these are LpqH [16, 17] , ESAT 6 [11] , PE PGRS33 [18] , and PstS-1 [19] . We undertook this study with the aim of knowing better the biochemical pathways used by LpqH to induce MO apoptosis, specially to know if mitochondrial factors were involved. LpqH is interesting for several reasons; it is one of the few mycobacterial proteins, which in addition to acyl groups possess mannose residues [20] . Recently, we demonstrated that LpqH behaves as an adhesin that interacts with the mannose receptor to promote phagocytosis of mycobacteria [21] . LpqH induces T cell-mediated immunity, although it might also behave as a TLR2 agonist that downregulates antigen presentation to T cells [22] ." ] },{ "paper_id": "72613cfcf7d9ce3ba6d87fa24e2c220a15914d73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses. Reovirus serotype 1 Lang (T1L) and serotype 3 Dearing, Cashdollar strain (T3D) are laboratory stocks. The viruses were grown and titrated in mouse L929 cell monolayers in Joklik's Suspension Modified Minimal Essential Medium (J-MEM) (GIBCO products, Grand Island, NY, USA) supplemented with 5% fetal bovine serum (FBS), and 200 mM l-glutamine, as previously described [26] .", "The 30 concatenated fractions collected from the first dimension high pH reversed-phase (RP) fractionations were analyzed separately by low-pH RP LC with on-line ESI/TOF Quadupole MS/MS detection (QStar Elite) as was previously described [13] . Raw MS/MS data were analyzed using the Protein Pilot TM (ABSciex) program that identifies proteins based on cumulative peptide scores, and generates Light:Heavy ratio scores based on intensity ratios of corresponding peptide peaks.", "Within each experiment, proteins identified with L:H ratios were normalized using z-score analysis, described previously [13] . Briefly, all L:H ratios were converted to log 2 , and average ratios and standard deviations were determined after removal of significant outliers. Each protein's ratio was then converted to a z-score using the formula: ", "Almost O of the cells demonstrated infection by 12 hpi and .99% of the cells showed virus infection by 24 hpi (Figure 2b) . Previous studies indicated that increasing the MOI exponentially causes virus replication to start earlier, but the same proportion of cells become infected [30] . For our proteomic analyses, we used an MOI of 5 to ensure that by 24hpi the vast majority of cells are infected and also allowed a greater window of opportunity to observe the earlier infection process before virus production occurs (6hpi)." ] },{ "paper_id": "7266d5a2b588f4bd08e301590247156d59a7f227", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mice were purchased from Jackson lab and kept in a specific pathogen free environment at Naitonal Jewish Health. All mice experiments were carried out in strict accordance with the guides for the Care and Use of Laboratory Animals of National Institutes of Health. The protocol AS2517-07-13 was approved by the National Jewish Health Institutional Animal Care and Use Committee.", "3-month old BALB/c mice were immunized intraperitoneally three times with 20 \u03bcg OVA protein mixed with LANAC (Liposomes and unmethylated DNA) with one week interval. OVA antibody titer in mouse serum was confirmed by ELISA using OVA coated plate. 20 \u03bcg OVA in PBS was then injected intraperitoneally for boosting three days before sacrificing the mice." ] },{ "paper_id": "7267644046c69d176e889933002a9c8819751ff8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Exon resequencing and variants identification. We used conventional PCR and Sanger sequencing to screen all protein-coding exons and splicing regions of SLC10A1 for 40 unrelated PI samples (Supplementary Table 1B ). Each fragment amplified by PCR from genomic DNA was sequenced on both strands with an ABI Prism 3700 sequencer. The Phred-Phrap-Consed-PolyPhred package (http://www.genome.washington.edu/) was used to assemble the sequences and identify variants.", "Significance values for each of the above three test statistics were estimated from 10 4 coalescent simulations of a Wright-Fisher equilibrium model that condition on the sample size and level of polymorphism as the observed data, with no recombination, using DnaSP Software 52 and Fay's H-test (http://www.genetics.wustl.edu/jflab/htest. html), respectively." ] },{ "paper_id": "7274f439641a1f4dc180a94cafe9b69d37e60415", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total and small RNA preparation, library construction and Illumina sequencing RNA was purified from 0.5 g of flies using the Ambion mirVana miRNA Isolation Kit (PE Applied BioSystems, Warrington, England) according to the manufacturer's instructions for total and small-enriched RNA. Additionally, the latter were DNase-treated. All RNA extractions were stored at -80\u00b0C and evaluated on a Bioanalyzer (Agilent Technology, Santa Clara, CA, USA).", "To further test for chimeric sequences and other misassemblies, selected contigs (see Table 1 ) were validated via Sanger sequencing of overlapping RT-PCR products (Genbank accession numbers KF298278 to KF298284). Samples were DNase-treated prior to RT-PCR The PCR products were A-tailed and cloned into the TA vector -pGemTeasy (Promega, Madison U.S.A.), followed by transformation into DH5\u03b1 cells. Plasmid DNA were extracted by Plasmid DNA miniprep kit (NBS Biologicals Ltd. Cambridge U.K.) and sequenced with both M13F and M13R primers as well as internal primers when necessary (primer sequences available from authors on request).", "Single nucleotide polymorphisms (SNPs) were identified by mapping raw trimmed reads onto assembled contigs." ] },{ "paper_id": "727602c6861782ad9eb87bfff3fc6824b7008af5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Losses of up to 1,500 kg\u00b7ha -1 of cotton seed have been reported in some states [2] .", "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "72761826ce01da1fe5599c79547746b44fe5ec49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The IBRV UL52 region fragment (300 bp) were synthesized by Jierui Biotech (Shanghai, China) and cloned into pEASY-T3 vector, designated as UL-T3-RPA. The UL-T3-RPA standard DNA was extracted with Plasmiad Mini kit (Tiangen, Beijing) and measured using a Nanodrop ND-1000 spectrophotometer (Thermo Scientific, Dreieich, Germany). The DNA copy number was calculated by the equation: DNA cope number = (M \u00d7 6.02 \u00d7 10 23 \u00d7 10 \u22129 )/(n \u00d7 660) 28 , M: molecular weight, n: plasmid concentration measured at 260 nm. DNA standard was stored at \u221220\u00b0C until further used.", "Determination of sensitivity and specificity of the assay" ] },{ "paper_id": "727ff12fcef223c2e2c4971ef237c80ee4e58162", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "who.int/__data/assets/pdf_file/0015/330225/LTCF-best-practiceguidance.pdf?ua=1).", "antivirals, infection control, influenza, long-term care, vaccines" ] },{ "paper_id": "7293d0d1c84570d510be54e720daecfcf7a77990", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "The purple module (IM0) contains the genes (LCK, SKAP1, MyD88, MAPK14, VAV1, JAK2, SRC, CD79A, PTPRC, AMBP, DOCK8, PTK2B, SMAD3, CSNK2B, UBE3A, ", "Supporting information S1 " ] },{ "paper_id": "729748c83fe9f501d28aae521d7528ec33d0c7ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "729e5d420ec1a80d31928dc8bb261610a93aa890", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was conceived and experiments designed by BJ, YM, and FZ. The experiments were performed by YM, LFC, and BY. Data were analyzed and interpreted by YM, LFC, BJ, and FZ. YusiZ, CZ, YunZ, KT, and RZ contributed to the reagents, materials, or analysis tools. While YM and BY drafted the paper, LC, KY, BJ, and FZ all critically revised the manuscript for important intellectual content.", "Statistical analyses and graphing were performed using SPSS 16.0 (SPSS Inc., Chicago, IL, USA) and Prism software, version 5.0 (Graphpad; La Jolla, CA, USA). The frequency of the CD8 + T cells and the cytokines secreted are presented as the medians and range values. The Wilcoxon rank-sum test was used for parameter comparison between the two subject groups. A twotailed P-value below 0.05 (p \u2264 0.05) was considered statistically significant.", "The HTNV 76-118 strain was kindly provided by the Department of Microbiology of our university. The commercial HFRS inactivated vaccine (YOUERJIAN \u00ae , Zhejiang Tianyuan Bio-Pharmaceutical Co., Ltd., China) derived from a mixture of both HTNV and SEOV was provided as a bivalent and purified HFRS vaccine.", "This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Health and Medical Research Council of China. The protocol was approved by the Committee on the Ethics of Animal Experiments of the Fourth Military Medical University with the license number XJYYLL-2014437. All procedures were performed under sodium pentobarbital anesthesia, and every effort was made to minimize animal suffering." ] },{ "paper_id": "72a39958a44d1a0664d01a1965b3afba46aea827", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The pathology of TBI, described as a primary injury, results from mechanical damage to neural and vascular structures together with a progressive cascade of molecular secondary events leading to secondary injuries 3 that impair function, damage other brain structures and promote further cell death 4, 5 .", "Traumatic brain injury (TBI) is the leading cause of death and disability among young adults. In the US, TBI has been called \"the silent epidemic\" 1 , where relatively young victims (mean, 29.5 years of age) pose a tremendous burden to families and society in terms of years of lost productivity and increased demands on the healthcare system 2 . According to the World Health Organization, by 2020 TBI will become the world's leading cause of neurological disability across all age groups.", "Whilst improvements in emergency response times have increased TBI survivability, the necessity for discovering reliable markers by which to identify patients at risk of the development of secondary injuries and thus requiring more active monitoring and intervention remains a significant challenge." ] },{ "paper_id": "72a5995cb9dc08122a069c6b02e72f2894e0b07c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2.1. Cell Culture and DAC Treatment. Human myelodysplastic syndrome cell line SKM-1 was a gift from Professor Li Chunrui at the Department of Hematology, Tongji Medical College, Tongji Hospital, China. SKM-1 cells were cultured in Dulbecco's modified eagle medium (DMEM; Gibco Life Technologies, Grand Island, NY, USA) containing 10% FBS (Gibco Life Technologies) and 1% penicillin-streptomycin at 37\u00b0C in 5% CO 2 . When cells reached the logarithmic growth phase, they were seeded at a density of 5 \u00d7 10 5 cells/ well in 6-well plates and treated with 0.5 \u03bcM DAC (Xian-Janssen Pharmaceutical, Xian, China) for 6 days. Every 48 hours, the medium in the wells was replaced with fresh medium containing 0.5 \u03bcM DAC.", "FOXO3A, also known as forkhead in rhabdomyosarcomalike protein 1 (FKHRL1), is a transcription factor with important roles in embryonic development, differentiation, and tumorigenesis [1] . It is characterized by the presence of the distinctive forkhead DNA binding domain, a highly conserved winged helix motif, and regulates the transcription of genes involved in a variety of processes, including cell cycle regulation [2, 3] , apoptosis [4, 5] , DNA repair [6] , and autophagy [7] [8] [9] . FOXO3A function is regulated by posttranslational modifications such as phosphorylation, acetylation, and ubiquitination, which ultimately affect its nuclear/ cytoplasmic transport and hence cellular location [10] [11] [12] . FOXO3A is considered to be a potential tumor suppressor gene and is involved in the regulation of differentiation in various cell types [13] [14] [15] [16] . Furthermore, FOXO3A is inactivated, and its target genes are downregulated, following phosphorylation by oncogenic kinases such as AKT, MAPK1, and IKK, which are upregulated in many tumors [17] [18] [19] . Interestingly, the reexpression and activation of FOXO3A in tumor cells reportedly have potential in antitumor treatment [20] .", "Results were obtained from three independent replicate experiments and are expressed as mean \u00b1 standard deviation. Data were analyzed using SPSS version 13.0 software (SPSS Inc., Chicago, IL, USA). The significance of differences between groups was assessed using Student's t-test, and statistical significance was defined as P < 0 05." ] },{ "paper_id": "72aaf5f39ed048ee9ebda9af6fba6d6d12082e68", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The method was used to denoise EM density maps of several complexes obtained at subnanometer resolutions by single-particle analysis or subtomogram averaging (betagalactosidase, ribosome, and empty and full virus particles) [44] (Figure 5 ).", "This new method should result in a 3D reconstruction (model) optimally representing all given (raw) images via the determined elastic (normal-mode-based) transformations between the model and the images.", "In this article, we review the mentioned applications of this EM-map approximation method while only briefly reminding the method. For algorithmic details (e.g., related to adding/removing grains), the reader is addressed to [43] that describes this method in detail." ] },{ "paper_id": "72ac928abb4394f723426f2e506d71d4892c1036", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The atomic coordinates and structure factors for the TcaR-RNA complex have been deposited in the wwPDB with accession numbers of 4EJT.", "Host sensitivity to phages was tested using a virulent variant of phage (M13, wX174 and c) and E. coli BL21 (DE3) RIL transformed with engineered pET-16b-TcaR plasmid containing lacI gene and lac operator as host [47, 48, 49] . Cells were grown in LB media until the optical density (OD 600 ) reached 0.6. TcaR protein was then induced by adding a final concentration of 0.1 mM IPTG and used in plaque assays as previously described [50, 51] . Plaque assays were performed in triplicate. Plates and topagar contained LB and above mentioned concentrations of inducers. The sensitivity of the host to phage infection was calculated as the efficiency of plaquing, which is the plaque count ratio of a non-IPTG set to the IPTG set [52] . Error-bars were calculated as one standard deviation.", "Furthermore, in order to examine whether TcaR shows a binding ability towards much longer ssDNA fragments such as viral wx174-ssDNA, the interaction between them was also examined with increasing concentration (0, 2.5, 10 mM) of viral " ] },{ "paper_id": "72ace5af731fdf4c384e912b074193d13902b7a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BC005248. tates Antibody Dependent Cell mediated Cytotoxicity (ADCC) by NK cells [13] ." ] },{ "paper_id": "72b1311ad0c502a391201bff5805dcc57ee1c9e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The HEV interactome sets up the basis for studying the function of these proteins in the viral replication cycle; the identified interactions may result in potential targets for new antiviral drugs.", "The relevance of the ORF3-X domain interaction is difficult to assess as the biological relevance of the X domain is unknown." ] },{ "paper_id": "72b1f124ded8f8297f0f02ea6dbc0f9b7b27873a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background", "In infectious disease epidemiology, contact networks consist of individuals (nodes) with connections (edges) between them representing interactions that may lead to infection transmission 1 .", "The general objective of this work is to utilize radio frequency close-proximity sensors to describe and understand the nature of human networks within a low-resource population that have the potential to transmit respiratory infectious diseases. Specifically:" ] },{ "paper_id": "72b6e571746493f62630cc8eb59cd6fae5cb71e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical significance of the data was analyzed by Student's two-tailed t test.", "Frozen lung tissues were lysed using lysis buffer (100 mM Tris, 250 mM NaCl, 0.5% sodium deoxycholate, 1 mM PMSF and 0.5% NP40). Tissue lysates were resolved by electrophoresis in SDS-polyacrylamide gels and electrotransferred onto Hybond-P PVDF membranes (GE Healthcare). Milk blocked blots were incubated with anti-actin and -NP antibodies at 4\u00b0C overnight and then washed and incubated with horseradish peroxidase (HRP)-conjugated secondary antibodies (Jackson ImmunoResearch) at room temperature for 1 hr. The proteins were revealed using the Immobilon Western Chemiluminescent HRP Substrate (Millipore)." ] },{ "paper_id": "72c358060f8600b70abafbe9faa93aed79d87ada", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "72d4e41eee56e6b1e8b7b361375c2e9160a6da49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses are thought to be the ultimate parasites, multiplying inside the host cells and utilizing the resources of their hosts to produce vast number of infectious progenies. Intriguingly, many viruses have their own parasites, including defective interfering (DI) RNAs, as well as satellite viruses and " ] },{ "paper_id": "72d786b072bf999b5925c527f2b1e8dcf326247e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Funding: This work was funded by the Department of Health, UK (Grant in Aid), the DEFRA Biochip Consortium fund, UK and Public Health England Pipeline Fund, UK.", "Meningitis is a disease caused by inflammation of the meninges, the cause of which is generally associated with infection [1] [2] [3] . It can present acutely or chronically with less severe symptoms over a prolonged period. Acute meningitis is a syndrome defined by meningeal symptoms (headache, neck stiffness, vomiting, and photophobia) in conjunction with cerebral dysfunction (confusion, coma) and progresses over hours to days. The cerebral spinal fluid (CSF) often presents with leukocytosis. The most common causes of acute meningitis in the United Kingdom are bacterial and viral infection." ] },{ "paper_id": "72ddf8d0c71b8b1ece743904f2acd2c1a00984c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We discuss the assumptions made in this algorithm below.", "We simulate viral spread under a reasonable range of values for the R and k parameters. We examine R \u00bc 1.5 (a typical estimate for the 2009 pandemic [8] ) and in addition the higher values of 2.0 and 2.5 which may be more realistic for 'typical' previous influenza pandemics [25] . Because the dispersion parameter k is unknown, we consider a wide range, from extreme superspreading (such as thought to apply to the severe acute respiratory syndrome epidemic [19] ) (k \u00bc 0.1) to more homogenous infectiousness (k \u00bc 1 and 10)." ] },{ "paper_id": "72e1bab73b7f05d68543660981e0c8cef749c045", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "pneumoniae are younger, less likely to have comorbidities, and have longer duration of fever before admission.", "The authors declare that they have no competing interests." ] },{ "paper_id": "72e1f47796b2283c03f3d7aa4f6044592f8c198d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Swine studies were performed at Newport Laboratories and were approved by the Newport Laboratories' Institutional Animal Care and Use Committee.", "Conclusions: These results demonstrate the immunogenicity of a PEDV inactivated viral vaccine with a U.S. strain via dose-titration. A future vaccination-challenge study would illustrate the efficacy of an inactivated vaccine and help evaluate protective FFN titers and ELISA and FMIA responses.", "Classically attenuated cell culture passaged PEDV also shows mutations in open reading frame 3 (ORF) and changes to restriction fragment length polymorphism (RFLP) cut patterns, which have been used to distinguish MLV from field strains [10, 20] . In vivo, high-passage (x > 100) MLVs were attenuated in sows and piglets while still capable of inducing a robust immune response [20] . While attenuated in their ability to cause disease, the safety of using MLV has been questioned, as MLV are shed in the environment. Virus was detected in feces of 3-day old piglets up to seven days after oral inoculation with DR13 passage 100 [12, 21] . In 2010, PEDV was isolated from diarrheic pigs in China that had a close phylogenetic relationship to two MLV vaccines, suggesting it may have evolved from a MLV [22] ." ] },{ "paper_id": "72e26f33ba7ffdd2ecd34c365e6c5fc9cf424113", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NS3 is a trypsin like serine protease which plays a role in post-translation in the virus maturation. This domain has a catalytic triad made up of His51, Asp75 and Ser135 and its activity is enhanced by NS2B as the cofactor [16, 17] . This cofactor contributes to the NS3 activity through its hydrophilic region which is responsible for holding and promoting the activation of NS3 while the hydrophobic region takes part in membrane association upon the cleavage process [18, 19] .", "Dengue, caused by Dengue Virus (DENV), is the most important mosquito-borne viral disease affecting the tropics and subtropics [1] . Endemic in more than 100 countries [2, 3] , the virus is estimated to cause 390 million infections each year [4] . DENV infections can result in serious diseases including dengue fever, dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and even death [5] . There are no approved antiviral drugs for these diseases and currently, patients are treated with supportive care to relieve fever, pain, and dehydration [6] . A tetravalent dengue vaccine (CYD-TDENV or Dengvaxia), the first dengue vaccine has recently been registered in several countries [7] . Despite being a leading cause of hospitalisation and death among children in some Asian and Latin American countries [8] , this vaccine is not recommended for use in children under 9 years of age due to safety concerns [7] . Therefore, there exists an urgent need for antiviral therapies to treat dengue.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "72e37ddb3310bf50385723819244148ab9a787f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that they have no competing interests. " ] },{ "paper_id": "72e9038e9738f001e0b050d11f9b05a6376919bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "From April 2010 onwards, we continued to register cases from all participating hospitals, but influenza diagnosis was offered only to patients from 4 hospitals covering roughly 13% of Berlin's population, resulting in a lower proportion of swabbed patients.", "Overall, we identified 1,025 patients fulfilling the broad CD1 definition (Table 1 ). Of these, 283 (28%) fulfilled CD4 criteria. The remaining 742 (72%) cases were classified as CD1b. Case definition criteria for CD2 were met by 63% (n = 648) and for CD3 by 53% (n = 539)." ] },{ "paper_id": "72f81539c6237420551180793d727062bdd043bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Methicillin-resistant Staphylococcus aureus (MRSA) is among the most important nosocomial pathogens in the intensive care unit (ICU) worldwide, including Taiwan. Since 1997, our neonatal ICUs (NICUs) had become endemic for MRSA.", "Specimens for surveillance culture were obtained with a cotton swab, placed in a transport medium (Venturi Transystem), and then processed in the microbiology laboratory within 4 hours. Identification of MRSA was confirmed according to National Committee for Clinical Laboratory Standards guidelines [24] .", "Chang Gung Children's Hospital is a university-affiliated teaching hospital, situated in northern Taiwan, that provides a range of care, from primary to tertiary care, and is a part of Chang Gung Memorial Hospital (CGMH). There are three NICUs, distributed on 2 floors, in this children's Hospital. Currently, there are 17 and 20 beds in NICU-1, and NICU-2, respectively. NICU-3 included two areas, 12 level -III beds in area 1 and 45 non-level-III beds in area 2 (special care nurseries). All the healthcareassociated infections (HAIs) in three NICUs from 1999 to 2007 were prospectively collected and recorded according to the standard definition of HAIs [20] .", "Surveillance cultures for health care workers (HCWs) were performed, during surveillance periods, and specimens were obtained from the nares of HCWs working in both units. Intranasal mupirocin treatment was applied to the nares of each HCW with MRSA colonization." ] },{ "paper_id": "72f9a628e9d59676c5cbed4485e64c5757a4c78a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The RT reaction (55uC for 30 min) was followed by 94uC for 2 min and 40 cycles of PCR (94uC for 30 sec, 50uC for 30 sec, and 68uC for 1 min 45 sec, for each cycle) and a final extension at 68uC for 10 min." ] },{ "paper_id": "731076fd240ebb00a9faf96ca9cedd40fb5fa50c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary File 1: Study questionnaire.", "Click here to access the data." ] },{ "paper_id": "7314f2ac32ead26d507b36cd305ffd76736f1007", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The viruses listed in Table S1 were tested for using realtime PCR and found to be negative using specific primers and TaqMan probes on an ABI 7500 thermocycler.", "Briefly, mRNA was isolated from total RNA using oligo dT beads to pull down poly-adenylated transcripts. The purified mRNA was fragmented using chemical fragmentation (heat and divalent metal cation) and primed with random hexamers. Strand-specific first-strand cDNA was generated using SuperScript II Reverse Transcriptase (Life Technologies) and actinomycin D. This allows RNAdependent synthesis while preventing spurious DNAdependent synthesis. The second cDNA strand was marked by performing synthesis incorporating dUTP.", "We estimated a maximum likelihood phylogenetic tree using RAxML [27] and 64 full MuV genomes from Gen-Bank (accessed on 20 June 2015)." ] },{ "paper_id": "731a1455688921b0d728c1ca833b7fa918c1e435", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Estimation of malaria incidence in northern Namibia in 2009 using Bayesian conditional-autoregressive spatialtemporal models", "PLoS Negl Trop Dis 2016", "West Africa; London, England" ] },{ "paper_id": "732933f36dc0c57fd8094f545c5e82d7192a13c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Compound IV was a white power (methanol). With the exception of having glucose features, its 13 C-NMR (see Supplementary Fig. S9 ) spectrum was the same as that of Compound 1. Its molecular formula was established as C 21 Compound V and VI were named isoliquiritin apioside and liquiritin apioside, respectively 21 .These name were given because their 13 C-NMR (see Supplementary Fig. S11, 13 ) spectra included a group of apiose signals thatcompounds4 and 3 did not have, and EI-MS indicated a molecular formula of C 26 H 30 O 13 for both of them.", "Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 12503 |" ] },{ "paper_id": "732dff5e34c82bab1a77fe07eeff62b1a0e44fa7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data from 322 adult patients receiving ECMO were analyzed. AKI and its stages were defined according to Kidney Disease Improving Global Outcomes (KDIGO) classifications. Variables within 24 h before ECMO insertion were collected and analyzed for the associations with AKI and in-hospital mortality.", "receiving continuous renal replacement therapy when ECMO were initiated (n = 66), if they initiated continuous renal replacement therapy on the date of ECMO insertion (n = 77). Therefore, 322 patients were ultimately analyzed in the present study." ] },{ "paper_id": "733c577e6a1dea9aab436bce4d918f08dfd27371", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "doi:10.1371/journal.pone.0133008.t005 commercial SDPP for a feeding duration of 3 to 4 times higher than typically used in commercial practice, have shown that SDPP is a safe protein ingredient that does not transmit PPV and porcine circovirus type 2 (PCV2) [11, 12, 17, 18] , which are two of the more thermal and solvent resistant known viruses.", "Samples of inoculated liquid plasma and irradiated plasma were frozen with dry ice prior to analysis of infectivity in SK6 cell cultures using the microtiter assay procedure [7] .", "Analysis of variance was performed using the GLM procedure of SAS (SAS Inst., Cary, NC).", "Average pen values were used as the experimental unit for the performance parameters. The model considered the effects of block and dietary treatment (5 diets). Data were adjusted by the covariant of initial body weight. Orthogonal contrasts were used to test the effects of SDPP processing (UV vs no UV) and dietary SDPP level (3% vs 6%). Results are presented as least squares means. The level of significance was set at P < 0.05 and trends were discussed at P < 0.10.", "Nutrients Tissue culture infection dose was determined by microtiter assay procedure [7] . 3 The theoretical limit of detection of the method used was estimated to be 0.23 viral particles per mL." ] },{ "paper_id": "73560247ea59c1db0dd80dc9022c7d6795f7d671", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We ran all statistical tests in R version 3.1.2 [106] . We fitted mixed-models using the package lme4 (version 1.1-7) [103] . We performed model averaging using the MuMIn package (version 1.12.1) [107] . We report mean \u00b1 standard error (SE)." ] },{ "paper_id": "735dca3ec505ecf1a2e01d913c945a7d18f3efcf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The primary coordinator coordinated the storage and shipment of human specimen materials to OUCRU laboratory in HCMC. All specimens were separated into three equal aliquots and preserved at \u221280\u00b0C until processing.", "The study was approved by the University of Oxford Tropical Research Ethics Committee (OxTREC No. 0109) and the Scientific and Ethical Committee of the Hospital for Tropical Diseases in Ho Chi Minh City. Written informed consent was required from patients and parents or legal guardians if children under age of 16 prior to participation in the study.", "Europe PMC Funders Author Manuscripts" ] },{ "paper_id": "7360f5cfdd468aea794a9eb68291950862c8fcb0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. All data were analyzed using GraphPad Prism (Version 5.03, San Diego, CA, USA) software. Differences among groups were examined using one-way analysis of variance (ANOVA), followed by Tukey's tests.", "Necropsy examinations showed that the virus inoculated piglets displayed typical PED-like lesions. The small intestine was thin-walled and contained soft to watery contents (Fig. 4d) . Small intestine contents obtained at necropsy were also tested by PEDV RT-qPCR and had 10 7.2 to 10 10.1 genomic copies/ml. Histopathological examination showed severe necrosis and villous atrophy of the small intestinal enterocytes in JSCZ1601 inoculated pigs (Fig. 4e) . Villus height and crypt depth were measured, and the mean villous height/crypt depth (VH/CD) ratio of the mock-inoculated piglets (6.5\u00b1 0.8) was higher than those of JSCZ1601inoculated piglets (1.3\u00b1 0.5)." ] },{ "paper_id": "7364053f8be4467970465443c10cc3b39e573137", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The emergence of Zika virus (ZIKV)", "For a negative control animal a male bat was trapped from the colony and euthanized under the same protocol as the experimental infection bats.", "Stained sections were imaged on a Ziess LSM 800 with Airyscan laser-scanning confocal microscope (Ziess, Oberkochen, Germany) using a 63\u00d7 oil immersion objective. Each field of view was imaged as a z-stack (8-10 planes, .5-\u03bcm step size) transformed into a single maximum projection image using the Ziess Zen (blue) imaging software.", "Hematoxylin and Eosin Stain (H&E). Heart, lung, liver, kidney, testes, prostate, urinary bladder, and brain were collected from all 9 animals as well as salivary glands from 3/9 bats. All samples were blindly read by one pathologist. A summary of the consistent histopathology findings is listed in Table 2 ." ] },{ "paper_id": "7366b56a55321eebcb1d38074932d23ad4346038", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our approach to C052 (IC2a) and C055 (IC3a) involved a convergent pathway whereby (1) the Gewald reaction was employed for the thiophene unit (IC4 of zone 1) and (2) a Horner-Wadsworth-Emmons reaction of 2-thiophenecarboxaldehyde (IC5) and 2-pyridinecarboxaldehyde (IC6) with malonic acid followed by acid chloride formation provided a means to IC7 and IC8, the zone 5 modifiers. Bringing these units (IC4 and IC7/ IC8) together produced IC9 and IC 10. Saponification of IC9 and IC10 gave the sodium salts IC2b and IC3b, which, upon acidification, yielded the desired final products C052 (IC2a) and C055 (IC3a) (Fig. 3) .", "Forward primer: 59-GATTGATGTTTACAGGGATGAGGT-39", "Reverse primer: 59-TCTTCCTCTGCTTGCGTCCT-39" ] },{ "paper_id": "736d5109d55feed08b21d5b95eff52f2e50eea59", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "73761176155e77d6873806dd9579f59e5419111a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In terms of detection sensitivity, EOPM could reliably detect EV71 when >10 6 copies of EV71 RNA were mixed into 10 12 copies of HeLa cell RNA, while 10 3 copies of spike virus RNA could be detected in 10 12 copies of host RNA by specific RT-PCR following agarose gel electrophoresis. Therefore, we inferred that when there was a high level of background nucleic acid, the detection sensitivity of random primer amplification was three orders of magnitude lower than specific primer amplification." ] },{ "paper_id": "7379b8c28321b7f9c78d2b4d35109a87b35cf883", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "M gene was cloned by digesting pIBVM with NcoI and EcoRI, and inserted into EcoRI/NcoI digested pGBKT7 to generate pGBKT7-M. The PCR fragment for actin was amplified by using primers 59-CGCGGATCCATGGATGATGATATCGCCGCG-39 and 59-CCGCTCGAGGAAGCATTTGCGGYGGACGAT-39. The PCR fragment was digested with BamHI and XhoI and ligated into BamHI and XhoI digested pXJ-myc to generate pXJ-myc-actin.", "The deletion constructs MD1, MD2, MD3, MD4 and MD5 were made by two rounds of PCR as described previously [15] . The primer used for MD1 is 59-AACTGCAGTTAAGC-AAGCCACTGACCCTC-39. The primers used for MD2 are 59-TCTTTTGTAGGTTATAAGTGTGAACCAGAC-39 and 59-GTCTGGTTCACACTTA TAACCTACAAAAGA-39. The primer for MD3 is 59-AACTGCAGCCGCTTT GGTCACCAG-39. The primers for MD4 are 59-TGTGAGGGTCCAGAC-CACTTG-39 and 59-CAAGTGGTCTGGACCCTCACA-3. The primers for MD5 are 59-GGTCAGTGGC TTTGTGAA-CCAGAC-39 and 59-GTCTGGTTCACAAAGCCACTGACC-3. All constructs were confirmed by automated nucleotide sequencing.", "H1299 and Vero cells were cultured in RPMI-1640 and complete Dulbecco's modified Eagle's medium (Invitrogen), respectively, supplemented with 10% new born calf serum (Sterile) and 1% penicillin/streptomycin (Invitrogen) and maintained at 37uC in humidified 5% CO 2.", "The actin-binding proteins are grouped into 60 distinct classes based on primary structures [35] . The sequence of the actinbinding sites ranges from 10-30 residues, which shows no obvious homology among different classes [36] . For example, Aldolase, a glycolytic enzyme, binds actin filaments to concentrate enzyme and substrate [37] . The sequence 32-ADESTGSIAKRLQSIG-TENTE-52 of aldolase has been identified as the actin-binding motif [38] . Furthermore, Carcinoembryonic Cell Adhesion Molecule 1 (CEACAM1) was found to bind F-actin. The actin binding site is FLHFGKTGSSGPLQ, which is not similar to other existing actin-binding sequences [39] ." ] },{ "paper_id": "737e13b0236c1e2a6ada9c31ad3d8987a559b244", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BAL used for bacterial culture was stored diluted 2 fold in skim milk tryptone glucose glycerine broth at -80\u00b0C. BAL for viral or bacterial analysis by PCR was stored undiluted at -80\u00b0C. Samples were maintained at -80\u00b0C prior to testing.", "Airway neutrophilia (>15%) was found in 41% of children. A clinically important level of bacterial infection (>10 4 cfu/ml BAL) was present in 20 children (28%) and one or more viral pathogens detected in 30 (44%). Non-typeable H. influenzae (15.5%), S. pneumoniae (15.5%) and rhinovirus (29.4%) were the most common pathogens identified (detailed microbiology is presented in S1 Table) .", "Routine clinical investigations (eg full blood count including white cell count, platelets, Creactive protein (CRP) and serum protein) [1] were performed using the regional reference laboratory Royal Darwin Hospital." ] },{ "paper_id": "7384db26f7f0a5f8c75844b2225b1783e6d783e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PAM8.1 was not tested by Western blotting with IEs expressing VSAPAM, but was tested with VAR2CSAspecific constructs (see below).", "Human monoclonal antibody PAM1.4 effectively selects for expression of VSA PAM and increased transcription of VAR2CSA", "Human VAR2CSA DBL3-X-specific monoclonal IgG antibodies recognize epitopes that vary between parasite isolates" ] },{ "paper_id": "7387ab0ad7fdb62b372043fc912931583e5c7af0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "738d255294896f43d6ac7546a891900714ef1d51", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coating of retrovirus with PEG-poly(L-lysine)(PLL) block copolymer improved transduction efficiency 3 to 7 fold without increasing cytotoxicity.", "Model Biological effects Ref.", "Reconstituted viral membranes containing 3 mol% poly(ethyleneglycol) grafted phosphatidylethanolamine retained 40% of their fusion activity." ] },{ "paper_id": "73939a4a3eff4347a97d4dbe05c46a3a1fc08a82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The quantitative data on the completed survey was collected in Microsoft Excel. OpenEpi (version 2.3) was used to calculate [8] , proportions, 95% confidence intervals and \u03c7 2 tests for significance. Alpha was set at the 5% level. We used logistic regression to compute odds ratios to evaluate the association of demographic variables and attitudes and beliefs.", "Universities are not immune to natural or manmade disasters, and past experience with these have illustrated the importance of continuity during and after these events [5, 9] . In an influenza pandemic, such institutions must maintain a balance between academic continuity, with infection control and minimising morbidity [5] .", "(2) modes of spread and common symptoms; (3) recommended health advice consistent with both the WHO and national recommendations; and (4) contact information for the relevant health departments [6] . Posters developed by the Commonwealth Department of Health and Ageing and UNSW were placed in high traffic areas and focused on: (1) encouraging faculty, staff and students to stay at home if symptomatic (i.e. with a fever, cough, and runny nose) and to protect each other; (2) cough/sneeze etiquette (i.e. \"cover your mouth and nose when you cough and sneeze\" and \"dispose of used tissues in the bin) and (3) hand hygiene (i.e. \"Wash your hands properly and regularly\")." ] },{ "paper_id": "73962bb05d0fa45657756857801fbb3f9e139b04", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All tissue samples were collected according to protocols that were approved by the TMU-Joint Institutional Review Board of Taipei Medical University (S1 Table) . Written informed consent was obtained from all patients before the collection of tissue samples.", "The profiles of the study participants were presented in S1 Table. Compared with the control group of normal endometrium or hyperplasia, women with adenomyosis or chocolate cyst had a younger (P = .005) age and a higher level of cancer antigen (CA) 125 (P = .04).", "The transfected cells were lysed in an ice-cold protein lysis buffer containing 50 mM Tris, 150 mM NaCl, 5 mM EDTA, 0.1% sodium deoxycholate, and 1% sodium dodecylsulfate (SDS) (pH 8) that was supplemented with a protease inhibitor cocktail (Roche). The cells were incubated in the lysis buffer for 30 minutes on ice, followed by centrifugation at 15 000 \u00d7g for 15 minutes. The supernatants were collected for western blot analyses. Cell lysate aliquots (30-100 \u03bcg of total protein) were subjected to SDS-polyacrylamide gel electrophoresis on a 10% acrylamide gel, and the protein bands were transferred to polyvinylidene difluoride membranes." ] },{ "paper_id": "7398c3a708a291677e55854601f643ba41d79916", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IndexOf(\"G\"+ temp), i);", "3. Set X' ; 4. Integer i; 5. //Step1 6. X 0 :\u00bc V ; 7. i :\u00bc 1; 8. //Step 2 9. while X 0 6 \u00bc do 10.begin 11.select an arbitrary x2X'; 12.C i :\u00bc connectedComponent\u00f0G; x\u00de; 13.X 0 : X 0 \u00c0 C i ; 14.i :\u00bc i \u00fe 1; 15.end 16.return C; Figure 2 Switch node. All contiguous nodes are merged in one node. This operation is named \"The path collapsing\"." ] },{ "paper_id": "739e01113e6c837a1fb973b1ab7e434cc9c27904", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are presented as means 6 standard errors of the means (SEM). Differences between two groups were determined by Student's two-tailed unpaired t tests or paired t tests (when normalized DI were compared), using GraphPad Prism 5.03 software. Differences with values of P,0.05 were considered significant. *, P,0.05; **, P,0.01; ***, P,0.001.", "A Foxp3 Staining Buffer Set (eBioscience) was used for Foxp3 or T-bet staining or when cells were analyzed for Foxp3 and cytokine expression simultaneously; otherwise, BD Cytofix/Cytoperm and Perm/Wash buffers (BD Biosciences) were used in intracellular cytokine staining assays. Cell sorting was performed with a FACSDiva or FACSAria and cell analysis with a FACSCalibur or LSRII (BD Biosciences).", "Specific pathogen-free C57BL/6 (B6) and B6/Thy1.1 mice were purchased from the National Cancer Institute, Bethesda, MD. Foxp3 gfp mice on a B6 background were kindly provided by Dr. A. Rudensky (Sloan-Kettering Institute) and were bred to a Thy1.1 background. IL-12Rb2 2/2 mice on a B6 background were obtained from Dr. J. Harty (University of Iowa). ", "This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Mice were housed in the Animal Care Facility at the University of Iowa. The protocol was approved by the University of Iowa Animal Care and Use Committee (Protocol Number: 1007161). All efforts were made to minimize animal suffering." ] },{ "paper_id": "73a2171fc7716dd485b9c3348902a7672213fc0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The activation of signaling pathways indicates that only cells in a defined activation state are susceptible for infection. What type of molecules may trigger that state? Is there a link between signaling and the entry complex?", "The following figure supplement is available for figure 6:", "Immunofluorescence microscopy (for analyses on Zeiss Axiovert microscope)", "Viral infections by human papillomaviruses (HPVs) cause benign warts and malignant tumors. The small, non-enveloped virus is constituted of a circular DNA genome surrounded by a capsid mainly built of the L1 protein. More than 240 papillomavirus types have been characterized in diverse hosts, including mammals, birds and reptiles. For instance, the oncogenic HPV types 16, 18, and 31 are responsible for severe human cancers, including cervical cancer and anogenital, head and neck tumors (Doorbar et al., 2012) ." ] },{ "paper_id": "73ae7423efc653849fa7d2b6b2770164dd02b2c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The dominant viral etiologies responsible for acute respiratory infections (ARIs) are poorly understood, particularly among hospitalized children in resource-limited tropical countries where morbidity and mortality caused by ARIs are highest. Improved etiological insight is needed to improve clinical management and prevention.", "Objectives: We conducted a three-year prospective descriptive study of severe respiratory illness among children from 2 months to 13 years of age within the largest referral hospital for infectious diseases in southern Vietnam.", "The study was approved by the Scientific and Ethical Committee of the Hospital for Tropical Diseases and the Oxford University Tropical Research Ethical Committee." ] },{ "paper_id": "73aea1df4694235764281acbc9a19b37525b773e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "73aec7f72de1b225ab650b78a7633aab4ebd97bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antibodies against IFITM1 (Cat# 11727-3-AP), IFITM2 (Cat# 12769-1-AP) and IFITM3 (11714-1-AP) were purchased from Proteintech Group (Chicago, IL, USA), while anti-FLAG M2 antibody was purchased from Sigma (St. Louis, MO, USA).", "Western blotting was performed as previously described [6] . Briefly, cells were lysed in pre-chilled RIPA buffer (1% NP-40, 50 mM Tris-HCl, 150 mM NaCl, 0.1% SDS and protease inhibitor mixture) for 20 min and protein samples were subjected to 10% SDS-PAGE. After proteins were transferred to PVDF membrane, primary antibodies of interest were applied and protein signals were detected using an Amersham Imager 600, GE Health Care. ", "All statistical analyses were carried out in GraphPad Prism6 (La Jolla, CA, USA), with student t-tests or one-way analysis of variance (ANOVA) used unless otherwise noted. Typical data from at least 3 to 5 independent experiments were used for the analysis." ] },{ "paper_id": "73af6e73949ec28b7c3b13d24a9168e891d7bb23", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2.1.6 The medical record writing (including admission notes, progress notes, discharge summaries and outpatient records) of students is complete and of appropriate quality." ] },{ "paper_id": "73b5a68dd7e80ad291c026145c875eb8338daa08", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since photoswitching properties can vary within different biological samples, the optimal conditions for imaging must be obtained by testing. For all dSTORM acquisition presented here, the switching buffer was composed of 100 mM MEA in PBS at various pH depending on the dye combination. As previously shown 8 , MEA acts already as an oxygen scavenger at higher concentration (e.g., 100 mM).. A combination of 50 mM MEA and additional enzymatic oxygen scavenging system as previously described 9 was also tested, but here it led to a worse photoswitching properties than with 100 mM MEA only (notably fast photoswitching rates leading to local high densities incompatible with our imaging capabilities).", "For single-colour dSTORM imaging using AF647, the optimal pH was found at pH 8.2. In combination with AF568, a buffer pH compatible with both dyes simultaneously was necessary and the pH had to be slightly increased to 8.7 in order to improve the photoswitching properties of AF568. Similarly, the pH was adjusted for the other dye combinations as follows: pH 7.2 for AF647 and AF546, and pH 8.0 -9.0 for AF647 and ATTO532. In all cases, the photoswitching properties of AF647 were not significantly affected by that pH change.", "Using a similar method, the effect of the linker length was investigated (see Supplementary Fig. 4b) ." ] },{ "paper_id": "73c2606bc45a573294360406628a8edd45bdd511", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Five influenza seasons were included in the data. The pandemic H1N1(pdm09) strain first arose in the 2008/2009 season, and predominated for the next two seasons, until 2011/2012 in which no H1N1 cases were detected.", "Multivariable analysis was performed adjusting for age, as a significant covariate, and sex, as an a priori confounder, but not co-infection or reason for admission as they were not significantly associated with death at univariable analysis. The adjusted RR for influenza A(H1N1)pdm09 increased to 0\u00b725 (95% CI 0\u00b708-0\u00b775, P = 0\u00b701), which suggests that the crude RR was partially confounded by these factors.", "The multiplex PCR assay for respiratory viruses used at this hospital includes a pentaplex influenza A/B/A(H1N1)pdm09/H3 detection and typing realtime assay with an internal control, which has been detailed previously [5, 6] , with additional multiplex real-time (Taqman) PCR assays to detect other common respiratory viruses including respiratory syncytial viruses (RSV) A and B, parainfluenza types 1-4, adenovirus, enterovirus, rhinovirus, human metapneumovirus, group 1 coronaviruses (HCoV-229E and HCoV-NL63), group 2 coronaviruses, and SARS-associated coronavirus [7] .", "About half (118, 51%) of the patients were male and the median age was 34\u00b75 years [inter-quartile range (IQR) 10-67\u00b75 years]. The majority of the patients (182, 79%) were admitted for a respiratory reason, and 32 (14%) tested positive for at least one other respiratory virus. Of these, five had one co-infection, 26 had two co-infections and one had three co-infections; the most common co-infecting viruses were rhinovirus and RSV (11 and 10 patients, respectively)." ] },{ "paper_id": "73c97b301049429f21da128565e117ee1d368046", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "On the 2nd day, mannitol infusion and other measures for cerebral edema (seen on brain computerized tomography) were administered. (predominantly partial type with staring) without loss of muscle tone, and lateralized on the left side.", "The focal convulsion continued with presentation of, ''jaw lock, drooling, lateral gaze, dystonia, corner of lip twitching and blinking''. On the 40th day of hospitalization; chorea and dystonia continued but the pattern of dyskinesia started changing gradually to a movement disorder, as they stopped during sleeping state. Therefore, trihexyphenidyl was added to the medication list. Magnetic resonance imaging (MRI) in FLAIR sequence on the 50th day of admission revealed \"abnormal right parietal cortico-subcortical high signal' (Figure 2 ).", "We present a 7 yr old boy afflicted with super-refractory seizure that responded poorly to antiepileptic drugs and sustained a long course of hospitalization and complications of high doses of medications as well as longstanding stay in hospital. The differential diagnoses were, fever-induced refractory epileptic encephalopathy (FIRES), and infectious and autoimmune encephalitis. However, work-ups had not revealed any evidence of any specific diagnosis, so we assumed that he was afflicted by viral infectious encephalitis as he had, fever, vomiting, and prodromal symptoms of infectious (most probably viral) disease prior to onset of the seizure attacks." ] },{ "paper_id": "73d7ae5e79b6ba07548cf38ddcaa2979bee6916b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MeV sequences were downloaded from GenBank and aligned using ClustalW. Additional file 1 includes a list of accession numbers for sequences used in this study. Sequences of the hemagglutinin (H) and nucleocapsid (N) genes collected worldwide between 1954 and 2009 were used. The H and N genes were selected for analyses since their sequences are registered commonly. Sequences associated with the persistent disease manifestation SSPE were removed because these were expected to exhibit different evolutionary dynamics [18] . To avoid weighting specific outbreaks, we also excluded sequences that had been collected at the same time and place and that were genetically similar to each other. Consequently, the final data sets comprised 149 taxa with an alignment length of 1830 bp for the H gene and 66 taxa with an alignment length of 1578 bp for the N gene.", "Measles is a common infection in children and is spread by the respiratory route. It is characterized by a prodromal illness of fever, coryza, cough, and conjunctivitis followed by appearance of a generalized maculopapular rash. Measles virus (MeV) infects approximately 30 million people annually, with a mortality of 197,000, mainly in developing countries [1] . In the prevaccine era, more than 90% of 15-year-old children had a history of measles [2] . Measles remains a major cause of mortality in children, particularly in areas with inadequate vaccination and medical care.", "The rates of nucleotide substitutions per site and TMRCA were estimated using the Bayesian Markov chain Monte Carlo (MCMC) method available in the BEAST package [19, 20] . This method analyzes the distribution of branch lengths among viruses isolated at different times (year of collection) among millions of sampled trees. For each data set, the best-fit model of nucleotide substitution was determined using MOD-ELTEST [21] in HyPhy [22] . All models were compared using Akaike's Information Criterion. For both the H and N genes, the favored models were closely related to the most general GTR + Gamma + Inv model. Statistical uncertainty in parameter values across the sampled trees was expressed as 95% highest probability density (HPD) values. Runs were carried out with chain lengths of 100 million and the assumption of an 'exponential population growth' using a 'relaxed (uncorrelated lognormal) molecular clocks' [23] . All other parameters were optimized during the burn-in period. The output from BEAST was analyzed using the program TRACER http://beast.bio.ed.ac.uk/Tracer. BEAST analysis was also used to deduce the maximum a posteriori (MAP) tree for each data set, in which tip times correspond to the year of sampling." ] },{ "paper_id": "73de62f8272982125df5a376a10f99267968c6e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Funding: E.S. was supported by the German Ministry of Education and Research (BMBF) through a GINAICO grant 16GW0105 and a SILVIR grant GGNATM06.", "Nishiyama and colleagues used an FDA approved drug library for an in vitro screen against a GT3 strain containing a Gaussia luciferase reporter [36] . Ciprofloxacin (CPFX) and IFN-\u03bb1-3 showed the best activity against the reporter genome. They also used an infection model, where cells infected with a full-length GT3 strain at a plateau phase were co-cultivated with na\u00efve cells. All IFN-\u03bb subtypes, but not CPFX, showed robust reduction of HEV RNA." ] },{ "paper_id": "73e3d6f3f33c747bffbbb8122ab855bfb59676db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As this study did not involve human subjects, patient consent and the approval of Internal Review Boards were not required. The study received approval for non-ionizing radiation and biological/chemical safety by the Chinese University of Hong Kong." ] },{ "paper_id": "73eb67835207270107c1e76b4675a92b3b58a575", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA from NPS was obtained by acid guanidinium thiocyanate-phenol-chloroform extraction (TRI-Reagent, Molecular Research Center)." ] },{ "paper_id": "73f93646de4efa4c3b8d02d07dea684c028763d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "China Center for Type Culture Collection (CTCC, Wuhan, China) and cultured in Dulbecco's modified Eagle medium (DMEM) (Invitrogen, Carlsbad, CA) supplemented with 10% heatinactived fetal bovine serum (FBS) (HyClone, Logan, UT), 100 units/mL penicillin and 100 \u03bcg/ mL streptomycin (Invitrogen) at 37\u00b0C with 5% CO2. An SS2 strain, 05ZY, was isolated from the brain of a diseased piglet in Sichuan Province, China in 2005. Colony forming units (CFU) were counted through serial dilutions of bacteria on tryptic soy agar (TSA) plates supplemented with 5% (v/v) FBS.", "The raw and processed data in this study have been deposited in NCBI's Gene expression omnibus and are accessible through GEO Series accession number GSE60172.", "Standard two-sample t-tests were used to compare virus titers, gene expressions, lung pathological damage score, and the apoptosis rate among infection groups. All data are expressed as the mean \u00b1 SEM. A value of P < 0.05 was considered statistically significant." ] },{ "paper_id": "73fcc68f1fe5bf9cae21d939f459968ebed64411", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total cholesterol was extracted from cells as described previously [62] . Cholesterol content was determined using the Amplex Red cholesterol assay kit (Molecular Probes, Eugene, OR, USA).", "Duplex miRNAs (10 pmol) were incubated with HeLa cell lysate (40 \u03bcg) in a 110-\u03bcl reaction buffer (50 mM Tris-HCl, pH 8.0, 150 mM NaCl, 0.1% NP-40, and 10% glycerol) supplemented with complete EDTA-free 1\u00d7 protease inhibitor cocktail (Roche Diagnostics) for 0, 30, 60, and 120 min. RNA was extracted from a 25-\u03bcl aliquot of the reaction mixture using Trizol LS reagent (Invitrogen) for northern blot analysis." ] },{ "paper_id": "740523d9e53ac786c0a45c790320c219cd0031a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "C-Jun N-terminal kinases (JNKs) play important roles in death receptor-initiated extrinsic as well as mitochondria-initiated intrinsic apoptotic pathways, in response to stress stimuli, such as cytokines, DNA damages, heat shock and osmotic stress et.al.", "b-actin, sense (AAAGACCTGTACGCCAACAC) and antisense (GTCAT ACTCCTGCTTGCTGAT); IFN-b, sense (AGATCAACCTCACCTACAGG) and antisense (TCAGAAACACTGTCTGCTGG); ISG15, sense (GGAACGAAAGGGGCCACAGCA) and antisense (CCTCCATGGGCCTTCCCTCGA); ISG56, sense (AGTGCA GGCAGAAATTCACC) and antisense (AGCAGTCAGTAGTTTCCTCC); IL-6, sense (GAGAGGAGA CTTCACAGAGG) and antisense (GTACTCCAGAAGACCAGAGG); IL-12, sense (GCTTCTTCATCAGGGACATC) and antisense (GTCAGGGAGAAGTAGGAATG);", "Luciferase reporter assays were performed as described previously [36] ." ] },{ "paper_id": "740a8ab7bf183f64284384c5dfaae0ae77d56558", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus-induced gene silencing (VIGS) in N. benthamiana was done as described [65, 66] . To generate the VIGS vector (pTRV2-eEF1BcNt), a 314-bp cDNA fragment of NteEF1Bc was RT-PCR amplified from a total RNA extract of N. benthamiana using the following pair of primers: #2993 (CGCGGATCCAAAG-GTTTCTGGGACATGTATGA) and #2994 (CGCCTCGA-GACACGCTCCTTCTGTGATTCATC) and inserted into the corresponding (BamHI/XhoI) restriction sites of pTRV2 plasmid.", "HIS3-based pEsc-His/Cup-FLAG plasmid [20] was digested with BamHI and XhoI restriction enzymes and then PCR product of the TEF4 gene was generated with primers #2089 and #2320 and digested with the same restriction enzymes, followed by ligationto obtain pEsc-His/Cup-FLAG-TEF4.", "For EMSA, 6xHis-Flag tagged Tef4p was purified from a yeast tef4D strain with anti-FLAG M2-agarose affinity resin. Different concentrations (0.6, 0.5 and 0.4 pmol) of HF-Tef4p protein was used for incubation with 0.2 pmol of 32 P-labeled SL3/2/1(+) RNA or mutated RNAs at 25uC in a binding buffer [50 mM Tris-HCl (pH 8.2), 10 mM MgCl 2 , 10 mM DTT, 10% glycerol, 2 U of RNase inhibitor (Ambion)]. Samples were incubated at 25uC for 15 min, then resolved in 4% nondenaturing polyacrylamide gel [23] . Similar experiments were also performed with 6xHis-affinity purified recombinant Tef3p obtained from E. coli (not shown).", "HIS3 based pESC-GAL1-His33/GAL10-DI-72 and LEU2 based pGAD-CUP1-Hisp92 plasmids were transformed into tef4D strain. In the in vivo complementation assay, non-tagged Tef4p protein was expressed from URA3 plasmid pYC-GAL1-Tef4 and TEF4 mRNA was detected with a specific probe generated by the T7 transcription of the PCR product obtained with primers #2089 and #3788 (TAATACGACTCACTATAGGATTATT-TCAAAACCTTACCGTCAACAATTTCC)." ] },{ "paper_id": "740bbfc884c50507fbf78e9424da319a49c48af0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "741b4227809cd635e7f0f06cf4f70331a9764b5f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RMSD values stabilized after 500 ps. This indicated that some residues of P3Arg and P3Ile remained in the active site cleft." ] },{ "paper_id": "741d9ac96e2951be86d4f57d5dac2121953fe3bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Using this benchmark, with a genetic distance of 0.26 \u00b1 0.02% between genotype D and lineage 1 and 0.27 \u00b1 0.02% between genotype D and lineage 2, it is suggestive that the two lineages, which are designated as genotypes F and G hereafter, may have arisen and diverged from genotype D.", "The whole genome of genotypes F and G strains was further subjected to nucleotide and amino acid sequence analysis to detect signature substitutions in their respective genomes given that the mosaic recombination pattern between genotypes F and G could not be clearly distinguished. However, both were evidently distinct from genotype D ( Figure 2 ). As observed in Figure 3 , using the prototype ATCC VR759 as the reference strain for nucleotide and amino acid positions, 34 and 32 nucleotide substitutions unique to genotypes F and G, respectively, were mapped across the whole genome.", "To determine the evolutionary relationship among the unique and global HCoV-OC43 strains, phylogenetic analysis was conducted using full-length genome sequences. All Table S2 ) using a web-based multiple sequence alignment program MAFFT. 24 Phylogenetic tree reconstruction using the neighbor-joining (NJ) method and inter-genotype pairwise genetic distance calculation for sequence divergence comparison were performed using MEGA 6.0. 25 The maximum-likelihood (ML) method was also performed for reconstruction of a phylogenetic tree, which was heuristically inferred using subtree pruning and regrafting and nearest neighbor interchange algorithms with a general time-reversible (GTR) nucleotide substitution model, a proportion of invariant sites (+I) and four categories of gamma rate heterogeneity (+\u0393 4 ), which were implemented in PAUP version 4.0. 26 Kimura's two-parameter model with a reliability of branching order analyzed by bootstrap replicates of 1000 was used. Subsequently, bootscanning was performed using SimPlot version 3.5.1 to determine possible recombination events and location of breakpoints in the viral genome of unique strains. This approach has been previously reported. 7, 9, 15, 27 Sub-genomic regions located between recombination breakpoints were subjected to additional phylogenetic analysis using the neighbor-joining method to infer the recombination structure and the parental genotype of each region. Signature nucleotide and amino acid substitutions of the unique strains were determined by Sequence Data Explorer in MEGA." ] },{ "paper_id": "7421d0a5937f6e1ec30547de88bc4b4148725995", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After the combined immunogold-immunoperoxidase stainings, sections were treated with osmium tetroxide, dehydrated in ascending ethanol series and acetonitrile, and embedded in epoxy resin. During dehydration, sections were treated with uranyl acetate. After polymerization, 70 nm thick sections were cut on an ultramicrotome, picked up on formvar-coated single-slot copper grids, and sections were examined using a Hitachi H-7100 electron microscope.", "A cerium precipitation method was used for electron microscopic investigation of ecto-ATPase activity [31] . The tissue blocks were then postfixed, dehydrated, treated and embedded into Taab 812 resin for ultrathin sectioning and microscopic examination.", "Total blood cell counts were calculated using 15 \u03bcm polystyrene microbeads.", "Coronal brain sections were incubated in the solution of the polyclonal NTPDase1 antibody. After secondary antibody incubation and chromogen development, sections were osmificated, dehydrated in ascending ethanol series, and embedded in Taab 812 resin. Ultrathin sections were examined using a Hitachi 7100 transmission electron microscope." ] },{ "paper_id": "743035cdbb5b95039bcf2297eecef6e2de640946", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "De-identified clinical urine specimens were collected from patients who signed a written consent form from an earlier IRB approved study and who agreed to participate in the study and have their de-identified achieved sample be utilized in future research for the development of new molecular tests for STIs. Original written consent forms were stored in a binder in a locked filing cabinet with access provided to study team coordinator only. Both the consent process and study protocol were written in accordance with the approved guidelines set forth by Johns Hopkins University School of Medicine and Institutional Review Board protocols (IRB numbers: NA_00012998 and NA_00023037).", "To demonstrate that our TTC is robust and versatile, we performed RT-PCR with extracted HIV RNA. Cultured HIV-1 Type B virus (8E5) in HIV-1 RNA negative, defibrinated human plasma was used as our sample (ACCURUN 315 Series 500, SeraCare). The 8E5 virus contains an intact but defective viral genome. This control is formulated for use with in-vitro diagnostic test methods that detect and quantitate HIV-1 RNA. The 500 series contains 130,000-300,000 copies/mL of sample. RNA extraction was carried out by a NucliSENS protocol or by using a spin-column extraction method by Qiagen. The extracted template was tested by qRT-PCR using a SuperScript III Platinum One-Step Quantitative RT-PCR system (Life Technologies) or a One", "After amplification by the TTC or the commercial unit, the PCR amplicons were typically evaluated using a 2.2% pre-casted gel (Flash Gel by Lonza) at 275 V for 7 min (4 \u03bcL mix added to 1 \u03bcL of loading dye). The resulting gel images were captured using a cell phone camera. The typical ladder sizes used in the gel were 50, 100, 150, 200, 300, 500, 800, and 1500 bp." ] },{ "paper_id": "7432dbac9b72daf18b639ba85a59b2e676b6b09c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experimental procedures were carried out according to the German animal care guidelines and were approved and supervised by the relevant authorities of the State Mecklenburg-Vorpommern, Germany (State Office for Agriculture, Food Safety and Fishery Mecklenburg-Western Pommerania (LALLF M-V), 7221.3-2.1-005/11).", "Particularly, the transition from pregnancy to lactation (comprising a period of 3-4 weeks before and after parturition) is marked by metabolic, hormonal and immunological changes that have an impact on the incidence of infectious and metabolic diseases of the cows [1] . It has been reported that periparturient cows undergo a period of immunosuppression of various immunological parameters associated with a high susceptibility to uterine and mammary infections (e.g., [2] [3] [4] [5] [6] ).", "Library preparation, sequencing, sequence assembly and locus annotation Preparation and sequencing of the libraries as well as all bioinformatic analyses comprising sequence assembly and locus annotation were performed as described previously [19] . Briefly, whole blood total RNA was extracted using the PAXgene Blood RNA Kit (PreAnalytiX, Hombrechtikon, Switzerland) according to the manufacturer's instructions. Elimination of residual genomic DNA and RNA quality evaluation were carried out as described previously [19] . For each individual, two RNAseq libraries were prepared from samples collected before and 14 days after booster vaccination. Libraries indexed by different adaptors were prepared from 1 \u03bcg total RNA applying the Illumina TruSeq RNA library preparation kit (Illumina, San Diego, USA). After quality control, indexed libraries were pooled, and paired-end sequencing (61 cycles for each end) was performed on a Genome Analyser GAIIx (Illumina, San Diego, USA)." ] },{ "paper_id": "7433a628e7fe85066cddc5c25a416fea3ffa87e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Found at: doi:10.1371/journal.pntd.0000446.s001 (0.05 MB PDF) ", "Alternative Language Abstract S1 Translation of the abstract and author summary into French by Stephane Daffis." ] },{ "paper_id": "743c5db7611d4af74204901e0ed3b6317a0bb3c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza vaccination is an effective measure against influenza." ] },{ "paper_id": "743ca1ab0d309c7904b737c78985687e594a04cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "WHO has planned to eliminate measles by the year 2020. Polio is currently seen in three countries, Afghanistan, Nigeria, and Pakistan, but efforts are underway for its complete eradication and, down from nearly 3.5 million cases in 1986, today there are just 126 cases of Guinea worm recorded globally [103] ; Guinea worm disease could be the second human disease after smallpox to be eradicated.", "The ultimate goal of infectious disease control, however, is to achieve total eradication. With smallpox having been eradicated, and a great wealth of lessons learned from previous epidemic events such as the West African Ebola crisis, there is optimism that eradication is a reality that must be pursued relentlessly.", "Naturally the host's elaborate defence mechanism, immune system, fights infectious agents and eliminates them. Infectious disease results or emerges in instances when the immune system fails to eliminate pathogenic 2 BioMed Research International infectious agents. Thus, all infectious diseases emerge at some point in time in a given population and in a given context or environment. By understanding the dynamics of disease and the means of contracting it, methods of fighting, preventing, and controlling are developed [2, 5, 6] . However, some pathogens, after apparent elimination and a period of dormancy, are able to acquire properties that enable them to reinfect their original or new hosts, usually in increasingly alarming proportions.", "Not only has advance in acquisition of genomic data contributed substantially to the development of vaccines and antimicrobials, but also it has important application in deciding and guiding successful treatment. Typical examples can be found in HIV antiretroviral therapy. Assay for the type of coreceptor usage by a patient's predominant virus population, whether CCR5-or CXCR4-tropic virus, is necessary before using the antiretroviral drug Maraviroc, which is a CCR5 coreceptor antagonist [95] ; the nucleoside reverse transcriptase inhibitor d, Abacavir (ABC), is associated with drug hypersensitivity reactions. This drug may lead to high rates of myocardial infarction in patients who are positive for human leukocyte antigen (HLA) type B * 5701 allele. Safe use of Abacavir therefore requires testing patients genetic data for HLA B * 5701 allele [96] ." ] },{ "paper_id": "7455510a39b00af17f318760b7da8b37cc336476", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fpls.2017. 00668/full#supplementary-material Data S1 | The full-length cDNA sequences of candidate genes. The ORF regions were highlighted in blue color.", "The frozen samples were ground to a fine powder in liquid N 2 using a pestle and mortar. The total RNA was extracted from all plant tissue samples using a Column Plant Total RNA Kit (TransGen Biotech, China) following the manufacturer's recommendations. The concentration of RNA samples was determined using a NanoDrop 2000 spectrophotometer (Thermo, America) at 260 nm, whereas its purity was assessed based on absorbance ratios at 260/280 nm. Samples with an optical density absorption ratio at OD260/280 between 1.9 and 2.2 and OD260/230 <2.0 were used for cDNA synthesis. The integrity of purified RNA was confirmed using agarose gel electrophoresis and ethidium bromide staining.", "YH, HT, LZ, and YD conceived and designed the study. YH, JY, GW, and YC collected the tissue material and performed the experiments. YH, JC, ZG, and QZ performed data analysis. YH wrote the manuscript. All authors read and approved the final manuscript." ] },{ "paper_id": "745f78dadf6e5a2feb79900688cd5fb9ead4d72e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Until recently, it was reported that various extracts and/or natural products derived from medicinal plants had the possibility of useful medical resources for treating infectious virus diseases,", "BALB-c/mice (six weeks, n = 25) were purchased from DaeHan Bio-Link Co., Ltd. (Chungcheongbuk-do, Korea), and all animals were kept at 23 \u00b1 0.5 \u2022 C and 12 h-light/dark cycle in a controlled environment of a central animal care facility. Food and water were provided ad libitum to all animals. The facility was strictly maintained in accordance with the guidelines of the National Institutes of Health for the Care and Use of Laboratory Animals.", "The anti-T. gondii drug, sulfadiazine (SF), was dissolved in DMSO and ursolic acid (UA) was also dissolved in DMSO to a concentration of 50 mg/mL, according to the manufacturer's instruction. Sulfadiazine was used as a standard drug to evaluate whether or not ursolic acid has an anti-parasitic effect and activity against T. gondii. All of the compounds were filtered using 0.2 \u00b5m membrane syringe filters (Roshi Kaisha, Ltd., Tokyo, Japan) before use, and were stored at \u221280 \u2022 C deep-freezer until use." ] },{ "paper_id": "7461fe0adbb9a865f8a79e994c6cd8b8ebdd4e78", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A qualitative content analysis research was conducted on relevant court decisions, laws, legislative proceedings, and legislative protocols (all issued or produced between 1948 and 2017). A further analysis was carried out on Health Ministry guidelines and on documented discussions of the Advisory Committee on Infectious Diseases and Immunization.", "The study was initiated by analyzing the aforementioned data which was then linked to the relevant theoretical literature such as to attain a cohesive entity. Credibility was established through persistent observation.", "All 50 US states have laws that require vaccination for school admissions. Exemptions vary from state to state, although all school immunization laws grant exemptions to children for medical reasons, and almost all states grant religious exemptions for people who have religious beliefs that prohibit immunizations. 18 states also currently allow philosophical exemptions to those who object to immunization on account of personal, moral or other beliefs [18, 19] ; In Canada, three provinces require proof of immunization for school admissions: Ontario, New Brunswick and Manitoba. Exceptions are permitted on medical or religious grounds and for reasons of conscience. Australia's New Tax System (Family Assistance) Act 1999 states that family tax benefits, child care rebates and child care benefits can only be paid for children who meet immunization requirements. A person may have a medical exemption from vaccination if they are undergoing treatment that compromises their immune system. Religious or conscientious objection is not an exemption category [19] [20] [21] .", "This examination is especially important in light of the current public health policy makers' ambition to eradicate contagious diseases as opposed to past interventions which sought to prevent epidemics." ] },{ "paper_id": "7478489aca4d8ade51ecf485914211cd3313d3b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Supporting information S1 File. Raw data. (XLS) " ] },{ "paper_id": "74813899dfd7ad7de15228fd014c735c3410d9d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "had no gross pathological changes, and no viral antigen or significant histological lesions were found in any tissues.", "Preparation and administration of m102.4", "Since their initial recognition, both viruses have repeatedly reemerged. In total, 13 HeV outbreaks have occurred in Australia in 1994, 1999, 2004, and 2006-2009 , and have always involved horses as an intermediate host with some human infections including four fatalities, the most recent in September 2009 (reviewed [2] ) [5, 6] . NiV has also repeatedly caused spill-over events involving hundreds of human cases since 1998 with at least nine recognized occurrences primarily in Bangladesh and India since 2001 (reviewed [2] ) with the most recent in March 2008 [7] . Several of the more recent NiV outbreaks have had higher rates of acute respiratory distress syndrome in conjunction with encephalitis, epidemiological findings consistent with multiple rounds of person-to-person transmission [8] , higher case fatality rates (,75%), and direct transmission of virus from flying foxes to humans via contaminated food has been demonstrated [9, 10] ." ] },{ "paper_id": "74a81638dc54bc8e0fee501f23723bda2761195b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "WT protein was further purified by size exclusion chromatography using Superdex 75 column.", "10 pmol noP ssRNA (with or without Cyanine3 tag at 3 end) was radioactively labelled at 5 end using T4 polynucleotide kinase 3 phosphatase minus (NEB) in presence of \u2425 32 P ATP (Perkin Elmer) and heated at 37 \u2022 C for 30 min followed by heat inactivation at 65 \u2022 C for 20 min. Radiolabelled oligo was further desalted on G25 column to remove any unincorporated ATP. This radiolabelled oligo was used as size marker as indicated in figures.", "To study the effect of NAD + concentration dependence of PARP10 cat and TRPT1 the assay was performed as described earlier with different concentrations (0-1500 M) of NAD + in reaction. NAD + concentration dependence study was performed in non-radioactive setup using Cya-nine3 labelled RNA." ] },{ "paper_id": "74af665d4b129e0ed662f50fa0d215f4ff2c2c52", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CD4 + t cell extraction. CD3 + , CD4 + , CD8 \u2212 T cells were isolated from freshly collected peripheral blood samples as previously described 12, 68 . Briefly, within 24 hours of collection, Ficoll-purified peripheral blood mononuclear cells (PBMCs) were stained and sorted into major lymphocyte populations. Sorted cells were immediately lysed and homogenized in RNA extraction buffer and stored for later purification." ] },{ "paper_id": "74badd024e394563add31baf5ec9d6fde58a43f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Exclude errata documents:", "Search query for vaccine related documents:" ] },{ "paper_id": "74bedf868bf72275e1d5a60150246aaae93d3be5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "E. histolytica is an enteric protozoan that causes human amoebiasis, which is considered the fourth cause of parasitic diseases 23, 24 . Metronidazole (a nitroimidazole derivative) is often the selected drug to treat amoebiasis, however, this drug is mutagenic, carcinogenic and genotoxic 25 and has many other undesirable side effects, amongst others neurotoxicity 26, 27 . Likewise, the appearance of strains of E. histolytica resistant to conventional drugs has been reported 28 .", "Statistical analysis. The data from control and treatment groups were analyzed using t-test analysis. Values were considered significantly different if p < 0.05.The SPSS software version 21 was used." ] },{ "paper_id": "74c245d5a0275629dce204354579d47071dffb85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To calculate the standard expected years of life lost (SEYLL), life expectancy at birth was set according to the 2000 global burden of disease study on levels 25 and 26 of West model life tables from Coale-Demeny at 82.5 and 80 years for females and males, respectively.", "MERS-CoV is an emerging novel beta coronavirus belonging to lineage C and the first case of this infection was reported in 2012 in Jeddah, Saudi Arabia [10, 11] . Since then, 27 countries were affected by MERS-CoV and have reported MERS cases to the world health organization (WHO) [9, 12] ." ] },{ "paper_id": "74c453c26b6159ac06a950e978525cd585cf3e5c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The fluorescence of EGFP in crude lysates or after purification was measured using a microplate reader (FLUOstar OPTIMA, BMG LABTECH, Ortenberg, Germany). The measurements were carried out using a 96 well plate at RT (excitation wavelength: 488 nm and emission wavelength: 520 nm). ", "For SEC, some of the fractions from the Ni-affinity chromatography were loaded on to a Superdex 200 Increase 10/300 GL column or a 10/300 Superose TM 6 Increase column (GE Healthcare, Chicago, IL, USA). Before loading, the gel filtration column was equilibrated with two column volumes of buffer [50 mM Tris-Cl (pH 7.5) and 300 mM NaCl]. Proteins were loaded at 3% column volume, and eluted at a flow rate of 0.3 mL/min using a NGC TM chromatography system (Bio-Rad Laboratories, Irvine, CA, USA).", "The EGFP gene was obtained by polymerase chain reaction (PCR) using specific primers. The PCR products were ligated into the pGE-hRID(2m) plasmid [14] via BamHI/HindIII sites. The secreted protein acidic and cysteine rich (SPARC) (GAA50260.1) gene was obtained by reverse transcription PCR (RT-PCR) from a crude lysate of Clonorchis sinensis, and the DNA fragments were ligated into the pGE-LysRS plasmid [10] via BamHI/SalI sites. The hexa-histidine tag for purification using Ni-affinity chromatography was located between the fusion partners and target genes." ] },{ "paper_id": "74c60786e7e6698fa54ae148689fa87501e1cca6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "74d95e321596279f3e8fcf1ad1f04508f48552e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dong Wook Jekarl https://orcid.org/0000-0002-6269-5501" ] },{ "paper_id": "74d9a4215dd1ab6d78bd9b6dbd2dc096c974cf4b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Timeline for confirmed human cases (in chronological order of reporting)", "The novel coronavirus can be cultured from sputum samples using monkey kidney cells, Vero and LLC-MK2 cells. Viral induced cytopathic changes are seen in these cells within 1-2 weeks of infection [2] . However, these changes are not specific for NCoV and confirmation using reverse transcription PCR (RT-PCR) is required. RT-PCR can also be performed directly on clinical samples such as respiratory swabs. An optimized realtime RT-PCR protocol for the specific detection of NCoV has been developed and is available [1] . Furthermore, an additional confirmatory RT-PCR assay and a serological test using convalescent patient serum has been established [38] .", "Whenever a new virus associated with an acute respiratory illness emerges, medical authorities around the world are put on high alert and vigilance, and quite justifiably. Emerging and re-emerging viruses causing respiratory infections have been responsible for outbreaks resulting in millions of deaths. The pandemic influenza viruses of 1918, 1957 and 1968 are our bleak reminders. Since 1968, major outbreaks with mortalities on the scale previously seen have not occurred, although there have been regular threats." ] },{ "paper_id": "74de948d0adbf472ee959b8521f40fb4a5aa034a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Shoot for the moon, because even if you miss, you'll land among the stars.", "Ever since the successful Apollo 11 Moon landing in 1969, a \"moonshot\" has come to signify a bold effort to achieve a seemingly impossible task. The Obama administration recently called for a moonshot to cure cancer, an initiative that has elicited mixed responses from researchers who welcome additional funding but worry about raising expectations. We suggest that a successful moonshot requires a sufficient understanding of the basic science underlying a problem in question so that efforts can be focused on engineering a solution. Current gaps in our basic knowledge of cancer biology make the cancer moonshot a uniquely challenging endeavor. Nevertheless, history has shown that intensive research efforts have frequently yielded conceptual and technological breakthroughs with unanticipated benefits for society. We expect that this effort will be no different.", "-Leslie Brown (18) " ] },{ "paper_id": "74e492f5464ab2ba5cc8d99b33223b6bc71956d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Only two complete genome sequences of HCoV-NL63 associated with acute respiratory illness have been obtained and reported in China. The complete genome sequence data from our study will provide insight into the evolution and genetic diversity of HCoV-NL63 in China. ", "We report the complete genome sequences of five human coronavirus NL63 (HCoV-NL63) strains obtained using next-generation sequencing. The five HCoV-NL63 strains were obtained from hospitalized children with severe acute respiratory infection detected in Guangdong, China. This study provides several complete genomes of HCoV-NL63 and improves our understanding of HCoV-NL63 evolution in China.", "H uman coronavirus NL63 (HCoV-NL63) is a member of the family Coronaviridae, genus Alphacoronavirus, and was first discovered in 2004 (1) . HCoV-NL63 is mainly associated with the common cold in children, the elderly, and immunocompromised patients (2, 3) . The genome of HCoV-NL63 is about 27 kb with a conserved gene order of 5=-orf1ab-spike (S)-orf3-envelope (E)-membrane (M)-nucleocapsid (N)-poly (A). The species tropism of HCoV-NL63 is determined by spike glycoprotein. HCoV-NL63 and severe acute respiratory syndrome coronavirus (SARS-CoV) share the same cell receptor, angiotensin converting enzyme 2 (ACE-2) (4, 5), for entry into host cells, and HCoV-NL63 is recognized as a common cause of upper respiratory tract infection and has been prevalent worldwide." ] },{ "paper_id": "74eda2d826f50948657d096912bb32ccfbb17d0f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Twitter Follow Theodore Cosco at @tdcosco Contributors The review was conceived by TDC, MR, RH, DK and MS. Title and abstract screening was carried out by TDC, AK and MS. TDC wrote the first draft which was edited and approved by all authors.", "Funding This study was funded by Medical Research Council (grant number MC_UU_12019/1).", "Provenance and peer review Not commissioned; externally peer reviewed." ] },{ "paper_id": "74f36e3fdaac0583dace5a4a9031bc79d154c798", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Digital images were acquired using the Openlab acquisition software (Improvision) and a microscope (Axiovert 200 m, Carl Zeiss MicroImaging, Inc.) connected to a 5 charge-coupled device camera (ORCA-479, Hamamatsu).", "Western blot analysis was performed as described [19] . The a-CBF1 rat monoclonal antibody RBP-7A11 (produced in collaboration with E. Kremmer, Helmholtz Center Munich) has been published [19] . The a-Flag (Sigma-Aldrich) and a-GAPDH (Millipore) antibodies were purchased. .", "Text S1 Chromatin immunoprecipitation (ChIP) analysis. (DOC) " ] },{ "paper_id": "74f823e968a2920c96c87977da7289f5363979da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The parental isolates used in this study were A-115, A-120, A-899 [33] ", "Natural recombination breakpoint distributions essentially mirror those of the functional recombinants generated in tissue culture", "HIV particles were produced by co-transfection of HEK 293T cells with an expression vector for a CCR5-tropic (ADA) HIV-1 envelope [45] kind gift of Dr. M. Alizon, together with a pNL4.3-Env 2 -Luc containing either a parental or recombinant RRE sequence or DdNK. Forty-eight hours post transfection, supernatants were filtered trough a 0.45 mM filter and p24 levels were determined using the HIV-1 p24 enzyme-linked immunoabsorbent assay kit (PerkinElmer Life Sciences, MA, USA).", "distribution found for the 133 breakpoints encountered in the natural HIV recombinants ( Figure 5B ), a remarkable overlap was observed, with the discrete statistically significant breakpoint clusters being consistently recaptured by our empirical model of env recombination. The substantial difference of recombination rates in region 4 was also clear.", "Adaptation of pathogens, either to on-going immune pressures within individual hosts or following transmission to new hosts of the same or different species, can result in infectious outbreaks that constitute major threats for public health [9] [10] [11] [12] . The human immunodeficiency virus (HIV) is an extremely recombinogenic pathogen in which recombination has been implicated in key aspects of viral pathogenesis such as immune evasion [13] , transmissibility [14] , the evolution of antiretroviral resistance [15, 16] and cross-species transmission [9, 12] . Indeed, the remarkable genetic flexibility of HIV is underlined by its large genetic diversity. The HIV-1 population is subdivided into three groups, named M, N and O, with group M (which is responsible for the vast majority of the infections worldwide) being further subdivided into nine subtypes (named A, B, C, D, F, G, H, J and K) [17] ." ] },{ "paper_id": "74faecf00d9247bc088c0cb084f69b2135062fe8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "75025fdc2dbeab398880d6e072274409f3dc14bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The present gene-finding method consists of the four steps:", "All the ORFs longer than a given value, for example 90 bp, are extracted as candidates of genes. For each ORF, which is represented by a point in the 33-dimensional space, the Euclidean distance of this point to the point O is obtained 6 90 .", "Future and more reliable comparison should be based on experimentally verified data, rather than RefSeq annotations. Two independent indices defined by formulas (1) and (2) are used to evaluate the performance of ZCURVE_V [13] where TP, FP and FN are the positively true, false positive and false negative predictions, respectively." ] },{ "paper_id": "7510fd5807ba58c1c3aee2def887c041331a4536", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tools and Techniques for Crystal Dehydration", "Crystal dehydration \u2022 HC1 \u2022 Free mounting system \u2022 In situ \u2022 Membrane proteins \u2022 Relative humidity 6." ] },{ "paper_id": "751163b36576e3b25e90b10c33528efc89204313", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.", "Author details" ] },{ "paper_id": "7516383abbd16005d507e7fb5bb6766a8b0f5894", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Critical Care Research and Practice 3", "(iii) Get nasal swab and inferior respiratory tract secretion for infection diagnosis or a BAL (infection diagnosis and proinflammatory mediators and procollagen III measurements).", "(iv) Get hemocultures and blood for infection detection. Start resuscitative measurements for septic shock and start appropriate antibiotics." ] },{ "paper_id": "7523a7acead9732b16e087fd2a3544533af20ce3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Seven fecal specimens collected from R. pusillus at Tengchong and Mangshi were identified with positive bands using nested RT-PCR and were sequenced. The 405-nt partial RNA-dependent RdRP gene F41 was grouped with the alphacoronaviruses (\u03b1-CoVs). F24 was located in an independent branch. This finding demonstrates great phylogenetic diversity, and the viruses were distributed in relatively separated branches (Figure 1 ).", "Novel coronaviruses in least horseshoe bats L Wang et al", "We collected ten Rhinolophus luctus, ten R. affinis and ten R. pusillus at Tengchong; ten R. affinis, ten R. pusillus and ten Myotis daubentonii at Mangshi; and six fruit bats at Wanding. A total of 66 urine and fecal specimens from the bats, representing various local bat species (Table 1) , were collected using plastic sheeting laid in the bat cages in the morning." ] },{ "paper_id": "752693d2137be042f6d7e42e1aa034f5bfb95d9f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chemical synthesis. Treatment of 1 [1] with trifluoroacetic acid followed by coupling with Boc-L-Val-L-Phg-OH (2) mediated by HATU afforded I2 with 83% yield (Scheme 1). Next, the Boc protecting group in I2 was removed, and liberated amine was coupled with 5-metylisoxale-3carboxylic acid (3) to produce I4 with 96% yield. Following similar procedures, the other six compounds in Table 2 were prepared.", "The general synthesis protocol for N3 and compounds listed in Table 3 is depicted by the preparation of N1 and N2 (Scheme 2). After removal of the Boc protecting group in (1), coupling with Boc protected tripeptide acid (4) was carried out to produce N2 with 81% yield. Switching the N-substituent was accompanied with treatment of N2 with trifluoroacetic acid and coupling with 5metylisoxale-3-carboxylic acid (3) to provide N1 with 82% yield. " ] },{ "paper_id": "7531c4305658b8cf4fa576ae050d7162043fe535", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Crohn's Disease is a debilitating chronic inflammatory bowel condition of unknown aetiology and multifactorial pathogenesis, with complex interactions between genetic and environmental factors [28, 29] . MAP infection has been suggested as a potential causative agent of CD and there is now an established association between MAP infection and Crohn's disease, although questions on its exact role remain unanswered [30, 31] . MAP has also been associated with, and is hypothesized to play a role in, other auto-immune diseases, such as type-1 diabetes and multiple sclerosis [32, 33] .", "Safety end points are described as frequencies and percentages alongside their 95% confidence intervals. Statistical analysis of immunogenicity data was conducted using GraphPad Prism version 7.03 for Windows (GraphPad Software Inc., California, USA). Median and interquartile range are given for each parameter. Comparisons between time points and baseline were performed using non-parametric tests, with an alpha value <0.05 considered significant.", "The vast majority of AEs were mild in nature (85%, 70.93-92.94% 95%CI) and all were self-limited. Pain at injection site resolved within 4 days and all other AEs resolved within 24-72 h." ] },{ "paper_id": "75356982697a153bdd8610fe024820f7308bb6a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data generated or analyzed during this study are included in this published article.", "Ethics statement. This study was approved by the Institution Review Board of Kaohsiung Chang Gung Memorial Hospital Medical Center, Taiwan (Document no. 102-5046B). Written informed consent from participants was obtained. This research adhered to the principles of the Declaration of Helsinki.", "In conclusion, the results of our study disclose that impaired immunologic reactions of mononuclear cells to a DENV2 infection in ESRD individuals. This implies that caution needs to be exercised in the immune dysregulation of ESRD population and it might be a key determinant for clinical outcome when treating dengue-affected ESRD patients. Our study highlights that further clinical investigation beyond in vitro study is needed to confirm this important finding." ] },{ "paper_id": "75396899537915606b74f2b600478ad066f9d594", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following assembly, lipopeptides were cleaved from the solid phase support and all side-chain protecting groups removed with 88% TFA, 5% phenol, 2% TIPS, 5% water for 3 hours at room temperature. Lipopeptides were analysed by reversed phase highpressure liquid chromatography (RP-HPLC) using a Vydac C4 column (4.66300 mm) installed in a Waters HPLC system. The chromatogram was developed at a flow rate of 1 ml/min using 0.1% TFA in H 2 O and 0.1% TFA in acetonitrile as the limit solvent. Lipopeptides were purified if necessary. All products presented as a single major peak on analytical RP-HPLC and had the expected mass when analysed using an Agilent series 1100 ion trap mass spectrometer.", "Virus-like particles (VLPs) possess features which make them ideal vehicles for the delivery of viral antigens to the immune system; (i) antibody epitopes are presented in the native conformation for induction of potentially neutralising antibodies (ii) multiple T cell, CD4 + and CD8 + , epitopes are packaged in VLPs (iii) VLPs lack regulatory proteins as well as genetic material that could pose a risk of reversion or mutation (iv) encouraging results have been obtained using insect cell-derived recombinant VLPs expressing HCV antigens which induce virus-specific humoral and cellular responses [16] [17] [18] (v) HCV VLPs appear to possess properties favourable for dendritic cell uptake [19] and (vi) they exhibit superior immunogenicity and antigenicity over recombinant protein and DNA-based vaccine approaches [16, 17] .", "The core/E1 and E2 amplicons were cloned into pGEMEasy (Promega) and subsequently subcloned and ligated to produce a construct which was verified by DNA sequencing. This construct was subsequently subcloned into pAdTrack-CMV (provided by B Vogelstein, Howard Hughes Medical Centre, Baltimore), digested with PmeI and transformed into AdEasier-1 cells by electroporation (Bio-Rad Gene Pulser) as previously described [24] ." ] },{ "paper_id": "753c41ab7d5d36c633e749aed6ce83334771bf7b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "753d7438fe0a32b2c68985a255f92661145d46d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the analysis of raw intensity data from arrays, we developed a simple sorting and averaging algorithm in Excel. The organization of the data was keyed to the probe name. (e.g.: Case 1) PosCntrl-ATRCA|Probe-031; Case 2) PosCntrl-Cab|Probe-004; Case 3)", "Traditional methods for the identification of URI pathogens, including culture and serology, are effective but are labor intensive and may require highly trained personnel and days to weeks to complete. Many rapid serological tests are not sensitive or specific enough to detect all infections. Enzyme immunoassays (EIA) generally show sensitivities of 85% and direct immunofluorescence (DIF) assays show sensitivities of approximately 60 to 80% [7] . Although viral culture is generally accepted as the gold standard for diagnosis, PCR can be more sensitive [8] . In one study, rhinovirus culture detected infection in 40% of patients while rhinovirus PCR detected infection in 51.5% of patients [3] . Similarly, an influenza virus surveillance study showed that 18% of samples were positive by culture and 28% were positive by TaqMan-PCR [9] .", "Increasing the annealing temperature of the reaction to 68uC, with 30 additional rounds of amplification, resulted in a predominantly one-way reaction favoring reverse primer extension. Biotin labeling occurred during amplification by incorporation of biotinylated dCTP/dATP in the reaction mix. Biotinylated reverse primers were also employed as an alternate method for biotin labeling." ] },{ "paper_id": "75435342678d143b3fea48a288d1baa113d28a42", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To promote healthy sexuality.", "To support healthy pregnancies.", "To prevent the occurrence of rabies in humans.", "To ensure that local programs address the health needs of the community, with costeffective, efficient, evidence-based approaches." ] },{ "paper_id": "75622daf6a8bde4809687a432c5bd991d8a849ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Refinements were carried out with PHENIX 45 with a cross validation (R free ) test set containing 5% of the data. Starting with torsion-angle simulated annealing with slow cooling, iterative manual model building was carried out in COOT 46 with maps generated from combinations of positional, individual B-factor and TLS refinement algorithms. Ordered solvents were added during each macro cycle. Structure validations were performed periodically during the model building/refinement process with MolProbity 47 . Final refinement statistics are summarized in Table 1 .", "Surface plasmon resonance binding. Surface plasmon resonance measurements were performed using a BIAcore X100 instrument (GE Healthcare). MERS-CoV S1 protein (Sino Biological Inc.) diluted in 10 mM sodium acetate buffer (pH 5.5) was immobilized on a CM5 biosensor chip using a primary amine coupling method. The running buffer was allowed to flow through the cells at a rate of 30 ml min \u00c0 1 . The analytes consisted of serial dilution of proteins between 500 to 0.05 nM (500, 50, 5, 0.5 and 0.05 nM).", "Crystallization and data collection. The antigen-binding fragment of antibody m336 was prepared using Lys-C (Roche) digestion with an IgG/Lys-C ratio of 4,000:1 (w/w) 2 . The RBD protein was then mixed with the m336 Fab in a 1:1.5 molar ratio and incubated for 30 min at room temperature. The complexes were purified by size exclusion chromatography (Superdex S200; GE Healthcare) and concentrated to B8 mg ml \u00c0 1 for crystallization screening." ] },{ "paper_id": "756448c2d7dda1e89c0ea4acf6ccd5e2ee02517e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "756a222d5348e4c876a19dde4c0ffcb5b9c23db2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Spatial heterogeneity in disease processes is a growing field of study. The identification of hotspots of all types can play an important role in research, policy, and practice, particularly in resource planning, allocation, and implementation in response to infectious diseases. However, public health, like all fields, is subject to fads in concepts and terminology. Hotspot is an evocative term for important concepts, but a useful term should not be rendered useless by imprecision or overuse. Policy makers and public health researchers should be sensitive to its multitude of uses within the health sciences, and take care in their own use of the term.", "We recommend that the meaning of a \"hotspot\" be made explicit by use of an appropriate modifier such as: \"burden hotspot,\" to denote areas of elevated disease prevalence or incidence; \"transmission\" or \"risk hotspot,\" to denote areas of elevated transmission efficiency or a higher risk of disease acquisition; and \"emergence hotspot,\" to denote areas with an increased probability of disease emergence or reemergence. Furthermore, when geographic scale is important, a precise, data-based definition of spatial extent and characteristics should be provided. Table 1 provides a summary of the various definitions of hotspot common in the literature, key citations, and suggested alternative or clarifying terms to reduce the risk of confusion and simplify policy recommendations.", "Still, targeting hotspots is not a panacea for control. In outbreaks, generalized interventions or those targeted at \"coldspots\" may prove more effective, particularly if implemented late in response to epidemics, since the local epidemics in hotspots may have run their course by the time interventions can be put in place. 36 Preventive vaccination strategies targeting hotspots may also be suboptimal if an intervention (e.g., vaccine) efficacy is incomplete and the transmission efficiency in the hotspot is sufficiently high so that even with high intervention coverage, close to 100% of the population will ultimately be infected in the hotstpot. 36, 37 Even with a proactive strategy and a nonleaky vaccine, the benefits could be larger in nonhotspot areas if transmission can be interrupted in these areas but not in hotspots (i.e., the reproductive number cannot be driven below one in the hotspot but can elsewhere)." ] },{ "paper_id": "757d0a46fdff943b64a2e8f7c6ac2132da44c6d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Key indicators: single-crystal X-ray study; T = 123 K; mean (C-C) = 0.005 \u00c5; R factor = 0.058; wR factor = 0.159; data-to-parameter ratio = 16.2.", "T min = 0.270, T max = 0.514 17300 measured reflections 8621 independent reflections 7227 reflections with I > 2\u03c3(I) ", "x (14) " ] },{ "paper_id": "75882d6856d4243248aa32fe119153efeb0dbe12", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Citation MacParland SA, Ma X-Z, Chen L, Khattar R, Cherepanov V, Selzner M, Feld JJ, Selzner N, McGilvray ID. 2016. Lipopolysaccharide and tumor necrosis factor alpha inhibit interferon signaling in hepatocytes by increasing ubiquitin-like protease 18 (USP18) expression. J Virol 90:5549 -5560.", "Quantitative real-time PCR was performed on an ABI Prism 7900HT machine (Applied Biosystems, Foster City, CA) with SYBR green realtime PCR master mix (Applied Biosystems) according to the directions provided by the manufacturer. All of the RNA samples and controls were assayed in duplicate. Real-time PCR conditions were as follows: 10 min at 95\u00b0C, followed by 45 cycles of 15 s at 95\u00b0C and 15 s at 60\u00b0C monitor fluorescence in SYBR channel during a 60\u00b0C annealing/extension step. The results were analyzed by using Applied Biosystems SDS2.2 software (Applied Biosystems).", "Liver Kupffer cell inflammatory responses are induced by and play a role in the control and clearance of multiple viral infections of the liver (10, 11) . Although the mechanisms underlying these patterns are undoubtedly complex, the association between liver macrophages and hepatocytes raises the question of how the hepatocytes react to the cytokines produced by the macrophages (and other inflammatory cells). If ISG expression in hepatocytes reflects a response to inflammatory stimuli, then how the liver responds to a viral infection will be modulated by the inflammatory milieu." ] },{ "paper_id": "758c1e9d8c3cb652fe8ffc25e4b2b333cfb11ee1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceived and designed the experiments: IJL LLC. Performed the experiments: IJL WTT. Analyzed the data: IJ; WTT LEH.", "Contributed reagents/materials/analysis tools: IJL LLC. Wrote the manuscript: ILJ WTT LLC. ", "Felis catus whole fetus-4 (fcwf-4) cells [23] , [24] (kindly provided by Professor Peter J. M. Rottier, Utrecht University) were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 5% fetal bovine serum (FBS), 100 IU/mL penicillin and 100 \u03bcg/mL streptomycin in 5% CO 2 at 37\u00b0C. The type II NTU156 strain of the virus was isolated locally [25] ." ] },{ "paper_id": "758d365d79d74aee483623c5abeab0c682bf1ad3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Immunoblot images have been cropped for presentation purpose. Full-size images are presented in Supplementary Fig. 3 .", "Virus and plaque assays. VSV, Indiana strain (VSV-IND, Mudd-Summers isolate), was originally obtained from Professor D. Kolakofsky (University of Geneva, Switzerland). Virus was propagated on BHK-21 cells at a multiplicity of infection of 0.01. VSV concentration was determined as described below, and was then plaquepurified on Vero cells 57 Serum was titrated 1:2 over 12 steps and was incubated with 1 \u00c2 10 3 PFU of VSV. After a 90-min incubation at 37\u00b0C, the virus-serum mixture was plaqued onto Vero cells. Overlay was added after 1 h, and the mixture was incubated again for 24 h at 37\u00b0C. Plaques were counted by crystal violet staining. Antibody titres are presented as two-or threefold dilution steps ( \u00c0 log 2 and \u00c0 log 3 ) times the predilution (that is, \u00c2 40).", "Statistical analysis. Data are expressed as mean \u00b1 s.e.m. Student's t-test was used to detect statistically significant differences between groups. Significant differences between several groups were detected by one-way analysis of variance (ANOVA) with Bonferroni or Dunnett post hoc tests. Survival was compared with log-rank (Mantel-Cox) tests. The level of statistical significance was set at Po0.05." ] },{ "paper_id": "75957355c6d3c199d42896dfcd2f0f168ef5d348", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "75964abb7d9b187aab3a205e851fa6c646e9f96b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supported by text-mining 320 269", "Not supported by text-mining 340 294", "The FANTOM Consortium performed cap analysis of gene expression (CAGE) using single-molecule cDNA sequencing to identify transcription start sites (TSSs) and quantify their expression in H. sapiens and Mus musculus primary cell, tissue and cell line samples [8] . In our analyses, we use only the 362 H. sapiens primary cell samples organized into facets by Andersson et al. [9] . Individual TSSs were identified by the FANTOM Consortium using decomposition peak identification [8] .", "Some of the facets defined by Andersson et al. [9] contain cell samples of different potency. For example, the mesenchymal cell facet contains both somatic amniotic membrane cells and pluripotent mesenchymal stem cells. It has previously been demonstrated that gene expression changes with cell differentiation [27] . Therefore, we split the mesenchymal cell facet into three facets (mesenchymal somatic cell, mesenchymal precursor cell and mesenchymal stem cell) and the monocyte facet into two facets (monocyte and cd14+ monocyte derived endothelial progenitor cell) and assigned sub-facets based upon the potency of the samples." ] },{ "paper_id": "759978859d988aaba2d6dcfde90663d797f89550", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: The cause of severe disease in some patients infected with pandemic influenza A virus is unclear.", "PBMCs were obtained using Ficoll separation and stored in DMSO/FCS at 280uC according to previously described methods [5] .", "We found both CD14 + and CD16 + monocytes significantly reduced after storage (the latter, thought to represent inflammatory monocytes [9] in humans were more markedly affected). Invariant NKT cells, possibly owing to the rare nature of the cells, showed variable degrees of loss but all other cells remained stable after storage (data not shown). We have therefore not reported on monocytes or invariant NKT cell frequencies." ] },{ "paper_id": "75a8ca179e8e0405a9c150507809c0f5c38aedb5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Respiratory syncytial virus (RSV) is an enveloped, non-segmented negative-sense, single-stranded RNA virus that causes upper and lower respiratory tract infections. Nearly everyone is infected with the virus in the first two years of life; while reinfections occur throughout life, disease severity is highest in infants and the elderly. RSV represents a serious health and economic burden, and is the leading cause of hospitalization in children under the age of 5 (ref. 1).", "infection in antigen-na\u00efve young infants, it is important to understand how viral inactivation affected antigenicity and immunogenicity of FI-RSV compared to native virus." ] },{ "paper_id": "75aa45fec583443ad040672ab48b2c90825a94bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following steps correspond to Figure 1 .", "Step 1", "Step 2" ] },{ "paper_id": "75ad8fc2d398fb3440035eb1a565b060c7ce3a04", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rhabdomyosarcoma (RD) cell line was obtained from The National Institute for the Control of Pharmaceutical and Biological Products. Cells were cultured in Dulbecco's modified Eagle's medium (DMEM, GIBCO) supplemented with 10% fetal bovine serum (FBS, Gibco) at 37 \u00b0C in an atmosphere of 5% CO2.", "siRNAs targeting human ERK1 (siERK1) and ERK2 (siERK2) were synthesized from Genepharma Co., Ltd. (Shanghai, China). The sequences, coming from Christopher A. Dimitri's paper [29] , are showing as follows:", "U0126 (Pierce, Thermo Scientific, Waltham, MA, USA), the inhibitor of ERK pathway, was dissolved in DMSO at the stocking concentration of 2 mM. Antibodies were purchased from Cell Signaling Technology (Danvers, MA, USA) (CST, anti-ERK1/2, anti-phospho-ERK1/2), Abcam (anti-EV71 VP1 and anti-VP3/4), Santa Cruz (anti-\u03b2-actin)." ] },{ "paper_id": "75af9aa0e63889abde2eedaf0e41738b8ab082df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "75bee23cd59f44b79301f951a5627c47a1adcee3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Unless otherwise stated, all statistical analysis was calculated with the unpaired, two-tailed Student T-test using GraphPad's free online software, QuickCalcs.", "Crystal violet plaque assays determined viral titer as previously described (Lundberg et al., 2013) .", "UV inactivation of VEEV TC83 was performed as described previously (de la Fuente et al., 2018) . Briefly, viral supernatants were exposed to 120,000 \u00b5joules five times, mixed, pooled, aliquoted, and stored at \u221280 \u2022 C. Titers were determined by plaque assay and virus stocks considered inactivated if there were no plaques." ] },{ "paper_id": "75c2dba50049d4ee01ac711d152c62b018f31cf9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Electron microscopy. FCoV particles were purified and concentrated by ultracentrifugation using a sucrose cushion that contained 2% (wt/vol) paraformaldehyde to preserve virion morphology. Material from the resuspended pellets was mounted on a Pioloform (Plano, Wetzlar), carbon coated, glow discharged using 400 copper-rhodium grids, washed with distilled water, and stained using 1% (wt/vol) uranyl acetate. The grids were examined with a Zeiss EM 910 transmission electron microscope at 80 kV. Images were taken using a magnification-calibrated side-mounted charge-coupled-device (CCD) camera (Megaview II; SIS, Muenster, Germany) at an instrumental magnification of \u03eb80,000.", "Detection of structural protein M in purified FCoV particles by Western blotting. For SDS-PAGE analysis, purified virus (stock and 1:2 and 1:10 dilutions) was mixed with protein sample buffer after ultracentrifugation, heated for 5 min at 94\u00b0C, and loaded on a 10% Tricine-polyacrylamide gel (71) . For Western blot analysis, proteins separated by SDS-PAGE were transferred onto a nitrocellulose membrane (GE Healthcare). After blocking, the membrane was washed with PBST (phosphate-buffered saline with 0.1% Tween 20) and incubated with primary antibody F51-1 (monoclonal mouse anti-FCoV-M [6] ; kind gift from T. Hohdatsu) for 1 h at room temperature. After washing with PBST was performed, the membrane was incubated with horseradish peroxidase-conjugated goat anti-mouse antibody (Dianova) for 1 h at room temperature. Bound antibodies were visualized with chemiluminescent reagent (Western Lightning Plus-ECL; PerkinElmer). The intensity of bands corresponding to the M protein was quantified using a ChemiDoc imaging system and Image Lab software (Bio-Rad).", "Capsid protection assay. To detect genomic RNA in purified recombinant virus particles, a capsid protection assay was performed (49) . Briefly, 10 l of purified virus (stock and 1:2 and 1:10 dilutions) was digested with 100 ng RNase A (Sigma-Aldrich) at 37\u00b0C for 30 min. The reaction mixture was supplemented with 40 U RNase inhibitor (RNaseOUT, Invitrogen) and was subjected to RNA extraction followed by qRT-PCR analysis.", "C oronaviruses (CoVs) are positive-strand RNA viruses with genome sizes of approximately 30 kb. They are most closely related to members of the Torovirinae, which form a second subfamily in the family Coronaviridae. Together with three other families (Arteriviridae, Mesoniviridae, and Roniviridae), the Coronaviridae are part of the order Nidovirales (1) . Coronaviridae are divided into four genera, Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. Feline coronaviruses (FCoVs) are closely related to canine coronaviruses (CCoVs) and porcine transmissible gastroenteritis virus (TGEV); all three have been classified as one virus species called Alphacoronavirus 1. Other more distantly related viruses in the genus Alphacoronavirus include, for example, porcine epidemic diarrhea virus (PEDV), human coronavirus 229E (HCoV-229E), and human coronavirus NL63 (HCoV-NL63) (2) ." ] },{ "paper_id": "75cc9a3d0d2fc4baea735c4090944046019c8d39", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "While pure soluble recombinant h (human) furin was obtained commercially from New England Biolabs (Boston, Ma, USA), recombinant m (mouse) PC5 and soluble hPC7 were obtained in partially purified form as described earlier [18] .", "Conclusion/Significance: These findings imply its potential as a therapeutic agent for intervention of cancer and other furin-associated diseases.", "subtracting the spectrum of the control solvent run in parallel from that of the sample spectrum and analyzed using CD. Estima and Contin software programs for a-helix, b-pleated sheet, b-turn, and random structures were used (Softspec Company, NJ, USA) [52] ." ] },{ "paper_id": "75cf3b144e29ca2e460e2700827543bb72ef0844", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "H7N9 almost always causes severe disease rather than subclinical infections although there have been reports of mild or asymptomatic cases [28] [29] [30] . This variation in case presentation may have led to a potential bias in screening and surveillance despite China having had an effective surveillance and reporting system since 2003.", "The manuscript does not contain clinical studies or patient data.", "This work was supported by Beijing Municipal Science & Technology Commission (Z131100005613048). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." ] },{ "paper_id": "75d78749fe0ededfadc860e8c5eb8562ddcc45f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Written informed consent was obtained from all parents or guardians prior to recruitment of each child. Scientific approval and ethical clearance for the study was obtained from the Medical Research and Advisory Committee (MRAC) of the Ministry of Health in PNG, the Institutional Review Board (IRB) from PNG Institute of Medical Research (IRB#1005) and the Human Research Ethics Committee of the Walter and Eliza Hall Institute.", "Bio-Plex carboxylated beads (Bio-Rad) were covalently coated with the different coiled coil polypeptides following the manufacturer's instructions (Bio-Plex Amine Coupling Kit). Briefly, microspheres (1.25 \u00d7 10 6 beads/mL) were activated with a mixture of N-Hydroxysulfosuccinimide (5mg/mL) and N-(3-Dimethylaminopropyl)-N 0 -ethylcarbodiimide hydrochloride (5mg/mL) in H 2 O for 20 min at room temperature (RT) in the dark. Microspheres were then washed twice in 250 \u03bcL PBS, pH7.4, re-suspended in 500 \u03bcL of PBS, pH 7.4, and 1 \u03bcg of each polypeptide was added. Microspheres were incubated at 4\u02daC overnight and re-suspended in 500 \u03bcL of blocking buffer (PBS + 1% BSA). After further incubation under rotation at RT for 30 minutes, beads were washed with PBS and stored at 4\u02daC protected from light until use.", "https://doi.org/10.1371/journal.pone.0179863.g003", "Due to limitations associated with classical malaria control measures, vaccination against malaria is currently considered a potentially valuable cost-effective complement for malaria control activities that would significantly contribute to its elimination [9] . During the last 2-3 decades, significant efforts have been invested on developing P. falciparum [10] , and more recently P. vivax vaccines [11] . However, discovery of new potential vaccine candidates is required. The use of bioinformatics tools has allowed to explore the malaria genome/proteome databases, and to identify parasite proteins containing specific domains with functional importance for the parasite that could be immunologically targeted and therefore represent novel candidate antigens for vaccine development." ] },{ "paper_id": "75e12afbacd0c6dcdb20697a093ed0835e9bbead", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "75e5e406f83b2f0a94abc8cbed71cbb900f9956e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Phosphatidylcholine \u201a Synthesis increases a \u201a Fatty acid tail length increases (from C14/C16 to C18/C18) b a. Radioactive pulse-chase [11] b. Mass spectrometry [24] Sphingomyelin \u201a Synthesis increases a a. Radioactive pulse-chase [11] PI4P \u201a Synthesis increases a,b a. Radioactive pulse-chase [11] b. Protein lipid overlay assay [36] Host long chain acyl-CoA synthetase \u201a Activity increases a \u201a Long-chain acyl-CoA (phospholipid precursor) increases a a. In vitro measurement of newly synthesized fluorescent long chain acyl-CoA [24] PI4KIII\u03b2 \u201a Generates PI4P a,b a. Fluorescence microscopy [23] b. Protein lipid overlay assay [36] Poliovirus protein 2A \u201a Activates free fatty acid import a,b a. Individual protein expression in cells [24] b. Measurement of uptake of fluorescent fatty acids [24] Poliovirus protein 3A \u201a Recruits PI4KIII\u03b2 to replication machinery a,b a. Fluorescence Microscopy [23] b. Immunoprecipitation [23] Lipid Transport and Lipid Redistribution", "\u201a Recruits OSBP to replication machinery a,b", "\u201a May increase membrane fluidity c,d a. Immunoprecipitation [37] b. Fluorescent Microscopy [37] c. Fluorescence correlation spectroscopy [38] a. Immunoprecipitation [41] b. Fluorescence Microscopy [41] PI4P: phosphatidylinositol-4-phosphate, acyl-CoA: Acetyl coenzyme A; OSBP: Oxysterol-binding protein." ] },{ "paper_id": "75f36f193e2cbaa2f34b23bfc645dd441551bd51", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "which we will use in later discussion." ] },{ "paper_id": "75fef1b487aa86d9904a1860ff8a0bc953a2856c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Blood was collected by venipuncture, serum was separated by a portable centrifuge on site after clotting and stored at 20\u00b0C for shipment and storage until testing at the Central Veterinary Laboratory in Kenya. Anti-MERS-CoV (IgG) antibodies were tested using the EUROIMMUN ELISA Camel test kit [24] .", "Individual animal data collected included age and sex. Herdlevel variables included production system: pastoral herds are defined primarily as camels that are raised extensively; ranch herds are raised semi-intensively or intensively. Differences between pastoral and ranch production systems also exist in how breeding stock are sourced, migration and marketing of camels and camel products. Other herd-level factors collected included herd size; survey respondent's role; presence/absence of a perimeter wall; interaction with other camels, wildlife and other domestic species; water source; and whether the camels were confined at night.", "While pastoral camels <1 year old had a relatively high FOI, as expected, the seroprevalence used to calculate this estimate may include young camels with maternal antibodies. Passive immunity may therefore be confounded with natural infection, resulting in an overestimate of the FOI. Figure 4 is an illustration of the distribution of within-herd seroprevalence among pastoral and ranching herds. Especially among pastoral herds, the distribution is wide (0-100%) and bimodal, with a cluster of low seroprevalence herds, and a large cluster of high (>50%) seroprevalence herds. This distribution indicates that perhaps there are other factors within pastoral herds that also influence transmission risk. For example, herd density, calving management, geographical location and herd movement patterns may all influence the risk of transmission and exposure to MERS-CoV." ] },{ "paper_id": "76241f85fbee07bdf466214c02c4bccd79706436", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rosario K, Schenck RO, Harbeitner RC, Lawler SN and Breitbart M (2015) Novel circular single-stranded DNA viruses identified in marine invertebrates reveal high sequence diversity and consistent predicted intrinsic disorder patterns within putative structural proteins. Front. Microbiol. 6:696. ", "CRESS-DNA viruses implies that marine invertebrates may serve as hosts for many of the sequences obtained from marine environments.", "If this observation is validated, IDP profile analysis of hypothetical proteins may provide a reliable tool to identify structural proteins encoded by small viruses." ] },{ "paper_id": "76260c67421abbf69da3c4b0c75204190188a2cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "objective. All images were acquired with 500-ms exposures under the same illumination conditions and analyzed using LAS AF 1.8.2 software (Leica Laser Technik; Germany).", "Statistical analysis. Statistical analysis was performed using SPSS 19.0 software. Variables are expressed as mean \u00b1 SD. Student's t test and one-way analysis of variance (ANOVA) were used to compare viral titers. A P value of < 0.05 was considered significant." ] },{ "paper_id": "7633ee09c0059b99608c1cfbeefd19775c0317ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Infectious bronchitis virus (IBV) is a single-stranded enveloped RNA virus that belongs to the genus Gammacoronavirus, family Coronaviridae [1] . The virus causes a clinical disease characterized by coughing, sneezing, tracheal rales, and watery eyes. In layer and breeder chickens, the disease is associated with both quantity and quality deterioration of egg production. Lesions in infected birds include the degeneration of renal and ciliated respiratory epithelia [2] .", "Collected sera were tested using ProFLOK \u00ae IBV Ab and ProFLOK \u00ae IBD Ab (Symbiotic, Edison, NJ, USA) for IBV and IBD viruses, respectively, following the protocols recommended by the manufacturer. Haemagglutination inhibition (HI) test was carried out using IBV antigens (IB-H120 and IBV-VAR2) prepared at our laboratory as previously described by the OIE manual [15] , using recent Egyptian strains as inactivated viruses. The Haemagglutination inhibition (HI) reactivity was determined using a 1% suspension of chicken red blood cells.", "The statistical analysis is done using a two-tail T-test with p value = 0.05, using SAS software version 9.4 [21] .", "Moreover, it appears that the combination of ME VAC IB-VAR2 \u00ae and live classical IBV vaccines confers a protective immune response; however, protection studies are needed to confirm the ability of different vaccine combinations to protect chickens from both homologous and heterologous viral challenges. " ] },{ "paper_id": "7636da046a6bdf1033f9078671187e65e0e231d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Those patients are admitted with higher frequency to receive total parenteral nutrition (TPN) because home parenteral nutrition is not available in the Brazilian public health system.", "Registred on: ClinicalTrials.gov number NCT02077816. reSUMo objetivo: Avaliar se a temperatura da superf\u00edcie corporal nas proximidades da \u00e1rea de inser\u00e7\u00e3o do cateter venoso central \u00e9 diferente quando os pacientes desenvolvem infec\u00e7\u00f5es da corrente sangu\u00ednea relacionadas ao cateter. M\u00e9todos: Estudo transversal observacional. Usando um term\u00f4metro infravermelho sem contato, 3 medi\u00e7\u00f5es consecutivas de temperatura da superf\u00edcie corporal foram coletadas de 39 pacientes com cateter venoso central nos seguintes locais: nas proximidades da \u00e1rea de inser\u00e7\u00e3o do cateter ou do reservat\u00f3rio do cateter totalmente implant\u00e1vel, na regi\u00e3o contralateral equivalente (sem cateter), e na fronte do mesmo paciente. resultados: Um total de 323 observa\u00e7\u00f5es foram coletadas. Respectivamente nos pacientes do sexo masculino e feminino, desconsiderando a ocorr\u00eancia de infec\u00e7\u00e3o, a temperatura m\u00e9dia na \u00e1rea do cateter menos a da regi\u00e3o contralateral (m\u00e9dia \u00b1 desvio padr\u00e3o: -0,3\u00b10,6\u00b0C versus -0,2\u00b10,5\u00b0C; p=0,36) e a da \u00e1rea do cateter menos a da fronte (m\u00e9dia \u00b1 desvio padr\u00e3o: -0,2\u00b10,5\u00b0C versus -0,1\u00b10,5\u00b0C; p=0,3) resultaram em valores negativos. Al\u00e9m disso, em pacientes infectados, foram obtidos valores mais elevados na \u00e1rea do cateter (IC95%: 36,6-37,5\u00baC versus 36,3-36,5\u00baC; p<0,01) e nas subtra\u00e7\u00f5es de temperaturas: \u00e1rea do cateter menos regi\u00e3o contralateral (IC95%: -0,17 -+0,33\u00b0C versus -0,33 --0,20\u00b0C; p=0,02) e a \u00e1rea do cateter menos fronte (IC95%: -0,02 -+0,55\u00b0C versus -0,22 --0,10\u00baC; p<0,01). conclus\u00e3o: Utilizando um term\u00f4metro infravermelho sem contato, os pacientes com infec\u00e7\u00f5es da corrente sangu\u00ednea associadas ao cateter apresentaram valores de temperatura mais elevados, tanto ao redor da \u00e1rea de inser\u00e7\u00e3o do cateter e na subtra\u00e7\u00e3o das temperaturas das regi\u00f5es contralateral e fronte, em rela\u00e7\u00e3o \u00e0quelas da \u00e1rea do cateter.", "Descritores: Cateteres venosos centrais; Infec\u00e7\u00f5es relacionadas a cateter; Termometria; Raios infravermelhos; Diagn\u00f3stico precoce; Terapia intensiva Registrado em: ClinicalTrials.gov number NCT02077816." ] },{ "paper_id": "76418514384003ef87ee3e6922525db0b8bf0bd3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Several supportive therapies and antivirals were proposed and examined for the treatment of MERS-CoV infections [16] [17] [18] [19] [20] . However, most of these strategies were based on the experience gained during the severe acute respiratory syndrome (SARS) outbreak or from MERS-CoV in vitro studies and require further preclinical and", "In vitro Protein expression. Prior to animal experiments, protein expression from all DNA constructs was confirmed in vitro in Vero E6 cells (Fig. 1b) . Briefly, 80-90% confluent Vero E6 cells in 6-well plates were transiently transfected with 1 \u03bc g of each DNA construct (pS, pS\u2206 CD, pS\u2206 TM, pS1, or pcDNA) using FuGENE 6 reagent (Roche) according to manufacturer's instructions, followed by incubation at 37 \u00b0C in a 5% CO 2 incubator for 48 h. Transfected cells were then washed twice with phosphate-buffered saline (PBS) and lysed with cell lysis buffer as previously described 50 , and subjected to western blot analysis for protein expression using rabbit anti-S1 Abs (Sino Biological). Western blot analysis confirmed that all gene products show bands at expected molecular weights. Notably, the large band that is observed in all blots in Fig. 1b is due to non-specific binding as it was also detected in an un-transfected cell control (data not shown).", "The rapid spread and high mortality rate of MERS-CoV infections in several countries of the Arabian Peninsula present a daunting challenge to the international community; the large zoonotic reservoir host of MERS-CoV makes it difficult to eliminate the source of transmission. While public health measures are critical to contain MERS-CoV spread and proven to be effective in limiting outbreaks, development of safe and preventive vaccine is urgently needed.", "clinical evaluation. The ideal strategy to rapidly control existing and potential outbreaks of MERS-CoV is to generate a safe and effective vaccine at least to target high-risk groups or animal hosts. The ability of more than 60% of the infected patients to recover, clear the virus and develop immunity suggest that a vaccine based on the viral components such as the spike (S) glycoprotein could be a suitable vaccine candidate. This is further supported by the isolation of several human neutralizing antibodies (nAbs) against the MERS-CoV S protein and their ability to neutralize and block viral entry and/or cell-cell spread at very low concentrations, and sometimes to confer prophylactic and therapeutic protection in animal models [21] [22] [23] [24] [25] [26] [27] ." ] },{ "paper_id": "76481505399740984fe9bf11fdfec984fbf11e32", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "765003fdad3ad535f5fd2d769ed5900e5013dda2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Focus quantitation. Dried, stained virus titer plates were scanned and digitized with a KS ELISPOT reader (Carl Zeiss). Well images were extracted in Photoshop (Adobe). Foci in each well image were characterized in ImageJ (16) . Well images were converted to binary form to separate foci and background. Then, the areas of foci in the binary image were quantitated (the number of pixels) using the \"Analyze Particles\" function.", "Construction of the expression plasmid. A CMV promoter was obtained by PCR amplification from pcDNA 3.1(\u03e9) Hygro (Invitrogen). HDV ribozyme and SV40 PA (sequence based on the work by Varnavski et al. [14] ) was synthesized and cloned on a high-copy-number vector with flanking NheI and BamHI sites (Invitrogen). The CMV promoter, HDV ribozyme, and SV40PA were assembled onto a pUC19 backbone first with In-fusion HD (Clontech) and later by conventional restriction ligation (NheI and BamHI sites). The plasmid construct was verified by sequencing.", "The mapping was done in three stages. First, we characterized the chimeric viruses derived from single-gene swaps to identify target genes (Fig. 3A and B) . Replacement of either E or NS4B in v17 with the sequences from 4.1 caused a dramatic reduction in focus size (Fig. 3B) . The reverse experiment, where single segments from v17 were moved into the 4.1 background, suggested a role for E which increased focus size but not to the level seen in v17 (Fig. 3A) ." ] },{ "paper_id": "7657f444f3aba83bd7db9420f565557a282fe4da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All measurements were performed in triplicate. The mean and standard deviations of the data collected were calculated using SPSS 17.0 software (SPSS Incorporated, Chicago, Illinois, USA).", "Construction of the recombinant plasmid cgt/pET-20b(+), which directs expression of the wild-type \u03b1-CGTase from P. macerans strain JFB05-01 (CCTCC M203062) fused to the pelB signal peptide, has been described in a previous report (Li et al. 2009 ). Peptone and yeast extract powder were obtained from Oxoid (Basingstoke, Hampshire, United Kingdom). Isopropyl \u03b2-d-1-thiogalactopyranoside (IPTG), O-nitrophenyl-\u03b2-d-galactopyranoside (ONPG) and N-phenyl-\u03b1-naphthylamine (NPN) were purchased from Beyotime Institute of Biotechnology (Nantong, China). Glycerin and methyl orange were purchased from Shanghai Chemical Reagent Ltd. (Shanghai, China). All inorganic compounds were of reagent grade or higher quality.", "The cyclic oligosaccharides \u03b1-, \u03b2-, and \u03b3-cyclodextrin consist of 6, 7, and 8 glucose units, respectively, linked by \u03b1-1, 4-glycosidic bonds. Cyclodextrins form inclusion complexes with many different small, hydrophobic guest molecules, improving their solubility and stability in aqueous environments. This property makes it have many applications in scientific, medical and industrial fields (Roy et al. 2017) . The industrial use of \u03b1-cyclodextrin is in its infancy, yet is still expanding because of its small internal cavity, high water solubility, and resistance to enzymatic hydrolysis. Previous reports have shown that \u03b1-cyclodextrin can be used as a carrier of active ingredients, a solubilizer of lipids, a stabilizer of oils, a modifier of flavors or aromas, and a natural soluble dietary fiber (Aytac and Uyar 2016; Li et al. 2010b Li et al. , 2014a .", "A single colony of E. coli BL21 (DE3) harboring plasmid cgt/pET-20b(+) was used to inoculate 50 mL of Luria-Bertani (LB) medium supplemented with 100 mg/ mL ampicillin (inoculum size, approximately 0.1%). This starter culture was incubated on a rotary shaker (200 rpm) at 37 \u00b0C until the optical density at 600 nm (OD 600 ) reached 0.6 (about 8 h). The resulting culture was diluted (1:25) into 100 mL of terrific broth medium in a 500-mL flask, and IPTG was added to a final concentration of 0.01 mM to induce protein expression. The induction was allowed to proceed on a rotary shaker (200 rpm) at the specified temperature for 90 h. Samples of the culture were taken at intervals and analyzed for cell concentration and enzyme activity." ] },{ "paper_id": "76585719cd2c0b067b878acf53964015a47bb917", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since 2010, the global swine industry has experienced outbreaks of severe diarrhea caused by variant porcine epidemic diarrhea virus (PEDV) 1-3 . The variant PEDV caused severe diarrhea, vomiting, dehydration, and high morbidity and mortality in newborn piglets as well as sporadic diarrhea in sows and finishing pigs in China in 2010. Afterwards, the outbreaks have been reported in Europe 4 , America 5,6 , and other Asian countries 7,8 . Pigs suffered from diarrheal syndromes were unresponsive to antibiotics treatment and common management practices, and were even not protected from prior immunization with attenuated and/or inactivated CV777-based PEDV vaccines 9,10 .", "Unexpectedly, we observed a high relative abundance of Bacteroides fragilis in all three piglet groups. A similar finding was previously reported in young children with diarrhea 16 . Enterococci were presented in both asymptomatic and diarrheal samples, including AS and AP. However, none of the sequences from HS and HP samples were assigned to this genus. Enterococcus is a large genus of Gram-positive lactic acid bacteria of the phylum Firmicutes, commonly resident in the intestines of humans and animals, including the pig 51 . Important clinical infections caused by Enterococcus include urinary tract infections, bacteremia, bacterial endocarditis, diverticulitis, and meningitis 52 . It has been reported that there is an association of Enterococci to neonatal porcine diarrhea, and also association with resistance to several antibiotics 53, 54 , which could explain why the inefficiency of antibiotic treatment of these diarrheal piglets.", "Most of previous studies were mainly focused on the characterization of PEDV, virus isolation, pathology, and molecular evolution. However, there were only limited studies about the effects of the mucosal microflora residents on health and their roles during PEDV infection. The mammalian gut is a complex ecological niche, containing bacteria, eukaryotes, viruses, and even archaeon 11 . It has been demonstrated that colonized gut microbiota (GM) are important for the health and development of animals via aiding colonic fermentation 12 , stimulating the immune system 13 , defensing pathogens 14 , and improving energy harvest 15 . Studies on humans unraveled that diarrhea 16 and bowel inflammation 17 would distort GM in normal gut. In pigs, a few studies that examined the GM of healthy pigs under different growth stages or breeds demonstrated Bacteroidetes and Firmicutes are predominant phyla regardless of ages and breeds, while dynamic changes in percentage of GM at both phylum and genus levels were observed under different growth stages and conditions including age, weaning and colitis [18] [19] [20] [21] [22] [23] [24] [25] . Remarkable alternations of fecal microbiota were reported in neonatal piglets with diarrhea (NNPD) of unknown etiology 26, 27 . It was reported genus Enterococcus was 24 times and phylum Fusobacteria was doubled in abundance in diarrheal piglets compared to that of the healthy piglets. Studies on diarrheal weaning pigs and newborn piglets with natural infection of PEDV" ] },{ "paper_id": "765e023ee18436394fa56d1b2a388422e6201804", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Evaluation of serum LPS levels. To measure LPS levels in serum samples from pigs, we used HEK-Blue LPS Detection kit 2 (InvivoGen, CA) according to the manufacturer's recommendations.", "Here we established a human infant fecal microbiota (HIFM)-transplanted neonatal gnotobiotic (Gn) pig model of childhood malnutrition and investigated the impacts of early-life protein malnutrition on innate immunity, pathogenesis of an enteric infection " ] },{ "paper_id": "766f315970750baecd98b7fcc1a0ba8d7368d1cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The M2e peptide SLLTEVETPIRNEWGCRCNGSSD was synthesized by Shanghai Sangon Biological Engineering Technology and Services Co., Ltd. (>95% purity).", "Mortality and morbidity (weight loss) were monitored for 21 days after challenge [30] .", "Specific-pathogen-free female BALB/c mice, 6-8 weeks old, were obtained from the Center for Disease Control and Prevention in Hubei Province, China. The animals were bred in the Animal Resource Center at the Wuhan Institute of Virology, Chinese Academy of Sciences. All mice were maintained in specificpathogen-free conditions prior to infection." ] },{ "paper_id": "767767546b54da4b2a51840674c68adfd4e1a0bf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For sensitivity assays, Vero cells were infected with MERS-CoV, and incubated for 4 days. Cell supernatants were then collected and centrifuged at 1,500 \u00d7 g for 30 min at 4\u00b0C, and the supernatants were treated with RNaseA (Nippongene, Tokyo Japan) at a concentration of 10 \u03bcg/mL for 30 min at 37\u00b0C to exclude miscellaneous RNA other than viral RNA." ] },{ "paper_id": "767be20d25c46180b734e76c469b8f63cf9af3b3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "OLS analyses were performed by R version 3.3.3 (https://www.r-project.org/).", "The equations for forgetting, storing, renewing, and outputting information in the cell are shown below, respectively." ] },{ "paper_id": "76928215c6c3533279239fa704b87c1d4283a205", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To assess variation within groups and among tissues, we conducted a principal component analysis using normalized read counts (FPKM) for 18,168 tested genes locations as input using the R statistical function 'prcomp.'", "Samples were analyzed at the University of Louisville Genomics Core (Louisville, KY) for library preparation and sequencing. SMART-Seq v4 Ultra Low Input RNA kits (Takara Bio USA, Inc.) were used to prepare cDNA libraries. Samples were barcoded with Illumina TruSeq Adapters. After library clean-up using Agencourt AMPure XP Beads, quality was assessed on an Agilent Bioanalyzer using the Agilent DNA 1000 Kit. This confirmed the final fragment size for all samples to be approximately 400 bp, as expected from the protocol. Samples were sequenced twice on an Illumina NextSeq 500 sequencer, with four biological replicates and four lanes per replicate.", "Further validation of these results can be done through RT-PCR. This would be best accomplished with multiple gene primers based on the sheer number of DEGs in our data. Custom primer design is recommended." ] },{ "paper_id": "769398f7e7d03582fd05a4fbf322133e4509f5b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "7694cd45d861b0363acf826f1ccb83b0f5a40e4c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Text S1, DOCX file, 0.04 MB. Figure S1 , TIF file, 0.5 MB. Figure S2 , TIF file, 0.4 MB. Figure S3 , TIF file, 0.4 MB. " ] },{ "paper_id": "7697fcf19fb5548783f66563f33f7977ff59cd7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Numerous works Colton, 2012; D'Agostino et al., 2012) emphasize the possible relevance of DCs in the CNS immunosurveillance as well as the function they can play in neuroinflammatory situations. However, the specific contribution of those cells is still not wellunderstood.", "The discovery of all of these subtypes of lymphocytes with putative new functions in the promotion and modulation of the acquired immune response and their still-unknown interactions with resident CNS cells, specially microglia, has contributed to becoming aware that the scenario of the neuroimmune response could be even more complicated than previously thought.", "While the expression of MHCs has been extensively reported in activated microglia, only a limited number of studies have addressed the question of whether activated MHC-II+ microglia simultaneously express co-stimulatory molecules (Summarized in Table 1 )." ] },{ "paper_id": "769d042233efa89198582de95656f0bb2198f379", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "76a1894ee3ade28e1fd11edd750b988c81ad459b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "All data generated or analyzed during this study are included in this published article (and its supporting information files).", "Supporting information S1 " ] },{ "paper_id": "76b1bad1aba249a858d1112096bbc4fbf3ae7d5d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data were evaluated by Student's t-test or one-way ANOVA followed by Tukey's post hoc test. The statistical significance of the data was considered at p < 0.05.", "Hepatitis B virus (HBV) causes acute and chronic infection in the human liver and subsequently hepatic cirrhosis and hepatocellular carcinoma (HCC) that severely affects human health [1] [2] [3] . Although a highly effective vaccine is now available for the prevention of new HBV infections, about 400 million people worldwide have already been chronically infected and suffer from chronic liver injury [4] ." ] },{ "paper_id": "76b96ffbbdea59714eba9d891362ceb32731ad90", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "76c35b758071bd154c5aa19cbacb5a044b1b6eb2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Define the type of IT resources are needed to coordinate a response (e.g., electronic connectivity, telecommunications).", "Methods and main illustrative estimates: Potential Ebola broad-scale transmission scenario", "Please see Additional file 1 for translation of the abstract into the six official working languages of the United Nations." ] },{ "paper_id": "76d39ac4634db5a0fcc8cddbefd965c463c0ace0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1:100), mouse anti-human TLR-8 (1:100) and rabbit anti-human GAPDH (1:1000) (Imgenex). Overnight incubation with primary antibody at 4uC was followed by 2 hrs incubation with rabbit antimouse (1:1000) and goat anti-rabbit (1:2000), horseradish peroxidase (HRP) secondary antibody conjugates (Santa Cruz Biotechnology). Proteins were detected using an enhanced chemiluminescence HRP substrate reagent (Millipore)." ] },{ "paper_id": "76d446112561ab0100feb5323f071191e0aa02c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A herd-level summary containing relevant pathological, virological and serological results is presented in Table 1 .", "All samples tested were negative against PRRSV, Mhyo and PRCV antibodies." ] },{ "paper_id": "76d6014c9fac61e50caf256e5ca92ea007219c29", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed using paired Student's one-way analysis of variance (ANOVA). Differences among treatments were determined by Tukey's test (P<0.05). Analyses were performed with PRISM version 5.02 software (GraphPad).", "Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped and positivestranded RNA virus of the family Arteriviridae, and causes significant economic losses in the global swine industry [1] . Based on genetic and antigenic characteristics, two major genotypes of PRRSV, type 1 (European; prototype strain Lelystad) and type 2 (North American; prototype strain VR-2332), have been identified and share 55-70% nucleotide identity [2] [3] [4] [5] .", "(DOC)" ] },{ "paper_id": "76d7fe0354828411a05ec3846931ffdf23cfe1cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Identification of the neutralizing epitope of HKU1 S protein.", "ELISA. To coat the plate, 0.5 mg of purified proteins were added into each well of Immulon 2HB plates (Thermo, Rochester, NY, USA) and incubated for overnight at 4\u00b0C. After washing three times with washing buffer (PBST, PBS \u00fe 0.05% Tween 20), the wells were blocked with blocking buffer (3% BSA in PBST) for 1 hr at room temperature (RT). After washing three times with PBST, fourfold serially diluted antibodies in blocking buffer were added into each well and incubated at RT for 1 h. The mAb bound to the truncated S proteins was detected using an horseradish peroxidase-conjugated goat anti-mouse Ig (Cat# 115-035-166, Jackson ImmunoResearch, West Grove, PA, USA) at a dilution of 1:5,000. After 1 h incubation and washing three times with PBST, 100 ml of o-phenylenediamine dihydrochloride (Beijing Wantai Biological Pharmacy Enterprise Co, Beijing, China) was added to each well and incubated for 15 min. The reaction was then stopped by addition of 2 M sulfuric acid, and the optical density at 492 nm was measured using a MultiSkan MK3 plate reader (Thermo, Rochester, NY, USA).", "Data availability. The coordinates and structure factors have been deposited in the Protein Data Bank under the accession codes 5GNB and 5KWB. The GenBank accession codes AGT17758.1, AY597011 and PDB accession codes 3JCL, 4L72, 4QZV, 5GYQ and 2AJF were used in this study. All other data are available from the corresponding authors upon reasonable request." ] },{ "paper_id": "76dae8b8fd43335310edca09c522640ac9027edf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The nsp4C monomer possesses a novel fold" ] },{ "paper_id": "76dcc76a0d6041517a4d88f763269bd0196488cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For sequence and phylogenetic analysis of the nucleocapsid (N) gene, RT-PCR was performed using the primer set ECoV-Nf (5\u2032-tcaggcatggacaccgcattgtt-3\u2032) and ECoV-Nr (5\u2032-ccaggtgccgacataaggttcat-3\u2032) [5] using Pri-meScript II High Fidelity One Step RT-PCR Kit (Takara Bio, Otsu, Japan). RT-PCR products were directly sequenced commercially by Fasmac (Atsugi, Japan).", "Real-time RT-PCR assay was conducted using a primer set described previously (ECoV-380f, ECoV-522r and ECoV-436p) [3] and TaqMan Fast Virus 1-Step Master Mix (Applied Biosystems, Foster City, CA, USA) according to the manufacturer's instructions. Thermal cycling was performed as [7] : 50 \u00b0C for 5 min and 95 \u00b0C for 20 s, followed by 40 cycles at 94 \u00b0C for 3 s and 60 \u00b0C for 30 s." ] },{ "paper_id": "76de3c0c853bd138ae36cf9128ee2fb0943764fc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(R)-1-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-N,N-dimethyl-1-oxopropan-2-aminium 2,2,2-trifluoroacetate (5a). Yellow solid; yield, 85%; 1 General procedure C for preparation of compounds 6a-6f", "The starting materials and reagents, purchased from commercial suppliers, were used without further purification. Emodin extracted from Polygonum cuspidatum was purchased from China Xi'an Sino-Herb Bio-technology Co., Ltd. (Xi'an, China). All reactions were monitored by thin-layer chromatography (TLC) on aluminum sheets (Silica gel 60-F254, E. Merck, Darmstadt, Germany). Compounds were visualized by UV light. Column chromatography was carried out using silica gel (200-300 mesh). All reaction solvents were dried prior to use according to standard procedures. All primary reagents were commercially available. Silica gel chromatography solvents were of analytical grade. NMR spectra were recorded in DMSO-d6 on a Bruker-250 spectrometer (Bruker Biospin, F\u00e4llanden, Switzerlahd), at 400 MHz for 1 H-NMR, 101 MHz for 13 C-NMR and 376 MHz for 19 F-NMR with TMS as the internal standard. Chemical shifts were expressed in \u03b4 (ppm) and coupling constants (J) in Hz. Multiplicity was indicated as follows: s (singlet), d (doublet), t (triplet), p (quintet), dd (doublet of doublets), brs (broad singlet), etc. Mass spectra were obtained on an Agilent 1100 Series LC/MSD Trap mass spectrometer (ESI-MS, Agilent, Santa Clara, CA, USA). Table S4 )." ] },{ "paper_id": "76e0bd45995e7799e0f52be915f66719e24265a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data Analysis. The analytical method used for this study was not necessarily specific; rather, estimated polyoxometalate concentrations reflected concentrations of metal (W) atom. Thus, the pharmacokinetic analysis described the overall disposition of parent polyoxometalate and possibly degradation and metabolic products as well.", "Quantization was based on the mean (n = 3) count of tungsten against a calibration curve by linear regression analysis, which was profiled with a series of standard tungsten solutions of different concentration.", "where C m was concentration measured, C b was blank concentration and C p concentration prepared." ] },{ "paper_id": "76f55ebed6baf41823e8d40954a7e2a62e244109", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Possible recombination was detected using bootscan analysis with software Simplot version 3.5.1 (SCRoftware, US). The nucleotide genome sequences of selected Merbecoviruses were aligned and further analyzed with 1000 bootstrap replicates. The sliding window was set with 1000 nucleotides together with 200 nucleotides moving steps.", "The time of the most recent common ancestor (tMRCA) of Ea-HedCoV ", "Amplified PCR products were examined by gel electrophoresis. Targeted products were purified and sequenced using the QIAquick gel extraction kit (QIAgen) and an ABI Prism 3700 DNA Analyzer (Applied Biosystems), respectively. A comparison between obtained viral sequences with known CoVs' sequences from the GenBank database was performed. The 383 bp fragments of RdRp genes were subjected to phylogenetic tree construction. The maximum likelihood method and General Time Reversible model were applied with Gamma Distribution and an allowance of evolutionarily invariable sites (GTR+G+I) in the analysis using PhyML v3.0 (The French Institute of Bioinformatics & France Genomique, Montpellier, France) [28, 34, 35] .", "Coronaviruses (CoVs) are classified into four genera, Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus, while Betacoronavirus is further subdivided into four lineages, A to D [11] [12] [13] [14] [15] [16] . In 2018, these four Betacoronavirus lineages were reclassified into five subgenera, namely Embecovirus, Sarbecovirus, Merbecovirus, Nobecovirus, and an additional subgenus, Hibecovirus [17] . Notably, four of the six CoVs known to infect humans belong to Betacoronavirus, with human CoV HKU1 and OC43 belonging to Embecovirus, Severe Acute Respiratory Syndrome CoV (SARS-CoV) belonging to Sarbecovirus and MERS-CoV belonging to Merbecovirus [18] [19] [20] [21] [22] [23] [24] [25] . The bloom in the discovery of novel animal CoVs since the SARS epidemic has uncovered bats as an important reservoir for alphacoronaviruses and betacoronaviruses, whereas birds are reservoirs responsible for gammacoronaviruses and deltacoronaviruses [14, 26] ." ] },{ "paper_id": "76f88935e279c736683360a22e61dbe41cc18661", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The prevalence (or detection rate) of viruses was calculated by dividing the number of positive cases by the total case numbers tested for that virus. The 95% binomial confidence interval (95% CI) for detection rates were calculated by the Pearson-Klopper method. To compare variables between subgroups of patients, we used Chi-square tests or Fisher's exact tests for categorical variables and Wilcoxon rank-sum or Kruskal-Wallis tests for continuous variables as appropriate. Two-sided p value of < 0.05 was considered statistically significant." ] },{ "paper_id": "76f9e58fe7a4be360490151b1d2fdeba380c1603", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All tests were two-tailed. p values < 0.05 were considered significant. All statistical analyses were carried out using the R 2.13.1 statistical platform (http://www.Rproje ct.org)." ] },{ "paper_id": "77138f50684f6b8c48752afd24cbb63abaad4aa4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In 2003, over 2 million Canadian children from the ages of 0-5 years were in some form of non-parental care and 28% of these children were in a daycare [3] . The cost of child care ranged from $300 to over $700/week and varied between provinces, territories and age in 2005 [4] . Two types of child care, regulated and unregulated, are present in Canada. There are approximately 11, 000 regulated child care facilities in Ontario which include nursery schools, preschools, centre-based full-day child care and regulated home child care. These centres must meet legislated requirements for operation of services as set out by provincial/territorial regulations. Unregulated arrangements may consist of care provided by a relative, by an unregulated family child care provider, or in-home caregiver [5] .", "A purposive sampling approach was used to recruit participants from regulated CCCs in southern Ontario. Centres were selected by the researchers and contacted by phone.", "Staff: You get to know the smell, like the regular smell of somebody's bowel movement, the colour, you get to know the timing, like something is different or not right." ] },{ "paper_id": "7721a5991adb22000506b40f511a800f879d5914", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "7722e2866e2b7849cc2f3175430a1048d97b71d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "today, it remains difficult to compare the efficiency of new and traditional methods for producing tAs.", "the demand for mAbs recently hit the several-hundred-kilograms-per-year mark. For example, world demand for anti-receptor cD20 mAbs exceeds 600 kg per year. It is estimated that a herd consisting of 210 transgenic goats whose milk contains mAbs at a concentration of 8 g/l can fully meet the world demand in anti-cD20 mAbs at an approximate cost of $100/g [85] . Meanwhile, 51,000 l of cell culture with the capacity of 1g/l and an approximate cost of $300/g are required to obtain an equal amount of mAbs. eases, generated profit of over $26 billion for American biotechnological companies in 2007 [84] .", "the group of methods based on infecting the organs or tissues of an organism with a replication-defective adenovirus containing the gene of the target protein should be specifically mentioned. this approach results in a short-term nonhereditary production of rPs in the organ or tissue under consideration." ] },{ "paper_id": "772730b5d9f1213ae01902ca77b544cef2ba59b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed using GraphPad Prism 7.03 software. Statistical significance was calculated using Student's-t test or Mann-Whitney test when appropriate.", "Competing interests: Involvement of one of the Bioceros BV does not alter authors' adherence to PLOS ONE policies on sharing data and materials.", "Tumors were cut into small pieces, digested for 30 min at 37\u02daC using Collagenase type IV (600U) (Sigma) and (400U) DNAse (Sigma). Next, tissue fragments were dissociated using a gentleMACS Dissociator, and filtered through a 100 \u03bcm cell strainer, washed with PBS containing 2 mM EDTA and 1% FCS, centrifuged and stained. Spleens were forced through the cell strainer (70 \u03bcm) and cells were centrifuged (500g) at 4\u00baC. When necessary, erythrocytes were lysed using a buffer containing 155 mM NH 4 Cl, 10 mM NaH 2 CO 3, and 0.1 mM EDTA, pH 7.3. For staining, cells were blocked in 5% normal rat serum and stained with fluorescently " ] },{ "paper_id": "7729f9d0b2d49fd43519f42d2637a55b03e1c778", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "-'Negative', when no characteristic amplification curve was present; -'Positive' (detection), when the characteristic amplification curve was present.", "-'Non-quantifiable', when the viral load was < Limit of Quantification (LoQ); -'Quantifiable' (quantification), when the viral load was \u2265 LoQ." ] },{ "paper_id": "772e7c8efc8fed6e7c27602dc255fd97f2f55a7e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analysis SPSS 14.0 (Chicago, USA) was employed for data analysis.", "All data were collected by a team of experienced researchers in 2008.Ethical approval was granted by the Ethical Committee for Health Policy Studies in Shandong University, China. All the subjects provided written informed consents. The dataset would be made available to researchers who formally apply through the corresponding author and comply with requirements of the Ethical Committee." ] },{ "paper_id": "773219a6abb0977144db395a5d94f63ce2eb03c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "target of neutralizing antibodies 11 , making an understanding of S structure and conformational states pertinent for investigating S antigenic surfaces and designing vaccines.", "Coordinate models were built for several of the high-resolution reconstructions using 5I08.pdb 16 , 2AJF. pdb 23 and 5X4S pdb 22 as template models with reference to a recently published wild-type SARS S ectodomain (5X58 pdb 22 ). Manual model building was performed in Coot 49 with coordinate refinement in Rosetta Relax 50 and real-space refinement in PHENIX 51 with final rounds of coordinate refinement and ADP estimation performed in PHENIX." ] },{ "paper_id": "7732ed94fb45c64d27fad1fad250e7937b3d4abc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "S1 Text-Details of the parametric dependence of the force of infection on specific humidity", "In the above equation, and unlike the work published by others, the values of the parameters a and \u2206 R are fitted. The effect of specific humidity can be combined with that of school vacation which is discussed in the following sub-section." ] },{ "paper_id": "77361db3ae17729e18971ae8641a20691e44afab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Funding for this study was provided by ADMA Biologics.", "Frontiers in Immunology | www.frontiersin.org" ] },{ "paper_id": "774e74e60cb62c3057145f6b98501fe532acdbdd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PDCoV S1 ELISA development", "PDCoV S1 ELISA development Protein production. The region encoding the putative S1 domain (amino acids 1-573) of the PDCoV strain PDCoV-IA2014-1 (GenBank accession number KM613173) was 3' terminally fused with a thrombin cleavage sequence followed by a human IgG Fc domain, which was subsequently cloned into a eukaryotic expression vector as previously described [25] . The S1-Fc fusion proteins were expressed by transfection of HEK-293T cells, purified using protein A column purification, cleaved with thrombin to remove the Fc tag, and treated for endotoxin removal.", "While there is limited information available regarding coronaviruses in the genus Deltacoronavirus, other porcine coronaviruses belonging to the genus Alphacoronavirus such as PEDV, TGEV and the porcine respiratory coronavirus (PRCV) are well characterized [1, 16] . In general, coronaviruses are enveloped, single-stranded RNA viruses and contain four major structural proteins: spike (S), envelope (E), membrane (M) and nucleocapsid (N) [17, 18] . The S protein region of coronaviruses contains major neutralizing epitopes and also stimulates induction of neutralizing antibodies in the host [17, 19, 20] . Previously, the entire S protein or portions thereof have been successfully utilized for PEDV and TGEV ELISA development [21] [22] [23] [24] ." ] },{ "paper_id": "7763fdd2366c612dc01aaf0173ea6bb8f1ed0bf9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The USA/Colorado/ 2013 PEDV sequence data have been deposited in GenBank under the accession no. KF272920.", "Porcine epidemic diarrhea virus (PEDV) is newly emerging in the United States. PEDV strain USA/Colorado/2013 (CO/13) was obtained from a 7-day-old piglet with severe diarrhea, and the complete genome was sequenced to further study the PEDV outbreak in the United States.", "In the United States, PEDV was identified on 29 April 2013 by the Iowa State University Veterinary Diagnostic Laboratory and was corroborated by the National Veterinary Services Laboratories (NVSL) on 16 May 2013 (http://www.aasv.org/news/story.php?id \u03ed6444). To determine the phylogenetic relationship of the new U.S. strain and global PEDV strains, the complete genome of PEDV CO/13 was sequenced and analyzed." ] },{ "paper_id": "77779295f3fcc05a193b349478b8730b226790c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Institutional Review Board (IRB) at An-Najah National University does not require submission of an IRB application for such study. The IRB considered that there is no risk for human subjects in such publications since the data are based on published literature and did not involve any interactions with human subjects.", "Data from ISI Web of Science were exported to Microsoft Office Excel\u00ae and then transferred to the Microsoft word program. The measurements of bibliometric analysis (e.g. countries, cited articles, institutions) were converted to the rank order using the standard competition ranking (SCR). We took into consideration the top 10 ranking in each item. If the measurements of bibliometric analysis have the same ranking number, then a gap is left in the following ranking numbers. The journal's impact factors (IF) were evaluated using the Journal Citation Report (JCR; Web of Knowledge) 2012 science edition by Thomson Reuters (New York, NY, USA)." ] },{ "paper_id": "778543806bc7ebe5596c085cf9a0421d0c0a1a2f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human T-lymphotropic virus type 1 (HTLV-1) was originally discovered in 1980, identified as the first human retrovirus, and currently infects more than 20 million people worldwide [1] [2] [3] [4] [5] . HTLV-1 is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in infected individuals. Oncogenesis is due primarily to the viral transactivator protein, Tax, a 40-kDa phosphoprotein that regulates not only viral transcription, but acts to manipulate host cellular functions such as cell cycle progression, apoptosis, chromatin remodeling, and other signal transduction pathways [6] [7] [8] . Recently, much interest has developed in elucidating the cross-talk between tumor development and HTLV-1 infection as it relates to the innate host response, in particular the small RNA regulatory network.", "Supernatants were collected at indicated time points to test for the presence of virus. Viral supernatants (10 mL) were incubated in a 96-well plate with a RT reaction mixture containing 16 RT buffer (50 mM Tris-HCl, 1 mM DTT, 5 mM MgCl 2 , and 20 mM KCl), 0.1% Triton-X100, poly(A) (1 U/mL), poly d(T) (1 U/mL), and [ 3 H]TTP. The mixture was incubated overnight at 37uC, 5 ml of the reaction mix was spotted on a DEAE Filtermat paper, washed four times with 5% Na 2 HPO 4 , three times with water, and then dried completely. RT activity was measured in a Betaplate counter (Wallac, Gaithersburg, MD). Data is shown as cpms (counts per minute).", "We also show that in the absence of Drosha, HTLV-1 viral replication increases by at least two-fold. The knockdown of DGCR8 also resulted in a significant increase in HTLV-1 replication, suggesting a dysregulation of the microprocessing complex. The downregulation of HTLV-1 replication with Ago2 knockdown was validated with a comparable downregulation when cells were treated with the RISC inhibitor ACF." ] },{ "paper_id": "77888e24fe540edda3d9cd2e0aadd2e699aa466d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "death (1) Al-Riyami et al. (1) Second (1), third", "venous (2) 14 days Recovery (4),", "(2), several (5) Arterial (6),", "Authors are deeply grateful to Hans-Hartmut Peter, Freiburg, Germany, for his careful reading of the manuscript, the valuable comments, and the correction of English." ] },{ "paper_id": "778e39cb165c72b4245262781d804c4e1f6da3d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "miR-34a involvement in cardiotoxicity: player, biomarker, or both?", "Funding This work was supported by GR-2011-02346742 grant (Ricerca Finalizzata) from Italian Ministry of Health to Yuri D'Alessandra.", "Doxorubicin regulation of ErbB4 via miR-146a" ] },{ "paper_id": "778e81157f2312199105d67938e88bf0ec559130", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A last mechanism that thermophilic organisms apply to survive at high temperatures is the reduction of asparagine and glutamine residues to prevent deamidation. This strategy has not been (intentionally) used for HIV vaccine design yet.", "When considering how to stabilize vaccine antigens, much can be learnt from nature. Extremophile bacteria and archea, which thrive in extreme environmental conditions such as high and low temperatures (between 45-122 \u00b0C and below \u2212 15 \u00b0C, respectively) or alkaline and acidic conditions (pH > 11 and pH < 1, respectively) [42] [43] [44] , have evolved highly stable proteins compared to their mesophilic homologues [43, 45] . In extremophile organisms, natural evolution has applied six methods of protein stabilization. Several of these methods have been applied, either intentionally or not, to HIV-1 Env trimer vaccine design.", "Immunization with SOSIP trimers also induced strong non-neutralizing antibody (non-NAb) responses against V3 epitopes and neo-epitopes at the bottom of the trimer [10, 15, 16, 66] . Heterologous primary isolates were not, or only weakly and sporadically neutralized, pointing to possible directions of further research to improve nativelike trimer immunogens." ] },{ "paper_id": "778eb107d6ddffb02ad911aa14802f662db00b30", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "AIARATEEDFCEEEEAKIRQRIFRPT--RKQRKEERASLGLVTGSEIRKRNPEDFKPKGK GIV_Human AYAQACGGDCDDIEISRIRNSIFRPS--RKQRKEERVKLGLVTGSEIRKRKPDDFQPKGK * * . ::.*: ** .****:*.:** *:* *:", "GV_Murine SWADDDRQVDYGEKINFE GI_Human EWADDDREVDYTEKINFE GII_Human LWADDDRSVDYNEKLSFE GIV_Human LWADDERTVDYNEKLDFE ****:* *** **:.**", "MNV-CW3 or 1. Infect at MOI 5 pfu/cell for 24 hours 2. Collect surviving cells 3. Determine gRNA abundance relative to moclk infected A.", "systems, in comparison to other positive sense RNA viruses, our knowledge of the intracellular life of noroviruses is significantly lacking (reviewed in Thorne and Goodfellow, 2014) ." ] },{ "paper_id": "77907b0bbf75ae10794ca69d97b9874159db1857", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "WL is a Postdoctoral Fellow of Geography Department at University of California, Santa Barbara. He was a Postdoctoral Research Assistant of Computing, Informatics, and Decision Systems Engineering at Arizona State University. He received his Ph.D. from Geography Department at Penn State University. His research focuses on developing new geo-social visual analytical methods to take advantage of human intuition, decision-making ability, and computational power to facilitate, and enable insight gaining process, as well as aid decision-making in related applications (e.g., international trade, public health)." ] },{ "paper_id": "77984a8d832663c5cd43e17e34a37470b3d95406", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "The study was approved by The Medical Ethics Committee of the Instituto de Salud Carlos III. Informed written consent was obtained from parents or legal guardians." ] },{ "paper_id": "779c1b5cb3afe3d50219aa2af791014a22eb355a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1.", "\"All hospitals should have infection control systems in place to ensure that alerts regarding changes in exposure risk factors for SARS or other potentially serious communicable diseases are conveyed promptly to clinical units, including the labour and delivery unit.", "\"Given the rapid global spread of the nCoV-2019 virus the world needs to act quickly and in unity to tackle this disease. Our intention with this work is to leverage our work on the MERS coronavirus and rapid response platforms to speed up vaccine development.\"" ] },{ "paper_id": "77a8c567572cf005f58dc577dc44f711aabe3fd4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For mitochondrial preparations from FHV-infected cells, ", "Monoclonal antibody. Mouse monoclonal antibodies against FHV protein A have been described previously [9] . MAb clone 2-1.1.2.4.8, which recognizes the protein A epitope between amino acids 230 and 399, was used for immunogold EM labeling." ] },{ "paper_id": "77aae7c898acfb4ff723de2af7928a38b169878a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA instillation: Double-stranded RNA (dsRNA, Poly IC) and single-stranded RNA (ssRNA, Poly C) were purchased from Sigma-Aldrich Corp. (St. Louis, Mo.) and reconstituted in sterile normal saline (20 \u00b5g/\u00b5l) and stored at 4\u00b0C prior to use." ] },{ "paper_id": "77b07d4814698f7531468fc1bef3251088beca64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vero (a kidney epithelial cell line from an African green monkey) and A549 (an human adenocarcinomic alveolar epithelial cell line) cells were purchased from the American Type Culture Collection (ATCC, CCL-81) and were grown and maintained at 37 \u2022 C and 5% CO 2 in growth medium, consisting in Dulbecco's modified Eagle's medium (DMEM) supplemented with 5% fetal bovine serum (FBS) (HyClone, ThermoFisher Scientific, Madrid, Spain), 2 mM L-glutamine (Sigma-Aldrich, Madrid, Spain), 1% nonessential amino acids (Sigma-Aldrich), 100 U/mL penicillin (Sigma-Aldrich) and 100 \u00b5g/mL streptomycin (Sigma-Aldrich).", "All animal protocols were approved by the University of Rochester Committee of Animal Resources (Protocol number: UCAR-2017-005/101851; approval date: 05/05/2017) and complied with the recommendations in the Guide for the Care and Use of Laboratory animals of the National Research Council [49] ." ] },{ "paper_id": "77b8307c0de7ad71378665456b43e4185d5e5477", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In September 1971, an air leak in a gasket around a research laboratory door was the cause of in an internal release of FMDv at PIADC [2] . This scenario represents the virus accidentally released through an aerosol.", "\"The Secretaries of Agriculture and Homeland Security will develop a plan to provide safe, secure, and state-of-the-art agriculture biocontainment laboratories that research and develop diagnostic capabilities for foreign animal and zoonotic diseases\" [15] .", "There are 14 foot-and-mouth disease virus incidents known or believed to have been released over the past 50 years from biocontainment research laboratories worldwide, including Czechoslovakia, Demark, Germany, Spain, Russia, United Kingdom, and United States [2] . Because of potential release and subsequent consequences of a contagious infectious disease, proper analyses and reviews must be conducted before constructing a new state-of-the-art biocontainment research facility." ] },{ "paper_id": "77b8d67e208f5ba81ff129e0d4ff7e1b73c45482", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data have been presented as mean \u00b1 S.E.M and analyzed by one-way ANOVA followed by least significant difference (LSD) using SPSS software (version 20.0, SPSS Inc., Chicago, IL).", "The rats were sorted into six groups, each containing eight rats as follows:", "TAA, NA, vitamin B2 and vitamin C were purchased from Sigma-Aldrich Corporation (St Louis, MO, USA). Remaining all chemicals were of analytical grade from authentic companies of International repute.", "At the end of the experiment, a portion of a liver from each of the sacrificed rat was fixed in 10% buffered formalin and processed for paraffin sectioning after dehydrating them in various concentrations of alcohol, cleared with xylol and embedded in paraffin blocks. Sections of about 5 \u03bcm thickness were stained with hematoxylin and eosin (H&E) for histological study." ] },{ "paper_id": "77c5a33cacec66e3eecf748902a04cd245df6e0f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Signs of meningeal irritation such as neck stiffness may be present. These clinical features are not unique to JE, thus, laboratory diagnosis is required to distinguish it from other neurological disorders.", "Recovery of leukocytes was performed by applying previously described methods [22, 54] . Briefly, after perfusion with cold PBS, brains and thymus were removed and placed on ice in RPMI containing 5% FCS (Nissui Pharmaceutical Co.). Brains were strained and homogenized gently with a 70 \u00b5m cell strainer (BD Biosciences). After washing with RPMI, the cell suspension was layered onto a 70% and 30% Percoll gradient (GE Healthcare Bio-sciences AB) and centrifuged at 800 \u00d7 g for 45 min at 23\u00b0 C. The leukocytes were collected from between the 70% and 30% interface. Thymocytes and splenocytes were also recovered from these mice. Cells were strained with a 70 \u00b5m cell strainer (BD Biosciences) and lysed with RBC lysis buffer (Sigma-Aldrich). After washing, cells were resuspended in RPMI medium. Isolated cells were counted and kept on ice until the staining procedure.", "Brain leukocytes were washed and blocked with Rat Anti-Mouse CD16/32 (Fc Receptor) (Beckman Coulter) in FACS buffer (PBS containing 0.1% BSA and 0.1% sodium azide). Cells were stained with a mixture of different fluorescentlabeled antibodies directed at surface phenotypic markers, CD45-FITC, F4/80-PE, NK1.1-PerCP-Cy5.5, CD4-PE-Cy7, CD8-APC, CD19-Alexa Fluor 700, CD3e-eFluor 450 (Beckman Coulter) and then fixed with 4% paraformaldehyde overnight. The stained cells were analyzed by Galios\u2122 flow cytometer (Beckman Coulter). Leukocytes were recognized by characteristic size (forward scatter), granularity (side scatter) and CD45 expression. Thymocytes were recognized by their characteristic size and CD4 + CD8 + double positive cells were recognized by the expression of CD4 + and CD8 + ." ] },{ "paper_id": "77c758dbd0cc50cb84be51107f421313cba47320", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MicroRNA hsa-miR:", "Human microRNA.", "Coronavirus miRNA:" ] },{ "paper_id": "77c8f24d21f25774e383052c028b90b178c7b3d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Not reported ARTD4 (PARP4, vPARP) MAR Vault particles [12] Multidrug resistance? [13] [14] [15] [16] Innate immunity? [13] ARTD7 (PARP15, BAL3) MAR Component of stress granules [17] Not reported ARTD8 (PARP14, BAL2, CoaSt6)", "In addition to the rather recently discovered and still poorly explored bacterial Sirtuins, bacterial ARTs have long been known to affect cellular behavior by ADP-ribosylating specific host cell target proteins. Bacterial pathogens use toxins, including ARTs, to alter and kill host cells. A main purpose of these toxins is to disrupt immune cell functions and by this promote pathogen dispersal and proliferation, which is summarized in excellent reviews [145, 146] .", "inactive mRNA regulation and miRNA silencing [36] Component of stress granules [17] Viral defense [36] ARTD14 (PARP7, TiPARP) MAR AHR signaling [37] [38] [39] [40] Translation [31] TCCD-induced hepatotoxicity [40] Inhibition of viral replication [31, 41] ARTD15 (PARP16) MAR Unfolded protein response [42] Not reported ARTD16 (PARP8) MAR Unclear Not reported ARTD17 (PARP6) MAR Regulates cell cycle progression [43] Inhibits cell proliferation, survival benefit in colorectal cancer [43] SIRT4 MAR Glutamine metabolism [44, 45] Tumor-suppressive [45, 46] SIRT6 MAR DNA repair [47] [48] [49] Retrotransposon silencing [50] Tumor suppressive [50] [51] [52] [53] [54] [55] [56] [57] and oncogenic functions [58, 59] MACROD1 (LRP16) Hydrolase ER\u03b1 signaling [60, 61] AR signaling [62] Promotes cell proliferation [60, 62] Metastasis, invasion and survival in gastric and colorectal cancer [63, 64] ." ] },{ "paper_id": "77ce5438ade47650db78180cf5f4612db3e31c7b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "77ced9eec3817dd81f3b38b19086ba07b271208f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All values represent the means \u00b1 standard error of the mean (SEM) of at least three independent experiments. Two-tailed t-tests and ANOVA were employed for the statistical analyses, which were performed using GraphPad Prism 5 software. Mortality was analysed using the Kaplan-Meier method with the log-rank test. P < 0.05 was considered significant.", "Histopathological detection. To evaluate pathological damage of the lung after mouse-adapted H9N2 or H1N1 virus challenge, pulmonary samples were removed from the mice, fixed in 4% paraformaldehyde and embedded in paraffin. Sections with a thickness of 8 \u03bc m were stained with haematoxylin and eosin (H&E) and scored by blinded pathologists (three independent readers). Briefly, alveolitis and peribronchiolar inflammation was blind scored on ascale of 0, 1, 2, 3, 4 or 5 corresponding to none, very mild, mild, moderate, marked, or severe inflammation, respectively 70 .", "In addition, we observed protection in immunized mice challenged with mouse-adapted H9N2 AIV and H1N1 influenza virus, as evidenced by reductions in the lung virus titers, improvements in lung pathology, and weight loss and complete survival. Our data are promising for the generation of effective, non-traditional influenza vaccines against AIVs." ] },{ "paper_id": "77d34e9158807dab65379240836e8a73dd02e2d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The distribution has two parameters (i.e., \u03b8 = {a, b}): scale parameter a and shape parameter b, such that the mean is", "Data that were used in the analysis of this study were extracted from a previous study [12] and hence did not require Human Resource Ethics committee approval.", "Here \u0394 ij,TYPE is defined as: \u0394 ij,TYPE =1 if infector case j is co-infected while the infectee case i is singly infected with type TYPE; otherwise \u0394 ij,TYPE =0. The strain interactions within co-infections are estimated as:" ] },{ "paper_id": "77dc09841a62d92ba5a40d4f848f34e3c4e27713", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "77dc3c4e78b6fe5c233613de24779897f673bb9c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consequently, the application of TCM to patients infected with HSV-1 to prevent the recurrence of latent HSV-1 should be encouraged.", "In addition to immunity enhancement, the regulation of autophagy also links to the anti-HSV-1 effect and this has become a field of interest for scientists. As a conserved physiological process, autophagy not only plays an important role in maintaining cellular homeostasis, but also participates in many crucial physiological processes, such as the elimination of exogenous microorganisms, antigen presentation, and inherent immune response.", "The authors declare that there is no conflict of interest. " ] },{ "paper_id": "77df12a2ea42f8702db5b87396eebc49d3d13085", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "77e7d43cae5e05f9a6937b0c3326871a41ea20cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Transitions from non-segmented to multipartite genomes Defective particles are routinely generated upon replication of viral genomes. 44 Mutants with changes that preclude their viability in isolation and deletion mutants that lack genes essential to complete the viral cycle can however survive if complemented by viable genomes. Indeed, under conditions of high MOI, defective genomes thrive thanks to the activity in trans of ", "The power of HGT to cause rapid evolution and adaptation in organisms is difficult to overstate. HGT is ubiquitous and strongly affects the architecture of coding and non-coding parts of genomes. The concept of network genomics 76 has been put forward to emphasize that the rates of gene gain and loss are comparable to those of point mutations. A recent advance in the quantitative analysis of how relevant gene sharing is to shape current viral diversity has arrived from a study linking genome composition in dsDNA viruses to network theory. 77 Genes are shared by non-identical subsets of viruses, such that single-gene taxonomy yields incongruent taxonomical trees, because cladograms for genes within a genome do not overlap. Instead, the idea of a network linking genes to the genomes where they are found substitutes the forced time-line of taxonomy by a graphical representation of how genes are shared. The studies carried out to date in this context 77, 78 shed light on possible mechanisms of construction of viral diversity.", "Mathematical models will be essential in uncovering the roots of multipartitism. Among others, they might establish under which ecological conditions would the emergence of segmented forms be favored or hindered in competition with non-segmented viral species, or how the presence of suboptimal segments might guarantee survivability. Analysis of gene-sharing networks through quantities defined in complex network theory 103 should also clarify the topological properties of such networks and how network structure affects their robustness and plasticity, as well as hint at the origins of their overall functionality." ] },{ "paper_id": "77f0ea2c96326d37a9a2a71d529fe7c29336f6ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus. The wild-type PEDV strain ZJ was obtained from intestinal contents of a 2-day-old diarrheic piglet on a farm in Jiangsu in 2012, and this strain clustered with the emerging virulent strain based on phylogenetic analysis. Viruses were purified using discontinuous sucrose density gradient centrifugation 55 .", "Statistical analysis. Results are expressed as the means \u00b1 SD and analyzed with SPSS 17.0. One-way analysis of variance (ANOVA) was employed to determine significant differences among multiple groups, and a t-test was employed to determine the differences between the two groups. *P < 0.05, **P < 0.01. Data were combined from at least three independent experiments unless otherwise stated.", "Received: 16 March 2018 Accepted: 8 August 2018" ] },{ "paper_id": "77f331c73a874a86f6109346c3b798593b75fa5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Willebrand factor (vWF) polyclonal antibody and rabbit anti-early endosome antigen 1 (EEA1) monoclonal antibody were purchased from Invitrogen (Carlsbad, CA). Rabbit anti-Akt polyclonal antibody and rabbit phospho-Akt (Ser473) polyclonal antibody were purchased from Cell Signaling Technology (Danvers, MA). Mouse anti-human Na+, K+ ATPase antibody was purchased from BD Biosciences (San Jose, CA). Unless otherwise indicated, all reagents were purchased from Thermo Fisher Scientific (Rockford, IL).", "EBOV (199510621 Zaire strain, GenBank accession number KR824526) and Marburg virus (200501379 Angola strain, GenBank accession number KU978782) stocks were propagated in Vero E6 cells in Earl\u02b9s modified Eagle\u02b9s medium (EMEM) with 2% FBS at 37 \u00b0C. The freeze-thaw technique was used for virus harvesting. EBOV titers were calculated using tissue culture infective dose (TCID50) assays done in a microtiter format using four replicates at 10-fold serial dilutions (10 -2 to 10 -8 ). After an 11-day incubation period at 37 \u00b0C, the cells were fixed with 10% buffered formalin overnight, and then stained with 0.5% crystal violet for 15 min. Virus titers were calculated using the method of Reed and Muench. All work with filoviruses was performed in the biosafety level 4 (BSL-4) facility of the Galveston National Laboratory.", "The recombinant vesicular stomatitis virus expressing the glycoprotein (GP) of Zaire EBOV (strain Mayinga) (EGP-VSV) was kindly provided by Drs. Thomas Geisbert and Chad Mire (UTMB). Viral stocks were prepared in Vero E6 cells using DMEM with 2% fetal calf serum, and stored at \u221280\u00b0C. The concentration of EGP-VSV was determined by plaque assay in Vero E6 cell monolayers under a 1.6% Tragacanth gum mixed with 2\u00d7 DMEM medium (1:1) with 2% FBS overlay. Plaques of EGP-VSV were counted after staining with 0.25% crystal violet in 10% buffered formalin." ] },{ "paper_id": "77f34000cd69ab822903562a0004012eeebe7605", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "77fc830cd32e8b07cd22a11a8d519f9d35f7d7ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For a general step-like intensity function, R 0 is given by" ] },{ "paper_id": "78057e9db3bebe6ecfc99fbc036414ebd4115cfd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After incubation, cells were washed with 1\u00d7 PBS and lysed in sample buffer (5% SDS, 12.5% \u03b2-mercaptoethanol, 0.5 M Tris-HCl (pH 6.8) and 25% Glycerol). The prepared samples were resolved on a 12% SDS-PAGE, electro-transferred onto a PVDF membrane (Millipore, Billerica, MA, USA), and reacted with various antibodies for 24 h. The target proteins were detected with horseradish peroxidase-conjugated secondary antibodies for 1 h and visualized using the enhanced chemiluminescence substrate (PerkinElmer, Waltham, MA, USA) on Fuji SuperFilms.", "Results were represented as the mean \u00b1SD from at least three independent experiments. The two-tailed Student's t test was applied to investigate the difference between groups. A p value of 0.05 and 0.01 was considered statistically significant.", "After seeding A549 cells for 24 h, the complete medium was removed and replaced by serum free DMEM medium for 24 h; TNF-\u03b1 was treated and incubated for the indicated time intervals.", "(TIF)" ] },{ "paper_id": "78138c22f695836b6da58f74c78a8066204a2b12", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No potential conflict of interest was reported by the authors.", "To further characterize the role of IRE1 during MARV infection, we analysed the progression of infection in HAP1 parental (wt) and IRE1 KO cells over a period of 6 days. As shown in Figure 7 , MARV titres were higher in KO cells at days three and six of infection leading to the assumption that IRE1 deficiency has a positive effect on MARV propagation in cell culture over time.", "It has been reported that RNA virus infections, e.g. infection by West Nile virus (WNV), Dengue virus and influenza virus, activate UPR processes [11] [12] [13] . Furthermore, it was shown that activated IRE1-dependent signalling may be beneficial or detrimental to viral propagation, and viruses have developed different strategies for coping with and even taking advantage of the ER stress response [13, 14] ." ] },{ "paper_id": "7816cee86e3c9d98dd7e426eb7b842918d36f0f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Global atlas of zoonotic viruses Dennis Carroll et al.", "Perspectives", "Despite the human and economic impact of viral epidemics, the world is not well enough prepared for the next emerging viral outbreak. Global trends indicate that new microbial threats will continue to emerge at an accelerating rate, driven by our growing population, expanded travel and trade networks, and human encroachment into wildlife habitat. 1 Most emerging viruses are zoonotic, that is, transferred between vertebrates and humans. 2 Nearly all zoonoses originate in mammalian or avian hosts; 3-5 for example, type 1 human immunodeficiency virus (HIV-1) originated in chimpanzees and Ebola virus in bats. 6 Estimations show that there are more than 1.6 million mammalian and waterfowl viruses, spanning 25 viral families known to cause human infections. 4 Compared to just over 260 viruses known in humans, 7 the unknown viruses represent 99.9% of potential zoonoses. These viruses usually remain undetected until they cause disease in humans." ] },{ "paper_id": "78233b5cc660bff6f716fa6cbb967775bf5c7417", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were transfected using the Viromer Blue system (Lipocalyx) with a SignalSilence Control siRNA (Fluorescein Conjugate) (#6201, Cell Signaling Technology) according to manufacturer's instructions." ] },{ "paper_id": "782bdb3d8291de8f51c2816a707833c165c3ea35", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "78326020e9f7cd75415a3a192729ccf0c0930281", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "78330b92514605d59bb22b99c517538f83c2e2b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The statistical analyses were performed using GraphPad Prism version 5.0 (USA). A Pearson correlation and linear regression test, ANOVA test and Student's t test were performed (P < 0.05). " ] },{ "paper_id": "7835feab0d31096fada1a14d10d67acc080a7d82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical data analyses were carried out using the SAS/STAT software version 9.1.3 (SAS Institute Inc., Cary, NC, USA). Associations between HRV species, infection site, and study cohorts were evaluated using chi-square tests when possible, or Fisher's exact tests when some expected values were smaller than 5.", "Genome analyzer run. Libraries were pooled and sequenced on an Illumina Genome Analyzer GAIIx (Illumina) single-read channel for 76 cycles using a version 4 sequencing kit. We performed base-calling using Illumina pipeline RTA SCS.2.6 and CASAVA 1.6, which produced over 24 million pass filter reads attributed unambiguously or 1.85G bases.", "Bioinformatics data analyses. Mapping was performed using the MAQ software version 0.7.1 (http://maq.sourceforge. net/maq-man.shtml). An average of 95% reads were mapped on the ''F78 URT 1.4 m'' consensus sequence for each sample analyzed with a mean coverage of 21.2K reads per nucleotide. Mapping results were used to extract a list of single nucleotide polymorphisms (SNPs) throughout the genome (see Supplementary method: bioinformatics data analyses)." ] },{ "paper_id": "78360444f3b4540339efc9e7e5f2610a7e46c023", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "7846c73c25fafce260659a9f9aefbef6b514bf15", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 100 dalton succinyl group is a large modification added to lysine residues that significantly changes the lysine side chain charge from +1 to \u22121, thus on surfaces involved in ionic interactions, the addition of a succinyl group would be of great significance. Succinylation is reported to occur on ezrin Lys60 [148] , and a global proteome analysis for human gastric cancers also identified Lys438 in ezrin [149] , human radixin Lys435, mouse radixin Lys83 [142] , and moesin Lys79 and Lys165 [148] . The biological relevance of these modifications is unknown.", "The authors declare no conflict of interest.", "Ezrin, radixin, moesin FERM Protein 4.1, ezrin, radixin, moesin domain CTD C-terminal domain PI(4,5)P 2 Phosphatidylinositol 4,5-bisphosphate PI(4,5)P 2 diC 8 Phosphatidylinositol 4,5-bisphosphate with two 8-carbon fatty acid moieties PPII Poly-proline type II helix ADP Adenosine diphosphate" ] },{ "paper_id": "784b8019936ae21771682f1184ff3fe10cc40b6f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Is the \"Evolution\" of Global Health Governance Underway?", "A UN High-Panel on Global Health: 21 st Century Global Health Governance?", "In January 2016, the World Health Organization (WHO) declared that the devastating 2014 Ebola virus disease (EVD) outbreak in West Africa was finally coming to an end and in March officially announced it was no longer a public health emergency [1] . These developments came after nearly three years of unprecedented international cooperation to combat the largest Ebola outbreak in history, one that has claimed the lives of over 11,000 people and wrought social and economic devastation to Liberia, Sierra Leone, and Guinea, the three countries most heavily impacted. Re-emergence of EVD through detection of new case clusters after countries had been declared \"Ebola Free\" by WHO have also personified the enduring risks and resilience of the disease [2, 3] . Despite these setbacks, the possibility of a widespread EVD pandemic is now much farther in the distance as the outbreak transitions to its post-endemic phase. International efforts to finally put an end to this devastating chapter of Ebola instead focus on ongoing concerns of treating survivors and averting any potential further transmission, while exercising vigilance in surveillance, prevention, and maintaining response capacity." ] },{ "paper_id": "7859dc5bc2c21103513a0d3d27e148496c2c617c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Moderate to severe inflammatory reactions have been reported for SC implants of polymer-opiate constructs [5] [6] [7] [8] [9] [10] .", "M. Guarnieri owns a significant financial interest in Animalgesic Labs.", "The authors declare that they have no conflicts of interest." ] },{ "paper_id": "785f1bfe60d4c4773e6492752396fc4ce8f61865", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "7862ffdcf951e5860a7e3dc66c9d3b07f5fbc281", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HeLa cells were maintained in Dulbecco's modified Eagle's medium (Gibco BRL, USA) supplemented with 10% fetal bovine serum, penicillin (100 U/ml), and streptomycin (100 U/ml). Each constructed pGL3-IFITM3 plasmid was transfected into HeLa cells with the pRL-SV40 plasmid (Promega, USA) by using Lipofectamine 2000 (Invitrogen, USA). Firefly luciferase and renilla luciferase (both via pRL-SV40 plasmid) activities were sequentially measured by a luminometer 48 h after transfection, with or without IFN-c treatment (final concentration of 100 pg/ml and 0 h, respectively) over a serial time span (5 h and 20 h), utilizing a Dual-Luciferase reporter assay system (Promega, USA). Results were expressed as relative light units of firefly luciferase activity over relative light units of renilla luciferase activity. All experiments were performed in triplicate and repeated three times.", "Expression levels of IFITM3 in lymphocytes with different genotype of rs3888188", "DNA extraction and genotyping. Genomic DNA was extracted from peripheral leukocytes by using a Genomic DNA Extraction kit (QIAamp DNA Blood Mini Kit; Qiagen, Hilden, Germany). The core promoter of IFITM3 was amplified by PCR using 59-GAG CCC TGA ACC GGG ACA GTG-39 and 59-TGG TGT CCA GCG AAG ACC AGC-39 primers and genotyped by sequencing using a 3730 DNA Analyzer (Applied Biosystems, Foster City, CA, USA).", "Children not only have an increased risk of developing progressive disease following exposure, but have a much greater risk of developing disseminated forms of the disease such as tuberculosis meningitis (TBM). Although this could be largely resulted from the immaturity of the immune response, certain pediatric TB reflects Mendelian predispositions, while adult TB seems to be more complex for genetic predisposition [11] ." ] },{ "paper_id": "78646cec8be584199a96490a43bf47b2fd542f63", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The season 2005-2006 also had a very high circulation of influenza B, with influenza B accounting for 70% of the circulating influenza that season.", "This study provides the most detailed quantitative data to date on the ILI burden in the UK. It should help to narrow the considerable uncertainties in modelling the potential impact of interventions [10] ." ] },{ "paper_id": "786da349a33148e24e09edd6378da80ea2f40e07", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The haplotype analysis was performed using PLINK software (version 1.07) (http://pngu.mgh.harvard.edu/ purcell/plink/) [44] .", "UC (n = 12) was obtained from normal full-termdelivery women. Briefly, after disinfection with 75% ethanol, the fresh UC was transferred to PBS where excess blood on the surface was removed. After removal of blood vessels, 2 cm of UC was sliced into very small pieces followed by treatment with 0.1% collagenase II (Gibco, USA), containing antibiotic solution (100 U/mL penicillin and 100 \u03bcg/mL streptomycin; CSPC, China) in Dulbecco's Modified Eagle Medium/F12 (DMEM/F12) (Gibco) overnight at 37\u00b0C. The cells were cultured in DMEM/ F12 supplemented with 10% fetal bovine serum (Hyclone, China) in 5% CO 2 in a 37\u00b0C incubator for 3-4 days to allow cells to adhere. The adherent cells formed colonies and grew rapidly, exhibiting spindle-shaped morphology. The medium was replaced every three days. When the cells reached to 60-80% confluence, they were harvested with trypsin-EDTA solution (Neuronbc, China) and subcultured at a density of 3-6\u00d710 3 cells/cm 2 [38] . Amplification of pluripotent stem cell markers, such as Oct-4 and Rex-1, was used to demonstrate primitive properties of the cultured cells, as described previously [39] .", "Among the 26 tag SNPs chosen first, four SNPs were eliminated because of low frequency (rs2853691), poor genotyping reliability (rs2736118), or departure from Hardy-Weinberg equilibrium (P < 0.05) (rs2853668 and rs10073340). We therefore selected the remaining 22 SNPs for the subsequent analyses." ] },{ "paper_id": "786e2292469a024a05dda14af4e9c6ffaa223d75", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2018, 10, x 7 of 26", "Funding: The University of South Africa through the Nanotechnology and Water Sustainability Research Unit (NanoWS) funded this research.", "The recovered DNA from the soil samples was sequenced under the Illumina Platform with some bioinformatics analysis carried out which detected biodiversity among the Caudovirales group [224] ." ] },{ "paper_id": "7870870602f0a4edb3a7ea468659e2eb23cb2202", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The comparison of the infection rates was done using Fisher's exact test. The Kruskal-Wallis test was used to compare antibody and proliferation of lymphocytes between groups. A value < 0.05 was considered statistically significant in these analyses. All statistical analyses were performed using SPSS statistical software version 19.0.", "sf9 insect cells (Spodoptera frugiperda) (Invitrogen, San Diego, CA) were cultivated as a suspension in Grace's medium (Invitrogen, USA) supplemented with 10% heat inactivated fetal bovine serum (Invitrogen, Carlsbad, CA), 1% penicillin/streptomycin (100 U/mL), and 0.1% pluronic F-68 (Invitrogen, USA). AcNPV-LC3 baculovirus production was described in [17] . Recombinant AcNPV-LC3 baculovirus was amplified by infecting sf9 insect cells at a multiplicity of infection (MOI) of 0.1 and purifying them from culture's supernatants 6 days after and concentrated by ultracentrifugation, resuspended in PBS and titered by using a plaque assay following the manufacturer's instructions (Invitrogen, USA).", "Axenic HM1: IMSS trophozoites were maintained in TYI-S-33 medium supplemented with 15% of adult bovine serum (Biofluids International Inc., MD, USA) and 3% of Diamond's vitamin mix (JRH Biosciences, Kansas, USA). Trophozoites virulence was maintained through successive passages into hamster's liver." ] },{ "paper_id": "7875c1a9783593b90bb90b99f285583067a3f433", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The total amount of protein in the cell lysates was determined by separating cell lysates on 12% SDS polyacrylamide gels which were stained with Coomassie Brilliant Blue. Gels were then quantified by using the Odyssey Infrared Imaging System Application Software (Version 2.1.12)." ] },{ "paper_id": "788295abb7003fc90fdadb54283b664724c83b33", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lung histology and immunohistochemistry. Lungs were removed, fixed in zinc formalin, and paraffin embedded. Sections were stained with hematoxylin and eosin and examined by light microscopy. For immunohistochemical staining of tissues, 10% formalin-fixed, paraffin-embedded lung sections (6 to 7 m in thickness) were microwaved in 10 mM citrate buffer (pH 6.0) for 5 min. Endogenous peroxidase was inactivated with 3% hydrogen peroxide (H 2 O 2 ) at room temperature for 10 min. Sections were then incubated (overnight at 4\u00b0C) with rabbit anti-N protein (IMG548; Imgenex, San Diego, CA) (1:1,000). Secondary labeling with biotinylated goat anti-rabbit IgG (1:200) was performed at room temperature for 1 h, followed by color development with 3,3=-diaminobenzidine for 3 min.", "This work, including the efforts of Ivan Ahel, was funded by Wellcome Trust (101794). This work, including the efforts of Ivan Ahel, was funded by EC | European Research Council (ERC) (281739). This work, including the efforts of Anthony R. Fehr, was funded by NRSA (T32-AI007260). This work, including the efforts of Anthony R. Fehr, was funded by NRSA (F32-113973). This work, including the efforts of Stanley Perlman, was funded by HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) (PO1 AI060699 and R01 AI091322)." ] },{ "paper_id": "789ab4d7c1e859c96e68389e03290355c30a03a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Figure S1 . MS and MS/MS spectra of the identiifed protein spots.", "Additional file 2: Table S1 . Cell proteins identified from the differential 2D DIGE analysis after TGEV infection. ", "The authors declare that they have no competing interests." ] },{ "paper_id": "789d8f8e801484da5740462f088a39aaf4e2a411", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HIV Env pseudotyped virus preparation and neutralization was performed as previously described. [32] The activity of each pseudovirus isolate with or without antibody treatment was expressed as a percentage of the corresponding control virus without antibody treatment, and the average percentages and standard deviations were then calculated.", "All the primers used in this study were purchased from Invitrogen (Carlsbad, CA). Bal gp120-CD4 was provided by Tim Fouts (University of Maryland, Baltimore, MD) and other recombinant proteins (gp120s and gp140s) were provided by Christopher Broder (USUHS, Bethesda, MD). Codonoptimized sCD4 D1-2 was cloned into the expression vector pSecTag2B (Invitrogen) attaching a His tag to the C terminus of the sCD4 D1-2, transfected into 293 freestyle cells and expressed according to the manufacturer's suggested protocol. The secreted sCD4 D1-2 was purified using a Nickle column from the culture medium (Qiagen, Hilden, Germany)." ] },{ "paper_id": "78a0953f03d4dd00f2b4234e3768d95a700202dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples. Nasopharyngeal swab specimens for URTI and bronchoalveolar lavage for LRTI were collected after obtaining written informed consent from the hospitalized patients. Ethical permission to perform this research study was granted by the Health Science Center and Kuwait Institute for Medical Specialization (KIMS) Joint Committee of the Protection of Human Subjects in Research. Clinical data were collected from medical record using a uniform data collection form.", "2.3.1. Extraction Method. The nucleic acid extraction was done using the automated nucleic acid extraction method, MagNA Pure LC 2.0 (Roche Diagnostics Ltd., Rotkreuz, Switzerland). All 850 respiratory samples were extracted using the MagNA Pure LC Total Nucleic Acid Isolation Kit (Roche Applied Science, Mannheim, Germany) according to the manufacturer's instruction. The extraction resulting in 60 L eluates of viral nucleic acid was stored at \u221270 \u2218 C until processing.", "Analysis. Data analysis was performed using the Statistical Package for the Social Sciences (SPSS version 20.0, IBM Corp, Armonk, NY, USA). The descriptive statistics of the continuous variables were compared using a nonparametric Mann-Whitney test or Kruskal-Wallis test. For the categorical variables, a Chi-square or Fisher's exact test ortest was applied to test the difference between proportions or to assess whether any association existed between the proportions. The two-tailed probability value < 0.05 was considered statistically significant." ] },{ "paper_id": "78a2a00aa8b0a7ab8cf82403e941085830445a5d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Overall, these methodologies could provide additional insights to assess the genetic relatedness between strains and help to distinguish new from resident strains, and identify and evaluate quantitatively the likelihood of implication of different potential sources of infection at a farm level on a case-to-case basis, what could help to inform and optimize control and prevention strategies.", "Bayesian phylodynamic models are becoming a wellestablished method for the study of the evolution of many infectious animal and human viral pathogens like avian influenza [67] or Ebola [68] . However, few studies have attempted to model the evolutionary dynamics of PRRSv [54, 56, 58, 69] . Still, those studies have revealed the potential for answering some major questions still unresolved about the evolutionary epidemiology of PRRSv of phylodynamic methods belonging to three different domains:", "The first are Bayesian coalescence models, which have shown to provide robust inferences about the demographic histories and population growth patterns of viral lineages and sub-lineages [53] . The inclusion of information on nucleotide substitution schemes obtained from the data, allowing for different model assumptions to assess the degree of genetic relatedness under time-scaled phylogenies, has provided a robust strategy to distinguish between potentially related PRRSv strains detected in air samples and swine farms in areas of high and low density of swine farms [58] . This approach can help to shed further light on several evolutionary and epidemiological characters of endemic PRRSv and provide realistic basis for PRRSv genotyping.", "A limitation common to these studies, performed at different geographical scales [with a database with national (SHMP) and regional (RCP-N212) coverages] is the lack of information on a proportion of the farms present in the area. Still, a remarkably significant spatial and spatio-temporal pattern was identified at both levels, and the value of the information extracted from these studies for the stakeholders is evidenced by the increasing number of enrolled participants at both levels, what in turn has and will continue to increase the power of the analysis." ] },{ "paper_id": "78a8d488d2fa21bd3fedcd4534718376e9333406", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. Younger children will be both more likely to acquire and more likely to transmit HRV infections within and between households, We refer to increased likelihood of acquisition as higher susceptibility, although this cannot be distinguished from higher exposure with these data.", "\u2022 human rhinovirus (HRV)", "\u2022 human bocavirus," ] },{ "paper_id": "78b008cc190700f5c0291d67cca3112f6b54aa1f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Parameter distributions for N and p were calculated using MCMC simulation using a standard Metropolis algorithm with flat prior information. It was necessary to compute a correlation matrix to define a joint proposal since N and p are closely correlated. We monitored convergence using two chains. Once they had converged, we had a burn in period of 10 5 samples.", "We used piecewise linear regression to test for changes in the slope of the discovery curve. The results suggested upswings in 1930 (95% CI, 1929 -1933 ) and 1954 (1953 -1956 . We therefore restricted detailed analysis to the period 1954-2006.", "\u00f02:1\u00de", "where year tZ1 corresponds to 1954. The binomial distribution B(N, p) can be accurately approximated by a Poisson distribution with parameter Np for the range of values of N and p of interest. We considered fitting a distribution for values of p; however, provided individual p-values are low there is minimal improvement in model fit. Thus, for a set of model parameters, the likelihood of observing data, XZ{x i }, the number of viruses discovered for years 1 to k, is given by" ] },{ "paper_id": "78b06344bf1d834407a41bceb4999839085b0082", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SDS-PAGE electrophoresis was used to determine the efficiency of tetramerization.", "Crystallization and Data Collection of pSLA-1 * 1502", "Finally, the complex was purified and tetramerized by mixing pSLA-1 * 1502-BSP with PE-labeled streptavidin (BioSource International, Camarillo, CA) at a molar ratio of 4:1, after which the samples were separated by using 100 KDa Millipore tubes.", "Determination of the Circular Dichroism Spectra and Thermal Unfolding of pSLA-1 * 1502" ] },{ "paper_id": "78b25bce9665a46183274a25151de342c9799ef3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Comparison of means was carried out with the Student's t-test or One-Way Analysis of Variance followed by Tukey's post hoc test using SigmaStat 2.03 software (Jandel Scientific Software). Non-normally distributed data were log-transformed prior to statistical analysis and experimental data are shown as the mean \u00b1 S.E.M." ] },{ "paper_id": "78b305688d964809c3cd62063d7fa6ecf30ebbc9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was conducted according to the protocol approved by the Human Research Ethics Committee, Chinese Academy of Inspection and Quarantine in compliance with the provisions for human research in the Helsinki Declaration (ES-0823696/2014/376HQ). Written informed consent was obtained from all the participants." ] },{ "paper_id": "78b3f2e613d0e2be8608c68c73b20c25d440a0b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A number of steps in the virus life cycle are potential trigger of ER stress e.g., the maturation of the viral envelope glycoproteins in the ER, formation of replication complex on the ER, virus assembly, and budding of virus particles into the ER (Scheel and Rice, 2013) .", "Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus of clinical importance. The virus establishes a chronic infection and can progress from chronic hepatitis, steatosis to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The mechanisms of viral persistence and pathogenesis are poorly understood. Recently the unfolded protein response (UPR), a cellular homeostatic response to endoplasmic reticulum (ER) stress, has emerged to be a major contributing factor in many human diseases. It is also evident that viruses interact with the host UPR in many different ways and the outcome could be pro-viral, anti-viral or pathogenic, depending on the particular type of infection. Here we present evidence for the elicitation of chronic ER stress in HCV infection. We analyze the UPR signaling pathways involved in HCV infection, the various levels of UPR regulation by different viral proteins and finally, we propose several mechanisms by which the virus provokes the UPR.", "IRE1 is a kinase/endoribonuclease activated by self-oligomerisation and autophosphorylation (Sidrauski and Walter, 1997; Bertolotti et al., 2000; Shen et al., 2002a) . The IRE1 pathway is an ancient pathway shared with yeast (Tirasophon et al., 1998; Hollien, 2013) . In yeast, there is evidence to suggest that IRE1 is activated by direct binding of unfolded protein ligands to its luminal domain whereas BiP plays a regulatory role by maintaining IRE1 oligomeric equilibrium (Credle et al., 2005; Gardner and Walter, 2011; Gardner et al., 2013) . The endoribonuclease activity of IRE1 mediates unconventional splicing of ", "NS5A/5B are integral to viral replication (Scheel and Rice, 2013) . Infection of humanized mice with NS5A/5B mutants of JFH1 led to increased expression of BiP and CHOP, suggesting a role of the NS5 proteins in ER stress although it is not clear whether they act directly or indirectly (Mishima et al., 2010) . It is possible that the enhancing effect of the NS5 mutants on the UPR may be an indirect result of a higher replication rate of these mutants leading to increased production of the responsible proteins i.e., core, E1, E2. Whether the NS5 proteins directly induce the UPR still needs to be shown but Hep3B cells stably expressing NS5B genotype 1b (k isolate) failed to induce ATF6 cleavage )." ] },{ "paper_id": "78b7a343a9ffffc005daf8a962cf9140f5dc8735", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data are representative of results from at least 3 separate experiments. All data points are the average of triplicates, with error bars representing standard deviations. The difference between two groups was statistically analyzed by a two-tailed Student's t test using SPSS software. P value <0.05 was considered significant.", "Cells were treated with Radioimmunoprecipitation Assay (RIPA) lysis buffer containing phenylmethyl sulfonylfluoride (PMSF). Protein concentration was tested with BCA Protein Assay Reagent (Pierce, Rockford, IL, USA). The proteins were separated on a 12% sodium dodecyl sulfate-polyacrylamide (SDS-PAGE) gel and subsequently transferred to a polyvinylidene difluoride (PVDF) membrane (Millipore Corp, Atlanta, GA, USA). The membrane was blocked with 5% non-fat dry milk for 2 h at room temperature and then incubated with the primary antibodies overnight at 4 \u2022 C. The HRP-conjugated secondary antibodies were used to incubate for 1 h at room temperature. The blotting was visualized using Enhanced Chemiluminescence (ECL) reagent.", "TGEV, a member of Coronaviridae family, is an enveloped virus with a positive-sense single-stranded RNA genome (Weiss & Leibowitz, 2011) . TGEV infection primarily causes transmissible gastroenteritis (TGE) that is characterized by highly contagious and fatal gastroenteritis for pigs of all ages, especially for piglets under 2 weeks old (Chae et al., 2000; Kim & Chae, 2001) ." ] },{ "paper_id": "78c1291690eec42eb88c56d3c1e878b43409a928", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The complete genome sequence of CCoV-IIa strain CB/05 was deposited at Gen-Bank under the accession no. KP981644.", "In conclusion, strain CB/05 is genetically similar to other CCoV-IIa isolates, with the exception of the ORF3b deletion. To what extent this deletion is associated with virus pathogenicity is currently unknown, since it was not detected in other recently reported pantropic strains (6) .", "Pantropic canine coronavirus (CCoV) was first detected in young dogs in Italy in 2005, but the complete genome sequence of this virus had not yet been determined. Here, we report the full-length genome sequence of the prototype strain CB/05, which showed that this virus is genetically similar to CCoV-IIa viruses." ] },{ "paper_id": "78c82f8e3198d5c95cbbcceabefddbe82e8f2442", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Epidemic potential of ZD (0.22)", "PLOS ONE |", "Responses and categories (score)" ] },{ "paper_id": "78c991a34ec87c73006a683cd641762d15597890", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviridae and is a single-stranded positive-sense RNA virus. PEDV was firstly identified in Belgium in 1978 [1] . The disease caused by PEDV was firstly observed in feeder pigs and fattening swine in England [2] and was proposed the name \"porcine epidemic diarrhea\" (PED) [3] . PED is an acute and highly contagious enteric disease characterized by severe enteritis, vomiting and watery diarrhea in swine.", "PCR was carried out in a two-step reaction, first with a pair of primers flanking the region to be amplified and then using a pair of primers within the amplified sequence in a total volume of 25 \u00b5L. Exactly, 1\u00b5L (10 ng) cDNA was mixed with a reaction mixture containing 12.5 \u00b5L 2\u00d7 EmeraldAmp TM PCR Master Mix (TaKaRa, Dalian, China), 0.5 \u00b5L each specific primer (10 \u00b5M), and 10.5 \u00b5L sterile deionized water. The first round of amplification was performed under the reaction conditions (pre-denaturation at 94 \u00b0C for 5 min followed by 30 cycles of denaturation at 98 \u00b0C for 10 s, annealing at 50 \u00b0C for 30 s, extension at 72 \u00b0C for 3 min, and a final extension at 72 \u00b0C for 7 min). The second round of amplification was performed: a 100-fold dilution in distilled water of the first PCR products ", "A total of 577 samples (504 small intestines of dead neonatal piglets and 73 sow milk) were collected from 177 farms in 29 provinces from February 2011 to November 2012. The collection procedures of milk were as follows. The sows' teats were washed three times with sterile physiological saline. The workers milked the teats with sterile gloves, and took the middle section of the milk in 1.5mL sterile microcentrifuge tubes. The milk samples were sent to our lab with ice bags or dry ice. All the samples were initially detected by reverse transcription-polymerase chain reaction (RT-PCR) using previously described methods [23] . The animal experiments were approved by Harbin Veterinary Research Institute and performed in accordance with animal ethics guidelines and approved protocols. The approval number of Animal Ethics Committee is Heilongjiang-SYXK-2006-032." ] },{ "paper_id": "78cc0a828b438df4987059241b39f933a1dfdfd0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Genome sequences of a novel Vietnamese bat bunyavirus 5 ;", "\u2022 Identification of coronavirus genomes from bats and rodents 10 ." ] },{ "paper_id": "78d5d3279bea15af4aaa52fe9b3302d52f657dc9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MS and MT-I conceptualized and designed the study. MT-I collected and assembled the data and drafted the manuscript. MS critically revised the manuscript.", "Keywords: severe fever with thrombocytopenia syndrome, severe fever with thrombocytopenia syndrome virus, antiviral, ribavirin, favipiravir Frontiers in Microbiology | www.frontiersin.org", "Some part of this review article was obtained through the studies financially supported from the Ministry of Health, Labour, and Welfare (grant number H25-Shinko-Shitei-009), Japan Agency for Medical Research and Development (AMED, 16fk0108002j, 17fk0108202j, 18fk0108002j, 19fk0108081j, 19fk0108072) . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." ] },{ "paper_id": "78ef6e101522626b8c7c7621ec50146ab57cf488", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "iBALT DeveLOPMeNT", "All authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication.", "This work was supported by grants, HL69409, AI100127, AI097357, and AR48311 from the National Institutes of Health." ] },{ "paper_id": "78f10dd6eb8860062bac9d5261b6881768bd7d7b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u00c2 f \u00f0w; k\u00deH \u00f0I ; k\u00de \u00c0 m w w\u00f0t\u00de;", "\u00c0 m z z\u00f0t\u00de and dI dt \u00bc k 1 w\u00f0t\u00de \u00c0 k 2 I \u00f0t\u00de:", "F\u00f0w; k\u00de \u00bc 1 \u00c0 \u00f01 \u00c0 g\u00de 1\u00fek 2p \u00f0 2p 0 1 \u00c0 cos u \u00f01 \u00fe g cos u\u00de 1\u00fek du; \u00f02:2\u00de" ] },{ "paper_id": "78f2ffac0503062687663d82d65f846290fb9c45", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In vivo experiments in this study were performed using Passage 7 human isolate MERS-CoV EMC strain (HCoV-EMC/2012) and passage 3 isolate MERS-CoV (Qatar15/2015; GenBank Acc. No. MK280984) that were propagated in Vero cells as described earlier [9] . Qatar15 was isolated from a 69 years old Qatari man that developed severe pneumonia and was PCR confirmed to have a MERS-CoV infection [17] .", "Collected serum samples were tested for MERS-CoV neutralizing antibodies using a virus neutralization assay and for MERS-CoV S1-specific antibodies using MERS-CoV S1 ELISA according to the previously published protocols [9] . Goat anti-rabbit IgG conjugated with HRP (1:2000, DAKO, Glostrup, Denmark) was used as a secondary antibody in the ELISA.", "Respiratory tract tissue samples were collected in formalin and embedded in paraffin for pathological analysis. Hematoxylin-eosin staining was performed for histopathological analysis. The presence of MERS-CoV nucleoprotein and MERS-CoV RNA was detected by immunohistochemistry and in-situ hybridization, respectively, using previously published protocols [15] . The localization of DPP4 in the respiratory tract of non-infected New Zealand rabbits was analyzed using an optimized immunohistochemical assay [15, 19] ." ] },{ "paper_id": "78f939545e7217684295ab63900119ab1ebdb173", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HCoV-EMC/2012 [21] was kindly provided by the Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands and propagated once in VeroE6 cells in DMEM (Sigma) supplemented with 2% fetal calf serum (Logan), 1 mM Lglutamine (Lonza), 50 U/ml penicillin and 50 mg/ml streptomycin (Gibco) (virus isolation medium). VeroE6 and LLC-MK2 cells were maintained in DMEM supplemented with 10% fetal calf serum, 1 mM L-glutamine, 50 U/ml penicillin and 50 mg/ml streptomycin.", "Weighed tissue samples were homogenized in a TissueLyzer II (Qiagen) after addition of 1 ml DMEM. Homogenates were centrifuged to pellet cellular debris and 10-fold dilutions of homogenate were made and subsequently inoculated onto VeroE6 and LLC-MK2 cells for virus isolation. After 1 hr, cells were washed once with DMEM and supplemented with virus isolation medium. Cells were scored for cytopathic effect 5 days following infection.", "GEO Accession #GSE55023. " ] },{ "paper_id": "78fb5545880b83bbbef7058bf5c99ff618b35f7b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Felis catus whole fetus-4 (fcwf-4; American Type Culture Collection, VA, USA) cells were maintained in Dulbecco's modified Eagle's medium (D-MEM, Sigma-Aldrich, Tokyo, Japan) supplemented with 10% fetal bovine serum (JRH, Nissui, Tokyo, Japan). We purified FCoV using linear sucrose gradient ultracentrifugation from FCoV 79-1146 strains (a gift from Tsutomu Hodatsu, Kitasato University, Japan) propagated in fcwf-4 cells.", "The authors declare that they have no competing interests.", "Submit your next manuscript to BioMed Central and take full advantage of: " ] },{ "paper_id": "790261c395cc8a2413ec034f450e67e36f5e8b0f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The MOS notwithstanding, most interviewees regarded the new interest in camels as an initiative of the people themselves. For example, Halake Elema, a knowledgeable Borana elder, explained:", "Another Borana woman explained:", "[During the drought] we followed the euphorbia all the way to town. When they [camels] feed on euphorbia they have more milk. It's like rainy day milk. 44" ] },{ "paper_id": "7902723eb8b21baa5eef8703832de11cc242a43b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "P-values were calculated in Microsoft Office Excel 2007 by using the student's t-test (single sided, type one). P < 0.05 was considered to indicate a statistically significant difference.", "Comparison of infectivities with and without neuraminidase treatment", "ST (swine testicular) and Vero cells were grown in Dulbecco's modified Eagle medium supplemented with fetal calf serum (10% for ST, 5% for Vero cells)." ] },{ "paper_id": "7902a01d7b2422e17f964afa1ecf05ec1e3088e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "790506537d41f8336265c309548c3f95759c7370", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chitosan (MW = 80 kD, degree of deacetylation = 80%) and mucin type III were purchased from Sigma (St. Louis, USA). Dioleoylphosphatidylethanolamine (DOPE) and 1, 2-Dioleoylphosphatidylglycerol (DOPG) were purchased from Lipoid (Ludwigshafen, Germany). Plasmid pGJA-P/VAX and recombination proteins PAc were provided by Prof. Mingwen Fan (School of Stomatology, Wuhan University, China). Plasmid pcDNA3.0-Rluc was donated by Dr. Sanjiv Sam Gambhir (Dept. of Radiology, Stanford University, USA). RQ1 DNase kit was purchased from Promega (Madison, MI, USA). Mouse standard serum (Bethyl, USA), goat anti-mouse IgG and IgA (SouthernBiotech, USA), and horseradish peroxidase conjugated goat anti-mouse IgG and IgA (SouthernBiotech, USA) were used. Cy5.5 Mono NHS Ester was purchased from GE Healthcare (Buckinghamshire, UK). All other used chemicals and used reagents were analytical grade.", "Statistical analysis of specific antibody levels was performed with SPSS 17.0 software. Differences between different groups were determined by one-way analysis of variance (ANOVA) followed by post hoc analysis with LSD test. Comparisons were deemed significant when p,0.05 and highly significant when p,0.01.", "The NPs were incubated with DNase I in reaction buffer at 37uC for 30 min, followed by the addition of DNase stop solution to terminate the reaction and DNase I was inactivated at 65uC for 10 min. Samples were analyzed by 0.8% agarose gel containing 1 mg/ml ethidium bromide in TAE buffer. The DNA was detected under UV light using the Gel Documentation System (Biorad, USA)." ] },{ "paper_id": "790c6002db87c03cd6bdab85964c52808d09a218", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To date, advances in technologies enable the generation of RCREVs, which have been successfully applied in diagnostic and molecular virology.", "Herpes simplex virus (HSV) Compartmentalization of protein by autofluorescent particles [54] Borna disease virus (BDV) In rodent brains [57] Canine distemper virus (CDV) Routes of virus spread in vivo [56] Vesicular stomatitis virus (VSV) Intracellular transport [55] Tetracysteine (TC)", "Green fluorescent protein (GFP)" ] },{ "paper_id": "7918e26f09ad06f1336fd3f15c8c5f875ecfcabd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "79233a0dcabd313110b3256113778d814f7bc902", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step 2", "Step 3", "Step 4" ] },{ "paper_id": "792417a1bbb50a19ce96e8354aa9f16f2424b850", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Introduction Acute myocardial depression in septic shock is common [1] . Myocardial depression is mediated by circulating depressant substances, which until now have been incompletely characterized [2] .", "Heart rate 78 \u00b1 6* 91 \u00b1 5", "Methods Experimental sepsis was induced by endotoxemia (LPS 10 mg/ kg i.p.) in Sprague-Dawley rats and by polymicrobial fecal peritonitis in Swiss mice. Brain glucose uptake was observed in vivo in endotoxemic rats using positron emission tomography with [ 18 F]fl uorodeoxyglucose and autoradiography with 2-deoxy-14 C-glucose." ] },{ "paper_id": "7927b8f05155e6933aaf8d9509dbd379d017dfe7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "TGEV (strain SHXB) was provided by the Jiangsu Academy of Agricultural Sciences and propagated in ST cells. The complete TGEV SHXB genome sequence is available in GenBank (KP202848.1) [41] . Viruses were labeled with the fluorescent probe DyLight 488 NHS Ester (Thermo Scientific) according the manufacturer's recommended protocol.", "Additional file 1: Figure S1 . TGEV invasion didn't affect with the treatment of TfR1 ligands, holo-Tf and apo-Tf. Figure S2 . ", "Caco-2 and IPEC-J2 cell lines (Guangzhou Jennio Biotech Co, Ltd., China), ST cell line (ATCC,USA), and HEK 293 T cell line (ATCC,USA) were cultured in Dulbecco's Modified Eagle's Medium (DMEM from Life Technologies) supplemented with 10% fetal bovine serum (FBS, GIBCO), 16 mM HEPES (Life Technologies), and 100 \u03bcg/ml penicillin/streptomycin (Invitrogen) in a humidified atmosphere containing 5% CO 2 at 37\u00b0C. Cells were routinely seeded at a density of 2 \u00d7 10 5 /mL in 25 cm 2 plastic tissue culture flasks (Corning) and passaged every 3-4 days for a maximum of 30 passages." ] },{ "paper_id": "79284efbde971538024ccbe888fa90bcd515d45c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Assay. The infectivity of residual virus was titrated in quadruplicate on 96-well microtitre plates containing 100 \u03bcL of confluent FRhK-4 cells. 100 \u03bcL of serial 10fold of dilutions of virus in maintenance medium starting from 10 \u22121 to 10 8 was added into FRhK-4 cells. The infected cells were incubated at 37 \u2022 C for 4 days. Appearance of CPE was recorded daily. TCID 50 was determined according to the Reed and Muench method [19] .", "Our studies indicate that SCoV is relatively more stable than the human coronaviruses 229E or OC43 and some other viral respiratory pathogens such as respiratory syncytial virus. These findings suggest that, while direct droplet transmission is an important route of transmission [23] , the role of fomites and environmental contamination in virus transmission may play a significant role in virus transmission. In particular, fomites may contribute to the continued transmission of infection in the nosocomial setting that continues to occur in spite of the great attention and stringent precautions taken to prevent droplet spread. In addition to droplet precautions, reenforcing contact precautions and hand washing is called for.", "Faecal contamination of SCoV coronavirus may thus be an effective route of transmission of the disease. The outbreak in Amoy Garden in Hong Kong which affected over 300 residents in a single-apartment block with thought to have been transmitted by contaminated sewage. The stability of the virus on environmental surfaces and its presence in faeces indicates the potential that fecal contamination of fresh-food production may pose a threat for virus transmission; especially in countries with poor sanitation and sewage disposal systems and that studies to address this possibility are needed." ] },{ "paper_id": "792956320e7955328ce6f1d6cfacff64d1338c5b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additionally, the inter-gene relationship for 10 RGs pairs was also estimated. Strong correlation coefficients (r) were observed for UXT/RPS23 (r = 0.654), RPS23/RPL4 (r = 0.650), UXT/RPS9 (r = 0.642), RPS9/RPL4 (r = 0.623), UXT/\u03b22M (r = 0.575) and UXT/HMBS (r = 0.536) ( Table 4 ). This analysis indicated that these pairs of gene have similar expression pattern across various tissues in buffaloes.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Gene Symbol ", "The qPCR reactions were performed in a final volume of 10 \u03bcL containing 4 \u03bcL diluted cDNA combined with 6 \u03bcL of master mix composed of 5 \u03bcL Maxima SYBR Green/ROX qPCR master mix (2X) (Fermentas Thermo, USA), 0.4 \u03bcL each of 10 \u03bcM forward and reverse primers, and 0.2 \u03bcL DNase/RNase free water. The reactions set up in Step one plus real time PCR instrument (ABI, California) were performed at 2 min at 50\u02daC, 10 min at 95\u02daC, 40 cycles of 15 s at 95\u02daC (denaturation) and 1 min at 60\u02daC (annealing+extension). The standard curves were made with 5 point relative standard curve of five-fold serial dilutions of the pooled cDNA. All Table 1 . Gene name, gene symbol, GenBank accession numbers, primer sequences, primer location, annealing temperature (T a ) and amplicon length for each evaluated RGs." ] },{ "paper_id": "792fa8ba0747cfa42ffa4247f036bc214e944185", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All 32 P-labeled RNA was detected by exposing Phosphor Imager screens to dried gels and scanning the screens with a Typhoon 9410 imager (GE Healthcare, Chicago, IL, USA). Incorporated label was quantified by Quantity One software (Bio-rad).", "Membrane-associated RCs are typical of all eukaryotic +RNA viruses. Membrane connection is indispensable, and two types of replication-associated membrane modifications have been recognized: membrane invaginations called spherules, as e.g., induced by alphaviruses; and double-membrane vesicles (DMVs), as e.g., induced by coronaviruses [17] . Alphaviruses form spherules at the plasma membrane, and CHIKV and Sindbis virus (SINV) spherules predominantly stay at the plasma membrane, while Semliki Forest virus (SFV) spherules are internalized to endoand lysosomal membranes [18] [19] [20] ." ] },{ "paper_id": "79316a90d0cd339b0d8d40407555b253994fd833", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results were analyzed by the DDCt method [90] and significance was calculated via students t-test. b-actin was used a normalizer to determine DCts. DDCts were calculated against the mean of DAPT treated WT-CHO DCts or the mean of healthy human brain cortex DCts. Results were expressed as relative quantification by 2\u02c6-(DDCt) [90] .", "RNA was dissolved in water, which was followed by ND-1000 spectrophotometer (Nanodrop Technologies, Wilmington, USA) quantification and pico chip quality control analysis (6000 Nanochip assay Agilent Technologies, Meno Park, USA)." ] },{ "paper_id": "793ff384663ce5425d0b61619d47fb0b306d7ec1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2012, 4 259 highlights the complex and highly orchestrated path of internalization and fusion that appears unique for filoviruses.", "Filoviruses (family Mononegavirales, genera Ebolavirus (EBOV) and Marburgvirus (MARV)) are single-stranded, negative-sense RNA viruses that exhibit a unique heterogeneous filamentous structure. Both EBOV and MARV infect a wide variety of mammals and this wide tropism has complicated the identification of cellular proteins required for viral entry. A hemorrhagic fever is caused by these viruses in humans, non-human primates and perhaps other mammals and is associated with high morbidity and mortality during outbreaks. No therapeutic drugs or vaccines are currently available to treat or prevent filoviral infection. Because of this and the high lethality associated with infection, filoviruses are considered Category A Priority Pathogens by NIAID and, in recent years, much research has focused on understanding how these viruses bind to and enter permissive cells." ] },{ "paper_id": "7941d4720a1cb228b2380a42885532440f5b7a0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Patients were randomly chosen from the large European EUfinanced GRACE study (https://www.grace-lrti.org). Ethics review committees in each country approved the study, Cardiff ", "Respiratory tract infection is the most common cause of hospitalization of children below the age of 5 years [1, 2] . In 5-40% of these hospitalizations no infectious agent can be identified but it is suspected that a viral infection is involved [3] [4] [5] . In these cases a yet unknown virus might be the cause of respiratory illness.", "However, VIDISCA-454 only becomes cost-effective in case a few thousand sequences are sufficient for virus detection, as one 454 plate can then be used to analyze 56 samples (roughly 200 J per sample). In that view VIDISCA-454 benefits strongly from the aforementioned reduction in rRNA amplification since fewer sequences are needed to detect a viral sequence.", "During the GRACE study, a large EU financed study on acute cough and antibiotic use in adults consulting their general practitioner, flocked nasopharyngeal swabs (Copan) in universal transport medium (UTM) were collected from all patients. Eighteen of these nasopharyngeal specimens were randomly selected (double blind) and included in this study and proven positive by specific diagnostic PCR's for either human rhinovirus (HRV), respiratory syncytial virus (RSV), human coronavirus OC43 (HCoV-OC43), HCoV-NL63, Influenzavirus A, Influenzavirus B, parainfluenzavirus 3 (PIV3) or adenovirus. The diagnostics for the respiratory viruses were determined by in-house multiplex real-time PCR assays [20] [21] [22] , all primers and probes are available on request. Viral loads were determined by virus-specific quantative real time PCRs using standard curves based on plasmids containing the virus sequence of interest (details available on request)." ] },{ "paper_id": "794b00331ade89870f1475a4c765b8c32ac855b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We generated the near-full genome sequence of Middle East respiratory syndrome coronavirus (MERS-CoV) from a collected nasal sample of dromedary camel in Egypt. The newly characterized Egyptian strain has high similarity to the previously characterized Egyptian virus and both of viruses fell into a cluster distinct from other MERS-CoVs.", "Nucleotide sequence accession number. The complete genome sequence of the MERS-CoV/Egypt/NRC163/2014 was deposited in GenBank under the accession number KU740200.", "A.K. and M.M.S. contributed equally to this work." ] },{ "paper_id": "794b9541d676d262ebca65c8b3f1d7ca64d4441f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "7958b1ebf2a14c0fa7482e96e7cc0b43fe156b2e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "795bd84388973214e4b97ea23b80a9dc4e481117", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Western blotting was performed with anti-myc (Developmental Studies Hybridoma Bank at the University of Iowa, deposited by Dr. J. Michael Bishop, catalog no. 9E 10), anti-HA (Clontech, catalog no. 631207), anti-hIFITM3 (Proteintech Group, catalog no. 11714-1-AP), anti-mIFITM3 (Abcam, catalog no. ab65183), anti-NEDD4 (Millipore, catalog no. 07-049), anti-FLAG (Sigma, catalog no. F7425), anti-actin (Abcam, catalog no. ab3280), or anti-GAPDH (Invitrogen, catalog no. 398600) antibodies. All primary antibodies were used at a 1:1000 dilution. Secondary antibodies, Goat Anti-Mouse IgG, HRP conjugate (Millipore catalog no. 12-349), Goat Anti-Rabbit IgG, HRP-linked (Cell Signaling, catalog no. 70745), and Goat Anti-Mouse, IgG1 Gamma 1 Heavy Chain Specific (SouthernBiotech, catalog no. 1070-05, specifically used for detecting immunoprecipitated protein ubiquitination) were all diluted at 1:20,000.", "The IFITM3 PPxY motif is required for ubiquitination by NEDD4", "IFITM3 knockdown in MEFs was performed using Silencer Select Ifitm3 siRNA (Ambion, catalog no. 4390816) and negative control (Ambion, catalog no. 4390844). Human NEDD4 knockdown in A549, NCI H358, and NCI H2009 cells was performed using Dharmacon ON-TARGETplus SMARTpool Human NEDD4 (GE Healthcare, catalog no. L-007178-00) and Dharmacon ON-TARGETplus Control Pool Non-targeting control (GE Healthcare, catalog no. D-001810- [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] . siRNAs were transfected into cells using Lipofectamine RNAiMax transfection reagent (Invitrogen). Transfection of siRNA was performed for 24 h for mIFITM3 knockdown, and 48 h for NEDD4 knockdown. For Western blotting, cells were lysed with 1% Brij buffer (0.1 mM triethanolamine, 150 mM NaCl, 1% BrijO10 (Sigma), pH 7.4) containing EDTA-free protease inhibitor mixture (Roche) and 25 \u03bcM MG132 (Sigma). Immunoprecipitations were performed using EZview Red anti-c-myc or anti-HA affinity gel (Sigma), or with Protein G Plus Agarose Suspension (Calbiochem) in conjunction with anti-mIFITM3. Chloroquine, bafilomycin, and leupeptin were purchased from Sigma.", "An additional intriguing aspect of our finding that IFITM3 steady state levels are regulated by NEDD4 is the previously described role of the IFN effector ISG15 in inhibiting NEDD4 [29, 30] . ISG15 is a ubiquitin-like protein that specifically binds to NEDD4, blocking its productive interaction with Ubiquitin-E2 ligase complexes [29, 30] . The importance of this pathway was highlighted by two independent studies demonstrating that ISG15 blocks NEDD4-mediated monoubiquitination of the VP40 matrix protein of Ebola virus, thereby inhibiting the budding of Ebola virus-like particles [29, 30] . Importantly, several studies have implicated ISG15 as a critical antiviral effector against IAV and IBV [42, 43, 44] . Two studies have demonstrated conjugation of ISG15 onto the IAV NS1 protein by the E3 ligase HERC5, and found that ISGylation of IAV NS1 antagonizes virus replication [44, 45] . Interestingly, IBV NS1 specifically blocks human ISG15 conjugation by preventing ISG15 interaction with the ISG15 activating enzyme UbE1L, effectively counteracting its antiviral effect [43, 46, 47, 48] . We posit that high levels of IFITM3 attained after IFN stimulation result from both IFITM3 gene induction, as well as increased IFITM3 protein stability as a result of ISG15 inhibition of NEDD4. We are currently investigating this exciting potential synergistic link between ISG15 and IFITM3." ] },{ "paper_id": "79641a9857d5320c10a6619c351f113b1940ce6f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Infectious bronchitis (IB) is a severe acute disease of poultry caused by IBV, which primarily infects the respiratory tracts, with respiratory disease being the most frequent sign. In addition, IBV can infect the kidneys and reproductive tracts and consequently cause kidney damage and decrease in egg production [8] . Generally, IB is controlled by serotype-specific vaccines [9] . The identification of field isolates is necessary for appropriate vaccinations because these vaccines exhibit little crossreactivity among different serotypes [10, 11] .", "To analyze the genetic characteristics of MG and MS, the gapA gene and the DNA fragment of vlhA gene were amplified using a PCR assay and sequenced. For sequencing, the amplicons were purified using a FastGene gel/ PCR extraction kit (NIPPON Genetics Co. Ltd.), and the nucleotide sequences were determined using the Geno-meLab\u2122 GeXP Genetic Analysis System (Beckman Coulter, Fullerton, CA, USA). The resulting sequences of the gapA, vlhA, and S1 genes were aligned using MEGA6 software [19] , and the phylogenetic trees were constructed with the same software using the neighborjoining method [20] . ", "Avian mycoplasmosis is caused by several pathogenic mycoplasmas. Among them, Mycoplasma gallisepticum (MG) and M. synoviae (MS) are the most impactful to the poultry industry. MG infections usually cause chronic respiratory disorders and are characterized by sneezing, coughing, and snicks as well as nasal and ocular discharges [5, 6] . MS infections most frequently occur as subclinical upper respiratory tract infections and may cause air sac disease. MS results in infectious synovitis, an acute to chronic infectious disease of chickens [5] . The co-infection by MG or MS with respiratory virus infections, such as IBV and Newcastle disease, can exacerbate the disease conditions [5] . Both MG and MS infections cause considerable economic losses in the poultry industry by reducing weight gains and meat quality in broilers, causing severe drops in egg production in layers, and increasing embryo mortality in breeders [7] ." ] },{ "paper_id": "7967040b2131b69fec61d9f1d5c14dd214c49989", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The mapping activity was conducted from December 2009 to November 2010, through survey and key informant interviews among researchers and institutions, and a review of Elsevier's Scopus database. The mapping activity gathered records on institutional data of R&D institutions across the ASEAN region.", "\u2022 To build a harmonious and sustainable partnership among ASEAN countries and networks to rapidly build up the needed human resource, technology, and financing for health and development security.", "The need for an ASEAN-led Health R&D innovation", "Additional file 1: Multilingual abstracts in the six official working languages of the United Nations.", "The Association of Southeast Asian Nations (ASEAN) has a continuum of member nations at different stages of economic and health development, with the majority of the countries belonging to the middle-and low-income categories [1] ." ] },{ "paper_id": "79695b2d02cc1106f7cbf9ab80e3a53cee4b054e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chloroquine phosphate (7-chloro-4-[4-(diethylamino)-1-methylbutyl]amino]quinoline phosphate, (Sigma) and oseltamivir, a kind gift from Roche was used as a positive control.", "The Coulomb potential was mapped to the protein surface by use of SPDBV using the default relative dielectric constant (solvent = water) of 80. Further information on the algorithm adopted by the program is available in the detailed online description of the program [31] .", "Hemagglutinin genes of H3N2 and H1N1 viruses were sequenced using gene-specific primers, as previously described [30] . Sequence data so far unpublished will be deposited in GenBank by the time of publication of the present article.", "After 24 hours of incubation of the virus-infected cells with different concentrations of the test compounds, under the appropriate conditions, pooled aliquots of the supernatants containing free viruses were subjected to RNA extraction and qRRT-PCR." ] },{ "paper_id": "7969e6c3564904ffb7928747d52f3edcc7f97fff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Purification and sequencing of PCLSR products. The PCLSR products were purified using DNA extraction. The DNA from the reference virus stock as well as the whole blood from wild boars and pigs was extracted using High Pure PCR Template Preparation Kit, accordingly to the manufacturer's procedure (Roche Diagnostics, Basel, Switzerland). The extracted DNA was stored at \u2212 20 \u00b0C for further testing.", "LAMP. LAMP has been conducted using previously described primers 13 in 15 \u03bcl reaction volume using the following concentration of reagents: 7.5 \u03bcl of Isothermal Mastermix 50 pmol of forward and backward inner primer (FIP and BIP), 10 pmol of outer primers (F3 and B3) and 25 pmol of loop primers (LF and LB), 1 \u03bcl of standard plasmid, containing a p72 gene. After incubation, 1 \u03bcl of a 1:10 stock dilution of 10,000 x DMSO concentrated SYBR Green I dye (Invitrogen) was added to the reaction vessel. The results were registered under UV illumination, to detect fluorescence.", "PCR. The PCR for PCLSR results verification was performed in 25 \u03bc l final volume using outer PCLSR primers accordingly to the procedure of MyTaq HS DNA Polymerase kit (Bioline, Gdansk, Poland). The reaction mixture contained: 12.5 \u03bc l of MyTaq \u2122 HS DNA Polymerase, 9.5 \u03bc l PCR-grade water, 1 \u03bc l of each primer and 1 \u03bc l (~200 ng) template DNA. The primer concentration was 40 pM of each primer. The obtained PCR products were subjected to electrophoresis in 1.5% agarose gels under voltage of 100 V/50 min. The gels were stained by addition of 5 \u03bc l of SimplySafe solution as for PCLSR product separation. The length of PCR products were estimated on the basis of 100 bp DNA Ladder Plus GeneRuler (Thermo-scientific, Waltham, Massachusetts, USA). All PCLSR were replicated to verify reproducibility." ] },{ "paper_id": "796abc8d89c17b85820bfd4a6466dc9cda531e4b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Poxviruses encode two families of proteins with intrinsic ubiquitin ligase activity; a membrane-associated RING-CH (MARCH) ubiquitin ligase, and a really interesting new gene (RING) finger protein (Figure 2A and B) [35] [36] [37] [38] .", "The Poxviridae are a large family of viruses that infect a wide range of vertebrates and invertebrates [7] . The best known member of the family is variola virus, the causative agent of smallpox. Global eradication of smallpox was achieved in 1979 through a vaccination program initiated by the World Health Organization (WHO) [8] . Smallpox eradication used vaccinia virus, a close relative of variola virus, as a live vaccine [9] . By virus standards, poxvirus genomes are large ranging in size from 150-300 kbp; encoding upwards of 200 or more open reading frames [7] . Much interest in poxvirus biology stems from the observation that poxviruses employ a vast array of effective immune evasion strategies [10, 11] . Additionally, the ease with which recombinant poxviruses are generated has made them attractive viruses for dissecting cellular signaling pathways [10] . Recently, protein ubiquitination has emerged as an important mechanism for the control of protein degradation and function, especially during virus infection [12] [13] [14] [15] [16] . In this review we focus on the strategies that poxviruses have developed to exploit the ubiquitin-proteasome system.", "Ubiquitination is a post-translational modification that plays an essential role in many cellular processes [17] . Ubiquitin is a small 76 amino acid protein that is highly conserved in eukaryotes. In fact, only four amino acids differ between yeast, plants and mammalian ubiquitin sequences [18] . Two classes of ubiquitin-encoding genes are present in eukaryotic genomes. These including polyubiquitin genes that encode back-to-back ubiquitin sequences that are cleaved to produce ubiquitin monomers, and ubiquitin-carboxyl extension protein (CEP) fusion genes that encode a single ubiquitin sequence fused to a ribosomal sequence at the C-terminus that is incorporated into the ribosome [19] . Ubiquitin contains seven lysine residues that can be used to build ubiquitin chains [1, 17, 20] . Traditionally, ubiquitination is associated with protein degradation; however, current evidence indicates that ubiquitination has additional regulatory functions [1, 17, 20] ." ] },{ "paper_id": "797c6ecb7d0eb5d6eb5ea5f081a3c4cc78be5bd2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by the Human Research Ethics Committee of the University of Adelaide (H-176-2006) and for the student focus groups by Community and Tertiary Liaison, Department of Education and Children's services.", "Miriam should comply, provided she has enough support at home.", "3" ] },{ "paper_id": "798026310eaadd09df393473a730d6935f91b4d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where represents the given GC 3 %.", "Analysis. ENC analysis can be used to quantify the absolute codon usage bias in coding sequences. ENC was calculated using the following formula [19] :", "The authors declare that they have no conflicts of interest related to this study." ] },{ "paper_id": "798a5016be0c05f728460661deff95d394346513", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Compound ", "[P] = v s t + [(v 0 \u2212 v s )/k obs (1 \u2212 e \u2212k obst )]", "where t is time, [P] is product intensity, v 0 and v s are the initial and steady-state reaction velocities, and k obs is the apparent first-order rate concentration." ] },{ "paper_id": "798d2643cbdd17b150ec009bd4b735e08f8f8e40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "in gD that is proposed to signal the gH/gL heterodimer to trigger the fusogenic activity of gB (1) (2) (3) . Entry receptors that bind to gD include herpesvirus entry mediator (HVEM) (4), nectin-1 (5, 6) , nectin-2 (7, 8) , and modified heparan sulfate (HS) (9, 10) . Another receptor, paired immunoglobulin-like type 2 receptor (PILR\u2423), binds to gB and can mediate viral entry, provided that gD also binds to a receptor (11) .", "The gB 3A mutations may provide tools to study the prefusion form of gB, potentially by contributing to the stabilization of prefusion gB in future crystallization trials. Future experiments will select for second-site revertant mutations to identify potential interaction sites within gB and to investigate how other viral proteins regulate gB fusion activity. The antibodies used in this study included rabbit anti-gB polyclonal antibody (PAb) serum R74 (kindly provided by Patricia Spear, Northwestern University) (26) and the anti-VP5 MAb (East Coast Bio).", "Western blot assays. Western blot assays were performed to examine the expression of HSV-1 gB (50). Viruses harvested from Vero cells infected at an MOI of 0.01 were lysed in 200 l of lysis buffer (25 mM Tris-HCl [pH 7.4], 150 mM NaCl, 5 mM EDTA, 10 mM NaF, 1 mM Na 3 VO 3 , 1% Nonidet P-40) containing protease inhibitors (Roche Diagnostics, Indianapolis, IN). Proteins were boiled for 5 min under reducing conditions, separated by SDS-PAGE on 4 to 20% gels, and transferred to nitrocellulose. Blots were probed with anti-gB PAb R74 at a 1:10,000 dilution for 1 h at room temperature, followed by IRDye 800CW goat anti-rabbit IgG (LI-COR, Lincoln, NE) at 1:10,000. The bands were visualized by Odyssey imaging (LI-COR). Incorporation of gB 3A into the virion was examined as previously reported (52) . Briefly, medium from infected Vero cells containing extracellular virus was subjected to low-speed centrifugation to pellet cells and debris. The supernatant was centrifuged at 48,000 \u03eb g for 1 h at 4\u00b0C over a 10% sucrose cushion. The pellet was dissolved in sample buffer and separated by SDS-PAGE on a 4 to 20% gel under reducing conditions. Western blot analysis was performed with R74 at a 1:10,000 dilution and anti-VP5 MAb (East Coast Bio) at a 1:2,000 dilution, followed by the addition of IRDye 800CW goat anti-rabbit IgG (LI-COR, Lincoln, NE) and IRDye 680LT donkey anti-mouse antibody at 1:10,000 (LI-COR, Lincoln, NE)." ] },{ "paper_id": "7992401d6ef4c8a20818079438362577895f25b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "79979652a864cef3a41342ccb1add48e5ad0cf85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Production of transgenic plants, at laboratory level or commercially, has traditionally been mainly through expression of transgenes in the nucleus [24, 25] . Among the ecological concerns raised about genetically engineered organisms is that transgenes could move (\"transgene flow\", the process of transgene movement by recurrent hybridisation) via pollen from the crop and into relatives growing in natural or semi-natural communities [59] . Such concerns have led to a new field of transgene containment [60, 61] .", "Apel & Bock, [42] demonstrated the potential of plastids genome engineering for the nutritional enhancement of food crops when they enhanced carotenoid biosynthesis in transplastomic tomatoes by induced lycopene-to-provitamin A conversion. The transplastomic technology could also be useful for engineering agronomic traits including phytoremediation [78] reversible male sterility [79] , and toler-ance/resistance of stresses such as diseases, drought, insect pests, salinity and freezing that can severely limit plant growth and development [3] .", "Two interesting applications of plastid transformation were carried out by (i) [55] for the construction of a tobacco master line to improve Rubisco engineering in plastids, and (ii), [4] who explored the possibility of engineering riboswitches (natural RNA sensors that regulate gene expression in response to ligand binding) to function as translational regulators of gene and transgene expression in plastids." ] },{ "paper_id": "79a70e09a449e41078a23b502c9a645a1e177eca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The experimental pipeline can thus be summarised as:", "1. Repeat for i = 1, . . . , 500:", "I thank David Hunter, Marcel Salath\u00e9, Mary Poss and an anonymous referee for useful comments and references that improved this paper. This work is supported by NIH grant R01-GM083603-01." ] },{ "paper_id": "79b67a52cb7757c9fae9636913c30b5ee39e68af", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:37124 | DOI: 10.1038/srep37124 effects of C478A, W479A and S482A mutations on CHIKV ns polyprotein processing observed in cell-free assays were also reproduced in cell-based assay.", "Scientific RepoRts | 6:37124 | DOI: 10.1038/srep37124", "EDANS standard curve was generated after considering the inner filter effect 45 " ] },{ "paper_id": "79be2bad7d0442947cec07b060a5b21f8eff7c72", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "79d2ee55b54d57041ab6d9a3ecac33bc98d11ff5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that they have no competing interests.", "Authors' contributions S.K. and J.R. framed the hypotheses, designed and performed the animal trial. S.K. analysed and interpreted data and drafted the manuscript. J.R. monitored the overall research project and critically revised the manuscript. S-B.W. designed gene expression experiments, analysed and interpreted the data and drafted the manuscript. All the authors read and approved the manuscript for publication." ] },{ "paper_id": "79da8c8e26960026682cb2daf09ec3357b1bec5a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The antigen used for the SARS detection ELISA was the detergent-extracted and gamma irradiated Vero E6 cells infected with SARS-CoV. Identical preparations from uninfected Vero E6 cells were used as the control. Patients' sera were 1:10 diluted and added to the ELISA plates, and goat anti-human IgG antibody conjugated with horseradish peroxidase (DAKO, Cambridgeshire, UK) was added ", "Robinson criterion [22, 28] is frequently used to assess the performances of sorting algorithms on symmetric proximity matrices. A Robinson Matrix, R = [r ij ], is a symmetric matrix such that r ij \u2264 r ik if j 0\" columns show the percent of papers that provided at least one citation for their incubation period statement or had at least one incoming citation. The maximum hub and authority score columns show the largest calculated value for an individual source, based on the algorithms developed by Kleinberg (1999 " ] },{ "paper_id": "7d8b8767e12fc4fee2b29c6473b7dd1f3244b933", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: S.J., A.K.D., and L.D. designed the study. Y.G., W.T., N.W., and X.L. performed the experiments and analyzed the data. Y.G. and N.W. carried out sequence alignment analyses. Y.G., S.J., A.K.D., L.D., and S.C. wrote and revised the manuscript.", "Materials and Methods", "Zika virus (ZIKV) is a mosquito-borne flavivirus in the same genus as other important human pathogens, including dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV) [1] . ZIKV was originally isolated in a rhesus macaque in 1947 [2] , but this virus has only recently claimed worldwide attention owing to its close association with congenital Zika syndrome (CZS), as represented by microcephaly, fetal demise, central nervous system abnormalities, and other neurological complications [3] [4] [5] [6] [7] . No antiviral therapeutics for the treatment of ZIKV-associated human diseases, particularly congenital syndrome " ] },{ "paper_id": "7d8f6f7c012e065e971832e990bcf5b9b5bc6928", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Aims-Lactate dehydrogenase (LDH)-A is highly expressed in diverse human malignant tumors, parallel to aggressive metastatic disease, resistance to radiation/chemotherapy and clinically poor outcome. Although this enzyme constitutes a plausible target in treatment of advanced cancer, there are few known LDH-A inhibitors.", "Hanks Balanced Salt Solution, (4- " ] },{ "paper_id": "7d92312dac3822da87cb86d3de9fe818e0ee2874", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Towne strain of HCMV containing the green fluorescent protein (GFP) expression cassette was obtained from Dr. Daniel Streblow at the Oregon Health Science University and was propagated in human foreskin fibroblasts (HFF). Viral supernatants were collected 5 days after 100% CPE was observed, centrifuged to clear cell debris, and filtered through a 0.45 \u03bcm filter. HFF were grown in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBS), penicillin G (100 U/mL), streptomycin (100 mg/mL), and GlutaMAX (2 mM).", "HFF cells were trypsinized, centrifuged, and resuspended in 1% FBS DPBS. GFP-positive cells were quantified using flow cytometry (Cytomics FC 500 Beckman Coulter, Fullerton, CA). " ] },{ "paper_id": "7d9e398e0de06f3fc877f3d67489e798b7c31c20", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "During the study period (2005) (2006) (2007) (2008) (2009) (2010) (2011) (2012) (2013) (2014) , the Netherlands' National Immunization Programme included a 3 + 1 infant vaccination schedule using pentavalent (2005) (2006) (2007) (2008) (2009) (2010) (2011) or hexavalent (2012-2014) combination vaccines containing acellular pertussis, with doses at 2, 3, 4 and 11 months of age [15] . Vaccination coverage of the infant series was 93.5-95.5% for all included birth cohorts [2] .", "To ensure privacy, a Trusted Third Party was used for certain steps in data collection and data linking. Researchers were allowed to use age only in months.", "Medical ethical approval was not needed because no one was subjected to imposed rules or acts. According to Dutch law, informed consent of patients was not required because the study served public interest, and asking permission was not feasible [16, 17] .", "We invited the participation of 87 hospitals. Of these, 4/8 university hospitals, 19/26 top clinical hospitals, and 27/51 local hospitals participated. Overall, data of 57% of eligible cases (676/1187) were available." ] },{ "paper_id": "7d9f6bae2b7ced5834b4e92e7ef805d85fdea405", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Transfection of plasmid DNA or in vitro synthesized RNA was performed by using TransIT-LT1 or TransIT-mRNA Transfection Kit (Mirus, Madison, WI) according to manufacturer's instructions, respectively.", "The pcDNA3.1mycHisA plasmids encoding CAT [32] or pcDNA3.1mycHisA-PTNSs or pcDNA3.1mycHisA-SFSVNSs were linearized, and in vitro transcribed by using mMESSAGE mMACHINE T7 Ultra kit (Ambion, Grand Island, NY) according to the manufacturer's instructions. The linearized CAT DNA contained myc-His tag at the 39end.", "Western blot analysis was performed as described previously [32] . The membranes were incubated with anti-human PKR monoclonal antibody (BD Biosciences), anti-mouse PKR monoclonal antibody (B-10, Santa Cruz, CA), anti-RVFV mouse polyclonal antibody (a kind gift from Dr. R.B.Tesh, UTMB), anti-Flag-tag M2 monoclonal antibody (Sigma), or anti-b-actin goat polyclonal antibody (I-19; Santa Cruz, CA.) overnight at 4uC and with secondary antibodies (Santa Cruz, CA) for 1 hr at room temperature.", "Statistical analyses were performed by using the Graphpad Prism 5.03 program (Graphpad Software Inc, La Jolla, CA). Unpaired t-test or Mann-Whitney U-test was used for the comparison of two groups. Survival curves of mice were analyzed by log-rank (Mantel-Cox) test." ] },{ "paper_id": "7da4fcd53b89c33706e7e63f8b2f527f27f07ef8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LTBI was defined as (1) positive by both IGRAs and TST, (2) exposure history to a known ATB case, (3) no clinical, radiological and microbiological evidence of active TB [36] .", "Each experiment was repeated independently at least three times. Data are expressed as the mean \u00b1 SD and differences between groups were evaluated with the Student t-test or Mann-Whitney U test. Values of P<0.05 were considered statistically significant.", "Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), continues to be a serious infectious disease worldwide [1, 2] . It is estimated that most active TB (ATB) cases originate from an initial latent TB infection (LTBI), a state without any clinical symptoms, radiological abnormality, and microbiological evidence. In contrast to adults, young children infected with MTB are more likely to progress to ATB within the first year of primary infection; however, the molecular mechanisms behind this have long been a mystery [3] .", "Because of the difficulty of enrolling LTBI pediatric subjects, a limitation of this study is the relatively small sample size used for verification. Thus, a larger sample size and further mechanism analysis should be the focus of future investigations." ] },{ "paper_id": "7dad7185f2f7dd28cfaa251822682e46bb5b26e6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total DNA was extracted using the DNeasy Blood & Tissue Kit (Qiagen, Hilden, Germany) from tissue samples according to the manufacturer's protocol. Viral RNA was extracted from lung tissues using the QIAamp Viral RNA Mini Kit (Qiagen) following the manufacturer's instructions, and cDNA was synthesized with M-MLV reverse transcriptase (Promega, Madison, WI, USA) in the presence of the primer P14 [25] .", "Preliminary sequence management and analysis were carried out using Geneious (Version 5.5.9, Biomatters Limited, Aukland, New Zealand) and sequence alignment and editing were performed using ClustalW (Version 2.0) [27] and BioEdit (Version 7.1.9) [28] . The potential in vitro recombinant sequences (i.e., PCR artifacts) were screened and discarded using Recombination Detection Program v2.0 [29] . The consensus sequences were compared with known hantavirus sequences available in GenBank. Phylogenetic trees were constructed using the maximum likelihood (ML) algorithm with bootstrap values determined by 1000 replicates in Geneious.", "In August 2012, 189 small mammals were captured in forests of the suburbs of Fugong county, Yunnan province. Animal species were identified based on morphology, and animal weight and sex were recorded. Species were further identified by DNA sequencing of the mitochondrial cytochrome b (CytB) gene following previously described methods [22] . Animal lung tissues were collected for further analysis." ] },{ "paper_id": "7db22f7f81977109d493a0edf8ed75562648e839", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The oldest known scorpions lived around 430 million years ago in the Silurian period, on the bottom of shallow tropical seas, hence regarded as the oldest terrestrial arthropods [1] . Scorpions use venoms for immobilization of prey and protection against predators. Scorpion venoms consist of a complex of several toxins that exhibit a wide range of biological properties and actions, as well as chemical compositions, toxicity, pharmacokinetic, and pharmacodynamic characteristics [2] .", "From the Metarhizium fungus with Scorpine gene of interest, which was a gift from Fang's laboratory [17] , Scorpine gene was amplified by PCR using primers (FW: 59-TAGGTCTCTAGG-TATGGGCTGGATTAACGAGGAGAAG-39 and RV: 59-AT-TACTCGAGTTAGTAGGAGAGAGGGGTGCC-39).The PCR fragments were separated using 1.0% gel electrophoresis, purified with a DNA gel extraction kit (Takara, China). The resulting PCR product was digested with Bsa I and Xho I, and ligated into the pSUMO plasmid at the corresponding restriction sites [18] . The ligation mixture was transformed into E. coli DH5a cells for verification by sequencing (Nanjing Genscript Bio. Co. Ltd).", "All experiments were conducted in duplicate for at least three replicates. Results were expressed as means6S.D. Statistical analysis was performed according to Student's t-test by one-way analysis of variance. Significant difference was taken as p,0.05." ] },{ "paper_id": "7dbdecefcd59460800cc11324be0595779ffde80", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Henipavirus G attachment glycoprotein sequences were aligned in CLC Main Workbench v5.7.1 using default parameters (gap open cost = 10; gap extension cost = 1).", "The panel of m102 derivatives was generated by light chain shuffling and heavy chain random mutagenesis. Among them, m102.4 was reported to have an equal or slightly higher affinity to henipavirus G glycoproteins in comparison to the others [19] .", "Growth curves were performed by inoculating cell cultures with NiV, HeV and their escape mutants at a multiplicity of infection (MOI) of 1 for 1 h, after which the cells were washed 3 times with PBS and overlaid with medium. Virus samples were obtained at various time points after infection and stored at 280uC until viral titers were determined by TCID 50 ." ] },{ "paper_id": "7dbe0bb2d5bfc8c90c1a0185c6ea608452b08276", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study defined feather pecking as pecking that damaged feather cover, leading to broken feathers and feather loss (slight skin damage caused by feather plucking may occur). Cannibalism was defined as pecking that damaged skin and underlying tissues.", "\"Dusky areas are needed, while even lighting in feeding and foraging area is good. However, during times of outdoor access, external bright natural light does not seem to cause problems.\"" ] },{ "paper_id": "7dc484e62b5a5e470b072184f55b023d5e751061", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal protocols were approved by the Memorial Sloan-Kettering Cancer Center (MSKCC) Institutional Animal Care and Use Committee (protocol #99-07-025)." ] },{ "paper_id": "7dd0d85115b61c06ca2cfc389b6dfd2517708011", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "From December 1 2014 to April 30 2015, nasal swabs (NS), nasopharyngeal aspirates (NPA), bronchoalveolar lavage (BAL) and broncho aspirates (Brasp), collected from patients with acute respiratory failure requiring ICU admission in Lombardy (10 million inhabitants), were prospectively analyzed as part of a Regional Influenza Surveillance Plan. Analyses were centralized at the Molecular Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia or at the Department of Biomedical Sciences for Health, University of Milan. Severe respiratory syndrome was defined as acute onset ( 1 week) respiratory failure, with hypoxemia (pO 2 /FiO 2 ratio <300 mmHg while on positive end-expiratory pressure (PEEP) or noninvasive CPAP !5 cmH 2 O) and bilateral opacities at chest imaging [13] .", "Amplicons were purified with Agencourt AMPure XP magnetic beads (Beckman Coulter, High Wycombe, UK) and quantified with the Quant-iT PicoGreen dsDNA Assay Kit (Invitrogen, Life Technologies, Paisley, UK) with a TBS-380 Mini-Fluorometer (Turner Biosystems, Sunnyvale, CA). A dilution of 1\u00d710 9 molecules/\u03bcl was performed for each amplicon and then pooled in an equimolar concentration. The mixture was further purified with Agencourt AMPure XP magnetic beads (Beckman Coulter, High Wycombe, UK) and diluted to 1\u00d710 6 molecules/ul. The purified pool was clonally amplified by emulsion PCR (emPCR), following the emPCR Amplification Manual for 454 GS Junior Titanium. A total of 500,000 enriched beads were deposited into a PicoTitrePlate (PTP) device and sequenced using the GS Junior 454 system (Roche Diagnostics, West Sussex, UK).", "Continuous variables (i.e. viral load, variant numbers) were compared using the Mann-Whitney U test for independent non-parametric data. The Spearman rank correlation coefficient was used for the correlation analysis of non-parametric data. All of the analyses were two tailed, and performed using GraphPad Prism version 5 (GraphPad Software Inc., CA, USA); p-values of 0.05 were considered statistically significant." ] },{ "paper_id": "7ddc27749844ce4dd2695ad282cc21c3f3629eec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Enrichment of CD11b + cells was performed by subjecting single-cell suspension of brain homogenates (as performed in CNS Cell Isolation and Flow Cytometry) to CD11b+ (microglia) Microbead MACS purification (Miltenyi Biotec) according to manufacture instruction.", "HEK-Blue mTLR2 or mTLR4 cells (InvivoGen) were used according to manufacturer's instruction to determine serum concentrations of TLR2 and TLR4 and if JHMV signals through TLR4. After passaging according to manufacturer instruction, a flat-bottom 96-well plate was loaded with 25,000 cells per well. Then, 20 mL of PBS, mouse serum, varying dilutions of JHMV or serial dilutions of 0.1 mg/ml LPS added to each well. Cells were incubated for 6 hr, spun down and supernatant isolated. 20 mL of supernatant was then incubated with 180 mL of QUANTI-Blue solution (InvivoGen) for 15 min. Optical density at 620 nm was then measured using a Biotek Synergy H1M plate reader.", "Pair-wise comparison of experimental groups were performed with an unpaired two-tailed Student' t-test or one-way ANOVA or Mann-Whitney test for viral titers. JHMV disease curves were analyzed using two-way ANOVA or area under the curve analysis. Outlier testing was performed using Grubb's test for outliers. If an outlier was detected (p<0.05), that data point was omitted from any analysis. All statistics were performed using Prism six software (GraphPad Software)." ] },{ "paper_id": "7de0d0ac71e79cba5b50ed89303cae6d89bb0130", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data collection, preprocessing, and the twelve judges", "For most viral infections, the acute phase is a time of drastic physiological and immunological changes, especially at the beginning of adaptive immune responses. Further similar studies performed in samples collected at later time points, when infection is already established, would help to evaluate the relationship between cytokine expression and viral replication.", "vitro and in vivo [29] , and CCL8 and CXCL10 are important chemoattractants for monocytes and activated lymphocytes, respectively [30] ." ] },{ "paper_id": "7de21b4df4bb390e0fba8c0938ef6eeef9a4630e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "7df37eb3cc184f38b1d97fe12f7176b5da78f77f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In summary, we found that providing timely and accurate information to the public during an outbreak was crucial to both risk communication and the control and prevention of further infection. Therefore, health authorities should bolster their capacity to disclose information in a timely, accurate, and transparent way. ", "These results also suggest that Korea health authorities should consult with experts and produce a crisis and risk communication guide to develop communication strategies such as informing the public and providing training for communicators who possess the necessary competence and expertise [6] . Overall, the provision of accurate and prompt information is one of the most important factors in saving lives and protecting people during public health emergencies. Naylor et al. have suggested that communication between authorities and the public is the cornerstone of crisis management in the healthcare and public health system [13] .", "The purpose of this study was to evaluate the effect of policy to avoid disclosure of information, the most controversial issue regarding the initial response, on the spread of MERS-CoV in South Korea. The study sought to determine whether changing this strategy and releasing a list of hospitals treating infected individuals was associated with containment of the disease [9] .", "The government revised its policy to disclose information in accordance with the public's opinion that nondisclosure of information would in fact cause MERS-CoV to spread and generate public anxiety. However, the South Korean government restricted and controlled information regarding MERS-CoV during the initial response. It has been claimed that inadequate information disclosure was the main reason for the spread of MERS-CoV. The lack of an appropriate management system and a prevention strategy for infectious disease has been raised as additional reason for the initial failure to contain the outbreak [6] ." ] },{ "paper_id": "7dfaa4c09d874ca072da1848411baba5c552b8f9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Searches for G4s and elucidation of their function in the viruses' genome have mainly focused on the human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS). Currently, \u223c35 million people are infected with HIV worldwide. With over 2 million new infections and \u223c1.6 million deaths from AIDS per year, the pandemic continues to spread. Even without a vaccine, development of highly active anti-retroviral therapies have allowed people to live with HIV as a chronic disease (96) . However, viruses within T cells remain fully capable of replicating and infecting other cells if the drug pressure is removed or when resistance emerges. Thus, new drugs must be developed to overcome the treatment's genetic barrier.", "Nucleic Acids Research, 2014, Vol. 42, No. 20 12361 ", "PDB IDs: 2KF8, 2LPW, 2M4P, 1Y8D and 2LE6. ", "In attempts to obtain natural-type oligonucleotide, Hotoda et al. identified a hexamer (TG 3 AG) also targeting HIV-1 entry through gp120 binding (167) . This 'Hotoda's sequence' adopts a tetramolecular G4 structure and submicromolar HIV-1 inhibition was described for derivatives with 5 -end substitutions. Once more, the antiviral activity of the molecule was directly linked to its capability to form G4s." ] },{ "paper_id": "7dffa969edbe8096420d429681024410840d4d20", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Proteins were separated by 10% SDS-PAGE and transferred to nitrocellulose membranes. These were blocked for 30-60 min with 5% powdered milk (Marvel) in PBST (137 mM NaCl, 2.7 mM KCl, 10 mM Na 2 HPO 4 , 1.5 mM KH 2 PO 4 , pH 6.7, and 0.1% Tween 20) and probed with polyclonal rabbit anti-MuLV p30 (ab130757; Abcam) (1:2000 in Marvel-PBST) and monoclonal mouse anti-GAPDH (G8795; Sigma-Aldrich) (1:20,000 in Marvel-PBST). Membranes were incubated in the dark with an IRDye-conjugated secondary antibody in PBST (IRDye 800CW donkey anti-rabbit IgG H+L and IRDye 680RD goat anti-mouse IgM [\u00b5 chain specific]).", "Glyco-Gag appears to function in maintaining viral capsid integrity and in facilitating viral evasion of the host innate immune response [17, 19, 20] ." ] },{ "paper_id": "7e0925a800d4d09380ac44584b5be257d83531d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were entered into sheet containing epidemiological, clinical, paraclinical data, and clinical evaluation of patient, as well as information regarding the patient's family members. e studied data are as follows:", "Infants, regardless of their gestational age or geographical origin, whose actual age was less than 4 months, hospitalized for suspicion of pneumonia.", "e data used to support the findings of this study are included within the article.", "Statistical analysis was performed with the Package for the Social Sciences (SPSS.18) and analyzed by using the software RChi2 of Pearson. A p value <0.05 was considered statistically significant.", "175 \u03bcl of TS samples were eluted in 40 \u03bcl of elution buffer. e assays comprised a preamplification step, which combines reverse transcriptase and multiplex target amplification PCR, followed by a probe hybridization step, a probe ligation step, and a probe amplification step. e Internal Amplification Control (IAC) was added at the beginning of the procedure to differentiate between samples with true-negative results and samples with false-negative results due to PCR failure. Targets are detected using capillary electrophoresis [13] ." ] },{ "paper_id": "7e216d0c059fbbc7cace4a9d12a48482ad781366", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The proportion of the 1606 respondents who expressed a high level of need for these modules are shown in Table 3 ." ] },{ "paper_id": "7e232c192b439ef6a844be6a2f40bbbae64469fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The left upper liver lobe was fixed in 4% formaldehyde solution, followed by paraffin embedding, preparation of 2-4 \u03bc m sections and staining with haematoxylin and eosin (H&E). Histological evaluation was performed by an animal pathologist certified by the American College of Veterinary Pathologists in a blinded fashion.", "Determination of serum ALT. For ALT quantification, 75 \u03bc l peripheral blood were mixed with 25 \u03bc l 1% heparin (Ratiopharm, Germany), centrifuged (10,600\u00d7 g, 10 minutes, room temperature) and 32 \u03bc l of the supernatant were used for detecting ALT activity using the scil Reflovet \u00ae Plus reflection-photometer (scil animal care, Germany)." ] },{ "paper_id": "7e2cac5308e11493311bc4a3e8d15c9b9e7885ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author summary ADP-ribosylation, an understudied post-translational modification, facilitates the host response to virus infection. Several viruses, including all members of the coronavirus PLOS Pathogens | https://doi.", "BMDMs plated on glass cover slips were infected with GFP-expressing MHV. At 14 hpi, cells were fixed with 4% paraformaldehyde, and coverslips were transferred to a glass slide. Vectashield Antifade Mounting Media with DAPI (Vector Laboratories) was applied, and a second coverslip was overlaid. Slides were visualized on an Olympus IX-81 inverted fluorescence microscope (Olympus), and images were analyzed using SlideBook software (Meyers Instruments)." ] },{ "paper_id": "7e4299dd78b35e5223c34355cd13c9c99ed72c25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The dataset in both analyses was composed of sequences in the BuV cluster. Adopting a parsimonious approach, this study accepted only those events suggested by Bootscan that also had support from the Bayesian hypotheses testing.", "Nested-PCR screening. Faeces suspended in RNAlater reagent (Ambion, Life Technologies, Carlsbad, CA) were subjected to DNA extraction using a High Pure Viral Nucleic Acid kit (Roche Diagnostics GmbH, Mannheim, Germany) or QIAamp Viral RNA Mini Kit (Qiagen, Valencia CA). DNA from spleen tissues was prepared using DNAzol reagent (Molecular Research Center, Cincinnati, OH) or QIAamp DNA Mini kit (Qiagen). For nested PCR screen targeting for NS1 gene of BuV, we followed the method of Sasaki et al. 9 .", "Nucleotide sequences. All the nucleotide sequences determined in this study were deposited in the DDBJ/ EMBL/GenBank databases under accession numbers LC085665\u2212 LC085676." ] },{ "paper_id": "7e43122d298db29a31acc538436b5f3a10621995", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All procedures involving animals were approved by the Institutional Animal Care and Use Committee (IACUC) of Konkuk University (Approval No.: KU16095).", "Supplementary Materials: The following are available online at http://www.mdpi.com/2076-2615/9/8/510/s1, Table S1 : Primers/probe sets used for quantitative real-time PCR. " ] },{ "paper_id": "7e4905089dd52ffd586f780d272e2cd951457196", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The structure of the simple, 2-parameter model is as follows:" ] },{ "paper_id": "7e55726d345571690d0e3046664cfac5003c2a89", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine epidemic diarrhea virus (PEDV) is a coronavirus of the genus Alphacoronavirus. Disease from PEDV is characterized by vomiting, anorexia, and watery diarrhea in swine. The virus is particularly deadly for neonatal pigs for which malabsorption and dehydration [1] [2] [3] can result in mortality rates approaching 80%-100% [2, 4] . Disease caused by PEDV is clinically indistinguishable from transmissible gastroenteritis virus and cannot be diagnosed on presentation alone [4] . Because attempts at virus isolation have only resulted in limited or temporary success, with virus isolation rates as low as 4% [5] , diagnosticians heavily rely upon RT-PCR tests to directly detect viral nucleic acid and diagnose PEDV.", "Five American Association of Swine Veterinarians (AASV) PEDV questionnaires were completed by a USDA epidemiologist and an Ohio Department of Agriculture Veterinary Medical Officer in conjunction with swine operation representatives and the operation's local veterinarian. Several potential pathways of pathogen introduction to the swine operation, including human introduction, delivery of contaminated supplies, aerosol spread, contaminated pig transport vehicles, and contaminated feed or feed ingredients were considered and evaluated.", "Since PEDV is very difficult to isolate, a bioassay was initiated to determine if the pellets in question could infect na\u00efve piglets. During the outbreak at the swine operation, the attending herd veterinarian aseptically collected aliquots (as described above) of the RT-PCR positive pelleted feed from the farm and mixed them with sterile phosphate buffered saline to make a mash. These moistened, mash aliquots were stored at \u221220\u00b0C until the bioassay could be performed." ] },{ "paper_id": "7e5ab55e74c377b2a3bd936030ffe0f92d4c2a78", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consider screening patients who:", "\u2022 Are close healthcare contacts to new cases.", "Author Contributions: All authors participated in literature review and writing. " ] },{ "paper_id": "7e5b5d16ffb537a8e940502af3011d18fe6eff9b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceived and designed the experiments: FESL SPC PMR. Performed the experiments: FESL SPC HFS TFT APMV. Analyzed the data: SPC ED. Contributed reagents/materials/analysis tools: PMR ACF. Wrote the paper: FESL SPC PMR ACF ED.", ". Standard precautions were taken to avoid contamination and negative controls were added to each batch of reactions. Five microliters of the PCR products were electrophoresed in 0.7% agarose gels and the products visualized on UV light after staining with ethidium bromide. The amplicons corresponding to the sizes ranging from 1-2 kb were purified and cloned into pCR 2.1-TOPO cloning kit (Invitrogen\u2122). Three insert-containing plasmids of each clone were sequenced with M13 forward and reverse primers as described above. The full-length sequence of genomes was constructed by \"genome walking\" using the Geneious software (version 7.1.3).", "Our study was based on the phylogenetic analysis and comparison to the sequences recovered. The finding of known insect viruses in bat feces simply reflects the diet of these insectivorous bats, which play an important role on predating insects. Viral DNA detection in bat feces does not allow one to differentiate between viral replication in bats or simple passage through the digestive track from ingested food [20, 35] ." ] },{ "paper_id": "7e6fc218bd723f70d305eadff23e036875076250", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, the molecular data form reasonable evidence to propose the existence of the novel virus WUPyV.", "Le and co-workers [41] presented evidence for viral persistence, Wattier et al. [36] for nosocomial infections with WUPyV.", "Recently, the WU polyomavirus was detected in respiratory tract specimens [10] .", "The first polyomaviruses were isolated in 1971 and named JC virus and BK virus. In 2007 and 2008 3 further viruses of this particular family were described for the first time: WU polyomavirus, KI polyomavirus, and Merkel cell polyomavirus [11] . WUPyV was discovered by shot gun sequencing of nasopharyngeal aspirate of a three-years-old child from Australia suffering from pneumonia [10] . The investigators isolated total nucleic acids from the nasopharyngeal aspirate, randomly amplified fragments, and cloned them. Sequences of the obtained clones gained by shot gun sequencing were subjected to automated editing and database searches." ] },{ "paper_id": "7e73ff88b8e995535a2783a7ba78a743afd557a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Histidine or arginine residues were introduced at positions 1020 and suitable rotamers were sampled through the rapid torsion scan utility in Maestro (Maestro. 9.1; Schrodinger). Intraprotein interactions were calculated with PIC (protein interaction calculator) 54 .", "In FoldX and I-Mutant the \u0394 \u0394 G values are calculated as follows: \u0394\u0394G = \u0394G mutant \u2212 \u0394G wild-type . In FoldX and I-Mutant \u0394 \u0394 G values > 0 kcal/mol indicate mutations that decrease protein stability, whereas in PoPMuSiC \u0394 \u0394 G values > 0 kcal/mol are mark of mutations increasing protein stability. Therefore, PoPMuSiC \u0394 \u0394 G values were multiplied by \u2212 1 to obtain homogeneous results." ] },{ "paper_id": "7e8409337e69a72191475029805c6776ad43b60b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The clinical picture", "Community and healthcare preparedness in response to coronavirus outbreaks remain ongoing obstacles for global public health. For example, delays between disease development and progression and diagnosis or quarantine can severely impact both patient management and containment [21, 71] . Deficiencies in outbreak preparedness and healthcare network coordination efforts must ultimately be considered in response efforts. It is strongly recommended that universal reagents be maintained and available at global repositories for future outbreaks.", "The coronavirus spike protein mediates coronavirus entry into host cells. The S1 subunit of spike contains the receptor binding domain, which binds to receptors on host cells and dictates virus tropism. Viral entry is mediated through viral and host membranes undergoing fusion via the S2 subunit of the spike protein [47] . Therefore, we analyzed and discuss the S1 domains, in particular the RBD, due to its role in determining host tropism and pathogenesis." ] },{ "paper_id": "7e84a68e753fa2734beff117c24743d13b021c82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "On " ] },{ "paper_id": "7e884f1a409543ae791d8c5926e126ddcaf2d9b3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One week later, the child was successfully extubated. After a 7-day high flow nasal cannula oxygen therapy, he was transferred to the escort ward on 26 days after PICU admission, and eventually discharged with a near normal neurologic examination. The time line of this case can be consulted in the Additional file 1.", "There was no change in cannula position shown by X-ray when changing position (Fig. 2a, b) , and there was no malfunction of blood access due to bending or dislodgement of the cannula when changing position. At day 4 after ECMO initiation, exhaled tidal volumes were increased to 6 mL/kg and effusion in lung were improved indicated by chest radiographs (Figs. 2c).", "From this case review, we speculated that ECMO management is challenging in patients with pertussis contributing to the high mortality of these patients under ECMO support. Prone position ventilation contributes to better oxygenation and lung compliance. And detailed care bundle is essential for patients with pertussis challenged by recurrent airway spasm. " ] },{ "paper_id": "7e889eb3dc54b352c2689b84be7a52f121f80b56", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Table S1 This is a record of all identified Dispanins together with their accession numbers, nomenclature and species belonging.", "The whole proteome dataset for the following eukaryotic species was included in the analysis: Homo sapiens, Mus musculus, Gallus gallus, Xenopus tropicalis, Danio rerio, Petromyzon marinus, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerviciae, Schistosoma mansoni, Apis mellifera, Anopheles gambiae, Pediculus humanus, Ixodes scapularis, Daphnia pulex, Oryza sativa, Pristionchus pacificus, Acyrthosiphon pisum, Trypanosoma brucei, Leishmania braziliensis and Ciona instestinalis were downloaded from Ensembl; Strongylocentrous purpuratus was downloaded from Spbase (www.spabase.org); Branchiostoma floridae, Nematostella vectensis, Trichoplax adhaerens, Phytophtera soyae, Thalassiosira pseudonana, Naegleria gruberi and Monosiga brevicollis were downloaded from the Joint Genome Institute; Dictyostelium discoideum was downloaded from dictyBase (www.dictybase.org); Arabidopsis thaliana was downloaded from TAIR (http://www.arabidopsis.org/); Entamoeba histolytica was downloaded from amoebaDB (http://amoebadb.org); Paramecium tetraurelia was downloaded from NCBI; Tetrahymena thermophila was downloaded from UniProt; Trichomonas vaginalis was downloaded from TrichDB (http://trichdb.org); Giardia lamblia was downloaded fromGiardiaDB (http://giardiadb.org).", "(XLS) " ] },{ "paper_id": "7e92385d74e531617394983f187f6b4c9ca2f328", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ". . Animals. Male Sprague-Dawley rats (300 \u00b1 10 g) were obtained from Samtako Co. (Osan, Korea). Rats were housed under consistent temperature (23 \u00b1 1 \u2218 C) and humidity (55 \u00b1 10%) on a 12-h light/dark cycle (light on at 07:00). Food and water were available ad libitum. The experiments were carried out in accordance with the Principle of Laboratory Animal Care (NIH Publication #85-23, revised 1985) and Kyung Hee University's Institutional Animal Care and Use Committee.", ". . Immunohistochemistry. Immunohistochemistry was performed by modifying the previously described [13] . Brains were removed, fixed, and cut into 40-m sections . . Statistics. Statistical difference between three groups was analyzed using one-way analysis of variance (ANOVA) followed by Dunnett's post hoc test. Difference between two groups was analysed using independent t-test (GraphPad Prism 5.0, GraphPad Software, USA). Statistical significance was accepted at p<0.05 in Dunnett's test. Data were expressed as mean \u00b1 standard error of the mean.", "The experimental data used to support the findings of this study are available from the corresponding author upon request." ] },{ "paper_id": "7e9494784505c616553ef19805fb9dd82c89dea9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, we examined regional differences in symptoms at presentation. All analyses were conducted in R version 2.3.1 [19] ." ] },{ "paper_id": "7e988b275962a05ab35cab7441de87933b306a2e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BS drafted and wrote all parts of the manuscript. WP provided substantial modifications and conceptual advice at all stages of manuscript preparation. ", "The World Health Organization (WHO) Traditional Medicine Strategy 2014-2023 was established to assess traditional and complementary medicine, including herbs and other plant materials (7) . Nonetheless, the mechanisms of action of most phytotherapeutic chemicals are not fully understood. However, their synergistic antimicrobial activity is generally assumed to damage the bacterial membrane by lipophilic compounds or reduce cell division by DNA synthesis inhibition (8) .", "Phytotherapy has become an important new concept in healthcare research that was prompted by the need for alternatives to ineffective conventional antibiotics. The development of novel and efficient extraction techniques has led to renewed and increasing interest in plant-derived bioactive compounds (8) . Examples of phytotherapeutic drugs include oleanolic acid, which is used as a natural adjuvant for aminoglycosides as it increases their membrane permeability (9) . Most plant-derived compounds have weaker antibiotic activity than the common chemicals produced by bacteria and fungi. This review attempts to provide knowledge about zoonotic diseases and insight into the rich variety of antimicrobial secondary metabolites (i.e., phytochemicals) from plants that can be applied in the treatment of zoonoses.", "Herbal remedies are generally characterized by wide therapeutic indexes (37) , and they consist of multicomponent mixtures acting as multi-target drugs with pleiotropic effects. In animals, self-medication remains a controversial subject because the evidence is mostly anecdotal (39) . Unlike the popular belief that most drugs are synthetic in origin, many important medicines, such as cocaine and atropine, are natural products of plant origin (40) . Plants are used as natural resources in the development of new drugs, over the counter drugs, and nutraceuticals. In recent years, the consumption of botanical supplements has increased globally due to their relatively low cost and the need to reduce antibiotic overuse (38) . For example, terpenoids and phenolic compounds extracted from plants have been extensively studied for their immunity-enhancing effects and antimicrobial activities against a broad range of infectious microorganisms ( Table 1) . As shown in Table 1 , typical phytochemicals with antioxidant activity include monoterpenes (aromatic plants), diterpenes (berries and essential oils), triterpenes (olive oil and leaves), tetraterpenes (colored fruits and vegetables), sesquiterpenes (essential oils), and polyphenols (from tea and grapes).", "A zoonosis is an infectious disease that can be transmitted from animals to humans. Currently 61% of pathogens known to affect humans are zoonotic (10) . Most emerging infectious diseases considered to be serious public health problems have zoonotic origins (11) , and approximately three-quarters have originated from wild animals (12) . Zoonotic pathogens can be transmitted by close contact with an animal, generally through inhalation, ingestion, or other routes that contaminate mucous membranes and damaged or, in some cases, intact skin (12, 13) . Aerosol-mediated transmission is occasional, particularly in confined spaces. Fomites can transmit some agents, and the likelihood of this route correlates with the persistence of the organism in the environment. Transmission of some organisms occurs via ingestion of contaminated food or water, and such organisms may infect large number of people. Sources of zoonotic pathogens in foodborne diseases include undercooked meat or other animal tissues, seafood, and invertebrates, as well as unpasteurized milk and dairy products and contaminated vegetables (14) . Insects serve as important biological or mechanical vectors in transmitting some organisms (15) . In this review, we have summarized representative bacterial zoonotic infections (Figure 1) ." ] },{ "paper_id": "7e9a78b8f365405455eb60c2645de7bd7359e7a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "(DOCX) S2(DOCX) S3" ] },{ "paper_id": "7ec36d372303be7d61deb6a7ef724495a6d90614", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD009975. All other data generated or analysed during this study are included in the manuscript and supporting files.", "All samples were imaged by acquiring 0.2 mm stacks over 10 mm using a DeltaVision Elite High-Resolution imaging system (GE Healthcare Life Sciences) equipped with a 60x or 100x oil immersion objective (1.4 NA). Images were deconvolved using the integrated softWoRx software and processed using Fiji (ImageJ). Brightness and contrast were adjusted identically for each condition and their corresponding control. Figures were assembled using the FigureJ plugin (Mutterer and Zinck, 2013) .", "The following dataset was generated: " ] },{ "paper_id": "7ec733f3684d6294483b03df183878ad777a78d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Frontiers in Immunology | www.frontiersin.org experiment. Gates were set to exclude 95% of isotype control antibody stained cells in all extracellular and intracellular staining experiments.", "Data were analyzed using Graphpad Prism software (Graphpad Software Inc., CA, United States). Data were presented as mean \u00b1 SD of 3-5 replicate values and significant differences between two groups or more than two groups were analyzed using twoway ANOVA using Tukey's multiple comparisons test. A P \u2264 0.05 was considered to be statistically significant.", "RK, NG, DK, and BA: Conception; NG, SG, SV, and RK: Experimental planning and execution; NG, RK, and BA: Data analyses and manuscript writing." ] },{ "paper_id": "7ed1dcfad7266bfda122685c0009ec526f77909f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Both the authors (AE and MS) have significantly contributed by writing the manuscript and designing the graphs.", "The authors thank Dr. Helena Seth-Smith (Applied Microbiology Research, Department of Biomedicine, University of Basel) for critically reading the manuscript.", "AE was supported by a research grant from the SNSF Ambizione Score PZ00P3_154709." ] },{ "paper_id": "7ed71c815f2ddd8160be8a574698fe6685fe9dda", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GRFT can prevent hepatitis C virus infection in vitro and mitigate hepatitis C virus infection in vivo [79] . Also, GRFT displayed low nanomolar activity against SARS-related coronavirus (SARS-CoV) [36, 80] . In fact, GRFT was active against coronavirus strains that utilize protein-protein interactions for viral targeting (e.g., ACE2 as a cellular receptor, SARS-CoV, and HCoV-NL63) and a b c d e those that utilize protein-carbohydrate interactions for viral attachment (i.e., \u03b1-2,3-linked sialic acid moieties, IBV-CoV, and HCoV-OC43) [80] .", "Hopefully, these lectins can contribute to the development of an efficient, safe and affordable microbicide.", "* * * * * * : * * * * * * * * * * * * : * * * * * * * * * * * * * * * * * * :", "Since the discovery of the Human Immunodeficiency Virus (HIV) almost 30 years ago, more than 25 million people have been killed by this virus and approximately 34 million people are estimated to live with HIV. The HIV epidemic continues largely unabated with approximately 8000 new infections every day. The existing HIV drug treatments can control, but are not able to cure HIV infection. The", "Lectins are proteins of non-immunoglobulin nature, capable of recognition of and reversible binding to carbohydrate moieties of complex glycocongugates without altering the covalent structure of any of the recognized glycosyl ligands. Lectins can be found across a wide variety of different species in nature including prokaryotes, sea corals, algae, fungi, higher plants, invertebrates and vertebrates and are involved in many biological processes, among them host-pathogen interactions, cell-cell communication, induction of apoptosis, cancer metastasis and differentiation, targeting of cells, as well as recognizing and binding carbohydrates. This review will focus on algal lectins with antiviral activity." ] },{ "paper_id": "7ed7b23c66b9c4ad156f37619f8b88bc1c1e996b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For blood tests of fasting and fed animals, including blood glucose and leptin, blood was obtained at 10 am and 10 pm (12h) for analysis.", "Energy expenditure and locomotor activity were analyzed by indirect colorimetry using CLAMS metabolic cages, HSC Cores Research Facility at University of Utah. Body composition was determined by nuclear magnetic resonance (NMR Bruker Minispec).", "BMDM were isolated and cultured using standard protocols (14) . Cells were fixed with 4% paraformaldehyde and permeabilized with 0.02% Triton (Sigma) and stained with Iba1." ] },{ "paper_id": "7ed9ceed11e8adac9aca2e5e53e8f863b6a2c42a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The different works corresponding to these articles were carried out in different geographical areas of several countries: China [2, [5] [6] [7] [8] 10] , Colombia [4] , Ecuador [3] , Korea [9] , and Taiwan [1] . One of the studies deals with the analysis of an intracellular geometric model [11] ." ] },{ "paper_id": "7ee508ec11743a3ef6f496edaee487e68ace2368", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ligand binding leads to dimerisation of the type I IFN receptor subunits IFNAR1 and IFNAR2 and causes their conformational change. The JAK kinase Tyk2, which is constitutively bound to IFNAR1, phosphorylates the receptor at tyrosine residues and creates a docking site for STAT2. Subsequently, Tyk2 phosphor-ylates STAT2 at Y690. At the same time the receptor-bound JAK1 phosphorylates STAT1 at Y701 [15, 16] .", "IFN-induced JAK/STAT signaling can be inhibited at different levels by several viral and cellular factors through various mechanisms. The large T-antigen of murine polyomavirus (MPyV) binds to JAK1 and inhibits downstream signaling [20] , whereas the VP24 of Ebola virus (EBOV) binds to karyopherina-1 thereby blocking nuclear accumulation of STAT1 [21] .", "Found at: doi:10.1371/journal.ppat.1000196.s002 (4.87 MB TIF)", "Binding of IFNa/b to its receptor is the initial step in this signaling process, followed by activation of the JAK family and subsequent activation of STAT proteins [14] ." ] },{ "paper_id": "7ee798b6104d800e4c3aee14cec31ada51dd26c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma (KS) 1 . To a lesser extent, KSHV is etiologically associated with rare neoplastic disorders like primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD) 2 . KS is a malignant vascular tumor characterized by lesions occurring mainly on the skin, but can also affect the mucosa and visceral organs 3 . Hallmarks of KS are angiogenesis, cell proliferation, and inflammation 4 . KSHV is among the list of viral pathogens estimated to cause 12-25% of human cancers worldwide 5 .", "Virus. The viruses used in this study were wild-type KSHV 26 , herpes simplexvirus-2 (HSV-2) 62 , and Epstein-Barr virus (EBV) 63 . We generated ultraviolet (UV) inactivated KSHV (UV.KSHV) as per early studies 20 .", "KSHV has a biphasic life cycle comprised of latent and lytic phases of replication that are distinguished based on divergent gene expression profiles 6 . The dynamics between latent and lytic phases of replication allows the virus to persist for the duration of the host's lifetime 7 . Notably, KSHV establishes latency in the majority of infected cells 8 ; at any given instance, only a subpopulation (<3%) of infected cells display evidence of lytic gene expression 9 . MicroRNAs (miRNAs) are one of the main classes of non-coding RNAs 10 . These are small non-coding RNAs that regulate expression of genes in cells 11 . The human genome encodes thousands of miR-NAs 12 . Of late, miRNAs have emerged as a pivotal component of host cell responses to a pathogen including viruses, bacteria, and fungi 13 ." ] },{ "paper_id": "7ef029ee55ef6b0a0e6443f8ca750e0569024789", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Rhinovirus (RV) causes the common cold and asthma exacerbations.", "Data are represented as mean \u00b1 SE. Statistical significance was assessed using an unpaired t test or one-way ANOVA, as appropriate. Group differences were pinpointed by a Tukey's multiplecomparison test.", "http://orcid.org/0000-0001-9436-5593" ] },{ "paper_id": "7f011d5856d476496de3e715d8f77908f2610e30", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "7f1f94a49e088244c897fd0bfc96de817d1b804a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In 2006, we first identified small amounts of PKresistant PrP aggregates in uninfected brains of humans, cattle and hamsters [4] . Since then, subsequent studies have revealed similar insoluble structures in a wide", "www.impactaging.com", "The physiology and pathophysiology of iPrP C currently remain unclear. While it has been proposed that iPrP C is involved in prion and Alzheimer diseases and in the long-term memory storage according to our recent findings [31] [32] [33] [34] , new insights into the mechanisms underlying the spontaneous formation of PrP aggregates obtained with cell models would be significant in enhancing our understanding of not only prion diseases but also other diseases involving protein misfolding.", "The general methods for preparing multiple overlapping peptides bound to cellulose membranes have been described in detail [35, 6, 12] . After blocking with 5% skim milk in TBS-T at 37\u00baC for 2 h, the prion peptide membrane was probed with 3F4 at 1:10,000, 1E4 at 1:500, V14 at 1:100, or V61 at 1:10 in 1% skim milk for 2 h at 37\u00baC. The membrane was washed with TBS-T, then incubated at 37\u00baC with 1:4,000 HRP-conjugated sheep anti-mouse IgG for 1 h. After a final wash and developing with ECL Western blotting detection reagent (Amersham Pharmacia), the membrane was visualized by using Bio-Rad Fluorescent Imager. The control membrane was probed only with HRPconjugated sheep anti-mouse IgG without primary antibody.", "After removal of the media, cells were rinsed three times with PBS and lysed in 1.2 ml of lysis buffer on ice for 30 min. The cell lysates were centrifuged at 1000 g for 10 min at 4\u00baC to remove nuclei and cellular debris. The supernatant was incubated with 5.5 ml of prechilled methanol at -80\u00baC for 2 h and centrifuged at 14 000 g for 30 min at 4\u00baC. The pellet was resuspended in 100 \u00b5l of lysis buffer." ] },{ "paper_id": "7f2079d6e5244be0e38c55fe08a1c1672ab645fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "3. The infection must replicate sufficiently in a zoonotic case to produce infectious virus in respiratory or other secretions.", ". technological limitations in molecular modeling and phenotypic assays that limit confidence in predicting and measuring viral traits (Russell, 2014) ;", ". uncertainties about the taxonomic level at which risk predictions should be made (Box 2);" ] },{ "paper_id": "7f2868688c3e1140f573628312738e2222fe5dfd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the lipid extraction, 100 \u03bcL of serum were vortexed with 1 mL of methanol containing stable isotope internal standards ( [16] [17] [18] . Next 1 mL of water and 2 mL of methyl-tert-butyl ether were added and the tubes were vigorously shaken at room temperature for 30 min. The tubes were next centrifuged at 5,000 xg for 15 min at room temperature and 1 mL of the upper organic extracts was dried by centrifugal vacuum evaporation and dissolved in isopropanol: methanol: chloroform (4:2:1) containing 7 mM ammonium acetate. Constant infusion lipidomics were performed utilizing high-resolution (140,000 at 200 amu) data acquisition, with sub-millimass accuracy on an orbitrap mass spectrometer (Thermo Q Exactive) with successive switching between polarity modes.", "The cations and anions of bromocriptine were used to monitor for potential mass axis drift. Between injections, the transfer line was washed with successive 500 \u03bcL washes of methanol and hexane/ethyl acetate/chloroform (3:2:1) to minimize potential ghost effects.", "Supporting information S1 Table. (XLSX)" ] },{ "paper_id": "7f3006a21336451caedf41ab1791299a49831cc1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Molecules 2019, 24, x 6 of 30 have therefore explored the technically more challenging approach of GCE for incorporation of single modified amino acid residues.", "Of note, some retroviruses could potentially increase the efficiency of modified deoxynucleotide incorporation into their genomes by degrading SAMHD1. The triphosphohydrolase SAMHD1 converts dNTPs to deoxynucleosides and inorganic phosphate, depleting intracellular dNTP pools, and thus impairing retroviral reverse transcription [92] . Some retroviruses, e.g., HIV-2 or simian immunodeficiency viruses encode the accessory protein Vpx which mediates proteasomal degradation of SAMHD1, and thereby increases dNTP levels. Depending on the specificity of SAMHD1 for the deoxynucleoside derivative used, this may also enhance intracellular levels of clickable dNTPs.", "The chemistry of the ncAA and clickable dye are also of relevance for measurements within virus-producing cells, in particular for live-cell experiments. A high rate constant of the click reaction is of fundamental importance when labeling intracellular POI for live-cell observation. Furthermore, low rate constants necessitate high dye concentrations to achieve reasonable labeling efficiencies, which will also promote unspecific attachment of dye to intracellular membranes and proteins. The resulting background may impair the sensitive detection of individual viruses or subviral structures. In addition, side reactions of ncAAs bound to aminoacyl-tRNA synthetase may occur, requiring extensive and prolonged washing of samples to remove non-incorporated ncAAs [47] . These concerns are less relevant when GCE modified viruses are purified and labeled in vitro." ] },{ "paper_id": "7f302add8b117514b8393d55f49c3ded276faf94", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Researchers can accelerate the collective pace of learning with greater attention to reporting comparable data. There have been a number of efforts to encourage the use of common data elements [46] . Standardized outcome data are particularly problematic for patient-reported outcomes. To address this problem, there have been consensus measurement efforts such as PhenX [47] as well as efforts to co-calibrate various patient-reported outcome measures on a single metric [48] .", "Large future investments are now being considered that could offer extraordinary opportunities for researchers and a faster, more efficient infrastructure for rapid learning research. The NIH Director has proposed a new national patient-oriented research system with electronic health records databases, including genomics, for 20-30 million patients [44] , and PCORI recently released a funding announcement to support development of the National Patient Centered Clinical Research Network [10] . The Big Data to Knowledge (BD2K) initiative [45] also provides the opportunity to leverage these large data sets for rapid research.", "Traditional study designs and procedures are wellestablished, rigorous, and notoriously slow and costly. This belabored research process typically begins with pilot trials that we posit have limited benefit, are used inappropriately to estimate effect size [14] , and often prematurely concretize a less than optimal intervention. Instead, we recommend replacing the traditional pilot trial with a more flexible iterative intervention testing and optimization approach, analogous to the agile software development process that places a premium on failing early to succeed later [15] . For example, N-of-1 trial designs provide intervention development flexibility. With the increasing availability of intensive longitudinal data from wireless sensors and mobile devices, N-of-1 trials can be rapidly implemented and provide results congruent with a more personalized medicine approach [16] , and Bayesian analyses from a series of such trials [17] may provide sufficient evidence of generalizability to limit the need for a larger trial.", "Intervention optimization designs such as fractional factorial and sequential multiple assignment research trials (SMART) are particularly valuable when the intervention development questions involve combinations or sequences of intervention components [18] . Dynamic system models have also been used to optimize treatments [19] . Some optimization approaches may take more time than the traditional pilot trial, but the pace of the overall research enterprise will be improved by more quickly discarding or modifying interventions that are unlikely to be found effective in larger and more expensive trials." ] },{ "paper_id": "7f3106f6c5402784319dd722bbbaaa5f5b59df1f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ": ifA i 2 fD; Eg", "D\u00f0n; n\u00de \u00bc", "PpcA-C, PpcE Node Vs. Node 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 1 * * * * * *" ] },{ "paper_id": "7f3637433b7c8dff7fc35f0b5e67794877bce0c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Alpaca immunization and blood collection were performed on one clinically healthy 4-year-old male alpaca (Vicugna pacos) on the \"Russian Alpacas\" Farm, private land located in Pokhodkino, Moscow Region, Russia. This sample collection did not involve endangered or protected species, and no specific permissions were required for these locations/activities.", "A total of 39 clones showing ELISA readouts higher than 0.2 ( Figure 3a ) and negligible reactivity with bovine serum albumin (BSA) were selected for sequencing. A total of 15 clones with different CDR3 amino acid sequences were selected for further research." ] },{ "paper_id": "7f3e18a9a954832a2335fa3c26c42f127a79855c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The statistical significance of differences between groups was evaluated by the unpaired Student's t test and indicated with *** P,.001, **/## P,.01, */# P,.05. All statistical tests were twosided.", "Protein extracts were separated on SDS-PAGE and electroblotted onto PVDF membranes according to standard procedures. The membranes were blocked with 5% nonfat dry milk and incubated with the respective primary antibodies: AKT, p-AKT, c-Myc, ERK, JNK, MEK, p38, and GAPDH obtained from Santa Cruz Biotechnology Inc. (Santa Cruz, CA) as well as p21, p27, p-ERK, p-JNK, p-MEK, p-p38, p-STAT1(Y701), p-STAT1(S727), STAT1, p-STAT3(Y705), p-STAT3(S727), STAT3, p- ", "Total RNA was isolated from HL60 cells treated with dasatinib or vehicle, using the Trizol reagent (Bio Basic Inc., Markham, Ontario, Canada). RNA was transcribed into cDNA using random hexamer primers and RevertAidTM M-MuLV Reverse Transcriptase (Fermentas International Inc., Burlington, Ontario, Canada). Equilibrated amounts of cDNA were taken for transcript PCR amplification, which was performed using SYBR Premix Ex Taq (Takara Biotechnology, Dalian, China). The housekeeping gene GAPDH was used as an internal standard. Primer sequences used for the PCR were as follows: RIG-G: Forward 59-AACTACGCCTGGGTCTACTATCACT-39, Reverse 59-ACACCTTCGCCCTTTCATTTC-39 [21] ; CXCL-10: Forward 59-GAATCGAAGGCCATCAAGAA-39, Reverse 59-GCTCCCCTCTGGTTTTAAGG-39 [22] ; GAPDH: Forward 59-GTCATCCATGACAACTTTGG-39, Reverse 59-GAGCTT-GACAAAGTGGTCGT-39 [23] . The PCR protocol consisted of thermal cycling as follows: initial denaturation at 95uC for 2 min, followed by 40 cycles of 95uC for 20 s, 58uC for 30 s, and 72uC for 30 s using an Eppendorf epGradient Mastercycler (Eppendorf, Hamburg, Germany). In all experiments, two negative controls were carried through all steps. Data quantitation was performed using the relative standard curve method [24] ." ] },{ "paper_id": "7f5ef8185f8934ab5b5eb4344dad20da84d104a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The nucleotide sequences of the NS1 gene were compared with those of HBoV strains available at the GenBank site. Phylogenetic analyses were conducted with MEGA, version 4.1. The 3/18 partial sequences of the NS1 gene were submitted to GenBank (accession numbers JX982976-JX982978). ", "The study protocol was approved by the medical ethics review board of the College of Medicine, Taif University and by the pediatric hospital ethics committee in accordance with the guidelines for the protection of human subjects. Informed written consents from the next of kin of the participants involved in the study were taken.", "To the best of our knowledge, this is the first report of HBoV1 in Saudi Arabia. Continuous surveillance and genome sequence analysis are needed to obtain more information on the genotypic variation and molecular evolution of HBoV in the country.", "The current study aims to screen the epidemiological status and molecular phylogeny of HBoV isolates prevailing in pediatric patients with respiratory infection in Saudi Arabia.", "Partial NP-1 gene sequence of the eighteen detected HBoV strains were obtained in our study. Multisequence analysis showed complete identity (100%) between each other, and phylogenetic analysis demonstrated that they belonged to HBoV1 (data not shown). Blast analysis revealed complete homology to the published sequence of HBoV1. Furthermore, the phylogenetic analysis results of three selected sequences showed that the Saudi HBoV1 strains obtained from respiratory samples belonged to group I human bocaviruses (Fig. 1) ." ] },{ "paper_id": "7f62acc34c68b857a7bf8a4868fdd75d312720e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The collected swabs were placed in viral transport media, stored and transported at 2-8uC to the icddr,b virology laboratory on the same day of collection. We tested swabs for RSV, influenza A and B viruses, human metapneumoviruses (HMPV), adenoviruses and human parainfluenza viruses (HPIV) 1-3 by real time reverse transcription polymerase chain reaction (RT-PCR) [primer/probe sequences and assay protocols for non-influenza respiratory viruses available from CDC upon request] [16] . Influenza A positive samples were further characterized for seasonal influenza A(H1N1), A(H3N2), A(H1N1)pdm09 and A(H5N1) using real time RT-PCR [16] .", "A pathogenic bacteria was isolated from blood cultures of 4 (6% [95% CI 2%-15%]) of 64 hospitalized cases. The pathogens included Streptococcus non pneumococcal species, Enterococcus faecalis, Acinetobacter hemolyticus and Candida species.", "The study team obtained written informed consent from the parents of the SARI cases. Icddr,b Institutional Review Board (Research Review Committee and Ethical Review Committee) approved the research protocol. CDC Institutional Review Board reviewed and approved reliance on icddr,b IRB approval." ] },{ "paper_id": "7f67490473a643ff59b8ad115149846bc36825ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ScienTific REPORTS | 7: 12194 | DOI:10.1038/s41598-017-12477-2", "i. Amyotrophic lateral sclerosis.", "In all cases, p \u2264 0.05 was considered significant." ] },{ "paper_id": "7f67a850db06d9b9e3f63d9943e2b1fc5a72ca8f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.ppat.1007046.g001", "and/or by using inducible expression systems. The advantages of optogenetics so far have far outweighed the stated concerns, as evident by its exceptional success." ] },{ "paper_id": "7f6d6d5cf7a484c164c955ff15a32758e1ab3943", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After collecting the test data from the formal questionnaire, we coded, collated, and stored the data in a computer in the form of data files. Statistical analysis was conducted using SPSS for Windows. Cronbach's \u03b1 and Kuder-Richardson reliability were used to test all sub-scales and their reliability, which ranged between 0.6579 and 0.8689, thus indicating good internal consistency among all the scales and sub-scales in this questionnaire.", "After collecting the questionnaires, Cronbach's \u03b1 was immediately applied to test the reliability of each scale; these results are shown in Table 1 .", "Conceptualization: CJC WKC.", "The Severe Acute Respiratory Syndrome (SARS) epidemic in 2003 revealed the years-old defects in Taiwan's health care and medical education systems [1] . After the epidemic subsided, the Ministry of Health and Welfare proposed a plan to reform the training of clinical doctors and officially announced the implementation of the Postgraduate Year Medical Training Project for Training Doctors in Response to the SARS Epidemic in July 2003 [2] . The project aimed to gradually rectify excessive and premature specialization in the training system of resident doctors and thus required all first-year resident doctors to undergo Postgraduate Year program training." ] },{ "paper_id": "7f7e7b0bb3f8e89fed253891b5632236d20a4cb7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Participants were scheduled to undergo assessment at the cardiopulmonary exercise laboratory in the Prince of Wales Hospital. Participants were asked to abstain from alcohol, any caffeinated drink and vigorous exercise for 24 hours prior to testing. They were also asked to eat only a light snack and drink only 0.5L of water within 3 hours of the test.", "Cardiopulmonary fitness is one of the most important predictors of lower cardiovascular and metabolic health risk and a valuable clinical diagnostic and prognostic tool. Identification of children who have relatively low cardiopulmonary function is important given improvements in cardiopulmonary function are possible with proper exercise training [43] ." ] },{ "paper_id": "7f8715a818bfd325bf4413d3c07003d7ce7b6f7e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .00898-18. TABLE S1, PDF file, 0.1 MB.", "Immortalized cell culture. CV-1 (African green monkey kidney) and 293T (human kidney epithelial) cells were grown in Dulbecco's modified Eagle's medium (DMEM) (Cellgro; Mediatech) supplemented with 10% fetal bovine serum (FBS) and antibiotics at 37\u00b0C in 5% CO 2 .", "altered to suit cultured cells and could no longer be considered clinical strains. There has been a relative dearth of sequence information available for HPIV compared to other respiratory viruses (23) , and more importantly a lack of information about strains prior to passaging in the laboratory and thereby being subjected to selective pressure." ] },{ "paper_id": "7f8fc0ff30e4455d834e829db27b8d529b2920df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Project name: HIV Clusters in Phylogenetic Trees Project home page: http://hiv.bio.ed.ac.uk/software.html Operating system(s): Platform independent Programming language: Java Other requirements: Java 1.6.0 or higher License: GNU GPLv3 Any restrictions to use by non-academics: no restriction" ] },{ "paper_id": "7f911fcc63f431561d8dc09ed831ce558ca2d773", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine epidemic diarrhea (PED), which is characterized by severe diarrhea, vomiting and dehydration, is a highly contagious enteric disease of swine and is caused by porcine epidemic diarrhea virus (PEDV) [1] . PED was first reported in England in 1971 [2] and the virus was identified in Belgium and United Kingdom for the first time [3] . Since then it has become prevalent in many swineraising countries and it is one of the most important viral causes of diarrhea, resulting in heavy economic losses to the swine industry, mainly in European and Asia [4] [5] [6] [7] [8] [9] [10] [11] . Although the commercial vaccines are available to prevent and control of disease, damage caused by PEDV infection is serious and continuous.", "Animal care and all procedures were performed in accordance with animal ethics guidelines and approved protocols. The animal experiment was approved by Harbin Veterinary Research Institute. The animal Ethics Committee approval number is Heilongjiang-SYXK-2006-032." ] },{ "paper_id": "7f923809d6875b38e21636801b4a50f8fbac6aef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were shown as mean values \u00b1 standard deviation (mean \u00b1 SD) and were compared by a one-way analysis of variance (ANOVA) and Student's t-test using SPSS 18.0 (SPSS Inc., Chicago, IL, USA) biostatistics software. p-values less than 0.05 were regarded as significant and those less than 0.01 were regarded as highly significant.", "30 ( ", "The authors have no conflict of interest to declare." ] },{ "paper_id": "7f9e15b30bfa7b75a43c5d9febf1b6f71240f80b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The swab kit contains the two swabs (two polyurethane foam tipped swabs on plastic shafts with break points, mounted on a single plug (swab tip 15 mm, shaft 110 mm, handle 30 mm) and clear plastic 13 mm diameter 84 mm long tubes, one with a purple cap for bacteriology testing (containing \u2211 TRANSWAB liquid Amies medium) and one with a green cap for virology testing (containing \u2211 Virocult virus transport medium and 3 plastic beads). The kit is provided in a sterile peel pouch.", "The authors declare that they have no competing interests." ] },{ "paper_id": "7fa2f5a443163614e02fa7b7d7c89fa535dc7b23", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were expressed as means \u00b1 SD. All statistical analyses were carried out using SigmaPlot\u00ae10.0 software (Stystat Software, CA), with a P value of <0.05 considered statistically significant.", "Background: Tick-borne encephalitis virus (TBEV) is one of the most important flaviviruses that targets the central nervous system (CNS) and causes encephalitides in humans. Although neuroinflammatory mechanisms may contribute to brain tissue destruction, the induction pathways and potential roles of specific chemokines in TBEV-mediated neurological disease are poorly understood." ] },{ "paper_id": "7fb385f3c0c5ce04f1c3d3c4f20678c0ae3a7031", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The conclusions from the interviews on the extent of knowledge among the respondents were then used to generate suitable domains for the questionnaire.", "The questionnaire is self-administered and consisted of open-ended and closed-ended questions and was well received by participants. There was a total of four domains in the final questionnaire consisting of 80 questions, the domains were (1) demography of participants;", "In this study the internal consistency (IC) of the items was measured by using Cronbach's alpha coefficient." ] },{ "paper_id": "7fbdfc090a8be95eb166a2d66dd91b7a51d11570", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "7fcbdac915f32c243a9c8bc7cc086b2ac65416af", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animal experiments were reviewed and approved by the Shandong Agriculture University Institutional Animal Care and Use Committee and performed in accordance with the Guidelines for Experimental Animals maintained by China's Ministry of Science and Technology. The research did not involve endangered or protected species, and animal suffering was minimized to the greatest possible extent.", "Male BALB/c mice were purchased from Shandong University Laboratory Animal Center. All animal experiments were conducted in a Biosecurity Level 2+ laboratory, with mice kept on a 12-h light-dark cycle in controlled temperature (23-25\u00b0C) and humidity (40-60%). Animals were allowed free access to tap water and regular rodent food. Mice that were 6 weeks old and weighing about 13 g at the beginning of the experiments were used. All animals were sacrificed by lethal sodium pentobarbital injection.", "The experiment was performed using six BALB/c mice per group.", "Frontiers in Immunology | www.frontiersin.org June 2016 | Volume 7 | Article 252" ] },{ "paper_id": "7fd0972f4d5eb0e4c7ec68efad48fc01a1f547c2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reporting summary. Further information on research design is available in the Nature Research Reporting Summary linked to this article.", "Protein production. The gene for SARS-CoV nsp12 encompassing the 931 N-terminal a.a. was chemically synthesized with codon optimization (Genscript).", "Received: 21 February 2019 Accepted: 2 May 2019" ] },{ "paper_id": "7fd0d03264447b79984a3a48e12470e08df672d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It is noteworthy that chronic colitis is a risk factor for colon cancer. Interestingly, a few reports have shown that exogenous and endogenous GLP-2 is a potential cancer promoter in mice models, although reduced inflammation was also observed (94, 95) . This might be resulted from the strong preference of GLP-2 for epithelium proliferation. Therefore, the surveillance of dysplasia and colon cancer must be vigilant in GLP-2 treatment.", "Here, we will discuss in-depth the actions of DPP-4/GLP axis in IBD.", "It is well accepted that dysregulated immune response plays a critical role in colitis (7-10). Tumor necrosis factor-\u03b1 (TNF-\u03b1) is a well-studied cytokine that is implicated in the pathological progression of human IBD. Inhibition of TNF-\u03b1 activity by anti-TNF-\u03b1 antibody has been widely Incretin in Inflammatory Bowel Disease Frontiers in Immunology | www.frontiersin.org" ] },{ "paper_id": "7fd305aac7f42ec53e85db85ac74f2d2a8ba8dd6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "7fd8ed092a2b2e87a796cc59ccf3f7122c05fd44", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All datasets generated for this study are included in the article/Supplementary Material.", "The animal study was reviewed and approved by The Ethics Committee and the Laboratory Animal Care and Use Committee of South China Agricultural University.", "EZ, JC, and MZ conceived the study. EZ, WC, YQ, SM, and SF performed the experiments. EZ, SM, JC, and MZ analyzed experimental results and data. WL, JF, KW, LY, and HD assisted with animal experiment. EZ wrote the manuscript. All authors read and approved the final manuscript. " ] },{ "paper_id": "7fd909b06fcb46cf45b5d099741e4a86138ac6f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Categorical variables are reported as numbers and percentages, and continuous variables are reported as medians and interquartile ranges (IQR) or as means and standard deviations (SD), depending on their patterns of distribution. All statistical analyses were performed using IBM SPSS software (version 22.0; IBM Corp., Armonk, NY), and graphs were created using Prism 5 software (GraphPad software, San Diego, CA). A two-tailed P-value of less than 0.05 was considered statistically significant.", "Supporting information S1 " ] },{ "paper_id": "7fddc064e4c4aac26961aa413f27193ad175095b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "7fdea1d57d5d3d0ee393379c8437b0393f0ce542", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Infectious diseases are a major threat to human health and remain among the leading causes of death and disability worldwide [1] . In the last decade, a variety of viruses such as Ebola virus, Hendra virus, Nipah virus, West Nile virus (WNV), and severe acute respiratory syndrome (SARS)and Middle East respiratory syndrome (MERS)-coronaviruses have emerged or re-emerged, all of which are of zoonotic origin [2] [3] [4] [5] ." ] },{ "paper_id": "7fedb6619c6cdd969d50307211e7a77aeb9a8893", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Only those viral species with copy number more than a threshold are selected for the next module.", "We were interested in exploring all viruses existing in humans. So we first obtained reference genomes of all known and sequenced human viruses obtained from NCBI 2 (745 viruses) and merged them into one file (referred to as the \"viral reference file\") in fasta file format (Wikipedia, 2004) . This file has been shared in our Github page.", "In detail, we saw several important findings as described below:", "Frontiers in Microbiology | www.frontiersin.org" ] },{ "paper_id": "7ffbca7e7e60e13461801769ad70f770879d0f81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Specimen collection and analysis. Nasopharyngeal swabs from both the left and right nasal cavities were collected from each participant using a Minitip flocked swab (Copan Diagnostics, Murrieta, CA). The samples were jointly stored in 2 ml DNA/RNA Shield (Zymo Research, Irvine, CA) for up to 30 days at 4 to 25\u00b0C and were subsequently divided into 2 aliquots and stored at \u03ea80\u00b0C until assay. Nucleic acids were extracted from 200-l samples, with the addition of 10 l of MS2 bacteriophage as an internal control, using an easyMAG NucliSENS system (BioM\u00e9rieux, Durham, NC). Samples were tested for infection using a multiplex PCR assay known as an eSensor XT-8 respiratory viral panel (RVP; GenMark Diagnostics, Carlsbad, CA) according to the manufacturer's instructions.", "Positive samples were identified using a threshold of 25 nA/mm 2 . The viruses detected by the XT-8 RVP include influenza A (any subtype), A/H1N1, A/H3N2, and AH1N1pdm2009 virus and influenza B virus; RSV A and B; PIV 1, 2, 3, and 4; hMPV; HRV; adenovirus B/E and C; and CoV 229E, NL63, OC43, and HKU1." ] },{ "paper_id": "80013c44d7d2d3949096511ad6fa424a2c740813", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Monocytes were purified from buffy coats of healthy donors (Karolinska University Hospital) using a RosetteSep\u2122 monocyte purification kit (Stem Cell Technologies) and Ficoll-Hypaque Plus (Amersham Biosciences) gradient centrifugation. Human MDDCs were seeded at 0.5-1 \u00a5 10 6 cells ml -1 in R10 (RPMI 1640, 2 mM L-glutamine, 10% FCS) supplemented with GM-CSF (40 ng ml -1 ) and IL-4 (40 ng ml -1 ) for 6 days. Cells were given fresh media and cytokines at a ratio of 1:1 on day 4, and cultured until day 6. The human MDDC phenotype was assessed by examination of CD11c and CD1a expression using allophycocyanin (APC)-conjugated mouse anti-human CD11c and fluorescein isothiocyanate (FITC)-conjugated mouse anti-human CD1a (BD Pharmingen). MDDCs used in these experiments were above 93% CD1a/CD11c + .", "Total RNA of MDDCs was isolated by using the RNeasy kit (Qiagen). Reverse transcription was performed by using the Quantitect RT kit (Qiagen) and generated cDNA was used for subsequent real-time PCR mRNA levels of human g-actin (QuantiTect primers QT00996415) and viral M1 (Kash et al., 2011) were detected using a QuantiTect SYBR Green PCR kit (Qiagen) and a QuantiTect Probe PCR kit (Qiagen) respectively. Real-time PCR was performed applying an ABI 7500 PCR system. Reactions were performed in duplicates and the Ct values were normalized to g-actin. DDCt method was applied to calculate the 'fold' induction relative to uninfected control cells.", "The influence of the different treatments and infections on the viability of the MDDCs was monitored using a cytotoxicity detection kit (Roche). Briefly, cell culture supernatants were collected and assayed for the presence of lactate dehydrogenase. The assay was performed according to the manufacturer's instructions." ] },{ "paper_id": "8013bbf01944aa3f25d0faf16386ea51c7586066", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "801aad4fa6fab8d6d0973eb4df2178454195e037", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Eight to ten weeks male C57BL/6 mice, weighing 16 " ] },{ "paper_id": "80229bc73fc274591a2f0c6472a0d8c6fb966dd0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Control (scrambled) siRNA and siRNA targeting ADAP2 (5'-GGACUGGUUCAAUGCC CUC-3') were purchased from Sigma.", "Rabbit anti-MAVS antibody was obtained from Bethyl Laboratories. Mouse anti-HA antibody, mouse anti-V5, goat anti-EEA1 and rabbit anti-GAPDH HRP-conjugated antibodies were purchase from Santa Cruz Biotechnology. Mouse anti-VSVG (P5D4) and mouse anti-DENV (clone D3-2H2-9-21) antibodies were purchased from Santa Cruz Biotechnology and Millipore, respectively. Alexa Fluor 488 or 594 phalloidin and Alexa fluor-conjugated secondary antibodies were purchased from Invitrogen.", "Data are presented as mean \u00b1 SD unless otherwise stated, and were analyzed with Prism software (Graphpad) by two-tailed unpaired Student's t-test. A p value <0.05 was considered significant." ] },{ "paper_id": "8029841b3e6b0267188b9c527b0e02dc472b9fdc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 5:11479 | DOi: 10.1038/srep11479" ] },{ "paper_id": "802ec789744669d95c380885412457a648a10e0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The further characterization of HCV trafficking signals has the potential to support the design of selective viral NLS/NEStargeted molecules with pangenotypic antiviral activity, targeting conserved regions among the HCV genotypes. Potentially, the same holds true for the discovery of new pieces of the cellular transcriptional puzzle altered by HCV, which may further help to forecast therapeutic outcomes after antiviral treatment.", "Therefore, both core and NS5A can localize in the cell nucleus and modulate transcription, promoting cell survival. In addition, NS5A also promotes immune evasion, while core specifically increases the translation rate of infected cells via increased ribosome biogenesis.", "It remains to be investigated how the two Kap-mediated transport systems affect each other in HCV-infected hepatocytes and whether trafficking to VFs differs from nuclear import at the molecular level. For sure, the striking news about HCV life cycle is that Nups do work outside the physiological environment of the NE during viral infection. The molecular basis responsible for functional and regulatory differences between the NPCdependent transport systems located on VFs or NE are elusive at present (including the role of the GTPase Ran in VF import), which requires further experimental efforts." ] },{ "paper_id": "803e5ac0891c5ae6a165ca754e04fcfbb6e06394", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "China and provide warning guidelines for the future when provinces fall into the risky windows. These findings revealed integrated predictive meteorological factors rooted in statistic data that enable the establishment of preventive actions and precautionary measures against future outbreaks.", "Group1 " ] },{ "paper_id": "8041d586dc357d38fb7e13f528d400a14ae64b8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Not only in humans but also in feline medicine, the use of type I IFNs as immune modulation therapy is common, particularly in retroviral infections [17] [18] [19] .", "Recognizing that, in clinical practice, rFeIFN-\u03c9 is very often a cost-limiting therapy, the use of an alternative oral protocol in FIV-infected cats has also been documented [25] . In fact, different authors reported the clinical benefits of oral low dose HuIFN-\u03b1 protocols in viral infections such as FIV [19, 21] .", "In clinical practice, the initial therapeutic approach in cats suspected of retroviral infections is always supportive and symptomatic. When the diagnosis of retroviral infection is established, antivirals and immune modulators can be considered on short-and long-term management. Taking into account that most of these drugs are licensed for use in humans, there is a lack of well-controlled clinical trials in cats and their efficacy is not entirely clear [1, 2] ." ] },{ "paper_id": "804533d11a3f44908f514922d18f2a79826471c2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The membranes were developed using the ChemiDoc-It TM TS2 Imaging System, and relative optical density was analyzed using Quantity one v4.4 software (Bio-Rad).", "All statistical analyses were conducted using SPSS 14.0 software. The BBB scores for each animal were averaged and used to determine the group mean each day. The BBB score data were expressed as mean \u00b1 SD. Comparisons among groups were performed by one-way analysis of variance (ANOVA) followed by a Tukey-Kramer multiple comparisons post hoc test.", "The authors declare that they have no conflicts of interest." ] },{ "paper_id": "804a9591280b7f64fa79cd3e4a9358976b084ffb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "804df67d9b05a58b34332c92efec930254f5ebe3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author of this manuscript completed the literature review and developed the manuscript without assistance. There were no contributors in the preparation and development of this manuscript. No funding was required to complete this work.", "An emerging concept regarding BOS is the possibility of autoimmunity rather than alloimmunity to hidden epitopes of collagen type V. These epitopes are exposed as a result of ischemia and reperfusion injury or other insults that may damage the respiratory epithelium [53] . Further research is ongoing to investigate these important findings.", "The author declares that they have no competing interests. " ] },{ "paper_id": "80514d274dfaa180080c8eb0bb261c0af5c95c49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human norovirus is estimated to account for a fifth of all acute gastroenteritis cases worldwide 1 , costing $2.8-$3.7 billion in annual economic losses in the U.S. alone 2 . Norovirus is especially troublesome in healthcare settings, as outbreaks result in consumption of resources, extended hospital stays, ward closures, and high morbidity 3 . Thus, early detection of clinical infection is important as it can facilitate more rapid implementation of rigorous controls, which can result in reduced health care costs and improved public health 4 .", "Development and Screening of RT-RPA primer and probe sets. Forty-eight combinations of candidate primers (8 forward and 12 reverse) were generated and screened for reactivity to purified GII.4 New Orleans RNA. Of these, 8 primer sets were identified as capable of amplifying target RNA, and a probe (NOP1) was", "RT-RPA reaction conditions. RT-RPA reactions were carried out using the TwistAmp exo RT kit (TwistDx Inc.)." ] },{ "paper_id": "8055b4c692a2717a904b71e948926aaf953896e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Specimens from sick pigs were homogenized and diluted five times in Dulbecco's Modified Eagle's Medium with a low concentration of glucose. Samples were then centrifuged at 5000 rpm for 10 min at 4 \u00b0C. Supernatants were stored and subsequently used for RNA extraction. For each PEDV sample, total RNA was extracted from 100 to 300 \u00b5L aliquots of supernatant using ReliaPrep \u2122 RNA Cell Miniprep kits (Promega Corpoation, WI, USA) in accordance with the manufacturer's instructions.", "Pairwise alignment of field Japanese PEDV isolates demonstrated high nucleotide and amino acid sequence identity between strains (99.1-100.0 and 97.2-100 %, respectively). Notably, 42 field PEDV isolates collected from 3 prefectures in this study had identical partial S gene sequence (100 % nucleotide homology). Japanese ", ", and 632 (L \u2192 F) as shown in Fig. 1 ." ] },{ "paper_id": "805dabb68b67c8ccf18480c096ffbff3fb90a745", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The most commonly reported symptoms among episodes of disease were respiratory (93.9%), including coughing, sneezing/runny nose, sore throat and dyspnoea, in decreasing order. Other disease episodes included: fever (90.5%), headache (63.2%), body aches (41.1%), and digestive disorders (11.3%), including diarrhoea and vomiting/nausea.", "Episodes of disease. HRSC members were instructed to notify a contact person (a medical doctor or a nurse)", "Human and animal sampling. Consenting HRSC members are sampled at recruitment (baseline sampling)" ] },{ "paper_id": "80637e7403f730cb2e22a4af53fade48a1e42a87", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Enterovirus 71 (EV71) is a highly infectious agent that plays an etiological role in hand, foot, and mouth disease. It is associated with severe neurological complications and has caused significant mortalities in recent large-scale outbreaks. Currently, no effective vaccine or specific clinical therapy is available against EV71.", "All data were expressed as means \u00b1 standard deviation (SD). Statistical analyses were performed using one-way ANOVA followed by Dunnett's post-hoc test. Differences with a P-value less than 0.05 were considered to be statistically significant (P < 0.05)." ] },{ "paper_id": "806a1df203eb5126eec25561bd4cb1b10df18c53", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BKV immune escape PLOS Pathogens | https://doi.", "Ninety-six transplanted patients between 2012 and 2013 from the Strasbourg University Hospitals (France) with high levels of post-transplant BKV viruria-as detected by routine BKV testing at the hospital's clinical virology laboratory-were enrolled in this study. Sixty-eight patients underwent kidney transplantation, 12 were lung recipients, 3 received double (kidney-heart; heart-lung or kidney-pancreas) transplants and 13 hematopoietic stem cell transplantation. A total of 225 samples, including 197 urine (from 94 patients) and 28 whole blood (from 13 patients) were included. Urine samples were collected longitudinally for 36 patients.", "All patients were enrolled in the study following the Helsinki guidelines. Written informed consent for genetic testing was obtained from all patients and the study was approved by the Strasbourg University Hospitals institutional review board (RNI DC-2013-1990)." ] },{ "paper_id": "80779b91bf8ddc59dc5391db98f6df3dc4bf930c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "3. Subspecific assignment/identification. It involves cases related with breed, variety, or populations such as \"was the attack perpetrated by a dog or by a wolf?\"", "Although microbes have long been recognized as important players in our daily life, present in areas such as medicine and public health, ecology, and in industrial applications, microbial forensics (MF) is still a relatively recent scientific field [168, 169] .", "Plant evidence can provide crucial information for the reconstruction of forensically relevant events or in cases where the crime scene and autopsy reports are not compelling [152] .", "Below, we begin by describing the commonly used methodologies, including genotyping and sequencing strategies, evolutionary frameworks, and statistical approaches. Next, we broadly describe applications of NHFG based on diverse biological sources. Finally, we discuss the future of the discipline, including needs and recommendations." ] },{ "paper_id": "80850d03f16060e460bd50e5622e2196c0622f54", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:24782 | DOI: 10 .1038/srep24782 TKM-Ebola-Guinea drug trial is an outcome of the collaborative efforts of Tekmira (a Canadian company) and Oxford University; unfortunately, the clinical trial was halted recently as therapeutic benefits to the patients were not observed after reaching the predefined endpoint 19 .", "Sequence of Genomes. We downloaded the protein, and mRNA sequences of five ebolaviruses:" ] },{ "paper_id": "8086b478a036f07fc6a809c63dc7d52acb659fe1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Flaviviruses are small, enveloped, positive-strand RNA viruses that infect a wide range of hosts. Flavivirus genomes are markedly smaller than coronaviruses at approximately 10-12 kb in size, and the transmission of most flaviviruses is dependent upon an arthropod vector (hence their common name, arboviruses). Flavivirus diseases range from asymptomatic to severe neurological disease such as encephalitis, meningitis, and myelitis [53] . Yellow fever virus (YFV), a deadly flavivirus associated with over 30,000 deaths annually (WHO), was identified in 1901 by Walter Reed and was the first human viral pathogen ever discovered [54] [55] [56] . Outbreaks and disease connected to flaviviruses have stressed the importance of developing reverse genetic platforms and efficacious vaccines.", "For many years, the trivalent vaccine that is currently provided consisted of three separated strains (2 A strains and 1 B strain), which were selected based on the WHO recommendations prior to the next flu season. However, these vaccines were made using either live-attenuated (through cold-adaptation) or inactivated virus grown in fertilized chicken eggs. Next generation vaccination strategies include tetravalent or quadrivalent vaccines, which may be grown in animal cell cultures (rather than chicken eggs) or virus-like particles (VLPs) in cultures of S. frugiperda insect (Sf9) cells [122] [123] [124] [125] [126] [127] [128] [129] . In 2013, the FDA approved a seasonal influenza vaccine comprised of purified HA proteins prepared using a baculovirus-expression system [130] . These recombinant vaccines were successfully used to vaccinate individuals between 18 and 49 years of age and represents a major step in influenza vaccine design and implementation because this system reduces production time compared to the conventional egg-based approach [131] .", "Coronaviruses are enveloped, positive-strand RNA viruses which encode the largest known RNA virus genomes varying in size from 26 to 32 kb [40] . Coronavirus infections in humans are associated with upper and lower respiratory illness ranging in severity from the common cold to severe acute respiratory syndrome (SARS). Over the last 12 years, four new human coronaviruses have been identified including SARS coronavirus and the recent Middle East respiratory syndrome (MERS) coronavirus [41] . Despite a high clinical and economic burden and potential for emerging infectious disease, no commercially available vaccines currently exist." ] },{ "paper_id": "8088d74438c31d5ca8f976c21ae9167c5c682d14", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data were collected in a Microsoft Excel5 database. A descriptive analysis was performed for continuous variables (median, 25th and 75th percentiles). Data distribution was checked using MedCal Statistical Software (Version 17.4 MedCalc Software, Ostend, Belgium).", "The associations between qualitative variables were evaluated with Chi-square test. Results were deemed as significant ", "Moreover, specific allergen-avoidance measures should also be addressed to all sensitized patients, for example, removing furry animals from the house in case of pet dander allergy, encasing mattresses in allergen-impermeable covers to reduce house dust mites exposure, cleaning from surfaces indoor molds using bleach solutions, and reducing pollen indoor exposure by closing windows and doors during high pollen counts in pollen allergic patients [29] ." ] },{ "paper_id": "808dfc4c59f3e2e9150aa5542ea227718741388b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In order to study the efficacy of coronavirus-based vectors in vivo, a small animal model is desirable. Therefore, we first established a reverse genetic system for MHV. Again we made use of vaccinia virus as cloning vector to stably propagate the full-length cDNA of MHV (strain A59). Recombinant viruses obtained from this cDNA clone were indistinguishable from the parental MHV-A59 strain in tissue culture (growth kinetics, plaque size and RNA synthesis) and in MHVrelated disease models in mice (Coley et al. 2005) .", "We have established a reverse genetic system for coronaviruses that allows the generation of recombinant coronaviruses (Thiel et al. 2001a (Thiel et al. , 2003 Coley et al. 2005) . One of the main advantages of our system is that the cloned full-length coronavirus cDNAs are amenable to site-directed mutagenesis using vaccinia virusmediated homologous recombination. This technique is well established and has been proven to represent an efficient and precise (on the nucleotide level) method to genetically modify recombinant coronavirus cDNAs. In Figure 1 , we show one example to demonstrate the ease of using vaccinia virus-mediated recombination to genetically modify coronavirus cDNA inserts.", "The E-and M-expressing cell lines can now be used to package MHV vector RNAs that encode (in addition to the replicase gene and the 5 0 and 3 0 cis-acting elements required for replication) the MHV structural proteins S and N (nucleocapsid protein). Therefore, we have generated a prototype MHV vector, designated MHV-Vec-A, containing the replicase gene, the 5 0 and 3 0 cis-acting elements required for replication, the structural protein S, the immunodominant CTL epitope GP33 of LCMV glycoprotein as a fusion protein with the green fluorescent protein (GP33-GFP) and the nucleocapsid protein. This vector RNA is currently being used to thoroughly assess the efficacy of VLP production in individual EM-packaging cells.", "Prevention of HIV infection. The thorough knowledge of the biology of HIV that has been generated over the last two decades has paved the way for a rational vaccine design. Furthermore, the progress in the understanding of the basic immunological mechanisms underlying antigen presentation (Steinman and Pope 2002) , lymphocyte trafficking and activation (Luther and Cyster 2001) , and immunological memory (Kaech et al. 2002) has been instrumental for the identification of the relevant parameters that ensure the induction of protective antiviral immunity. Accordingly, an efficient HIV vaccine should induce long-lasting, broad humoral and cellular responses against the immunodominant HIV antigens. In particular, the vaccine should (i) target and activate DCs, (ii) contain the immunodominant antigens recognized by CTL and Th cells, (iii) be able to display antigenic determinants that induce broadly neutralizing antibody responses, and (iv) be applicable via mucosal surfaces." ] },{ "paper_id": "808eb805948a72da00d370c274656653679536b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Flag-tagged human domain antibody m36 was expressed in E. coli HB2151 as described previously [18] . In brief, the bacterial pellet was collected after centrifugation at 5,000 g for 10min and resuspended in PBS (pH 7.4) containing 0.5 million-unit polymixin B (Sigma-Aldrich). After 30 min incubation with rotation at 50 rpm at room temperature, it was centrifuged at 25,000 g for 25 min at 4uC. The supernatant was used for purification of m36 by immobilized metal ion affinity chromatography by using Ni-NTA resin (Qiagen, Valencia, CA) according to manufacturer's protocols.", "Louis, MO, USA) was added. The absorbance was measured at 450 nm.", "Conceived and designed the experiments: YH. Performed the experiments: CW JS WC XY HC PP. Analyzed the data: CW YH. Contributed reagents/materials/analysis tools: WC DD. Wrote the paper: CW WC DD YH." ] },{ "paper_id": "8095e2bbc38cfeb18180deca4796293f5ce24eae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NIH3T3 cells (ATCC CRL-1658) were propagated in Dulbecco's modified Eagle's medium (DMEM) supplemented with glutamine and 10% Newborn Calf Serum (NCS). 293T cells (ATCC CRL-11268) were propagated in DMEM supplemented with glutamine and 10% Fetal Calf Serum (FCS). All cells were grown at 37\u00b0C, 10% CO 2 and 95% humidity.", "The confocal images were captured with a Leica TCS SP confocal Microscope (Leitz). YFP and Rhodamine were excited individually using argon laser 488 nm line and green helium neon laser 543 nm line, respectively. The two single-color images were subsequently merged into an RGB-image. Brightness and contrast were adjusted." ] },{ "paper_id": "80993091f576dc7fdbec10552b45b4af5eec2b8b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: K.R. and G.C. conducted forecasts and data analysis; Y.L. retrieved and managed data; all authors contributed to writing and revising subsequent versions of the manuscript. All authors read and approved the final manuscript.", "Funding: G.C. is supported by NSF grants 1610429 and 1633381." ] },{ "paper_id": "80a03c5cca3549c6bedad185f73950ce1213bf1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "80a278b4912f11c65a1e2ecc75897b6609f6820e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "80a735987ea3897dc5e33a859e1a80310babb2da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "First a cDNA strand was generated using Superscript II RT (Invitrogen, Carlsbad, CA). A 10 ul reaction consisting of 10 ug of RNA, 2 uM of primer, 10 mM dNTP mix, and H2O was incubated at 70\u00b0C for 10 minutes. Following incubation, 5\u00d7 RT buffer, 0.1 M DTT, RNA guard (RNase) (40 U/ul), and Superscript II RT (200 U/ul) were added respectively. The reaction was incubated in a H 2 O bath at 42\u00b0C for 50 minutes followed by a second incubation in dry bath at 70\u00b0C for 10 minutes. Amplification of specific target sequences in the cDNA was performed using 10 \u03bcl cDNA, forward and reverse primer pairs, dNTPs, Taq polymerase buffer and Taq-polymerase in thermocycler (Applied Biosystems) with cycling conditions of 94\u00b0C, 10 min followed by 35 cycles of 94\u00b0C, 1 min, 55\u00b0C, 1 min, 72\u00b0C, 1 min. Presence of the amplicon was analyzed on a 1%-2.5% agarose gel in 1\u00d7 TAE buffer. ", "DNA was precipitated from the supernatant by isopropanol, washed by 70% ethanol and air dried. The DNA was re-hydrated in nuclease free water and stored at -20\u00b0C for subsequent PCR work.", "The PCR product was purified from an agarose gel and ligated into TOPO vectors (Invitrogen, Carlsbad, CA) according to manufacturer's instruction. Cloned plasmid DNA was purified from transformed E. Coli using Wizard \u00ae " ] },{ "paper_id": "80a8911f3ccc06ddfc7581569014032487688283", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "List of abbreviations RT-qPCR: real-time reverse transcription polymerase chain reaction.", "Obtainment of MRCV-infective planthoppers and sample processing", "Isolation of partial sequences of candidate Delphacodes kuscheli genes for the design of qPCR primers" ] },{ "paper_id": "80ab1037161868297a622ae5e5e24a7f91d10bf5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Historical circumstances make this case a unique natural experiment well-suited to mathematical modelling and statistical inference for multiple reasons: (i) moderate size and free social mixing of the community under study, (ii) full isolation of the community throughout the epidemic rules out the hypothesis that a second influenza virus was introduced from outside, (iii) incidents of influenza in the community were remarkably low and uniform before the 1971 epidemic, and (iv) the daily reported incidence counts are almost exhaustive [13] ( \u00a72a).", "Our predictive simulations emphasize the paramount role of demographic stochasticity in the multiple-wave infection dynamics on this small island. In particular, given the elevated risk of epidemic fade-out during the low-prevalence inter-wave period, we find that only a stochastic framework can accurately assess alternative reinfection hypotheses.", "In their original paper from 1973, Mantle & Tyrrell [13] proposed that this two-wave epidemic could have been caused by either the initial introduction of two separate viral agents or reinfection by the same viral agent. Although this second hypothesis appeared to them as the only possibility, they were unable to determine whether antigenic changes in the virus had occurred, allowing for second infection, or whether some patients did not acquire an efficient immune protection and either suffered a recrudescence of infection or were reinfected by other patients. We expand upon these possibilities as follows:", "Our study reveals that, when demographic stochasticity is appropriately accounted for, the second epidemic wave can only be explained with mechanisms attributable to delayed or deficient humoral immune responses. Our strictly mechanistic interpretations enable us to quantitatively compare our results with empirical data and we close with an evaluation of the potential genetic and ecological determinants of variation in host susceptibility.", "The generation time (average time between primary and secondary cases) can be estimated by the sum of the mean latent period plus half the mean duration of infectiousness [31] . ML estimates under the two best models are 3.2 days (Win) and 3.3 days (AoN) and in agreement with those previously published for A/H3N2 [32] ." ] },{ "paper_id": "80ae0645a59c66f34ce7fe53fba4a00404b1c740", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1) ''infectious tolerance'': Infection tolerance is an in vivo process in which tolerance is transferred from one group of lymphocytes to another. In this way, short-term treatment aimed at producing infection tolerance may lead to long-term, self-sustaining immune homeostasis in clinical settings (Kendal & Waldmann, 2010) . IL-35 plays an important role in infection tolerance (Olson, Sullivan & Burlingham, 2013; Tao et al., 2015) .", "The authors received no funding for this work.", "We used CiteSpaceV to analyze keywords. Over a period of time, a knowledge map of the cooccurrence of keywords may reflect hot topics, whereas trending keywords may indicate frontier topics. Generating a visual knowledge map of keyword cooccurrence resulted in 130 nodes and 431 links (Fig. 5) . The strongest citation bursts keywords were as follows: ''central nervous system,'' ''dendritic cell,'' and ''IL-27'' (Fig. 6 )." ] },{ "paper_id": "80ae2988547a9163342117a914b53b6a63487901", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The mutagenic PCR conditions were as follows: 50 mM KCl, 10 mM Tris (pH 8.3 at 25uC), 7 mM MgCl 2 , 0.3 mM MnCl 2 , 1 mM dCTP and dTTP each, 0.2 mM dGTP and dATP each, 0.2 mM of each primer, 20 pM of template DNA and 10 units of Taq polymerase in a 10 ml reaction volume in 10 aliquots. The PCR was performed for 30 cycles at 94uC for 1 min, 50uC for 1 min, and 72uC for 1 min in a conventional thermal cycler. Three overlapping ,300-500 bp N-, central-and C-terminal segments of the TEF1 gene were amplified separately by PCR using primer pairs: #2767 (GTT-TCAGTTTCATTTTTCTTGTTC)/#2788 (GAGTCCATCT-TGTTGACAG), #2787 (CATCAAGAACATGATTACTGGT-AC)/#2790 (GACGTTACCTCTTCTGATTTC) and #2789 (CGGTGTCATCAAGCCAGGT/#2771, (TTCGGTTAGAGC-GGATGTGG), respectively.", "One of the major advantages of studying TBSV replication is the availability of genomic and proteomic datasets on virus-host interactions [4, 5, 6, 7, 10, 15, 25, 26, 27] . For example, systematic genome-wide screens of yeast genes have revealed that TBSV repRNA replication is affected by over 100 different host genes [5, 7] . Additional genome-wide screens with TBSV also identified ,30 host genes affecting TBSV RNA recombination [4, 6, 28] . The identified host genes code for proteins involved in various cellular processes, such as translation, RNA metabolism, protein modifications and intracellular transport or membrane modifications [3, 5, 7] .", "Fractionation of the whole cell extract was done according to [52] . The total extract was centrifuged at 21,0006 g at 4uC for 10 min to separate the ''soluble'' (supernatant) and ''membrane'' (pellet) fraction. The pellet was re-suspended and washed with buffer A (30 mM HEPES-KOH pH 7.4, 150 mM potassium acetate, and 5 mM magnesium acetate) followed by centrifugation at 21,0006 g at 4uC for 10 min and re-suspension of the pellet in buffer A. In vitro TBSV replication in the fractions was performed as described [31] ." ] },{ "paper_id": "80b0747661793f45be4bc78da3223c63354331ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Black grain eumycetoma represents the most common fungal mycetoma worldwide. This chronic, erosive infection of subcutaneous tissues particularly affects the lower extremities and leads to severe disability [1] . The disease is considered a major health problem in tropical areas and is prevalent among people of low socio-economic status [2] .", "Mycetoma presents as a subcutaneous mass with multiple sinuses that discharge pus, serous fluid and grains, i.e. the characteristic compact grains of the causative agent formed inside the lesion [3] .", "The sensitivity of the RCA probes was also determined by 10fold serial dilution of MYC and MFAH probes tested with amplified ITS of M. mycetomatis and M. fahalii respectively." ] },{ "paper_id": "80beb71c4b247cf32525097f28568b49f71cf08b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Haemagglutinin-tagged GSK3\u03b2 wild-type plasmid (HA-GSK3\u03b2 wt pcDNA3) was a gift from Jim Woodgett (Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada) (Addgene plasmid #14753) (He et al., 1995) . Transfection of GSK3 constructs for overexpression was performed with a final DNA concentration of 0.75 \u00b5g/ml using X-tremeGENE HP DNA transfection reagent (Roche Diagnostics, Mannheim, Germany).", "Total RNA extraction was done using RNeasy Mini Kits and miRNeasy Mini Kit for mRNA and micro-RNAs, respectively (Qiagen, Hilden, Germany). Reverse transcription of mRNA and micro-RNA was performed using the PrimeScript RT reagent kit (Takara Bio, Otsu, Japan) and the TaqMan MicroRNA Reverse Transcription Kit (Applied Biosystems, Foster City, CA, United States), respectively.", "Frontiers in Microbiology | www.frontiersin.org 5 -TACTCA CCGGTTCCGCAGA-3 , HCV TaqMan probe, 5 -TCCTGGAGGCTGCACGACACTCA-3 . TaqMan Gene Expression Assay containing the pre-designed primers and TaqMan probe from Applied Biosystems was used for GAPDH. For miR-122 and miR-16, pre-designed primers (Assay ID no. 2245 and 2420, respectively) from Thermo Fisher Scientific were employed. For HEV, the procedure and primers have been previously described (Dao Thi et al., 2016) . Results were calculated using the 2 \u2212 CT method and shown as fold change compared to control." ] },{ "paper_id": "80c9179236f8b034ec0763a86209141ea894b2ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Of the 11 countries contacted, 8 Table S1 ).", "Influenza is responsible for substantial morbidity and mortality worldwide. About 3-5 million cases of severe influenza disease and 250,000-500,000 deaths occur every year [1] . Among the most affected risk-groups are young children, pregnant women, the elderly and persons with chronic illnesses. A recent review estimates that each year over 250,000 African children aged less than 5 years are hospitalized with influenza and have influenza-associated hospitalization rates more than 3 times higher than those of children in industrialized countries [2] .", "We found no association between peak month and monthly percent positive. However, because countries provided aggregate monthly data and, not weekly aggregate data, we cannot say if there would be significant correlations using weekly aggregate data. Additionally, for this analysis, we grouped data from ILI and SARI surveillance in all participating countries. Grouping data in this way may have affected the outcomes of this analysis." ] },{ "paper_id": "80ce020acc7d023a1bc60a5f42c2afc937e3a200", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 177 nasopharynx specimens of 177 patients were collected and analyzed. Ninety-eight (55.4%) patients were males and 79 (44.6%) were females. The median age was 8 months (range 3 days to 16 years). Thirty-five (19.8%) children had an underlying medical condition. Demographic characteristics of the patients are presented in Table 1 .", "All samples had been spiked before extraction with internal control viruses, Phocine Herpes Virus (PhHV; DNA virus), and Phocine Distemper Virus (PDV; RNA virus) to monitor efficient extraction and amplification. For each target a positive and negative control was used. (RT)-qPCR results were expressed in cycle threshold (Ct) values. Ct values are inversely correlated with viral load, i.e., low Ct values indicate high viral loads." ] },{ "paper_id": "80e940d11337db34b2dc48dc4002c5d79aff96d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Utilizes libraries with the artificially expanded genetic code.", "Immobilization of target and aptamers required.", "Time consuming (many rounds required).", "Poor recognition of the unnatural bases by natural DNA polymerases." ] },{ "paper_id": "80ea83eb20c374075380eadb6df930f2d356ea62", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The term ''zymogen'' refers to an inactive enzyme precursor that is converted to its active form following a biochemical modification, usually proteolytic processing. Among the known and important groups of enzymes that are activated in such a way are the cysteine aspartic acid proteases (caspases) which play an essential role at various stages of the apoptotic process [1] ; secreted digestive enzymes like pepsin and trypsin [2, 3] and blood coagulating factors [4] .", "The following Escherichia coli strains were used: XL-1 Blue (Stratagene, USA) for plasmid propagation and Rosetta (DE-3) (Novagen, USA) for expression of the T7 promoter-driven recombinant toxins.", "Until these days, vaccination is considered to be the most efficient method for fighting viral infections. However, active vaccination is generally taken as a prevention act and usually when the patient is still uninfected. Moreover, for some viral pathogens which cause world-wide health problem like human immunodeficiency virus (HIV) and HCV, no efficient vaccine had yet been developed." ] },{ "paper_id": "80eae3b5b1d0ba7f1806d637628b15ae10e342c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "80f244134084f44bfc86bbe102f338d18e219dbc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: F.S. and J.Y. composed this review paper.", "Vegetables also contain a variety of phenolics; for instance, parsley and celery possess apigenin, chrysin, and luteolin, and broccoli has a considerable amount of quercetin, kaempferol, and myricetin, leading to their potent inhibition of inflammation and different types of cancers such as gastric, breast, and prostate [109] .", "Coumarins show a variety of bioactivities such as anti-inflammatory, antimicrobial, antiviral, antioxidant, antitumor, antiasthmatic, antidepressant, anti-HIV, and anti-Alzheimer's [11] [12] [13] [14] . In addition, coumarin possesses anti-coagulant activity, which inhibits blood coagulation by suppressing the hepatic biosynthesis of vitamin K-dependent coagulation factors. Thus, coumarin is also used as an anticoagulant for the treatment of diseases such as thrombotic phlebitis and pulmonary embolism." ] },{ "paper_id": "8103f6b3e1b33043c0a2836e1e5c45cf80e665a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "810749401200c77f19d5a7950070e0c2d4d2629e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments were performed at least three times with reproducible results. Data are presented as mean \u00b1 standard deviation (SD). Statistical analysis was performed using oneway analysis of variance (ANOVA) without interaction terms followed by Dunnett's for multiple comparisons. A P-value of <0.05 was considered statistically significant.", "For co-immunoprecipitation analysis, Cells were washed with phosphate-buffered saline and lysed for 20 min at 4\u00b0C in lysis buffer containing 50 mM Tris-HCl, pH 7.4, 150 mM NaCl, 1% NP40, 10% glycerin, 0.1% SDS, and 2 mM Na 2 EDTA. Lysates were then cleared by centrifugation, and proteins were immunoprecipitated with affinity antibodies and protein A+G agarose beads (Beyotime, China) at 4\u00b0C. Immunoprecipitates were washed three times with 1 mL of lysis buffer. The precipitates were analyzed by standard immunoblot procedures.", "(TIF) " ] },{ "paper_id": "811159783691dd3e398010444f7b1564bc885d08", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at www.mdpi.com/1660-4601/14/12/1571/s1. Table S1 : The material types and areas of surfaces. Table S2 : Transfer rates between surfaces of different materials. Table S3 : First-order inactivation rates at different sites. Table S4 : Behavior frequencies and assumed touching surfaces during the behaviors. Table S5 : Other parameters. Figure S1 ", "Gellert et al. [19] suggested airborne transmission mainly to explain the lack of evidence of direct fecal contact among several cases of infection. However, as the fluorescence experiments [36] indicated, contaminants can spread to remote areas via the surface contamination network, wherein most contaminant transport between surfaces does not require direct contact with the original source.", "Norovirus was first reported in 1968 and has since placed a considerable disease burden upon economies and societies worldwide [1] [2] [3] . This pathogen, which is characterized by high excreted viral loads [4] , remarkable environmental survivability [5] , extreme infectivity [6] and short-term immunity [7] , is now a leading cause of acute gastroenteritis across all age groups [1] and is responsible for approximately 685 million cases and 200,000 deaths annually worldwide [2, 8] ." ] },{ "paper_id": "8111c472b27463ca0dfae56c5196eb4c92fdd14f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The CQ administered during immunization had no effect on the challenge infection, since all control mice that received CQ-prophylaxis showed the same prepatent period as untreated na\u00efve mice.", "Challenge infections were performed by intravenous injection of 10,000 or 50,000 sporozoites around four or eleven weeks after the end of CQ/MQ prophylaxis. Giemsa-stained blood smears were screened for parasitized red blood cells every other day from days 3-14 and finally on day 21 after challenge. Protection was defined as the absence of blood-stage parasites until day 21 post-challenge (Additional files 1A, B and C)." ] },{ "paper_id": "811ba28ec90198a294812d7b1deadf16b4fc66ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experimental protocols were approved by the institutional committee of Fudan University. All methods were carried out in accordance with relevant guidelines and regulations. Informed consent was obtained from all subjects.", "K on (M -1 s -1 ) = 8.41\u00d7 10 5 K off (s -1 ) = 3.33 \u00d710 -3" ] },{ "paper_id": "8125e22d2dc5ad5fe51394fc08dc89212c833d2c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .01524-18.", "DATA SET S1, XLSX file, 0.03 MB. " ] },{ "paper_id": "8126e29c1a00af5300f325021430faf4dfecbdc0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We are interested in estimating R and how it evolves over time as new cases are reported. That is, we want to know the probability distribution of R that best fits the available data. From Bayes theorem:" ] },{ "paper_id": "812cc3ff2d36c2d370f943c6fd0d2d45b918296e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HR and GH contributed equally to the writing of the manuscript. MS, TJ, and DB also helped to write the manuscript.", "We would like to thank USDA-AFRI award #2016-67015-24911 and also the Department of Food Science and Nutrition and the College of Food, Agricultural and Natural Resource Sciences at the University of Minnesota for providing the funds needed to perform and complete this study.", "Though it was previously proposed that the entire SFB lifecycle occurred while attached to the host tissue (Chase and Erlandsen, 1976) , filaments containing intracellular offspring have not been observed in published TEM and SEM images of filaments attached to enterocytes (Caselli et al., 2010) ." ] },{ "paper_id": "8133996ea269ebe90ba8c1715cf462607997d975", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The probabilities express how likely an individual changes its states at a step, and thus highly depend on how long a step takes (called unit time t). These probabilities were calculated as below.", "Scientific RepoRts | 6:31484 | DOI: 10.1038/srep31484", "Our simulation starts with one of the individuals (called index individual) being exposed and the others being susceptible, and stops when no individuals are exposed or infectious. To remove the potential biases in index selection and state transition, a total of 10,000 simulations were performed with index individuals selected at random." ] },{ "paper_id": "8134e0946079f5ef0bbbd7b65ce13657483b8160", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Another level of understanding will also come with solving the structural mechanisms of virus-CRL interactions. Although recent structures have helped initiate these studies, very little is known about the stoichiometry, orientation and subunit contacts with viral proteins in CRL complexes with a few exceptions (such as the SV5-CRL4 interaction [56] ).", "Great strides have been made over the past decade in defining CRL mechanisms. A key advance in this understanding came with the solving of a number of high-resolution CRL structures [21, 90, 92, 93] .", "HBx CRL4 Causes genome instability through an unknown mechanism [64, 66] * also includes mumps and para-influenzavirus; 1 Four ectromelia proteins: EVM018, EVM027, EVM150 & EVM167.", "Murid herpesvirus-4 (MuHV-4), which causes mononucleosis in infected mice, expresses its ORF73 protein to target the NF\u021bB family member RelA/p65 for proteasomal degradation. To do this ORF73, using a non-conventional SOCS-box motif, forms an active complex with CRL5. This inhibition of NF\u021bB by RelA degradation is critical for the amplification of latent MuHV-4 and persistent infection within the host [39] .", "Ubiquitination occurs through a direct transfer of ubiquitin from the ubiquitin bound-E2 enzyme to a specific lysine residue of the substrate via the formation of a covalent bond. Repeated ubiquitination cycles lead to the poly-ubiquitination of the substrate (Figure 2 ; [80] ).", "Further interesting evidence of a Group-I virus targeting CRL3 was uncovered in a recent host genome-wide RNAi screen with Vaccinia virus (VACV, the smallpox vaccine). This screen successfully identified two CRL components: Cul3 and Rbx1 as being required for viral replication. This also points towards a role for CRL3 in driving replication of certain viruses [25] . Identification of the mechanism and affected substrates (if any) in these cases will help decipher the physiological role of CRL3-VACV interactions in vivo." ] },{ "paper_id": "813d4108f75af14e71c3b9fdc9281c30ba90b39e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8142d13b88328405d5302f1e899e5c2a8c1df196", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pathogen ARSs induce immune responses", "The innate immune response helps the body resist deviant native cells and foreign organisms, which is the key to maintaining health. Typically, each person may be infected with hundreds of pathogens during their lifetime, which will not cause diseases under normal immune function conditions. New evidence suggests that pathogen ARSs are associated with host immune responses.", "Actually, the incorporation of tRNA Lys into the virion was closely related to its interaction with KRS 95 . When KRS in the infected cells was specifically inhibited, the resulting virus showed reduced tRNA Lys packaging and tRNA Lys,3 annealing to viral RNA. In particular, the tRNA Lys incorporation was dependent on the ability of KRS to bind to tRNA Lys , rather than its ability to aminoacylate tRNA Lys96 . Furthermore, KRS bound to a tRNA-like element located near the primer-binding site within the HIV-1 genomic RNA, thereby facilitating efficient annealing of tRNA Lys,3 to viral RNA prior to reverse transcription [97] [98] [99] (Fig. 3a) . All together, these studies strongly elucidate that KRS plays a major role in HIV-1 assembly." ] },{ "paper_id": "8147b5b09a09887d1b4c4871d9d49746d8c4d418", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "S. aureus (ATCC 25923) were purchased from Wenzhou Kont Biology and Technology. The bacteria were grown in tryptic soy broth at 37\u00b0C with 250 rpm shaking for overnight. After centrifugation at 6000 rpm for 10 min, the pellet was resuspended and subsequently washed with sterile phosphate-buffer saline (PBS) for two times. The pellet was then diluted with PBS to an appropriate cell concentration as determined by spectrophotometry at 600 nm.", "Results were expressed as means \u00b1 SEM. Statistical analyses of data to compare the different groups were performed using SPSS version 16.0 software. Data for specificity of antibody, cytokine production and ELISPOT were analyzed using either one-way ANOVA or Student's ttest. Data for flow cytometry and bacterial load were analyzed by Mann-Whitney U of nonparametric Test. For comparison of survival in murine lethal challenge model, individual experiments were analyzed using log-rank test statistic (Mantel-Cox test) from the Prism software (Prism for Windows, version 5.01, GraphPad Software). Probability (P) values <0.05 were considered significant. 4 to 9 mice were used in each experiment and each experiment was repeated two or three times with consistent results.", "doi:10.1371/journal.pone.0136888.g007" ] },{ "paper_id": "814ec1dc13c5f446a41d1b3f1becb6495897455a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The family Polyomaviridae contains viruses that are among the smallest known to infect humans, in terms of both their particle sizes and genome lengths. The 40-45 nm nonenveloped icosahedral particles carry a circular doublestranded DNA genome of approximately 5000 bp, which is divided into three functional regions: the noncoding control region, the early gene region encoding the large T antigen and the small T antigen, and the late coding region, encoding capsid proteins VP1, VP2, and VP3 [1] ." ] },{ "paper_id": "814ecf9043112382eaae1310c6359ddc70557bba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "815b5e537a3e7bdb7d5c7c7cd51181b9b2e245c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An animal model of polyomavirus-induced CNS disease that mimics pathologic hallmarks of PML would circumvent these obstacles and enable us to address important unanswered questions, including:", "Mouse polyomavirus, the founding member of the Polyomaviridae family, is structurally and genomically similar to JCV, BKV, and SV40 polyomaviruses. All polyomaviruses consist of a doublestranded, covalently closed circular~5-kb DNA genome encapsidated by a non-enveloped icosahedral shell composed of 72 pentameric VP1 capsomers. The genomes of all polyomaviruses have a~500-bp NCCR containing the origin of replication bidirectional promoters separating the genome into early and late genes, with respect to the onset of viral DNA synthesis: an early region encoding the non-structural small T and large T antigens; and a late region encoding the viral capsid proteins VP1, VP2, and VP3. Unlike JCV, the MPyV genome does not encode an agnoprotein in its late region and contains an additional early region sequence encoding the non-structural middle T antigen, which mediates cellular transformation and tumor induction (116) .", "Several lines of evidence suggest that humoral immunity selects VP1 mutant polyomaviruses. Exposure of a library of VP1mutagenized SV40 variants to a neutralizing monoclonal antibody selected viruses with mutations in solvent-exposed loops of VP1 that were resistant to neutralization by this antibody (32) . BKV serotypes have been shown to vary in their level of crossrecognition by neutralizing antibodies generated by VLP immunization (33) . Interestingly, BKV isolates from kidney transplant patients with nephropathy and viremia also had a high frequency of VP1 substitutions (34) . These findings raise the possibility that VP1-specific neutralizing antibody responses select variant polyomaviruses with mutations in VP1 that enable escape from antiviral humoral immunity. Whether T cell immunosuppression/modulation favors neutralizing antibody-driven selection of such polyomavirus escape variants is unknown." ] },{ "paper_id": "8161866d70fb76ec6e2c5d78f06c2884b92fb39e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "816189230d6a7194892b0f10e0dcdd3a6a025647", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine epidemic diarrhea virus (PEDV), which belongs to the genus Alphacoronavirus and the family Coronaviridae, is an enveloped single-stranded positive-sense RNA virus [1, 2] . PEDV is a highly effective pathogen responsible for causing porcine epidemic diarrhea (PED), a disease characterized by severe and acute watery diarrhea, dehydration and vomiting that results in high mortality rate of one-week-old piglets [3, 4] . Since the first appearance in England in the early 1970s, outbreaks of PED have been reported in several European and Asian countries [5, 6] . PED was first reported in China in 1973, followed by a large-scale outbreak of PED in December 2010 that led to heavy economic loss [7, 8] . Therefore, it is of great importance to properly and routinely monitor PEDV.", "Absorbance of the HRP-based ELISA was measured using a Synergy H1 Hybrid Multi-Mode microplate reader (Bio--Tek Instruments, Inc., Winooski, VT). The following equipments were also utilized in this study: centrifuge 5810 R (Eppendort, Germany), XW-80 Avortex Mixers (Shanghai, China), magnetic stirrer (Beike, Beijing), dynabeads MX mixer (Invitrogen, America), programmable strip cutter HGS201 (AUTOKUN, China), XYZ3060 platform (Bio-Dot Scientific Equipment, China), and electrothermal forced air convection drying oven (TAISITE Instrument, China)." ] },{ "paper_id": "816359485f5bb752e2024fae9fe790cc1ff80f81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Effects of parameter settings on capture of database structure fragments", "Effects of parameter setting on capture of database structure fragments", "LGA_S cutoff 55%, and window_size/distance_cutoff combinations 50/2.5\u00c5, 70/3.5\u00c5, 80/4.0\u00c5, and 90/4.0\u00c5." ] },{ "paper_id": "816fc25c7f0997c17db295c0a77b18b1a2375338", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The general idea of vaccination is to resemble a viral infection but avoiding the associated pathology. There are several strategies to address this goal with varying efficacies. Currently approved viral vaccines for use in humans are listed in Table 1 . They have resulted from one out of three main types of vaccine design strategies referred to as (i) live attenuated vaccines, (ii) inactivated vaccines, and (iii) recombinant vaccines and peptidederived vaccines.", "Overall, only few antiviral drugs targeting viral proteins are currently approved for use in humans [32] . Viruses that can be fought with chemical compounds include HIV, influenza virus, RSV, HCV, HBV, and the herpes viruses, including herpes simplex virus, varicella-zoster virus (VZV), and cytomegalovirus.", "List of abbreviations used HIV: human immunodeficiency virus; HCV: hepatitis C virus; HVB: hepatitis B virus; RSV: respiratory syncytial virus; SIV: simian immunodeficiency virus; FMDV: foot-and-mouth disease virus; Ad5: adenovirus serotype 5 vector; LAV: live attenuated vaccine; IV: inactivated vaccine; NA: neuraminidase; HA: hemagglutinin; MHC: major histocompatibility complex; UPGMA: Unweighted Pair Group Method with Arithmetic mean; MRCA: most recent common ancestor; CTL: cytotoxic T lymphocyte; HLA: human leukocyte antigen; LD: linkage disequilibrium; PDNs: phylogenetic dependency networks; CBNs: conjunctive Bayesian networks; ODE: ordinary differential equations; HI: herd immunity.", "The experimental and theoretical results indicate that less virulent strains are more efficient in outcompeting the virulent ones in coinfected cells. Therefore, the fitness of variants of different virulence is density-dependent [168] . The cell competition model offers an explanation of several previous observations of suppression of high fitness mutants in dissimilar viral systems [169] [170] [171] [172] . This density-dependent selection due to varying efficiency of viral replication alone or in coinfection is reminiscent of the concept of a competition-colonization trade-off in ecology [173] . Here, virulent viral variants play the role of colonizers and viruses efficient within coinfected cells are competitors. The attenuating effect of competitor-colonizer competition appears even more pronounced if many viruses from a broad spectrum of virulence are considered." ] },{ "paper_id": "8171299fc5073dfe98c4c56d5760ccb5f802f8f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Is A 4 Enrichment Involved in Translation Initiation?", "Genome sequences of 3,731 bacterial genomes were downloaded from the European Molecular Biology Laboratory (EBML) database (http://www.ebi.ac.uk/Tools/dbfetch/embl fetch? db\u00bcembl, last accessed 12th January 2016). Genomes were filtered to include one genome per genus to control for phylogenetic nonindependence (additional genomes of that genus were discounted) larger than 500,000 base pairs leaving 651 genomes. Of these, 646 used translation ", "Supplementary data are available at Molecular Biology and Evolution online.", "A simplistic model of protein-coding gene evolution assumes that amino acid composition is a reflection of selection optimizing the biochemical function of the encoded protein." ] },{ "paper_id": "81b992164d368b01c45fa3cc4ffd54d525e1d4b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "B19 exerted its G4 stabilizing activity also in the HSV-1 genome, where multiple G4s can form. Treatment with B19 led to a significant antiviral effect (IC 50 = 8 M), with reduction in viral DNA synthesis and late proteins production (69) .", "Despite its good solubility in aqueous solutions and strong G4 binding, poor permeability across biological barriers, which characterizes most G4 ligands, restrains B19 pharmacological application (104) . Nonetheless, B19 is still considered a reference compound in G4 research.", "Despite their high molecular weight, NDIs are highly versatile structures, suitable for further medicinal chemistry modifications to improve their pharmacological profile (124, 125) .", "Herpesviridae is a large family of viruses with long linear double-stranded DNA genomes. Among the nine herpesvirus species that can infect humans, at least five are extremely widespread, i.e. herpes simplex virus 1 and 2 (HSV-1 and HSV-2), varicella zoster virus, Epstein-Barr virus (EBV) and cytomegalovirus, which cause orolabial and genital herpes (63) , chickenpox and shingles (64), mononucleosis (65) and some cancers (66) . More than 90% of adults have been infected with at least one of these (63) . Herpesviruses also tend to display latent, recurring infections, with the virus remaining in some part of the infected organism and typically maintaining its genome as extrachromosomal nuclear episome (67) ." ] },{ "paper_id": "81bc2f3c1d93804b0abc16686fe66673dda487f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Numbers of strains Substitution models Clock models Tree prior models Evolutionary rates (95% HPD intervals)", "The studies involving human participants were reviewed and approved by the Research and Ethical Committees for the Use of Human Subjects of the National Institute of Infectious Diseases, Tokyo, Japan (No. 576). Informed consent was obtained from all participants, which was acquired from the subjects or their legally acceptable representatives for sample donation.", "This work was partly supported by a commissioned project for Research on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development, AMED (Grant numbers; 19fk0108103h0201 and 19fk0108033h0003) ." ] },{ "paper_id": "81bf72bed294b556985ff244cc7d00d7b0b2235e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "81cc511fb2f42c6f79346aab7b1277ee0a6e78a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data available from the Dryad Digital Repository: http://dx.doi.org/10.5061/dryad.f0k4j ", "Supporting information S1 Appendix. (DOCX) " ] },{ "paper_id": "81d66de97e0d60ca4e91efa3aa95f684b914a865", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The project was reviewed by CDC's Human Subjects Research Office and approved as a public health evaluation activity." ] },{ "paper_id": "81ef62610df1e107053f06e2fa745a33912e299f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plus-stranded +RNA viruses replicate in the host cells by recruiting a set of host factors, such as proteins, membranes and metabolites. The recruited host factors then perform novel functions to promote various steps during virus replication, including assembly of viral replicase complexes (RCs) on intracellular membranes [2] [3] [4] [5] [6] [7] [8] . The outcome of the viral infection is that many original cellular processes and pathways are \"rewired\" during viral infections, rendering the cells dramatically different from the uninfected ones. +RNA viruses can also induce anti-viral responses by infected host cells, leading to the activation of the innate immune responses. Altogether, viruses are successful pathogens because they can reprogram host cell metabolism to support the infection process and to suppress host defense mechanisms.", "Positive-stranded RNA (+RNA) viruses exploit host cell machinery by subverting host proteins and membranes and altering cellular pathways during infection. To achieve robust replication, some +RNA viruses, such as poliovirus (PV), build special intracellular compartments, called viral replication organelles. A recent work from the Altan-Bonnett laboratory [1] gave new insights into the formation of poliovirus replication organelles, which are unique subcellular structures containing many individual replication complexes as a result of dynamic cellular membrane remodeling.", "OPEN ACCESS" ] },{ "paper_id": "81f6d476d70cdce38efdd5e0448e565d78f4b85c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To obtain bronchoalveolar lavage fluid (BALF), mice were terminally anaethetised, and lungs were cannulated and inflated with 500 \u03bc L PBS. The liquid was retrieved and spun at 300 g for 10 min at 4 \u00b0C. Supernatants were obtained and kept at \u2212 80 \u00b0C till further analysis." ] },{ "paper_id": "820acf55c4e52411482f6eb44360ffa35288b89a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Histopathology testing was done at the Centers for Disease Control and Prevention, Atlanta, USA.", "Participants identified as patients were referred for free treatment at Hoima Regional Referral Hospital. To protect participants' confidentiality, personal information were de-identified during data analysis and the interview forms were locked up." ] },{ "paper_id": "820f3633db1b3b98889e6a0d257d10d385be85c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The US Food and Drug Administration (FDA) licensed the first RV vaccine (Rotashield\u2122) in 1998. However, this vaccine was withdrawn only one year later due to a common side effect, intussusception [3] . In recent years, two more live RV vaccines, Rotarix\u2122 (an attenuated human RV strain developed by GlaxoSmithKline) and Rotateq\u2122 (a pentavalent humanbovine reassortant developed by Merck) were licensed in several countries [4] [5] [6] . Yet the protective mechanisms of these RV vaccines have not been fully understood [7] .", "Authors' contributions HZ, LG and MW: constructed and characterized VLP2/6 and rAdVP6, immunized mice and evaluated the immune response. JQ: characterized VLP2/6 with electron microscopy. HZ and ZZ, JW: wrote the manuscript. ZZ, Zhou et al.", "Ninety-six-well polystyrene microtiter plates (Costar, Bethesda, MD) were coated overnight at 4\u00b0C with 0.1 \u03bcg/well VP6 antigen diluted in carbonate buffer after optimization of the experiments. Wells were washed three times with 0.05% (vol/vol) Tween 20 in PBS (PBS-T) and blocked with 200 \u03bcl of 1% BSA (Sigma, St. Louis, MO) in PBS (PBS-BSA) for 2 hours at 37\u00b0C. After washing, 100 \u03bcl/well of serum or stool homogenates diluted in PBS-BSA were added, and plates were incubated for 1 hour at 37\u00b0C to prevent non-specific binding. Subsequently, plates were washed and incubated for 1 hour at 37\u00b0C with 100 \u03bcl/well of horseradish peroxidase (HRP)-labeled anti-mouse immunoglobulin G (IgG) or IgA (Sigma, St. Louis, MO) at a dilution of 1:5000 in PBS-BSA. Color was developed by adding 100 \u03bcl/well of Sure Blue TMB (Sigma, St. Louis, MO) peroxidase substrate, and absorbance was read at 450 nm (A450) using an BioRad 550 ELISA plate reader (BioRad, Hercules, CA). Serums were two-fold serially diluted to determine antibody titers." ] },{ "paper_id": "82114e8ec9b0ac800be54578d1fd23d945209f12", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus isolation was conducted using embryonated duck eggs, and methods and procedures referred to Yun's report [28] . Briefly, the liver samples were homogenized in sterile PBS (pH 7.2) containing antibiotics (10,000 units/ml penicillin and 10,000 mg/ml streptomycin) to obtain a 20% suspension (w/v). After centrifuged at 10,000\u00d7g for 10 min, the supernatants were filtered through 0.2 \u03bcm Supor Membrane Acrodisc Syringe Filter (PALL, Ann Arbor, USA), and inoculated on the chorioallantoic membrane of 10-day-old duck embryos (0.2 mL/embryo). Embryos were incubated at 37\u00b0C and candled twice daily for 5 days. The allantoic fluids, allantoic membranes and embryos of dead duck embryos were harvested, homogenized, and centrifuged. The supernatants were diluted at 1:10 for further passage in the embryos. The supernatant fluid was stored at \u2212 70\u00b0C for further use." ] },{ "paper_id": "8213f353876b2eba6110eae70dae057a2f08b93f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics statement. Fish were maintained in Aquainnovo facilities in recirculating water at 15 \u00b0C under a photoperiod of 12:12 (light:dark) and fed a maintenance diet of commercial pellets once a day. Water quality indicators, such as dissolved oxygen, pH, nitrite, and ammonia, were analyzed periodically, and the measured values were acceptable considering the particular requirements of this species. All animal procedures were carried out under the guidelines of \"International Guiding Principles for Biomedical Research Involving Animals\" of European Union Council (2010/63/EU) and fulfilling the statements of the Animal Welfare Protocol (AWP) from Aquainnovo. All experimental protocols were approved by the ethical committee of the University of Concepci\u00f3n.", "Among the most well studied lncRNAs, Xist and Air epigenetically silence transcription by targeting chromatin-modifying complexes of particular genes in trans and cis isomers, respectively 9,10 . Other lncRNAs act at the post-transcriptional level. These include H19, which is the precursor of miR-675, a moderator of cell growth 11 ; and MALAT1, which forms a molecular scaffold for several proteins present in nuclear speckles and which regulates pre-mRNA alternative splicing 12 ." ] },{ "paper_id": "821adc5f0139622999cf4d6a2f622b51b15a07bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two hundred microliters of the cell culture supernatant sample were collected and inoculated into 24-well tissue culture plate with chicken embryo fibroblasts. Culture was incubated at 37 \u2022 C with 5% CO 2 and examined daily for the appearance of CPE.", "Since reads related to NDV were found abundantly in the phylogenetic tree by MEGAN analysis, corresponding sequenced reads of 453,417 were extracted, yielding an average NDV genome coverage of >4000\u00d7. The extracted paired-end reads were de novo assembled into contigs using accurate mode with MIRA version 4.9.6 [22] . The assembled contigs were subject to additional genome analysis by comparing with their corresponding closest relatives.", "Necropsy of the fresh female 75-cm long fetus with greyish edematous placenta revealed swollen body lymph nodes, excessive bloody fluid in thoracic and abdominal cavities, non-ventilated lung, and brownish fluid in the gastrointestinal tract. Histopathology showed marked edema of the organs and diffuse mineralization of the placenta with no inflammation. Moreover, no microorganism or viral inclusions were observed." ] },{ "paper_id": "82210c1cb5ac59acd1468cedcaf6fb8d951f4903", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "822233763421a1e054abbc49c00a8726cb3ebfe1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work did not involve any human participant and include any animal work that would require an ethics statement.", "Tomato plants of the susceptible cultivar Monalbo (INRA) were grown in containment growth chambers under 14 h light at 26uC, and 10 h dark at 24uC. Seeds were initially grown in batches and were transplanted to individual pots after 7 days. During development, plants were irrigated with 15:10:30 NPK+ oligoelements.", "Here, using a huge bank of viral recombinants generated randomly in vitro, and with a cloning system enabling straightforward biological testing, we challenge the general assumption described above. Because the numerous recombinants tested in this study were generated in the absence of any selection pressure, our results provide information on all recombinant types, regardless of whether or not they resemble those found in natural populations." ] },{ "paper_id": "823305045f63acc52d90c2a299b25fc8f4ebe587", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Combining Equations (1) and (2), and assuming uninformative priors for qi, gives,", "Pr Disease X | observed characteristics", "The authors declare no conflicts of interest." ] },{ "paper_id": "8233e375e79b4e93b9d9a614d44762dba52b342f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To detect other respiratory viruses, we used CDC protocols for molecular (PCR) detection of human influenzaviruses, human adenoviruses, human parainfluenzaviruses, human metapneumoviruses, hRSV, HSV1, coronaviruses (including SARS-CoV and MERS-CoV), and respiratory enteroviruses including coxsackieviruses." ] },{ "paper_id": "8235178d45091e3c395321a0af42c92ef0c504ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In brief, there are four main outputs expected from an initiative of this kind:", "(4) provision of a process-oriented evaluation and consolidation of adaptive and effective learning and teaching tools for building ecosystem approaches to health.", "Clearly livestock are important in poverty alleviation and health maintenance, but the threat of losing that source of income or possible infection of the livestock keepers themselves increases with each new outbreak of HPAI or other zoonotic disease." ] },{ "paper_id": "82441199a6d3222ad51244e351b5df2d53aecc0f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "82448eac471a17fd751603f9b91450b6961d3a0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To analyze the effect of LiCl on proliferation of cells infected with TGEV, MTT colorimetric assays were performed [19, 21, 22] . ", "PEDV and BRV used to infect Vero and MA104 cells in 24-well plates at 37uC for 1 h. Then the culture was kept at 37uC for 36- Table 1 . Information on primers and RT-PCR products. ", "To determine whether pretreatment of either cells or virus affects the viral infectivity, cells or the TGEV inoculum were treated with concentrations up to 25 mM of LiCl prior to infection. Subsequent infection of either LiCl-treated cells with untreated virus or untreated cells with LiCl-treated virus indicated that there is no inhibitory effect regardless whether infection was analyzed by plaque or MTT assays (data not shown).", "Transmissible gastroenteritis virus (TGEV) belongs to the family Coronaviridae and is one of the most important causative agents of enteric infections in pigs. The infection is associated with high morbidity in animals of all ages and with high mortality rates (up to 100%) in seronegative suckling piglets [1] [2] [3] . TGEV is an enveloped virus with a positive-stranded RNA genome approximately 28.5-kb in size, and it consists of four structural proteins: the spike (S), the integral membrane (M) glycoprotein, and the nucleocapsid (N) protein [1, 4, 5] . About two-thirds of the entire RNA from the 59 end comprise open reading frames 1a and 1ab, which encode a number of nonstructural proteins including the replicase. The 39 third of the genome contains the genes encoding the structural and some nonstructural proteins (59-S-3a-3b-E-M-N-7-39) [6] . The glycoprotein S is primarily responsible for inducing neutralizing antibodies and for initiating infection [7] [8] [9] . The appearance of porcine respiratory coronavirus (PRCoV), a respiratory mutant of TGEV has drastically decreased the risk of TGE in Europe, since neutralizing antibodies elicited by the avirulent PRCoV can provide cross-protection against TGEV infection [10] . In contrast, TGE prevalence is still reported and some TGEVs have been isolated in different parts of the world, e.g. in various geographical locations in China, implying that TGEV infection is still threatening pig industry [11] [12] [13] [14] .", "At present, several commercially available vaccines are commonly used for prevention of TGEV infection in China. However, current traditional inactivated and attenuated vaccines are less effective than desired due to failure of vaccination to prevent viral shedding or reversion of the attenuated to a virulent phenotype. The lack of therapeutical treatment of TGE underlines the importance of development of effective antivirals Lithium salts have been used to treat diseases such as 'gout and rheumatic gout', 'Bright's disease', epilepsy, syphilis, acute mania and depressive episodes [15] . There are several reports regarding the inhibitory effect of lithium salts on the replication of several DNA viruses, such as type 1 and 2 herpes simplex virus and vaccinia virus [15, 16] . More recently, we and another research group demonstrated that lithium chloride (LiCl) inhibits infection of cell cultures by infectious bronchitis coronavirus (IBV), an avian coronavirus [17, 18] ." ] },{ "paper_id": "8249b9b7e4846415737d263b7187056c4733ba39", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To illustrate the diversity within one specific phage set, Martha Clokie presented the work from her lab on phages that infect the gut pathogen Clostridium difficile [15] [16] [17] . They have identified sets of phages that target clinically-relevant and prevalent strains. Despite the most effective phage set being isolated from one geographical location, they are strikingly variable ( Figure 3 ) with very few identifiable genes in common.", "To conclude, phylodynamic methods using viral sequence data with time, space and species metadata reveal complex transmission patterns and can be used to understand, track, model and ultimately inform disease control measures.", "Using avian influenza as an example of a widespread multi-species disease system, it was shown that wild birds (wild Anseriformes) were responsible for long-range transmissions of highly-pathogenic H5N8, by using a combination of discrete host traits and continuous spatial traits on time-resolved phylogenetic trees [58] . Furthermore the clade to which the H5N8 strains belong is unusual because unlike the highly-pathogenic H5N1 strains, they reassort frequently, picking up different neuraminidase subtypes. By using both host and neuraminidase subtype as discrete traits, it was also shown that reassortment was preferentially occurring in Anseriformes species (ducks, geese, etc.).", "A major limitation for our ability to develop therapeutic phages and also understand fully the ways that phages impact bacteria is that the vast majority of phage gene functions are hypothetical or unknown. In bacterial genomes, there are around 25% unknown genes, or genes that have no known ascribed function, but in phage genomes, only around 25% of the genes are generally known! Thus, when trying to establish how phages specifically interact with their hosts, there is large number of genes of which we need to try and make sense." ] },{ "paper_id": "824c9c7d7d8c1ec672e85def94cee3bb471cb5a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We successfully constructed 120 RNA-seq libraries from UAFI samples (94 singletons and 26 pools) comprising a total of 195 individuals, and 58 RNA-seq libraries from afebrile apparently healthy control samples (34 singletons and 24 pools) comprising a total of 328 individuals (S5 Table) . Illumina sequencing generated a total of 3.71 billion 100 base pair (bp) paired-end reads. We analyzed these samples using a bioinformatics and computational pipeline devel- ", "We processed individual afebrile controls as described for UAFI samples; however, the method of pooling differed. We pooled and filtered unadulterated plasma (without AVL) samples and centrifuged them at 104,000 x g for 2 hours at 4\u00b0C. We resuspended the viral pellet in buffer and used it to construct libraries for sequencing. AVL denatures viral particles, thus preventing centrifugation of the particles. We have observed comparable results between samples inactivated by AVL and those that are not.", "EKV-1, EKV-2, and BASV cluster within the genus Tibrovirus", "We constructed RNA-seq libraries as previously described [10] . We prepared some of the libraries from extracted RNA for either single individuals (referred to as singletons) or from RNA pooled from several individuals (referred to as pools) (S2 Table) . We treated all samples with DNase. We primed RNA using random hexamers, or modified hexamers (5'-NNNNNNV-3' from Integrated DNA Technologies) if carrier RNA was present in the sample. We amplified the resulting libraries by PCR, pooled, and sequenced on an Illumina HiSeq 2500 according to the manufacturer's specifications. Primers used for Sanger sequencing are listed in S3 Table. The raw data has been deposited to SRA under BioProject ID PRJNA271229." ] },{ "paper_id": "825b65e57d2aa49eb507cf377561ce4ea950c644", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was conducted with 200 undergraduate and graduate students from the Federal Rural University of Pernambuco, Northeast Brazil, including 107 women and 93 men aged between 18 and 51 years (average = 23 and 17 years, respectively; standard deviation (SD) = 5 and 7, respectively).", "The stimuli were composed of 15 plant-disease pairs printed on 15 cards made of paper. On each card, the vernacular name of a medicinal plant and its therapeutic target, separated by a hyphen, were printed. The pairs together totaled 30 words for memorization.", "Therefore, our assumption is consistent with the results reported in other studies. For example, Ruin, Gaillard and Lutoff [38] observed that some people perceive a rare event of great magnitude and serious consequence as posing a lower risk due to its infrequency. Sachs et al. [39] obtained similar results, which suggested that most of the patients in the study with diabetes focused their attention on less serious and more prevalent adverse events during treatment rather than on more serious and less prevalent adverse events." ] },{ "paper_id": "825bf8562f3e44a02f8f2bcbf055586d42771f0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thus, the vLR2 vector has a dual capacity for recombinant gene expression in the phloem and systemic VIGS targeting endogenous host genes or, potentially, genes of pathogens or pests that parasitize the grapevine. Thus, this vector provides powerful tools for functional genomics and pathogen control in grapevine. Because GLRaV-2 is known to be transmitted only by grafting, potential genetically modified organism (GMO) safety concerns are greatly reduced promoting commercial application of this vector.", "The mechanisms whereby Alphavirus-like viruses including closteroviruses express their proteins involve polyprotein processing by proteases and expression of sgRNAs Miller and Koev, 2000) . Because the closterovirus leader proteases appear to cleave only in cis, the proteolytic expression of recombinant protein can be ensured either by fusing the protein to L-Pro, or by inserting a new proteolytic cassette, similar to original designs of the potyviral vectors ( Figure 1B ; Carrington et al., 1993) .", "A more advanced BYV vector capable of expressing recombinant protein from an autonomous cassette has become a prototype for the subsequent designs of vectors based on other closteroviruses . In this vector, the recombinant ORF encoding green fluorescent protein (GFP) was inserted downstream from the native CP sgRNA promoter, whereas a heterologous CP promoter derived from a closely related Beet yellow stunt virus (BYSV; Karasev et al., 1996) was used to express the BYV CP ( Figure 1C) . The infectious RNA transcripts for plant inoculation were obtained in vitro using bacteriophage SP6 RNA polymerase and plasmid linearized near the 3 -end of the viral cDNA . This vector was useful for mechanical inoculation of a highly susceptible BYV local lesion host Claytonia perfoliata, whereas systemic infection of a convenient systemic host, Nicotiana benthamiana, using RNA transcripts was inefficient." ] },{ "paper_id": "826307b42adef6c0aa282ada8ec07afb1b35cb3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HeLa cells were lysed with RIPA buffer containing protease inhibitor cocktail, NEM, and PMSF. Lysates were adjusted to 1% SDS (w/v) and incubated at 95 \u2022 C for 10 min, subsequently diluted to 0.1% SDS and were then cleared by centrifugation at 20,000\u00d7 g for 10 min. Gag content was recovered by immunoprecipitation with antibodies derived from HIV-1 patient sera pre-bound to GammaBind Plus Sepharose (GE Healthcare). For detection of ubiquitinated Gag proteins directly by western blotting, RIPA lysis buffer was supplemented with 20 \u00b5M lactacystin and 20 \u00b5M carbobenzoxyl-leucine-leucine-leucinal.", "Viability of infected and treated cells was assessed by the water-soluble tetrazolium salt (WST)-1 assay (Roche) according to the manufacturer's instructions.", "Virus containing cell culture supernatant was harvested 48 h after transfection of HEK293T cells with proviral expression constructs and passed through a 0.45 \u00b5m pore-size filter. Virus was pelleted", "The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of the Medical Faculty of the Friedrich-Alexander University Erlangen-N\u00fcrnberg (Project identification code: 3761)." ] },{ "paper_id": "826b7e6b690a85314484d1eaf93fb020603b3479", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Flag-NFKBIA was synthesized by Genecreate (Wuhan, China) and cloned into pCDNA3.1+ using the BamHI and XhoI restriction sites. Similarly, Flag-SOCS1 was cloned into pCDNA3.1+ using the BamHI and EcoRI restriction sites. Plasmids harboring the 3 UTRs (pmirGLO-SOCS1, pmirGLO-NFKBIA, pmirGLO-NSFL1C, pmirGLO-PDLIM2, and pmirGLO-NKIRAS) were cloned from the mRNA of M. mulatta by RT-PCR, and ligated into the pmirGLO plasmid (Promega, Madison, WI, USA) using primers listed in Table 2 . To obtain mutated miR-221-5p TSs within the 3 UTRs, seed regions were mutated according to previously described mutagenesis protocol [49] .", "Cells were lysed with radioimmunoprecipitation assay buffer for 30 min on ice, followed by centrifugation at 12,000\u00d7 g for 15 min at 4 \u2022 C. Protein samples were added to 5\u00d7 loading buffer, boiled for 10 min, subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis, and transferred to polyvinylidene fluoride membranes, which were blocked with 5% nonfat milk in PBS containing Tween-20 (0.02%), and probed using the primary monoclonal antibody. Horseradish peroxidase-conjugated secondary antibodies were used to detect the primary antibodies, and proteins were visualized by ECL. ", "Student's t test was used for all statistical analyses. All data are presented as the mean \u00b1 SD of three independent experiments. Asterisks indicate statistical significance. * p < 0.05. ** p < 0.01 and *** p < 0.001." ] },{ "paper_id": "826cfd170048c1d41191762143991575452b0746", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the Hospital Data Inspectorate and the Regional Committees for Medical Research Ethics in Norway (reference number 2012/4b S-07505b). Only patients who gave informed consent participated; written consent was administered 3 months after ICU discharge. The study is also registered in Clinical Trials: NCT02279212.", "The mean age of the sample was 55.1 years (SD 14.4), 63.6% (n = 75) were male, 62.7% (n = 74) were married or had a partner, and 77.1% (n = 91) had children (either young or adult children) ( Table 1 ). The mean SAPS II and SOFA score was 44.9 (SD 16) and 8.8 (SD , and cancer at 15.8% (n = 15). The two interference items with the highest mean scores were \"interference with normal work\" and \"interference with daily activity\" after ICU discharge and both mean scores increased slightly compared with 1 year [57] .", "Comorbidities. Comorbidities were assessed using the Self-Administered Comorbidity Questionnaire (SCQ) [36] , which includes 13 common and three optional medical conditions. The SCQ allows the informant to report both severity of comorbidities and their impacts on their daily life. For this study, four common comorbidities (headache, skin diseases, bowel diseases, and muscular diseases) were added to the standard 13. Only the total number of comorbidities was used in our analyses, but the most common comorbidities are presented." ] },{ "paper_id": "826d74c66a4c9bf882880d1dccc50690c8cdaffb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In order to determine a cut-off point to classify samples as seropositive or seronegative all OD450 ELISA values were taken and operationally separated into 2 groups by means of a cutoff of 0.150, as previously published by Kahn et al. [21] Next, the mean and standard deviation of all values OD450,0.150 were calculated. The cut off point to classify samples as seropositive or seronegative was calculated as the mean of all OD450,0.150 plus three standard deviations. For this calculation, negative OD450 values were set to zero. Based on these calculations, a serum specimen negative for HBoV was defined as having an OD450#0.234 (at dilution of 1:40).", "Conclusion: HBoV infection is common in children in Jamaica. HBoV seroprevalence rates in the Caribbean are similar to those previously reported in other areas of the world." ] },{ "paper_id": "8275311de465e4fdbb25ebddf76302cd4603c36c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8276d64861e070805d56b292163da25b0240253f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords. Bayes theorem; etiologic estimations; pneumonia; epidemiologic methods; statistical models.", "Clinical: Similar to how a clinician approaches a pneumonia patient with a set of prior beliefs regarding their etiology.", "The choice may be made at the organism level, enabling use of data from past studies even when only available for a subset of pathogens." ] },{ "paper_id": "828433debf53d822b26035b951ec78a6f3009de1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses are usually divided into three groups based on genetic and serological relationship [7] . HEV, togather with murine hepatitis virus (MHV), bovine coronavirus (BCoV), human coronavirus OC43 (HcoV-OC43), rat coronavirus (RCoV), belongs to group 2 [8] .", "Clinical signs of piglets", "Negatively stained cell culture supernatant was examined under an electron microscope, and typical coronavirus-like viral particles with a diameter of about 110-130 nm were observed (Figure 1 ).", "Comparisons of the field isolate sequences with those of PHEV available in the Genbank database were performed using the online BLAST. The resulting sequences were aligned by ClustalW http://www.ebi.ac.uk/Tools/clustalw/index.html. Deduced amino acid sequences were assembled into a multiple sequence alignment. A phylogenetic tree derived from deduced amino acid sequences was constructed for the PHEV using the bootstrapped maximum parsimony method of MEGA version 4.0 [9] ." ] },{ "paper_id": "82946d26f79e85f1b37f6fd965dc1d8a2ceb0c4d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Similarly, rotavirus replication was also negatively affected by the addition of COX inhibitors early, but not late in the infection cycle [15] . In conclusion, our results clearly show that COX activity is required for efficient virus replication in vitro early during MHV infection. These findings may offer new possibilities for anti-CoV therapy. ", "Cyclooxygenases (COXs) play a significant role in many different viral infections with respect to replication and pathogenesis. Here we investigated the role of COXs in the mouse hepatitis coronavirus (MHV) infection cycle. Blocking COX activity by different inhibitors or by RNA interference affected MHV infection in different cells. The COX inhibitors reduced MHV infection at a post-binding step, but early in the replication cycle. Both viral RNA and viral protein synthesis were affected with subsequent loss of progeny virus production. Thus, COX activity appears to be required for efficient MHV replication, providing a potential target for anti-coronaviral therapy.", "Coronaviruses (CoVs) constitute a family of enveloped, positive-stranded RNA viruses. They are known pathogens in the veterinary field, causing severe diseases in several domestic species [21] . Recently, their relevance has increased considerably with the discovery of several new human CoVs (HCoVs) such as the severe acute respiratory syndrome (SARS)-CoV [22] , HCoV-NL63 [23] , and HCoV-HKU1 [24] . The role of COXs during CoV infection and pathogenesis is not well understood. MHV strain 3, which causes fulminant hepatitis, was shown to induce the synthesis of PGE 2 in macrophages [25] . However, the exogenous administration of PGE 2 could completely prevent the development of hepatic necrosis [26] . More recently, two structural proteins from the SARS-CoV were shown to induce the expression of COX-2 in vitro [27] [28] [29] , whereas elevated levels of PGE 2 were found in the blood of SARS-CoV-infected individuals [30] , suggesting a role for COXs and PGs in CoV pathogenesis. However, the requirement for COX activity for CoV replication remains unexplored." ] },{ "paper_id": "82a002a89d1e48ac636317b09d01d9d7da18113e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study protocol was approved by the institutional review board or ethical review committee at each of the study site institutions and at Johns Hopkins Bloomberg School of Public Health. Parents or guardians of participants provided written informed consent.", "Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author." ] },{ "paper_id": "82b043ec316b0bfb8350d65b09f6028d4ea9e564", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PknotsRG (Janssen and Giegerich, 2015) , DotKnot (Sperschneider and Datta, 2010) , Pknots (Rivas and Eddy, 1999) .", "Not predicted by most 2D software. Alternative forms of pseudoknot are found." ] },{ "paper_id": "82bc247394e2e55f46bdb295bd2a3f6d19f1365b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Several sulfated molecules (i.e., heparin, carrageenan, dendrimers, nanoparticles, and others) inhibit HSV infection, further supporting the role of HS in viral attachment [27, [92] [93] [94] (Table 2 ). Cellulose sulfate [95] Cellulose sulfate [95] PRO 2000 [96, 97] PRO 2000 a [96, 97] SB105-A10 dendrimer [98] VivaGel (SPL7013) a [99] Sulfated K5 derivatives [100] SB105-A10 dendrimer [98] Agmatine-derived polymers [93] Sulfated K5 derivatives [100] MUS:OT * nanoparticles [92] Agmatine-derived polymers b,c [93] DSTP27 ** [94] MUS:OT * nanoparticles b [92] DSTP 27 ** [94] HCMV Heparin [10] DENV2", "Heparin [101] SB105-A10 dendrimer [98] Carrageenans [102] Sulfated K5 derivatives [103] Sulfated K5 derivatives [101] Agmatine-derived polymers [ [105] Carrageenans d [27, 106, 107] Carrageenans c,e [105, 108, 109] Cellulose sulfate d [95, 107, 110] Cellulose sulfate [111] PRO 2000 d [96, 107] SB105-A10 dendrimer [112] VivaGel (SPL7013) a [99] Sulfated K5 derivatives [113] SB105-A10 dendrimer b [114] Agmatine-derived polymers [115] Sulfated K5 derivatives [116] MUS:OT* nanoparticles [92] DSTP27 ** [94] DSTP27 ** [117] RSV Heparin [118] HMPV Heparin [119] SB105-A10 dendrimer f [16] Carrageenans [33] Sulfated K5 derivatives f [15] SB105-A10 dendrimer f [33] MUS:OT * nanoparticles c [92] Sulfated K5 derivatives f [33] Agmatine-derived polymers [104] DSTP27 ** [94] EBOV Heparin [53] MARV Heparin [53] Carrageenans [53] Carrageenans [53] SB105-A10 dendrimer [53] SB105-A10 dendrimer [53] VV ", "Tan et al. reported that suramin was effective against ZIKV; however, the infectivity of ZIKV in cell lines was not diminished after sodium chlorate wash or heparinase I/III treatment, nor was it possible to observe any interaction between the virus and heparin-Sepharose beads. Through molecular dynamics simulation, the authors evidenced a strong interaction between suramin and ZIKV helicase, possibly explaining the inhibitory activity [40] .", "Moreover, the same considerations can be extended to other members of the Pneumoviridae family, particularly human metapneumovirus (HMPV), which also binds HSPG, infects ciliated cells on HAE, and whose inhibition with sulfated molecules has also been shown in HAE [33, 34] (Table 2) ." ] },{ "paper_id": "82bf46aebd99e6e67368b9c789d01e561ed147af", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2 Hou et al.", "Establishing a lymphocyte repertoire database starts from sample collection from carefully selected populations and isolation of interested T cell or B cell subgroups. Due to the well-acknowledged heterogeneity of TCRs and BCRs between individuals, longitudinal studies tracking dynamic alterations in certain population help to reduce difficulties in data interpretation at unraveling the infection course. Classification of subgroups of T cell and B cells, e.g., naive and memory T/B cells, CD4+, and CD8+ T cells, is necessary if distinct behavior of these subgroups is considered in detail.", "However, immune responses show dramatic differences in CDR3 sequences responding to same pathogens across individuals and age groups. This intrinsic divergence between individuals is the major obstacle in finding \"public\" sequences as optimal biomarkers. Nevertheless, we hold a promise for the application of HTS data in differential diagnosis because it provides a large number of candidate sequences for biomarker investigation. Instead of using single biomarkers such as PSA or AFP in diagnosis, a combination panel of selected sequences may establish a pathogen-specific sequence library for diagnosis, which holds the potential of unprecedented sensitivity and specificity.", "DH was involved in study design, wrote the first draft of the manuscript, conducted the literature search, reviewed the abstracts, performed the analysis, and contributed to the final draft; CC and SC were involved in study design and reviewed the abstracts. ES revised the manuscript. YS designed and supervised the study, revised the final draft, and contributed to the analysis. All authors have read and approved the final manuscript. " ] },{ "paper_id": "82c17f8de937704b2522db77b863f8f01ab19414", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were analyzed with SPSS statistical software (version 19.0; SPSS Inc., Chicago, IL), as described previously [18] . The \u03c7 2 test and Fisher's exact test were used for comparisons of data. All tests were two tailed and p < 0.05 was considered statistically significant.", "This study had some limitations, however. First, selection bias may have occurred due to the lack of healthy subjects without ARTI. Second, collecting biological samples using oropharyngeal swabs may be less reliable for detecting the presence of HCoV and other pathogens than obtaining bronchoalveolar lavage fluid. One advantage of this method, however, was that it is non-invasive and more suitable for routine analysis.", "Our study has several strengths, including its large sample size and long duration. Furthermore, given that few studies to date have simultaneously tested for all four strains of HCoV in ARTI pediatric patients, the present study addresses an important gap in the literature." ] },{ "paper_id": "82d76d619e7be4f0ef2490f933d140ec9f722a55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses (CoVs) are widely found in humans as well as in mammalian and avian species, causing asymptomatic infections or respiratory tract disorders, and gastroenteritis of varying severity 1 . CoVs belong to the genus Coronavirus of family Coronaviridae, and are classified into four genera, Alphacoronavirus (\u03b1 -CoV), Betacoronavirus (\u00df-CoV), Gammacoronavirus, and Deltacoronavirus based on phylogenetics and serology 1 . To date, \u03b1 -CoV [including human CoV (HCoV)-229E and NL63] and \u00df-CoV [including HCoV-OC43, HKU1, Severe Acute Respiratory Syndrome CoV (SARS-CoV) and Middle East Respiratory Syndrome CoV (MERS-CoV)] are known to infect human beings 1 .", "Interspecies transmission is a common phenomenon for CoVs that may be responsible for generation of new CoV epidemics during viral evolution 2-5 . For instance, the feline CoV (FCoV) type II, a member of \u03b1 -CoV, might be generated by a double recombination between FCoV type I and canine CoV 4 . Interestingly, porcine hemagglutinating encephalomyelitis virus, bovine CoV (BCoV) and HCoV-OC43 of \u00df-CoV are thought to have evolved from the same common ancestor 5 . During evolution, high frequencies of homologous RNA recombination and gene mutations are considered the main forces that push CoVs to adapt to specific hosts. Such events can lead to emergence of new strains or genotypes within a certain species, and even to new species, causing epidemic or zoonotic outbreaks that continuously threaten human health 2,3 . This phenomenon is exemplified by the recent emergence of SARS-CoV and MERS-CoV 6,7 . However, the detailed evolutionary mechanism of interspecies transmission and the persistence of CoVs in specific hosts have yet to be fully elucidated.", "The relatively long epidemic time and more available sequences of genotype D allowed us to analyze in detail the nonsynonymous changes throughout the evolutionary history of OC43. The ancestral (Fig. 2) ." ] },{ "paper_id": "82e33ea1413ab8560304175a8281348a156c2e47", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(i) Each active link (i, j) is inactivated with probability t z (1 + \u03c4 (i,j) ) \u22121 , where the parameter z controls the rate with which contacts end;", "We initialize the network with all agents isolated (i.e. all links inactive). We set t i = 0 and t (i,j) = 0 for all agents and links, respectively. At each time step t, all active links and all agents are updated as follows:", "Mathematical models provide a theoretical framework that can be applied to improve our understanding of the spread of infectious diseases in a host population [1] [2] [3] [4] . A vast range of approaches has recently been developed for the analysis and interpretation of epidemic data," ] },{ "paper_id": "82e479c9e81790fa8a0dc356b36d389616bf7bad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "82e600f01e9caa5ae2c03497d8454e5d10e87369", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Not applicable.", "The authors declare that they have no competing interests.", "Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. ", "Ethics approval and consent to participate This work complied with the Ethical Standards of the Committee on Publication Ethics (COPE)." ] },{ "paper_id": "82ebbe8f7da98684d3f627254627253f080e09b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "corresponding P-values and ratios are listed in Table 9 . The top diseases and disorder clusters,", "The number on an arrow indicates the remaining genes after the previous step. ", "including inflammatory response, immunological disease, hematological disease, cancer, and ", "All of the chickens were kept in a pathogen-free facility at the Avian Disease and Oncology Laboratory (ADOL, East Lansing, MI, USA). All animals were approved by the United States Department of Agriculture (USDA), Agricultural Research Service, and ADOL Animal Care and Use Committee. Their guidelines (revised April 2005, Approval Number: 6040-31320-009-00-D) were followed, along with the Guide for the Care and Use of Laboratory Animals published by Institute for Laboratory Animal Research (ILAR Guide) in 1996 (http://www.nap.edu/openbook.php?record_id=5140) and University of Maryland (R-08-62). All efforts were made to minimize discomfort and suffering." ] },{ "paper_id": "82ec1cd41017fab2d523840ae9fb3f30dbeeab55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hepatitis C virus (HCV) causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) [1] . There are approximately 170 million infected people worldwide [2] and no therapeutic or prophylactic vaccines currently available. Therefore, HCV continues to represent a significant public health problem that mandates intensified efforts and investment in both clinical management and research." ] },{ "paper_id": "82ef5d93dc7dd6b35e8411969e33633b402e5acc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 3-D surface-rendered reconstructions of viral structures and adjacent cellular features were processed using AMIRA Visualization Package (TSG Europe) by surface rendering and thresholding. During this process, some volumes were denoised using the nonlinear anisotropic diffusion filtering [78] . Denoised volumes were used only for producing the surface-rendered masks. Final analyses and representations were done using undenoised data (either masked or unmasked).", "Video S2. Animation Illustrating the Derivation of the Model Presented in Figure 3D ", "For IEM, infected cell monolayers were cryofixed by either plunging them into liquid ethane or by high-pressure freezing using a Leica EM PACT2. The freeze substitution was performed using anhydrous acetone containing 0.25% glutaraldehyde and 0.1% uranyl acetate. After washing with ethanol, samples were infiltrated with Lowicryl HM20 and polymerized under UV light at \u00c050 8C. Thin sections were labeled with specific antisera [28] , which were detected with protein A-gold particles (10 or 15 nm). A bridging rabbit-antimouse IgG antibody (DakoCytomation) was used for mouse monoclonal antibodies. Grids were contrasted with uranyl acetate and lead hydroxide, and subsequently viewed with a Philips CM-10 transmission electron microscope.", "Previously, we experienced that, compared to more traditional chemical fixation protocols, the preservation of the fragile coronavirus DMV structures could be significantly improved by using a combination of cryofixation and freeze substitution (FS) [28] . We now further refined the FS protocol, in particular by improving membrane contrast by adding 10% water to the FS medium [38] ." ] },{ "paper_id": "82f3e5abcabd0756aae8c054832a80658915bde3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Based upon the predicted and experimentally determined amplicons, these primers effectively resolve all known Orthopoxvirus species from one another. All experimentally determined basecount signatures were found to agree with bioinformatically predicted signatures based upon published genomic sequences.", "Research was conducted in compliance with the Animal Welfare Act and other federal statues and regulations related to animals and experiments involving animals and adhered to principles stated in the guide for the Care and Use of Laboratory Animals, National Research Council, 1996. The facility where this research was conducted is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International. ", "We would like to thank Carson Baldwin and Nicole Garza for their excellent technical assistance. This manuscript is approved for public release, distribution unlimited.", "All of the vaccinia isolates tested including rabbitpox and horsepox, which are sub-species of vaccinia, have a common base count signature for primer pair VIR9888 ( 34A, 16G, 19C, 30T). Vaccinia, Copenhagen strain and horsepox (gi|111184167) can be distinguished from each other and other vaccinia isolates based upon their unique base-count signatures for primers pairs VIR985 and VIR979." ] },{ "paper_id": "8303edd7c319344d34223d60c9578385684a7f28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To better understand RSV evolutionary dynamics, we sequenced RSV whole genomes from acutely infected infants from middle Tennessee who were enrolled as part of the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure (INSPIRE) longitudinal observational birth cohort 25 . The objective of our sequencing efforts was to assess the epidemiological and evolutionary dynamics of RSV from Tennessee within a global context, which is important for identifying RSV strains that feed into the global circulation.", "Human Respiratory Syncytial Virus (RSV) was first isolated in 1955 1-3 and has been associated with mild to severe acute lower respiratory tract infections (ALRIs), especially in infants, premature babies, the elderly, and immunocompromised individuals 4-7 . In 2005, RSV caused an estimated 33.8 million new episodes of ALRIs in children under five worldwide, with 3.4 million cases requiring hospitalization due to severe illness 1,7,8 . Global estimates of disease burden show RSV to account for 30 million ALRIs and 50,000 annual deaths of children < five years of age 1, 7, 8 . Nearly all children have had at least one RSV infection by two years of age 7 . It is well established that RSV infections during infancy (< six months of age) are associated with an increased incidence of subsequent childhood wheezing and asthma 9 . Despite its global public health impact, no licensed vaccines nor effective treatments for acute infection are currently available for RSV 9 . The only approved prophylaxis is passive immunization with palivizumab, a humanized mouse monoclonal antibody against the RSV fusion (F) protein 10,11 . The efficacy trials of palivizumab resulted in a 39-78% decrease in hospitalization rates for RSV in premature infants and children with chronic lung disease 10 ; however, a recent review shows inconsistent cost-effectiveness of palivizumab 12 .", "RSV is an enveloped virus with a negative-sense, single-stranded, non-segmented RNA genome belonging to the Paramyxoviridae family. The 11 RSV proteins include the polymerase (L), nucleocapsid (N), phosphoprotein (P), transcriptional regulators (M2-1, M2-2), matrix (M), small hydrophobic protein (SH), non-structural proteins (NS1, NS2) and two major surface glycoproteins (F and G) that are responsible for virus entry and are the major target of human immune responses. The F protein is responsible for the fusion of the viral envelop with the host cell membrane for the viral entry into the cell. The attachment G protein has a short cytoplasmic domain followed by a transmembrane domain and two hypervariable mucin-like domains joined by a conserved sequence, which is responsible for cellular attachment. The G protein also has an immune decoy function in its soluble, extracellularly secreted form.", "For samples requiring extra coverage, in addition to Ion Torrent sequencing, Illumina libraries were prepared using the Nextera DNA Sample Preparation Kit (Illumina, Inc., San Diego, CA, USA) with half reaction volumes. Briefly, 25 ng of pooled DNA amplicons were tagmented at 55 \u00b0C for 5 min. Tagmented DNA was cleaned with the ZR-96 DNA Clean & Concentrator Kit (Zymo Research Corporation) and eluted in 25 \u03bc l resuspension buffer. Illumina sequencing adapters and barcodes were added to tagmented DNA via PCR amplification, where 20 \u03bc l tagmented DNA was combined with 7.5 \u03bc l Nextera PCR Master Mix, 2.5 \u03bc l Nextera PCR Primer Cocktail and 2.5 \u03bc l of each index primer (Integrated DNA Technologies, Coralville, IA, USA) for a total volume of 35 \u03bc l per reaction. Thermocycling was performed with 5 cycles of PCR, as per the Nextera DNA Sample Preparation Kit protocol (3 min at 72 \u00b0C, denaturation for 10 sec at 98 \u00b0C, annealing for 30 sec at 63 \u00b0C and extension for 3 min at 72 \u00b0C) to create a dual-indexed library for each sample. After PCR amplification, 10 \u03bc l of each library was pooled into a 1.5-mL tube, and the pool was cleaned two times with Ampure XP reagent (Beckman Coulter, Inc.) to remove all leftover primers and small DNA fragments. The first cleaning used a 1.2\u00d7 volume of the Ampure reagent, while the second cleaning used a 0.6\u00d7 volume of the Ampure reagent. The cleaned pool was sequenced on the Illumina MiSeq v2 instrument (Illumina, Inc.) with 300-bp paired-end reads." ] },{ "paper_id": "8309dc172cf91ff580779bbc1394a9692b798a86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Citation: Catic A, Fiebiger E, Korbel GA, Blom D, Galardy PJ, et al (2007) Screen for ISG15-crossreactive Deubiquitinases. PLoS ONE 2(7): e679.", "USP2 and USP18 cDNAs were cloned from a human kidney cDNA library (BioChain Institute, Inc.). The cDNAs encoding the other human DUBs were obtained from ATCC. All cDNAs encoding fulllength DUBs were subcloned into pcDNA3. " ] },{ "paper_id": "8312f3f0b20525b23f371ec985efe9f5e721f437", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Figure S1 . Specificity of avian macrophage staining. The power point slide contain lung sections stained with anti-chicken macrophage antibody (KUL-01) and isotype control. The sections were also stained with nuclear staining (DAPI). (DOCX 271 kb).", "For the sampling of tissues, the chickens were euthanized using overdose of isoflurane anesthesia followed by cervical dislocation.", "Day old white leghorn (SPF) layer chickens (White Leghorn) were obtained from the Canadian Food Inspection Agency (CFIA), Ottawa, ON, Canada and housed in high containment poultry isolators at the Prion-Virology Animal Facility of the University of Calgary's Foothills Campus with ad libitum access to feed and water." ] },{ "paper_id": "832b1861e334121672bb60f1d917481353cf4327", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We used Y mtv to denote the observed count of pathogen v during the mth month of year t conditional on expected count E mtv and relative risk RR mtv Y mtv jE mtv ; RR mtv \ufffd Poisson\u00f0E mtv RR mtv \u00de log \u00f0RR mtv \u00de \u00bc a v \u00fe \ufffd mtv with \u03b1 v an intercept term specific to virus v and \u03d5 .t. = {\u03d5 .t1 , . . ., \u03d5 .tV } a vector of random effects modelled conditionally through a MCAR prior \ufffd :t: j\ufffd :t\u00c0 1: \ufffd MVN\u00f0s v \ufffd :t\u00c0 1: ; \u00bdO \ufffd L\ufffd \u00c0 1 \u00de:", "From the 28,647 patient episodes, defined as aggregated samples taken from each patient over a 30-day window, 4,759 were positive to at least one virus group and detection was most common in children aged between 1 and 5 years. Detection of any virus in a given episode was Temporal interactions in pathogen dynamics most common in December and least common in August. We observed differing patterns between the five viruses ( Fig 5, black lines) . IBV, RSV and CoV were more prevalent in winter months (November, December and January), AdV was generally less common with a slight increase in prevalence in spring months (April, May and June) and MPV shifts from winter peaks (January and February) to spring peaks (March, April and May) after 2010. IBV was the only virus not to display a regular seasonal pattern. This virus peaked in winter during 2005/ ", "More precisely, our model captured winter peaks in CoV, winter and spring peaks in MPV and irregularities in AdV and IBV validating the model fit to these data." ] },{ "paper_id": "832fab67c299fb2682948d33858e58a5db71e6f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The M segment nucleic acid sequence of CCHF strain IbAr10200 (Accession number U39455) was modified by removal of untranslated regions, initiation and termination codons. To enable Gateway recombination, attB1 and attB2 sequences were added to the beginning and end, respectively, of the remaining open reading frame (i.e. nucleotides 34 to 5082). Two poxvirus transcription stop signals (TTTTTNT) at positions 3894 and 4767 were altered without introducing coding changes. The resulting sequence was synthesised and then recombined into pDONR (Life Technologies) by Entelechon (Germany), to generate plasmid pENTR-GP.", "Plasmids pDEST44-TPA-V5 and pENTR-GP were recombined using Gateway technology to generate plasmid pTP-GP.", "Primary antibodies used were mouse anti-V5 (AbD Serotec) diluted 1/5000, polyclonal rabbit serum (kindly provided by A. Mirazimi, Sweden) raised against glycoprotein peptides and diluted 1/2500, or serum from vaccinated mice diluted 1/1000. Secondary antibodies were anti-mouse IgG (Sigma-Aldrich) diluted 1/8000, anti-mouse IgG/A/M (AbD Serotec) diluted 1/ 4000, or anti-rabbit IgG (Sigma-Aldrich) at 1/5000." ] },{ "paper_id": "83447780f68227bd566b75739a926149c96ff3d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the calculations were carried out on Dell Precision TM T5500 computer with Schrodinger software package [34, 36] and Desmond 2.4 [39] .", "Consequently, we have a total of 1|5|5~25 different combinations for the GW409544 derivatives thus generated.", "The QikProp [68, 69] is a program for predicting the ADME (absorption, distribution, metabolism, and excretion) properties of the compounds. With the QikProp software, a total of 44 properties of compounds can be predicted, including the principal descriptors and physiochemical properties." ] },{ "paper_id": "8357e742ce4e988fbae529ff603c81ac5b974b27", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For mice experiments, nine mice in each group for evaluating mouse survival and three biological triplicates at each time point for detecting the infection are the commonly used sample sizes which are appropriate for statistical analysis while minimizing animal use. The inbred and cohoused mice were randomly grouped, which minimized the subjective bias. No blinding was done. Mouse survival data were analyzed with Mantel-Cox test. In all the experiments, no sample was excluded for data analysis. Unpaired twosided Student's t-test analysis was used for data analysis of all in vitro experiments which were performed at least three times. A P < 0.05 was considered to be statistically significant. Data are presented as mean and SD of representative experiments.", "Expanded View for this article is available online. extracellular environment to prevent influenza A virus maturation. Cell 160: 631 -643", "The paper explained" ] },{ "paper_id": "836ec77a81730c540b750253cc4ee9f8fed0fb49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A liner epitope is composed of residues that are sequentially consecutive, whereas a conformational epitope consists of sequential segments that are brought together in spatial proximity when the corresponding antigen is folded. It has been reported that more than 90% of B-cell epitopes are discontinuous B-cell epitopes [2] ; therefore, the prediction of conformational epitope is more significant.", "To ensure the effectiveness of prediction, we deal with the imbalance data through the following ways.", "Firstly, the method extracts 6 epitope related features as EPCES: residue epitope propensity, conservation score, side chain energy score, contact number, surface planarity score, and secondary structure composition. The detailed calculation of these six features is described in EPCES [29] ." ] },{ "paper_id": "8377296478e62e2cd582fed23e9e20f512d5e92d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Single B cell sorting, RT-PCR, sequencing, and cloning", "ZIKV particles were successfully isolated from the infected patient's blood plasma or urine. The virus was passaged once in suckling mouse brains and cultured in Vero cells to prepare stocks, which were stored at \u221280\u00b0C before use. DENV1 (Hawaii strain), DENV2 (New Guinea-C strain), DENV3 (H87 strain), and DENV4 (H241 strain) were prepared in Vero cells.", "Nunc MaxiSorp plates (Thermo Fisher Scientific, Waltham, MA) were coated with ZIKV E or E domain III protein (1 \u00b5g/mL) and incubated at 4\u00b0C overnight. After blocking for 2 h, the plates were washed six times with phosphate-buffered saline (PBS) and transfected with antibody supernatants at a 1:2 dilution with blocking buffer or a serial dilution of purified mAbs. Secondary antibody (goat anti-human IgG; ab6858; Abcam, Cambridge, UK) was applied at a 1:5000 dilution in blocking solution and then the plates were incubated at room temperature for 1 h, and TMB substrate. Absorbance values were determined at 450 nm using a BioTek plate reader (BioTek Instruments, Winooski, VT)." ] },{ "paper_id": "83779b8c44857750b3b75b5d83cc3fdbb7441a50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that they have no competing interests.", "All the authors helped to draft the manuscript, read and approved the final manuscript.", "Submit your next manuscript to BioMed Central and take full advantage of: " ] },{ "paper_id": "837935e5f921344c58f824f262566bd688ceddb2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sera collection was approved by the Legal Department of the Israeli Ministry of Health.", "In a sensitivity analysis performed for the classification of the equivocal samples as positive or negative, no significant difference was observed.", "R. Bassal et al.", "Author ORCIDs. R. Bassal, 0000-0002-0086-2968." ] },{ "paper_id": "837abf94f591d8288f0b9faa53055d2724ff783f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recent work indicates that persistent phagocytic microglia contribute to prolonged cognitive dysfunction following WNV encephalitis [8] , and thus, limiting microglial activation may alleviate the associated neurological sequelae.", "All experiments were performed in strict compliance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and according to the international Guiding Principles for Biomedical Research Involving Animals. The protocol was approved by the Washington University School of Medicine in St Louis Animal Safety Committee (#20170064)." ] },{ "paper_id": "839063ca98beeac93cfb9243045c7d14728420a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After vaccination -No adverse local or systemic effects were observed upon vaccination.", "The study was conducted in compliance with the provisions of Directive 86/609/EEC and KB 29/05/2013 and received approval number EC 2013/157.", "This study was funded by Laboratorios Hipra, S.A., Spain. The authors declare that there is no conflict of interest." ] },{ "paper_id": "83a6a45a591e9222cf68f14d60dce7d3c810c1f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells 2012, 1 410 minimize apoptosis of the cells. Therefore, this study should draw attention to the need to optimize freezing and thawing conditions for successful T cell work.", "Because T cells are key mediators of immunity, monitoring antigen-specific T cells has become central to progress in many fields of medical research, including infectious diseases and vaccinology [1 3] , transplantation [4, 5] , allergies [6] , autoimmunity [7 9] , and tumor immunology [10 12 ]. Among the techniques available to measure T cell immunity, ELISPOT has found wide use because it is simple, reliable, sensitive, quantitative, and efficient in cell utilization [10, 12, 13] .", "Total CD3 + ; CD3 + /CD4 + , and CD3 + /CD8 + T cell subsets were assessed by flow cytometry. Briefly, 500,000 cells were stained in 5 mL Falcon round-bottom tubes with human anti-CD3 FITC (clone HIT3a), and CD4 PE (clone RPA-T4), or anti-CD8 PE (clone RPA-T8) (all BD Biosciences, San Jose, CA, USA) and fixed in 2% formaldehyde. A minimum of 200,000 events were acquired using BD FACSCanto III (BD) and analyzed with FACSDiva TM , version 4 software [43] (BD)." ] },{ "paper_id": "83a9e757fc42183eef4f36f50cf84044f7b780fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A schematic representation of MERS-CoV S protein is shown with the N-terminal domain (NTD) highlighted in yellow, receptor binding domain (RBD) in pink, heptad repeats 1 and 2 (HR1 and HR2) in blue, and transmembrane domain (TM) in green. Eight MERS-CoV S sequences published in GenBank were aligned with the England1 strain. The amino acid differences are shown in red with the England1 strain as the referent. Phylogenetic distance between strains is represented by branch length on the phylogenetic tree to the left of the sequences.", "(a) SARS receptor binding domain (RBD) (violet) with the receptor binding motif (RBM) (orange) and the ACE2 receptor (green) are shown in cartoon representation. The ACE2 interacting region is mapped onto the SARS RBD (surface representation, rotated) and colored in green. The RBD region that interacts with the ACE2 glycan is shown in yellow. (b-d) SARS RBD and M396 Fab 1,2 , F26G19 Fab 3 and 80R Fv 4 are shown in cartoon representation. The antibody interacting region is mapped onto the RBD and colored green (Light chain) and blue (Heavy chain).", "Supplementary Figure 1. MERS-CoV pseudovirus utilizes human DPP4 to transduce target cells. (a) DPP4 expression on the cell surface. Huh7.5 cells (left panel), DPP4-untransfected HEK 293 cells (middle panel), and DPP4-transfected HEK 293 cells (right panel) were stained with goat anti-DPP4 antibody (in blue) and control antibody (in red) and analyzed by flow cytometry. (b) Transduction of DPP4-expressing cells by pseudotyped MERS-CoV England1 virus. Huh7.5 and HEK 293 cells without and with DPP4-transfection (in grey and black bars) were transduced by MERS-CoV pseudotyped virus. Relative expression of luciferase activity was measured (CPS). Untransfected and untransduced cells were used as the background control (open bars). Each bar represents the mean of triplicate assays with standard errors. One representative of two experiments is shown. (c) Transduction of Huh7.5 cells by MERS-CoV pseudovirus was blocked by soluble human DPP4 (sDPP4). MERS-CoV England1 pseudovirus was incubated with soluble human DPP4 before transduction of Huh7.5 cells. Relative luciferase activity (CPS) is shown. (d) Transduction of Huh7.5 cells by MERS-CoV pseudovirus was blocked by anti-DPP4, but not anti-ACE2 antibody. Huh7.5 cells were incubated with anti-DPP4 or anti-ACE2 polyclonal antibodies and then transduced with MERS-CoV England1 pseudovirus. Relative luciferase activity (CPS) is shown. Each data point in (c) and (d) represents the mean of triplicate assays with standard errors. One representative of two repeated experiments is shown." ] },{ "paper_id": "83b05e8afa6cbe7a68170ee155f7eca37c91d51f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The PSI-Blast search for viruses in the NCBI nr protein sequence database was initiated with ALKB_ECOLI (NCBI gi113638), restricted to residues 110 to 210 and using the default inclusion threshold of 0.005 on E-values. The [11] .", "The 2OG-FeII oxygenase superfamily is widespread in Eukaryotes and bacteria [1] , and is currently the largest known family of oxidising enzymes without a heme group [5] . The 3D structure of several of these oxygenases is known, and they share a common fold with a structurally conserved jelly roll \u03b2-sheet core with flanking \u03b1-helices. Very few residues are totally conserved across these structures, basically just the residues involved in coordination of the Fe(II) ion and the 2-oxoglutarate." ] },{ "paper_id": "83b302c75378ce58e35ef93b6214a6ec330998c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.", "The CC mouse strains are an extraordinarily powerful platform to establish novel mouse models for emergent and pre-emergent isolates of respiratory coronaviruses. Harnessing the power of CC host genetic mapping will support the identification of novel hCoV-host molecular interaction networks that can be subsequently validated in genetically engineered mice. Innovations in gene editing technologies such as CRISPR/Cas9, TALENs, and synthetic zinc fingers have augmented the efficiency of genetic engineering in mice, making genomic modifications (i.e., allele-specific mutations, allele swaps, knock-outs, knock-ins) feasible in multiple mouse species, on a large-scale (Doench 2018; Kim and Kim 2014) . Coincidentally, advances in the CRISPR/ Cas9 technology overlapped with the outbreak of MERS-CoV in 2012, which was fortuitous for the development of lethal MERS-CoV mouse models.", "The emergence of highly pathogenic human coronaviruses (hCoVs) in the last two decades has illuminated their potential to cause high morbidity and mortality in human populations and disrupt global economies. Global pandemic concerns stem from their high mortality rates, capacity for human-to-human spread by respiratory transmission, and complete lack of approved therapeutic countermeasures. Limiting disease may require the development of virus-directed and host-directed therapeutic strategies due to the acute etiology of hCoV infections. Therefore, understanding how hCoV-host interactions cause pathogenic outcomes relies upon mammalian models that closely recapitulate the pathogenesis of hCoVs in humans. Pragmatism has largely been the driving force underpinning mice as highly effective mammalian models for elucidating hCoV-host interactions that govern pathogenesis. Notably, tractable mouse genetics combined with hCoV reverse genetic systems has afforded the concomitant manipulation of virus and host genetics to evaluate virus-host interaction networks in disease. In addition to assessing etiologies of known hCoVs, mouse models have clinically predictive value as tools to appraise potential disease phenotypes associated with pre-emergent CoVs. Knowledge of CoV pathogenic potential before it crosses the species barrier into the human population provides a highly desirable preclinical platform for addressing global pathogen preparedness, an overarching directive of the World Health Organization. Although we recognize that results obtained in robust mouse models require evaluation in non-human primates, we focus this review on the current state of hCoV mouse models, their use as tractable complex genetic organisms for untangling complex hCoV-host interactions, and as pathogenesis models for preclinical evaluation of novel therapeutic interventions." ] },{ "paper_id": "83bee2f8fff1d0da5230174abcd935d8b1113665", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The recent Ebola and Zika epidemics highlighted how poorly prepared we were to deal with these new and emerging diseases. There has therefore been a global drive to develop vaccines against these diseases and improve preparedness. The Coalition for Epidemic Preparedness Innovation's (CEPI's) was established in 2016 with a mandate of financing and coordinating the development of new human vaccines to prevent and contain infectious disease epidemics. CEPI selected NiV, Lassa virus and Middle East respiratory syndrome-coronavirus, three pathogens from the WHO's list of priority diseases needing urgent R&D attention as its initial focus (50, 51) . The WHO's list of priority diseases is part of the R&D Blueprint, which identifies priority diseases and addresses gaps in the global scientific community to increase preparedness for future outbreaks. The main aim of the Blueprint is to fast-track the availability of effective tests, vaccines, and medicines that can be used to save lives and avert large scale crises (51) .", "The first and still most devastating NiV outbreak occurred in peninsular Malaysia from September 1998 to May 1999 (15, 16) . The link to pigs in this outbreak was obvious as 93% of the infected patients had contact with pigs (17) . If a NiV strain were to become human-adapted and infect communities in Southeast Asia where there are high human and pig densities and pigs are a primary export commodity, infection could rapidly spread and humanity could face its most devastating pandemic (8, 11, 18) .", "The name proposed for the disease caused by NiV infection of pigs was \"porcine respiratory and neurological syndrome\" (also known as \"porcine respiratory and encephalitis syndrome\"), or, in peninsular Malaysia, \"barking pig syndrome\" (28) . NiV infection was included as the sixth pig disease notifiable to the OIE World Organization for Animal Health (31) . The OIE approve diagnostics and recommends preventative and control measures for a range of transboundary livestock diseases.", "Pigs also suffered during the 1998/99 Malaysian outbreak, but this was only diagnosed as part of the investigation following the human cases. The severity of symptoms of NiV infection in pigs varied with age. In suckling pigs (<4 weeks old), mortality could be high (up to 40%) and labored breathing and muscle tremors were evident. In growing pigs (1 to 6 months), an acute febrile (>39.9 \u2022 C) illness was observed with respiratory signs ranging from increased or forced respiration to a harsh, loud non-productive cough, open mouth breathing, and epistaxis (26) . In some cases these respiratory signs were accompanied by one or more of the following neurological signs: trembles, neuralgic twitches, muscle fasciculation, tetanic spasms, incoordination, rear leg weakness, or partial paralysis. Pigs of this age had high morbidity and low mortality (<5%) (26) (27) (28) . Some animals over 6 months of age died rapidly (within 24 h) without signs of clinical disease. Respiratory signs were reported in adult pigs, as with younger animals, although these were less obvious (labored breathing, bloody nasal discharge, increased salivation) and neurological signs included head pressing, bar biting, tetanic spasms and convulsions. First trimester abortions were also reported (26) (27) (28) ." ] },{ "paper_id": "83c2c8a726eb4a9959ecfbba7b491f733b45f425", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CPP-ASO approaches have also been developed as antibacterial agents, (reviewed in [56] ), as ASOs alone have poor capability to penetrate the bacterial cell membrane. In an exemplar study, intranasal administration of (RXR) 4 -PMO targeting acpP in a mouse Acinetobacter pneumonia model showed increased survival time and reduced pulmonary bacterial levels compared to saline controls [21] .", "One of the limitations of positively charged CPPs is that conjugation to negatively-charged nucleic acids such as siRNAs and 2 -O-Me ASOs results in electrostatic interactions that can self-aggregate and potentially interfere with oligonucleotide target binding. In an attempt to address this, a 7-mer phage display was performed to identify noncharged homing peptides that would enhance delivery of 2OMePS SSO in the mdx mouse model [19] . Conjugation of a candidate peptide (LGAQSNF) increased exon skipping activity approximately 5-10% in skeletal and cardiac tissues following a 6-week subcutaneous administration protocol, although notably an increase in protein restoration was not observed.", "The field of CPP delivery of oligonucleotides clearly shows promise as evidenced by the number of successful preclinical studies in a wide range of disease indications that have arisen over the last decade. The greatest success is likely to come for targeting organs that are most refractory to systemic naked oligonucleotide delivery such as the central nervous system, heart, and skeletal muscle where the need for effective delivery is paramount to realize the power of specific gene and disease mutation targeting that oligonucleotides offer. With advancement of design algorithms and better understanding of uptake mechanisms and intracellular trafficking, the therapeutic potential of this field will improve and likely we will see more CPP-ASO candidate's move towards clinical drug development." ] },{ "paper_id": "83c33f01d7a8c1abca6dedf7e12e485fc7ed6ed3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2.1. C. phellodendri Extraction. C. phellodendri, bark of Phellodendron chinensis Schneid. (Rutaceae), were collected in Sichuan Province, China, and were authenticated by Professor Dr. Ding-Rong Wan of our university. A voucher specimen (SCUN201310010) is deposited at the Herbarium of College of Pharmacy, South-Central University for Nationalities, China.", "The results are expressed as the mean \u00b1 SEM. Comparisons of 2 groups were performed using Student's t-test. Differences with < 0.05 were considered significant.", "Mouse ASM contraction was measured as previously described [14] . Adult male BALB/c mice were sacrificed by an intraperitoneal injection of sodium pentobarbital (150 mg/kg), and their tracheae were isolated and quickly transferred to ice cold PSS (composition in mM: NaCl 135, KCl 5, MgCl 2 1, CaCl 2 2, HEPES 10, glucose 10, pH 7.4). The connective tissue was removed, and tracheal rings (\u223c5 mm) were cut from the bottom of the tracheae. Each ring was mounted with a preload of 0.5 g in an organ bath with a 10 mL capacity containing PSS bubbled with 95% O 2 and 5% CO 2 at 37 \u2218 C. The rings were equilibrated for 60 min, precontracted with high K + (80 mM) or ACH (10 \u22124 M), washed, and rested for a total of 3 times. The experiments were performed following an additional 30 min rest.", "Sexually mature male BALB/c mice were purchased from the Hubei Provincial Center for Disease Control and Prevention (Wuhan, China). The mice were housed at room temperature (20-25 \u2218 C) and constant humidity (50-60%) under a 12 h light-dark cycle in an SPF grade animal facility. The experiments on animals were approved by the Animal Care and Ethics Committee of the South-Central University for Nationalities and conformed to the guidelines of the Institutional Animal Care and Use Committee of the South-Central University for Nationalities (QHL-6, 12-10-2013)." ] },{ "paper_id": "83c96f2a481be06a5c58552cbad2ca67ce789dc2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The conditional probability of the event given the event , say, is computed as ", ": out of responded cases are identified through the algorithm out of have responded to the survey.", "(iv)" ] },{ "paper_id": "83d150bdc1e4fdc24ecc74e0fd09d5fd7791cc65", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Materials of plant species were ground, extracted with the indicated solvent for one week. The extracts were concentrated under vacuum. Plant materials of the species no. 13 (leaves) was subjected to an additional one-step extraction with ethyl acetate (EtOAc) and filtered and dried as described before. The volumes (5 ml) of solvents were used per gram of plant material.", "Significant differences between groups were analyzed by 2 tailed Student t test with the software GraphPad Prism 6 (La Jolla, CA, USA). Data are presented as mean \u00b1 SD. P < 0.05 was considered statistically significant. The statistical datasets are showed in the supplementary information.", "WST-1 assay (Roche, Basel, Switzerland) was used to monitor cell proliferation (Chou et al., 2014) ; cells were trypsinized and resuspended in culture medium, then plated at 5\u00d710 3 cells per well in 96-well plates and incubated overnight. After plant extracts treatment for 48 h, the cells were incubated with 10 \u00b5l WST-1 reagent for 2 h. The cell viability was quantified by multi-well spectrophotometry (Anthos, Biochrom, Cambridge, UK). The absorbance at 450 nm was monitored, and the reference wavelength was set at 620 nm." ] },{ "paper_id": "83d77dc0616b9b240d13a844c7135dc250773fe0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The monoclonal antibodies used in this study were: CD3-pacific blue (PB) (clone UCHT-1; Dako, Trappes, France), CD4-peridin chlorophyll protein-cyanine 5.5 (PerCP-Cy5.5) (clone L200; BD, Le-Pont-de-Claix, France), CD45RA-phycoerythrin (PE) (clone HI100; BD), CCR7-allophycocyanin (APC) (clone 150503; R&D Systems Europe, Lille, France); CD8-phycoerythrin-cyanine 7 (PE-Cy7) (RPA-T8; BD), CD31-biotin (clone WM59; AbDSerotec, D\u00fcsseldorf, Germany); Ki-67-fluorescein isothiocyanate (FITC) (clone MIB-1; Dako), Bcl-2-FITC (clone 124; Dako) and strepatavidin-PE-Texas-RED (BD).", "The hepatitis C virus (HCV) causes persistent infection in approximately two thirds of cases leading to chronic liver disease, liver failure, and, eventually, hepatocellular carcinoma in a substantial proportion of infected individuals. The most common therapy for chronic hepatitis C consists of pegylated interferon-a (IFNa) and ribavirin administration which results in viral clearance in 43-46% (genotype 1) to 80%, (genotype 3) of treated patients [1] . Interferon will continue to be a major component of new direct acting antivirals for treatment of HCV [2] .", "Immunophenotyping and flow cytometry analysis FACS analyses were performed on cryopreserved samples. After thawing blood cells were incubated for 15 minutes at 4uC with conjugated monoclonal antibodies (mAbs). For intracellular labeling, cells were permeabilized with the Cytofix/Cytoperm Kit (Becton Dickinson) before incubation with specific mAbs according to the manufacturer's instructions. Samples were then washed, fixed in 2% paraformaldehyde phosphate-buffered saline (PBS/PFA 2%) and acquired using a Cyan cytofluorometer (Dako) and analyzed with FlowJo 8.7 software.", "Statistical analyses (Spearmans rank correlations and Wilcoxon matched -paired signed-rank tests) were performed using the Stata/IC 10.0 (Stata corporation, College Station, Tx U.S.A.). Due to the exploratory nature of the study there was no correction for multiple comparisons, and calculated p values are reported herein. " ] },{ "paper_id": "83d82d42b92c964ba7bd7bd9f456a16c9d3cbaaf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The natural killer cell is an innate lymphoid cell which can have a profound impact on adaptive immunity, but is also able to induce an early and rapid innate response against pathogens through a variety of mechanisms. NK cells produce cytokines, such as IFN\u03b3, show cytotoxic activity against infected cells not expressing MHCI, can induce dendritic cell maturation, and effect the destruction of infected cells in ADCC [161] . However, NK cells may deploy even more extensive and important functions in porcine immunity than are currently realized.", "On balance, the immunological evidence for PRRSV inducing a state of immunosuppression does not appear to be compelling. Secondary infections following PRRS disease outbreak in swine herds, suggesting a reduced ability to fight infection, is an alternative indicator of immunosuppression. An early study showed concurrent pulmonary bacterial infections in 58% of 221 PRRS cases [73] .", "However, the study did not determine if bacterial infections were present before the PRRS outbreaks. The immunosuppression question also was addressed in more controlled settings using dual infection models with PRRSV and various bacterial species. A summary of published literature in 2003 showed no predisposition to bacterial disease in 8 of 15 coinfection models, three ambiguous outcomes, and four cases in which severity of disease was increased [74] . More recent studies found a positive association between PRRSV infection and replication of porcine circovirus 2 (PCV2) or swine influenza virus [75, 76] .", "The name PRRSV was introduced in 1992 and encompasses PRRSV-1 (genotypes first isolated in Europe) and PRRSV-2 (genotypes first isolated in North America) [4, 5] . Today, both virus types are globally distributed, with PRRSV-1 viruses predominantly in Europe and PRRSV-2 viruses largely in North America, Asia and South America [6] . Recent discovery of multiple arteriviral nucleotide sequences in nonhuman primates has led to a reclassification of PRRSV as two distinct viruses, PRRSV-1 and PRRSV-2 [7] . Here, we use the generic PRRSV to refer broadly to both viruses when evidence indicates that are equivalent, and the specific PRRSV-1 and PRRSV-2 is used when a distinction is desired. The reasoning is based on the many similarities of the two viruses in fine details of genome structure and organization, transcriptional strategy, host preference, clinical signs of disease, and" ] },{ "paper_id": "83ded158834351502d802279e29b00a98d7cd4e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All 24 participants completed the study, and their general characteristics are shown in Table 1 . Eighteen participants received a Model 1860 respirator and six participants received a Model 1860S respirator, based on their face and lip measurements.", "The changes of the respiratory rate and intensity could influence the result of respirator fit [30] . The respiratory rate and intensity could be influenced by characteristics of procedures such as workload, degree of stress, and environment. It would be needed to create a well-designed simulated workplace which reflects the changes of respiration rate and intensity for physicians who perform procedures with a high risk of infection.", "The authors declare that they have no conflicts of interest." ] },{ "paper_id": "83e137405afc87914e9128afa5aec46cc2b152cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Adenoviruses have a wide range of virulence, and infection can vary from subclinical disease to significant mortality [91] . Given the potential for mortality from adenoviruses, pathogen isolation and characterization using molecular methods, and continued monitoring of this pathogen are warranted.", "Age confounded the association between rearing site and WNV serologic status and was therefore included in the model.", "While we found strong evidence of exposure for many avian pathogens, improved testing methodologies and characterization of pathogens are needed to more completely understand the true infection status, epidemiology, and potential pathogenicity of these viruses and bacteria in scavenging birds. Because the tests used in this study were not validated for the species tested, it is possible that cross-reactivity may have occurred with similar pathogens. It is also possible that some tests failed to detect antibodies, resulting in underestimation of the seroprevalences." ] },{ "paper_id": "83e2abcbaa73c0654cdfcd23bf817beeafbc6e37", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The datasets generated for this study are available on request to the corresponding author.", "All results were plotted and analyzed using GraphPad Prism 6 software (GraphPad Inc., La Jolla, CA, United States). The data were presented as the mean \u00b1 standard deviation (SD) of three independent experiments. Data were statistically compared using the t test. A p value < 0.05 ( * p < 0.05 and * * p < 0.01) was considered statistically significant.", "The GenBank sequences of the TGEV N gene (GQ-374566.1) coding sequence (CDS) conserved region, the porcine MX1 CDS (MX dynamin like GTPase 1; AH015318.2), the MX2 CDS (MX dynamin like GTPase 2; AY897395.1), the ISG15 CDS (interferon-stimulated protein, 15 KDa; NM_214303.2), the OASL CDS (2 -5 -oligoadenylate synthetase like; NM_214303.2), the PKR CDS (double stranded RNA-dependent protein kinase; AB104654.1), the ZAP CDS (zeta-chain associated protein; GU_563332.1), and internal reference pig \u03b2-Actin gene (ACTB; XM_003124280.2) were obtained and pairs of specific primers were designed using Primer 5.0 software for quantitative realtime PCR [performed using SYBR Premix EX Taq II (Takara, Shiga, Japan)] as follows: TGEV-N (Forward: 5 -TTCAACCCC ATAACCCTCCAACAA-3 and Reverse: 5 -GGCCCTTCAC CAT GCGATAGC-3 ), MX1 (Forward: 5 -ATCTGTAAGCAGG AGACCATCAACTT G-3 and Reverse: 5 -CTCGCCACGTCCA CTATCTTGTC-3 ), MX2 (Forward: 5 -TTCACTCGCATCCGC ACTTCAG-3 and Reverse: 5 -AGCTCCTCTGTCGCACTC TGG-3 ), ISG15 (Forward: 5 -GGCAGCACAGTCCTGTT GATGG-3 and Reverse: 5 -TGCGTCAGCCAGACCTCAT AGG-3 ), OASL (Forward: 5 -CGTTGGTGGTGG AGACACA TACAG-3 and Reverse: 5 -TCAGGCGACACCTTCCAGG ATC-3 ), PKR (Forward: 5 -ACAGGACCTGCACATAACT TGAGG-3 and Reverse: 5 -TGCTGTCGGCAGTGATGAAGA AC-3 ), ZAP (Forward: 5 -GCTCAGTGCGAAC ACCTGGA TG-3 and Reverse: 5 -TGACAGATGAAGGCGTGGAG AGG-3 ), and ACTB (Forward: 5 -CTCTTCCAGC CCTCCT TCC-3 and Reverse: 5 -GGTCCTTG CGGATGTCG-3 ). The designed primers were synthesized by Shanghai Shenggong Biotechnology Service Co., Ltd. (Shanghai, China)." ] },{ "paper_id": "83ee38f0c4d9191d4f6cad59de96a20a50c18417", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Citation Brand\u00e3o PE, Ayres GRR, Torres CA, Villarreal LYB, Hora AS, Taniwaki SA. 2016. Complete genome sequence of a Brazil-type Avian coronavirus detected in a chicken.", "Avian coronavirus is the causative agent of infectious bronchitis in chickens, leading to multisystemic disease that might be controlled if adequate vaccine strains are used. This paper reports the first complete genome sequence of a Brazil type of this virus (27,615 nucleotides [nt]) isolated from the kidneys of a chicken.", "Accession number(s). The Gammacoronavirus/AvCoV/chicken/Brazil/23/2013 complete genome sequence is deposited in GenBank under the accession number KX258195. " ] },{ "paper_id": "83f15da5d4de38afb2d1ba4b482f66d4e623c11e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ebolaviruses (EBOVs) and marburgviruses (MARVs) comprise the filoviruses, a family of enveloped, nonsegmented negativesense (NNS) RNA viruses [1] . These zoonotic pathogens, which are associated with increasingly frequent outbreaks in humans, cause lethal hemorrhagic fever and are of concern as potential bioterrorism agents [2] . Currently, approved therapeutics to treat these infections are not available. New treatment strategies could be facilitated by improved insight into mechanisms regulating filovirus replication and gene expression.", "The EBOV L-59UTR uAUG mutant virus is impaired for RNA synthesis at early time points post infection", "The plasmids used in the EBOV transcription/replication assays were described previously [57, 85] . The coding sequences of L and the other viral proteins were cloned into pTM1 (no virusderived UTRs were present)." ] },{ "paper_id": "83f5dbddb15c7cc6ad9d27d00ba1226462845440", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Another consideration is the possibility of an upper limit on the distance between exons that permit lariat formation and subsequent splicing.", "162" ] },{ "paper_id": "83f6440ed5fdcf297d2728df93830c842076c33c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mtb strains and growth conditions. Mtb strain H37Rv was grown at 37 \u00b0C in Middlebrook 7H9 containing 0.5% glycerol and supplemented with 10% bovine serum albumin (BSA) -D-dextrose -NaCl (ADN), 0.05% Tween 80. Middlebrook 7H10 medium supplemented with ADN and glycerol was used as solid medium." ] },{ "paper_id": "8412853deda865020fb0f86ee6be9acb3ca7408b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA replication of (+)ssRNA viruses that infect eukaryotic cells results in virus-induced membrane remodeling [46, 47] . The remodeled structures have been designated as virosomes, virus inclusions, virus factories, viral replication factories, cytopathic vacuoles or viroplasm. Sometimes they are incorrectly called inclusion bodies, a term borrowed from aggregates observed in bacteria.", "So far it is clear that PSs are necessary but not sufficient for most viruses. In such cases, replication and/or translation are required to make a viral RNA suitable for packaging. As it turns out, RNA replication modifies cellular membranes. This rearrangement is mostly caused by the viral non-structural proteins; therefore, we will now discuss the role of such cellular modifications on packaging specificity.", "Genus ", "Packaging signals (PSs) have long been associated with the specific incorporation of the genome of (+)ssRNA viruses, retroviruses and hepadnaviruses. While retroviruses and hepadnaviruses switch their genome from ssRNA to dsDNA, the molecule that is packaged during assembly is ssRNA; thus most of the packaging-related aspects described for (+)ssRNA viruses are applicable to these two types of viruses." ] },{ "paper_id": "842863c4f79b4d13ef260ef46b9882e8afe2b8ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MinKNOW v1.14.1 (GUI 2.1.14) interface. Live basecalling was turned off.", "Since the common heuristic for variant calling with Illumina reads requires 10\u00d7 coverage (Illumina, https ://www.illum ina.com/Docum ents/produ cts/ techn otes/techn ote_snp_calle r_seque ncing .pdf ), we assumed the criterion that at least 10 reads were correctly called and mapped to a single base (k = 10).", "Author details 1 Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. 2 A*STAR Graduate Academy, Singapore, Singapore. 3 University College London, London, UK. 4 Bioinfomatics Institute (BII), A*STAR , Singapore, Singapore. 5 National University of Singapore, Saw Swee Hock School of Public Health, Singapore, Singapore.", "where m is the gradient of the regression line of < C q > on log 2 (copies/\u00b5L).", "Absolute quantity (copies/\u00b5L) was calculated using the respective equations of the regression lines." ] },{ "paper_id": "842df6edd1fa0ce2684a79447ad591b1093d83f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cytokines were determined by ELISA using antibody pairs and recombinant cytokine standards from BD Bioscience. IL-27 was measured using QUANTIKINE Mouse IL-27p28 Immunoassays (R&D Systems Inc., Minneapolis, MN).", "Frozen tissues were homogenized in TRIzol (Invitrogen, Carlsbad, CA) and cDNA prepared as described [47, 48] . Quantitative real-time PCR was performed using 4 ml of cDNA and SYBR Green Master Mix (Applied Biosystems, Foster City, CA) in duplicate on a 7500 Fast Real-Time PCR System (Applied Biosystems). Expression levels were normalized to ubiquitin or GAPDH using the following formula: ", "Mixed glial cultures (,70% astrocytes) were established from neonatal GFAPcR1D and wt mice as previously described [47] . IL-27 secretion was determined 48 h after rIFN-c (100 ng/ml) stimulation." ] },{ "paper_id": "84323c90f9a4e2e339105377d6a0769cc2fa0fbc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Methods were approved by the University of Saskatchewan committees on Animal Care (Protocol #20100120) and Biosafety (Permit #VMB03).", "Tissues were homogenized in 2 ml sealed vials with a 5 mm steel bead, 0.1 g of 0.1 mm zirconium silica beads, 350 mL of RLT buffer (with b-mercaptoethanol) (RNeasy Plus Kit, Qiagen, 74136) using a Retsch MM400 tissue homogenizer at 30 Hz twice for 2 minutes each. RNA from tissues was extracted using the procedure provided with the RNeasy Plus Kit.", "cDNA Synthesis cDNA synthesis was performed with 1 mg of RNA per reaction using the Quantitect Reverse Transcription Kit (Qiagen, 205313). cDNA samples were either stored at 4uC if proceeding to use in qRT-PCR, or stored at 280uC until they were needed.", "Bats, members of the mammalian order Chiroptera, have evolved a range of characteristics that allow them to adapt to changing environmental conditions. They are the only mammals capable of powered flight, most bat species undergo torpor to conserve energy and species that inhabit high northern latitudes hibernate for up to eight months with body temperatures below 10uC [1] . Bats are extremely diverse, making up a fifth of all known mammalian species. They occupy a variety of niches across most of the world where they contribute in many ways to ecological balance [2] .", "Interleukin 23 is a multifunctional pro-inflammatory cytokine involved in both innate and adaptive responses [30] . It is an important mediator of Dectin-dependent response of the protective neutrophils to lung infections by Aspergillus [31] . It is also important in the maturation of T helper cells. In addition to being protective IL23 may also play a negative role by inducing chronic inflammation and exacerbating the effects of Aspergillus and Candida infections [32] ." ] },{ "paper_id": "8437870dfb10809764da7204fd758ff3e9ee85db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It was recently discovered that many people of African origin harbor a high frequency of mutations and single-nucleotide polymorphisms (SNPs) that cause a deficiency in the CD36 gene, yet", "The cyto-adhesive property of infected red blood cells to the microvasculature and sequestration within vital organ systems is an important survival strategy that allows the parasite to escape immune-mediated destruction (Urban et al., 1999) . Cyto-adherence is mediated by an orchestrated set of interactions between specific regions within the ectodomain of PfEMP-1 [notable among them being the cysteine-rich interdomain region (CIDR1\u03b1)], with a variety of host molecules on the surface of capillary endothelial cells. A well-characterized host receptor that mediates cyto-adherence of most Pf isolates to the peripheral vasculature is human CD36 (Ockenhouse et al., 1989) , although other cell adhesion molecules are also involved in execution of strain and tissue-specific cyto-adhesive events (Ockenhouse et al., 1991; Baruch et al., 1997 ; Figure 1 ).", "In spite of evidence from case-control studies that show a disproportionately high KS prevalence in areas of currently or previously high malaria endemicity, a molecular link between KS pathogenesis and Pf malaria has not been rigorously examined at a micro level, and the correlation is even more difficult to establish at a population level because of the indeterminate nature of the mechanisms by which malaria might influence KS pathogenesis outside the known clusters of endemic disease co-incidence. On one hand, the role of malaria as a co-factor for eKS has been hypothesized based on the potential of the Anopheles mosquito vector to contribute to person-to-person spread of KSHV, and to establish an immunosuppressed state at the site of the mosquito bite, which would then create a local permissive environment for KSHV infection (Coluzzi et al., 2003; Ascoli et al., 2006a,b,c) . However, we propose an alternative model based on the provocative hypothesis that both the malaria parasite and KSHV exert bidirectional influences upon each other that operate at a much more complex level beyond the permissive benefits of immune suppression or the modifying effects of occupational, socio-economic, or environmental co-factors.", "With respect to malaria control, approaches that interrupt the parasite life cycle are ideal, yet in spite of many multi-national efforts in this regard, successful elimination of the disease remains a major challenge, as more than half of the world's population still lives in areas where there is a risk of contracting the disease. There are many reasons for this sobering report card, chief among them being persistent endemicity as a result of drug and insecticide resistance, inadequate support for malaria control programs, poor environmental management, the complex biology of the disease, as well as the regional variability not only in the parasite but also in the nature of its impact on specific populations and age groups. Another major challenge remains the lack of practical and affordable animal models that can faithfully reflect mechanisms of malaria pathogenesis and immunity in humans. Such platforms would be valuable for evaluating the efficacy of drug and vaccine candidates, and for predicting the benefits of drug combinations that can maximize safety and efficacy while minimizing the development of drug resistance.", "The fact that the mutations and their phenotypes occur at high frequency in malaria-endemic areas with a high prevalence of viruses associated with endemic cancers underscores a pathobiological paradigm whereby an inherently persistent tumor virus such as KSHV (or EBV) could provide the selective pressure for introduction or maintenance of such a mutation into the genetic registry of populations living in regions of high malaria endemicity. Given that PfEMP-1 interactions with CD36 result in induction of the viral lytic cycle, such a virus-induced genetic output would conceivably be designed to promote virus escape from immune surveillance by limiting virus reactivation that might result from interactions between PfEMP-1 and CD36 on latently infected cells. The impact of such a genetic influence, can only be measured against the host's ability to restrict virus replication and dissemination, and it could be achieved by interrogating viral genomic variability or stability in a given population against a profile of polymorphisms within the genetic registries at the CD36 locus on a population basis. Availability of patient samples with known patho-status and disease severity from regions in which the distribution of malaria overlaps with the incidence of virus-associated endemic cancers would facilitate such a retrospective analysis." ] },{ "paper_id": "843ef80437031ed9f9adcf3e7b6183b6b898d433", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Not applicable.", "The author declares no conflict of interest, financial or otherwise." ] },{ "paper_id": "8446bfae882d6ec192e572e9bbcb858eeae83cc8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We connect adjacent dots with lines and then obtain a dual-vector curve form. This process is shown in Figure 2 .", "Obviously, this index is relatively simple for calculation so that this index can provide some convenience for long sequences.", "Here, we use the as an alternative sequence invariant proposed by Liao et al. [35] :" ] },{ "paper_id": "844b876f1636f5d031fe856cd7a63ae5f5c11fe7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "WTO 3 -1 Cy5", "Statistical analyses were then done using these values.", "Next, we picked many of the 454 spots detected and subjected them to analysis with tandem mass spectrometry." ] },{ "paper_id": "845b2c4662c9d7db919b0f257acecf15d97dfc81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Bioinformatics Materials and Methods are described in S1 Materials and Methods in detail.", "For various analyses we used the following databases: PlanMine [119] , Smed Unigene [102] , scop70_1.75, pdb70_06Sep14 and pfamA_28.0 supplemented with profiles of conserved nidovirus domains [172] [173] [174] , Uniprot [175] , genome sequences representing the current 57 nidovirus species that were delineated by DEmARC [176] and recognized by ICTV on year 2016 [177] , NCBI Viral Genomes Resource [178] , GenBank [179] and RefSeq [180] ." ] },{ "paper_id": "845bf0e6613fbb4dfd669bd913f7ebe6020b2cf4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There is no previously published case of AFOP and UCTD.", "After excluding any infection etiology including bacteria, virus, mycobacteria, and fungus, she received pulse therapy with cyclophosphamide 1 g and methylprednisolone 1 g for three days. Despite treatment, the patient developed respiratory failure by pulmonary hemorrhage.", "At that moment the pulmonologist considered three possible diagnosis: nonspecific interstitial pneumonia, pneumonia caused by Pneumocystis carinii, or pneumonia caused by virus (CMV, adenovirus, herpes 1 and 2).", "The natural history of these rare entities is variable: a high percentage of patients with UCTD maintain an undifferentiated clinical course and do not evolve to a distinct CTD, whereas some patients can evolve over time [11] . Lung involvement as the first clinical manifestation of UCTD is rarely reported and usually appears as a complication in established UCTD [11] ." ] },{ "paper_id": "846f108dcf44ed854491112e1de0c86b5193cb86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Panel at CQUniversity (H09/06-037) and the incorporation of the influenza-related questions was approved by the Human Research Ethics Committee at James Cook University (H3456)." ] },{ "paper_id": "84737ac767f2be6c8623fb433c75e0fa5faf95b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two serial multiple mediator models can translate into three equations:", "where x (i) represents the i-th ordered value and \u03c8 = \u2211 n i=1 S i,n . The amount of the average increase in \u2206\u00b5 is:", "In order to obtain another value \u2206 \u00b5(r), the weights can be generalized as:", "The assigned weight , is the selected probability for the observations after scaling and adjustment. The average of the resampled data is shown in Equation (2): ", "The assigned weight S i,n is the selected probability for the observations after scaling and adjustment. The average of the resampled data is shown in Equation (2):" ] },{ "paper_id": "84785c6c2c5a963376b6314c430402e4fe3654e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Anti-JEV Potential Reference Aspirin", "Aspirin suppressed JEV propagation in neuronal and nonneuronal cells [27] Chlorpromazine", "where" ] },{ "paper_id": "8485271eeb378baa284392c0d7174a5612463048", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IC and MHB conceived the idea. MHB, KA and GR drafted the review manuscript. IC, MHB, KA and GR critically reviewed the article. IC edited the language and corrected the errors within the manuscript.", "Jagota and Rajadas (2013) synthesized three short D-peptides, that is, KKLVFFARRRRA, PGKLVYA and KKLVFFA, based on residues of the central hydrophobic core of A\u03b2 (residues 16-20), and examined their effects on A\u03b2 aggregation. Observations suggested these D-peptides effectively inhibited A\u03b2 fibrillogenesis, and two of the three (KKLVFFA and PGKLVYA) were found to improve survival in transgenic C. elegans.", "Today, due to the extensive efforts of researchers and pharmaceutical companies, peptide-based drugs have emerged as a major class of therapeutics, and as a result, the last decade has witnessed extraordinary scientific and industrial interest in their therapeutic uses (Vlieghe et al., 2010) . Such studies are very much on-going and currently, a number of natural and synthetic therapeutic peptides are undergoing clinical trials (Mandal et al., 2014) . Generally, these drugs have several advantages over small molecule therapeutics, particularly in terms of their efficacies and fewer side effects (Craik et al., 2013) ." ] },{ "paper_id": "848c234214cbc5eeb1d64a043ff097e32e8ebff0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Limbs from euthanized animals were preserved in buffered formalin, decalcified, embedded, sectioned, and stained with hematoxylin and eosin (H & E) in the USC Research Model Pathology Core. Microscopic images were acquired with a Nikon-Microphot FXA with SPOT 5.1 image capture software.", "Adult DA or Sprague-Dawley rats were challenged s.c. with 5 mg/kg RTD-1 every day (15-42 injections) , or every other day (8 injections). Several animals were boosted 2 months later, prior to serum or plasma collection. Immune responses were analyzed by dot blot on nitrocellulose membranes as described in legend to the figure.", "https://doi.org/10.1371/journal.pone.0187868.g006" ] },{ "paper_id": "849323d550c05b7686a3ce258800f42fbd5f46be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Slides were examined with an Olympus FV10000 laser-scanning confocal microscope equipped with a super corrected 60\u00c2/1.4 NA oil-immersion objective and a dichroic mirror DM405/488/543/635 was used for all experiments. The pinhole was maintained at 1 Airy unit and images were acquired in two separate channels to prevent bleed-through. The excitation/emission wavelengths were 405 nm/425-520 nm for DAPI, 488 nm/500-520 nm for Alexa Fluor 488, 543 nm/555-647 nm for Alexa Fluor 594 or PKH26, and 635 nm/647-700 nm for Alexa Fluor 647. Intensity plot profiles were generated using the ImageJ software and co-localization indexes (Mander's coefficients) were obtained with the Just Another Colocalisation Plugin (JACoP) module for ImageJ. All micrographs are representative of at least 10 images for each sample per experiment, and each experiment was performed at least twice. Images were processed for presentation using Photoshop CS4.", "It was not clear how these two different types of virus particle are both able to enter cells despite their surface being so different. To address this question, Rivera-Serrano et al. used a microscopy approach to observe Hepatitis A particles infecting human liver cells.", "Unless stated otherwise, significance was assessed by unpaired t tests or ANOVA calculated with GraphPad Prism seven for Windows software. Significance values are shown as ****p<0.0001, ***p<0.001, **p<0.01, *p<0.05." ] },{ "paper_id": "849541788c0fe480a2fb9e13b20f3937e759b249", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The studies utilised a randomised complete block design, and Tables 1, 2 and 3 illustrate each study design." ] },{ "paper_id": "8495f7c65f4a6cbce0e0d53c0900f10f6740826e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "tHe nUCLeoLUs-strUCtUre, FUnCtion, and dynaMiCs", "The author has no funding other than as a Research Assistant Professor in the Chemistry Department at the University of South Florida, Tampa, FL USA. ", "The author confirms being the sole contributor of this work and approved it for publication." ] },{ "paper_id": "84a52dad0aab6d229fa21d15308819c3f792e539", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2) or a suspected case with any of the last three abovementioned laboratory test results (B, C or D).", "Please see Additional file 1 for translations of the abstract into the five official working languages of the United Nations.", "R statistical software (version 3.4.1, R Foundation for Statistical Computing, Vienna, Austria) was utilized to generate graphs and perform statistical analyses, and ArcGIS software (version 10.2.2, ESRI, Redlands, CA, USA) was used to plot geographical patterns." ] },{ "paper_id": "84a964d5dde5ffc12076b7c43ac5fff52210ad61", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "mulated the idea for this study and also provided critical comments regarding this manuscript. All authors read and approved the final manuscript." ] },{ "paper_id": "84aa85f8690419badcdb6d6777763e6fc3235af1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human cardiomyocytes were lysed in 250 \u03bc l of 2\u00d7 SDS loading buffer (62.5 mM TrisHCl, pH 6.8, 2% SDS, 25% glycerol, 0.01% bromphenol blue, 5% 2-mercaptoethanol), and incubated at 95\u00b0C for 10 min. Equal amount of proteins (100 \u03bcg) for each sample were separated by 8-15% SDS-polyacrylamide gel and blotted onto a polyvinylidene difluoride microporous membrane (Millipore, Billerica, MA, USA). Membranes were incubated for 1 hour with a 1:1000 dilution of primary antibody, and then washed and revealed using secondary antibodies with horseradish peroxidase conjugate (1:5000, 1 hour). Peroxidase was revealed with a GE Healthcare ECL kit. Proteins were quantified before being loaded onto the gel.", "We used the Predicting Risk of Death in Cardiac Disease Tool (PREDICT) score to create an index of severity as previously described [19] . It was used to provide a simple, long-term admission-day prognostic score for patients hospitalized for MI or unstable angina. Score components include shock (0 to 4 points), clinical history (MI, stroke, angina; 0 to 2 points), age (0 to 3 points), ECG findings (0 to 3 points), congestive heart failure (0 to 3 points), and Charlson Comorbidity Index (0 to 6 points) for a maximum severity score of 21 points [19] .", "Between July 2010 and October 2012, 351 subjects with first-time acute MI (mean age 62.7\u00b115.9 years; range, 27-78 years) were recruited to this study at the Second Xiangya Hospital of Central South University. Inclusion criteria were: (1) patients who had undergone a first attack of ST-elevation myocardial infarction (STEMI);" ] },{ "paper_id": "84ad793db6fd5878929791f4a2f50943881206f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "84b4e11342098e8595165eff814c004ec50d3e0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "YY, XC and ZX wrote this review article. XC, ZX, SZ, XW, WL, LQ, JW, XY, QS and ZG performed administrative and technical support. YY designed the study and contributed to manuscript preparation. All authors reviewed and approved the final version of the manuscript. ", "significantly up-regulated phosphorylation of GSK-3\u03b2 and promoted cellular apoptosis comparing to NM or PP2A alone, suggesting NM may improve the therapeutic outcomes of pancreatic cancer (38) . Taken together, NM, alone or in combination with other anticancer treatments, plays a powerful role as a candidate intervention in NF-\u03baB signaling for cancer therapy.", "Tryptase, a trypsin-like serine-proteinases with a molecular weight of 134 kDa, is the most abundant secretion of mast cells (MCs) (42) . Tryptase contains a hydrolyzing peptide that binds to the carboxyl terminus of basic residues and a tetrameric structure consisting of non-covalently linked subunits, with an adequately active form stored in MCs (43) . Two types of tryptase are expressed on human MCs, alpha and beta. Tryptase\u03b1 is the major circulating isoform, and tryptase-\u03b2 is the major form stored in secretory granules (42) . Normally, tryptase acts as an indicator to provide information about the distribution and activation status of MCs, so levels of serum tryptase may reflect disease states, such as allergy reaction, mastocytosis, and other inflammatory reactions (44, 45) . Nevertheless, there is increasing evidence to support the view that tryptase is a vital mediator in biological pathways, including tissue remodeling and carcinogenesis (46) ." ] },{ "paper_id": "84b4f6a6bca69d4387ae4f6c276ce370a9def7c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MEGAN assigned the reads to 30 taxa. These included some species and genera but most were families (Supplementary Table S2 ).", "P\u00f0XjM species present \u00de P\u00f0XjM species absent \u00de .", "Conflict of Interest: none declared.", "The posterior probability of the model M k is:" ] },{ "paper_id": "84bafc34e5e1118ed2da16a02c87e472e0dd0d4c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest.", "Autoimmune hepatitis ALP Alkaline phosphatase AP1, AP2", "Gene " ] },{ "paper_id": "84bb5b317c837c22b090bc10357a3542f58402bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "E. coli serogroups O5, O15, O26, O45, O55, O76, O91, O103, O104, O111, O113, O118, O121, O123, O128, O145, O146, O157, O165, O172 and O177 are the O-antigen types of the most clinically significant Shiga toxin-producing E. coli serotypes. These 21 serotypes were identified using three serotype-specific multiplex PCR assays, and it can also detect the respective O-antigens even when they are not expressed by the E. coli strains (S\u00e1nchez et al. 2015) ." ] },{ "paper_id": "84bdc3ec8b4e9ba8a0c4eac3105208064704d50f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "84befea7ee1f85d2e9367d83bdb4834d56f9682a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All samples, including heparinized blood, were shipped cool (5-10 \u00b0C) and arrived within 24 h to the Norwegian Veterinary Institute laboratory after sampling. Tissue samples on RNAlater \u2122 were placed at \u221220 \u00b0C until further analysis. A sub-sample of 200 \u00b5L from each heparinized blood sample was subsequently shipped cold, together with heart samples on RNAlater \u2122 , to PatoGen AS for virus analysis.", "Two pieces of 2 mm 3 from heart were collected on prefilled 1.0 mL tubes (FluidX \u00ae Ltd, UK) with 0.5 mL RNAlater \u2122 for RTqPCR analysis. Heparinized blood was collected from the caudal vein.", "The cohabitant challenge experiment is displayed in ", "Protection to a secondary virus infection induced by an unrelated primary virus infection has been recognized since the 1950s [25] , and has also been described for several viruses infecting salmonid fish [26] [27] [28] [29] [30] . However, the duration of the protection of rainbow trout to infectious hematopoietic necrosis after primary infection with the non-virulent cutthroat trout virus was found to be no more than 4 weeks [26] . In addition, some viral infections in terrestrial animals are shown to aggravate disease development of a secondary viral infection [31, 32] ." ] },{ "paper_id": "84bf3b3e1716be122763fef2463f88970a8306d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Prior to use, virion stocks, mock stocks, VLPs, and media were analyzed for endotoxin presence using the Limulus amebocyte lysate test (BioWhittaker, Walkersville, MD).", "Electron-microscopic evaluation of VLPs was performed on a Phillips CM100 microscope with low dose software and Compustage attachments. Negative staining was performed on formvar carbon-coated copper grids (Electron Microscopy Sciences, Hatfield, PA). Purified VLP solution (13 ml) was exposed to a freshly glow-discharged grid for 2 min, and the grid then transferred to a drop of 1% sodium silicotungstate (pH 7.5) for", "Reverse transcription and subsequent quantitative real-time polymerase chain reaction (qPCR) were performed as described previously [19] . Strand-specific qPCR was performed using strand-specific primers for the reverse transcriptase reaction. As controls for non-specific or self-priming events, control reverse transcriptase reactions lacking primer were performed in parallel. Relative amounts of different strands were determined by normalizing against the house-keeping gene GAPDH and by subtracting the amounts of PCR product resulting from selfpriming from strand-specific products. Relative quantification was performed using the comparative CT method (Applied Biosystems User Bulletin #2, Dec. 11, 1997)." ] },{ "paper_id": "84cdd2606c5e32c3573a6c70e5c9b14d22c5acc2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Convergence of all Bayesian models used was achieved according to the Gelman diagnostic test. Model validity assessed by comparing posterior predictions or simulations ", "We assumed a negative binomial distribution for the number of HFMD cases, Y t , observed in week t, with mean", "Data were collected under Singapore's Infectious Disease Act, and because aggregate non-identifiable data were used, institutional review board approval was not deemed necessary for this study." ] },{ "paper_id": "84db97911a7abce47876c5732ac570d78f253aaa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Six months after the 4-week IMPHI course ended all 12 participants who were interviewed for this evaluation reported implementing a change in management practice at their places of work. Only one participant interviewed could not provide any hard evidence for any of the changes she implemented. ", "Major activities undertaken by GFELTP residents over the years are summarized as follows:", "Placement of Graduates Table 2 shows the placement of graduates, pre and post certification." ] },{ "paper_id": "84dfb0723d3a0b1243850099eef4def974f44a8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Evaluating D j \u2208D\u03c0 (D j |D B , H j , \u0398) in practice becomes computationally difficult as D B increases in size, as it involves the evaluation of arrays of dimension |D B | \u00d7 |D| \u00d7 |codon sequence|. To increase computational efficiency, we restrict D B to a subset D B j for each member of D. In our simulations and analyses we use a simple Hamming distance restriction: the closest n sequences by Hamming distance to define each D B j . Now that we are able to evaluate approximate likelihoods rapidly, we can perform MCMC to obtain posterior distributions for our parameters of interest:", "\u2022 Recombination probabilities between neighbouring sites, r i ." ] },{ "paper_id": "84dfdd13ab7bf0544b5939a86b0c24b9a06e9700", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "84e3663e6544caf4cac64a937e7e3f6159717c3c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "populations. It is likely that new models and transgenic animals will be developed in the near future.", "We thank everyone involved in Team Ferret, whose names we will not list for fear we might miss someone, as well as others producing reagents for the ferret model. We also thank Diane Post (NIAID) and the members of the CEIRS network for feedback, advice, and constructive criticism. ", "Despite its relevance for biomedical research, there are limitations of the ferret model for immunologic studies due to the dearth of reagents. Screening of commercially available antibodies for cross-reactivity with markers on innate and adaptive cell subsets and cytokines in ferrets has yielded limited success ( Table 2) . To resolve this, a group of researchers from around the world are working together to develop validated reagents and assays to improve our understanding of the innate and adaptive immune responses in the ferret." ] },{ "paper_id": "84e5418129fec4b8872d40a2888a175550c0a6c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Intens.", "[%] ", "All ESI-MS experiments were performed on a micrOTOF-Q mass spectrometer (Bruker Daltonics, Bremen, Germany) equipped with standard ESI source. The instrument was operated in the positive-ion mode and calibrated with the Tunemix\u2122 mixture (Agilent Technologies, Palo Alto, CA, USA). The scan range was between 200 -1700 m/z. The mass accuracy was better than 5 ppm. Samples were dissolved in 200 \u00b5L of the water/MeCN/HCOOH (50:50:0.1, v/v/v) mixture. Analyte solution was infused at a flow rate of 3 \u03bcl/min. The instrument parameters were as follows: scan range: 50-1600 m/z; drying gas: nitrogen; flow rate: 4.0 L/min, temperature: 200 \u00baC; potential between the spray needle and the orifice: 4.2 kV." ] },{ "paper_id": "84e8a4145f06c604f8542ee458480c8fa50bd1cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Determination of nanoparticles concentration", "Manipulate particle spacing to observe various particle conditions [40] Liquid pumping manipulation in microchannel electrode", "Obviate pumping and leakage problems in close channel [41] Cylindrical electrodes" ] },{ "paper_id": "84efaac896e551763256fd4d16e56a99b416c175", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Admittedly, individuals who succumb to death shortly after oncogenesis will not display skeletal indications of either benign or malignant cancer tumours (i.e., osteosarcoma, chondrosarcoma and multiple myeloma), while those that did survive long after the formation of tumours might, in some instances, have developed skeletal lesions (Brothwell, 2016) . In addition, extraskeletal tumours leave ab- Figure 1 ). Thus, and on account of this \"osteological paradox\" (Wood et al., 1992) , disease incidence is often unnoticed or misconstrued, which leads to unverified statements that some diseases were either rare or nonexistent in prehistory.", "The past provides a prologue for discussions regarding emerging diseases, whether it concerns the biological origins of a potential pandemic or its social repercussions (Heymann, 2007) . Disease epidemics are not new and they will continue to affect and potentially devastate human populations. Significantly, the exclusive focus on diseases that have emerged within the past decades is cited as responsible for the lack the temporal depth necessary to examine the changes in the behaviour of emerging diseases and the long-term interactions between pathogens and human hosts (DeWitte, 2016).", "Guillain-Barr\u00e9 syndrome (undiagnosed) Panama 1 0 0 ", "Because of the paucity of aDNA sequences from Africa, these novel pathogen genomes will be highly valuable and decidedly revealing, providing novel revelations concerning human-pathogen coevolutionary processes (Slatkin & Racimo, 2016) . The unique combination of an unrivalled archaeological record and a thriving and highly skilled academic community therefore places southern African archaeologists, geneticists and medical scientists in a prime position to explore past pathogenic influences and to contribute to the improvement of human health and longevity." ] },{ "paper_id": "84f5fad8c5f0702b6816a479ae152a2dd58fa7f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The emergence of avian influenza viruses is linked to intensification of the poultry sector, both in high-income countries, where evidences link de-novo HPAI emergences to intensive poultry production systems, as well as in rapidly growing economies such as China, where the intensification of chicken and duck production at the interface with the wild virus reservoir supported the emergence and maintenance of several viruses of global public health relevance, such as the H5N1 and H7N9 viruses. In the short term, better biosecurity and prevention practices, improved and more frequent cleaning and disinfection at the level of farm and live-poultry markets may contribute to reduce the circulation of the disease in poultry and the human exposure to prevailing viruses in countries sharing similar conditions. In the long run, if one consider the wider set of direct and indirect impact and benefits of animal production, one could act on both ends of the livestock production systems intensification spectrum, through deindustrialization of production in HICs and sustainable intensification in LICs, and thereby optimize the societal benefits of ASF production while reducing its main externalities on human and ecosystem health.", "Although these conditions are somewhat specific to parts of Asia, it would be wrong to consider that the processes that they reveal are equally specific. Several other recent emerging zoonoses followed decades of increases in stock, as quantified from FAOSTAT [7] : the emergence of Q-fever in the Netherlands in 2007 [21] followed a period of rapid increase in goat populations, the emergence of the Middle-East Respiratory Syndroms (MERS) in the middle-east in 2012 [22] followed decades of increases in camel numbers in the Arabian peninsula. Similarly, the recent emergence of an indigenous HPAI H5N1 (distinct from the Asia one) in France [23] followed several years of increase in duck populations. Of course, intensification of animal production is usually paired with better bio-security and investment in animal health prevention and control. However, as the emergence of HPAI viruses in numerous high-income countries demonstrates, biosecurity is far from perfect and allows these emergences to take place occasionally, with devastating consequences for the livestock sector when these diseases are not zoonotic, and with significant public health implications when they are.", "The emergence of zoonoses is only one of the many challenges faced by the livestock sector in terms of sustainability and public health. Another important challenge is the question of antimicrobials uses in ASF production, either used as food additive (a practice that is increasingly forbidden), or overused as preventive or curative drug, which contributes to the increasingly important problem of antimicrobial resistance [24] . However, the role played by the livestock sector differs greatly depending on the context. In high-income countries (HICs), cheap production of ASF, mainly milk, eggs, meat, and their over-consumption by some, contributes to the obesity epidemic, plays a significant role on the global level of disrupts nutrient cycles and contributes to greenhouse gases emissions. By contrast, in low-income countries (LICs), 165 million children are stunted or live in a state of poor nutrition that could be addressed through local production and consumption of ASF, rich in energy and essential nutrients. In addition, in those most vulnerable countries, livestock play important and diverse roles for agricultural populations through the provision of manure and traction power, an alternative to bank systems, and insurance against hard times. It is estimated that livestock contributes to the livelihood and resilience of nearly 800 million poor smallholders throughout the world [8] . Depending where in the world it is located, and how it is managed or integrated, the livestock sector can thus both have very positive and very negative impacts on human and ecosystem health." ] },{ "paper_id": "850087dea2553c4099418c170742e85fcc4a5feb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protocols and procedures followed throughout the study were approved by the University of Minnesota Institutional Animal Care and Use Committee (IACUC1110A05802), and the Institutional Biosafety Committee (IBC1208H18341).", "The mean indoor temperature (mean \u00b1 standard deviation) was 23.2\u00b0C\u00b10.7\u00b0C with a mean relative humidity of 32.6% \u00b17.4% and a mean air pressure of -27.4 Pa \u00b1 0.15Pa relative to the hallway pressure." ] },{ "paper_id": "850295bc1049a0609b4568610f3b27bf9a150878", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Baseline characteristics (including age, sex, residency in a long-term care facility, comorbidities, presenting symptoms, and complications) at date of admission for cases and control patients were summarized using descriptive statistics, such as proportion and means (standard deviation, SD). A Chi-squared test was applied for comparison between categorical variables, and two-tailed t-tests, for comparison between continuous variables.", "Supporting information S1 File. The dataset for this study. (XLSX) ", "The current study was approved by the institutional review board (IRB) at Dongsan Hospital, Keimyung University School of Medicine. The IRB waived the requirement for informed consent. This study was conducted in compliance with the Declaration of Helsinki." ] },{ "paper_id": "850be0ae2ae61513057e7b44b0b2e7b2f326746c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consequently, to ensure an accurate temperature estimate, recorded thermograms were compensated for non-ideal blackbody emissivity, \u03b5 g , (e.g., non-zero reflectivity) per the Stefan-Boltzmann formula for a graybody. Thus, IR emission of an object can be expressed as [40] :", "Assuming the standard uncertainties due to drift (u D ), stability (u S ), uniformity of WTP (u U ), MRTD (u MRTD ), and ETRS (u ETRS ) are independent and random, u ST can be calculated as: ", "https://doi.org/10.1371/journal.pone.0203302.t005", "As the temperature of a blackbody increases, the intensity of its thermal radiation increases and the spectral distribution shifts towards shorter wavelengths. The peak wavelength (\u03bb max ) of the spectral distribution of a blackbody is described by Wien's displacement Law:", "The following is a summary of the terms and conditions described in the IEC 80601-2-59 standard [30] " ] },{ "paper_id": "850c8a23db306b9410adc341809d40d8b46635aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Porcine circovirus type 3 (PCV3) is an emerging circovirus species, that has been reported in major pig-raising countries including the United", "In June 2015, an outbreak of porcine dermatitis and nephropathy syndrome (PDNS) was reported in a commercial pig farm in North Carolina, United States. Compared with the historical data, the mortality rate of sows increased by 10.2% and the pregnancy rate dropped 0.6%. The affected sows were anorexic and their skin presented multifocal papules, plaques and superficial dermatitis. The manifestation of infected foetuses included weak, stillborn and mummified individuals. A new virus was isolated from these animals with the help of next-generation sequencing technology and was identified as porcine circovirus 3 (PCV3) [1] . PCV3 was subsequently widely detected in China, Korea, Brail and many other European countries including Poland, Italy, Spain, Denmark, Germany, and the United Kingdom [2] [3] [4] [5] [6] .", "Sensitivity and specificity of the real-time LAMP assay for rapid detection of PCV3" ] },{ "paper_id": "850d93fde366090620b90ed908b64de128048119", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Institutional review board approval for the randomised controlled trial was given by the Johns Hopkins University Bloomberg ", "Potential risk factors for transmission included maternal and household characteristics. Some households included more than one enrolled mother-infant pair. Among households with more than two mothers, household characteristics were compared with a sensitivity analysis using one mother's descriptors vs. the others. Data were analysed using SAS/STAT 9.4 (SAS Institute Inc.) and Stata 15 (STATA Corp) statistical software.", "Acute lower respiratory infection (ALRI) is the primary cause of child morbidity and mortality worldwide with the vast majority of childhood deaths related to ALRI occurring in resourcelimited settings [1] . Respiratory viruses are increasingly recognised as a cause of severe ALRI in young children [2] . In many global regions where access to healthcare is limited, especially in rural areas, the true community-based burden of respiratory virus-associated ALRI remains poorly characterised [3] [4] [5] . In these settings, household surveillance studies can provide a more comprehensive evaluation of viral incidence, transmission and molecular epidemiology patterns in the community [4] [5] [6] [7] [8] .", "Household surveillance can provide valuable information regarding the transmission networks within households. Such knowledge may guide the development and implementation of preventative interventions to protect vulnerable groups from ALRI. For example, infants are at highest risk for severe ALRI from respiratory syncytial virus (RSV) [9] . Major challenges to developing a safe and effective RSV vaccine in young infants have resulted in the development of alternative strategies including maternal RSV vaccination and delayed vaccine administration until >6 months of age [10] . Targeting older groups for vaccination may protect vulnerable populations by interfering in transmission chains to young infants, the elderly and other high-risk groups." ] },{ "paper_id": "85166a1c79d32bc2df2984260f1facc1a4d6148b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA extraction and cDNA synthesis. Total RNA was extracted from the tracheas using CinnaPure RNA (Sinaclon Co., Tehran, Iran) based on the kit instructions. The extracted RNA was used in reverse transcription (RT) reaction to generate cDNA through cDNA synthesis kit (Thermo scientific, Waltham, USA). The cDNA was stored at -20 \u02daC until use.", "The aim of the present study was to detect of three IBV genotypes including (Massachusetts; Mass), 793/B and D274 in the south of Iraq.", "Sampling. Tracheal tissue samples were collected from 46 IB suspected broiler farms, located in Basra, Thi-Qar and Muthana governorates. All chicks were 20-35 day-old and vaccinated with H120 and 4/91. Five tracheal tissue samples per flock were selected for RNA extraction." ] },{ "paper_id": "85172df4b29cb30c4e98011ed79e9da2ca63fbd6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Leishmania donovani (MHOM/SD/001S-2D) promastigotes were cultured as described previously [63] . Hamsters were infected by intracardial injection of 10 6 peanut agglutinin purified metacyclic promastigotes [63] .", "Hamster cDNA sequence assembly, characterization, and annotation" ] },{ "paper_id": "851a02ef7408469b2f8f97736a4515044daf805c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Functional predictions for all OTUs were performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) databases, based on the PICRUSt-established structure of gastrointestinal microbiota [34] .", "Genes 2020, 11, x FOR PEER REVIEW 5 of 13", "Genes 2020, 11, x FOR PEER REVIEW 6 of 13", "To minimize the effects of random sequencing errors, raw fastq files were demultiplexed, quality-filtered using Trimmomatic version 0.33, and merged using FLASH version 1.2.7 [25, 26] . To obtain high-quality tag sequences, initial base sites with Phred score <20 were truncated, tags were filtered out if their continuous high-quality base length was less than three-quarters of the whole sequence, and chimeric sequences were removed in UCHIME version 4.2 [27] . Sequences with \u226597% similarity were assigned to the same operational taxonomic units (OTUs) using USEARCH version 10.0 [28] . A representative sequence for each OTU was screened and taxonomically analyzed against the 16S rRNA database Silva, using Ribosomal Database Project Classifier version 2.2 [29] . Representative sequences were subjected to multiple sequence alignment and a phylogenetic tree was constructed. Next, the composition of each sample community was determined at the phylum, class, order, family, genus, and species level." ] },{ "paper_id": "8525c0b448a38d6453441a36426ce4c7a28c4e18", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Multiple outbreaks of infectious diseases, including yellow fever, severe acute respiratory syndrome (SARS), Ebola, dengue, chikungunya, are occurring with increasing frequency. At least three major factors have influenced the increasing incidence of infectious disease epidemics: population concentration at the epicenter of an infection, the underlying characteristics and vulnerabilities of the population at the epicenter [1] and extensive air travel to spread the PLOS ONE | https://doi.org/10.1371/journal.pone.0192398 February 5, 2018 1 / 17 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "ZIKV strain PRVABC59, NR-50240 was obtained through Biodefense and Emerging Infections Research Resources Repository (BEI Resources), NIAID, NIH and propagated in Vero cells. ZIKV stock was obtained from infected cells supernatant.", "Vero E6 cells (ATCC 1 CRL-1586TM) were maintained in tissue culture flasks at 37\u02daC in an atmosphere containing 5% CO 2 with Eagle's minimum essential medium containing Earle's balanced salt solution, non-essential amino acids, 2 mM L-glutamine and 1 mM sodium pyruvate, 100 units Penicillin, 0.1 mg/ml Streptomycin, 1.25% Amphotericin, supplemented with 2% fetal bovine serum (Atlanta Biologicals, S11150H)." ] },{ "paper_id": "8538c23b7be59b19a8376c51d6ec269c00b34bec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For more details, see S1 File.", "Abundances were visualized in heatmaps produced using the R package 'pheatmap'. For the AMR heatmaps, Euclidean distances between AMR features were clustered using complete linkage to draw dendrograms. For visualization, each AMR feature was transformed to Zscores to enable easy between-sample comparison within a single AMR feature.", "Metagenomic surveillance in an informal settlement PLOS ONE | https://doi.org/10." ] },{ "paper_id": "853fa72687a51e0a938d05ef0c6c6fde3fbc361f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RANTES -28C/G (rs2107538) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) as described previously [12] ." ] },{ "paper_id": "854e623d1f875e4605b2ffd3f72599d063a56cc0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The presence of Rotavirus and Coronavirus was detected by polymerase chain reaction (PCR) amplification [23, 24] .", "The presence of this type of fimbria has been reported in clinical human and animal isolates of Salmonella + + ----+ ---2 15228 -+ --------3 66761 -+ --------3 72827 -", "Bacterial DNA was extracted from 1 mL of overnight cultures using Chelex 100 Resin (BioRad, Hercules, CA) and used as the template for the PCR detection of genes listed in Table 2 , as described previously [8] [9] [10] [11] [12] [13] 18] . The primers used to amplify the genes sspH1, sspH2, ssaQ, sopB, siiD, stfE, safC, csgA, ipfD, bcfC, stbD, and fimA were designed using the Primer3 software (version 0.4.0; http:// frodo.wi.mit.edu/), and PCR was performed in a final volume of 25 \u03bcL containing HotStar Taq Master Mix (Qiagen, Valencia, CA) 1\u00d7, 0.4 \u03bcM each primer and 1 \u03bcL of extracted DNA. The thermal profile included an initial denaturation step at 95\u00b0C for 15 min, followed by 35 cycles at 95\u00b0C for 30 s, 58\u00b0C for 30 s, and 72\u00b0C for 1 min, and a final extension step at 72\u00b0C for 5 min. Amplification products were visualized under ultraviolet (UV) light after electrophoresis on 3% agarose gels and staining with SYBRsafe (Invitrogen, Carlsbad, CA)." ] },{ "paper_id": "85544c40199592db3f81823f341f19f303fef7ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Enteroviruses (EV) are small, non-enveloped viruses with a single-stranded, positive-sense RNA in the family Picornaviridae 1,2 . The length of enteroviruses is approximately 7.5 kilobases, and divided into 15 species (EV-A to L and rhinovirus A to C) 3-6 . Seven species, including EV-A to D and rhinovirus (RV) A to C, caused a wide spectrum of diseases in human 7,8 .", "was extracted from the clinical specimens by Thermo Scientific \u2122 KingFisher \u2122 Flex Magnetic Particle Processors (Thermo Fisher). EV-D68 and other enteroviruses were simultaneously detected in one tube with a commercial real-time RT-PCR kit (cat. no. CN08-4G-100, Jiangsu uninovo biological technology company, China). A panel of respiratory pathogens, including influenza virus A (pandemic influenza virus H1N1, seasonal influenza A virus H3N2) and B, respiratory syncytial virus, parainfluenza virus 1 to 4, human adenovirus, human rhinovirus, human metapneumovirus, human coronavirus (NL63, OC43, 229E and HKU1), human bocavirus, mycoplasma and chlamydia, were also detected in these specimens with commercial real-time RT-PCR kits (cat. no. CN12-33-100 and cat. no. CN09-4-100, Jiangsu Uninovo Biological Technology Co. Ltd., China). The serotypes of enteroviruses were identified with the the seminested and conventional RT-PCR method for amplification of VP1 sequences (cat. no. C81401180, Invitrogen GoldScript, United States) 40 .", "Results" ] },{ "paper_id": "85581e91ad30b4385cbd57496aaaf5f19ff33080", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "85657444327cc8301d257fbda39df1a02e9d1d40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "++ ++ ++ ++ +++ + +++ ++ + - +++ - + - ++ - Endothelial cells +++ +++ (+) (+) + (+) - - ++ (+) ++ (+) + + (+) -", "Every immunohistochemically stained slide was photographed with a digital microscope (HS All-in-one Fluorescence Microscope BZ-9000 Generation II, BIOREVO, KEYENCE Deutschland GmbH, Neu-Isenburg, Germany) and afterwards analyzed using analysis software (analySIS 3.1 software package, Soft Imaging System GmbH, M\u00fcnster, Germany). Percentage of immunopositive areas are shown as Box-and-Whisker plots with median, minimum and maximum in a logarithmic scale." ] },{ "paper_id": "856b6b5e0e5baedd6eef6801c3f59305438c47eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Frontiers in Veterinary Science | www.frontiersin.org \"BIOSUIS PRRS Inact EU+Am\" is approved to be used in the US. However, new strategies are being evaluated to overcome these problems (115) , including nanoparticle entrapped antigens (116) (117) (118) (119) , plant based approaches (120) or vectored vaccines (121) .", "be necessary and sufficient for the induction of membrane modifications resembling those found in infected cells (14) . Most importantly, all positive RNA viruses seem to induce one of two basic morphotypes of membrane modifications: invaginations or double-membrane vesicles.", "SM-T: wrote the first draft of the manuscript. MM, HdP, and LF: wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version. This review received support from the FEDER project (COMRDI16-1-0035-03)." ] },{ "paper_id": "857137889eef45edb1a66c1950f0e0ca27ad63a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Text S1 List of the accession numbers (UniProtKB/Swiss-Prot Knowledgebase) of all the proteins described in this article. ", "Poliovirus (PLV) infection causes paralytic poliomyelitis, an acute disease resulting in flaccid paralysis associated with caspasedependent apoptosis of motor neurons [S129]. Similar to HBx, the PLV viroporin 2B localizes to mitochondria, induces a perinuclear redistribution of these organelles and alters their morphology, suggesting that 2B might exert proapoptotic effects by directly promoting MMP [S130]. As discussed below, this is not the sole mechanism accounting for PLV-induced neurodegeneration (see the section ''Indirect MMP Facilitators'').", "Throughout the process of pathogen-host co-", "A complete list of accession numbers (UniProtKB/Swiss-Prot knowledgebase, http://www.expasy.org/sprot/) for the proteins discussed in this manuscript can be found online in Text S1." ] },{ "paper_id": "8589358e390499b6c9d95a5eb20b0bfb4bc75466", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Informed consent for publication of this case report was obtained from the volunteer who participated in this clinical trial.", "In the current case the cardiac event occurred during the three days when the subject was receiving curative Malarone treatment for P. falciparum malaria. There are no previous data indicating that anti-malarial treatment with atovaquone/proguanil (Malarone\u00ae), or its metabolite cycloguanil causes myocarditis or any other significant cardiovascular toxicity [27] . Furthermore, the product monograph of Malarone does not mention cardiotoxicity or myocarditis, only palpitations and tachycardia.", "Apart from the single short episode of chest pain and a longer period of fatigue with occasional mild headache during and shortly after hospitalization, no other complaints were reported. The fatigue diminished after Table 1 Laboratory findings Haematology and biochemistry tests Normal range Inclusion C +11 C +12 C +13 C +14 C +15 C +16 C +17 C +20 C +28 D-dimer (ng/mL) \u2264 500 < 500 < 500 570 < 500 < 500 < 500 < 500 < 500 < 500" ] },{ "paper_id": "858f420ea81730f250e270096dc9efef9831c1dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that they have no conflict of interest.", "Ethical approval This article does not contain any studies with human participants or animals performed by any of the authors.", "Northern pintal AstV (MPJ1433 isolate) JX985651 n/a n/a n/a 20.3 " ] },{ "paper_id": "8590276b817018ff7fea07592055689f3d325d3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells and Viruses. HEK293T cells and PK-15 cells were cultured in Dulbecco's modified Eagle's medium (Hyclone, Logan, USA) containing 10% (v/v) fetal calf serum supplemented with penicillin (100 U ml \u22121 ) and streptomycin (100 g ml \u22121 ). Sendai virus (SeV) was obtained from the Centre of Virus Resource and Information (Wuhan Institute of Virology, Chinese Academy of Sciences).", "Coimmunoprecipitation Analysis. Coimmunoprecipitation experiments were performed on HEK293T cells transfected with the indicated expression plasmids as described in an earlier report [14] .", "Our results collectively suggested that TGEV PL1 suppressed IFN-transcription by interfering with NF-B-, IRF3-, and AP-1 signaling-mediated IFN expression." ] },{ "paper_id": "859085c2184a2ca5829809632648e1c80c725d2b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Genomes store information for building and maintaining organisms. Complete sequencing of many genomes provides the opportunity to study and compare global information properties of those genomes.", "i. Convert the n-mer at location i into an array index (coding it as a 2n bit number with each nucleotide represented by 2 bits).", "The Lempel-Ziv algorithm [49] is a computationally efficient scheme for universal data compression. The algorithm requires no a priori knowledge of source statistics (hence is \"universal\"), is particularly elegant, has a very low computational complexity, and produces very compact descriptions of large alphabets. These virtues have established the algorithm firmly as the standard data compression algorithm for the transmission and storage of large files over the Internet and on computers." ] },{ "paper_id": "859410b0052a50da3868ab631c6e1a58ff3d4c49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CGHRF, joined by other panels, urged $1 billion incremental funding per year from combined governmental and private sources to jumpstart research innovations (Table 10 ). Beyond ", "The Ebola and Zika epidemics revealed systemic deficiencies in R&D for diagnostic tests, vaccines, and therapies. The paucity of medical technologies stem primarily from low commercial priority, limited funding, and practical challenges of conducting human trials for episodic infections. Yet medical countermeasures are vital to contain outbreaks and minimize their impact.", "Supporting Information S1 " ] },{ "paper_id": "8597d9f2e677de02b0166ad69f8045b979b3a82a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To inhibit expression of Sec63, siRNA duplexes targeting the nucleotide positions 1942 to 1960 of Sec63 (CAA-GAATGGTGGTGGCTTT) or esiRNA were used (Sigma-Aldrich). As a control, a nonsense siRNA with no known homology to mammalian genes was used (Quiagen).", "For immunostaining, cells grown on cover-slips were fixed and permeabilized with ice-cold methanol containing 2 mM EGTA. Cells were blocked in PBS containing 2% animal serum, incubated with the indicated primary antibodies for 1 h at 37uC, rinsed with PBS, and then incubated with AlexaFluor-tagged secondary antibodies for 1 h at 37uC. DNA was stained with Hoechst 33342 (Sigma-Aldrich). Z-stack images were acquired separately for each channel using a Zeiss Axiovert 200 M microscope equipped with a Plan-Apochromat 1006 (1.4 NA) and a Zeiss Axiocam digital camera and were optically deconvoluted using the software supplied by Zeiss. Phase contrast images were obtained with the same microscope using phase contrast optics. For quantitative immunofluorescence analyses, images of randomly selected cells (about 100 cells per coverslip; n = 5) were collected at 1006 magnification with identical settings.", "Microsomes were prepared from homogenized cells and subjected to a trypsin protection assay as described [22] . Briefly, microsomes were proteolyzed with trypsin in the presence or absence of 0.5% NP-40 for 60 min on ice. After inactivation of trypsin with aprotinin, solubilized samples were subjected to SDS-PAGE and immunoblotting." ] },{ "paper_id": "859ab03f9d7e647783e8ac0e112b8bf63207693f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cyclodextrins: synthesis, structure and physicochemical properties.", "a Taken from [44, [47] [48] [49] [50] [51] [52] [53] . b Randomly methylated \u03b2-CD.", "2644" ] },{ "paper_id": "859e22ac7ded4f546d8f58cc6d8515bd261b5289", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mathematical modeling 16 (11) Molecular studies 11 (7) Diagnostic studies 14 (9) Case-definition ( " ] },{ "paper_id": "85a6db45e29636f124b7b1adc5230dfca7b37f9f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "85bab4f8869727adbe47f5ddc6e18af508dc57a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The XBP1 splicing was checked by RT-PCR using forward primer 5\u2032-CCAAGGGGAATGAAGTGAGGC-3\u2032 and reverse primer 5\u2032-AGAGTTCATTAAT GGCT TCCAG-3\u2032, which produces un-spliced XBP1 of 335 bp and spliced XBP1 of 309 bp. The PCR products were digested with the restriction enzyme Pst I, cleaving XBP1u into 72 and 263 bp. The digestion products were resolved on 2.5% agarose gel to separate un-spliced and spliced XBP1.", "cDNA was reverse transcribed from total RNA using expand reverse transcriptase (Roche, USA) and oligo-dT primer. Equal volume of cDNA was PCR-amplified using SYBR Green qPCR Mix in a CFX96TM real-time PCR system (Bio-Rad, USA). Primers used for amplification of \u03b2-actin, NP, IRE1\u03b1, XBP1u, XBP1s, P58 IPK , ERdj4, EDEM1, IFN-\u03b2, TNF-\u03b1, IL6, and IL8 were listed in Table 2 . The mRNA levels of specific genes were calculated using \u03b2-actin as an internal reference and normalized to mocktreated controls. All assays were performed in three replicates.", "For construction of PXJ40F-CHOP plasmid, full-length CHOP (NM_004083.5) was amplified by PCR from human cDNA using forward primer 5\u2032-CCCAAGCTTA TGGCAGCTGAGTCATTGCCTTTC-3\u2032 and reverse primer 5\u2032-GGAAGATCTTCATGCTTGGTGCAGATTC ACCATTC-3\u2032. The restriction enzyme sites were underlined. The PCR product was digested with Hind III and Bgl II, ligated into vector PXJ40F (with a Flag tag in amino terminus). For construction of pCMV-IRE1\u03b1 plasmid, full-length IRE1\u03b1 (GenBank: AF059198.1) was amplified by PCR from human cDNA using forward primer 5\u2032-GCAATCAAGCTTATGCCGGCCCGGCGGCTGCTG C-3\u2032 and reverse primer 5\u2032-GACGTGGAATTCGAGGG CGTCTGGAGTCACTGGGGGC-3\u2032. The PCR product was digested with Hind III and EcoR I, ligated into vector p3\u03c8Flag-CMV-14. For construction of pCMV-XBP1u plasmid, full-length XBP1u (NM_005080.3) was amplified by PCR from human cDNA using XBP1 forward primer 5\u2032-GCAATCAAGCTTATGGTGGTGGTGGCA GCCG-3\u2032 and XBP1u reverse primer 5\u2032-GACGTGTC-TAGAGTTCATTAATGGCTTCCAGCTTGGC-3\u2032. The PCR product was digested with Hind III and Xba I, ligated into vector p3\u03c8Flag-CMV-14. For construction of pCMV-XBP1s plasmid, full-length XBP1s (NM_ 001079539.1) was amplified by PCR from human cDNA using the forward primer 5\u2032-GCAATCAAGCTTATG GTGGTGGTGGCAGCCG-3\u2032 and reverse primer 5\u2032-GA CGTGTCTAGAGACACTAATCAGCTGGGGAAAGA G-3\u2032. The PCR product was digested with the restriction enzyme Pst I to remove the XBP1u fragment, followed by Hind III and Xba I digestion, finally cloned into vector p3\u03c8Flag-CMV-14." ] },{ "paper_id": "85bc7c0784157ee7c3d3091e40aa1e45b560d26b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The core iSOCKET algorithm and associated convenience functions are available as the knobs_into_holes add-on module for ISAMBARD (Wood et al., 2017) , our recently-described opensource software package for the analysis and rational design of biomolecules (https://github.com/woolfson-group/isambard). iSOCKET builds on the AMPAL framework that ISAMBARD uses for representing biomolecules computationally, allowing seamless integration with its suite of analysis tools.", "A second add-on to ISAMBARD written for this study is the parmed_to_ampal module, which enables the parsing of mmCIF files into ISAMBARD, using the ParmEd library (https://github.com/ ParmEd/ParmEd). This ensures that, unlike SOCKET, iSOCKET can be used to interpret the KIH packing within mmCIF files and therefore arbitrarily large structures.", "The initial set of PDB accession codes was taken from the latest update of CC\u00fe (10 August 2016), filtered for canonical, nonredundant (70% redundancy cutoff) coiled coils containing at least 11 residues. The expanded set was taken from the PDB on 23 November 2016. We filtered all the available structures to include all X-ray crystal structures with resolution 3 \u00c5 and used the option to omit large structures. The representative structures at 90% sequence identity were chosen, resulting in 35 476 accession codes.", "At looser cutoff values, 200 large barrels (!7 helices) were detected, almost half of which (99) contained 8 helices. On closer inspection, many of these octamers including human dihydropyrimidinase (2vr2, depicted in Fig. 5 ) did not fit the intuitive notion of a barrel (i.e. cylindrical) shape, although the underlying graphs were cyclic. For the future, we aim to learn more about packing in a-helical barrels by investigating these examples in more detail. To date, the only oligomer states from 5 to 20 without example structures are 13, 17 and 19. These are the largest prime numbers in this range. This suggests that larger assemblies are unlikely to be formed other than as the composition of smaller repeating arrangements. The largest barrel, containing 39 helices, is in the 10 MDa vault ribonucleoprotein particle (4hl8) (Fig. 5) .", "The Atlas Classification was implemented in Python, and made extensive use of the networkx module (Hagberg et al., 2008) . In particular, the graph_atlas_g method was used to generate the initial graph Atlas, and the is_isomorphic function to categorize graph pairs as being isomorphic." ] },{ "paper_id": "85bf8bcd3494765f259e8903ed153dff0ff40a4f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Attempts have been made to predict the secondary structure of TMV 3\u2032 -UTR using a variety of chemical and enzymatic tools 9,32 . SHAPE combines a novel chemical probing technology with reverse transcription, capillary electrophoresis, and secondary structure prediction software to rapidly determine the structure of RNAs in a single-nucleotide resolution. It is particularly useful in predicting RNA secondary and tertiary interactions [33] [34] [35] . We applied the SHAPE approach to gain insight into TMV 3\u2032 -UTR conformation. This methodology employs an electrophilic reagent that reacts selectively with the 2\u2032 -hydroxyl ribose group of single-stranded nucleotides to create a covalent 2\u2032 -O-ribose adduct, while the 2\u2032 -hydroxyl group of structurally constrained residues shows reduced nucleophilic reactivity. In contrast to conventional chemical and enzymatic probing techniques, SHAPE provides structural information at every nucleotide position 36 ." ] },{ "paper_id": "85c008e20de23c6313b57d7e638a61c3c611d315", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Written informed consent was obtained from the patient's parents for publication of this Case Report. A copy of written consent is available for review by the Editor-in-Chief of this journal.", "As shown in Figure 1 , RT-PCR results for HKU-1 was positive. This result was confirmed by neuclotide sequencing. To exclude bacterial infections such as mycoplasma and chlamydia pneumonia, ELISA and bacterial culture were carried out on the patient's samples which all yielded negative results.", "The authors declare that they have no competing interests." ] },{ "paper_id": "85c6f63e581817cce1d68e6a5bb856fdbe390d17", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "85d7376aca04b7df9b23618734948c2814ccfe19", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One-way analysis of variance (ANOVA) tests (Tukey's Multiple-Comparison Test) were performed to analyze the differences among multiple experimental groups. All values are expressed as mean \u00b1SD. P< 0.05 is believed to be statistically significant. The statistical analyses were performed using Prism 5.0 software.", "Supporting information S1 File. ARRIVE Checklist.", "(DOCX)" ] },{ "paper_id": "85d80ad717017002446bd0be2d5f369096c31517", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A similar study, using a DNA vaccine encoding for CD99, was also successfully conducted. CD99 is a protein expressed in leukocytes and endothelial cells involved in leukocyte recruitment in atherosclerosis lesion areas. The CD99 vaccine was consumed orally with S. typhimurium aroAas the carrier. The vaccine generated CD8+ T cells that lysed CD99 expressing cells, so fewer leukocytes were detected in the lesion area. The vaccination also decreased lesion formation by 69% in carotid arterial [80] .", "Other bacteria that were developed as DNA vaccine carriers include Listeria monocytogenes [65, 81] , Shigella spp. [51, 82] , and Yersinia enterolica [54] .", "The polyadenylation sequence has a significant effect on transgene expression. The common polyadenylation sequences used in DNA vaccine construction are SV40, rabbit \u03b2-globin, and bovine growth hormone polyadenylation sequence [29, 44] . 5 UTR is located upstream transgene and regulates transgene translation. Optimization of the regulatory element by inserting a sequence from the R region of the long terminal repeat from human T-cell leukemia virus type 1 (HTLV-1) to CMV enhancer/promoter markedly increased DNA vaccine immunogenicity in both mice and non-human primates [45] ." ] },{ "paper_id": "85d9c134bccd818e9487193754d8c71a710161d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "POCT with a higher level of connectivity and data analytics could dramatically change the diagnosis and management of both communicable and non-communicable diseases. Moreover, incorporation of findings from the human genome project with decentralized POCT could dramatically change our understanding of disease epidemiology and population health.", "Store and allow access to comprehensive health data including the medical history of the patient; 2.", "Allow efficient access and assist in statistical analysis of data.", "Also focusing on rapid AST testing, the work by GeneFluidics Inc. (2019) [156] has resulted in a fully automated system that uses a reagent kit and disposable sensor array to quantify species-specific 16S ribosomal RNA (rRNA). An approach based on multi-channel potentiostat measurement for the enzymatic cycling amplification is used.", "In dealing with epidemics within LMIC, the data would be acquired through support pathologists and response teams. Non-invasive and minimally-invasive tactics both enable a suitable entry point. They facilitate the examinations of the dead while respecting attendant considerations, including increasing public acceptance [102] . Utilizing this methodology, diagnosis can be forthcoming thus obviating contamination and spread of disease in poor or remote regions, for example, the recent Ebola response in Africa (e.g., opposition of invasive autopsy due to traditional or cultural beliefs) [103, 104] ." ] },{ "paper_id": "85e67a0122ea002985fd0e498a7f94df64957701", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For MRSA detection, specimens are obtained from the anterior nares and the perineal area (surveillance sample); and from any skin lesions, wounds, incisions, ulcers, and exit sites of indwelling devices if present (surveillance and/or clinical sample) [14] .", "The authors declare that they have no competing interests." ] },{ "paper_id": "85eb641e06b0d6b1a0b202275add0c5d27e53d71", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The free trade agreement with the USA raised controversies about attempts to include the Pharmaceutical Benefits Scheme (PBS) in concessions demanded by US negotiators. These issues have been outlined in the account of developments in the PBS elsewhere in this series of review articles.", "These developments have furthered Australian foreign policy concerned with establishing trans-Tasman free trade, commenced some two decades ago with the negotiation of the Closer Economic Relations agreement with New Zealand. The new regulatory arrangements have created a virtual trans-Tasman free market in food (subject to plant and animal quarantine considerations) and therapeutic drugs." ] },{ "paper_id": "85efed2c84dba208203669ef115bb9dc750e24c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recognizes dsRNA, triggering IFN production.", "rs not annotated; F303S (NonSyn). rs5743313 (NCR).", "rs786205223; F410V (NonSyn) rs375323253; Q421X (NonSyn) [113] IRF-9" ] },{ "paper_id": "85f3c300e460e62364ef4a74fb1289334a5c2317", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Marek's disease (MD) is a transmissible, malignant T-cell lymphoma in chickens caused by Marek's disease virus (MDV) [15] . MDV strains are classified into the following three serotypes: Gallid herpesvirus 2 (MDV serotype 1), Gallid herpesvirus 3 (MDV serotype 2), and Meleagrid herpesvirus 1 (MDV serotype 3/herpesvirus of turkeys) [16] .", "391.6 \u00b1 50.9 b (n = 14)" ] },{ "paper_id": "85f48fe473305b86d997f44a5801859364b8952b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In a recent study [35] , it was described that hepatitis C virus, vesicular stomatitis virus, and influenza A virus induce MVP expression. In turn, MVP affects viral replication by triggering the expression of type-I IFNs." ] },{ "paper_id": "8602709a812146a012e16df450b991f6343d2f46", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antibodies specific for Akt, phospho-Akt (Ser473), phospho-GSK-3\u03b1/\u03b2(S21/S9), phospho-mTOR (S2448), phospho-Bad (S136) and mouse monoclonal \u03b2-actin were purchased from Cell Signaling Technology, Inc. ", "The virus titer was determined by the 50% tissue culture infectious dose (TCID 50 ). Vero cells monolayers grown in 96 well plates and inoculated with 100 \u03bcl of 10-fold diluted cell culture supernatants. After 48 h of incubation, the CPE was observed by Nikon inverted microscope. The TCID 50 was calculated using the method of Reed and Munch.", "Statistical analysis was performed using Prism 5.0 software (GraphPad). Significance was determined by using two-tailed independent student t-tests. Statistical significance: \u00c3 p < 0.05, \u00c3\u00c3 p < 0.001." ] },{ "paper_id": "8605d9a84e827e232a47861c65c61605c789acf7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Outbreaks of disease have often been reported after air travel. However, outbreaks on trains are less commonly reported.", "Following a standard protocol, respiratory specimens (nasal, throat, and nasopharyngeal swabs) were collected from suspected case-patients and placed in sterile viral transport media for 2009 H1N1 testing. 16 RNA was extracted from specimens using the RNeasy Mini Kit (Qiagen, Valencia, CA, USA) per the manufacturer's protocol and tested by rRT-PCR following the US CDC protocol. 17 Assays were performed in provincial Centers for Disease Control and Prevention and confirmed by the National Influenza Center of the China CDC.", "There was a dose-response relationship between time of exposure (time spent in the train) and attack rate, which increased from 0% among the 413 passengers who were exposed for less than 10 hours to 1.13% among the 796 passengers with exposures exceeding 30 hours (Table 3) ." ] },{ "paper_id": "8607aac9046864becdec9a89df48524d61192e09", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NiV-G or NiV-sG", "Materials and Methods", "Author Contributions: G.K., S.V., C.C.B., G.S. and A.V. conceived and designed the experiments; G.K., S.V., S.J. and A.V. performed the experiments; G.K., S.V., U.K., C.C.B., G.S. and A.V. analyzed the data; G.K., G.S. and A.V. wrote the paper. All authors have read and agreed to the published version of the manuscript. " ] },{ "paper_id": "860ddc48c73d4757ceb161a9b43e73138b6b94a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The potential role of cyclophilins in the replication of influenza virus has been detailed in a separate review in this special issue [131] . In yeast, the CyPA homolog Cpr1p inhibits viral replication proteins of tombusvirus [132] . Interestingly, a parvulin PPIase could also inhibit tombusvirus in this model, supporting overlapping functionality among PPIase classes. West Nile virus RNA and its nonstructural protein 5 (NS5) were found to interact directly with CyPA in infected cells in a CsA-sensitive manner [133] , although the CsA was much less active in inhibiting WNV than HCV. The replication and pathogenesis of many other human viruses have been reported to be regulated either by CsA or cyclophilins. These include polyomavirus BK [134] , arterivirus [135] , rotavirus [136] , human cytomegalovirus [137] , vesicular stomatitis virus [138] , vaccinia virus [139, 140] , measles virus [141] , human papillomavirus [142, 143] , coronaviruses [144] [145] [146] , and hepatitis B virus [147] [148] [149] .", "Unlike other infective agents, viruses do not encode a full complement of proteins that allow them to proliferate independent of the host. Consequently, the life cycles of all viruses depend upon numerous host proteins which may be generally termed host cofactors. Increased understanding of how viruses co-opt host cofactors to generate and maintain a permissive environment for their replication has highlighted targets for antiviral intervention. A substantial body of evidence supports a role in diverse viral life cycles for the cyclophilins, a family of highly conserved peptidyl-prolyl cis/trans isomerases. parvulin-like proteins, has also been described and includes two human genes encoding at least three distinct proteins [14] . ", "While the diversity of potential functions of host cyclophilins in viral life cycles is evident, what is less apparent is the conservation of these roles. For example, whether most cyclophilin-virus interactions are unique to particular viruses or part of larger, broad themes is uncertain. Furthermore, the cellular and viral substrates of cyclophilins are not fully defined, nor are the implications of catalytically altering the conformation of folded protein. CLD-containing proteins are found in all domains of life and are even found within the genome of at least one virus, the mimivirus [7, 8] , highlighting the conserved and critical role cyclophilins likely play in the host cell. Further research effort towards understanding the role cyclophilins play in both viral life cycles and normal cell physiology will expand our understanding of the cell as a whole and reveal new host drug targets. " ] },{ "paper_id": "8613777458478918e5fd17250ca0dc7dcb92e259", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The annealing temperature of the assay was optimized at 57\u00b0C using a gradient of annealing temperatures from 51\u00b0C to 61\u00b0C. The optimal amount of input cRNA templates was 0.2 \u03bcg per reaction, and each primer in the reaction tube was used at a final concentration of 0.4 \u00b5M. ", "Different parameters, such as the gradient of annealing temperature (ranging from 51 to 61\u00b0C), the gradient of primer concentrations and amounts of cRNA templates in 25 \u00b5l of reaction volume, were tested for the optimization of the amplification of specific HTNV products.", "In clinical practice, the commonly used diagnostic methods for detecting of HTNV are primarily based on serological techniques, such as the enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA). Other molecular biological methods, such as conventional RT-PCR and nested PCR, have also been developed but are mainly used for experimental research. Because it is time-consuming (usually requiring 5-7 days to perform the test), a plaque assay, which is the classical virus titration approach, is seldom used in laboratories. However, none of these detection methods provides information about the load of the infectious virions." ] },{ "paper_id": "861f05718b673306c2044167d92bb31d68a0d9bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "861fcade6995d79dfc98e9a584edc8cdd779324d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author declares no conflicts of interest." ] },{ "paper_id": "8620ebc72710ffd02328954e8447585ffcb5cae2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1) to prevent dehydration, (2) to treat dehydration,", "(ii) However, well-designed prospective studies of efficacy and safety should be carried out in outpatient children.", "(iii) Cost-effectiveness analyses should be undertaken before routine pharmacological therapy with diosmectite is universally recommended.", "Combined data from four RCTs showed that loperamide compared with placebo reduced the risk of (i) diarrhoea at 24 hours and at 48 hours." ] },{ "paper_id": "86239535bbc306bd90a85a6145840c784fa35d82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For a single short term intervention from T 1 to T 2~T1 zD, the final epidemic size, a SI , is given by", "The parameter b t \u00f0 \u00de is the transmission rate, i.e. the number of contacts an infective has per day in which the infection is passed on, and has the baseline value b 0~R0 c~1:8=2:6. Simulations were started with 1 infective, n21 susceptibles, and no immunes.", "As well as stockpiling antivirals, it may be possible to reduce transmission and severity of disease by stockpiling a partially-Box 1. Epidemic-Specific Characteristics Affecting Suitability of Interventions.", "to give specific policy guidance. Box 1 outlines a number of factors which should be considered in designing policy which are not covered here. Our aim is to develop an understanding of how different policy objectives determine the optimal mix, timing of introduction and duration of implementation of the available mitigation strategies." ] },{ "paper_id": "8624ce91f316d2aae5c09273f9308cc08ffcc25c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "replication, and transcription of the foreign gene at different levels. Moreover, our results and the previous findings all indicate that the PRRSV body TRSs could be a useful tool for controlling foreign gene expression. Compared with the expression levels of six different recombinant PRRSVs expressing EGFP gene, body TRSs of GP2, GP5, M and N genes have shown relatively higher levels of EGFP expression without altering the viral replication. Therefore, our results provide new clues useful for the rational design of next generation effective PRRSV vaccine vectors.", "In order to gain insight into the role of the transcription regulatory sequences (TRSs) in the regulation of gene expression and replication of porcine reproductive and respiratory syndrome virus (PRRSV), the enhanced green fluorescent protein (EGFP) gene, under the control of the different structural gene TRSs, was inserted between the N gene and 3\u2032-UTR of the PRRSV genome and EGFP expression was analyzed for each TRS. TRSs of all the studied structural genes of PRRSV positively modulated EGFP expression at different levels. Among the TRSs analyzed, those of GP2, GP5, M, and N genes highly enhanced EGFP expression without altering replication of PRRSV. These data indicated that structural gene TRSs could be an extremely useful tool for foreign gene expression using PRRSV as a vector.", "the ratios of the N protein and EGFP protein [20] [21] [22] . Moreover, six recombinant HP-PRRSVs were subjected to Northern blot analysis by measuring the ratios of the EGFP mRNA. Overall, the body TRSs of GP2, GP5, M and N genes produced the higher level of EGFP expression when this reporter gene is cloned upstream of the N gene and 3\u2032-UTR, suggesting that these body TRSs at this position would assure effective regulation of the gene of interest. It is possible that HP-PRRSV has evolved to have unique body TRSs for each structural gene, and they are most effective in regulating the expression of the corresponding structural genes at their original positions. In summary, we have evaluated the role of six PRRSV body TRSs in expression of a foreign gene by using HP-PRRSV reverse genetics system. We showed that HP-PRRSV body TRSs have the ability to regulate gene expression, with six different recombinant HP-PRRSVs expressing EGFP and the parent strain were separated on a Tris-borate-EDTA-urea-15% polyacrylamide gel. The gel was transferred onto a piece of membrane (Hybond N+; Amersham). The blot was UV cross-linked using a cross-linking system (HL-200 HybriLinker; UVP), and DIG-labelled oligonucleotides were used as probes for EGFP sgRNA detection. The sequences for the probes used were as follows: SNB041-F, 5\u2032-GTGAGCAAGGGCGAGGAG-3\u2032; and SNB041-R, 5\u2032-GTAGTGGTTGTCGGGCAGCA-3\u2032. Numbers below the northern bands indicate relative levels of EGFP sgRNA of each recombinant virus compared to EGFP sgRNA of rHP-PRRSV/SD16/TRS2-EGFP. ImageJ software (NIH) was used to quantify the signal from the gel." ] },{ "paper_id": "863ffba681e73f1174a2949a281340f82ed241e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by BBSRC grant BBS/E/I/00001256 and strategic funding to The Pirbright Institute.", "Infectious bronchitis virus (IBV) is a gammacoronavirus that is responsible for an acute highly contagious and economically important respiratory disease, infectious bronchitis, in domestic fowl. IBV possesses a large (27.5 kb) single-stranded positive-sense RNA genome. The 5\u00a2-end encompassing approximately two-thirds of the genome encodes 15 non-structural proteins (nsps), which collectively are commonly referred to as the replicase gene. The 3\u00a2 third of the genome encodes the structural and accessory genes in the following order; spike (S), accessory genes 3a, 3b, envelope (E), membrane (M), accessory genes 4b, 5a, 5b and nucleocapsid (N). Previous research has investigated the role of the IBV structural and accessory genes, as well as the replicase gene, in pathogenicity, with the latter demonstrated to be a pathogenic determinant [1] .", "The largest nsp within the coronavirus replicase gene repertoire is nsp 3, which is a multi-functional protein containing a number of putative domains that are found to be conserved amongst different coronaviruses (reviewed in [2] ). One such domain is the X domain, also known as the macrodomain or ADRP domain due to its ADP-ribose-1 \u2020phosphatase activity [3] [4] [5] [6] . The binding of ADP-ribose and poly(ADP)ribose, and the subsequent catalytic action, have been well characterized in several coronaviruses, with a number of essential residues identified. Work by several groups involving the mutation of these residues in the betacoronaviruses SARS-CoV and MHV, as well as the alphacoronavirus HCoV-229E, demonstrated that ADRP activity is not required for viral replication in vitro [5, 7, 8] .", "The growth kinetics of all four rIBVs were determined using primary CK cells, and were found to be comparable to those of the parental viruses, Beau-R and BeauR-M41(S) (Fig. 2) . The Beaudette S gene confers extended in vitro cell tropism [17] . To evaluate whether the ADRP modification effects could be cell-specific, the growth kinetics were also investigated in DF-1 cells, a continuous cell line derived from chicken embryo fibroblasts; no difference in replication kinetics were observed. In addition, the plaque morphology for all rIBVs was comparable to that of the parental viruses in both DF-1 and CK cells (data not shown). The restoration of the triple-glycine motif thought to activate ADRP in the Beaudette replicase either by a complete domain swap or by an amino acid substitution had no observable effect on viral replication in vitro." ] },{ "paper_id": "8640647aeb5d12e17f9fce436b6548f68c80dba2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "86410d14ac553ca694a7f5324a56b34a0fb6b8fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "86431a5391ad8d12589fe686d0486cf2a0e912f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "**Data taken from Walker et al. [47] . doi:10.1371/journal.pntd.0001666.t001", "Fluke burdens and morphometrics. At necropsy, gallbladders and bile ducts were opened and flukes recovered. Llivers were cut (,1 cm pieces) and washed in hot water to collect the remaining flukes. Flukes were counted, measured and weighed.", "Fecal egg counts. Sedimentation techniques at 12 and 13 weeks after infection using four grams of feces were conducted to give eggs per gram (EPG)." ] },{ "paper_id": "864336d3d1a34686efdd078534a092fc888c2c3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MS concordance rate is greater in fraternal twins than for siblings [3, 4] showing the involvement of genetic factors. Besides genetic factors, environmental factors are also considered to have a significant role e.g. Epstein-Barr viral infection [5] [6] [7] and some dietary factors. Vitamin D and turmeric play a protective role in MS and neurodegeneration.", "Both the transitions are presented next, as follows:", "All local state transitions entitle global evolving of the system. These state transitions can be described locally as events that occur and modify the state of one or more agents. They mainly happen two reasons: natural statetransitions (i.e. death) and interactions among agents." ] },{ "paper_id": "865949791a49615aa67ae0444e5987348c82ba65", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Spots of interest were excised and subjected to in-gel tryptic digestion using a commercially available kit (Calbiochem, Germany). MS analysis and database searches were performed at the Proteomic Center within the Faculty of Biological Sciences at the National University of Singapore. Digested peptides were mixed with 1.2 ml of CHCA matrix solution (5 mg/ml of cyano-4hydroxy-cinnamic acid in 0.1% trifluoroacetic acid [TFA] and 50% acetonitrile [ACN]) and spotted onto MALDI target plates. An ABI 4800 Proteomics Analyzer MALDI-TOF/TOF Mass Spectrometer was used for spectra analysis (Applied Biosystems, USA), and the MASCOT search engine (version 2.1; Matrix Science, UK) was employed for database searches. In addition, GPS Explorer software (version 3.6; Applied Biosystems, USA) was utilized along with MASCOT to identify peptides and proteins. Search parameters allowed for N-terminal acetylation, C-terminal carbamidomethylation of cysteine (fixed modification), and methionine oxidation (variable modification). Peptide and fragment mass tolerance were set to 100 ppm and 60.2 Da, respectively. The peptide mass fingerprinting (PMF) parameters were set as follows: one missed cleavage allowed in trypsin digest; monoisotropic mass value; 60.1 Da peptide mass tolerance; and 1+ peptide charge state.", "1) Host specific proteins:", "Antigenic Proteins Category" ] },{ "paper_id": "865f101ce80657e1347a4a35dabfa911a3072429", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8666c802be0f784cd46d8a002832de0d7a2e62e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.ppat.1008169.g004", "Repurposing cellular UPR by PRRSV ", "https://doi.org/10.1371/journal.ppat.1008169.g007" ] },{ "paper_id": "86680d2981c3e641e014e777c8769031b89f933e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The primary aim of this research is to enhance contingency planning and national preparedness by:", "The secondary aims are:", "2 \u00d7 nurses across specialities and grades -including students, health care assistants (HCAs) and midwives." ] },{ "paper_id": "8688ca00892a6134485b2d9dd30f95e7aad1a3d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These risk factors are analyzed below:", "With this in mind, workers can be severely traumatized not only by actual violence but also from any potential violence . For instance, terrorism is quickly spreading (Leistedt, 2013) .", "The measure is composed of two dimensions:", "The sample consisted of only men in managerial positions. Workers were, on average, relatively young: 18.9% 30 years old or younger, 48.3% from 31 to 40 years old, 23.4% from 41 to 50 years old, and only 9.4% were over 50. Regarding job tenure, 23.8% of the participants had worked from 0 to 5 years, 30.9% of participants had worked from 6 to 10 years, 30.9% of the participants had worked from 11 to 20 years, and 14.3% of participants more than 20 years. Finally, the majority of employees had long working hours (17.4% 50 h per week, 26.6% 50-60 h per week, 56% more than 60 h per week)." ] },{ "paper_id": "868b9ab09cae7afe1d1e2ad2f547adecd4d18ac6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IAV and RSV fusion proteins are made up as a trimer with 3 copies of a single protein. Comparatively, the fusion envelope protein of HIV is made up of 2 non-covalently associated glycoproteins (of 120 kDa and 41 kDa) i.e., gp120 and gp41, respectively (reviewed in [63] ).", "Many enveloped viruses, including all paramyxoviruses discovered to date, express a homotrimeric type I fusion protein called \"F protein\". Like other class 1 fusion proteins, such as those of influenza, Ebola, and HIV, F proteins have a hydrophobic fusion peptide (FP) and 2 heptad repeat regions (HRA and HRB), are anchored at the surface by a single-pass transmembrane domain (TM), and they contain a C-terminal cytoplasmic tail.", "The development of new clinical treatments against infectious diseases is critical, particularly at this point in time when both bacterial and viral strains resistant to current treatment options are on the increase [119] [120] [121] . The dual function of these collectins could be of particular advantage when considering therapeutics for inflammatory lung diseases, such as severe asthma or chronic obstructive pulmonary disease, where there is a deficiency in the level of SP-D in the lungs [122, 123] . Notably, these diseases are characterised by chronic inflammation with periodic exacerbations which are often triggered by viruses." ] },{ "paper_id": "869eacf84d79a5b176e43988c2dea3be54f6b2ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An MDCK cell line (obtained from Dr Nakajima, Nagoya City University School of Medicine, Nagoya, Japan) was grown in Eagle's minimum essential medium (MEM; Nissui Pharmaceutical Co., Ltd., Tokyo, Japan) containing 5% fetal bovine serum. Influenza virus A/PR/8/34 (H1N1) (obtained from Dr Nakajima) was used throughout the experiments. The viruses were propagated in MDCK cells cultured in MEM supplemented with 0.1% bovine serum albumin (BSA) and acetylated trypsin (4 \u00b5g/ml). The viruses were stored at -80\u02daC until required for further use. The amount of infectious virus was measured using a plaque assay on the MDCK cells, as described previously (13) .", "To examine the role of indirect transmission by the virus-contaminated clothes in epidemics of influenza A virus, the present study quantitatively examined the viability and transmissibility of the virus from the contaminated surfaces of various types of clothing.", "Previously, a non-physiological pH was shown to cause the inactivation of certain enveloped viruses (14) ; thus, pH alteration may be involved in the observed decrease in the virus infectivity recovered in the extracts. The pH of the sample cloths was measured by soaking in 20 volumes (volume/weight) of distilled water at room temperature for 3 or 48 h, with occasional mixing using a Vortex mixer. However, " ] },{ "paper_id": "86a11741a321a657e22fd7d94af6193d27cc6f5f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The National Influenza Surveillance Network coordinated by the Taiwan CDC was established more than 10 years ago. Policies favoring government funding for vaccines and antiviral agents have been consistent during the subsequent intervals. Between 2009 and 2015, government-funded vaccines have been administered primarily to those aged 6 months to 12 years, elderly individuals aged \u226565 years, healthcare workers, and individuals with underlying diseases. Individuals aged 13-64 years were not included in the government-funded vaccination program. Elementary school children aged 7-12 years had the highest influenza vaccination rate, with coverage reaching 60-70% annually 11 .", "Among the hospitalized patients with laboratory-confirmed influenza A(H1N1)pdm09 infection, male patients and those with underlying conditions were significantly at risk for 30-day mortality (overall death within the first 30 days after hospital admission) and all-cause in-hospital mortality (overall death during hospital admission) as assessed using the multivariable Cox proportional hazard model ( Table 6 ). The same analysis showed that season was not associated with an increased risk for 30-day and all-cause in-hospital mortality (Table 6 ).", "Genetic characterization of the virus. A total of 82 isolated influenza A(H1N1)pdm09 virus were randomly selected for the analysis of viral hemagglutinin (HA) and neuraminidase (NA) genes across the five seasons. The RNA was extracted using the QIAamp Viral RNA mini kit (Qigen, Germany) according to the manufacturer's instructions. RT-PCR and primer pairs used for sequencing HA and NA genes were performed, as previously described 33 . Sanger sequencing of the viral HA and NA genes was performed to establish clade designation and to detect differences in amino acid 33 . The obtained amplicons were assembled into a full-length 1,701-bp span for HA and 1410-bp for NA using DNASTAR Lasergene (DNAStar, Madison, WI). Newly reported sequences in this study were deposited at the GenBank database under the accession numbers shown in Fig. S1 for HA and NA genes. The evolution history was inferred by the maximum likelihood method based on the Hasegawa-Kishino-Yano model 34 . The percentages of replicate trees (1,000 replicates) are shown next to the branches in which the associated taxa clustered together in the bootstrap test. Phylogenetic analysis in this study was conducted using MEGA7 35 ." ] },{ "paper_id": "86adefc2b5acac8a4ca321db6db5ec03408f07bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Timelapse microscopy was performed on a Nikon TE2000 inverted microscope with a 10061.4NA PlanApo objective. Images were collected through a Yokogawa CSU-10 spinning disc confocal scanner. Image data was acquired with a Cascade 512B CCD camera (Photometrics) using Metamorph software for device control and data collection. For imaging experiments, cells were transferred to Leibovitz L-15 without phenol red, and supplemented with 10% FBS. Cells were maintained at 37uC on the microscope stage using a custom designed stage incubator. Fixed cell immunofluorescence images were acquired using an Olympus IX-70 inverted microscope with a 10061.4NA PlanApo objective. Three-dimensional data was collected by axial sectioning with an automated stage and images were acquired and deconvolved using DeltaVision SoftWorx software (Applied Precision). All fluorescence images represent maximum intensity projections in two dimensions of three dimensional image data.", "We are grateful to Alexey Khodjakov for providing the GFP-tubulin PtK 2 cell line and Charlie Anderson and Tim Stearns for the GFP-centrin HeLa cell line. We thank Wei-Meng Zhao and Guowei Fang for MgcRacGAP antibody and Christine Field for human anillin antibody. We appreciate Ben Moree's assistance with timelapse imaging. We thank Alison Farrell and members of the Straight laboratory for critical reading of the manuscript. We also thank Mark Petronczki and Jan-Michael Peters for communication of results before publication.", "BTO-1 [33] and BI-2536 [52] were synthesized as previously described. Antibodies DM1A anti-tubulin antibody was purchased from Sigma and used at 1 mg/ml. Antibodies to MKLP1, Rho, ECT2 (Santa Cruz Biotechnology) and human nonmuscle myosin II (BTI) were used at 1 mg/ml. MgcRacGAP antibody was provided by Wei-Meng Zhao and Guowei Fang and used at 0.5 mg/ml. Anillin antibody was a gift from Christine M. Field and used at 1 mg/ml." ] },{ "paper_id": "86ba599c91bdbd03345c42fab209766f19f3c5dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "POWV is found in Russia and North America, and is the only TBFV present in America ( Figure 1 ) [48] . It is transmitted by Ixodes scapularis, Ixodes cookei, and several other Ixodes tick species, to small and medium size mammals, whereas humans are accidental dead-end hosts. Milk-borne POWV transmission might also be possible since POWV virus has been found to be secreted in milk under experimental settings [49] .", "Upon recognition, the different PRR will recruit distinct adaptor molecules. TLR3 recruits TIR-domain-containing adapter-inducing interferon-\u03b2 (TRIF) [121] , TLR7 and 8 recruit myeloid differentiation primary response 88 (Myd88) [122] , whereas the RIG-I-like helicases, RIG-I and MDA-5, recruit interferon-beta promoter stimulator-1 (IPS-1) (also known as mitochondrial antiviral-signaling protein (MAVS), virus-induced signaling adapter (VISA) and CARD adapter-inducing IFN-beta (Cardif)) [123] [124] [125] [126] . Ligation of PRRs and downstream recruitment of the adapter molecules result in the activation of transcription factors NF-\u03baB and interferon regulatory factor (IRF) 3 and IRF7, which translocate to the nucleus and induces the expression and subsequent secretion of type I IFN [127] .", "TBFVs are enveloped viruses around 50 nm in diameter. The envelope carries two surface proteins, the envelope (E) protein and the membrane (M) protein. The latter is derived from a precursor protein, prM. The nucleocapsid (NC) lies inside the viral envelope and consists of multiple copies of capsid (C) protein and the viral genome. The TBFV genomes are single stranded, positive-sense RNA of approximately 11,000 nucleotides. It has a 5 -cap with a single open reading frame (ORF). The ORF is flanked by 5 and 3 untranslated regions (UTRs). The viral protein is encoded by the ORF as a single polyprotein, which is co-and post-translationally cleaved by cellular and viral proteases into individual viral proteins (three structural and seven non-structural). The polyprotein is arranged in the order 5 -C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5-3 [70, 71] .", "During the last 10 years there has been an increase of POWV in the USA with approximately 100 reported cases [54, 55] . The recent rise in incidence could be due to increased surveillance and diagnosis of POWV, or it may represent a true emergence of the disease in endemic areas, or both [55] . The incubation period ranges from 1 week to 1 month. The symptoms of POWV infection may include fever, headache, vomiting, weakness, confusion, seizures, and memory loss with a case fatality rate of 10% [54] . Approximately half of the survivors experience permanent neurological symptoms, such as recurrent headaches, muscle wasting, and memory problems (https://www.CDC.gov). There are no antiviral treatments or vaccines available against POWV.", "Taken together, studies so far have demonstrated the importance of the RIG-I-like-IPS-1 pathway in tick-borne flavivirus infection, whereas the role of the TLR pathways remains unclear." ] },{ "paper_id": "86bd9005ed7a8aa7f895a9d0769b8dd8e4990e06", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Single Likelihood Ancestor Counting (SLAC), codon-based maximum likelihood method available in the HYPHY package on the Datamonkey web server [86] was used to evaluate the strength of selection pressure on these datasets.", "RNA viruses are responsible for a disproportionate number of emerging human diseases, including influenza, ebola hemorrhagic fever, hantavirus pulmonary syndrome, and Middle East respiratory syndrome, which place tremendous health and economic burdens on both the developing and developed world [1, 2] . In 2008, rotavirus and measles virus caused the deaths of 570,000 children under the age of five, making them two of the leading killers of children worldwide [3] . In 2009, it was estimated that rotavirus infections alone result in $325 million in medical treatment costs and $423 million in societal costs each year [4] . Further, the implementation of many intervention strategies has either failed or been delayed as a result of the evolutionary dynamics of these pathogens [1, 5, 6, 7, 8, 9] .", "As recombination events can lead to over-estimation of nucleotide substitution rates, each dataset was scanned for recombination using seven different algorithms (RDP, GENE-CONV, Bootscan, MaxChi, Chimaera, SiScan, and 3seq) implemented in RDP v3.44 [83] . Sequences implicated as recombinant by two or more algorithms were excluded from further analysis. These finalized alignments were deposited into Dryad (doi:10.5061/dryad.58ss8). Modeltest v3.7 [84] was used to determine the best-fit model of nucleotide substitution for each dataset (by AIC)." ] },{ "paper_id": "86c378531ecb4b4d351c844fc4e3e5c9cf49f269", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The " ] },{ "paper_id": "86dfb3c7e72f3aec8bc2f425f4fd5c4c3aab2ca4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bovine serum albumin (BSA, 0.5%) was added to nasal wash sample supernatants after centrifugation at 800 g for 5 minutes at 4\u00b0C.", "c SEM = standard error of the mean (n = 3 per relative humidity condition)." ] },{ "paper_id": "86e3f31b72109395a9dd02071bf83aeb7fa6803c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Methods S1 Supplementary methods. (DOCX)", "Eight-week-old golden hamsters (Mesocricetus auratus, Janvier, France) were anesthetized and infected intraperitoneally (i.p.) with 0.4 ml of wild-type NiV (10 000 PFU) in the BSL-4 laboratory in Lyon. Each day post infection (p.i.), one hamster was euthanised and organs were frozen at 280uC.", "Autopsies of human brain tissue were performed after receiving written patient's relatives consent for autopsy studies at the Pathology Department of University of Malaya, Kuala Lumpur, Malaysia and their analysis was approved by review board of Faculty of Medicine of University." ] },{ "paper_id": "86effe356ffd602c096c4252ef1775dab6f62e1f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Several approaches have been developed to gain 3D information of cellular structures by EM ( Figure 4 ). In the following sections these approaches and their applications to study viral infection (summarized in Table 1 ) are described. ", "Cryo-ultramicrotomy has shown its capability in producing samples of vitrified cells and tissues for visualization by cryo-TEM and tomography [191] [192] [193] . However, sectioning at cryogenic temperatures is notoriously difficult and artifact-prone: sections inevitably suffer from adverse distortions caused by the harsh mechanical interactions of a diamond knife and a moving specimen block during the cutting process [194] . These technical limitations have prevented both CETOVIS, but also CEMOVIS (described above) from becoming more commonly used approaches [195] .", "As already pointed out by Small 34 years ago [24] , the majority of ultrastructural alterations might occur during the post-fixation processing of the samples for embedding (described below), rather than during fixation. Thus, a tailored protocol must be designed for the highest preservation of cells/tissue of interest, including both optimal fixation and post-fixation conditions.", "However, FIB-SEM has also some limitations: it requires a quite expensive specialized instrument and the sections cannot be re-examined again. Furthermore, processes like charging and electron beam damage can result in unsuccessful imaging of the surface of interest [179] .", "Along these lines, a recent multimodal approach named COIN (correlation optical and isotopic nanoscopy) combines three different imaging techniques: super-resolution microscopy, nano-SIMS (Secondary Ion Mass Spectrometry) [222] and EM, to provide information about the isotopic composition of many organelles and subcellular structures [223] ." ] },{ "paper_id": "86f450394e3530589eed829b5114c96d87513528", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "From 91 necropsied calves (30%; 91/308) additional samples for bacteriology and virology were taken. Of these calves, 57 5 .5% (5/91) pericarditis, 4.4% (4/91) congenital heart defects (3 interventricular septum defects, 1 tetralogy of Fallot), 4.4% (4/91) omphalitis (2 umbilical abscesses, 1 omphalophlebitis with liver abscesses and 1 omphaloarteritis) and 3.2% (3/91) an intussusception. Arthritis, meningitis, hydronephros, abomasal displacement, fistulating hepatitis or orchitis each accounted for one calf. Concurrent enteritis and pneumonia occurred in 22 (24.2%) cases, but the association was not significant. Of the 22 young (< 5 weeks old) calves with enteritis, 50%, 18.1%, 13.6% and 4.6% were Cryptosporidium parvum, bovine rotavirus, bovine coronavirus and Escherichia coli F5 positive respectively. Salmonella spp. could not be cultured from any of the examined (n = 13) cases with suspicious lesions.", "Mortality risk mean \u00b1 SD (min-max)", "To analyze the effect of the production system on morbidity, separate multivariable models were fit with total morbidity, BRD, enteritis, otitis and arthritis as binary outcome variables. PROC GLIMMIX with binomial distribution and logit link function with Wald's statistics for type 3 contrasts was used with herd as random effect. Associations between the different pathological lesions (pneumonia (acute-chronic-pulmonary abscess), enteritis (catarrhal-hemorrhagic), pleuritis, pericarditis, abomasal ulceration, ruminal bloat and peritonitis) and between the lesions and additional diagnostic test results (BVDV PCR and bacteriology of lung lesions) were determined by logistic regression (PROC GLM). Significance was set at P < 0.05." ] },{ "paper_id": "86fca5af635ee9425e3375140fb48cbe6d429411", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To enhance the detection of non-human sequences, RNA samples that passed the quality control step above were subjected to rRNA removal using the RiboMinus kit (Invitrogen Inc., Carlsbad, CA). Recovered RNA (post rRNA removal) was again quantified and subjected to Bioanalyzer analysis.", "The recovered sequence of GBV-C UU1 contained a open reading frame of 2842 codons, containing the structural and to GBV-C UU1 was the East African isolate GBV-C (EA) (gi:1666805). [32] At the amino acid level the viral polyprotein was 97.7% identical to GBV-C (EA) (64 coding differences). The sequence of GBV-C UU1 has been deposited with GenBank (GB JN127373).", "Thirty-two specific primers to the MS-6 GBV-C isolate were designed using the GAII sequences that were highly homologous to known GBV-C isolates. Overlapping amplicons were obtained using RT-PCR with freshly extracted total RNA from sample 3840. Amplicons were TOPO-cloned and sequenced using an ABI 3730 sequencer. The Sanger sequences were processed and assembled using the phred, phrap and consed programs using a known GBV-C scaffold (gi: 1666805). [29, 30] The GAII reads were added to this intermediate assembly using consed.", "Three anti-GBV-C antibody preparations and controls were kindly provided by the Jack Stapleton laboratory at the University of Iowa. These included pre-and post-immune rabbit polyclonal antiserum against GBV-C E2 protein [24] , mouse monoclonal anti-E2 #7067 [24] , and mouse monoclonal 1C4 [28] , plus control mouse IgG1 (Vector Laboratories, Burlingame, CA). Frozen MS and control brain tissues were thawed and fixed in 4% paraformaldehyde. Five micron paraffinized sections were used. Antigen retrieval was performed (Vector product H-3300). The tissues were penetrated with Triton-X and endogenous peroxidase was quenched. Sections were blocked with 5% normal goat serum (Vector product S-1000). Appropriate goat anti-rabbit or goatanti-mouse IgG secondary antibodies (Santa Cruz Biotechnology, products sc-2004 and sc-2060) were diluted 1:500-1:000 as recommended by the manufacturer. Signal was developed with NovaRed (Vector product SK-4800).", "DNase treated RNA was extracted from the tissue sections using Qiagen RNA-lipid kits (Valencia, CA) on dry ice, under laminar airflow. Purified RNA was quantified on a Thermo Scientific Nanodrop spectrophotometer (Waltham, MA). Samples with absorbance (A 260 /A 280 ) ratio ,1.8 were rejected and re-extracted. Fifty ng of RNA from each sample was submitted the Huntsman Cancer Institute (HCI) Microarray Core Facility lab for analysis on an Agilent 2100 Bioanalyzer Nanochip (Agilent Technologies, USA). The extracted RNA samples were evaluated for their distribution of RNA sizes, their relative abundances, the height and relative ratio of the 28S and 18S rRNA peaks, and for RNA integrity (RIN) as determined by the Agilent software. Each sample was evaluated by an experienced technician and then independently by one of the investigators. Samples with an unfavorable electrophoresis trace or RIN were not sequenced." ] },{ "paper_id": "86fe00ed292aab3fd191a7f8253d33dad3be59b3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "86fe86ce31570f771ef1b5f8f8c92a97a9fe22c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Study setting. This was a retrospective study conducted at two acute large tertiary care teaching hospitals within the same academic and health care system in Rhode Island. Rhode Island Hospital is a 713-bed tertiary care center, and The Miriam Hospital is a 247-bed community hospital. The study protocol was approved by the institutional review board for both institutions.", "Z.W. designed the study protocol, was involved in data collection, data analysis, and manuscript preparation. C.B.C. assisted with study design and manuscript preparation. A.B.C. assisted with study design, statistical analysis, and interpretation. A.V.C. helped with data collection, data management, and manuscript preparation. C.R. helped with literature review and manuscript preparation. M.R.-D. helped with data collection. A.A. helped with data collection and data management. D.M.P. helped with manuscript preparation. L.A.M. helped with study design and manuscript preparation. L.S. assisted with manuscript preparation. K.C. helped with study design, data collection, and manuscript preparation.", "K.C. served on an advisory panel for Genmark." ] },{ "paper_id": "86febf1edc351777b6424be2ee9a2e521176dd98", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Relatively benign viruses can be converted into highly virulent viruses via the introduction of genes of interest. For example, Ectromelia virus, a natural pathogen of mice that causes mousepox, recently was recombined with interleukin-4 as part of an effort to develop a live virus immuno-contraceptive vaccine. Surprisingly, the recom-bined virus caused 60% mortality in 2 strains of mice, whereas the wild type virus caused no death [1] . A credible bioterrorism scenario might entail the release of such a recombined or chimeric virus tailored for maximum infectivity and pathogenicity but not readily detectable using our current \"state-of-the-art\" diagnostics (i.e., PCR and micro-array chips.) Accordingly, there is a need for methods that can identify unknown viral pathogens and which can reveal extensive genomic information. Such methods would not only prove useful for our defense against bioterrorism, but also would improve our capacities to identify and control outbreaks of naturally occurring pathogenic viruses.", "c t : 2 6 6 6 7 a c t g g t a a g g t t g t t g g g t a t t t c a a t a c c g t c g t t g g c g c a g g c g t t g g a g a c t g c g a a 2 6 6 0 8 Q u e r y : 3 6 3 g g a a g t g t t t t t a a a a a g c c a g a g g a t g t a t t t g t c c c c c a g t c t g c a g t t g a a t t t t a c 4 2 2", "c t : 2 6 6 0 7 g g a a g t g t t t t t a a a a a g c c a g a g g a t g t a t t t g t c c c c c g g t c t g c a g t t g a a t t t t a c 2 6 5 4 8 Q u e r y : 4 2 3 c t c a g t c t g g t t g g t g a g g t t g a a g 4 4 7 | | | | | | | | | | | | | | | | | | | | | | | | | S b j c t : 2 6 5 4 7 c t c a g t c t g g t t g g t g a g g t t g a a g 2 6 5 2 3" ] },{ "paper_id": "8705d3a93c346b8b21e349c6263e680d844e7aea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vaginal resident NK cells in humans are different from their uterine counterparts in that they are CD16 + and CD94 \u2212 [39] . They also had a high potential of producing inflammatory cytokines including IFN and lower cytotoxic potential. They express CD56 to a similar level as immature [41] . Given their importance, a more thorough analysis of their phenotype would be interesting and informative to pursue.", "NK cells functioning to control influenza can also cause severe pathology in the lungs [56] . In mice given a high dose of influenza, depletion of NK cells resulted in better outcome against infection. A reason behind these differences could be attributed to the proinflammatory cytokines produced during initial viral encounter that help NK cells respond. IL-12 and type I IFNs stimulate NK cells to produce IFN [61] . However, high production of these cytokines in response to pulmonary infection can lead to overproduction of IFN resulting in tissue destruction.", "NK cells are found in many tissues. This includes bone marrow (BM), blood, liver, thymus, and spleen. Mucosal sites that harbor NK cells include the lung, the small and large intestine and colon of the gastrointestinal tract (GI), and the uterus, cervix, ectocervix, and vagina of the female reproductive tract (FRT). Much of how they gain access to these sites and provide function (protection, immunoregulation) is just beginning to be understood. The review focuses on recent work and the current understanding of the regulation of mucosal tissue residency of NK cells and NK cell functional importance at mucosal sites relevant to both mouse and human systems. We will not address ILC2 and ILC3 populations as those have been reviewed elsewhere [6, 7] ." ] },{ "paper_id": "870c8d63bfe7cbede0c0779b7991b8296dfede1c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consistently, SHFV nsp1\u2424 displayed similar activity in stimulating \u03ea2/\u03ea1 PRF on the reporter mRNA of PRRSV-1 (Fig. 10A, right) .", "Simarteriviruses comprise a rapidly expanding subfamily of undercharacterized arteriviruses now known to infect a wide range of nonhuman primates. The most notorious simarteriviruses, Pebjah virus (PBJV), simian hemorrhagic encephalitis virus (SHEV), and SHFV, repeatedly caused highly lethal hemorrhagic fever epizootics among captive macaques in the United Kingdom, United States, and the Soviet Union throughout the 1960s to 1990s (reviewed in reference 8), but their natural host reservoirs are unknown. In contrast, other simarteriviruses found in nature, specifically, those in subclinically infected African nonhuman primates, have not been implicated in epizootics. These viruses include De Brazza's monkey virus 1 (DeBMV-1) in De Brazza's monkeys (Cercopithecus neglectus), Drakensberg Mountain vervet virus (DMVV-1) in vervet monkeys (Chlorocebus pygerythrus) (6) , Kafue kinda-chacma baboon virus (KKCBV) in Kinda baboons (Papio kindae), Kibale red colobus viruses 1 and 2 (KRCV-1 and KRCV-2) in Ugandan red colobus (Procolobus rufomitratus tephrosceles) (9) , Kibale red-tailed guenon viruses 1 and 2 (KRTGV-1/2) in red-tailed monkeys (Cercopithecus ascanius) (10) , Mikumi yellow baboon virus 1 (MYBV-1) in yellow baboons (Papio cynocephalus) (11) , southwest baboon virus 1 (SWBV-1) in olive baboons (Papio anubis) (11) , and Zambian malbrouck virus 1 (ZMbV-1) in malbrouck monkeys (Chlorocebus cynosuros) (6) . In experimental settings, KRCV-1 can cause mild disease in crab-eating macaques (Macaca fascicularis) (12) , whereas SWBV-1 infects but does not appear to cause disease in rhesus monkeys (Macaca mulatta) (13) . Since wild nonhuman primates are historically important sources/reservoirs of human pathogens and because of their broad and diverse distribution among African monkeys, there is concern that some simian arteriviruses may be preemergent zoonotic pathogens (14) . Hence, increased molecular characterization of simarteriviruses is becoming a priority in arterivirology.", "Most RNA viruses have polycistronic genomes and have evolved strategies to overcome a limitation of the eukaryotic translation apparatus, namely that in general, only the 5=-most open reading frame (ORF) on an mRNA is translated. These include noncanonical translation mechanisms, such as programmed ribosomal frameshifting (PRF) and alternative initiation, and in addition, the expression of polyproteins that are subsequently cleaved by viral or host proteases. Viruses may also produce subgenomic mRNAs that are functionally monocistronic. Arteriviruses use several of these strategies to coordinate their complex replication cycles (15, 16) ." ] },{ "paper_id": "87154b31b741f39ec7e34f3590f80b9a01105e33", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study used data from a community--based interview survey conducted with 2.486 male (n=923) and female (n=1.563) subjects 60 years of age and older who provided voluntary consent to participate in the questionnaire survey. To enhance the validity of research, exclusion criteria were prior urological surgery; prior treatment for BPH, prostate cancer or OAB; evidence of a neurological condition; history of a malignancy; evidence of urinary tract infection; evidence of psychiatric illness; and evidence of alcohol or substance abuse.", "Age is an important factor that has an impact on generation-specific prevalence of BPH and OAB. Therefore, this study queried each participant's date of birth.", "ARTICLE InfO" ] },{ "paper_id": "871bb1d475d0dbb910cce25e16d066adf9706a4c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "TLR9-forward 5'-GGCCCATTGTGATGAACCTG-3' and TLR9-reverse 5'-GCAGAGGGTTGCTTCTCACG-3'; NF-kappaB-reverse 5'-CTGGACATGGCTGCCAACT-3' and NF-kappaB-reverse 5'-CGGTTTCCCATTTAGTATGTCAAA-3'; IL-6-forward 5'-CTATGAAGTTCCTCTCTGCAAGAGACT-3' and IL-6-reverse 5'-GGGAAGGCCGTGGTTGTC-3';", "MyD88-forward 5'-CCTTGATGACCCCCTAGGACA-3' and MyD88-reverse 5'-CAGATAAAGGCATCGAAAAGTTCC-3'; TLR7-forward 5'-GATCGTGGACTGCACAGACAA-3' and TLR7-reverse 5'-GGAATGCCCTCAGGGATTTC-3';", "TNF-alpha-forward 5'-GACCCTCACACTCAGATCATCTTCT-3' and TNF-alphareverse 5'-CCACTTGGTGGTTTGCTACGA-3'; E2-2-forward 5'-CCTGACTTGAACCCACCCC-3' and E2-2-reverse 5'-GAGGCCTGGTGGCATCC-3';" ] },{ "paper_id": "871bc5983e4188a32f9cfda1adb07fdbf760f891", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Both HEK293 and Vero cells are being studied for basic research regarding influenza as well as for vaccine research (reviewed in Milian E., 2015 [44] ).", "Below, we describe in brief the current models and elaborate on new models.", "2.2.2. Immortalized Lung Cells, e.g., A549 and Calu-3", "Almost ninety years after the virus causing the disastrous influenza epidemics was identified [1] , 3-5 million people are still affected annually with severe symptoms and 500,000 die [2] . Furthermore, highly virulent strains still appear and result in local epidemics or global pandemics, such as the", "In summary, primary human tissue cultures open a new window into specific effects of the virus and, perhaps much more important, into patient-specific effect and patient-specific response to drugs and treatment. These systems are thus of great value not only for basic research, but also for immediate patient-specific translational therapeutic values." ] },{ "paper_id": "871eb9f53e30a9b67bd226ca8235a50c576a2755", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Detection of CGMMV demonstrates that the method can identify viruses present in human diet providing further indication of the validity and accuracy of the presented method.", "and occasionally lead to death. Furthermore, every few decades, respiratory virus pandemics emerge, putting the entire world population at risk. thus, there is an urgent need to quickly and precisely identify the infecting agent in a clinical setting. However, in many patients with influenza-like symptoms (ILS) the identity of the underlying pathogen remains unknown. In addition, it takes time and effort to individually identify the virus responsible for the ILS. Here, we present a new next-generation sequencing (NGS)based method that enables rapid and robust identification of pathogens in a pool of clinical samples without the need for specific primers. The method is aimed at rapidly uncovering a potentially common pathogen affecting many samples with an unidentified source of disease.", "The control viruses that were included in the pooled assay sample were identified only in the control samples (Fig. 5) . One patient (number 10, Fig. 5 ) was infected with parainfluenza 1 virus and three patients with CGMMV, that is not known to cause illness in humans (Fig. 5) . Human picobirnavirus was detected in one of the contigs assembled. This virus causes gastroenteritis symptoms and is not associated with ILS 35 ." ] },{ "paper_id": "871ebc4ba030dbc666e9520d28b5f64e7a0ebf17", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Several animal CoV are economically important pathogens [11] . For example, transmissible gastroenteritis virus (TGEV) causes diarrhea in pigs [12] [13] [14] , feline infectious peritonitis virus (FIPV) leads to a fatal systemic disease in cats [15] [16] [17] , the bovine coronavirus (BCoV) causes respiratory tract diseases and diarrhea in cattle [14, 18] and the avian infectious bronchitis virus (IBV) is the etiological agent of severe respiratory tract and kidney diseases in chickens [14, 19] . The mouse hepatitis virus (MHV) has been extensively used to study the replication and assembly of CoV in cell culture models as well as in whole animals and is thus considered as a prototype CoV [11, 14] .", "These data explain previous observations. Originally, it was reported that the ATG5 gene is essential for MHV replication in MEFs [73] . Careful reassessment of these findings in low passage atg5 \u2212/\u2212 MEFs and bone marrow derived macrophages lacking ATG5 by virtue of a Cre recombinase mediated gene deletion, revealed that an intact autophagy pathway is not required for MHV life cycle [74] . In addition, these data also reconcile previous contrasting reports about LC3 association with CoV-induced DMVs. The works describing a co-localization were analyzing endogenous LC3, while those affirming the contrary used ectopically expressed GFP-LC3 [72] [73] [74] [75] [76] [77] .", "Pathogens of bacterial and viral origin hijack pathways operating in eukaryotic cells in many ways in order to gain access into the host, to establish themselves and to eventually produce their progeny. The detailed molecular characterization of the subversion mechanisms devised by pathogens to infect host cells is crucial to generate targets for therapeutic intervention. Here we review recent data indicating that coronaviruses probably co-opt membranous carriers derived from the endoplasmic reticulum, which contain proteins that regulate disposal of misfolded polypeptides, for their replication. In addition, we also present models describing potential mechanisms that coronaviruses could employ for this hijacking." ] },{ "paper_id": "872b314b2512ccf6e934ab4e07358b85dcef3040", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that they have no competing interests.", "Sequences generated in this study have been deposited in GenBank under the accession numbers MH013965 to MH013995.", "Not applicable." ] },{ "paper_id": "873d2ca5817ad916b491680ffc9e3260a8469e60", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8745be1dc78adeffdc2f243e3597390ddd07b456", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This paper reports the results of analysis of the PEDV from a historic field case in England, including comparisons with currently circulating North American/Asian viruses, INDEL strains and the European prototype strain CV777 (Kocherhans et al., 2001) .", "PCR testing of the faecal sample from 2000 confirmed the presence of PEDV nucleic acid and the absence of TGEV, indicating involvement of PEDV in the outbreak of diarrhoea in the finishing pigs.", "As shown in Fig. 1 , phylogenetic analysis of the consensus whole genome sequence obtained directly from the archived faecal sample indicates that the virus, while clearly belonging to the PEDV species, lies distinct from any of the genogroups described by Huang et al. (2013) ." ] },{ "paper_id": "874e540a730ee1060365af8d2caa03f537508e33", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tissues were dissected, immediately immersed in RNAlater \u00ae stabilization reagent (Invitrogen, USA) and stored at \u221280 \u2022 C. Total RNA was extracted from individual tissues using TRIzol and quantified using a spectrophotometer at a wavelength of 260 nm. Random hexamers were used to prime reverse-transcription reactions using a reverse transcription (RT)-PCR kit containing SYBR green dye (Takara, Shiga, Japan).", "To establish an in vitro neutralization assay, the cellular tropism of pHIV/MERSS/Fluc was tested in various cell lines. All 12 cell lines tested were permissive to pHIV/MERSS/Fluc infection, but Huh7 cells showed the highest infection efficiency (Supplementary Figure S2F) , demonstrating the wide cellular tropism of the pseudotyped virions. As a result, the Huh7 cell line was chosen to establish a chemiluminescence-based, high-throughput antibody neutralization assay. The assay displayed good sensitivity and specificity." ] },{ "paper_id": "87620b2fa94ff9b59a3a84382dceae62f83259a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The bone marrow 6D10 + immature granulocytes were increased and targeted by CSFV in persistently infected piglets", "In addition to the epidemiological and economic significance of persistent CSFV infection, this model could be useful for understanding the mechanisms of viral persistence.", "Thus, the virulence of CSFV might be a critical factor in determining the outcome of early post-natal infection, considering the capacity of the Cat01 moderate virulence strain to induce persistent disease. Nevertheless, it is not known whether this outcome could also apply to trans-placental infections at mid-gestation. The proportion of persistently infected piglets could likely vary between reports with different viruses [13, 20, 21] ." ] },{ "paper_id": "8762daff0f7890b72f611247c1a15133ea291afb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2.6. Nanotechnology Based Detection. Recent advancements in nanotechnology have changed the perception and perspective of research. When scaled down to nanometers, the properties of matter change and nanotechnology exploits these new properties and harnesses them with the existing technologies to exceptional capabilities. Techniques discussed below are examples of the nanotechnology based detection approaches which utilize basic traditional but indispensable detection techniques.", "Another approach of RNAi treatment to combat RSV is to decelerate the adverse effects of RSV mediated Th2 type immune response because the aggravated host immune response is more harmful than RSV infection itself.", "Sometimes DNA microarrays do not confer their utility in very specific investigations in the case of personalized medicine wherein the manifestation of disease occurs at the transcription level. This situation may arise in complications of RSV with other associated disorders like asthma [70, 71] . As protein is the abundant functional biomolecule, reflecting the physiological or pathological state of the organ, protein microarray profile is an option to access under this situation [72] . Protein microarray has analytical and functional applications to study the protein-protein, protein-DNA, and protein-ligand interactions. These features enable the profiling of immune responses and are thus important for diagnostics and biomarker discovery. Protein microarray can serve as a rapid, sensitive, and simple tool for large-scale identification of viral-specific antibodies in sera [73, 74] . An extensive study was done during the 2002 SARS pandemic using coronavirus protein microarray to screen antibodies in human sera (>600 samples) with >90% accuracy and at least as sensitive as, and more specific than the available ELISA tests [73] . Thus, this system has enormous potential to be used as an epidemiological tool to screen viral infections.", "The utility of a metagenomics based strategy for broadspectrum diagnostic assay using microarrays was demonstrated for screening viruses like Rhino virus, Parainfluenza virus, Sendai virus, Poliovirus, Adenovirus, and RSV from clinical samples [62] . A well-known example is \"Virochip\" which is a pan-viral microarray, designed to simultaneously detect all known viruses, and has comparable or superior sensitivity and specificity to conventional diagnostics [63, 64] . Similarly, an influenza microarray, \"FluChip-55 microarray\", for the rapid identification of influenza A virus subtypes H1N1, H3N2, and H5N1 was developed [65] . The procedure is simple and follows few steps including RNA extraction from clinical samples, subsequently their reverse transcription, second-strand cDNA synthesis, and then PCR amplification of randomly primed cDNA. The hybridization of nucleic acids with probes is done by fluorescent dyes or by an alternative method of electrochemical detection. The latter method relies on a redox reaction to generate electrical current on the array for measurement. Incorporation of Cy3 fluorescent dye and hybridization to the microarray [66] has been empowered by specific algorithms to match the diagnostic needs, leading to the final and critical step of scanning and analysis [67] .", "A novel method of developing RSV DNA vaccine was devised by replacing the structural genes with RSV genes in an attenuated strain of Venezuelan equine encephalitis virus (VEEV). VEEV has an ssRNA (+) genome and contains a strong subgenomic promoter. The replicon particles were prepared by providing helper RNAs encoding VEEV capsid and envelope glycoprotein which comprise structural proteins, and all of these, when transfected into Vero cells, resulted into a replicon particle that could independently synthesize the RSV protein, thereby activating the immune response and protection. The system could be modulated by the administration of helper RNAs. This strategy was applied to the mice and rhesus monkey models, conferring protection against RSV and a desirable extent of a balanced Th1/Th2 type immune response was received [115] ." ] },{ "paper_id": "8763c9240b22a0e841ddb6e7e9a22ef3a566e97e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data were compiled in Microsoft Excel 2016 and analyzed using GraphPad Prism 8 (Version 8.1.0; GraphPad Prism Software, La Jolla, CA, USA). The frequencies were compared using Fisher's exact test (p F ). The ages of the cats in different groups were compared using the Mann-Whitney U-test (p MWU ). p-values < 0.05 were considered statistically significant.", "The diagnostic sensitivity (true positives/all positives) of FIV-TM ELISA was 82% (441/536); the diagnostic specificity (true negatives/all negatives) was 91% (375/411), and the diagnostic efficiency (correct tests/all tests) was 86% (816/947).", "WB has been considered the gold standard to accurately identify FIV positive and negative samples. The diagnostic sensitivity, specificity and efficiency of FIV-TM ELISA were calculated.", "We found 247 samples with inconclusive WB results ( Table 2) . Of these samples, the majority showed antibodies against p24 (230/247, 93%); only a few had a p15 band (17/247; 7%). Of the 247 samples, 36 were ELISA-positive, of which 30 had OD values ranging from 100% to 440% of that of the positive control; 205 tested ELISA-negative and six had an ambiguous result in the FIV-TM ELISA ( Table 2) . Animals with inconclusive WB results are recommended to be retested two to three months later." ] },{ "paper_id": "8764d0cec1713833f147b13fd476ae8fac42c600", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "876ae65a682f1bf2941f54851442532ae722382c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The transformation X = (p/q)-1 has the desired effect of subtraction of random background in p and rendering it a stationary time series suitable for subsequent cross-correlation analysis. X can also be regarded as the relative difference between p and q.", "The words in the brackets given above are the abbreviations of the names of these species and their NCBI accession numbers.", "Then we use X(s 1 s 2 ...s K ) for all possible K-mers s 1 s 2 ...s K as components and arrange them according to a fixed alphabetical order to form a composition vector X = (X 1 ,X 2 ,...,X N ) for genome X, and likewise Y = (Y 1 ,Y 2 ,...,Y N ) for genome Y." ] },{ "paper_id": "8778a5efe2618f5d7c1873b4f1d6c6b49464e2c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using GraphPad Prism versions 7.0-8.1 for macOS (GraphPad Software), using statistical tests as mentioned in the figure legends. P-values considered statistically significant are represented with * for p < 0.05, * * for p < 0.01, and * * * for p < 0.001.", "Human embryonic kidney HEK293T cells (ATCC-CRL-3216), human foreskin fibroblast BJ cells (ATCC-CRL-2522), human muscle RD cells (ATCC-CCL-136), and African green monkey kidney Vero E6 cells (ATCC-CRL-1586) were grown in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBS, Gibco); and for BJ cells supplemented with 1\u00d7 Penicillin-Streptomycin (Gibco). All cells were maintained at 37 \u2022 C with 5% CO 2 .", "GC conceived and designed the experiments and analyzed the data. GC, Y-HC, AU, FA, and T-KC performed the experiments. GC, AM, and LN wrote the manuscript. AU and AM contributed reagents and materials. All authors reviewed and approved the final manuscript.", "We thank Prof. Ooi Eng Eong for providing passage one of the IND isolate used in this study. We would also like to thank Drs. Kai-Er Eng, Teck-Hui Teo, and Fok-Moon Lum who critically read the manuscript." ] },{ "paper_id": "87795a5783981250b35b32635c37fd2a098c4ed6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the National Center for Health Statistics mortality files that we used for this research, all information that could allow an individual to be identified has been removed. This research utilized only mortality counts for a large metropolitan area. These de-identified counts are stored in governmental archives for the purposes of retrospective research; because all personal identifying information is redacted, consent is not required. Thus, this research is exempt from IRB review under the auspices of Title 45 Part 46 exemption category 4.", "Theories proposing that factors other than weather/climate are responsible for influenza seasonality include cycles in viral interference [20] and intrinsic temporal viral dynamics that operate independent of external forcing factors [21] . Some research suggests that the seasonality is driven by the school calendar in which students reconvene after a summer break, but this timing is not consistent with the typical onset of influenza in early winter [22] .", "Conceived and designed the experiments: RED CER KBE. Performed the experiments: CER. Analyzed the data: CER RED KBE. Wrote the paper: RED CER KBE.", "For the daily SSC analysis, lower frequencies of moist moderate (MM) air (p = 0.019) and higher frequencies of moist polar (MP) air (p,0.001) occurred 15-19 days before high mortality events (Table 3) . No relationship was found for dry polar (DP) air (p = 0.277)." ] },{ "paper_id": "87797599a00816e5bc19e3804da8af1778d61b0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ability to predict whether an animal is susceptible to bovine respiratory disease (BRD) would benefit producers. Cost savings may be realized by managing animals with higher potential susceptibility to BRD differently by attempting to reduce their exposure to illness or by monitoring susceptible animals more closely for illness. Alternatively, these animals might be treated prophylactically at an earlier stage to mitigate the risk of illness.", "The expression of CCL16 has been widely reported in the liver [15] , but its expression can also be induced in activated monocytes by IL-10, IFN-\u03b3 and bacterial lipopolysaccharide [16] . The cattle with BRD in this study displayed increased levels of CCL16. We detected a positive animal correlation between monocytes counts and CCL16; thus, a higher level of CCL16 expression among animals with BRD could suggest that these animals have greater numbers of activated circulating monocytes.", "Many of the previous studies of hematology parameters for calves available in the literature are limited by small sampling sizes and include only one breed or a specific cross of cattle [17] [18] [19] . A recent study by Leach et al. [1] is the only example of CBC data on a large population of 2182 crossbred calves. Our study sampled 796 crossbred calves at 120 days and 791 at 150 days for normal hematology parameters, and also includes hematology and cytokine gene expression data from animals that developed BRD (up to 192 days of age). In addition, the data presented here includes crossbred heifers and steers representing 18 breeds of origin." ] },{ "paper_id": "8780e9524d9271a7b8e789f0f8c4eb6860ca8c50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Throughout this study 95% confidence intervals (95% C. I.) for sample proportions and prevalence estimates were calculated using the Jeffreys method [56], while statistical analysis was carried out using the Fisher exact chi-squared test [57].", "cDNA synthesis. SuperScript\u2122 III Reverse Transcriptase (Invitrogen) was used to synthesise cDNA from aliquots of extracted nucleic acid in preparation for screening of samples for the presence of paramyxoviruses and coronaviruses by PCR. The reverse transcriptase (RT) reaction was performed according to the manufacturer's instructions using 100 ng random primer oligonucleotides (Invitrogen), and 10 \u03bcL of nucleic acid extract as template. All assays included a no template control with sterile water, and the appropriate positive control as described for each assay.", "Supporting information S1 " ] },{ "paper_id": "87810195a429d5f1d8b494f1170c9e82bc24f9a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tables of contents and indices of textbooks and reference books addressing public health issues were identified through Google, Amazon, and other online searches. Twelve highly ranking and relevant books were selected for tabulation. Inclusion criteria comprised Amazon rankings, public health content relevant to POCT, recent publication (2015 and later), and/or emphasis on global health, in view of the impact of POCT worldwide. Foreign language books were excluded." ] },{ "paper_id": "8792b598db3c64a2da937a9cefc989a7fd0a67aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The genome sequences of AMCV (X62493), CBLV (NC_004725), CIRV (NC_003500), CuNV (NC_001469), CymRSV (NC_003532), GALV (AY830918), PLV (NC_004723), PNSV (AJ607402), TBSVc (NC_001554), TBSVnf (AY579432), TBSVp (U80935), and TBSVs (AJ249740) were obtained from the NCBI GenBank database. RNA secondary structures were predicted at 37uC using Mfold version 3.5 [30, 31] .", "Construction of TCV mutants was performed using the genomic construct T1D1 [61] employing standard PCR-based mutagenesis. PCR-derived regions containing the designed modifications that were introduced into constructs were sequenced completely in order to verify that only the desired changes were present. All mutations are shown schematically in Figure 11 .", "RNA-RNA electrophoretic mobility shift assays were performed as described previously [39] , with some modifications. Briefly, unlabelled RNAs were used and equimolar ratios of RIV and SL-PRTE RNAs (16 pmol each) were incubated for 30 min at 25uC in RNA binding buffer (5 mM HEPES at pH 7.8, 100 mM KCl, 6 mM MgCl 2 , 3.8% glycerol) in a total volume of 8 mL. Samples were subsequently cooled at 4uC for 10 min, mixed with loading buffer (50% glycerol, 50% RNA binding buffer), and separated at 4uC in a nondenaturing 15% polyacrylamide gel containing 6 mM MgCl 2 using 1X TBE running buffer containing 6 mM MgCl 2 . Gels were then stained with ethidium bromide to visualize bands and the negative image is shown in Figure 3C ." ] },{ "paper_id": "879387ff0282d3823d01dded6b50b383e1741342", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PLOS ONE | https://doi.org/10.1371/journal.pone.", "Some viruses have the potential for cross-species transmission, with spillover episodes from humans to wildlife and vice versa, a phenomenon referred to as zoonosis [1] . Current research on the dynamics behind host/virus interactions and inter-and intra-specific transmissions is of scientific interest and important implications for emerging zoonoses and consequently for public health.", "Non-lethal sampling was based on permits 201710730002961/IRM/MDCG/mes issued by Direcci\u00f3n General de Gesti\u00f3n del Medio Natural y Espacios Protegidos (Consejer\u00eda de Medio Ambiente, Junta de Andaluc\u00eda, Spain), 10/085545.9/17.9/17 issued by 'Consejer\u00eda de Medio Ambiente, Administraci\u00f3n Local y Ordenaci\u00f3n del Territorio, Comunidad de Madrid', and PNSNG_SG_2018_0093 issued by 'Servicio Territorial de Medio Ambiente de Segovia, Junta de Castilla y Le\u00f3n'. For this study, permits for the collection of punch biopsies of wing membranes from bats were issued by Comit\u00e9 de \u00c9tica del Consejo Superior de Investigaciones Cient\u00edficas and by Consejer\u00eda de Agricultura y Pesca y Desarrollo Rural, Junta de Andaluc\u00eda (permit reference: SSA/SSI/MD/ps). The techniques used meet the guidelines published by the American Society of Mammalogists on the use of wild mammals in research [35] Data collection" ] },{ "paper_id": "879b0904d411e88c1be90f0660e7bb4377ae29d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Supplementary Material for this article can be found online at: http://www.frontiersin.org/journal/10.3389/fcimb. 2014.00020/abstract ", "The Chlamydiaceae are Gram-negative, obligate intracellular bacteria that cause a large spectrum of diseases in both humans and agriculturally important animals. For example, Chlamydia suis, C. abortus, C. pecorum and C. psittaci cause syndromes in swine ranging from conjunctivitis to abortion . Asymptomatic chlamydial infections are also common in pigs and can render them more susceptible to other infections (reviewed in Schautteet and Vanrompay, 2011) . Related chlamydial species, such as C. trachomatis, also cause medically important conditions, like trachoma, in humans. Though chlamydial infections can cause acute symptoms, they are most associated with chronic inflammation and scarring, which can result in significant host tissue damage (Schachter, 1999) . However, to play a causative role in chronic diseases, chlamydiae would need to persist within infected cells/tissues for extended periods of time. How the organisms maintain long-term host infection is a central question in chamydial biology.", "Robert V. Schoborg and Nicole Borel designed the experiments, conducted all experiments and analyzed the data. Both authors contributed to drafting the manuscript and figures." ] },{ "paper_id": "879b563cbe739c7ec914ce9eef39d9a85d6d3801", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "If CD59 is downregulated in the ECs due to either gene mutation or acquired diseases [25] , activated terminal complement MAC could exert destructive effects to ECs in sepsis, trauma and other critical illnesses [26] [27] [28] . When MAC attacks innocent bystander ECs, channel (transmembrane pores) formation could occur on the endothelial membrane [22] and trigger endothelial dysfunction [3, 22, 29] .", "In addition to hypoxic microvascular dysfunction, endotheliopathy causes the release of various inflammatory cytokines [7, 35, 36] and bioactive biomarkers from ECs when infected by different types of pathogen [37] . Unlike adaptive immune mechanism that produces antigen-specific protective antibody response from each pathogen to each host, sepsis-induced endotheliopathy triggers similar, if not the same, endothelial molecular response without specificity among different types of pathogen ( Fig. 3 and Table 1 ). This endothelial dysfunction causes independent inflammation different from vascular microthrombosis. The manifestations of inflammation and microthrombosis are universally similar among each class and each type of pathogens and display no specificity.", "In addition to protective \"", "Anti-microthrombotic therapy can be utilized with a close monitoring of the platelet count, intravascular hemolysis, and evaluation of organ dysfunctions. Streamlined therapeutic trials with recombinant ADAMTS13 should be proposed for the patients with septic syndromes associated with EA-VMTD/DIT as soon as possible." ] },{ "paper_id": "87a937ec2cd698b7d24ade1803a22852747ec8c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The distributions of significant improvement, slight improvement, no change and worse were similar between the two regimens ( Table 2 ). ", "Trial Registration: Clinical trial registered with", "Lung scans were independently reviewed and evaluated by two specialists using the methods described previously [12, 13] . Each anatomic segment of the lung was reviewed and the defect within each segment was scored according to the level of perfusion reduction.", "The location and severity of thrombus obstruction of the pulmonary vascular bed were reviewed and evaluated by helical CTPA score system described in previous studies [14, 15] . The index is defined as the product N \u00d7 D, where N is the value of the proximal clot site (equal to the number of segmental branches arising distally) and D is the degree of obstruction. Partial obstruction is scored as 1 and total obstruction is graded as 2." ] },{ "paper_id": "87ad4bcfb14f3ae9f7eb1a0642d50fad167349e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2) Information acquisition, management, and dissemination: development of digital libraries, data archives, institutional repositories, and related tools (e.g. data curation).", "The BIS skill set will focus specifically on the following areas:", "3) Information organization and integration: ontology development, structuring information for optimal use and sharing, and standards development.", "1) Evaluation and implementation of information systems: user based assessment and continual quality improvement for the development of tools that work and are used." ] },{ "paper_id": "87b2f2205b9dea38eeaeddd6e3ddbb6e45f542ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The significance of differences between groups was evaluated using one-way analysis of variance (ANOVA) and Tukey's multiple-comparison test. The graphs were plotted and analyzed using Origin 8.0 (OriginLab Corporation, USA).", "Keywords: rabies virus, transcriptome, pathogenic and attenuated strains, innate immunity, pathogenesis, MHC class II", "The mouse brain tissues were lysed in the lysis buffer (50 mM Tris-HCl, pH 7.4, 150 mM NaCl, 1 mM EDTA, 1% NP-40) supplemented with 0.02 mM phenylmethanesulfonyl fluoride (PMSF). After electrophoresis, the separated proteins were then transferred onto a polyvinylidene difluoride (PVDF) membrane. Rig-I monoclonal antibody (Cell Signaling Technology, USA), STAT1 and p-STAT1 polyclonal antibodies (Bioworld Technology, USA) and horseradish peroxidase (HRP)-conjugated goat anti-mouse or rabbit IgG (Sigma, USA) were used, respectively, as the primary and secondary antibodies at the dilutions recommended by each manufacturer. The protein bands were detected by BeyoECL plus (Beyotime Biotech, China)." ] },{ "paper_id": "87c3f3ef6a719daba2049b5d7981486a6f1259c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following set of deterministic differential equations are obeyed by the densities:", "The removed population in the model in ref. 20 was fitted to the form:" ] },{ "paper_id": "87c6c45d9946889a9a3551b31adff4c32c6c237e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The computer modeling of 8a protein structure was performed with the raptorX server http:// raptorx.uchicago.edu [83] . The predicted structures were visualized using Pymol (http://www. pymol.org/).", "Student\u00b4s t test was used to analyze differences in mean values between groups. All results are expressed as means \u00b1 standard errors of the means. P values of <0.05 were considered statistically significant.", "(DOCX)" ] },{ "paper_id": "87cb1c3bdd1b8701c07a17f66a17e5d7a55797e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ". Virus-derived small RNA can be assembled into long contig sequences 7 Supplementary Figure ", "Supplementary Figure S3. Viruses identified by small RNA sequencing belong to diverse viral families. (A) PCLV in mosquitoes from Rio de Janeiro, Brazil clusters with other viral strains from Thailand on the phylogenetic tree with 74% bootstrap confidence at p-distance of 0.038. The dinucleotide profile reinforces the relationship between Rio and Asian strains of PCLV. (B) HTV also identified in mosquitoes" ] },{ "paper_id": "87cc7c4ce4f857e235f5fe0fffc2513cf9e653d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It was not until spring 2013 that the highly virulent PEDV was introduced into the United States (US) and caused epidemic outbreaks in PEDV-na\u00efve swine population [2] , leading to the death of 10% (~seven million) US pigs, and economic losses of $900 million to $1.8 billion from 2013 to 2014 [28, 29] .", "Highly virulent G2 PEDV outbreaks have caused immense economic losses in the pork industry and are still causing epidemic and endemic outbreaks in many countries. However, effective and safe vaccines" ] },{ "paper_id": "87cce3d733ad6f5f0d283d58b8a2b1a0dc47f99e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.pntd.0006981.g001", "Written informed consent was obtained from all the adult volunteers who participated in the study and for inclusion of young children written consent was obtained from their parents or guardians. For Ethiopian samples, the study protocols were reviewed and approved by the ethical review committee at the Medical Faculty, Addis Ababa University and the National Research Ethics Review Committee (NRERC) at the Ethiopian Ministry of Science and Technology. For Sudanese samples, the study protocols were approved by the National Ethical Committee of the federal Ministry of Health, Sudan. Each volunteer was treated in accordance with international bio-ethical rules and laws for human sampling. Blood was sampled by certified trained Health officers or nurses." ] },{ "paper_id": "87d031191cd30614cfded9fbea64d0a4db44952a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We retrospectively reviewed all MERS-CoV cases admitted at King Abdulaziz Medical City, Jeddah, since the onset of the epidemic in 2012. We identified a total of 120 confirmed cases of MERS-CoV infection. Two patients with neurological complications of MERS-CoV were the subjects of our study. They were admitted to different wards and were managed by different medical teams prior to admission to the intensive 2 Case Reports in Neurological Medicine care unit (ICU). The clinical, laboratory, and radiological findings of these cases were reviewed. Testing for MERS-CoV was performed using real-time reverse transcription polymerase chain reaction (RT-PCR). This study was approved by the institutional review board (IRB) of King Abdullah International Medical Research Center (KAIMRC), and since this is an observational study, the consent was waived as per the institutional policy.", "A thirty-four-year-old female, who was newly diagnosed with diabetes mellitus, presented to the emergency room with a history of high-grade fever of one-day duration. Fever was documented at home and relieved by oral paracetamol. She denied any history of cough or shortness of breath but complained of generalized bone pain and fatigue. Systemic examination showed a febrile ill-looking lady with no lymph node enlargement or skin rash. Chest examination showed decreased air entry bilaterally with crepitation. Neurological examination was normal including higher mental functions, cranial nerves, and motor system, sensory system, and coordination. Laboratory investigations on admission revealed white blood cells of 4.7 with lymphopenia, hemoglobin of 11.3, platelets 203, ESR 47, and CRP 56.5. Chest imaging showed right lung homogenous opacity and the patient was started on intravenous hydration, tazocin, and azithromycin. RT-PCR came back positive for MERS-CoV from sputum. She started to improve, and her condition was stabilized. Unfortunately, two weeks following admission, the patient developed a severe headache, nausea, and vomiting. Few hours later, her consciousness level deteriorated and GCS dropped to 3/15. Urgent CT showed right frontal lobe intracerebral hemorrhage with massive brain edema and midline shift ( Figure 1 ). She was intubated and mechanically ventilated, and she received intravenous mannitol and dexamethasone. Laboratory investigations revealed pictures of disseminated intravascular coagulation including thrombocytopenia and prolonged coagulation profile. Unfortunately, she started to develop multiorgan failure and signs of irreversible brain stem dysfunction and she died two months later.", "In our cases, none of the theories mentioned above are contributory since our patients presented with sequelae of systemic complications. The first case was explained by an intracerebral hemorrhage as a result of thrombocytopenia, disseminated intravascular coagulation, and platelet dysfunction. The second case was a case of critical illness polyneuropathy complicating a long ICU stay. He made a full recovery with supportive measures, immune modulating treatment, and physiotherapy. The three cases reported in the literature previously along with our cases are summarized in Table 2 .", "Coronaviruses are a family of enveloped, single-stranded, positive-sense RNA viruses that are prevalent in bats and can affect many other species including humans. The name corona denotes the crown-like appearance of the surface projections of the virus under the electron microscope. They may cause respiratory, gastrointestinal, hepatic, and neurological diseases in various species [1] . They are grouped into four different genera which are alpha, beta, gamma, and delta coronaviruses. There are six types of coronaviruses that afflict humans and thus are called human coronaviruses (HCoV) which are HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, and MERS-CoV (Table 1 ) [6] . Bats are thought to be the natural reservoir of coronaviruses, and the viruses can spread to human through an intermediate reservoir. These viruses have been proven to have the ability to cross the species barrier to infect humans and other animals [7] . The human infection by coronaviruses has been mostly mild and harmless except in SARS-CoV and MERS-CoV where they cause severe morbidity and mortality. Among the human coronaviruses, HCoV-229E, HCoV-OC43, SARS-CoV, and more recently MERS-CoV were proven to be associated with neurological diseases [4, 5, 8] ." ] },{ "paper_id": "87d23553b1e4abc9f23750121d6259b10da73387", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Prescott et al.", "6 Prescott et al.", "histopathology Tissues were fixed in 10% neutral buffered formalin with two changes, for a minimum of 7 days and processed with a Sakura VIP-5 Tissue Tek, on a 12 h automated schedule, using a graded series of ethanol, xylene, and ParaPlast Extra. Embedded tissues were then sectioned at 5 \u00b5m and dried overnight at 42\u00b0C prior to staining." ] },{ "paper_id": "87dda3063b97a87338264b45ae16045e46cb237b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Patients all gave written consent to the participation in scientific studies. Permission to perform scientific studies was given by Comitato Etico di Area Vasta Romagna Et IRSTof the Servizio Sanitario Regionale Emilia-Romagna, Italy.", "The Chikungunya virus infection zones have now quickly spread from Africa to parts of Asia, North America and Europe.", "Inflammatory Cytokines Resolve Chikungunya Disease www.plosntds.org evaluation. After sampling, serum was extracted and immediately frozen at 280uC until serum analysis." ] },{ "paper_id": "87e2c4caa0401de97f31022abe3d31b9313978e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples including nasopharyngeal aspirates, sputum, throat swabs, blood and bronchoalevlar lavage fluid were collected by qualified medical personnel. The demographic information and medical records of the participated patients were also collected. All samples were delivered to the Microbiology Laboratory of Department of Public Health Laboratory Sciences, Sichuan University immediately after collection samples via cold chain transportation and stored at \u2212 80\u00b0C.", "The cross-sectional study was conducted monthly at a sentinel tertiary women's and children's hospitals in Chengdu, West China, from September 2009 to February 2014. A total of 1992 hospitalized children younger than 6 years old that presented symptoms of ARIs were recruited. Inclusion criteria for cases were (i) acute infection, for example fever, WBC anomaly, shivering; (ii) respiratory symptoms such as cough, rhinorrhea, pharyngalgia, expectoration, nose/throat congestion, shortness of breath, abnormal breathing sounds or dyspnea. The study protocol was approved by the Medical Ethics Committee of Sichuan University and written informed consents were obtained from the parents or the caregiver before collecting samples.", "The collected data were analyzed through SPSS version 19.0. Descriptive statistics were done in the form of means, frequencies and ranges of the variables. Continuous variables were expressed as means with their standard deviations. Categorical variables such as age groups and their associations with proportions of certain pathogens were analyzed using the chi-square test or the Fisher's exact test. Significant differences, associations and interrelationships of the variables were assessed at a level of P < 0.05." ] },{ "paper_id": "87e6ba2c7e5748b172c7530dbb9e8a040e74a719", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The proportions of African, European and Amerindian genetic ancestry of the infected patients were estimated using a panel of 48 ancestry-informative markers as described previously [13] ." ] },{ "paper_id": "87ea5f33f033c465a124321613ad36f96a560eba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "880359b9dd6158ec31280e45a077f9d59b68e22f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human adenoviruses (HAdVs) are non-enveloped, icosahedral, double-stranded DNA viruses that are classified into seven species (A-G) based on their nucleotide homology, haemagglutination, biochemical and biological properties; at least 51 serotypes are recognized 1-3 . HAdV can cause a wide range of clinical syndromes, including respiratory tract illnesses, conjunctivitis, cystitis, gastroenteritis, neurological diseases; in some cases infection directly results in death 1,4 . HAdV is reported to be one of the primary causes of acute respiratory disease (ARD) worldwide, which is responsible for 5-10% of lower respiratory tract infections in children throughout the world 2,5 . Serotype 7 (HAdV-7) accounts for nearly 20% of all HAdV infections reported to the World Health Organization 4,6 , and is more frequently associated with severe illnesses, particularly in children aged < 7 years and persons with underlying health conditions 7,8 .", "neighbor-joining phylogenic trees with 1000 bootstrap replicates were constructed based on WGS and individual gene sequences by using the MEGA software version 6.06. All experimental protocols were approved by the Medical Ethics Committee of the Academy of Military Medical Sciences. The methods were carried out in accordance with the approved guidelines. Written informed consents for the use of their clinical samples were obtained from the corresponding patients." ] },{ "paper_id": "8806d2b5dd6c0709ed0fc8e99153cbef69fd4614", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "animals was performed prior to both the BAL and TA by an intramuscular injection of 0.1 mg/kg of xylazine.", "The difference in mean herd size of the herds with only one viral agent detected by serology versus those with several viral agents was analysed with a One-way analysis of variance." ] },{ "paper_id": "8806dfedc1367125f90ab8479b99ae5a50438c1a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NKV viruses are primarily restricted to bats and rodents. ISF viruses are restricted to mosquitoes, such as Culex and Aedes [1] , Creek virus (PCV) [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] .", "Mosquito cell cultures have been used as suitable models to study flavivirus persistence (Table 1 ) because these models are easy to manage, they have several variables and can be controlled, and their results are typically easy to interpret.", "Toxorhynchites amboinensis DENV-1-4 [32] Sf9 Spodoptera frugiperda SLEV [49] Ad1, Ad2 Ct1, Ct2 Aa1, Aa2" ] },{ "paper_id": "8808dc1135689cb864eb28ea3e5d8da320d8b225", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These SARS cases caused extreme emotional sadness. Psychologically it is entirely possible that an event destroyed a person. They needed psychological counselling.", "Panic, criticized (i) Information was \"doctored\" and delayed.", "We followed the methods of Qiu W. et al., 2017 [5]. This research uses a qualitative case study approach including literature review, document analysis, and in-depth interviews.", "The high mortality of H7N9 changed the attitude of the public towards chickens and it became apparent that few " ] },{ "paper_id": "880b3f24a1f3678dd29cb446dae24298863b8676", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition, liposomal delivery systems represent an alternative method to administer Ang-(1-7) [137] . Administration of liposomes containing Ang-(1-7) in rats led to prolonged hypotensive effect for several days in contrast to the response observed when the free peptide was used [137, 138] .", "A strategy used to protect the Ang-(1-7) against proteolytic degradation was proposed by Kluskens and coworkers [139] . Using the ability of prokaryotes to cyclize peptides, they synthesized a cyclic Ang-(1-7) derivative [thioetherbridged Ang-(1-7)] which presented an increased stability in homogenates of different organs and plasma and enhanced the Ang-(1-7) bioavailability in rats [139] . Furthermore, cyclized Ang-(1-7) induced a relaxation in precontracted aorta rings of rats which was blocked by the Ang-(1-7) receptor antagonist D-Pro 7 -Ang-(1-7), providing evidence that cyclized Ang-(1-7) also interacts with Mas [139] .", "Early studies have reported the endothelium as the major site for generation [67] and metabolism [41] of Ang- (1) (2) (3) (4) (5) (6) (7) . In addition to Ang-(1-7), endothelial cells also express ACE2 and Mas [80, 81] . Thus, now it is recognized that the ACE2/Ang-(1-7)/Mas axis is present in vascular endothelial cells and modulates its function promoting vasorelaxation [82] , reduction of the oxidative stress [83, 84] , and antiproliferative effects [85, 86] ." ] },{ "paper_id": "8812b0579ea75d59a8dca6407431a3f716728556", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus Culture Collection (CCGVCC) and grown in Dulbecco modified Eagle medium (DMEM; Gibco) supplemented with 10% fetal bovine serum (FBS; Gibco) at 37\u00b0C with 5% CO 2 . SFTSV WCH-2011/HN/ China/isolate 97 (53), Heartland virus isolate Patient1 (5), and GTV strain DXM (7) were obtained from the CCGVCC and propagated in Vero cells in a biosafety level 3 laboratory.", "Western blot analysis. Mouse monoclonal antibodies against \u2424-actin (ProteinTech, China) and GRP78 (HuaBio, China), and rabbit polyclonal antibodies against PERK, ATF6, XBP1, and HSP90AB1 (ProteinTech, China) and eIF2\u2423 and phospho-eIF2\u2423 (Ser51; Cell Signaling Technology) were purchased from the indicated manufacturers.", "PBMC preparation. Mouse PBMCs were isolated from blood samples by density gradient centrifugation method using Histopaque (Sigma). Briefly, the blood was layered on lymphocyte separation medium gently in the ratio of 1:1 and subjected to centrifugation at 100 \u03eb g for 30 min. The white layer representing PBMCs was aspirated out gently and transferred aseptically into sterile centrifuge tubes. The suspension of cells was then washed and cultured in DMEM supplemented with 20 mM L-glutamine, 10% FBS, 100 U/ml of penicillin, and 100 g/ml of streptomycin.", "Newly emerging phlebloviruses, such as SFTSV, HRTV, HRGV, etc., pose a serious threat to public health. Currently, there are no FDA-approved drugs or vaccines to combat phlebovirus infection, and this is in part due to a lack of comprehensive understanding of the molecular interactions occurring between phleboviruses and host cells. Although loss-of-function-based screenings at a whole-genome scale have been performed on different phleboviruses, including Rift Valley fever virus (RVFV) (9, 27) , Uukuniemi virus (UUKV) (28) , and SFTSV (9, 24), a global map showing how phleboviruses regulate and manipulate host biological processes for viral infection is still unavailable." ] },{ "paper_id": "881abbe78ba9d6d7a690c15464342d1730f327cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Construction of PM-milR-M1 gene knockdown plasmid of P. marneffei" ] },{ "paper_id": "881d4ffd2d9422f853b3140e834479d6d6db79b3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Citation: Nasir NH, Mohamad M, Lum LCS, Ng CJ (2017) Effectiveness of a fluid chart in outpatient management of suspected dengue fever: A pilot study. PLoS ONE 12(10): e0183544. https://doi.", "For those who defaulted their follow-up with the research team, an attempt to contact the participant via telephone was made, with a maximum of three attempts. The reasons for defaulting follow-up were elicited and if the patient was admitted, details regarding the admission were obtained." ] },{ "paper_id": "88249503fb8dd13282a60ceac441edd59e1c5be3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Carter reviewed the articles and concluded that because of confounding factors and the fact that no large randomized clinical trials were conducted, it was not possible to gain any conclusions, but GCs may take effect if given at a low dose and administered for a sufficient time (7-10 days) [60] .", "In October 2003, WHO established an International SARS Treatment Study Group in managing SARS and demonstrated optimal treatment options to deal with SARS. This systematic review reported summary effects of ribavirin, lopinavir, ritonavir (LPV/r), GCs, type I IFN, intravenous immunoglobulin (IVIG), or convalescent plasma in relation to (1) SARS-CoV replication inhibition in vitro, (2) mortality or morbidity in SARS patients, and (3) effects on ARDS in adult patients [81] .", "Felinda Ariani and Kaixiong Liu contributed to this paper equally.", "Another mechanism is GC signaling through membraneassociated receptors and second messengers described as nongenomic pathways. This mode of action entails mechanisms that do not directly and initially influence gene expression, and their effects are not blunted by inhibitors of gene transcription. Nongenomic mechanism involves the activation of endothelial nitric oxide synthetase (eNOS). Binding of GCs to the GR stimulates phosphatidylinositol-3 -kinase and Akt kinase, leading to eNOS activation and nitric oxide-dependent vasorelaxation. Nitric oxides participate in many of the inflammatory manifestations, including vasodilation and inflammatory cell recruitment [23, 24] . Dysregulation systemic inflammation stated with excessive production of proinflammatory transcription factor nuclear factor-kappaB (NF-B) and failing inhibitory action of antiinflammatory transcription factor GCs receptor is central to the pathogenesis of pulmonary and extrapulmonary organ dysfunction within ARDS patients." ] },{ "paper_id": "8826961991932d2c6c8f72d0ad2b02a625faa4f5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Site-Directed Mutagenesis. Multiple sequence alignment of Rv0888 with related homologs indicated that nine targeted residues (N131, E267, G303, H353, D387, N389, D438, D472, and H473) were highly conserved in the endonuclease/exonuclease/phosphatase family (Fig. 6A ). To identify residues in Rv0888 that are necessary for catalytic activity, specific codons corresponding to the important residues were altered by site-directed mutagenesis." ] },{ "paper_id": "882b4b4a41b772d31e8f9e860882088336f26e26", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using the MedCalc software version 8.0." ] },{ "paper_id": "882f40d2ce4eceeb438b59e25e2e023fb5e169ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study factor X (i.e., influenza variable) was introduced into the established core model one at a time as follows:", "A total of 802 influenza viruses were isolated during 2007-2009; of them, 257 were seasonal influenza A (H1N1 118, H3N2 149), 95 were seasonal influenza B, 358 were pandemic influenza A (H1N1), and 82 were untyped viruses. Each subtype presented a certain trend of seasonal variation (Fig 1) . (i) The prevalence of seasonal influenza A (H1N1) varied by year, with ", "The GAM was adopted to fit the regression model for weekly respiratory deaths. By using the average weekly temperature and relative humidity with the cubic spline smoothing function to control for the confounding influence of potential meteorological factors, an additional time (t = 1, 2, . . ., 105) smoothing function was constructed to filter out the long-term death trends, seasonality, and other confounding factors that failed measurements. The established core models were as follows [3, 5] :" ] },{ "paper_id": "883477472cfef01bbb0a10297e0f7268c0cee845", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "88395bf2fdca68c0eb033b14655275547bdcd714", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mouse monoclonal anti-V5 antibody was purchased from Invitrogen. Mouse anti-FLAG antibody (clone M2) was from Sigma-Aldrich.", "Western blotting and dual luciferase reporter assay were carried out as described [42, 59] . Control plasmid pRLSV40 expressing Renilla luciferase (Promega) was cotransfected into cells and firefly luciferase activity was normalized to that of Renilla luciferase in all experiments." ] },{ "paper_id": "883b77a8f0dfe0d099e0ceb77531f18fc8a6b2a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusions/Significance: Our results suggest that MHC class I variation mirrors the variation in selection pressure imposed by viruses in free-ranging cheetahs across Namibian farmland. This is of high significance for future management and conservation programs of this species.", "Whereas seroprevalence data reflect the percentage of the population exposed to certain pathogens, it does not reflect the effects of multiple infections in individuals or differences in pathogen diversity in a population. However, it may be the " ] },{ "paper_id": "883cb0158d0026f5e0b986a72e80266b60dfe98f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the purposes of this paper, the following definitions will be used:", "A person who is a fugitive from justice.", "An alien (other than one lawfully admitted for permanent residence) who is a national of a country as to which the Secretary of State has made a determination (that remains in effect) that such country has repeatedly provided support for acts of international terrorism.", "Botulinum neurotoxin producing species of Clostridium b Conotoxins (short, paralytic alpha conotoxins containing the following amino acid sequence: X 1 CCX 2 PACGX 3 X 4 X 5 X 6 CX 7 ) c" ] },{ "paper_id": "883d9e249c839788d9c21c7da412175a1314c7c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GTs and glycosidases have long been thought to be two classes of proteins. Herein, in an effort to characterize flexible GTs, we unexpectedly found a flavonoid GT, designated as OcUGT1 from O. caudatum, with glycosidase activity (Fig. 1) .", "flavonoid glucosides, galactosides, arabinosides and rutinosides were present in O. caudatum [19] [20] [21] , suggesting the existence of corresponding flavonoid GTs. Thus, O. caudatum was chosen as the plant template for flavonoid GTs isolation in the present work." ] },{ "paper_id": "884b19f49da8930b2222b5669f387ed974d1f3f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Outbreaks/epidemiological events Regional collaboration ", "Over time, MBDS priorities have evolved to reflect its three phases of development (Table 1) (see reference 17 for a discussion of the three phases). During the first phase (1999 to 2003), country representatives met regularly, set up committee structures, established the MBDS Coordinating Office in Thailand, and began developing capacity.", "The flow of the Mekong river and its tributaries provide environmental continuity and shared livelihoods, but also common health challenges for people of diverse nationalities closely linked by cultural, historical, and linguistic ties. For example, cholera is a constant threat to livelihoods in all countries in the region; its reporting is politically sensitive particularly because of its threat to tourism (4) . In 1999, when MBDS was coalescing into a network, there was a serious outbreak of cholera in a remote northern province of Cambodia bordering Vietnam during which 874 cases and 56 deaths were reported (5) . Cambodia recognized that not only did it need to strengthen community-based surveillance, but also that it could better contain such epidemics if Cambodian and Vietnamese epidemiologists and officials worked together." ] },{ "paper_id": "88511032b2c7ac3a42adf31909cb0c281c079922", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To calculate the DE, RASM, and DASM features, we used the formulae proposed by Zheng et al. [4] , which are replicated in Equations (3)-(5):", "Jaques et al. [13] Eye-tracking 67 Jang et al. [10] HR, GSR, Temperature, PPG 217 HR -Heart Rate, BP -Blood pressure, ECG -Electrocardiogram, PPG -Photo Plethysmo Graphy.", "\u2022", "Accurate classification of boredom can be considered of particular importance because boredom affects multiple facets of our lives. In a technical report published by the United States Air Force, unmanned aerial vehicle pilots' reaction times were longer when they felt bored [14] . Furthermore, boredom can contribute to serious medical issues such as cardiovascular disease [15] . Additionally, it can have negative effects on learning [16] [17] [18] [19] . If computing devices could accurately classify the occurrence of the user's boredom and administer a suitable intervention to compensate for it, they could be used to tackle the aforementioned boredom-related issues." ] },{ "paper_id": "8856e1f2644acc2d51c57d3ead6dd14a929a014b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical and Developmental Immunology 5", "Antitumor Agent" ] },{ "paper_id": "8857ba8944f2ae93f5af2424992a8cfcac85765a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In this globalized era, along with small and large outbreaks that persist in the Arabian Peninsula, MERS outbreaks may recur in any other regions, especially if a super spreader introduces a MERS infection to a", "PowerChek \u2122 MERS real-time PCR kits (Kogene Biotech, Seoul, Korea). All rRT-PCR reactions were performed using the 7500 Fast Real-Time PCR System (Applied Biosystems, Foster City, CA, USA). The PCR reaction was performed in a total volume of 20 \u03bcL (15 \u03bcL PCR reaction mixture and 5 \u03bcL template RNA). Thermocycling conditions included a step at 50 \u00b0C for 30 min, followed by 95 \u00b0C for 10 min and then 40 cycles of 15 s at 95 \u00b0C and 60 s at 60 \u00b0C. Positive viral template control and no-template control were included in each run. The glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene was amplified simultaneously as a heterologous internal control to monitor PCR inhibition. A positive test result was defined as a well-defined exponential fluorescence curve that crossed the cycle threshold (Ct) < 35 cycles for both upE and ORF1a. A sample was considered \"equivocal\" if the upE result was positive but the Ct value for ORF1a was >35 and <40. We interpreted the result as \"indeterminate\" if (1) the upE result was positive but the Ct value for ORF1a was undetected or if (2) the Ct value for upE was >35 and <40.", "Institutional review board statement. The study was performed in accordance with the declaration of Helsinki and experimental protocols were revised and approved by IRB at Samsung Medical Center. (IRB No. SMC 2016-08-156-002)." ] },{ "paper_id": "8863943c0c9153a3677761f16e704854c65c3783", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All results in the figures are presented as the mean \u00b1 the standard deviation (SD) from three independent experiments, and were analyzed using GraphPad Prism 6 software (GraphPad Inc.). For each assay, a t-test was used for statistical comparison and a p-value < 0.05 was considered statistically significant.", "5 -AATGTCCTCGATGGCCGAGA-3 ), \u03b2-Actin (Forward: 5 -CTCTTCCAGCCCTCCTTCC-3 and Reverse: 5 -GGTCCTTGCGGATGTCG-3 ), under the following conditions: 30 s at 95 \u2022 C, and then 39 cycles of 5 s at 95 \u2022 C, followed by 30 s at 60 \u2022 C. Triplicate measurements were applied to calculate the average cycle threshold (Ct) for each individual test using the QuantStudio TM 3 System software (Applied Biosystems, Carlsbad, CA, United States).", "Protein samples separated by SDS-PAGE were transferred to nitrocellulose membranes (Bio-Rad). The membranes were incubated with the following primary antibodies: rabbit polyclonal anti-NHE3 (Affinity), rabbit polyclonal anti-EGFR (Biorbyt), rabbit polyclonal anti-phospho-EGF (Tyr1068) (Cell Signaling), rabbit polyclonal anti-phospho-ERK1/2 (Thr202+Tyr204) (Bioss), rabbit polyclonal anti-\u03b2-tubulin (Proteintech), with goat anti-rabbit IgG (H+L) antibodies (Sangon Biotech) as the secondary antibody. Images of blots were obtained using a VILBER Fusion FX5 imaging system (VILBER) and the gray levels of all bands were analyzed." ] },{ "paper_id": "8866d2274d3ecb0ef50ccf806d9e03839ad2edbc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethical approval was obtained from both The College of Medicine Research and Ethics Committee and the Liverpool School of Tropical Medicine Research and Ethics Committee. Information was provided in English and Chichewa. Written consent was obtained from all participants.", "Increased work of breathing: Recession, grunting, nasal flaring, or use of accessory muscles of respiration.", "Of the 89 cases in whom immunisation was completely recorded, 82 (92%) were reported to have completed 3 doses of primary immunisation, including Hib. Cases presented throughout the year, but the peak of pneumonia cases occurred between August and November, the hot dry season." ] },{ "paper_id": "886c69ba9b7fb6441b3dc9c06d77abf30e3a0703", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Unless stated otherwise, all Arabidopsis plants were grown in a growth chamber with a 14 h photoperiod (100 \u03bcmol photons m -2 s -1 ) and a relative humidity of 75% at 23/21\u00b0C (light/ dark). The N. benthamiana plants were grown in a growth room with a 16 h photoperiod (80-100 \u03bcmol photons m -2 s -1 ) and a relative humidity of 75% at 22\u00b0C.", "For complementation assays by IRE1A or IRE1B, transgenic lines were made previously [28] .", "Multiple sequence alignment was generated by ClustalW [84] . Domain and NLS motif were predicted using SMART (http://smart.embl-heidelberg.de/) and NucPred (http://www.sbc.su. se/~maccallr/nucpred/), respectively. Figures were created by SigmaPlot 12.5." ] },{ "paper_id": "8871ee344c8ca239b4aa5077f5e438075663299b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Involvement with the universities ensures that the courses are offered on time every year through a competitive selective process which helps in ensuring sustainability.", "Increasingly countries are being encouraged to develop national public health institutes which can be a natural location of an FELTP at the central level [26] .", "Training Programs (FELTPs) in Sub-Saharan Africa in 2010", "The pre-assessment visits were conducted by a small team consisting of staff from CDC and existing FELTPs and PHSWOWs who visited the potential FELTP host country for about 1 week. The objectives of the visits were to gauge the interest of the MOH and its partners in starting an FELTP, to encourage the formation of an MOH-led Steering Committee, and to plan for the formal FELTP assessment and program planning visit." ] },{ "paper_id": "8880ca1de9ca704b6b0af29fd6c181457663ac40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SAS statistical software (version 9.4, SAS, Cary, NC, USA) was used for data collation. All statistical analyses were performed using R software (version 3.5.1, The R Project for Statistical Computing, www.r-project.org). A P value < .05 was considered statistically significant." ] },{ "paper_id": "88836be43482650dfdb4fc0cc47ca6e2d6afd759", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Furthermore, there are approaches that have been exploited in particular fields-such as the use of chromatic pupillometry to measure the response of different sub-types of photoreceptor, specifically ipRGCs, in diabetes [66] and glaucoma [14, 64, 65] -which could be applied to other conditions including neurodegenerative disorders.", "The cholinergic system is key to normal pre-and postnatal neurodevelopment, and numerous studies, ranging from neuroimaging data [92] , to post mortem histopathological analysis of brain tissue [93, 94] , animal models [95, 96] and molecular genetic studies [97] , have suggested that alterations in the cholinergic system may be a contributing factor to the aetiology of autism spectrum disorder (ASD). Moreover, an atypical PLR is reported in both children and adults with ASD [60, [98] [99] [100] .", "Pupillometry offers a reliable and convenient tool for illicit drug and alcohol screening [110] [111] [112] .", "From the EW nuclei, the efferent pre-ganglionic axons pass into the right and left fascicles of the oculomotor nerve (third nerve) to join the motor axons destined for the eye muscles ( Figure 3 ). The oculomotor nerve bifurcates into a superior and inferior division near the anterior cavernous sinus. The parasympathetic fibres travel with the inferior division through the superior orbital fissure toward the orbital apex and synapse at the ciliary ganglion (CG).", "The afferent limb of the PLR begins with photoreceptive inputs from rod, cone and intrinsically photosensitive retinal ganglion cells (ipRGCs) located in the retina (summarised in Figure 2 )." ] },{ "paper_id": "888a2dcee2c34b07d19a0528febb54aad70bdf00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One thousand and five hundred microliters aliquots of phosphate-buffered saline (PBS) were pipetted into 60 mm diameter petri dishes that each contained a filter, and these petri dishes were then placed on an orbital tabletop shaker at a speed of 150 rpm for 60 minutes at room temperature. All samples were stored at 280uC until DNAs were extracted.", "Viral respiratory infection is the most common infectious disease. The viruses, such as enterovirus, influenza virus, and adenovirus, were most often isolated from the pediatric outpatients [1] . Adenovirus causes acute respiratory tract infections in children younger than 5 years old. Mycoplasma pneumoniae is a common causative pathogen of community-acquired pneumonia (CAP) in children and young adults. In Taiwan, Mycoplasma pneumoniae was reported to account for 20-30% of CAP cases [2, 3] . Airborne viruses are known to be associated with larger particles and aggregate in nature [4] . Most aerosolized droplet nuclei are between 0.58 and 5.42 mm in diameter [5] . One investigation found 53% of detectable influenza virus particles in the respiratory aerosol fraction (1-4 mm) [6] .", "The air quality indices (air temperature, relative humidity (RH), carbon dioxide (CO 2 ) and suspended particular matter) in the pediatric public areas of the hospital were evaluated during the study period. The indoor temperature, RH and CO 2 concentration were determined using a digital psychrometer (TSI incorporated 500 Cardigan Road, Shoreview, MN 55126, USA). The portable DUSTcheck monitor (Grimm, model 1.108, Germany) was used to measure the mass concentrations of particulate matters.", "SPSS (Statistical Package for Social Science) version 13.0 (SPSS Inc., Chicago, USA) was used for the statistical analyses. The level of significance was set to 0.05. The figures were constructed using GraphPad Prism 5.0 software. A two-sample t test was used to assess the differences of detection rates between adenovirus and Mycoplasma pneumoniae in the pediatric emergency room and pediatric outpatient department, respectively." ] },{ "paper_id": "888f3a42d4361d36b3ffbe619427ace11fae0e1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by departmental research committee, department of pharmacy, Al-Qassim hospital (Ref # M17/SAH/2014). Furthermore, written consent was obtained from the respondents prior to participation in the study.", "The association of demographic characteristics and mean knowledge and attitude questions is expressed in Table 4 . Among the demographic variables, gender and ", "A total of 153 healthcare workers responded to the questionnaire giving the response rate of 54.64%. Majority of them were male (55.6%) and belonged to all major health care professions with pharmacists most in number (35.3%). The characteristics of respondents are mentioned in Table 1 . The main source of MERS information reported by participants was the internet as depicted in Figure 1 . Table 3 ." ] },{ "paper_id": "8894267c458259ec6e58acbfad98a82c84519711", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HBV DNA was extracted from 400 mL of serum by QIAamp UltraSens Virus Kit (Qiagen GmbH, Germany), then resuspended in 50 mL water and stored at 220uC until analysis. HBV genotypes, including C/D recombinant, were initially assigned using the PCR based restriction fragment length polymorphism (RFLP) methods described previously [9] , [8] .", "In 15 clones of fragment A, there were five genotype C (Y2-6,9,13,14,15,); two genotype D (Y2-11,12); one CD1 (Y2-10) and seven novel different C/D recombination (Y2- 1, 2, 4, 7, 8, 3, 5) .", "Not all viruses are equally prone to recombination. Recombination has not been detected in several viruses despite repeated searches [1] . Whether recombination does or does not exist is important for understanding the evolution and replication mechanism of a specific kind of virus. Hepatitis B virus (HBV), a major human pathogen, has been classified into 10 genotypes and several sub-genotypes [2, 3] . Many sub-genotypes were identified by polygenetic analysis as recombinants. But there is no direct evidence to indicate that these subgenotypes arose as a result of recombination or perhaps a result of convergence.", "Based on phylogenetic topology changes of different regions of HBV, it was hypothesized that some of the genotypes that are conventionally regarded as ''pure,'' actually were recombinant. Genotype E strains show evidence of recombination with genotype D at 1950-2500. new reported genotype ''I'' actually belongs to genotype C. Furthermore, Subgenotype Ba possesses the recombination with genotype C at 1740 to 2485 [31, 32, 33] . Recombinants comprising regions with different histories have important implications for the way we think about HBV evolution. It means that there is no single phylogenetic tree that can describe the evolutionary relationships between genotypes.", "In Of the 56 clones of fragment C(in which genotype B HBVDNA were added as an in-tube control to exclude the recombination by PCR procedure), there were 32 pure genotype B clones; nine genotype C clones(Y2-B10,B5,B8,B9,B13,B16.B17.B18,B24); five genotype D clones(Y2-B22,B3,B4,B21,B23), two CD1 clones (Y2-B1,B11) and eight novel C/D recombinants (Y2-B6,B7,B14,B15,B19,B2,B12,B20). No recombinants of genotype B were found." ] },{ "paper_id": "889915a03b21c44b0c3d21f13fb8d04a7cdd0f50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by Comisi\u00f3n Nacional de Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica (CONICYT) Programa Formaci\u00f3n de Capital Humano Avanzado-Beca de Doctorado en Chile N \u2022 21160962 and N \u2022 21170620. FONDECYT (N \u2022 1150862 and 1190830). AK is a Helen C. Levitt Visiting Professor at the Department of Microbiology and Immunology University of Iowa; Programa Semillero de Investigaci\u00f3n, DGI, Universidad de Antofagasta (grant N \u2022 5311) and the Millennium Institute on Immunology and Immunotherapy (P09/016-F).", "Finally, other live attenuated vaccines as is the case of rBCG-N-hRSV are based in attenuated hRSV that lack some particular proteins such as M2-2, NS2, or both (Mazur et al., 2018) .", "Together, these data indicate that it is of vital importance to delineate the mechanisms contributing to hRSV induced pathology in order to prevent or treat infection.", "OA and FD are responsible for the writing of this review article. TB, FB, JE-V, JS, and PG reviewed the manuscript. AK is the leading investigator and assisted in the organization and revision of this article. All authors listed approved the version to be published and have made a substantial and intellectual contribution to the work." ] },{ "paper_id": "88a0b7d6447839c09069588d1761364ce9045d61", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A few studies have addressed conjunctivitis [13] . Chlamydiae were seen in eight pigs by ultrastructural examination and were isolated in two pigs [4] , and subclinical conjunctivitis was experimentally induced in 3-day-old gnotobiotic piglets [14] .", "The necropsies were carried out at the Department of Pathology at the National Veterinary Institute, Uppsala, or at AnalyCen, Skara. The animals were stunned with electricity, weighed and exsanguinated, and necropsy was immediately performed. All gross lesions were noted, and specimens for histological examination were taken from ileum and from all macroscopically visible lesions. The samples were fixed in 10% buffered formalin, embedded in paraffin blocks, sectioned and stained with haematoxylin and eosin according to standard protocols." ] },{ "paper_id": "88a48452ce073c9968ca2e2794fc0bccfb5dfc0f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell viability % \u00f0 \u00de \u00bc \u00f0Treated Cells \u00c0 Medium Background\u00de \u00f0Untreated Cells \u00c0 Medium Background\u00de", "x 100", "Short oligomeric biomolecules with sufficient affinity are of high interest for diagnostics and drug design, as development, synthesis and further chemical modifications are easy to implement." ] },{ "paper_id": "88b18a2771249ead085fdebfab0aea7839176e05", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Incomplete understanding of biology or epidemiology for appropriate target selection.", "1.", "\u2022 Development of relevant, sensitive, specific and preferably quantitative biological assays." ] },{ "paper_id": "88c599b1de8a17cd519f9f72aaaea28392f697f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by grants from the National Natural Science Foundation of China (31270198 and 81672007 to WZ, 81571999 and 81871652 to ZZ, and 81772188 to YanW).", "The Supplementary Material for this article can be found online at:", "https://www.frontiersin.org/articles/10.3389/fmicb.2019. 01633/full#supplementary-material" ] },{ "paper_id": "88c6e8b041b0eceb7b8282f3dbb066848fd554b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mice were euthanized and slowly perfused with an intracardiac PBS flux. Livers were homogenized through a tissue strainer and intrahepatic leukocytes were obtained after a 20 min centrifugation (600 g) in a 35 and 70% bilayer Percoll gradient (Sigma). Viable cells were counted on a Newbauer's chamber by trypan blue exclusion.", "Oxidation-sensitive dye 10 \u00b5M H2DCFDA (Invitrogen) and 10 \u00b5M DAF-FM (Molecular Probes) were used to measure ROS and NO production, respectively (33) . After washing, the samples were examined using a BD FACS Canto II flow cytometer (BD Biosciences), and then analyzed using the Flow Jo Software. Gate strategies are indicated in Figure S1 in Supplementary Material.", "Liver samples were lysed (1% Triton X-100, 0.5% sodium deoxicholate, 9% SDS, 1 mM sodium ortovanadate, and 10 \u03bcg PMSF in PBS), separated on a 10% SDS-PAGE and transferred to nitrocellulose membranes. After blocking, they were incubated with goat polyclonal anti-caspase-1-p20 (Santa Cruz) and rabbit polyclonal anti-NLRP3 (Abcam), detected with IRDyes and analyzed on an OdysseyCLx Imaging System (Li-cor). Protein loading was assessed with a polyclonal anti-actin Ab (Santa Cruz). Bands were quantified using Gel-Pro Analyzer software." ] },{ "paper_id": "88ccb20962dc958fc239c0ef5bed963cfd782b65", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition, Traditional Chinese Medicine has a place in preventing and treating emerging infectious diseases. In 2009 H1N1 epidemic, the Chinese medicine Maxingshiganyinqiaosan formula showed the similar efficacy with oseltamivir in treating human H1N1. Traditional Chinese herbal therapy may be considered for a treatment option for Ebola [32] .", "Chinese scientists have developed several detection kits for EBOV in August, including a fluorescence RT-PCR nucleic acid detection kit, colloidal gold immune chromatography antigen detection kit and ELISA antigen detection kit, which have been used in the laboratory examination of Ebola.", "In the 2014 Ebola epidemic, after receiving an experimental drug called ZMapp, two American aid workers who fell sick with EVD in Liberia survived successfully. ZMapp was developed by San Diego-based private biotech firm Mapp Biopharmaceutical. A previous study suggests that ZMapp supplies the best option for experimental therapeutics used for treating EBOV-infected patients [30] . Potential treatments, including monoclonal antibody administration and small inhibitory RNA molecules, are still under scientific investigation." ] },{ "paper_id": "88d360849c4d9dddb7c9d16db3e9c4bbb52b7b75", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the ethical committee at Institute of Tropical Medicine and Queen Mary University. All participants gave written informed consent." ] },{ "paper_id": "88d9d333b7b85d34405f27fc2e469cad48a1f8c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Secondary antibodies were all raised in donkey: Alexa Fluor (AF) -488 labelled anti-goat, AF-555 conjugated anti-mouse, AF-555 labelled anti-rabbit (all from Thermo Fischer Scientific-Invitrogen-Molecular Probes; 1:500) and Rhodamine Red X-anti guinea pig, Cyanine 5-anti mouse, Cyanine 5-anti rabbit (all from Jackson ImmunoResearch; 1:100).", "Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RePoRts | (2018) 8:3490 |" ] },{ "paper_id": "88e421b846bdacb07fbf712e5ed5c4394be25fac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "88e8809f280ef47d36f3e56b7f8558c303f36742", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "During certain clinical activities and treatments, the virus might aerosolize, thereby becoming spread by the airborne route, rather than the droplet method. Past studies looking at the SARS CoV showed that healthcare workers are more at risk of becoming infected with that coronavirus while participating in certain nursing procedures [9] . For example, the pooled odds ratio for risk of transmission for healthcare workers exposed to suction before intubation is 3.5 (0.5, 24.6). Healthcare workers exposed to tracheal intubation had a 6.6 OR pooled (4.1-10.6).", "The main messages that the MERS-CoV task force at the Princess Nourah University wanted to get across was the following:", "Hospitals that provide for patients suspected or confirmed to be infected with MERS-CoV should take appropriate measures to decrease the risk of transmission of the virus from an infected patient to other patients, health-care workers and visitors.", "Take the epidemic seriously, but do not be afraid Use only accurate information to guide your practice from reputable sources Share that accurate information with your family and community Follow hospital and university infection control policies and protocol Stay home if you are sick Use droplet precautions with all patients of suspected MERS-CoV or any respiratory illness, and to use airborne precautions when you are involved in any treatment or activity that aerosolizes the virus.", "Additional resources were provided with constant reminders to students and staff to increase hand sanitization and hand washing. Additional materials for the clinical labs were purchased to ensure correct infection control measures would be taught.", "Questions were written by the committee to capture the participants' awareness of the most important facts, identify gaps in the participants' knowledge and to guide the follow-up activities. Table 2 outlines the different content provided to each group of participants.", "Health care workers should be educated, trained and encouraged to practice skills that aid in infection prevention and control. It is not always possible to identify patients with MERS-CoV early because some have mild or unusual symptoms. For this reason, it is important that health-care workers apply standard precautions consistently with all patientsregardless of their diagnosisin all work practices all the time." ] },{ "paper_id": "88f00457544e21a031e4b643cd71affe006a5d7e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At ICU admission, all four patients had a sequential organ failure assessment (SOFA) score greater than 11, predicting a mortality rate higher than 50%, while the median acute physiology and chronic health evaluation (APACHE) score was 20 (range: [18] [19] [20] [21] [22] .", "Ethical approval of the study was granted by the local ethics committee for each patient.", "The clinical conditions of the four patients progressively improved with IV zanamivir and adjuvant therapies despite superimposed multi-drug resistant infections. As summarised in Table 1 , patient #1 was diagnosed with concomitant extensively-drug resistant (XDR)" ] },{ "paper_id": "88f1de42ca135e68ca9aa6a10081091fc4443028", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the long term, we envisage that social protection could be designed in various ASEAN wide packages \u00c1 including health insurance and elderly care, making health coverage regional. A regional health fund, into which ASEAN countries contribute based on national income levels, could be used to contribute to disease outbreaks and surveillance. Countries could apply to this fund for proposed UHC or HSS initiatives/structural improvements.", "T he World Health Organization (WHO) proposes the concept of Universal Health Coverage (UHC) as a 'single overarching health goal' for the next iteration of the Millennium Development Goals (MDGs) (1) . UHC is defined as a situation where all people who need health services (prevention, promotion, treatment, rehabilitation, and palliative) receive them, without undue financial hardship (2) . UHC includes three key aspects: the beneficiary \u00c1 who is covered (population coverage or breadth coverage), the scope \u00c1 which service is covered (service coverage or depth coverage), and the coverage \u00c1 what is the level of financial contribution (financial coverage or height coverage) (2) .", "We regret, given the shortage of data, that we could not provide a complete picture on the situation of UHC in each country as well as across ASEAN. We also did not have sufficient longitudinal data to discuss time trends beyond selected indicators pertaining to UHC and associated factors." ] },{ "paper_id": "88f92fbe9b0ef301ed99a0f84c88beca964fad97", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "rat and wallaby and only 1 common gene between cow and wallaby.", "DATA SHEET S4 | The networks for DEGs were constructed using the neighbor joining algorithm.", "All participants provided written and informed consent.", "Ten, out of 31 DEGs, were identified only by the current metaanalysis and not in the original studies. These include four downregulated (TNNC1, FIS1, HES5 and THTPA) and six up-regulated (MRPS18B, SF1, UQCRC1, NUCB1, RNF126 and ADSL) genes. The detailed information of the discovered DEGs is reported in Table 2 ." ] },{ "paper_id": "88fb5713a61697d45f7d08a3b36012f955d354c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "If present, macroscopic lesions in the abdomen and thorax and external fecal soiling were recorded." ] },{ "paper_id": "8903ed70c0e66c2bad50f57df3c885f7253cc2b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, the antiviral activities of compounds 26, 27, 29, 30, 31, 32 and 33 were assessed against human coronavirus 229E (HCoV-229E) in MRC-5 cells. The seven tested compounds inhibited HCoV-229E replication with EC 50s ranging from 7.2 to 71.5 mM, without associated cytotoxicity ( Table 2) .", "Compound synthesis. Chemical reagents were obtained from Aldrich Chemical (Saint Louis, Missouri), Acros Organics, abcr GmBh (Karlsruhe, Germany), ACB Blocks (Toronto, Canada) and Chembridge, and were used without further purification. Compound synthesis is described in the Supplementary Methods and their associated comments.", "Neither compound 29 nor compound 30 significantly inhibited CYP1A2, CYP2B6, CYP2C9, CYP2C19 or CYP2D6. Both compounds were moderate inhibitors of CYP2C8 and potent inhibitors of CYP3A, suggesting possible drug-drug interactions through the inhibition of CYP3A enzymes." ] },{ "paper_id": "891adb48f822d8e7f4749448ea5e2b4828c9aae5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lung tissue histopathologic sections were made as described elsewhere [45] . Briefly, the removed lungs were fixed in 10% neutral buffered formalin, dehydrated and embedded in paraffin. Five micrometer sections were cut and stained with hematoxylin and eosin (H&E), and reviewed for histopathologic changes." ] },{ "paper_id": "891be4e9dc60d9b0c9ff79d35e11576ceeb8a592", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8923bae528dc7e9ed10fbb6e823707dd1018be9d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NormFinder calculates the expression stability value (SV) for each gene, taking into account intraand inter-group variations of the samples set 28 . A low SV-value indicates the high expression stability of this gene." ] },{ "paper_id": "892e0a43f862ce5adb7611e7f5243e2a30724800", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Probes Master kit (Roche diagnostics, France) according to the recommendations of the manufacturer. The SDD gene of H. influenzae, nucA gene of S. aureus, phoE gene of Klebsiella pneumoniae, lytA CDC gene of S. pneumoniae, were amplified with internal DNA extraction controls TISS, as previously described 22 ." ] },{ "paper_id": "8936f7734e68b14b079a2645b8df710c8958e943", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Logistic regression analyses showed that male HCWs Table 5 .", "In Saudi Arabia, a series of modifications was applied to the patient pathways while visiting the emergency departments or admitted as in-patients. This included segregating patients during triage based on prioritizing the inflow of patients by their chief complaints, bed availability and screening of flu symptoms/history of exposure. The infrastructure of the medical facility, particularly the ventilation system and isolation capacity of rooms, was subject to changes. Some hospital wards and staff (especially nurses) were dedicated specifically to confirmed MERS-CoV cases to limit the chance of cross-contamination across wards and HCWs. The Infection Prevention and Control Department (IPCD) at SMNG-HA, in particular, was on high alert for such MERS-CoV outbreaks, especially with the evident transmission of viral infections between patients and HCWs at SMNG-HA. Crisis management required a rapid implementation of adequate infection prevention, control procedures and case isolation, in addition to collaboration and coordination with local and international consultations.", "This study has been conducted at one setting, yet the struggle against MERS-CoV has not ended and will continue against future emerging strains of viruses and bacteria causing communicable diseases in other settings too. Knowledge is a valuable asset, and its holders within any healthcare institution should be retained and motivated so that they continue to spread their benefit among other HCWs. All healthcare institutions should always identify and refer to reliable sources of knowledge. For instance, the center for disease control and prevention is a leading national public health institute and accountable for disseminating up-to-dates on various infectious topics. In Saudi Arabia, the ministry for public health has designated communication channels to release updates on MERS-CoV on their websites, through scientific arenas, memorandums and helpdesks." ] },{ "paper_id": "893e7344ac32678f26385d12f05ab2a06ed3544c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The project captured data on diseases with potential human health implications, including confirmed or highly suspicious cases of salmonellosis, avian chlamydiosis (Chlamydophila psittaci), Australian bat lyssavirus in bats, mycobacteriosis (unspeciated) in a koala (Phascolarctos cinereus), and cryptosporidiosis in a hand-raised macropod. The cases of salmonellosis occurred in a variety of birds, marsupials and reptiles, and typing of these isolates contributed to the National Enteric Pathogens Surveillance Scheme [31] . Multiple cases of neurological signs in tawny frogmouths (Podargus strigoides) in urban areas of Sydney were of interest as this species has been suggested as a sentinel for the emerging zoonosis angiostrongylosis [32] , [33] .", "A particular thank you to the participating zoo veterinarians and staff, without whom the program could not run: Emerging Diseases -Zoo Surveillance Program PLOS ONE | www.plosone.org Conceived and designed the experiments: KCW AR RW VG RTB DJB WB SC CL HMcC M. Pyne IS SV LV DW M. Phillips CB LP. Performed the experiments: KCW AR RW VG RTB DJB WB SC CL HMcC M. Pyne IS SV LV DW." ] },{ "paper_id": "89444dffc7f46f0f52709e43550ddb363a720340", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Amongst medically important pathogenic viruses, arboviruses form an important subset of viruses due to the complexity of their host preferences 18 . These viruses, mainly constituted by genera flavivirus and alphavirus,", "For small RNA northern. RNA was isolated using GITC method followed by small RNA enrichment. 50 \u03bc g RNA was run on 15% PAGE containing 8 M Urea. RNA was transferred onto a Hybond-N + membrane (GE Healthcare) for 60 min at 15 V and immobilised by UV cross-linking at 1,200 \u00d7 100 \u03bc J. GFP probe was prepared by DIG labelling kit (Roche, USA). Northern hybridisation and development was performed according to instruction manual. Small RNA marker (NEB) lane was cut from the blot and radioactively labelled with [\u03b3 \u221232 P] ATP separately." ] },{ "paper_id": "894676819b105b56f30438858631fce2958592e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The score values ranged from 0 to 14. The median score value of 7 or greater was used to define severe ALRTIs infection and scores less than 7 were considered as mild or moderate disease.", "Data analyses were performed using SPSS 19.0. A two-tailed independent-samples t-test method was used to compare continuous variables between two groups. Univariate analysis was conducted using \u03c7 2 tests or Fisher's exact test for categorical data. Probability < 0.05 was considered to be statistically significant.", "Clinical information was collected using a standardized data form. A clinical scoring system for ALRTIs, which related with hospitalization time, pediatric intensive care unit (PICU) admitted time, oxygen supplemented time, maximal FIO 2 , was used to assess severity of illness [8] ." ] },{ "paper_id": "8954feaa230060999c4f698c1582ffadfd79b0b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All relevant data are available from the corresponding authors upon request." ] },{ "paper_id": "8966ac6675efb0bad372010ed73b82e30c4f1624", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data analysis. All paired end FASTQ files were processed with Trimmomatic v0.30, removing the Illumina adaptor sequences, then trimming leading and trailing bases with phred scores below 20. Reads were discarded where the length of either trimmed end was below 50 bases." ] },{ "paper_id": "896cfa254a80c192a7aa872d955e750d6280e071", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 257 SARS serum samples belonged to infectors hospitalized respectively in General Hospital of Guangzhou Military Region, the 2nd Hospital of Zhongsan University, 177th Hospital of Guangdong Province, the 8th People's Hospital of Guangzhou Municipal and Peking Tiny Tang Mount Hospital during Feb. and Mar. of 2003. As of the 1453 healthy samples, 935 were from servicemen quartered in Hongkong and 158 from those quartered in Macao in Jun. 2003, 160 were from medical practitioners around Peking that having close contact with SARS infectors and 200 were healthy body checked persons at Guangzhou.", "By detecting 257 SARS patients from 3 to 360 days after onset of SARS, we found that their serum antibodies titers increased steadily in 4to 6 months (5). The antibodies of most patients reached the peak in the 6th month and lasted to the 24th month. The antibodies of some patients began to descend after reaching the peak. Though the antibody could be detected positive on the 360th day, the titer declined. This study put forward that the duration of SARS-CoV IgG would last for more than 2 year. We will further trace the falling curve of SARS-CoV IgG antibodies.", "Severe Acute Respiratory syndrome (SARS) is a newly discoverable acute respiratory infection, which is also called infectious atypical Pneumonia (IAP) in domestic .The pathogenicity is a new coronavirus, different from any virus of its virus family in the bodies of human beings or animals, namely SARS-CoV (1) . Till now, it is not clear about the infecting chart and prevailing rules of SARS-CoV. In order to find out changing rules of the clinical SARS cases serum specific IgG antibodies and whether there is inapparent infection in health population, this study adopts the indirect immunofluorescent assay diagnosis reagent developed by Institute microbe epidemic, Academy of Military Iatrology Sciences (2) and the antigen -capturing enzyme- " ] },{ "paper_id": "897261feca5f934f8a39599d294f9147941bfcad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Promoting disaster resilience represents one approach to mitigate the consequences of disasters. The Sendai Framework for Disaster Risk Reduction describes disaster resilience as the ability of an entity to resist, acclimate to, and recover from the effects of a hazard, including through the preservation and restoration of essential structures and functions. Disaster resilience theory further categorizes resilience as being either inherent or adaptive (3) , with inherent resilience referring to the conditions, characteristics, and properties associated with absorptive capacity; and adaptive resilience involving the activation of resources and blending preplanned and reactive actions in response to disaster-related demands.", "Still, this guidance prescribes a national-level workforce and assumes that capacity will be dispersed throughout a country. This assumption is rarely a reality, particularly in lowresource or unstable regions where healthcare workforces may be concentrated in wealthier areas of a country. Although the recently released JEE 2.0 places greater emphasis on building subnational level capacities (4), the impacts of this reality are acutely felt at the community-level during public health crises where health systems assets can be limited or nonexistent.", "With regard to pandemic preparedness, the adaptive resilience roles of CHWs are more complicated. Although CHWs receive Box 1 | Selected community health worker roles that promote inherent resilience." ] },{ "paper_id": "8984416a285ced3a8855c5b4a473d02ab50e73d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "JFH_dg, pFKi389LucNS3-39_dg_JFH-1_NS5Aaa2359_emGFP and the full-length genome pFK-JFH-dg have been described elsewhere [23, 24, 63, 65] . Synthesis of in vitro transcripts and RNA transfection by electroporation has been described in detail elsewhere [66] .", "Text S1 Supporting information. Supplementary materials and methods (Protocols S1, S2 and S3) and supplementary Table S1 . (DOC)", "Correlative microscopy identifies sites of high fluorescence as complex HCV-induced membranous compartments A main limitation of fluorescence microscopy is the difficulty to allocate viral and cellular proteins to distinct subcellular structures." ] },{ "paper_id": "8987e37e0598cf67e121bc72d1b95b8f1d9fde73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Understanding the mechanisms underlining pathogenicity and persistence of pathogens in human populations is an important aspect of disease epidemiology and control. Fixation of mutations into nucleotide substitutions, a key principle behind phylogenetic signatures, is shaped by major evolutionary forces such as selection (molecular adaptation deriving from an increasing fitness of a corresponding phenotypic trait) and genetic drift (stochastic gene sampling process at reproduction) [23, 24] . A useful tool to detect and measure selection in viral gene sequences is the ratio between synonymous (dS) and nonsynonymous (dN) substitutions. Whereas a ratio above 1.0 is an indicator of positive selection operating at the amino acid sequence level [25] , significantly lower values are generally referred to as purifying selection and refer to preservation of the phenotypic trait." ] },{ "paper_id": "898be097851a56d857d6cdb8ccbbdd3666eb4963", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8996c8a004bc82aca37ba1f1f4265868503ce69f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were incubated for 30 min at 4uC with FITC-and PEconjugated antibodies against CD25 and CD69 (ImmunoTools) and the respective isotype controls in PBS containing 0.5% BSA. After one wash with ice-cold PBS-BSA, cells were analyzed by flow cytometry with a FACSCalibur (BD Biosciences). " ] },{ "paper_id": "899c5959f51505b0935e46c2e77129156026806e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As shown in Table 2 " ] },{ "paper_id": "89a3e7a6691f7cc1f79dc465fca8968f1a1739f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study aims to identify a cross-reactive and conserved potential vaccine candidate with the help of a comprehensive bioinformatics approach. In silico approach may prove as a beneficial and directive approach, whereas conventional methods focus more on pathogen cultivation and protein extraction, where testing of these proteins on a large scale is expensive and time-consuming 27, 28 . Several in silico vaccine candidates have been reported by researchers which were known to produce promising preclinical and clinical trial results 29, 30 .", "Protein sequence retrieval. Whole proteome of the LIC, encoding 3654 proteins was retrieved from the Universal Protein (UniProt) database (Proteome ID: UP000007037) (http://www.uniprot.org/proteomes/) in FASTA format and used for further analysis. UniProt is a comprehensive resource for protein sequences and annotation information which provide functional information about proteins with accuracy and consistency.", "Moreover, except for a strong binding affinity, the peptides with strong immunogenicity are more probable CTL epitopes than those with weak immunogenicity. Therefore, the immunogenicity of candidate epitopes was evaluated using IEDB immunogenicity prediction tool (http://tools.immuneepitope.org/immunogenicity/) with default parameters. Allergenicity assesment. The allergenicity of the predicted epitopes was analysed using AllerHunter server (http://tiger.dbs.nus.edu.sg/AllerHunter), which is based on support vector machine (SVM) and pair-wise sequence similarity. AllerHunter predicts allergen in addition to non-allergen with high sensitivity and specificity, and efficiently distinguish allergens and non-allergens from allergen-like non-allergen sequences, which make AllerHunter a very constructive tool for allergen predictions.", "In the present study, putative antigenic protein has been identified, of which B-cell (linear and conformational) and T-cell epitopes (HTL and CTL) have been predicted for the designing of peptide vaccines against leptospirosis." ] },{ "paper_id": "89a5f1619085d08f719fbf0b8bd1ac5bebd12187", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Genomic data and virion size of each virus used in this study are displayed in Table 1 .", "A standard 'Cleaning in Place' (CIP) process as described by Keyser et al. [38] based on a treatment with NaOH 5%, was implemented prior to and following each UV-C treatment.", "logN \u00bc log\u00f0\u00f010 log N0 \u00c0 10 logN res \u00de\u00de \u00c0 e \u00f0k max d\u00de \u00fe 10 logN res \u00f06\u00de", "The objective of this study was to evaluate the effectiveness of the SurePure" ] },{ "paper_id": "89a70f5a269900d9e7e4a8b2e325ea1b4adf1bb5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "EToV (also called Berne virus [BEV] ) was the first to be discovered, and is the prototype species of the genus Torovirus. EToV was initially isolated in 1972 (but not reported until 1983) from a rectal swab taken from a horse in Berne, Switzerland which showed pseudomembranous enteritis, miliary granulomas and necrosis in the liver at necropsy. The isolated pathogenic agent couldn't be neutralized by antibodies against equine viruses known at the time. By electron microscopy, the virions appeared pleomorphic, mostly with smooth surfaces and spherical, though some were C-shaped, and some particles in damaged membranes had a \"sausage-like\" internal structure with transverse striations (1) .", "Another unclassified virus, BToV (also called Breda virus [BRV] ) was discovered in 1982 in calves with diarrhea in Breda, Iowa, and confirmed to have antigenic differences from known diarrhea-related bovine viruses. The isolate was infectious when orally inoculated into gnotobiotic and conventionally reared calves (2).", "Z-MH, Y-WH wrote the manuscript. All other co-authors edited the manuscript." ] },{ "paper_id": "89a7453ca8998a3018064029e6c9d6d8db6b513d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "89abb573b10d9a38b4724a0d38d91dfa6e162657", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "89ac1ba1b647165fe0cf9cefd3dc65df8c162749", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following formula was used to calculate the concentration HCV RNA of each sample. ", "Toxicological study of GL in liver and fibroblast cells", "HCV: Hepatitis C virus; GL: Glycyrrhizin; Huh-7: Human Hepatoma Cell line." ] },{ "paper_id": "89c52fc69362dbc2c29ed79aa72928ad14dc4c80", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequence analysis and statistics. Sequence alignments were performed with BioEdit (BioEdit Software Inc). Phylogenetic analysis was generated using program MEGA (MEGA Software Inc). Half-maximal inhibitory dilutions (ID50) and half-maximal effective dilutions (ED50) were calculated for each serum using GraphPad Prism 5 software (GraphPad Software Inc). IC50 for monoclonal antibodies were estimated by GraphPad. Data were expressed by means or means \u00b1 standard deviations and significance in their differences were analysed using Student's t-test. Statistical significance for survival studies was calculated using the log-rank (Mantel-Cox) test with 95% confidence intervals (CI). Results are graphs with mean \u00b1 SEM.", "Lung virus titres. To determine lung virus titres, hDPP4-KI mice infected with MERS-CoV-MA were euthanized at 4-days post-challenge. Lungs were removed after transcardial perfusion with PBS and homogenized in PBS. Viral titres were determined on Vero E81 cells and represented as plaque-forming units (PFU)/lung. Cells were fixed with 10% formaldehyde and stained with crystal violet at 3 d.p.i.", "Epitope mapping through competitive binding between antibodies. Antibodies 1A8, 1C11, 1D5, and 2C1 were first labelled with biotin. Then, antibodies MERS-4, MERS-27, 17b, MERS-GD27, 1A8, 1C11, 1D5, and 2C1 were serially diluted three-fold before biotin-labelled antibody (50 \u03bcl) was added at fixed concentrations. The mixture of antibodies was applied to S1 protein-coated plates, and incubated at 37\u00b0C for 1 h. After thorough wash with PBST, 250 ng/ml of streptavidin-HRP (Sigma, USA) were added and incubated at ambient temperature for 30 min before developed with substrate TMB as described above." ] },{ "paper_id": "89cc8249f1595458ab949c3e6fad98dbb19a40d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We identified scientific articles through a MEDLINE search that combined communicable and infectious disease with non-vaccine and non-pharmaceutical intervention search terms. We Table 1 . Using a modified rating scale derived from West et al., we then formally rated the strength of the scientific evidence presented in each of the relevant articles [11] . Table 2 presents the modified rating scheme and reports the number of individual articles that fell into each rating category. We have presented a list of the final articles selected for full review and classification [see Additional file 2].", "Experts also recommended respiratory etiquette as an important means of preventing transmission for all patients and providers in all pandemic phases, and in the community and/or home when the US pandemic is early and localized. Respiratory hygiene and cough etiquette is generally held to include covering the mouth and nose with a tissue or into the upper sleeve when coughing or sneezing, and refraining from spitting [35] . However, they urged that the promotion of respiratory etiquette be coupled with a compelling public education campaign that includes information regarding the signs and symptoms of influenza." ] },{ "paper_id": "89d0e2ff08a2a140032fffa032af6dffb1ddae07", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Several computational approaches have been developed for analyzing and predicting drug-protein interactions. The most commonly used are docking simulations [9, 10, 11, 12] , literature text mining [13] , and combining chemical structure, genomic sequence, and 3D structure information [14] , among others (see, e.g., [15, 16, 17] ).", "Conclusion/Significance: Our results indicate that the network prediction system thus established is quite promising and encouraging.", "where V x : V y is the dot product of the two vectors, and V x k k and V y their modulus, respectively. When V x :V y we have D(V x ,V y )~0, indicating the ''distance'' between these two sample vectors is zero and hence they have perfect or 100% similarity." ] },{ "paper_id": "89d27a03696c2c515c9477eb696580d6041835e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Committee of Care and Use of Laboratory Animals of our institution approved all animal care and experimental procedure. Experimental procedures for animals are reported in accordance with the Animal Research Reporting of In Vivo Experiments (ARRIVE) guidelines [39, 40] .", "Male 5-6 week old Sprague-Dawley rats (DBL, Chungcheong Buk-Do, Korea) were maintained at a temperature of 23\u02daC \u00b1 2\u02daC under a 12 light-dark cycle per day. Animals were ", "For Western blot analysis, the extracted protein from frozen tissue samples was resolved on 4-12% Tris glycin SDS-PAGE gels and transferred to Immobilon (Millipore, Bedford, Mass., USA). The blots were blocked with PBS-T containing 1% skim milk and then incubated with anti-PER1, anti-PER2, anti-BMAL1 (all diluted to 1:500), anti-CLOCK antibody (diluted to 1: 200), or a mouse monoclonal anti-aquaporin 5 (1;100 dilution, sc-514022) (Santa Cruz Biotechnology, Inc., Santa Cruz, Calif., USA) in PBS-T overnight at room temperature. As an internal control, \u03b2-actin expression level was measured in parallel blots using a \u03b2-actin antibody (Santa Cruz Biotechnology, Inc., Santa Cruz, Calif., USA). The intensity of detected bands was quantified using Scion Image Beta 4.0.2" ] },{ "paper_id": "89d98e705490a5ab2eb7fd40de4541bba9051abb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A question that comes into our mind is whether the hardness of the shell (and not only its complex multi-layer structure) supports this observation. We shall see that the use of disorder predictors (e.g., PONDR \u00ae VLXT) represents a means to answer this question and to gain important knowledge about the shells of variola and other important viruses.", "An even more intriguing potential area of application is virotherapy against bacterial infections or cancer. Viruses that infect bacteria are known as phages or bacteriophages. They were first discovered in the early 20th century by Frederick Twort and Felix d'Herelle [3, 4, 67] . With the rise of the antibiotic-resistant bacteria, phage therapy is becoming a more viable alternative treatment for bacterial infections [68] . Similarly, advances in cancer treatments have allowed the cancer virotherapy to gain greater spotlight [69, 70] . Viruses do have oncolytic potentials or abilities to lyse cancer cells, because they share the same signaling systems, and cancer cells often over-express receptors necessary for viral entry [71] . The oncolytic herpes virus, T-Vec, has been approved by the Food and Drug Administration [72] .", "A recent review of past literature has led to the revelation that the mechanisms involved in the here described correlation between the intrinsic disorder levels and virulence of the viral shells had actually been unknowingly discovered in the 1920s by the legendary scientist, Oswald Avery [13] [14] [15] .", "Additional experiments on bacteria provide further support for the hypothesis presented herein, namely that highly flexible proteins and regions and (e.g., IDPs and IDRs) frequently make poor antigens. The fibronectin binding protein (FBP), which is anchored onto the surface of Staphloccoccus Aureus, has been shown experimentally to be entirely disordered except for its membrane anchor region [73, 74] , and, accordingly, the IDR extension is predicted to be so by PONDR VL-XT (unpublished). As is commonly observed for IDRs, FBP undergoes a disorder-to order transition as it binds tightly to its partner, fibronectin [75] . While in principle antibodies against FBP would be an effective therapy against S. aureus, attempts to raise such antibodies have not been successful [74] . Similar failures to obtain antibodies against the host-targeting proteins have been observed for several pathogens not counting the three viral examples discussed herein, suggesting that the evolution and utilization of disorder-to-order transitions for binding to host targets may be a strategy commonly used by pathogens to avoid immunological neutralization [27, 76] . ", "Although the absence of effective vaccines and the presence of a relatively disordered outer shell represents the common traits, they are, by no means, the only common characteristics defining virulence. In fact, one should also take into account the uncanny ability of viruses to hide in latency [2, 5] . In our view, the promiscuity of the disordered proteins or proteins with disordered regions is likely to play a role in infecting a greater number of cells where the virus can hide in [11, 30] ." ] },{ "paper_id": "89dc30e7b46b476142978f461feb4ecca1bf89b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For infections with B. subtilis: B. subtilis (from colonies scraped from a plate) were added to 5 mL of BHI broth containing 1 mM IPTG. Cultures were grown at 37uC with shaking to an optical density at 600 nm OD 600 of 0.8 to 1. " ] },{ "paper_id": "89e039e0e861069bedfb158e43844d3730b5abbb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Objective: Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-c) plays an important role in inflammation, this work assessed IFN-c single nucleotide polymorphism (SNPs) that may be associated with sepsis.", "Our results suggest that functional IFN-c SNPs and their haplotypes are associated with pneumonia-induced sepsis.", "Methods: A total of 196 patients with pneumonia-induced sepsis and 213 age-and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinical information was collected. Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation) and SOFA (sepsis-related organ failure assessment) scores and discharge rate. Four functional SNPs, 21616T/C (rs2069705), 2764G/C (rs2069707), +874A/T (rs2430561) and +3234C/T (rs2069718), were genotyped by Snapshot in both sepsis patients and healthy controls. Pearson's chi-square test or Fisher's exact test were used to analyze the distribution of the SNPs, and the probability values (P values), odds ratios (OR) and 95% confidence intervals (CIs) were calculated." ] },{ "paper_id": "89eb2ddb11e00fa7652c170a84d919d2428d90f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We used EPI-INFO version 6.04dfr software (EPI-INFO; CDC, Atlanta, GA, USA) for data collection, and used EPI-INFO and SAS version 9.1 software (SAS Institute Inc., Cary, NC, USA) for data analysis." ] },{ "paper_id": "89ec194732e513702a5ec1539e1941140c476068", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "D101 macroporous resin was supplied by Sinopharm Chemical Reagent Co. Ltd. (Beijing, China). HP-20, HPD100 and AB-8 resins were purchased from Solarbio (Beijing, China). All chemicals and solvents were of analytical grade and used without further purification.", "The moisture contents of the tested resins were determined by drying the beads at 100 \u2022 C to a constant weight in an oven. The moisture contents of D101, AB-8, HPD100 and HP20 resins were 52.12%, 62.11%, 72.17%, and 57.67%, respectively.", "CVBs is one of the most commonly identified agents for infection that is associated with acute and chronic myocarditis. However, there is no approved vaccine or antiviral drug for the prevention or treatment of CVB-induced diseases to date [40] . HME exhibited strong antiviral activities against CVB3 and B6 with better safety, which may provide an important strategy for anti-CVB and myocarditis therapy. ", "African green monkey kidney cells (Vero) were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA) and cultured in MEM supplemented with 10% FBS and antibiotics (100 U/mL penicillin G, 100 \u00b5g/mL streptomycin) at 37 \u2022 C in a humid atmosphere (5% CO 2 \u221295% air). Coxsackie Virus B3 (CVB3, strain Nancy) and B6 (CBV6, strain Schmitt) were obtained from ATCC and propagated in Vero cells.", "Fresh roots of H. cordata were obtained from Yizhou (Guangxi, China). The botanical identification of the plant material was performed by Renyun Wang from Institute of Materia Medica and a voucher sample was sealed and stored at \u221240 \u2022 C. Fresh roots were washed, dried in the dark and cut into pieces with appropriate length before extraction." ] },{ "paper_id": "89f41c87c8849ce37e609c1010087291a4679a37", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "89f70b62cc7e6aa71fbebcc3194b4ea5ad756c99", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nasopharyngeal aspirate (NPA) or blood or induced sputum (IS) was collected from the patients at the first day of admission and transferred into virus transport medium and stored at -70 o C until tested. Demographic information and medical test result were collected with standardized forms.", "Several viruses are more frequently detected among suburb/ rural patients( " ] },{ "paper_id": "89fc23ed55ad474b4b4056c0a3dadd315573f57e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Middle East respiratory syndrome coronavirus (MERS-CoV), a beta coronavirus, causes severe and lethal acute respiratory disease in humans and is remarkably different from other human coronaviruses,", "The purified RBD antigen has been tested to produce similar background responses in PBS or GEM immunized animals.", "RBD-F 1,3 5 -TGCTCTAGACATCACCATCACCATCACCAAGCCGAAGGAGTTGAA-3 (XbaI) Linker-RBD-R 2 5 -ACCAGAACCACCACCAGAACCACCCAACTTAGGGCAGACGCT-3 RBD-R 5 -GTTACCAGCTGAAGAAGCACCATCCAACTTAGGGCAGACGCT-3 PA3-F 5 -ACCAATAGCGTCTGCCCTAAGTTGGATGGTGCTTCTTCAGCTGG-3 Linker-PA2-F 2 5 -GGTGGTTCTGGTGGTGGTTCTGGTACTACCGTTAAGGTGAAGTC-3 Linker-PA3-F 2 5 -GGTGGTTCTGGTGGTGGTTCTGGTGATGGTGCTTCTTCAGCTGG-3 PA3-R 1 5 -CGGGGTACCTTACTTGATACGCAGGTATTGAC-3 (KpnI) 1 restriction enzyme sites are underlined and italicized. 2 Middle linker (Gly-Gly-Ser-Gly)x2 base sequences are underlined. 3 His-tag base sequences are in bold.", "The treatment of all mice was in accordance with the welfare and ethical guidance of Chinese laboratory animals (GB 14925-2001). The agreement was approved by the Animal Welfare and Ethics Committee of the Institute of Veterinary Medicine of the Military Academy of Sciences (Laboratory Animal Care and Use Committee Authorization, permit number JSY-DW-2018-02)." ] },{ "paper_id": "8a00f7c5a0cfb0b083ba29ea141ddb78e942b6aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2.6. PCR Analysis. RNA extraction was carried out using ISOGEN II (Nippon Gene, Tokyo, Japan) and cDNA synthesis with a prime script RT reagent kit with gDNA eraser (Takara, Tokyo, Japan), according to the manufacturer's instructions.", "For the attachment of virus to the cell surface, suspended virus at a moi of 1-100 was added to confluent monolayers of A549 cells in 12-well tissue culture plates for 1 hr, on ice. Cells were washed twice with cold PBS to remove the extracellular viruses and then cultured for the indicated amount of time with or without antivirus reagents at 37 \u2218 C.", "The authors declare that they have no conflicts of interest." ] },{ "paper_id": "8a016307c6c178384d6819b68cab3b1045486b9a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The datasets supporting the conclusion of this article is available. We presented the datasets in the additional supporting file. Data is available upon request. If someone wants to request the data should be contacted with Won-Il Choi.", "During the study period, nasopharyngeal specimens were obtained using flocked swabs and stored and transported using the universal transport medium (COPAN, Brescia, Italy). Nasopharyngeal specimens were submitted for respiratory virus detection. Nucleic acids were extracted from 300 \u03bcL specimens using a Viral Gene-spin\u2122 Viral DNA/ RNA Extraction Kit (iNtRON Biotechnology, Seongnam, Korea). cDNA was synthesized from each of the extracted RNA samples with cDNA Synthesis Premix (Seegene, Seoul, Korea) and a GeneAmp PCR System 9700 thermal cycler (Applied Biomaterials, Foster City, CA, USA).", "Log-Rank test P = 0.72" ] },{ "paper_id": "8a05548f8c34051d47f568ce2135978de0f9515d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Canine distemper (CD) is a highly contagious and fatal disease of dogs caused by the canine distemper virus (CDV), which is a single-stranded negative RNA virus belonging to the Morbillivirus genus within the Paramyxoviridae family. Other members of the genus include measles virus (MV) and rinderpest virus (RPV). The genome of CDV is approximately 15,690 nucleotides (nt) in length, containing several genes encoding N, P, M, F, H, and L proteins. Only one serotype has been characterized [1] .", "To date, CDV remains one of the most important canine diseases worldwide. Surveillance represents a primary concern in the control of CDV. In addition to traditional methods using virus isolation, several promising antigen-ELISA, AGP, and FA methods have been developed and evaluated. However, these methods are laborious and time consuming. Moreover, these tests cannot differentiate CDV wild-type strains from vaccine strains [13, 14] .", "A phylogenetic tree based on the H genes of various CDV strains was generated using the MegAlign of DNAStar software. As shown in Fig. 2 , the selected two samples were grouped into wild-type viruses and belonged to a genotype that is obviously different from the CDV vaccine strain." ] },{ "paper_id": "8a0731d1284b815e6139b1a40a4cc1f3b68dd4f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Genome3D features include:", "\u2022 A fully interactive point-and-select 3D environment", "\u2022 Loading of multiple resolution user-created models with an open XML format" ] },{ "paper_id": "8a096b3f838ccc2fab01f191ea2aacd2005f3f68", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "allow us to obtain a quadratic equation for T c with only one stable Disease Spreading in Multiplex Networks solution [38] given by,", "and the total fraction of recovered individuals R is given by", "where G A=B 0" ] },{ "paper_id": "8a0a29d6e80385dfdfd8ea1a301cc15e430bb11e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA oligonucleotides SAV557R (59-GCUAUGUGAGAU-UAAGUUAU-39), SAV481R (59-UUUUUUUUUUAUAACUU-AAUCUCACAUAGC-39) and poly(U) 18 (59-UUUUUUUUU-UUUUUUUUU-39) were purchased from Eurogentec, purified from 7 M Urea/15% PAGE gels and desalted through NAP-10 columns (GE healthcare). To anneal the RNA duplex SAV557R/ SAV481R, oligonucleotides were mixed at equimolar ratios in annealing buffer (20 mM Tris-HCl pH 8.0, 50 mM NaCl and 5 mM EDTA), denatured by heating to 90uC and allowed to slowly cool to room temperature after which they were purified from 15% non-denaturing PAGE gels.", "Citation: te Velthuis AJW, van den Worm SHE, Sims AC, Baric RS, Snijder EJ, et al. (" ] },{ "paper_id": "8a0b13901e64c9c2b9c0449cdcd7411ae0f1eac4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We investigated whether Anv extract could affect other important neutrophil functions such as degranulation.", "Anv inhibited superoxide production by neutrophil in response to PMA", "All results are expressed as mean \u00b1 SEM. One-way analysis of variance with the Tukey-Kramer post hoc test for multiple comparisons was implemented using GraphPad Prism version 6.0 for Windows (GraphPad Software, San Diego, CA)." ] },{ "paper_id": "8a1127271041cb420bec9aa4be4afa5d62b2b3b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "By definition, in PP patients disease progression is characterized by a progressive course without relapses or remissions from the onset of the disease [4] . PP patients tend to have lower inflammatory lesional activity, for which no immunological or genetic explanation has been identified yet. The scarce compar-ative neuropathological studies show a large overlap in lesional pathology, but indicate less inflammatory activity for PP, with still substantial axonal damage [5] . The general picture is that relapse onset and PP forms share substantial characteristics. In other words, it has remained a challenge to identify the biological parameters that determine a PP disease course.", "In order to place the identified proteins in a biological context, they were uploaded to the Ingenuity Pathways Analysis service (Ingenuity Systems) for to network analysis. Six of the seven differentially abundant proteins were placed in a network relating to neurological disease (Figure 1 )." ] },{ "paper_id": "8a14b75626a9cad7cac350437b7af5e0e4bd5127", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Authors' contributions ZS developed the structural design of the review. BH and XG drafted the manuscript. LFW was involved in revising the manuscript. All authors read and approved the final manuscript. ", "SARS first emerged in late 2002 in Guangdong Province, southern China, as a novel clinical severe disease (termed \"atypical pneumonia\") marked by fever, headache and subsequent onset of respiratory symptoms including cough, dyspnea and pneumonia. Being highly transmissible among humans, SARS rapidly spread to Hong Kong and other provinces across China and then to other 28 countries [6, 7] . By July 2003, it had caused 8096 confirmed cases of infection in 29 countries, 774 (9.6 %) of which were fatal (http://www.who.int/csr/sars/ country/table2004_04_21/en/). The second outbreak in 2004 only caused 4 infections with no mortality nor further transmission [8] .", "The authors declare that they have no competing interests." ] },{ "paper_id": "8a18be6bbec92094276f843c39fa9ea509e20215", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Neglected Diseases section focuses attention either on a specific disease or describes a novel strategy for approaching neglected health issues in general.", "Alternative Language Text S1. ", "Treatment: Rapid diagnosis and treatment are essential to reduce the risk of complications and death. Streptomycin, tetracyclines, and sulfonamides are the standard treatment. Gentamicin and fluoroquinolones may represent alternatives when the above antibiotics are not available. Patients with pneumonic plague must be isolated to avoid respiratory transmission." ] },{ "paper_id": "8a1da932b899d2a04b8e8ce1ccd2ce02bc352c9e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Commentary on Wolf, M.C.; Freiberg, A.N.; Zhang, T.; Akyol-Ataman, Z.; Grock, A.; Hong, P.W.; Li, J.; Watson, N.F.; Fang, A.Q.; Aguilar, H.C.; et al. A broadspectrum antiviral targeting entry of enveloped viruses.", "LJ001 is an aryl methyldiene rhodanine derivative that was found during a high-throughput cellbased screen for inhibitors of Nipah virus (NiV) entry using a vesicular stomatitis virus (VSV) luciferase reporter pseudotype system. LJ001 caused minimal cellular toxicity at in vitro inhibitory concentrations. The authors employed several independent approaches to show that LJ001 acts at the level of virus entry. For example, inhibition was only achieved if LJ001 was added before or during virus absorption onto cells -if it was added after virus adsorption, infection occurred normally. A betalactamase content mixing assay further demonstrated a role during entry, though a binding assay showed that viral attachment occurred normally, thus implicating virus-membrane fusion as a potential target.", "Though LJ001 associates with both viral and host membranes, it is only the viral membrane whose function appears to be impaired: LJ001 inhibits virus-cell fusion, but it fails to inhibit cell-cell fusion reactions mediated by the same viral glycoprotein. The authors hypothesize that this is due to the fact that host membranes are continually remodeled and can repair themselves by metabolizing or extracting membrane-active agents, thus escaping gross membrane perturbation [8] . Consistent with this, synergistic disruption of plasma membrane integrity was observed when cells were exposed to an inhibitor of fatty acid synthesis (TOFA) and LJ001. This again suggests that simply associating with lipid membranes is not sufficient for antiviral activity, though the precise mechanism has not yet been determined. One mechanism by which LJ001 could potentially prevent fusion is by altering membrane curvature, as a variety of non-bilayer lipids that impact membrane curvature have been shown to inhibit fusion [9] ." ] },{ "paper_id": "8a2a859f5920d1a81d0ab2e619f00f729331fedc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Materials and Methods", "Histology and immunohistochemistry. HapT1 tumors were dissected and fixed in 10% neutral buffered formalin at room temperature for 48 hours, and then tumor tissues were dehydrated and embedded in paraffin wax. 5 \u00b5m thick sections were cut and stained with hematoxylin-eosin. For immunohistochemistry, 5 \u03bcm paraffin-embedded sections were de-paraffinized in xylene and rehydrated with graded ethanol and deionized water, then boiled in acidic pH citrate buffer (Vector Laboratories) for 20 min in a steam cooker. Endogenous peroxidase was blocked with 3% hydrogen peroxide in methanol for 20 min, and then washed with PBS followed by blocking with horse serum (Vector Lab) for 30 min. Then sections were incubated with the anti-Ki67 ", "Clinically relevant animal models help in understanding the pathogenesis of different human and animal diseases and play crucial roles in developing new therapeutics against them 1 . In spite of the dominance of the mouse as an experimental model animal, the hamster has carved its niche as a potential model animal for studying many diseases and for the evaluation of therapeutic agents. Hamsters are frequently used in various disease pathogenesis studies due to the ease of handling them and the similarity to humans in disease development. Hamsters are important animal models for studying various infectious diseases of humans 2-9 . The hamster models of pancreatic and oral cancer have gained importance in their respective fields 10-15 . Moreover, these animals have also been instrumental in studying metabolic and/or inflammatory diseases like diabetes and pancreatitis 16, 17 . Despite the fact that the hamster is an important clinically relevant animal model for different diseases, it is not used to its full potential. In this aspect, the non-availability of complete genetic information of these animals and lack of biological reagents like recombinant proteins and antibodies related to them are the major constraints." ] },{ "paper_id": "8a2b2c72af5a57c21d912a3f1e543bcd75345883", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Instruments 454 sequencing (Roche Diagnostics) . dsDNA in solution is first sheared by nebulization (converted into a fine spray) or amplified by PCR, and fragments of the appropriate size are selected (Fig. 2) . These fragments are blunt-ended and dephosphorylated, followed by the ligation of two separate adapters (A and B). The B adapter is biotinylated, allowing subsequent purification using streptavidin-coated beads.", "PCR reagents ", "Genome sequencing" ] },{ "paper_id": "8a2ca0a9b9108a56a79d6a610c6537102c124697", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleoside analogues belong to a group of important antiviral and antitumor drugs [1] [2] [3] [4] . However, resistance to drugs and their toxicity are considered major factors limiting the effectiveness of therapies. Structural modifications of available drugs from a class of nucleoside analogues, including sugar and/or nucleobase residues, resulted in the discovery of a variety of therapeutically-useful antiviral [5] (e.g., azidothymidine (AZT) [6] , carbovir [7] , lobucavir [8] , dioxolane T [9] and lamivudine [10] ) and anticancer [11, 12] (e.g., cladribine [13] , gemcitabine [14] , azacitidine [15] and cytarabine [14, 16] , clofarabine [17] ) agents ( Figure 1 ).", "Antiproliferative properties of the obtained isoxazolidines and \u03b3-lactams were evaluated on nine cancerous cell lines and several of them exhibited moderate inhibitory activity, and at the same time they were inactive toward normal retina cells.", "To a solution of a nitrone (1.00 mmol) in methanol (9 mL), methyl acrylate (10.0 mL) was added. The mixture was stirred at 60 \u2022 C for 24 h. The solvent was removed in vacuo and crude products were purified on silica gel columns using chloroform-methanol (100:1, 50:1, 20:1, 10:1, v/v) as eluents. The respective fractions were subjected to HPLC on a X Bridge Prep, C18, 5 \u00b5m, OBD, 19 \u00d7 100 mm column using water/methanol (90:10, 85:15, v/v) to afford pure isoxazolidines. ", "All assays were performed in 96-well microtiter plates. To each well was added (5\u22127.5) \u00d7 10 4 tumor cells and a given amount of the test compound. The cells were allowed to proliferate at 37 \u2022 C in a humidified, CO 2 -controlled atmosphere. At the end of the incubation period, the cells were counted in a Coulter counter. The IC 50 (50% inhibitory concentration) was defined as the concentration of the compound that inhibited cell proliferation by 50%." ] },{ "paper_id": "8a2d2e38286fa86dcf60a8a1b0b95658f2d70850", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CUSUMs. CUSUMs are methods that are used to detect small aberrations from an in-control process [15, 16, 17] . The m-week standardized upper CUSUM is calculated as:" ] },{ "paper_id": "8a2fd6ad99f53bb749e4ccaf50fdd36a14bd4aba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Little/no effect Little/no effect Little/no effect Little/no effect [106] Polyhydroxylated fullerene Glutathione (2.0 mM) SFV VSV no effect no effect [50] Hydroquinone (2.0 mM) SFV VSV no effect no effect [50] Merocyanine 540", "Glutathione (10 and 30 mmol L \u22121 ) Cysteamine (10 and 30 mmol L \u22121 ) SOD (1.5 to 29 U mL \u22121 )", "HSV-1 30-50% 60-70% no effect [45] Methylene blue Mannitol (100 mM) Glycerol (10 mM) SOD (300 U mL \u22121 ) Q\u03b2 20% no effect [107] L-cysteine (100 mM) T4 phage 9% [107] 5,10,15,20-tetrakis(1methylpyridinium-4-yl)porphyrin D-mannitol (100 mM) T4 phage no effect [107] Proflavine L-cysteine (0.025 M) T3 phage 75-80% [63] Polyhydroxylated fullerene SOD MS2 phage no effect [90] 3." ] },{ "paper_id": "8a3678c3ee2208d7417bfdc62558fe0e32588eab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The complete genome sequence of P23_15_TT_1115 has been deposited in GenBank under the accession number KU984334.", "The results in this study suggest that P23_15_TT_1115 is a novel isolate, closely related to PDCoV isolates from China. The studies investigating the molecular epidemiology, prevalence, and evolution of PDCoV in Thailand are urgently required.", "In Thailand, porcine deltacoronavirus (PDCoV) was first identified in November 2015. The virus was isolated from piglets experiencing diarrhea outbreak. Herein, the full-length genome sequence of the Thai PDCoV isolate P23_15_TT_1115 is reported. The results provide a clearer understanding of the molecular characteristics of PDCoV in Thailand." ] },{ "paper_id": "8a387a670706c2009e6c5e7a39c112a9e645f963", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rabbit embryonic brain cells were generated in the early 1990s by S. Herzog and frozen until usage. Generation of these primary cells was licenced (Gi 23-1/89) by the administrative district of Giessen." ] },{ "paper_id": "8a45b8b7e677272ce3d5d750e943fe6584134a97", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Filoviruses have a broad cell tropism in susceptible host species. Among the target cells supporting viral replication are monocytes, macrophages, dendritic cells (DCs), hepatocytes, adrenal cortical cells, fibroblasts and endothelial cells [43] [44] [45] [46] [47] [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] .", "The first reported MARV outbreak occurred in Germany and Yugoslavia in 1967 and was caused by infected African green monkeys imported from Uganda [18, 19] . Since this outbreak was associated with a case fatality rate of 22%, it was believed for a long time that MARV was less pathogenic than EBOV. However, recent outbreaks of MARV in the Democratic Republic of the Congo in 1998-2000 and in Angola in 2004 were associated with fatality rates up to 90%, indicating that MARV can be as virulent as EBOV [20] [21] [22] .", "Multiple expression studies have implicated the EBOV surface protein GP in cytotoxicity and cell damage, inducing cell rounding, detachment, and membrane permeabilization [92, [171] [172] [173] [174] [175] [176] [177] , while other EBOV proteins did not induce cell detachment [171] . Expression of GP also leads to a general downregulation of cell surface proteins including adhesion molecules, MHC class I proteins, and EGF receptor [92, 174, 176, 178] . Moreover, GP expression in explanted blood vessels resulted in endothelial cell loss and increased vascular permeability [171] .", "The first step that determines if a cell will be a target for infection is the ability of the virus to attach. Filoviruses are able to infect multiple cell types in vivo and in cell culture by exploiting cellular entry machineries. However, some cells are more susceptible to infection than others, and some are not permissive to infection." ] },{ "paper_id": "8a584984728d9dd104a0d3928686d4a2e02e2ebf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our research conformed to the Helsinki Declaration outlining the principles for medical research involving human subjects. Participants provided informed consent to participate in the study. Committees from Rutgers University institutional review board approved the research protocol.", "Perceived risk and precautionary behavior by age, sex and household size", "The mean perceived likelihood showed a slight increasing trend (Figure 1 ). Conditioned on demographic variables, regression analyses revealed a positive linear trend (b = 0.008, p = 0.004) and a negative quadratic trend (b = -0.0002, p = 0.01), indicating that the increase is steeper initially and then levels out. Predicted death toll showed a significant decrease over time (b = -0.06, p = 0.002) with a positive quadratic trend (b = 0.002, p = 0.01), indicating a more rapid decrease during the very early stage of the pandemic." ] },{ "paper_id": "8a58dd3509470bd8a8a25fa473991ca6681066d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords: Porcine deltacoronavirus (PDCoV), Monoclonal antibodies, Serology, ELISA, Fluorescent microsphere immunoassay (FMIA)", "PDCoV-NP fwd (5\u2032-CGCGGATCCATGGCCGCACC AGTAGTC -3\u2032);", "PDCoV-NP rev (5\u2032-CACACTCGAGCGCGCTGCTG ATTCCTGCTT-3\u2032)." ] },{ "paper_id": "8a5accd8df7fcfcef5fb8b467e2cc8caa7c631a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step 1", "Step 2", "By means of standard FastMoc chemistry, all peptides were synthesized on a peptide synthesizer (Model 433A, Applied Biosystems, Foster City, CA) by the Core Laboratory of the Center for Biologics Evaluation and Research, FDA as described previously [12] . Biotinylated peptides were synthesized with a Fmoc-Lys(Biotin-LC)-Wang resin (AnaSpec, San Jose, CA).", "One of the major challenges in eliciting an effective immunity against HCV is the genetic diversity of the virus [4] [5] ." ] },{ "paper_id": "8a5e57ed05714b7baedeaece51bec78b4b8d1447", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Proteins are extremely variable, flexible and pliable building blocks of life that are crucially involved in almost all biological processes. Many diseases are caused by protein aberrations, and proteins are frequent targets of intervention. A plethora of highthroughput methods are currently being used to study genetic associations and protein interactions, and intense on-going international efforts aim at understanding the structures, functions and molecular interactions of all proteins of organisms of interest (e.g. the Human Proteome Project, HPP). In some cases, linear peptides can emulate functional and/or structural aspects of a target structure. Such peptides are currently identified using simple peptide libraries of a few hundreds to thousands peptides whose sequences have been systematically derived from the target structure at hand -that is, if this is known. Even when the native target structure is unknown, or too complex (e.g. discontinuous) to be represented by homologous peptides, the enormous diversity and plasticity of peptides may allow one or more peptides to mimic relevant aspects of a given target structure [1, 2] .", "Trypsin data. Peptide arrays were incubated for 30 min at room temperature with 0.1 g/L bovine Trypsin (Sigma T9201) dissolved in 0.1 M Tris/Acetate pH 8.0. After washing in the same buffer containing 0.1% SDS, the slides were washed with deionized water and air-dried. Staining of amino groups exposed by enzyme cleavage was made by incubation the slide for 30 min in 0.1 mg/mL Dylight549-NHS (Thermo Scientific) in 9:1 v/v nmethyl pyrrolidone:0.1M n-methyl morpholine/HCl pH 8 for 10 minutes.", "Characterizing the binding motif of HLA-DR molecules using the NNAlign method", "Chymotrypsin. Peptide arrays were incubated for 30 min at room temperature with 0.1 g/L bovine Chymotrypsin (Sigma C4129) dissolved in 0.1 M Tris/Acetate pH 8.0. After washing in the same buffer containing 0.1% SDS, the slides were washed with deionized water and air-dried. Staining of amino groups exposed by enzyme cleavage was made by incubation of the slides for 10 min in 1 mM 5(6)-TAMRA (carboxytetramethylrhodamine, Fluka 21953) activated with 1 eq HBTU, 2 eq DIEA in nmethylpyrrolidone.", "Recording of signals from peptide arrays. After incubation with activated fluorochromes, the peptide array slides were washed in the incubation buffer without fluorochrome followed by washings in n-methylpyrrolidone and dichloromethane and airdried. Images of the arrays were recorded using a MVX10 microscope equipped with a MT10_D fluorescence illumination system and a XM10 CCD camera (all from Olympus). The excitation wavelength was 530-550 nm and the emission filter was 575-625 nm. The images were analyzed using the PepArray analysis program (Schafer-N, Copenhagen Denmark)." ] },{ "paper_id": "8a665903721dadcf01c1dd7476a7715709cee0ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleic acid extraction was performed on the MagNA Pure LC 2.0 (Roche Diagnostics, Mannheim, Germany) using a MagNA Pure LC Nucleic Acid isolation kit I (Roche Diagnostics) according to the manufacturer's instructions. More than fifty microliters of clinical samples were used for nucleic acid extraction and eluted in 50 \u03bcl of elution buffer.", "Cidofovir (Mylan Institutional) was initiated upon confirmation of AdV infection. Cidofovir, at a dosage of 5mg/kg weekly, was administrated in combination with oral probenecid. Hydration consisted of 1-2 L of normal saline before cidofovir infusion and 1-2 L immediately thereafter to prevent renal toxicity. A total dose of 2-g probenecid was given orally 3 h before infusion, and 1 g at 2 and 8 h after the cidofovir infusion. The number of cidofovir courses administered was determined by the attending physician.", "Multiplex real-time PCR was performed to screen for 15 commonly isolated respiratory viral pathogens, including adenovirus, rhinovirus, influenza virus A/B, respiratory syncytial virus A/B, bocavirus, coronavirus 229E/OC43/NL63/HKU1, parainfluenza virus 1/2/3, and metapneumovirus, using a Real-Q RV Detection kit (BioSewoom, Seoul, Korea) on a Roche Light Cycler 480 II instrument (Roche Diagnostics, Mannheim, Germany) according to the manufacturer's instructions. The presence of specific viral sequences in the reaction was detected by an increase in the FAM, VIC and Cy5 fluorescence from the relevant dual-labeled probe. Five primer/probe sets were used to detect respiratory viruses. The serotype of human-AdV-positive samples was evaluated by sequence analysis using the partial hexon genomic region." ] },{ "paper_id": "8a696028212fb6b878bf7143927566fdb6215f06", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The m\u00e9nage a trois between IAV HA, NA and (decoy) receptors largely determines viral fitness and host cell tropism. Here, by studying their highly dynamic but poorly understood interplay using BLI, we obtained novel mechanistic and quantitative insights into IAV-host interactions.", "Before the application of samples, 400-mesh copper grids with a pure carbon film were exposed to a glow discharge in air for 20 s to make them hydrophilic. Ten microliters of the virus preparations was applied to the grids and incubated for 2 min. Excess sample was blotted with a filter paper. For negative staining, 10 \u03bcL of 2% phosphotungstic acid at pH 6.8 was applied. After 1 min, excess stain was blotted and grids were left to dry. The specimens were examined in a JEOL JEM1400 transmission electron microscope at 120 kV and images were taken at a magnification of 30.000x with a Matataki 2K x 2K camera.", "PLOS Pathogens | https://doi." ] },{ "paper_id": "8a6f367d81903273daadb6e142149f2feff80d6e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Significant differences were determined with SigmaPlot v11 using the Sum Rank Test (P < 0.005).", "Unsorted and sorted (see below) PBMC were cultured in Dulbecco's modified Eagle's minimal essential medium (DMEM) plus GlutaMAX \u2122 -I (GIBCO, Life Technologies, Basel, Switzerland) supplemented with 20 \u03bcM of \u03b2mercaptoethanol (Life Technologies) at 39\u00b0C at 6% CO 2 . Baby Hamster Kidney (BHK) 21 cells were grown in Glasgow's minimum essential medium (GMEM, Life Technologies) supplemented with 5% v/v Fetal Bovine Serum (FBS, South America Origin, Biowest, Nuaill\u00e9, France). For virus preparation and serum neutralization test, cells were cultured in FBS-free GMEM at 37\u00b0C, 6% CO 2 .", "For pDC enrichment, monoclonal antibodies against following cell surface markers were used: CD172a (mAb 74-22-15A), CD14 (mAb CAM36A), CD3 (mAb 8E6) and CD4 (mAb PT90A). For phenotyping, mAb against CD172a and CD4 were used. Hybridoma for mAb 74-22-15A was kindly provided by Dr A. Saalm\u00fcller (Veterinary University, Vienna, Austria). mAbs CAM36A, 8E6 and PT90A were purchased from VMRD (Pullman, WA, USA)." ] },{ "paper_id": "8a7647890f01aa9c0d085a1209235e832369bb44", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by Marthaler Start-up fund and the University of Minnesota Veterinary Diagnostic Laboratory. ", "The family Picornaviridae are single-stranded positive-sense RNA viruses that contain 31 genera, including Aphthovirus (including the species Foot-and-mouth disease virus, FMDv), Senecavirus, Teschovirus, Sapelovirus and Enterovirus. The genus Enterovirus comprises 12 species (enterovirus A-H and J, and rhinovirus A-C) [6] . The species Enterovirus G (EV-G) currently includes 16 serotypes/genotypes, where the two most common genotypes are EV-G1 (previously called porcine enterovirus 9) and EV-G2 (previously called porcine enterovirus 10) [6, 7] . Picornaviruses encode a single polyprotein that is proteolytically processed into three precursor protein products that are further processed into four structural proteins (VP1-4) and seven non-structural proteins (2A pro , 2B, 2C, 3A, 3B, 3C pro and 3D-RdRp). Molecular subtyping based on VP1, VP4/2 or 3D sequence alignments have revealed a large diversity of EV-G genotypes (www.picornaviridae.com/enterovirus/ev-g/ev_g_seq.htm).", "In conclusion, we have developed a metagenomics sequencing and analysis approach for rapid identification of unknown pathogens in porcine samples. We identified and assembled an EV-G genome from the faeces of two 25-dayold piglets experiencing diarrhoea without any clear cause." ] },{ "paper_id": "8a8463146cf8f61c2d62df2adaa251adbe2f9dc1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Interaction effects and collinearity between variables were tested. To assess whether any variables in the final model were subject to confounding by any variables that had been omitted from the final model, each omitted variable was re-introduced individually and tested for significance. Confounding was determined by looking for a change of \u226530% in regression coefficients. Data analyses were performed using Stata 9.2 W (StataCorp, USA).", "At the second stage, one person aged \u2265 5 years and one child < 5 years (if any) were randomly selected among the household members by selecting the person who had the next birthday. If the selected person was aged between \u2265 12 and < 18 years, a parent could choose to answer for the child or allow the child to answer. If the child was < 12 years old, one parent was asked to answer on the child's behalf.", "Limitations of this study are those common to other retrospective telephone surveys, in particular the refusal of households to respond, the non inclusion of households with mobile phones only, and potential recall bias. As shown in the results, recall bias seems to be limited as the estimated incidence using a 1-week recall period was not significantly different." ] },{ "paper_id": "8a973597ea07d63537723d0324a68fe3759b90ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pgen.1007718.g001", "https://doi.org/10.1371/journal.pgen.1007718.g002", "ffl ffl ffl ffl ffl ffl ffl ffl ffl ffl ffl ffl ffl ffl ffl ffl {zffl ffl ffl ffl ffl ffl ffl ffl ffl ffl ffl ffl ffl ffl ffl ffl ffl }" ] },{ "paper_id": "8abf33baca8c7abbbf6ca5f56b404b79f658dd26", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pharmacological methods (local anaesthesia, systemic analgesia using non-steroidal anti-inflammatory drugs, xylazine sedation) are available that are highly beneficial in alleviating the acute pain caused by castration, dehorning or disbudding [57, 63] . National legislation regarding animal welfare and regulations concerning the usage of these drugs by veterinarians or producers vary between countries and have to be taken into account.", "It has been suggested that pneumonic animals should be isolated in appropriate facilities [42] . However, there is little experimental evidence to quantify the benefits and it may lead to practical difficulties.", "Many aspects of respiratory disease in cattle have recently been reviewed [66] , including issues specific to beef [67] and dairy [68] calves.", "To prevent adverse conditions, at least 4 air changes per hour are needed in winter and up to 40 in summer [30] . Natural ventilation is achieved through wind and buoyancy in monopitch or duopitch houses, given that adequate air outlets (ridge opening: 5 cm width for every 3 m width of the building) and inlets (eave openings: at least half the space of ridge openings) [31] , as well as sufficient difference in height between the openings is provided (not less than 1.5 m, but preferably 2.5 m) [6] . Recommended air space per calf is not less than 6 m 3 up to 6 weeks and 10 m 3 up to 12 weeks of age [6] ." ] },{ "paper_id": "8aca747989e024abacecae2fcc95186972c3f5df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8ace20b674c2bc5f71e195f68c703f66efd97b8b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nasal washes, oral and rectal swabs were collected in 1 ml of DMEM supplemented with penicillin and streptomycin and vortexed for 30 sec. Whole blood was collected in EDTA Vacutainers. Following sampling, 140 \u03bcl of individual samples was added to 560 \u03bcl of AVL viral lysis buffer (Qiagen, Inc) for RNA extraction. For tissue, approximately 100 mg was stored in 1 ml of RNAlater (Qiagen, Inc) to stabilize RNA. RNAlater was completely removed, and tissue was homogenized in 1 ml of Trizol (Sigma).", "Tissues were processed by routine histological methods and sections of tissue (5\u03bcm thickness) were stained with Hematoxylin and Eosin (H&E) to examine histological changes. Tissues for immunohistochemistry (IHC) were stained as previously described [8] , using a rabbit anti-N-nucleoprotein (N) antibody (kindly provided by Dr. C. Broder, Uniformed Services University, Bethesda, MD)." ] },{ "paper_id": "8ad351ba522675d0ec4fa73713649bcfa9453447", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Treatment outcomes for patients with H1N1 acute respiratory failure improved from 2009 to 2016 in two tertiary referral centers in South Korea. ", "Baseline characteristics are summarized in Table 1 . The median age of all patients was 62 years (IQR, 53-69 years) and 63% of all patients were male. Patients in 2016 were older (67 Table 1 . Baseline characteristics of patients with H1N1 acute respiratory failure. ", "Multiple aspects of ICU patient management have improved in recent years, including the more widespread application of lower tidal volume ventilation [8] , restrictive blood transfusion [9] , reduced sedative use [10] , early mobilization, and more appropriate intervention in patients with sepsis [11, 12] . Also, some lessons were learned while managing patients with 2009 H1N1-related critical illnesses, and extracorporeal membrane oxygenation (ECMO) therapy has been applied for the most severe ARDS associated with H1N1 infection [13, 14] ." ] },{ "paper_id": "8ad6fe3d0031f1dffb84dec640ac0bb7c5ba84fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8ad769c159358842b5ccacbd383987335844ad86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8ae561e754ff3e094cd9d1e92f8517f8f9f4506a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza A/PR/8/34 (H1N1), A/Virginia/ATCC3/2009 (H1N1), and A/England/42/72 (H3N2) viruses purchased from American type culture collection (ATCC) were propagated and titered as described [16] . were maintained in growth medium and harvested 16 hours after inoculation. Infected cells were labeled with 0.5 mg/ml murine anti-influenza H1 IgG2a (C179; Clontech) or with 1 mg/ml antiinfluenza viral H3 IgG1 (F49; Clontech), followed by an Rphycoerythin (PE)-conjugated secondary antibody (Thermo scientific). Fixed cells were analyzed by flow cytometry. Student's t test was used for statistic analysis.", "Human embryonic kidney 293T and African green monkey epithelial Vero E6 cells (American Type Culture Collection) were maintained in Dulbecco's modified eagle medium (DMEM; Invitrogen). Human lung epithelial A549 cells were grown in Roswell Park Memorial Institute (RPMI) 1640 medium (Invitrogen). All media were supplemented with 10% fetal bovine serum (FBS; Invitrogen), 100 U/ml penicillin, and 100 mg/ml streptomycin (Invitrogen). A549 cells transduced with a vector or to express tetracycline (tet)-inducible IFITM3 isoforms were selected with 3 mg/ml puromycin (Invitrogen) and 400 mg/ml gentamicin (Invitrogen).", "Subcellular localization of FL IFITM3, D21 IFITM3, and Y20A IFITM3 was measured by confocal microscopy. IFITM3expressing A549 cells were washed twice with phosphate buffered saline (PBS) and fixed in 4% formaldehyde at 25uC for 20 minutes. Fixed cells were then permealized with 1% Triton X-100 (Sigma) for 20 min, blocked in 1% bovine serum albumin (BSA; Sigma) at 25uC for 1 hour, and labeled with primary antibodies for 2 hours or overnight. Primary antibodies used in this study included a murine anti-lysosomal-associated membrane protein 2 (LAMP2; H4B4 conjugate with Alexa 488, 1:100 dilution; Santa Cruz Biotech) and a goat anti-IFITM2/3 (5 mg/mL; R&D Systems) antibodies. After primary antibody staining, cells were labeled with an anti-goat Alexa 633-conjugated secondary antibodies (1:2000 dilution; Invitrogen) for 1 hour, counterstained with 49,6-diamidino-2-phenylindole (DAPI; Thermo Scientific), and then analyzed by confocal microscopy using the Leica TCS-SP5 laser confocal imaging system (objective 63X)." ] },{ "paper_id": "8aef75d2d213cab0a2b4661fc9971507863ff9ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The effort for preparing this review was supported by the Office of Science, Office of Biological and Environmental Research, of the U. S. Department of Energy under Contract No. DE-AC02-05CH11231 through ENIGMA -Ecosystems and Networks Integrated with Genes and Molecular Assemblies (http://enigma.lbl.gov), a Scientific Focus Area Program at Lawrence Berkeley National Laboratory and the Oklahoma Applied Research Support (OARS), Oklahoma Center for the Advancement of Science and Technology (OCAST), the State of Oklahoma through the Project AR062-034.", "There are commercial kits available for microbial RNA amplification such as the MessageAmp TM II-Bacteria RNA Amplification Kit (Life Technologies, Grand Island, NY, USA). There are also other commercially available methods for WCGA. Wang et al. (2011) compared two of these (Bacillus stearothermophilus DNA polymerase (Bst) and REPLI-g; Qiagen, Valencia, CA, USA) with the modified Templiphi kit (Wu et al., 2006a) . The amplification bias for all methods was relatively low (<3-fold). Less bias was observed with REPLI-g and Templiphi for pure culture DNA and with REPLI-g for community DNA while Bst showed the least inhibition by lesser quality DNA.", "The amplified (or unamplified) nucleic acids are directly labeled with a fluorescent dye (Cy3 or Cy5) using random priming with the Klenow fragment of DNA polymerase for DNA (Wu et al., 2006a) or Superscript TM II/III RNase H-reverse transcriptase for RNA (He et al., 2005b) . The labeled DNA/RNA is then purified and dried for hybridization." ] },{ "paper_id": "8af0901c4f1252ca252a8618a346c88b3b65ae1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The source of H7N9 human infections is unclear, but it appears to be carried by poultry, in their secretions or excretions [7] [8] ." ] },{ "paper_id": "8b11ed8edd1f59ac713ddcc3282ad5a98b8b68b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bleeding and care of donor pigs was carried out in accordance with EU standards and National laws (Tierschutzgesetz SR455). Specifically, approval of the protocol employed was obtained by the Animal Welfare Committee of the Canton of Bern, Switzerland (animal license BE26/11). Cell preparation and cell culture", "IFN-a was quantified by enzyme-linked immunosorbent assay (ELISA) using the mAbs K9 and F17 (kindly provided by Dr. B. Charley, INRA, Jouy-en-Josas, France) as described previously [31] . For detection of IFN-a by intracellular staining mAb F17 with a previously published protocol was employed [63] .", "A 50-mer RNA oligonucleotide probe complementary to nucleotides 12242-12193 of the vA187-1 genome sequence (GenBank accession number X87939.1) and carrying a Dyomics 781 modification at the 59 end (Dy-781-O1-RNA) was synthesized by Dr. Fabian Axthelm (Microsynth AG, Balgach, Switzerland). The Dy-781-O1-RNA probe was mixed at 40 nM final concentration with MEM containing 3610 23 U RNase A/ml as digestion control, with 50 mM TrisHCl pH 7.4 as negative control, and with the samples to be tested for RNase activity, and incubated for 1 h at 37uC. The treated probes were mixed with 2 volumes of 97% Formamide (Sigma) and separated on a 10% polyacrylamide and 35% urea gel in 133 mM TrisHCl, 45.5 mM boric acid and 3.2 mM EDTA. Image acquisition was performed with the Odyssey Infrared Imaging System (LI-COR)." ] },{ "paper_id": "8b12db91c31cd4a723270f3cbb56f7919581bb02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The weekly meetings and case conferences were a resource for the clinical ethicists and clinical ethics fellows to receive collegial support and networking opportunities. The weekly seminars featured local, national and international speakers on a wide range of topics.", "The fellowship helped prepare the fellows to make the transition to clinical ethicists by providing real-time clinical opportunities. Although there were opportunities to attend lectures, seminars and conferences and to participate in research projects and the activities of research ethics boards, the focus of this fellowship was clinical practice.", "The fellowship enabled each of the fellows to assume confidently and competently a position as a clinical ethicist upon completion." ] },{ "paper_id": "8b13309e21cd13564b46ef8d78bf927cf558f6f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The primary antibodies against viral proteins used were: mouse monoclonal anti-prM 13A10, IgG2a; mouse monoclonal anti-E 11H12, IgG2a; mouse monoclonal anti-NS1 6E11, IgG2a (all kind gifts from Dr. Connie Schmaljohn, USAMRID, Fort Detrick, Frederick, MD), chicken poly-clonal anti-NS3 (sequence: CZRDIREFVSYASGRR) and chicken polyclonal anti-NS5 (sequence: CZDRHDLHWELKLESSIF) (custom prepared by Aves Labs), mouse anti-dsRNA clone J2 (purchased from English & Scientific Consulting, Szirak, Hungary). Markers against cellular organelles used were: Alexa Fluor 594-conjugated wheat germ agglutinin (WGA, Invitrogen), and mouse monoclonal Dylight 488-conjugated protein disulfide isomerase 1D3 (PDI, Enzo Life Sciences). Secondary antibodies used were: Alexa Fluor 488-and 594-conjugated anti-mouse-and anti-rabbitspecific IgG and Alexa Fluor 647-conjugated anti-chickenspecific IgG (Invitrogen).", "Samples were processed further in a Biowave model laboratory microwave oven, equipped with a Coldspot water circulator (Ted Pella, Inc.) as follows: washed twice in 0.1 M sodium phosphate buffer, pH 7.2, for 1 minute each; post-fixed in 1% osmium tetroxide in phosphate buffer for two cycles of 2 minutes on, 2 minutes off, and 2 minutes on; washed once in phosphate buffer for 1 minute and twice in water for 1 minute each; contrasted with 1% uranyl acetate in water for two cycles of 2 minutes on, 2 minutes off, and 2 minutes on; dehydrated in three changes of ethanol for 1 minutes each; and embedded in Spurr's resin using steps of 50%, 75%, and two changes of 100% resin in ethanol for two periods of 5 minutes each. The power output of the oven was set at 250 watts for dehydration and embedding. All other steps were performed at a setting of 167 watts. The cover slips were placed cell-side down onto resin block molds, polymerized overnight at 65uC, and removed from hardened blocks after a 5 second immersion in liquid nitrogen.", "Thin and semi-thick sections of approximately 70 and 250 nm, respectively, were cut using a diamond knife and a model EM UC6 microtome (Leica Microsystems). Thin sections were collected on uncoated 200 mesh copper grids. Once thoroughly dried, the sections were stained with fresh 1% lead citrate using 1 minute of microwave irradiation at 167 watts, followed by a 1 minute water wash at 167 watts and standard drop-wise washing." ] },{ "paper_id": "8b17b1580dd61644c73c3c579212f45640cd107c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cytometric measurements were performed with a BD LSR II flow cytometer (BD Biosciences, San Jose, CA, USA).", "(Continued on next page) (Continued from previous page)", "Microfluidic devices were fabricated using standard soft lithography procedure [26] . A positive mold was created with SU-8-negative resins (MicroChem, Westborough, MA, USA) on silicon wafers (Sil'Tronix, Archamps, France). Replicas were made in polydimethylsiloxane elastomer (SYLGARD\u00ae 184; Dow Corning, Auburn, MI, USA) and were sealed on glass cover slides via plasma activation (Harrick Plasma, Ithaca, NY, USA). The channels were incubated with a 1 % Pluronic F 108 solution (BASF, Florham Park, NJ, USA) for 1 h to deter cell adhesion. Observations were made using an inverted microscope (Axio Observer 200; Carl Zeiss Microscopy, Oberkochen, Germany) equipped with a phase contrast objective (Plan-Neofluar 100\u00d7/1.30 Oil Ph3; Carl Zeiss Microscopy) and a Burle TC65 camera (Burle)." ] },{ "paper_id": "8b1ef7f0f343414329cefb9a014bffcf3f92f117", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was partially supported by Marthaler's start up fund.", "Bocaparvoviruses (BoVs) belong to the genus Bocaparvovirus and are emerging pathogens of the Parvoviridae family. BoVs are nonenveloped, single-stranded DNA viruses with an icosahedral symmetry and were originally named according to their first identified members, bovine parvovirus (BPV) and minute virus of canine (MVC) [1] . In the past few years, novel BoVs have been identified in a variety of animals, including bats [2] , camels [3] , gorillas [4] , marmots [5] , pigs [6] , and rodents [7] . BoVs are comprised of 21 species, including carnivore BoV 1-6, chiropteran BoV 1-4, lagomorph BoV 1, pinniped BoV 1 and 2, primate BoV 1 and 2, and ungulate BoV (UBoV) 1-6. A few new UBoVs have been identified in dromedary camels (tentatively UBoV7 and UBoV8) [3] but have yet to be classified by the International Committee on Taxonomy of Viruses (ICTV).", "Alpaca (Vicugna pacos) are domesticated members of the new world camelids closely related to llama (Lama glama), guanaco (Lama guanicoe), and vicuna (Vicugna vicugna) [13] . Over the past couple of decades, alpacas have gained significant popularity as pets, show animals, and fiber animals in the United States, with a total of 264,587 alpacas registered in the US as of May 2019 [14] . A variety of viruses have been identified in alpacas, including bovine viral diarrhea virus, coronavirus, adenovirus, equine viral arteritis virus, rotavirus, rabies, bluetongue virus, foot-and-mouth disease virus, bovine respiratory syncytial virus, influenza A virus, bovine papillomavirus, vesicular stomatitis virus, parainfluenza-3 virus, West Nile virus, and equine herpesvirus [12, [15] [16] [17] [18] [19] [20] . However, BoVs have yet to be reported in alpacas." ] },{ "paper_id": "8b221945f093d8d13835556a56c2a1d8f02e2705", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thirty-six 1-day-old specific-pathogen-free (SPF) White Leghorn chickens were hatched from eggs (Guangdong Da Hua Nong Animal Health Products Co., Ltd) and housed in isolator cages.", "Three 140-day-old sick yellow chickens with neoplasms (designated SC1, SC2, and SC3) and three 140-day-old normal yellow chickens (designated NC1, NC2, NC3) were collected from the same flock from a farm in Guangdong Province, China.", "Statistical comparisons were made by GraphPad Prism 5 (GraphPad Software Inc., San Diego, CA, USA) and statistical significance was represented by P values of >0.05, <0.05,0.01, or 0.001." ] },{ "paper_id": "8b248d30d63f97ce5c6aa8f1a6c61a8d7f4c914e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Gene amplification: This was done as described by Fouchiers and others [16] .", "The authors declared they have no competing interests. This publication was made possible by support from the President's Emergency Plan for AIDS Relief through cooperative agreement ", "Data analysis: Percentages, means and standard deviations were determined using Microsoft Excel, 2003. Statistical significance was determined using Chi squares test at 95% confidence intervals using Epi-Info version 3.3. Probability level of less than 5% (P<0.05) was accepted as significant." ] },{ "paper_id": "8b25bae266584f12c3b5af9e5cf3e81c84808c36", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.ppat.1007532.g002", "Alexa " ] },{ "paper_id": "8b264d2d749532dff506b14356b606029bb94035", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8b27b57e5226ffb254f5d747bf115690e2c73546", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Much of the difficulty in treating diseases caused by viruses, especially RNA viruses, stems from their high evolutionary potential [39] [40] [41] . Infection of new hosts, adaptation to antivirals, or the emergence of variants that cannot be neutralized by antibodies are only a few examples of the great Pathogens 2019, 8, x FOR PEER REVIEW 4 of 18", "The transfer number at which relative fitness reached a value of 2 was determined through a linear interpolation of the data shown in Figure 3 ." ] },{ "paper_id": "8b30547cc365344758ee0e97c23d673d40302cb2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(S14)" ] },{ "paper_id": "8b33d1cedd5e6f39a2609b233d7070e3ddf52831", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "doi:10.1371/journal.pntd.0004167.g003 (Fig 6A, panel c) ." ] },{ "paper_id": "8b369168263656b024f65707b9bb501d1b75a56e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Pulmonary IAV antigen quantification and viral load in ferrets infected with R11 and R61 pH1N1 viruses. ", "The pathogenic features of severe IAV infection result from complex and dynamic processes that involve various components of the host immune system and their responses to virus-induced changes. Understanding both virus and host response characteristics in individuals who develop mild or severe disease is important for the future development of therapeutic strategies for cases of severe influenza infection.", "Right lung lobe sections (cranial, medial and caudal), nasal turbinate and trachea were taken for histological examination according to standard protocols. The tissues were fixed for 48 h in neutral-buffered 10% formalin, then embedded in paraffin wax, sectioned at 3 \u03bcm, and stained with haematoxylin and eosin (HE) for examination by light microscopy.", "Quantifications of the different inflammatory cell populations for the animals grouped by histopathological score are illustrated in Figure 3 ." ] },{ "paper_id": "8b38aa40712b9033fb9a8c29c35e26aecc0e8a28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations CPE, cytopathic effect; EV71, Enterovirus 71; miRNAs, microRNAs; PSGL-1, P-selectin glycoprotein ligand-1; SCARB2, scavenger receptor class B, member 2; UTR, untranslated region.", "The luciferase activities were measured using a dual-luciferase reporter system (Promega).", "FEBS Open Bio 7 (2017) 747-758 \u00aa" ] },{ "paper_id": "8b47882ebbc8d2e9d217dcc10b2328eff5bf8b46", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mice 10-to 16-week-old female C57BL/6 mice were obtained from Jackson Laboratory. All animal experiments complied with the standards stated in the Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Resources, National Academy of Sciences, Bethesda, MD) and were approved by the Mayo Clinic Institutional Animal Care and Use Committee.", "Conventional western blotting was used to identify PDI in cellular proteins and was described previously. [22] Affinity Measurements by Surface Plasmon Resonance (SPR) SPR measurements were performed at 25\u02daC on a Biacore T200 biosensor (GE Healthcare). PDI full-length protein (Sigma, St. Louis, MO) was immobilized onto a CM5 sensorchip using an amine coupling immobilization kit (GE Healthcare) as instructed by the supplier. After the chip was washed with Biacore running buffer (150 mM NaCl, and 0.005% (w/v) Polysorbate 20, 10 mM HEPES, pH 7.4), peptides ANP, BNP or CNP were injected at 40 ul/min for 30 s and allowed to dissociate for 150 s. Residual bound peptide was desorbed with 350 mM NaCl. Binding kinetics were derived from sensorgrams using Bioevaluation software version 4.1.1 (GE Healthcare).", "Data are expressed as the mean+SEM. Statistical analyses were performed using Student's t test for in vitro studies and one-way ANOVA for in vivo experiments. p,0.05 was considered significant." ] },{ "paper_id": "8b478a28315d64c252456c44fe8ead59d389f615", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "YZ, SJ, and SY designed the experiments. YZ, SJ, and RZ wrote the manuscript. XZ and BC performed the protein purification and crystallization. CW, QW, and WX participated in the viral experiments.", "Crystals were obtained at 16 \u2022 C for 7 days using the hanging drop vapor diffusion method by mixing equal volume of protein solution [LASV-6-HB: 6 mg/mL] and reservoir solution, [0.17 M Ammonium Acetate, 0.085 M Sodium Citrate: HCl, pH 5.6, 25.5% (w/v) PEG 4000, and 15% (v/v) Glycerol]. Then crystals were flash-frozen after immersing in paraffin oil for about 10 s, followed by transfer to liquid nitrogen for further data collection.", "The datasets were collected at beamline BL-18U1, Shanghai Synchrotron Radiation Facility, at a wavelength of 0.97930 \u00c5. The crystals were kept at 100 K during X-ray diffraction data collection. Data were indexed and scaled with HKL2000 (Otwinowski and Minor, 1997) . Phases were solved by the molecular replacement method using PHENIX.phaser (Mccoy, 2007) . All refinement procedures were carried out with PHENIX.refine (Zwart et al., 2008) and COOT (Emsley and Cowtan, 2004) . Table 1 shows the detailed statistics of data collection and refinement. " ] },{ "paper_id": "8b4bf48f0df4492821623ee6951fc65503514846", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "spleen, thymus, liver and bone-marrow derived macrophages [27] . Thus, loss of USP18 catalytic activity cannot be compensated by any other ISG15 isopeptidase. In addition, USP18-mediated deISGylation in vitro is approximately 40-fold faster than deISGylation by the cross-reactive deubiquitinating enzymes (DUB) USP21 [15] raising the question whether deISGylation by Ub/ISG15 cross-reactive DUBs is relevant in vivo.", "of USP18 is in an inactive conformation. Two different conformations for USP18 were crystallised which differ with respect to the orientation of the finger domain. These two conformations represent an open and a closed state, i.e. states compatible and incompatible with ISG15 binding and highlight the flexibility of the finger domain ( Figure 2A) . Likewise, the so-called switching loop in the thumb domain of USP18 occured in an inactive or an active conformation that allows or prevents ISG15 binding, respectively.", "In 2016, Meuwissen et al. [52] described five patients from two families with autosomal recessive loss-of-function mutations in USP18 that resulted in no or abnormal transcription from the mutated allels and a complete lack of the USP18 protein. The patients developed Pseudo-TORCH syndrome that resembles a congenital infection in the absence of an infectious agent and manifests with microcephaly, enlarged ventricles and cerebral calcifications. All patients died within a few days after birth [52] . Patient-derived fibroblasts showed enhanced IFN-induced inflammation and enhanced and prolonged STAT phosphorylation which could be reversed by transduction of cells with wild-type USP18. Based on these findings, USP18 deficiency was classified as a type I interferonopathy and hence as a disease associated with up-regulated interferon signalling [52] . This highlights the critical role of USP18 in negatively regulating type I interferon signalling in humans.", "ISG15 comprises a characteristic hydrophobic patch in the C-terminal domain which is centred around a tryptophan residue (Trp 121 in mouse ISG15) [16] . USP18 accomodates this hydrophobic patch of ISG15 in a shallow pocket on the surface ( Figure 2C and D) . This region was defined as ISG15-binding box1 (IBB-1) and is absent from ubiquitin-deconjugating USPs. Exchanging the residues in IBB-1 of USP18 with those of ubiquitin-specific USP7 rendered USP18 inactive, highlighting the importance of this pocket for the enzymatic activity. Interestingly, IBB-1 in USP18 of fish harbours more polar and hydrophilic residues. This change in surface properties is compensated by an exchange of the residues of the hydrophobic patch (tryptophan and proline in mouse ISG15) with the polar residues arginine and glutamine in fish ISG15. In contrast with mouse and human USP18, fish USP18 cannot only be modified by ISG15-but also with ubiquitin-derived activity-based probes. These probes covalently bind to the active site cysteine in an active DUB. Thus, the hydrophobic nature of IBB-1 is critical for the strict ISG15-specficity in human and mouse USP18." ] },{ "paper_id": "8b4eff9d625d8aa4d5795f4b07a9df388d2acfab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8b585680add23a7959772b785c2cb2afd82db152", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consequently, in combination with these newly developed methods, we believe with the further improvement of sensitivity, selectivity, and reproducibility of GNP-based plasmonic biosensors, plasmonic biosensors will find more impactful applications in biological, biochemical, and medical fields. ", "(2) controlling the interparticle gap distance of GNPs to generate \"hotspots\" for the SERS-based biosensor; (3) controlling the distance between a fluorophore and a GNP for enhancing or quenching the fluorescent signal; and (4) controlling the dispersion stability in a solution for construction of a colorimetric biosensor ( Table 1) .", "The authors declare no conflict of interest. " ] },{ "paper_id": "8b61716032c98b87bbc4276d9fcec91025574467", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Aerobic demands, ROS, nutritional starvation, or virus infections are all physical stressors that challenge cellular homeostasis [37] . Virus exploitation of host cell transcriptional and translational machinery ensures successful replication, but can trigger the unfolded protein response [38] , and dysregulation of cellular homeostatic mechanisms [39] . Therefore, if bats have evolved mechanisms to dampen cellular damage caused by the by-products of heightened aerobic respiration through improved proteostatic mechanisms, then these same proteostatic mechanisms might also function as anti-viral defenses.", "This combination of host-viral richness and apparent lack of clinical disease presentation after NiV, HeV, EBOV, or MARV infection raises the question how novel intrinsic traits or host adaptations might promote tolerance of virus infection in bats [11, 12] .", "Viruses 2019, 11, x FOR PEER REVIEW 6 of 18" ] },{ "paper_id": "8b67993220966ebef79688b594d852e4da9bbadb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SDS-PAGE. Protein samples were mixed with 4\u03eb loading buffer containing 100 mM dithiothreitol (DTT), boiled for 10 min, and separated on a 15% acrylamide gel (35 mA) for 1 h. Gels were stained with Coomassie blue stain. Images were recorded on a UVP MultDoc-IT digital imaging system. A 10-to 180-kDa PageRuler prestained ladder was used for reference.", "Transmission electron microscopy. Samples (5 l, 0.1-mg/ml total protein) were applied to carbon-coated grids (Electron Microscopy Sciences), incubated for 30 s, and washed with distilled water. Grids were stained with 2% uranyl acetate for 20 s. Images were taken on a JEOL 1010 transmission electron microscope at an accelerating voltage of 80 kV to determine particle assembly and purity (17) .", "P22 CP subunit purification. Unassembled P22 coat protein (CP) subunits were generated by combining 2-mg/ml samples of expanded P22 1:1 with 6 M guanidine HCl in PBS and incubating them at room temperature for 1 h. Samples were dialyzed against PBS overnight at 4\u00b0C and used within 24 h of recovery. Complete disassembly was confirmed by SEC-MALS. mFn and PfFn. pET30A plasmids harboring either the murine ferritin (mFn) or P. furiosus ferritin (PfFn) were transformed into ClearColi via electroporation (63) . Expression of the genes was induced in 1-liter LB cultures by addition of isopropyl-\u2424-D-thiogalactopyranoside (IPTG) to a final concentration of 0.3 mM once the cells reached mid-log phase (OD 600 of 0.6). Cultures were grown for 16 h after addition of IPTG, and then the cells were harvested by centrifugation (4,000 rpm at 4\u00b0C) and cell pellets were stored at \u03ea80\u00b0C overnight. Cell pellets were resuspended in Dulbecco's PBS (10 mM sodium phosphate, 138 mM sodium chloride, 2.7 mM potassium chloride, pH 7.4) with lysozyme, DNase, and RNase added and were incubated at room temperature for 30 min. The cell suspension was lysed by sonication. Cellular components were removed by centrifugation at 12,000 \u03eb g for 45 min at 4\u00b0C. Postlysis supernatant was then heated to 60\u00b0C for mFn and 80\u00b0C for PyFn in a hot water bath for 10 min to precipitate E. coli proteins. Aggregated proteins were removed by centrifugation at 12,000 \u03eb g for 20 min at 4\u00b0C. The remaining supernatant was dialyzed into PBS (50 mM sodium phosphate, 1 M sodium chloride, pH 7.4) overnight to facilitate additional removal of nucleic acids. The supernatant was then concentrated by spin filtration and loaded onto a Superose 6 10/300 GL (GE Healthcare Life Sciences) size exclusion column using a Bio-Rad Biologic DuoFlow FPLC. Fractions were checked by SDS-PAGE, and those containing ferritin were pooled and dialyzed into PBS (20 mM sodium phosphate, 50 mM sodium chloride, pH 7.4) overnight. To further remove impurities, ferritin fractions were loaded onto a Fast Q Sepharose ion exchange column (GE Healthcare Life Sciences), and ferritin was eluted with a sodium chloride gradient (PBS [20 mM sodium phosphate, 50 mM sodium chloride, pH 7.4] to PBS [20 mM sodium phosphate, 1 M sodium chloride, pH 7.4]). Fractions were again checked by SDS-PAGE, and those containing pure ferritin were pooled. Combined fractions were then dialyzed into Dulbecco's PBS overnight and stored at 4\u00b0C. All columns and containers were endotoxin free.", "P22 and TMV capsid constructs. The construction of the P22 capsid expression vector has been previously described (62) . For the construction of TMV mutants (D77N and E50Q), the TMV coat protein was purchased as an Escherichia coli codon-optimized gene from GenScript Inc. and cloned in a pRSFDuet vector for expression. Mutations (D77N and E50Q) were introduced through site-directed mutagenesis with the following primers (Eurofins MWG Operon and Integrated DNA Technologies) to create a capsid that does not allow RNA inclusion: TMV-CP D77N FP, CCGGATAGCGACTTCAAAGTTTATCGCTACAATGCC GTTCTGAACCCGCTGG; TMV-CP E50Q, AAAACGCACGGTGACCTGCGGAGACGGTTTCCAGACTTGGCTGAATT GGCGC." ] },{ "paper_id": "8b71af2afcb6a76e746d1a9d77d018d28efd4969", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "FMDV is a major concern for the international trade in animals and animal products, particularly because it can establish subclinical persistent infections in ruminants [3, 4] . Experimental studies with FMDV in cattle have reported 50% to 100% incidence of viral persistence, even in vaccinated animals that were fully protected against clinical disease [5] [6] [7] [8] [9] [10] .", "doi:10.1371/journal.pone.0162750.t002", "All cattle were Holstein breed, between 6 and 8 months of age and weighing approximately 200 kg and were obtained from an experimental livestock provider (Thomas D. Morris Inc., Reisterstown, MD, USA) accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International and licensed by the U.S. Department of Agriculture (USDA). All cattle were bred and raised specifically for research.", ". This is achieved via immune mechanisms that trigger the apoptosis of infected cells followed by phagocytic removal of the apoptotic cells [77] . Phagocyte-mediated clearance of intact apoptotic cells is essential to protect the surrounding tissue against the uncontrolled leakage of cellular contents [78] . Factor H plays an important role in this process by preventing complement activation, membrane attack and cell lysis [71, 79] , and its downregulation in FMDV carriers could lead to an uncontrolled release of infectious viral progeny from apoptotic cells." ] },{ "paper_id": "8b7d76ba81c3eb5ddf6e9330e16ce1189fe1f08b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "EVs (10 \u03bcl) were applied to a formvar/carbon-coated grid for 5 min; after blotting, the grid was stained with 2% aqueous uranyl acetate for 1 min. After blotting, the grids were air-dried and examined under TEM (HITA-CHI, H-7500, Japan).", "A 10% (w/v) lung homogenate was prepared from left apical lobe lung tissue and virus titer was determined by titration in MDCK cells as described [33] . Virus titers were calculated by the Reed and Muench method.", "(Continued on next page)", "Five-week-old conventional large White-Duroc crossbred pigs were obtained from the OSU herd. Maintenance of pigs and all experimental procedures were conducted in accordance with the guidelines of the Institutional Laboratory Animal Care and Use Committee, The Ohio State University (protocol #2014A00000040)." ] },{ "paper_id": "8b86e36ed4cc2b952e49ea978844332007c00439", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. The decolonialisation of many nations, including those in Africa, the Middle East, Asia, Latin America and the Caribbean;", "Against this backdrop of political, social and civil societal change, the nature, speed and access to international travel has also undergone marked evolution. Travel patterns have been affected by changes in transportation technology, accessibility, and affordability. Growth in air travel has functionally reduced previous limits on the rapid international movement of large numbers of individuals. In 1960, there were approximately 70 million international journeys globally. The number of similar international journeys in 2004 was in excess of 760 million [59] . The high volume of international travel supports greater population exchange and return flows between migrant origin and destination locations.", "2. Large refugee movements following conflicts and civil disturbances, including South East Asia, the Balkans, Central America and Central Africa; and", "3. The political, social and economic consequences of the collapse of the former Soviet Union." ] },{ "paper_id": "8b8eca79a2c4625f1ebc17b342a1755253ba473f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Commons Attribution License (CC BY 4.0).", "Profiling. Cells were first treated with cycloheximide (100 g/mL) for 3 min at 37 \u2218 C to immobilize the translating ribosomes. After ice-cold PBS solution wash, CAAGCAGAAGACGGCATACGATT TTTTTTTTTTT-TTTTTTTVN-3 ; LGT03, 5 -pGTGATCGTCGGACTGTAGAACTCT\u00d8-CAAGCAGAAGACGGCATACGATT TTTTTTTTTTT-TTTTTTTVN-3 ;", "YAG04, 5 -pAGGATCGTCGGACTGTAGAACTCT\u00d8-CAAGCAGAAGACGGCATACGATT TTTTTTTTTTT-TTTTTTTVN-3 ;" ] },{ "paper_id": "8b9727ae8713013fe82481d87cf57529201353d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8b9bec3c317211d347532e8991d2494098d16dc2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dengue virus (DENV) is a positive-stranded RNA virus of the family Flaviviridae. It is composed of a group of four serotypes (DENV1-4). DENV is transmitted to vertebrate hosts via the mosquito vectors Aedes aegypti or Aedes albopictus. Infection with DENV can lead to a spectrum of clinical diseases ranging from subclinical infection to dengue fever to the most severe forms, dengue hemorrhagic fever and dengue shock syndrome [25] . Globally, there are an estimated 50-100 million infections annually, making DENV the most important arbovirus to human disease [26] . Due in part to the large impact on human health, basic research on DENV has expanded in recent years.", "Complementary immuno-EM studies demonstrated that the viral replicase proteins are present on the ER invaginations as well as double-stranded RNA, the viral replication intermediate [35] .", "Following these initial characterizations of DENV-induced autophagy, an electron tomography study was performed by Welsch et al. which showed the 3D structure of DENV2 replication complexes in hepatocytes [35] . While traditional thin section EM appears to show virally induced replication complexes to be a cluster of independent double membrane vesicles [36] , the 3D reconstruction clearly showed that these vesicles were actually contiguous invaginations of the ER.", "Soon after this publication, work from the same lab (Khakpoor et al.) examined the role of autophagy in DENV3 infection [32] . Similar to DENV2, DENV3 infection also induced and required autophagy. LAMP1 was observed to co-localize with autophagosomes, but in contrast to the previous DENV2 study, treatment with a lysosomal fusion inhibitor decreased DENV3 replication. This indicated a role for mature autolysosomes in DENV3 infection. The mechanism for how autolysosomes could contribute to viral replication remained unclear." ] },{ "paper_id": "8ba20a12c92103d82364b8abca49cfcd91d91c13", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For microarray printing, polysaccharides and glycoproteins were dissolved in saline and lipids were prepared as liposomes as described [29] [30] [31] [32] . Antigen solutions or liposome suspensions were spotted onto nitrocellulose-coated FAST slides (Schleicher & Schuell) by a high-precision robot designed to produce cDNA microarrays (Cartesian Technologies' PixSys 5500C). Immediately before use, the printed microarray slides were washed in 1xPBS at room temperature (RT) for 5 min and blocked with 1% BSA-PBS at RT for 30 min. They were incubated with 50 \u03bcl of sera (1:25) at RT for 1 hour, washed and then incubated with titrated secondary anti-human IgG antibodies coupled with Cy3 at RT for 30 min. The stained slides were then rinsed five times and air-dried at RT before being scanned. The ScanArray5000A Microarray Scanner (PerkinElmer Life Science) was used to scan the stained microarrays for fluorescent signals. Fluorescent intensity values for each array spot and its background were calculated using ScanArray Express software (PerkinElmer Life Science).", "Padler-Karavani et al. [15] found that human carcinomas can metabolically incorporate the dietary non-human sialic acid Neu5Gc. That monosaccharide differs from the human sialic acid N-acetylneuraminic acid (Neu5Ac) by one oxygen atom but is able to trigger a differential antibody response. Using a novel sialoglycan microarray presenting multiple Neu5Gc-glycans and control Neu5Ac-glycans, these investigators found that antibodies against Neu5Gcalpha2-6GalNAc\u03b21-O-Ser/Thr (GcSTn) are more prominent in patients with carcinomas than in patients with other diseases. Thus, these xeno-autoantibodies and xenoautoantigens are considered potential targets for diagnostic, prognostic and therapeutic applications in human carcinomas.", "Refer to Web version on PubMed Central for supplementary material." ] },{ "paper_id": "8ba5919b2b4c229c9c1685852cf19a1d727ac220", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The concept of using genetically modified infectious agents to deliver antigens to wildlife is not new. Recombinant vaccinia virus expressing rabies glycoprotein delivered in baits to wild foxes has proved to be a highly effective strategy to combat rabies [5] . Since then other vaccines developed against diseases of wildlife include a rabies virus based vector used to immunise wildlife against SARS [6] . Extension of this concept has seen recombinant viruses developed to control a host's biological processes. An example is recombinant viruses expressing zona pellucida antigen that successfully deliver immunocontraception to pest animal species in laboratory trials [7, 8] .", "BIV was detected in all of the infected groups, with more infected animals detected as the inoculum increased. The control " ] },{ "paper_id": "8badcfcd8aba68dceea84099e3d0f733e050109f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The findings indicate that CAstVs commonly circulate in pet dogs, and our sequencing results have shown the genomic diversity of CAstVs leading to increasing number of clusters.", "Background: Astroviruses (AstVs) have been reported to infect and cause gastroenteritis in most animal species. Human AstVs were regarded the causative agent of viral diarrhea in children. In dogs, little is known about the epidemiology and clinical significance of AstV infection. Findings: In this study, we collected and tested 253 rectal swabs from pet dogs; of which 64 samples (25.3%) tested positive for AstVs with diarrhea and 15 more samples (5.9%) also was identified as AstVs, however without any clinical signs. Phylogenetic analysis of 39 partial ORF1b sequences from these samples revealed that they are similar to AstVs, which can be subdivided into three lineages. Interestingly, out of the 39 isolates sequenced, 16 isolates are shown to be in the Mamastrovirus 5/canine astrovirus (CAstV) lineage and the remaining 23 isolates displayed higher similarities with known porcine astrovirus (PoAstV) 5 and 2. Further, analysis of 13 capsid sequences from these isolates showed that they are closely clustered with Chinese or Italy CAstV isolates.", "Canine astrovirus (CAstV) was first identified in the early 1980s and recently, it was characterized as a distinct Mamastrovirus species, which is the causative agent of gastroenteritis in pet dogs [10] [11] [12] . Evidently, CAstVs has spread widely in the dog population and produced higher genetic diverse, as shown Martella et al., where a novel CAstV was identified from dogs with gastroenteritis [13] . However, data on the clinical significance or association of astrovirus infection with other infectious diseases are limited. The aim of our study was to understand the prevalence, genetic diversity and evaluate the risk factors of co-infection with other infectious diseases from the samples collected." ] },{ "paper_id": "8bae8e6308d50b3a053a98be3b0fd641c775c1ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "agaAY (SSU05_1258/9), bgaC (SSU05_0449), and gad-VWEF (SSU05_0450, SSU05_0451, SSU05_0452 and SSU05_0453), respectively.", "984" ] },{ "paper_id": "8bb39b846b0bd9548526bad9e74fed1e4a8ac4cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Discs (3 mm) from FTA cards were incubated at 4\u00b0C for 24 h in 1 mL of phosphate-buffered saline (PBS).", "The aim of this study was to detect and characterize chicken respiratory viruses found in commercial Pakistan poultry, which is the first step of control measures implementation. Five major chicken respiratory viruses were investigated: AIV, AAVV-1, IBV, aMPV and ILTV.", "The main limitations of this study are (i) the type of samples collected (no virus isolation is possible from FTA cards), (ii) the thus limited amount of viral nucleic acids, and (iii) the limited knowledge available on most avian viruses circulating in the country for comparison. Further studies are warranted to fully characterize the virus strains and evaluate vaccines efficacy to counter the different pathogens." ] },{ "paper_id": "8bb5f822c7bae1c50b1d5b7a9da329a1f9d8aee2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The antibodies used for immunoblotting were rabbit polyclonal C1038 antibody against total TDP-43 [28] , rabbit monoclonal anti histone H3 (Cell Signaling #4499P, Danvers, MA), and rat monoclonal anti HSP90 (Enzo 16F1, Farmingdale, NY). Immunoblots were visualized using an Oddysey Sa Infrared Imaging System (LiCor, Lincoln, NE) after application of fluorescent secondary antibodies (LiCor).", "Animal care and performed procedures were in accordance with the NIH Guide for the Care and Use of Experimental Animals and approved by the University of Pennsylvania Institutional Animal Care and Use Committee (Permit Number: 803385).", "Conceived and designed the experiments: EBL LSW VML JQT LKK AAW. Performed the experiments: AAW YX ES ID. Analyzed the data: AAW PR RT EBL. Contributed reagents/ materials/analysis tools: BDG VVD JQT VML EBL. Wrote the paper: AAW EBL LSW LKK VML JQT." ] },{ "paper_id": "8bb9d8f7eeb8272924275f349e5c63a5bb006445", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasmids containing wild-type (pFS-cass5) and mutant (pFS-cass5.15) pseudoknot sequences from IBV genomic RNA were generous gifts form Dr. Ian Brierley (University of Cambridge) [3] . Bovine ANXA2 cDNA was kindly provided by Dr. Anni Vedeler (University of Bergen) [12] .", "Construction of ANXA2 expression clone and RNA interference cDNA for ANXA2 was polymerase chain reaction (PCR)amplified and ligated into pCMV-Tag2B vector (stratagene). ANXA2 was amplified with primers 59 -CAGGATCCATGTC-TACCGTTCA-39 and 59 -CCGAATTCTCAGTCATCCCCA-C-39. To knock-down ANXA2 mRNA, small hairpin RNA (shRNA) was designed using the Ambion small interfering RNA (siRNA) converter website. The ANXA2 target sequence was 59-UGCAUAUGGGUCUGUCAA-39 corresponded to coding region nucleotides 66-83. To make pSUPER-ANXA2 (shANX2-1), specific oligonucleotides were synthesized (Bioneer, Korea) and ligated to pSUPER vector as previously reported [45] . Also, two different siRNAs corresponding to coding region nucleotides 109-129 (siANX2-2: 59-CGGGAUGCUUUGAACAUUGAA-39) and 772-792 (siANX2-3: 59-AACCUGGUUCAGUGCAUUCAG-39) were designed. siRNA duplex were chemically synthesized and contain dTdT 39 overhangs (Bioneer, Korea).", "Human embryonic kidney cell line HEK293T were purchased from the American Type Culture Collection (ATCC) and maintained in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum (FBS; BRL Life Technology). Human prostate cancer cell line LNCaP were purchased from the ATCC and cultured in RPMI1640 with 10% FBS. Human lung fibroblast IMR90 and human lung adenocarcinoma SK-Lu I cells were purchased from ATCC and cultured in MEM containing 10% FBS using standard techniques." ] },{ "paper_id": "8bcd1c3897124adec322dffb8a315fc4e24cb17e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8bcd86c97a06dbdff096f6cb164f9dab35f879f9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: In March of 2003, an outbreak of Severe Acute Respiratory Syndrome (SARS) occurred in Northern Vietnam. This outbreak began when a traveler arriving from Hong Kong sought medical care at a small hospital (Hospital A) in Hanoi, initiating a serious and substantial transmission event within the hospital, and subsequent limited spread within the community.", "Exposure and demographic variables used for analyses were dichotomous categorical; unknown or missing data was rendered as a negative response. Non-parametric tests (Fisher's exact, Cochran's Chi-square) or odds ratios (OR) with 95% confidence intervals (CI) were used to assess differences between groups using negative responses as the referent. The threshold for statistical significance was established at a p-value < 0.05.", "Results of the survey regarding symptoms of illness experienced by study participants are summarized in Figure 3 ." ] },{ "paper_id": "8bcded9bf20651adee9df9dc56030291f0b881fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8be33a516142d0fa91dd2355a5d41a5357895188", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.ppat.1006473.g005", "SINV.nt9300F 5'-GCACCGCCATCAAGCAATGTGTGGC-3'; SINV.nt9300R 5'-CAATTTC CCTTGGGCCGTGTGGTCG-3';" ] },{ "paper_id": "8be925093133c499cb2c93e36d9bf0fdb24c2eda", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8be9f1b18de44f61ed5a342dac1e47d12c943dca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We initialize the starting distribution over N network nodes of the Markov chain as:", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.pcbi.1007587.g001" ] },{ "paper_id": "8befdc2bb43130a5e90c11061e8bc8955718a825", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The NHC addressed internal and external coordination issues by establishing cross-cutting response mechanisms. The Department coordination system of NHC synchronizes 31 different relevant departments that all play a part in emerging infectious disease response. The system focuses on information sharing, prevention activities, training and drills [8] . These activities and an ongoing coordination effort better prepared China prior to the next public health emergency.", "A picture is worth a thousand words, experience is worth a million ", "China is the world's most populous country with approximately 1.374 billion people [24] in a landmass nearly the size of the U.S. To change risk communication policy, it's natural to work with national level ministries, but for practice to be well absorbed into the health response system throughout the nation it had to be adopted at provincial and sub-provincial levels." ] },{ "paper_id": "8befe1b5905e502b127ae478f3b9de1d6e25e317", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "synapses to provide a means by which the virus can cross the biophysical and immunological obstacles to infection [4] . The membrane penetration mechanism differs fundamentally in non-enveloped viruses, but similar strategies are used for their entry [5] . In general, enveloped animal viruses possess greater adaptability than non-enveloped animal viruses, and consequently, cause a number of severe diseases, such as acquired immunodeficiency syndrome (AIDS), influenza, severe acute respiratory syndrome (SARS), hemorrhagic fever, hepatitis, encephalitis, and microcephaly.", "Below, we will focus on the roles of ERAD played in virus replication, which is the main target of this review. " ] },{ "paper_id": "8bf3d561863300dbcb9ba92ad94807dfb8775f7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2) neurological diseases (Alzheimer's disease, Parkinson's disease, ischemia, central nerve system injury): a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), \u03b3-secretase, \u03b2-secretase 1, and MMP-24; (3) inflammation (arthritis, chronic obstructive pulmonary disease (COPD), asthma, Crohn's disease, inflammatory bowel disease, colitis, diverticulitis, chronic liver disease): MMPs, cathepsins, neutrophil elastase, and ADAM17; (4) blood coagulation: thrombin, factor Xa; (5) diabetes: dipeptidyl peptidase 4 (DPP4); (6) cardiovascular disease (atherosclerosis, hypertension, cardiomyopathy, congestive heart failure, myocardial infarction, neovascularization and cardiac remodeling, cardiac fibrosis, aneurism, ischemia-reperfusion injury): angiotensin converting enzyme, renin, MMPs, chymase, neprilysin, calpain; (7) osteoporosis: cathepsin K; and (8) autoimmune diseases (multiple sclerosis, lupus, Guillain-Barre syndrome, psoriasis): activated protein C, kallikreins; ageing (skin), MMPs, neutrophil elastase [1, 2] .", "Author Contributions: K.C., Y.K., S.L., A.D.R. and W.C.G. carried out the experiments and K.C., Y.K. and W.C.G. wrote the manuscript.", "The authors declare no conflict of interest." ] },{ "paper_id": "8bf449477aff84ef0591f10731a654610a5126b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Small hairpin RNAs interference and lentivirus construct. We used pGLV-U6-EGFP (pGLV1-1) containing U6 expression cassette, an RNA polymerase III-dependent transcription of shRNA transcript. This vector also expressed green fluorescent protein from a cytomegalovirus promoter, which allowed for monitoring of the transfection efficiency. Small hairpin RNAs were designed to contain 21-nucleotide sense sequences identical to the target molecule(s), followed by a short (7-nucleotide) nonspecific loop sequence and an antisense sequence, followed by two thymidines, which served as a stop signal for RNA polymerase III. The TACE target sequence consisted of 4 duplex sequences of target-specific 21nt siRNAs including: 5\u2032 -atagagccactttggagattt-3\u2032 , 5\u2032 -ggatttaaaggttatggaata-3\u2032 , 5\u2032 -ggacttcttcagtggacatgt-3\u2032 , 5\u2032 -ggaacacttcatgggacaatg -3\u2032 in TACE splice variant. As a control, we used 21-nucleotide scrambled small hairpin RNA, which did not give more than an 18-nucleotide match against any rabbit genomic sequence. The oligonucleotides were annealed and cloned into pGLV1-1 between the HpaI and XhoI sites. The vector was transfected into 293T cells together with the viral packaging vectors by GenePhama, Shanghai, China. ", "Quantification of Neovascularization. Neovessels were identified as channels surrounded by a layer of endothelial cells highlighted by immunostaining with anti-CD31 antibody. We calculated the adventitia neovessels in the area encircling the EEL within one \u00d7 200 optical field. All neovessels in the section were counted by two observers by use of fields at \u00d7 200 magnification with Image Pro-plus (Media Cybernetics, USA).", "ELISA and biochemical assay. Soluble inflammatory factors of the plasma were measured by ELISA assay and biochemical assay was conducted in accordance with the manufacturer's instruction." ] },{ "paper_id": "8c02fccc9fb52bd1be9498cdf8dda1f4a39962a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8c17c17e58e174ba99b3964a2ddd1a0a4b9a35d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8c2cfca9f2eee4a00231a2a3a2cfe1e60e798672", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lymphocytes were cultured and purified as described previously [31] . Briefly, PBMCs were purified on a density gradient and splenocyte cultures were obtained by passage through a cell strainer (BD Pharmingen). IPV for stimulation were all used at 2 mg/mL. Supernatants from triplicate cultures (2610 5 cells per well) were harvested from cultures after 72 h of incubation for the investigation of cytokines.", "Studies were performed with 6-to 8-wk-old female CB6F1 C57BL/6xBALB/c mice from Harlan, Scandinavia. Animals were housed in appropriate animal facilities at Statens Serum Institut.", "A sandwich ELISA was used to determine the concentration of IFN-c in culture supernatants as previously described [31] . Alternatively, the cytokines were analyzed by Multiplex cytokine assay." ] },{ "paper_id": "8c2e819ffac93b6796d3d9fdf7ccc8e67c397a31", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In domain swapping, a protein molecule exchanges its structural region with the corresponding region of another molecule of the same protein. Domain swapping was first reported by Eisenberg and co-workers for diphtheria toxin in 1994 1 . Since then, domain swapping has been reported for many proteins [2] [3] [4] . For example, ribonuclease (RNase) A swaps its N-terminal \u03b1 -helix or C-terminal \u03b2 -strand, forming two different domain-swapped structures 5, 6 . The domain swapping of RNase A occurs during folding from its partially unfolded state 7 .", "Preparation of HT apo cyt c 552 . WT and quintuple mutant HT apo cyt c 552 were prepared according to the published method 43, 44 . A detailed description of the procedures can be found in supplementary information.", "Similarly, serine protease inhibitors antithrombin and \u03b1 1 -antitrypsin also form oligomers by domain swapping 30, 31 . A disulfide variant of \u03b1 1 -antitrypsin has been shown to form oligomers in two model-cell systems, Pichia pastoris and COS-7 tissue culture cell, by trapping the domain-swapped structure 31 . When the C-terminal domain of severe acute respiratory syndrome coronavirus main protease (M pro -C) was expressed in Escherichia coli (E. coli), domain-swapped dimers were observed in addition to monomers 32, 33 . The monomer-to-dimer ratio of M pro -C was three to two when purified from E. coli, whereas it was nine to one for the equilibrium at 37 \u00b0C in vitro 34 . Domain swapping has also induced two types of splicing when intein was expressed in E. coli 35 ." ] },{ "paper_id": "8c2f3b308f203b56e322c637bd1eec3e228fa524", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "8c34e09a2de5c62460eaf9258b999db404719dcb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Either the Student's or the Welch's t-test was applied to analyze differences between mean values in all parameters. Values are shown as mean \u00b1 SE. Differences between mean values were considered significant at P < 0.05 and a tendency to be significant at P < 0.1 in all statistical analyses. All calculations were made using Statcel3 (OMS, Tokyo, Japan) as add-in application for Microsoft Excel \u00ae (Microsoft, Seattle, WA, USA).", "This experiment was approved by the ethical committee of Inatomi Animal Hospital in Japan. Takio Inatomi belongs to Inatomi Animal Hospital informed consent to animal owners. Improvement of PED Symptom by Probiotic Administration Frontiers in Immunology | www.frontiersin.org", "reFerences" ] },{ "paper_id": "8c401abe39d57c49059788cdc3b95bbcceaa7d40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hemorrhagic bowel syndrome JHS:", "FACH: Food animal and camelid hospital HBS:", "Jejunal hemorrhage syndrome TMR: Total mixed ration." ] },{ "paper_id": "8c433501a618d6a3f93463393f4ce58007abec95", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "E-mail address: ncespedes@inmuno.org (C\u00e9spedes N), avallejo@inmuno.org (Vallejo A), marevalo@inmuno.org (Arevalo-Heerera M), sherrera@inmuno.org (Herrera S ) Colombia M\u00e9dica colombiamedica.univalle.edu.co", "La malaria es una de las enfermedades transmisibles de mayor impacto socio-econ\u00f3mico a escala mundial, y es inducida por par\u00e1sitos del g\u00e9nero Plasmodium transmitidos por mosquitos del genero Anopheles. El Plasmodium vivax ocupa el segundo lugar en prevalencia mundial, pero es la especie m\u00e1s frecuente en Am\u00e9rica Latina y otras regiones del planeta. Se considera que las vacunas representan una estrategia costo-efectiva para el control de enfermedades transmisibles y que podr\u00edan complementar las dem\u00e1s medidas de control de la malaria; sin embargo, la complejidad qu\u00edmica e inmunol\u00f3gica del parasito han dificultado el desarrollo de vacunas efectivas. La reciente accesibilidad a los genomas de varias especies de Plasmodium, y el desarrollo de herramientas bioinform\u00e1ticas est\u00e1n permitiendo la selecci\u00f3n de numerosas prote\u00ednas y el an\u00e1lisis de su potencial inmunol\u00f3gico. Aqu\u00ed revisamos las estrategias recientes para el descubrimiento de nuevos ant\u00edgenos para el desarrollo vacunas contra la malaria. N\u00ba 2, 2013 (Apr-Jun) C\u00e9spedes ", "The authors declare that there is no real or potential conflict of interest regarding the possible publication of this work." ] },{ "paper_id": "8c43b5c8a56828ee5687a2b572dc05333c2815a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 2014 International Symposium on HIV and Emerging Infectious Diseases (ISHEID) was held in Marseille, France, on May 21-23. This meeting attracted more than 900 delegates from all over the world (75% outside France) and allowed interactive discussions around HIV, viral hepatitis, new influenza strains, MERS-CoV and Chikungunya infection. In this article we focus on some aspects of these discussions.", "There are key factors in deciding to treat a patient or to wait. Patients' factors include urgency to treat, likelihood of response, HCV genotype, treatment experience, IL28B genotype, degree of fibrosis and patient motivation. Treatment factors include efficacy of current options, safety of current options, duration of therapy, pill burden, dosing frequency, future options and their timelines, access and cost.", "As exposed by Bruno Lina [47] , humans are usually not infected by avian influenza A viruses from aquatic wild birds. However, sporadic cases of avian influenza virus infection are observed every year, mostly in Asia. By subsequent adaptation of these emerging viruses may result into human pandemic strains.", "A lecture on new anti HCV agents by Fabien Zoulim [43] made clear that pharmaceutical companies are still active in this area. Professor Vicente Soriano [44] spoke about treatment of co-infected HCV/HIV patients and expressed hope that Sofosbuvir (SOF) would represent a huge improvement in our ability to treat HCV. Professor Marc Bourliere [45] spoke about new anti-HCV drugs would limit the use of the much more toxic Interferon/ (IFN)/Ribivirin(RBV) approach that has dominated the field for decades." ] },{ "paper_id": "8c4450ec40a0642f9c28bb561ae210baacc032fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using GraphPad Prism version 5.00 for Windows, GraphPad Software, San Diego California USA, www.graphpad.com and p value < 0.05 was considered as indicative of statistical significance. One-way ANOVA and t-test analyses were performed. ", "THP-1 monocytic cell line was maintained in suspension in RPMI 1640 medium, supplemented with 1% L-glutamine, 1% sodium pyruvate, 50 \u03bcM \u03b2-mercaptoethanol, 10% fetal bovine serum (FBS) and antibiotics (10,000 U/ml penicillin and 10,000 \u03bcg/ml Streptomycin) [33] . For differentiation experiments, THP-1 cells were seeded at a final density of 1\u00d710 6 cells/ml in 6-well plates. Cell differentiation was induced by 10 ng/ml phorbol 12-myristate 13-acetate (PMA) (Sigma-Aldrich) to the medium. Differentiated (adherent) THP-1 macrophages were used for infection experiments. Peripheral Blood Mononuclear Cells (PBMCs) were isolated from buffy coats obtained from human peripheral blood of healthy donors by Ficoll density gradient centrifugation. Monocytes were selected by adherence to plastic in RPMI for 2 hours.", "GCTGGCCTCCTTGATGAATA3' and 5' TTGGGCTCCATAAAGTCACC3'; DPP4: 5' GGTTCTGCTGAACAAAGGCA 3' and 5' TCTCCAAGAAAACTGAGCTGT 3'. Actin-b was used www.impactjournals.com/oncotarget as a reference gene: 5' GCCGTGCTGTCCCTCTAC 3' and 5' AGCGCG TAGCCCTCATAAAT -3' . Denaturation was carried out at 95\u00b0C for 20 seconds, annealing at 60\u00b0C for 15 seconds and extension at 72\u00b0C for 30 seconds, for 40 cycles.", "Transient transfection was performed using the Lipofectamine Reagent (RNAiMAX, Life Technologies) as per manufacturer's instructions. In short, THP1 cells with PMA added were seeded at approximately 80% confluency. The next day silencing RNA molecules (siRNA) were used at a final concentration of 20nM to transfect the cells. Cells were cultured for 24 hours in the presence of the transfection reagents prior to infection and LPS treatment, the following, pre-validated siRNAs used were: IRAK-M siRNA (sc-39098, Santa-Cruz), PPAR\u03b3 siRNA (sc-29455, Santa-Cruz), CD26 siRNA (sc-42762, Santa-Cruz) and Silencer Negative Control (SCR) siRNA (AM4611g, Ambion).", "The S glycoprotein of MERS-CoV binds on DPP4 receptor allowing its entry into the host cell. Our studies showed that this interaction does not only facilitate viral entry but it also initiated signals that mediated immunosuppressive action to allow the virus to propagate itself. This immunosuppression may account for increased pathogenicity of the virus." ] },{ "paper_id": "8c44e37bccf0c2a493e1b1754081384fc802d3d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Metabolomics aims to measure and characterise the complex composition of metabolites in a biological system. Metabolomics studies involve sophisticated analytical techniques such as mass spectrometry and nuclear magnetic resonance spectroscopy, and generate large amounts of 2 of 55 high-dimensional and complex experimental data. Open source processing and analysis tools are of major interest in light of innovative, open and reproducible science. The scientific community has developed a wide range of open source software, providing freely available advanced processing and analysis approaches. The programming and statistics environment R has emerged as one of the most popular environments to process and analyse Metabolomics datasets. A major benefit of such an environment is the possibility of connecting different tools into more complex workflows. Combining reusable data processing R scripts with the experimental data thus allows for open, reproducible research. This review provides an extensive overview of existing packages in R for different steps in a typical computational metabolomics workflow, including data processing, biostatistics, metabolite annotation and identification, and biochemical network and pathway analysis. Multifunctional workflows, possible user interfaces and integration into workflow management systems are also reviewed. In total, this review summarises more than two hundred metabolomics specific packages primarily available on CRAN, Bioconductor and GitHub.", "Once the analytical data has been pre-processed, it is generally subjected to different statistical approaches to find features that are \"interesting\" in the context of the experimental design, e.g., differentiating diseased patients from healthy controls." ] },{ "paper_id": "8c5bd7a3606dc60cc568fb2614c8a5bdc00bffbb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8c640872048570b0a671ec08c83ef6cbebcdd78e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each reaction was run in duplicate, whereby a no-template control was included." ] },{ "paper_id": "8c6ca63f974a55bcab6f773fc9cda85c938b93eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were done using Epi Info\u2122 7.1.3 (Centers for Disease Control and Prevention, Atlanta, Georgia) and Stat 13.0 (StataCorp). All tests were 2-tailed and a p-value of less than 0.05 was considered significant." ] },{ "paper_id": "8c6dd0cad7b723b44a8b557ca0f67d1ee38d88fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Another major challenge to the control of DURC information is the emergence of preprint servers in biology that allow the posting of research findings before peer review and the proliferation of predatory open access journals that will publish essentially any paper for a fee. Consequently, there now exist alternative systems for publication even if standard journals decline to publish a particular article over DURC concerns. Bypassing traditional publication methods could also allow authors to avoid government scrutiny.", "Against this backdrop of dissatisfaction is the fact that science continues to progress very rapidly, introducing new technologies such CRISPR/Cas9, gene drives, and more efficient synthetic biology, each of which brings with it new possibilities for research that improves the human condition as well as new tools for nefarious purposes. Furthermore, as the technologies improve they are increasingly accessible to more individuals and countries for whom this type of research was previously beyond reach. Hence, the problem of DURC is likely to become significantly more urgent in the near future.", "revolution in the late twentieth century that the potential of biology, and in particular microbiology, in biological warfare and terrorism came into focus. These fears came true with a single act of terrorism involving the mailing of anthrax spores in the U.S. in 2001, which caused several deaths and considerable disruption to government facilities such as congressional offices and the postal system (Bush and Perez, 2012) . This act of bioterrorism catalyzed a series of events that led to greater awareness of the potential of using biological knowledge in nefarious ways, new regulations in biological research in the U.S. such as the Select Agents and Toxins list, and heighted concerns about some types of microbiology research." ] },{ "paper_id": "8c701ddbdb052d08eabd99191bd51916a2656ef4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Questionnaire S1 Survey Questionnaire. (DOC)" ] },{ "paper_id": "8c71f856263c447ba7983e1f7087259008ca8505", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recombination analysis. The putative recombinant sequence and its parent sequences were identified using the SimPlot 29 and RDP 3.0 30 software packages, as previously reported 31 . Analyses were also carried out with the Bootscan program in SimPlot using the putative recombinant sequence as a query. Mosaicism is suspected when high levels of phylogenetic relatedness are obtained between the query sequence and more than one reference sequence in different genomic regions. Finally, recombination breakpoints were analyzed by maximizing \u03c7 2 , employing a combination of SimPlot and RDP 3.0." ] },{ "paper_id": "8c73602b18bc6b2fb17e8f37552995f6e310c6fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Non-small cell lung cancer (NCI-H460)", "Active Compound", "(RANTES), IP-10 (CXCL10) production " ] },{ "paper_id": "8c78151fa23bf78cc20b2e2c5c0b47d79d12a1a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hits s N s" ] },{ "paper_id": "8c9382eed553c5cbe1de32cd4dc4c9975250e274", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "if individual j is a primary=background case;", "b\u00f0E j \u00de; if c j 2 w I at time E j :" ] },{ "paper_id": "8c97d3d01a4d77e5f4f458ed46ba5399f3647a74", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu. 2018.02640/full#supplementary-material", "SH and JD co-wrote the manuscript. SH, JD, and MP designed the figures and table. KC and MP edited and provided critical revisions of the manuscript. All authors approve the final version and agree to be accountable for the content of the manuscript.", "JD is supported by a research grant from the National Institutes of Health (grant no. R01HL108949). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US government. We thank Cat Meyer for her assistance with the figures." ] },{ "paper_id": "8c9c650f233ed3a031c995a887d8dfbc8b41e78c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CRFK cells and HEK293T cells (American Type Culture Collection, ATCC) were grown in Dulbecco's modified Eagle medium (DMEM; Gibco, Thermo Fisher Scientific, Waltham, MA, USA) containing 8% fetal bovine serum (FBS). The cells were incubated at 37 \u2022 C in a 5% CO2 humidified cabinet.", "Antibodies, namely, mouse anti-Myc (catalogue no. Ab56), rabbit anti-Myc (catalogue no. ab9106), rabbit anti-NEMO (catalogue no. ab188569), rabbit anti-IRF3 (catalogue no. ab68481), and rabbit anti-IRF3 (phospho-S386) (catalogue no. ab76493) were purchased from Abcam. Antibodies, namely, mouse anti-HA and mouse anti-Flag (catalogue no. 62216), were purchased from Sigma. The mouse anti-N polyclonal antibodies were prepared by our laboratory. Briefly, the complete N gene was amplified using a forward primer (5 TTT GGA TCC ATG GCC AAC CAG GGA CAA CGC 3 ) and a reverse primer (5 TTT GCG GCC GCTTA GTT CGT TAC CTC ATC AAT 3 ). Then, the products were cloned into the vector pGEX6p-1. Purified GST-N recombinant protein was used as an antigen to inject female BALB/c mice. After three immunizations, serum was collected and stored at -80 \u2022 C. The caspase inhibitor Z-VAD-FMK, the proteasome inhibitor MG132, and the lysosome inhibitor NH4Cl were purchased from MCE.", "The FIPV strain DF2 and Sendai virus (SEV) were obtained from ATCC." ] },{ "paper_id": "8ca0739bd39a043e0e9e2f67f58e899497d2658e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The endotoxin free pcDNA3 plasmids encoding or not pseudorabies virus glycoprotein B (PrV-gB-pcDNA3) were produced and purified as previously described [9, 17] .", "host DNA since the probability of integration is low (<30,000 copies of plasmid/ g of host DNA).", "long, and 10 mm apart) introduced on either side of the injection point of pigs of groups 2 to 4. The electric current was applied with a BTX ECM 830 pulse generator (Harvard Apparatus, Holliston, MA, USA). Pigs were observed daily. Body temperature and body weight were measured daily and weekly, respectively. Pigs were sacrificed six weeks after injection. The muscle injection site identified through the tattooed dots was sampled using a disposable 2 cm long and 0.8 cm diameter biopsy punch (Figure 2 ), frozen in liquid nitrogen, and stored at \u221280 \u2218 C until DNA extraction.", "Prior to DNA extraction, the 2 cm long pieces of muscle excised were divided into six equal samples (from the superior to the inferior part of the muscle). Each muscle fraction was weighed and resuspended in PBS buffer according to the measured mass. Then homogenization was carried out using a Teflon pestle at 30 Hz for 1 min or until all major tissue clumps were dispersed. Host DNA extractions were performed on 30 mg of the homogenized tissue sample using the QIAamp DNA Mini Kit (Qiagen) after overnight proteinase digestion according to the manufacturer's instructions. Thereafter, plasmid DNA concentration was measured in each muscle sample by quantitative PCR (qPCR). The target of the qPCR is a 92 nucleotides sequence located in the neomycin gene of the plasmids. Primers, probes, and qPCR conditions were those previously described [19] . Measurements were performed in triplicate. Experimental data were analyzed using the nonparametric Mann-Whitney test [20] included in SYSTAT 9 software (SYSTAT Software, Inc., Point Richmond, CA, USA)." ] },{ "paper_id": "8ca98b59fa6bb5b1d4dfdb0b89cfcdbcaa1a0474", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8cd344d423cfae8a07936b58eb1e172fa62bcc5d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8cd645b337ac36abbd467302eb73b4ae086e60ac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was conducted using one-way analysis of variance (ANOVA) followed by Tukey's multiple comparison test or unpaired t test. A p value of less than 0.05 (p < 0.05) was considered to be statistically significant. All data are expressed as means \u00b1 standard error of the means (SEM) from three independent experiments.", "Materials and Methods" ] },{ "paper_id": "8ce3ae4141f74a6ef60175581277687d6c185b4d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A program offering grants for start-up of community and school-based snack programs directed at children and youth and BC that include an educational component." ] },{ "paper_id": "8cef766849d0d8ad7a5ff33d7f66299de03cf583", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The MNCs from the spleen, MLN, ileum, and blood were isolated by following routine procedures in our laboratory [37] . Fragments of ileum were washed twice, first with washing solution (RPMI 1640 with 10 mM HEPES [N-2-hydroxyethylpiperazine-N9-2-ethanesulfonic acid], 200 mg of gentamicin per mL, and 20 mg of ampicillin per mL) followed by Hanks' balanced salt solution. The tissues were cut into small pieces, placed in HBSS containing 1 mM dithiothreitol and 5 mM EDTA, and vigorously shaken for 30 min to dislodge the epithelial cells. Subsequently, the segments were minced, suspended in RPMI 1640 containing 10% fetal bovine serum and 300 U of type II collagenase (Sigma Chemical Co., St. Louis, Mo.) per mL for digestion at 37\u00b0C for 30 min with gentle shaking. Afterward, the supernatants were collected, and the remaining tissues were pressed through stainless steel Collectors fitted with an 80 \u03bcm mesh screen (Collector, FL, USA). Similarly, spleen and MLN were also minced and pressed through stainless steel 80-mesh screens. Single cellular suspensions were then collected and subjected to gradient centrifugation in Percoll (Sigma). Blood was collected aseptically in 25% (v/v) acid citrate glucose. The peripheral blood lymphocytes were isolated by Ficoll-Paque (Ficoll-Paque Research Grade, Pharmacia Biotech., Uppsala, Sweden) density gradient centrifugation. Collected MNCs were subjected for frozen in liquid nitrogen as described [38] .", "Twenty-four conventional weaned pigs at 28 days of age were purchased from The Ohio State University (OSU) specific pathogen-free (SPF) herd that has no history of PEDV, TGEV, or porcine reproductive and respiratory syndrome virus (PRRSV) outbreaks. Nasal and rectal swabs were collected from all pigs and confirmed as negative for PEDV, TGEV/porcine respiratory coronavirus (PRCV), porcine delta coronavirus, and porcine group A and group C rotaviruses as described previously [30] . Conventional RT-PCR [35] revealed a weak positive for group A porcine rotavirus (data not shown). After 12 days of acclimation in our biosafety level 2 (BSL2) facilities, at 40 days of age, no pig had diarrhea and their rectal swab samples were negative for rotavirus RNA by RT-PCR." ] },{ "paper_id": "8cf02f23f08f2b7c8b0e83dcc85d080f9c1cf615", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the following equation, the SHRs, (m t ), are aggregated by block as follows:", "To test the sensitivity of the results to the time of analysis, we repeated the above analysis by ", "This study demonstrated improved air quality and population health ameliorated in relation with the closure of an oil refinery. As a natural experiment, it provides evidence supporting a link between refinery emissions and adverse health effects.", "Natural experiments represent a powerful tool in establishing a causal link between exposure and response. In many cases, the experiment acts as an intervention, with correspondingly large changes: the Utah Valley steel mill closures [7] being one of the most clear and famous examples. In our study the evidence suggests that even closures of smaller-scale industrial sites like the Oakville refinery, if the sites are emitters of pollutants associated with health effects, can have immediate and measurable effects on the health of the surrounding community." ] },{ "paper_id": "8cf5055e0ca001204109a5455b58a42aaa79f431", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study protocol was registered with the National Institute for Health Research international prospective register of scientific reviews (PROSPERO; #CRD42013004865) prior to executing the literature search strategy. 15 The PRISMA checklist is available as supporting information.", "We identified a total of 1133 unique records of which 43 studies met protocol eligibility criteria (see Figure 1 ). Two ", "Data S1. PRISMA 2009 checklist." ] },{ "paper_id": "8cff063c436820e2c85479244dcf7b5f123d4446", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. Each column has the sum of 1.", "1. The i th column has the sum of i. \u03b1\u2208{A,C,G,T}\u0169", "Therefore, we use" ] },{ "paper_id": "8d0367ee4b4bcd6fea276d8daa9bd2f50e401a34", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Wide virus diversity was found by different methodologies and high frequency of rhinovirus occurrence was confirmed in population in winter, showing its relevance for public health.", "METHODS Nucleic acids were extracted from samples collected in winter period of 2016 and subjected to HTS. The results were confirmed by the multiplex PR21 RT-qPCR, which identifies 21 respiratory pathogens.", "LCS participated in study design, accomplished the laboratory assays, contributed to data analysis and writing of the manuscript; RB analysed and interpreted the data; JMFS analysed and interpreted the data; TN participated in study design, contributed to data analysis, writing of the manuscript and coordinated the study. The authors declare that there are no conflicts of interest, either of financial or nonfinancial origin, involved in the publication of this article." ] },{ "paper_id": "8d03e1689613cf8af353a27d62adaf44e1b20e67", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We can now examine some hypotheses in an attempt to explain the results and to draw the evolutionary scenario associated with the pattern of diversity of the ABCA1* Arg230Cys polymorphism.", "Ethical approval for the present study was provided by the Individual and tribal informed oral consent was obtained from all participants, since they were illiterate, and they were obtained according to the Helsinki Declaration. The ethics committees approved the oral consent procedure as well as the use of these samples in population and evolutionary studies.", "Maize is considered the most important native crop of the Americas [44] [45] [46] [47] [48] [49] [50] [51] [52] [53] . Several lines of evidence indicate that the Mesoamerican village lifestyle began with maize domestication [44, 45, [49] [50] [51] 57, 58] . Originating in the Mexican southwestern lowlands, maize journeyed southwards, traveling hand-in-hand with pottery and bringing sedentary life to the Andes, although the date of its entry, as well as the dispersion pattern of this crop into and throughout South America, remain controversial [52] .", "Although more than 100 regions/genes had been identified as the likely targets of recent positive selection resulting from cultural pressures in newly constructed niches [1] , well-documented examples are scarce. One of the best-known cases of gene-culture coevolution is lactase persistence (LP; the ability of adult humans to digest the lactose found in fresh milk) and dairying. High frequencies of LP are generally observed in traditional pastoralist populations. For example, LP reaches ,64% in Beni Amir pastoralists from Sudan, whereas its frequency in a neighboring non-pastoralist community is only ,20%. In Europe, LP varies from 15-54% in eastern and southern regions, 62-86% in central and western regions, and 89-96% in northern regions [5, [7] [8] [9] [10] [11] [12] [13] ." ] },{ "paper_id": "8d095d0275e474dbb9d9b63a75591ff2c0667d73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical specimens (n = 827) from NPSs were collected from children under 14 years old, who experienced a lower respiratory tract infection, and who were consulting the pediatric department of Shanghai Nanxiang Hospital during the period October 2006 to October 2008.", "Human rhinoviruses (HRVs) are a highly p revalent cause of the acute respiratory infection (ARI) defined as the common cold [1, 2, 3] , which is frequently associated in children with bronchitis, bronchiolitis, wheezing, pneumonia, asthma and otitis [4, 5, 6, 7, 8, 9] . HRVs are classified in genus Enterovirus (HEVs) in family Picornaviridae [10] . HRVs are non-enveloped, single-stranded, positive-sense RNA viruses of approximately 7200 nt, composed of a 59 untranslated region (UTR), followed by a long open reading frame coding for capsid proteins VP4, VP2, VP3 and VP1, and seven non-structural proteins 2A, 2B, 2C, 3A, 3B, 3C and 3D, and terminated by a short 39UTR and poly A tract.", "This study was approved by the ethical committee of Shanghai Nanxiang Hospital and written informed consent was obtained from the parents of the children." ] },{ "paper_id": "8d0b98bb0c601d8a636e49bad7d2449b7dce32ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Supporting information S1 Checklist. STROBE checklist. (DOC) " ] },{ "paper_id": "8d0dc902f68228a84345abe956a41bb58ea01ef3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conjugating drug molecules directly to specific DNA aptamers is a potential way to deliver the drugs specifically, and thus reduce the risk of off-target drugs. By linking DNA aptamers to drugs or packing the drug into an aptamer-folded structure, DNA aptamers-drug conjugates can efficiently deliver drugs to target cells with increased specificity. Many DNA aptamers have been selected to efficiently deliver chemotherapy drugs in vitro or in vivo, such as doxorubicin (DOX) [104] , fluorouracil [105] and epirubicin [106] . Dimeric or dendrimer DNA aptamers in conjugation with drugs have been developed to further enhance the efficiency of target delivery [107, 108] .", "For example, Li et al. selected DNA aptamers for metastatic colon cancer cells using SW620 cells derived from a metastatic site lymph node in the positive selection and SW480 cells from a primary colon adenocarcinoma of the same patient in the negative selection [30] . The resulting aptamer (XL-33) was found to possess specific affinity to the metastatic colon cancer cells (K d = 0.7 nM). Its truncated form (XL-33-1) was used to image the cancer tissue after labeling with fluorescein amidite (FAM), displaying an 81.7% detection rate against colon cancer tissue with metastasis in regional lymph nodes and 66.7% specificity against nonmetastatic colon cancer tissue.", "With regard to small oligonucleotides delivery, DNA aptamers were directly linked to the small oligonucleotides to form a DNA aptamer-oligonucleotide chimera, which could help to prevent non-specific internalization as well as decrease the cellular toxicity towards non-target cells. We have reported that a DNA aptamer-siRNA chimera could specifically enter into CD4 (+) T cells and efficiently decrease the expression of exogenous the HIV protease gene [18] . An anti-mucin 1 DNA aptamer covalently linked to miRNA-29b was found to deliver miRNA-29b into ovarian cancer cells specifically and induce significant apoptosis of the cancer cells [109] ." ] },{ "paper_id": "8d14b700a065187eb4d8b01e0e9b6e3e37e5d09b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Not all sequences appear to be fully successful within this scheme.", "When tRNA has sufficiently many contiguous base pairs located around the D-T loop overlap, a pseudoknot is predicted for E. coli tRNA (Phe) - Fig. 1a .", "For a given instance, we cannot say that this model will definitely yield a better result than any other approach. However, for the biologist who must confront the unknown structure of a new sequence, we think this tool is definitely helpful. ", "Alternatively, after a stable interval of structure has developed, the existing structure can then collect up the surrounding left over free strand and form a pseudoknot.", "The tandem frame shift pseudoknots of the tobacco mosaic virus (TMV) [7] are predicted for a minimum PK stem length 4 nt and a minimum stem length 3 bp (Fig. 1e ). Using the same parameters, the turnip yellow mosaic virus (TYMV) is also predicted (Fig. 1e) [5] ." ] },{ "paper_id": "8d1543ffb6bf876bc0a8fb927068f6f3c6938497", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results present the first standard proteomic profile of IBV and may facilitate the understanding of the pathogenic mechanisms.", "Background: Infectious bronchitis virus (IBV) is the coronavirus of domestic chickens causing major economic losses to the poultry industry. Because of the complexity of the IBV life cycle and the small number of viral structural proteins, important virus-host relationships likely remain to be discovered. Toward this goal, we performed two-dimensional gel electrophoresis fractionation coupled to mass spectrometry identification approaches to perform a comprehensive proteomic analysis of purified IBV particles.", "Purified virus particles treated with bromelain (BB0243, BBI) at 0.2 mg/ml in 50 mM DTT (pH 7.2) in Dulbecco's phosphate buffered saline (PBS) at 37\u00b0C for 15 min. After incubation, the treated virus was directly centrifuged to equilibrium in 11.5 ml non-linear 20%-50% sucrose-TNE gradients at 75,000 \u00d7 g for 2.5 h in a SW41 rotor (Beckman Coulter, Optima\u2122 L-100XP Preparative ultracentrifuge). Purified virions were diluted with TNE buffer and pelleted by sedimentation at 75,000 \u00d7 g for 1.5 h in a SW41 rotor to remove the sucrose and then subjected to immunogold labeling and electron microscopy analysis.", "Some host proteins may be specially incorporated into the virions. In this study, 21 of the total host proteins are reported for the first time. The identified host protein functions in diverse biological processes and some functional groups are analyzed. These proteins participate in a broad array of cellular functions and are involved in many processes in the viral life cycle. The potential roles of some of these proteins are discussed below in relation with IBV infection, pathogenesis and early host antiviral response.", "To identify the proteins associated with IBV particles, all protein spots detected in the gels were excised and in-gel digested with trypsin followed by MALDI-TOF/TOF (Matrix-assisted laser desorption/ionizationtime of flight mass spectrometry) analysis. Database search analysis revealed that 2 virus-encoded structural proteins and 60 host proteins were successfully identified. Detailed information of the full set of the identified proteins is listed in Table 1 ; additional file 1." ] },{ "paper_id": "8d1ae8aa93426fbd79c96483ab83e0841ff8893c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords. pneumonia; viral load; viral density; RSV; PERCH.", "Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the author to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the author, so questions or comments should be addressed to the author. " ] },{ "paper_id": "8d27cf597c7bb3029c304801e4413396e8731d4b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(a) Spatial expansions underlie a recent doubling of rabies spillover to livestock", "Data accessibility. Data used in this study were provided by the Servicio Nacional de Sanidad Agraria (SENASA) of Peru, publicly available online at http://www.senasa.gob.pe/senasa/reportes-epidemiologicos-semanales. Bat bite data may be requested from the Apurimac Regional Project for Rabies Control.", "(iii) Questionnaire data from vampire bat-transmitted rabies-free communities" ] },{ "paper_id": "8d2f1769c1de3d813cf910561ff0401fb9d75121", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The emergence and worldwide dispersal of novel human pathogens is increasingly challenging global public health [1] .", "To identify air transportation communities, we approximate a maximal-modularity subdivision of the 1,227-largest-airport network by employing a recently described stochastic Monte-Carlo approach [18] . Modularity provides a measure of how well the connectivity of a network is described by partitioning its nodes into non-overlapping groups; for a definition we refer to [19] . For any given partition, modularity will be high if connectivity within groups is high and connectivity among groups is low. For large networks, a variety of methods have been introduced to approximate their optimal subdivision. The method we employ here generates an ensemble of high modularity subdivisions and computes the consensus in this ensemble by superposition. For further details we refer to [18, 20] and in Text S1 we describe how we incorporate subdivision uncertainty in our phylogeographic approach.", "We complemented a previously collected hemagglutinin sequence data set, comprising 1,441 sequences sampled globally from 2002 to 2007 [3] , with publicly available sequences sampled within the same time interval. The allocation of the sequence data into 15 and 26 geographic regions as well as into 14 air communities is described in detail in Supporting information Text S1." ] },{ "paper_id": "8d355f050721e1e9d9288c7824cc38546b6ef2a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author(s) declare that they have no competing interests." ] },{ "paper_id": "8d3f0c18b7b274179244f57cd8f66e185a009dd5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "African green monkey kidney Vero E6 cells were grown and maintained in DMEM supplemented with 10% FBS and incubated at 37 \u00b0C with 5% CO 2 . The PI3K-specific inhibitor LY294002, STAT3-specific inhibitor S3I-201 and Akt inhibitor MK-2206 2HCl were purchased from Selleck Chemicals (Houston, USA), and were diluted to 10 mM in DMSO.", "The medium from the cell cultures was collected, pooled, and stored in aliquots at \u221270 \u00b0C until analysis. The cell supernatants were measured for IL-11 levels using an IL-11 ELISA kit (R&D Systems, Minneapolis, MN, USA) according to the manufacturer's instructions.", "Cells were lysed in RIPA buffer containing a protease inhibitor cocktail (Thermo Scientific). The proteins were separated on 10% SDS-PAGE and transferred to polyvinylidene fluoride (PVDF) membranes (Millipore, Bedford, MA, USA). Antibodies against total STAT3, p-STAT3 (S727), p-STAT3 (Y705), total Akt, phospho-Akt (Ser473), total ERK, ERK1/2 (Thr202/Tyr204) were purchased from Cell Signaling Technology (Beverly, MA, USA). Monoclonal antibodies against IL-11 and GAPDH were purchased from Proteintech (Wuhan, China) and Beyotime Institute of Biotechnology (Shanghai, China), respectively. Monoclonal antibodies against PEDV N was purchased from Medgene labs (USA). After washing three times with TBST, membranes were exposed to species specific horseradish peroxidase (HRP)-conjugated secondary antibodies (Vazyme, Nanjing, China) followed by enhanced chemiluminescence (ECL, Thermo Scientific) detection by autoradiography. Western blotting was quantified by Quantity One (Quantity One 1-D Analysis Software 170-9600, Bio-Rad). The intensity of the bands in terms of density was measured and normalized against GAPDH expression." ] },{ "paper_id": "8d40046d4ced2a558530e5e242fabbee66b213d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analyses were made using Prism 5 software and data were expressed as means + standard error from mean (SEM). All data sets were tested for normality. Data with parametric distribution were compared using student's t-test, or one-way ANOVA with Tukey's multiple comparision anlaysis where appropriate. Non-parametric data were compared with a Kruskal-Wallis test. For every assay, a minimum of 3 separate, independent experiments were conducted with all experimental groups assayed in duplicates or triplicates. Statistical significance was established at P < 0.05.", "Some macrolides such as tilmicosin and tylvalosin have been recently demonstrated to possess direct anti-viral effects against PRRSV [69, 70] , while others like erythromycin do not [71] .", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "In its natural host, the virus targets alveolar macrophages (AM) [7, 8] , and is able to infect most cells of the monocyte-macrophage lineage such as intravascular and lymph node macrophages [7, 9, 10] . These cells play a crucial role in immune surveillance, pathogen killing and adaptive immune response stimulation [11] . PRRSV impairs macrophage phagocytic and bactericidal functions, induces host cell death often resulting in an inflammatory response, and perhaps most importantly predisposes the pig to secondary infections [12] [13] [14] [15] [16] . Indeed, opportunistic pathogens, whether viral-swine influenza virus, pseudorabies virus-or bacterial-Streptococcus suis, Bordetella brochiseptica-potentiate PRRSV-induced pneumonia [14] . These synergistic effects promote a self-sustaining inflammatory response increasing the severity and the duration of the disease [17] [18] [19] [20] [21] ." ] },{ "paper_id": "8d67e5c1683885f28d8b023224e65998d8e73411", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pigs were monitored weekly post-challenge by blinded personnel for changes in physical conditions and clinical respiratory disease symptoms. Respiratory disease severity was scored on a scale ranging from 0 (normal) to 6 (severe dyspnea and abdominal breathing) as previously described [28] .", "RNA was extracted from serum samples to assess PRRSV viremia, as previously described [23] . PRRSV genomic cDNA copies were quantified with real-time PCR for both the challenge and vaccine PRRSV strains [23] .", "Quantification of PCV2 DNA in blood DNA extraction using a commercial kit (QIAamp DNA Mini Kit, QIAGEN) was performed followed by realtime PCR to quantify the PCV2 genomic DNA copy numbers from serum samples [29] . " ] },{ "paper_id": "8d6ac4365bc4ab3f85ea3a5c287cddfaef482707", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The result of the semiconducting metal oxides irradiation is the excitation of an electron (e \u2212 ) from VB to CB, whereby a positively charged electron hole (h + ) emerges. Therefore, a specific \"hole-electron\" pair (h + + e \u2212 ), called exciton, is generated [38, 39] (Fig. 1) .", "Recent studies prove that nanosized metal oxides, such as nano-TiO 2 or nano-ZnO, can be applied to inactivate many species of molds (filamentous fungi), e.g., Fusarium oxysporum [83, 188] , Aspergillus niger [81, 82, 181, 189] , and Penicillium expansum [190, 191] .", "Superoxide anion radicals ( \u2022 O 2 \u2212 ) cannot penetrate the cell envelope since they are negatively charged. However, contrary to hydroxyl radicals, they show a relatively long living period [36] (Fig. 3) ." ] },{ "paper_id": "8d7027f9c0c85c6aad1c9459d1c16f2b3b918280", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Selective autophagy plays a pivotal role in maintaining the integrity of intracellular organelles by degrading damaged organelles ( Figure 2 ) [100, 102, 112] . The selective elimination of organelles, termed organellophagy, supplies recycled nutrients for the regeneration of mitochondria, peroxisomes, ER, lipid droplets (LDs), ribosomes, lysosomes and nuclei ( Figure 2 ). The removal of mitochondria by selective autophagy, termed mitophagy, could be activated by hypoxia [113, 114] , accumulation of reactive oxygen species (ROS) [115] [116] [117] and mitochondrial depolarization [118] [119] [120] . The major route for clearing damaged mitochondria originates from the loss of PTEN-induced putative kinase 1 (PINK1) cleavage by presenilin-associated rhomboid-like protein (PARL) within the inner mitochondrial membrane and the inhibition of PTEN degradation via the ubiquitin-proteasome pathway [121, 122] . The PINK1 accumulated on the outer mitochondrial membrane, in turn, phosphorylates ubiquitin and then recruits the ubiquitin E3 ligase Parkin [118] [119] [120] [123] [124] [125] . Parkin, in turn, ubiquitinates the surface proteins on the outer mitochondrial membrane [118] [119] [120] 123, 126] , triggering the recognition of cargo receptors for the removal of mitochondria by autophagy [127] . PINK1 specifically recruits Calcoco2/NDP52 and OPTN to mitochondria and subsequently induces the translocation of phagophore-generating factors, including DFCP1 and WIPI, for autophagosome maturation proximal to degradative mitochondria [127] . Notably, the TANK binding kinase 1 (TBK1)-mediated phosphorylation of p62/SQSTM1 at serine residue 403 and OPTN at serine residues 177, 473 and 513 are critical for promoting mitophagy [128] [129] [130] . In addition to the PINK1/Parkin-mediated mitophagy pathway, several outer mitochondrial membrane proteins, such as FUN14 domain-containing 1 (FUNDC1), BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L) and yeast ATG32, have been shown to mediate mitophagy in a ubiquitin-independent manner [131] [132] [133] [134] [135] . Not surprisingly, several new molecules were recently identified as new cargo receptors of mitophagy, including prohibitin 2 (PHB2) and Toll-interacting protein (Tollip) [136, 137] . Reciprocally, the dequbiquitination enzymes USP30 and USP35 have been shown to antagonize the mitophagy process by deubiquitinating Parkin [138, 139] .", "HCV was first discovered to be the infectious agent underlying non-A, non-B hepatitis in 1975 [228] and the HCV viral RNA sequence was cloned in 1989 [229] . Currently, seven isolates of HCV have been cloned and classified, including genotypes 1 through 7 and each genotype is further divided into an array of different subtypes [230] . The high genomic variability among the different HCV genotypes may lead to poor cross-genotype immunity and varying levels of disease progression [231, 232] . In recent decades, the combined therapy of pegylated-interferon (IFN) and ribavirin has been standardized for treating HCV infection [233] . However, the genotype of the infecting virus, genetic polymorphisms, disease stage and severe side effects often hamper the successful rate of treatment [225, 233, 234] . IFN-free and DAA-based anti-HCV therapy has led to an HCV infection cure rate of more than 90% [225, 226] . However, the emergence of resistance to DAA drugs [225, 235] and the uncertain and controversial effects of DAA treatment on disease progression in chronically infected patients still impede the complete eradication of HCV infection [236, 237] . For instance, data on the impact of DAA treatment on the risk for HCC occurrence in chronic HCV patients are still conflicting. Several studies have demonstrated that the rate of HCC development is significantly reduced in patients who have achieved a sustained virological response (SVR) after DAA therapy [238] [239] [240] . However, numerous reports have indicated that the rates of HCC recurrence and de novo development of HCC in patients after DAA-induced SVRR are unexpectedly increased [241, 242] , possibly due to uncontrolled liver immunity resulting from the DAA-mediated eradication of HCV-specific T cells [243] .", "The entry of HCV into hepatocytes relies on several cell surface molecules, termed entry (co)receptors, including tetraspanin CD81 [251] [252] [253] , scavenger receptor class B member 1 (SCRAB1) [254, 255] , tight junction proteins, claudin 1 (CLDN1) [256] and occludin (OCLN) [257] ." ] },{ "paper_id": "8d7400a2b387820cd391d7df8194642e50402a0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Stationary-phase ", "higher protein stability at the cell surface for several heterologous proteins [10] .", "Future works should investigate the L. lactis capacities for protein modifications. For example, we showed that proteins that require a disulfide bond (DSB) to acquire their native conformation can be efficiently produced and secreted in L. lactis [5, 22, 27] . However, no equivalent of E. coli dsb or B. subtilis bdb, the genes involved in DSB formation, was found by sequence comparison in L. lactis. Similarly, other folding elements (i.e. PPIases, so-called maturases...) are still to be identified and the L. lactis capacities for post-translational modifications are still to be investigated." ] },{ "paper_id": "8d81ebbd42382fd503dc2aaf88eb5f790ddebe64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8d882efc1f6cf141ce6b4283acd7f87b1b280313", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "What to expect during a pandemic. What is resilience? Normal stress responses. How to help others with stress (psychological first aid). Working outside your comfort zone. Moral and ethical dilemmas. An approach to coping. Active listening.", "Expressing yourself constructively. Balancing family and work. How to talk to children about disasters and emergencies. Personal and home preparation. Managing drugs and alcohol. Danger signals & resources for getting help.", "Q: What is your initial reaction? A: It makes me angry." ] },{ "paper_id": "8d8ab6d3f0c6ff09e306c23c87f823f9382ff32e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human HEEBO (Human Exonic Evidence Based Oligonucleotide) Arrays, consisting of 44,544 70mer probes representing 30,718 known genes, were purchased from Microarrays Inc. (Nashville, TN). 5 to 20 mg of total RNA from uninfected control and infected samples was used to generate cDNA labeled with aminoallyl (aa)-dUTP through a reverse transcription reaction using anchored oligo(dT) primers. The purified aa-dUTP-labeled cDNAs were coupled in 10 ml 0.1 M NaHCO 3 with either Cy3 or Cy5 NHS-ester dye. Cy-dye labeled cDNA was purified using a Cyscribe GFX column (Amersham Biosciences, Piscataway, NJ). The two differently labeled cDNAs were mixed and hybridized using Pronto Microarray Hybridization Kit in a hybridization chamber (Corning, Corning, NY), with the same array slide for 38 to 42 hr according to manufacturer's instruction. After a series of washes using the buffers provided in the kit, slides were spun dry and scanned under two laser channels in a Scanarray 4000 scanner (Packard Bioscience, Meriden, CT).", "The human microvascular endothelial cell line of dermal origin (HMEC-1) [15] was obtained from Dr. Ades (Centers for Disease Control and Prevention, Atlanta, Georgia) and cultured in endothelial basal medium (Clonetics, San Diego, CA) supplemented with 15% heat-inactivated fetal bovine serum (Hyclone, Logan, UT), 1 mg/ml hydrocortisone (Sigma-Aldrich, St. Louis, MO) and 10 ng/ml epidermal growth factor (Sigma-Aldrich). The immortalized human macrovascular endothelial cell line EA.hy926 [16] was kindly provided by Dr. C.-J. Edgell (University of North Carolina, Chapel Hill, NC) and grown in Dulbecco's modified Eagle medium with high glucose supplemented with 10% heat-inactivated fetal bovine serum (Gibco, Grand Island, NY) and HAT Media Supplement (Sigma-Aldrich). Both cell lines were cultured in the medium recommended by the supplier in a humidified atmosphere of 5% CO 2 and both cell media were supplemented with 1 U/mL penicillin, 1 mg/mL streptomycin, and 2 mM L-glutamine for routine propagation. Cells to be used for experimental infection with Leptospira strains were cultured without the antibiotics.", "Endothelial Cell Responses to Leptospira www.plosntds.org endothelial damage by blocking L. interrogans Copenhageni attachment to the cells, but no inhibition of adhesion of 35 Slabeled bacteria [17] was seen even at a concentration of lisinopril 10 fold over the concentration used for these experiments ( Figure 5 )." ] },{ "paper_id": "8d94c10b7cac018c7bd1b9c1c58365b78b35b458", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the Children's hospital Hebei Province Ethics Committee (number 2017016). The legal guardian(s) or parent(s) of the children provided written informed consent for sample collection and clinical record review.", "For multiplex reverse transcription (RT), the mix of all reverse primers (RT primer) from target pathogens (Additional file 1: Table S1 ) was used. RT was performed in a total volume of 20 \u03bcL containing 5 \u03bcL of nucleic acid sample, 14 \u03bcL Premix, 1 \u03bcL (40 units) RT-PCR reverse transcriptase. RT was carried out as follows, 25\u00b0C for 5 min; and then 50\u00b0C for 15 min. The reaction was terminated by incubation at 95\u00b0C for 2 min. Multiplex PCR was performed in following steps: step 1, 94\u00b0C for 30s, 65\u00b0C to 60\u00b0C touchdown PCR for 30s and 72\u00b0C for 1 min, repeated for 6 cycles; step 2, 94\u00b0C for 30s; 60\u00b0C for 30s; 72\u00b0C for 1 min, repeated for 29 cycles; step 3, 72\u00b0C for 10 min, step 4, 4\u00b0C. The 10 \u03bcL amplified products were added into the 287 \u03bcL loading buffer and 3 \u03bcL SizeStandard-400, and then assessed using the GenomeLab GeXP Genetic Analysis System (Beckman Coulter).", "Nucleic acids were extracted using the nucleic acid extraction kit on an automated extraction workstation (Smart LabAssist-16/32) according to manufacturer's instructions (Health Gene Technologies, Ningbo, China)." ] },{ "paper_id": "8d9c4ed5074e68cc26a911f277ad05fa0cd7c0e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "following order: 1. Supplementary Figures and Legends. 2. Supplementary references.", ". Three nucleotides (in red) were inserted to destroy the slippery sequence and shifting the reading frame into -1 frame." ] },{ "paper_id": "8da1231a64d73bc59f2af993bf1a2466265ffa4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Phylogenetic tree was constructed using MEGA 5.0 software package [30] based on the neighbor-joining method and Kimura 2-parameter method. 1000 replicates of Bootstrap resampling was used to ensure the reliability of individual nodes in phylogenetic tree." ] },{ "paper_id": "8da224b5eba13cee28c3a95cb3c1e3c4d26e5a3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We do not plan to make any changes to this protocol. However, if substantial changes occur during the review process, they will be reported in the published results.", "This study will include the following: Table S2 . This search strategy will be adapted to fit other databases. The references of the eligible articles and relevant reviews will be manually searched to identify additional studies." ] },{ "paper_id": "8da5d4c7d3f991b1538e839ed944dcd2167112d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Angiotensin converting enzyme (ACE)2 is an enzymatically active ACE homologue, which shares 42% of its amino acidic sequence identity in its catalytic domain; however, ACE and ACE2 show several differences. Whereas ACE is a dipeptidylcarboxypeptidase, presenting both N-and C-terminus catalytic domains with two zinc-binding motifs (HEXXH, where X is any amino acid); ACE2 is a monocarboxypeptidase with only one zinc-binding motif at its N-terminal domain [1] [2] [3] . Through this catalytic domain, ACE2 hydrolyzes AngII (angiotensin II) to generate Ang1-7, a peptide that binds to the MAS receptor (Ang1-7 receptor) and activates vasodilation, anti-fibrosis, anti-proliferation, and anti-inflammatory effects as well as counterbalances the ACE-AngII-ATR1 axis actions [4] [5] [6] .", "Serum was obtained after 10 min of centrifugation at 6000\u00d7 g and stored at \u221280 \u2022 C. Tissues were quickly removed and snap frozen in liquid nitrogen. They were then stored at \u221280 \u2022 C until use.", "Values of each data are expressed as mean \u00b1 SEM. Comparisons between groups were assessed by Kruskal-Wallis for multiple comparisons and Mann-Whitney U-test for two group comparisons (SPSS version 18 for Windows). Statistical significance was considered when p \u2264 0.05." ] },{ "paper_id": "8dab25c25f6598446d3b229d821402278b2bc0b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Phylogenetic relationships were analyzed using MEGA version 5.5 [21] . The Poisson correction parameter and pair wise deletions of gaps were applied. The reliability of branching was assessed by the bootstrap re-sampling method using 1000 bootstrap replications.", "Isatisindigotica Fort. (Brassicaceae) is a biennial herbaceous plant used as an important and popular herbal medicine in TCM with a long history. Isatidis Radix (Banlangen, Isatis root) and Isatidis Folium (Daqingye, Isatis leaf ) are widely used for antibacterial, antiviral, and immune regulatory effects in the treatment of colds, fever, and influenza [1] [2] [3] , especially for the treatment of severe acute respiratory syndrome (SARS) and H1N1influenza [4] [5] [6] ." ] },{ "paper_id": "8dad44cafa563c90b07152ef2038e530b19edb31", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral hemorrhagic fevers (VHFs) caused by mammarenaviruses represent a serious and increasing public health concern [1] . Arenavirus-associated VHFs are zoonotic diseases, with humans acting as accidental hosts after contact with a viral reservoir, typically rodents [2] . The old-world (OW)", "All images were acquired using a confocal Zeiss LSM 510 (Zeiss, Oberkochen, Germany) with an Axioscope 63\u00d7 oil immersion lens objective. The images were analyzed using ImageJ/Fiji (version 1.52" ] },{ "paper_id": "8dada285162e466f7867f6b657853905bd778933", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Of the 60 eligible participants, 44 submitted their responses (35 complete, 9 incomplete). The incomplete responses were excluded from analysis yielding a response rate of 58%.", "Abbreviation MPH: Master of public health.", "The authors declare that they have no competing interests." ] },{ "paper_id": "8dc3e3104105b1c360fdfe01de88e4f35d6977d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For virus amplification or expression in cells, the cells were infected at an MOI of 0.1 (multiplicity of infection of 0.1 p.f.u. per cell) for 1-2 h.", "Since its inception more than 30 years ago, the baculovirus expression vector system (BEVS) has been widely used to express heterologous foreign proteins [1] [2] [3] . Autographa californica nucleopolyhedrovirus (AcMNPV)-Sf9 and Bombyx mori nucleopolyhedrovirus (BmNPV)-silkworm are two typical BEVSs [4] [5] [6] . The BmNPV-silkworm offers several advantages in comparison with the AcMNPV-Sf9 system [7] .", "A novel reBmBac expression system was developed though the steps described above. Fig 3 illustrates an overview of this system (with reference to Airenne et al. [45] )." ] },{ "paper_id": "8dcc9848e421e45ac829203e4e6fe58e6ac130e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The governing equations in a dimensionless form are", "\u2202C \u2202\u03bd = 0, on \u2202\u2126 0 .", "*Note that\u03b2 \u2020 =\u03b2,\u03b4 \u2020 =\u03b4 under the assumption of x * = y * = n * ; otherwise\u03b2 \u2020 ,\u03b4 \u2020 from\u03b2,\u03b4, respectively." ] },{ "paper_id": "8dd14ffdb898c891d284cff71623b3e43ec0b0fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8dd45f6f44956863508e44c1e6c7338b51a7524d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Process model:", "Parameter model:", "For data as counts in P model we have\u2026 Data model:" ] },{ "paper_id": "8dd8d40c08edb208f9a32333f21a24d4dbfdb6c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Transmissible gastroenteritis virus (TGEV) belongs to the genus Alphacoronavirus, family Coronaviridae and contains a single-stranded, positive-sense RNA genome of approximately 28.5 kb in length. The enteropathogenic coronavirus causes watery diarrhea, severe villous atrophy, high mortality in piglets, and severe morbidity in different stages of pig development. In the epidemic form, TGEV causes significant economic losses to the global pork industry (Brazil 13 ). Recent TGEV epidemiological studies are lacking in the US while sporadic outbreaks have been reported from China 14-16 .", "Harboring one of the largest RNA genomes, the TGEV genome includes four structural genes (spike [S], envelope [E], membrane [M] and nucleoprotein [N]) and five non-structural open reading frame (ORF): ORF1a and ORF1b, ORF3a, ORF3b, and ORF7. The single segment genome is organized as 5\u2032UTR-ORF1a/1b-S-ORF3 a-ORF3b-E-M-N-ORF7-3\u2032UTR 3 . The ORF1a/b can be divided into 15 ORFs, encoding non-structural proteins (NSP)1-10 and NSP12-16. The NSPs contribute to regulation of host translation and localization of the RNA-dependent RNA polymerase (RdRp) during viral replication 3 . In coronavirus, NSP1 is a major factor associated with pathogenicity 17 . The NSP2, 3 and 8 of TGEV can incorporate into the viral articles 18 while the NSP3", "is also associated with protease and ADP-ribose 1\"-monophosphatase activities 19 . The functions of other NSPs of TGEV are unknown. The S glycoprotein attaches to the host cellular receptor porcine aminopeptidase N (pAPN) or sialic acid, induces cellular fusion, stimulates neutralizing antibodies, and has hemagglutination activity [20] [21] [22] [23] . The pAPN-binding domain of the S protein has two major antigenic sites, A and B 24 . In addition, deletions in the ORF3 gene led to attenuation and reduced pathogenesis of TGEV and in vivo 25 ." ] },{ "paper_id": "8de35b5317b0ebc437a5d5dbe94100f93ff88ab1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The PHG Foundation is an independent, not-for-profit think-tank that derives some income from the provision of private consultancy services and commissioned work. In 2015 Oxford Nanopore sponsored the networking session of a PHG Foundation expert meeting on pathogen genomics, and may receive fee-based consultancy services from them in 2016.", "Abbreviations STEC: Shiga toxin-producing Escherichia coli; WGS: Whole-genome sequencing.", "Most importantly, health systems must adapt to the reality of rapid innovation in genomics. Current approaches to implementation of innovation in health systems are often characterised by pilots, trials and regulatory hurdles so numerous that by the time they are completed the technology is already becoming obsolete. These approaches must be replaced with more agile and streamlined approaches that are properly resourced and that empower clinicians and scientists to operate services that are being continuously updated and improved in light of new knowledge and technology.", "The ability of WGS to improve the sensitivity and specificity of such challenging outbreak investigations is acting as a strong driver for the implementation of WGS services by public-health authorities worldwide. Notably, the Global Microbial Identifier project (http:// www.globalmicrobialidentifier.org/People), which was established to support the development of an international system of genomics-based infectious disease surveillance, has members from 42 nations." ] },{ "paper_id": "8deca5b29c3d3c0b11f1c9032a981f95dc8d1619", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Combining the described screening method with expression libraries derived from C. jejuni cDNA allows for the fast analysis of hundreds of different proteins. Thus, suitable immunodominant proteins can be detected, isolated and identified via sequencing the encoding cDNA sequence.", "Although prediction-based strategies for antigens and linear epitopes have been published [55] [56] [57] [58] , their accuracy is often lacking [59] . In contrast, our approach offers an attractive dual procedure as it rests on experimental data that are complemented by a widespread support of bioanalytical tools. Thus, such a thorough approach facilitates to focus on relevant epitopes quickly, while rapidly evaluating their suitability for prospective diagnostic applications as compared to prediction-based or experimental methods alone.", "with rf f i control the median of all rfis of the control used:", "The RIN values for the C. jejuni RNAs isolated were above 8.5 in all cases (see S1: RIN). After polyadenylation of the RNA, it was reverse transcribed and subsequently normalized using a duplexspecific nuclease (DSN). Assessing the performance of normalization, we sequenced a sample set of 96 individual clones after transformation with trimming and without trimming. Without DSN treatment 28% of clones contained 23S rRNA derived cDNA and 8% other rRNA derived cDNA (16S and 5S). In comparison, after incubation with DSN only one clone in 96 showed a 23S rRNA derived cDNA.", "Modelling of cj0669's structure was performed by SWISS-MODEL using automated mode. The template chosen during automatic identification was pdb1ji0A from the RCSB Protein Data Bank [35] , which referred to the Crystal Structure Analysis of the ABC transporter from Thermotoga maritima [36] ." ] },{ "paper_id": "8dedaee19e09c9fd5a849dda12a4521ea675b1a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chlorine (Cl 2 ) is a yellow-green gas or boiling yellow liquid, slightly water soluble, and about two times heavier then air [1, 2] . It has a pungent, irritating odor and is a strong oxidizing agent [1, 2] . Chlorine releasing agents are frequently used for industrial, household chemicals and water purification in swimming pools or city water sources [2] [3] [4] .", "The authors determined 39 patients' routine physical examinations were done at admission. Depending on the patient's clinical picture by the discretion of the physician, the necessary diagnostic tests (e.g. chest X-Ray (CXR)), complete blood counts, electrocardiograms (ECG), arterial blood gases (ABG), and consultations were ordered.", "All the data that we have presented are mean \u00b1 SD and in percentages." ] },{ "paper_id": "8df741c3cb3a548994916cbc0db540c43f374bc7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Valacyclovir is an alternative prophylactic agent with good bioavailability [107] [108] [109] . Acyclovir is recommended as the therapy for severe mucocutaneous or visceral HSV disease in transplant recipients [25] . Valaciclovir and famciclovir are considered as alternatives for less serious manifestations of HSV diseases [25] . The recommended drug for acyclovir-resistant HSV is foscarnet [17] . Cidofovir might be effective to treat HSV infection which is resistant to both acyclovir and foscarnet [110] .", "The authors declare that they have no competing interests.", "The manuscript is derived from literature summarizing reports prepared by RL and QFL. Both authors wrote the manuscript and have read and approved the final version.", "Strict isolation and hygiene measures are advocated in patients shedding the adenovirus to prevent horizontal transmission and nosocomial outbreaks. Bordigoni et al. [182] suggested cidofovir or DLI seemed encouraging approaches to prevent adenovirus diseases, whereas ribavirin and vidarabin were ineffective.", "For HBV-negative recipients, pre-transplant vaccination and HBV-specific immune globulin should be considered if the donors are HBV surface antigen positive. For HBV-positive recipients, administration of antiviral agents (i.e. lamivudine, famciclovir, Entecavir and adefovir) pre-and post-transplantation is advocated to reduce HBV replication [189, 190] ." ] },{ "paper_id": "8e014e2133b319d93ba7e9341ffe33bab3f9e265", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The statistical significance of differences between mean values of the experimental groups was determined using one way analysis of variance (ANOVA). The differences were considered statistically significant if the P value was < 0.05.", "Lung cancer is one of the leading causes of malignancy-related death because of its frequency and its highly metastatic potential. Currently, immunotherapy for lung cancer is considered as a promising treatment capable of inducing systemic tumor-specific immune responses without provoking serious side effects [1, 2] . The critical factor for immunotherapy is to choose potential cancer specific antigens as targets without affecting normal tissues.", "The ELISPOT assay was performed as previously described [19] . In brief, 5 \u00d7 10 5 spleen cells with 10 \u03bcg/ ml of the indicated peptides were added to a 96-well PVDF-membrane plate coated with anti-IFN-\u03b3 antibody. Spots were developed using a 3-amine-9-ethyl carbazole (AEC, Sigma) solution. The reaction was stopped after 4-6 minutes by running the plate under tap water. The spots were then counted using an ELISPOT reader (Cellular Technology Ltd., Shaker Heights, OH)." ] },{ "paper_id": "8e0621d9c791cda1b772290d37ab245bf7023514", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Differences in viral titer between groups were evaluated by unpaired parametric two-tailed t-test using GraphPad Prism 7 (GraphPad Software, Inc., La Jolla, CA, USA), version 7.04. Differences with p < 0.05 were considered to be statistically significant.", "Accordingly, we describe here using standardized in vitro assay systems the cytotoxicities and antiviral activities of arbidol against three representative flaviviruses; ZIKV and WNV as emerging mosquito-borne pathogens, and TBEV as an important tick-borne pathogen. Since antiviral compounds are extensively inactivated/metabolized in the intracellular environment [14, 15] , different cell lines were utilized to assess simultaneously both the antiviral and corresponding cytotoxic effects of arbidol.", "In Vero cells, arbidol administration was found to inhibit viral replication in all cases. In fact, a rapid reduction of viral titer was observed within the first 6 h p.i.; then the titer remained low (or even below detection limit) until the end of the experiment. In untreated cells, there was a peak in virus production between 12 and 30 h p.i. reaching a maximum of 10 6.5 to 10 8 PFU/mL (Supplementary Figure S1) ." ] },{ "paper_id": "8e08171efdeefb1359c606284d75271667ef8252", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Values are presented as the mean \u00b1 s.d. for three or four independent experiments, determined on the basis of pilot experiments to estimate the effective numbers. Statistical comparisons were made using a paired two-tailed Student's t-test, and a P < 0.05 was considered statistically significant." ] },{ "paper_id": "8e08fc4e2bad1f9e32a4034e66d96014978e070f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Only reports using PCR-based diagnostic techniques were included.", "Frontiers in Microbiology | www.frontiersin.org infection and cohorting of infected patients are most effective to prevent RSV transmission in NICUs and pediatric wards (Groothuis et al., 2008) .", "Several authors highlight that of all infection control methods, adequate hand washing/hand disinfection, rapid screening for ", "KP and OA performed the review of the current literature as well as data analysis. KP and AB drafted the manuscript. All authors have read and approved the final manuscript." ] },{ "paper_id": "8e15c84010f5ea9e602ae6e51f9ac12ee754a9c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Unfounded policies, such as the Louisiana DOHH response, also have the potential to encourage potentially exposed individuals to travel outside of monitored routes, deny their exposure, and avoid diagnosis and isolation when symptomatic. Instead, the DOHH should adopt policies based on evidence, such as the established protocols of M\u00e9decins Sans Fronti\u00e8res and the CDC, 6 which advise monitoring returned asymptomatic health workers. These are effective and should continue to be the basis for a response to EVD in the United States.", "Ironically, the ASTMH is the pre-eminent professional society in tropical medicine, and the annual meeting of the society is an ideal place to share scientific advances in response to EVD, an interchange that benefits both the United States and all countries facing the current epidemic. Prospective conference attendees who are actively engaged in the EVD response were prepared to share their experiences in scientific sessions, but some could not attend. Numerous attendees from west Africa, including countries not directly affected by EVD, may have been afraid to attend because of not knowing whether they would be turned away on arrival. Moreover, the DOHH reiterated their travel ban for attendees of the annual conference of the American Public Health Association held November 15-19 in New Orleans.", "In the case of the current EVD epidemic and other public health crises, there is a need for greater advocacy on the part of health professionals and academic and professional institutions. Beyond the responsibility of providers to care for individual patients, health professionals should raise awareness about the public health implications of inappropriate responses and policies to public health crises. The medical community should unite and attack inappropriate policies to better protect our patients and their communities. Broader advocacy at the national level and within professional societies is needed to eschew fear-induced and political decisions and maintain evidence-based, neutral, and destigmatizing responses. Such actions would serve to refocus discussion on the evidence and show solidarity on the part of health professionals with the affected population as well as the heroic providers who have chosen to combat Ebola at its source." ] },{ "paper_id": "8e16bcce21552d6bb63b2407557f0a8dbd8b007e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "According to adenoid size, as determined by lateral X-ray and/ or nasal endoscopy, the 119 patients who underwent adenoidectomy (2 patients who underwent tonsillectomy did not have adenoids removed), were grouped as follows:", "-Group 1: Included 15 patients (12.6%) with 3 to 13 years of age (mean of 7 years), with less than 50% airway obstruction. -Group 2: Included 58 patients (48.7%) with 1 to 14 years of age (mean of 6.3 years) with 50-75% airway obstruction. -Group 3: Included 46 patients (38.7%) with 2 to 14 years of age (mean 5.3 years), with airway obstruction greater than 75%.", "After processing, all samples were aliquoted and kept at 270uC until further testing." ] },{ "paper_id": "8e29fa03ad2ae833e99f41652cc543877d415c44", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Marburg virus (MARV) is also a negative sense RNA virus belonging to the family Filoviridae that causes hemorrhagic fever (86 ", "Schistosoma haematobium (urinary blood fluke) is the etiologic agent for urogenital schistosomiasis, a source of morbidity and mortality for over 112 million people worldwide (139) . ", "YFV is an arthropod-borne virus of the genus Flavivirus (family Flaviviridae) and has high morbidity and mortality rates in regions of sub-Saharan Africa and South America (53) . It was one of the first viruses of humans to be identified, isolated, propagated in vitro and studied by genomic sequencing (54) ." ] },{ "paper_id": "8e2bd29ae5f88af72cf04f8e7da51a3eb9c8258f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2015, 7 4120 Keywords: Dengue virus (DENV); non-structural protein 4A (NS4A); amphipathic helix; curvature sensing; peptide membrane interaction", "The lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) in chloroform solution was purchased from Avanti Polar Lipids (Alabaster, AL, USA). Small unilamellar lipid vesicles (SUVs) were prepared from chloroform-free POPC dispersions (20 mg\u00a8mL\u00b41) in sample buffer as described earlier [12] . SUVs were obtained by sequential extrusion through 50 nm (15 times) and 30 nm (15 times) Nuclepore polycarbonate membranes (GE Healthcare) with nominal pore diameter of either 50 or 30 nm, followed by sonication with a 3 mm microtip of a Branson 250 sonifier (15 cycles of sonication, 20 s each, interrupted by cooling for 2 min after each cycle). Sonicated SUVs were centrifuged for 10 min at 16,100\u02c6g and 10\u02ddC in a refrigerated Eppendorf 5415 R tabletop centrifuge to remove any titanium abrasion of the microtip from the sample. The hydrodynamic radius of each liposome preparation was determined by dynamic light scattering (DLS) using a Dyna Pro instrument (Protein Solutions, Lakewood, NJ, USA) equipped with a 3 mm path length 45 \u00b5L quartz cell. Liposome solutions (20 mg of POPC per mL) were diluted 100-fold with buffer directly after extrusion or sonication and measured immediately. Data were analyzed with Dynamics V6 software distributed with the instrument. Experimental data were fitted to the model of Rayleigh spheres.", "NMR experiments were conducted at 30\u02ddC on Bruker Avance III HD NMR and Varian VNMRS instruments, equipped with cryogenic Z-axis pulse-field-gradient (PFG) triple resonance probes operating at proton frequencies of 700 and 900 MHz, respectively. Samples for resonance assignment contained 300 \u00b5M [U-15 N, 13 C]-labeled NS4A(1-48) in sample buffer (50 mM sodium phosphate, pH 6.8, 150 mM NaCl) as used for the liposome flotation experiments but supplemented with 10% (v/v) deuterium oxide and 0.03% (w/v) NaN 3 (referred to as NMR buffer). Assignment of protein backbone resonances was accomplished using a combined set of heteronuclear multidimensional NMR experiments: 2D ( 1 H-15 N)-HSQC [14, 15] , 2D ( 1 H-13 C)-HSQC [16] , 3D HNCA [17] , 3D BT-HNCO [18] , and 3D HNcaCO [19] . 1 H and 13 C chemical shifts were referenced directly to internal 4,4-dimethyl-4-silapentane-1-sulfonic acid (DSS) at 0 ppm and 15 N chemical shifts were referenced indirectly to DSS using the absolute ratio of the 15 N and 1 H zero point frequencies [20] . NMR data were processed using NMRPipe, v.8.1 [21] and evaluated with CcpNmr v.2.4 [22] . " ] },{ "paper_id": "8e30d311467bd72abd1a319a9f841158b6b685fc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PLOS Neglected Tropical Diseases | https://doi.org/10.", "\u2022 Duplicated studies", "\u2022 Animal and mosquito in-vivo pre-clinical models (e.g mouse, non-human primates)" ] },{ "paper_id": "8e3230d271fea2714dd544af802180200812419d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Compound RD K i (\u00b5M); k 2nd (M \u22121 min \u22121 ) FP K i (\u00b5M); k 2nd (M \u22121 min \u22121 ) CL K i (\u00b5M); k 2nd (M \u22121 min \u22121 ) CB K i (\u00b5M)", "K i (\u00b5M) " ] },{ "paper_id": "8e3f518b27782ac9cc19e7556d74100ff23d972b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were calculated using one way analysis of variance (ANOVA). Significance was attained at p < 0.05. ", "Here we showed that mitochondrial membrane potential was significantly reduced in manner of time-dependent, which is consistent with the finding that MVC infection induced the disruption of MOMP." ] },{ "paper_id": "8e3f91d0836afefc7a5e71a8e7db1155af4c2c8c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.ppat.1007009.g002" ] },{ "paper_id": "8e47f269f449983eb0dc70d257f09f27b1e81247", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To detect cholesterol distribution we used Filipin staining (Sigma), as previously described [20] . Cholesterol was visualized in a conventional Leica DM RB microscope by combining a 63X immersion oil objective and a UV filter set. Images were captured with Leica Application Suite advanced fluorescence software (LAS AF) and ImageJ software. Finally, digital images were processed with Adobe Photoshop 8.0.", "Bonferroni's multiple-comparison test was used to compare different experimental groups. Prism software (GraphPad Software, Inc.) and INSTAT3 software were used for the statistical analysis. Values were expressed in graph bars as mean \u00b1SD of at least three independent experiments unless otherwise noted. Metrics were normalized to control values and represented in graphics. Asterisks denote statistically significant differences ( \u00c3\u00c3\u00c3 p<0.001, \u00c3\u00c3 p<0.01 and \u00c3 p<0.05).", "doi:10.1371/journal.pone.0154366.g005" ] },{ "paper_id": "8e4a1132b0301964add6af40ca83b222d7f6d9e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For genomic DNA, intron-exon boundaries were identified from conserved splice signals (GT/AG) and, where possible, by comparison with published cDNA sequences. Sequences were aligned using CLUSTALX 1.81 [57] , and checked by eye. We obtained .90% of continuous coding sequence for each species we examined.", "All new and published gene sequences were intact with no premature stop codons or frameshift mutations, which, together with the evidence of expression of mRNA in bat retinae, strongly indicate that these mammals have a functional rhodopsin protein.", "Light sensitive pigments comprise a membrane bound Gprotein-coupled receptor (GPCR) known as an opsin and a chromophore group (typically 11-cis retinal in mammals) [10] . Absorption of light results in photoisomerisation of the chromophore, which induces conformation changes in the opsin that leads to signal transduction. Most mammals possess three classes of opsins, which differ in their absorption spectra. The SWS1 (short-wavelength sensitive type 1) and M/LWS (middle/long-wavelength sensitive) are restricted to cone photoreceptor cells and are typically responsible for color vision in bright light [8, 11] , whereas rhodopsin occurs on the rod cells and is extremely sensitive, so enabling dim light (scotopic) vision [8, 9] ." ] },{ "paper_id": "8e549a3356d7bd16111c4f682ae12a21ad4c5633", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The detailed survey visits were not repeated at the large markets and so only offer a glimpse at practices which may be impacted by seasonal events, providing an entry point for more focused research.", "Wildlife Trade and Human Health in Lao PDR PLOS ONE |" ] },{ "paper_id": "8e631c0c0bdbb5cf13818b5b71d39c145b045955", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A basic feature of innate immune cells is the ability to start a transcriptional response program that is specific to the stimulus, and then mounting a signal with a high degree of cell type and stimulus specificity [96] [97] [98] .", "Recent studies have involved epigenetic factors in every aspect of activation and shaping innate and adaptive immune responses. Major contributions are the: \u2192 Recruitment of transcription factors/machinery; \u2192 Prevention of unwanted expression of potent mediators; and \u2192 Repression or activation of secondary gene programs [98, 99] .", "The histone tails of the nucleosome are subject to post-translational modulations. These modulations are covalently attached to the tails and include methylation of arginine residues, and methylation, acetylation, ubiquitination, phosphorylation, and sumoylation of serines (S) and threonines (T) (Table 1, Figure 2A ).", "Innate immunity is one of the earliest barriers to coronavirus infection. Following infection, pathogen recognition receptors (PRRs) such as retinoic acid-inducible gene I (RIG-I), melanoma The 5 end is capped and contains a leader sequence (L). SARS-CoV encodes for 14 ORFs, including ORF1, which is processed into nsp1 to nsp16, 4 structural ORFs (S, E, M, and N) in grey, and luxury downstream ORFs (3a, 3b, 6, 7a, 7b, 8a, 8b and 9b). nsp: nonstructural protein; S: spike; E: envelope; M: matrix; and N: nucleoprotein. " ] },{ "paper_id": "8e67618920b0226e661e20a2c36b4436857d9590", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Participants were asked eight items about recent influenza-related behaviours. Five items related to avoidance of places, activities or behaviours. Three items related to recommended pathogen avoidance activities; increased cleaning or disinfecting of surfaces, washing hands with soap and water more often than usual and using alcoholic hand gel more than usual. All items measured recent behaviour and were phrased \"Over the past month, I have ... because of swine flu\". The wording for this question was adapted with permission from a survey undertaken on influenza (H1N1) 2009 by Rubin et al [13] .", "children under 5 years of age [6] . As of February 19 th 2010, there have been 37,713 confirmed cases of pandemic (H1N1) 2009 in Australia, including 191 pandemic influenza-associated deaths [7] ." ] },{ "paper_id": "8e6ef0f551beb549a3e0d523f5b1472cd11110f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In domestic birds, enteritis is the most frequent clinical sign associated with astrovirus infections, although they have also been correlated with other pathological conditions such as nephritis or hepatitis 22, 23 . However, astrovirus infections usually occur asymptomatically in this group of animals, only causing mild disease. The most frequent transmission route is fecal-oral 19, 24 , a circumstance that increases the risk of cross-infection among species that share habitat or get in close contact, for instance, in farms. Furthermore, astroviruses are also important for public and environmental health as a causative agent of encephalitis in cattle 25 .", "Metagenomics has become a powerful tool, capable of characterizing the diversity of viral communities in different ecosystems. A large amount of novel astroviruses has been discovered during the last decade, which lead to the redefinition of the Astroviridae classification 12, 13 . In this study, four novel and genetically distinct astroviruses, provisionally designated as PavAstV-1-4 have been described in cloacal samples from apparently healthy populations of Neotropical passerines from French Guiana.", "Genomic analysis of the four novel pasAstV. The ORFs were predicted using ORFfinder (NCBI: https:// www.ncbi.nlm.nih.gov/orffinder/). TMHMM server v2.0 41 was employed for prediction of transmembrane helices in proteins; cNLS Mapper 42 for nuclear localization signals and NCBI Conserved domains (NCBI: https:// www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi) for the location of serine protease domains, RdRp and the conserved region of the capsid. Secondary structures were predicted by FoldIndex 43 for locating the viral protein associated with the genome (VPg), and by Multicoil scoring form 44 for locating the coiled-coil regions. Hairpin loops were analysed using Mfold 45 . phylogenetic and taxonomic analysis. Genome sequence analysis, genomic organization and multiple alignments were performed using Geneious v11 (Biomatters, New Zealand), EditSeq and SeqMan tools of the DNASTAR 5.0 software package (DNASTAR, Madison, WI), and BioEdit Sequence Alignment Editor 46 ." ] },{ "paper_id": "8e7aa7140ee7e3c82c78c1aa4cf0cb2583e8d9bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data are presented as mean \u00b1 SEM with an error bar that represents at least three independent experiments. Statistical analysis was performed using GraphPad Prism version 5.0 (GraphPad Software, San Diego, CA, USA). Differences in indicators between treatment groups and controls were assessed using the Student's t-test. A two-tailed p-value < 0.05 was considered statistically significant and are marked as \"*\" in the legend. p < 0.01 and p < 0.001 values are marked as \"**\" and \"***\" to indicate corresponding results were highly significant.", "Peste des petits ruminants (PPR), a severe contagious viral disease of domestic and wild small ruminants, particularly affects goats and sheep [1] . The disease was first reported in the Ivory Coast area of West Africa in 1942 [2] . Since then, PPR has markedly spread from the Ivory Coast to numerous other regions, including countries in Africa, the Middle East, Asia, and Europe [3] [4] [5] [6] . Currently, PPR represents a global threat to about 62.5% of goat and sheep populations and is considered by the goat and sheep industry to be an economically important infectious disease worldwide [7] .", "Total RNA was extracted from cells using TRIzol Reagent (Thermo Fisher Scientific) following the manufacturer's protocol. The cDNA was reverse transcribed using M-MLV (Thermo Fisher Scientific) and random hexamers, and TB Green Premix ExTaq Reagent (Takara, Dalian, China) were used for real-time quantitative PCR using a QuantStudio 5 Real-Time QPCR System (Applied Biosystems, Waltham, MA, USA) as described previously [29] . Transcript levels of the gene for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined to normalize total RNA input. Relative gene expression was evaluated using the 2 -CT method. All specific primers in this study were listed in Table 2 . " ] },{ "paper_id": "8e7d05c2e304aa0430befd8259b9bb6c863a0f29", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An astrovirus positive PCR product from a blacknaped monarch (Hypothymis azurea) was purified using a Qiagen PCR purification kit (Qiagen). This product was cloned using a Promega p-Gem T easy kit (ProMega). Plasmids were purified using an Omega MiniPrep (Omega) purification kit and sent for sequencing. Two sequences generated from the same individual in this study were deposited in GenBank (accession numbers KT965674-KT965975). Attempts to generate additional genetic data using a 3\u2032 RACE PCR and culture in embryonated chicken eggs were unsuccessful.", "The RNA dependent reverse polymerase (RdRp) sequences from representative mammal and bird species were aligned using MUSCLE in Geneious 7.1.6 [8] and then manually curated (see Additional file 2: Table S1 ). Nucleotide pairwise p-distances were calculated using Mega 6.06 [9] . Maximum-likelihood (ML) trees were constructed in Geneious 7.1.6 using PHYML v2.2.0 [10] using a combined NNI and SPR topology search and support calculated with 500 ML bootstrap replicates. Bayesian analysis was conducted in Geneious 7.1.6 with MrBayes v3.2.2 [11] using two replicates of 5,000,000 generations sampled every 1,000 generations. The convergence of chains and estimation of burn-in were assessed and Bayesian posterior probabilities were calculated from the consensus of 8,000 trees after excluding the first 2,000 trees as burn-in. Both analyses implemented a GTR + G nucleotide substitution model. Phylogenetic trees were visualized in FigTree v1.4.2 (http://tree.bio.ed.ac.uk/ software/figtree/).", "From February until December 2010 the Wildlife Conservation Society collected samples from wild birds in Cambodia to study circulating viruses in the country's avifauna. Birds were trapped at Toul Krasang, a wetland located in Kandal Province, and Jee Tour, a secondary forest in Tak\u00e9o province under the University of Minnesota IACUC number 0702A02841. Paired oropharyngeal and cloacal swabs were collected from 119 birds at the two field sites (Table 1) . Duplicate samples were taken and stored in either guanidine isothiocyanate or virus transport media for detection or culture, respectively. Samples were kept at \u221280\u00b0C until shipped to Duke-NUS Graduate Medical School Singapore for PCR screening." ] },{ "paper_id": "8e875cc9628872c52aea9d9c298e1b87cf82f1e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Before the extraction procedure, 5 \u03bcL of Equine herpesvirus 1 and 5 \u03bcL of Equine arteritis virus isolates were added to all samples for external DNA and RNA control. Specific target sequences of these viruses were subsequently amplified in separate real-time reverse transcription polymerase chain reactions (RT-PCRs) as an internal control to ensure that negative results were not caused by poor nucleic acid extraction or inhibition of the RT-PCR assay [21, 22] .", "In 12 HCoVs the 805-bp-long region of the polymerase 1b gene for coronaviruses from Alphacoronavirus and 912-bp-long region for coronaviruses from Betacoronavirus were amplified and sequenced. Five of 12 sequences were unique and were deposited in GenBank (acc. no. KF668028-KF668032).", "Supporting Information S1 Appendix. Ethics Approval. (PDF) " ] },{ "paper_id": "8e89329ba5682ffd98598d5b5c6ccd2067abdd12", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In order to find relevant articles with data on NAAT parameters, we performed literature searches from December 2014 to February 2018.", "Articles were initially screened on the title, and secondly on the abstract. Any articles that relied on microfluidic platforms or commercialized extraction devices were excluded. Publications that required complex pre-processing with enzymatic treatment or chemical purification were not selected. Studies were included if they involved direct amplification and detection of genetic material from one of six representative sample types: blood, dried blood spot, serum and plasma, saliva and sputum, swabs, urine, and stool. The full text of appropriate articles was read to extract the necessary information.", "From each of the 174 published works surveyed, we extracted and recorded data that corresponded to test performance. There are many parameters that cannot be ignored when considering NAATs: accuracy, specificity, user-friendliness, training requirements, and so on. As such, we provide an extensive examination of nucleic acid template specificity (including single or multiplexed reactions), amplification methodologies (enzymes, operating temperatures, and amplification technology), and user-friendliness (storage considerations, pretreatment requirements, and physical involvement) in Supplementary Table S1 ." ] },{ "paper_id": "8e8e5b1a4c76cea327ba95e100445f08ffebf9be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Given two different types of individuals, the generating function for the offspring distribution of individual i was", "P\u00f0z cases of type i generated by n cases of type j\u00de \u00bc T n ij \u00f0z\u00de \u00f06\u00de", "Inserting the relevant part of Equation 4 into Equation 7, we obtained", "P\u00f0n; m; a 21 ; a 12 \u00de \u00f011\u00de" ] },{ "paper_id": "8e9605de5913710c88b1107fd65dcc26ab372805", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Study population and design. Since August 2009, the Kenya Medical Research Institute (KEMRI), in partnership with the U.S Centers for Disease Control and Prevention (CDC), has carried out surveillance for ALRI (defined as cough or difficulty breathing with an onset within the last 14 days from hospital admission date) among patients aged \u2265 18 years, at Siaya County Referral Hospital, in Western Kenya. The study population is culturally homogeneous and the area is known for high malaria, tuberculosis and HIV prevalence [7] [8] [9] . A structured questionnaire was programmed using Microsoft Visual Studio.net (Microsoft, Redmond, USA) and installed into netbooks (Mercer classmate) for collection of demographic and clinical examination data from patients by surveillance officers i.e. trained clinical officers and nurses. The data were stored in password protected Microsoft SQL databases (Microsoft, Redmond, USA). All patients were managed and discharged according to the Kenya Ministry of Health standards and guidelines." ] },{ "paper_id": "8e96ff3220b7201598d2c5099ff9a4d03e529b3b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To eliminate variation, three biological repetitions were performed for total RNA isolation. Equal amounts of highquality RNA from the three biological repetitions were mixed for cDNA synthesis. Total RNA was extracted using TRIzol5 reagent (Invitrogen, San Diego, USA) and then treated with DNase I (Invitrogen). RNA purity was checked using a NanoPhotometer5 spectrophotometer (Implen, CA, USA). The RNA concentration was measured with the Qubit5 RNA Assay Kit on a Qubit 2.0 Fluorometer (Life Technologies, CA, USA).", "Total RNA was isolated from a mixture of equal amounts of leaves and shoots.", "However, we should notice more than half of unigenes generated were not annotated according to existing databases. Therefore, according to these results, there is a need to generate a large collection of unigenes and further characterize the gene structures and expression patterns in T. sinensis.", "T. sinensis has a long history of cultivation in China and is widely distributed throughout Asia [15] . Most of the previous studies on this species have focused on its cultivation, effective ingredients [2, 7] , and pharmacological value [4] . Very limited information on the genetic basis of T. sinensis is available [16, 17] , and there have been only a few reports addressing its genetic diversity using random amplified polymorphic DNA (RAPD) and isoenzyme analyses [16] and by examining terpene synthase genes [17] . Transcriptome researches would clearly improve understanding of the phylogeny and diversification of T. sinensis [18] ." ] },{ "paper_id": "8eb3bdc336b90a70201e28477934062f67afcbcf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Joffe and Miller give the example of an epidemic of avian influenza and note that, just as firefighters or rescue workers facing a large-scale disaster take on higher risks than they would in the ordinary course, so too could research participants [6] .", "Application to a \"Disease X\"", "Supplementary information accompanies this paper at https://doi.org/10. 1186/s13063-019-3843-0. " ] },{ "paper_id": "8eb469fc4a148699ffdf0969e3ea75048412472d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All common reagents were purchased from Sigma Chemical Co. (St. Louis, MO, USA) unless stated otherwise." ] },{ "paper_id": "8ec3cfefcf560550c37dbc48107102bf2c893036", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tissue samples were disrupted and homogenized with plastic pistons using specific buffers including in the Allprep DNA RNA Mini kit (Qiagen) or in TriReagent (Euromedex) for liver and lungs or for brain, respectively. Total RNA was then extracted according to the manufacturer's protocols. In addition, a final step of purification was performed for RNA extracted from brain using RNeasy kit (Qiagen). All RNA were eluted in 30 ml of RNase-free water and stored at 280uC until use. They were then subjected to reverse transcription followed by amplification with the wholetranscriptome amplification (WTA) protocol (QuantiTect Whole Transcriptome kit, Qiagen), as previously described [30] . The WTA products obtained from the various organs collected from a single bat specimen were pooled (mixing of equal volumes) before sequencing.", "The GenBank accession numbers for the sequences of the partial viral genomes (high-scoring segment pairs (HSPs) or sequenced PCR products) obtained during this study and used in the phylogenetic analysis are KF170221-KF170229. The data from Illumina sequencing have been deposited in the GenBank Sequence", "Reads Archive under accession numbers SAMN02437308-SAMN02437316." ] },{ "paper_id": "8ecb2c48d129fe9df101cb136f9496000d4bb581", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are presented as mean 6 S.E. Data were analyzed using SigmaStat (version 3.01A; SYSTAT). For multiple comparisons, analysis was by one-way analysis of variance followed by Bonferroni correction. For comparisons involving two groups, Student's t-test was used. A p value , 0.05 was considered significant.", "In some experiments, prior to immunoblot analysis for ACE2, concentrated medium and cell lysates were subjected to deglycosylation using peptide N-glycosidase F (PNGase F, New England Biolabs, Ipswich, MA, USA), according to the manufacturer's instructions. Samples were denatured in 0.5% SDS, 40 mM DTT at 100uC for 10 min. After cooling to room temperature, the samples were incubated in 50 mM sodium phosphate (pH 7.5), 1% NP-40 (vol/vol), and 1000 U PNGase F at 37uC for 3 hrs.", "The deglycosylated immunoprecipitated ACE2 polypeptides from conditioned cell culture medium were separated on 10% SDS-polyacrylamide gels, and subjected to silver staining using SilverQuest silver staining kit (Invitrogen). The polypeptide bands matching those identified on immunoblots were excised and destained. Proteins were in-gel digested using trypsin (Promega, Madison, WI, USA), as described [24] . The resulting peptide extracts were purified by ZipTip (Milllipore), concentrated by vacufuge (Eppendorf, Hamburg, Germany), and resuspended in 0.1% formic acid (Thermo Fisher Scientific, Waltham, MA, USA)." ] },{ "paper_id": "8ecf2ad1996b1e93edd3eb7a8b2207114a33818a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A retrospective review was conducted to all reports of Gramnegative and Gram-positive isolates from all units at SQUH which is a 570-bed tertiary care teaching hospital in Muscat, Oman. The study has been conducted for a period from January 2012 to December 2012.", "Gram-negative and Gram-positive organisms were identified and tested. Definition of MDRO was based on the recently proposed joint definition by the European Center for Disease Prevention and Control (ECDC) and the Centers for Disease Prevention and Control (CDC) [25] .", "To our knowledge, this study is the first of its kind that comprehensively explores monthly variations, prevalence rates, sites of infection, and type of MDRO in a tertiary care hospital." ] },{ "paper_id": "8ed0914312a47f0d8c127bc1db47446c1792e1de", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1) Details of the model in its stochastic form are provided in the Appendix." ] },{ "paper_id": "8ed6b522481e264a5d691f7f5fbd5d142b5f82f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In these examples, mortality rates were very high, and paradoxically, mortality rates were highest in the healthiest age group (i.e., 20-40 years of age), which typically comprises individuals with the most active immune function [5, 42, 43] . These findings suggest that host factors (i.e., immune reactions against insults from pathogen infection) may determine the phenotype, severity, and prognosis of a disease.", "Acute respiratory distress syndrome (ARDS) or severe acute lung injury is a critical syndrome caused by heterogeneous etiologies, and is characterized by acute progression of respiratory symptoms and signs, bilateral diffuse infiltrates on chest imaging, and severe hypoxemia [1] . The severity of ARDS is associated with poor prognosis and higher mortality, and, by the Berlin definition, diagnostic hypoxemia is defined as decreased arterial PaO 2 /FiO 2 ratio with parameters of 201-300 mmHg for mild ARDS, 101-200 mmHg for moderate ARDS, and \u2264100 mmHg for severe ARDS [2] .", "The author declares no conflict of interest. " ] },{ "paper_id": "8ed7e985c1bef92952d4626090ac1c31c9566a23", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\"We can deliver information among people during Friday prayers, the special prayer day for Muslims.\"" ] },{ "paper_id": "8ee7ec977aa10ef8bbe5633d5dc6bb9793572508", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and CsA (C), as quantified by RT-qPCR. ", "Supplementary Figure 1: Schematic representation of the HCV replicons. Schematic representation of subgenomic (top) and full-length (bottom) HCV replicons. The genotype and the name of plasmids are indicated in italic. RLuc: Renilla Luciferase; FLuc: Firefly Luciferase; Neo: neomycine resistance gene; EMCV: internal ribosome entry site of the encephalomyocarditis virus; NS: non-structural; C: core; E: envelope; GT: genotype. Supplementary Figure 2: Cellular toxicity of C31 and ALV in Huh7.5 and MRC5 cells. Cellular toxicity of C31 (black circle) and ALV (open triangle) was evaluated in Huh7.5 cells (A) and MRC5 cells (B) by means of a MTT assay.", "SMCypI compounds (C31, C32, C34, C35 and C36) synthesis was performed as described in our previous report (1) . The synthesis of compound C33 was performed as described in Scheme 1. Ester S1 (330 mg, 0.90 mmol) was dissolved in 10 ml of MeOH and 10 ml of water, LiOH (86 mg, 3.60 mmol, 4.00 equiv) was added and the reaction mixture was heated to 50\u00b0C for 2 h. The reaction mixture was concentrated and 100 ml of water was added; it was then extracted twice with AcOEt. The aqueous phase was acidified to pH 3 with concentrated HCl 36%, then extracted twice with AcOEt. The combined organic phase was dried over Na 2 SO 4 , filtered and concentrated to yield S2 (283 mg, 93%) as a white solid. 1 " ] },{ "paper_id": "8eefe017d2a4fedeac3243fb76f3b417b16023f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the capture events, animal handling, euthanasia and transfer of samples across country borders were performed in accordance with the guidelines of the American Society of Mammalogists (http://www.mammalsociety.org/committees/ animal-care-and-use) [22] :", "Bats were captured following recommendations by Kunz and Parsons [23] . Captured bats were removed carefully from nets as soon as possible to minimize injury, drowning, strangulation, or stress. Safe and humane euthanasia was achieved through the use of inhalant anaesthetic (halothane) prior to autopsy.", "All work (capture, euthanasia and autopsy) was carried out with authorization from the respective wildlife authorities of each [4, 24, 25] ." ] },{ "paper_id": "8ef0cd02635a7841b2b26cb159038427c31c39b3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The World Health Organization classifies dengue as a major international public health concern. Some 2\u00c15 billion people or two-fifths of the world\u00d5s population are at risk of infection. Dengue haemorrhagic fever (DHF) is endemic in more than 100 countries in Africa, the Americas, Eastern Mediterranean, South-East Asia and the Western Pacific regions (World Health Organization, 2008) .", "A prototype dengue RNA transcription-mediated amplification (TMA) assay (Gen-Probe, Inc., San Diego, CA, USA) was developed for use in large-scale screening of blood donor samples and uses target genomic sequences that are highly conserved across all four serotypes. The analytical sensitivity of the assay has been established at a detection of 14\u00c19 copies mL 21 at 95% detection limit and 3\u00c15 copies mL 21 at 50% detection limit for DEN-1, with comparable sensitivity for all four serotypes, and with a specificity of 99\u00c191% .", "The following must be present:", "Rapid and weak pulse Narrow pulse pressure [<20 mmHg (2\u00c17 kPa)] Or manifested by:" ] },{ "paper_id": "8ef53001824bab46d02f6968b8ee1a148a7406d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For Western blotting, cell lysates were prepared in RIPA buffer [50 mM Tris-HCl, pH 7.4, 150 mM NaCl, 2 mM EDTA, 1% Nonidet P-40 (vol/vol), 0.1% SDS (w/vol)] containing Protease Inhibitor Cocktail (Roche) and quantified by Bradford assay (Bio-Rad). Equivalent amounts of each sample were resolved by SDS-PAGE, transferred to a PVDF membrane, and Western blotted with anti-HA 12CA5 monoclonal antibodies (Invitrogen; 1:5,000) and HRP-conjugated goat anti-mouse secondary antibodies (Southern Biotechnology; 1:5,000).", "For Northern blotting, total RNA was harvested using RNA-BEE (Tel-Test) and resolved by agarose-formaldehyde gel electrophoresis. RNAs were transferred to a 0.45 mm nylon membrane and probed with 32 P-labeled GFP DNA probes generated using the Rediprime II random prime labeling system (GE Healthcare).", "HEK293T, COS7, NIH 3T3, NIH 3T12, and Vero cells were maintained in Dulbecco's modified Eagle's medium (DMEM; Invitrogen) supplemented with 10% fetal bovine serum (FBS, Invitrogen). 293T cells were transfected with Effectene (Qiagen) following the manufacturer's protocol.", "Gammaherpesviruses include the human pathogens Epstein-Barr virus (EBV/HHV-4) and Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) [8] , the etiologic agents of some of the most common AIDS-associated cancers, such as Burkitt's lymphoma, nasopharyngeal carcinoma, and primary effusion lymphoma. The related murine gammaherpesvirus 68 (MHV68) is often used as a model for human gammaherpesviruses because, unlike KSHV and EBV, it is genetically tractable, readily replicates in tissue culture without the use of chemicals or overexpression to overcome latency, and infects small rodents including laboratory mice [9, 10, 11] . MHV68 has therefore been instrumental in the identification of factors that contribute to in vivo replication and pathogenesis of the gammaherpesviruses." ] },{ "paper_id": "8ef6b31ac51e4560b97074574711f05a2a30c845", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "APRI index = (AST (IU/L)/upper normal limit) x 100/platelets (10 9 /L) [20] ; FIB\u22124 score = age (years) x AST (IU/L)/platelets (10 9 /L) x (ALT (IU/L)) 1/2 ) [21] ; GPR ratio = GGT (IU/L)/platelets (10 9 /L), where GGT is -glutamyltransferase [22] .", "The data used to support the findings of this study are available from the corresponding author upon request.", "The authors declare that they have no conflicts of interest." ] },{ "paper_id": "8f11a3876dfbf3ba4a143b9e2ad122b8c2b9c2be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The source code of our method can be obtained at http: //ensembleassembly.sourceforge.net, or https://github.com/ xutaodeng/EnsembleAssembler.", "A, S and V. Among all individual assemblers, M took the longest to run on average, taking anywhere from a few minutes to a few hours to finish. Thus, any ensemble assembly with M as a component took significantly longer to run.", "When comparing the timing for each assembler ( Figure 2E ), we found that assemblers A, S, V and T were relatively fast, typically finishing within seconds to minutes. As expected, OLC assembler W took longer to complete than e46 Nucleic Acids Research, 2015, Vol. 43, No. 7" ] },{ "paper_id": "8f14ee043acb5f880df53ebdd12d6edc71ddb851", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8f240d93eda7d04def440b93acf64e41910f4e7c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The factor provided by the experimentalist in the 'Phase' column", "The value of the current variable" ] },{ "paper_id": "8f25c12cb9bed748932b23030b88070649e67810", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8f26b1ab1d54522ce151927a8cb48cf52058961a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PFCs were isolated by lysing erythrocytes using ammonium chloride solution and resuspended to a final concentration of 2610 6 cells/mL in complete RPMI 1640 medium (Invitrogen, Grand Island, NY) supplemented with 10% heat-inactivated fetal calf serum (FCS; HyClone, Logan, UT), 100 U/mL penicillin, 100 mg/mL streptomycin, 2 mM L-glutamine, and 50 mM 2mercaptoethanol. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Hypaque gradient centrifugation of heparinized venous blood obtained from healthy individuals or TB patients.", "Written informed consent was obtained from all patients and healthy donors. Ethics approval for the present study was obtained from the ethics committee of the Zhongshan School of Medicine, Sun Yat-sen University (Guangzhou, China) and the Chest Hospital of Guangzhou (Guangzhou, China).", "Conceived and designed the experiments: CYW. Performed the experiments: LL. Analyzed the data: LL. Contributed reagents/materials/ analysis tools: DQ XYF SHL XLZ. Wrote the paper: LL." ] },{ "paper_id": "8f3221b42c66b835706134994f7b71f10f9b104d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Preventive strategies directed at individual cats have also been evaluated within shelters, including supplementation with lysine and vaccination for FHV-1 and FCV [18, 19] . No preventive benefit was found for lysine supplementation, while at best modest benefits have been reported for vaccination [19] [20] [21] .", "Supporting information S1 Doc. Shelter URI criteria. (DOCX) S1 Survey link. (DOCX) ", "Pathogen prevalence is shown in Table 4 ." ] },{ "paper_id": "8f44e4d806117b957383a7ee870d2dd38213f094", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2015, 7, 5428-5442", "Considering the fact that viral infection is often followed by secondary bacterial infections [17] , it would be highly advantageous if peptide therapy can target both the primary viral and a secondary bacterial infection. There is a possibility of complementing treatment of standard antiviral drugs with antibacterial drugs, such as neuraminidase inhibitors (oral oseltamivir and inhaled zanamivir) or M2 ion channel blockers (amantadine and rimantadine). The synergic effect and immune-modulatory role of such drug combinations have not been studied yet in protection against potential secondary bacterial infection.", "The great advantage of peptides against viruses consists in the reduced possibility of developing resistance during the treatment [28] ." ] },{ "paper_id": "8f4aac04423c7ebb955c7f006665728fe95f1498", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The global human immunodeficiency virus (HIV) epidemic continues to grow, with more than 36.7 million people now estimated to carry the virus (UNAIDS Report 2017: http://www. unaid s.org/en/resou rces/docum ents/2017/2017_data_book).", "Sterile tobacco (Nicotiana tabacum cv. Petit Havana) plants were grown on agar-solidified MS medium (Murashige and Skoog 1962) containing 30 g/L sucrose. For seed production and generation of material for molecular analyses, plants were transferred to soil and cultivated under standard greenhouse conditions. For inheritance assays, seeds were surface sterilized and sown on agar-solidified MS medium containing 20 g/L sucrose and the appropriate antibiotics for selection (spectinomycin: 500 mg/L, gentamycin: 200 mg/L).", "The online version of this article (https ://doi.org/10.1007/s1110 3-018-0744-7) contains supplementary material, which is available to authorized users." ] },{ "paper_id": "8f5fc8690f47c0c30dd99bd8d84f9e80f25fdcc8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The mRNA of the infected cells were collected at 3 h, 6 h and 24 h post infection for viral gene quantification using qPCR as described [5] ", "A confluent 96-well tissue culture plate of MDCK cells was prepared one day before the virus titration (TCID 50 ) assay. Cells were washed once with PBS and replenished with serum-free MEM medium supplemented with 100 units/ml penicillin and 100 mg/ml streptomycin and 2 mg/ml of TPCK (tosylsulfonyl phenylalanylchloromethyl ketone) treated trypsin. Serial dilutions of virus supernatant, from 0.5 log to 7 log, were performed before adding the virus dilutions onto the plates in quadruplicate. The plates were observed for cytopathic effect daily. The end-point of viral dilution leading to CPE in 50% of inoculated wells was estimated using the Karber method [19] .", "NHBE cells were grown and subcultured according to the suppliers instructions in serum-free and hormone supplemented bronchial epithelial growth media (BEGM) (Lonza, Walkersville, Inc.) as described [5] . The cell suspensions were seeded on transwell inserts (Corning, New York, USA) with a cell density of 1610 5 cells/cm 2 and cells were incubated in a humidified atmosphere (5% CO 2 , 37uC) under submerged conditions." ] },{ "paper_id": "8f7a0834ec2f0e699772cf4c647b0f3cb213b54e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "How are antibiotic-producing or resistance gene-carrying populations controlled?", "How are toxins controlled?" ] },{ "paper_id": "8f7db32196a87deaa43589b325f60156efc5a63a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1.) Donor eligibility: To reduce asymptomatic donor bacteremia, subjects with recent dental treatments, minor surgery or increased body temperature at presentation should be excluded from donation.", "2.) Optimal product processing, handling and storage: Continuous training and supervision of the responsible personnel for donation and product processing are key elements for high quality standards and product safety. Also, consistent storage temperatures (4\u00b0C for RBC and 22-24\u00b0C for PLT) need to be maintained to ensure product integrity.", "3.) Skin preparation: Improved donor arm disinfection has been shown to be crucial in reducing the numbers of remaining bacteria on the phlebotomy puncture site [16] [17] [18] .", "6.) Pathogen reduction methods: Pathogen reduction is a pro-active approach to further reduce the risk of TTI and could prove effective for most known and emerging pathogens. The goal of pathogen inactivation is to reduce transmissible pathogens (bacteria, viruses and protozoa) without compromising therapeutic efficacy of the blood product or introducing secondary risks. These techniques and their current limitations are discussed in more detail below." ] },{ "paper_id": "8f8bd6796570957dcf2c62e70faa1f1ca3769182", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We performed one-and two-way analysis of variance (ANOVA) with either Dunnet's (comparison of multiple samples with a single reference sample) or Sidak's posttest (multi-step comparison of two samples over time) using the GraphPad Prism 7 software package (GraphPad Software). Only p values of 0.05 or lower were considered statistically significant (p > 0.05 [ns, not significant], p \u2264 0.05 [*], p \u2264 0.01 [**], p \u2264 0.005 [***])." ] },{ "paper_id": "8f962ad62ba3d5af7c52898283c4827ff71a5949", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide and amino acid sequences were analyzed using the BLAST server at NCBI. The alignment of the amino acid sequences of the N-termini of TMPRSS2 isoform 1 (NP_001128571.1) and isoform 2 (NP_005647.3) was constructed using the Clustal Omega software.", "Respiratory viruses pose a significant threat to human health. In particular, annual influenza epidemics are associated with several hundred thousand deaths every year, and interspersed pandemics may wreck even greater havoc [1] , as documented by the 1918 Spanish influenza, which caused 30 to 50 million deaths [2] . Antiviral drugs against influenza are available but their effectiveness is compromised by frequent acquisition of viral resistance. Moreover, no drugs with broad antiviral activity are available to combat emerging and highly virulent respiratory viruses, including severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS) CoV. In order to close this gap, novel antiviral strategies are being sought, which allow inhibition of a broad spectrum of viruses and which are associated with a high barrier against resistance development. Host cell factors which are essential for viral spread but dispensable for cellular survival are attractive targets for such approaches to antiviral therapy.", "Total RNA was isolated from human cell lines with RNeasy Mini Kit (Qiagen), as recommended by the manufacturer. The Human MTC\u2122 Panel I (Clonetech) cDNA was used to analyze mRNA expression in human organs. This cDNA was obtained from pooled tissue samples from 1-15 Caucasian donors aged 18-69 and representing both sexes. Using a Cloned AMV First-Strand cDNA synthesis kit (Invitrogen) and random hexamers, the first strand cDNA synthesis was performed from 1 \u03bcg of total RNA, previously treated with DNaseI (Roche), according to the manufacturer's protocol. The subsequent PCR was performed with Taq polymerase (New England Biolabs) using gene-specific primers for tmprss2 transcript variant 1 (forward 5' GTG AAA GCG GGT GTG AGG A 3' and reverse 5'CTG TGC GGG ATA GGG GTT TT 3'), tmprss2 transcript variant 2 (forward 5'GCG AGG GGC GGG GAG CGC C 3' and reverse 5' GGT AGT ACT GAG CCG GAT GC 3') and GAPDH (forward 5' ATG GGG AAG GTG AAG GTC GG 3' and reverse 5' ATA CTT CTC ATG GTT CAC AC 3'). All PCRs were run for 40 cycles of 30 sec denaturation at 95\u00b0C, 30 sec annealing at 58\u00b0C, and 30 sec elongation at 72\u00b0C. Amplicons were analyzed by agarose gel electrophoresis." ] },{ "paper_id": "8f98c8621da6438169976931b2bc2cce12959a70", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the frameshifting measurement, the FY1619 S. cerevisiae strain was used (MATa ura3-52 trp1D63 his3D200 leu2D1).", "The structure of the -1 translational frameshifting motif of PaYIP3", "Pictures were taken with a Leica DMIRE 2 microscope coupled with a 10-MHz Cool SNAP HQ charge-coupled device camera (Roper Instruments). They were analyzed with ImageJ. The GFP filter was the GFP-3035B from Semrock (Excitation: 472 nm/30, dichro\u00efc: 495 nm, Emission: 520 nm/35).", "The anti-GFP monoclonal antibodies from Roche Applied Science (catalog number 11814460001) were used for the detection of GFP-fusion proteins by western blot analysis. Proteins were extracted as described [32] ." ] },{ "paper_id": "8f9e4f6b34a4b30f54abef008fc8c0fde00ff02f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "L\u00f0t; u\u00de dt: \u00f02:3\u00de", "L\u00f0t; u\u00de dt:", "\u00f02:6\u00de" ] },{ "paper_id": "8f9eda12b9470bd15725025244000aeb69b9ebb7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "If not explicitly stated in the figure legends, unpaired and paired Student t-tests were performed to analyze data pairs originating from individual experiments or mean data of multiple experiments, respectively. One-way ANOVA with Bonferroni post-test analysis was carried out for combined comparison of multiple groups ( \u00c3 , p 0.05; \u00c3\u00c3 , p 0.005; \u00c3\u00c3\u00c3 , p 0.001).", "Here, we show that VSV-G counteracts tetherin in transfected cells. However, no evidence for a contribution of tetherin-antagonism to spread of authentic VSV in tetherin-positive cells was obtained.", "Vesicular stomatitis virus (VSV) is a negative-stranded RNA virus within the Rhabdoviridae family, and VSV New Jersey and Indiana are major VSV serotypes. VSV is transmitted from insects to ungulates (mainly cattle, horses and pigs), in which it can cause mucosal lesions [1] [2] [3] . In addition, the virus can be transmitted to humans and such infections usually induce influenza-like symptoms [3] . VSV replicates fast, is highly immunogenic and is frequently used to model infection by negative-stranded RNA viruses. Moreover, VSV is used as a tool for diverse scientific endeavors [4] . For instance, VSV has oncolytic properties [5] and is developed for cancer therapy [6] . Moreover, VSV variants in which the open reading frame for the viral glycoprotein (VSV-G) has been replaced by that of the Ebola virus (EBOV) glycoprotein (GP) are currently tested as vaccines against EBOV infection [7] [8] [9] ." ] },{ "paper_id": "8f9f22f0d245cf41e5047230fa1c907b47a734ac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Blasi, F., Damato, S., Cosentini, R., Tarsia, P., Raccanelli, R., Centanni, S., et al. (2002) . Chlamydia pneumoniae and chronic bronchitis: association with severity and bacterial clearance following treatment. ", "Allergic bronchopulmonary aspergillosis (ABPA) is a unique form of asthma caused by colonization of the LRT (Vlahakis and Aksamit, 2001). ABPA is caused by an exaggerated T helper type 2 response to the ubiquitous mold Aspergillus spp., by which colonization leads to allergic and/or asthma symptoms (Edwards et al., 2012) .", "Other factors. The diverse etiologies for asthma exacerbation are well known, including viruses, allergens (dust mite, pollen, animal dander), smoking, gastroesophageal reflux disease, obesity, rhinosinusitis, stress, occupational exposures, hormones (menstrual asthma), drugs (acetylsalicylic acid, non-steroidal anti-inflammatory drugs, beta-blockers), exercise, and air pollutants. Physicians should be aware of these risk factors for asthma exacerbation (Dougherty and Fahy, 2009 ).", "Respiratory virus infection affects the pathogenesis of asthma. Bronchial epithelial cells are at the site of respiratory virus infection and replication. Respiratory virus infection induces production of various cytokines or chemokines and causes injury to epithelial cells or disruption of tight junctions. This inflammatory process may be amplified by intrinsic factors (susceptibility gene, family history of atopy, lung development) or environmental factors (respiratory virus infection, allergen exposure, smoking, and air pollutants, etc.; Hashimoto et al., 2008; Dougherty and Fahy, 2009) . Some studies showing a deficiency in interferon (IFN)-\u03b2 and IFN-\u03bb production in response to HRV inoculation in airway epithelial cells cultured from asthmatic versus normal subjects (Holtzman, 2012) suggested that asthmatic patients have deficient IFN-\u03b2, IFN-\u03bb, and perhaps some of the IFN-\u03b1s, but the precise mechanism or mechanisms behind deficient IFN production in these patients remain unknown." ] },{ "paper_id": "8fa2be5d5abb0473dda3892cf6f42a318f87b39b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Table S1", "The statistics and annotations of unigenes.", "(XLS) ", "where n is the number of alleles at one locus; Pi and Pj are the frequencies of the ith and jth alleles at one locus; j = i+1." ] },{ "paper_id": "8fb937ce37aa1ad36478e6bc9c1df60d7f594f78", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "8fc0e17fe32585f3e3216b48c7beba4b15221e57", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DH5\u2423 E. coli cells competent for transformation with DNA were prepared according to Hanahan et al. (34) .", "Microscope analysis for filamentation. Cells were observed with a Leica DM RXA microscope (Leica Microsystems) with an x40 oil-immersion objective.", "Proteins were separated on an Invitrogen 8% Nu-Page gel, transferred onto nitrocellulose. TAP-and 3HAtagged proteins were detected using peroxidase-coupled anti-peroxidase and anti-HA-peroxidase antibodies (Sigma and Roche, respectively) and an ECL kit (GE Healthcare)." ] },{ "paper_id": "8fcf1d545d5c10fbe83bbbd9dab8391fb748be7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The macrophages were harvested and resuspended in phosphate-buffered saline. The cellular suspension was mixed with equal amounts of trypan blue solution and the number of live (transparent) and dead (blue) cells were counted using a hemacytometer (Assistent, Sondheim, Germany).", "Acute respiratory distress syndrome accounts for the major mortality of acute lung inflammation [1] , which can be triggered by various pathogens including atypical infection; that is, severe acute respiratory syndrome. Cytokine storm-mediated extensive lung injury is the ultimate pathomechanism of acute respiratory distress syndrome and severe acute respiratory syndrome [2, 3] . In addition to specific antibiotics and antiviral agents, steroid treatment and plasma exchange are therapeutic strategies to reduce local and circulating inflammatory cytokine levels. There is no safe and effective therapy to eliminate cytokine storm in critical patients since severe steroid-related and plasmapheresis-associated complications may occur in severely ill patients [4, 5] .", "The malondialdehyde level in lung tissue was detected by the Lipid Peroxidation (MDA) Assay Kit (Abcam). Tissue (10 mg) was homogenized on ice in 300 \u03bcl of the MDA Lysis Buffer (Abcam) and then centrifuged at 13,000 \u00d7 g for 10 minutes to remove insoluble materials. Then 200 \u03bcl of the supernatant and 600 \u03bcl TBA solution were incubated at 95\u00b0C for 60 minutes before cooling down to room temperature in the ice bath for 10 minutes. The absorbance at 532 nm was read and proportioned to the malondialdehyde level." ] },{ "paper_id": "8fddf78a6b3a823c0ebeb2dfbfe274e46fee97f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Interestingly, samples (com3, com5, com7, UCD2, and UCD4) that were previously diagnosed with PhV-1, which belongs to the genus Varicellovirus, were indeed found to have sequence assignments to PhV-1 in 3 of the 5 cases (Fig 1) . All PhV-1 infected comparative samples (com3, com5, and com7) had sequence annotations to PhV-1, but no UCD animals showed any reads associated with this virus.", "Additionally, coverage information for C. burnetii RSA 493 plasmid pQpH1 (AE016829.1) was analyzed. After FqTrim, all sequences from sample UCD6 were aligned using bowtie2 to plasmid pQpH1. SAMTools Version: 0.1.19-44428cd [31] was used to obtain coverage information for each base position on the 37Kb plasmid.", "Emerging infectious diseases are on the rise in both humans and wildlife. Hence, preemptive pathogen surveillance is necessary to better-forecast disease outbreaks [1, 2] . Currently, it is thought that about 61% of emerging human diseases arise from zoonotic pathogens and~70% of these originate from wildlife [1, 3] . Evidently, emerging diseases are likely to be zoonotic, such as the Ebola outbreak of 2013-2014 and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) of 2012 and 2014 [3] [4] [5] . Recent outbreaks like these exemplify the severity and need to evaluate the origins of zoonoses.", "Phylogenetic analysis. A phylogenetic tree of the harbor seal associated Coxiella sp. was constructed using the 16S rRNA gene and the following bacteria (for reference we included the corresponding NCBI accession numbers): Rickettsia conorii strain Malish 7 (NR_ 074480.1), Rickettsia montanensis str. [32] and RaXML was used to build a maximum likelihood tree using a 1000 boot strap iterations [33] ." ] },{ "paper_id": "8feaa6f0bac0c30c9b3cf6634082e8923d99b070", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples separated by SDS-PAGE were transferred to nitrocellulose membranes (Bio-Rad). Membranes were incubated with the following primary antibodies: rabbit polyclonal anti-PI4KA (Cell Signaling), rabbit polyclonal anti-PI4KB (Upstate), rabbit polyclonal anti-OSBP (ProteinTech), rabbit polyclonal anti-EMCV capsid (kind gift from Ann Palmenberg) and mouse monoclonal anti-\u03b2-actin (Sigma). Secondary antibodies included IRDye 680-conjugated goat anti-mouse or IRDye 800-conjugated goat anti-rabbit (LI-COR). Images of blots were acquired with an Odyssey Fc Imaging System (LI-COR).", "Where indicated, unpaired one-tailed Student's t-test or two-tailed Mann-Whitney test were applied as statistical analyses using the GraphPad Prism software.", "Competing Interests: The authors have declared that no competing interests exist." ] },{ "paper_id": "9000d72e1e522099e6a53feeda6aa6d884a1b179", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PCR reactions were carried out in a PCT-200 Peltier Thermal Cycler (MJ Research). The PCR reactions were performed with HotStarTaq Polymerase (Qiagen) according to manufacturer's instructions.", "Supplementary Materials: The following are available online at http://www.mdpi.com/1999-4915/11/2/125/s1, Table S1 and Table S2 . ", "The authors declare no conflict of interest.", "The coronavirus sequences generated in this study were deposited in GenBank under the accession numbers MK163627 and MK249067-MK249069." ] },{ "paper_id": "9002b1efb25414c9e3ea87ad89e6c9be39fdff24", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Infections can be averted with vaccines and hygiene-related recommendations. However, adherence to pre-travel advice, including the vaccination, is poor.", "Britto and Colleagues systematically reviewed historical trends of drug resistance to first-line antimicrobial therapy in typhoid fever (1973-2018, for 13,833 isolates) ( Table 3) . The majority were isolated in South Asia (63.2%), Africa (15%), and Southeast Asia (12.8%). Moreover, during 2006-2015, a significant increasing trend of drug resistance was described for the nalidixic acid and fluoroquinolones [63] .", "Currently, three typhoid vaccines are available:", "Several studies suggested a cross-protection against S. paratyphi A, B and C with the administration of the oral vaccine Ty21a (common O-and Vi-antigens) [38] , even if a study which recruited US military personnel described a weak immunity against S. paratyphi A [46] ." ] },{ "paper_id": "9009370b71d913612356de26f968966c3399da2d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The first-dimension separation was performed using 18 cm Ready Strip IPG strips (non-linear, pI 3-10, GE Healthcare) for isoelectric focusing (IEF). The IPG strips were rehydrated with 400 \u03bcl rehydration buffer (7 M urea, 2 M thiourea, 2% (w/v) CHAPS, 65 mM DTT, 0.2% IPG buffer pH 3-10) containing 150 \u03bcg protein for 12 h at 20\u00b0C by a passive rehydration method. IEF was carried out at 20\u00b0C on an Ettan IPGphor III electrophoresis unit (GE Healthcare), and performed as follows: 100 V, linear, 100 Volt-Hours (Vhs); 200 V, Gradient, 200 Vhs; 500 V, linear, 500 Vhs; 1,000 V, linear, 1000 Vhs; 4,000 V, Gradient, 4,000 Vhs; 8,000 V, linear, 32,000 Vhs. The IPG strips were incubated for 15 min with gentle shaking in an equilibration buffer (6 M urea, 30% glycerol, 2% SDS and 0.375 M Tris-HCl, pH 8.8) with 1% (w/v) DL-Dithiothreitol (DTT) followed by additional equilibration for 15 min in SDS equilibration buffer containing 2.5% iodoacetamide (IAA).", "Protein digestion extracts were resuspended with 5 \u03bcl of 0.1% TFA, and then the peptide samples were mixed (1:1) with a matrix consisting of a saturated solution of \u03b1-cyano-4-hydroxy-trans-cinnamic acid (\u03b1-CCA, Sigma) in 50% ACN containing 0.1% TFA. Digested proteins (0.8 \u03bcl) of each sample were spotted onto stainless steel target plates and allowed to air-dry at RT. Peptide mass spectra were obtained on an Applied Biosystem Sciex 4800 MALDI-TOF/TOF Plus mass spectrometer (Applied Biosystems, Foster City, CA). Data were acquired in positive MS reflector using a CalMix5 standard to calibrate the instrument (ABI 4800 Calibration Mixture). Mass spectra were obtained from each sample spot by accumulation of 900 laser shots in an 800-3500 mass range. For MS/MS spectra, the 5-10 most abundant precursor ions per sample were selected for subsequent fragmentation and 1200 laser shots were accumulated per precursor ion.", "The authors declare no competing interests." ] },{ "paper_id": "900f9612d2b06b3e32f4d460305a282d259f370d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results are reported as mean 6 S.E. of at least three independent experiments for each sample analyzed. Errors in the values were within 5-7%. The correlation coefficients (CC) between sets of different samples were analyzed.", "Fifteen patients (11 women and 4 men) satisfying the criteria for clinically or laboratory-supported definite MS according to [29, 30] were retrospectively selected for the study. Of these, 13 were relapsing-remitting (RR), and 2 were primary progressive (PP) in agreement with the criteria of Lublin and Reingold [31] . Clinical course (RR and PP), clinical activity (relapse at time of sampling), and MRI activity (the presence of gadolinium enhancing lesions at MRI examination) were analyzed as described previously [32] . The characteristics of the MS patients are summarized in Table 1 .", "At entry none of the patients had fever or other symptoms or signs of acute infections. Moreover, at the time of sample collection none of the patients had received any potential disease-modifying therapies during the 6 months before the study.", "Multiple sclerosis (MS) is a chronic demyelinating pathology of the central nervous system presenting a serious medical and social problem. Its etiology remains unclear, and the most valid theory of its pathogenesis assigns the main role in the destruction of myelinproteolipid shell of axons to inflammation related with autoimmune reactions ( [1] and refs therein). Although the T-cell immune system plays a leading role in MS pathogenesis, normal functioning of the B-cell system is also important for the disease development. An enhanced synthesis of immunoglobulins (usually IgGs), their free light chains, and of polyspecific DNA binding antibodies (Abs) interacting with phospholipids are observed in MS patients [1] ." ] },{ "paper_id": "9016b018eebc8b664e98f9ff2cd6f05ea1742dc7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "single species with a highly derived diet and lifestyle, has been the subject of at least five microbiome studies (15) (16) (17) (18) (19) . Because it is not feasible to sample the microbiomes of all mammal species, it would be helpful to identify a clade that can be used as a tractable starting place for understanding patterns and processes of microbiome evolution across closely related species with different ecologies. With so many mammal groups to choose from, what would make any one clade an attractive choice? Here, we review the reasons why we believe bats are a good system within which to investigate new questions about the role of microbes in driving host evolution, physiology, and fitness.", "Bats represent an untapped resource for understanding microbiome evolution in mammals. Because of their exceptional diversity, longevity, and ecological importance, we believe that studies of their microbial symbionts will reveal exciting new roles for microbes in driving host evolution and fitness and may help us to better understand the dynamics of emerging zoonotic pathogens. We provide applications of bat microbiome research in the hopes that more researchers will realize the potential that this system has to offer. Multi-omics approaches can be used to parse apart the contributions of host genome, metagenome, and microbial metabolites to the processes described above, and as the costs of these methods continue to decrease, such studies will only become more feasible. The results of studying bat microbiomes using these approaches will undeniably advance the fields of host-microbe interactions, comparative physiology, and public health.", "Mammals evolved in a microbial world, and consequently, microbial symbionts have played a role in their evolution. An exciting new subdiscipline of metagenomics considers the ways in which microbes, particularly those found in the gut, have facilitated the ecological and phylogenetic radiation of mammals. However, the vast majority of such studies focus on domestic animals, laboratory models, or charismatic megafauna (e.g., pandas and chimpanzees). The result is a plethora of studies covering few taxa across the mammal tree of life, leaving broad patterns of microbiome function and evolution unclear. Wildlife microbiome research urgently needs a model system in which to test hypotheses about metagenomic involvement in host ecology and evolution. We propose that bats (Order: Chiroptera) represent a model system ideal for comparative microbiome research, affording opportunities to examine host phylogeny, diet, and other natural history characteristics in relation to the evolution of the gut microbiome.", "Similar avenues of research can also consider what impact, if any, the host microbiome has on susceptibility of bats to white nose syndrome (WNS), a frequently fatal cutaneous infection that has reduced hibernating bat populations by up to 90% in North America (52) . Because not all individuals are killed by the infection, there may be selection on the skin microbiomes of surviving individuals to become enriched with antifungal bacteria. Indeed, one study discovered that in WNS-positive populations, the skin microbiome of bats was enriched with Rhodococcus and Pseudomonas spp., which are known to have antifungal activity (53) . Additional studies in this area can answer the questions of how exactly these bacteria inhibit the growth of the causative agent of WNS and what enrichment of the microbiome with these bacteria might mean for the long-term survival of affected host populations." ] },{ "paper_id": "9018234c987db8e1aec9ca3cae1806b75e4835ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following background subtraction, inhibition was measured as percent relative to untreated infected cells. Non-linear regression analysis was performed, and IC 50s were calculated from fitted curves (log [agonist] vs response [variable slope] with constraint to remain above 0; GraphPad Software, La Jolla, CA). Error bars of dose-response curves represent the standard deviation of three replicates.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "9027b4d1324273bed34f667f3d61d2536e9fd316", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lymphocyte subpopulations and T cell activation profiles in patients' PBMC were analyzed by flow cytometry with florescentconjugated T cell surface markers: florescent-conjugated mouse anti-human CD3-PerCP Cy5.5, CTLA-4-PE, CD4-FITC, CD28-PE, CD8-PE, CD69-FITC, CD25-PE, CD56-PE, HLA-DR-FITC, and isotype controls: mouse IgG1-PE and mouse IgG1-FITC (BD Bioscience, CA, USA). Cell populations were analyzed with FACS Calibur Flow Cytometer and CellQuest software (BD BioScience).", "The RT-PCR reaction system was in a volume of 25 ml; reaction conditions were 50uC for 15 min with 1 cycle; 95uC for 15 min with 1 cycle; 94uC for 15 sec, 55uC for 45 sec, and 55uC with 45 cycles. Fluorescent signals were collected by FAM channel.", "Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease recently discovered in China [1] [2] [3] [4] [5] . The causative agent of this illness, severe fever with thrombocytopenia syndrome virus (SFTSV), was identified as a novel tickborne Bunynavirus in genus Phlebovirus; it is also named Huaiyangshan virus, since the original cases were identified in the Huaiyangshan Mountains in 2009 [1, 6, 7] . It was reported that SFTSV can be transmitted in several ways: 1) patients can be infected through a tick bite; the virus has been detected in Haemaphysalis longicornis ticks [1, 7] and/or 2) through personto-person transmission via contact with blood from patients with SFTS [8] . Sporadic and clustered SFTS endemics have been documented in at least six provinces in Northeastern, Eastern, and Central China since 2009 [1, 3, 9] ." ] },{ "paper_id": "902ec7158906ac390bdc04cd55350a12c8a39281", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HIV-1 Env, Gag, Tat-Rev and Nef-RT (clade C) clinical [314] HIV-1 Env, Gag-Pol, Nef-Tat (clades B/C) clinical [315] HIV-1 Gag, PR, RT, Env (clade B) clinical [316] HIV-1 Env/Gag, Tat/Rev/Nef-RT (clade B) clinical [127]", "HIV-1 Env, Gag-Pol-Nef (clade B) clinical [305] 21 CTL and 18 HTL epitopes from HIV-1 Gag, Pol, Vpr, Nef, Rev and Env clinical [317] HIV-1 Nef clinical [318] Influenza A NP+M1 clinical [319] HA from H5N1 clinical [320] Hepatitis B", "HBs clinical [321] 30 CTL and 16 HTL epitopes preclinical [322] Hepatitis C NS3, NS4 and NS5B (genotype 1b) preclinical and clinical [323, 324] E1 and E2 (genotype 1b) preclinical [325] C, E1 and E2, p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B (genotype 1a) preclinical [326] Chikungunya C, E3, E2, 6K and E1 preclinical [327] E3 and E2 preclinical [328] E3-E2, 6K-E1 or E3-E2-6K-E1 preclinical [ Measles HA preclinical [352] F and HA preclinical [94, 353] CMV Soluble GP B (gB) preclinical [354] UL55 (surface glycoprotein), UL83 (tegument protein) and UL123/e4 (nuclear protein) preclinical [355] pp65 (tegument protein) and CMV immediate early gene IE1 preclinical [356] pp65-2, gB and IE1 (Rhesus CMV) preclinical [357, 358] pp65, IE1, IE2 preclinical [359] pp65 preclinical [360] glycoproteins gH/gL, UL128, UL130 and UL131A (UL128C) preclinical [361] gH, gL, UL128, UL130 and UL131A preclinical [362] BoHV-1 Secreted GP D preclinical [363] EHV-1 Complement-receptor GP C preclinical [364] HSV GP D (gD) (HSV-2) preclinical [365] Parainfluenza virus F and/or HN glycoproteins (parainfluenza virus 3) preclinical [366] [367] [368] Bacterial diseases" ] },{ "paper_id": "902feae616d8f0ffb508ef3a4a1fbc344bb63133", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The infected snails were placed in 100 ml beakers filled with tap water; cercariae of T. regenti emerged after illumination for 1 h. Suspensions of cercariae were cooled to 0\u00b0C, concentrated by centrifugation at 1600 \u00d7 g, washed once with cold water and finally re-suspended in a minimal volume of cold 10 mM phosphate buffer pH 7.2 containing one tablet per 10 ml of a mixture of protease inhibitors (Complete Mini EDTA-free, Roche). Homogenates from cercariae (TrHc) were prepared by 3 cycles of sonication (10 W, 30s) and centrifugation at 16 000 g for 20 min. Supernatants were collected and protein concentration was measured using Quant-iT Protein Assay Kit (Invitrogen). Samples were used immediately or stored at \u221220\u00b0C.", "Repeated infections of mammals including man lead to an inflammatory reaction known as cercarial dermatitis, which develops after destruction of cercariae in the skin. In sensitive individuals, intensive itching may be accompanied by fever and local lymph node swelling [6] [7] [8] .", "The ", "Here we show the antibody response during the infection by T. regenti in specific hosts (ducks). Bird humoral immunity has some specifics compared to mammals. Since the divergence of birds and mammals ca. 300 million years ago, some differences in the antibody responses of those two vertebrate groups have evolved [13] . The most significant departures from mammals include a partly different set of antibody classes, lower variability of Ig binding sites and maturation of B lymphocytes in a specialized immune organ, bursa of Fabricius. Also, mammals generate new antigen-binding sites throughout their life; in contrast, bird antibody diversity is generated only during a brief period of the embryonic development [14] ." ] },{ "paper_id": "9030e63a77c9fa25f099a8c8ea43d678f3693309", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses. Statistical analyses were performed using GraphPad Prism version 7.02. Individual statistical tests are specified within the figure legends. All statistical analyses were performed prior to normalization. For data with two groups, two-tailed t-tests were used under the assumption of normality. Grouped data with more than two groups were analyzed by analysis of variance (ANOVA) under assumption of normality.", "Pseudoparticle generation. Lentiviral pseudoparticles using the TRIP lentiviral backbone were generated as previously described 1 . Stable cell lines were generated using the SCRPSY lentiviral backbone as described previously 5 . When stated, p24 ELISA (Clontech) was used per manufacturer's instructions to normalize lentiviral input.", "Determining amino acid sequence identity and similarity. Protein sequences of select LY6/uPAR family members were obtained from UniProt 66 . LY6E ortholog nucleotide sequences were obtained from GenBank (NCBI) and translated to obtain the protein sequence using MEGA7 65 . Both analyses were performed using the Ident and Sim feature of the Sequence Manipulation Suite 67 ." ] },{ "paper_id": "9033d46664d7ded6d2cd79ddb75c2c36beab4802", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The existing data has so far highlighted microorganism-vimentin interactions that partly depend on the localization of vimentin ( Figure 1 ):", "Here, we have summarized the current knowledge of vimentin interactions with microorganisms, focusing on bacterial pathogens. Also, several viruses can interact with vimentin in similar ways as bacterial species and similar cellular consequences have been reported. For example, vimentin can act as a virus receptor for the severe acute respiratory syndrome coronavirus (SARS-CoV) and for Enterovirus 71 [32, 33] .", "Besides its function as a cytosolic protein, several studies reported a role of cell surface-located and extracellular vimentin [5] . Here, we highlight the main findings from investigations of the significance of vimentin in bacterial infections." ] },{ "paper_id": "90394841ad2cbaec78bf51646d5ca1ae26fadba6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Emerging epidemics are of increasing topical interest [1] . These emerging diseases pose new threats to human health [2] [3] [4] [5] [6] , livestock [7] [8] [9] [10] [11] and crop production [12] [13] [14] , as well as wildlife populations [15] [16] [17] and natural plant communities [18] [19] [20] [21] . Such epidemics occur most frequently when exotic pathogens are introduced into new environments or when novel strains arise that enable a pathogen to grow in a previously unfavourable environment [1] .", "where", "In Figure 3A , (Figures 3F-I) ." ] },{ "paper_id": "90403742f692b74ea175eef945ff8560a1a6c2b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Streptococcus pneumoniae, one of the most common bacterial respiratory pathogens worldwide, causes several infectious diseases including community acquired pneumonia, otitis media, meningitis and septicemia 1,2 . In the developing world, pneumococcal pneumonia leads to 25% of all preventable deaths in children under 5 years old and over 1.2 million infant deaths every year 3, 4 . Unfortunately, the reported incidence rates for laboratory confirmed invasive pneumococcal disease underestimate the true burden, as only a small portion of presumptive cases can be confirmed by conventional techniques.", "Signal amplification is of importance for molecular detection. To date, a variety of amplification strategies have been applied to further enhance the sensitivity. Most of them need the participation of enzyme 14, 15 , label 16 , or materials 17, 18 , with the drawbacks including specific reaction conditions, exorbitant price, poor stability, complicated operation and so on. Recently, catalytic hairpin assembly, developed from DNA nanostructure organization, has been received particular interest. CHA relies only on hybridization and strand-exchange reactions to achieve signal amplification circuit [19] [20] [21] , which overcomes the weaknesses of enzymatic amplification and the utilization of materials 22, 23 . However, CHA currently has the disadvantage of requiring complicated engineering for adaptation to various analytes 24 . Redesigning the entire circuit each time is unnecessarily arduous for the clinical analytical applications.", "Scientific RepoRts | 5:11190 | DOi: 10.1038/srep11190 cerebrospinal fluid samples using and bacterial culture method, indicating the feasibility and acceptable accuracy of proposed method for detection of S. pneumoniae in complex clinical samples. In addition, the assaying values of the proposed method were slightly larger than bacterial culture plating count. These results may be attributed to detected DNA from dead bacteria. In the future research, a large number of clinical samples will be applied to further verify the developed method." ] },{ "paper_id": "904be1b54f8b7ce0eba0f553eedc70dbb78f138d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 It only partially evaluates pre-and post-analytical steps [18] ; for example, PT samples are often coming in modified forms (e.g. dried, synthetically produced, pre-treated as with serum samples instead of whole blood), which can prevent their inclusion into regular lines of sample handling.", "Negligible discrepancies 5", "Accompanied by a comment suggesting a request for AST via phone call 5" ] },{ "paper_id": "90570e69d4ac4b2e72385123ba09f6b754707b61", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2) Adverse Events. If there were any abnormal signs and symptoms during treatment, adverse events would be discussed.", "A SDs were calculated if data on sample size and SE were available:", "\"a\" is the upper confidence limit, and \"b\" is the lower confidence limit, so" ] },{ "paper_id": "906246292449c131afd43009c5863e51ab99efc1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "90662d7dc7b09e018829ae2bc13e167b218931d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Selected experiments were done with IgG purified on protein A columns (Biorad, Milano, Italia) from serum-free supernatants (natural IgG).", "Recombinant mAb was purified with a Protein G column on an Akta Prime chromatography unit following the manufacturer's standard programme (recombinant IgG).", "Values are expressed as means \u00b1 sd. Data were analyzed for significance using a one-way analysis of variance (ANOVA) with Bonferroni post-test correction for multiple comparisons. Data were considered significant at P < 0.05." ] },{ "paper_id": "90672df8690ad900302e0e94fbe073b7cb762458", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data are expressed as the mean \u00b1 standard error of the mean (SEM) from three independent experiments performed in triplicate. The statistical analyses were conducted using Student's t-test in GraphPad Prism version 5 (GraphPad Software, San Diego, CA, USA). A p-value < 0.05 was considered significant, and a p-value < 0.01 was considered highly significant.", "Viruses 2017, 9, 198 9 of 14", "Fas" ] },{ "paper_id": "906902ba01987282a83ec42c2776de9c9bde3834", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "QuantiFERONH -TB Gold in Tube Assay This was performed according the manufacturer's instructions (Cellestis Plc, Sydney, Australia).", "(XLS) " ] },{ "paper_id": "90706dd8b172f0aeb996ea828c356155c32e0682", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "907094f2d7dba9a0cab6c5b0aa566ff69d124f02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No financial support was obtained for this study.", "All of the descriptive data were summarized as percentages and frequencies. Categorical variables were compared using the chi-square test. All statistical analyses were performed using IBM SPSS Statistics 21 (IBM Inc., Armonk, NY).", "Our findings are similar to those of other non-MERS viral outbreaks reported from different parts of the world." ] },{ "paper_id": "9086eb76194c342aad54afa61106a7c8883ef43b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses causing severe RTI in elderly individuals include influenza A and B virus, respiratory syncytial virus (RSV), human parainfluenza virus (HPIVs), rhinovirus, enterovirus, human coronavirus (HCoVs). The effects of obesity have only been described for a few of these viral infections.", "Obesity is associated with changes in gut microbiota at phylum-level and with reduced bacterial diversity in mice and humans (85, 86) . Mouse studies have identified intestinal microbiota products that protect the host from pneumococcus infection and have shown the mechanisms involved. Briefly, it was shown that the gut microbiota increases phagocytosis of alveolar macrophages and protects from tissue damage during pneumococcus-induced sepsis (87) . Human studies are necessary to confirm the positive results obtained in mice.", "Nursing homes represent one of the settings for outbreaks of pneumococcal infection in the elderly. Vaccination has been reported to protect <10% of elderly individuals in nursing homes during outbreaks of pneumococcal infection (70) (71) (72) ." ] },{ "paper_id": "90967c73d3f3e10ba8ab863b3deba3a40ca22fd1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total cellular RNA was extracted using Trizol reagent (Life Technologies, 15596-018) according to the manufacturer's protocols. One microgram of total RNA was reverse transcribed in a 20 \u03bcl volume using Improm-IITM reverse transcriptase (Promega, A3500) following the manufacturer's instructions. Real-time PCR was performed using 1 \u03bcl cDNA as the template with PowerUp SYBR Green Master Mix (Applied Biosystems, Life Technologies, A25742). The reaction was run on a 7900HT Fast Real-Time PCR machine (Applied Biosystems, Life Technologies), and levels of gene mRNAs were normalized to GAPDH mRNA. Results were analyzed as fold-change using the \u0394\u0394C T method. The primers for EV71 RNA quantification were described previously [100] , and the sequences of other primers were as follows:", "igh-pressure freezing and transmission electron microscopy (TEM)" ] },{ "paper_id": "90a31cc826fade05b0a3670af7a5d47d6f972b07", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "90a7c8a2e1be47616b2f04bd011c148fcbc8adba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Capped reporter mRNAs were prepared using the mMES-SAGE mMACHINE high-yield capped RNA transcription kit (Ambion) following the manufacturer's instructions. Reticulocyte lysate (Progema or Ambion) was used to generate shifted and nonshifted protein products. In each assay, a reaction totaling 5 ml of reactants (i.e., 50-250 ng of capped reporter mRNA, 2.5 ml of reticulocyte lysate, and 0.2 ml of 10 mCi/ml 35 S-labeled methionine (NEN)) was incubated at 30uC for 1.5-2 hours. Samples were then resolved by 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and exposed to a phosphorImager screen for quantification on BAS-2500 phosphorImager (Fujifilm) or Typhoon FLA7000 phosphorImager (GE) after drying.", "A slippery sequence (XXXYYYZ) and optimally placed downstream stimulator structures on mRNA are the two in-cis elements required for efficient eukaryotic21 PRF [6] . However, the precise21 PRF stimulation mechanism remains unclear [7] . Most models of21 PRF stimulation propose that a specific structural or mechanical feature of the stimulator resists the unwinding activity of ribosomal helicases [2] . This is done either passively by serving as a roadblock to pause ribosomal movement or actively by creating tension/strain to communicate with transfer RNA (tRNA)-mRNA linkages to destabilize the P site codon-anticodon helix in the 0-frame (XXY). It also eventually facilitates re-pairing of tRNA with the21 frame mRNA (XXX) [2, 3, 8, 9, 10] .", "Further experiments, such as measuring stimulator unwinding and attenuator hairpin refolding times (by the single-molecule approach) [2] as well as elucidating how translational machinery responds to a refolding hairpin should help reveal the interplay responsible for the intricacies of reading-frame switch adjustment." ] },{ "paper_id": "90b065409490de2813ab71b65ca8b401ec55b356", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "90b1c08620b3bcc5694e31a241e2be2589003030", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PCR ribotyping was performed using capillary gel electrophoresis with primer pairs as described previously [12] . The size of each peak was determined using Genemapper ID-X software 1.3 (Applied Biosystems). The capillary sequencer-based PCR-ribotyping data were analyzed using the WEBRIBO website (https://webribo.ages.at/) [13] .", "Statistical analysis was performed by SPSS 20.0 (Chicago, IL, USA). First, an R \u00d7 C contingency table was established to consolidate the quantitative data. The data were then divided into different groups. The chi-squared test was used to analyze categorical data. The F-test and T-test were conducted for hetero or equal variance analysis. Significance of variables was determined by univariate Cox regression analysis (Figure 1 ). Statistical significance for all tests was defined as p < 0.05.", "Immunological indicators and C. difficile-positive rate", "The ribotypes of the 82 C. difficile samples were determined. The results yielded 12 ribotype patterns, including ribotype 001 (n = 22), ribotype 017 (n = 15), ribotype 017/1 (n = 16), ribotype 014/0 (n = 12), ribotype 017/2 (n = 10), and one each of ribotypes 666, 650, 555, 445, 220, 037, and 087. None of the strains belonged to ribotype 027." ] },{ "paper_id": "90b225bb89b9c6cd53621102fb383cf4fa090891", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Splice modification might produce an mRNA that is expressed as an altered protein and that protein might retain some activity and might still bind antibodies that would also bind to the unaltered protein.", "Percent protein and mRNA are compared with wild-type muscle as 100%.", "The activity of a translation blocking oligo is assayed by an immunochemical method, typically Western blotting. Halting translation of a protein will not immediately cause a detectable change in the protein's signal on a Western blot. Some preexisting protein must be degraded over time before the protein signal decreases. The time needed between knockdown and assay varies with the protein, as different proteins have different stabilities in cells.", "Another class of targets consists of the binding sites on RNA where splice-regulation proteins normally bind, such as exonic splice enhancers or intronic splice suppressors. These proteins are important in directing alternative splicing, a natural process by which cells make alternative forms of mRNA from a single gene. For some targets, preventing a splice-regulatory protein from binding is an efficient method by which Morpholino can change the pattern of RNA splicing and therefore change the sequence of a mature mRNA [10, 36] .", "Global Therapeutics, the cardiology unit of Cook Medical (http://www.cookmedical.com), is developing PPMO-coated stents for balloon angioplasty using PPMOs from AVI BioPharma Inc. The Morpholino moiety targets c-myc to inhibit proliferation of the vascular endothelial cells, which might otherwise cause restenosis." ] },{ "paper_id": "90b43fc0b556b97bcc6ccc57f87f4e2811e0d4ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bats belonging to the order Chiroptera, which is known as the second largest order of mammalians, are distributed into more than 1,000 species globally 10 . It has been shown that bats play crucial roles as natural reservoirs of some zoonotic pathogens such as Marburg virus, Hendra virus, Nipah virus, Lyssa virus, SARS, and MERS coronaviruses 11-14 . Thus, it is important to investigate the ecology of bat-derived pathogens and to clarify their potential risks as zoonotic pathogens.", "Our previous study revealed that vesicular stomatitis viruses (VSVs) pseudotyped with BatIV glycoproteins efficiently infected cultured cells derived from particular bat species (e.g., Miniopterus fuliginosus) but not those commonly used for IAV propagation and other bat cells tested, providing key information on cell lines that are Published: xx xx xxxx opeN www.nature.com/scientificreports/", "Influenza A viruses (IAVs), which belong to the family Orthomyxoviridae, cause highly contagious diseases in a wide variety of avian and mammalian species, including humans, pigs, horses, dogs, and poultry, and are recognized as one of the most important zoonotic pathogens. IAVs have 8 segmented negative-sense RNA genomes and are divided into subtypes based on combination of two viral envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). IAVs with H1-16 HA and N1-9 NA subtypes have been identified in wild aquatic birds, especially migratory ducks, the natural reservoir of IAVs 1-4 . Importantly, due to their propensity for genetic reassortment, a variety of IAV subtypes are distributed in many host species." ] },{ "paper_id": "90b97cb0a6ce9135c3a299462773ee94856ff22d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:23752 | DOI: 10.1038/srep23752" ] },{ "paper_id": "90c1ab8b02263998f809915b0629da5aa1cbc47a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Health Research Ethics Board of the University of Alberta approved this study and parents and older children signed a consent form." ] },{ "paper_id": "90d04764b497a224a1d969f4e317fc19a5feab35", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The timely response by stakeholders in regard to this new outbreak are commendable compared to previous cases. The latter includes the Severe Acute Respiratory Syndrome (SARS) outbreak in 2002 that took substantial time (from November 2002 to April 2003) to identify and be dealt with [24] ; the Ebola outbreak in West Africa in 2013 that took months to determine; and the Zika Virus that was first reported in 2014 before being successfully identified in 2015.", "Healthcare 2020, 8, 46 7 of 9" ] },{ "paper_id": "90d54e33891390c4539182390d2976123d5ddc2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 direct: Only relevant for human-to-human transmission.", "\u2022 unspecified: Lacked sufficient epidemiological evidence to classify a human case as zoonotic or direct.", "\u2022 diagnostic: testing of symptomatic patients." ] },{ "paper_id": "90d553a545579b2e27d0899c558e004ff33cd0f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication. ", "High sensitivity, high specificity AD -Confirmatory assay .", "Less sensitive and less specific than EIA AD -Subjective interpretation." ] },{ "paper_id": "90de2d957e1960b948b8c38c9877f9eca983f9eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "90f28a7925b8350d3a484cac6ed454a328d08b67", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Specimens are collected from patients by submitters and sent to PHOL for testing as part of routine clinical service. These data are also used for routine laboratory surveillance, which is a mandate of Public Health Ontario. Therefore, consultation with our organization's privacy office or ethics committee was not required. To protect patient privacy and confidentiality, data are reported in an aggregated anonymized format.", "It is difficult to know the true burden of disease related to EV-D68 since EV infections are not reportable in North America and some patients infected with the virus don't seek medical care or even when they do, routine testing does not differentiate this serotype [12] . Thus, the reported incidence of infection is likely an underestimation of the true incidence [1] .", "Conceived and designed the experiments: TB AE. Performed the experiments: AL SP. Analyzed the data: AP ALW JBG. Contributed reagents/materials/analysis tools: AMA EK. Wrote the paper: AP ALW JBG BW RO TB AE.", "While more recent investigations reported on EV-D68 infection in children who present to hospital [13] , the virus has also been identified in both children and adults seeking community-based care [9, 14] . Consistent with previous reports [15] , a higher proportion of individuals in whom the virus was identified were male." ] },{ "paper_id": "90f2e2a33f7f6bae27a703b4c30a99f87d404474", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Genotyping. Genomic DNA was extracted from 5 mm tail tips which were digested with 0.8 mg ml Table 5 .", "DNA was purified using standard phenol/chloroform extraction, precipitated in ethanol, resuspended in TE buffer (1 mM EDTA pH 8, 10 mM Tris pH 8) and quantified by Qubit (Life Technologies).", "SAP, haptoglobin and AAT concentrations were determined by interpolation of optical density units for standard curves generated from purified proteins or standards. SAP was purified from normal mouse serum using phosphorylethanolamine-sepharose 4B affinity chromatography and anion exchange (DE-52) chromatography, as previously described 28 . Standards for haptoglobin and AAT were purchased from Immunology Consultants Laboratory.", "We constructed a pairwise distance matrix of the number of genotyped nucleotide differences among individuals, and included reference genotypes for other laboratory strains (C57BL/6J, NOD/Ltj, 129S1/SvlmJ, CBA/J, AKR/J, FVB/NJ, C3H/HeJ, BALB/cJ, DBA/2J, SJL/J) provided by Illumina (http://support.illumina.com/array/array_kits/mouse_md_linkage/ downloads.html). The distance matrix was then used to construct a nearest neighbour joining tree in MEGA6 (ref. 27) ." ] },{ "paper_id": "9104d87ad3991408937aa1e1739e7df0f51d01b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results of this study demonstrate a modular organization in Ebola virus that accommodates a wellordered, symmetrical nucleocapsid within a flexible, tubular membrane envelope.", "Single particle image analysis: software and hardware", "Background: Filoviruses, including Ebola virus, are unusual in being filamentous animal viruses. Structural data on the arrangement, stoichiometry and organisation of the component molecules of filoviruses has until now been lacking, partially due to the need to work under level 4 biological containment. The present study provides unique insights into the structure of this deadly pathogen." ] },{ "paper_id": "910a5b6256028ed6f3d360a28f14f49488b56db4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Double-stranded transcription factor decoy oligonucleotides are a powerful tool to modulate gene expression. Decoys compete with response elements within the promoter regions of genes that bind transcription factors.", "bPrPp, bovine prion protein derived peptide; CLSM, confocal laser scanning microscopy; CPP, cell-penetrating peptide; FCS, fetal calf serum; EIPA, ethylisopropylamiloride; GFP, green fluorescent protein; hCT, human calcitonin; HEPES, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; HIV, human immunodeficiency virus; IL, interleukin; IFN, interferon; LF, Lipofectamine\u2122; LF2000, Lipofectamine\u2122 2000; MAP, model amphipathic peptide; MEND, multifunctional envelope-type nano device; miRNA, microRNA; mPrPp, murine prion protein derived peptide; NLS, nuclear localisation sequence; OMe, O-methyl; PAMAM, polyamidoamine; PEG, polyethylene glycol; PEI, polyethyleneimine; PMO, phosphorodiamidate morpholino oligomer; PNA, peptide nucleic acid; PTD, protein transduction domains; RNAi, RNA interference; SAP, Sweet Arrow Peptide; siRNA, small inhibitory RNA; STR-R 8 , stearyl-R 8 ; TAR, transactivator responsive region; TFO, triplex forming oligonucleotide; TLR9, toll-like receptor 9; TNF, tumour necrosis factor; TP10, transportan 10.", "Cell-penetrating pentapeptides (CPP5)" ] },{ "paper_id": "910f8cb2d8f7ceb37d996bcbf327b4f5b26ed6d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus culture HSV-1 strain NC1, CMV strains Towne and Toledo, VZV strain Schenke and HIV-1 strains BaL, NL4.3 and RFW were propagated according to standard protocols [16] [17] [18] [19] [20] .", "Total RNA from cells derived from four independent experiments was extracted using the RNAqueous-Midi kit (Ambion, TA), quantified by UV spectroscopy and the integrity confirmed using an agilent 2100 bioanalyzer. 1 \u03bcg of the total RNA was then DNase treated using 1 U RNase free DNase (Promega, Madison WI).", "In order to measure housekeeping gene expression, cDNA was subject to QPCR using the platinum QPCR super mix kit (Invitrogen) and pre-designed certified LUX primers (Invitrogen) designed to amplify the following transcripts: B2M, PPIA, EEF1G, SDHA, GAPDH, HMBS, TBP, 18sRNA, PGK1, BACT. Fluorescent PCR amplicons were detected using a Stratagene Mx3005 QPCR thermocycler using 96-well microtiter plates in a final volume of 25 \u03bcl under the following cycle conditions: 50\u00b0C for 2 minutes, 95\u00b0C for 2 minute, 45 cycles of 95\u00b0C for 15 seconds 55\u00b0C for 30 seconds and 72\u00b0C for 30 seconds." ] },{ "paper_id": "911e313c1ff9ff3edb62e71b7aea6224f771fadd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/ mSphere.00152-18. ", "We thank Mara Sullivan at the Center for Biologic Imaging, University of Pittsburgh, for providing the transmission electron micrograph. We thank George Tsao (University of Hong Kong) for providing the HK1 and HK1-EBV cells. ", "TEM. HK1 and HK1-EBV ALI cultures harvested at week 2 were fixed in cold 2.5% glutaraldehyde-0.01 M PBS. Specimens were rinsed in PBS, postfixed in 1% osmium tetroxide with 1% potassium ferricyanide, rinsed in PBS, dehydrated through a graded ethanol series, and embedded in Poly/Bed 812 (Luft formulations). Semithin (300-nm-thick) sections were cut on a Leica Reichart Ultracut ultramicrotome, stained with 0.5% toluidine blue-1% sodium borate, and examined under the light microscope. Ultrathin sections (65 nm thick) were stained with uranyl acetate and Reynold's lead citrate and examined on a JEOL 1011 transmission electron microscope with a side-mount AMT 2-k digital camera (Advanced Microscopy Techniques).", "In addition to analysis of protein levels, RNA sequencing (RNA-seq) was performed to assess the global induction of EBV lytic transcripts. Of the 78 open reading frames (ORFs) annotated in the NCBI database, 65 were analyzed (Table S2 ) and 62 were represented as a heat map (Fig. 3A ). Three ORFs, EBER1, EBER2, and BNLF2A, had extremely high numbers of reads and were not represented on the heat map but are illustrated in Table S2 . The lytic genes were globally induced by week 2 to 3 in ALI culture, except for LMP1, LMP2B, EBER1/2, and BNLF2a, which showed a consistently decreasing trend overall (Fig. 3A ). By comparison, host genes that were differentially regulated by at least 2-fold did not show an overall increase but a decrease in transcript levels which likely represented host shutoff ( Fig. 3B ; see also Table S3 )." ] },{ "paper_id": "91276b1c72c7bff1b7b796b8efaa9215519289a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Here we highlighted the importance of building structural HMI networks. However, not only HMIs are important; although to date data are scant, crosstalk among microorganisms is also emerging as critical. Alterations in their population dynamics may lead to dysbiosis. Signals from gut microbiota resulting from population shifts can affect profoundly several tissues, including the central nervous system. Dysbiosis of microbiota is involved in several diseases, such as inflammatory bowel disease [101] , autoimmune diseases (e.g. multiple sclerosis) [102] , neurodegenerative diseases (e.g. Parkinson's) [103] , and cancer [104, 105] . Identifying bacterial effectors, or effector combinations, which are responsible for specific phenotypes, is challenging. In line with this, recently, Parkinson's disease (PD) patients are found to have altered gut microbiota composition [106, 107] . Transplanted microbiota from PD patients, but not from healthy controls, induce motor dysfunction and trigger PD in mice. It is not clear however whether dysbiosis triggers PD or it arises as a consequence of the disease [103] .", "HMIs have complex and dynamic profiles. Studies often focus on individual protein interactions and try to explain the pathogenicity of a microorganism with a single interaction. However, considering host-microbiota interactions one-at-a-time may not reflect the virulence scheme [18] . For instance, replication of vaccinia virus necessitates the establishment of a complex protein interaction network [19] and hence focusing on only one HMI is incomplete and may be misleading. At any given time, hundreds of different species reside in the gut. Different microbial compositions and hence effector protein combinations from these microbial species may have additive (cross-activation) or subtractive (cross-inhibition) [4] impacts on the host pathways, which lead to signal amplification or inhibition, respectively (Fig 1) .", "https://doi.org/10.1371/journal.pcbi.1005579.g001", "Both experimental and computational approaches have false-positives and false-negatives with varying rates depending on the approach. Although the coverage of interface-based methods is higher, their false-positive rate is also higher. Despite this, attempts to complete the host-microbiota interactome will improve our knowledge of microbiota and their roles in health and disease." ] },{ "paper_id": "91312e3e01c328ebc4c8007586a84e8cfbdf45e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal use followed the guidelines of the Weatherall Report on the use of non-human primates in research and was approved by the Uganda Wildlife Authority, the Uganda National Council for Science and Technology, and the University of Wisconsin Animal Care and Use Committee prior to initiation of the study. Biological materials were shipped internationally under CITES permit #002290 (Uganda)." ] },{ "paper_id": "9138f2909ac88cdf8463d08e4559197edc2c60ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data set supporting the results of this article is included within the article. ", "Nidoviruses infect a broad range of hosts including humans and other mammals, birds, fish, insects and crustaceans [8] [9] [10] [11] . Although reptiles are susceptible to infection by a wide variety of viruses (as reviewed in [12] ), nidovirus infections have not previously been described. Viruses affecting the reptile respiratory tract include herpesviruses [13] , iridoviruses [14] , adenoviruses [15] , flaviviruses [16] , and, of particular importance in snakes, paramyxoviruses [17] and reoviruses [18] .", "Gross and histologic findings in all four snakes were primarily restricted to the respiratory and upper gastrointestinal tracts ( Table 1 ). Hematoxylin and eosin stained sections ( Figure 1A through F) revealed marked hyperplasia of epithelial cells lining air exchange areas (pneumocytes) with significant mononuclear (lymphocytes and plasma cells) and granulocytic (heterophils) interstitial inflammation and epithelial necrosis ( Figure 1B ). Similar inflammatory and hyperplastic changes were also present in the trachea ( Figure 1D ), esophagus ( Figure 1F ) and oral cavity. Gram-negative stained bacteria are shown in lung tissue from a snake with bacterial bronchopneumonia ( Figure 1H ).", "Nidovirales is a large order of positive sense, singlestranded RNA (ssRNA) viruses that consists of the many genera and species in the families Coronaviridae, Arteriviridae, Roniviridae and Mesoniviridae. Although the genomes of nidoviruses vary in length, ranging from 13 to 32 kilobases (kb), the organization of the genomes are similar across the entire order [1] [2] [3] [4] . The 5\u2032 end of the genome encodes two replicase polyproteins (pp1a and pp1ab), structural proteins and accessory proteins. Genes downstream of the replicase polyprotein gene are expressed from a nested set of 3\u2032-coterminal subgenomic mRNAs, a replication strategy unique to the Nidovirales [5] [6] [7] ." ] },{ "paper_id": "913a4c390684cea254cbece18764a7bc005badac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "913e8bcf134a8415f7aa9d3285e15e1425a60d26", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keratoconus is a progressive, asymmetric corneal ectasia. It is characterized by the thinning and protrusion of the cornea leading to irregular astigmatism and myopia thereby affecting the visual performance [1] .", "The genomic studies thus far have remained inconclusive in terms of a molecular explanation for the phenotypes observed and do not strongly correlate with the molecular expression data from patient corneas. However, the gene and protein expression data from the keratoconic cornea do show deregulation of important factors and pathways such as collagen synthesis, inflammation, extracellular matrix, structural genes, TGF\u03b2 pathway and Wnt signaling, to name a few. However, in a clinic, it is difficult to obtain corneal tissue for diagnosis and molecular profiling. This makes profiling tears of patients an attractive prospect.", "Both genetic and environmental factors contribute to the disease pathology [17] [18] [19] . Although atopy, eye rubbing, ocular allergies, Down's syndrome and tapetoretinal degeneration have been associated with keratoconus [13] , the etiology and pathogenesis still remains unclear. Despite the association of various genetic loci in twin and familial studies, [19] the general consensus remains that the disease is polygenic and is dependent on ocular surface and tear molecular expression changes [20] ." ] },{ "paper_id": "914636db7f8a6361126e805e4abd3c8a8d5ab31f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9146df7c1faca31203b1e903f59662067faebb69", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9148852f390403699eb166e03dc4147520b7ed5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Notably, analysis of the detected pathogens revealed that none of the pathogens is dominant (Fig. S3B) . ", "The pathogenic strains found in this study are responsible for the vast majority of acute infectious diseases in the Western world and included key pathogens such as influenza A/B, respiratory syncytial virus (RSV), parainfluenza, E. Coli, Group A Streptococcus, etc." ] },{ "paper_id": "914b5fc6d3984b981a1e36e545cc2a74e3fbd58a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Considering the most common pathologies in humans and other animals, cardiovascular and infectious diseases and cancer are among the leading causes of deaths. The cultural and educational background of affected people largely influences the prevention and treatment of human diseases; nevertheless, the availability of new drugs contributes greatly to mitigating diseases.", "More than 200 viruses are known to cause human diseases [1, 2] . Some of them present high public health importance, such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), hepatitis B and C viruses (HBV and HCV, respectively), herpes simplex virus (HSV), human immunodeficiency virus (HIV), rabies virus and Ebola virus. The most recent worldwide estimates presented by the World Health Organization (WHO) reported 1.5 million deaths caused by HIV in 2012, 400 million people living with hepatitis B or C, 80% of liver cancer deaths caused by hepatitis viruses, 500 thousand cases of cervical cancer caused by HPV infection, and over 250 thousand cervical cancer deaths each year [3] .", "Recently, the antiviral activities of Scorpio maurus palmatus and Androctonus australis crude venoms were shown against HCV. They presented IC 50 values of 6.3 \u00b1 1.6 and 88.3 \u00b1 5.8 \u03bcg/mL, respectively. S. maurus palmatus venom was considered a good natural source for characterizing new anti-HCV agents targeting the entry step, since it impaired HCV infectivity in cell culture, but not intracellularly, through a virucidal effect. This effect was not inhibited by a metalloprotease inhibitor or heating at 60\u00b0C [44] ." ] },{ "paper_id": "914c8d326beaccabd37199a9903b27fa7f9b0586", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Catalytically Active Pseudoknots", "Primer", "June 2005 | Volume 3 | Issue 6 | e213" ] },{ "paper_id": "914d646494f09cbb34bbe5da9dfea4c93ad35bb9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Increased hydration without potassium was administered, but no alkalinization of the urine or forced diuresis was required. CPK reached up to 21,425 U/L and AST and ALT up to 843 U/L and 245 U/L, respectively. Potassium peaked at 5.5 mEq/L (normal 3.5-5.0) and phosphorus at 5.1 mEq/L (normal 2.4-4.3). CPK decreased to 6,756, and electrolytes normalized on discharge two days later. The child's clinical condition had much improved.", "There is not a clear distinction in the literature between acute benign myositis and rhabdomyolysis. Some use the term acute benign myositis for uncomplicated cases of muscle inflammation with elevated CPK and arbitrarily reserve the term rhabdomyolysis when, in addition, myoglobinuria is present [12] . Others refer to rhabdomyolysis only when serum CPK is >1000 U/L [2] . Since rhabdomyolysis means disintegration of striated muscle with resultant leakage of muscle cell constituents, we choose to include all reports of clinical myositis with elevated serum CPK.", "The median time to clinical recovery was 12 days (range 4-52, mean 18.8). In some children complications occurred, but the outcome was favorable. Three out of seven children developed ARF, and two of them received renal replacement therapy [3, 4] . One child died because of cardiorespiratory arrest and brain edema [7] ." ] },{ "paper_id": "9151f784207180e12703758211d31c6d0ee84423", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Individual pig immune response data are shown in all figures. Average values from 25 pigs +/-standard deviation for cytokines and for immune cells from 7-13 pigs are shown. Statistical analyses were performed using a paired t-test or Wilcoxon t-test when the sample number was more than 10 or less than 10, respectively(SAS software, SAS Institute Inc., Cary, NC). ", "A rapid increase in IL-12 but not IFN-g secretion in PRRSV infected pigs", "Plasma samples collected after initial centrifugation of unclotted blood were analyzed for the IFN-\u03b1, Th1 (IFN\u03b3, IL-12), Th2 (IL-4), and immunosuppressive (IL-10) cytokines by cytokine sandwich ELISA as described previously [71] ." ] },{ "paper_id": "915266f52a5f9c7360670df5de7b51d20e0a8cfa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although President Richard Nixon terminated the offensive biological weapons program in 1969 and 1970 by executive order, research efforts in biowarfare countermeasures continue (115) . During Operation Desert Shield before the Persian Gulf War and after the 9/11 events and the anthrax attacks on US institutions, it has become evident that BW remains a potential threat to US soldiers.", "biOTeRRORiSM Not only are endemic diseases of concern for the military, so are potential exposures to agents deliberately introduced into the environment through biological warfare (BW) or bioterrorism (114) .", "(1) diseases that spread easily in densely populated areas (respiratory and dysenteric diseases); (2) vector-borne diseases (disease carried by mosquitoes and other insects);", "The value of vaccinating law-enforcement and emergency response personnel, who must respond to threats (real or otherwise), depends on the nature of their work and the immediacy of the threat. Laboratory personnel who must work with unknown materials and with high concentrations of known infectious materials must be vaccinated. These are additional justifications for moving ahead with a vigorous development program for anthrax and smallpox vaccines." ] },{ "paper_id": "9153d6b8fb3af63f68f15f52198cdbc308c97333", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In general, the cells subjected to immunofluorescence were seeded in 24 well plates on 10 mm glass cover slips. For immunoblotting, cells were seeded in 6 well plates.", "Influenza A virus (IAV) is the major cause for a contagious illness of the upper and lower respiratory tract during the seasonal influenza epidemics with peaks in fall and winter for each hemisphere [1] [2] [3] . Besides the acute risk through circulating human specific strains, the zoonotic reservoir (e.g., birds, swine) poses a constant threat of new influenza pandemics [4] [5] [6] [7] .", "The 2D object counter and coloc2 plugin in Fiji software (https://fiji.sc/, 64-bit version)were used for the cluster and Mander's Coefficient Correlation (MCC) analyses, respectively. MCC was performed using the Costes regression threshold. The defined objects were assigned as a cluster being larger than 10 5 nm 2 based on STED images with approximately 50 nm resolution. All graphs show the mean values of three independent experiments plotted with the standard error calculated as a two tailed unpaired t-test. A statistical analysis was performed using GraphPad Prism software (version 5)." ] },{ "paper_id": "91565229659527cb4c0a635614b5add5980a4b59", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Because the discovery of PA-X is relatively recent, many aspects of its biology and mechanism of action remain unknown, such as its potential cofactors and regulation of its activity by signaling events. A recent study by Oishi et al. described the first post-translational modification of PA-X, an acetylation at the N-terminal M-E residues of the protein by the host acetylase NatB [36] . This acetylation was present on PA-X isoforms from WSN, Cal (pH1N1), H3N2, H5N1, and H7N9, and stimulates host shutoff activity. However, it is unclear whether the modification is constitutive or regulated, and how it promotes RNA destabilization by PA-X [36] . In general, further mechanistic studies are necessary to define the activity of PA-X and its variations across influenza A strains.", "Influenza A virus has only eight gene segments but devotes a significant percentage of its coding capacity to proteins that directly or indirectly interfere with host gene expression. This \"investment\" raises the question of why such a small virus has evolved many different mechanisms of host shutoff and suggests that remodeling of host gene expression is critical for successful influenza A infection. One potential explanation for this phenomenon is the broad host range of influenza A viruses. Influenza A strains (unlike influenza B) infect not only humans but also many other species, including mallard ducks, chickens, seals, dogs, pigs, Owston civets, and horses [109] . In order to successfully establish infection in many different species, influenza A virus may need a wide range of mechanisms to overcome host responses. This may arise from different host biology, so that one mechanism may not prove as efficient in one species as it is in another. Alternatively, NS1 and PA-X may not work at all in some species without prior adaptation, because of differences in the cellular proteins that these viral factors interact with. Influenza A virus could thus make use of these different mechanisms to adapt as it moves through different hosts with different selective pressures.", "The most commonly proposed function of host shutoff is to reduce induction of immune-related genes. In this model, by preventing general host gene expression, host shutoff also reduces the induction of innate immune chemokines and cytokines, in particular the anti-viral type I and III IFNs, and/or of IFN-stimulated genes (ISGs). This process would therefore block the initial cell-intrinsic protective responses, as well as the recruitment of circulating immune cells like macrophages, neutrophils, B and T cells. For most of the described host shutoff proteins, experimental evidence exists that this is indeed the purpose or at least one of the purposes of host shutoff." ] },{ "paper_id": "9170d2682a483c1480ce002486cff53e99789484", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analyses. Data were analyzed in SPSS 19.0. The agreement between assays was measured using the kappa statistic. The sensitivity and specificity were also compared for both tests.", "The nasal mucus specimens were cultured according to China national standard protocols to detect respiratory bacterial (or fungi). Colony identification was undertaken using a VITEK 2 Compact system (Biom\u00e9rieux, France). Nine bacteria were measured, including Acinetobacter baumannii, Enterobacter aerogenes, Escherichia coli, Klebsiella ornithinolytica, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus haemolyticus, and Bordetella pertussis. One fungus (yeast) was also detected.", "Detection. The patient's serum was collected and placed in \u221280 \u2218 C. Mycoplasma pneumoniae and Chlamydia pneumoniae antibody (IgM) were detected by commercial kit (KANGHUA, China), in accordance with the instructions." ] },{ "paper_id": "91781004fcf2142034de62e1212be3d885139060", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "File S1 Supplementary Methods. ", "Node degree of N L Number of other places a place is connected to given the mobility of its visitors.", "Dynamic contacts. Figure 3A shows N P (t) for different time slices of a single day (ranging from early morning to evening) and" ] },{ "paper_id": "917928bee48f4118e1f14349d4176df8281e9cac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A complete blood count showed leukocytopenia with marked monocytopenia (Table 2) . Immunological assays detected B-cell lymphopenia with predominance of memory B cells. Despite the very low numbers of B cells, normal serum immunoglobulin levels of IgM and IgA and increased levels of IgG were present (23.6 g/l). Antibody response to routine vaccination was normal. No serum autoantibodies were found. Functional testing of granulocytes (respiratory burst test: analysis of the ability of granulocytes to release reactive oxygen species after in vitro stimulation) and of T cells (evaluation of proliferative response of T cells to various in vitro stimuli) excluded chronic granulomatous disease and T-cell proliferation defects.", "Defects of transcription factor GATA-2 have recently been identified in a few overlapping phenotypes associated with myeloid malignancies: dendritic cell, monocyte, B-and NK-cell deficiency; MonoMAC syndrome (monocytopenia with Mycobacterium avium complex infections); Emberger syndrome (early onset primary lymphedema, multiple warts, sensorineural deafness, dysmorphism); and familial MDS/AML with no additional known phenotype. These syndromes share autosomal-dominant inheritance with variable manifestation of immunodeficiency [1] [2] [3] [4] [5] [6] [7] [8] [9] . The respiratory tract is frequently affected by viral, fungal or mycobacterial infections. Chronic lung tissue changes and pulmonary alveolar proteinosis (PAP), as well as pulmonary arterial hypertension, have been described in adult patients [1, [7] [8] [9] .", "The prognosis of individuals with GATA2 mutations is difficult to establish due to high clinical variability, incomplete penetrance and lack of close phenotype-genotype correlation data [8, 9, 18] . Antibiotics (e.g. azithromycin) and HPV vaccination are the recommended prophylactic measures [9] . Use of steroids or other immunosuppressive therapy is not indicated and exclusion of immunodeficiency in DPLD prior to use is warranted. A large proportion of patients will develop myeloid malignancy later in life [1, [7] [8] [9] . The only curative therapy is allogeneic hematopoietic stem cell transplantation. Two patients with GATA-2 deficiency with pulmonary involvement transplanted for advanced MDS were reported to have profited significantly from this procedure [7] .", "Diffuse parenchymal lung disease may become the first manifestation of the GATA-2 deficiency. Early genetic diagnosis is critical to direct clinical management, prophylaxis, transplantation, and family screening. " ] },{ "paper_id": "9179c5c9df6bf1ac1aab2f413d18c1954e680fd2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ion channel activity Interact with S, E, M Enhance cellular DNA synthesis Inhibit IFN production and signaling", "3-HP03E_GZ02, 15-HP03M_BJ02, 31-HP03L_Tor2, 106-HP04_GZ0402, 110-PC04_PC4-136, 130-PC03_SZ13)." ] },{ "paper_id": "917fc85b2bd24410181d77246ad89c49e5d6f7b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9182c40a4be4e5849c1bcf4a0fbe20e5ca86e168", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "918502b9ff6b04705babfc9e08f9b0f7c7ece9cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Table S1 . Terms used in the electronic search strategy, adjusted as required for each database. (DOCX 12 kb)" ] },{ "paper_id": "91895a1125e6b20cc3e8439e5a223763b5cb694e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The coordinates of L successively-drawn points (CGR i \u00f0x; y\u00de; i \u00bc 1; 2; \u00c1 \u00c1 \u00c1 ; L) can be given by:", "Then, we consider all the successive four bases in \u03c9,", "(2)", "With the rapid development of both highthroughput sequencing techniques and machine-learning algorithms, an increasing number of biological problems demand bioinformatic methods to achieve satisfactory solutions. However, in the area of RPI identifications, the research history is brief, and there are not many existing computational tools [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] because of the scarcity of available data." ] },{ "paper_id": "918a69132dead88bca9d30666a4eb1d3834206a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step 2 of the 8 steps of hand washing? 176 73.3", "Step 3 of the 8 steps of hand washing? 152 63.3", "Additional file 1: Demographics and question odds ratio analysis between participants with and without diarrhoea." ] },{ "paper_id": "9197060a4f302bde85b29584b40a2c75ba28f837", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A tertiary structure of S, E, M, N proteins was predicted and validated using in silico approach", "Additional file 1: Table S1 . Sequence related information. (XLSX 12 kb)", "Coronaviruses are the most diverse groups of virus which have emerged as deadly viruses in course of time." ] },{ "paper_id": "919c524f19f79213e6f81aa38502c70287d273dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflicts of interest.", "Despite initially restricting what information on the outbreak was shared publicly, the Chinese government has begun to respectfully provide updates on the situation on a daily basis. This encourages the real-time release of information by means of regularly updated situation reports, including epidemiological information with dates of exposure, illness onset, and hospitalization among cases.", "For researchers to be able to contribute to control efforts by improving situation awareness via an explicit risk assessment, it is crucial that detailed epidemiological data are posted to a public domain in real-time. Such datasets should include not only a deidentified line list of cases but also updates on the infection status of traced contacts. Information on exposure period and illness onset can assist with the estimation of important natural history parameters such as the incubation period. It is critical for the public health community and the public at large to understand more about the process of case ascertainment, including the current case definition and reporting system mechanisms. " ] },{ "paper_id": "91ac78d2a3c677d322fc8b14bc23e6b4244b5bdc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were analyzed by Prism software (GraphPad, version 5.0d). Statistical analysis was performed using unpaired t-test to compare two groups and represented as two-tailed p-value with a confidence interval of 95%. One-way ANOVA with Bonferroni post-test analysis was used where more than two groups were compared. Presented results show the mean of measurements within a group. For all statistics, the following notations are used to indicate significance between two groups: *p,0.05, **p,0.01, ***p,0.001, ****p,0.0001.", "Six to eight week old female BALB/c mice (NIH) were maintained at the Thomas Jefferson University Animal Facilities. All animals were handled in strict accordance with good animal practice as defined by the relevant international (Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) (Accreditation Status TJU: Full)) and national regulations (TJU Animal Welfare Assurance Number: A3085-01), and all animal work was approved by the Institutional Animal Care and Use Committee (IACUC) at Thomas Jefferson University TJU. Animal use protocols are written and approved in accordance with Public Health Service Policy on Humane Care and Use of Laboratory Animals, The Guide for the Care and Use of Laboratory Animals. TJU IACUC protocol number 414 A.", "The potential of these vectors as vaccine against HIV-1 Gag has previously been established [15] [16] [17] [18] 52] ." ] },{ "paper_id": "91b3ef8e5827c66d841a773d4d1190b6007f4735", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 18.0. All P-values were two-tailed and values of < 0.05 were considered as statistically significant. Oneway analysis of variance (ANOVA) was applied to identify differentially expressed genes (DE genes). ANOVA with post hoc comparison using Tukey test was used to compare mean viral load between time points. Student's independent sample t-test was applied to each data set for validation study by qRT-PCR. The data were expressed as the means \u00b1 SEM.", "Functional Annotation Cluster tool provided by Database for Annotation, Visualization and Integrated Discovery (DAVID) bioinformatics resources 6.7, at NIAID/NIH, (available at: http://david.abcc.ncifcrf.gov/) was used for gene annotation and to identify functional categories enriched in differentially expressed genes at each time points. Modified Fisher's exact test (EASE score of 0.01) was used to determine the probability of overexpressed gene ontology (GO) biological process terms. The tables were arranged according to enrichment score of ! 1.5.", "H1Hela cells were plated over 6-well plates at a cell density of 4-5 \u00d7 10 5 cells per well and incubated overnight at 37\u02daC. Tenfold virus suspensions were inoculated in duplicates and absorbed for 1.5 hrs. Then the inoculum was replaced with agarose overlay containing 1.5% of carboxymethylcellulose sodium salt (low viscosity; C5678 Sigma-Aldrich), magnesium chloride (0.04 M) and 2% FBS. When the layer was solidified the plates were turned upside-down and incubated for 5 days at 34\u02daC. The cells were fixed with 3.7% formaldehyde and stained with 0.1% crystal violet solution. The number of plaques at each dilution was calculated as PFU [21, 22] . The titer of the purified virus was 5.2 \u00d7 10 9 PFU/mL, as depicted in S2 Fig.", "The association between CXCL8 and reduced lung function, severity of asthma and airway hyper-responsiveness [32] and allergic inflammation [33] has been demonstrated in previous studies. Our findings further support the notion that HRV-induced release of CXCL8 [32, 34] and other members of CXC chemokine family (CXCL 1, 3 and 5) [35] from alveolar epithelial cells could function as neutrophil chemoatracting signal and that perpetuate the pathogenesis of the HRV-B in LRTIs. CC chemokines including CCL2 and CCL20 were significantly induced upon HRV72 infection suggesting that non-neutrophilic immune response could be potentially provoked by this virus. Association of CCL2 level with respiratory symptoms has been shown in allergic individuals [36] . Previous studies demonstrated that CCL2 was implicated in HRV induced airway hyper-responsiveness as a mechanism underlying asthma exacerbation [36, 37] . Further in vivo studies would address the relationship between immune parameters e.g. chemokine level and severity of the disease." ] },{ "paper_id": "91b6e6a867abca446f467eeadcdbbfda198af6a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(i) Set the initial value X(0) and time interval (0,T ) (ii) Set time increment d; define t n \u00bc nd and N \u00bc T/d. (iii) FOR n \u00bc 0 to N 2 1 (iv) Generate independent noise increments, DG ij $ Gamma(d/s ij 2 ,s ij 2 ). (v) For i in 1, . . . ,k, generate process increments \u00f0DN i0 ;...;DN i;i\u00c01 ;DN i;i\u00fe1 ;...;DN ik ;R i \u00de $Multinomial\u00f0X i \u00f0t n \u00de;p i1 ;...;p i;i\u00c01 ;p i;i\u00fe1 ;...;p ik ; 1\u00c0S '=i p i' \u00de;", "\u00f0A 2\u00de", "\u00f0A 5\u00de" ] },{ "paper_id": "91c146beba875fde88ed4e4770cfb6325ad2f038", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chitosan-a linear hetropolysaccharide derived from chitin was previously shown to have anti-inflammatory properties, and its use for drug delivery and tissue regeneration was proposed [20] [21] [22] . Further, chitosan has antibacterial activity against Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Actinobacillus actinomycetemcomitans, Streptococcus mutans, Pseudomonas aeruginosa and Staphylococcus aureus [23] [24] [25] [26] [27] .", "The envelope and membrane proteins form the virion shell, while the nucleocapsid protein interacts with viral RNA to form the virus core. Some species belonging to the Betacoronavirus genus encode an additional structural protein, hemagglutinin esterase (HE), which is thought to act as a receptor-degrading enzyme or mediates interaction with co-receptors, depending on the species [1] .", "Coronaviruses (CoVs) are the largest group within the Nidovirales order, which is comprised of mammalian and avian pathogens. Based on their phylogenetic clustering, CoVs are sorted into four genera: Alpha-, Beta-, Gamma-, and Deltacoronaviruses, of which the Alpha-and Betacoronavirus genera encompass six human pathogens identified to date. CoVs are enveloped, positive-stranded RNA viruses with large genomes of approximately 27-32 kb, and their genomic RNA is capped and polyadenylated. The 5' two-thirds of the CoV genome encode a polyprotein that is post-translationally processed to yield all proteins required for RNA replication (non-structural proteins), whereas the 3' one-third of the genome encodes a canonical set of four structural proteins: spike (S), envelope, membrane, and nucleocapsid. The S glycoprotein of CoV belongs to class I viral fusion proteins and facilitates virus-receptor interactions." ] },{ "paper_id": "91c30e7428918ea501a35e683a5d89c6b45f020a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made." ] },{ "paper_id": "91c7bd831dbc0f6dbbdb2b6f344419a3cb970794", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "mentioned above are designed to be pathogen specific or are aimed at a limited group of infectious agents. The narrow scope of these methods significantly limits their ability to discover new, unknown pathogens and hampers our ability to reveal the full diversity of a given clinical specimen 6, 7 .", "High-throughput sequencing (HTS) technologies, developed in recent years, have substantially improved the capability of comprehensive detection of pathogens without any prior assumptions about the characteristics of the organisms (i.e., \"unknown\" samples). These massive parallel sequencing platforms can sequence mixtures of genetic materials from heterogeneous samples with high sensitivity and speed and at a lower cost per base than traditional Sanger sequencing 8, 9 . In addition, HTS technologies, have benefits other than the improved detection of known and unknown pathogens in different samples. Among these benefits is the ability to detect nonculturable organisms as well as coinfection, drug resistance or response to therapy 10, 11 ." ] },{ "paper_id": "91d5bd7d7d109d8f4ab66a54a4c6f9f5369fb19b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To facilitate comprehension, we choose the Ebola virus disease (EVD) as an example. Currently, the vaccine for EVD is being developed and under phase I, II, and III clinical trials; we want to know whether this vaccine is safe and can induce sufficient immunogenicity to the subjects.", "One has to exhaust all possibilities to reduce bias by performing an explicit hand-searching for retrieval of reports that may have been dropped from first search [12] . We apply five methods to make manual searching: searching references from included studies/reviews, contacting authors and experts, and looking at related articles/cited articles in PubMed and Google Scholar.", "Looking at the funnel plot, the number of studies at the left and right side of the funnel plot is the same; therefore, the plot is symmetry, indicating no publication bias detected." ] },{ "paper_id": "91dc59536a7c1113cc9bef3fbb8972ea8555b0f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed using GraphPad Prism Version 7.0 (GraphPad Software). Statistical differences between groups were evaluated using two-way ANOVA, Tukey-Kramer HSD, and unpaired Student's t tests. Significant differences were indicated with *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. Densitometry analysis was carried from western blot band intensity in ImageJ software v1.52i (National Institutes of Health, USA) and then analyzed by two-way ANOVA.", "Supplementary information accompanies this paper at https://doi.org/10. 1186/s12915-019-0701-1." ] },{ "paper_id": "91df62f28da6d25c7b5ba9383b75fff8e546f6db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and", "By substituting\u015c = N \u2212\u00ce \u2212\u0108, \u03bb(\u0108,\u00ce) = \u03b2(\u03b7\u0108 +\u00ce) and\u0108 = P\u00ce into the second expression in equation (S5) we see that", "Dividing by\u00ce, this becomes" ] },{ "paper_id": "91e6020c65dd5a92c89040f9e209d65e26ef2b7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Increasing epidemiological evidence indicates that perinatal infection with various viral pathogens enhances the risk for several psychiatric disorders. The pathophysiological significance of astrocyte interactions with neurons and/or gut microbiomes has been reported in neurodevelopmental disorders triggered by pre-and postnatal immune insults. Recent studies with the maternal immune activation or neonatal polyriboinosinic polyribocytidylic acid models of neurodevelopmental disorders have identified various candidate molecules that could be responsible for brain dysfunction. Here, we review the functions of several candidate molecules in neurodevelopment and brain function and discuss their potential as therapeutic targets for psychiatric disorders.", "Matrix metalloproteinases (MMPs) are known to have deleterious roles in various nervous system diseases [100] [101] [102] [103] [104] [105] [106] . In particular, MMP 3 degrades the extracellular matrix (ECM) such as integrins, N-syndecan, and non-ECM proteins and activates other MMP subtypes [107] [108] [109] [110] [111] [112] [113] . Up-regulated MMP 3 in the brain following neuronal damage and inflammation is thought to underlie the pathophysiology of neurologic and neuropsychiatric diseases [105, [114] [115] [116] [117] [118] . Notably, associations have been reported between schizophrenia and Alzheimer's disease of polymorphism on the MMP3 promoter, which seems to regulate the transcriptional activity [119, 120] , raising a possibility that the alternation of MMP3 expression may be involved in the etiology of these diseases. We have identified MMP3 as a humoral factor released by astrocytes following polyI:C treatment, by which the dendritic development of cultured neurons is partially but significantly impaired in vitro [63] . These results suggest that MMP3 released by astrocytes disrupts the neuron-glia interaction, leading to neurodevelopmental impairments. Hence, further studies are required to elucidate which MMP3 substrates contribute to the impairment of neuronal development. Understanding the molecular pathways involved in these events would provide insight into novel therapeutic approaches to neurodevelopmental disorders following perinatal viral infections.", "Abnormalities in early brain development contribute to the etiology of many neuropsychiatric disorders in later life [1] [2] [3] [4] . Recent advances in genome-wide analysis indicate that large numbers of common variants shape individual disease risks, including those for mental illnesses [5] [6] [7] . However, the biological mechanisms by which environmental factors affect brain development are poorly understood. Environmental insults include maternal stress, nutritional deficiencies, perinatal infections, season of birth, and obstetric complications [8, 9] . Several lines of epidemiological evidence suggest that prenatal infection and postnatal central nervous system (CNS) infection with various pathogens such as viruses, bacteria, and protozoan parasites enhance the risk for several neurodevelopmental disorders including schizophrenia [10] [11] [12] [13] [14] [15] and autism spectrum disorder (ASD) [16, 17] . These findings indicate the possible interference in brain development triggered by perinatal immune activation. Recent studies with animal models have identified various candidate molecules that could be responsible for the brain dysfunction after perinatal immune activation. Here, we discuss and review the potential therapeutic targets for drug discovery for neurodevelopmental disorders such as ASD and schizophrenia." ] },{ "paper_id": "91e807f991ce190a25835b2cb4d0ee92ec63545d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The emergence of novel pathogens that threaten public health is unpredictable. The 2003 SARS epidemic, with a novel coronavirus variant diffusing widely while its biological identity was still unknown, is a paradigm that illustrates two essential requirements of biothreat preparedness: the ability to identify yet unknown agents, and to do it rapidly. The threat of deliberate release of infectious agents in areas where they are not generally encountered, or the natural evolution of novel combinations of genetic material, exemplified by the H1N1 2009 pandemic variant [1] , further stress the need for rapid identification of unexpected agents. Efficient identification platforms must also cope with the large diversity of pathogens and the need to differentiate them from closely related non-pathogenic species [2] .", "Nucleic acid sequences allow pathogen identification by homology search and phylogenetic positioning, and can achieve species-or strain-level precision. One strategy relies on the amplification and sequencing of conserved target genes, such as bacterial 16S rRNA genes or viral RNA-dependent RNA polymerase genes. Even though broad range primers are used with success in many diagnostic and discovery applications, these approaches are limited in their phylogenetic span, fail to identify species with incompatible sequence variation in priming sites, and do not detect genetic reassortants. High throughput sequencing platforms offer a novel and powerful approach for identifying known or yet unknown pathogenic organisms [3] , but the current time to results may still represent a limitation in the event of a public health emergency.", "DNA of each bacterial strain tested was extracted using the Wizard kit (Promega, France) according to the manufacturer's instructions. Nucleic acid amplification was performed by Repli-g Mini Kit according to Qiagen's instructions. Five micrograms of DNA, quantified by the Quantit kit provided by Invitrogen, were fragmented and labeled using the GeneChip Resequencing Assay Kit (Affymetrix Inc.), hybridized overnight at 45uC and washed, stained and scanned according to manufacturer's instructions (Affymetrix, Inc. Santa Clara, CA).", "After the scan of the microarray, the raw image file (.DAT) is transformed using GeneChipH Operating Software (GCOS) (Affymetrix Inc.) to a fluorescence intensity file (.CEL). Bases are called by the GeneChipH Sequence Analysis Software (GSEQ) which uses a derivative of the ABACUS base-calling algorithm [36] . Sequences are outputted in FASTA format." ] },{ "paper_id": "91eedbad589b474aad1ac0b96957078885146537", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "None." ] },{ "paper_id": "920282c7a0656a43143be9b656b36367cf871c08", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Given that there is a possibility of a human H5N1 pandemic and the fact that the recent H5N1 viruses are resistant to the anti-viral drugs, newer strategies for effective therapy are warranted. Previous studies show that single mAbs in immune prophylaxis can be protective against H5N1 infection. But a single mAb may not be effective in neutralization of a broad range of different strains of H5N1 and control of potential neutralization escape mutants.", "Previous studies with other viruses have shown that combination of two or more than two mAbs directed against different epitopes could lead to a two to ten fold increase in neutralization titers [28, 29] and provided greater protection against many other diseases [30, 31, 32] . Moreover, Meulen et al. [33] reported that much better control of potential neutralization escape variants could be achieved with an antibody combination against SARS Coronavirus. However, no studies have been done so far to demonstrate the efficacy of combination therapy against H5N1 infection.", "Groups of SPF female BALB/c mice aged 4-6 weeks were used for the challenge studies. Mice (n = 10 per group) were inoculated intranasally with 10 MLD 50 (Mouse lethal dose 50%) of two different H5N1 strains (A/Vietnam/1203/2004 from clade 1 and A/Indonesia/TLL013/06 from clade 2.1). All animal experiments were carried out in accordance with the guides for animal experiments performed at NIID and experimental protocols were reviewed and approved by Institutional Animal Care and Use Committee at Temasek Life Sciences Laboratory, National University of Singapore.", "Chimeric monoclonal antibodies (ch-mAbs) were generated for both the mAbs such that the constant regions were replaced with those from human origin but variable regions remained from murine origin. The chimeric mAbs generated in this way were 66.6% humanized. The chimeric antibodies still retained the original properties of the murine mAbs (results not shown). The in vitro microneutralization titers dropped a little compared to the murine mAbs but still retained significant viral neutralization activity (Table 3) ." ] },{ "paper_id": "921a97ffd33121fd2623fb899b386adce87a8562", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We used the following definition of ILI: \"any person with a sudden onset of fever (\u226538\u00b0C) and cough or sore throat fewer than three days in duration, and may be accompanied by general symptoms such as myalgia, prostration, headache, or malaise\" [49] .", "The epidemiological forms were entered into a database created in Microsoft (MS) Office Access 2003, and data were analyzed using dynamic tables in MS Excel 2003. Bivariate correlation used to analyze associations between each viral infection and meteorological parameters and the Chi-square test used to compare between-group differences in percentages were performed with SPSS software version 11.5 (SPSS Inc. Chicago, IL, USA). P values less than 0.05 (P < 0.05) were considered significant." ] },{ "paper_id": "92219161c16ed7c1719549677c40a821fbb54853", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The multivariate risk factors are shown in Table 2 . During the 3 days of follow-up, 91 (13.8%) MERS-CoV patients died. Cox proportional hazard multivariate analysis identified several independent predictors of 3-day mortality in MERS-CoV patients. Elderly, non-healthcare worker, severity of illness, and hospital-acquired infections ( ", "Several factors were identified that could influence mortality outcome at 3 days and 30 days, including being elderly, being a non-healthcare worker, along with illness severity and hospital-acquired infections. The findings can serve as a guide for healthcare practitioners when monitoring and managing the virus, especially at the early stages. Implementing outcome measures and strategies to improve patients' survival in MERS-CoV patients should be an ultimate goal for public health policymakers. ", "A total of 660 MERS-CoV infections in confirmed cases was reported by the Saudi Ministry of Health between December 2, 2014 and November 12, 2016. Of these, 39.2% were elderly (aged \u226560 years). The sample was relatively old, with a mean age of 53.9 (\u00b1SD 17.9) and with ages ranging between 2 and 109 years. More than two-thirds (68.6%) of the sample were males, 15.9% were healthcare workers, 68.6% had pre-existing illnesses, and 41.9% had severe illness conditions. Camel exposure was found in 41.6% of the cases. The majority (64.4%) of the cases were reported in the Central region of Saudi Arabia. Refer to Table 1 for the sample characteristics." ] },{ "paper_id": "9221c3ed344b506c1208f8c2c4f9bf31f60b89da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the following, we will discuss about how TRP channels are connected to respective factors and mechanisms that can activate/modulate inflammation through innate immunity.", "Factors that affect innate immune response via TRP channels (see Fig. 1 )", "TRP channels may link to persistent activation of inflammasome (see Fig. 2 ", "In sharp contrast with a protective role of TRPM4 against dilated cardiomyopathy (see above), the deletion of the trpm4 gene in mice rather improved survival and \u03b2-adrenergic cardiac reserve after experimentally induced ischemic heart failure [175, 185] . In addition, several lines of evidence support the ameliorative role of TRPV1 in myocardial infarction as found in atherosclerosis [176, 177, [179] [180] [181] [182] ." ] },{ "paper_id": "9223fd6478822761845291fe2ac429ca6ddbb45a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The views expressed in this article are those of the authors and do not necessarily represent the views of the Chinese Center for Disease Control and Prevention.", "NPAs were collected from all patients admitting hospitals. Five milliliters of sterile saline was squirted into one nostril, and a 6Fr suction catheter was placed into the nasopharynx using the opposite nostril, pointing the end of the tube directly backward, with the patient aspirating while the suction catheter was gently removed. After ensuring that the specimen was cloudy and had mucus and cells, it was immediately placed on ice and mixed with a universal transport medium (UTM, Copan Diagnostic, Inc., Murrieta, CA) before transporting to ultra-low temperature freezer in district hospital. Next, batches of specimens were transported to Beijing CDC in 5 days, on dry ice, where they were divided into aliquots for culture and PCR, and the remainder was stored at \u221280 \u2022 C.", "From January 2011 to December 2011, participants for radiologically verified CAP were enrolled from Beijing Pneumonia Surveillance. The data on all hospital admissions, other important medical events, culture results of mycoplasma and viral infections were collected. Among these participants, the patients with complete information regarding demographic character, radiological results and clinical manifestations were enrolled in this study. A total of 110 CAP patients (62 of whom were female) meeting the criteria, aged from 1 month to 96 years, were selected in this study (Table 1) .", "All aspects of this study were performed in accordance with national ethics regulations and approved by the Institutional Review Boards of the Center for Disease Control and Prevention of China and the Ethics Committee of the Beijing Center for Disease Control and Prevention (Beijing CDC). The participants received written information regarding the purpose of the study and of their right to confidentiality. Individual written informed consent was obtained from adult participants or children's parents or guardians." ] },{ "paper_id": "9235abaf9b34976f68a8d0031a94201fe371d364", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9235d0eee63bf8da637b7b63b983d58d2372f0d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DNA was extracted by treating 0.5% SDS lysis buffer, and then adding protease K (1 mg/ml) for digestion of nuclear protein for 4 h at 60uC. After using Gentra extraction kit and followed by 70% alcohol precipitation, the total DNA was harvested." ] },{ "paper_id": "923eca0b4175d09814a117b685e434c2f93bc25c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The samples from 1243 animals were collected from April 2012 to June 2012 as shown in Table 1 . Blood samples were collected by jugular or coccygeal vein puncture using disposable needles and vacuum tubes. Samples remained at room temperature for 1 h for coagulation and after being transported refrigerated to the laboratory, they were centrifuged at 1080\u00d7g for 10 min to obtain the sera. The sera were aliquoted in 1.5 mL identified microtubes that were stored in freezer at \u2212 20\u00b0C until analyses." ] },{ "paper_id": "924313134ea2e38b9e48ceaa1177afb92f7a5c03", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where D represents the data conditioning the estimate, and \u03b5(q) is defined by", "and let", "3. Continue at step 2 until total assembly cost can no longer be reduced." ] },{ "paper_id": "925782695d6de40cdf2d0e94622ce06d277ccf74", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "925d90afe2cf113f16a0e28943763916963fdf24", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was conducted, where relevant, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.", "This review was registered on PROSPERO (CRD42014015633).", "Seventeen of the 25 studies reported finding a proportion of isolates recovered from different individuals that were identical, either because there was no diversity or they were unable to capture it. The proportion of " ] },{ "paper_id": "9267b60cb1ef8cf0cff3abb351e73dac5d7d7dea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9268d8f6495e6c459fbd82a4ffaea504fd816751", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "associated with ZIKV infection (microcephaly in newborns and Guillain-Barr\u00e9 syndrome in adults [7] [8] [9] ), indicate an urgent need for research into the biology of the pathogen.", "One may conclude that furin or a furin-like enzyme activates progeny viruses, while no second protease is required during entry to susceptible cell (as reported for other members of Flaviviridae family) [60, 61] . By contrast, some results advocating a role for furin during virus maturation may be due to an artifact, linked to the low specificity of the protease inhibitors used [73] ." ] },{ "paper_id": "926c0d5330eefdb58452c054c8387da92e9d0590", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Leukocyte isolation. Blood mononuclear cells were separated on Ficoll-Paque. Maximum 2 \u00d7 10 7 cells ml \u22121 were resuspended in RPMI supplemented with 30% FBS, 100 U penicillin ml \u22121 , 0.1 mg streptomycin ml \u22121 , and 10% dimethyl sulfoxide (DMSO). Subsequently, cells were frozen by lowering the temperature with 1 \u00b0C min \u22121 until \u2212 30 \u00b0C, followed by a 15 min incubation period at \u2212 30 \u00b0C and finally lowering the temperature to \u2212 150 \u00b0C at a rate of 1 \u00b0C s \u22121 . Next, cells were stored in liquid nitrogen.", "Ethical statement. All experimental procedures were approved by the Local Ethical and Welfare Committee of the Faculty of Veterinary Medicine, Ghent University (EC2012/042), and all methods were carried out in accordance with the approved guidelines." ] },{ "paper_id": "926d8dc84a667e11dfea30fac3824fd17e175398", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Serial dilutions of single-cell suspensions from FrCas E -infected mouse spleens prepared as in ref. [22] were plated on 25% confluent indicator Mus dunni cell cultures. After 3 days of coculture, ffu were score by FIA [see 18, 62] ", "The FccR-blocking 2.4G2 mAb [35] , which recognizes both CD16 and CD32, was purchased from BioXcell and the antiasialo GM1 mAb used for NK cells depletion was from Wako.", "Monoclonal antibodies (mAbs) constitute the largest class of biomedical proteins [1] . They are increasingly being considered as therapeutic agents to fight both acute and chronic severe human viral diseases, with many of them developed in the most recent period [1, 2] . Non exclusively, one can cite neutralizing mAbs against Ebola- [3] , West Nile (WNV)- [4] , cytomegalo (CMV)- [5] , avian H5N1- [6] and human influenza- [6, 7] , severe acute respiratory syndrome (SARS)- [8] , respiratory syncytial (RSV)- [9] , hepatitis B (HBV)- [10] , hepatitis C (HCV)- [11] and human immunodeficiency virus (HIV) [1, 12] that have shown antiviral activity in preclinical studies. One of these (Pavilizumab), directed against RSV, is commercially available, whereas others (see [2] for more information and references) are currently being tested in clinical studies for treating either acute cytopathic infections by WNV and CMV or severe chronic infections by HBV, HCV and HIV, which figure amongst the heaviest health burdens worldwide.", "All experimental procedures performed in this study are in accordance with the local animal facility ''ComEth'' Institutional Review Board guidelines, and have been approved by the local animal facility ''ComEth'' Institutional Review Board under the supervision of the French LR Regional CEEA ethic committee on animal experimentation (Chairman: Pr M Michel, Montpellier)." ] },{ "paper_id": "9271f0b0a1dc37e0a0fa6edf79da42f98bb87026", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All employees present at their respective sites on the day of sampling were asked to participate. Employees were enrolled through face-to-face interaction, and were invited to participate if they were over the age of 18 and not pregnant. Participants were asked to complete a survey about their perceptions of cross-species infection risks and personal protective equipment (PPE) usage (supplemental information S2 Survey), as well as to permit collection of a nasal wash sample.", "More details regarding specimen collection are in the supplemental methods (S2 Text). DNA/RNA extraction and RT-PCR. All samples were temporarily stored on ice after collection, then stored at -80\u02daC until DNA and RNA extraction was performed. For each sample, 200 \u03bcL was extracted using the QIAmp Cador Pathogen Mini Kit (cat. 54106 QIAGEN) per the manufacturer instructions. Previously reported real-time polymerase chain reaction (rPCR) and real-time reverse transcription-polymerase chain reaction (rRT-PCR) probebased assays for human adenovirus (ADV) [12] , human coronavirus (CoV; multiplex assay) [13] , encephalomyocarditis virus (EMCV) [14] , panspecies enterovirus (EV) [15] , influenza A, B, C, and D viruses (IAV, IBV, ICV, IDV) [16] [17] [18] , porcine circovirus 2 (PCV2) [19] , and porcine rotavirus A and C (RVA and RVC; multiplex assay) [20] were validated and performed with DNA or cDNA positive controls and nuclease free water negative controls using a BioRad CFx96 C1000 Touch Thermocycler Real Time detection system (primers and probe sequences are shown in supplemental S1 Table) . The SsoAdvanced Universal Probes Supermix Real-Time PCR Kit (cat. 172-5281 BIORAD) was used for DNA viruses (ADV and PCV2), and SuperScript III Platinium One-Step qRT-PCR Kit (cat. 11732088 ThermoFisher) was used for RNA viruses (CoV, EMCV, EV, IAV-IDV, RVA, and RVC). A standard curve of known positive controls to validate the assay in laboratory was conducted prior to use in the field. A 38-40 C T value range as suspect positive was used as a conservative cut-off to acknowledge that positivity at 38+ could be the result of cross-reactivity or non-specific amplification and thus have potential to be a false positive.", "The large livestock operations and dense human population of Southeast Asia are considered a hot-spot for emerging viruses.", "Odds ratios and 95% confidence intervals were calculated for potential predictors of positivity of virus. Fisher's exact test was used to measure statistical association of predictors for positivity of the viruses of interest amongst each of the sample types and were reported for variables determined to have a positive association at p<0.10. Statistical analyses were performed using STATA 15.0 (StataCorp, College Station, TX)." ] },{ "paper_id": "928c0266f9fede929216a7c6f3370d32ff638401", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cytopenia was determined with decreases in the three main cell groups which are leukocytes, platelets, and erythrocytes. Decreases in leukocytes and leukocyte subgroups (lymphocytes, granulocytes) were also analyzed according to age [9] .", "Bacterial blood cultures were obtained from 37 patients. Three to five milliliters of serum was obtained from each subject for complete blood counts, C-reactive protein (CRP) and erytrocyte sedimentation rate (ESR) analyses. CRP was evaluated as normal (<2.8 mg/L), mildly elevated (2.8-15 mg/L), moderately elevated (16-50 mg/L) and excessively elevated (>50 mg/L) in 91 children. ESR was evaluated in 60 children." ] },{ "paper_id": "92911175d25c9f4bce7ace3050a4ddea1f5105eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the majority of cases, common colds are caused by respiratory viruses such as rhinovirus, coronavirus, parainfluenza, influenza, respiratory syncytial virus, adenovirus, enterovirus, or metapneumovirus [2] [3] [4] [5] [6] [7] .", "The PP population consisted of 178 patients. Main reasons for exclusion were the use of prohibited medications (n = 14) and non-compliance (n = 10). Additionally, one patient was enrolled with violation of inclusion/ exclusion criteria (chronic obstructive pulmonary disease as concomitant disease).", "Each subject was randomised to one of the two groups according to a randomization schedule using random permuted blocks (block size of 4). The randomization list was prepared by a third party and was unblinded after trial review and data base lock." ] },{ "paper_id": "92af993d895fbe5ec7c8ba631624b1a66171a7c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each experiment was independently repeated at least three times. Data were expressed as the mean \u00b1 SD and evaluated by Student's t-test. P < 0.05 was considered statistically significant.", "Age range (years) 1.9-12.4 3-12 1-12 -1. " ] },{ "paper_id": "92bda2372547fcfde4183483335747be9802976b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HCV and host ISGs show a much more complex interaction. For example, cellular pattern recognition receptors detect molecular patterns of HCV [14, 15] , thereby forming a positive feedback loop to amplify IFN signaling. Many ISGs are reported to inhibit HCV RNA replication or viral protein translation, either directly or indirectly, including RNA-specific adenosine deaminase [16] , viperin [17] , and 2 -5 -oligoadenylate synthetase [18] . IFN also induces transmembrane protein 1 (IFITM1) which was reported to inhibit HCV entry [19] .", "Student's unpaired two-tailedtests were performed with GraphPad Prism 5.0a (GraphPad Software, La Jolla, CA, USA). Data are means \u00b1 s.d. Twosided values < 0.05 were considered significant. * < 0.05, * * < 0.01, and * * * < 0.001.", "Current address of Yuchen Xia and Xiaoming Cheng is as follows: Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD 20892, USA." ] },{ "paper_id": "92c932118ed311b25d35527281e7b8568aeb2dcf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In signal transduction processes, adaptor proteins are critical for activating downstream signals via specific protein-protein interactions, including those involving MyD88, IRAKs, TRIF, MAVS, TRAFs, RIP, and TAK1." ] },{ "paper_id": "92cbe76cf67a384ebfb531cd7d8331d2fde3fb49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "land-cover change, climate change, unplanned urbanization and human migration [5] .", "Public engagement and a participatory process, inclusive of all stakeholders: farmers, milk consumers, planning officials, public health personnel, and community organizations, would improve the quality and impact of all interventions aimed at preventing and mitigating harm from outbreaks." ] },{ "paper_id": "92ced556ed66213053dfc7abfa35deb9c1f8ef8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "92e99304d6df52227598a5da5996127ee119f6fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Different UPLC parameters were examined and compared, including various columns, mobile phases, detection wavelengths, and gradient elution conditions to obtain as much chemical information as possible and to determine the best separation mechanism in chromatograms. Four kinds of reversed-phase columns, namely, Waters ACQUITY UPLC BEH C 18 (1.7 \u03bcm, 2.1 mm \u00d7 50 mm/100 mm) and Thermo Syncronis C 18 /Waters ACQUITY UPLC HSS T 3 (1.7 \u03bcm, 2.1 mm \u00d7 100 mm) were investigated and compared. The Waters ACQUITY UPLC BEH C 18 (1.7 \u03bcm, 2.1 mm \u00d7 100 mm) column had good peak separation and sharp peaks.", "HPLC-grade acetonitrile, triethylamine, and formic acid (Tedia, Fairfield, OH, USA) were used for mobile phase preparation. Purified water was prepared with a Mili-Q water-purification system (Millipore, Bedford, MA, USA). Other solvents used for analyses were of analytical grade. ", "Int. J. Mol. Sci. 2012, 13 9036 " ] },{ "paper_id": "92ed9b003b6c24304a7bad059d22c286735ed839", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The median method calculates the global median value for each array. It should be noted that this method assumes that most probes will not hybridize to anything. If this assumption is false then this method should not be used. However, if the assumption holds, then the median is a good representation of that value we would expect to see from probes that have not hybridized to anything.", "In all instances, after taking the log2, groups of probes that have not hybridized to anything should be normally distributed and have mean zero. We can therefore split the probes into groups and perform a t-test for each one. DetectiV does this using the do.t.test function. The normalized (or raw) data are split into groups as defined by the unique values of a user defined annotation column. Providing each group has more than two probes, a t-test is performed to test the difference of the observations from zero. The average value is also calculated. The output is a table, sorted by p value.", "Developing a quick and reliable test for the presence/absence of thousands of bacterial and viral species in a single experiment is an attractive proposition, and a function that DNA microarrays are ideally suited to. Microarrays are extremely high-throughput and relatively cheap. In the case of pathogen detection, the aim must be to quickly and clearly identify those pathogens present in a sample with high confidence, keeping false positives and false negatives to a minimum.", "DetectiV is written in the native R language and uses standard functions within R. As R is available on Microsoft Windows, Unix (including linux) and MacOS, DetectiV represents a platform independent solution for the analysis of pathogendetection microarray data." ] },{ "paper_id": "92f24acca725725852dd170c673f8adac4250faa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although mAbs are not considered as the drug of choice in ophthalmology, they may possibly become the innovative treatment for neovascular glaucoma and diabetic macular edema as shown in Table 3 .", "In terms of versions, among the eight mAbs approved in China, three are murine, one is chimeric, two are humanized and two are recombinant fusion protein. At present, there is no fully human mAb approved for marketing in China.", "myelopathy. Rituximab which is indicated in lupus myelopathy has gained a great success in clinical application and it is now being explored further for any new indications." ] },{ "paper_id": "92f465e2f870b70dfea013a01bc9ccfa46c511de", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The values were expressed as the mean\u02d8SD. Statistical analysis of the results was performed using SPSS 19.0 for Windows, by one way ANOVA or repeated-measures analysis of variance followed by the Student-Newman-Keuls test for multiple comparisons. p < 0.05 was considered statistically significant.", "Glucocorticoids (GCs) are frequently used for the management of inflammation and autoimmune disorders. However, prolonged and/or overdosed GC therapy is the leading cause of secondary osteoporosis, and an important contributor in osteonecrosis development [1] . Among the severe acute respiratory syndrome patients, approximately 39% develop osteonecrosis within a few months of GC treatment [2] . Although previous studies reported changes in the bone microenvironment [3] , the underlying molecular mechanisms of GC-induced side effects are still not fully understood.", "MC3T3-E1 cells were harvested and seeded in 96-well plates at a concentration of 1\u02c610 4 cells/well. After DEX treatment, cell viability was assessed by CCK-8 assay. The absorbance at 450 nm was measured by a microplate reader (BioTek Synergy 2, Winooski, VT, USA). Mean optical density (OD) values from six wells for each group were used to calculate cell viability percentages. Cell culture medium with CCK-8 was used as a negative control." ] },{ "paper_id": "92f4de5e3cd8e63cd679d4af3db2d4d44e929ecd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Three-dimensional protein structure of allele 5 PLY was built by comparative modelling using the MODELLER 9.11 software [36] . The crystal structure of perfringolysin O (PDB: 1PFO) was used as a template for modelling [37] .", "Bacteria were lysed for 1 h at 4\u00b0C (5 mg/mL lysozyme (Sigma-Aldrich), 25 mM Tris-HCl, 50 mM NaCl, protease inhibitor cocktail (Roche)) followed by sonication. The cellular fraction of human blood was PBS-washed, diluted in PBS (2%) and incubated with pneumococcal lysates for 1 h at room temperature. After centrifugation, red blood cell lysis was assessed. The highest amount of pneumococcal lysate used were generated from 5x10 6 CFU S. pneumoniae. Adjacent wells in a row represent a 2-fold dilution.", "For analysis of transcriptional Il1b regulation, total cellular RNA was isolated, transcribed to cDNA, and amplified by quantitative RT-PCR using Gene Expression Master Mix and Il1b TaqMan Gene Expression Assay (Applied Biosystems)." ] },{ "paper_id": "92f5ed730f359773e8b3af4bca2d6d6b9cc224c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following completion of the observations, baseline questionnaires were distributed for return within 2 weeks to a drop box.", "During the 2-month intervention, all HCW received a pocket-sized ABHR and a pamphlet describing correct use. To facilitate hand hygiene, a further 20 ABHR dispensers were strategically placed beside each examination table, computed tomography examination bed, and radiographers' work console of each room. The WHO formulation II (isopropyl alcohol 75 %, 1.45 % glycerol, 0.125 % hydrogen peroxide) was used. An HCA checked and restocked dispensers daily. Additional pocket-sized ABHR were freely available.", "The questionnaire's content validity, as assessed by three infection control experts, was high (average congruence percentage rating of 93.3 %). The Chinese translation was independently back-translated into English and compared with the original. Reliability was determined by test-retest using 20 Accident & Emergency department nurses whose responses were compared on two occasions 2 weeks apart. Spearman's rho coefficient was determined as 0.836 (P < 0.05).", "To somewhat minimize the Hawthorne effect, the observer, a trained infection control nurse, was a staff member of the unit. HCWs were familiar with her presence and therefore, less conscious of her observation. The RD is generally busy and this also helped reduce awareness of observation. Observation was performed unobtrusively using a separate chart for each HCW. The exact date of each person's observation was not announced." ] },{ "paper_id": "9301787667eb36e650623c8dc753399f3e1b4b7c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step 5. Output the terminal template as target genome.", "This study was approved by the Institutional Review Board (IRB) of Chang Gung Medical Foundation, Linkou Medical Center, Taoyuan, Taiwan (Approval No. 100-4378B).", "doi:10.1371/journal.pone.0151495.g001" ] },{ "paper_id": "9313219675ddfa18b0667b701433123acc3c39da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. The data that support the findings of this study are available in this article and its Supplementary Information files or from the corresponding author upon request.", "Statistical analysis. All data were analyzed using the Prism 5 software (GradphPad Software, Inc). All data were analyzed using a two-tailed Student's ttest with a minimum of n = 3. p-Values < 0.05 were considered significant.", "Received: 15 June 2017 Accepted: 9 January 2018" ] },{ "paper_id": "931813f78c97a77e36fb83d93728cffc0106d427", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "933a1b843db9eb0d98835f9359622ba8cb8bdc05", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "933e9eb0d544bb5afe34f6d6049b4c8bc5e96d19", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Univariate analysis was used to determine frequencies and proportions. For bivariate analysis Kruskal-Wallis test was used to contrast qualitative variables and ANOVA for quantitative variables. Multivariate analysis was performed to detect correlation among clinical features, clinical diagnosis, risk factors, municipalities, and viral or bacterial detection. A p < 0.05 was considered statistically significant." ] },{ "paper_id": "93507716d80b9834a1ee584b038c1be54c0790a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animal experiments were carried out in compliance with animal care protocols and all efforts were made to minimize suffering. The protocol was approved by the Animal Care Committee of South China Agricultural University (Guangzhou, China) with approval number SCAU#0014.", "Proteins were extracted from muscle tissues by using a urea lysis buffer (7 M urea, 2 M thiourea and 1% SDS) containing 1 mM PMSF. Total proteins (50 \u00b5g) were separated on a 12% SDS-PAGE, and transferred to a polyvinylidene difluoride membrane (Millipore, Bedford, MA). The membrane was blocked in 5% BSA blocking solution for 1 h at room temperature and incubated overnight at 4 \u2022 C with primary antibodies (Abcam, Cambridge, UK) as follows: MYL1 (ab97427, diluted 1:500), MYL3 (ab137767, diluted 1:1,000), RPL4 (ab154907, diluted 1:1,000), STMN1(ab194670, diluted 1:1,000), RPS3A (ab101690, diluted 1:500), and TNNT3 (ab82784, diluted 1:500). After that, the membrane was washed with PBS-T and then developed with anti-mouse or rabbit horseradish peroxidase conjugated secondary antibodies (Sigma-Aldrich, diluted 1:5,000). Protein bands were visualized using enhanced chemiluminescence (ECL) system (GE Healthcare, USA) and quantified with an ImageQuant LAS4000 system (Fujifilm, Tokyo, Japan).", "HO: performed the experiments, analyzed the data and wrote the manuscript. ZW and XC: Collected the samples and analyzed the data. JY and ZL: analyzed the data. QN: designed the study and reviewed the manuscript. All authors have read and approved the final manuscript. " ] },{ "paper_id": "936a08054b4018e58ae70402e8918715904451ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MHW devised the project, conceived the research design, handled collaborative works with external partners, collected samples, and performed laboratory as well as experiments. TEG performed computational preparations and led the writing of first manuscript draft in consultation with MHW and WA. WA verified laboratory and data analysis methods. MHW, TEG, and WA analyzed and interpreted the data and results of experiments. MHW worked out all revisions in consultation with WA and TEG. MHW conducted manuscript revision. All authors read and approved the final manuscript." ] },{ "paper_id": "936d646d345dd1d9e2df55574f53ebae22c29146", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "936e6e20342454e2646bd840d70148c893262146", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tissue samples were treated and fixed in 10% formalin according to approved standard operating procedure. Fixed samples were processed and either stained with hematoxylin and eosin (H&E) or N 1028 polyclonal antiserum for histopathology or IHC, respectively, as described previously [12] . Slides were examined by a veterinary pathologist and scored as follows: 0 = no obvious pathological changes; 1 = minimal increase in the number of inflammatory cells and hepatocellular necrosis; 2 = mildly increased numbers of inflammatory cells, hepatocellular necrosis or lymphocytolysis; 3 = moderately increased numbers of inflammatory cells, and hepatocellular necrosis or lymphocytolysis; and 4 = highly increased numbers of inflammatory cells and multifocal hepatocellular necrosis or lymphocytolysis.", "CCHFV S segment specific quantitative RT-PCR and tissue titration were carried out as previously described [12] .", "All physiological parameters were compared and analyzed using one-way or two-way analysis of variance (ANOVA) with Dunnet's posttest on GraphPad Prism v5.00 (GraphPad Software).", "The adenovirus (Ad) expressing the complete open reading frame (ORF) of the N of CCHFV Strain IbAr 10200 (Ad-N) (NCBI Ref seq U88410.1 nucleotide 56-1504) or wild type Ad (Adwt) were constructed and rescued using the Adeno-X Adenoviral System 3 and titered using the Adeno-X Rapid Titer Kit according to manufacturer's instructions (both from Clontech). Ad were propagated in 293 cells (ATCC) maintained in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% FBS, 100 mM L-glutamine, and 50 U/mL penicillin, 50 \u03bcg/ mL Streptomycin (obtained from Sigma-Aldrich)." ] },{ "paper_id": "937c21d92c53102251dc79fb436701d149789d4d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "937d7695ba3f5f31a54eef142d6865c6460d5032", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors confirm that there are no conflicts of interest. ", "http://orcid.org/0000-0002-6998-9828", "---" ] },{ "paper_id": "938354ea93017c47a439518c4d67178f63e70088", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To improve transfection efficiency in various hepatoma cell lines like Huh-7, HepG2 and Hep3B different strategies were employed including lipofection, electroporation and microinjection. Microinjection (100 \u03bcg/ml) and Cationic lipids 47-60% 45-55% 65% 60% - [73, 74] Non-viral ---6 0 % - [ 71, 75] E.coli (modified Salmonells/Listeris sp.)", "In contrast to bioluminescence where the enzyme catalyzed reaction initiates the excitation of luminescent molecule, fluorescence is triggered when photons from an external source excites the light absorbing pigments. Green Fluorescent protein (GFP) was the first fluorescent protein to be discovered in jelly fish (Aequorea victoria). Wild type GFP (wtGFP) is a 26.9 kDa protein with a major and a minor excitation peak (395 and 475 nm, respectively) and a single emission peak at 509 nm. The chromophore of this FP is formed by three amino acid residues consisting of ser65-tyr66-gly67 and held by a single \u03b1helix surrounded by 11 \u03b2-barrel sheets to prevent its quenching by water [8] .", "A variety of methods have been developed for a robust and efficient gene transfer without causing toxicity to the host cell.", "Among all promoters used CMV and SV 40 are most efficient in a wide range of cell lines. Apart from these cell specific promoters such as pgk1 and GPAT enhance expression levels in hepatoma cell lines.", "Several modifications have been made to wtGFP to enhance its fluorescence intensity as well as stability by minimizing photobleaching. In the year 1995, Heim et al. [9] introduced a single point mutation at the S65T residue that resulted in enhanced fluorescence at the same emission spectra but with a shift in excitation peak from 395 nm to 488 nm. The mutation also significantly reduced the time required for formation of the fluorophore from 2 hours to 0.45 hours." ] },{ "paper_id": "9399460a7a75b8ae8a4f5610fd1ecf05d21d2f17", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One-day-old White Leghorn specific-pathogen-free (SPF) chickens were obtained from the Laboratory Animal Center, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, China. The chickens were maintained in isolators with negative pressure, and food and water were provided ad libitum. This study was approved by the Animal Welfare Committee of Heilongjiang Province, China.", "Conclusions: The proteomic alterations described here may suggest that these changes to protein expression correlate with IBV virus' virulence in chicken, hence provides valuable insights into the interactions of IBV with its host and may also assist with investigations of the pathogenesis of IBV and other coronavirus infections." ] },{ "paper_id": "93a3e9ccff1d9991907c8f959fbfd99f07af5c29", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "93aab5344693c6df1630f5dcd54b16ad82d7966a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For Western blot analysis, the cells were lysed with Pierce RIPA, and the cell lysates were resolved and separated by 12% SDS-PAGE and transferred to polyvinylidene fluoride membrane. The membranes were probed with primary antibodies against FMDV VP1 protein (dilution, 1:1000) to detect virus replication. A monoclonal antibody to \u03b2-actin (dilution, 1:4000) was used as a loading control. The membranes were incubated with goat anti-mouse and anti-rabbit conjugated with horseradish peroxidase for 1 h at room temperature and examined by Pierce\u2122 ECL Western Blotting Substrate.", "Thirty-two (32) two-and three-day-old BALB/c mice weighing 3-4 g were used to investigate the efficacy of mizoribine in vivo. All the animal trials were performed in a Biosafety level-3 laboratory and approved by the Animal Ethics Committee of Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Science (No. LVRIAEC2018-007). FMDV type O (O/MYA98/BY/2010) strain was used for viral challenge.", "All the data are expressed as mean \u00b1 standard deviation (SD) for at least three independent experiments. One-way ANOVA was used to analyze the difference between mizoribine and control groups using GraphPad Prism 7 (GraphPad Software, Inc., La Jolla, CA, USA), version 7.04, and significant differences were defined at p < 0.05. Selective index (SI) = CC 50 /EC 50 . " ] },{ "paper_id": "93ad47dfe9435a6c7dac0510494626398fbe5ca2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The virus working stock EBOV/Makona used for exposure (GenBank accession no. KX000400.1, BioSample: SAMN04490241)." ] },{ "paper_id": "93b0077bb11f6325fe62ea73f92250f3585872c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral RNA was extracted from clinical samples using either the MagNA Pure 96 platform (Roche Applied Science, Darmstadt, Germany) or the QIAamp Viral RNA Mini kit (QIAgen GmbH, Hilden, Germany) following the manufacturer's instructions.", "PCR products of the 2nd round PCR were analysed in agarose gel, purified with cold ethanol and were then subjected to DNA sequencing using the Big Dye Terminator v3.1 Cycle Sequencing Kit (Applied Biosystems Inc., Foster City, CA, USA)." ] },{ "paper_id": "93b3fcce1e0a7c9a82091bd832b1b3a286133679", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hsp40 cellular levels were elevated after IAV infection, as compared to uninfected cells ( Fig. 3 C and D, upper right panels)." ] },{ "paper_id": "93bc12e23681301901cc72598ded5258b4455eb1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "replication, intrinsic and extrinsic factors that contribute to disease outbreaks, and the role of the host immune system in protection from disease.", ": Sizes and coding potentials of iridovirid genomes. Iridovirus IIV-9 206,791 191 31 GQ918152 IIV-6 " ] },{ "paper_id": "93d080273b1f33330243dd140a35ba890ddd2973", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This overview included data from qualitative, quantitative and mixed methods reviews published in English from 1990 onwards. Inclusion criteria were as follows:", "Review selection, study characteristics and quality assessment Review selection", "Quantitative 6" ] },{ "paper_id": "93d7989c46a48482600c23e05c2594c4c7465ba6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A rabbit anti-ubiquitin protein C (UBC) polyconal antibody was purchased from ABclonal Technology (Woburn, MA, USA). A rabbit anti-RIG-I monoclonal antibody was purchased from Enzo Life Technology (Farmingdale, NY, USA), and rabbit polyclonal antibodies against IRF7, STAT1 and Occludin were obtained from Santa Cruz Biotechnology (Santa Cruz, CA, USA). A rabbit antiphospho-IRF7 monoclonal antibody was purchased from Cell Signaling Technology (Washington, DC, USA), and rabbit anti-IFIT1 and IRF3 monoclonal antibodies were purchased from Abcam (Cambridge, MA, USA). A rabbit polyclonal anti-claudin-5 antibody, a biotinylated goat anti-rabbit or mouse 594 antibody, and an Alexa Fluor 488-conjugated goat antimouse or rabbit antibody were purchased from Invitrogen (Grand Island, NY, USA). Mouse monoclonal anti-Zoluna occludens-1 (anti-ZO-1) antibodies were obtained from Sigma (St. Louis, MO, USA), and mouse monoclonal anti-GAPDH antibody was purchased from ProteinTech (Wuhan, China). The mouse anti-RABV N and P monoclonal antibodies were prepared in our laboratory, and the fluorescein isothiocyanate (FITC)-conjugated anti-RABV nucleoprotein antibody used herein was obtained from ", "confocal Microscopy TaBle 1 | Primers used for quantification of viral mRNA, IFN-stimulated genes, chemokines, and cytokines.", "Retinoic acid-inducible gene I (RIG-I) F", "resUlTs comparison of the Pathogenicity of DrV-ah08 and cVs-B2c in Mice" ] },{ "paper_id": "93db9dda052bb8f92973c8c0ffe4ab8a1364a7ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The synthetic route to the title compounds 3a-3u. RNHCSNHNH ", "Melting points were taken on a Fisher-Johns melting point apparatus and are uncorrected. Elemental analyses were performed on a Leco CHNS-9320 (USA) elemental analyzer. Infrared spectra (KBr discs) were run on Shimadzu Prestige-21 FT-IR spectrometer. The 1 H-NMR spectra were recorded in DMSO-d 6 on Bruker (Rhenistetten-Forchheim, Germany) AM 300 spectrometer, operating at 300 MHz and using TMS as an internal standard. 1 (7), 69 (7) (7), 216 (12) , 188 (20) , 183 (15) , 166 (7), 148 (21) , 120 (7), 106 (7), 89 (8), 77 (7) ", "This study illustrates the synthesis and in vitro determination of the toxic effects of nineteen new and two previously reported [15] N 4 -aryl substituted 5-trifluoromethoxyisatin-3-thiosemicarbazones 3b-3d, 3f-3u and 3a, 3e, respectively." ] },{ "paper_id": "93edcf98f17f9827882fbaed728fb18a8a51cc1d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since cats may be exposed to different influenza virus subtypes, including human-avian and avian-origin influenza viruses, their potential role in the epidemiology of influenza ", "Background: Influenza A virus has a wide range of hosts. It has not only infected human, but also been reported interspecies transmission from humans to other animals, such as pigs, poultry, dogs and cats. However, prevalence of A (H1N1) pdm09 influenza virus infections in cats in northeastern China is unknown. Therefore, the prevalence of A (H1N1) pdm09 influenza virus infections was performed among cats in northeastern China in this study." ] },{ "paper_id": "93f8a441807d1356ad516a8681e14fc093ab016b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Another strategy involves an immuno-precipitation step and was developed to select aptamers against the Toll-like receptor 2 [82] . In this study, Toll-like receptor 2 fused to an Fc fragment was transiently expressed in HEK293T cells. The DNA library was incubated with whole cells before lysis or directly to cell lysates and the sequences specifically bound to the receptor recovered using protein A beads.", "Recently, SELEX has been performed directly against cancerous tissue [98] . Li et al. performed SELEX against paraffin-embedded tissue sections from infiltrating ductal carcinomas and counter-selection against the adjacent normal tissue from the same case. An advantage of this method is that it's possible to select aptamers to all fractions of tissue including extracellular matrix, membrane components and intracellular targets. One aptamer, BC15, was identified to specifically recognize breast cancer cells from clinical tissue sections of different pathological types and breast cancer cell lines. The target of this aptamer was identified to be the intracellular protein hnRNP A1.", "The first SELEX against a membrane protein was performed against L-Selectin by NeXstar Pharmaceuticals Inc. (Boulder, CO, USA) in 1996 [20] . The L-selectin is a calcium-dependent cell surface lectin that is constitutively expressed on most leukocytes and mediates their adhesion to endothelial cells through interaction with cell-specific carbohydrates. A pool of nuclease-stabilized 2'-aminopyrimidine RNA library was selected at 4 and 22 \u00b0C against a human L-selectin-Ig chimera immobilized on Protein A-Sepharose beads. After extensive washing, bound oligonucleotides were eluted with 5 mM EDTA. This SELEX identified aptamers with high affinity at 4 and 22 \u00b0C but they had much lower affinity at 37 \u00b0C. To isolate aptamers with improved thermal stability, the same group performed the same SELEX at higher selection temperatures (either 22 or 37 \u00b0C) using a DNA library [11] . These results highlight that aptamers have to be selected as close as possible to physiological conditions (i.e. 37 \u00b0C) in order to be potentially usable in vivo." ] },{ "paper_id": "9403349de7bef7b3dfd86c83988cb24ade9a9ec9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data accessibility. We have made the source code and data files for our analysis available at https://github.com/kgustafIDM/diseasemobility.", "Other spatial models, such as the well-known, scale-free L\u00e9vy flights, depend solely on travelling distance and have been used to describe a wide-ranging set of phenomena from epidemiology [18] , ecology [19] and plasma physics [20] .", "A closely related probabilistic model is the L\u00e9vy flight model, which has a rich mathematical basis in the framework of fractional diffusion equations and scale-free non-diffusive random processes [43] . We write the discrete space power-law model as", "The joint likelihood for the parametric gravity model, L G , is defined as the product of model evaluations over the set of virus genome linkages S:", ". Note that the normalization depends solely on the destination population and distance. This formulation of the gravity model predicts where a future linked case will appear." ] },{ "paper_id": "9405b40aa26445cd02d7382bf256641ca774de46", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the last few decades, outbreaks of emerging infectious diseases such as severe acute respiratory syndrome (SARS) [1] and avian/swine influenza [2] impacted humanity's disease control systems to reconsider and have raised demand for the development of next-generation vaccines.", "CHP is a partially (1-3% of glucose units) modified polysaccharide, pullulan, with cholesteryl residues (PURE-BRIGHT CP-100T). It was purchased from NOF Co. (Tokyo, Japan).", "Influenza ", "Two hundred fifty g/mL TNF-and 12 mg/mL CHP were mixed, sterilized by filtration, and incubated at 37 \u2218 C for 5 d. During the incubation, CHP encapsulated TNF-molecules to form nanoparticles. Unencapsulated TNF-was removed by sizeexclusion chromatography with a PD-10 column (GE Healthcare, Fairfield, CT). The size of the particles was determined by dynamic light scattering (DLS) with a Zetasizer Nano ZS (Malvern Instruments Ltd., Malvern, UK). To estimate the amount of TNF-encapsulated, nanoparticles were treated with 100 mg/mL methyl--cyclodextrin (Me--CD, Sigma-Aldrich Co., Saint Louis, MO) at 37 \u2218 C for 2 h to disrupt the particle structure and release TNF-, as described [21] . The amount was determined by an enzyme-linked immunosorbent assay (ELISA) system described below." ] },{ "paper_id": "940de307debf3a9042f73ef7cd17fa7a2464d408", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza is an RNA virus that packages eight separate gene segments, including an error-prone polymerase complex, into each glycoprotein-coated virion. These genes segments code for hemagglutinin (HA), neuraminidase (NA), matrix protein (M1), ion-channel protein (M2), nucleoprotein (NP), non-structural protein (NS) and three polymerase proteins (P1, PB1, and PB2). The polymerase complex typically generates one spontaneous mutation during each replication cycle [3] , thereby accounting for a mean substitution rate of 10 \u22123 substitutions per site per year [3] . Moreover, a single host that has been simultaneously infected with two or more different virus strains can serve as a mixing vessel in which novel virions are formed. This process, known as virus reassortment, can cause outbreaks of infection, with potentially dire consequences, if the new virus is both pathogenic and readily transmitted.", "(2) amended consensus files with mixed base calls (customizable) and phasing distance matrices; (3) a read count table for primary and secondary data that makes it easier to infer if there might be mixed subtypes in the sample; (4) per segment figures for read counts, coverage diagrams with highlighted SNVs, and phasing heat maps; and (5) per segment VCF files and IGV-ready assembly files via Samtools.", "(3) a read count table for primary and secondary data; (4) per segment figures for read counts, coverage diagrams with highlighted SNVs, and phasing heat maps (see Additional file 6); and (5) per segment VCF files and IGV-ready [34] assembly files via Samtools [35] .", "For an assembly control (Table 1) , we assembled against both unmixed parent donor viruses. Such references will not be available in a real-world scenario without a priori knowledge (as here) or some kind of iterative refinement strategy. The results for the IRMA control (run non-iteratively) and Bowtie2 control (our representative of a standard approach) differ very little.", "Influenza genetic diversity is too varied for majority consensus to capture Influenza genetic diversity is vast. To illustrate this diversity, we combined sequence data for 1097 influenza A(H3) viruses collected in 2012 and assessed differences amongst members of the set. Viruses of this subtype may circulate in humans, swine, horses, dogs, and other animals. Figure 2a shows that host groups (human, swine, or other) are, on average, 16, 32, or 33 mutations apart (per 150 nucleotides) while variation within a host group is quite appreciable (2, 7, or 24 mutations respectively). Figure 2b shows the pairwise sequence distances as a density plot, revealing that the shape of the viral genetic landscape of one gene from one HA subtype isolated in 1 year is multi-modal and complex. Figure 2c supports this observation with a maximum likelihood phylogenetic tree." ] },{ "paper_id": "9413ac12d29207f16ff2983940960e00f296ec15", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are representative of at least 2 independently repeated experiments and presented as mean \u00b1 SEM. The statistical significance was examined using Student's ttest. P value of <0.05 was considered significant." ] },{ "paper_id": "94156e6941fe78191b5997cdeb10cb3fd06e1221", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples AVNV infected scallops, C. farreri, were collected from Qingdao, China, in 2007. All diseased animals showed clinical signs including slow reactions, weak water-spray, shrunken mantle, blemished ocelli and an enlarged digestive gland. Virus particles were observed in specimens by electron microscopy.", "The complete genome sequence of AVNV reported in this paper has been released in the GenBank database under accession number GQ153938.", "Purification of virus particles was conducted as described by Wang et al. [33] and LeDeuff and Renault [48] , with minor modifications. Seawater was filtered through 0.22 \u03bcm membranes (Millipore, USA) and used in the following purification steps. Mantle, gill and kidney tissues from scallops were rinsed 3 times and homogenized in seawater (1:9) using an Ultra-Turrax tissue homogenizer. After centrifugation at 3,500 \u00d7 g and 7,500 \u00d7 g for 15 min at 4\u00b0C, the supernatant was overlaid onto a 30% (w/v) sucrose solution and centrifuged at 125,000 \u00d7 g for 1.5 h at 4\u00b0C. The pellet was resuspended in seawater by mixing gently. The virus suspension was then layered on a 30-55% (w/v) sucrose gradient and centrifuged at 125,000 \u00d7 g for 3 h at 4\u00b0C. The viral band was removed from the tube by side puncture, and AVNV DNA was extracted using a Takara MiniBEST DNA Extraction Kit Ver. 3.0 (Takara Bio Dalian Co. Ltd. Dalian, China) according to the manufacturer's protocol. The concentration of viral DNA was determined using a spectrophotometer.", "Although viral infection in marine molluscs is a relatively young science, pathogens of this type have been reported worldwide in association with massive mortality outbreaks in economically significant species. Massive mortality of Portuguese oysters, Crassostrea angulata, in French stocks from 1967 to 1973 was associated with irido-like virus infections [1, 2] . Other viruses infecting molluscs were interpreted as being members of the families Togaviridae, Retroviridae, Reoviridae, Birnaviridae or Picornaviridae [3] [4] [5] [6] [7] [8] [9] . Disseminated neoplasia, which was a proliferative cell disorder of the circulatory system in bivalves, was linked to the retroviral infections [10] . However, mollusc virology is still in its infancy and is based largely on morphological features because relevant biological and molecular tools are scarce." ] },{ "paper_id": "942326084a2892419bebfb4508ed7158c158fac9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "94305928dcc0731a946af0b72fa89c5e79a86546", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Prevalence of CAP in community elderly (%)", "YL and BD conceived and designed the project. YL, YZ, WZ has contributed significantly to the submitted work and wrote the first draft. YL, XL, and FH revised the manuscript. All authors read and approved the final manuscript.", "Cephalosporins, including ceftobiprole and ceftaroline, is the \"new-generation\" which is effective against MRSA, MSSA, penicillin-resistant S. pneumoniae, Escherichia coli, and Pseudomonas aeruginosa (Green et al., 2014) ." ] },{ "paper_id": "943491914a5f52c713070accbde7e0e868771e91", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GPI-0100 was purchased from Hawaii Biotech, Inc. (Aiea, HI, USA) and was stored at 4 \u00b0C. A 10 mg/ml stock solution was prepared in HBS buffer (5 mM Hepes, 150 mM NaCl and 0.1 mM EDTA, pH 7.4) as described previously [27] .", "A stock of A/Puerto Rico/8/34 (H1N1) influenza virus (PR8) propagated on Madin-Darby canine kidney (MDCK) cells was kindly provided by Solvay Biologicals (Weesp, Netherlands) and further propagated on embryonated eggs. Virus titer was determined by measuring the tissue culture infectious dose 50 (TCID 50 ) [27] .", "(TIF)", "The protocol for the animal experiments described here was approved by the Ethics Committee on Animal Research of the University of Groningen." ] },{ "paper_id": "9439183d2e5253d1641a64c775dbc17767b01690", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Between 2002 and 2003, severe acute respiratory syndrome (SARS) caused by coronavirus (SARS-CoV) affected over 30 countries on five continents. Soon after, HCoV-NL63 was identified in a seven-month-old infant with bronchiolitis and conjunctivitis in 2004 1 , and followed by HCoV-HKU1 in 2005 2 . Later, the Middle East Respiratory Syndrome coronavirus (MERS-CoV) rapidly spread worldwide with fatality rates up to 30% 3 . Several reports have recently demonstrated the existence of a SARS-like coronavirus, which indicates that coronavirus-associated respiratory tract infections continue to have a significant epidemic potential 4-6 . Therefore, there remains an urgent requirement for standardization of treatments in order to develop more effective interventional strategies for coronavirus-associated diseases.", "Ethics Statement. Written informed consent was obtained from all study participants. The institutional review board of Tianjin Haihe Hospital provided written approval and judged that all methods in the study met relevant ethical guidelines and regulations (ethical # 2013HHKT-01)." ] },{ "paper_id": "9447f072b9c3281b75034071b735888370faab25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thus, we constructed the network to link CEBPA-miR-1772-ROR1 (Fig. 6b, Additional file 10 ).", "Our mice, including all the 6 to 8 wk. SPF BALB/c or C57BL/6, were purchased from Yang Zhou University (Center Comparative Medical). Whilst 3 to 4 wk. SPF ROSS 308 avian were bought from the Jiangsu Academy of Agricultural Sciences (JAAS) (Nanjing, China). All animals were maintained at an animal facility under pathogen free conditions. IBV strain Massachusetts-41 [30] containing 1 \u00d7 10 6.6 EID 50 (egg infectious dose) of IBV was kindly provided by Nanjing Tian bang Bio-Industry Co. Ltd. (Nanjing, China). The infectious bronchitis virus was inactive by UV light (260 nm, with in 15 cm) for 4 h and tested for complete loss of the infectivity before using.", "Phenotypic alteration and T-cell proliferation of DCs stimulated by IBV Surface marker analysis of avian bone marrow-derived dendritic cells (BMDCs)", "All our data are expressed as the mean \u00b1 standard error. Statistical analyses were performed using GraphPad Prism 5 software. Pairwise comparisons were performed using an unpaired two-tailed Student t test. Multiple groups were compared by one-way ANOVA followed with Tukey's multiple comparison tests. P values less than 0.05 were considered to be statistically significant. FlowJo software was selected for the analyzing of our FACS data." ] },{ "paper_id": "9448084d08566af7477c4611211d1072159b6127", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: A.C.B. and A.R.F. conceptualized the review. A.C.B., R.S., J.A., G.W. and E.W. generated a draft of the review. All authors contributed to developing and finalizing the review and agreed on the final version of the manuscript. ", "Buildings not only encourage heterospecific co-roosting in summer, when activity is much greater, but also facilitate \"super roosts\", by presenting unnatural combinations of environmental qualities, such as size, as well as, occasionally, additional anthropogenic heat, enabling unnaturally large aggregations of many tree roosting species that would be impossible in natural sites. Virus epizootiology would theoretically benefit from these increased opportunities for intra-specific and inter-specific transmission.", "From a risk perspective, the known host ranges for lyssaviruses give an indication as to the areas where bat species can be found, and hence, a risk, albeit low, of human-bat interaction must exist. For the most commonly detected lyssaviruses, this range extends across much of the European Union ( Figure 2 ). However, to date, only two human infections with bat lyssaviruses have been described within Europe, both involving fatalities associated with EBLV-2 ( Table 2 ) [30] [31] [32] . ", "The only currently available vaccine for coronaviruses is a canine vaccine although multiple studies are focused on creating vaccines for SARS-CoV and MERS-CoV. All coronavirus vaccine candidates are directed against the Spike protein (S protein), the most immunological component of coronaviruses. Both DNA vaccines and subunit viral vectored vaccines, such as Adenovirus, Venezuelan equine encephalitis virus and modified Vaccinia virus Ankara expressing the S protein, have been demonstrated provide a sufficient protective neutralising antibody response against MERS-CoV in a murine model [159] . Of note, the route of administration was a key determinant in the scale of the resulting antibody response with intranasal administration being the most effective method for both SARS-CoV and MERS-CoV protection as it stimulated significantly higher IgA antibody response than subcutaneous inoculation [160, 161] . Clearly, vaccines for zoonotic viral pathogens of bats need further development." ] },{ "paper_id": "944c456c9127a0b83f1c01d996b9290c291790f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Microcystis viridis is a unicellular freshwater bloom-forming cyanobacterium. It showed transient hemagglutinating activity in laboratory culture during stationary phase under nonaeration conditions. This lectin is composed of a single 13-kDa polypeptide with 113 amino acid residues and two tandemly repeated homologous domains of 54 amino residues.", "The lectin inhibited the production of viral p24 antigen and cytopathic effect induced by HIV with EC50 values of 0.23 and 0.15 \u03bcg/mL, respectively [88] .", "Microcystis viridis lectin binds oligomannosides with sub-micromolar affinities and that two novel carbohydrate recognition domains composed of four non-contiguous regions. The residues make numerous intermolecular contacts with their carbohydrate ligands. This lectin inhibits HIV type 1 envelope-mediated cell fusion with an IC50 [83] ." ] },{ "paper_id": "944f574a3d37e76e4d5a5d23c870733622b02dc9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We identified eligible information products available on 24 April 2016, from lists of technical documents related to each emergency assembled by the WHO Department of Communicable Disease Surveillance and Response. We had difficulty identifying relevant documents and therefore searched multiple potential sources such as WHO's global digital library (Institutional Repository for Information Sharing (IRIS)), hand-searched WHO websites, consulted key WHO staff in technical units and reviewed WHO resource toolkits.", "We report the prevalence of key characteristics for information products in each emergency. For continuous data, we report the mean and standard deviation (SD). We summarize AGREE II scores for each domain (scaled to a percentage of the maximum score) across guidelines using the median value and the interquartile range, as scores were not normally distributed and sample sizes were small for some emergencies. All statistical analyses were conducted using Stata 12.1 (StataCorp LP, College Station, Texas, USA).", "Supporting information S1 " ] },{ "paper_id": "9450e90f9c678f1eb0ce33caac814ebc1b2e97e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2015, 7 5 involves fusion of the autophagosome with lysosome or late endosome for cargo degradation. Detailed mechanisms regulating vesicle fusion are not completely understood. However, the small GTPase Ras-related protein 7 (Rab7), the lysosomal associated membrane protein 2 (LAMP2) and other proteins have been proposed to mediate this process [35] . The vesicle after fusion is called autolysosome and the sequestered cargos are degraded by lysosomal enzymes to recycle biomolecules to the cytoplasm.", "In the following sections, examples of viroporins modulating the ER stress and autophagy pathways will be reviewed in detail.", "In the recent decades, extensive structural and functional characterizations have been performed on several viroporins, revealing their importance in viral replication and pathogenesis. This is further facilitated by the identification of specific viroporin inhibitors, which have been proven to be promising antivirals for the treatment of several devastating and emerging viral infections (reviewed in [3] )." ] },{ "paper_id": "945a7da3231e06eeb8a4a39471338e279c2e6f28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The animal study was approved by the local ethic commitee of the state Berlin (Landesamt f\u00fcr Gesundheit und Soziales, Berlin, Germany) under the accession number G 0350/09." ] },{ "paper_id": "945fd47a82b49774675d732d27f6b806c0e6aeb1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The GenBank accession numbers for the cloned nonhuman primate IFITMs are KU570002-KU570015.", "The experiments were performed as previously described [15] . Briefly, 10 \u03bcL virions containing culture supernatants were incubated with 40 \u03bcL of reaction mixture at 37\u00b0C for 3 h. The mixture contains 50 mM Tris-HCl pH 7.9, 5 mM MgCl2, 0.5 mM EGTA, 0.05% Triton X-100, 2% (V/V) ethylene glycol, 150 mM KCL, 5 mM DTT, 0.3 mM GSH (reduced glutathione), 0.5 U/ mL poly (rA) oligo (dT), and 0.1 \u03bcCi/\u03bcL 3H dTTP (Perkin-Elmer). The reaction was stopped by adding 10% (V/V) cold Trichloroacetic Acid (TCA) at 4\u00b0C for 30 min, and the mixture was transferred to Millipore MultiScreen Glass Fiber FC plate. After being washed twice with cold 10% (V/V) TCA and cold ethanol, the membranes were inserted into Beta Gamma vials and read in Microbeta counter (Beckman Coulter).", "To knockdown IFITM3 in gorilla fibroblasts (Cat #), HEK293T cells were cotransfected with pHIV-\u03948.2-Gag-Pol, lentiviral shRNA (Sigma), and VSV-G. Produced virions were used to infect gorilla fibroblast. Transduced fibroblasts were selected for with 1 \u03bcg/ml puromycin." ] },{ "paper_id": "946087e7d17c7256e8c90187ee7d27f3df870919", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Symmetric or asymmetric cell divisions refer to the mode of cell division which results in two phenotypically identical-or differentdaughter cells, respectively. The phenotypic features could be the cell size, cell surface receptors, intracellular components such as proteins (including those labeled with CFSE), transcription factors, or messenger RNA (17) . Hence, these phenotypic differences provide the basis for the functional differences in the daughter cells, i.e., their cell fates.", "Another class of recently developed mathematical models which allow a direct fitting of the CFSE histograms is based on branching processes (12, 41) . The approach allows for probabilistic characterization of cell activation, proliferation, and death from the CFSE dilution data and does not require the assumption about equality of CFSE division between the two daughter cells.", "2 DDE, delay differential equations; hPDE, hyperbolic partial differential equations; ODE, ordinary differential equations; IE, integral equations." ] },{ "paper_id": "9464670c290cbe53aef50f1aca3011de96a1333c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NGS has been employed to detect zoonotic pathogens and in numerous cases of virus discovery and metavirome descriptions, including bats in China, Myanmar, New Zealand and North America [11] [12] [13] [14] [15] . This technique has also detected novel poxviruses and adenoviruses, divergent papillomaviruses, and unique paramyxoviruses [16] [17] [18] . More recently, genetic regions from a novel filovirus were identified from Rousettus bat in China in 2015, indicating the utility of this approach to ascertain the presence of potentially pathogenic viruses in reservoir hosts [19] .", "Notably, insect viruses and plant/fungal viruses were frequently identified in our bat samples from Singapore. The most common invertebrate viruses were dicistroviruses (65,353 reads), but there were several other virus families present (Alphatetraviridae, Balculoviridae, Carmotetraviridae, Caulimoviridae, Nodaviridae, Nudiviridae, Permutotetraviridae and Polydnaviridae). Moreover, detectable plant/fungal viruses include Alphaflexiviridae, Betaflexiviridae, Edornaviridae, Luteoviridae, Narnaviridae, Partitiviridae, Phycodnaviridae, Potyviridae, Secoviridae, Tymoviridae and Virgaviridae. Taken together, our study identifies a broad diversity of viruses present in Eonycteris bats in Singapore.", "Viruses exhibit specific tissue tropisms based on available cellular receptors and compatibility of the intracellular environment. Detection of these viruses depends on what tissue or sample type is being screened. Previous studies have indicated which viruses are more likely to be shed in feces (adenoviruses, astroviruses, parvoviruses, picornaviruses), urine (paramyxovirues), or tissues [60, [78] [79] [80] [81] . Receptors can be widely available, such as in paramyxovirus (CD46 in measles and sialic acid in Sendai virus) and picornavirus infections (ICAM-1 in Coxsackie virus), or narrowly restricted in adenovirus infections (integrin on monocytes) [82] . Due to limited commercial reagents and the difficulty of maintaining experimental colonies, little work has been done to characterize receptors and viral tissue preference in bats, though progress is being made in determining coronavirus tropism [83] [84] [85] ." ] },{ "paper_id": "948028bf6ac0f66ea490a476c599db04fb42a50f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The microarray data were previously deposited in the GEO database under accession number GSE33266 (23).", "Platelet counts. For bronchoalveolar lavage (BAL), immediately following euthanasia, 1 ml of PBS was injected into the lung through the trachea by using a 22-gauge Exel Safelet catheter tip (Fisher). This fluid was then drawn back out and used for subsequent analysis. Two hundred fifty microliters of BAL fluid was used for absolute counting of gross cell types using an Abaxis VetScan HM5 analyzer.", "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .01753-18. ", "The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH." ] },{ "paper_id": "94827ed2231500b8b66fde9844d2aebe81a4aba9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reverse ( " ] },{ "paper_id": "9484a7c6359d1364cd37bb1d80bdefd118d7ffe6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bacteriophages show widely diverse structures and types of nucleic acid genomes; they have helical or icosahedral capsids and may not include a lipid envelope. Phages range in structural complexity from very small and simple non-enveloped icosahedral viruses (e.g. the ssDNA phage 'X174) and long but simple helical viruses (filamentous phages), to large tailed viruses (e.g. the dsDNA phages T4 or '29).", "The viral fusion glycoproteins structurally characterized to date fall into three classes, although the membrane-fusion pathway seems to be very similar for all the enveloped viruses studied so far.", "In another recent advance, the E1 protein of rubella virus, which belongs to the same Togaviridae family as alphaviruses, was found to have a class II fold, although with a more divergent structure that shows important differences in the fusion loops (DuBois et al., 2013) . In addition, rubella E1 does not form icosahedral assemblies.", "Since the first virus structures were determined at almost atomic resolution, about 35 years ago, virus X-ray crystallography has continued to provide an ever deeper and wider understanding of the virus world. However, many of the questions still remaining in virus structure and function will require an even bolder use of X-ray studies in combination with new experimental approaches, such as high-resolution electron microscopy and single-molecule techniques. Technological developments associated with synchrotron radiation with the advent of in situ diffraction and X-ray free-electron lasers, that will allow the possibility of single-virus-particle analysis, will undoubtedly influence our research on structural virology in the near future." ] },{ "paper_id": "9491f89b53c527904943035f8b4a1f997c3609ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "[OH]D in plasma samples were compared between study groups using Kruskal-Wallis test with Dunn's multiple comparison for selected groups. The P values from Dunn's multiple comparison for selected groups were provided.", "The authors declare that they have no competing interests" ] },{ "paper_id": "94a14012df753e9d47400bf1b660d7559e4976d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This prospective follow-up study investigated the association between virus detection and predefined clinical outcomes in elderly hospitalized patients. STROBE criteria were respected.", "In basic statistics, two sample t-test, \u03c7 2 test and Fischer exact test (when counts < 5) were used when appropriate. Logistic regression with full model was used to analyse the association between clinical outcomes and virus etiology, pneumonia, chronic illnesses (cardiovascular diseases, respiratory diseases, other diseases), age, gender and laboratory findings (WBC, CRP). Statistical significance was established at the level of P < .05. For statistics SAS Enterprise Guide 4.3 (SAS Institute Inc., Cary, NC, USA) was used.", "This study gives valuable information about the significance of virus findings in nasopharynx and inflammatory markers among frail elderly patients with respiratory symptoms." ] },{ "paper_id": "94a4251b88b47417be1ebffe98259c1d4c1e0b36", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Perkinsus marinus and dinoflagellate cultures, RNA isolation and cDNA construction Perkinsus marinus isolate ATCC 50439 and P. chesapeaki ATCC PRA-65 were grown in tissue culture flasks with liquid media, samples (3-4610 6 cells) were collected by centrifugation and total RNAs were isolated as reported previously [14] . Dinoflagellates Amphidinium carterae (CCMP1314) and Karlodinium veneficum (CCMP2778) were grown in f/2 seawater medium at 20uC at a 12 h:12 h light:dark photocycle with a photon flux of approximately 50 mE?m 22 s 21 . When the cultures were in the exponential growth phase, ,1610 6 cells were harvested and total RNAs isolated according to Zhang et al. [8] . These RNAs were used for cDNA synthesis as described previously [8] .", "Poly (A) mRNA was depleted from P. marinus total RNA and a poly (A) tail was added to the remaining population using Escherichia coli Poly (A) Polymerase (Takara Mirus Bio) as reported [8] . First-strand cDNA synthesized using GeneRacer Oligo dT primer (Invitrogen) was used as PCR template. Two rounds of touch-down PCR were carried using the same conditions as above, with the extension time of 5 sec at 72uC. The first round of PCR was performed using PmaSL-LSF1 and GeneRacer3 primers. The PCR products were diluted 100-fold and used in the second round PCR with PmaSL-LSF2, PmaSL-LNF2, PmaSL-LNF3, PmaSL-S2F2, or PmaSL-S2F3, each paired with GeneRacer3, as the nested primers (Table 1) .", "Predicted aa sequences of each gene were aligned with homologs from related organisms using CLUSTAL W (1.8) and inspected manually. Phylogenetic relationships of P. marinus with alveolate relatives and other eukaryotes were inferred using Neighbor Joining (NJ), Maximum Likelihood (ML), and MrBayes (MB) analyses. NJ analysis was performed online [http://clustalw. ddbj.nig.ac.jp/top-e.html] with the default setting. For ML tree reconstruction, the datasets were run through ProtTest [25] to identify the best-fitting aa substitution models (Table 3) , which were then employed in the phylogenetic analysis using PhymLv3.0 [26] . MB analysis was carried out with 20,000-1,000,000 MCMC generations depending on when the average standard deviation of split frequencies reached below 0.01, a tree sampling frequency of 10-100, and 25% of generations discarded as burn-in [27] . To verify the reliability of the tree topologies, branch support was estimated based on bootstrap (1,000 resamplings) in NJ, approximate Likelihood Ratio Test (aLRT) in ML, and posterior probability in MB." ] },{ "paper_id": "94ba61be5805b1b0caef6716c00ed234be78b021", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "94c6aacd8aeb83b9798d43627bcf867944fb8afd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Feline coronavirus (FCoV), a common pathogen in cats, is an enveloped, positive-sense, single-stranded RNA virus. Together with canine coronavirus (CCoV), transmissible gastroenteritis virus (TGEV), porcine respiratory coronavirus and human coronavirus 229E (HCoV 229E), FCoV is classified into the genus Alphacoronavirus [1] . Two pathotypes of FCoV have been well demonstrated, i.e., feline enteric coronavirus (FECV) and feline infectious peritonitis (FIP) virus (FIPV). The former causes mild enteric infections, and the latter causes a fatal immune-mediated disease known as FIP [2] .", "In a prior study, a competitive ELISA was used to discriminate the serotype of infection [11] . However, certain sera could not be typed once inhibition reached 30-80%." ] },{ "paper_id": "94cad8eb2f7ef7b18edd43115de077da98425871", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chaperone Chaperonin containing TCP1 subunit 7 (CCT7) [69] Heat shock protein 90 alpha family class B member 1 (HSP90AB1) [60, 69, 70] Heat shock protein family A (Hsp70) member 1A (HSPA1A) [60, 69] Heat shock protein family D (Hsp60) member 1 (HSPD1) [60, 69] Ion channel Chloride intracellular channel 1 (CLIC1) [60, 69] Annexin A6 (ANXA6) [69] Other functions Creatine kinase, mitochondrial 1B (CKMT1B) [69] Ubiquitin-like modifier activating enzyme 1 (UBA1) [69] Leucine aminopeptidase 3 (LAP3) [60] 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) [60, 69] clathrin heavy chain (CLTC) [60, 69] Queuine tRNA-ribosyltransferase accessory subunit 2 (QTRT2) [60] Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH) [69] ATP binding cassette subfamily F member 2 (ABCF2) [60] ", "Acyl-CoA thioesterase 8 (ACOT8) [60] Complement C1q binding protein (C1QBP) [69] Receptor for activated C kinase 1 (RACK1) [60] Solute carrier family 25 member 5 (SLC25A5) [69] Solute carrier family 25 member 6 (SLC25A6) [69] Staphylococcal nuclease and tudor domain containing 1 (SND1) [69] Negative regulation of apoptotic process NME/NM23 nucleoside diphosphate kinase 2 (NME2) [69] Annexin A1 (ANXA1) [69, 70] Glutathione S-transferase pi 1 (GSTP1) [60] Heat shock protein family A (Hsp70) member 5 (HSPA5) [69] Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) [60] Positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Stratifin (SFN) [69] Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta (YWHAB) [69] Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein \u00e9psilon (YWHAE) [69] Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG) [69] Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) [69] Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) [69] ATP biosynthetic process ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1, cardiac muscle (ATP5A1) [60, 69] ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide (ATP5B) [60, 69] ATP synthase, H+ transporting, mitochondrial Fo complex subunit G (ATP5L) [70] Oxidation-reduction process Aldehyde dehydrogenase 18 family member A1 (ALDH18A1) [70] Fatty acid synthase (FASN) [60, 69] Glutathione-disulfide reductase (GSR) [69] Lactate dehydrogenase B (LDHB) [69] Malic enzyme 1 (ME1) [68] Peroxiredoxin 1 (PRDX1) [60, 69, 70] Peroxiredoxin 4 (PRDX4) [69] Sorbitol dehydrogenase (SORD) [68] Superoxide dismutase 1, soluble(SOD1) [69] Thioredoxin reductase 1 (TXNRD1) [60, 69] Thioredoxin (TXN) [69] Aminoacyl-tRNA synthetase Alanyl-tRNA synthetase (AARS) [68] Glycyl-tRNA synthetase (GARS) [68] Phenylalanyl-tRNA synthetase 2, mitocondrial (FARS2) [60] Tricarboxylic acid cycle Malate dehydrogenase 1 (MDH1) [69] Malate dehydrogenase 2 (MDH2) [69] Glycolisis Oxoglutarate dehydrogenase (OGDH) [60] Pyruvate kinase, muscle (PKM) [60, 69, 70] ", "In the following sections, we discuss the antiviral mechanisms mediated by ISGylation of both viral and cellular proteins, with a focus on mitochondrial proteins, as we recently showed that ISG15 modulates essential mitochondrial metabolic processes such as respiration and mitophagy in macrophages, with important implications for innate immune responses [29] ." ] },{ "paper_id": "94ccf97f5df377bf432fa3a831e38f11985965bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The PCR tests were done by a certified laboratory that has routinely used the CE-marked Respiratory MWS r-gene for the detection of respiratory viruses since 2012.", "Results are represented as coefficients (Coeff), incidence rate ratios (IRR), or odds ratios (OR) with 95% confidence intervals (CIs) and P values; P values of \u03fd0.05 were considered statistically significant. All analyses were done using Stata13 (College Station, TX), R (\"vegan package\" \"Adonis function\") version 3.1.1 (R Foundation of Statistical Computing), and GraphPad Prism 5.", "This work, including the efforts of Urs Frey and Philipp Latzin, was funded by Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung (SNF) (324730_144280/1). This work, including the efforts of Urs Frey and Philipp Latzin, was funded by Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung (SNF) (320030_159791)." ] },{ "paper_id": "94cd1610fd21b8fc289d65a96973216217a955dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A cross-sectional study design was used." ] },{ "paper_id": "94d2ebfc7a2a0ffc00b05ce8031fdfef3255af4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Upon admission to our hospital on day 7, the patient's vital signs were normal (temperature, 37\u00b0C; heart rate, 90 beats per min; respiration ", "RVFV nucleic acids were detectable in the serum and saliva samples with Ct values of 28.7 and 31.0, respectively, on day 7.", "J Liu et al", "Computed tomography scanning showed pneumonia in the double upper and lower lobes of the lung, pleural effusion, cholecystitis and a small amount of ascites; however, the head CT scan was normal ( Figure 1 ). An ultrasonic cardiogram showed that the left ventricular ejection fraction was 60% and that the heart structure had no obvious abnormalities." ] },{ "paper_id": "94f391ebd1b25ac7fb8159d7b24b7414c582a630", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Minimize", "x i = 2 (expansion coefficient), \u03b3 = 0.5 (contraction coefficient), and \u03c3 = 0.5 (shrinkage coefficient)." ] },{ "paper_id": "94f67a30df65c02cf339d2276e04afda40f59072", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The binding populations were sequenced via Illumina MiSeq resulting in 4.2x10 5 sequences, including 1.1x10 5 unique sequences. Analysis of similar sequences, identified and clustered using an in-house algorithm, revealed 3,590 unique families of unrelated sequences. Thus, a broad set of evolutionary solutions was identified for Fn3HP-based ligands.", "The gene libraries were transformed into a yeast surface display system [57] , which yielded 2.0x10 8 transformants. DNA sequencing of 57 random na\u00efve clones indicated 61% had fulllength sequences, 16% contained stop codons naturally arising from the CDR' diversity, and 21% contained frameshifts. This finding was supported by flow cytometry analysis that revealed 64% of proteins were full-length as evaluated by the presence of a C-terminal c-myc epitope. Thus, the library contained 1.2x10 8 unique, full-length Fn3HP clones.", "In the pursuit of a broadly functional combinatorial library capable of yielding binders to numerous targets, the benefit of diversification is unclear for sites peripheral [52, 85, 86 ] to a 'hot spot' that enthalpically drives high-affinity binding [51, 52, 87] . Moreover, the location of the hot spot can differ across different epitopes being targeted by a scaffold. These peripheral sites can (a) directly contact target, (b,c) impact neighboring residue orientation to improve interfacial enthalpy or reduce entropic penalty upon binding, and/or (d) stabilize the protein.", "The probability of evolution from the constrained population versus the original population was also evaluated on a sitewise basis (Fig 3B) . Sites exhibit a range of evolutionary enhancements. For example, sites 52 and 54 have 107% and 213% increased likelihood of ligand discovery from the constrained repertoire whereas sites 78 and 81 are essentially neutral (1% and 2% increase towards constrained repertoire)." ] },{ "paper_id": "94fc08607ba07e9f5a0239d27251d4cdcc6bfd9a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The design and construction of this systematic review was informed and in compliance with PRISMA (2009) [15] (see S1 PRISMA Checklist). Published literature, including conference abstracts, was searched via PubMed database and only original articles with an English abstract were retrieved and reviewed. Publication dates were restricted from January 1 st , 1970 to August 30 th , 2014, with five different search strategies used, as detailed below.", "The following terms were used in five literature searches:", "\u2022 Search 1-Asian region: (otitis media (Asia (aetiology, otopathogens, pathogens, microbiology, bacteriology, bacteria))) or (otitis media (Bangladesh, Brunei, Cambodia, China, India, Indonesia, Iran, Israel, Japan, Korea, Laos, Lebanon, Malaysia, Pakistan, Philippines, Saudi Arabia, Singapore, Taiwan, Thailand, Turkey, Vietnam)) (S1 Fig) \u2022 Search 2-American region: (otitis media (America (aetiology, otopathogens, pathogens, microbiology, bacteriology, bacteria))) or (otitis media (Argentina, Brazil, Chile, Colombia, Costa Rica, Cuba, Dominica Republic, Ecuador, Honduras, Mexico, Panama, Paraguay, Uruguay, Venezuela, Canada, The US)) (S2 Fig) \u2022 Search 3-African region: (otitis media (Africa (aetiology, otopathogens, pathogens, microbiology, bacteriology, bacteria))) or (otitis media (Algeria, Cameroon, Cote D'lvoire, Egypt, Mozambique, Namibia, Nigeria, South Africa, Zambia, Zimbabwe)) (S3 Fig) \u2022 Search 4-European region: (otitis media (Europe (aetiology, otopathogens, pathogens, microbiology, bacteriology, bacteria))) or ( " ] },{ "paper_id": "9503694069cf157e33e29033469edc8d1794a35e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "h c \u00f0x\u00de \u00bc h\u00f0x\u00de \u00fe Q \u00c0 x; x9 \u00c1 :", "Solving for Q\u00f0x; x9\u00de gives", "With this, we are ready to address the last approximation required to find an analytical expression for I c \u00f0x\u00de: Since F is concave, it follows that F\u00f0ah\u00de $ aF\u00f0h\u00de for a 2 \u211d: Thus, setting a \u00bc \u00f01 \u00fe R\u00f0x; x9\u00de\u00de 21 ; and using definition (4), we find a lower bound for I c \u00f0x\u00de:" ] },{ "paper_id": "95375dac99b10d7628f9c154db3799825c2f101f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Claudia A. Garay-Canales is a doctoral student from Programa de Doctorado en Ciencias Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM). This paper constitutes a partial fulfillment for her degree in this Program.", "The authors declare that they have no conflicts of interest.", "Aminopeptidase N (EC 3.4.11.2, APN) is an integral membrane protein with zinc-dependent peptidase activity, first isolated in 1963 by Pfleiderer and Celliers [1, 2] . APN preferentially removes N-terminal neutral amino acids from unsubstituted oligopeptides, amides, or arylamides. Through its peptidase activity, it is known to participate in regulation of the activity of various neuropeptides, as well as vasoactive and chemotactic peptides. APN has been also shown to participate in several other processes, like differentiation, proliferation, apoptosis, motility, chemotaxis, antigen presentation, and tumor cell invasion, among others [3] . Participation of APN in these processes not always depends on its peptidase activity. In 1989, Look et al. established the identity of APN with the myeloid marker CD13 [4] ." ] },{ "paper_id": "9538da236dd88828d491e85addc5b2c6669e7c5a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two parallel groups independently extracted the following data from eligible studies: general information, methodological quality and outcome data. Inconsistencies between two groups were checked after data extraction. Any disagreements were solved by the third reviewer.", "Publication bias was tested using the Egger' s test. No publication bias was detected when verifying the 132 publications that reported RSV positive rates in all patients (-0.27, 95% CI -1.19 to -0.65, P = 0.563)." ] },{ "paper_id": "953d78fb78ffe2bd8db79fac2390d45bd28a4952", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CCR5 is essential for protection against JE but dispensable for control of viral replication" ] },{ "paper_id": "953e146785a16b34f944a8dacec8816d0df49e0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A schematic representation of an IgG antibody comprising of two heavy (green) and light (blue) chains. Carbohydrate elements are attached via the asparagine 297 amino acid residue. A more in-depth discussion of antibody glycosylation is provided in reference [30] . Key: V H -variable heavy, V L -variable light, C H -constant heavy, C Lconstant light. ", "The principle behind these assay formats is the coupling of a specific antibody with an electrode transducer which functions to convert a binding event into an electrical signal. In general, electrochemical biosensors can be based on four transducer types; namely amperometric, impedimetric, potentiometric and conductimetric.", "In conclusion, electrochemical, piezoelectric and magnetic immunosensors can all be applied to foodborne pathogen detection. Optical platforms also offer a powerful and 'label-free' methodology that permits 'real-time' pathogen detection, and these are discussed in section 11." ] },{ "paper_id": "9543d56a69a743e9472e1955f27bfa935ae43942", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "955b36f4b007abbfaa28385a627b03e2102313d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Melbourne is the state capital of Victoria, Australia, and has a population of approximately 4.7 million, making it the second-most populous city in Australia. It is located in south-eastern Australia and has a temperate climate, and so the city experiences seasonal influenza epidemics in the winter months (typically spanning July to October).", "The Australian Statistical Geography Standard defines six hierarchical levels, from mesh blocks that typically contain 30-60 dwellings, to whole states and territories. In between these two extremes are four levels of statistical areas: SA1s, SA2s, SA3s, and SA4s. SA2s are the lowest level for which Estimated Resident Population data are available, and typically have populations of 3,000 to 25,000 persons. SA3s typically have populations of 30,000 to 130,000 persons, and respect geographic and socioeconomic similarities, while SA4 regions typically have populations of 300,000 to 500,000 persons and are designed to reflect labour markets [36] .", "We are concerned here with urban scale models that capture the dynamics of disease transmission at the level of a single city. Modern cities represent some of the densest concentrations of human populations ever observed. Larger cities also represent the highly connected hub nodes in global mobility networks. They thus represent ideal settings for incubating and amplifying outbreaks of infectious diseases [28] [29] [30] . Urban authorities have responsibility for coordinating public health preparedness and response activities, and detailed models at this scale can provide valuable support for decision making [31] ." ] },{ "paper_id": "955cb107f58aff48a58de2473c2fe04e42bfa1e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments were repeated at least 3 times and the results are expressed as mean6standard deviation of the mean (SD). Statistical analysis was performed using the Independent-Samples t test or two-side paired t test between groups using the SPSS 14.0 program (SPSS, Chicago, IL). Differences were considered statistically significant at p,0.05.", "The separated protein bands in SDS-PAGE gels were electroblotted onto PVDF membranes, at a constant current of 250 mA in transbuffer (50 mM Tris, pH 8.0, containing 0.192 M glycine and 20% methanol), using a Bio-Rad Trans-Blot Cell. The strips were incubated for 1 hr at room temperature in blocking buffer (TBS containing 5% nonfat milk), followed by a overnight incubation at 4uC with constant agitation in indicated antibody diluted in blocking buffer. After 3 washes with TBS containing 0.05% Tween 20, strips were incubated for 1 hr with HRPconjugated secondary antibody (Southern Biotechnology Associates Inc., USA) and visualized using the ECL detection system as recommended by the manufacturer (Applygen Technologies Inc., Beijing, China).", "Finally, the region of aa150-230 of CRT has a 98% homology between mouse and human. It would be of interest to examine if there is a functional relationship between the SE binding site and the IAS of CRT. Irrespective of such a relationship, oligomerization might occur to extracellular CRT released by tissue cells thereby converting CRT into a highly active form, which may play important roles in the development and pathogenesis of autoimmune disorders in humans.", "Female C57BL/6 mice between the age of 6-8 weeks were purchased from the Model Animal Research Center, Nanjing, China. All animals were maintained under specified-pathogen-free (SPF) conditions and animal usage was conducted according to protocols approved by the Soochow University Institutional Animal Care and Use Committee. For immunization with rCRT, mice were immunized s.c. at the base of the tail with 100 mg protein in total 100 ml PBS. When booster immunization was needed, 50 mg of protein in 200 ml PBS was injected intraperitoneally (i.p.). For immunization with PAGE gel slices containing Cp32, the band was cut out with a razorblade and then frozen in liquid nitrogen and emulsioned with CFA, which was then injected s.c. into female C57/BL6 mice. Serum samples were collected by tail bleeding, aliquoted and kept at 220uC until use." ] },{ "paper_id": "95648e7d8513a790e6e07df43a7ffac9bf882db5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusions. HCoV is associated with a substantial proportion of illnesses among young infants in rural Nepal. There is an increased risk of HCoV infection beyond the first month of life.", "Knowledge of risk factors for symptomatic human coronavirus (HCoV) infections in children in community settings is limited. We estimated the disease burden and impact of birth-related, maternal, household, and seasonal factors on HCoV infections among children from birth to 6 months old in rural Nepal.", "Methods. Prospective, active, weekly surveillance for acute respiratory infections (ARIs) was conducted in infants over a period of 3 years during 2 consecutive, population-based randomized trials of maternal influenza immunization. Midnasal swabs were collected for acute respiratory symptoms and tested for HCoV and other viruses by reverse-transcription polymerase chain reaction. Association between HCoV incidence and potential risk factors was modeled using Poisson regression." ] },{ "paper_id": "956d1b132a0bb6b7ebd9ca19e312ef0fd7ca7cb9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Figure S1 and S2.", "To evaluate specificity, the RT-LAMP test was performed on a panel of viral isolates from bovine's reference viruses, ( Table 1 ). The panel included three rectal and one nasal swab samples from a normal bovine, one blood sample from a normal bovine, one cell sample (repeated five times) as a negative control, ten strains of BRV, and five different bovine DNA and RNA pathogens ( Table 1) .", "Nevertheless, RT-LAMP is not without caveats: First, the main challenge in development of molecular tests for BRV is the large genetic heterogeneity of this virus [3.4] . This emphasizes the need for constant updating of primers of molecular diagnostic tests for BRV, with FIP and BIP being the most important primers in the entire assay, and they need to be conserved across many strains. Second, due to its high amplification production, the issue of potential cross-contamination problems needs to be addressed. We have added dye into the reaction system before the actual amplification in order to eliminate contamination." ] },{ "paper_id": "9574215db9b33b5a09628c58401bb06f0433e5c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Choline chloride and endotoxin (E. coli lipopolysaccharide, LPS, serotype 055:B5) were purchased from Sigma Chemical Co. (St. Louis, Missouri, USA).", "Endotoxemia is defined as the presence of endotoxins in blood. This situation can occur by Gram-negative bacterial infections which liberate endotoxin (lipopolysaccharides; LPS) during rapid growth. This results in the fact that Gram-negative sepsis is associated with high mortality rates, despite comprehensive treatment in intensive care patients [1] . Studies are underway with regards to understanding the complex pathophysiological mechanism of endotoxemia, describing criteria for early diagnosis and developing new treatment approaches in order to decrease mortality [2, 3] .", "Results were expressed as mean \u00b1 SEM. Data were evaluated by one-way analysis of variance by repeated measures, followed by Tukey test for pairwise comparisons. Clinical scores were compared by a non-parametric test (Friedman Repeated Measure ANOVA on Ranks). P values less than 0.05 were considered significant." ] },{ "paper_id": "957ab1fcf790e8dd9d681f1f216287db1177cb78", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Descriptions of epidemics in ancient and medieval times frequently used the term \"plague\" because of a general belief that epidemics represented divine retribution for sinful living. This view has not disappeared entirely. Some have described AIDS as punishment for sinful activities and such views have delayed or hampered attempts to control this modern epidemic.", "\u2022 How large a supply of drugs and medicines is needed?", "\u2022 How can the necessary drugs and medicines be distributed?", "The first attempt to construct the Panama Canal (1881-88) had to be abandoned because of yellow fever and malaria; the second attempt, beginning in 1907, was suc-cessful because of eradication of the mosquitoes which acted as vectors to spread these diseases.", "Current concerns about a possible influenza pandemic are magnified by knowledge of the 1918 influenza pandemic, which caused a number of deaths estimated as between 50,000,000 and 100,000,000." ] },{ "paper_id": "957d77501f48dcd482bfa9491c169ffb781a3277", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MBL genotyping was performed as previously described [39] ." ] },{ "paper_id": "9580bfcbdb77b78a21887a8911bb9b69444182a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Orenstein's screening method was used to calculate vaccine effectiveness with the following formula:", "For laboratory-confirmed data, a single study period, spanning weeks 46/2009 to 04/2010, was defined." ] },{ "paper_id": "9586f483c1144f2e1b3105d587b826f467d02832", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the plasmids used in this research for transient expression were prepared by standard molecular cloning protocols. The indicated genes, gene truncations, and genes with epitope tags were generated by PCR or site-directed mutagenesis (Transgene) and inserted into pIZ-V 5 /Ha vectors (Invitrogen).", "Introduction cytoplasm (Reviewed in [33] ). After its nuclear export, RanGTP is hydrolyzed to RanGDP, and the complex releases the cargo protein to the cytosol.", "The fluorescence quantification data were obtained using Volocity 6.3 software (PerkinElmer) and Student's T-test was performed to compare the differences between the tested samples.", "Maps of the plasmids and bacmids prepared in this research are diagramed in S1 Fig." ] },{ "paper_id": "958d5304e142a24fffd0ea22672840e340efa309", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "958d54d13cbc0341fe590ba4eeb59e2a0b4fca51", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antibodies, reagents, and plasmids. Various commercially available antibodies were used in this study.", "Mouse monoclonal antibodies against Flag-tag and HA-tag, rabbit polyclonal antibodies against Flag-tag, Cy3 or FITC-conjugated goat anti-mouse antibodies, and FITC-conjugated goat anti-rabbit antibodies were purchased from ABclonal Biotech Co., Ltd (USA). Horseradish peroxidase-conjugated (HRP) goat anti-mouse and goat anti-rabbit IgG (H + L) secondary antibodies were obtained from Boster Bioengineering Ltd (China). Rabbit anti-JEV NS3 polyclonal antibodies and EasyBlot anti mouse IgG (HRP) were acquired from GeneTex Inc (USA). Mouse anti-GAPDH, anti-GST and anti-His monoclonal antibodies were purchased from Proteintech Group Inc. (USA). Rabbit anti-ubiquitin (linkage-specific K48) was purchased from Abcam (Cambridge, MA). Anti-Flag M2 affinity gel, dimethyl sulphoxide (DMSO), NH4Cl, and proteasome inhibitor MG132 were obtained from Sigma (St. louis, MO)." ] },{ "paper_id": "9599f421f59c01ea41789ba70c79330cdea8e1d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dengue hemorrhagic fever (DHF) viral disease is a serious global mosquito-borne infection. The clinical manifestation ranges from mild febrile illness to severe sickness which may include dengue shock syndrome [171] . The DHF virus belongs to the genus Flavivirus in the Flaviviridae family, which can usually be spread by mosquitoes of the genus Aedes aegypti, but less often through the genus Aedes albopictus [172, 173] . Also, this virus is a single-stranded positive-sense RNA virus that exists as four different serotypes (DEN-1, DEN-2, DEN-3, and DEN-4) [174] .", "Funding: This research received no external funding.", "The authors declare no conflict of interest. ", "RVF is not considered a major type in the arboviruses family, which mostly are adapted to a narrow range of vectors; however, among this family, the RVF infection has a very wide range of vector including mosquitoes such as Aedes and Culex, flies, and often, ticks [148] . Interestingly, for different RVF species, RVF vectors have special roles about how they sustain the transmission of the disease ecologically to humans [149] . In some cases, the impact of rainfall, soil type, water, the persistence of breeding, and often wind, have significant effect on vector distribution [150] . Epizootics studies indicate that RVF disease follows unusually severe rainy seasons, a situation that may likely favor the breeding of a very large insect population, needed as a vector prerequisite." ] },{ "paper_id": "959b3431d24276e1b5d1bcfa7885979a4310bd98", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .00819-17. S.V.K. is an inventor with patents and patent applications related to IFN-s that have been licensed for commercial development.", "F.D. and A.P. conceived the study, designed and performed experiments, analyzed data and wrote the manuscript. F.D., Y.E.S.A., G.H. and A.P. performed experiments. E.S. and C.D. performed the histopathology analysis. S.V.K. provided the mouse models used in this study and edited the manuscript.", "Mouse infection and monitoring. C57BL/6, \u2423\u2424R \u03ea/\u03ea , R \u03ea/\u03ea , and \u2423\u2424R \u03ea/\u03ea R \u03ea/\u03ea adult male and female adult mice (2 to 6 months of age) were infected through intravenous injection in the tail vein with YFV-17D (10 6 or 10 7 PFU) diluted in 200 l of PBS. Clinical manifestations of disease were monitored daily, and signs of clinical disease progression were recorded through weighing, clinical scoring, and temperature measurements using a rectal probe. Overall appearance was assessed using a clinical scoring matrix assigned as follows: 0, posture normal, appearance with smooth, shiny fur; 1, posture hunched, appearance with ruffled fur, loss of muscle tone, loss of weight; 2, posture hunched, trembling, shaky, appearance with ruffled fur, loss of weight, rash; 3, posture severely hunched, appearance disheveled, significant (greater than or equal to 20%) body weight loss; 4, death." ] },{ "paper_id": "959c580ae16696d820337df5f221ea7869b71d69", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bioaerosols are present virtually anywhere in the environment, and their exposure is shown to cause numerous adverse health effects [1] [2] . In addition, there is also a possible release of biowarfare agents in a man-made bio-terror event. A number of studies demonstrated that the respiratory tract can be colonized with disease organisms [3] [4] [5] . Through talking, coughing, sneezing or singing, the potential virulent organisms can be exhaled and spread into the ambient environment [6] , which accordingly causes air contamination. For example, SARS in 2003 and H1N1 in 2009 outbreaks were shown to be attributed to the airborne route of disease transmission [7] [8] [9] [10] .", "The differences in collected EBC volumes and culturable bacterial aerosol concentrations obtained by the EBC collection device were analyzed by Analysis of Variance (ANOVA). A pvalue of less than 0.05 indicates a statistically significant difference at a confidence level of 95%. Collection of EBC from human subjects was approved by Peking University Ethnics Committee.", "In this study, a novel EBC collection method was developed by using hydrophobic surface, a layer of ice, and a droplet scavenging procedure. The physical collection efficiency (amount of EBC collected per unit of time) of the device was evaluated. In addition, biological analysis and characterization of EBC samples collected from human subjects were conducted using culturing, DNA stain, SEM, qPCR and species identification tool VITEK 2. This work contributes to the effort in applying EBC together with molecular tools as a non-invasive method in rapid disease diagnosis." ] },{ "paper_id": "95a69a957cdea565f23167cabf3a322fa72bc3c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This one step RT-LAMP established in this study will provide an effective technique tool for the rapid diagnosis, surveillance, and the investigation of molecular epidemiology of PDCoV." ] },{ "paper_id": "95ab4b0ddc015a430ed865c9cdd105f1e50faf31", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Annually, seasonal influenza epidemics cause between 250,000 and 500,000 deaths, the majority in persons age 65 or older [1] . Licensed seasonal influenza vaccines provide only moderate protection against influenza and take significant resources and time to manufacture each year [2, 3] .", "Twenty healthy subjects between ages 24-70 years enrolled; 55% of study subjects were female. Mean age of all subjects was 42 years and mean BMI was 25 (range from 20-38). Table 1 " ] },{ "paper_id": "95af044a0d57fffb101b547ff1f58122d05771bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "What success was achieved and how? The local projects, their rationale, their mechanisms and their outcome", "What are the lessons about determinants of success in partnerships?" ] },{ "paper_id": "95b1f681cfe2bb33c6433b07cd38f0ed3ce3667d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Inhibition of mucin-type O-glycosylation was achieved by cultivating CHO wild-type and CHO lec1 cells for 3 weeks in medium supplemented with 2 mM benzyl-N-acetyl-a-galactosaminide (benzyl-a-GalNAc; Calbiochem).", "SDS-PAGE and immunoblotting. Proteins were separated by SDSpolyacrylamide gel electrophoresis under reducing conditions and proteins were either stained with Coomassie Brilliant Blue (Roth) or transferred to polyvinylidene difluoride membranes (GE Healthcare) for western blot analysis. Myc-tagged proteins were detected using mAb 9E10 (5 mg ml \u00c0 1 , Roche), followed by goat anti-mouse IgG horseradish peroxidase (HRP) conjugate (1:20,000; Jackson Immunoresearch) and enhanced chemiluminescence detection.", "LC-ESI-MS. MS analysis of peptides and DMB-labelled sugars was performed on a nanoACQUITY UPLC system (Waters) equipped with an analytical column (Waters, BEH130C18, 100 mm \u00c2 100 mm, 1.7-mm particle size) coupled online with an ESI Q-TOF (Q-TOF Ultima, Waters). DMB-labelled sugars dissolved in acetonitrile/methanol/H 2 O (9:7:84, v/v) and peptides dissolved in 2% acetonitrile and 0.1% formic acid were separated by reverse-phase chromatography using acetonitrile as eluent. MS spectra were recorded in positive reflection mode and analytes were automatically subjected to fragmentation (MS/MS). Spectra were analysed using MassLynx V4.1 software (Waters). MS/MS protein spectra were automatically analysed using the program ProteinLynx Global Server (Version 2.1, Waters).", "Tissue culture supernatants from transfected HEK293T cells and conditioned medium of the CHO cells were collected and adsorbed to Protein A Sepharose (GE Healthcare). After washing with 20 column volumes of 20 mM sodium phosphate pH 7.0, bound protein was eluted with 0.1 M glycine-HCl pH 2.8 and neutralized by 1 M Tris-HCl pH 8.5. After addition of NaCl to a final concentration of 150 mM, purified Fc chimeras were stored at -80\u00b0C." ] },{ "paper_id": "95bd6a3d04bd47a4a7683ea948e6de05125a34c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "95beff3302bdaccd3ce824cdbf374a20b1a987b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To assess whether protein synthesis occurred during IVRAs, we determined whether 35 S-labeled amino acids were incorporated", "Proteins were separated by SDS-PAGE and transferred to Hybond-P PVDF membrane (GE Healthcare) by semi-dry blotting. After blocking with 1% casein in PBS containing 0.1% Tween-20 (PBST), membranes were incubated with anti-nsp3, anti-nsp5 or anti-nsp8 rabbit antisera, diluted 1:2000 in PBST with 0.5% casein and 0.1% BSA. Peroxidase-conjugated swine anti-rabbit IgG antibody (DAKO) and the ECL-plus kit (GE Healthcare) were used for detection.", "One volume of 6% paraformaldehyde in 60 mM PIPES, 25 mM HEPES, 2 mM MgCl 2 , 10 mM EGTA, pH 6.9 was added to P10 fractions. Formvar-coated grids were placed on 10ml drops of these fixed P10 fractions and incubated at room temperature for 1 min. After blocking with 1% BSA in PBS, grids were incubated for 30 min with rabbit antisera directed against nsp3, nsp4 or nsp6 (1:200) in PBS containing 1% BSA. Bound rabbit IgG was detected with protein A carrying 15-nm gold particles. After negative staining with 2% phosphotungstic acid, grids were viewed in a FEI T12 transmission electron microscope at 120 kV." ] },{ "paper_id": "95c03885392135d1ba49d3db5480fd91750e5b73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The prediction of potential N-liked glycosylation sites was performed with an online server: NetNGlyc 1.0. [20] . This server considers the amino acid alignment Asn-X-Ser/Thr, where X can be any amino acid except Asp or Pro. A threshold value of >0.5 suggests glycosylation.", "Influenza A(H3N2) virus sequences included in the analysis were submitted to Genbank under accession numbers KY653817 to KY653919. S2 Table provides detailed information for the Cameroon influenza gene sequences.", "Supporting information S1 " ] },{ "paper_id": "95c1dc78f1775a83d61ad2517a26844f9a3c46b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The yeast two-hybrid system used for screening was purchased from Clontech Laboratories (USA). The experimental procedures were conducted according to the manufacturer's instructions.", "Cells with recombinant proteins were fixed with 1% methanol/acetone at 0\u00b0C for 10 minutes, washed with incubation buffer (0.05% NaN 3 , 0.02% saponin, 1% skim milk in PBS) twice for 2 minutes each, and then incubated with the anti-V5 antibody (1:200 dilution) at 37\u00b0C for 30 minutes. Cells were washed with PBS at room temperature for five minutes three times, and then incubated with Cy3-conjugated goat anti-mouse IgG antibody (1:20 dilution) at 37\u00b0C for 30 minutes. Cells were washed three more times with PBS. DAPI (Merck, Germany) was used to stain the nucleus.", "Our previous procedures were followed for Western blot analysis [7, 10] . Rabbit polyclonal antibodies against ERK-2 and eIF4G were purchased from Santa Cruz Biotechnology (USA). Monoclonal antibodies against PARP were purchased from SEROTEC (UK). Monoclonal antibodies against V5 tag were purchased from Invitrogen (USA). Rabbit antibodies against EV71 2A protease were generated in the lab." ] },{ "paper_id": "95cc317541d97e3dbaa1662894fdbed842098910", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A comprehensive list of livestock farms across the country was generated in consultation with various regional veterinary officers, and information on herd size and husbandry practices was also obtained. Some of these farms were shortlisted, and after confirmation of the information provided, shortlisted farms were then sensitized and informed consent was obtained before conducting the sampling.", "Permission for livestock sampling was obtained from the wildlife division of the Ghana Forestry Commission (Approval Number: AO4957, 28.04.2009)." ] },{ "paper_id": "95cd65dbf317e24c13557dbf46ffbaa4c206f8be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: S.Q. and Z.L. conceived and designed the experiments and wrote the manuscript; S.Q., X.J., Z.G. and W.Z. performed the experiments; S.Q., X.J. and Z.G. analyzed the data; S.Q., Q.X. and Z.L. writing-review and editing; Z.L. Funding acquisition. All authors have read and agreed to the published version of the manuscript.", "The clinical symptoms of PDCoV-infected piglets are like that of other porcine enteric pathogens, such as porcine epidemic diarrhea virus (PEDV) or transmissible gastroenteritis virus (TGEV), including diarrhea, vomiting, dehydration, and mortality [5] . TGEV and PEDV replicate in enterocytes of the", "Funding: This work was supported by the National Natural Science Foundation of China (31572500 to Z.L.)." ] },{ "paper_id": "95cff929be1b2765e78d6293e4722f404a814011", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There are also well-recognized disadvantages:", "(c) Risk modelling Here, risk modelling is defined as the formal, quantitative estimation of the probability of specified adverse effects from defined hazards [15] . A variety of approaches can be used in risk modelling, sometimes in combination for complex problems.", "In the past decade, there has been a shift away from the deterministic differential equation models-sometimes referred to as mean field models-that were the foundation of epidemiological modelling for almost a century [3] . Much recent modelling work on both human and animal diseases has used stochastic, individual-based models (IBMs; see [26] for an overview). This approach has a number of advantages:", "(c) Environment Here, 'environment' is taken to refer to any factor that is not an attribute of the pathogen or the host(s). This encompasses a vast range of possible influences on disease dynamics, ranging from levels of hygiene in hospitals to land use and climate, including factors that influence disease vectors or intermediate hosts, or those that influence reservoir host populations." ] },{ "paper_id": "95d1135211f245b882e54f2842ab328b89066452", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequence", "Data were compared and the differences were determined by one-way repeated measurement ANOVA and least significance difference (LSD). A P-value < 0.05 was considered statistically significant [21] .", "viruses that can cause a significant concern to animal health industry.", "The OAS/RNase L system is one of the early recognized IFN effector pathways [6] [7] [8] [9] . The presence of double strand RNA (dsRNA) activates OAS, which in return initiates the synthesis of short oligonucleotides, 2' ,5'-linked oligoadenylates (2-5A) that act as second messengers to activate the latent cellular RNase L [10] . RNase L is an endoribonuclease with a ubiquitous expression in all mammalian animals and it contains three major domains: an N-terminal regulatory ankyrin repeat domain (ARD), a protein kinase (PK)-like domain, and a C-terminal ribonuclease domain (RNASE) [6] . Active RNase L destroys both viral and cellular RNAs (mRNA and rRNA) within the cells [7, 8] . The degradation of 28S and 18S rRNA is associated with suppressed viral proteins synthesis [9] . In addition, activation of RNase L induces apoptosis in virus-infected cells through the mitochondrial pathway to limit viral spread [11] . Antiviral effects of RNase L have been extensively illustrated in RNA viruses, while its roles in counteracting DNA viruses have been rarely studied." ] },{ "paper_id": "95d3f266c79f401f0db216cf320eb2b28b5ed8b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "During 2009 influenza pandemic there was some uncertainty as to which NPI to recommend, especially whether facemasks should be endorsed [10] .", "There were no refusals to participate in the study." ] },{ "paper_id": "95d6b47d51b17a1f41ab4df0ed64086ebc11e589", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HI assays were performed on a 100 \u03bcl aliquot of the samples at University Health Network (UHN), Toronto, Ontario, Canada. The sera was treated with Receptor-Destroying Enzyme (RDE) of V. cholerae by diluting one part serum with three parts enzyme and were incubated overnight in a 37\u00b0C water bath. The enzyme was inactivated by a 30-minute incubation at 56\u00b0C followed by the addition of six parts 0.85% physiological saline for a final dilution of 1/10. HI assays were performed in V-bottom 96-well microtiter plates (Corning Costar Co., Cambridge, MA, USA) with 0.5% turkey erythrocytes, as previously described [21] , using inactivated pandemic influenza A/California/07/2009 (nvH1N1) antigens.", "(reverse); nvH1N1 neuraminidase: 5'-TCAGTCGAAATGAATGCCCTAA-3' (forward) and N1R 5'-CACGGTCGATTCGAGCCATG-3'(reverse).", "The following Additional files are available online: Predominant cytokine profiles paralleling early nvH1N1 disease by clinical severity Predominant cytokine profiles paralleling early nvH1N1 disease by clinical severity. " ] },{ "paper_id": "95e5e02c5d10df5d4559adba6bdf7a834b4d5329", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "95ee3b41047edd02d74ab869375f1dcb7b83c31c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The plasmids have been deposited in Addgene.", "After anion exchange chromatography, the AtRNA/MS2 coat protein assembly was adsorbed on carbon/Formvarcoated grids and negatively stained with 1% uranyl acetate. The samples were examined in a JEOL JEM-100 S at 100 kV and at a screened magnification of 100 000\u00c2. Imaging was performed at the Cellular and Molecular Imaging facility of the IMTCE (Faculte\u00b4de Pharmacie, Universite\u00b4Paris Descartes).", "tRNA Lys 3 methylation Modified species of tRNA Lys 3 were purified as previously described (26) . Briefly, total RNAs were recovered from cells by phenol extraction and loaded on a Resource Q column (GE Healthcare, 50 ml) previously equilibrated in 20 mM potassium phosphate (pH 6.5). The m 1 A 58 e150 Nucleic Acids Research, 2013, Vol. 41, No. 15 tRNA Lys 3 eluted at 400 mM NaCl, whereas the nonmethylated tRNA Lys 3 eluted between 410 and 460 mM. The protocol used for in vitro methylation of tRNA Lys 3 was adapted from a previously reported protocol (29) . Briefly, the reaction mixture (2 ml) was composed of 50 mM Tris-HCl (pH 8.0), 10 mM MgCl 2 , 5 mg of tRNA Lys 3 , 1 mM AdoMet (S-adenosyl-L-methionine) and 450 mg of purified TrmI (30) . After 60 min of incubation at 60 C, the reaction was stopped by phenol extraction and ethanol precipitation. The methylated tRNA Lys 3 was purified on a Resource Q column (GE Healthcare, 50 ml) equilibrated in 20 mM potassium phosphate (pH 6.5) and eluted with a gradient of NaCl. The eluate was then extensively dialyzed against 10 mM potassium phosphate (pH 6.5) and 50 mM KCl. NMR experiments were recorded at 288 K on a Bruker AVANCE 600-MHz spectrometer equipped with a TCI 5-mm cryoprobe. Two dimensional NOESY experiments with a mixing time of 150 min were recorded using a watergate sequence for the solvent signal suppression (31) ." ] },{ "paper_id": "95f0f21246953b8b6258cdf4afd61011c32a686f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "effective and economical chemical treatment for rice leaf blight has not been established, although research and development are ongoing.", "Xoo-mediated leaf blight is one of the most devastating rice diseases worldwide. For the past two decades, substantial efforts have been made to identify and isolate bacterial blight-resistance genes. In this study, we used an alternative chemical approach to protect rice from Xoo infection.", "More than 30 drugs, including antibiotics, have been utilized to protect crops from pathogen attack. Some of these have broad-spectrum bactericidal and fungicidal activity, whereas others specifically target bacteria or fungi. Oxytetracycline and streptomycin are commonly used antibiotics in humans and plants 15 , suggesting that some types of human drugs can positively control diseases in plants. Therefore, we screened human drugs for their ability to prevent rice leaf blight disease. Our long-term goal is to identify a master regulator that inhibits pathogenic disease in both plants and humans." ] },{ "paper_id": "95f3513f4173df6761cba6c75b1b518b66ce5502", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Measurements of liver and kidney functions. Plasma levels of AST or ALT and BUN or Cr were measured as markers of liver and kidney damages, respectively, by using FUJI DRI-CHEM slide kits (Fujifilm Corporation).", "Reporting summary. Further information on research design is available in the Nature Research Reporting Summary linked to this article.", "The data that support the findings of this study are available from the corresponding author upon reasonable request. Source data used to generate Figs " ] },{ "paper_id": "960f5c1ce2c58eaa9e271f8246d3844aac1082f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As the only viral protein on the surface of HIV-1 particles, the Env protein represents the chief target for recognition by the host adaptive immune system, leading to the production of antibodies that", "In addition to targeting Env in the infected cells and preventing its incorporation into virus particles, some cellular factors such as IFITM3 and SERINC5 also find their way into virus particles and block the fusion of viral membrane and cellular membrane.", "In order to replicate and transmit, viruses need to counter and evade the multi-layered host restriction defense system. Identification of viral antagonism against a host restriction factor also demonstrates the presence of this restriction in the context of in vivo viral infections, which have driven the selection and evolution of specific viral counter measures. Indeed, viral antagonistic strategies have been discovered for some host restriction mechanisms targeting HIV-1 entry, which began to illuminate the diversity of viral evolution in evading host restriction." ] },{ "paper_id": "961eb2f08c480672f033054cfce36910d0d37b7d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The intestinal tissues of bats infected with SARS-related (SARSr)-CoV or HKU4 were gifted by professor Changchun Tu from the Institute of Military Veterinary Medicine. RNA was extracted using a commercial RNA extraction kit (RNeasy Mini Kit, Qiagen, Hilden, Germany) in the BSL2 Laboratory.", "The throat swabs were collected at the Institute of Military Veterinary Medicine in accordance with the approved guidelines and relevant regulations. Written informed consent was obtained from all the subjects prior to their participation in the study. The Ethics Committee and Institutional Review Board of Use Committee of the Chinese People's Liberation Army (No. SYXK2009-045) approved all the experimental procedures.", "HW, SY, and XX designed the experiments. PH, HJ, ZC, HC, FY, XH, FW, CJ, PFH, SX, YZ, JW, WS, and TW performed the" ] },{ "paper_id": "962349fd2566b8fb0ebe7e69aa8998151de7d9ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additionally, there were errors in the Case Representation section which should be corrected as follows: ", "In the article titled \"A Rare Cause of Childhood Cerebellitis-In uenza Infection: A Case Report and Systematic Review of Literature\" [1] , Dr. Candan \u00c7i\u00e7ek was missing from the authors' list. e corrected authors' list is shown above.", "i) \"CSF cultures were bacteriologically sterile. Polymerase chain reaction [PCR] assays of CSF for inuenza virus, herpes simplex virus 1 and 2, adenovirus, enterovirus, cytomegalovirus, human herpesvirus-6, epstein-barr virus, and varicella zoster virus were all negative\" should be corrected to \"Multiplex polymerase chain reaction [PCR] assays of CSF for herpes simplex virus 1 and 2, adenovirus, enterovirus, cytomegalovirus, human herpesvirus-6 and -7, Epstein-Barr virus, varicella zoster virus, parechovirus, parvovirus B19 (Neuro 9 Detection, Fast Track Diagnostic, Malta) and in uenza virus type A and B, parain uenza virus, adenovirus, respiratory syncytial virus, human metapneumovirus, human bocavirus, human coronavirus, enterovirus, and rhinovirus (Allplex Respiratory Panel Assays, Seegene, South Korea) were all negative.\" (ii) \"Serologic tests of his blood showed negative results for epstein-barr virus, herpes simplex virus, varicella-zoster virus, cytomegalovirus, measles, mumps, rubella, and mycoplasma pneumoniae. Respiratory viruses such as adenovirus, rhinovirus, respiratory syncytial virus, parain uenza virus, human bocavirus, human metapneumovirus, and coronavirus were not detected in the nasopharyngeal swab specimen by multiplex PCR. However, we identi ed in uenza A H1N1 virus on the third day of the onset of the symptoms, which was when we started treatment with oseltamivir as 4 mg/kg orally twice a day. e patient was diagnosed with in uenzaassociated cerebellitis based on the clinical ndings\" should be corrected to \"Serologic tests of his blood showed negative results for Epstein-Barr virus, herpes simplex virus, varicella zoster virus, cytomegalovirus (Vidas \u00ae , bioMerieux, France), measles, mumps, rubella, and mycoplasma pneumoniae (Diesse Chorus ELISA, Italy). Respiratory viruses including adenovirus, rhinovirus, respiratory syncytial virus, parain uenza virus, human bocavirus, human metapneumovirus, and coronavirus were not detected in the nasopharyngeal swab specimen by multiplex PCR (Allplex Respiratory Panel Assays, Seegene, South Korea).\"" ] },{ "paper_id": "962b1eed7da37d26000eb9232c49851420b1e662", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Feline coronavirus (FCoV) (Nidovirales; Coronaviridae; Coronavirinae; Alphacoronavirus 1) is a widespread pathogen among the domestic cat population. FCoV occurs as two pathotypes, feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV), both of which with strains of serotypes I and II [1] .", "Phenotypically, the main difference between the pathotypes is that FIPV is able to infect monocytes and macrophages, causing systemic infection and fatal disease, while FECV is limited to replication in the mature intestinal epithelium, which mainly results in asymptomatic infection. However, FECV may undergo a short systemic viremia phase that also involves monocytes [2, 3] .", "This study has been approved by Commission on Ethics on Animal Use from School of Veterinary Medicine, University of S\u00e3o Paulo (CEUA N. 2055211113).", "All tissues were complete homogenized after tissue maceration and before RNA extraction. Total RNA extraction and RT-PCR to detect mRNA of the M gene of FCoVs were performed in all samples as previously described [21] as a screening test for FCoV replication.", "For an easier identification of the clones, the following nomenclature was used: cat identification/sample source/ presence (+) or absence (\u2212) of FIP/cat origin/clone number." ] },{ "paper_id": "962c3880e4fee95b974d6d754a568278cc72e6d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It is important to consider that the amount of active constituents in plants depends on environmental factors. [454, 455] 77 [456, 457] 78 [138, 458, 459] 79 [460] 80 [460] 81 [344] 82 [461] 83 [461, 462] ", "The authors declare that they have no competing interests'.", "Not applicable because this manuscript does not contain any individual persons' data." ] },{ "paper_id": "962c58e6dc9c1ea550eb51ce70b0d7c83dc7eff6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Geometric mean titers for the VLP vaccine groups were similar (p.0.05).", "Additionally, a live virus ''vaccination'' group was added in this experiment for comparison of challenge results following vaccinations with inactivated vaccines to those following earlier infection.", "The different groups of vaccinated animals showed similar trends in severity of pathology and of eosinophils in inflammatory infiltrates; however, the DIV and BPV preparations at high dosage tended to produce a greater infiltration with eosinophils." ] },{ "paper_id": "963285bb042097a1c7b9053b74db098d24818b25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The original Vero cells on which Frankfurt-1 was primarily isolated (hereafter termed Vero FM, obtained from Jin- ", "Growth properties of rSCV and r7b\u0394TMD on different cell lines were compared. Plaque morphology was determined for both viruses, with no discernible differences ( Figure 5B ). Because plaque assay could only show cells that die from virus infection, the same experiment was repeated and read out by immunofocus assay, using serum of a human SARS survivor. There was no difference in immunofocus morphology ( Figure 5B ).", "Plaque assays were done with Avicel overlays (RC581, FMC BioPolymer, Belgium) as described elsewhere [71] . Immunofocus assay used the same overlay and was otherwise performed as described previously [72] . Viral RNA quantification using in-vitro transcribed RNA standards was done as described previously [2] ." ] },{ "paper_id": "9633dd466a1f1c402c18d7db00bae7bf1eea5250", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dengue fever is endemic in tropical and subtropical areas, especially Southeast Asia. International air travel facilitates the spread of dengue across and within borders. To date, no predictive factors have been established for assessing risk of dengue among febrile travelers.", "Since 2006, Taiwan has operated a program of infrared thermometer-based non-contact active surveillance at Taoyuan International Airport (TPE). All inbound passengers from dengue-endemic countries who are febrile (tympanic temperature \ufffd38\u02daC) undergo routine laboratory testing for dengue. We analyzed clinical and epidemiological characteristics of all tested passengers entering Taiwan via TPE in 2011 to identify the predictive factors of dengue infection. 14(12): e0225840. https://doi.org/10.", "Upper respiratory symptoms, including cough, rhinorrhea, and sore throat, are often recognized as uncommon presentations among patients with dengue infection. However, a review of patients with laboratory-confirmed dengue in Taiwan showed that approximately 40% of patients had cough [40] . A study conducted in Vietnam revealed that the frequency of cough was similar in both dengue and non-dengue cases [41] . Even though this study found a negative association between upper respiratory symptoms and dengue virus infection, the upper limit of the 95% confidence interval was very close to 1. This association could also be influenced by the activity of other respiratory pathogens that could cause febrile illness, for example, influenza virus. Hence, in a primary care setting or at the airport border, physicians or quarantine officers should not use only upper respiratory symptoms to exclude a diagnosis of dengue in febrile travelers.", "Among the 74 inbound passengers with laboratory-diagnosed dengue infections, 38 (51%) were positive by NS1 antigen rapid test and PCR; 5 (7%) were positive by NS1 but negative by PCR; and 23 (31%) were negative by NS1 but positive by PCR (Table 1) . Of the 18 (24%) patients who were positive for recent dengue infection by ELISA, only one patient was diagnosed by a fourfold increase in IgG. The median age of patients was 32.5 years (range, 1-72 years), and 44 (59%) of the patients were male. Among the 74 patients, 21 (28%) went to visit family and relatives, 12 (16%) were on business, 11 (15%) were independent travelers, and 2 (3%) were group travelers. For the departure country, 16 patients (22%) reported traveling from Philippines, 14 (19%) from Indonesia, 10 (14%) from Thailand, 8 (11%) from Malaysia, and 6 (8%) from Vietnam. The majority of dengue patients had stayed in dengue-endemic countries for \ufffd29 days (58%), followed by 8-14 days (14%), 22-28 days (11%), \ufffd7 days (9%), and 15-21 days (7%)." ] },{ "paper_id": "963a2753dda05c4a8a3a67d725477f4b7c5aa850", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The analyzers were calibrated according to the manufacturer's specifications.", "Portability and access to diagnostic tests is of great importance particularly with rare diseases. It has been known that PCD is underdiagnosed [2, 12] . The effects of underdiagnosis may have a stronger impact in remote areas where inhabitants have little chance of being diagnosed and treated properly without leaving their jobs and travelling long distances, sometimes taking days to reach the closest PCD referral center. Wrong diagnosis in patients with bronchiectasis can be harmful, because other disorders (e.g. Common variable immunodeficiency syndromes) are treated differently than PCD, and timely diagnosis and early treatment may produce a decrease in morbidity [13] .", "All image recordings and processing were performed with the Sisson-Ammons Video Analysis (SAVA) system [7] , which was highly customized to perform ciliary analysis for both ciliary beating frequency (CBF) and patterns. Images were captured initially into RAM in real-time at 120 fps and immediately compressed and stored to disk. At a sampling rate of 120 fps, approximately 3 s of video were recorded for each image. Each digital image frame consisted of 640 columns X 480 rows of pixels.", "Using this mobile system we have so far performed HVMA tests in 203 subjects in 14 different pediatric pulmonology centers throughout the country. With an approximate 20 minutes testing time per patient, from brushing to complete analysis of the ciliary beating pattern, we were able test 10-15 subjects per day. Apart from individual transport time to each center location, it took another hour to reassemble and disassemble the system in each location." ] },{ "paper_id": "963cc6ca5e9eecf735dfcb89e2320a22fa4bcec6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The genome sequence of PEDV strain CH/HNYF/2014 has been deposited in GenBank under the accession number KP890336.", "Sow's milk is a potential route for the vertical transmission of porcine epidemic diarrhea virus (PEDV) from sow to suckling piglet. We report here the complete genome sequence of PEDV strain CH/HNYF/2014, which was isolated from milk samples. This information provides further understanding of the transmission mechanisms and genetic diversity of PEDV.", "of porcine epidemic diarrhea (PED), an acute and highly contagious enteric disease characterized by watery diarrhea and vomiting. PEDV was first recognized as the causative agent of PED in Europe in 1971 (1) , and it has occurred on pig farms in many Asian countries and more recently in the United States and Germany (2, 3) . It was previously reported that PEDV can be transmitted vertically from sow to suckling piglet via milk (4) . Here, we report the complete genome sequence of a variant PEDV strain (CH/HNYF/2014) isolated from sow milk samples." ] },{ "paper_id": "9642cb44e010ca78890c7021b2641ad7d3fcdc69", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "964442dc964b2d97ceef1883ce2353e866efd8c2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using the Statistical Package for the Social Science for Windows version 12.0 (SPSS, Chicago, IL, USA). Continuous variables are reported as the mean \u00b1 standard deviation. Statistical significance was assessed using the \u03c7 2 test for categorical variables, and the independent sample t-test, paired ttest, and one-way analysis of variation (ANOVA) for continuous variables. A p value < 0; 0.05 was considered statistically significant.", "The pre-publication history for this paper can be accessed here:" ] },{ "paper_id": "9644dba679eaf2bd1ce6c96769f5be2aff16ee40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All fluorescent antibodies are listed in \"fluorochrome-target (clone; annotation if desirable)\" format below.", "Human TruStain FcX (Fc receptor blocking solution) was from Biolegend; cell fixable viability dye eFluor 506 was from eBiosciences.", "Non-parametric Mann-Whitney tests and one-way ANOVA were performed using GraphPad Prism v5.00 (GraphPad, San Diego, CA), with p \u2264 0.05 considered statistically significant. \"NS\" refers to \"No Significance.\"" ] },{ "paper_id": "96456a955d56878dc1e53c0feeb14bf307518b17", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BHK, Vero76, LLC-MK2 and DF-1 and MEF cells were propagated and maintained in Dulbecco's Modified Eagle Medium (DMEM, Gibco) containing 5% fetal calf serum (FCS), 50 U/ml penicillin, 50 mg/ml streptomycin, 2 mM glutamax and 10 mM HEPES at 37uC and 5% CO 2 .", "Linearized DNA template from KUNV replicon plasmids was transcribed using SP6 RNA polymerase (Roche) as per manufacturer instructions and the resulting KUN replicon RNA transcripts were electroporated into BHK cells (Bio-Rad GenePulser II apparatus; 25 mF capacitance, 1.5 kV voltage, infinite resistance, two pulses with 10 second interval, with the optimal time constant between 0.7 and 0.8 ms). Electroporated cells were then resuspended in 10 ml of DMEM containing 5% FCS, seeded into culture plates, and incubated at 37uC under 5% CO 2 and humid conditions. 72 h post electroporation (hpe) total cellular RNA was extracted using Trizol reagent (Invitrogen) following manufacturer instructions and separated in a denaturing 1% agarose gel. After transfer of total RNA onto nitrocellulose membrane viral genome-specific RNAs were detected by hybridization with P 32 -labelled KUNV 39-UTR-specific probe.", "House sparrows (HOSPs) were collected under approved animal care and use protocols and field studies did not involve endangered or protected species. All animal studies presented herein were approved by Institutional Animal Care and Use Committees at the Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (approval number 13-009). All protocols and practices for the handling and manipulation of sparrows were in accordance with the guidelines of the American Veterinary Medical Association (AVMA) for humane treatment of laboratory animals as well as the ''Guidelines to the Use of Wild Birds in Research'' published by the ornithological council 3 rd edition (2010)." ] },{ "paper_id": "96464179873570564cc07be6219abb043caad44a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The disease-free equilibrium (DFE) for this model is x 0 = (0, 0, N, 0). Then,", "The conditional distribution of X i given \u03b8 i = \u03b8 is:", "giving:" ] },{ "paper_id": "965d0f74c85dad6e4119bee49d3026fbb91c80b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pone.0174980.g002", "https://doi.org/10.1371/journal.pone.0174980.g006", "[59] solely identify the entire north-eastern corner to have high AIV suitability, albeit their study focused only on AIV in wild bird hosts.", "EMPRES-i records included information on the locality, and an evaluation of the quality of location coordinates. All records where the precision of coordinates were labelled either administrative region centroids, or unknown were classified as \"unexact\"-only records where the precision of coordinates were specifically assigned \"exact\" were included in our \"exact\" data set." ] },{ "paper_id": "965f06d2f9a87b69f59b1656c979e04eaa5d75be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virology. All swabs and tissues were negative in virus titration for influenza virus.", "Supporting Information S1 Detailed description per virus of histopathologic changes and antigen expression by immunohistochemistry. (DOC)", "Animals were housed and experiments were conducted in strict compliance with European guidelines (EU directive on animal testing 86/609/EEC) and Dutch legislation (Experiments on Animals Act, 1997). The protocol was approved by the independent animal experimentation ethical review committee of the Netherlands Vaccine Institute (permit number 200900201) and was performed under animal biosafety level 3 conditions. Animal welfare was observed on a daily basis, and all animal handling was performed under light anesthesia using a mixture of ketamine and medetomidine to minimize animal suffering. After handling atipamezole was administered to antagonize the effect of medetomidine." ] },{ "paper_id": "96602c07c439a97e001abcd2e9c85fda998d64c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "have intact C-terminal tail (i.e. ending at residue 694) to preserve the capability of de novo-mode synthesis.", "Single crystal X-ray diffraction data were collected at the Shanghai Synchrotron Radiation Facility (SSRF) beamlines BL17U1 (wavelength = 0.9792\u00c5, temperature = 100 K) and BL19U1 (wavelength = 0.9785\u00c5, temperature = 100 K). At least 130-150 \u2022 of data were typically collected in 0.3-0.5 \u2022 oscillation steps. Reflections were integrated, merged and scaled using HKL2000 (Table 1 ) (47). The initial structure solution was obtained using the molecular replacement program PHASER (48) using coordinates derived from BVDV NS5B structures (PDB entries 1S4F and 2CJQ) as the search model (38, 39) . Manual model building and structure refinement were done using Coot and Phenix, respectively (49, 50) . The 3,500 K composite simulated-annealing omit 2F o -F c electron density maps were generated using CNS (51) . Unless otherwise indicated, all polymerase superimpositions were done using the maximum likelihood based structure superpositioning program THESEUS (52) .", "The chemically synthesized 30-mer template strand (T30, Integrated DNA Technologies) was purified by 12% (w/v) polyacrylamide/7 M urea gel electrophoresis, excised from the gels, and electro-eluted by an Elu-Trap device (GE Healthcare). Purified T30 was stored in an RNA annealing buffer (RAB: 50 mM NaCl, 5 mM Tris (pH 7.5), 5 mM MgCl 2 ) at \u221280 \u2022 C after a self annealing process (a 3-min incubation at 95 \u2022 C followed by snap-cooling to minimize intermolecular annealing). For all the in vitro RdRP assays, T30 was annealed with a GG dinucleotide primer bearing a 5 -phosphate (P2, Jena BioSciences) at a 1:1.25 molar ratio via a 3-min incubation at 45 \u2022 C followed by slow-cooling to r.t. in the RAB to yield the T30/P2 construct. Reaction quenching, sample processing, denaturing polyacrylamide gel electrophoresis (PAGE), RNA visualization by Stains-All (Sigma-Aldrich) staining and quantification were as previously described in a JEV RdRP study (53) . All Stains-All based gels were shown in greyscale-mode by converting from the original RGB-mode without any brightness/contrast adjustment.", "Cell lysis, protein purification and protein storage were performed as previously described for the JEV NS5 study (41) , except that Tris (pH 7.0) was used as the buffering agent in the cation exchange chromatography and the final protein samples were stored in a buffer with higher concentration of NaCl (500 mM) and 10% (v/v) glycerol. The molar extinction coefficient for the NS5B constructs were calculated based on protein sequence using the ExPASy ProtParam program (http://www.expasy.ch/tools/ protparam.html). The yield is typically about 15 mg of pure protein per liter of bacterial culture." ] },{ "paper_id": "96759aa0dce56dd50709ab124ae0255e0cad79d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Primary antibodies used in this study were monoclonal antibodies against dsRNA (English and Scientific Consulting Kft, Szir\u00e1k, Hungary), TGN46 (Sigma) and PDI (Enzo, Farmingdale, NY, USA), and polyclonal antisera against GIANTIN (Abcam, Cambridge, UK) and GM130 (Abcam). Secondary antibodies were Alexa488-or Alexa568-conjugated goat anti-rabbit or anti-mouse antibodies (Life Technologies, Waltham, MA, USA).", "Cells were fixed with Karnovsky (2% para-formaldehyde (PFA), 2.5% glutaraldehyde (GA) in 0.1 M sodium cacodylate pH 7.4) for 140 min at room temperature and then post-fixed with 1% OsO 4 , 1% KCNFe in 0.1 M sodium cacodylate buffer (pH 7.4) for 1 h on ice. Samples were subsequently dehydrated stepwise with increasing concentrations of ethanol before rinsing them with 1,2-propylene oxide (Merck, Darmstadt, Germany) at room temperature and embedding them in Epon resin [41] . After resin polymerization for 4 days at 60 \u2022 C, 65-70 nm sections were cut using an UC7 ultra-microtome (Leica Microsystems) and contrasted with uranyl acetate and lead citrate [41] , before being analyzed in a CM100bio TEM (FEI, Eindhoven, The Netherlands).", "Supplementary Materials: The following are available online at www.mdpi.com/1999-4915/9/9/251/s1." ] },{ "paper_id": "96775ec12c4441b3acb9b9743a9827cc381471cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "i, ii. Nosocomial transmission [6, 31] i. Likely association with AGMPs [6] ii. Causes human respiratory disease. Viral antigen in human lung [32] Coronaviridae i. MERS-CoV ii. SARS-CoV ii. Laboratory and health-care workers infected by inhaling aerosols [23] i, ii. Known human-to-human aerosol transmission Upper respiratory:", "The ambiguity of which procedures and viruses require additional protective measures during AGMPs may lead to breaches in protocol. During many of the cited nosocomial transmission events, HCWs did not use proper eye or respiratory protection. Even when aware of the need for respiratory protection, HCWs may mistakenly wear surgical masks or unfitted N95 respirators, which do not provide proper protection. Additionally, HCWs may not have access to approprtiate PPE depending on the health-care environment. Therefore, while determining the risks of certain viruses and procedures is essential, communicating their respective precautions and providing resources is equally important. Likewise, proper patient triage and diagnosis are the first steps to ensuring that precautions are undertaken when performing AGMPs.", "While on-site sampling works for current nosocomial transmission events, we can design experiments to gain prospective knowledge. Procedures such as bronchoscopy and intubation are performed on animal models of the high-risk viral diseases we identified, and air sampling during these procedures could determine whether they are aerosol-generating. Experimentally generating virus-laden aerosols of different sizes and under different environmental conditions could also help determine the risks of different viruses based on their stability in aerosols [57, 58] . Researchers could then create risk models for different viruses based on aersol stability, as well as data on the quantity, concentration, travel distance, and size of aerosols formed during AGMPs." ] },{ "paper_id": "96782ada9704aca0076d39f6e2592c521d8a5383", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sensing of pathogen-associated DNA in the cytoplasm to trigger host defense is of major interest since several DNA pathogens represent serious threats for aquaculture development.", "The multiple alignments of STING sequences were generated using the software alignX from VectorNTI Advance 11 (Invitrogen) and the TM predictions using the TMpred server (http:// www.ch.embnet.org/software/TMPRED_form.html).", "(TIF) " ] },{ "paper_id": "9680a6922144725138edc920dbf6c3dc48e822b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Design PCR primers to amplify specific virus sequence(s) based on the data within ViPR", "Following import into ViPR, these public data are further processed to produce novel derived data through the use of various automated bioinformatics and comparative genomics algorithms implemented by ViPR and run behind the scenes, as well as information from manual curation. Such pre-calculated data includes: molecular weight, isoelectric point, and Pfam and other domains/motifs determined using InterProScan [23] for all proteins; predicted CD8+ T-cell epitopes using the NetCTL algorithm [24] ; nearest BLASTp hits; predicted ortholog groups using OrthoMCL [25] ; and all linked PubMed references (Table 1) .", "The World Health Organization (WHO) became involved in responding to this outbreak by using modern communications technologies to establish a worldwide Collaborative Multi-Centre Research Project on Severe Acute Respiratory Syndrome (SARS) Diagnosis tasked with identifying the etiological agent of the outbreak. Multiple labs worked concurrently to determine the sequence of this new pathogen [10] , investigate the structure of virions by electron microscopy [11] , and generate other data that contributed to the correct identification of the causative agent [12] . Meanwhile, public health specialists implemented control measures and mitigation procedures to prevent the spread of the disease [13] ." ] },{ "paper_id": "9683ced158e728a9be859ddbeaf2930584e4dea8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Evaluating the performance and discriminatory ability of the filovirus IgG indirect ELISA system.", "www.nature.com/scientificreports www.nature.com/scientificreports/", "Unlike the spillover events leading to marburgvirus disease, those for ebolavirus disease have been difficult to associate with a specific environment, such as caves. Furthermore, the evidence linking ebolavirus spillover to a particular species of bat is largely circumstantial. For example, the 1976 and 1979 index cases of Sudan virus disease both worked in a cotton factory in Sudan, where a retrospective investigation eight to nine months after the initial outbreak identified a large roof colony of Trevor's free-tailed bats (Mops trevori) directly over the working area of the index case 19 . The putative index case of the 2007 Ebola virus disease outbreak in the Kasa\u00ef-Occidental province of the DRC was said to have purchased bats for consumption following a reported annual migration of hammer-headed bats (Hypsignathus monstrosus) and Franquet's epauletted fruit bats (Epomops franquetti) 20 . Lastly, the presumed index case of the 2014 Ebola virus disease outbreak that started in Guinea was reported to have played in a tree hollow, where DNA traces of Mops condylurus were later identified 21 ." ] },{ "paper_id": "9685fb039a5be9e5466be1ee3b0f38a5dd7cc217", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Canadian Society for Virology (CSV) was founded in 2016 to provide support for the Canadian virology research community, including basic, clinical, government, and industry researchers working on a broad range of viruses. To launch the new society, CSV planned a satellite workshop in conjunction with the annual American Society for Virology (ASV) meeting in Blacksburg, Virginia in June 2016, which was supported by then-ASV president and ex-pat Canadian Dr. Grant McFadden [1] . ", "Fecal microbiota transplants (FMTs) are increasingly used to treat human intestinal diseases including ulcerative colitis [26] and antibiotic-resistant Clostridium difficile infections [27] . However, documenting successful transplant of gut microbiota in FMT recipients remains challenging. FMT inevitably transfer bacteriophages as well [28] , but little is known about how transferred phage affect the recipient microbiome. Dr. Alexander Hynes (McMaster University) described studies designed to address this directly by studying crAssphage, the most abundant phage in humans. crAssphage was recently discovered by metagenomic sequencing [29] but its natural bacterial host had not yet been identified. Using PCR and metagenomic analysis, Dr. Hynes's group tracked crAssphage transfer from phage-positive human donors to human FMT recipients or germ-free mice. Studying the bacteria transferred along with the crAssphage into na\u00efve recipients may provide opportunities to discover the elusive crAssphage host.", "Viruses 2019, 11, x FOR PEER REVIEW 11 of 17 required for polyprotein processing. N-terminal sequencing by Edman degradation method enabled precise mapping of two protease cleavage sites with the consensus sequence P\u2193xFP. Together, these findings suggest that SMoV polyprotein processing requires two viral proteases, the 3C-like cysteine protease encoded by RNA1, and a novel protease encoded by RNA2 that features two putative glutamic acid residues in the catalytic site. The novel protease domain is only found in the RNA2 polyproteins of two other definite or putative members of the family Secoviridae, suggesting that it was recently acquired." ] },{ "paper_id": "968aa40cb4dd0cab313ecc59ff2f85800cbc1b8b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sensitised 2h 6h 12h", "NM_002984.1 CCL4 Chemokine (C-C motif) ligand 4 3.5 4.7 1.6 -3.0 NM_001511.1 CXCL1 Chemokine (C-X-C motif) ligand 1 2.3 2.5 1.1 -2.9 NM_006273.2 CCL7 Chemokine (C-C motif) ligand 7 2.1 3.6 5.3 2.2 NM_002090.1 CXCL3 Chemokine (C-X-C motif) ligand 3 1.6 2.5 1.6 -1.8 NM_002985.1 CCL5 Chemokine (C-C motif) ligand 5 1.6 1.8 2.1 1.8 AF015524 CCRL2 Chemokine (C-C motif) receptor-", "B the nuclear factor of activated T cells, NFATC1 (Table. 1f )." ] },{ "paper_id": "968b32a7e4c4d6ec64f01fab3e247e4114a32490", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by the Natural Science Foundation of China (A0201200499) and the Agricultural Science and Technology Innovation Program (ASTIP) of Chinese Academy of Agricultural Sciences.", "Histone acetyltransferase inhibitor Garcinol (GAR), SIRT1 activator Resveratrol (RES), SIRT1 inhibitor Nicotinamide (NIC) and NF-\u03baB inhibitor BAY 11-7082 (BAY) were obtained from Santa Cruz (Santa Cruz, CA). Antibodies against HMGB1 and \u03b2-actin were purchased from Cell Signaling Technology (Danvers, MA). Antiacetyl lysine antibody (clone Kac-01) was purchased from PTM Biolab (Hangzhou, China). siRNAs were purchased from biotend (Shanghai, China). The bovine serum albumin (BSA) was purchased from Dingguo (Nanjing, China).", "There is no conflict of interest", "The acetylation of key lysine residues in HMGB1 is important for its migration and secretion [38, 39] . The proteins in sirtuin family (SIRT1-SIRT7) are class III histone deacetylases (HDACs) that utilize NAD+ as the cofactor [36] . SIRT1 is expressed in most cells, which specifically deacetylates the histone or nonhistone proteins. HMGB1 has been reported as one of the deacetylation targets of SIRT1 [37] ." ] },{ "paper_id": "968d0b07b0b65a15cedfd2357e3ba9649742836e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All procedures followed were in accordance with the ethical standards of the Helsinki Declaration of 1975, as revised in 2000. The Regional Ethical Review Board in Lund, Sweden advised us that signed consent from the patient's parents was sufficient for publication of this case and the consent was obtained." ] },{ "paper_id": "9692bb55e1e2eec083333ee2139137e6ddf3a4d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral infections pose a significant global health burden, especially in the developing world where most infectious disease deaths occur in children and are commonly due to preventable or treatable agents. Effective diagnostic and surveillance tools are crucial for reducing disability-adjusted-life-years (DALYs) due to infectious agents and for bolstering elimination and treatment programs [1] . Previously unrecognized and novel pathogens continually emerge due to globalization, climate change, and environmental encroachment, and pose important diagnostic challenges [2, 3] .", "For microarray hybridization, a fraction of each library was amplified by PCR as above but with a modified dNTP mixture including 5-(3-aminoallyl)-dUTP (Ambion) in lieu of 75% of the dTTP normally in the mixture. The resulting amino-allylcontaining DNA was purified using a DNA Clean and Concentrator-5 column (Zymo Research). The eluate was heat", "(c)", "These two samples were prepared from aliquots of the same serum sample." ] },{ "paper_id": "9693080ead2c95fe79e8bf077637b5585cac664f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A panel of 27 cultured enterovirus (HEV) prototype strains was purchased from Center for Disease Control and Prevention (CDC, Atlanta, GA). The prototype strains of 34 rhinoviruses (HRV) and HEV69 with known titers were purchased from the American Type Culture Collection (ATCC, Manassas, VA). Total nucleic acids were extracted from 125 \u03bcl cultured samples by using the Mas-terPure\u2122 DNA purification kit (Epicentre Technologies, Madison, WI) and dissolved in 20 \u03bcl of nuclease-free water." ] },{ "paper_id": "9697849eeaed7f72a196d9ca4d4d8cfad6a8031e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Surface plasmon resonance measurements were performed using a BIAcore 3000 instrument with CM5 chips (GE Healthcare) at room temperature (25\u00b0C). All proteins were exchanged into PBST buffer (phosphate-buffered saline with 0.005% (v/v) Tween-20, pH 7.4) by gel filtration. The purified mAb was first immobilized on a CM5 chip. The HA1 proteins were serially diluted to between 0.078 and 2.5 nM (0.078, 0.156, 0.3125, 0.625, 1.25, and 2.5 nM) and were then flowed over the mAb. The binding kinetics were analyzed with BIAcore 3000 analysis software (BIAevaluation Version 4.1) using a 1:1 Langmuir binding model.", "The binding of HNIgGA6 to viral HA1 proteins was measured by enzyme linked immunosorbent assay (ELISA). The 96-well plates were coated overnight at 4\u00b0C with viral HA1 protein (50 ng per well). Serial four-fold dilutions of antibodies (beginning with 100 ng) in PBS were made and assayed for binding to recombinant HA1 proteins. After washing, bound antibodies were detected by horseradish peroxidase (HRP)-conjugated goat antihuman IgG Ab (Sigma-Aldrich) at a 405 nm absorbance using an ELISA plate reader (Tecan).", "A total of 65 influenza A H7N9 strains isolated during the 2013-2017 seasons throughout China were selected and genetically characterized. The retrieved full-length HA amino acid sequences of influenza A H7N9 viruses were aligned with the reference sequences available in the GISAID database (http://platform.gisaid.org/) by \"Clus-talW\" using Molecular Evolutionary Genetic Analysis (MEGA) version 7. Multiple alignment sites with gaps in any of the sequences were excluded. Phylogenetic trees were generated by the maximum-likelihood method in MEGA7 with 1000 bootstrap replicates. The constructed phylogenetic trees were analyzed for possible geographical linkages.", "Genetically and antigenically novel H7N9 influenza viral strains will continue to emerge due to the genetic nature and broad host range of this virus. In the absence of an effective vaccine, direct administration of H7N9neutralizing antibodies could be used as an intervention to prevent H7N9 infections in humans. This approach could be especially helpful for those at high risk for contracting H7N9. When administered prophylactically, HNIgGA6 conferred 100% protection in virus-infected mice 22 , supporting this rationale. Alternatively, the RBS-directed neutralizing antibody HNIgGA6 can be used together with other antiviral drugs (e.g., oseltamivir and zanamivir) to control the production of the escape mutants that limit the effectiveness of these NA inhibitors 10, 11 ." ] },{ "paper_id": "969c9813397caecc9597daa9679e1bff3bc42635", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the T2A-containing constructs, the Thosea asigna virus (accession: AF062037) 2A sequence (Figure 2A ) was inserted in frame and preceding the FLuc gene by using an overlapping PCR strategy as described previously [31] .", "Unless indicated, cells were harvested 6 hour after transfection by centrifugation at 9600 g for 1 minute, followed by wash with 1 ml of PBS. The cells pellets were then resuspended in 40 ml of Passive Lysis Buffer (Promega) and stored at -20uC. The concentration of protein in each lysate was determined by Bradford assay.", "Capped reporter RNAs were obtained by in vitro transcription in the presence of cap analog [m 7 G(59)ppp(59)G] (Ambion) to GTP at a 5:1 ratio as previously described [31] . RNAs were purified by RNeasy (Qiagen), their integrity confirmed by denaturing agarose gel analysis, and RNA concentration determined using a Nanodrop ND-1000 spectrophotometer." ] },{ "paper_id": "96a1e9e95b2ab796897177f18a1d3e148b83e57e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A comparative sequence analysis to revise the current taxonomy of the family Coronaviridae.", "Statistical analysis was performed with either Student's t -test or one-way ANOVA with a Bonferroni post hoc test with software provided by GraphPad Prism version 5. Data were presented as means \u00b1 S.E.M. P values of <0.05 were considered statistically significant. " ] },{ "paper_id": "96a20376534b0725c4cbd316e15d003d2183436b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Detection of an unknown virus requires specialized techniques. Nowadays, next generation sequencing platforms combined with viral purification and library preparations provide and excellent method to identify viruses of which the genome composition is unknown. The VIDISCA method (Virus discovery cDNA-AFLP) is one of the library preparation methods which has been successfully used to identify several novel viruses [3] [4] [5] [6] [7] . Our aim was to detect a possible viral pathogen using this approach.", "The Kaplan Meier survival curve of fish vaccinated with placebo was significantly different from those of the vaccinated fish (p<0.001, Tarone-Ware test), thus all three vaccines provide protection against death caused by SDDV infection. The recMCP had the highest relative protection percentage (91%), which may suggest that this vaccine provides a better protection than inactivated virus, however statistical tests showed that the difference between the protection by recMCP and the inactivated virus vaccines was not significant. The commercial MSD vaccine Aquavac IridoV against red seabream iridovirus (RSIV) showed no cross protection against SDDV (47% survival in placebo-vaccinated and 47% survival in Aquavac IridoV-vaccinated fish).", "Asian seabass or Lates calcarifer is a large, valuable fish kept in maricultures. Scale drop syndrome is an emerging disease in this species that currently results in significant economic losses for affected farms. Mortality rates can become as high as 50%, both in PLOS Pathogens |", "An efficacious protection against SDDV would be very beneficial for the industry. Formalin-inactivated and BEI-inactivated SDDV whole virus vaccines established in this study show promising protection, although these vaccines have to be further developed. Previous studies on RSIV have shown that inactivated whole virus vaccines offer good protection against disease [17, 18] . An efficacious commercial formalin-inactivated vaccine against RSIV is available from MSD (Aquavac IridoV, an oil-adjuvanted vaccine). We tested if the Aquavac IridoV vaccine provides cross-protection against SDDV, but such cross-protection could not be shown. Most likely, SDDV and RSIV do not have sufficient antigenic epitopes in common, which is not unexpected based on the fact that the genetic differences and biological mechanisms of replication differ considerably between the viruses. The RSIV vaccine from Biken [19] , which is a formalin-inactivated RSIV culture supernatant of GF cells, was not tested.", "Kaplan Meier survival curves were constructed using SPSS v22 (IBM). Analysis of the similarity of the curves was performed using the Tarone-Ware test." ] },{ "paper_id": "96a89e5c0df1a32d5e2864966057fab04d2e3a23", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mice C57BL/6 (wild-type (WT)) mice and IFNAR \u2212/\u2212 mice on C57BL/6 background were bred at Ume\u00e5 Transgene Facility.", "Data from quantitative reverse transcription PCR (qPCR), bioassay, focus forming assays, and viral spread assays were analyzed with unpaired t test using GraphPad Prism software. Statistical analyses of RNASeq data were performed by GATC Biotech using Cufflinks [55, 56] .", "Additional file 1: Supplemental Table S1, Table S2, Table S3, and Table S4 " ] },{ "paper_id": "96ae683c7f824b0810ce750d60c15181b93181a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results were expressed as means \u00b1 standard deviations. The data were statistically analyzed using the SPSS statistical software, version 17.0 (SPSS Inc, Chicago, Illinois, USA). Differences between means were determined by analysis of variance (ANOVA) with Duncan's test on the level of significance declared at P < 0.05.", "Establishment of I. tinctoria hairy roots", "doi:10.1371/journal.pone.0119022.g007" ] },{ "paper_id": "96b070fe442137ec80f7736790ad13105c549dfd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Probability density (scaled)" ] },{ "paper_id": "96ba8069882d695675b9e2e6d32c3640910735b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We defined the distance (D n ) using n-tuples between two sequences, S 1 and S 2 , as", "Each subject was genotyped for three polymorphisms (rs1801252, rs1042713 and rs1042714), and genomic DNA was isolated using the PUREGENE DNA purification system (Gentra Systems, Minneapolis, MN, USA). The genotypes of rs1042713 were determined using polymerase chain reaction and restriction fragment length polymorphism analysis. Briefly, primers and probes were designed with SpectroDESIGNER software (Sequenom, San Diego, CA, USA). PCR was then performed, and unincorporated double-stranded nucleotide triphosphate bases (dNTPs) were dephosphorylated with shrimp alkaline phosphatase (Hoffman-LaRoche, Basel, Switzerland) followed by primer extension. The purified primer extension reaction product was spotted on to a 384-element silicon chip (SpectroCHIP, Sequenom) and analyzed in a Bruker Biflex III MALDI-TOF Spectro-READER mass spectrometer (Sequenom). The resulting spectra were then processed with SpectroTYPER (Sequenom). All samples were genotyped for eight unrelated SNPs for DNA quality examination. The samples were diluted onto 96-well plates, and only the plates on which each of the eight unrelated SNPs had a successful genotyping rate greater than 95% were used for further study. All experiments were performed by investigators who were blind to phenotype. Failure in genotyping for rs1801252 polymorphism was noted in 6 cases." ] },{ "paper_id": "96c886c9234855e0fb6ef46ea3c5b7c1c7abc652", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where q i is the partial charge of each atom and r COM is the position of the center of mass of the protein.", "Two kinds of molecular surfaces, such as electrostatic potential map and lipophilicity map, of the complex structure snapshotted at the initial and final simulation times were generated under MOE software package platform to study the ligand-receptor interaction.", "The root-mean-square deviation (RMSD) of the backbone and the root-mean-square fluctuation (RMSF) of C a atoms were calculated. Orientation angle of the ligand binding to the receptor was also measured to identify the orientation changes during the MD simulations. Distances between the charged groups of acidic and basic residues forming ionic interactions were measured to represent electrostatics." ] },{ "paper_id": "96c9c57127b558f145ddd7d2566a427f7d12592e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Approximately 48-h post-transfection, HeLa cells were lysed in radioimmunoprecipitation assay (RIPA) buffer (10 mM Tris-HCl, pH 7.5, 150 mM NaCl, 1 mM EDTA, 0.1% SDS, 1% Triton X-100, 1% sodium deoxycholate).", "The media was clarified using a 0.45 \u03bcm filter. Virions were pelleted through a 20% sucrose cushion in phosphate-buffered saline (PBS) solution for 2 h at 20,000\u00d7g. The pellet was resuspended in 2\u00d7 loading buffer (60 mM Tris-HCl (pH 6.8), 10% \u03b2-mercaptoethanol, 10% glycerol, 2% sodium dodecyl sulfate (SDS), 0.1% bromophenol blue). Cell lysates and virions were resolved by SDS-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane. The primary antibodies used were specific to HIV-1 p24 Gag [66] , Hsp90 (sc7947: Santa Cruz Biotechnology), phosphoSTAT1 (612132: BD Transduction), IFIT1 (GTX118713-S: Insight Biotechnology) or \u03b2-actin (ac-15: Sigma). Dylight \u2122 800-conjugated secondary antibodies (5151S and 5257S: Cell Signaling) were used to detect the bound primary antibodies with the Li-CoR infrared imaging (LI-COR UK LTD).", "These nucleotide biases cause the HIV-1 open reading frames to have a codon usage pattern that differs substantially from that of human mRNAs [36] [37] [38] [39] [40] [41] 43] . The genetic code is redundant in that there are 61 codons for 20 amino acids and all of the amino acids except methionine and tryptophan are encoded by at least two codons. The preferred codons in cellular mRNAs are thought to correlate with the availability of the aminoacyl-tRNAs but HIV-1 contains many rare codons [36] [37] [38] [39] [40] [41] ." ] },{ "paper_id": "96cb8642bc772cbc519af39243eec2809cbba57e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza A virus is a major public health problem, causing seasonal epidemics in humans and occasionally lethal global pandemics, as happened in 1918-1919 (H1N1), 1957 (H2N2), 1968 (H3N2), and 2009 (swine-origin H1N1) [98] . Currently, the H5N1 subtype circulating in wild and domestic birds is capable of crossing the species barrier into humans and constitutes huge threats to both animals and public health [99] . As many as 500 million people a year are infected with influenza A virus worldwide, with more than 500,000 deaths [100] . Characterized by its high potential for mutations and adaptations, influenza virus presents a significant challenge to disease control and the pharmaceutical industry [101] .", "Compared with other etiological agents, the genome of viruses encodes fewer proteins. Consequently, numerous host factors are harnessed by viruses to complete their life cycles, among which some are pro-viral host factors while others are anti-viral host factors. Viral DNA/RNA replication may be the prime target for the development of efficient and safe novel vaccines or anti-viral therapeutics [62] [63] [64] .", "Porcine reproductive and respiratory syndrome virus (PRRSV), the causative agent of one of the most economically important global swine diseases, is classified in the genus Arterivirus of the family Arteriviridae [93] . PRRSV contains a single-strand, positive-sense RNA of approximately 15 kb in length, composed of at least 10 open reading frames (ORFs), and a poly-A tail at the 3 -terminus [94] . ORF1a and ORF1b encode the replication-related polymerase proteins and are processed into at least 13 nonstructural proteins (nsps) by self-cleavage [95] ." ] },{ "paper_id": "96cd80ad6f658fdc8b0d5e8ce4e1eb1f1daa87f5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We recommend that future policies can be managed through public-private consensus building and investor sensitization than panic announcements.", "where r it and r mt are the excess returns on asset i and the market at time t, respectively, \u03b2 imt is the systematic risk measure, and E t (\u22c5) is conditional expectation at time t. In equilibrium, only \u03b2 is needed to price an asset i.", "where E c (\u22c5) represents the cross-sectional expectation." ] },{ "paper_id": "96e0e866617d780ddfa44b216491a00a049afd90", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "96e35195482d8911571c2242d612a317c7808caf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Signal peptides were predicted using the SignalP program [54] , version 4.1, with all three training models tested.", "All statistical tests (Chi-squared and nonparametric Mann-Whitney-Wilcoxon tests, and Pearson correlation) were performed using standard methodology." ] },{ "paper_id": "96ec828983678df332879221419bed8196b6b85f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics statement. Ethical approval was granted by the Liverpool East NHS Research Committee (14-NW-1460) and all participants gave written informed consent.", "Reporting summary. Further information on research design is available in the Nature Research Reporting Summary linked to this article.", "16S-rRNA sequencing data from this study are available from NCBI under BioProject accession number PRJNA421976. All other data are available in the manuscript (and its Supplementary Information files) or from the corresponding author upon reasonable request." ] },{ "paper_id": "96f0cf86f03bfe173c1b161ae5936757fb6a9b0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "diagnostic, influenza A (H7N9), PCR, sensitivity, specificity", "In vitro transcribed RNA (IVT RNA) was generated from a plasmid con- ", "Briefly, the lyophilized reagent was reconstituted with 50 \u03bcL Premix Buffer B and mixed with 5 \u03bcL nucleic acid extract.", "Subsequently, 50 \u03bcL of the final mixture was transferred to an R-tube " ] },{ "paper_id": "96f1b9981028f5954b8f93c8dec9a69c236c124d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "96f74d611693ebad68d8cd10862e9a972bd3bdc5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "M iddle East respiratory syndrome coronavirus (MERS-CoV) has emerged as a highly fatal cause of severe acute respiratory infection. Since April 2012, 1,348 cases and 479 deaths in over twenty-five countries have been attributed to this novel beta-coronavirus 1, 2 . As human-to-human transmission of the virus is not sustained, a large zoonotic reservoir may serve as a principal source for transmission events [3] [4] [5] [6] . The high case fatality rate, vaguely defined epidemiology, and absence of prophylactic or therapeutic measures against this novel virus have created an urgent need for an effective vaccine should the outbreak expand to pandemic proportions.", "RBD England1 crystals were obtained using a reservoir solution of 0.1 M Tris-HCl pH 8.5, 10% 2-methyl-2,4-pentanediol (MPD) and 29% polyethylene glycol (PEG) 1,500. Crystal form 1 of the D12 Fab:RBD England1 complex was grown in 0.1 M sodium acetate pH 5.5, 50 mM sodium chloride, 10% PEG 400 and 11% PEG 8,000. Both crystals were cryo-cooled in liquid nitrogen using mother liquor containing 20-22% ethylene glycol as a cryoprotectant. Crystal form 2 of D12 Fab:RBD England1 was grown in 0.1 M sodium Cacodylate pH 6.5, 80 mM magnesium acetate, 14.5% PEG 8,000 using 15% 2R-3R butanediol as a cryoprotectant.", "Pseudovirus neutralization assay. Huh7.5 cells (10,000 cells per well) were plated into 96-well white/black Isoplates (PerkinElmer) the day before infection. Serum serial dilutions were mixed with different strains of titrated pseudovirus, incubated for 30 min (min) at room temperature and added to Huh7.5 cells in triplicate. Following 2 h of incubation, wells were replenished with 100 ml of fresh media. Cells were lysed 72 h later and luciferase activity was measured. IC 90 neutralization titres were calculated for each individual mouse serum sample." ] },{ "paper_id": "96fc4a051f2ecc366f49ca34902324d059577798", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.pone.0197418.g005 ", "Author Contributions" ] },{ "paper_id": "96feece020f44e5c14a7c30ef9de6c5086299eb1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA was extracted from 20 mg of tissue with a NucleoSpin RNA II kit (Macherey-Nagel) using methods previously described [23] . Total RNA was extracted from 100 \u00b5L body cavity fluid or 10 mg of faeces or faecal swab using either the NucleoSpin RNA II kit or using an automated platform Chemagic 360 instrument (Perkin-Elmer) in combination with Chemagic body fluids NA kit (Perkin-Elmer) eluted in 100 \u00b5L elution buffer.", "Abbreviations bp: base pair; CCoV: canine coronavirus; CNS: central nervous system; CSF: cerebrospinal fluid; FCoV: feline coronavirus; FIP: feline infectious peritonitis; IHC: immunohistochemistry; RT-qPCR: reverse transcriptase quantitative polymerase chain reaction; S protein: spike protein.", "Pyrosequencing was performed as previously described [20] using either PyroMark Q24 (Qiagen) or Pyromark Q96 (Qiagen) platforms. The dispensation order of the nucleotides was defined as; CGCTCATG for nucleotide position 23531 and CGACTGC for nucleotide position 23537.", "See Figure 1 for the diagnostic pathway used in this study for sample selection.", "Reverse transcription was performed using a MJ Mini Gradient Thermal Cycler and ImProm II Reverse Transcriptase (Promega). Ten microlitre of total RNA were combined with ImProm II 5 \u00d7 Reaction Buffer, 3 mM MgCl 2 , dNTPs (0.5 mM each), random hexamers (25 ng/ \u03bcL) and ImProm II reverse transcriptase in a total volume of 20 \u03bcL. The following thermal profile was used; 20 \u00b0C for 5 min, 42 \u00b0C for 30 min, 70 \u00b0C for 15 min and 10 \u00b0C hold. The resulting 20 \u03bcL of cDNA was added to 30 \u03bcL of RNase-free water and stored at \u221220 \u00b0C. Randomly selected samples were checked for inhibition of the RT reaction using an RNA internal amplification control. No inhibition was detected (results not shown)." ] },{ "paper_id": "970253c7b4ba9e8d8e33f39cd13a21b2b1ae2c35", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9702e48b8bce2e6a2e17f0252dbf5c1b0958b9f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using SPSS version 19.0 (SPSS Inc., Chicago, IL, USA). The data are expressed as median and IQR (Inter Quantile range). Statistical comparisons were made using Kruskal Wallis test and Mann-Whitney U test, Significance Probability (P value) of < 0.05 was considered statistically significant. A Kruskal Wallis test was used to compare concentrations of serum ", "No significant differences were found among groups regarding the concentrations of serum IL-6 and TNF-\u03b1 (Fig. 2b,e)(Fig. 3b,e) ." ] },{ "paper_id": "97103b4636fa1bf6d381d6bda00d0e5d126b331c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "971794b30f2ec41a9c9708c25873f3cf55129518", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Phylogenetic analyses were performed using MEGA software version 6 [26] . Briefly, sequences in FASTA format were aligned using Clustal W algorithm. Genetic distances were measured with the Kimura-2 parameter model. A phylogenetic tree was constructed with the neighbor-joining algorithm and robustness of the tree was evaluated with 1000 bootstrap resamplings.", "All consensus nucleotide sequences obtained in this study were submitted to GenBank Database under accession numbers KX121135 to KX121163." ] },{ "paper_id": "9718efa7298b28b740938eeca415b1703ec6f689", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Assessment of growth kinetics for ribavirin-resistant mutants in the presence of ribavirin at several concentrations using multi-step growth curve analysis", "Ribavirin (Sigma-Aldrich, St. Louis, MO, USA), 5fluorouracil (Sigma-Aldrich), 5-azacytidine (Sigma-Aldrich), and amiloride (Sigma-Aldrich) were used in this study. All of these mutagens were dissolved in RPMI-1640 medium (Sigma-Aldrich) at stock concentrations of 15 mM (ribavirin) and 20 mM (5-fluorouracil, 5-azacytidine, and amiloride), sterile-filtered using a 0.22-\u03bcm syringe filter, aliquoted, and stored at \u221220\u00b0C until use.", "The effects of the four mutagens on PRRSV replication were analyzed by repeated measures analysis of variance (ANOVA). The Wilcoxon signed-rank test was used to compare the mutation rates of the ribavirin-resistant mutants with that of their parental virus strain. Nucleotide sequences were aligned and analyzed using Laser-gene\u00ae MagAlign software (DNASTAR Inc., Madison, WI, USA)." ] },{ "paper_id": "9721af1b88d60abbff468d841941f85a13731861", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Age, gender, presence of current exacerbation of disease, height, weight and body mass index were recorded.", "The significance of aerosol-positive sputum-negative results for isolation in low numbers of S maltophila (n = 2) and A xyloxidans (n = 1) is uncertain, but it is possible that separating respiratory particles by size negates the obscuring of individual colony morphotypes by other flora which may occur with direct sputum culture.", "Subjects were instructed to cough into the CASS as frequently and as strongly as was comfortable for 5 min. At the onset of coughing the timer (set for 5 min) controlling the power to the vacuum pump was started. Cough strength was assessed as strong, moderate or weak and cough frequency was assessed quantitatively." ] },{ "paper_id": "97229e8af52b75aa9ac0f0eb530bf89f7f5ec134", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Treating with CypA did not enhance the binding of EV71 virions to functional receptors", "TRIzol reagent and a Super Script III First-strand Synthesis System for RT-PCR kit were purchased from Invitrogen. A MEGA script T7 High Yield Transcription kit was purchased from Ambion. A QuantiTect SYBR Green RT-PCR kit was purchased from Qiagen. A cell viability and proliferation assay (WST-1) was purchased from Roche.", "Binding assays of viruses with HS, PSGL-1 or SCARB2", "Cyclophilins (Cyps) are key cellular factors that function in numerous cellular processes, including transcriptional regulation, immune response, protein secretion, and mitochondrial function [1] . Cyps possess peptidyl-prolyl cis-trans isomerase activity and have high affinity for the immunosuppressant cyclosporine A (CsA). Cyclophilin A (CypA) is a key member of the Cyp family and was first shown to mediate the immunosuppressive function of CsA through the formation of a CsA-CypA complex. This complex binds to and inhibits the function of the phosphatase calcineurin, which normally functions to dephosphorylate NF-AT, a transcription factor important for T cell activation [1] ." ] },{ "paper_id": "9728dc7174668523338b32a9608f43a91e8b797d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA was extracted employing an EasyPure Viral DNA/RNA kit (Transgen, Beijing, China) according to the manufacturer's protocol and was stored immediately at \u221280 \u00b0C until use.", "A novel duck reovirus (NDRV) disease, called \"spleen necrosis disease, \" \"new liver disease in Muscovy ducks\" or \"duck hemorrhagic-necrotic hepatitis, \" was recently found among several duckling species, including shelducks, Pekins, wild mallards and Muscovy in China 1 . Similarly, avian reovirus (ARV) infection was recorded in Muscovy ducks (Cairina moschata) in south western Poland during the summer 2012 2 . NDRV is a member of the genus Orthoreovirus in the family Reoviridae 3 .", "Ethics statement. This study was approved by the Animal Ethics Committee of the College of life science and engineering, Foshan University, Guangdong, China. The College did not issue a number or ID to this animal study, because the studied ducks are not an endangered or protected species. Specimen collection was carried out based upon the protocol issued by the Animal Ethics Committee of the College of life science and engineering. Furthermore, all methods were performed in accordance with the relevant guidelines and regulations." ] },{ "paper_id": "9736b5e6c933555a1afd1a78ec449757476278a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Participants were given a choice of test site: either right away in a quiet classroom in a local school, at a 3 min walk, or later at their private homes. Seventy-eight per cent chose to be tested at the school.", "Lonzozou Kpanake et al.", "The patterns of data that correspond to four of the five clusters are shown in Figure 1 , and the distribution of participants in each cluster is shown in Table 1 . Mean ratings for each scenario, overall and for each cluster, are available from the corresponding author." ] },{ "paper_id": "9740b9f6f49dc554d7be515871bd31123bda5473", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Published: xx xx xxxx OPEN www.nature.com/scientificreports/", "In this study, we found a natural yellow material by extracting Phellodendron chinense Schneid. This yellow-emission phosphor is believed to replace rare earth ion-doped phosphors and reduce their usage in LED applications. Phellodendron phosphor could be pumped by near-UV light or blue light because of its nature of wide absorption band. We construct a series of LED package data by using YAG, CaAlSiN 3 :Eu 2+ and Phellodendron phosphor for comparison. The proposed approaches may be alternative combination for LED applications in the future." ] },{ "paper_id": "974446ae540829dc1b4c7ce8ea1b8dd3843fb3dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CV Sensitivity CV Specificity CV Class Error For species discrimination, three categories were incorporated to cross-validate the model: either category 1: growth medium control (GMC); category 2:", "The cell wall-less prokaryote Mycoplasma pneumoniae is a major cause of respiratory disease in humans, accounting for 20% to 40% of all community acquired pneumonia (CAP). M. pneumoniae is the leading cause of CAP in older children and young adults, while the incidence of infection in the very young and the elderly is on the rise [1] [2] [3] [4] [5] . For adults alone the annual economic burden of CAP is > $17 billion [6] . Macrolide resistance is a growing concern, particularly in children [5] , and extra-pulmonary sequelae occur in up to 25% of infections. Finally, evidence continues to indicate a contributing role for M. pneumoniae infection in the onset, exacerbation, and recurrence of asthma [5] .", "NA-SERS substrates were prepared by OAD as described [21, 29, 36, 37] . Prior to their use, substrates were cleaned for 5 min in an Ar+ plasma using a plasma cleaner (Model PDC-32G, Harrick Plasma, Ithaca, NY) to remove any surface contamination [38] and then patterned into 40 3mm diameter PDMS-formed wells. 1,2-bis(4-pyridyl)ethylene (BPE; 10 -4 Molar in methanol) was used as an external control to ensure consistency between substrates. Raman spectra were acquired using a Renishaw inVia Reflex multi-wavelength confocal imaging microscope (Hoffman Estates, IL). A Leicha apochromatic 5\u00d7 objective (NA 0.12) illuminated a 1265 \u03bcm 2 area on the substrate, which allows spatial averaging and minimizes the effect of potential random hot spots. A 785-nm near-infrared diode laser (Renishaw) operating at 10% power capacity (28 mW) provided the incoming radiation, and spectra were collected in 3 10-sec acquisitions. An internal silicon standard measurement was obtained at the beginning of each SERS analysis as an internal control for instrument performance." ] },{ "paper_id": "97472ef04ad420815a0fa19076162835fad47af4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quantitative data from at least three independent experiments are expressed as means \u00b1 standard deviation (SD). Student's t-tests were used to compare the differences between groups. Survival curves were obtained using the Kaplan-Meier analysis. P < 0.05 is considered statistically significant.", "Cells were seeded in a 24 well ultra low-attachment plate (Corning) at a density of 1,000 cells per well and grown in serum-free DMEM, supplemented with 2% B27 (Invitrogen), 20 ng/mL EGF, and 20 ng/mL bFGF (Invitrogen). After cultivation for 14 d, primary spheres were harvested using centrifugation, dissociated with trypsin, and re-suspended in this medium. The secondary spheres (> 70 \u03bcm) were photographed and quantified after 10 d.", "Telomerase activity was measured using the telomerase repeat amplification (TRAP) assay. Cells were homogenized in a TRAP lysis buffer. Protein (20 \u03bcg) was used in the telomerase reaction, along with 50 \u03bcL of a TRAP reaction buffer containing 20 mM Tris-HCl (pH 8.3), 1.5 mM MgCl 2 , 63 mM KCl, 0.05% Tween-20, 1 mM EGTA, 50 \u03bcM deoxynucleotide triphosphate (Pharmacia), 0.1 \u03bcg each of labeled TS, ACX, and U2 primers, 5 \u00d7 10 -3 attomoles of an internal control primer (TSU2), 2 units of Taq DNA polymerase (Invitrogen), and 2 \u03bcL of CHAPS extract. After incubating at 3\u00b0C for 30 min, the telomerase-extended products were amplified through PCR under the following conditions: 30 cycles with each cycle comprising incubations at 94\u00b0C for 30 s, 60\u00b0C for 30 s, and 72\u00b0C for 45 s. The reaction mixture was heated to 94\u00b0C for 5 min to inactivate telomerase. Amplified products were resolved on a 12% polyacrylamide gel electrophoresis, stained with ethidium bromide and viewed under UV light." ] },{ "paper_id": "9751ae6c4cdecf8bfb8934f93a9b2aadf3d4737f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After electrophoresis, proteins were electrotransferred onto polyvinylidene fluoride membranes (Millipore, Billerica, MA, USA). The proteins of interest were incubated with primary antibodies for 1 h and then incubated with appropriate secondary antibodies. Proteins were detected by using an enhanced chemiluminescence western blotting detection system (Millipore). Polyclonal antibodies against 3A and a monoclonal antibody against 3C were as described [31, 32] .", "GFW exerts its anti-EV71 effects by inhibiting viral entry without producing cytotoxic side effects and thus provides a potential agent for antiviral chemotherapeutics.", "Viruses must deliver their genome into the host cells to initiate replication. Most of them enter cells by endocytosis during which they hijack cellular machinery for the attachment to receptors and subsequent penetration across the plasma membrane. Several receptors to facilitate EV71 entry have been reported, including scavenger receptor B2, human P-selectin glycoprotein ligand-1 and sialylated glycans [5] [6] [7] . A strategy to disrupt the interaction between viral particles and their receptors would be ideal for antiviral development.", "Data are expressed as the mean \u00b1 standard error of the mean [37] and analyzed using two-tailed Student's t-tests with p < 0.05 taken as significant." ] },{ "paper_id": "9752210c4ae3a172559d5d7b3df9575e26b7359c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data collection was two staged:", "\u2022 the capacity for surveillance, case detection, case management and community control;", "\u2022 the deployment of strategies of prevention, containment, mitigation and recovery;" ] },{ "paper_id": "9756bb3c608ed790d2306fc8db815a694eeca45f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "975a7b5f0f9a7f9a03195cb5cd1a633ecd4e36f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antibodies. The antibody (Ab) against TMEV protein VP1 (mouse monoclonal) has been described previously (21) . Rat monoclonal antitubulin Ab, mouse monoclonal anti-HA Ab, and agarose-conjugated V5 and HA antibodies used for the immunoprecipitation of tagged viral proteins were from Sigma. Mouse monoclonal anti-V5 Ab was from Life Technologies, and IRDye-conjugated secondary antibodies used for immunoblotting were from Li-Cor.", "Finch et al.", "Recombinant viruses and plasmids. QuikChange mutagenesis (Agilent Technologies) was performed on a template containing the fulllength viral insert to create the full-length recombinant TMEV shift site mutant (SS), stop codon mutant (SCM), and StopGo mutant (LVWT). All constructs were verified by sequencing of the complete virus genome." ] },{ "paper_id": "9761b5e2c50841879b9ec0fff753ec88ece36744", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Taxonomically, the family Coronaviridae is classified into two subfamilies, the coronavirinae and the torovirinae. The coronavirinae is further classified into three genera, namely the Alphacoronavirus, Betacoronavirus, and Gammacoronavirus (Masters, 2006) . The classification was originally based on antigenic relationships and later confirmed by sequence comparisons of entire viral genomes (Gorbalenya et al., 2004) . Almost all Alphacoronaviruses and Betacoronaviruses have mammalian hosts, including humans. In contrast, Gammacoronaviruses have mainly been isolated from avian hosts.", "In this review, current studies on the involvement of the UPR in coronavirus infection and pathogenesis will be summarized. The role of UPR activation in host response, in particular the induction of apoptosis, will also be reviewed.", "possible that other viral proteins of SARS-CoV (such as the E protein mentioned below), function as an antagonist of IRE1-XBP1 activation.", "The virions budded into the ERGIC are exported through secretory pathway in smooth-wall vesicles, which ultimately fuse with the plasma membrane and release the mature virus particles (Krijnse-Locker et al., 1994) . For some coronaviruses, a portion of the S protein escapes from viral assembly and is secreted to the plasma membrane. These S proteins cause fusion of the infected cell with neighboring uninfected cells, resulting in the formation of a large, multinucleated cell known as a syncytium, which enables the virus to spread without being released into the extracellular space (Masters, 2006) ." ] },{ "paper_id": "976496c92ea74a516df11ebb445433f724e7f522", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human metapneumovirus (hMPV) infection can cause acute respiratory illness in young infants, the immunocompromised, and the elderly [1] [2] [3] . HMPV infection has been detected in 4 to 15% of pediatric patients hospitalized with acute lower respiratory infections [4] [5] [6] [7] [8] [9] [10] . Cur-rently there are no licensed measures to prevent hMPV disease.", "Based on analyses of genomic sequences hMPV has been assigned to the metapneumovirus genus of the pneumovirus subfamily within the paramyxovirus family [11, 12] ." ] },{ "paper_id": "9764af198bccd196d117b460ad8112059b4f6b00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In Greece, the recruitment of veterinarians was unsuccessful, while in Romania samples were collected, but owing to problems with shipping none were received by the laboratory in Switzerland. Data were provided for 6005 of the 6720 returned samples using the online questionnaire (69.7%). Subsequently, these 6005 samples accompanied with a complete data set were included in the further analysis. ", "When testing the stability of FeLV in RNA shield buffer at room temperature for up to 60 days and at 37 \u2022 C for up to 14 days, no significant loss of FeLV viral RNA was observed (<10-fold decrease).", "The stability of FeLV in the RNA shield was tested in a pre-experiment using cell culture supernatant from FeLV-infected FL-74 cells. Cell culture supernatant was diluted in PBS to reach a FeLV copy number concentration that corresponded to that in the saliva of viraemic cats (threshold cycle values of approximately [22] [23] [24] [37, 38] . Aliquots of diluted cell culture supernatant were stored at room temperature for 7, 14, 21, 28, 50, and 60 days and at 37 \u2022 C for 2, 3, 5, 7 and 14 days, respectively. After incubation, TNA was extracted and analysed by FeLV real-time RT-qPCR as described above.", "According to the classification tree analysis (Figure 5 ), the origin of cats within Europe (discriminatory power (DP) of 100, with a scale between 0 and 100), having a pedigree (DP = 55.60), and living outdoors only (DP = 29.08) were the three important predictors (or splitters) regarding a cat's FeLV status, with a relatively good tree sensitivity and specificity: 82.98% (95% CI: 75.74-88.78) and 61.89% (95% CI: 60.63-63.13), respectively. The areas under the ROC curve for the learning data and the test data set were 0.73 and 0.69, respectively. These values indicate the potential of the proposed tree to discriminate between the diagnoses (FeLV-negative versus FeLV-positive).", "With the support of the country representatives, 861 veterinary facilities were enrolled, 93.6% of the initially intended total of 920 facilities (Table 1 ). Subsequently, 6720 samples (78.0% of the 8610 shipped tubes) were returned to the laboratory; these samples originated from 30 of the 32 originally included countries (Table 1; Figure 1a )." ] },{ "paper_id": "97699e1e790ab279013460ac4478cc6b9832d2e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "have a crown appearance under the electron microscopy due to the spike protein on the surface. The coronavirus subfamily is classified into genera: alpha, beta, gama, and delta. Human coronaviruses belong to alpha, and beta coronaviruses [4] .", "A vaccine expressing the MERS-CoV spike protein was shown to confer mucosal immunity in dromedary camels with evidence of serum neutralizing antibodies and significant reduction in excreted infectious virus and viral RNA transcripts in vaccinated animals [25] .", "Experimental MERS-CoV inoculation of other domestic animals will help define predisposed groups and should be considered so as to guide screening efforts for other potential reservoirs. " ] },{ "paper_id": "976dd497031581e697cbf2d98042f7c184e9fb40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thus, it is difficult to compare patient populations in the hBoV studies." ] },{ "paper_id": "977007f901c5697f613ad1b475532ebaf7baef86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rabbit anti-human polyclonal-HRP conjugate was procured from Dako, Denmark, while Goat anti-mouse IgG-HRP was obtained from Genei, Bangalore.", "for their help with histopathology and Mr. Kumar from Department of Neurovirology for help with the animal experiments. We would like to thank Late. Dr. V. Kumaraswami for being inspiration for the study." ] },{ "paper_id": "977f8bf86c08dd49d32dc09682e69cd99b30f4f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To do so, we used the hypergea (B\u00f6nn, 2016) R package, which uses a conditional maximum likelihood estimate to compute the odds ratio (OR) on adjusted cell counts (to avoid empty cells) and obtains two-sided p values from the hypergeometric distribution.", "interferon gamma response 12.15 4.28 6.1E-13 3.1E-11", "reac\u019fve oxigen species pathway 0.12 -0.07 7.5E-01 1.0E+00 0 0" ] },{ "paper_id": "9791652bce8752738f1bfb75305fd5faa6e30374", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The measures comprising the study instruments were used to build the conceptual model ( Figure 3 ) and are described below and in Table 1 ." ] },{ "paper_id": "979d953fe8641bdfaf6479a9b479923aae95c86b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 5-year probability of recurrence was 7% and 21%, respectively (p = 0.001, log-rank test). The 10-year probability of recurrence was 13% and 58% in these same groups, but fewer patients were followed. (With permission of John Wiley and American Journal of Transplantation).", "compared to tacrolimus was associated with eight-fold reduction in the risk of PBC recurrence, in agreement with other liver transplant centers [11, 13, 19] .", "For our in vitro studies, we used the MM5MT mouse breast cancer cells containing integrated MMTV provirus for testing the sensitivity of antiviral and immunosuppressive agents to diminish MMTV production. By design, this model cannot be used to test early events in the retrovirus life cycle, such as viral internalization, uncoating, disassembly, reverse transcription, nuclear import of the preintegration complex and proviral integration ( Figure 3) . Nevertheless, the downstream production of infectious particles from integrated provirus can be studied." ] },{ "paper_id": "979eb6ed6241fecc3000a963222725a6439b2e19", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Publish with Bio Med Central and every scientist can read your work free of charge http://www.virologyj.com/content/3/1/106" ] },{ "paper_id": "97a0381dad9c04b6a53300885acd274d88d4f4d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting information S1 ", "This study was conducted according to the animal welfare guidelines of the World Organization for Animal Health and approved by the Animal Ethics Committee of China Animal Health and Epidemiology Center (CAHEC). The ethical board was provided by the Animal Ethics Committee of CAHEC (No.00501). Samples were collected with permission given by multiple relevant parties, including China Animal Health and Epidemiology Center, and the relevant farm owners.", "In this study, we implemented viral infection surveillance in six poultry farms in two provinces of eastern China using short read sequencing with Ion Torrent and compared it with traditional viral infection surveillance methods." ] },{ "paper_id": "97ab5bad794553f1af287d9ee88c0113e1ba80ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Methods. Data were statistically analyzed using the Statistical Package for Social Science software (SPSS v20.0; IBM Crop, Armonk, NY, USA). Descriptive statistics for continuous variables were compared using the nonparametric Mann-Whitney test or the Kruskal-Wallis test. For categorical variables, the 2 test, the Fisher exact test, or the test was applied to evaluate the difference between proportions or to assess whether there were any associations between the proportions. A two-tailed probability value < 0.05 was considered statistically significant. Values were expressed as mean or standard deviation and percentages wherever necessary.", "Extracted RNA from all samples was subjected to MERS-CoV upstream E-gene (UpE) detection using real-time RT-PCR on LightCycler 2.0 (Roche, Germany) as previously described [29] in a final volume of 20 l. Negative (no-template control (NTC)) and positive controls were always included.", "When comparing the overall clinical symptoms of infected and noninfected patients (Table 4) , we found a significant association between the positive detection of viral infections and presentations of runny nose ( = 0.014), wheezing ( = 0.007), or lethargy ( = 0.035) to healthcare facilities. While the small number of patients limited our ability to examine the association between each viral infection and clinical symptoms, we observed a significant association between nasal congestion and single infections ( = 0.0163) compared to dual infections (Table 5 )." ] },{ "paper_id": "97b03849d178cb08d39be44ebab0a2aa41b6a4d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results were expressed as means \u00b1 SD. Analysis of variance and unpaired Student's t-tests were employed to determine statistical differences among multiple groups. P values < 0.05 were considered significant (*P < 0.05, **P < 0.01).", "FITC-MHCII, PE-SWC3a were from Abcam (New Territories, Hong Kong). Dylight 488-, 594-,-conjugated secondary antibodies were purchased from MultiSciences (Lianke) Biotech Co., Ltd. (China). 4\u2032, 6-diamidino-2-phenylindole (DAPI) solution were obtained from Jackson ImmunoResearch Laboratories (West Grove, PA, USA). CFSE (carboxyfluorescein succinimidyl amino ester) were purchased from Invitrogen (USA). The Cytokine test kits were purchased from Shanghai Huyu Biotechnology (Shanghai, China). Cell Counting Kit-8 were purchased from Beyotime Biotechnology (China)." ] },{ "paper_id": "97bdba1d4a122241576c1e180ca7ce848cb657a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No. of sows MNCs.", "This study was carried out in strict accordance with the recommendations by ", "All data were expressed as the mean \u00b1 standard error of mean (SEM) of six sows. Statistical analyses were performed by one-way ANOVA followed by Tukey's post hoc test (GraphPad InStat 5.0 prism software), and the P value of <0.05 was considered significant.", "Vero cells (ATCC \u00ae CCL-81) were cultured in Minimum Essential Media (Gibco, CA, USA) supplemented with 10% heat inactivated fetal bovine serum (Atlanta Biologicals, GA, USA), 2 mM l-glutamine (Gibco) and antibiotic/antimycotic solution (HyClone, UT) at 37 \u00b0C in a humidified atmosphere with 5% CO 2 . For preparation of virus stocks and in virus neutralizing (VN) assay, the MEM was supplemented with tocylsulfonyl phenylalanyl chloromethyl ketone (TPCK)-trypsin (1 \u03bcg/mL) (Sigma, MO, USA), 0.3% tryptose phosphate broth (Sigma), 0.02% yeast extract (BD, MD) and antibiotic/antimycotic solution (HyClone, UT, USA)." ] },{ "paper_id": "97c615d915000b15e55f71d20e045bf939c6bca5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ARF. Six of 9 (67%) patients with ARF had a fatal outcome, while one of three patients without ARF died. However, the differences found for the fatality rates in cases with and without ARF during MERS-CoV infection were not statistically significant.", "Coronaviruses (CoVs) cause human disease with symptoms ranging from mild respiratory symptoms to severe pneumonia [1] . In September 2012, a novel CoV termed the Middle East Respiratory Syndrome (MERS)-CoV emerged on the Arabian Peninsula with 163 laboratory-confirmed cases including 71 deaths so far (World Health Organization, December 2nd, http://www.who.int/csr/don/2013_12_ 02/en/index.html). Due to its distribution in several countries of the Arabian Peninsula there is a risk of global spread through travel and pilgrimage, posing a potential threat to global public health." ] },{ "paper_id": "97ccb371dde90e32d62250fa0a00cacc8b67066e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "97d0e0033e74b01cefd3c71a23aa1fec45a72296", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "97e0348076235024d8bf38647c8db27abc7ffef2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "First Second Third Total ", "First, second, and third refer to the priority level of the zoonotic diseases and total is a sum of all the times that disease was prioritized in such categories." ] },{ "paper_id": "97e07d83db421faee2a7a42a0e2c8a117c08b016", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PCR amplification of amplimers was performed in 10 ul reactions in 384-well plates. The reaction conditions were as described above." ] },{ "paper_id": "97e4ef6563c15d0a2291272e99cdc11dd4c02134", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Study selection and methods of the analysis were specified in advance and documented accordingly.", "From the trials identified during the search, we extracted information regarding study methods and assessments.", "EPs 7630 is an extract from the roots of Pelargonium sidoides, drug-extract ratio 1: 8-10, extraction solvent: ethanol 11% (w/w). The marketed medicinal product is available as a liquid solution, with a recommended daily dose of 3 \u00d7 10 drops for young children aged 1-5 years, 3 \u00d7 20 drops for children aged 6-12 years, and 3 \u00d7 30 drops for adolescents over 12 years and for adults, and as film-coated tablets containing 20 mg of extract, with a recommended daily dose of 3 \u00d7 1 tablet licensed for adolescents over 12 years and for adults. A syrup formulation for children aged 1-12 years is also available but was not used in any of the identified studies." ] },{ "paper_id": "97f0a7e6ca8d48ac37eb4bf5c1aa47f9ab80ffd6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Attending pediatricians prospectively reported medical information on a standardized data sheet, including the duration of clinical symptoms, demographic and clinical data.", "Five hundred eighteen samples (97% of 533 collected NPS) from 492 children were included in the final analysis (Fig. 1) . Demographic and clinical characteristics of the study participants are summarized in Table 1 ." ] },{ "paper_id": "97f0de00cdfd52961c9a8611c306de5778556eb0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data used for this project are publicly available and accessible online (GN accession no. GN160).", "Cardiac troponin T2 Myh6", "Cardiac myosin heavy chain 6 (a-MHC)" ] },{ "paper_id": "97f1fe02cd9244df3c903856dcb615d9fb6ec02a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study protocol ( ", "Please refer to the Study S1 Protocol. Briefly, adverse events as have been reported are described in the product monograph for AVONEX. The study protocol indicated dose adjustment or withdrawl for severe adverse events (worsening and severe clinical symptoms ", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "9800de42f4f105fbd335179bef0fd6a57036d5ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Paraffin-embedded normal human tracheal tissue sections were purchased from Auragene Bioscience (China). Formalin-fixed normal swine (5 months old domestic pig) and bovine (8 months old cattle) tracheal tissues were obtained from Zhongmu institutes of China animal husbandry industry with approval.", "Madin-Darby canine kidney (MDCK) cells (NBL2, obtained from cell resource center of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences) were cultured in Dulbecco's modified Eagle's medium (DMEM, Gibco) supplemented with 10% fetal bovine serum in a humidified chamber containing 5% CO 2 at 37\u00b0C." ] },{ "paper_id": "98086d212b4a5249cfc45f05953fd0abf43891d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Overall, these quarantinable diseases persist at low endemic levels, but still pose potential threats.", "Case fatality rate measures the percentage of deaths among people who contracted a disease. During 1975-2008, the disease type with the highest fatality rate is zoonoses, consistently causing 5-15% of deaths among the infected population. Following that, quarantinable diseases killed 1.4-5.6% of its infected population during the same period. In comparison, fatality rates in vaccinepreventable (0. (Table 1) .", "Conceived and designed the experiments: LZ DW. Analyzed the data: LZ. Wrote the paper: LZ DW." ] },{ "paper_id": "9809fd94325b39bffb3a2414a3d7f3e1429fa539", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations IF: impact factor ", "The analysis in this study is based on a retrospective bibliometric technique; therefore, no ethical approval was required.", "Microsoft Excel\u00ae and version 15 of SPSS\u00ae for Windows were used to perform statistical analysis. These software packages were used to generate data on frequency distribution, percentage, sum and average, and to create Fig. 1 . Further analysis was introduced to obtain the top tenranked prolific countries, most prolific journals, most prolific institutions and most cited papers by using the 1-2-2-4 rule, which is known as the standard competition ranking." ] },{ "paper_id": "9816051343f6acf13246fd5957e876a4db2c1ab7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data checks for consistency and internal validity were performed using Microsoft Excel software. These included internal validity such as valid range of years or uniform country names.", "Two authors independently reviewed the sample (AHR and TA). At the end of the process, the coding by reviewers was compared, and any discrepancy was resolved by consensus. The following process was used:", "Automated data-mining techniques were used to classify grants by health category. JavaScript and Microsoft Excel were used for this analysis." ] },{ "paper_id": "982210556d79705b5b48d86ca09aadf517bd0edb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This Sabouraud agar (Oxoid) worked for the cultivation and differentiation of fungi." ] },{ "paper_id": "9834386da0ccac785aad715b6fc38e3123d8afc8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was exempt from institutional review board assessment. Firstly, policy documents and statistics data related to notifiable disease on public websites of China Health Department, CISDCP, Zhejiang Health Department, and Zhejiang Statistical Bureau were collected and understood. Secondly, data were acquired from secondary sources and analyzed anonymously, therefore no participant was required to provide written informed consent.", "Other infectious diarrhea Hand-foot-and-mouth disease ", "Year Acute hemorrhagic con junctivitis Mumps" ] },{ "paper_id": "983e9c303f6c0082aa4fad58a82da11a16262a01", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The few existing studies on the diet of rats indicate varied food elements. 64, 65 From our results it remains unclear if the investigated individuals forage on plant species also consumed by humans. Also it cannot be confirmed if the rats foraged on waste, stored human food or both sources.", "Dilution series of the amplicon library were made and quantified against a set of synthetic oligonucleotides of known molarity to determine the appropriate MID-tagged amplicon ratio required for the high-throughput sequencing platforms. Sequencing was carried out following the manufacturer's protocols (Life Technologies and Illumina).", "Examples such as Influenza A virus subtype H5N1, 9 or middle east respiratory syndrome coronaviruses, 10 Nipah-or Hendravirus, 11 Lassavirus 12 or recently Ebolavirus 13 show that important emerging diseases may result from infections by viruses belonging to many different taxonomic classes.", "The introduction of NGS has started a new era for the screening of pathogens carried by vectors like R. norvegicus. In this study, we have conducted metagenomic analyses of reads and de novo assembled contigs, allowing simultaneous identification of both known and unknown viruses.", "Likewise, the SEPP approach enabled placement of short contigs (4100 nt) into the picornavirus phylogeny. 41 Almost all of the small contigs aligned with high confidence (HMMER e-value o10 \u2212 5 ). In virus discovery studies, where full-length novel genomes are rarely detected, identification may rely on small contigs and single reads. 19 Our results demonstrate the use of this placement approach as a supplement to virus discovery." ] },{ "paper_id": "98451e334c51db917c85e62573eabd5bfaeac9e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In this review, we refer to the salt-induced CKD under hypertension and normotension, from the classical to recent insights.", "Blood pressure CKD Chronic kidney disease Kim-1", "GSHPx against ROS toxicity, causing free radical production to overwhelm antioxidant defense systems [66] . Thus, vanin-1 is involved in oxidative stress in tissues [67] ." ] },{ "paper_id": "9853f82beb2aa6e757484232afa30dba030c50fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chemicals and reagents. Ammonium hydroxide (28-30%), tetraethyl orthosilicate (TEOS, 96%), ethanol absolute (99.7%), silver nitrate (99.5%), sodium chloride (99.5%), potassium chloride (99.5%), and trifluoroacetic acid (TFA, 99%) were purchased from Sinopharm Chemical Reagent Beijing Co., Ltd (Beijing, China). Acetonitrile (ACN, 99%), \u03b1-cyano-4-hydroxycinnamic acid (CHCA, 99%), dithiothreitol (DTT, 99%), cetyltrimethylammonium chloride (CTAC, 99%), albumin from bovine serum (BSA, 98%), polyvinylpyrrolidone (PVP, MW = 40,000), D-glucose (99.5%), L-methionine (99%), D-mannitol (99%), L-lactic acid (98%), L-arginine (99.5%), L-tryptophan (98%), uric acid (99%), and DL-phenylalanine (99%) were purchased from Sigma, USA. Tris base and phosphate-buffered saline (PBS, 10\u00d7, pH 7.4, cell-culture grade) were purchased from Yeason Biotechnology Co., Ltd (Shanghai, China). The isotopic internal standards of glucose (labeled with six 13 C or one 13 C) and mannitol (labeled with one 13 C) were purchased from Cambridge Isotope Laboratories (CIL, USA). Thiol-aptamers were obtained from Sangon Biotech Co., Ltd. (Shanghai, China). All aqueous solutions were prepared using deionized water (18.2 M\u03a9 cm, Milli-Q, Millipore, GmbH) throughout the experiments.", "Data availability. The data that support the findings of this study are available from the corresponding author upon reasonable request.", "Received: 19 October 2016 Accepted: 13 June 2017" ] },{ "paper_id": "985a0071613514c5f07592dc4d94d8916c2052d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "alcoholism, diabetes mellitus and splenectomy." ] },{ "paper_id": "985bcaae91f49b39ffb29301edef221c46c66034", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Whole cell extracts were prepared in NP-40 lysis buffer (50 mM Tris, pH 7.4, 150 mM NaCl, 30 mM NaF, 5 mM EDTA, 10% glycerol, 1.0 mM Na 3 VO 4 , 40 mM b-glycerophosphate, 0.1 mM phenylmethylsulfonyl fluoride, 5 mg/ml of each leupeptin, pepstatin, and aproptinin, and 1% Nonidet P-40). WCE was then subjected to electrophoresis on 7.5% native acrylamide gel, which was pre-run for 30 min at 4uC. The electrophoresis buffers were composed of an upper chamber buffer (25 mM Tris, pH 8.4, 192 mM glycine, and 1% sodium deoxycholate) and a lower chamber buffer (25 mM Tris, pH 8.4, 192 mM glcine). Gels were soaked in SDS running buffer (25 mM Tris, pH 8.4, 192 mM glycine, 0.1% SDS) for 30 min at 25uC and were then transferred to nitrocellulose membrane (Amersham Biosciences). Membranes were blocked in PBS containing 5% milk (wt/vol) and 0.05% Tween-20 (vol/vol) for 1 h at 25uC and blotted with an antibody against IRF3 (IBL, Japan). Antibody signals were detected by chemiluminescence using secondary antibodies conjugated to horseradish peroxidise and an ECL detection kit (Amersham Biosciences, Inc, NJ, USA)", "All five lobes of the lungs were collected and fixed in 10% neutral-buffered formalin for 24 h. The organs were paraffinembedded and 4 mm sections were cut and stained with hematoxyline and eosin staining (H&E). The slides were analysed by a board-certified independent veterinary pathologist.", "Cell culture, transfections, and luciferase assays" ] },{ "paper_id": "985f2253ef842c0bd15013ac3314061d880d12a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. All relevant data are available from the authors.", "In Figs 2a-d, nonlinear regression was performed using a log(inhibitor) versus normalized response-variable slope model. R 2 of curve fit is larger than 0.97 for all curves in Fig. 2a- the extra sum-of-squares F test (***, Po0.001; 12 different dilutions of each mAb, 4 measurements at each dilution for each mAb).", "All statistical analyses were performed using GraphPad Prism 6 software." ] },{ "paper_id": "98936f4aa8ad9759352811bbb4aa531c2f061cd7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data interpretation and statistical analysis. If the absorbance rate was lower than the control, this was considered to indicate a reduction in cell proliferation. By contrast, if the absorbance rate was higher, this indicated an increase in cell proliferation. The difference in the inhibition rate between the groups was analyzed using one-way analysis of covariance. P<0.05 was considered to indicate a statistically significant difference. ", "Materials. Synovial tissue was obtained from a patient at the Department of Orthopedics and Pathology, Shanghai Third People's Hospital (Shanghai, China). SH was purchased from Unattached cells were then transferred into centrifuge tubes and centrifuged for 10 min. A total of 4 ml 0.25% trypsin was added and the cells were incubated for 30 min. The solution was then filtered using a 200-mesh nylon net. Following centrifugation for 10 min, the cells were incubated as aforementioned for 24 h. The unattached cells were discarded, leaving primary cells from a patient with RA (Fig. 1) .", "MTT assay. Sequential dilutions of cells in the culture medium between 10 6 and 10 3 cells/ml were prepared. A total of 100 \u00b5l each dilution was analyzed in triplicate, using a microplate reader (Bio-Rad, Hercules, CA, USA) and three control wells containing medium only were used as an absorbance reference. The cells were then incubated for 24 h. A total of 10 \u00b5l MTT reagent (0.25% MTT) was added to each well and the cells were further incubated for 4 h until a purple precipitate was observed. A total of 100 \u00b5l detergent reagent was added to each well and swirled gently, and the plate was then incubated in the dark overnight at room temperature. The absorbance in each well at 570 nm was measured using a microplate reader. Finally, the data were recorded and the results were analyzed.", "The results from the present study provide a potential theoretical basis for the treatment of RA. Furthermore, due to the dose-dependent reaction of SH observed in the present study, a suitable dose of SH may almost completely inhibit synovial proliferation and therefore be highly effective in the clinical treatment of patients with RA." ] },{ "paper_id": "98948855a76926474a0ca576cf984b00053fcac3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "African green monkey kidney cells (Cos7) were cultured in Dulbecco's modified Eagle's medium (DMEM) (Invitrogen, Germany) supplemented with 10% fetal calf serum (FCS), glutamine (100 mg/l) and gentamicin (350 mg/l). HCMV was propagated in human fetal lung fibroblasts (MRC-5) or human foreskin fibroblasts (HFF) grown in DMEM supplemented with 10% FCS, glutamine and gentamicin as above. For immunofluorescence cells were grown on 13-mm glass coverslips in 24-well plates. HB15-UL84prluc represents a recombinant AD169-based HCMV which expresses the firefly luciferase gene under the control of the HCMV UL84 promoter.", "Ethics approval for the sample collection has been obtained from the Ethics Committee of the Medical Faculty of the Friedrich-Alexander Universit\u00e4 t Erlangen-N\u00fcrnberg. Written informed consent was obtained from all donors.", "To produce selected recombinant human monoclonal antibodies the Ig heavy and corresponding light chains were amplified by RT-PCR from clonally expanded activated memory B cells and cloned into eukaryotic expression vectors exactly as described by Tiller et al. [68] . The respective cloning vectors were kindly provided by H. Wardemann, Berlin. V gene usage and CDR sequences are supplied in Table S1 .", "Human cytomegalovirus (HCMV) is an important, ubiquitously occurring, human pathogen in immunocompromised hosts. The virus can cause severe disease in transplant recipients [1] . In large parts of the world HCMV is also the most common viral infection acquired in utero. In the USA and Europe an estimated 0.2%-1.2% of all live born infants are infected with HCMV [2, 3] . Congenital HCMV infection is a leading cause of sensorineural hearing loss in children and the leading infectious cause of central nervous system damage in children [4, 5] . As a consequence of the importance of congenital HCMV infection for public health, the Institute of Medicine of the National Academy of Sciences, USA, has ranked the development of a HCMV vaccine as a top priority [6] ." ] },{ "paper_id": "989b3ab9e08bcef68a844c9a522771d41ddf7cad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The optimized rHA ORF genes were cloned into the pFastBac vector plasmid to make recombinant Bacmid baculovirus DNAs using DH10Bac competent cells (rAcNPV, Invitrogen, Carlsbad, CA, USA). A recombinant baculoviruses (rBVs) expressing influenza rHA protein was generated by transfection of Sf9 insect cells according to the manufacturer's instruction. Sf9 cells were infected (1.0 multiplicity of infection, MOI) with rBVs expressing HA. After 4 days, the cell culture supernatants were harvested for preparation of vaccines.", "The indirect immunofluorescence assay (IFA) was carried out to test the expression of HA in infected Sf9 cells after 72 h. The primary antibody was chicken anti-sera against Re6 antigen at a dilution of 1:800, and the secondary antibody was FITC labeled goat anti-chicken IgY (1:500) (Southern Biotech, Birmingham, AL, USA).", "The functionality of rHA protein incorporated into VLPs was quantified by hemagglutination assay (HA assay) using 1% (v:v) chicken red blood cells. The concentration of protein was measured by Pierce BCA Protein Assay Kit (Thermo Fisher Scientific)." ] },{ "paper_id": "989be59a0cd5354610ff80be6e50fa6617c077bf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Remodeling of the cardiovascular structure occurs in response, not only to changes in BP and flow, but also to modifications in the neurohormonal environment, in which the rennin-angiotensin-aldosterone system (RAAS) exerts a most predominant influence [2] .", "All epidemiological studies show that the risk of adverse cardiovascular (CV) outcomes, such as stroke, myocardial infarction (MI), heart failure (HF), and kidney disease [1] , increase progressively with increasing blood pressure (BP). On the other hand, clinical trials demonstrate that lowering BP reduces such risks [1] . All antihypertensive medications lower BP, but specific drug classes display effects beyond BP reduction (pleiotropic effects) that might contribute to cardiovascular risk reduction.", "AT2R stimulation activates the NO-cGMP-dependent pathway [41] . This occurs either directly or indirectly through bradykinin or by increased endothelial NOS activity or expression. AT2R activation is associated with phosphorylation of JNK, PTPs, I\u03baB\u03b1 (inhibitor of NF-\u03baB), and the transcription factor ATF2, and dephosphorylation of p38MAPK, ERK1/2, and STAT3, which are linked to antiproliferative and antiinflammatory effects and apoptosis [38, [42] [43] [44] . AT2R may induce relaxation by opening large-conductance Ca 2+ -activated K + channels (BKCa) [45] and by negative regulation of the vascular Rho A/Rho kinase pathway. The AT2R also enhances the activity of tyrosine phosphatases and vanadate-sensitive phosphatases MKP1 (DUSP1), SHP1 (PTPN6) and PP2A [46, 47] ." ] },{ "paper_id": "98a3b0606a67d829816c1d934e2d1a7196985151", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Focus groups were recorded, transcribed verbatim and subsequently analyzed. Themes were identified and unique perspectives on key issues noted [16] .", "A total of 17 intensivists at four community hospital intensive care units (ICUs) in the Greater Toronto Area participated in the present prospective interventional study.", "All handheld devices were equipped with backup software that allowed the content to be rapidly restored in the event of a hardware failure (BackupBuddy VFS; Blue Nomad Software, Redwood City, CA, USA). The devices were also equipped with software capable of generating a log of the applications used (AppUsage; Benc Software Production, Slavonski Brod, Croatia)." ] },{ "paper_id": "98aca16ac6513c25abcf54bc1dbe7b6fe65e9c49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We thank the staff at the National Institute of Infectious Diseases, ", "Influenza virus is highly transmissible and causes mild to severe illness, including high fever, headache, myalgia, and pneumonia.", "In this study, using the ResPlex II assay, we analyzed the specific pat- its low ability to multiply influenza viruses and to eliminate the contaminating viruses." ] },{ "paper_id": "98b07ff87d658b09a3284a78b88ebe5687475d5a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "EBV (Epstein-Barr virus); HBV (hepatitis B virus); HCV (hepatitis C virus); HIV (human immunodeficiency virus); HLA (human leukocyte antigen); HPV (human papilloma virus); IEDB (Immune Epitope Database); LCMV (lymphocytic choriomeningitis virus); MHC (major histocompatibility complex); SARS (severe acute respiratory syndrome)." ] },{ "paper_id": "98bc863e44dea730a7952a8b6bc62292fe5da07a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Microbiological evaluations were conducted according to standard procedure as previously described [23] . These included three sets of blood culture, gram stain and culture of sputum or endotracheal aspirates, or BAL fluid, and urinary antigen testing for Streptococcus pneumoniae and Legionella pneumophila (Binax Inc., Portland, Maine, USA). PCR was used to detect atypical bacterial pathogens such as L. pneumophila, Mycoplasma pneumonia and Chlamydophila pneumoniae, using the BD ProbeTec ET Atypical Pneumonia Assay (Becton Dickinson, Sparks, USA). Microorganisms identified from specimens which had been collected within 72 hours after the diagnosis of pneumonia were included as pathogens.", "The need for informed consent was waived in view of the observational nature of the study with no interventions performed. The protocol and standardized clinical form, including the waiver of informed consent, were approved by the Asan Medical Center Institutional Review Board (IRB number: 2010-0079)." ] },{ "paper_id": "98bf14e077d911ddc7450d48a7e79f3573d9e52a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "98c1b2325128b3573b2793ba5d77dc07329c0195", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reporter plasmids were linearised with HpaI and capped run-off transcripts generated using T7 RNA polymerase as described [30] . Messenger RNAs were recovered by a single extraction with phenol/chloroform (1:1 v/v) followed by ethanol precipitation. Remaining unincorporated nucleotides were removed by gel filtration through a NucAway spin column (Ambion). The eluate was concentrated by ethanol precipitation, the mRNA resuspended in water, checked for integrity by agarose gel electrophoresis and quantified by spectrophotometry." ] },{ "paper_id": "98c2af7070735431908c6d271df6b49f01924f96", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Most neurotropic viruses encode one or more proteins aimed at interfering with the IFN pathway. These proteins are often multifunctional and sometimes interfere with different targets of the same pathway.", "Viruses 2013, 5 835", "As is the case in neurons, IFN production may be restricted in oligodendrocytes. A recent study showed that microglial but not oligodendroglial cells isolated from mice infected with MHV expressed detectable IFN-\uf062 levels although both cell types were infected by the virus. Low basal expression of sensors and of signaling molecules in oligodendrocytes was proposed to limit the rapid responsiveness of these cells [65] .", "As an example, rabies virus is a highly neurotropic virus responsible for a fatal disease in a wide range of animals and in humans. The P phosphoprotein is one of the five proteins encoded by the virus. Besides its involvement in viral RNA synthesis as a cofactor of the polymerase, the P protein of rabies virus is a paradigm of non-structural protein interfering with IFN induction, IFN signaling as well as IFN-induced antiviral effectors." ] },{ "paper_id": "98c8f0c6a7721035d1b32934f84b8b7b18834c81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "adenovirus, global health security, influenza virus, respiratory syncytial virus, rhinovirus, severe acute respiratory infection, Vietnam | 633 ALROY et AL.", "The process of expanding the suite of pathogens for routine testing by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) included laboratory trainings, procurement/distribution of reagents, and strengthening and aligning SARI surveillance epidemiology practices at sentinel sites and regional institutes (RI).", "The Government of Vietnam has demonstrated that expanding respiratory viral surveillance by strengthening and building upon an influenza platform is feasible, efficient, and practical." ] },{ "paper_id": "98ce22d0a0cab728f1aab48170f1769bb0bc3454", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Methodology 2 followed sample preparation as described before [17] . In short, RNA was prepared using a protocol combining Trizol and a semi-automated MagMax\u2122 (Applied Biosystems/Thermo Fisher Scientific, Waltham, MA, USA) extraction system. Subsequently, dsDNA for input into library preparation was generated by reverse-transcription polymerase chain reaction (RT-PCR), yielding overlapping amplicons of the RABV genome (Tables S1 and S2, Supplementary File). The generated amplicons were individually quantified for each sample utilizing a Qubit fluorometer (ThermoFisher Scientific) and pooled equimolarly followed by library generation using the Nextera XT kit (Illumina, San Diego, CA, USA). Sequencing was performed with an Illumina MiSeq instrument generating 250 base paired end reads.", "The results of this study clearly demonstrate the benefits of utilizing deep sequencing followed by a comprehensive stepwise data analysis focusing on consensus, population, and variant level. While each of the analyses may lead to biased conclusions, only the combination allows for a holistic assessment, and thus should be standard in similar scenarios. ", "Viruses 2020, 12, x FOR PEER REVIEW 9 of 12", "Vaccination programs are one of the most effective means of controlling infectious diseases [1] and with the development of oral vaccines and bait delivery systems, the elimination of diseases circulating in wildlife populations has become a realistic possibility. The large-scale oral rabies vaccination (ORV) campaigns that have eliminated fox-mediated rabies from Western Europe and North America [2, 3] and substantially reduced disease incidence in central Europe [2] are pre-eminent examples for the success of such control programs." ] },{ "paper_id": "98d0756af42f78bb74a9df2846729c36ba2f05ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "98d83658e5a7c2174de3524a9a3b7c057a34b085", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Novel roles for ACE2 may yet remain to be discovered and a new twist to the ACE2 story has emerged with the discovery of autoantibodies targeting ACE2 in the sera of patients with connective tissue diseases [127] . This, coupled with results showing that administration of an ACE2 inhibitor improved the pathology of inflammatory bowel disease [12] , suggests that inhibition of ACE2 may be beneficial in inflammatory diseases such as arthritis.", "The effects of all-trans-retinoic acid have been investigated on ACE2 expression revealing an increase in ACE2 mRNA levels and reportedly in protein [53] . A decrease in blood pressure in the treated rats was also seen, which was attributed to the increased ACE2 levels.", "When angiotensin-converting enzyme-2 (ACE2) was serendipitously discovered ten years ago, neither of the two groups at the centre of its discovery [1, 2] could have guessed at the disproportionate number of distinct roles it plays in biology, from cardiovascular regulation to viral infection. As so often happens in modern biological research two independent approaches converged on the same discovery, to give us ACE2 or angiotensin-converting enzyme homologue (ACEH), back in 2000. Over the past ten years our knowledge of this protein's role in the body has increased exponentially, resulting in recombinant ACE2 protein entering clinical trials back in 2009. This paper will focus on what we currently know about ACE2 and its regulation, highlighting some of the gaps and discrepancies that still remain in our knowledge." ] },{ "paper_id": "98db52b9c67490372213988b16fbd56918e3d52f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "From the 15 mL collecting solution of the Coriolis \u00b5 Biological Air Sampler (Bertin Corp.), a 1.5 mL aliquot was centrifuged for 10 min at 14,000\u00d7 g (J. Pilote protocol = 3 mL aliquot, 10 min, 21,000\u00d7 g).", "Total genomic DNA from air and nasopharyngeal samples was extracted with a PowerLyser \u00ae Powersoil Isolation DNA kit (MO BIO Laboratories, Carlsbad, CA, USA) following the manufacturer's instructions. DNA samples were stored at \u221220 \u2022 C until subsequent analyses.", "For example, particles with a size of 4 \u00b5m to 10 \u00b5m tend to get deposited in the upper airways, while larger particles may remain in the nasal cavity [10, 11] .", "Bioaerosols can be a transmission vector for infectious diseases and are responsible for a variety of health problems, principally through inhalation [9, [12] [13] [14] [15] . Human exposure to bioaerosols is associated with a wide variety of acute and chronic diseases ranging from allergies, asthma, rhinitis, sinusitis and bronchitis, mostly due to occupational exposure [4, [16] [17] [18] [19] . However, health risks from bioaerosols also exist just from living in close proximity to an intensive source of airborne biological particles [20, 21] . Additionally, other health problems linked to bioaerosols include fatigue, headache, mucous membrane irritation syndrome, nasal congestion, sore throat, and irritation of the nose and eyes [17, 22, 23] .", "The supernatant was discarded and the pellets were kept at \u221220 \u2022 C until DNA extraction. Likewise, the tips of the swabs were cut and vortexed thoroughly in 1 mL PBS (Lonza) and discarded. Suspensions were then centrifuged for 10 min at 21,000\u00d7 g, the supernatants were discarded and the pellets were stored at \u221220 \u2022 C until DNA extraction." ] },{ "paper_id": "98e17ce4c9a1abdcba6c87d592e36be5db704d64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: With sequencing technologies becoming cheaper and easier to use,", "To illustrate our vision of how VAPiD will be useful to the scientific community we are providing two example use cases.", "Not applicable." ] },{ "paper_id": "98e35a687137cb2b91458118347ad93f7ad188fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by the Institutional Review Board of Policlinico San Matteo, Italy. Participants were administered a written informed consent which they signed, and is conserved in our files. The study complied with the recommendations of the 1975 Declaration of Helsinki.", "Hepatitis B virus (HBV) is one of the world's most common infectious agents causing millions of infections each year [1] . Between 500,000 and 700,000 people die each year from chronic infection-related cirrhosis, hepatocellular carcinoma (HCC) or from fulminant hepatitis B [1, 2] . Transmission occurs via percutaneous and mucosal exposure to infectious body fluids. Therefore, the most common route of transmission is sexual transmission. However, infection through blood transfusions and blood products has not been completely eliminated [3] and contaminated injections during medical procedures, sharing of needles, syringes and paraphernalia among intravenous drug users still represent a major public health problem. Vertical transmission is common, especially in Asia, where HBV titers in maternal blood are high, and in developing countries which have not yet implemented hepatitis B vaccination. Further, HBV poses a risk to healthcare workers exposed to accidental needle-stick injuries.", "Prior to the routine use of HBIG as immunoprophylaxis, recurrence of HBV in the liver allograft occurred in up to 80%, and infrequently was associated with an aggressive fibrosing cholestatic variant that caused progressive graft dysfunction and significant mortality. The subsequent availability of safe and effective antiviral drugs led to additional survival benefits by improving prophylactic efficacy and preventing disease progression in those with recurrence [5] ." ] },{ "paper_id": "98e52cb0b81f381ecd6138f73e6596de35d7566f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following compounds used as inhibitors were purchased from Sigma-Aldrich, St Louis, MO, USA: genistein, filipin, methyl b-cyclodextrin (MbCD), chloroquine, and ammonium chloride (NH 4 Cl). chlorpromazine (CPZ) was obtained from Alexis Biochemicals.", "Our observations demonstrate that the route of internalization of EV71 particles in SCARB2-expressing cells involves clathrin, dynamin and is dependent on endosomal acidification and membrane cholesterol level.", "Generally, enveloped viruses attach to the host cells through bind to the receptor on the surface of host and then enter either at acidic pH or at neutral pH. Acidic pH-dependent group includes VSV, influenza A virus, adenovirus and rubella virus [65] . Some viruses like RSV, SV40, measles virus, herpes simplex virus I, vaccinia virus and HIV-1 are insensitive to lysosomotropic agents [27, 65, 66, 67] which are able to block endosomal acidification. For most viruses using clathrin-mediated endocytosis, transition from early-to-late stage endosome is pH-dependent [65] . After endocytosis, viruses containing early endosmoes are configured to form acidic (pH 6.0 to 6.5) vesicles and become progressively more acidic as they mature to form late endosomes (pH 5.5 to 6.0). Progressive acidification of endosomes is required for the internalized viruses to establish their infection [65, 68] ." ] },{ "paper_id": "98e6190d06a8d8774c690be39634a1d64a926dc3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Introns 1, 5, and 3 UTR were far longer in \"type A\" than in \"type B\" (intron 1: 660 vs. 285 bp, intron 5: 171 vs. 84 bp, 3 UTR: 244 vs. 199 bp). " ] },{ "paper_id": "98ebefa9ea63cabfcfac33fb259adf77a19428af", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "98f3c099dcd497b42efa3082b1e631d07378a5e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step 1:", "Step 3:", "Ebola virus disease GP:" ] },{ "paper_id": "98f9843f4b024272b6514db6e53546839101a839", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The dengue surveillance dataset used in the current study are publicly available in Taiwan CDC Open Data Portal, https://data.cdc.gov.tw. The data analysis tutorial is included in Supplementary Information files. ", "where h is called the kernel bandwidth or smoothing parameter (i.e., the parameter controlling the extent of smoothness), d ij denotes the distance between case i and the locality of case j, and K(\u00b7) is a spatial smoothing function characterizing the contribution of each individual over the relative distance d h / ij .", "To calculate the population-level effective reproductive number from individual estimates, the R j values can be further aggregated to form the Adjusted R t given a specified time step \u03c4 13 : " ] },{ "paper_id": "99035541b28958c03a36978cdff0aa13b7fcd8e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9903fc2ee43aca54acf2469fdc2ae8de2e62a09c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vero cells (African green monkey; ATCC CRL 6318) were cultured in Eagle's minimal essential medium (MEM) containing 5% fetal calf serum (FCS), 100 U/mL penicillin and 100 mg/mL streptomycin. Recombinant measles viruses expressing the rodent adapted haemagglutinin of the strain CAM/RB (CAMH) and/or not the enhanced green fluorescent protein (eGFP) rMV Edtag EGFP-CAMH (rMV-green) and rMV Edtag CAMH (rMV) [35, 45] were propagated using Vero cells.", "For analyzes, animals were anesthetized with CO 2 and perfused with 4% (w/v) paraformaldehyde (PFA). Brains were fixed in 4% PFA at least 18 h, and free-floating sections (100 mm) were prepared using a vibratome (Technical Products International) as described [33, 35] . Slices were analyzed directly by UV microscopy. Photomicrographs were taken with a digital camera (Leica). Numbers of infected eGFP-positive neurons were counted and statistical analyzes done using the student's t test and the program Prism (GraphPad, Inc.).", "For identification of peptides presented by MHC class I that can be used in ELISPOT and pentamer staining experiments we used the software programs SYFPEITHI (University of T\u00fcbingen, Germany) and BIMAS (BioInformatics and Molecular Analysis Section, National Health Instituts, Bethesda, USA) to establish a ranking of potential peptides. From 12 potential H-2 K b and D bpresented peptides of MV-N and MV-H with the highest probability scores, we found that D b MV-H 22-30 and D b MV-H 446-454 (RIVINREHL and SNHNNVYWL, respectively) were most efficiently recognized. ELISPOT experiments were performed using the Mouse IFN-c ELISPOT set (BD Biosciences) according to the manufacture's protocol." ] },{ "paper_id": "990adafb33c7402d0a1753fb05c351e6bf7fc80d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Phylogenetic trees were reconstructed with FastTree 2.1.7 [31] under the GTR+\u0393 model of evolution [32] ; note that FastTree was recompiled locally to use double-precision arithmetics, as recommended by its authors to estimate very short branch lengths accurately. Those with a nonzero tree length were midpoint rerooted using the phytools package ver. 0.4-60 [33] in R ver. 3.2.3 [34] .", "We thank three anonymous reviewers for providing us with constructive comments, as well as Compute Canada and Ontario's Centre for Advanced Computing for giving us access to their servers.", "The " ] },{ "paper_id": "9915073ee985307fd682c4df24810387ae83c338", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study did not require ethics approval from an ethics review committee or board because the study did not involve animals, humans, human data or material directly collected from humans or animals." ] },{ "paper_id": "991aed7275084ce0661be421e281a8f47dcc8637", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Parallel and anti-parallel DNA triplexes (Sequences 1-19 in Table 1 ), were built conforming to a 12-fold helix [92] with stereochemistry of the third strand regularized by constrained-restrained molecular geometry optimization and van der Waals energy minimization using X-PLOR [93] . Generated models were then subjected to steepest descent energy minimization using the Sander module of AMBER 12.0 [94] and were used as starting model for MD simulation.", "doi:10.1371/journal.pone.0152102.g008 that the GA step triplex junction interface also exhibits bending of~17\u00b0. Besides, it is known that a tethered GT rich TFO induces a bend in the triplex formed [84, 85] which regulates the transcription of Luciferase gene [86] . Therefore it might be speculated that bent triplexes could serve as recognition sites for triplex binding proteins. Interestingly, an intramolecular triplex formed by GT rich TFO is demonstrated to bind a few hnRNP family proteins [87] . Likewise an intermolecular triplex formed by a CT rich TFO is shown to bind the GAGA transcription factor from drosophila melanogoster [88] .", "PLOS ONE |" ] },{ "paper_id": "991fb0c5b5cd686d096e2b05d8dc19ca22213df4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An endpoint ELISA and serum neutralization assay were performed as previously described [9] .", "of transgenes under a promoter that is active in mammalian cells [7] , baculoviral vectors have been exploited as versatile vaccine vehicles to produce candidate vaccines against various pathogens [8] [9] [10] . It has also been reported that a pseudotype baculovirus displaying the glycoprotein of vesicular stomatitis virus (VSV-G) on its envelope can extend the host range of the baculovirus and enhance its resistance to inactivation by animal serum complement [11] [12] [13] .", "Immunofluorescence assay PK-15 cells were seeded at a concentration of 2.5 \u00d7 10 5 cells/well into six-well tissue culture plates (Nunc, Rochester, NJ, USA) and transduced with purified baculovirus particles at a multiplicity of infection (MOI) of 10. After incubation for 48 h, the cells were fixed for 15 min with absolute methanol (100%) and incubated with anti-ORF2 monoclonal antibody (Ingenasa Inc.), and then with fluorescein-isothiocyanate (FITC)-conjugated rabbit antiporcine IgG (Sigma, St. Louis, MO, USA). Fluorescent images were examined under an inverted fluorescence microscope (Olympus IX70, Japan)." ] },{ "paper_id": "992365f92b227163487b5b2aa46063f842e7b36e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plethysmography equipment is calibrated for baseline parameters and checked for structural integrity and functionality. Minute volume is calculated from a calibration curve that is produced by injection of a known volume of air into the plethysmograph over a wide range of simulated respiratory frequencies. Such calibrations can capture simulated animal-to-animal variations in pulmonary function but cannot account for changes in respiratory function caused by the use of anesthetics, differing individual animal metabolisms, respiratory effects caused by the agent under investigation, or changing stresses on the animal during exposure [14] .", "The IRF-Frederick Aerobiology Core employs an Automated Aerosol Management Platform (AAMP) AeroMP \u00ae (Biaera Technologies, Hagerstown, MD, USA) to control and monitor aerosol experimentation (Figure 8 ). This platform was developed at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) maximum containment laboratory [14] . All AAMP components are selected and manufactured to withstand repeated decontamination with paraformaldehyde gas and hydrogen peroxide vapors. The system does not require tools to assemble and is designed without any cut, catch, or tear points to avoid compromising the integrity of protective gloves worn by staff. Multiple institutions have successfully used this technology, and the results are well documented [14] [15] [16] [17] [18] .", "Experiments involving animals are more complex than calibration experiments and must be coordinated with the veterinary technical staff to provide anesthesia and monitoring of animal vital signs. The AAMP notifies the researcher when any environmental parameter (e.g., temperature, relative humidity, pressure, aerosol concentration, flow velocity) falls outside of upper and lower limits defined by the researcher [14, 25] ." ] },{ "paper_id": "994021cbe306f8833d4124d53771d0038d248860", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9940375ae218bef442080efc4b430cf27323a4a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Are the locked targets we described actually druggable pockets?", "To determine the maximal cliques contained in our graph, we used a program (Eric Coissac, personal communication).", "Most SL sets are not maximal cliques, but some SL sets are quite close to being maximal cliques. Then we wanted to determine the degree of connectivity of a graph." ] },{ "paper_id": "9952cfc72ce630cae558e4f98680a44b43494247", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In this study, we have focused on inward patients only. Therefore, we may have missed a significant number of outpatients, who would have had milder form of hMPV associated ARTI.", "Additional file 1. Questionnaire of the respiratory study. Questionnaire was used to gather demography and clinical manifestations in study subjects. " ] },{ "paper_id": "99560951f295587952ccb543ccc8c214e6df62ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethical approval for anonymisation, archiving and screening of diagnostic specimens was obtained from the Lothian Regional Ethics Committee (08/S11/02/2). Information retained through anonymisation included age band, partial postcode, any recorded symptoms or clinical information, referral source, month of sample collection, and results of other virological testing of each sample.", "Excluding those samples from September 2006 and February 2007 already tested as controls for assay validation, the assay was used for screening the remaining samples between September 2006 and September 2007. These comprised a total of 2787 samples collected from 1540 study subjects initially combined into pools of 10 and with positive pools split and re-tested as previously described [22] .", "Statistical tests were conducted using chi squared test with Yates' correction and 95% confidence intervals unless stated." ] },{ "paper_id": "99667e42abcab43a18c22be949ee54fb1822f34e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "996fc493a4d72390383d242d35515dc8144bb36d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Introduction the course of PEDV replication and clinical disease in the neonatal pig using a passive transfer model.", "2. During PEDV viremia, binding of circulating PEDV antibodies (neutralizing and non-neutralizing) to viral antigenic determinants may have resulted in neutralization, agglutination, and/or complement fixation. This process could have facilitated the humoral and/or cellular immune responses by presenting antigen to the appropriate cells (dendritic cells, macrophages, and B cells) [53] [54] [55] .", "4. Passively-transferred, circulating PEDV IgG could have passed directly from capillaries into the small intestine by paracellular leakage and neonatal Fc receptors [42, 45, 58] . If so, the transported IgG may have neutralized PEDV in the intestinal lumen and/or assisted the humoral and CMI responses by facilitating uptake of PEDV antigen through receptors on apical surfaces of microfold cells [58] [59] . Again, there is no PEDV research against which to test this hypothesis, but IgG is known to play an important role against parvovirus infection in crypt cells [60] . Evidence against this hypothesis is the fact that IgA is believed to play a primary role in protecting against enteric viruses that infect villous enterocytes, e.g. TGEV and rotavirus [61] , and PEDV primarily infects villous enterocytes [17] .", "Real-time RT-PCR. The eluted RNA, primers, and probe were mixed with commercial reagents (Path-ID 1 Multiplex One-Step RT-PCR kit, Life Technologies) and the RT-PCR reactions were conducted on an ABI 7500 Fast instrument (Life Technologies) as follows: 48\u00b0C for 10 min, 95\u00b0C for 10 min, 95\u00b0C for 15 s (45 cycles) and 60\u00b0C for 45 s. The real-time RT-PCR (rRT-PCR) results were analyzed using an automatic baseline setting with a threshold at 0.1. Quantification cycle (Cq) values 35 were considered positive for the corresponding coronavirus. Data were reported as \"adjusted Cq\":" ] },{ "paper_id": "9976bf51302bf33a5384a30c73231d4077c63ffe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reference sequences were obtained from the National Center for Biotechnology Information (NCBI; http://www. ncbi.nlm.nih.gov). Comparisons of nucleotide and deduced amino acid sequences were made using DNASTAR software.", "Chinese strains", "Identical amino acids are represented by -." ] },{ "paper_id": "997ebf63461efa3e7cb1fc3014fc957659705202", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Indicator of resilience AND (factor* OR indicator* OR variable* OR characteristic* OR examination* OR assessment* OR measure* OR association* OR predictor* OR determinant* OR psychometric*)", "For truncated search terms (e.g. resilienc*), a search is submitted for all words starting with these letters and would in this example search for \"resilience,\" \"resiliency,\" etc. For non-truncated search terms with \"*\" (e.g. disaster*), a search for plurals of the term (e.g. disasters) is performed.", "Ethnicity played a different role in different settings and its use as an indicator is neither clear nor straightforward. In Bonanno's study [20] , being Asian played a positive role on resilience, while other minorities (other than African American and Hispanic) were at higher risk of a worse psychological outcome. In Hobfoll's study, being Jewish was associated with higher likelihood of resilience [25] .", "Europe will face important environmental and social challenges in the next decades. Recent research predicts important losses in household welfare and health due to climate change in Europe by 2080, in absence of adequate adaptation [5] . As occurred with past economic crises, the current ongoing one has been suggested as already affecting important aspects of human health and well-being [6] [7] [8] . The current crisis will probably contribute to set a worse overall health status for the populations which will face new adversities. Neither will the evolving global economic situation will be helped by the already increased number of disasters and associated economic losses [9] , which were reported to be especially costly in most recent years [10] , and are expected to worsen in a foreseeable future [10, 11] ." ] },{ "paper_id": "997f6355fdf8531d31a8bdadd1067f651e2e3d41", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A more detailed rationale for the assignment of viruses to existing and proposed new genera is provided as supplementary text.", "PLOS Pathogens |" ] },{ "paper_id": "9984d00caafab39f1c5673c4f7cc53fbddf0b8e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the collection of organs birds were sedated with 300 \u00b5L of tiletamine and zolazepam via the intramuscular route and humanely killed via an intravenous administration of 200 \u00b5L of tetracaine.", "Tracheal and cloacal swabs were eluted into 0.5 mL and 1 mL, respectively of PBS containing antibiotics. Viral RNA was extracted from 100 mL of either clarified-andultracentrifuged blood, tissue homogenates or pelleted blood cells, using the commercial NucleoSpinRNA kit (Macherey-Nagel, Duren, Germany) for manual extraction and from 50 \u00b5L of PBS containing a swab suspension, using the Ambion MagMax-96 AI-ND Viral RNA Isolation kit for the automatic extractor.", "Organ samples were weighed and homogenized, in a solution of phosphate buffered saline (PBS) and antibiotic-antimycotic (penicillin, streptomycin and amphotericin B). Homogenates were clarified by centrifugation at 10 000 g, for 10 min at 4 \u00b0C, and stored at \u221280 \u00b0C.", "AIV quantitative real time RT-PCR (qRRT-PCR) was performed using the published probe and primers targeting the avian gene M from Spackman et al. [27] .", "we have no sufficient evidence to clearly support or discard any of the aforementioned routes." ] },{ "paper_id": "9984fe671d61d99ab39e8e95787e9000093ea7df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Design of a codon-optimized gp140 for expression in S. cerevisiae", "Mapping selected mutations onto the structure of BG505 SOSIP.664", "Influence of N-glycosylation on binding of conformational HIV antibodies to yeast-produced gp120", "The mutations found within gp41 could not be mapped due to disordered electron density in this particular region of the SOSIP crystal structure. Since 4.3.B01 and 4.3.D01 showed virtually identical binding profiles and expression levels (Fig. 4) , these gp41 mutations do not appear to strongly contribute to either improved protein expression or Ab recognition." ] },{ "paper_id": "9992ffbec7c8256d057b05a858cde82d36d64ae3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Policy Forum allows health policy makers around the world to discuss challenges and opportunities for improving health care in their societies.", "T he Global HIV Vaccine Enterprise convened a two-day workshop in May of 2007 to discuss humoral immune responses to HIV and approaches to design vaccines that induce viral neutralizing and other potentially protective antibody responses. The goals of this workshop were to identify key scientific issues, gaps, and opportunities that have emerged since the Enterprise Strategic Plan was first published in 2005 [1] , and to make recommendations that Enterprise stakeholders can use to plan new activities.", "Participants in the workshop identified four areas that, if given proper attention, could provide key information that would bring the field closer to an effective antibody-based HIV-1 vaccine: (1) structure-assisted immunogen design, (2) role of Fc receptors and complement, (3) assay standardization and validation, and (4) immunoregulation of B cell responses." ] },{ "paper_id": "9998f6aa94bb384f3a93381c404f85506d2a8f7d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A case of ILI was defined as an outpatient of any age presenting with a recorded temperature \u2265 38\u00b0C and cough or sore throat of duration of \u22647 days [6] . A case of SARI was defined as a hospitalized person who had illness onset within 7 days of admission and who met age-specific clinical inclusion criteria. A case in children aged 2 days to < 5 years included any hospitalized patient with cough or difficulty breathing and at least one of the following danger signs: unable to drink or breastfeed, lethargic, vomits everything, convulsion, chest indrawing or stridor in a calm child. A case in persons aged \u22655 years included any hospitalized patient with fever (\u226538\u00b0C), cough and shortness of breath or difficulty breathing [6] . All patients with SARI were eligible for enrollment; whereas 5 patients with ILI (the first patient every day from Monday to Friday) were targeted for enrollment per week and per facility.", "The questionnaire was completed by 43/44 (97.7%) surveillance staff at sentinel sites. Of these, 35 (81.4%) were nurses, 5 (11.6%) were clinical officers, 2 (4.7%) were paramedics and 1 (2.3%) was a laboratory technician.", "\u2022 Circulating influenza types/ subtypes, including pandemic strains (Yes) [3] \u2022 Proportion of ILI/SARI illness attributable to influenza virus infection (Yes) [3] \u2022 Risk factors for influenzaassociated severe illness (No)" ] },{ "paper_id": "999baa06c2bdc67ba7e4707ddcf5b3b296f85985", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the sequences generated have been deposited in NCBI Genbank with accession numbers MK026166 and MK205369 -MK205391. Additional datasets analysed in the paper can be made available from the authors upon reasonable request.", "This study has shown that NGS can be useful in veterinary diagnostics in both detecting co-infections, and in providing potential useful epidemiological information as to the possible origin of those infections. However, the main current limitation is the time taken to perform the data analysis from a single sample. As computational power increases, it is likely that these results could be made available in a clinically relevant time frame and therefore become part of routine laboratory testing.", "was detected in both of the two faecal samples collected from puppies in November 2017 using the ORF1b PCR. Sanger sequencing of the PCR products found that the sequence of the amplicons was 100% identical to the sequence obtained by NGS in the targeted region. In contrast, all seven faecal samples collected in January 2018 were all negative for astrovirus by PCR." ] },{ "paper_id": "99a643136f67ee7f56c5abdea714a2a2ca89c10e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No ethical review was required since all results are from the published literature." ] },{ "paper_id": "99acb5c35e12a8faa8d0f4bc507642a63713414f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Eligibility criteria included the following: diagnosis with prostate cancer within two years prior to enrollment, residence in Maryland or adjacent counties in Pennsylvania, Delaware, Virginia, or District of Columbia, 40 to 90 years old at the time of enrollment, born in the United States, either African-American (AA) or European-American (EA) by self-report, can be interviewed in English, had a working home phone number, physically and mentally fit to be interviewed, not severely ill, and not residing in an institution such as prison, nursing home, or shelter. A total of 976 cases (489 AA and 487 EA men) were recruited into the study between 2005 and 2015.", "Genotyping of IFNL4 rs368234815. Genomic DNA was isolated from buffy coats, when available, and from cell lines using the DNeasy Blood & Tissue Kit (Qiagen). For a subset of men (100 cases and 112 controls), genomic DNA was obtained from a mouthwash sample using the Gentra Puregene Buccal Cell Kit (Qiagen). In total, genomic DNA was available for 828 cases (84.8% of study participants) and 953 controls (92.2%). Genotyping of rs368234815 was done as previously described 16 with a custom-designed assay purchased from Thermo Fisher. The genotyping was performed using ABI 7900 (Applied Biosystems) according to the standard protocol. Genotype concordance among duplicates was 97%. There was no deviation from the Hardy-Weinberg equilibrium in controls. Genotyping success rate was 98.6%. The genotyping failure rate was similar (1.4%) for DNA extracted from blood and mouthwash samples. The genotype along with the clinical information for the 976 cases and 1034 controls is presented in Supplementary Data 1.", "To further buttress the validity of our observations, we also found a significant relationship between a gonorrhea infection history and prostate cancer in a very consistent manner with recent meta-analyses 32, 33 . Yet, it remains a limitation that we could not validate our findings in a second cohort. Our study population is rather unique having AA subjects, an in-depth survey about sexual activity, and germline DNA for genotyping, making it difficult to replicate our findings without the requirement for additional recruitment. Nevertheless, the fact that we observed a dose response relationship that fits a biologically plausible mechanism suggests that the associations we observed warrant further investigations, including prospective cohorts." ] },{ "paper_id": "99b91c8b0a5455bca54167c5abb7c0dfdbf032c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sequence of \"Con H3\" is designed from collected strains from 2006 to 2009. The sequence of \"Con H3\" is given as follows:", "Although ferret is more frequently used to assess influenza antigenicity, a number of reports have recently adopted mice 1-5 to evaluate vaccine immunogenicity and efficacy as mice model is much more cost-effective and readily available; In addition, the mice is capable to mount vigorous both humoral and T-cell immune responses.", "Red scatter diagram represent Vregion similarity (positive). Blue scatter diagram represent V-region similarity (identities)." ] },{ "paper_id": "99c5eece9bcc42ce3056f49db1fe5c164af99834", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For an adequate choice of diagnostic tests to run and for a correct interpretation of results, a minimum of information on the patient history is required [22] [23] [24] .", "Most laboratories (26/44) indicated that they could directly contact physicians to ask for more information about the requested samples or look up record sheets and laboratory reports. However, in practice the feasibility of this strongly depended on the daily sample load.", "Twenty-one laboratories that conducted ZIKV molecular detection only used commercially available tests, 14 laboratories only in-house tests, while nine laboratories indicated using both. The RealStar Zika virus [26] . Primary RT-PCRs were mostly carried out with a single ZIKV genome target (42/44). However, two laboratories performed a multiplex PCR targeting multiple viruses which were not specified further.", "Pending the development of more specific serology tests, a broader implementation of the current most specific neutralisation tests (PRNT, VNT) is desirable, ideally in a comparative setting with other relevant flaviviruses. Increased awareness is needed among clinicians to provide all necessary background information, and systems should be implemented that assure provision of necessary interpretation data. National and/ or EU contingency funding should be established to ensure adequate and robust laboratory preparedness and response. " ] },{ "paper_id": "99cbce9d58b005643a2402b10d8ec96ec8aea7c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "T. gondii RH strain was used in our study. Tachyzoites were maintained in Vero cell monolayerand cultured in Dulbecco Modified Eagle Medium (HyClone, USA) supplemented with 5% fetal calf serum(FCS, HyClone, USA) at 37\u02daC, in 5% CO 2 atmosphere for 3 to 4 days. Tachyzoites were purified with a 27-gage needle syringe and a 5.0 \u03bcm pore filter (Millipore, MA, USA) by previously described method [24] . Purified tachyzoites were stored at -70\u02daC for further use.", "In brief, PCR was carried out in a 25 \u03bcL reaction volume which contained 2\u03bcL DNA template, 0.5 \u03bcL forward primer and 0.5 \u03bcL reward primer (529F and 529R as described before), 12.5\u03bcL 2\u00d7 TaqMix (Transgene, Beijing), 9.5 \u03bcL double distilled water. The amplification was performed with a PCR machine (T-Gradient, Biometra1), that consisted of initial denaturation at 94\u02daC for 5 min, followed by 30 cycles of 94\u02daC for 45 sec, primer annealing at 55\u02daC for 30 sec, extension at 72\u02daC for 1 min and a final extension at 72\u02daC for 10 min. PCR products were electrophoresedin a 1.2% agarose gel and stained with ethidium bromidefor visualization.", "Copies/mL = Conc. of Plasmid (g/mL)\u00d7Avogadro's Constant/Molecular Weight of Plasmid (g/mol) Molecular Weight of Plasmid (g/mol) = Average Molecular Weight of Bases\u00d7Total Number of Bases in Plasmid" ] },{ "paper_id": "99d730ff4e80cd42f0304b9d80d7d0df0689888d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords: visualization, phylogenetics, phylogenomics, phylodynamics, infectious disease, epidemiology, evolution", "in sample collection and sequencing, the design of more complex analytical inference models and powerful hardware infrastructure will be complemented by a new era in visualization applications that will collaboratively foster visualizations that track virus epidemics and outbreaks in real-time and with high resolution.", "Across disciplines, adequate visualizations are pivotal to communicate, disseminate and translate research findings into meaningful information and actionable insights for clinical, research and public health officials. The aim to improve datadriven decision making fits within a broader scope to establish a universal data visualization literacy (16) . To this end, enhancing collaborations and dissemination of visualizations is increasingly achieved through sharing of online resources for hosting annotated tree reconstructions (17) , online workspaces (18) and continuously updated pipelines that accommodate increasing data flow during infectious disease outbreaks (19) (see further sections for more information and examples of these packages). Given the plethora of options for presenting and visualizing results, and its importance for effectively communicating with a wide audience, choosing the appropriate representation and visualization strategy can be challenging. Recent work on this topic focuses on navigating through all the available visualization options by offering clear guidelines on how to turn large datasets into compelling and aesthetically appealing figures (20)." ] },{ "paper_id": "99da41d8c3a3aebdaf5d889c3958181ae52ff6a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "99e6b617ea3f4d122410160e631c4021e6a8969c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Collected data were entered, refined and analyzed by using SPSS, version 23 software package (IBM, North Castle, NY, USA). Chi square and odds ratio with a concomitant 95% confidence interval (95% CIs) were computed to assess the determinants of non-vaccination.", "Among the high-risk groups that should be vaccinated against seasonal influenza is T2DM patients with real complication [23] .", "Globally, type-2 diabetes mellitus (T2DM) is a highly significant public health problem because of its health and economic impacts and its raising prevalence [1] . In Saudi Arabia, it affects about 46% of men and 44% of female in the \"above 50 years\" age group [2] . T2DM patients are at higher risk by six times to be hospitalized with influenza or pneumonia and three times more likely to die from influenza complications than others in general population [3] .", "Abha City is the capital of Aseer region and situated at an elevation 7500 feet above sea level. It included 11 Primary Health Care Centers (PHCCs) serving a population of 421,921. Aseer region is one of the largest regions in Saudi Arabia and located to the southwestern." ] },{ "paper_id": "99e788920d9bc9e4792a54d4daa546045c04f9cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two-dimensional gel electrophoresis (2-DE) was performed as previously described [6] [7] [8] [9] [10] . Unfractionated whole human serum samples (10 \u03bcl) were subjected to isoelectric focusing in rehydrated precast immobilized dry strips pH 47 (GE Healthcare Bio-Sciences, Uppsala, Sweden). Focused samples in the strips were then subjected to electrophoresis using 818% gradient polyacrylamide gels in the presence of sodium dodecyl sulfate (SDS-PAGE). All samples were analyzed in duplicate.", "Levels of proteins in the gels are presented as means %vol \u00b1 SD of the respective number of samples in each cohort of patients or controls analysed. The Normal test (Z) was used to analyze the significance of differences between control subjects and patients and to examine the correlation between variables. A P-value of less than 0.05 (p < 0.05) was considered statistically significant." ] },{ "paper_id": "99e7ae6647b3aef265d79aa84720e5e5b584118d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Although several therapeutic options have become available for patients with Cutaneous T-cell Lymphoma (CTCL), no therapy has been curative. Recent studies have demonstrated that CTCL cells overexpress the CC chemokine receptor 4 (CCR4).", "Larger quantity of the AAV serotype 8 vectors encoding scFvFc 11A, control minibody specific for SARS [21] , and scFvFc h1567 were produced at Harvard Gene Therapy Initiative (Harvard Institute of Medicine, Boston, MA) and used in the animal studies. ", "Cutaneous T cell lymphomas (CTCLs) are a clinically heterogeneous group of lymphoproliferative malignancies characterized by the clonal accumulation of mature and skin-homing memory T cells. Mycosis fungoides (MF), which is the most common and indolent form of CTCL, accounts for 50%-60% of CTCL cases [1] ; primary cutaneous CD30 + lymphoproliferative disorders, more specifically primary cutaneous anaplastic large cell lymphoma (PC-ALCL) -the second most common CTCL, accounts for circa 30%; and S\u00e9zary syndrome, which is an aggressive leukemic variant of CTCL, affects approximately 5% of patients. These patients exhibit significant immune dysfunction [2, 3] because of the global dysregulation of T cells, which is due to an unknown etiology [4, 5] . Bacterial sepsis is the terminal event in most patients with advanced cancer. Current therapies for patients with advanced CTCL, including its leukemic variant, are only palliative, and extensive long-term remissions are rare. The poor 5-year survival rate of these patients receiving existing therapies clearly emphasizes the need for the development of new targeted therapies in this fatal disease [6] ." ] },{ "paper_id": "99f2888fb4a7fd7ab3cb2e7e9f43f66f7e6a23ce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "99f61ec3a18d65b10e7df69531368c3afae01e45", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Seaweed refers to a diverse group of macroscopic, multicellular, and marine algae. Marine algae have been consumed as sea vegetables for the diet and ingredients in medicine since ancient times in countries including Korea, China, and Japan [1] . One of the earth's affluent sources of natural antioxidants and antimicrobials are seaweeds [2] [3] [4] [5] . They also contain a rich variety of vitamins, such as A, B l , B 12 , C, D, and E; riboflavin; niacin; pantothenic acid; and folic acid, as well as minerals, such as calcium, phosphorus, sodium, potassium, and iodine [6] . Polysaccharides (laminarins and fucoidans), polyphenols such as phlorotannins [7] , carotenoid pigments such as fucoxanthin [8] and astaxanthin, sterols, and mycosporine-like amino acids have been isolated from seaweeds in the past. ", "Ecklonia cava Brown algae Methanol/Ethanol [11, 12] Ecklonia stolonifera Brown algae Methanol/Ethanol [13, 14] Ecklonia kurome Brown algae Methanol/Ethanol [15, 16] Ecklonia maxima Brown algae Methanol [17] Eisenia bicyclis Brown algae Methanol [18] Eisenia arborea Brown algae Methanol:Chloroform [19] " ] },{ "paper_id": "99f6ca41bcf6a11e4a3c722d5e00a9bfec79ca19", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral genome sequencing and modified 5=-3= RACE. Viral RNA was isolated using a QIAamp viral RNA minikit (Qiagen), and cDNA libraries were prepared using Superscript III (Invitrogen). Sanger sequencing was performed on PCR templates generated using Phusion High-Fidelity DNA polymerase (New England BioLabs) and analyzed using Sequencher (Gene Codes) and Lasergene (DNAStar) software.", "Virus capture ELISA. Virus particles were captured using mouse anti-DENV MAbs 4G2 and 2H2 in carbonate buffer. MAbs (see Table S1 in the supplemental material) were diluted to a concentration of 20 ng/l and added to captured virus for 1 h at 37\u00b0C. After incubation with alkaline phosphataseconjugated secondary antibodies (Sigma), p-nitrophenylphosphate substrate (Sigma) was added and absorbance at 405 nm was measured (Bio-Rad). Background signal (optical density at 405 nm [OD 405 ] with no primary antibody) was subtracted from each virus sample, and absorbance was normalized to binding of an antiflavivirus human polyclonal serum sample.", "Phylogenetic analysis. Full-length sequences (\u03fe10,000 nt) were obtained from GenBank and from sequencing of laboratory clones/isolates. Sequences were either manually edited to remove the 5= UTR, left as downloaded, or manually modified to provide the viable 5= UTR sequence variants for Haiti/1225/ 2014 and SPH2015. Multiple sequence alignments were performed using MAFFT (54) . The best substitution model for each alignment was evaluated using jModelTest (55) and identified to be a general time-reversible (GTR) model with an estimated proportion of invariable sites and estimated gamma shape parameter (GTR \u03e9 I \u03e9 G). Maximum likelihood phylogenetic trees were generated using RAxML (56) using 100 bootstrap replicates. Trees were visualized using EvolView (57) ." ] },{ "paper_id": "99f70ba1e268514c14cbbebc998becbc92e2c386", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We did not seek research ethics board approval because this course and its evaluation were designed and conducted as part of routine WHO activities. ", "We report the results for pilot courses by country because the content was iteratively modified after each course. For the implementation in Central Asia, the courses were delivered over 4 months, with the materials unchanged, and we therefore reported results from all participants together. In addition, we report qualitative comments from course participants and facilitators.", "Our approach also has limitations. First, the timeline was long, ", "Facilitators noted that many international critical care guidelines, such as those of the Surviving Sepsis Campaign, were not readily available to participants; therefore, this course introduced some core concepts." ] },{ "paper_id": "99fbfb118e293a937583b9338256f9d216cf8c5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9a0fe7316ddd2f7cfcaa5e7500f781357477f3d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, the present signature has broader applications beyond the scope of the present study that warrant further investigation. Future studies should seek to replicate our findings with patients of different ethnic populations, particularly in countries with a high prevalence of endemic chronic pathogens (e.g. Mycobacterium tuberculosis, Plasmodium and HIV). Follow-up time course studies that assess whether the signature can predict response to treatment and patient prognosis are also warranted.", "Venous blood samples were stored at 4\u00b0C for up to 5 hours, subsequently fractionated into plasma, serum and total leukocytes, and stored at -80\u00b0C. Nasal swabs and stool samples were stored at 4\u00b0C for up to 72 hours and subsequently transported to a certified service laboratory for multiplex PCRs. In the screening phase, host-proteins were measured using enzyme-linked immunosorbent-assay (ELISA), Luminex, protein-arrays and flow-cytometry. The three proteins used in the final signature were measured as follows: CRP using either Cobas-6000, Cobas-Integra-400/800, or Modular-Analytics-P800 (Roche); TRAIL and IP-10 using commercial ELISA kits (MeMed Diagnostics).", "PLOS ONE |" ] },{ "paper_id": "9a13ccd6be3536af404c25e748c34eac997c5d16", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The human enteric ganglia were identified based on their location and morphology. They were composed of small cell groups of enteric neurons, glial cells and nerve fibers. The number, shape, size and orientation of the neurons in each ganglion varied in the different gastrointestinal segments.", "Human Tissue Collection. Human tissue samples of gastrointestinal tracts were obtained from a total of 16 patients, 11 from patients undergoing surgery and 5 autopsy cases from the Peking University Third Hospital (Beijing, PR China) and Shantou Medical University Hospital (Shantou, PR China). None of the subjects was diagnosed with any disease of the nervous system or CF. All methods were carried out in accordance with the approved guidelines of the Institutional Animal Care and Use Committee Guide of Peking University. All experimental protocols were approved by Peking University. The study received local hospital ethics committee approval. Informed consent was obtained from all patients. General information about these cases is listed in Table 1 ." ] },{ "paper_id": "9a1ed211481f2c4e15f48ec3f712e73901eb628a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Organism Disease", "Sequences of multiple isolates of a species are required. Similar limitations as described above.", "Similar limitations as for the above two approaches." ] },{ "paper_id": "9a24a0a85d33c5665889c6de594c961478260c0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations AIC: Akaike Information Criterion; CI: Confidence interval" ] },{ "paper_id": "9a283bfd56827aac7e25105d2d9488714de7769a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at http://www.mdpi.com/1999-4915/11/5/398/s1, Table S1 : Percent identity between NS1 proteins of chapparvoviruses ", "Here an unexplained diarrhea outbreak among dogs was analyzed using viral metagenomics after diagnostic tests were negative for common canine enteric pathogens. The genome of a novel chapparvovirus was characterized and used to perform an epidemiological study to measure its prevalence and possible clinical significance.", "Stool samples were grouped into three pools of three and vortexed in phosphate buffer saline (PBS) with zirconia beads followed by microfuge centrifugation at 14,000 rpm for 10 min. The supernatants were passed through a 0.45 \u00b5m filter (Millipore, Burlington, MA, USA) and digested with a mixture of nuclease enzymes to enrich for viral particles [20, 21] . RNA was extracted using the MagMAX kit (ThermoFisher, Waltham, MA, USA) which was transcribed into cDNA using a random RT-PCR step. The library was generated using the transposon-based Nextera\u2122 XT Sample Preparation Kit (Illumina, San Diego, CA, USA) which was deep sequenced with the MiSeq platform (250 bases, paired-end reads) with dual barcoding. After demultiplexing the reads, they were trimmed and de novo assembled to produce contigs [22] . Both singlets and contigs were compared to all eukaryotic viral protein sequences in GenBank's non-redundant database using BLASTx [23] .", "Pairwise identity matrices using the amino acid sequence of the NS1 wasgenerated using Geneious R11 (Newark, NJ, USA). Amino acid sequences from the NS1 region of all available chapparvoviruses were aligned using MUSCLE and a Maximum likelihood tree was created using the Jones-Taylor-Thorton matrix-based model with 1,000 bootstrap replicates in MEGA6.0 [24] [25] [26] ." ] },{ "paper_id": "9a2c1193b96d3e54da56f17d1060e236df5b0e38", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "9a31e63c4ec26320695ef383dfd8c772d6afc92b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9a4eb1665b578ba6744d7c2a62775379f6fcfc00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Andalusia is a region located in the south of Spain and has an area of 87597 km 2 . The ruminant population comprises approximately 2.6 million sheep, 1.2 million goats and 0.6 million cattle, divided into 13346 sheep flocks, 10789 goat flocks, 8745 cattle herds and 4339 mixed farms.", "The algorithms were programmed in R software [19] . Maps were generated using QGIS [20] .", "Variables assessed included (S1 Table) :" ] },{ "paper_id": "9a512204e9b43d11f12458baaa3db5cb71e5ae16", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9a5586078edf5a43100db04f987d635d39fee4a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To minimize documentation bias, entries were read through in full and assessed for possible re-labelling of ICD-10 codes for outcomes. The review was performed by the principle author (JP), who was blinded to study data from the inclusion. Ambiguous medical entries were discussed with KH. Both researchers are general practitioners.", "Protocol data was merged with inclusion data and transferred to SPSS 23.0 software (IBM, Armonk, NY, USA) for descriptive statistics and for two-sided \u03c7 2 -testing of proportions of categorical variables. Where expected numbers were low, a two-sided Fisher's exact test was used.", "Centor 0-2 (n = 15) 20 (3) 60 (9)" ] },{ "paper_id": "9a63f7c66c750e9076dfb9d04319c1811cd49e00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was supported by a grant from the Deutsche Forschungsgemeinschaft to M. S. (SCH632/17-1) and the Excellence Initiative of the German Research Foundation (GSC-4, Spemann Graduate School) to T. T.", "bat and conventional IAV might have evolved differentially in their respective hosts and probably have undergone co-evolutionary adaptation resulting in an optimal interaction of the eight distinct vRNPs during the genome packaging process. Hence, reassortment of the newly discovered HL17NL10 and HL18NL11 subtypes with conventional IAV and emergence of pandemic reassortant viruses seems rather unlikely.", "The identification of bat IAV expanded the host reservoir of IAV and immediately raised the question of their zoonotic potential. Only recently, it became possible to reconstruct infectious bat IAV from synthetic DNA using reverse genetic approaches [18] . In this review, we recapitulate recent findings on cell tropism, entry processes and the ability of these bat IAVs to exchange genetic information with conventional IAV." ] },{ "paper_id": "9a679e9fdf3590b7f9204c3dc3ff6307c3d4642b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No funding was received for writing this study.", "Availability of data and materials Not applicable.", "Not applicable." ] },{ "paper_id": "9a87a6bf36af7342e6bbb2e13da6181a8c0bab27", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Anti-Flag (M20008), anti-Myc (M20002), anti-His (M20001L), and anti-HA antibodies (M20013) were purchased from Abmart. Anti-\u03b1-tubulin (ab15246) and anti-GFP antibodies (G1544) were purchased from Abcam and Sigma, respectively. Goat anti-rabbit IgG-HRP, goat anti-mouse IgG-HRP, Alexa Fluor 488-labeled goat anti-mouse IgG, and Alexa Fluor 555-labeled goat anti-rabbit IgG secondary antibodies were purchased from Invitrogen.", "HA-K63Ub plasmid was purchased from Rebio (Shanghai, China).", "All statistics were calculated using SPSS version 20. Differences between control and treatment groups were assessed by one-way ANOVA. P < 0.05 is considered statistically significantly different. P < 0.01 was considered highly significant." ] },{ "paper_id": "9a89705854ab91a21b721dd3900a91d6332c1eaf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vital dyes may exhibit non-specific binding, compartmentalization, and leakage (97) . Therefore, it is necessary to minimize variations in preparation of dye, location of dye administration, dye incubation time, imaging duration, and location of imaging. While transgenic animal lines may seem superior in consideration of these limitations, the additional data that can be easily gained with these dyes makes them an irreplaceable boon to live imaging at this current time.", "Abbreviations: 2d2, MOG peptide 35-55 TCR transgenic; APP, amyloid precursor protein; ATP, adenosine triphosphate; CerTN-L15, troponin C expressing Ca 2+ sensing transgenic animal; CFP, cyan fluorescent protein; EAE, experimental autoimmune/allergic encephalomyelitis; EB3, end-binding protein 3; FAD, focal axonal degeneration; FRET, F\u00f6rster resonance energy transfer; GECI, genetically encoded Ca 2+ indicator; GFP, green fluorescent protein; JHMV, John Howard Mueller strain of murine hepatitis virus; LFB, Luxol fast blue; MHC, major histocompatibility complex; MOG, myelin oligodendrocyte glycoprotein; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; MS, multiple sclerosis; NAWM, normal appearing white matter; NPC, neural precursor cell; OT-2, ovalbumin peptide 323-339 TCR transgenic-binding MHC Class II; PLP, proteolipid protein (promoter for mature oligodendrocytes); RAG, recombination activating-gene; RFP, red fluorescent protein; RNS, reactive nitrogen species; ROS, reactive oxygen species; SMI31, Sternberger monoclonal incorporated monoclonal antibody 31; SMI32, Sternberger monoclonal incorporated monoclonal antibody 32; TCR, T-cell receptor; Thy1, thymocyte antigen 1 (promoter for neuron subset); TMEV, Theiler's murine encephalomyelitis virus; TN-XXL, troponin C expressing Ca 2+ sensing transgenic animal; XFP, \"X\" fluorescent protein (any spectral variant of GFP); YFP, yellow fluorescent protein." ] },{ "paper_id": "9a8ffdaee3a800f0e6867b63ffd109e9c30621b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary information accompanies this paper at https://doi.org/10. 1186/s12890-019-0990-8. " ] },{ "paper_id": "9a98026855729dd7aa175ca9ed534a73c7fd9a84", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antibodies against HCV-core, STAT1, IRF-7, PKR, OAS, Mx, IFN-a/b Ra, IFN-a/b Rb, phosphor-NF-kB p65, NF-kB p65, phosphor-ERK, ERK, phosphor-JNK, JNK, phosphor-c-Fos, c-Fos, phosphor-c-Jun, c-Jun, MyD88, IRAK1, and anti-mouse normal IgG were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA). Antibodies against phospho-STAT1, STAT2, and phospho-STAT2 were purchased from Cell Signaling Technology (Cell Signaling Technology, Beverly, MA, USA). The actin antibody was purchased from CWBio (CWBIO, Beijing, China), and the human IFN-a antibody and IFN-a-neutralizing antibody were purchased from PBL Interferon Source (PBL, Piscataway, NJ).", "Whole-cell lysates were prepared by lysing cells with PBS (pH 7.4) containing 0.01% Triton-100, 0.01% EDTA, and 10% cocktail protease inhibitor (Roche). Protein concentration was determined by the Bradford assay (Bio-Rad, Redmond, WA Bio-Rad). Cell lysates (100 mg) were separated by 12% SDS-PAGE and then transferred to a nitrocellulose membrane (Amersham, Bucks, U.K.). The membranes were blocked with 5% nonfat dried milk before incubating with target-specific antibodies. Protein bands were detected with SuperSignal Chemiluminescent reagents (Pierce).", "All experiments were repeated at least three times with similar results. Data were compared by Student's t-test. Results are expressed as mean 6 SD. P,0.05 was considered significant.", "All research involving human participants was approved by the Institutional Review Board of the College of Life Sciences, Wuhan University, China, in accordance with their guidelines for the protection of human subjects. Written informed consent was obtained from each participant.", "The following inhibitors used in this study were used: LY-294002, H-89, Sp600125, U0126, PD98059, SB203580, MG132 and GF10203 were purchased form Tocris Bioscience (Tocris Bioscience, Missouri, USA). ALL of the inhibitors were dissolved in dimethylsulfoxide (DMSO; Sigma, Abitibi belt, Canada)." ] },{ "paper_id": "9a98d242545d1ff31799bc6197ac31e3f2cd4447", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Experimental analysis of an endogenous SOX cleavage sequence confirms role of oligo A sequence and potential structural element", "In practice, for a given control read count, we can compute a threshold for the test read count, beyond which the difference in underlying rates is significant. The software builds a table of the thresholds using bicubic splines so that many locations can be tested efficiently. The peak finding python scripts are attached as S1 Files." ] },{ "paper_id": "9a9f30acc275c64c016770509f9b90eb091e272a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical specimens were homogenized in phosphate-buffered saline and added at different dilutions to confluent layers of Vero cells (ECACC, Cat. No 85020206) cultivated with media with 2% fetal calf serum supplemented with penicillin/streptomycin in 24-well cell culture plates. Once cytopathic effects were evident under the microscope, passaging was initiated.", "https://doi.org/10.1371/journal.pone.0187089.g003", "Inst Lion (Panthera leo) 13 Serostatus was determined by IFA and/or ELISA, whereas an IgG ! 1:320 or differential ELISA > 0.05 is considered positive. Anti-OPV antibodies were detected in multiple animals from different species.", "The female Grey with respiratory symptoms died 12 days after onset of symptoms and was found partly eaten by the others. The other animals recovered uneventfully. Only one of the five animals (Split) did not show any symptoms." ] },{ "paper_id": "9aa51dd5b5755afa670398027272f2e6b4f3d83b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The statistical analysis for the comparison of positively selected sites between different groups was performed using one-sided \u03c7 2 test or one-sided Fisher's exact test in GraphPad Prism version 4.03 for Windows demo. " ] },{ "paper_id": "9ab49a277ef0a3a15aba628771a22b8c2af6ede0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One extreme example of interspecies recombination is in circoviruses that arose by recombinants between plant DNA nanoviruses and mammalian RNA caliciviruses. In this case, the likely mediator has been a retrovirus that retro-transcribed the RNA into DNA (Davidson and Silva, 2008) . Although likely, such events have not been experimentally confirmed and further research is required.", "The author thanks Margaret Bujarska for valuable comments on this manuscript. Jozef J. Bujarski was supported through a grant from the National Science Foundation (MCB-0920617) and through the Plant Molecular Biology Center at Northern Illinois University. The author apologizes to any author that has been omitted in this review for either space reasons or due to the nature of composition of this article.", "Another, not well answered question is how RNA template substrates come together in order to facilitate the switch. One possibility is that secondary structure regions can hybridize in trans bringing the two RNA templates into a local interaction. Such data are available, for instance, based upon limited observations in BMV (Nagy and Bujarski, 1993; Dzianott et al., 1995) or analogously, during switches between dimeric RNAs (within kissing loops) during reverse transcription inside the Human immunodeficiency virus Type-1 (HIV-1) virions , an atypical (+) sense RNA virus.", "The generally accepted mechanism of RNA recombination is currently explained by a copy-choice model where the viral RNA polymerase (RdRp) complex in mRNA viruses [reverse transcriptase (RT) in retroviruses] changes templates during synthesis of the nascent strand (Galetto et al., 2006) . This swapping process generates recombinant RNA molecules of mixed ancestry. Although we begin to understand the nature of these processes, many questions are waiting for an answer. One group" ] },{ "paper_id": "9abc1a92424ffc51803613392c22320da59ebfb1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pntd.0006674.t004" ] },{ "paper_id": "9ac01047c360e0def0d96adf2e59f6e5bd68b3b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The experimental design used in these leaching tests reflects the environment the materials would experience in their intended end application. These results indicate that negligible leaching would occur during normal skin contact or wipe cleaning with detergent.", "Photosensitizer-incorporated samples (30620 mm) were cut and pressed firmly 1000 times with one clean, washed finger.", "While we have focused on the antibacterial activity of our developed materials, future work shall investigate their ability to resist colonization with other pathogens, such as yeasts. Alvarez et. al. (2012) have reported successful inactivation of Candida albicans using polysilsesquioxane films doped with porphyrin [40] .", "Platen pressing was achieved using a Dr Collin P 200 P platen press, capable of maintaining a maximum temperature of 300uC and maximum pressure of 250 bar, with an effective operating area of 1966196 mm 2 . Sections of extruded sheets, one pure HDPE and a second sensitizer-incorporated HDPE, were cut to approximately 1906190 mm 2 and placed one on top of the other inside a PTFE envelope. The envelope was placed on a tray and set in the platen press, pre-heated to 150uC, after which a five stage automated program was initiated, with temperature and pressure not exceeding 150uC and 70 bar respectively." ] },{ "paper_id": "9ac6114492dec5eb4c4afe605b1a83c689df0dec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This assumption leads to the alternative disease severity for-", "Funding statement. This work was funded by National Science Foundation grant no. NSF-EF-08-27416 and by a Complex Systems grant to K.K. from the James S. McDonnell Foundation. K.K. was further supported by the RAPIDD programme of the Science and Technology Directorate, Department of Homeland Security and the Fogarty International Center, National Institutes of Health.", "Based on [42, 49] , we assume NK cells have a half-life of 10 days, corresponding to a value of d N of 0.07 per day. This model has three free parameter combinations (br, k, and q N (q/d)) and one free initial condition I(0). Table 1 provides the specific parameter values used.", "Dengue is estimated to infect 390 million individuals annually [1] , making it the most prevalent arthropod-borne viral disease in the world. The virus is classified into four related, but distinct, serotypes, DENV-1 through DENV-4, each of which is transmitted between humans primarily by the mosquito Aedes aegypti. While most cases are asymptomatic, disease symptoms, occurring in approximately one quarter of dengue infections [1] , range in severity from 'breakbone' dengue fever (DF) to life-threatening dengue haemorrhagic fever (DHF), which is characterized by vascular plasma leakage and may lead to circulatory shock known as dengue shock syndrome (DSS) [2] ." ] },{ "paper_id": "9ac7ff68cae35ddd75b3e7ca8d267ac78d46daa6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting information S1 File. Data file. (XLSX) " ] },{ "paper_id": "9ad61dcfb0a71ebe88c497995cf569eba5e73f8c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Immunofluorescence staining BHK-21 cells were seeded on the chamber slides (Nunc International, Denmark) and transfected as above. 24 h post transfection, the slides were dried, fixed with acetic acid and ethanol (1:3) for 15 min and rinsed thoroughly in distilled water. Fixed cells were re-hydrated in PBS, and incubated for 24 h at 4\u00b0C with anti-HCV core rabbit polyclonal antibodies (1:50) in the blocking buffer (PBS with 2.5 mM EDTA and 1% BSA). Secondary antibodies were goat anti-rabbit immunoglobulins labeled with TRITC (1:200; DAKO, Denmark). Slides were then mounted with PermaFluor aqueous mounting medium (Immunon, Pa., USA) and read using a fluorescence microscope.", "Peptides covering core amino acids 1-18, 1-20, 23-43, 34-42, 133-142 and a control peptide TTAVPWNAS from gp41 of HIV-1 were purchased from Thermo Electron GmbH (Germany). Core proteins representing aa 1-152 of HCV 274933RU and aa 1-98, and 1-173 of AD78P1 were expressed in E. coli and purified by chromatography as was described earlier [69, 70] . Purified proteins were dissolved in PBS." ] },{ "paper_id": "9adb161f0e769ea8de09f4138cc40f206d586003", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As expected, the 20 ISs possessing a stimulatory structure all display a higher than average G.nt \u22121 (Supplementary Table S8 ).", "Our objective was to statistically assess the prevalence of each X XXZ ZZN motif in the genome of various E. coli strains. The rationale was that if a given motif induces by itself frameshifting at a significant level (i.e. at a biologically detrimental level), then it should be counterselected and, therefore, be underrepresented in E. coli genes.", "We selected a subset of 18 X XX.Z ZZ.N patterns with a negative z-score and an in vivo frameshifting efficiency of more than 0.10% in the absence of stimulators listed below. Three non-underrepresented patterns (C CC.U UU.C, A AA.G GG.A and A AA.G GG.G) were also considered because they exhibit high level frameshifting.", "above background probably not as a result of frameshifting but because these sequences, together with the following G, could act as SD sequences and direct low level initiation on the -1 frame AUA codon present 7 nt downstream (see legend of Figure 3 ). The other oddity, C AA.G, was nearly 10 times above background (0.93%) but only when the PK stimulator was present: this was likely due to -1 frameshifting caused by the high shiftiness of the lysyl-tRNA UUU (41, 49) combined to the high efficiency of the PK stimulator." ] },{ "paper_id": "9adcc3de8f703fe97f002f97da996f4924d5f5ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9ade0372676abdf2b9bcc87c5d924bc945be0a92", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coding-complete genomes of two human coronavirus OC43 strains and one NL63 strain were obtained by metagenomic sequencing of clinical samples collected in 2017 and 2018 in Kilifi, Kenya. Maximum likelihood phylogenies showed that the OC43 strains were genetically dissimilar and that the NL63 strain was closely related to NL63 genotype B viruses.", "Sequencing reads (paired, 2 \u03eb 250 bp) were filtered, kmer normalized, and de novo assembled as previously described (5) by using the settings specified in Table 1 . Reference OC43 and NL63 genomes (GenBank accession numbers AY391777 and NC_005831, respectively) were used to transfer annotations to assembled contigs using Geneious (R9). MAFFT v.7.221 (6) was used for sequence alignment using the param-eters \"-localpair -maxiterate 1000.\" Maximum likelihood phylogenies were estimated in RAxML v.8 (7) using the general time-reversible (GTR) nucleotide substitution model and gamma distribution of among site rate variation.", "Viral RNA was extracted from nasopharyngeal swabs using TRIzol LS reagent (Invitrogen) followed by TURBO DNase treatment (Invitrogen), according to the manufacturer's instructions. cDNA was synthesized with SuperScript III reverse transcriptase (Invitrogen) with random hexamers, and double-stranded cDNA was synthesized with Klenow polymerase (5 U; New England BioLabs). Libraries were prepared using the Nextera XT kit (Illumina) according to the manufacturer's instructions and sequenced using the MiSeq reagent kit v2 (500 cycle) (Illumina) on an Illumina MiSeq sequencer." ] },{ "paper_id": "9ae5509495e79b5d077ce582f092950b38982dfa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The normalized intensity texture is defined by:" ] },{ "paper_id": "9ae96559416973a6d3bb6ddd5d446bfb4aaf40a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request." ] },{ "paper_id": "9aed1e2e3dc529e3863b89a60bb4e377e8c3a3e6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following the release of the viral genome, replication takes place in specialized membrane compartments or virus-induced inclusion bodies via reconditioning of the host intracellular machineries.", "Recent categorization places viroporins into two major classes based on the number of TMD that are then further classified into A or B subclasses based on their membrane topology [2] . Single TMD viroporins in subclass A have their N terminus facing the ER lumen while those in subclass B have their C-terminal tails in the ER lumen. For Class IIA and IIB viroporins, both N-and C-terminus are inside the ER lumen or the cytoplasmic matrix, respectively (Figure 1 ). An additional third class of viroporins may be necessary as viroporins with three-pass TMD have been proposed, such as the non-structural protein 4 (NSP4) of rotavirus [49] and 3a of severe acute respiratory syndrome SARS-CoV [31]. Due to their high structural variability under different conditions, solving the architecture of viroporins under physiological environment has been difficult. However, recent advancement in technology such as the ability to characterize protein structure at the atomic resolution using nuclear magnetic resonance (NMR)" ] },{ "paper_id": "9aee0cad00998f83f85e815527be1a7ac00881ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Isatis indigotica is an herb distributed widely in China and traditionally used in clinical treatment of viral diseases like influenza, hepatitis, and encephalitis [1, 2] . Accumulated experimental evidence indicates it and related components as associated with antiviral activity against influenza A, SARScoronavirus, foot-and-mouth disease, rabies, and human immunodeficiency virus type 1 (HIV-1), among others [1, [3] [4] [5] [6] [7] [8] [9] . Among natural compounds identified from I. indigotica-for example, indican, isatin, indirubin, and indigotin [9] -indirubin exhibits multiple immunomodulatory and antiviral effects [5, 8] .", "JEV strain T1P1 was used as previously described [13] , vero cells for JEV amplification maintained in Dulbecco's modified Eagle's medium (DMEM), as well as BHK-21 cells used to determine JEV plaques grown in minimum essential medium (MEM) supplemented with 10% fetal bovine serum (FBS). Human promonocytic HL-CZ cells cultured in RPMI-1640 medium served to determine JEV yield in vitro.", "2.9. Statistical Analysis. ANOVA using SPSS program (version 10.1, SPSS Inc., IL, USA) or Student t-test analyzed data, P value less than 0.05 considered statistically significant. " ] },{ "paper_id": "9b034efc9d262e8687f1ad7adb78fa7374d3e5ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Instantaneous hazard curves were constructed for each timeinvariant covariate with the 'epiR' library in R [56] , categorising continuous variables into quartiles. The instantaneous hazard rate, h(t), is the rate at time t, that a randomly-selected individual from the population yet to experience an event, experiences the event at time t [43] , and is mathematically defined as:", "Daily rainfall data were available from 127 weather stations in the study extent.", "(DOCX)" ] },{ "paper_id": "9b0c87f808b1b66f2937d7a7acb524a756b6113b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "[47] Molecules developed by the university scientists inhibit two coronavirus enzymes and prevent its replication. The discovered drug targets are said to be more than 95% similar to enzyme targets found on the SARS virus. Researchers note that identified drugs may not be available to address the ongoing outbreak but they hope to make it accessible for future outbreaks.", "Rapid diagnostics plays an important role in disease and outbreak management. The fast and accurate diagnosis of a specific viral infection enables prompt and accurate public health surveillance, prevention and control measures. Local transmission and clusters can be prevented or delayed by isolation of laboratory-confirmed cases and their close contacts quarantined and monitored at home. Rapid diagnostic also facilitates other specific public health interventions such as closure of high-risk facilities and areas associated with the confirmed cases for prompt infection control and environmental decontamination [11, 101] .", "Supplementary Materials: The following are available online at www.mdpi.com/xxx/s1, Table S1 : Example of full search strategy in Pubmed, Table S2 : Google Search: 2019-nCoV diagnostics, Table S3 : Summary of diagnostic assays developed for 2019-nCoV, Table S4 ", "Laboratory diagnosis can be performed by: (a) detecting the genetic material of the virus, (b) detecting the antibodies that neutralize the viral particles of interest, (c) detecting the viral epitopes of interest with antibodies (serological testing), or (d) culture and isolation of viable virus particles." ] },{ "paper_id": "9b1ed09206bdc3bc05e88bd694bf863dbd1f973b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Study Identifiers:", "\u2022 Title: Expression profiling in patients presenting to hospital with fever.", "\u2022 Ethics:" ] },{ "paper_id": "9b26e1267786a1ec02d8ede9599ec416b7e9f3cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported in part by the SIRIC BRIO (Site de Recherche Int\u00e9gr\u00e9e sur le Cancer-Bordeaux Recherche Int\u00e9gr\u00e9e Oncologie). The authors would like to thank Patricia Th\u00e9bault for helpful discussions as well as the referees for their constructive comments.", "To compare the classification hardness of the three tasks, we generated from a representative subset of sequenced organisms from Genbank (September 2014 download, 25,624 bioprojects, 100% of viruses, archaea and bacteria, 24 eukaryotes with 18 plants) 100 sets of 10,000 randomly chosen contiguous genomic", "(1) Given a sample of bacterial sequences, to assign each of them to a phylum (e.g., Proteobacteria) or to a class (e.g., Gammaproteobacteria); (2) Given a sample of viral sequences, to assign each of them to a group (e.g., dsDNA) or to a family (e.g., Plasmaviridae); and (3) Given a sample of sequences, to assign each of them to a firstlevel domain (e.g., bacteria, archaea, eukaryota, or virus)." ] },{ "paper_id": "9b2cf86c30314f63a3aeafcf615dc9a5dee997df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Toxoplasmosis is a disease of major medical importance. Toxoplasma gondii causes congenital infections responsible for stillbirths and spontaneous abortions [1] [2] [3] [4] [5] . In addition, it causes neurologic disorders, uveitis, and systemic infections in immune-compromised patients. Toxoplasmic encephalitis is a cause of morbidity and mortality in those with congenital disease and persons with AIDS [6] . T. gondii is acquired by consumption of lightly cooked meat, especially lamb and pork contaminated with bradyzoites [7, 8] or by ingestion of food or water contaminated with oocysts containing sporozoites, which are the product of a sexual cycle in the intestine of the cat [8, 9] .", "Mice were euthanized 7 to 14 days after immunization. Spleens were harvested, pressed through a 70 \u03bcm screen to form a single-cell suspension, and depleted of erythrocytes with AKC lysis buffer (160 mM NH 4 Cl, 10 mM KHCO 3 , 100 M EDTA). Splenocytes were washed twice with Hank's Balanced Salt Solution (HBSS) and resuspended in complete RPMI medium (RPMI-1640 supplemented with 2 mM L-GlutaMax" ] },{ "paper_id": "9b2ee0cdb3b92a377acec0e84a63090005b6b7ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sequence of amino acids constituting the protein", "The variability of the individual peptide ratios used to calculate a given protein ratio", "The authors declare that they have no competing financial interests." ] },{ "paper_id": "9b4d56c6c289c7f86b4f01b1b5569ae7e2bf6920", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9b4e7443a59fb1fd764f172bd67a0f73da1ec3cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In negative and positive ion modes, flavone aglycones mainly gain fragment ions by the reverse Diels-Alder (RDA) reaction and the loss of CO (28 Da). The characteristic fragmentation behavior of compound 35 is shown in Figure 4 ", "The Scientific World Journal ", "The Waters ACQUITY UPLC instrument (Waters, MA, USA) coupled with Waters Synapt HDMS G1 (Waters, Manchester, UK) via an electrospray ionization (ESI) interface. The UPLC analytical conditions were the same as the UPLC analysis described above. The full scan mass spectra data were acquired in positive and negative ion modes. Acquisition parameters are as follows: capillary voltage was 3000 V for ESI (+) and 2600 V for ESI (\u2212); cone voltage was 45 V; the ESI source temperature was 100 \u2218 C; the desolvation temperature was 350 \u2218 C; the nitrogen (N 2 ) was used as desolvation gas at flow rates of 600 L/h for both ESI (+) and ESI (\u2212); and the range of full scan was set at m/z 150-1000 Da. The version of analysis software was Mass Lynx V4.1." ] },{ "paper_id": "9b56c6e647ccdb8b5d534c0689a71efb7728a311", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An influenza virus with a deficient RBS was generated using reverse genetics. The amino acids at the positions 194 and 195 were targeted since they are crucial for receptor binding [11, 12, 27, 28] .", "To this end, the HA gene segment of influenza virus A/Puerto Rico/8/34 (A/PR/8/34) was modified by site directed mutagenesis (QuikChange multi site-directed mutagenesis kit, Stratagene, Leusden, Netherlands) to yield HA with L194A and Y195F amino acid substitutions [11, 12, 27, 28] .", "Finally we demonstrated that human DC can capture influenza A virus through interaction with DC-SIGN which leads to infection of these cells." ] },{ "paper_id": "9b5a336dab77072af21829b37a7b8318ae1dec6d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Richard E. Lloyd (Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA) described RNA granules and how these unique cytoplasmic structures may cross-talk with the innate immunity system. Two types of dynamic cytoplasmic RNA granules are conserved from yeast to mammals. Stress granules (SGs) contain stalled translation initiation complexes, and processing bodies (PBs) are enriched with RNA decay factors. Since both types of RNA granules sequester translationally silenced mRNAs, RNA viruses antagonize RNA granules for replicative advantages. Enteroviruses and other picornaviruses repress SG and PB formation via multiple mechanisms, however, enteroviruses principally block SG through cleavage of the dominant SG-nucleating factor Ras GTPase-activating protein-binding protein 1 (G3BP1). The Lloyd lab has shown that G3BP1 functions as an activator of innate immunity via stress-induced recruitment of PKR to SGs and also activates NF-\u03baB. In addition, G3BP1 undergoes reversible phosphorylation and methylation changes during stress and recovery which are required for G3BP1 to nucleate stress granules, and which regulate innate immune activation. These findings support an emerging concept that SGs function as signaling platforms to activate or enhance innate immunity and better define the antagonistic relationship of viruses with RNA granules.", "Claire Birkenheuer (Louisiana State University, Baton Rouge, LA, USA) showed high resolution mapping of host RNA polymerase II following herpes simplex virus type 1 infection, to more clearly understand how the virus repatriates the enzyme for viral transcription. Precision nuclear run-on (Pro-seq) is used to map RNA Polymerase II (Pol II) location on actively transcribed genomes to a single base pair resolution. Using this technique, the Baines' lab characterized Pol II occupancy on host genes 3 h post-infection with herpes simplex virus 1 (HSV-1). Their data shows that even at this early time point Pol II is removed from most host genes. However, they also noted gene-specific effects in which HSV-1 increases Pol II occupancy and modulates its location at every stage of transcription: from Pol II recruitment and initiation, to promoter proximal pausing, elongation, and termination. To assess the effects of this modulation, the Baines' lab used quantitative reverse transcription PCR (qRT-PCR) with total RNA, nuclear messenger RNA (mRNA), and cytoplasmic mRNA to analyze transcript levels of STUB1, USP8, MYC, EGR1, FOSB, c-FOS, and JUNB. Most genes with increased Pol II occupancy or recruitment had higher levels of total RNA and nuclear mRNA. In contrast, termination extension usually decreased cytoplasmic mRNA levels. Functional clustering revealed a profile that, they hypothesize, reflects a cellular environment permissible for virus replication. Thus, HSV-1 reduces host gene expression, working in combination with the virion host shut-off protein (vhs) in some cases, while ramping up host gene transcription to transcend the effects of vhs in other cases. They note that Pro-seq overcomes technical difficulties associated with Pol II chromatin immune precipitation and sequencing while providing higher resolution, and holds promise for use with other viruses that alter Pol II activity." ] },{ "paper_id": "9b5d40c82f807736a65c47b53824f36e220ef9d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "FIGURE 4. One-year mortality rates of ARDS between 1997 and 2011 in Taiwan. Blue diamonds: male; red squares: female; green triangles: total population.", "Most epidemiological studies of acute respiratory distress syndrome (ARDS) have been conducted in western countries, and studies in Asia are limited. The aim of our study was to evaluate the incidence, in-hospital mortality, and 1-year mortality of ARDS in Taiwan.", "We conducted a nationwide inpatient cohort study based on the Taiwan National Health Insurance Research Database between 1997 and 2011. A total of 40,876 ARDS patients (68% male; mean age 66 years) were identified by International Classification of Diseases, 9th edition coding and further analyzed for clinical characteristics, medical costs, and mortality." ] },{ "paper_id": "9b5f7347b52c46ad29b1991560e6251bfdfd8df2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The RT-qPCR was performed using QIAGEN OneStep RT-PCR Kit (QIAGEN, Hilden, Germany) with SYTO 9 (Life technologies, Carlsbad, CA, USA) as the fluorescent dye. Thirty \u00b5L reactions including 3 \u00b5L template input were run on a Light Cycler 96 RT-qPCR System (Roche Diagnostics, Mannheim, Germany). Reaction conditions were: 30 min RT at 50 \u2022 C, 15 min at 94 \u2022 C for inactivation of reverse transcriptase (RT), followed by 40 cycles of 94 \u2022 C for 30 s, 50 \u2022 C for 30 s and 72 \u2022 C for 1 min. Melting curve analysis was performed under the condition of 95 \u2022 C for 60 s, 40 \u2022 C for 60 s, 65 \u2022 C for 1 s, then followed by a slow increase from 65 \u2022 C to 95 \u2022 C with a speed of 0.07 \u2022 C per second.", "The human coronaviruses (HCoVs) are enveloped, nonsegmented positive strand RNA viruses. They belong to the family coronaviridae, genus coronavirus [1, 2] . Their genomes are 27-31 kb in length. The 5 end of their genome contains two large open reading frames (ORFs), ORF1a and ORF1b, encoding the replicase complex. Genes encoding the structural proteins, i.e., spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins, are downstream of the ORF1b [1] . Six coronaviruses (HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HCoV-HKU1, and MERS-CoV) are known to infect humans [2] . HCoV-229E and HCoV-OC43 were identified in the 1960s [3, 4] . HCoV-NL63 and HCoV-HKU1 were identified in 2004 and 2005, respectively [5, 6] . SARS-CoV was identified during the severe acute respiratory syndrome (SARS) epidemic in China in 2003 [7, 8] , and MERS-CoV was identified during the Middle East respiratory syndrome (MERS) epidemic in the Middle East in 2012 [9] .", "To obtain well performance, the primer concentration of the assay was optimized as 0.8 \u03bcM, 0.8 \u03bcM, 0.8 \u03bcM and 0.2 \u03bcM of HCoV-229E, -NL63, -HKU1, and -OC43 specific primers, respectively, by orthogonal experiments (Supplemental result and Figure S2 )." ] },{ "paper_id": "9b7a0ad7b6c7f59e7a6cf1dc9d07912a273d19b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Text S1 Estimating the daily probability of epidemic initiation Found at: doi:10.1371/journal.pone.0000143.s001 (0.08 MB PDF)", "This paper adds to previous work [5] [6] [7] [8] by simultaneously including a wider range of epidemiological factors and possible interventions, such as elevated in-flight transmission, flight duration, the effect of wearing of mask during flight, early presentation of cases among travelers, and quarantining all passengers from a flight with a detected case at arrival.", "Authorities are assumed to implement one of two control options when detecting an infected traveler by arrival screening. Under option one (individual-based removal), all passengers who test negative are released immediately and only passengers who test positive are isolated. Under the second option (flight-based quarantining), authorities prevent all passengers from dispersing into the community until the last person has been screened from that flight. Should any one passenger be detected as infected then all passengers will be quarantined, as previously recommended [5] ." ] },{ "paper_id": "9b8a2314912eaeb1c509cf88492f463148a0a9ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses (CoVs) are a type species of enveloped viruses with a single-stranded positive RNA genome of approximately 26-32 kilobases. CoVs belong to the Coronaviridae family, classified into the order Nidovirales along with Arteriviridae [1, 2] . All CoVs share similarities in the organization and expression of their genome, which is arranged into open reading frame (ORF) 1a, ORF1b, S, ORF3, E, M and N in order, with both termini flanked by 5\u2032-and 3\u2032-untranslated regions. CoVs are separated into four genera based on phylogeny: alpha-CoV, beta-CoV, gamma-CoV and delta-CoV. The beta-CoV genus contains important veterinary and human etiological agents, such as mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV). MHV infects mice liver or neuron, but it is a well-studied coronavirus model for similar patterns of pathogenesis [5] . SARS-CoV is the etiological agent behind an outbreak of severe respiratory disease through China during 2002-2003 [6] [7] [8] .", "Oncotarget 49657 www.impactjournals.com/oncotarget MHV N protein blocks IFN-\u03b2 production by targeting molecule(s) upstream of RIG-I and MDA5" ] },{ "paper_id": "9b960b5f7c871b2dbb4ee3ba78392ca6a333224b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "If quantitative PCR (qPCR) assays of both 5'UTR and envelope RNAs are performed serially, and data expressed as [5' UTR RNA]/[Env RNA] for each sample, then a numerical expression describing changing quasispecies complexity over time may be obtained.", "Frequency Genetic Distance 0", "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "9bacd5e08a587ec2c4a6f367044249fa7c0129bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All work with WNV was performed at BSL-3 following CDC guidelines. Vero E6 cells (ATCC CRL 1586) were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and 2 mM L-glutamine. WNV strain NY-99 was used for the assays and was propagated in a complete Minimum Essential Medium Eagle (MEM-E) media obtained from Sigma-Aldrich (St. Louis, USA), supplemented with 10% FBS, 100 units/mL penicillin, 100 \u00b5G/mL streptomycin and 2 mM L-glutamine. The virus stock was divided into 1 mL aliquots and stored at -80 \u00baC.", "Virus plaque forming units were measured using an agar overlay method described previously [17] with minor modifications." ] },{ "paper_id": "9bad9c5864165815b35dd2c78cd0ed7b285f0517", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An AIDS vaccine could also be designed to induce a combination of antibodies targeting different sites, such as CD4bs and CD4i, in gp120 to confer breadth, potency, and protection [34] .", "The global pandemic of acquired immunodeficiency syndrome (AIDS) caused by HIV continues to expand, and this is still a serious global health problem. It is reported that about 34 million people are living with HIV globally in 2012. The Joint United Nations Programmed on HIV and AIDS (UNAIDS) reported that 2.5 million people became newly infected in 2011 and 1.7 million people died that year from AIDS related causes [1] . Unfortunately, there is no effective preventive vaccine in the world. Therefore, whether we can get safe and effective preventive vaccines is a hotspot and difficulty in the field of current international AIDS research.", "The second wave of candidate vaccines was designed of vectors, such as weakened adenovirus that encodes the HIV-1 proteins Gag, Pol, and Nef, to stimulate HIV-1-specific cellular immunity. One such vaccine candidate is V520 developed by the researchers at Merck & Co. [4] [5] [6] . Although this vaccine could elicit strong immune response and showed protection in animal models, the clinical trial for V520 (STEP) was discontinued in 2007 because this vaccine did not provide protection in vaccinated human subjects and was even associated with increased risk of HIV infection in some recipients [7] [8] [9] ." ] },{ "paper_id": "9bb4db31c5490bc2f6f5e3c54d3a2ed7ce69048a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9bbac1f67fbab1d4f3e9a20387a63989bf40bfad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These results show that APCs, including DCs, are essential for the GA-mediated shift in Th-cell phenotypes and indicate that DCs are an important target of the immunomodulatory effects of GA.", "Currently, a head-to-head race for approval had initially developed between two under-the-spotlight oral immunomodulatory agents-fingolimod and cladribine [109] .", "The immunomodulatory effect of fingolimod acts in two pathways:" ] },{ "paper_id": "9bbaed357d3aa8c39af2508fb1ca775f8708ec41", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The expression vectors were transformed into E.coli strain BL21(DE3). A 5-ml overnight culture of these transformed bacteria in Luria-Bertani (LB) medium containing 50 mg/ml kanamycin was used to inoculate 1 liter of LB medium containing 50 mg/ml kanamycin and 20 mM ZnCl 2 . Bacteria were cultured at 37uC with shaking, until reach an optical density at 600 nm of 0.6, then transferred to 16uC, induced by 0.4 mM IPTG overnight.", "All antibiotics used in this study were purchased from J&K SCIENTIFIC LTD., except for kanamycin purchased from Sangon biotech(Shanghai) Co., Ltd.. ", "Comparison the complex structure of NDM-1/ meropenem with VIM-2/meropenem and FEZ-1/ meropenem" ] },{ "paper_id": "9bbe789148466f6667a673885d4adddedf6b74e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The third-generation virus sub-cultured in MDBK was used for complete genome amplification. Twelve pairs of primers (described in Table S2 in the supplementary material) were used for the whole genome amplification. PCR products were purified, cloned into pMD18-T, and sequenced. Sequences data were compiled to generate the complete genome sequence of BPIV3. Sequences were assembled using SeqMan (DNASTAR, Madison, WI, USA).", "Bovine parainfluenza virus type 3 (BPIV3) was one of the most important viruses associated with BRDC in cattle [3, 5] . It was first isolated in 1959 and first identified in cases of BRDC [3] . BPIV3 is an enveloped, non-segmented negative-strand RNA virus within the genus Respirovirus. BPIV3 induces respiratory tract damage and immunosuppression. More severe secondary bacterial and mycoplasma infections are caused in susceptible animals in instances of high stress, such as transportation and feedlot situations [4] .", "Up to now, based on phylogenetic analysis, BPIV3 has been divided into three genotypes: Genotype A, genotype B, and genotype C [6, [8] [9] [10] [11] [12] [13] [14] [15] [16] . Multiple BPIV3 genotype A strains have been isolated in USA, China, Argentina, and Japan [8, 10, 12, 16] . Genotype B was initially identified in Australia [6, [8] [9] [10] [11] [12] [13] [14] [15] [16] . Isolation of BPIV3 genotype C, first identified in China, has also been conducted in South Korea, Japan, Argentina, and USA [5, 8, 10, 11, 15, 16] . A high seropositivity rate for BPIV3 in dairy cattle indicated that a high level of BPIV3 infections occurs. Many efforts have been made focusing on the prevention and control of BRDC in order to reduce production losses in the livestock industry [17, 18] ." ] },{ "paper_id": "9bbf07c4bf022a0695b79b87cb4299f6a8d18831", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For homology searches against known genes, unigenes longer than 200 bp are widely accepted as valid sources, making them sufficient for the effective assignment of functional annotations [21] . Most of the unigene sequences were longer than 200 bp and were valid in this study (85%; 23,158/27,229)." ] },{ "paper_id": "9bcf1d2a543d586018a6b55fd349a8c8b6b614a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was carried out in accordance with the recommendations of the USDA-ARS-National Animal Disease Center Animal Care and Use Committee and the protocol was approved by the Committee.", "pneumonia consisting of alveolar septal thickening with mononuclear cells as well as fibrin and collagen ( Figure 3E) .", "B. bronchiseptica strain KM22 is a virulent phase I swine isolate initially cultured from a herd with atrophic rhinitis, and has been used extensively by our group for studies (17, 18, (24) (25) (26) . B. bronchiseptica inoculum was prepared as previously described (18) . Pigs were inoculated intranasally (IN) with 1 ml (0.5 ml/nostril) of the final inoculum, which was confirmed to be 6(log 10 ) CFU/ml. LAIV vaccine was prepared and used as previously described (8 " ] },{ "paper_id": "9bd22fc1297bd20710ca26f6e79b6339d576bb74", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 7: 37 | DOI:10.1038/s41598-017-00084-0", "Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 37 |" ] },{ "paper_id": "9be40fd878c72fc18e2557ccc3cc8b4ef95a926d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Funding: This work was supported in part by Public Health Service awards F30 AI122563, R01 AI032539, T32 AI060525, and T32 GM007347 as well as by the Vanderbilt Lamb Center for Pediatric Research and the Heinz Endowments." ] },{ "paper_id": "9be5f21d6d5bc49f664d559e63c68f6410a39ae4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Horse anti-WNV serum was diluted with equal volumes of saline, and 1/2 volume of a saturated ammonium sulfate solution was then added. The solution was mixed gently at room temperature for 30 min and then centrifuged at 5000 rpm for 20 min. The precipitates were dissolved in saline before 1/3 volume of ammonium sulfate was added. After incubation at room temperature for 30 min, the solution was centrifuged at 5000 rpm for 20 min. The precipitates were dissolved in saline and dialyzed overnight at 4 \u2022 C to remove the salt.", "Two 4-6-year-old healthy brown horses (300-350 kg in weight) that had no detectable antibodies against WNV were provided by the Military Hongshan Stud Farm (Changchun, China), and were intramuscularly multi-point injected in the submandibular region and backside with 0.5, 1.5, 2.0, 3.0, and 5.0 mg of WNV-VLP with Freund's adjuvant (complete/incomplete) (Sigma, St. Louis, MO, USA) on days 0, 7, 14, 28, and 42 (5 times), respectively. The sera were collected from the jugular vein 2 weeks after each immunization, and were stored at \u221220 \u2022 C for further analysis. ", "The pH of the horse anti-WNV serum was adjusted to 3.3 with 1 mol/L HCl. Pepsin was activated by a NaAc solution (pH 3.3) and then added to the diluted horse antiserum and digested at 30 \u2022 C for 2.5 h. The reaction was stopped by adjusting the pH to 7.2 with 1 mol/L NaOH. Then, the solution was applied to a Protein-A column, followed by a Protein-G column. The purified protein was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by Coomassie blue staining. The F(ab ) 2 purity was analyzed with a thin slice scan, and the protein was stored at 4 \u2022 C until use." ] },{ "paper_id": "9be783afc22075545d893250f5c7f1ef7317cf37", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Third, some new TCM drugs are being successfully developed based on many years of clinical practice; these drugs can generally have precise effects and have only less adverse side effects [14] . Only minimal adverse effects were reported for Chinese medicines used in treating type 2 DM indicating certain advantages in the prevention of diabetes and delay of its complications [15] .", "TCM is more complex and comprehensive than Western medicine in terms of finished product quality, whether for a single drug prescription (prescriptions consisting of a single medicinal material) or a compounded Chinese medicine (prescriptions consisting of two or more medicinal materials). There is a lack of studies on material basis, active ingredients, and mechanism of action and no scientific and reasonable quality control indicators and methods [35] . Therefore, the uniformity, safety and effectiveness of inter-assay stability for TCM products cannot be guaranteed.", "With the SWOT analysis of the internal and external environments, we can observe the advantages, disadvantages, opportunities and threats of TCM during the internationalization process (Table 2) . Overall, the advantages outweigh the disadvantages, and the opportunities outweigh the threats.", "In the process of the internationalization of TCM, we must emphasize the advantages to avoid the disadvantages, seize the opportunity to overcome the threats, carry out specific internationalization processes, avoid detours and promote a rapid internationalization process. " ] },{ "paper_id": "9be8c80283a7fed59057d7788eb2850708f45450", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where A is the absorbance at \u03bb exc .", "Furthermore, polymer microgels are frequently used as nanoreactors for the in situ synthesis of metallic NPs 4 , and small particles decorating the microgel are successfully formed 5 . However, the control over the metallic NP structure and distribution is rather difficult.", "The exciting electronic, optical, catalytic and antimicrobial properties of metal NPs can be stymied by their tendency to aggregate. To overcome this issue and provide metallic nanoparticles with additional features, the hybridization with polymeric materials is a successful strategy. In this regard, polymer micro/nanogels exhibit high colloidal stability, great versatility in their chemical and topological composition, drug loading and functionalization capabilities 1 that make them unique vehicles and reservoirs for metal nanoparticles 2,3 . Additionally, the permeability of the gel-system coating allows a controlled loading and release of bioactive molecules and drugs." ] },{ "paper_id": "9becd2019e0ff5052d47d3d23201cc521375cb03", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We used two databases to illustrate our method: one from GPs in private practice and the other from an HED.", "Data on outpatients consulting at an HED were obtained during 2006 (n = 45,055) in a major university hospital in Paris. The chief complaints of every consulting patient during 2006 were recorded in free text by the triage nurse.", "Each patient-practitioner encounter is described with a chain of linguistic information describing the chief purpose of the consultation. That information is then translated into ICPC-2 code [19] . It can be coded automatically [19, 20] or by an expert." ] },{ "paper_id": "9bf1241b4b35efdf7be808ce9bc8d44939f1e21e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9bfc043d8a0d90892e9183f75dbe141a30fd68b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MetaPhlAn2 pipeline: https://bitbucket.org/biobakery/metaphlan2 MEGAN6 tutorial: https://software-ab.informatik.uni-tuebingen.de/download/ megan6/manual.pdf Source code for SORTMERNA: https://github.com/biocore/sortmerna/releases/tag/2.1", "Animal (n = 25) 289 \u00b1 64 *** 214 \u00b1 64 5 \u00b1 0.1 *** 4.5 \u00b1 0.5 0.9 \u00b1 0.1 0.9", "Biomethanization BF1 (n = 16) 161 \u00b1 13 ** 119 \u00b1 54 4 \u00b1 0.7 *** 3.8 \u00b1 0.4 0.8 0.8 BF2 (n = 16) 273 \u00b1 73 *** 117 \u00b1 48 4 \u00b1 1 4 \u00b1 0.7 0.9 0.9", "The asterisk (*) indicates the statistical significance of the Mann-Whitney U test (ns P > 0.05; * P \u2264 0.05 * * P \u2264 0.01; * * * P \u2264 0.001; * * * * P \u2264 0.0001).", "\u2022 Guillaume Bilodeau and Caroline Duchaine conceived and designed the experiments, authored or reviewed drafts of the paper, and approved the final draft." ] },{ "paper_id": "9bfe62e7518a5ca9952dac249961763cd167523f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9bff285847e6573b613d937df23f57355afcbd5f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NS2 interacts with p7 in a fluorescence resonance energy transfer with fluorescence lifetime imaging microscopy (FRET-FLIM) assay", "293T human embryo kidney cells (HEK293T), U2OS human osteosarcoma cells (American Type Culture Collection) and Huh-7 human hepatoma cells [55] were grown in Dulbecco's modified essential medium (Invitrogen) supplemented with 10% fetal bovine serum.", "The endoglycosidase digestions were performed following the manufacture's instructions (NEB). Briefly, cell lysates containing 20 mg of protein were denatured in EndoH (PNGase) denaturing buffer (0.5% SDS, 1% 2-mercaptoethanol) for 10 min at 100uC. Then, the lysates were incubated or not with 1 ml of EndoH (PNgase) for 20h at 37uC.", "A dedicated photo-counting and timing electronic card (SPC 830 TCSPC card, Becker and Hickl) was coupled to the Leica internal detector and used to classify the photon emission in time to determine the lifetime of the donor protein. To excite the samples, Chameleon Ultra2 (Chorent Inc) biphoton was used at 830 nm at an average power of 0.13 mW/mm2 [60, 61, 62] ." ] },{ "paper_id": "9c135ad34ff29dfceef573e3fd18be8b3599ac72", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9c1b3d1c613332e439a3a925588b2ee3b9bcf18e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Raw mass spectrometry data were analyzed using MaxQuant version, 1.5.2.8 (Cox and Mann, 2008) , using default settings and LFQ/iBAQ enabled, and searched against the Human Uniprot/ Swissprot database (downloaded June 26, 2016, 20197 entries). The data was further processed using Perseus software, version 1.5.8.5 (Tyanova et al., 2016) .", "Total RNA was isolated using the RNeasy Mini Kit (QIAGEN), and cDNA was generated using the iScript cDNA synthesis kit (Bio-Rad). For quantitative RT-PCR, cDNA was amplified using SsoAdvanced SYBR Green Supermix (Bio-Rad) on a MyIQ thermocycler (Bio-Rad). Primer sequences can be found in Supplementary file 6.", "Tags within a given region were counted and adjusted to represent the number of tags within a 1 kb region. Subsequently, the percentage of these tags as a measure of the total number of sequenced tags of the sample was calculated.", "Heatmaps and bandplot profiles were generated using fluff (Georgiou and van Heeringen, 2016) ." ] },{ "paper_id": "9c1c6037784f97a987e79a92077dad0d252b7236", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "EV-B93 3C protease expression and purification was conducted as previously described 41 . Other proteases were obtained from the European Virus Archive (http://www.european-virus-archive.com/).", "When determining the inhibitory parameters of an inhibitor, the assay set-up was as mentioned but 1 ml DMSO solution of inhibitor was used instead of probe or nucleophile. Different concentrations of inhibitor were tested at least as duplicates and the pseudo-first-order association kinetics (k obs ) were determined using GraphPad Prism. The slope of a plot of the different k obs values against the inhibitor concentration yielded k inact /K I .", "Step 2", "alone was investigated as an inhibitor of the 3C protease of Coxsackie virus B3 (Fig. 2) ." ] },{ "paper_id": "9c2755f8ae42badb521b1c6afcb99874d21657e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceived and designed the experiments: DT. Performed the experiments: DT. Analyzed the data: TZ. Contributed reagents/materials/analysis tools: TZ. Wrote the paper: DT. Manuscript submit and revise: DT.", "With regards to biodefense, international cooperation is even more absent. Biodefense is often considered as a sensitive field, and it may be simpler to collaborate well in other scientific areas such as cancer or HIV research. Lessons from such fields could be applied to the area of biodefense collaboration.", "The development of laboratory biosafety and biodefense capabilities require shared experience to face the pressing questions of modern-day threat. Cooperation can benefit each other, including further discussions into the making or revision of biological agent category lists." ] },{ "paper_id": "9c2aa72aa0640f5224c2663ae55c35f75b8889c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Under the constant threat of an infection, cellular organisms have developed multiple layers of different defence mechanisms (not solely) against these genetic parasites to protect themselves and their genomic integrity.", "This phylogenetic reconstruction of the NCLDVs demonstrated a 'turbulent evolution', which was dominated by gene gain, while on other branches substantial gene loss was apparent. The branches that include giant (protist) viruses are the most prominent gene gainers, whereas NCLDVs infecting animal hosts have undergone considerable gene losses, a sort of 'genome contraction' during their evolution from ancestral protist viruses. It was hypothesised that in animals, the selective pressure for virus genome size is stronger than in protists, yet its mechanism needs to be analysed .", "After this short general introduction on the highlights of the topic, we focus on the coevolutionary processes of selected DNA viruses: adeno-, herpes-, NCLD-, polyomaand circoviruses." ] },{ "paper_id": "9c2c85e5e00aed9437ada6a93643d1aa660b59c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data analysis. Data were analyzed using the Statistical Package for the Social Sciences (SPSS v19; SPSS, Chicago, IL). Categorical variables were summarized by frequencies and numerical variables were summarized by means with standard deviations if normally distributed and medians, interquartile ranges (IQRs), and ranges if not normally distributed.", "Ethical approval. Experimental research reported in this study has been performed with the approval of the ethics committee of Zhejiang Provincial Center for Disease Control and Prevention (Zhejiang CDC). Human research was carried out in compliance with the Helsinki Declaration. All participants provide their written informed consent to participate in this study.", "Despite widespread elimination and control efforts during the 20th century, malaria continues to be the most important parasitic disease known to humankind. According to the World Health Organization (WHO) estimate in 2014, there were 3.2 billion people at risk of being infected with malaria and developing disease; 198 million cases of malaria and 584,000 deaths occurred globally in 2013. 1 Over the span of the last century, almost half of the world's countries have successfully eliminated malaria. 2 Although great success has been achieved since the launch of national malaria control program in 1955, malaria remains a serious public health problem in China. [3] [4] [5] The Chinese Notifiable Disease Reporting System (NDRS), which was initiated in the 1950s, is the fundamental communicable disease surveillance system in China. After the outbreak of severe acute respiratory syndrome (SARS) in 2003, the Chinese government strengthened the construction of public health information system. On January 1, 2004, the Real-Time Notifiable Infectious Disease Reporting System was put into use nationwide, realizing the timely online monitoring of individual cases, which marks a leap in the surveillance of communicable diseases in China." ] },{ "paper_id": "9c33102dc55e225f5836f9cf9c9d5f5b918820d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IFN-alpha2 (Mm00833961_s1), IFN-alpha4 (Mm00833969_s1), IFN-alpha5 (Mm00833976_s1), IFN-alpha6 (Mm02524285_g1), IFN-alpha9 (Mm00833983_s1), IFN-alpha11 (Mm01257312_s1), IFN-alpha12 (Mm00616656_s1), IFN-al-pha13 (Mm00781548_s1), IFN-alpha14 (Mm01703465_s1),IFNbeta (Mm00439546_s1). The gene for mouse hypoxanthine guanine phosphoribosyl transferase-1 (HPRT-1, Mm00446968_m1) was used to calibrate the mRNA levels. Quantitative analysis was performed using the SDS 2.1 software (Applied Biosystems). mRNA levels were calculated by the following formula: relative expression = 2'(2(Ct(Target)-Ct(Endogenous control))*f, with f = 10 000 as an arbitrary factor.", "Chromatin Immunoprecipitation (ChIP) assays were performed as described [104] . Briefly, cells were cross-linked with 1% formaldehyde and sonicated nuclear extracts were mock-immunoprecipitated or immunoprecipitated with anti-tetraacetylated histone H4 (Upstate). Recovered DNA aliquots from these samples and from input extracts were amplified with real-time PCR using the LightCycler II system (Roche) and Quantitect SYBR Green PCR Kit (Qiagen). Enrichments at specific chromatin loci are shown as the amount of immunoprecipitated DNA in the percent of total input chromatin. The following primers were used: IL -6 promoter: TGG GGA TGT CTG TAG CTC ATT and CAT AGC GGT TTC TGG AAT TGA, TNF promoter: GGG CAG CCC CAG AGG GAA TGA ACT C and TAT GGC AGA GGC TCC GTG GAA AAC TCA CT, Topoisomerase 3b promoter: AGT CCG AGA ACA GCC TGG GT and AGT TGT GCT GCC CAC AGA GG, l5 promoter: TCC CCA TTG CCA GAT AGA GAC ACA and TGG GCC CAA CAG ATT AAC ACA GAG.", "The critical role of IRF-7 but not IRF-3 in Ad-induced type I IFN production", "Type I IFNs represent one of the host's most important antiviral defense mechanisms. The type I IFN family comprises different IFN-a subtypes, a single IFN-b and other less well characterized proteins [11] . All IFN-a species and IFN-b interact with the same IFN-ab cellular receptor, the activation of which mediates a wide range of direct and indirect innate antiviral or antimicrobial effects and modulates the antiviral adaptive immune response [12, 13, 14] ." ] },{ "paper_id": "9c35a7f4d301162bfc79c1d7174a234ab94c2c46", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "None of the authors has any potential financial conflict of interests related to this paper.", "Dogs were euthanized at chronic phase (11 months after infection) using sodium pentobarbital (Barbithal, Holland Animal Health, Mexico) as a general anesthetic at a dose of 30 mg/kg applied intravenously, and then a lethal dose of intravenous 15% potassium chloride was administered.", "In some reports that used mongrel dogs for experimental CD cardiomegaly, chronic myocarditis with variable reduction levels of cardiac muscle, fibrosis, and adipose tissue replacement was the most frequent findings [10, 13, 14] ." ] },{ "paper_id": "9c39ab56559377e3b362be55e8e989e059a01fb0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mammalian lungs are designed to optimize exposure of blood to oxygen. To achieve this, two intertwined and highly branched tree-like tubular systems, one conducting air and the other conducting blood must develop in a coordinated way to generate the millions of functional alveolar gas-exchange units [1, 2, 3] .", "Animals were housed in individually ventilated cages under specific pathogen free conditions, in full compliance with FELASA (Federation of Laboratory Animal Science Associations) recommendations, at the Animal House Facility of the Foundation for Biomedical Research of the Academy of Athens (Athens, Greece). All procedures for care and treatment of animals were approved by the Institutional Committee on Ethics of Animal Experiments and the Greek Ministry of Agriculture (Permit Number: K/1054).", "One way analysis of variance (One-way ANOVA) combined with ''Bonferoni's Multiple Comparison Test'', was done using GraphPad Prism. (*/ # ) P,0.05, (**/ ## ) P,0.01, (***/ ### ) P,0.001.", "Total RNA from mouse lungs was isolated using the Tri-Reagent protocol (Sigma, St. Louis, MO) and the yield and purity of RNA was determined electrophoretically and spectrophotometrically. After DNase treatment with RQ1 RNase-Free DNase (Promega, M160A), 2 mg of RNA were reverse transcribed into cDNA using M-MLV Reverse Transcriptase (Promega, M170B) and random primers (Invitrogen, 58875) according to the manufacturer's instructions. The primer pairs for real-time PCR were designed using Beacon Designer v7.01 software (Premier Biosoft International, Palo Alto, CA). Sequences for the primer pairs used are given in table S1. The PCR reactions contained SYBRH Green ER TM qPCR Super Mix Universal (Invitrogen, 11762-500), 200 nM of each primer (Invitrogen, Carlsbad), and 0.2 ml of cDNA template in a 20 ml reaction volume. RT-qPCR cycling parameters were initial incubation at 50uC for 2 minutes, denaturation at 95uC for 10 minutes followed by 50 cycles of 15 seconds at 95uC and 40 seconds at 60uC. Data collection was carried out using a Chromo4 Real-Time PCR detector (BioRad) and analyzed with Opticon Monitor 3 expression analysis software (BioRad). Relative levels of mRNA expression were calculated according to the DDCt method [34] ." ] },{ "paper_id": "9c3a27a40bb77b4b2663e8033413b4036b1ef43c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animals. All animal procedures were conducted in strict accordance with federal and institutional guidelines and were approved by the Kansas State University Institutional Animal Care and Use Committee. The animal care protocol included provisions for a humane endpoint as determined by the discretion of the attending clinical veterinarian. Methods to minimize pain and distress included the avoidance of prolonged restraint and the inclusion of euthanasia as an intervention strategy.", "VA supplementation is an obvious solution to VAD. The WHO currently recommends large-dose, oral Vitamin A supplementation at immunization contact points 1 . VA supplementation has a significant positive impact on incidence of measles [54] [55] [56] . However, its effects on other diseases are less clear. Some studies have reported significant reductions, while others have found little effect or even increased incidence and severity of diarrhea and respiratory infections in children receiving vitamin A supplementation 36, [57] [58] [59] [60] . Studies specifically examining the impact of oral VA supplementation during RSV infection have shown no effect 36, 57, 61 or in one study, have observed increased length of hospital stay for infants receiving VA 58 . We speculate that oral supplementation at the time of vaccination may not be ideal for addressing VAD and its effects on the respiratory immune response, primarily due to kinetics. A similar principle applies to supplementation during acute infection. Changes in VA homeostasis due to acute inflammation likely limits VA access to inflamed tissues and prevents any modulation to the ongoing immune response. Thus, in the future, we are interested in investigating the utility of a mucosal VA supplementation strategy, which may be a more efficient approach to addressing the immunologic lesions observed in VAD individuals during respiratory vaccination or infection.", "Bronchoalveolar lavage fluid collection. Pre-challenge bronchoalveolar lavage (BAL) fluid was collected from all animals, 4-5 days prior to BRSV infection, using a protocol we have previously described 63 . A modified stallion catheter was blindly passed through the nose and advanced through the trachea until lodging in the bronchus. A total of 180 mL of sterile saline was divided into three aliquots. An aliquot was introduced to the lower respiratory tract, followed by immediate suction to obtain lower airway washes. The procedure was repeated twice more. All three aliquots were pooled at the end of the procedure. BAL samples were kept on ice, filtered over sterile gauze, and centrifuged at 200 x g for 10 minutes. Contaminating red blood cells were removed using hypotonic lysis. Cells were washed, counted and stimulated as described below for antigen recall assays.", "Human respiratory syncytial virus (RSV) is a leading cause of severe acute lower respiratory tract disease in infants and young children worldwide 20, 21 and accounts for up to 70% of hospitalized bronchiolitis cases in industrialized countries 22 . Globally, there are an estimated 33 million new episodes of HRSV-associated disease in children under 5 years of age with more than 100,000 resultant deaths 23 . Severe RSV infection has been linked with the development and exacerbation of recurrent wheezing and asthma 24 , and is a predisposing factor to the development of otitis media 25 . Despite the high burden, treatment for RSV infection is largely supportive, and there is no vaccine available to prevent or reduce disease." ] },{ "paper_id": "9c437ea3972c987ed041833f65535b2d4300e095", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Methods: Cellular flu-specific immune responses were assessed by whole-blood antigen stimulation assay, and humoral responses by a single radial hemolysis test.", "The 2009 H1N1 pandemic H1N1 influenza (flu) A (pdmH1N1) was first reported in Mexico and California [1] . As the virus spread globally, it became evident that the infection was of moderate severity with a broad clinical spectrum of symptoms [2] . Early data from Mexico suggested that pdmH1N1 may cause severe respiratory illness in otherwise healthy young and middle-aged people [3] . It is now estimated that in the United States pdmH1N1 caused higher rates of hospitalizations and deaths in children and adults 18-64 years of age than the flu of the previous season, but lower rates of clinical events in adults over 65 years of age [4] . This finding supports the notion that previous exposures to H1N1 in older individuals provides higher cross-protective immune responses than in younger individuals [5] . In the autumn of 2009, pdmH1N1 vaccines (pdm vaccines) were available across the globe, it was estimated that pdmH1N1 vaccination prevented 4,000-10,000 hospitalizations and 200-500 deaths in the US [6] ." ] },{ "paper_id": "9c438a13c9083e842b860ae7b477e671e60fb4cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recently it was reported that compounds such as dihydroartemisinin-fluoroquinolone, synthesized using both artemisinin and fluoroquinolone, induced selective anti-tuberculosis activity [45] .", "The Loss of Body Weight Vomiting Diarrhea", "Currently, various infectious diseases such as tuberculosis, Influenza, Severe acute respiratory syndrome (SARS), Middle east respiratory syndrome (MERS), Zika, and Ebola have caused serious concerns in public health fields worldwide. Tuberculosis, among these infectious diseases, is one of the most dangerous infectious factors, and it was responsible for the most deaths of the world's population in 2014 and 2015 [1, 2] . The increase of HIV co-infection and the rapid appearance of MDR or XDR strains represent an urgent need to develop novel, effective, and safe anti-Mtb drugs for treating TB.", "(A) (B) Figure 6 . Changes of the body weight in rats following administration of artemisinin and artesunate." ] },{ "paper_id": "9c492e76efc05b17e67a3e09c7e3ac44cca89e29", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total WBC counts in EDTA-stabilized blood were measured using Beckman-Coulter Ac.T diff 2 automated haematological analyzer (Coulter Corp, A Beckman Coulter Co, Miami, Florida)." ] },{ "paper_id": "9c5447c495379f968aacd114e73a03039ccfd69d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "antigenic studies, as well as for the development of effective preventive and control vaccines against PEDV.", "All data were analyzed using one-way ANOVA and values of P < 0.05 were considered statistically significant. Submit your next manuscript to BioMed Central and we will help you at every step:" ] },{ "paper_id": "9c59d3a8be1e640d85fc5105dca9e530680c230a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Before each survey, trained research assistants would give detailed instructions. The participants were then asked to finish the questionnaire independently.", "(DOC)" ] },{ "paper_id": "9c6df064dc7aedea41eca964a69131e37f330f6b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lungs were dissected en bloc and right lobe was inflated with 10% neutral buffered formalin to their normal volume, and submersed in the same fixative solution. Following fixation, lungs were embedded in paraffin, sectioned, and stained using hematoxylin and eosin (H&E). Four parameters of pulmonary inflammation were evaluated: peribronchiolitis (inflammatory cell infiltration around the bronchioles), perivasculitis (inflammatory cell infiltration around the small blood vessels), interstitial pneumonia (inflammatory cell infiltration and thickening of alveolar walls), and alveolitis (cells within the alveolar spaces). Slides were scored blindly on a 0 to 4-severity scale (absent, minimal, mild, moderate and marked).", "All animal work presented in this paper was conducted under strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The animal protocols (protocol # 2 and 7) were approved by the Institutional Animal Care and Use Committee (IACUC) of Sigmovir Biosystems Inc. (SBI) (OLAW assurance #A4642-01). SBI has USDA breeding and Research licenses (51-A-0031 and 51-R0091, respectively), and is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC).", "Consistent with the results of pulmonary inflammatory gene expression, lung pathology was moderate and peaked at 48 h p.i., and was characterized by the presence of a mild, but significant, increase in cumulative pathology that included bronchiolitis, perivasculitis, interstitial pneumonia, and alveolitis ( Fig 3A) . Examination of H&E-stained lung sections revealed areas of extensive peribronchial and alveolar cellular infiltration in VANBT-infected animals, which were not evidenced in the lungs of control UV-VANBT inoculated animals ( Fig 3B) ." ] },{ "paper_id": "9c776ca426a931dbbd3e34cd0b817adb19add3f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In immunocompromised patients such as in patients infected by human immunodeficiency virus and suffering acquired immune deficiency syndrome (HIV/AIDS), JC PyV-induced PML is rather common. Despite the fact that PyVs were discovered 45 years ago, effective treatments are currently lacking. However, recent advances in PyV research have made therapeutic development a realistic possibility.", "While ERAD's ability to rectify the protein-misfolding problem is essential to maintain overall cellular protein homeostasis (proteostasis), its central feature-presence of a physical conduit between the ER luminal and cytosolic space-can be exploited during pathogen-host interactions. And indeed, nowhere is this more evident than during ER-to-cytosol membrane penetration by SV40. ", "In the first step, a misfolded ER luminal (or transmembrane) client is identified ( Figure 2 , step 1). Identification is accomplished through recognition of improper carbohydrate residues or erroneous disulfide bond pairing, resulting in aberrant exposure of hydrophobic patches or oligomer formation in a misfolded polypeptide. ER-resident factors including protein disulfide isomerase (PDI) family members [26] , BiP [30, 31] , and enzymes involved in carbohydrate recognition and processing such as ER class I \u03b1-mannosidase (ER ManI) [32] , ER degradation-enhancing \u03b1-mannosidase-like (EDEM)1/3 [33] , and osteosarcoma amplified 9/(OS-9/XTP3) [34] [35] [36] , all serve critical roles during this initial committed step of the ERAD pathway." ] },{ "paper_id": "9c7ef724d9e2d25e32eceb1ed8a9fe417fe32309", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Many studies that have evaluated bovine serum administration have shown this to be an effective source of exogenous passive Ig for newborn calves [2, 5, 6, [12] [13] [14] [15] .", "Fractionated blood products in farm animal transfusion medicine include packed RBCs, platelet-rich plasma (PRP), leukocyte-rich plasma, normal bovine plasma, and hyperimmune serum. Of these, only two are frequently used in cows and are bovine plasma and hyperimmune serum [1, 2] .", "This prospective study was performed as an internal quality control at the Veterinary Transfusion Unit Blood Bank of University of Milan (REV). Blood was collected from 20 healthy lactating adult Holstein Friesian donors. Before and after blood collection all cows were given a standard physical examination [19] . A total volume of 4 L of blood was collected from each cow. The protocol for this study was approved by the Institutional Ethical Committee for Animal Care at University of Milan (http://www.unimi.it/cataloghi/comitato etico/CE 19dic2012 verbale.pdf). A closed-collection system was used, consisting of sterile human 450 mL blood bags (TERUMO CPDA-1 triple blood bag, GRIFOLS, Italy) containing 20 mL of citrate-phosphate-dextrose-adenine-1 (CPDA-1) anticoagulant, used to collect blood from each cow. From each cow 8 bags of whole blood were collected. Whole blood was collected in a standard fashion from each cow by jugular venipuncture, using a 16-gauge needle attached to a triple-bag closed-collection system on a blood mixer. The closed-collection system consisted of a primary bag containing 63 mL of citrate phosphate-double dextrose solution as anticoagulant, an additive bag that contained 100 mL of additive solution (SAG-Mannitol), and 1 empty satellite bag." ] },{ "paper_id": "9c85321b0b17004a81cb40cc67c05d8939d03f12", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Serum-amyloid alpha (SAA) is an endogenous FPR2 agonist secreted by liver or macrophages in response to inflammatory stress and, more notably, tissue damage. In endothelial cells, SAA enhances the expression and activity of Tissue Factor-a protein necessary for clotting and wound repair-while additionally inhibiting the activity of Tissue Factor Pathway Inhibitor. Both functions were demonstrated to be the result of FPR2 activation [88] . SAA, via FPR2 activation, additionally increases the production of the wound-healing chemokine, CCL2, by vascular endothelial cells [89] . More recent studies have demonstrated the role of an SAA-FPR2 axis in neovascularization in the cornea as well [90, 91] .", "Leukocyte infiltration is a hallmark of inflammatory responses. This process depends on the bacterial and host tissue-derived chemotactic factors interacting with G-protein-coupled seven-transmembrane receptors (GPCRs) expressed on the cell surface. Formylpeptide receptors (FPRs in human and Fprs in mice) belong to the family of chemoattractant GPCRs that are critical mediators of myeloid cell trafficking in microbial infection, inflammation, immune responses and cancer progression. Both murine Fprs and human FPRs participate in many patho-physiological processes due to their expression on a variety of cell types in addition to myeloid cells. FPR contribution to numerous pathologies is in part due to its capacity to interact with a plethora of structurally diverse chemotactic ligands. One of the murine Fpr members, Fpr2, and its endogenous agonist peptide, Cathelicidin-related antimicrobial peptide (CRAMP), control normal mouse colon epithelial growth, repair and protection against inflammation-associated tumorigenesis. Recent developments in FPR (Fpr) and ligand studies have greatly expanded the scope of these receptors and ligands in host homeostasis and disease conditions, therefore helping to establish these molecules as potential targets for therapeutic intervention.", "FPRs are a class of seven-transmembrane, G-protein-coupled receptors (GPCRs) that interact with a remarkably diverse range of ligands. As demonstrated, these ligands may originate from pathogens, the host, the synthetic peptide or compound library, or even non-host multicellular organisms. With such diverse agonist binding capacity, it is not surprising that FPRs may be either detrimental or beneficial in different pathophysiological conditions. Though the majority of these agonists have been known for more than a decade, newer studies are finding novel roles for these ligands in treatments for conditions ranging from anxiety and mental health disorders to arthritis and wounds. The field of FPR agonist studies has demonstrated the potential of these molecules to have therapeutic mechanisms useful for medicine. In addition to the vast number of agonists summarized here, there are also extensive lists of antagonistic ligands that may also provide protective mechanisms in various diseases [23, 44] . Thus, further exploration of FPRs and ligands as therapeutic targets would be highly beneficial to diseases including cancer, sceptic shock, arthritis, and many other inflammatory pathologies. ", "Human LL-37 is an antimicrobial peptide that induces Cxcl13 and Tnfsf13b transcription, as well as B cell activation and proliferation via FPR2. It also contributes to the maintenance of B-cell germinal centers in Peyer's Patches of the gut [92] . LL-37 also promotes the growth of both colorectal and ovarian cancer cells [93, 94] . The murine homologue of LL-37, Cathelicidin-related antimicrobial peptide (CRAMP), is similarly an Fpr2 agonist and has been shown to promote atherosclerosis and DC maturation [95, 96] . CRAMP also plays a pivotal role in maintaining the homeostasis of the colon mucosa and microbiota balance, demonstrating its potential as a therapeutic molecule [97] . The list of host-derived FPR (Fpr) ligands is shown in Table 4 . Vasoactive intestinal protein FPR2 [65] Lipoxin-A4/Apsirin-triggered lipoxins Fatty Acid FPR2 [103] " ] },{ "paper_id": "9c85b0dd795a95e53b5cdc4b3bc8c46d1bd5e154", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA extraction was done with Purelink RNA Mini Kit, P/N: 12183018A by Invitrogen, USA, as per manufacturer's instructions." ] },{ "paper_id": "9c8a35cb4e5844ead3ef3214b059ba238cd70362", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome [62] 2000 Gut 776 Article", "Title", "Antibiotic resistance in Campylobacter strains isolated from animals, foods, and humans in Spain in 1997-1998 [72] 2000 Antimicrobial Agents and Chemotherapy", "The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences [61] 2000 Nature 1223 Article" ] },{ "paper_id": "9c8a4fff809abaa0b5ede6a28db62da5edd082e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The software to use after the assembly step has been uploaded at https://github.com/ jensfriisnielsen/sequence_recurrence. Sequence clusters that have been described in detail throughout the manuscript have been included as supplementary files.", "Supplementary Materials: The following are available online at http://www.mdpi.com/1999-4915/8/2/53, Table S1 : Virus discovery pipelines, Table S2 : Distribution of library types, Table S3 : Methods in cancer samples, Table S4 : Clustering parameters, Table S5 : Feature descriptions, Table S6 : Datasets in clusters, Figure S1 : Clustering performance.", "The International Agency for Research on Cancer (IARC) lists several biological species with carcinogenic potential in humans [1] . This list comprises a bacterium (species Helicobacter pylori), three parasitic flukes (Clonorchis sinensis, Opisthorchis viverrini and Schistosoma haematobium), and seven viruses: human papillomaviruses (HPV), human immunodeficiency virus-1 (HIV-1), Epstein-Barr virus (EBV), hepatitis B and C virus (HBV and HCV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human T-cell lymphotropic virus type 1 (HTLV-1).", "The datasets went through a sequential pipeline with modules (in order) of preprocessing, computational subtraction of host sequences, low-complexity sequence removal, sequence assembly, clustering, association to metadata features, and taxonomical annotation. Figure 1 provides a schematic representation of the pipeline used to identify recurrent sequences across related samples." ] },{ "paper_id": "9c930b820306b68f83b4706c10aae46bf2ed70b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PG-4 -+ + + + + + + + +", "PG-5 -+ + + + + + + + +", "PG-6 -+ + + + + + + + +", "PEDV is a member of the Coronaviridae family and is an enveloped, single-stranded, positive-sense RNA virus with a 28 kb genome encoding non-structural proteins and four major structural proteins including spike, envelope, membrane, and nucleocapsid proteins [8] . The main method of PEDV transmission is fecal-oral; however the ability of the virus to aerosolize and be transported over large distances by air is being considered as an additional important route of virus transmission [9] ." ] },{ "paper_id": "9c983db27cc8ff3e50008d8d2bc803e14da7d38b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The virus titers were determined by plaque assay on porcine kidney stable cell (PS) monolayers under a carboxymethyl-cellulose overlay, as described previously [25] . Infectivity was expressed as plaque-forming units (pfu) per ml (or g of brain tissue).", "The differences in survival time of infected mice were analyzed by survival analysis (log-rank Mantel-Cox test). All other data were analyzed by one-way ANOVA (Newman-Keuls multiple comparison test). Data without normal distribution were transformed by use of the X' = ln(X) formula. All analyses were performed using GraphPad Prism 5.00 (GraphPad Software, Inc., USA); p-values < 0.05 were considered significant." ] },{ "paper_id": "9ca17c3afd9591b30a57bb00f6af2957f37c1b8a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consequently, further immunological methods should be established to develop a more robust serological surveillance of PToV.", "Meishan SC-2011-A1 - - C T G T T - - - C - G - T T A T T G G C T G T SC-2011-A2 - - C T G T T - - - C - G - T T A T T G G C T G T Mianyang SC-2011-B1 - - C T G T T C G - C C G - T T A T T G G C T G T SC-2011-B2 - - C T G T T C G - - C G - T T A T T G G C T G T Dazhou SC-2011-E T C C T G T T - - - C - G - T T A T T G G C T G T Ziyang SC-2011-F - - C T G T T C G - C - A T T T A T T G G C T G T Chengdu SC-2012-C1 - - C T G T T C G - C - A T T T A T T G G C T G T SC-2012-C2 - - C T G T T C G - C - A T T T A T T G G C T G T Deyang SC-2012-D1 - - C T G T T - - - C - A G T T A T T G G C T G T SC-2012-D2 - - C T G T T - - - C - G - T T A T T G G C T G T Suining SC-2012-G - - C T G T T C G C C - A G T T A T T G G C T G T Zigong SC-2012-J T C C T - T T - G - A T G - T T A - T G G C T G TLuzhou", "The PCR products were gel-purified using a Gel Extraction Kit (Tiangen Biotech, Beijing, China). The purified target fragments were ligated into a linear vector pMD19-T (Takara, Dalian, China), and the recombinant plasmids were transformed into Escherichia coli DH5\u03b1 competent cells (Invitrogen). The identity of the constructs was confirmed by sequencing (Invitrogen)." ] },{ "paper_id": "9cab4a22cd4bba56a4f3a8fb9040bb96a8ea48a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. Statistical analysis was performed with Prism 5.0 or 7.0 software. Data are presented as mean \u00b1 S.E. Statistical significance of differences between groups was evaluated using student t-test, one-way or two-way ANOVA as indicated. A value of p < 0.05 is considered to be statistically significant.", "Published: xx xx xxxx OPEN www.nature.com/scientificreports/" ] },{ "paper_id": "9cac297cbe600d362c95485037335e959e4cf36e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9cb23e4f04ec3120b42a3c5bb0d21053f9f8a8ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dogs as the most popular pets have spread globally, leaving a tremendous ecological paw print and market potentiality [1] . In the world wide, there is an increasing interest in keeping of dogs for various reasons hence it is necessary to prevent important fatal infectious diseases of dogs [2] .", "Polymerase chain reaction was set up by adding 10 \u03bcL Premix Taq\u2122 (TaKaRa Taq\u2122 Version 2.0) (TaKaRa, Dalian, China), 1 \u03bcL PCR primers (10 \u03bcM each), 1 \u03bcL DNA template and the reaction volume was made up to 20 \u03bcL using nuclease free ddH 2 O. PCR amplification was performed with an initial denaturation step of 94\u00b0C for 5 min, 35 cycles of denaturation at 94\u00b0C for 20 s, annealing at 50\u00b0C for 20 s, and elongation at 72\u00b0C for 20 s, followed by a final extension step of 72\u00b0C for 8 min. characterised to assess the antigenic type according to previous report [33] .", "The swabs were squeezed and the liquid was extracted using the Magnetic Viral DNA Kit (Nanoeast, Nanjing, China) according to manufacturer's instructions. Viral RNA of non-CPV strains was extracted using Trizol Reagent (TIANGEN, Beijing, China) according to manufacturer's instructions. The concentration of DNA templates was quantified by Nano-300 Micro Spectrophotometer (Allsheng, Hangzhou, China). All DNA/RNA templates were stored at \u2212 80\u00b0C till further use.", "The polymerase chain reaction (PCR) primers were especially designed from consensus genome regions of VP2 gene according to previous study [32] . The biotin-labeled forward primer was 5'-Biotin-AATGTACCACCAGT TTATC-3\u2032 and the digoxigenin-labeled reverse primer was 5\u2032-digoxigenin-TGGGAGGCTCTTAGTTTAG-3\u2032. The primers were assessed using NUPACK web software (http://www.nupack.org/) and their specificity was further verified by BLAST tool (http://blast.ncbi.nlm.nih.gov/Blast .cgi). The upstream and downstream primers are located in the conserved region of the VP2 gene and reasonably avoid the mutation sites [33] . Primers were synthesized by GENEWIZ (GENEWIZ, Suzhou, China)." ] },{ "paper_id": "9cd6f7eef808b5362ce36f7b92a50cb28238136c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SQ and ZL wrote the paper and conceived and initiated the study. SQ, WZ, and XJ extracted the data set. SQ, WZ, XJ, ZS, YZ, and YX performed the analysis. All authors reviewed the manuscript.", "This work was supported by the National Natural Science Foundation of China (31572500 to ZL).", "Data were analyzed as mean \u00b1 SEM. Differences among groups were performed by one-way ANOVA using GraphPad Prism software. The significance level for all analyses was set as *p < 0.05, **p < 0.01 and ***p < 0.001." ] },{ "paper_id": "9cda7cc79c0dee43d486d8165181e5b5ca09a817", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Controlling zoonotic disease outbreaks has become ever more important; it has been estimated that since 1940, about 60 % of the emerging infectious diseases affecting humans globally, but mainly in developing countries, have originated from animals, both domestic and wild [16] . Additionally, One Health research potentially offers great benefits compared to traditional, singledisciplinary research, with participatory research adding people's own cultural logic and potentially alternative, policy-relevant perspectives compatible with local cultural values and livelihood priorities.", "In contrast, ABMs are in-silico experiments able to incorp orate comprehensive and detailed biological, physical, en vironmental and behavioral factors. Compared to analyt ical approaches, they require a minor level of abstractions, which might be ad advantage for integration with participatory modeling.", "Example V. Diversity of modelling approaches challenges the conclusions of other types of modelling", "relative comparison between different options, and to make a detailed analysis of how much, why and how people make decisions. More detail can be found in published research e.g. [17] ." ] },{ "paper_id": "9cdbf5aaebee9f6b33cb9fbbdcd1a68d53727289", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quantification of lectin + microglia and evaluation of the CD68 + and GFAP + particle perimeter was performed using ImageJ threshold/analyze particle features. For high magnification images (CD68/Iba1 and GFAP/ lectin immunofluorescence) sections were analyzed using a BX61 microscope equipped with a confocal disk scanning unit (Olympus).", "Cytokine and chemokine mRNA determination by quantitative real-time polymerase chain reaction Total RNA was isolated and purified from aliquots of homogenized brain samples using Trizol reagent (Sigma-Aldrich). Homogenates with Trizol were roughly shaken and disrupted using the Precellys homogenizer system (Bertin technologies). RNA quantity was determined using a NanoDrop 1000 (Peqlab). Up to 3 \u03bcg of total RNA was reverse-transcribed into cDNA by using SuperScript III Reverse Transcriptase (Invitrogen). Realtime quantitative PCR assays were performed on a StepO-nePlus Real-Time PCR System (Applied Biosystems) using TaqMan\u2122 Gene Expression Assays (Applied Biosystems) for Gapdh, Plp1, Mbp, Cnp, Cxcl9, Cxcl10, Tnf, Il6, Ifng, Ccl2, Ccl3, Ccl5. Samples were analyzed simultaneously for Gapdh mRNA as the internal control. Each sample was assayed in duplicate, normalized to the internal control and data was presented as copies of mRNA/Gapdh (means \u00b1 SEM).", "For all statistical analysis, differences between groups were tested using GraphPad Prism 5 (GraphPad Software Inc). One-way-ANOVA followed by Tukey's post hoc test was applied to evaluate differences between studied groups. Statistical significance has been considered with a P value \u22640.05. All data are given as arithmetic means \u00b1 SEM." ] },{ "paper_id": "9cdd0959f4a3ba21a9d0b4c5e8707780f5c464ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9ce08e8f877a798f4ff11d70112b69f92fc2427f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The relevance of human parainfluenza viruses (HPIVs) to the epidemiology of acute respiratory infections (ARI) in China is unclear. From", "Viral genomic RNA was extracted from 140 ml of each NPA specimen, using the QIAamp viral RNA minikits (Qiagen, Shanghai, China) according to the manufacturer's instructions. RNA pellets were resuspended in 60 ml of sterile distilled water and store at 270uC.", "Acute respiratory infections (ARI) are associated with significant morbidity, especially among infants and young children [1, 2] . One estimate suggested that pneumonia accounted for 19% of the 10.6 million yearly deaths in children younger than 5 years in 2000-03, and was the leading cause of childhood mortality among this age group globally [3] . Human parainfluenza viruses (HPIVs) are not only a common causative agent of ARI among infants and young children, but these viruses are also associated with nosocomial acute respiratory illness in the immunocompromised, hematopoietic stem cell transplant patients [4, 5, 6] . In the USA, it is estimated that 7600 to 48000 among children age ,1 year old and 8100 to 42600 children age 1 to 4 years were hospitalized with HPIVs infection annually [7] ." ] },{ "paper_id": "9ce0da57763dfa3cebfb1463093ff0bba3333a25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by Biosecurity, Animal use and Ethics committee, Faculty of Veterinary Medicine, University of Nairobi. The farmers were recruited into the study, signed a consent form.", "Wilkins during the field work. Special thanks also go to the leadership of Mukurwe-ini Wakulima Dairy Limited for their assistance in identifying the farms and to the farmers for their great cooperation.", "The formol-ether parasite concentration technique was used to harvest Giardia cysts, as described by Cheesbrough [46] . The sediment content was placed on a microscope slide and examined under the light microscope at \u00d7100 magnification. The presence of one Giardia cyst in a sample was reported as an infection.", "GS, SR, and JV conducted the field data collection. GS and GKG wrote the draft manuscript. All authors were involved in the preparation of data collection materials, and the revision and approval of the final manuscript. SR, JV, GKG, and JW were involved in funding acquisition. GS, SR, JV, GKG, JW, FU, CMM, and OM were all involved in formulating the study design and methods of implementation of the study." ] },{ "paper_id": "9ce30445b5bd0de8a1b013393e53d17aa8bcb409", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ebolavirus is part of the Filoviridae family, which consists of three genera: Marbugvirus, Cuevavirus, and Ebolavirus. There are currently six known, genetically distinct, species of Ebolavirus-Ebola virus (EBOV), Sudan Ebolaviurs (SUDV), Tai Forest Ebolavirus (TAFV), Bundibugyo Ebolavirus (BDBV), Reston Ebolavirus (RESTV), and Bombali Ebolavirus (BOMV) [1, 2] . No virus has triggered fear in the general population more than the filovirus Ebolavirus [3] . EBOV is categorized among the deadliest viruses, with mortality rates up to 90%. The zoonotic origin of outbreaks are often the result of transmission from primates, although the suspected natural reservoir for EBOV, bats, is still being questioned.", "Overall, experimental works conducted so far have shown that EBOV infection induces respiratory complications, that the virus can be shed via the respiratory secretions, and that it can cause similar pulmonary lesions both in animals exposed to aerosols and in those kept nearby in separate cages with no close contact.", "Currently, full body protection is recommend by WHO and CDC [79, 80] . All HCW involved in the care of EVD patients must receive training and demonstrate competency in performing all Ebola related infection control practices and procedures, specifically in proper donning and doffing PPE even if using an N95 mask or a powered air-purifying respirator (PAPR). The risk of infection via inhalation of contaminated aerosols from exposed individuals has not been documented. However, droplets containing EBOV that have become aerosolized (e.g., from coughing sneezing, vomiting, invasive medical or surgical procedures, or surfaces) may have the potential to come into contact with a person's mucous membrane in their nose or mouth or non-intact skin. Therefore, respiratory protection may be helpful in providing a barrier to help prevent infectious materials from contacting a wearer's mucous membranes.", "The detection of RESTV in domestic swine raised important biosecurity concerns about the potential for the disease's emergence in humans and other livestock, mainly in animals for food consumption [32, 33] . The evidence of RESTV seropositive individuals further increased the concern for human infections and the worries of researchers, farm owners, and the public at large (World Health Organization. WHO, 2009, Available online: https://www.who.int/csr/resources/publications/HSE_ EPR_2009_2.pdf). Interestingly, so far RESTV has not been seen to result in any human disease, even if there is concern that its passage through swine may allow RESTV to diverge and shift its potential for pathogenicity [58] .", "Acute respiratory tract infections (ARTIs) remain a leading cause of mortality, morbidity, and economic loss, and viruses are one of the main causes of such disease. WHO estimates that ARTIs cause nearly four million deaths per year, a rate of more than 60 deaths/100,000 people [81] . The microbial etiology of ARIs is varied, with viruses being the most common cause in humans [82] , leading to a high level of awareness and the necessity to develop countermeasures to control them (Table 3) ." ] },{ "paper_id": "9ce462cb0807906c475d4b600afac950c7e8c4e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In this section, we study short-lived outbreaks and we delegate the discussion of long-lived outbreaks to Text S1.", "Media Influence Function 1. f (S,I)~kIS", "We use the term media in a broad sense to include any news reports, ranging from public health agency announcements to social media sites such as Facebook or Twitter. Any of these reports may contain false information and rumors. For example, in March 2003, the Center for Disease Control and Prevention recommended that all non-essential travel to SARS infected areas be canceled (recommendation made March 17, 2003 , reported by The New York Times March 18, 2003 [4] ), while in Chinatown, New York, a false internet rumor spread that a local restauranteur had died from SARS [5] . Both reports led some people to cease travel to these areas, though only one report was correct.", "In the following, S final denotes the final (limiting) fraction of the susceptible population." ] },{ "paper_id": "9cfada440e426dd4dabdb499d47ab2e7f9bad08c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Oudshoorn et al." ] },{ "paper_id": "9cfaf4c8791d75c45d2d5c52a6e2da74363d2565", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ADV ", "Information regarding RVPs including time of collection/ report, type of specimen, patient location at time of collection, and resulting findings were obtained from an internal database." ] },{ "paper_id": "9cffe5458f4b3268545d147dd3409b165c5f6ba5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Piglets showed softened feces (FS 2) or diarrhea (FS 3 or 4) as described. No condition related to the experimental infection requiring veterinary treatment was observed.", "Additional file 1: Table S1 . Mean body weights and body weight gains in grams with standard deviations in brackets. SD: Study day. ", "Pooled fecal samples of each litter were screened on SD 8 for the presence of any other pathogens causing diarrhea in neonatal piglets including rotavirus, coronavirus, E. coli and C. perfringens." ] },{ "paper_id": "9d047b01dc671b0c722c5cbdbc6f0d2ccb8481e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9d0653aa163675efb2e832369ae48761148b43ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9d089a2632f7a6fc75d5e723ebe2ac9db15c0048", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mice, viral infections and treatments C57BL/6 experimental mice were obtained from Harlan UK. CD200R -/mice were originally generated and provided by Reginald Gorczynski (University Health Network, Toronto), and David Copland (University of Bristol) provided the OX-2 -/mice, with kind permission from Jonathon Sedgwick (Eli Lilly, Indianapolis). IL-10 -/mice were purchased from Jackson Laboratories and maintained in-house.", "All experiments were conducted according to the UK Home Office guidelines at the designated facility at Heath Park, Cardiff University under UK Home Office-approved project licenses PPLs 30/2442 and 30/2969.", "All data were acquired on a BD FACS Canto II. Electronic compensation was performed with antibody-capture beads (BD Biosciences). Data was analyzed using FlowJo software version 10.0.3 (TreeStar Inc, Ashland, OR). Total numbers of different cell populations were calculated by multiplying % positive viable cells detected by flow cytometry x the total number of viable leukocytes (assessed by trypan blue exclusion)." ] },{ "paper_id": "9d08aa9bb599cb599ceaa62f31cb480a5708a5d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Among these patients, most cases of TB infection in Taiwan were males, which is consistent with previous studies. This gender difference may partly reflect epidemiological differences, including differences in exposure, infection risk, progression from infection to disease, socio-economic status, cultural factors and quality of health care received [1, [17] [18] [19] [20] [21] [22] .", "However, although a gender difference in incidence was noted, no gender difference was noted in number of days of delay after definite diagnosis. Taiwan National Health", "The study analyzed 31 Table 2) .", "However, a Bangladesh study showed that women experience longer total delay, total diagnostic delay, patient delay and treatment delay (males1.9 days, females 2.0 days) [25] . These inconsistencies highlight the impact of different communities and cultures on gender differences in tuberculosis treatment delays. Hence, a better understanding of the people and communities affected by tuberculosis is needed to provide consistent and high quality care [26] ." ] },{ "paper_id": "9d08ea3b664cb3fce5ee8ff79426b5dc211352bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These findings are largely consistent with the actual numbers found in the sample ( Table 6 ). None of the senior cats or dogs included in the study sample were ultimately euthanized due to behavior reasons. ", "By determining the gaps in shelters' programs for older cats and dogs, shelter management can address the factors that have driven this population to be one of the most at-risk for euthanasia. Furthermore, this research highlights the importance of preventative outreach, specialized medical and behavior programs, and a strong foster care system that are equipped to address the needs of older animals in their homes and in a shelter." ] },{ "paper_id": "9d0ae9643da1b47c2234dd758a36ed3c3abc1aa2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9d16d9dcd360578447fca314b4f8b873b23acf0b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The limitations of conventional antiviral therapy and prevention were illustrated in 2002 with the sudden appearance of the SARS (severe acute respiratory syndrome) pandemic. The novel coronavirus responsible for the disease (SARS-CoV) was quickly isolated and its genome sequenced [15] ; however no adequate antiviral treatment was deemed to be available at that time.", "Several studies have reported the effects of Echinacea preparations on cellular gene expression, mostly in uninfected cultured cells relevant to the immune system, although it is not feasible to compare the studies because of the different cellular systems and because the Echinacea preparations were different.", "It was shown by hemagglutination assays that this extract (EF) inhibited the receptor binding activity of influenza A viruses, over a range of EF concentrations including that recommended for oral consumption, suggesting that EF interfered with viral entry into the cells, thus effectively rendering the virus non-infectious [26] . EF also inhibited neuraminidase activity in vitro (unpublished results), suggesting that the active compounds could block influenza virus entry and spread by acting on at least two virion targets. However, the susceptibility of other viruses, which do not rely on HA or NA functions, to Echinaforce \u00ae indicates that additional molecular targets must be accessible.", "Since most of the symptoms reflect this common non-specific host response to infecting agents, rather than to the direct cytolytic or cytopathic effects of a specific virus [5, 7, 8] , then a more rational therapeutic approach would be the application of anti-inflammatory agents, especially if the intention of the therapy is to ameliorate symptoms. If a potential safe anti-inflammatory agent also contains multiple antiviral activities, then this would provide a bonus.", "In contrast Echinaforce \u00ae was found to be less effective against intracellular virus [25] . Consequently virus already present within a cell could be refractory to the inhibitory effect of Echinaforce \u00ae , but virus particles shed into the extracellular fluids would be vulnerable [25, 26] . Therefore the actions of the Echinaforce \u00ae would be manifest during initial contact with the virus, i.e. at the inception of infection, and also during transmission of virus from infected cells." ] },{ "paper_id": "9d18d8401ce2aa056ff228fce06c4a2d8c7f67f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CGA is a potent phenolic acids that is considered to have many important biological activities [14, 15, 16, 17] . CGA is a group of esters created from certain trans-cinnamic acids, such as caffeic acid, ferulic acid and quinic acid [18, 19] . Thirty different types of CGA have been identified in plants [19] . CGA is an important class of dietary antioxidants in a variety of fruits and vegetables, including apples, pears, tomatoes and potatoes [20] as well as other members of Asteraceae, Solanaceae and Rubiaceae [21] . CGA accumulates in the flowers, stems and leaves of Lonicera [22, 23] .", "Tissue samples were processed in a series of steps, including lyophilization, grinding and passage through a 40 mesh sieve before CGA extraction. Then, 50 mL of ethanol (70%, v/v) was mixed with 0.5 g of the processed samples, and the mixture was subjected to ultrasonic extraction for 30 min. It was then centrifuged at 4000 rpm for 10 min. The supernatant was filtered through 0.45 \u03bcM microfiltration membrane for CGA analysis.", "Experiment was carried out in the field own by College of Forestry and Life Science, and no specific permissions were required for these locations/activities. No endangered or protected species or locations were involved in this study." ] },{ "paper_id": "9d2c6b24e096eac147115b77f295e0ddcb5435c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The HI test quantitates serum antibody to influenza virus which can prevent agglutination of turkey RBCs (Fitzgerald Industries International Inc., MA). Heat-inactivated serum samples were treated with receptor-destroying enzyme (Sigma-Aldrich) for removing nonspecific inhibitors (followed by RBC adsorption) and were diluted 2-fold serially from initial dilution of 1:10. HA antigen (8 HA units in 25 mL) were added onto each well and incubated for 1 h at RT. Following antigen-antibody reaction, 50 mL of 0.5% turkey RBC were added to each well and incubated for 1 h at RT. HI negative wells were scored based upon a diffuse sheet of agglutinated RBCs covering the bottom. HI positive wells were scored if they showed a well circumscribed button of nonagglutinated RBCs.", "All statistics were performed using R version 2.13.0 and GraphPad Prism 5. For each image, mean SUVMax and standard deviations were obtained. For each ferret, SUVMax values were correlated with histopathologic scoring using Spearman's Rho (r).", "For CT analysis, image interpretation was performed by a radiologist (in consultation with the scientific team) having more than ten years of diagnostic experience along with formal certifications by the American Board of Radiology (ABR) and the American Board of Nuclear Medicine (ABNM). Lesions on CT were identified using conventional criteria and terminology; Ground-glass opacity (GGO) is defined in this study as hazy increased lung opacity, with discernible underlying lung architecture such as visible bronchial and vascular structures, representing partial displacement of air in interstitial and alveolar airspaces; Consolidation is defined in this study as high density lung lesions (more dense than GGO) in which vascular and bronchial margins are obscured, representing complete displacement of alveolar air [27] .", "Ferret studies were approved by the University of Louisville Institutional Animal Care and Use Committee. University of Louisville has Veterinary Medicine tasked to monitor and support all animal experiments. Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals, National Research Council, 1996. The facility where this research will be conducted is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International.", "Lungs were inflated and stored in 10% neutral-buffered formalin. Three lung sections were placed into cassettes per lung section (right cranial, left cranial, left caudal, and right middle lobe) until they were trimmed, paraffin-embedded, and sectioned. Sections were mounted on glass slides and stained with hematoxylin and eosin for microscopic evaluation at Experimental Pathology Laboratories, Inc. by a veterinary pathologist. Sections were examined for the presence of abnormal findings including supprative and necrosupprative inflammation; epithelial hyperplasia and cytokaryomegaly; and fibrinous and exudative changes. Changes were graded with a standardized scale of 0-5, with 0 classified as ''not present'', 1 as ''minimal'', 2 as ''slight/mild'', 3 as ''moderate'', 4 as ''moderately severe'', and 5 as ''severe/high.'' For each ferret, a composite score for pathological changes was generated based on the locations in the respiratory tract (alveoli, bronchioli, bronchi) for statistical evaluation.", "In March of 2009, an outbreak of a novel variant of H1N1 influenza A virus was reported in cases of influenza illness in Mexico [1] . By June 11, the World Health Organization raised the pandemic alert level to its highest level, declaring the first influenza pandemic in over 40 years [1] . Unlike seasonal influenza viruses, this novel H1N1 pandemic strain (H1N1pdm) tended to affect younger healthier populations and had an increased risk of morbidity and mortality [2] [3] [4] with 12-30% of the population developing clinical influenza, 4% of those requiring hospital admission, and 1 in 5 requiring critical care [5] . In general, however, infection of the H1N1pdm was relatively mild in most persons, although a fatal viral pneumonia with acute respiratory distress syndrome occurred in approximately 18,000 cases." ] },{ "paper_id": "9d3e94d800e4c0263d01a9ceed3cc7b6af5a7478", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The S group, which has never contracted Ebola virus, is exposed", "The S group, which has never contracted Eb 117 ", "Supplementary materials are available at http://www.e-epih.org/. Korean version is available at http://www.e-epih.org/." ] },{ "paper_id": "9d4ce1e58828bc78c7c83f40c14765df96feb277", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The structure model of the DBL4e sequence (C1576-C1910) was created using the same method as described for other VAR2CSA DBL-domains [20] , but using as a template the newly published structure of DBL3X-VAR2CSA (3BQK) [43] .", "Background: In Plasmodium falciparum malaria endemic areas placental malaria (PM) is an important complication of malaria. The recurrence of malaria in primigravidae women irrespective of acquired protection during childhood is caused by the interaction between the parasite-expressed VAR2CSA antigen and chondroitin sulfate A (CSA) in the placental intervillous space and lack of protective antibodies. PM impairs fetal development mainly by excessive inflammation processes. After infections during pregnancy women acquire immunity to PM conferred by antibodies against VAR2CSA. Ideally, a vaccine against PM will induce antibody-mediated immune responses that block the adhesion of infected erythrocytes (IE) in the placenta.", "For analyses of the capacity of serum to inhibit binding we used 2610 5 tritium-labeled late-stage IE and 15 ml serum in a total volume of 120 ml which were added in triplicates to wells coated with 2 mg/ml of the commercially available chondroitin sulfate proteoglycan Decorin (D8428; Sigma-Aldrich). Decorin was used as a source of CSA as this has a protein core resulting in more efficient coating to plastic than CSA. After incubation for 90 min at 37uC, unbound IE were washed away by resuspension performed by a pipetting robot (Beckman Coulter). The proportion of adhering IE was determined by liquid scintillation counting on a Topcount NXT (Perkin-Elmer)." ] },{ "paper_id": "9d63191505e7cdb2dc1436228923fc97515e2ea1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Histopathology. Sections of the ileal tissues were stained with haematoxylin and eosin (H&E) for assessment of the general ileal morphometry. For each slice, fields were randomly selected, from which all villi were quantified by Image-Pro Plus 6.0.", "In short, the total genomic DNA in the ileal contents was first extracted, and then, using the genomic DNA as a template, the 16S rRNA gene of the V3-V4 region was amplified using specific primers (forward 341 F: CCTAYGGGRBGCASCAG and reverse 806 R: GGACTACNNGGGTATCTAAT) tagged with the unique barcode. Then the desired size (approximately 400-450 bp) of the PCR products was selected to prepare the sequencing libraries, and the index codes were added. Finally, the samples were sequenced on an Illumina HiSeq. 2500 platform.", "Statistical analysis of the data. Samples were created from the paired-end reads by cutting off their unique barcode and primer sequence. The paired-end reads were merged using Fast Length Adjustment of SHort reads (FLASH) software (version 1.2.7, http://ccb.jhu.edu/software/FLASH/) 63 , and raw FASTQ data has been submitted in the SRA database of the NCBI with accession number PRJNA 533742. To obtain high-quality clean tags, quality filtering of the raw tags was performed using the Quantitative Insights Into Microbial Ecology software (QIIME, version 1.9.1, http://qiime.org/scripts/split_libraries_fastq.html) 64 quality-controlled process. The chimaeric sequences were removed by using the UCHIME Algorithm (http://www.drive5.com/usearch/manual/uchime_algo.html), and then the effective tags were obtained 65 . The sequences were clustered into OTUs at 97% similarity by UPARSE software (version 7.0.1001, http://drive5.com/uparse/) 25 . In addition, the GreenGene database and MUSCLE software (version 3.8.31, http://www.drive5.com/muscle/) were used to annotate the taxonomic information and conduct the multiple sequence alignment, respectively 66 ." ] },{ "paper_id": "9d689209d9886db326dc65759ef929ac56832d93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9d6c0c6b233bdffc9a3a85e7fe255163b54ca658", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Human N7 methyltransferase (hN7 MTase) protein was expressed, extracted and purified as previously described (35) .", "The 3D structures have been deposited in the Protein Data Bank under the accession numbers: 4P37 (Mg561) and 4WSE (R341).", "Supplementary Data are available at NAR Online." ] },{ "paper_id": "9d7be8a36427c181f25d57999d889ac99807ece3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9d8252afd663371d83c2e28943f2df1bec3f4780", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9d82ed9e4eab5525576c427521c25aca625ecd59", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All reactions were performed using oven-dried glassware under a nitrogen atmosphere with magnetic stirring. Reagents were purchased from Sigma-Aldrich ( ", "Selective inversion of the H11 proton resulted in strong NOE enhancement of 4.3% at H1', whereas other NOE enhancements were relatively weak ( Figure 4B ). The lack of strong NOE Selective inversion of the H11 proton resulted in strong NOE enhancement of 4.3% at H1', whereas other NOE enhancements were relatively weak ( Figure 4B ). The lack of strong NOE enhancements between H11 and H6 suggests that anti-orientation along the C11-C10-C5-C6 torsion angle is the predominant conformation of compound 1 in solution. Additionally, inversion of the H6 proton showed no NOE enhancements ( Figure 4C ), which confirms that H6 and H11 are spatially apart, overall supporting anti-conformation.", "The difference in activity between the Ac, EtAc, and i PrAc is an interesting trend, as the EtAc analogues were consistently the least active analogues. In order to analyze if this trend was due to a change in lipophilicity or due to branching, the logP values were determined for each analogue ( Table 2) .", "First, protection of the 4-amino group was tried using two equivalents of di-tert-butyl dicarbonate to give a di-boc protected amine, which could easily be deprotected after coupling to the sugar using mild acidic conditions (Scheme 6)." ] },{ "paper_id": "9d8670d2d8e18f181af7f6fc61db4424026f384e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The continuous emergence of new IBV variants in several countries [3, 10, 11, 12, 13] are routinely pointed out as a cause of outbreaks in vaccinated flocks, leading to significant economic losses to the poultry industry [14] .", "All analyses were conducted using the SAS 9.4 software (2012), and the probability level for significance was set as p 0.05.", "The comparisons of relative changes in gene expression, viral load and microscopic lesions between the experimental groups were performed using the Kruskal-Wallis test followed by Wilcoxon test." ] },{ "paper_id": "9d9347a3f4d7fe21a8d2bdc9aa593830a6856630", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sobemoviruses have isometric nonenveloped virions with regular T = 3 icosahedral symmetry and a diameter of 25-30 nm [21] . MBV, in contrast, has nonenveloped virions that exhibit \"bacilliform\" morphology, with typical dimensions of 19 \u00d7 50 nm [20] and probable T = 1 icosahedral symmetry at the virion ends [16] . The name barnavirus reflects this bacilliform shape. This type of structure is unusual, but not unique; for example, bacilliform particles with probable T = 1 symmetry are also formed by members of the unassigned genus Ourmiavirus [15] .", "The positive-sense sequence of MBV has been previously noted to encompass three smaller ORFs (ORF5-ORF7) in addition to the four longer ORFs described above [16, 19] . Whether these smaller ORFs are expressed remains open to question. They are not conserved at similar positions in CqABV1 or RsBV1 (Fig. 1) , suggesting to us that they are probably not expressed.", "The family Barnaviridae is currently represented by one species, Mushroom bacilliform virus, in genus Barnavirus [16] . The originally reported sequence for mushroom bacilliform virus (MBV) (GenBank U07551.1; also NC_001633.1) is from an Australian strain of the cultivated button mushroom (basidiomycete) Agaricus bisporus [19] . A closely related sequence for MBV (97% nt sequence identity) (GenBank KY357511.1) has been reported recently from a second strain of A. bisporus [6] . In addition, the sequence of another apparent member of the genus Barnavirus, Rhizoctonia solani barnavirus 1 (RsBV1; GenBank KP900904.2), has been reported recently from the phytopathogenic basidiomycete Rhizoctonia solani [12] but has not yet been recognized by the ICTV as a member of a separate species." ] },{ "paper_id": "9d941db9f06f446ae113c5f76f7597553a2f365b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The unpaired two-tailed t-test was used to evaluate the significant differences of datasets obtained from at least three independent experiments. P<0.05 was considered statistically significant.", "The sandwich ELISA for CXCL10 (BD Biosciences) was used according to the manufacturer's protocol.", "Middle East respiratory syndrome coronavirus (MERS-CoV) is a nidovirus and etiologic agent for respiratory disease. MERS-CoV emerged in Saudi Arabia in 2012 and is still causing respiratory infections with 2220 and 790 (35%) reported cases and deaths respectively [1] . Manifestations of MERS disease are similar to severe acute respiratory syndrome (SARS) with patients usually developing acute pneumonia that progresses to respiratory failure and acute respiratory disease syndrome [2] . Patients also exhibit extrapulmonary manifestations include renal failure, hepatic dysfunction, and diarrhoea with some severe cases of deranged coagulation profile and hematological changes [3] [4] [5] ." ] },{ "paper_id": "9db44eda8b352d1e7e5f73d7b5587659aa256151", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ELISA CXCL1/KC concentrations in mice BAL fluids were determined using DuoSet ELISA kits obtained from R&D Systems (Minneapolis, Minnesota, United States).", "This study was carried out in accordance with INRA guidelines in compliance with European animal welfare regulation. The protocols were approved by the Animal Care and Use Committee at \"Centre de Recherche de Jouy-en-Josas\" (COMETHEA) under relevant institutional authorization (\"Minist\u00e8re de l'\u00e9ducation nationale, de l'enseignement sup\u00e9rieur et de la recherche\"), authorization number: 2015100910396112v1 (APAFIS#1487). All experimental procedures were performed in a Biosafety level 2 facility.", "Conceptualization: AV RLG. " ] },{ "paper_id": "9db78243c51590cfaaef835ded1163dc55d67cc0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two-tailed independent samples t-test or Mann-Whitney U-test (on condition of non-normal distributions) was used to compare continuous variables between the two groups. For the categorical data, univariate analysis was performed using the chi-square test or Fisher's exact test. Significance was fixed at p value < 0.05. Data analysis was performed using SPSS 15.0 (SPSS Inc; Chicago, IL).", "The study was reviewed and approved by the institutional review board of Beijing Chao-Yang Hospital (the project approval number is 10-KE-49). Written informed consent was provided by all adults and the parents of patients aged less than 18 years. Adults with communityacquired pneumonia (CAP) (Age14yrs) admitted to Beijing Chao-Yang Hospital from March to June 2013 were prospectively included. Patients with HIV infection or neutropenia; receiving immunosuppressive chemotherapy or steroids equivalent to prednisone >15 mg/d for 30 days; who were pregnant or breast feeding women; or who were known or suspected to have active tuberculosis were excluded." ] },{ "paper_id": "9dbde5d85011e2cb16e7d996421db75323ea21c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The N gene sense primer was: 5'-CCATGGCAAGCGGTAAAGCAR-3', and the anti-sense primer was: 5'-CCACTCAAAGTTCATTCTCTCC-3'. The anticipated amplification segments for M and N genes are 750 bp and 1236 bp respectively.", "Infectious bronchitis (IB) is an acute, highly infectious and contagious disease of domestic chickens worldwide caused by avian infectious bronchitis virus (IBV), a member of genus Gammacoronavirus, subfamily Coronavirinae, family Coronaviridae [1] . IB affects chickens of all ages and IBV replicates primarily in the respiratory tract, and also in some epithelial cells of the kidney, gut and oviduct, resulting in reduced performance, reduced egg quality and quantity, increased susceptibility to infections with other pathogens, and condemnations at processing [2] . Multiple IBV serotypes or genotypes have been identified worldwide and different serotypes of IBVs confer little or no cross-protection against the others." ] },{ "paper_id": "9dc436e46261781fe2991baeff4ddc7dd2e96c9b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animal and Human Rights Statement This article does not contain any studies with human or animal subjects performed by any of the authors.", "(1) it can investigate conformational epitopes with sequentially discontinuous residues on icosahedral virions;", "Conflict of interest The authors declare that they have no conflict of interest." ] },{ "paper_id": "9dc767a57df46887166f86194ad8fd2d94b6dba5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In CT, the most common reported change in Influenza A(H1N1) was ground glass shadowing. Other changes recorded on CT were focal or multifocal consolidation, interstitial changes and pulmonary embolism [4, 13, 14] . CT was valuable in detecting positive findings in the presence of normal CXRs and showed more extensive pattern of involvement when compared to CXR [14] . These findings were similar to the authors' series although they did not find any evidence of pulmonary embolism in their sample population.", "The Influenza A (H1N1) CXR findings are similar to those reported for SARS and H5N1. Although imaging will play an important role in detecting lung changes, and to monitor disease progression as well as response to treatment; knowledge of the current epidemic status is essential for correct diagnosis.", "Currently, radiographic criterion is not included in the WHO diagnosis of Influenza A(H1N1). In this series, only 42% of patients demonstrate positive findings and this is likely due to the range of clinical presentation of the study population. Several studies have a similar initial CXR positive findings of 42-50% for this disease [12, 13] ." ] },{ "paper_id": "9dc7d12caa315d1608b7e1310aa4ba033d50d8e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Operational effectiveness of protection measure vs cost effectiveness.", "Acknowledgments The current work has received funding from EPSRC Grant Reference: EP/G029881/1. The comments from Dr. Simon Parker (Dstl) and Professor Sean Tyrell (Cranfield University) are gratefully acknowledged.", "Modelling of passenger movement and proximity in transport infrastructures." ] },{ "paper_id": "9dcd697b97cd39fbeaf2c5f8be7d0bc139b84629", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "The RT-PCR assay used for MERS-CoV diagnosis confirmation targets the upstream of the E protein gene (upE) and the region within open reading frame (ORF)1b as previously described [12] ." ] },{ "paper_id": "9dd6e3df008179b4c54ac823f76192a8a174b62d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Small molecules. GS-5734 and Nuc were synthesized at Gilead Sciences, Inc., and chemical identity and sample purity were established using NMR, HRMS, and HPLC analysis 4 . To determine concentration response curves against each virus, we used either a 7-point or a 10-point 3-fold dilution series, with each compound concentration tested in quadruplicate. 7 was propagated and quantitated as above using Huh7 cells. The rgRSV was propagated and quantitated as above using HeLa cells 12 . Both hMPV-GFP (CAN97-83) 13 and hPIV3-GFP (JS) 11 were obtained from ViraTree.", "EC 50 values for all infectious virus yield reduction assays were calculated using four-parameter variable slope non-linear regression fitting of mean values derived from quadruplicate or triplicate samples.", "GS-5734 is a monophosphate prodrug of an adenosine nucleoside analog that showed therapeutic efficacy in a non-human primate model of Ebola virus infection. It has been administered under compassionate use to two Ebola patients, both of whom survived, and is currently in Phase 2 clinical development for treatment of Ebola virus disease. Here we report the antiviral activities of GS-5734 and the parent nucleoside analog across multiple virus families, providing evidence to support new indications for this compound against human viruses of significant public health concern." ] },{ "paper_id": "9dd7a29452ebf3285c47109ce0c72e2099347622", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at http://www.mdpi.com/2072-6643/9/4/341/s1." ] },{ "paper_id": "9dd88265053594d2736a884a8b972b6ae94218c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed by t-test using GraphPad Prism version 5 software (GraphPad software, San Diego CA, USA); P-values less than 0.05 were considered to be statistically significant." ] },{ "paper_id": "9de48553eac5b5676f0e796f544e04634d39aaa4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9df0801be110f632c616bf9e91cb72d59383b086", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Institutional Review Board (IRB) of Nanjing Medical University approved the study. Written informed consent was obtained from all of the participants. Ethical practices were used throughout the study period." ] },{ "paper_id": "9df4e2297f45f9a30993d6c526bb9bc87afa9ca4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. All data are publicly available online and can be found based on the information provided in Materials and Methods part.", "With the availability of various databases containing different types of pathogenic microbial species, one of the most commonly used approaches for identifying the origin of the new pathogen responsible for an EID is to find similar sequences in the pathogen databases using alignment by the Smith-Waterman algorithm 6 , BLAST 7 , or other alignment tools." ] },{ "paper_id": "9df9c07c5571ea37b99d01b8ecbfcac5625fa1ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At the core of IHR practice is reliable information. In most African settings, laboratory data is stored in a format that makes retrieval, analysis and summarization for public health action diffi cult. Laboratory information is often captured in multiple reports and may be inaccurate, non-standardized and illegible.", "With readily available and timely information, public health responses to diseases of international concern can be guided appropriately.", "Preliminary data received from the fi rst PT round reported 80% and 91% response rates in Uganda and Tanzania, respectively. Reasons for poor performance were identifi ed per sites. Common problem areas include failing to follow national testing algorithms, not mastering proper pipetting tech nique, failing to follow DTS reconstitution procedures, new or untrained testing staff , and clerical errors in recording test results in both registers and PT report forms. Proper corrective actions, including on-site train ing and demonstrations, were taken.", "To address the paucity of accredited laboratories in the African region, the WHO Regional Offi ce for Africa (WHO AFRO) established a stepwise approach for laboratories to attain the required standards. Th is approach supports laboratories at all levels through a series of evaluations using demonstrated improvements, which are recognized and rewarded for the progress [14, 15] ." ] },{ "paper_id": "9e009084059ebea290ba99f450faff6e4372a4c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Why is RNA virus replication more error-prone?", "Host-encoded protein families such as apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) and adenosine deaminase acting on RNA (ADAR) can modify viral nucleic acid. APOBEC3G is packaged into HIV-1 virions and deaminates cytosine bases to uracil within viral complementary DNA (cDNA) [25] . This results in G-to-A base substitutions and generates 98% of mutations within HIV-1 in vivo [26] . Though predominantly antiviral, APOBEC-mediated editing could also contribute to pathogenesis in situations in which edited viruses are viable. Whereas APOBEC proteins modify DNA, ADAR proteins modify genomic RNA or viral transcripts containing double-stranded RNA (dsRNA) structures. ADAR deaminates adenine bases to inosine, resulting in A-to-G base substitutions, and occurs across RNA virus families resulting in either pro-or antiviral effects [27] . In summary, multiple mechanisms can impact viral mutation rates and whether and to what extent each is proor antiviral is an important focus of future research." ] },{ "paper_id": "9e0828fc0cba2f4c01abe363c059bb7c0036176d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In total, 10 bands representing JcDV interacting proteins are reproducibly obtained with VOPBA. Noteworthy, each band probably include several proteins and/or isoform/glycoform of the same proteins.", "Calcofluor white M2R (Calcofluor; F3543), N-Acetyl-D-glucosamine (GlcNAc; A4106), N-Acetyl-D-galactosamine (GalNAc; A2795), D-(+)-Fucose (Fucose; F8150), D-(+)-Mannose (Mannose; M6020), Mucin from porcine stomach (Porcine mucin; M2378) and WGA-FITC conjugate (L4895) were all purchased from Sigma-Aldrich (Lyon, France).", "The authors declare no conflict of interest.", "Insect parvoviruses, named densoviruses, can be highly pathogenic, a feature that can both represent threats for insect mass rearing or opportunities for biocontrol against harmful insects as alternative to chemicals. Developing methods against infections or tools for biocontrol requires a deep understanding of the mechanisms driving host range and pathogenesis." ] },{ "paper_id": "9e0f14131900d5136cabf11f654a5cbb9d88ad48", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequences were confirmed by commercial dideoxy sequencing (using the facility at the Department of Biochemistry, University of Cambridge).", "Purified eIF3 was a kind gift of Dr. Chris Fraser (Department of Molecular and Cell Biology and Howard Hughes Medical Institute, University of California). Dominant-negative eIF4A-R362Q was prepared as described [14] .", "In vitro transcription and translation p2luc-BM2 reporter plasmids were linearised with HpaI and capped run-off transcripts generated using T7 RNA polymerase as described previously [25] . Messenger RNAs were recovered by a single extraction with phenol/chloroform (1:1 v/v) followed by ethanol precipitation. Remaining unincorporated nucleotides were removed by gel filtration through a NucAway spin column (Ambion). The eluate was concentrated by ethanol precipitation, the mRNA resuspended in water, checked for integrity by agarose gel electrophoresis and quantified by spectrophotometry." ] },{ "paper_id": "9e102fc4487f4b9cdc7f7426ad24ba33aa1a4d42", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Extracorporeal membrane oxygenation, n (%) 9 (33.3) a APACHE II, Acute Physiology and Chronic Health Evaluation II; PaO 2 : FiO 2 , ratio of partial pressure of arterial oxygen to fraction of inspired oxygen. Continuous data were expressed as mean \u00b1 SD or median (range), and categorical data were represented as number (percentage). 2014, 18:R43", "Introduction: Currently, little is known about the immunological characteristics of patients with avian influenza A (H7N9) virus infection.", "We are interested in further investigating the levels of galectin-9 and T-cell function to discern the precise mechanisms underlying immune responses to H7N9 virus infection in humans." ] },{ "paper_id": "9e115f050e9a4bfa777fcbf79204014270383274", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The plant sample was obtained from the Heinrich-Heine University`s botanical garden (D\u00fcsseldorf, Germany) in March 2005. The plant was taxonomically authenticated and identified by Peter Westhoff, Prof. of Plants Molecular Biology and Development (Heinrich-Heine University, Germany). A specimen (Registration code AJB-2005) was kept at the Faculty of Pharmacy, Department of Pharmacognosy, Al-Azhar University, Egypt.", "All data were expressed as mean \u00b1 standard error of mean using the student t test. ANOVA (one-way analysis of variance) was used for evaluation of statistical significance. The values were considered to be significantly different when P < 0.01.", "The TLC analysis was performed using the following systems: MeOH:CHCl 3 (10:90, S 1 ), MeOH:CHCl 3 (15:85, S 2 ), and n-BuOH:H 2 O:HOAc (4:5:1, S 3 ). Pre-coated silica gel 60 F 254 TLC plates (0.2 mm, Merck) was used for TLC. Propyl gallate (PG), 2,2-diphenyl-1-picrylhydrazyl (DPPH), carrageenin, and indomethacin were provided by Sigma-Aldrich Co. (Taufkirchen, Germany)." ] },{ "paper_id": "9e17fa07642900d9491bf957db97cbe70bc39610", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following immunization, we conducted parallel differential robotic hybridoma screening to identify specific MAbs against each of the three toxins. The integration of automated robotic liquid-handling systems can significantly improve the overall screening capacity of hybridoma [10] .", "Since the emergence of hybridoma technology [1] , the research and the development of monoclonal antibodies (MAbs) has rapidly progressed. MAbs, well-characterized individual full or partial immunoglobulin molecules, are currently being developed for a broad range of indications, from diagnostics and imaging to the treatment of medical conditions such as cancer and infectious diseases. In recent years, MAbs and related products have been the fastest growing class of therapeutic agents [2] .", "Eran Diamant, Amram Torgeman, Eyal Ozeri and Ran Zichel conceived the review and wrote the manuscript.", "In rare cases, a single MAb can be as protective as a PAb-based preparation [53, 70] via the blockade of a pivotal epitope that results in complete neutralization. This evidence for the existence of 'hot spot' epitopes that display a unique functional impact suggests that interfering with more than one such epitope might be highly beneficial for toxin neutralization.", "In a previous study conducted by our lab, specific monoclonal antibodies against the three botulinum serotypes A, B and E were generated by immunizing mice with a trivalent mixture of the recombinant C-terminal half of the heavy chain (Hc) of botulinum neurotoxins A, B, and E [16, 57] ." ] },{ "paper_id": "9e3db9f0b5e4e5811a8b21576cb08297043ddb84", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The genome of PRRSV is about 15 kb in length with 10 open reading frames (ORFs) [3] . ORF1a and ORF1b comprise 80% of the viral genome and encode viral enzymes involved in virus replication. In addition, polypeptides from the two ORFs are processed into 14 nonstructural proteins (nsps), including nsp1 , nsp1 , nsp2, nsp2TF, and nsp3\u223c12 [3, 4] . ORF2a, ORF2b, ORF3 through ORF7, and ORF5a code for eight structural proteins: GP2, envelop protein (E), GP3\u223c 5, membrane protein (M), nucleocapsid protein (N), and ORF5a protein [3, 4] .", "It is not known if PRRSV interferes with other ISGs. Considering the important roles of the ISGs in deterring invading pathogens, one can imagine that PRRSV must have evolved strategies to evade them during its replication. Further study on the interplay of PRRSV and ISGs will provide insights into such strategies.", "Other PRRSV proteins including nsp7, nsp12, GP3, and N were also found to be able to inhibit IFN-activated signaling [55] . N protein inhibits IFN-activated STAT1 nuclear translocation, albeit less effective than nsp1 [55] .", "Porcine reproductive and respiratory syndrome (PRRS) is an important infectious disease, causing huge economic losses to the swine industry worldwide [1, 2] . The PRRS clinical signs include respiratory disorders, abortion in pregnant sows, and variable mortality in piglets. PRRS was first identified in the USA in 1987 and subsequently in Europe. The causative agent of the disease is the PRRS virus (PRRSV), a positive-sense single-stranded RNA virus, belonging to the Arteriviridae family in the order Nidovirales [3] . According to the genetic differences, PRRSV is grouped into two genotypes: European (Type 1) and North American (Type 2), represented by Lelystad virus (LV) and VR-2332 strains, respectively." ] },{ "paper_id": "9e45efb86c7c552be221e4d1356d9374a7ebc204", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using the paired Student's t test. A p value of less than or equal to 0.05 was considered statistically significant. " ] },{ "paper_id": "9e4f6e2dd8f847c11cc774c7083aa426f42a530e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using Chi2 test. P value was considered significative is below or equally to 0.05. " ] },{ "paper_id": "9e4f96618ed7ba4ba54c5c479ed595f1eb12fe9a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "verified by direct DNA sequencing before digestion with restriction enzyme and prior to insertion into linearized pET32a.", "The PLPs stability was analyzed by agarose gel electrophoresis (1%) and staining with gel red dye. The intact AR was confirmed by transmission electron microscopy (TEM), followed by negative staining with 1% phosphotungstic acid.", "AR particles were precipitated with PEG 6000 and negatively stained with 1% phosphotungstic acid. The TEM image confirmed that AR particles had icosahedral shape and a 30-nm diameter (Fig. 3) .", "uman immunodeficiency virus (HIV) infection is one of the most critical challenges to global public health [1, 2] . The accurate evaluation of HIV type 1 (HIV-1) RNA levels is the most important factor for understanding the natural history of HIV infection, monitoring the progression of the disease to acquired immune deficiency syndrome (AIDS) and determining the efficacy of antiretroviral therapies. [3, 4] ." ] },{ "paper_id": "9e5c4cfb4582c7aa5e60455ae948554981054c47", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations LUS: Lung ultrasound; CXR: Chest X-ray; ICU: Intensive care unit; CT: Computerized tomography; ED: Emergency Department.", "Pneumonia is considered a major healthcare and economic problem with a considerable effect on morbidity and mortality worldwide [1] [2] [3] [4] [5] . The incidence of communityacquired pneumonia has remained constant over the last few decades affecting 3-5 people per 1000 person-years, predominantly among the young and elderly [6, 7] . Even if discharged, patients are still at risk of returning to Emergency Departments (EDs) or clinics and being readmitted with more severe disease [8] . Pneumonia is also an important health-care related complication: it is the second most common type of nosocomial infection and has the highest mortality [9] . Due to this high burden, physicians with patients suspected of pneumonia are constantly challenged to determine if the clinical syndrome is pneumonia rather than alternative diagnosis.", "The authors declare that they have no competing interests." ] },{ "paper_id": "9e61bd6c5144017a9405d0c8bd84b09608eef00b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "High water absorption and retention, good air access, lower density for easy flower insertion, and particularly optimal pH to ensure durability are the required properties for synthetic phenol-furan synthetic foams for floral, hydroponic, and horticultural uses [112] [113] [114] [115] .", "Acid catalyzed tannin/furfuryl alcohol resins in proportion 45/54% by weight were also tried for this application, yielding flax fiber lightweight composites with good performance.", "Finally, ferric inks, the main source of writing inks for several past centuries, is definitely out of interest as more performant materials exist today, and no further interest in them is apparent.", "Tannic acid is one of the most important substances in relation to hydrolysable tannins. Tannic acid exists de facto in the form of a mixture of very similar substances, for example penta-(digalloyl)-glucose and tetra-(digalloyl)-glucose or tri-(digalloyl)-di-(galloyl)-glucose, etc. [4] [5] [6] .", "As a consequence of the public awareness generated by the \"French paradox\" diet complements rich in flavonoid and hydrolysable tannins are on sale \"over the counter\" in North America." ] },{ "paper_id": "9e716720f4daa4c2f5f85df4b4ee6838255d4f80", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mouse monoclonal antibody against phosphorylated form of ERK1/2 was from Santa Cruz Biotechnology Inc. Mouse monoclonal antibody against cleaved PARP and rabbit polyclonal antibody against ERK1/2 were from Cell Signaling Biotechnology. Rabbit polyclonal antibodies against Puumala hantavirus N have been described previously [39] . Recombinant human TNF-\u03b1 was from R&D Systems." ] },{ "paper_id": "9e7a93b167e9c3ffc970caf4a644d63439410cc5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The enzyme digestion reaction system was 10 ul, including 2 ul PCR product, 1 ul 10X buffer, 0.5 ul corresponding restriction endonuclease, and 6.5 ul ddH 2 O. It was kept at 37\u00b0C over night. 5 ul enzyme-digested product was applied to 3% agarose gel (containing 0.5 ug/ml ethidium bromide). Electrolytic buffer solution: 0.5xTBE solution; voltage for sample application: 120 V; electrophoresis: 40 min. Gel imaging processing system was used to observe the electrophoresis results, determine the genotype, and take photos.", "Sample size estimation was based on an estimated rs6695096 frequency of 14%; OR = 1.8, \u03b1 = 0.05 (paired) and \u03b2 = 0.10. Based on the above assumptions, 419 subjects were to be selected as cases and healthy controls.", "The study protocol was approved by Ethical Review Committee of the Central South University Ethics Review Committee (XYSM HSP#: 2007122002A). All subjects enrolled in this study were over 19 years old and so parental consent was not required. Written informed consent was obtained from all subjects according to guidelines from the ethical review committee." ] },{ "paper_id": "9e7bb369224888a04493301fe9b7e1d4e31531c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Let N(t) denote the viral population size at time t since infection (expressed in days), such that", "doi:10.1371/journal.pcbi.1005316.t001", "To address these issues, we used a two-phase coalescent model described by a linear growth from a single transmitted variant (transmission bottleneck) to a maximum population size followed by either stabilization or decline of the effective population size [21] ." ] },{ "paper_id": "9e8410e170ac72b3ccb909c2807403fc777fdf4c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where II d i , II p i and II f i are the node's indirect degree influence, indirect pathogen influence and indirect frequency influence, respectively (equations (2.2)-(2.4)).", ", \u00f02:5\u00de j, k \u2208 n i ; \u03c9 ij is the phylogenetic distance between j and k,", "Data accessibility. The data reported in this paper are accessible from the " ] },{ "paper_id": "9e881f35d3222748d7c2cb9a2a8b9b0d99246564", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was supported by JSPS KAKENHI Grant Number 16K08148, and a grant from the Ministry of Agriculture, Forestry, and Fisheries of Japan (Genomic-based Technology for Agricultural Improvement, AGB-1002 and -1004).", "TT and HK performed the experiments and wrote the manuscript. SS, MN, DF, MT, HS, MS, and HU contributed reagents, materials, and/or analytical tools.", "The Supplementary Material for this article can be found online at http://journal.frontiersin.org/article/10.3389/fvets.2017.00132/ full#supplementary-material.", "We thank the staff of Prime Tech Ltd. (Tsuchiura, Ibaraki, Japan) for their great contribution in generating LDLR-KO pigs. We also thank the staff of the Pig Management Section of NARO Institute of Livestock and Grassland Science for assistance with animal management." ] },{ "paper_id": "9e951559a8cbef877c02296db2e3c2f0ccc8ddec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In modern bioinformatics, finding an efficient way to allocate sequence fragments with biological functions is an important issue. This paper presents a structural approach based on context-free grammars extracted from original DNA or protein sequences. This approach is radically different from all those statistical methods. Furthermore, this approach is compared with a topological entropy-based method for consistency and difference of the complexity results.", "Sequence arrangement can produce many different results, but only few codons exist in living bodies. Some sequences do not contain any information which is known as junk DNA. Finding an efficient way to analyze a sequence fragment corresponding to genetic functions is also a challenging problem.", "(ii) +: the following string will express the right subtree;" ] },{ "paper_id": "9e953d462385492fa9cc2ada05c1fd357de8afed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CLEC2 is highly expressed by platelets and megakaryocytes and low level expression of this Syk-coupled CLR has also been reported in mouse dendritic cells (32) and neutrophils (33) .", "The superfamily of C-type lectin-like domain (CTLD)containing carbohydrate-binding proteins comprises \u223c150 members that can be classified into 17 groups in humans (17) . While most CTLD family receptors do not contain cytoplasmic domains capable of transducing signals, several are Syk-coupled receptors have been reported to play critical roles in host immunity against fungal and non-microbial infections (18) .", "Activation of all TLRs (except TLR3) initiates signaling via MyD88-dependent and TRIF-dependent pathways. It has been shown that activated MyD88 triggers two signaling pathways: (1) the TRAF3-TBK1-IKK\u03b5-IRF3/IRF7 pathway to induce type I interferon (IFN-\u03b1 and IFN-\u03b2) expression; and (2) the TRAF6-TAK1-IKK-NF\u03baB pathway to induce proinflammatory cytokine expression. In contrast, activated TRIF primarily triggers the TRAF3-TBK1-IKK\u03b5-IRF3/IRF7 pathway to upregulate type I interferon production." ] },{ "paper_id": "9ea1a900f1243ce3264700e9eec29b402892674c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Determination of the nucleotide sequences of penton base, hexon, and fiber gene", "Virus isolation for the adenovirus-positive specimens was performed by using HEp-2 cell lines (from American Type Culture Collection, ATCC Number CCL-23) following the standard protocol [13] . Cells inoculated with clinical samples were incubated at 37\u00b0C for 7 days. If no cytopathic effect was observed, the culture was used to inoculate fresh cells for up to 2 additional passages; the cultures with adenovirus-like cytopathic effects were passaged again to confirm the presence of the virus." ] },{ "paper_id": "9ea62d48ba2e9f9c122aa34759f9bcb5451a09f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, outbreak cases were randomly distributed according to a lognormal distribution with mean 0 and standard deviation 0.5.", "\u2022 the OutbreakP method [35] ,", "We evaluated the performances of the methods with three different \u03b1 values: \u03b1 = 0.001, \u03b1 = 0.01 and \u03b1 = 0.05." ] },{ "paper_id": "9ea81809febb5da9242f91f23bc9e2fa4bfdeed6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Non-systematic control is carried out on an individual herd basis, with no coordinated simultaneous actions in other herds. Vaccination is normally a major component of such programmes.", "\u2022 Calf phase (January 2009 to September 2009) After the initial phase, all newborn calves were tested. This was done by the farmer taking an ear tissue sample at tagging.", "\u2022 Phase One. From 22 September 2010 until 31 March 2011, financial support is available for testing for breeding herds and an awareness programme." ] },{ "paper_id": "9eb3ea6224aabe868a10af37dc829b9636be5856", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "related to MVA, which implicated an important role for cell surface proteoglycans in VACV attachment 10, 11 . Identical or similar proteins could be involved in attachment and entry of MVA into target cells.", "Direct confocal laser scanning microscopy (CLSM). Slices obtained from muscle tissues or agarose-inflated lungs were directly analysed for GFP fluorescence using CLSM with a LSM700 system fitted on an Axio Observer Z1 inverted microscope (Zeiss). Images and videos were generated using Zen software. GFP + muscle from mice and lungs slices from cynomolgus macaques were transferred to 4% (w/v) paraformaldehyde in PBS, permeabilized with 0.1% (v/v) Triton-X100 for 30 min and subsequently counterstained for nuclei with TO-PRO-3 (Invitrogen).", "observed after respiratory administration, although subtle differences were observed between the respective animal species. Following intramuscular injection, rMVA-GFP was detected in interdigitating cells between myocytes, but also in myocytes themselves. These data are important in advancing our understanding of the basis for the immunogenicity of MVA-based vaccines and aid rational vaccine design and delivery strategies." ] },{ "paper_id": "9ebef419c2970287a5fd24ea38695453e0bbfffa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using SPSS software version 13.2 (SPSS Inc., Chicago, Ill., USA). Chi-square test and Spearman's rank-correlation coefficients were applied where appropriate. For all analyses, a P value of less than 0.05 was considered statistically significant." ] },{ "paper_id": "9ec445cf691671bf14bc883bbb07dc5b3e8026b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "WILD (warts, depressed cell-mediated immunity, primary lymphedema, and anogenital dysplasia) is also correlated with severe warts without a known genetic etiology (60) . Of note, this diagnosis does not lead to EV-defining HPV strain infections. A recent study demonstrates a case of a patient whose warts improved after quadrivalent HPV vaccination (61).", "MR, SH, and KS collectively conceived and wrote the manuscript.", "The Wallace Chair of Pediatrics supports KS. SH and MR are supported by T32-HD043021-13.", "CVID and agammaglobulinemia can rarely have prolonged asymptomatic shedding of vaccine-strain polio following immunization with live-attenuated oral polio vaccine, which can pose risk to other immunocompromised members of the community (112) (113) (114) . Additionally, central nervous system (CNS) infection can occur in agammaglobulinemia (see below). These are the main reasons that live polio vaccination is no longer used in the USA." ] },{ "paper_id": "9ee05def9e9c177e9c22bf4ef9bfcca045572916", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(3) Neutralize the receptor binding sites to prevent influenza disease with a clear path towards clinical proof of correlation for protective efficacy in humans", "(3) Potentially avoid the detrimental effects of antigenic drift with ancestral sequences; (4) Incorporate protein functional and structural domains", "(1) More sophisticated and advanced models to incorporate protein domains are still under development;" ] },{ "paper_id": "9ef23d86bba041d9fc573624cdf17e94a30fb8f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data in this study provide an insight into the prevalence of the recent circulating HCoVs in the region.", "The study of coronaviruses has sometimes been difficult due to limitations in cell culture and serology. Thus, epidemiological and viral prevalence data are valuable in investigating the emergence of HCoV infection. Using reverse-transcription polymerase chain reaction (RT-PCR) and phylogenetic analysis, we characterized HCoVs identified in Thai patients with respiratory tract infection between 2012 and 2013." ] },{ "paper_id": "9eff33e415aeff95305afd9a4914f15b1eafab84", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by the Gabonese National Ethics Committee (number 0024/CNE/SG/P). Individual oral consent was required for nasal sampling. The test results were transmitted to the participating health centers." ] },{ "paper_id": "9effda40334841573b2aa2600f56566a9faf71ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9f13bcae6ae451b9a0c4d2f22c6557fcfbc2c3f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9f1936809149b1ca45c64b1468ba966bcdc4e331", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations CV-A4: Coxsackievirus A4; HEV: Human enterovirus; HFMD: Hand, foot, and mouth disease.", "The authors declare that they have no competing interests.", "Submit your next manuscript to BioMed Central and take full advantage of: " ] },{ "paper_id": "9f234fa9b0d6d7c0809106111104ad8843f3a931", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Then the recency sample is defined as:", "Multivariable Regression Model. We developed multivariable linear regression models to estimate and predict weekly percent ILI for Mexico, Chile and Argentina.", "S t~Xn{t , y n{t \u00f0 \u00de , \u00c1 \u00c1 \u00c1 , X n , y n \u00f0 \u00de f g \u00f04\u00de" ] },{ "paper_id": "9f27a960236a99c8b1dc60e71e111257a1d5e862", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For both cases and controls, venous blood specimens totalling 5-10 ml were collected from subjects and genomic DNA was then extracted from the lymphocytes using the QIAamp DNA Blood Midi Kit (Qiagen, German) following the manufacturer's protocol. These procedures were reviewed and approved by the Human Ethics Approval Committee of SYSUCC.", "PCR products were recovered, and further purified. Sequencing reactions were performed using PCR primers and all nucleotide sequences were obtained using the 3730 automated sequencer (Applied Biosystems). Sequence alignment and SNP search were inspected using DNAStar analysis programs (DNAStar, Madison, WI, USA) using the nucleic acid sequences from Genebank at National Center for Biotechnology Information (NCBI) as the prototype sequence [GenBank:" ] },{ "paper_id": "9f2a5b356d46600dfa40b61958808eaaa105bef4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Competing interests: PR, MBN, and JT are paid employees of Predictive Science Inc. DPB is a paid employee of Leidos. SR received consulting fees from Predictive Science Inc. The authors have declared that no other competing interests exist." ] },{ "paper_id": "9f3ce3644f26781fd3d232942e4b5a36291545b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Primary murine embryonic fibroblasts (MEFs) were stimulated with 1000 U/ml murine IFN-b (PBL, Inc., Piscataway, NJ) for 16 h and lysed in lysis buffer [50 mM Tris pH 7.6, 150 mM NaCl, 0.5% Triton X-100, 1 mM sodium orthovanadate, 10 mM sodium fluoride, 5 mM sodium pyrophosphate, 10 mM bglycerophosphate and 16 complete EDTA-free protease inhibitor (Roche, Indianapolis, IN)]. 10 mg of whole cell extract were separated via 10% SDS-PAGE, transferred to PVDF membranes, blocked with 5% dry milk in Tris-buffered saline/0.05% Tween-20 overnight and labeled with anti-Ifit3/P49, anti-Ifit2/P54 or anti-Ifit1/P56 polyclonal rabbit sera [17, 38] .", "Statistical significance of mouse survival differences was calculated by Mantel-Cox log rank test. To assess significance of differences in gene expressions or virus titers, the two-tailed Mann-Whitney test was used. All calculations were performed using GraphPad Prism 5.02 software.", "Ifit2 and Ifit1 are induced in VSV-infected regions of OB and brain" ] },{ "paper_id": "9f4050b9399c1b4b744d79edca2d37ed021ad362", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9f548a03c496ef67ce743572cca4201debbf9910", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition, physicians' professional duty of care to each individual patient can remain intact and they can follow the rule of rescue, as described earlier, without compromising the wider public health effort. With cluster designs, there will be no single physician-scientist handing out a drug to one patient and then refusing to treat the next in line (Sabin et al. 2008) .", "September, Volume 13, Number 9, 2013 ajob 7", "12. I thank David Spiegelhalter for his insights on incorporating arbitrary clusters.", "We have seen that people are divided into groups, prior to any consideration of research, in order to contain the disease within defined geographical areas. However, clusters formed for the purposes of running controlled research would have to be compatible with strategies for social isolation. Depending on how local communities are formed, providing access to promising new therapies sequentially according to geographically defined clusters may exacerbate any preexisting social inequalities.", "Cooperative methods for trying out new treatments and for sharing epidemiological and effectiveness data seem crucial (Langat et al. 2011 ). However, the prospects for sharing data between countries may be more limited than we might imagine, even with coordination provided by the WHO. 11 A lot of the information flows informally, but the formal sharing of confidential documents has previously proved impossible. With time, there might be formal agreements in place to facilitate sharing." ] },{ "paper_id": "9f5eb4cb37108793e2cf0ed3d5a68fea14620866", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although there has been considerable interest in applying machine learning methods to predict the effects of non-synonymous mutations, the majority of the work focused on deleterious mutations or disease associated mutations [16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27] . Previous efforts outlined structure-and sequencebased criteria for designing TS mutations of globular proteins [14, 15] . They suggest first the identification of buried sites or ligand binding sites and then random mutation of one site. As these ad hoc criteria have no underlying statistical framework, it is infeasible to compare them with our TS prediction models.", "We calculated five measures to assess model performance. By taking 0.5 as the threshold to define TS and neutral mutations, we calculated accuracy (ACC), Matthews correlation coefficient (MCC), and Kullback-Leibler divergence (KL) [52] . ACC and MCC were defined as ACC~T PzTN TPzFNzTNzFP and MCCT", "We evaluated the classification accuracy of TS models by tenfold cross-validation, where the classifier was built from 90% of the training set and evaluated with the remaining 10%, and the process iterated 10 times. We further applied a leave-one proteinout strategy to evaluate the model performance. Mutations from four proteins were used for building the classifier while mutations from one reserved protein were held out for evaluation. Finally we evaluated our models using independent datasets.", "We applied a Lasso regularized procedure to select a parsimonious feature set from all studied features. Lasso minimizes the usual sum of squared errors, with a bound on the sum of the absolute values of the coefficients [50] . We implemented Least Angle Regression [51] , an efficient Lasso model selection algorithm, to select a subset of features. The subset features were then included in the logistic regression model to predict TS mutations." ] },{ "paper_id": "9f63dea0f76ee477d2e8e5209d40179db431ab1d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sources of data. We recruited kindergartens, primary and secondary schools in February-May, 2015 and September 2015-January 2016, covering the major peak HFMD seasons in Hong Kong. We recruited all students from the classes which reported HFMD cases. Classes with \u22652 HFMD cases were selected for the present analysis of incubation periods.", "Hand, foot and mouth disease is a childhood disease caused by various viruses that belong to the enterovirus genus including coxsackieviruses, echoviruses and enteroviruses 1 , characterized by fever and vesicular sores on the hands, feet and mouth 2 . Large outbreaks of HFMD have occurred frequently in Asia 3 and occasionally in Europe 4 and the US 5 mainly affecting children under 5 years old 6 . Severe complications may sometimes arise with neurological, cardiovascular or respiratory problems 7 . HFMD causes an average of 500-900 deaths each year in China 3 . The incubation period, defined as the time from infection to symptom onset, is one of the important parameters to guide disease control and prevention 8 .", "We distributed questionnaires to the parents or legal guardians of the participated students to collect demographic and epidemiological information. We also collected key information related to disease transmission and progression of HFMD, such as dates of symptom onset (specifically for fever, oral ulcer and rash), dates of sick absence, and potential epidemiological link to other HFMD cases in household. Incentives were provided for the HFMD cases who provided more detailed information. We also collected attendance records from the schools, stratified by HFMD cases and non-cases to assess data completeness." ] },{ "paper_id": "9f63ebfaab049c0968d72166761217b3aaa1fe00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We conducted a prospective, clinical study. Forty-one mechanically ventilated SARS patients were included in our study. All SARS patients were sedated and received mechanical ventilation in the isolation ICU.", "pneumomediastinum (12%) in a general population of SARS patients [3] . Choi et al. had also shown that subcutaneous emphysema, pneumothorax and pneumomediastinum were detected in six SARS patients (2.2%) who had not received positive-pressure ventilation [18] .", "R441" ] },{ "paper_id": "9f75752eb62482a4e2919951414267f541e419db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal-related experimental protocols were approved by The Ohio State University Institutional Animal Care and Use Committee. Six conventional sows and their litters (litter A-F) were assigned randomly to three groups: (1) S-INDEL PEDV Iowa106 inoculation (litters A-D);", "One to two piglets in each litter was randomly selected and euthanized for histopathology evaluation at 3 dpi; others, unless they were moribund and fit early removal criteria, were retained to evaluate the duration of clinical signs, mortality and fecal viral shedding.", "At necropsy, both intestine and other major organs were examined. Duodenum (5 cm distal to the pylorus), jejunum (three samples taken at 40-60 cm intervals), ileum (5 cm anterior to the ileo-caecal valve), cecum, the middle segment of colon and mesenteric lymph nodes were collected. After 48 h fixation in 10% neutral buffered formalin, tissue sections were trimmed, processed, and embedded in paraffin. Four micron sections were cut and routinely stained with hematoxylin and eosin. For each jejunum section, at least ten villi and crypts were measured using a computerized image system with villous height and crypt depth (VH:CD) ratios calculated as previous described [9] ." ] },{ "paper_id": "9f7ed2037968c63fa97eb6fc7c35e9738a654541", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two cross-sectional studies were separately conducted in the study site." ] },{ "paper_id": "9f8273bc745daf5c556f52ab081af19bb679db36", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Text S1 Supplemental Material and Methods. Includes additional details on experimental procedures and a list of primers, siRNA and shRNAs used in the study. (DOC) ", "is closely linked to its ability to degrade mRNAs, consistent with the two-step model for SOX-mediated mRNA degradation.", "Viruses use a number of strategies to commandeer host machinery and create an optimal environment for their replication. One strategy employed by oncogenic gammaherpesviruses such as Kaposi's sarcoma-associated herpesvirus (KSHV) is to block cellular gene expression through extensive destruction of mRNAs. A single viral protein called SOX is sufficient to drive this phenotype, but the mechanism by which it does so has remained unclear." ] },{ "paper_id": "9f88c05ff539e0fd17ef61d08a51757f1e93b55a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was funded by a Natural Environment Research Council (NERC) grant to We thank Wendy R. Hood, Mark R. Liles, Anna M. Tucker, Carla C. Stout, P. Sankey, R. Mills, and Hill lab undergraduate students for assistance with this project. We also thank Hill and Hood lab members for providing feedback on the manuscript.", "Overall, there was a significant quadratic relationship between the production of M. gallisepticum-specific antibodies and time (linear mixed model; time: F 1,53.9 \u03ed 35.8, P \u03fd 0.0001; time 2 : F 1,54.5 \u03ed 8.2, P \u03fd 0.0001) (Fig. 3) . However, the strength and pattern of this relationship differed significantly between the two treatment groups, leading to a significant treatment-by-time interaction (F 1,53.9 \u03ed 8.2, P \u03ed 0.045). For example, while HF1995 triggered antibody responses to increase at a rate of 0.06 enzyme-linked immunosorbent assay (ELISA) units (EU)/ml between 7 and 14 dpi, Rlow did so at a rate of 0.01 EU/ml over that same period, generating a 130% increase in the amplitude of the response of HF1995-inoculated birds relative to Rlow-inoculated ones (treatment, F 1,58.8 \u03ed 18.6, P \u03ed 0.022).", "M. gallisepticum presence and load. We tested the respiratory epithelia of all house finches for M. gallisepticum at 0, 2, 7, 14, 21, 28, 42, and 56 dpi. Choanal swabs were tested for the presence of M. gallisepticum via PCR followed by agarose gel electrophoresis (49) . Briefly, swabs were placed in 100 l of sterile nuclease-free water. Swabs were then placed at 100\u00b0C for 10 min, placed at \u03ea20\u00b0C for 10 min, and finally centrifuged at 13,000 rpm for 5 min. We tested the supernatant of each sample in duplicate for the presence of M. gallisepticum using the forward primer 5= GCTTCCTTGCGGTTAGCAAC 3= and reverse primer 5= GAGCTAATCTGTAAAGTTGGTC 3=. PCR parameters were as follows: 94\u00b0C for 5 min, 35 cycles of 94\u00b0C for 30 s, 55\u00b0C for 30 s, and 72\u00b0C for 30 s, and a final 5-min extension at 72\u00b0C (49) . In each assay, M. gallisepticum DNA extracted from pure culture served as a positive control.", "M. gallisepticum-specific antibody (IgY) detection. Comparisons of M. gallisepticum-specific antibody concentrations in plasma at 7, 14, 21, and 28 dpi were made using an enzyme-linked immunosorbent assay (ELISA) and a standard curve of pooled house finch plasma from experimental house finches. Briefly, the goat anti-passerine immunoglobulin Y (IgY) secondary antibody (53) was conjugated to horseradish peroxidase (HRP) using a Lightning Link HRP kit (Innova Biosciences) according to the manufacturer's instructions. Samples and standards were diluted in 1\u03eb sample-conjugate diluent (Affinitech, Ltd.), and then 100 l of each was plated in duplicate onto M. gallisepticum-coated plates (Affinitech, Ltd.). After a 1-h incubation at room temperature (RT), plates were washed three times with 1\u03eb wash buffer (50 mM Tris-buffered saline, pH 8.0, with 0.05% Tween 20; Bethyl Laboratories). The HRP-conjugated antibody was diluted 1:10,000 in sample-conjugate diluent (50 mM Tris-buffered saline, pH 8.0, with 1% bovine serum albumin and 0.05% Tween 20; Bethyl Laboratories), and 100 l of the diluted antibody was then added to each well. Plates were incubated for 1 h at RT and then washed three times in 1\u03eb wash buffer. One hundred microliters of the enzyme substrate 3,3=,5,5=-tetramethylbenzidine (TMB) one-component HRP microwell substrate (Bethyl Laboratories) was added to each well, and plates were incubated at RT for 15 min. The reaction was then stopped with 100 l of ELISA stop buffer (0.18 M H 2 SO 4 ; Bethyl Laboratories), and plates were read at 450 nm using a BioTek PowerWave XS plate reader. Samples were considered positive for M. gallisepticum-specific antibodies if the absorbance at 450 nm was at least three times the background. For the pooled standard curve, this cutoff was between dilutions of 1:6,400 and 1:12,800. All samples were run at the same dilution, allowing for comparison of concentrations between treatments based on the pooled standard curve but not determination of absolute concentrations. Because of this, antibody concentrations are reported as ELISA units (EU) per milliliter, with the starting concentration in the undiluted pooled sample being arbitrarily assigned." ] },{ "paper_id": "9f8d663bc0388e20995d91618f776fa6a61a5258", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9f9e925d9999ab39745f2ee8be3efffb5277d082", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "3) The wasp injects VLPs capable of molecular mimicry and/or direct defence suppression." ] },{ "paper_id": "9faf6a32a170b3fc5950af6a7d34cf710c79321d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Non-targeting siRNA(10nM) ST6GAL 1-siRNA(10nM) " ] },{ "paper_id": "9fb0b05599ed5c64ffbec62cf896434ed1c56349", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9fb2d27c92ebc1fc7804e55e557fe8c126da62f9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sigma Stat 2008 software (SPSS Science, San Rafael, CA) was used for analyses. Differences between groups were tested using the one-way ANOVA or Kruskal-Wallis test according to data distribution. When these tests demonstrated a significant difference between groups (p < 0.05), the Tukey test to correct for multiple comparisons was used. Pearson or Spearman Rank Order test were used for correlations. In all analyses, a two-tailed p value < 0.05 was considered to be statistically significant." ] },{ "paper_id": "9fb5556c3b5fdb3bff762a42f16c21a7fa65d801", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data represent the means + \u2212 S.E.M. and statistics were calculated using a two-way ANOVA with bonferroni post-test. P values <0.05 were considered statistically significant. Graphs were plotted using GraphPad Prism 4.0c software.", "Carine Savarin designed and performed the experiments, analyzed data and wrote the paper; Cornelia Bergmann and David Hinton analyzed data and wrote the paper; Stephen Stohlman designed the research, interpreted data and wrote the paper." ] },{ "paper_id": "9fb9a39c7e68fd9c32ab53a6a6ce9af6f1fd2e09", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To identify cellular proteins that interact with UL44, Y2H screens were carried out with a bait consisting of full-length UL44 protein (amino acids 1-433) fused to the E. coli LexA protein.", "For confocal laser-scanning microscopy (CLSM) analysis, COS-1 were transfected using the Arrest-IN TM (Biosystems) reagent, according to the manufacturer's recommendations. At 24 h posttransfection, cells were fixed with 4% paraformaldehyde. Cells were imaged using a Leica TCS-SP2 confocal microscope equipped with a 636 oil immersion objective.", "(TIF) ", "Most replicative DNA polymerases include a catalytic subunit, responsible for DNA polymerization, and a processivity factor that holds the catalytic subunit on DNA to allow continuous DNA synthesis. One of the best-studied processivity factors is proliferating cell nuclear antigen (PCNA) of eukaryotic DNA polymerases d and e [1] . PCNA, which belongs to the family of so-called ''sliding clamps'', has no inherent DNA-binding capacity, but with the aid of clamp loader proteins is assembled onto DNA as a toroidal homotrimer [2] . In addition to DNA replication, PCNA has been implicated in DNA recombination and repair, as well as in DNA methylation, chromatin remodeling, and cell cycle regulation [1] . Consistent with its pleiotropic functions, it interacts with a plethora of proteins [3] and undergoes a number of posttranslational modifications, including phosphorylation, acetyla-tion, ubiquitination and sumoylation, which are believed to regulate its subcellular localization, stability and protein binding specificity [4, 5, 6] ." ] },{ "paper_id": "9fc349caa11e13a92c959d5f8b1669f4b425e2d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chaihu alleviates a wide spectrum of disorders in a multi-target manner through its immunomodulatory [7] , antipyretic [10] , hepatoprotective [13] , choleretic [15] , autophagy-inducing [16] , sedative and analgesic [15] , antihyperlipidemic [15] , antiviral [9] , and anticancer [14] effects.", "The authors declare that they have no competing interests.", "Authors' contributions VKWW conceived and planned the review. BYKL and JFO carried out the review plan and wrote the manuscript. All authors read and approved the final manuscript." ] },{ "paper_id": "9fd83230962e678e8ec4d5dffee0bb431e19c2d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Next-generation sequencing (NGS) is an attractive approach to diagnosis of infection and might serve as a great potential method to identify viruses, bacteria, and fungi from a range of biological and environmental samples in clinical diagnostic and reference labs [1, 2] . Various NGS approaches provide solutions for detection of purified and concentrated viruses from culture, however, direct identification of viral genomes from clinical specimens using NGS methods still has its challenges, including noise from the host or microbiota cells and the limited viral RNA and DNA quantities [3, 4] .", ", and 45 s at 55\u00b0C.", "Author details" ] },{ "paper_id": "9fd85ed07e4b503e9ddb2f5dd4c94f0a12ba4361", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9fdb08f94d250800ca69a84cb21c110adbe1476b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "9fdf9d656c7c79e8d8746fb3a5beeff11894dc8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that they have no competing interests.", "C.C. investigated and wrote the manuscript, but he benefited from talking to many friends and colleagues at the 2017 China Primatological Society in Xi'an.", "Primates are very charismatic and are generally liked by both the Chinese people and international groups, thus they can act as \"Flagship\" or \"Guardian Angel\" species to promote the value of restoring these lands to a native forest (Bicca-Marques & De Freitas, 2010; Simberloff, 1998) . It is my opinion that this is an exciting time to integrate restoration into conservation strategies to make informed and effective conservation and management decisions for the primates of China." ] },{ "paper_id": "9fe4bb195ffbcf6f450478fa94e72e099fb7d335", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The harvested viruses were clarified by low-speed centrifugation (8000 g/min) and used as viral stocks.", "The protocol was approved by the Ethics Committee of the First Affiliated Hospital, School of Medicine, Zhejiang University." ] },{ "paper_id": "9ff6863b239e533b93dd1147c0c9a36a01d7ad66", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Graphical Abstract Highlights d Temporal proteomic analysis quantifies host and viral dynamics during vaccinia infection d Host protein families are proteasomally degraded over the course of vaccinia infection d Vaccinia protein C6 targets HDAC5 for proteasomal degradation d HDAC5 is a host antiviral factor that restricts different families of DNA viruses SUMMARY", "Further information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact, Michael Weekes (mpw1001@cam.ac.uk)." ] },{ "paper_id": "9ffa106061fd815e4bb93389274819e640dfb840", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The outbreak of the pandemic flu, Influenza A H1N1 (Swine Flu) in early 2009, provided a major challenge to health services around the world. Previous pandemics have led to stockpiling of goods, the victimisation of particular population groups, and the cancellation of travel and the boycotting of particular foods (e.g. pork). We examined initial behavioural and attitudinal responses towards Influenza A, H1N1 (\"Swine flu\") in the six days following the WHO pandemic alert level 5, and regional differences in these responses.", "Conclusion: Initial responses to Influenza A show large regional differences in anxiety, with Malaysians more anxious and more likely to reduce travel and to buy masks and food. Discussions with family and friends may reinforce existing anxiety levels. Particular groups (homosexuals, prostitutes, the homeless) are perceived as at greater risk, potentially leading to increased prejudice during a pandemic. Europeans underestimated mortality of seasonal flu, and require more information about the protection given by seasonal flu inoculation.", "Following ethical approval by the relevant University ethics boards in London and Malaysia, data was collected from a total of 328 respondents (mean age 31.2, SD 13.37, 62% female). A paper version of the questionnaire was distributed in Malaysia, with students recruiting 180 respondents from their own classes, and community members from residential areas and local offices in Kuala Lumpur (age range 18-70, mean age 29.0 (SD 13.36), 59% female)). Response rate was generally good, with 180 out of 200 approached to participate (90%) completing the questionnaire. In Europe, data was collected between 30 th April and 6 th May 2009 from 158 respondents (age range 18-69, mean age 33.9, SD 12.8, 68% female) via an online questionnaire in English or Portuguese, linked to the website http://www.swinefluques tionnaire.com. The website link was pasted onto a variety of general, non-health networking websites (e.g. 'I love London'). Respondents were primarily from the UK and Portugal but also included 30 respondents living outside these countries and resident in Finland (19 respondents), Poland (6 respondents), Malta (3 respondents) and France (2 respondents). Ten non-European based residents were then removed from the online survey before analysis." ] },{ "paper_id": "9ffdd59ae97f369bdf0202cd78308225f399b3fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The recent Zika outbreak in the Americas, Ebola epidemic in West Africa and the increased frequency and impact of emerging and re-emerging infections of animal origin have increased the calls for greater preparedness in early detection and responses to public health events. One-Health approaches that emphasize collaborations between human health, animal health and environmental health sectors for the prevention, early detection and response to disease outbreaks have been hailed as a key strategy. Here we highlight three main efforts that have progressed the implementation of One Health in Kenya.", "The challenges associated with enhancing this approach practically within countries remain daunting. These challenges include competing priorities, funding deficiencies and breaking a silo mentality within and between human and animal professions. It is, however, our opinion that three specific efforts in Kenya; the establishment of the ZDU, One-Health workforce development including joint trainings for Veterinarians and Physicians through the FELTP program and the deliberate efforts to foster collaboration between institutions working on zoonosis have not only significantly accelerated the uptake and practice of One Health in Kenya, but have contributed to increased visibility of zoonotic diseases in Kenya and improvement of Kenya's preparedness against health threats of animal origin.", "The World Health Organization's (WHO) International Health Regulations (IHR), the World Organization for Animal Health (OIE) Performance of Veterinary Services and the more recent Global Health Security Agenda are all aimed at supporting countries to prepare, detect and respond to health threats and all recognize the critical role that One Health collaborations play. While implementation of the One Health approach at national level is notable, there remain significant gaps in its implementation at subnational administrative levels under the devolved governance adopted in Kenya in 2013. Veterinary and health services including surveillance and laboratory diagnosis for zoonoses have been devolved to 47 counties, thereby creating a necessity to also devolve the One Health coordination mechanisms. This is currently a focus for implementation of One Health in Kenya in both creating One-Health coordination units and improving surveillance and response to outbreaks at the county level." ] },{ "paper_id": "9ffde004c991e9cf3c63e9143946a64ffaa9ee2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks.", "The Microbial Rosetta Stone is available at http://www.microbialrosettastone.com/. The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.", "Several viruses responsible for human epidemics have made a transition from animal host to human host and are now transmitted from human to human. Human immunodeficiency virus (Figure 7) , responsible for the AIDS epidemic, is one example [25] . Although it has yet to be proven, it is suspected that severe acute respiratory syndrome (SARS), caused by the SARS coronavirus ( Figure 6) , also resulted from a species jump [26] . For many years, Robert G. Webster has studied the importance of influenza viruses in wild birds as a major reservoir of influenza viruses and has clarified their role in the evolution of pandemic strains that infect humans and lower animals [27] .", "The goal of the database is to provide an informative, readily accessible, single location for basic information on a broad range of important disease causing agents. The database will help users to avoid the pitfalls of confusing nomenclature and taxonomic relationships and allow access to literature on in-depth studies. The database can be accessed at http://www.microbialrosettastone.com/." ] },{ "paper_id": "a0016598cd0ea40803d8ab461f4ebdba9abe94c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Text S1 Adaptive contact networks change effective disease infectiousness and dynamics. 1 ", "which is valid for both SIR, SIS (r~0) and SI (d~0,r~0) models.", "-remain valid for a wide range of intermediate time scales, strengthening the power of the analytical predictions derived here." ] },{ "paper_id": "a007977dad90a07b3beb9f689e3be8b3f7d2a7f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HCV is a single-stranded, positive-sense, enveloped flavivirus. The viral RNA genome is ~9.6 kb in length and contains a single open reading frame encoding a large polyprotein. The polyprotein is processed by viral and host proteases, resulting in three structural proteins and seven nonstructural proteins ( Figure 1A ) [6, 7] .", "Viruses 2015, 7 1154", "The Virus Pathogen Database and Analysis Resource (ViPR) supports virology researchers studying select agents and other significant public health pathogens belonging to 14 virus families including HCV [222] . Cross-referencing data and integrated computational tools into the online ViPR resource allow complex analyses. ViPR captures data from external and internal sources and makes them accessible through custom searches. ViPR is primarily focused on viruses of human interest; however, families isolated from other host species are also available for comparison. ViPR features a suite of data analysis and visualization tools to perform custom correlative analyses. ViPR uses the NCBI RefSeq strains to extend the manually optimized annotations to the rest of the taxon. Thus, the ViPR resource provides the scientific community with friendly tools capable of performing complex analytical workflows [222] ." ] },{ "paper_id": "a013535d6925d423b5d999a4b2e1ded678e190a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pilgrims " ] },{ "paper_id": "a015401a1cdf151bd0bca060bd8eb96d6683a147", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(TIF) " ] },{ "paper_id": "a02952893a51f2255a8d9d84b3eba6fe1b113996", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Toxoplasma gondii infects all mammals. It can cause severe brain and eye damage in the fetus, in newborn infants, and in immunecompromised individuals. 1 Although anti-parasitic medicines such as sulfadiazine and pyrimethamine are available, some patients experience side effects including toxicity and hypersensitivity. Latent, encysted parasites are not eliminated by these treatments. 2 Therefore, development of a potent, safe, effective vaccine is greatly needed.", "The data that support the findings of this study are available from ToxoDB (http://toxodb.org/toxo/) and the corresponding author on reasonable request.", "Preparation and characterization of CD8 + -SAPN and empty-SAPN The SAPN constructs were expressed, purified and folded to form nanoparticles ( Fig. 1c-e) . The protein has a relative molecular weight of about 48 kDa on a Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) (Fig. 1c , e). Transmission electron microscopy (Fig. 1d) showed a relatively uniform distribution of non-aggregated nanoparticles of about 30 nm in diameter." ] },{ "paper_id": "a02d5fbeef1d5139b09a0e0017e7fe5e5c885e2c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Table S1 Exonuclease Assay. The indicated number of units of enzyme were incubated with [33P]-labeled PCR product for 10 minutes at 70uC as described in methods. Shown are the percent counts released with background (water-only control) subtracted. Not detected is indicated when counts are not significantly above background counts, i.e. ,10%.", "Despite their wide use and general reliability, existing twoenzyme RT-PCR systems have several documented performance problems attributed to deficiencies inherent in retroviral RTs: 1) poor reagent stability, 2) low fidelity, 3) frequent rearrangements during cDNA synthesis, 4) secondary enzymatic activities (i.e. RNase H and strand switching), 5) bias for specific primers and templates, and 6) inhibition of PCR Pol enzymes [3, 4, 5, 6, 7] .", "(DOC)" ] },{ "paper_id": "a03298211c385b7bd1d1ebdc98b1cc69efe7f54d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protein extraction, Western blotting, and total protein analysis Total protein was extracted as previously described [24] and equal volumes of cell lysates were separated on 4-15% Criterion TM TGX TM precast polyacrylamide gels (Bio-Rad, Hercules, CA). Proteins were transferred to PVDF membrane and expression of target proteins was detected with the following antibodies and dilutions: rabbit anti-BMV 1a at 1:10,000, mouse anti-BMV 2a Pol at 1:3,000, and mouse anti-Pgk1p (Molecular Probes, Carlsbad, CA) at 1:10,000 using HRP-conjugated secondary antibodies (Thermo Scientific, Rockford, IL) and Supersignal West Femto substrate (Thermo Scientific, Rockford, IL).", "Viruses survive with limited genetic material by interacting with and exploiting host factors at essentially every replication step [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14] . Identifying the host factors and pathways exploited in virus replication and the nature of their contributions and interactions with virus-encoded replication factors represent major challenges and opportunities for understanding and controlling viruses.", "The 19 confirmed dox-repressed genes that enhanced BMV RNA accumulation encode proteins with functions in varied cellular processes, including ribosome biosynthesis (DHR2, ECM16, NOP7, PWP1, RIO2, RPA43, UTP4, UTP18, and YGR251w), cell cycle/ DNA maintenance (ADE13 and SPC29), mRNA metabolism (RNA15, SPT6, and SWD2), protein homeostasis (PFY1), translation (DED1), trafficking (NUP57) and lipid synthesis (ALG14) ( Table 4 ). Possible relations of these functions to viral replication are considered further in the Discussion." ] },{ "paper_id": "a034fc1a3e926d0e12339678c32e892c37f514cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Text S1 Methods supplement. Detecting Differential Transmissibilities of Self-Limited Outbreaks", "In summary, we have introduced and validated a method for comparing case data grouped into different categories and applied this method to a number of different scenarios. The versatility of the method has been explored through examination of a variety of diseases and data types. By providing quantitative information on transmission, surveillance needs, or the effectiveness of control interventions, each type of analysis has the potential to assist in epidemiological assessments and public health planning.", "generating function, Q(s)~P ? j~0 q j : s j , in which the polynomial coefficients are the offspring probabilities [26] [27] [28] .", "The stochastic nature of infectious disease transmission is particularly important when R eff v1, as it can result in substantial variation in the size distribution of transmission chains. In this case it is helpful to model transmission as a branching process [26] . In this formulation, the offspring distribution specifies the probability that an infected individual will cause 0,1,2, . . . new infections. We specify the corresponding offspring probabilities to be q 0 ,q 1 ,q 2 , . . ., with P ? j~0 q j~1 . To facilitate likelihood calculations (as seen below), the offspring distribution can be represented as a" ] },{ "paper_id": "a03517f26664be79239bcdf3dbb0966913206a86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Swabs and feces were maintained in 1 ml of UTM\u2122 Viral Transport Medium (Catalog Number: 360C; Copan Diagnostics, Corona, California) and stored at \u221220\u00b0C. Before any further analyses took place, the presence of the rabies virus antigen was investigated on dead animals by direct immunofluorescent staining in a BSL3 Laboratory, after necropsy. Once rabies infection has been excluded, samples underwent a pre-treatment before being submitted to automatic nucleic acid purification with magnetic beads.", "Upon amplification, 20 \u03bcl of PCR products were run in 1.5% agarose gel electrophoresis and visualized by GelGreen Nucleic Acid Gel Stain (Biotium) staining; bands of the expected size were excised from the gel for sequencing.", "PCR products (20 \u03bcl) were run and recovered from a 1.5% agarose gel, as described before." ] },{ "paper_id": "a040109f4ae97738c7940d711a60f07f573b9754", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The complete nucleotide sequences of Y55 (H9N2) and Vac1 (H5N1) have been registered in GenBank/ EMBL/DDBJ (Accession numbers: AB256671-AB256678 [36] and AB259709-AB259716 [37] , respectively).", "All experiments were carried out in self-contained isolator units (Tokiwa Kagaku, Tokyo, Japan) at a BSL3 biosafety facility at the Graduate School of Veterinary Medicine, Hokkaido University, Japan. The experiments were performed according to the guidelines of the institutional animal care and use committee of the Graduate School of Veterinary Medicine. ", "H5N1 mutant viruses acquired intravenous pathogenicity by passaging twice in chicks; all of the chickens rgY55 (H9N2) CCT GCT AGA TCA AGT AGA / GGA" ] },{ "paper_id": "a04371951c94976a9b879f321764eb6dbeb4a9ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses. Data shown in each figure are derived from three independent experiments using different donors. Data are presented as mean 6 SEM. Survival curves were analyzed using the Kaplan-Meier method. Chimera groups were statistically compared using a Student's t test. If the P-value was less than 0.05, the result was considered to be significant.", "Written informed consent for blood sampling was obtained from all adult subjects. For blood sampling from children, written parental consent was obtained. Ethical approval was obtained from the Ethical and Scientific Committee of the University of Texas Medical Branch.", "Assays of IMC activities." ] },{ "paper_id": "a0444a2148ffe99348088aa7c04e21dcea70d602", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed using Prism software (GraphPad). Unless otherwise noted, comparisons were performed using one-way analysis of variance, followed by post hoc analysis using Tukey's procedure where appropriate.", "Active TGF-\u03b21 and TGF-\u03b22 production by EB-NPCs and DD-NPCs was determined using human Quantikine ELISA Kits from R&D Systems in accordance with the manufacturer's specifications.", "PLOS ONE |" ] },{ "paper_id": "a04811d55a6f779546cf0c2bf5d46982fb989908", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The samples taken during the present study knew no ethical requirements. In fact, these samples were taken from animals slaughtered by legal and illegal hunters.", "To achieve our goal, we used a stereo-microscope (Zeiss Stemi 2000) with a 60\u00d7 resolution, a microscope with a 100\u00d7 resolution, a Geographic Position System, 70\u00b0 of ethanol, plastic bottles, pliers, a pencil, and adhesive papers, A4 papers.", "Avg." ] },{ "paper_id": "a05173bdf26286064e4e13b8f5253330d9a9089b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We developed a feline model of lentiviral cross-species transmission using a puma lentivirus (PLV or FIV Pco ) which infects domestic cats but does not cause disease.", "Prior to PERMANOVA data were square root transformed to reduce the dominance of high proviral, FIV mRNA and cytokine levels, among individual tissues, on the analysis. PERMANOVAs were based on Bray-Curtis similarity matrices and graphically represented using non-metric multidimensional scaling (NMDS) plots. PERMDISP analyses were based on the same transformation and similarity matrix as PERMANOVA. GLM models were generally based on a normal data distribution and identity link function, except where a more optimal dispersion (poisson or gamma) or link function (log) could be identified, as determined by Akaike Information Criterion. All analyses described were undertaken using programs PRIMER [34] and R [35] .", "Viral mRNA expression was measured relative to GAPDH expression." ] },{ "paper_id": "a05a9d684b2b6de28b18e78a82585b76a973e258", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a0682c2b9aabc40d6daca4496ceec2ccd0583aab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary information accompanies this paper at https ://doi. org/10.1186/s1296 7-019-2116-8." ] },{ "paper_id": "a068f1ec98befb3d767ba602df5f314604f0aee8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One-way ANOVA with Dunett's multiple comparisons test ( Figure 7A -E) or Sidak's multiple comparisons test ( Figure 7F -G) were performed using the GraphPad Prism 8 software.", "CCLV-RIE 1018) and Huh7 (human hepatocarcinoma) cells (kindly provided by Stephan Becker, Philipps University Marburg, Marburg, Germany) were maintained in Dulbecco's modified Eagle's medium (DMEM; ThermoFisher Scientific, Waltham, MA, USA) supplemented with 10% fetal bovine serum (FBS), 100 U/mL penicillin and 100 \u00b5g/mL streptomycin (PS; ThermoFisher Scientific) and 1\u00d7 GlutaMAX (ThermoFisher Scientific). All cells were grown at 37 \u2022 C with 5% CO 2 .", "For immunofluorescence analysis, Huh7 cells in ibidi 8-well chamber slides were infected with rgEBOV-wt [44] at an MOI of 1. Sixteen hours p.i., cells were washed with PBS and fixed using 10% formalin. The subsequent procedure for immunofluorescence staining was performed as described above. All experiments involving infectious EBOV were done in the BSL4 laboratory of the Friedrich-Loeffler-Institut following approved SOPs." ] },{ "paper_id": "a0797dceb80b7f1c136590f3ba4b16da218de23f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, many examples of successful intrabodymediated proteins knockdown in vitro, obtained using cytosolic intrabodies, have been reported in literature [45] ." ] },{ "paper_id": "a07e1b3380d19de30b382b8d64c6c820965e8091", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Taken together, the results indicate that interference with furin activity by furin inhibitor I affects ZIKV maturation.", "Results are described as mean \u00b1 standard deviation (SD) from at least 3 independent experiments. The significance of the results was analyzed by Student's t test using GraphPad Prism 7 (GraphPad Software, La Jolla, USA)." ] },{ "paper_id": "a086b50101fcfa29f699b41cbf034ae71ac70bff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequence editing, assembling and alignment were performed using BioEdit Sequence Analysis Editor (version 7.0.9.0) [22] . Basic Local Alignment Search Tool (BLAST, http://www.ncbi. nlm.nih.gov) was used to find homologous hits in the sequence databases. Phylogenetic analysis (Neighbor-Joining) with bootstrap (1,000 replicates) was conducted using MEGA version 5.03 [23] . Identity matrices were calculated without removing the gaps and with no distance correction.", "In conclusion, the results of this study demonstrate that: i) members of two distinct calicivirus genera (vesivirus and norovirus) infect domestic cats; ii) NoVs detected in cats are similar to NoVs found in other carnivores (lions and dogs), thus suggesting interspecies circulation for GIV.2 NoV in these animal species. Larger epidemiological investigations and animal experiments are warranted to assess firmly the role of NoV infections in cats. Also, these findings pose a challenge for epidemiological studies of feline enteric pathogens, highlighting the need for reliable NoV-specific diagnostic assays.", "A total of 24 fecal samples were collected in 2010 from domestic cats (Felis catus) by the veterinary clinics of The Ohio State University (OSU) (10 samples, collection A) and Cornell University (CU) (14 samples, collection B). Diarrheic specimens were collected from hospitalized cats with gastroenteric symptoms. The 14 CU fecal samples, collected in July and August 2010, originated from young cats (8-12 weeks old) housed in a New York State animal shelter. The OSU cat specimens were collected in three different periods (July, November and December 2010) from animals of different ages (4 months to 8 years old) ( Table 1) . During the period of hospitalization, cats were located in single cages and feces were collected directly from the cat litter and identified individually with an alpha-numeric code. Fecal samples were stored at 220uC until processing. The fecal samples, collected during this study, were negative for common feline parasites." ] },{ "paper_id": "a087143ccafb8699cca687a6548e99633a98fe21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bat All virus stocks were purified using CsCl gradients (Smith et al., 1969; Hand and Tamm, 1971 ) and stored at \u221280\u00b0C for further use.", "JT conceived the study and wrote the paper. XZ, HW, and CL designed, performed and analyzed all the experiments. ZL and XH provided technical assistance and prepared all the figures. LQ, LW, and SS designed the study and revised the manuscript. All authors reviewed the results and approved the final version of the manuscript.", "The statistical significance of differences between experimental groups was determined with a paired t test and one-way ANOVA with Prism 5.0 software (GraphPad Software). A p-value < 0.05 was selected to indicate significance." ] },{ "paper_id": "a08f5fd1ac9fc3e33a771787d584a845a8558cae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where N: Expected number of quanta.", "where:", "The authors declare no conflict of interest. ", "the three-dimensional model, the continuity equation, momentum equation, and equations related to the degree of turbulence were applied. For the turbulence analysis, the Realizable k-\u03b5 Turbulence model was used. The segregated flow model was selected for the fluid model. " ] },{ "paper_id": "a0916fa29144e650632aba916141809195ab6809", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Integration of [2.0] over t also provides a complex expression which predicts total outbreak size, such that:", "Here erf is the so-called ''error function''.", "Simulations were performed using the Berkeley Madonna dynamic systems modeling package (University of California, Berkeley; http://www.berkeleymadonna.com), and model fits for Nunavut data were performed using the ''Solver'' application for Microsoft Excel (Frontline Systems, Incline Village, Nevada; http://www.solver.com)." ] },{ "paper_id": "a093f4ef60a47e5419181f6826ad4a45af198056", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples were collected between 1997 and 2014 from California, Washington, Arkansas, Tennessee, Louisiana, Georgia, and Florida. Veterinarians in private practice or at university teaching hospitals collected samples. Samples were submitted to the University of Florida or the University of California San Francisco for further processing and storage. Blood samples were collected by cardiac or tail vein puncture and frozen until further processing. Tissue samples were collected during necropsy and frozen until further analysis or placed in formalin for histopathology. For histopathology, samples were preserved in 10% formalin, paraffin embedded, sectioned, and stained with hematoxylin and eosin. Board-certified pathologists blinded to infection status of samples examined H&E stained sections.", "RNA was extracted from tissues as previously described [23] . Sequencing libraries were prepared as previously described [69] . Paired-end 2x135 bp sequencing was performed on an Illumina HiSeq 2500 in the Center for Advanced Technology at UCSF., producing an average of 2.0x10 6 read pairs per sample.", "doi:10.1371/journal.ppat.1004900.g008", "doi:10.1371/journal.ppat.1004900.g009 ensemble of 10 L genotypes. It is possible that within animals the S and L segments inhabit different fitness landscapes. Another, not mutually exclusive, possibility is that differential replication kinetics or packaging efficiencies of the two segments may underlie the observed imbalance. Additional experiments in vitro and in animals will clarify this issue." ] },{ "paper_id": "a09a978336b5c98928dbfb37b12da84d327bfe2d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical significance was evaluated using the Mann-Whitney U-test. A P value < 0.05 was deemed to indicate statistical significance." ] },{ "paper_id": "a0acb3cda6288d12ce50136a88c013a3098ee3fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "After 2 days of acclimation, each pig was administered the dust suspension from swabbed surfaces by orogastric gavage using an 8\u2212gauge French catheter and 60 ml syringe (8 ml/pig), which marked day 0 post inoculation (0 DPI). The 8 ml aliquot combined eight 1-ml dust suspensions sampled from 4 buckets and 4 adjacent belt areas after manufacturing each food treatment from one replicate. Thus, each pig represented 1 of 3 replicates per treatment and each room represented each treatment.", "Writing -original draft: Loni L. Schumacher." ] },{ "paper_id": "a0b13baa35ff28471952e5011f9411529d217f50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The second group (Group 2), housed in an independent isolation unit at the BSL-3 facility of CReSA, consisted of four pigs (numbered 5-8) from a sow of the same origin as Group 1. Group 2 was free from Pestivirus, porcine circovirus type 2 and porcine reproductive respiratory syndrome virus. Both groups had an average weight of 12.6 kg per pig.", "Classical swine fever (CSF) is one of the most devastating diseases for the pig industry throughout the world affecting both domestic pigs and wild boars [1, 2] . It is endemic in Asia, areas of Central and South America and in many Eastern European countries [3, 4] with sporadic occurrence in Western Europe. The CSF virus (CSFV), the etiological agent of CSF, is an icosahedral and enveloped positive stranded RNA virus that, together with bovine viral diarrhoea virus (BVDV) and border diseases virus, belongs to the Pestivirus genus of the Flaviviridae family [5] .", "A trained veterinarian recorded rectal temperature and clinical signs daily in a blinded manner. The pigs were scored daily as follows: one point: pyrexia; two points: pyrexia + mild clinical signs; three points: severe clinical signs; and four points: death. After euthanasia (with intravenous pentobarbital sodium injection), animals were subjected to an exhaustive necropsy in which pathological signs in different organs and tissues were evaluated." ] },{ "paper_id": "a0c2551d031c6dd3f59392c3f75dffc7b694a186", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Checklist S1 STARD Checklist Found at: doi:10.1371/journal.pntd.0000450.s001 (0.10 MB DOC)" ] },{ "paper_id": "a0d73d877a6bcede67ac884d7e5ada5dd3eb810c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An RNA substrate of 32 nucleotides (59-GGGCACACA-CAGTCGACCACACAAAACCACCC-39) was synthesized with the MAXIscript kit (Ambion) using T7 RNA polymerase. The 59triphosphate RNA substrate was purified on a denaturing 8% polyacrylamide gel and visualized by ultraviolet shadowing. The corresponding band was excised and then eluted from the gel by an overnight incubation in 0.1% SDS and 0.5 M ammonium acetate. The RNA was then precipitated with ethanol and quantitated by spectrophotometry. Alternatively, radiolabeled RNA substrates were also synthesized by adding radiolabeled nucleotides to the transcription reaction.", "Historically, very few GTase inhibitors have been developed, neither as scientific tools nor as therapeutic agents. More recently however, novel GTase inhibitors have been discovered [32] . They include the allosteric inhibitor mycophenolic acid, the pyrophosphate analog foscarnet which acts as a product inhibitor, and ribavirin triphosphate, a GTP analog that is transferred to acceptor RNAs by GTase, leading to stable but inefficiently translated pseudo-capped RNA. The current study identifies MZP as a novel allosteric GTase inhibitor, which is speculated to block a crucial conformational change. The GTase activity being the ratelimiting step of the essential capping apparatus, all these GTase inhibitors are promising lead candidates for the development of novel selective capping inhibitors and lead the way to a new class of anti-cancer, antifungal, and antiviral drugs.", "(TIF) " ] },{ "paper_id": "a0e4e330c82c1b1a043345891bef190baa73980f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study protocol was approved by the Ethics Committee of Hannover Medical School (No. 2380-2014) and reviewed by the Federal Commissioner for Data Protection and Freedom of Information. Written informed consent was obtained from all participants.", "We thank all participants in the study for their commitment. Furthermore, we thank all cooperating DCCs in Braunschweig for the opportunity of recruitment. ", "In a longitudinal study on ARI and AGI in households with preschool children comparing prospective and retrospective data collection, we demonstrated that for short recall periods (2 months) both designs produce similar incidence estimates." ] },{ "paper_id": "a0e91efcafa0a743be0342254943e8d31cd36558", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In our previous work [13] several scFvs had been screened out from a phage library using recombinational HCK as antigen.", "Chaperone-like Function of an scFv PLOS ONE | www.plosone.org", "Therefore antibodies with a chaperone-like function were considered as the therapeutic drug candidates for protein misfolding diseases because they only affect mutant proteins, leaving normal proteins intact. In addition, antibodies with a chaperone-like function were helpful research tools for protein folding researches.", "The CDRs are the major region of the antibodies that bind to antigens. Since the CDRs of the scFv ACZ28696.1 was known, the CDRs of scFv-A4 was inferred from the alignment result of the two sequences ( Figure 1 ). The resulted CDR assignment was checked to be complied with the Kabat numbering rules [45] ." ] },{ "paper_id": "a0f13b751004e29186fa070fdffa2e876815e41a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Resistance mechanisms may develop over months or years [6] . Once established, a single resistance mechanism can often allow a bacterium to resist multiple drugs. It remains unclear whether resistance is reversible, and thus whether drug effectiveness is a renewable or non-renewable resource [10] [11] [12] [13] [14] [15] . Drug resistance raises the cost of treatment for infectious diseases, sometimes manifold, as well as increasing morbidity and mortality from such diseases [16] [17] [18] [19] [20] [21] [22] [23] ." ] },{ "paper_id": "a0f4a467be80972f434dabf027d2b5260b608740", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We calculate the probabilities ( ) for any atomic property including ( ) using a Markov Chain model for the gradual effects of the neighboring atoms at different distances in the molecular backbone. This method has been explained in detail in many previous works so we omit the details here [59] .", "Equation (3) described before opens the door to test different hypothesis. A simple hypotheses is H 0 : existence of one small and constant value of the perturbation function \u0394 = 0 for all the pairs of peptides and a linear relationship between perturbations of input/output boundary conditions with coefficients , , , and . Consider", "QSAR/QSPR models are also important in immunoinformatics to predict the propensity of different molecular structures to play different roles in immunological processes. They include skin vaccine adjuvants and sensitizers [30] [31] [32] [33] [34] [35] [36] [37] [38] , drugs and their activity/toxicity protein targets in the immune system [39] , and epitopes [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] . Moreover, Reche and Reinherz [50] implemented PEPVAC (promiscuous epitopebased vaccine), a web server for the formulation of multiepitope vaccines that predict peptides binding to five distinct HLA class I supertypes (A2, A3, B7, A24, and B15). PEPVAC can also identify conserved MHC ligands, as well as those with a C-terminus resulting from proteasomal cleavage. The Dana-Farber Cancer Institute hosted the PEPVAC server at the site http://immunax.dfci.harvard.edu/PEPVAC/. To close with a last example, Lafuente and Reche [51] reviewed the available methods for predicting MHC-peptide binding and discussed their most relevant advantages and drawbacks." ] },{ "paper_id": "a106bdc3abdca61cda30b7f968c388e320e547e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "within an SIR model to account for the psychological effects of a large population infected with SARS, and many authors (e.g. [28, 29] ) set", "3)", "within an SEI model, Xiao & Ruan [27] used", "button within the Twitter interface or by appending the string 'RT' to the beginning of the original message. Such messages account for approximately 30% of the corpus and are mainly resharings of flurelated articles from major news outlets, but can also contain retweets of messages authored by regular Twitter users." ] },{ "paper_id": "a1086d8acf9fe3ae22d83443b0935ecb80f3142a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The statistical package IIBM SPSS Statistics 24 (IBM Corp., Armonk, NY, USA, 2013) was used to analyse the data. Summary and descriptive statistics were performed on aerosol concentrations. All data are expressed as mean, minimum and maximum.", "Several factors influence inhalation dose [5, [25] [26] [27] , and all of these are likely to affect the quantity of released aerosol. Environmental factors (including room dimensions and layout, air turbulence, ventilation, and temperature) also affect the released aerosol distribution [28] [29] [30] . The current observations should therefore be extrapolated with caution, but nevertheless, it can be noted that this study provides compelling evidence that a caregiver or bystander receives an inadvertent drug dose which is intended for the patient.", "Each nebuliser was individually assessed under simulated real use conditions. The laboratory room had a volume of 55 m 3 , three internal doors, but no external doors or windows; the room was mechanically ventilated with an air exchange rate of 2.70 h \u22121 . The ambient temperature and relative humidity in the test room were typically 22 \u2022 C and 35%, respectively, during the test period.", "Aerosol therapy is a mainstay of drug administration in both home and clinical settings for acute and long-term treatments. A variety of aerosol generation technologies deliver drugs to the lungs through patient interfaces across the full range of neonatal to adult patients. The size distributions of generated medical aerosols are typically 1-5 \u00b5m [1]. When released indoors, particles can remain airborne for times ranging from minutes to hours [2] [3] [4] ." ] },{ "paper_id": "a11b3479a9f0e004870ecefa643c4c311c6066cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hybridization was carried out overnight with each probe in concentration of 5 ng/\u03bcl hybridization buffer (1 M Tris-pH 7.2, 5 M NaCl, 10 % sodium dodecyl sulphate) at 45\u00b0C. The sections were then washed 3 \u00d7 3 min in prewarmed (45\u00b0C) hybridization buffer and 3 \u00d7 3 min in prewarmed (45\u00b0C) washing buffer (1 M Tris-pH 7.2, 5 M NaCl). The samples were finally rinsed in water, air dried and mounted in Vectashield (Vector Laboratories, Burlingame, CA, USA) for epifluorescence microscopy.", "Clostridium perfringens S-S-C.perfring-1 5'-TGGTTGAATGATGATGCC-3' 16S [13] Clostridium difficile S-S-C.diff-193 5'-TGTACTGGCTCACCTTTG-3' 16S [14] * The probes were purchased from Eurofins MWG Operon, Ebersberg, Germany." ] },{ "paper_id": "a11d517c9cdd68c3671429751ed8420fb9fc1485", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The animals were housed under controlled light (12 h light/12 h dark; lights on at 8 am) and temperature conditions (23 \u00b1 1 \u2022 C), with free access to water and food. All animals were obtained from the Animal Facility of the University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil.", "No differences were observed in the number of macrophages between groups.", "All datasets generated for this study are included in the manuscript.", "The normality of variables was evaluated using the Kolmogorov-Smirnov normality test. The statistical differences between the groups were analyzed using One-way ANOVA followed by Tukey test (for the comparison of three or more groups for Gaussian data) or Kruskal-Wallis followed by Dunn method (for nonparametric data). Percentages of inhibition were calculated as the mean of the inhibitions obtained for each individual experiment. p values <0.05 were considered statistically significant. Data are expressed as mean \u00b1 standard deviation (SD).", "Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory failure and one of the most challenging clinical conditions. It results in nearly 75,000 deaths annually, and is associated with high morbidity and mortality rates (1) . There are more than 3 million ARDS cases annually worldwide, and they account for 10% of intensive care unit admissions (1) ." ] },{ "paper_id": "a11eb58857b227cdd846083d87304eef58b52ac2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The chemokine (C-C motif) ligand 2 (CCL2) is a monocyte chemoattractant protein that mediates macrophage recruitment and migration during peripheral and central nervous system (CNS) inflammation.", "Immunohistochemistry was quantified using Image-Pro Plus software (Media Cybernetics, Rockville, MD, USA).", "The authors declare that they have no competing interests." ] },{ "paper_id": "a1213a37009cf0d561bdfe620cbeabf8de2778d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SARS-CoV was incubated with ACE2 for one hour, and 4 ml samples were applied to glow-discharged holey carbon films supported on 400-mesh copper grids. After blotting immediately for 2-5 seconds with filter paper, grids were plunged into liquid ethane cooled by liquid nitrogen, using a custom built gravityoperated freezing device. Specimens were transferred to a Tecnai 20 G2 transmission electron microscope (FEI) operated at 200 kV, equipped with a Gatan 626.DH low-temperature specimen holder. Observations were made at temperatures of ,2185uC and images recorded at 29,0006 magnification on Kodak SO-163 electron image film at a dose of 10-20 electrons/\u00c5 2 with an exposure of 1-2 seconds. Film was developed in Kodak D19 for 12 minutes at room temperature, rinsed for 2 minutes in water, and fixed for 10 minutes with Kodak fixer.", "The vero E6 cells were observed by light microscopy 2 and 4 days post treatment for the presence of syncytia. Virus growth was not detected at either dilution of irradiated virus, and no cytopathic effect was observed. The presence of nucleic acid in syncytia was investigated by propidium iodide staining and observation by fluorescence microscopy.", "To test for spike fusogenic activity Vero E6 cells were cultured in 96 well plates (Corning). Once the cells were confluent the medium was removed from each well and 20 ml of gamma irradiated SARS-CoV containing 10 10 pfu/ml diluted 1:1 and 1:9 in culture media. The virus dilutions were incubated with the cells for 1 hour at 37uC. After the incubation the plates were washed three times with fresh culture medium to remove unbound virus." ] },{ "paper_id": "a126c62ed8ff8781b618d13b3b1127fde81076f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In conclusion, on the basis of the comparative epidemiology of MERS-CoV in KSA and SK, both countries had differing risk factors and epidemic patterns, thus adding to the complexity of this disease. The varying and complex epidemiology in KSA is consistent with multiple introductions, which may comprise a mix of animal-tohuman, human-to-human (healthcare-acquired, communityacquired), and other modes of transmission. A large proportion of KSA cases have unknown exposure, thus warranting further study. MERS-CoV has an epidemic pattern that has varied from country to country and has disproportionately affected KSA for reasons that are not yet fully understood. Further research, enabled by high quality surveillance data, is required to understand and mitigate the risk factors for MERS-CoV.", "On the basis of the reported date of onset of symptoms, the epidemic curve in KSA from 2012 to 2015 by week is shown in Figure 2A . During the four years after the emergence of MERS-CoV, several peaks were observed in week 18 in 2014 and weeks 7, 10, 34 in 2015. In addition, numerous clusters and sporadic cases were noted with no clear seasonality, comprising a very protracted and mixed pattern. The epidemic curve of MERS-CoV in SK in 2015 ( Figure 2B ) exhibited a classic epidemic curve over a short time (8 weeks) with a small number of early cases beginning in week 20 followed by a rapid rise in new cases over two weeks, an epidemic peak at week 23 and then a decline in cases ending at week 28. ", "All cases in SK (excluding the index case) were associated with a single chain of transmission and healthcare facilities. 18, 39 The index case was a 68-year-old man who traveled to the United Arab Emirates (29-30 April), Saudi Arabia (1-2 May), Qatar (2-3 May), and Bahrain (4 May) and returned to Seoul on the same day without a history of exposure to camels or contact with MERS cases. 39 20 A range of hospitalized patients, healthcare workers and family members were exposed during this period, thus leading to the nosocomial disease outbreak in SK. The MERS-CoV isolated from inpatients formed a single monophyletic clade with high similarity to strains from Riyadh. 40 An unreported sequence was detected in the MERS-CoV circulating in SK, 41 thus suggesting increased genetic variability and mutation rates during the outbreak in 2015." ] },{ "paper_id": "a127919cf960d1c72c3e29ce2ec08c67d6aba59f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Aim: Generation of recombinant human adenovirus type 5 expressing foot-and-mouth disease virus (FMDV) capsid protein genes along with full-length 2B, 3B and 3C pro and its characterization.", "All the genetic manipulation for producing recombinant adenoviruses expressing FMDV capsid proteins were carried out after obtaining necessary approval from the Institute Biosafety Committee (IBSC) and Review Committee on Genetic Manipulation (RCGM), Department of Biotechnology, Government of India.", "ELISA absorbance readings from duplicate wells were used to calculate mean +/-SD upon testing of expressed antigens collected at various time points. Regression analysis was performed to correlate incubation temperature to the incubation time using SAS 9.3.", "FMD is an important disease of transboundary importance affecting cloven-hoofed animals worldwide [1] . Seven serotypes of FMDV with many subtypes in each serotype and no cross-protection against each other make the disease control difficult. Serotype O virus is antigenically poor compared to A and Asia-1 serotypes, and thus large amount of serotype O antigen is required to achieve same level of protection in the inactivated vaccine [32] . Vaccines based on inactivated whole viruses emulsified with adjuvant have been effectively used to control and prevent the disease in enzootic countries. But due to several limitations of the inactivated vaccine, various alternate approaches have been tried to develop a better vaccine candidate [33] ." ] },{ "paper_id": "a135f7028fe8bfd36c791323bf28623c06c7b7fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses are the causative agents of various dreadful diseases in humans and animals (1, 2) . For majority of viruses like Hepatitis C virus (HCV), Influenza, Dengue virus (DENV), Severe acute respiratory syndrome (SARS), Herpes simplex virus (HSV), etc., antiviral therapeutics are limited or lacking (3) . Moreover, owing to increasing drug resistance, conventional antiviral therapy is continuously challenged these days (4, 5) . Therefore, scientific efforts are underway to search for novel antivirals (6, 7) . Antiviral peptides (AVPs) are being regarded as such new promising entities to combat the viral infections.", "Relevant data were retrieved from the PubMed database, a free repository of abstracts and references on biomedical and life sciences. Exhaustive literature search was accomplished by building search queries having combination of many keywords including virus, viral, peptide, inhibit, block, etc. A typical text mining query is given below:", "Full text search returned 37 842 articles as on 1 July 2013.", "One of the earliest reports stating the direct involvement of peptides in inhibiting Herpes simplex virus (HSV) multiplication dates back to 1985 (14) . Since then researchers have been extensively working on peptidebased antiviral development. Bultmann et al. (15) used FGF4 signal peptide derivatives to inhibit HSV-1 entry and the best performing AVP had a half maximal inhibitory concentration (IC 50 ) of 0.7 mM. Budge and Graham (9) used r-A derived peptides to inhibit Respiratory syncytial virus (RSV) replication and achieved a maximum IC 50 of 1.23 mM. Also, a peptide derived from spike (S) protein of SARS-CoV has been proved to be effective against SARS virus entry with an efficacy of 11 mM (16). The peptide 'FluPep' inhibits Influenza virus attachment to the cells with an IC 50 of 0.10 mM (17) . Similarly, Xu et al. (18) were able to inhibit DENV protease using AVPs with a minimum IC 50 of 3.3 mM. An AVP named 'Ctry2459' has been synthesized, which possesses anti-HCV activity with an EC 50 of 1.84 mg/ml (19) . Therapeutic potential, mode of action and importance of AVPs has been further reviewed (8, 10, 20) ." ] },{ "paper_id": "a137eb51461b4a4ed3980aa5b9cb2f2c1cf0292a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Harvested lung tissues were frozen at \u221280\u00b0C in 1 mL PBS. At the time of titration tissues were thawed, homogenized for 60 s at 6000 rpm and plated in serial dilutions on Vero cells as described previously.", "This assessment revealed that network measures could predict phenotype very well yielding ROC AUCs of 0.9, 0.93, and 0.83 for betweenness centrality, degree centrality, and WGCNA K me , respectively. Differential expression after infection performed slightly worse than network measures, giving an ROC AUC of 0.77. Though these results were promising we wanted to validate the approach on novel predictions to further characterize the method." ] },{ "paper_id": "a138ff680ae9e158019717356e8fcab523e7cad2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Every epitope and its binding HLA alleles were added, and different geographic areas were also selected.", "The allergenicity of the epitopes was analyzed by the AllerHunter server [46] (http://tiger.dbs. nus.edu.sg/AllerHunter). AllerHunter is a SVM-pairwise system for assessment of allergenicity and allergic cross-reactivity in proteins. It aims to predict allergens and non-allergens with high sensitivity and specificity, without compromising efficiency at classification of proteins with similar sequences to known allergens [46] .", "The entire viral proteome sequences of all MERS-CoV isolates that include structural proteins spike protein (S), envelope protein (E), membrane protein (M), nucleocapsid protein (N), and non-structural proteins ORF3, ORF4a, ORF4b, ORF5 and ORF8b, and two replicase polyproteins ORF1ab and ORF1a, were retrieved from the National Center for Biotechnology Information database (http://www.ncbi.nlm.nih.gov/) and used as an input for various bioinformatics tools for antigenicity assessment, secondary structure and 3D model prediction, and epitope prediction. These sequences come from different geographic regions such as Saudi Arabia, England, Qatar, Spain, Germany, Jordan, and Korea with time ranges from 2012 to 2015." ] },{ "paper_id": "a13c79aab29bf6afdf2fe0cbd6269b1941e77ee0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study obtained ethics approval from the Institutional Review Board (IRB) of Korea University.", "The IRB waived the requirement for written informed consent because the data were analyzed anonymously, but verbal consent was obtained from all respondents before the interview was started." ] },{ "paper_id": "a16aeee3d8878ab6dd536c418742d58b946b4699", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Disadvantages:", "Immunostimulatory effects may decrease potency via multiple pathways:", "Decreased translation into protein c." ] },{ "paper_id": "a1a6c0067edf3605299df62d104c31661bbccaec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We also note that the applied statistical tests do not take the interdependence structure within our sampled data into account. The RDS data files are available online, doi: 10.6084/m9.figshare.1147465. R version 3.0.3 was used for statistical analysis and RGraphviz for creating Figure 1 . See Text S2 for the full R source code and applied libraries.", "where c denotes the population mean of the c i and v the variance of the c i (see Anderson and May [3] ; p 233).", "Although we chose to use an aggregated contact diary design to limit the burden for each participant and to stimulate online peer-recruitment, this prevented us from collecting other determinants relevant for infection transmission, such as contact duration and intensity. Earlier studies have shown the importance of contact duration for understanding the transmission dynamics of close-contact pathogens [37, 38] . Also, contact duration influences the probability that a contact is reported by a participant [39, 40] . Although it is possible to derive contact durations from earlier conducted diary surveys, we cannot preclude the effect of heterogeneities in motivation or recall capabilities on the reported degrees, between both country samples, and between participants in same country (e.g. differences in reporting quality between females and males [39] ).", "In addition, we assessed for each country sample the validity of the first-order Markov assumption [23] , i.e. that correlations found between recruiter and recruitee are only dependent on the direct recruiter. This was done by calculating the correlations for age and sex between seeds (wave 0) and their recruitees in consecutive waves (maximum up to 3 waves, due to limited number of participants in waves >4). For the numeric variable ''age'' we compared r waves0-3 with r waves0-1 * r waves1-2 * r waves2-3 ; for the categorical variable ''sex'' we raised the 1-step transition matrix to the third power to obtain r waves0-3 .", "participants for their age, sex, educational level, postal code, and the number and ages (specified in age groups) of persons living in their household during the past seven days. Furthermore, we included a question to record any symptoms (provided in a list, see Table S2 ) that participants and/or household members experienced in the past seven days. A combination of the symptoms fever, headache and muscle pain was indicated as influenza-like-illness (ILI) symptoms, and a combination of the symptoms runny nose, sore throat and cough as common cold-like symptoms." ] },{ "paper_id": "a1add6ab708156c28d4dfa6e0bd825a53c38e418", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The CoVs are also excellent tools to reveal new host cell components facilitating entry. Of relevance to disease are the possible species and organ-specific variations in CoV receptors and S-activating proteases. One of the next key steps in CoV research will be to move toward in vivo dissection of entry mediators and relate disease manifestations to their presence and abundance in distinct tissues and species.", "Increasingly sophisticated in vivo CoV models will also be useful in evaluating new antiviral strategies. Notably, the infection models and the prototype antiviral agents promise to deliver therapies that will both guard against potentially serious zoonotic CoVs and reveal more broad-spectrum antivirals. For example, TTSP inhibitors may be suitable therapeutics for a variety of respiratory viruses that rely on proteolysis for cell entry. CoV research will continue to reveal features of virus operating mechanisms and clinically applicable antiviral strategies for the foreseeable future.", "Notably, the existence of two CoV RBDs can make one dispensable. The MHVs, having CEACAM-binding sites on NTDs, readily delete CTD segments during passage in tissue culture [49, 50] . These deletion-mutations have profound influences on CoV virulence, greatly decreasing the murine virus neurovirulence [51] . Another interesting example is with the porcine CoVs. Transmissible gastroenteritis virus (TGEV), with two functional RBDs (Table 1) , can infect both respiratory and enteric tracts [52] . However, naturally-occurring mutants with substitutions or deletions in N-terminal RBDs lack lectin activities [53] and are strictly limited to the respiratory tract and therefore are attenuated [54, 55] . Thus a dual RBD architecture may correlate with in vivo tropism and virulence, likely due to a complexity of multiple receptor interactions that the CoVs employ in the natural animal environment.", "The CoV S peplomers directing cell entry are the principal viral components communicating with diverse extracellular environments. These arrays of extracellular selective pressures fix diversity into the genetically-plastic CoV S proteins. Novel S structures allow the CoVs to expand into different ecological niches; zoonotic emergence of the SARS-CoV being the prime example of this emergence and its consequences. Understanding S variation, structure, and entry mechanisms are therefore central to combating potential epidemic CoV transmissions." ] },{ "paper_id": "a1b6c2b3b808e995697f94d9676d5d5c85180177", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As noted, many HCPs acted in a supererogatory manner during the SARS outbreak [7], none more so than Dr. Carlo Urbani of the World Health Organization, who himself died of SARS after being exposed to the yet unknown virus in the course of carrying out his professional duties. Likewise, scores of nurses, doctors, respiratory technicians, and other professional and nonprofessional health workers laboured extremely long hours at personal risk. This demonstration of going above and beyond the call of duty, which proved necessary to control the disease, was highly morally commendable.", "Given that the response by HCPs to the SARS crisis was generally regarded as exemplary, one might ask whether an ethical problem truly exists. There is little doubt that the vast majority of HCPs performed their jobs admirably under considerable stress and significant personal risk. Many HCPs provided exemplary care, and still others behaved in truly heroic fashion. So why, then, formally problematize something that is not a problem?", "What is clear is this: the issue of duty to care has emerged as a matter of paramount concern among health care professionals, hospital administrators, public policy makers, and bioethicists [11] [12] [13] [14] ." ] },{ "paper_id": "a1ccc7fe4c6c4ae77f84bb48011f0ee0b5900045", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a1d863f8297bd6185abeb6564af22eac8bdd3fd3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rickettsial pathogens are among the leading causes of morbidity and mortality during military operations. In recent years, emerging rickettsial diseases have been reported throughout the world and are a significant medical concern for local and deployed personnel and travelers [1] [2] [3] . These pathogens include spotted fever group Rickettsia (SFGR, Far eastern spotted fever, Japanese spotted fever, Siberian and Queensland tick typhus, and Thai tick typhus just to name a few), typhus group Rickettsia (TGR, epidemic and murine typhus) and Orientia tsutsugamushi (scrub typhus, ST). Due to the high mortality rate of untreated rickettsial infections, early treatment with appropriate antibiotics is critical [4] . Doxycycline is the drug of choice, except in cases of pregnancy and tetracycline hypersensitivity. Symptoms of rickettsial infections are nonspecific and can be confused with a variety of other pathogens (e.g., dengue, malaria, leptospirosis) that require different treatment regimens. To ensure that appropriate treatment is initiated promptly, early diagnosis of rickettsial infections is critical.", "The animal study protocol (#D11-06) was reviewed and approved by the Naval Medical Research Center Institutional Animal Care and Use Committee (IACUC) in compliance with all applicable Federal regulations governing the protection of animals in research. The experiments reported herein were conducted in compliance with the Animal Welfare Act and in accordance with the principles set forth in the \"Guide for the Care and Use of Laboratory Animals,\" Institute of Laboratory Animals Resources, National Research Council, National Academy Press, 1996." ] },{ "paper_id": "a1ddcd1a96b072bef649cc450c4bf5bc850a6957", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "OH OH Scheme 20. Tandem reaction of 5-(2,4-dihydroxyphenylmetylidene)iso(thio)rhodanines with ethyl acrylate and acrylonitrile.", "Sci. Pharm. 2018, 86, x 2 of 24 mentioned Michael acceptors properties ( Figure 1 ) [15] [16] [17] . The combination of thiazole and thiopyran cycles in condensed heterosystem is a precondition for the creation of \"centers conservative\" of the ligand-target binding complex and promotes potential selectivity to biotargets. Considering the mentioned arguments, the directed search for new chemotherapeutic agents among thiopyrano [2,3-d] thiazole derivatives is a justified and promising direction in modern medicinal chemistry. In this review, we tried to systematize the data on chemistry and pharmacology of thiopyrano [2,3-d] thiazoles from the perspective of medicinal and pharmaceutical chemistry. ", "Author Contributions: R.L. conceived and designed the review; O.R. and A.L. analyzed the literature data; R.L. and A.K. wrote the paper. All authors read and approved the final manuscript. " ] },{ "paper_id": "a1dde82e18ad108c7eedb452d50a661e647b7cf2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no competing interests.", "Authors' contribution HRJ wrote the review, designed tables and figures. RD revised the text, tables and figures. Both authors read and approved the final manuscript.", "Received: 17 December 2015 Accepted: 27 January 2016", "In animals, CoV infections are mainly associated with respiratory and enteric disease and can have large economical impact on the veterinary industry, e.g. Porcine Epidemic Diarrhea Virus (PEDV) causes gastrointestinal disease in pigs [4] , Infectious Bronchitis Virus (IBV) causes severe kidney and respiratory disease in chicken [5] and Bovine Coronavirus (BCoV) causes both respiratory disease and diarrhea in cattle [6] . Additionally, CoV infections can have other disease manifestations, such as central nervous system (CNS) involvement, hepatitis and peritonitis [7] [8] [9] [10] .", "In humans, CoV infections are mainly associated with respiratory diseases that are considered to have a large impact on the economy due to reduced productivity of the working population. Currently, 6 coronaviruses that cause disease in humans have been discovered. Four of those are commonly circulating and two have caused epidemics of severe acute respiratory disease.", "Coronaviruses (CoVs), a subfamily of the Coronaviridae family, are positive strand RNA viruses with the largest genome of all known RNA viruses (\u226527 Kb). The genomic RNA is capped, polyadenylated and associated with nucleocapsid proteins within an enveloped virion. The envelope is covered by the characteristic surface glycoprotein that gives the virus particles their characteristic crown-like (latin: corona) appearance [1] .", "However, in 2002, an unknown respiratory illness, termed Severe Acute Respiratory Syndrome (SARS), surfaced in Asia. Research determined it to be caused by a novel coronavirus [13, 14] . At the end of the epidemic, this virus had infected over 8000 people, most in China, and caused 774 deaths [15] ." ] },{ "paper_id": "a1efb6bb6211fc7190f9e06ac0929d340e7aafa1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The purified IgYs from egg yolks were analyzed by SDS-PAGE. Samples were boiled for 5 min in loading buffer containing 1% SDS, 2.5% \u03b2-mercaptoethanol, 6.25 mM Tris-HCl (pH 6.8), and 5% glycerol and loaded onto a 12% polyacrylamide gel. Proteins were visualized by Coomassie blue staining.", "HuNoV-specific IgY is a potential passive immunization and therapeutic agent for HuNoV. HuNoV is a leading cause of viral gastroenteritis worldwide. Despite significant social, health, and economical burden it causes, no FDA-approved vaccine or therapeutic strategy is available. Epidemiology studies showed that HuNoV could cause lethal infection in humans, particularly in high-risk populations, such as infants, young children, the elderly, and immunocompromised individuals. Thus, there is a need to develop a safe and effective therapeutic strategy.", "Quantitative analysis was performed by either densitometric scanning of autoradiographs or by using a Typhoon PhosphorImager and ImageQuant TL software (GE Healthcare, Piscataway, NJ, USA). Each experiment was performed three to six times. Statistical analysis was performed by one-way multiple comparisons using SPSS software 13.0 (SPSS, Chicago, IL, USA). A p-value of <0.05 was considered statistically significant." ] },{ "paper_id": "a1f20fd6adb16f74b5c4a7c0543c55e80e500e02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a204aafa38365dbcc0a26af3ca2c6d3313d7fab2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "| METHODS", "The university hospital has 700 beds and is a referral hospital with both basic services and specific care from patients attended at primary care health service in ambulatory or specific units.", "MOREIRA Et Al.", "The sample size was calculated to be sufficient to determine a prevalence of RSV at least up to 10%, with 90% confidence interval and a relative precision of 0.25 of the a priori estimated proportion." ] },{ "paper_id": "a20dad1dae885e38b8aeadb93c22d14a54c6388a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Using (1)- (3), we derive the total likelihood L for each single interpretation scenario, computed as", "where L 1 \u00f0 p; s; n; m\u00de \u00bc Y i n i \u00fe m i n i \u00f0 p\u00f01 \u00c0 s\u00de\u00de ni \u00f01 \u00c0 p\u00f01 \u00c0 s\u00de\u00de mi ; L 2 \u00f0 p; q; s; m; y\u00de", "x i q xi \u00f01 \u00c0 q\u00de \u00f0ni\u00c0xi\u00de :" ] },{ "paper_id": "a21809b3622fbd0f1a0ef01eab221fb05ada15e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The datasets supporting the conclusions of this article are included within the article.", "Combining NGS with metagenomic analysis provides an important clinical tool to identify unexpected or novel pathogens in patients. The advantage of this methodology is maximized when the causative pathogen presents a low-level signal compared to all other signals representing environmental and commensal pathogens. Improving the optimization and implementation of protocols suitable for clinical samples will no doubt improve microbial diagnosis in clinical practice.", "Next-generation sequencing (NGS) accompanied with metagenomic analysis can be used as a nonselective method for pathogen discovery and is increasingly applied as a diagnostic tool to investigate the causes underlying unexplained encephalitis in patients. Two key features of this methodology are: (1) it makes no assumptions about the type of pathogen and has the potential to detect nucleotides from all species, and (2) the causative pathogen may not necessarily be the most abundant signal in the NGS results and may sometimes be present as only a low-level signal compared to all other signals associated with commensal pathogens. It can, however, provide unbiased and sensitive identification." ] },{ "paper_id": "a21bbf97490642e6230c9c6eeece5cb99447b566", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Confidence intervals for seroprevalence were estimated using the Wilson method [11] in the Epitools calculator (http://epitools.ausvet.com.au/).", "Fecal samples from 74 hedgehogs were analyzed and 37 samples were positive. The estimated prevalence for all the animal shelters was 50% (CI95%: 38.89; 61.11), with no statistical difference between the three animal shelters.", "Coronaviruses (CoVs) infect a wide variety of animals and are common throughout the world. They cause respiratory, enteric, hepatic, and neurological diseases with variable severity, from asymptomatic to severe. Coronaviruses that infect mammals (except pigs) belong mainly to two genetic and serologic groups: The Alphaand Betacoronavirus genera.", "Of the 330 trapped rodents ( Table 2) , most of the animals belonged to Apodemus spp. (n = 206) and Myodes glareolus (n = 80), and were collected at four sites (Bitche, Forbach, La-Petite-Pierre, and Murbach) in mixed coniferous and deciduous forests. Other species of rodents were Arvicola terrestris (n = 35) and Microtus spp. (n = 9), and were mainly collected in an apple orchard in Wissembourg (Bas-Rhin)." ] },{ "paper_id": "a21bd16035d028aae34bab89c3be720ffec176a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(7) Fostering innovative interventions and best practices amongst professional, health workers and the community resilience and participative engagement in response to emerging threats and disasters." ] },{ "paper_id": "a21f16327c9af00dfc25321123ac2a5b6eb7f690", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the United States, pandemic 2009-2010 influenza A (pH1N1) was first identified in April 2009 [1] . Two waves of infection followed, accounting for an estimated 61 million cases, 274,000 hospitalizations, and 12,470 deaths [2, 3] . Compared to seasonal averages, there was an increase in hospitalizations and a decrease in mortality. Children experienced a greater burden of disease and a disproportionately increased burden of mortality [4] [5] [6] [7] [8] [9] [10] . However, the majority of children did not progress to severe disease [11] . In contrast, fewer adults were afflicted but proportionally more experienced severe disease [12] . The clinical characteristics of pH1N1-infected individuals are well described [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] ." ] },{ "paper_id": "a21f8d21e09607e555468d0ed155126daaeb37cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "West Nile virus in a dromedary S Joseph et al", "Negative-contrast electron microscopy was performed as previously described. 15 Tissue culture cell extracts infected with dromedary WNV were centrifuged at 19 000g at 4\u00b0C. Then, the pellet was resuspended in phosphate-buffered saline and stained with 2% phosphotungstic acid. Samples were examined with a Philips EM208s electron microscope (Philips Scientifics, Eindhoven, The Netherlands).", "The complete genome of the isolated virus was sequenced and assembled. The size, G+C content and genome structure were similar to other WNVs. The single polyprotein is putatively cleaved by proteases into three structural proteins (capsid (C), premembrane/ membrane (prM/M) and envelope (E)) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5)." ] },{ "paper_id": "a22be780c7774b48b0f4415ed03d2e62ee098518", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The mannosylparomomycin from the training set.", "The molecular structures were standardized by normalizing tautomeric groups and by removing small disconnected fragments using JChem Standardizer tool version 5.12.3 (ChemAxon Ltd., Budapest, Hungary). Three-dimensional models of the molecular structures were generated with CORINA version 2.4 (Molecular Networks GmbH, Erlangen, Germany). Empirical Molecular descriptors were then calculated using the CDK Descriptor Calculator 1.3.2 [55, 56] . A total of 270 descriptors were calculated including electronic, topological, geometrical, constitutional and hybrid (BCUT and WHIM) descriptors.", "As expected the predictive power of CT is lower than that obtained for the other two ML techniques for the three activity models, but has the advantage in establishing a few simple rules that provide insights into the drug profile." ] },{ "paper_id": "a232d55159ae4e3d7eb30a4e9bb04494dd438344", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations: CBM = Chinese Biology and Medicine database, CI = confidential interval, CNKI = Chinese National Knowledge Infrastructure, HED = Houttuynia eye drops, RCT = randomized controlled trial, VKC = vernal keratoconjunctivitis.", "Remission rate is considered as cure rate." ] },{ "paper_id": "a234c5ac982ffc63b7be9d7c1b3473f92849192e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 45 hospitalized patients with laboratory-confirmed H1N1pdm were enrolled in the study. Patients were divided into two groups along two different criteria: the requirement of critical (n = 35) or non-critical (n = 10) care and survival (n = 35) or death (n = 10). A single serum sample was collected from each patient within 48 hours of hospital admission, according to a unified protocol for all the participant centers. Samples were adequately centrifuged and the serum was separated and stored at 280uC until immune mediator profiling.", "Microarray expression data are MIAME compliant and are available publicly in the MIAME-compliant Gene Expression Omnibus database (www.ncbi.nlm.nih.gov/geo/) under accession number GSE31022.", "For clinical studies, written informed consent was obtained directly from each study participant or their legal representative before enrolment. Permission to perform scientific studies was granted by the Comisi\u00f3n de Investigaci\u00f3n del Hospital Clinico Universitario de Valladolid, Spain. Scientific and ethical approval of the study protocol was also obtained from the Scientific Committees for Clinical Research of each one of the participant centres.", "For animal studies, all work was performed in strict accordance with the Canadian Council of Animal Care guidelines. Animal use protocols were approved by the Animal Care Committee of the University Health Network (Toronto, Canada). The University Health Network is certified under the Animals for Research Act (Permit Numbers: #0045 and #0085 under the jurisdiction of the Ontario Ministry of Agriculture, Food, and Rural Affairs) and follows NIH guidelines (OLAW #A5408-01). All infections and sample collections were performed under 5% isofluorane anaesthesia with every effort made to minimize suffering." ] },{ "paper_id": "a23e98e1cc196167116f87f71aae771739bdf0d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "By integrating these data with our transcriptome results, it is reasonable to believe that the dynamics of cytoskeleton has a major role in virus infection.", "The concentration and quality of total RNA were determined by a Nano-Drop spectrophotometer (Thermo Fisher Scientific, Wilmington, DE, USA).", "Background: The white backed planthopper (WBPH), Sogatella furcifera (Horv\u00e1th), causes great damage to many crops by direct feeding or transmitting plant viruses. Southern rice black-streaked dwarf virus (SRBSDV), transmitted by WBPH, has become a great threat to rice production in East Asia." ] },{ "paper_id": "a25045aa52c78b89840287b2cff9d7dffe0bb07f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although already informative in its own right, mutation data can be significantly different among species due to dissimilar metabolisms, generation times, population sizes, life-Table 1. List of Public Resources and Databases Relevant to Domain Analysis Resource URL Protein domain databases Pfam Alignment software BLAST http://www.ncbi.nlm.nih.gov/blast/Blast.cgi ClustalW", "of an expression network resulted via a merge of conserved and newly evolved modules [95, 112, 113] ." ] },{ "paper_id": "a257c576fef2e2aee2702b5179d2d09473f16543", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Where SARS and MERS have attracted much media coverage, it should not be forgotten that the plague bacillus (Yersinia pestis) still affects a great number of people each year [27] . The pneumonic plague has seen endemic outbreaks in certain parts of Africa, with sporadic cases occurring worldwide.", "The clinical course of leptospirosis is variable, with symptoms from myalgia to fever with cough and shortness of breath. Weil's disease is its severest form and may develop in 1-5% of cases. Patients progress from mild flulike symptoms to signs of organ failure (jaundice and spontaneous bleeding) [54] .", "We identified references for this review by searches in different databases (PubMed, Ovid MEDLINE, Embase and Cochrane) and references from relevant articles. The following MeSH headings were used: \"pulmonary\", \"respiratory\", \"tropical disease\" 'travellers\", \"travel\", \"returning traveller\".", "Treatment of influenza remains a controversial topic but generally supportive management is adopted. Current recommendations are early administration of a neuraminidase inhibitor (e.g., oseltamivir) to the affected individual and their close contacts [18] . A recent meta-analysis of the H1N1 pandemic showed that hospitalized patients treated with a neuraminidase inhibitor had a lower mortality, and that this was further reduced by early instigation [20] .", "Prevention of avian influenza has proved difficult due to the antigenic diversity of the circulating viruses, which has hampered vaccine development [21] . Healthcare professionals should take post-exposure prophylaxis (e.g., oseltamivir) after a patient has been diagnosed with avian influenza and personal protective equipment is highly recommended.", "Pertussis is a worldwide endemic-epidemic disease with outbreaks most likely during summer/autumn time. Pertussis is thought to still cause around 63,000 deaths per year in children under 5 years of age, although there is uncertainty over these estimates in view of the paucity of reliable surveillance data [48] ." ] },{ "paper_id": "a259f7115e26c97fee193b205ec7542b1267829b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Frontiers in Microbiology | www.frontiersin.org Frontiers in Microbiology | www.frontiersin.org", "\"Including the hypothetical ancestor during tree estimation amounts to a priori character polarization.\"" ] },{ "paper_id": "a25c99e62ee57a207f77bcba9f484a2416f11849", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The PDCoV Chinese \"Hunan\" strain was used in this study [22] . The virus cultivation was done in a porcine kidney epithelial cell line, LLC-PK1 (ATCC CL-101), at 37 \u2022 C in 5% CO2 in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and 1% (w/v) antibiotics (penicillin and streptomycin).", "PDCoV infected LLC-PK1 cells were lysed in CelLytic M lysis buffer (Sigma, St. Louis, MO, USA). The protein concentration was quantified by the BCA (bicinchoninic acid) protein assay kit (Beyotime Biotechnology, Shanghai, China). Samples were separated by 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The proteins were transferred onto a polyvinylidene difluoride (PVDF) membrane that was subsequently blocked with Tris-buffered saline (TBS) containing 3% bovine serum albumin (BSA) at room temperature for 2 h and then incubated overnight at 4 \u2022 C with primary antibodies. Rabbit anti-LC3 (A7198, ABclonal, Wuhan, China) and rabbit anti-p62/SQSTM1 (P0067, Sigma, St. Louis, MO, USA) polyclonal antibodies were used in this study. The blots were then incubated with corresponding horseradish peroxidase (HRP) conjugated secondary antibody (Thermo Fisher Scientific, Waltham, MA, USA).", "LLC-PK1 cells were infected with PDCoV at an MOI of 1. The cells were harvested and fixed with 2.5% glutaraldehyde in phosphate buffer (0.1 M, pH 7.0) and 1% Osmium tetroxide (OsO4) in phosphate at 2, 4, 6, 8, 12, 16, and 24 hpi. Specimens were dehydrated in a series of ethanol dilutions (30%, 50%, 70%, 80%, 90%, 95% and 100%) for 15-20 min at each step, then transferred to absolute acetone for 20 min. The specimens were then placed in one of three mixtures of absolute acetone and Spurr resin (1:1, 1:3, and pure Spurr resin) for 1 h, 3 h, and overnight, respectively. Finally, ultrathin sections were stained by uranyl acetate and alkaline lead citrate for 5-10 min and observed using a Hitachi Model H-7650 transmission EM [25] ." ] },{ "paper_id": "a263f1ec26e982b0f070dcb721f6e51e7d970889", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Competing Interests: This study was conducted in part with funding from National Pork Board. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.", "PEDv has occurred in European and Asian countries for several decades. In China, vaccination was widely used in the swine industry and PEDv prevalence was relatively low. However, in late 2010 China began experiencing an epidemic that was attributed to newer strains of PEDv that could circumvent immunity developed from current vaccines [7] .", "Funding: This study was conducted in part with funding from National Pork Board. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." ] },{ "paper_id": "a2707740419f3f999535e908845471d220054dfb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The function of FPR3 is less well characterized, although it is expressed on eosinophils, monocytes, macrophages, and dendritic cells. Evidence suggests that FPR3 plays role in allergic reaction and dendritic cell maturation [35] .", "Many acute cardiovascular events, such as acute ischemic stroke (AIS) and myocardial infarction (MI), are due to, e.g., unhealthy vascular states, resulting from prolonged atherosclerosis, coronary artery disease, diabetes, uncontrolled hypertension, and aging [1] . Additional studies have suggested behavioral, psychosocial including bereavement [3] and environmental factors can also trigger and contribute to acute cardiovascular events [4] .", "Inflammation [122] HIV-2 peptides (FPR1) Inhibits fMLP interaction in CHO cells Viral pathogenesis [120] Isopropylureido-FLFLF (FPR1) Inhibits chemotaxis Inflammation [123] Spinorphin (FPR1) Inhibits calcium mobilization and fMLP induced neutrophil chemotaxis Inflammation [124] WRW4 (FPR2/ALX) Inhibits chemotaxis, calcium flux, superoxide generation and ERK phosphorylation Neurodegenerative diseases, AIS [125] MI, myocardial infarction; MI/R, myocardial ischemia reperfusion; AIS, acute ischemic stroke; IFN-\u03b3, interferon gamma; MAPK, Mitogen-activated protein kinase; ERK, extracellular signal-regulated kinase; AKT, serine/threonine-protein kinase; PMN, polymorphonuclear leukocytes; CHO cells, Chinese hamster ovary; ATL, aspirin triggered lipoxin; ASA, aspirin ; IgG, Immunoglobulin G; fMLP, formyl-Met-Leu-Phe (fMLP), G proteins; FLIPr, FPR2/ALX inhibitory protein", "AnxA1 and its mimetic peptides, such as the N-terminal derived Ac2-26, bind to the formyl peptide receptor (FPR) family of seven transmembrane G-protein-coupled receptors (GPCRs) [28] . Various cell types express FPRs, especially myeloid cells, e.g., neutrophils and monocytes. Three FPR members exist in humans and they are termed: FPR1, FPR2/ALXR (also known as the LXA 4 receptor), and FPR3. FPR2/ALXR shares 69% amino acid sequence homology with FPR1, and FPR3 shares 56% amino acid homology to FPR1 and 72% to FPR2/ALX [7, 29] . In mice, the FPR family is more complex, consisting of at least eight members. Mouse Fpr1 shares 77% sequence homology with human FPR1, and Fpr2 has 76% homology to FPR2/ALXR [29] ." ] },{ "paper_id": "a274eabdee76dfe956dc3fdcaa5a105e8fd465bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Wild birds of the orders Anseriformes (such as ducks and geese) and", "The complete role of PB1-F2 in the virus lifecycle still remains to be elucidated, as it has been shown to both aid and disrupt viral virulence. It is generally understood that PB1-F2's role is subtype and host dependent.", "The non-structural protein 1 (NS1) protein has been implicated in variable virulence and pathogenicity within different hosts through its interactions of PDZ-binding motif at the C terminus of the protein. 83, [132] [133] [134] In a large-scale comparative genomic approach of all IAV, a specific 11 amino acid long sequence feature variant type (SFVT) located between residues 137-147 of the NS1 protein was statistically associated with a host restriction phenotype, 135 although this has yet to be tested experimentally. Nonetheless, discovery of this SFVT emphasizes the importance of further studying this protein and its potential role in interspecies species transmission.", "Influenza A virus (IAV) has caused significant morbidity and mortality globally in humans, with an estimated 14 pandemics that have occurred since the 1500s. 1 Wild aquatic birds are well known to be the natural reservoirs for IAV subtypes harbouring H1-H16 subtypes, 2-4 with the exception of H17 and H18 subtypes that were recently discovered in bats. 5, 6 The phylogenetic relationships of all IAV subtypes are displayed in Fig. 1 . In addition to its natural reservoir species, influenza viruses infect a wide range of hosts including canids, equids, humans and swine. 2 IAVs' ability to generate novel gene constellations through reassortment between subtypes poses a risk for immune escape in these new hosts. 7 Furthermore, IAV undergoes rapid genetic and antigenic evolution, which makes vaccination control difficult in humans and other domestic species." ] },{ "paper_id": "a2759c88de238c2a28c8084c108538c8985104a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a27702025191a260051091b84a0d5c9b68829440", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To produce transducing retroviruses, 293FT cells were transfected using the PEI method with a 1:3:4 DNA ratio of pCMV-VSV-G, pMLV gag-pol (Dr. Jerome Schaack) and transfer vector, respectively. After 48 and 72 h, culture supernatants were combined, passed through a 0.45 mm syringe filter and concentrated 100 times by centrifugation at 25,000 rpm for 3 h at 4uC.", "Human papillomaviruses (HPVs) are small, non-enveloped double-stranded DNA viruses causally associated with multiple human cancers. Over 170 different genotypes have been identified and collectively categorized into high-risk or low-risk genotypes depending on their oncogenic capacity [1, 2] . The high-risk types are most commonly associated with cervical cancer [3, 4] and increasing evidence points to a contributing role in other cancers including head-neck [5, 6] and anogenital cancers [7] . HPV16 is the most prevalent high-risk genotype and serves as the main vaccine target along with HPV18 [8, 9] .", "293FT cells purchased from Invitrogen (Grand Island, NY) and HeLa cells obtained from Dr. Paul Lambert (University of Wisconsin-Madison) were maintained in Dulbecco's modified eagle's medium (DMEM) (Thermo Scientific/HyClone, Logan, UT) supplemented with 10% fetal bovine serum (FBS) (HyClone)." ] },{ "paper_id": "a279441c0873b6bfdfbd63cee1220cf9596acaee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Because exponential growth occurs between t s \u00bc 1 h and t e \u00bc 24 h, then using the formula g(t) \u00bc g(1) . 2 t/d , the doubling time, d, is deduced as", "is the fold increase and T \u00bc t e 2 t s . Using equation (2.6), the intracellular doubling time is found to be 3.50 h.", "( 1 :1)" ] },{ "paper_id": "a27adabfa89d32df634f7e7a9a6056b36ded5031", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a27cb38e8670f317f707a16661115a42b5b1b9fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As expected, the major core protein P4a (D-3) of Vaccinia virions is further identified in both infected cell culture approaches [45] .", "All of the electrophoresis apparatus (IPGphor II, Multiphor II chamber Electrophorese, EPS 3500 power supply) were purchased from Amersham Pharmacia Biotech (Uppsala, Sweden). IPG DryStrips and Pharmalyte pH 3- " ] },{ "paper_id": "a280d2019f9957487f81e4c5cf2d94a2a2f391a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Descriptive statistics (frequencies and percentages) were used to quantify the categorical study variables.", "The study targeted health care specialists in internal medicine, critical care, respiratory disease, infectious disease, hematology, and pediatrics, along with clinical microbiologists, hospital epidemiologists and blood bankers. The survey consisted of voluntary anonymous responses to a web-based questionnaire and did not include actual patient data." ] },{ "paper_id": "a2813c4975ae511e8e156daa2c5d81cb93bdcc05", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where \"\u00c1\" denotes the element-wise multiplication between vectors,", "where \u03c9 i , \u03bc r , \u03c3 l , and \u03bd h (8i, r, l, h) denote the preferences of DI, DO, UI, and UO, respectively,", "proof. See Appendix B." ] },{ "paper_id": "a28353cd5af668e408edfbc98b21224f3b04c232", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the present study, the seasons were defined as follows: spring (from March to May), summer (from June to August), autumn (from September to November) and winter (from December to February) [13] . In all statistical analyses, a p-value smaller than 5% was considered to be statistically significant. All of the statistical work was performed using the SAS statistical software package for Windows, version 9.1.", "Significant temporal variations were observed in the daily patterns of charcoal burning suicides ( Table 2 ", "To adjust for differences in age and sex in the suicide rate and population structure, we included the age, sex, and economic activity status of the suicide victims, the year of incidence and the offset term of population size in the regression equation as the confounding variables. Mathematically, the regression equation is written as follows:" ] },{ "paper_id": "a286c95345592981acce2ffe297605fd083d9fe7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceived and designed the experiments: DBS LF.", "Performed the experiments: EYW CQL SW ZHW QJL.", "Analyzed the data: DHG BZ." ] },{ "paper_id": "a286d1120f3b36b22f1b9e4e6409cad9b8471370", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Here w l is used to limit the contribution from a particular scale of histogram, as inversely proportional to its scale, w l = 2 \u2212l . N l is the partial increment from level l \u2212 1 to level l,", "\u03c4 denotes the histogram intersection:", "which can be equivalently written as" ] },{ "paper_id": "a293d2836c440402c8f71b2785b853473d188f5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(TITLE(\"carbapenem resist*\" OR \"imipenem resist*\" OR \"meropenem resist*\" OR \"ertapenem resist*\" OR \"doripenem resist*\" OR \"carbapenemase produ*\" OR \"carbapenem non-susceptible\" OR \"carbapenem hdroly*ing\") AND PUBYEAR < 2016) OR ((TITLE-ABS-KEY(Ndm-1 OR \"New Delhi metallo*\" OR \"carbapenemase\" OR \"extended-spectrum *lactamase*\") AND TITLE-ABS(\"carbapenem resist*\")) OR ((TITLE (\"coli\" OR \"enterobacter*\" OR \"aeruginosa\" OR \"baumannii\" OR \"klebsiella\")) AND KEY(\"carbapenem resist*\")) AND PUBYEAR < 2016) AND (LIMIT-TO(SRCTYPE, \"j\")) AND (EXCLUDE(DOCTYPE, \"er\"))" ] },{ "paper_id": "a2a873c09a0bc1b59d326245310e25a83031cd62", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The diagnostic utility of serology generally is limited by the need to collect both acute and convalescent sera to identify either seroconversion or a fourfold rise in antibody titer. As such, serologic methods that detect IgG responses usually have little impact on patient management.", "Future research on respiratory virus diagnostics should aim towards the ability to accurately detect a spectrum of clinically significant viruses rapidly enough to affect patient management and initiation of infection control measures while keeping the costs affordable. Commercial kits provide standardization not achievable with laboratory-developed tests, but at a substantially higher cost. Ultimately, the utilization of molecular testing, particularly highly multiplexed tests in routine patient management will depend on the cost/benefit ratio.", "Current and future diagnostic options will include antigen, molecular, and culture-based methods. The performance characteristics and limitations of these methods will vary greatly with the new generations of assays. It is important that diagnostic virologists and clinicians understand these characteristics and limitations." ] },{ "paper_id": "a2b0f19c4b1270624987ede418ab8da1e8b55cdf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In developing countries, RSV is a significant cause of death, with global estimates of more than 70,000 deaths in young children. hRSV is the third most important cause of deadly childhood pneumonia after Streptococcus pneumoniae and Haemophilus influenzae [105] . The epithelial cells of the respiratory tract are the major sites of virus replication, but hRSV can infect a wide variety of human and animal cells.", "Viruses 2015, 7 13 e.g., mutations H22A, T25A and S29A, and mutants that disrupt channel structure, i.e., obtained by introducing bulky side chains in residues involved in TM helix-helix interactions.", "Currently, no effective licensed treatments exist against coronavirus infection [8] [9] [10] , although live vaccines consisting of attenuated viruses are a promising strategy [11, 12] , along with fusion inhibitors (reviewed in [13] ). However, the possibility of reappearance of virulent phenotypes, drug side effects, and resistance calls for continued antiviral development. The latter depends on an intimate knowledge of the coronavirus molecular biology, described extensively elsewhere [14] and, increasingly, of their accessory proteins [15] . In this review, only the coronavirus envelope (E) proteins will be described in some detail." ] },{ "paper_id": "a2c46da8970ae5d4e6b3b1f4d4d30a2ea426d1ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was completed using Prism Windows 5.03 (GraphPad Software Inc., La Jolla, USA)." ] },{ "paper_id": "a2cf9e5c6c99b221516c4ce927b3c389d78c7620", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For transfections in 96 well plates for GFP analysis, 2 \u00d7 10 4 HEK293T cells were seeded into 96 well plates containing 0.3 \u03bcl Lipofectamine 2000 (Thermofisher) diluted in OptiMEM (ThermoFisher) with 100 ng total plasmid DNA per well.", "As viruses depend on cells to complete their replication cycles, this has driven the evolution of a series of antiviral factors that directly subvert viral replication within cells. Recent work has revealed the striking scale of antiviral mechanisms employed by cells -almost every step of viral replication is apparently targeted by host encoded antiviral factors. For HIV the best defined examples are APOBEC3G/3F and SAMHD1 that inhibit viral reverse transcription, TRIM5\u03b1 that targets viral capsid uncoating, and tetherin that prevents viral egress (reviewed in 1, 2 ). However, genomic and proteomic screens can aid identification of further antiviral factors, and so there is an expanding list being described 3, 4 . Such studies identified the MxB/Mx2 protein that targets HIV-1 replication around nuclear entry 5, 6 , and the SERINC3 and SERINC5 proteins that target HIV-1 entry 7, 8 .", "Plasmids. Human pQCXIP IFITM1-3 plasmids bearing an N-terminal FLAG were previously described 58 ." ] },{ "paper_id": "a2d455f2d873e1be7f2db4b069b6e40f3faf168b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell lysates were prepared in lysis buffer and quantified by Bradford assay. Equivalent amounts of each sample were resolved by SDS-PAGE and Western blotted with the following anti-MHV68 primary antibodies: hybridoma supernatants T1A1 anti-gp150, MG-2C10 anti-gB, and 9c7 anti-gp70, diluted 1:10 (kindly provided by Phillip Stevenson, University of Cambridge); anti-M9, anti-ORF26, and anti-ORF45, diluted 1:500 (kindly provided by Ren Sun, UCLA); anti-ORF72, diluted 1:500 (kindly provided by Linda van Dyk, University of Colorado, Denver); anti-ORF49, diluted 1:500 (kindly provided by Moon Jung Song, Korea University). Primary antibodies were followed by HRP-conjugated goat anti-mouse or goat anti-rabbit secondary antibodies (Southern Biotechnology, 1:5000).", "A particularly striking finding was that muSOX-induced degradation of viral mRNAs influenced events that occur during the first 6 hpi, before either its expression or host shutoff initiates.", "Table S1 Complete list of proteins identified through mass spectrometry. All proteins identified by MS, accession number, molecular weight, and peptide count and normalized to protein length and total counts. a First MS run. All proteins listed were identified in either DHS or MR samples. b Second MS run. All proteins listed were identified in either DHS or MR samples. (DOCX) ", "This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University of California Berkeley (approval number R292). All animals were anesthetized prior to infection with isoflurane, and all efforts were made to minimize suffering." ] },{ "paper_id": "a2e2beb6ce9597d9a4162f1399ed1a92cc010b66", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: H.P. and B.L. performed the major experiments of this study. Y.H. provided technical assistance for the experiments. Z.l.Q. analyzed the data and wrote the paper. Z.t.Q. conceived this research and analyzed the data. The remaining authors provided substantial assistance during the experiment and critical comments on the manuscript.", "Human umbilical vein endothelial cells (HUVEC) and Vero cells were grown at 37 \u2022 C in complete Dulbecco's Modified Eagle Medium (DMEM) containing 10% (v/v) heat-inactivated fetal bovine serum (FBS) (Gibco BRL, Carlsbad, CA, USA) supplemented with 100 nM nonessential amino acids (NEAA) (Invitrogen, Shanghai, China), 1 mM L-glutamine, 100 \u00b5g streptomycin/mL, and 100 U penicillin/mL. C6/36 cells (kindly provided by Professor Jing An from Capital Medical University, Beijing, China) were cultured in RPMI1640 (Gibco) supplemented with 10% FBS.", "Viruses 2018, 10, x FOR PEER REVIEW 8 of 12" ] },{ "paper_id": "a2e8d9291e399c6d8adc6d39318de197e86b3f4e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The inoculated cells were fixed with methanol and immunostained with a mouse monoclonal anti-core antibody and a rabbit polyclonal anti-NS5A antibody [22] , followed by an Alexa Fluor 555-conjugated anti-mouse secondary antibody (Life Technologies Japan Ltd.).", "Quantification of triglyceride Triglyceride (TG) was measured with a Triglyceride kit (Wako, Tokyo, Japan) according to the manufacturer's instructions.", "GL is the major component of licorice root extract, and is composed of glycyrrhetinic acid. GL has been shown to possess several beneficial pharmacological activities, including anti-inflammatory activity [2] , anti-tumor activity [3] , anti-allergic activities [4] , and anti-viral activities [5] . Several mechanisms of the GL-induced anti-inflammatory effect are reported, such as inhibition of thrombin-induced platelet aggregation [6] , inhibition of prostaglandin E2 production [7] and inhibition of phospholipase A2 (PLA2) [8] ." ] },{ "paper_id": "a2ea85a02fee49f55f485a2b5d808636cb38a0bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a2f53651474ffa6ede94371fa2d2e735395d965e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a2f961fd82a92373256efd31318904eaa6cf6c64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Over the years, control of IBV infection largely depends on vaccination using live attenuated and killed vaccines.", "A total of 86 M41 and 72 CR88 IBV isolates were considered in this study. However, to build the consensus sequence, one isolate from each data set was removed due to some unidentified amino acid at one or two positions. The M41 IBV isolates were found to have an average nucleotides sequence length of 1614 (537 aa) while CR88 isolates had an average length of 1653 (553 aa).", "As with the M41 IBV strains, most of these epitopes are shown to interact with the surface at varying threshold (yellow) as depicted in Figure 2 . " ] },{ "paper_id": "a2fc621a71cddf750d46902684501f5f18eba3a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mice were immunized with 35 \u03bcg MERS-CoV rS combined with 150 \u03bcL Freund's complete adjuvant (Sigma, St Louis, CA, USA) via subcutaneous immunization and boosted twice at 2-week intervals beginning three weeks after the initial immunization. The mice were killed 3 days after the last immunization, and their splenocytes were fused with mouse myeloma cells.", "The surface was regenerated with 10 mM glycine-HCl (pH 1.5). Sensorgrams were fit with a 1:1 binding model using BIA Evaluation software (GE Healthcare).", "Vero E6, 293FT and Huh7.5 cell lines were cultured in Dulbecco's Modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 1% penicillin-streptomycin (P/S), 1% L-glutamine and 1% HEPES. Non-essential amino acids (1%) were added to Huh7.5 cell cultures. SP2/0 cells were grown in RPMI 1640 containing 20% FBS, 1% P/S, 1% L-glutamine and 1% HEPES. After fusion with immunized mouse spleen cells, the hybridomas were cultured in DMEM with 20% FBS, 2% hypoxanthine aminopterin thymidine (HAT) and 1% P/S. All cells were cultured at 37\u00b0C with 5% CO 2 . All reagents were purchased from Gibco (Life Technologies, Grand Island, NY, USA), except for DMEM, which was obtained from HyClone (Life Technologies, South Logan, UT, USA)." ] },{ "paper_id": "a2fedab38bf51ed90c37c61d4f84838c56e5f18a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the fluorescence-activated cell sorting (FACS) and Western blot analysis, Vero E6 cells were transiently transfected with pXJmyc-GST, pXJmyc-3a or pXJmyc-3amut1 as previously described (3a and 3amut1 are also known as U274 and U274mut1, respectively, in ref. 6 ). All these constructs were tagged with the c-myc epitope at the N-terminus. All these experiments were performed as previously described [6] .", "Total RNA was extracted from 8 patients confirmed with SARS-CoV infection, as defined by WHO guidelines. The use of clinical samples for this study was approved by the Tan Tock Seng Hospital ethics committee. Reverse transcription (RT, Superscript II RT, Invitrogen) was performed on all samples, according to the manufacturer's protocol, and was followed up by a nested polymerase chain reaction (PCR). The PCR conditions and subsequent cloning steps have been described elsewhere [6] . Essentially, 15 independent clones from each of the eight SARS patient samples were sequenced. As a polymerase fidelity control of the RT and PCR system, full-length 3a RNA was in vitro transcribed from pXJ40-3a, a cDNA construct for expressing 3a in mammalian cells [6] , and subjected to an identical follow-up PCR and cloning protocol.", "In other RNA viruses, such as the foot-and-mouth disease virus (FMDV) and human respiratory syncytial virus, internal poly(A) extensions have been identified before as a hot spot for mutations [11, 12] . Similarly, these extensions also create frameshift mutations in the affected genes. FMDV populations with longer poly(A) extensions seem to have a lower fitness value as compared to those Distribution of 3a sequence variants within a population of SARS-CoV obtained from clinical and culture-derived samples with shorter extensions [11] . This is despite the fact that both the wild-type and mutant forms of the affected FMDV protein, the L protease, have equal functionality [13] . In addition, viral genomes possessing different lengths of the poly(A) tract could be recognized even from just a single PFU of FMDV [11] ." ] },{ "paper_id": "a3032ce8a80f772cc9150de358b980aa489cd924", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nanolayer on the PET Substrate, and Immobilization of the gp120 Antibody", "Ammonium molybdate tetrahydrate (0.35 g) and 0.76 g of thiourea were mixed with 50 mL of DI water. Then 0.25 g of PVP was added to the mixture. The resulting solution was reacted at 800 rpm for 1 h at 60 \u2022 C. The solution was transferred into a Teflon-lined stainless-steel autoclave. The autoclave was set at 200 \u2022 C for 24 h. After the reaction was complete, the resulting black precipitate was cooled down to room temperature and washed with DI water and ethanol using centrifugal filtration with 8000 rpm for 30 min. The final product was air-dried at 60 \u2022 C for 24 h. The PVP-modified MoS 2 NPs (concentration: 1 mg/mL) were characterized by high-resolution TEM using a JEOL JEM-3010 operated at 300 kV and by XRD (Rigaku, Tokyo, Japan).", "Recently, transition metal dichalcogenide (TMD) materials such as tungsten diselenide (WSe 2 ) and molybdenum disulfide (MoS 2 ) have been widely researched for their application in biosensors due to unique properties including electric charge effect and semiconducting property [11] [12] [13] . In particular, MoS 2 has many advantages for biosensor development due to its electrochemical property and biocompatibility [14, 15] . In addition, in order to maximize the benefits of MoS 2 on a large activated surface area, MoS 2 nanoparticles (MoS 2 NPs) have recently been synthesized and applied to develop various sensors [16] . However, most studies related to flexible biosensors composed of nanomaterials have been done through complex manufacturing methods. To replace the complex manufacturing water from a Millipore Milli-Q water purifier operating at a resistance of 18 M\u2126\u00b7cm. Myoglobin (Mb) (\u226590.0%, Sigma-Aldrich, Burlington, MA, USA), hemoglobin (Hb) (Sigma-Aldrich, Burlington, MA, USA), thioredoxin (Trx) (Sino biological, Wayne, PA, USA), and prostate-specific antigen (PSA) (Abcam, Cambridge, UK) were used to investigate the selectivity of the fabricated biosensor." ] },{ "paper_id": "a309fbcf24f3b728a280f67805614ddffca0f8c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a30cef8b3428aa804aa2cbf0ec0303827bb09514", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We previously constructed a replication-competent vaccinia Tiantan strain infection model using an in vivo bioluminescent imaging (BLI) method and found that immunodeficient rats were more susceptible to vaccinia virus than Sprague Dawley (SD) rats and also displayed prolonged infections 9 . The BLI technology has the advantages of rapidity, simplicity, and quantitative precision, which allows the dissemination and clearance of viral vectors in intact and living animals to be carefully evaluated 10 . The aim of this study was to characterize the risk Published: xx xx xxxx OPEN www.nature.com/scientificreports/", "differently predict the outcome in humans. However, in both species, the distributions and residence times in immunodeficient animals were different from those in immunocompetent ones, suggesting that Adv5 should be used with caution in various groups of immunosuppressed patients because considerably more serious adverse effects can be expected in these patients. Consistent with this, adenovirus is ubiquitous and causes generally mild, self-limiting infections in immunocompetent adults, but it can lead to a serious, often life-threatening illness in solid-organ transplant recipients and AIDS patients 13, 14 ." ] },{ "paper_id": "a30fd6139467d0ef97598274d3d926ddf4623e88", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "From", "The first diamond makes this unclear.", "No competing interests were disclosed. Competing Interests:" ] },{ "paper_id": "a3149d976fd2e03be5159c041a0241f00597e097", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HAI assays were performed on a 100-\u03bcl aliquot of the samples at University Health Network (UHN), Toronto, Ontario, Canada. The sera were treated with receptordestroying enzyme (RDE) of V. cholerae by diluting one part serum with three parts enzyme and were incubated overnight in a 37\u00b0C water bath. The enzyme was inactivated by 30-min incubation at 56\u00b0C followed by the addition of six parts 0.85% physiological saline for a final dilution of 1/10. HI assays were performed in V-bottom 96-well microtiter plates (Corning Costar Co., Cambridge, MA, USA) with 0.5% turkey erythrocytes as previously described [14] using inactivated pandemic influenza A/ California/07/2009(p2009A(H1N1)) antigens.", "Introduction: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown.", "Immune mediator levels in serum were measured in patients and controls by using the multiplex Bio-Rad 27-plex assay (Hercules, CA, USA) in the Infection & Immunity Unit (Hospital Cl\u00ednico Universitario-IECS-CYL, Valladolid, Spain). This system allows for quantitative measurement of 27 different chemokines, cytokines, growth factors and immune mediators while consuming a small amount of biological material. A number of additional soluble mediators were measured by using enzyme-linked inmunosorbent assays (ELISAs): interferon \u03b1 and \u03b2 (Verikine kits purchased from Pbl Interferon Source, Piscataway, NJ, USA), IL-23, TGF-\u03b21 (Quantikine kits purchased from R&D Systems, Minneapolis, MN, USA), IL28A (Legend Max kit purchased from BioLegend, San Diego, CA, USA). Immune mediator's concentration of each individual sample was normalized against the median of the concentration of the control group (n = 15), and the resultant ratios were compared between groups of patients." ] },{ "paper_id": "a3156b64bff879eba0b2b9a0e81adc1c5dead42c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IFN-I transduce intracellular signals through a single receptor, IFNAR, but via a multitude of downstream signaling pathways.", "\u2020 Elena Tomasello, Emeline Pollet and Thien-Phong Vu Manh have contributed equally to this work." ] },{ "paper_id": "a31ae2d95b283ef7da701d343b992b25afa779d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "S3b " ] },{ "paper_id": "a336fd69f73d0debd55b454b97ff45cf9f39d82a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Community-based measures focused mainly on: involvement and training of community volunteers [33, 35, 36, 38, 49] (n = 5, 16%); awareness campaigns [20, 30, 31, 40, 41] (n = 5, 16%); and public education [31, 33, 41, 49] (n = 4, 13%). They also included community-based surveillance or case-finding [30, 35, 36] (n = 3, 10%) and social mobilization [22, 36] (n = 2, 6%). Materials used included pamphlets, posters, videos, social media platforms, and print and electronic media [24, 27, 35, 38, 49] (n = 5, 16%).", "Please see Additional file 1 for translations of the abstract into the five official working languages of the United Nations." ] },{ "paper_id": "a33e3ade1bf2a47195051d6d458baa2001ab72a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IDWRs are very important for clinicians, enabling them to identify the seasonal prevalence of known diseases. However, these reports become available after a minimum of 10 days following patient examinations. Therefore, traditional and official surveillance systems have the distinct disadvantage of being slow and are limited to reporting pathogens chosen in advance.", "The finding that M. pneumoniae infection was not detected in infants and children, but rather in elementary school pupils and minors, was consistent with reports that M. pneumoniae may often cause asymptomatic infections before the age of 5 years, after which immunity decreases as children become susceptible to symptomatic M. pneumoniae infections [5] .", "In some cases, an infectious outbreak can be detected on the same or the following day. Although syndromic surveillance provides rapid results, it has the disadvantage that There are approximately 500 sentinel medical institutions in Japan, which are selected from those equipped with departments of pediatrics and internal medicine and with more than 300 beds.", "Evaluation of the incidence of various symptoms in patients infected with different pathogens showed that rhinoviruses were detected in nasal swab specimens more often than other viruses and patients with rhinovirus infections were less likely to present with fever ( Table 3) ." ] },{ "paper_id": "a3436bd86402190ee99045fd5a87c277288d585a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Calculations were performed at sciCORE (http://scicore.unibas.ch/) scientific computing core facility at University of Basel. The maps were generated using OpenStreetMap contributors. Katya Galactionova and Lisa Crump are greatly acknowledged for language editing." ] },{ "paper_id": "a348cf052e162d6156b8179a82058aff4a0af407", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following source data and figure supplements are available for figure 1:", "Preparation and purification of phage-scFvs for ELISA or neutralization assays", "The coordinates and structural factors have been deposited into the Protein Data Bank with accession code 5YAX." ] },{ "paper_id": "a34b4ae8ac728d948a40b4c6f0d825b319d88ad7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "They recognize virally encoded fake MHC self-molecules that are expressed by virus infected cells thus overcoming viral immune escape by NK cell activation [1] ." ] },{ "paper_id": "a35a9ab63e50b5eed8710a67b89d6c31d53cd191", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Neonatal diarrhoea is a well-known disease complex in modern swine production influenced by individual, maternal and environmental factors. The aetiology in specific herd-cases may differ and is often incompletely diagnosed. Until recently, this complexity was not of major practical concern, since most problems could be controlled by vaccination or antibiotics. Around 2008, however, a new syndrome that did not respond to antibiotics or commercial vaccines seemed to emerge ([1] + Personal communications, S.E. Jorsal, National Veterinary Institute, Technical University of Denmark and B. Svensmark, Pig Research Centre, Danish Agriculture & Food Council, Denmark). The number of affected herds is unknown, but 80% of Danish swine practitioners report to experience these problems [1] .", "The study was conducted in accordance with the guidelines of the Danish Ministry of Justice with respect to animal experimentation and care of animals under study. According to Danish legislation this type of study does not require ethical approval.", "Vulva discharge 0 (0%) 2 (10%) 0 (0%) 0 (0%) 2 (2%)" ] },{ "paper_id": "a36b65d00944ef78c5bc2b7bf759122c2ac4eaf1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus isolation was attempted by inoculation with tissue samples of different cell lines such as VERO cells (African green monkey kidney), MARC-145 (foetal monkey kidney), HRT-18 (human colorectal adenocarcinoma), FRhK 4 (foetal rhesus kidney), LLC-Mk2 (rhesus monkey kidney) and TB1 LU (lung, Mexican free-tailed bat, \"Tadarida brasiliensis mexicana\"). Confluent monolayers of cell lines were inoculated with samples, incubated at 37\u00b0C with 5% CO 2 and observed daily for seven days for the development of cytopathic effects.", "Libraries were prepared following sequence independent single primer amplification (SISPA) with several variations as described by Djikeng et al. [17] ." ] },{ "paper_id": "a3718ef8f5fc2e8b32992c568bc66646a870656c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data analysis was performed using the Statistical Product and Service Solutions (SPSS v19.0) software (IBM, USA). The odds ratios (ORs) and 95 % confidence intervals (CIs) of categorical variables were calculated using the chi-square test or the Fisher's exact test with two-tailed. A value of p < 0.05 was considered to be statistically significant.", "A molecular evolutionary genetics analysis was employed to perform the phylogenetic analysis (MEGA v5.2). A phylogenetic tree was constructed using the neighborjoining method with 1,000 bootstrap replicates. Reference strains were downloaded from GenBank." ] },{ "paper_id": "a374cb0eaeb9e3cf7b9e3d4f08ff21907437c159", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The four Coronavirus (CoV) genera, alpha-, beta-, gamma-, and deltacoronavirus are clustered in the Coronavirinae subfamily [1, 2] . CoVs are pleomorphic, enveloped, single-stranded, positive-sense RNA viruses, with genomes ranging from 26.2 to 31.7 kb [3, 4] . The genomes of CoVs encode four structural proteins: spike (S), membrane (M), envelope (E), and nucleocapsid (N).", "This study was approved by Harbin Veterinary Research Institute and was performed in accordance with animal ethics guidelines and approved protocols. The animal Ethics Committee approval number is Heilongjiang-SYXK-2006-032.", "Sequence" ] },{ "paper_id": "a3778f543ef74ff3a0dd90250221b77ee38d7533", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The notion of mfe-structure is based on a specific concept of pseudoknot loops and respective loop-based energy parameters. This thermodynamic model was conceived by Tinoco and refined by Freier, Turner, Ninio, and others [13, [20] [21] [22] [23] [24] ." ] },{ "paper_id": "a382a62bbd387279327333abd96be2aa76445ace", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Multiplex reverse transcriptase (RT)-PCR for viruses. Multiplex RT-PCR was performed using the DiaPlexC\u2122 RV13 Detection Kit (Solgent, Daejeon, South Korea). We used a viral primer panel targeting influenza A and B; respiratory syncytial virus; parainfluenza virus 1, 2, and 3; coronavirus 229E and OC43; human metapneumovirus (hMPV); enterovirus, rhinovirus; human bocavirus; and adenovirus [18] . RT-PCR was performed using a C1000 Touch\u2122 Thermal Cycler (Bio-Rad, Hercules, CA, USA).", "Although acute bronchitis is quite common, there is relatively limited information regarding the microorganisms that are involved in this illness.", "Categorical variables were analyzed using the chi-square test or Fisher's exact test. Continuous variables were analyzed using Student's t-tests or the Mann-Whitney U-test. A p-value <0.05 was considered statistically significant. All analyses were conducted using SPSS statistical software (IBM SPSS Statistics version 21; IBM, Armonk, NY, USA)." ] },{ "paper_id": "a3980dbebf9ade61200fc033a91383e5974912ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SCIENTIfIC RepoRTS | (2018) 8:13814 | DOI:10.1038/s41598-018-32072-3 modifications with both types of modifications being used for protein quantification. The 10plex reporter ion intensity matrix for the study participants was extracted from the Maxquant proteingroup matrix file and batch corrected using an in house platform.", "Data analysis was done using R. Cluster analysis to determine differences in protein expression between children with respiratory infections and healthy controls was done using nonmetric multidomensional scaling analysis. The accession number for the data reported in this paper is proteomeXchange: PDX009403.", "Cell-specific marker protein analysis. In order to further characterise the proteomes identified in protocol Cii, the expression of signature proteins that are typically expressed by upper-airway cells was assessed. High expression levels of the signature nasopharyngeal proteins BPIFA1 and BPIFA2 was noted (Fig. 4a) . The coefficients of variation for these proteins as well as other proteins in the pooled control was less than 20% (Fig. 4b) ." ] },{ "paper_id": "a3a2b5d607691f30dd1b1baeca0e41817e2fde86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mice. COS7 cells were grown in Dulbecco's modified Eagle's medium (DMEM) supplemented with 5% fetal bovine serum (FBS) in a humidified 5% CO 2 incubator at 37 \u2218 C.", "Analysis. Data were analyzed using the software SPSS (version 16.0) and presented as the mean \u00b1 SEM. Differences between two groups of mice were compared using Student's -test. A value less than 0.05 was considered to be statistically significant.", "Rheumatoid arthritis (RA), a chronic symmetrical autoimmune disease, is characterized by synovial inflammation and proliferation accompanied by cartilage erosion and bone loss [1] . More than one-third of patients eventually experience employment disability and lower quality of life because of this disease, which is largely responsible for the high socioeconomic burden of RA [2] . Furthermore, mortality rates in RA patients are higher than in the healthy population [3] .", "Six-week-old female BALB/c (H-2d) mice and 5-weekold male DBA/1 mice (a CIA-susceptible mouse strain, H-2q) were both purchased from HFK Biotechnology Co. Ltd. All mice were maintained in a specific pathogen-free environment. All animal experiments were performed according to the guidelines of the Animal Care and Use Committee of Capital Medical University." ] },{ "paper_id": "a3ad970870495c1bc1fd7cc4eb6f815b486479c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Considering these facts, the enormous importance of early identification and mitigation of infectious disease threats is a critical component of a national defense strategy to \"deter war and protect the security of our country.\"", "These numbers attest to the scientific rigor with which partners conduct their work, their ability to leverage funding to create a relatively balanced portfolio covering all five pillars of infectious disease threats of military importance, and their emphasis on military populations.", "Because of its unbiased membership policy, ICMM is the only military organization with a formal in-force memorandum of agreement with WHO. Through direct engagements or indirect facilitation and empowerment with ICMM, opportunities are being explored to work with foreign militaries, to further facilitate IHR (2005) compliance, and to facilitate force health protection and global public health in concert with WHO. Joint initiatives include co-sponsoring a forum titled \"Emerging " ] },{ "paper_id": "a3bd2c7d348548cb21d4e9f4eb63ac51ea015e10", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In multivariate analysis of recorded symptoms, fever (odds ratio (OR) 1.98, 95% confidence interval (95% CI) 1.30 to 3.03, P = 0.002) and pleuritic chest pain (OR 1.72, 95% CI 1.04 to 2.86, P = 0.04) remained independently predictive of a positive PCR result (with M. pneumoniae and C. pneumoniae excluded from the analysis)." ] },{ "paper_id": "a3bf6f0444bb71c6d5b232122353d551a15d0a5f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Data are available at NAR Online.", "Circular dichroism (CD) spectra were recorded in a JASCO J-710 circular dichroism spectrophotometer at ambient temperature. DnaG (2.17 M) and the variant DnaG-K6AY7A (2.21 M) were measured in a cell with 0.05 cm path in 10 mM Na 2 HPO 4 -NaH 2 PO 4 (pH 8.0), 50 mM NaCl 2 .", "Binding assays were carried out at room temperature for 5 min in a 10 l reaction mixture containing 20 mM HEPES (pH 7.9), 60 mM KCl, 10 mM MgCl 2 , 10% glycerine, 2 mM DTT and 0.1 mM EDTA with the indicated amounts of proteins and RNA substrates. The reaction samples were resolved in 5% native PAA gels at 200 V and 4 \u2022 C, and were visualized by phosphorimaging using a Bio-Rad molecular imager and Quantity One (Bio-Rad) (5, 33) .", "We thank Tom Rische (Institute for Microbiology and Molecular Biology, University of Giessen) for help and discussion, Wolfgang Wende (Institute for Biochemistry, University of Giessen) for the opportunity to perform CD measurements and for helpful advices and Stephanie Glaeser (Institute for Applied Microbiology, University of Giessen) for creating the 16S rRNA phylogenetic tree. We are grateful to Christian Lassek (Institute for Microbiology and Molecular Biology, University of Giessen) for cloning of truncated DnaG proteins and Michael A. Trakselis (University of Pittsburgh) for sending us the plasmid for expression of recombinant DnaGE175Q. " ] },{ "paper_id": "a3c3313dedf5e05ca7bc7388ff9471ff7032ef54", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Approval of the study was obtained on May 20th 2015 from the Ethical Committee for Animal Experiments of the Northwest A&F University.", "Viral RNA/DNA Kits (OMEGA, USA) were used to extract different viral nucleic acid (RNA and DNA) from culture supernatants of different viruses or fecal samples. The extraction procedure was performed according to manufacturer's instructions. Then the RNA extracted from RNA viruses were reversely transcripted into complementary DNA (cDNA) using the reverse transcriptase kit (Takara Corp., Japan) according to manufacturer's protocols." ] },{ "paper_id": "a3c3b7c38ad32e1042d78aae2027ca491e9f2197", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 1,709 confirmed cases (out of 1,755 total cases) were extracted for the analysis. Forty-six cases (i.e., 2.6% of the total) could not be pinpointed at an exact location because of inconsistencies in the address entries (So 2002) .", "Data sources. We used spatial and nonspatial data in this study. Spatial data are geographic in nature and have a physical dimension or location in the real world. These are represented as points, lines, or area symbols, and they form the map base upon which SARS occurrences are depicted. Data on SARS incidence were derived from case-contact interviews that are text based; associated residential address data were first cleaned, checked for completeness and accuracy (e.g., Chinese-English transliteration of building and street names), and then geo-referenced to enable mapping.", "Log \u2022 \u2022 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25b2 \u25a0 \u25a0 \u25a0 \u25a0 \u25a0 \u25a0 \u25a0 \u25a0 \u25a0 \u25a0 \u25a0 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022 \u2022" ] },{ "paper_id": "a3c43cf529fc26a2f6b039c7e2aa9f0825a9a19f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We first used reverse transcription-PCR (RT-PCR) to isolate and sequence DrNPC1 domain C. Alignment of domain C amino acid sequences from HsNPC1 and DrNPC1 revealed a substantial degree of conservation (80% amino acid identity), with identical arrangements of cysteine residues and similar predicted secondary structures, suggesting a similar overall fold for the two proteins ( Fig. 1) .", "E bola virus (EBOV) is the causative agent of highly lethal zoonotic infections in humans and nonhuman primates in sub-Saharan Africa (1) (2) (3) . Despite the emerging roles of EBOV and related members of the family Filoviridae (filoviruses) in human disease, our knowledge of the ecological host range of these agents remains limited. Bats are thought to be important reservoirs for filoviruses; however, conclusive evidence in favor of this hypothesis has been obtained only for Marburg virus (MARV) and Ravn virus (RAVV), which were recently found to circulate in Egyptian rousettes (Rousettus aegyptiacus) (4) (5) (6) (7) ." ] },{ "paper_id": "a3d1def9eb134591e3d0b38dc1c1330745da34a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It is important that limitations be considered when interpreting results from this study. The observed variability in infection could be reflective of diagnostic submissions specifically to IDEXX laboratories. This could lead to admission risk bias, a form of selection bias, as is common with registry or hospital based studies, particularly if preference of diagnostic lab by sample submitters in an area is related to the true prevalence of either FIV or FeLV.", "The evidence of distinct clusters of infection necessitates the need to investigate overall spatial dependence in the occurrence of cases (clustering), and if these are identified, to adjust for their presence when evaluating the association of putative risk factors to these infections. Ignoring clustering may result in biased standard errors and thus can compromise risk factor studies [45] ." ] },{ "paper_id": "a3f75f7f759c60426c7a47b9cd2470a70ef244c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Note that this conclusion is drawn majorly from the transfection system and indirectly from viral infection.", "Real-time PCR was performed using ABI Sequence Detector System (ABI Prism 7000 Sequence Detection System and software; Applied Biosystems) in a final volume of 25 \u03bcl containing 2.5 \u03bcl of cDNA from the reversed transcribed reaction, primer mix (2.5 pM each of sense and antisense primers), 12.5 \u03bcl of SYBR Green Master Mix (Applied Biosystems) and 5 \u03bcl of distilled water. The oligonucleotide primers were designed using Vector NTI software (Invitrogen) or obtained from literatures (S1 Table) . The amplification parameters were 40 cycles of two steps each cycle comprised of heating to 95\u02daC and 60\u02daC. The final mRNA levels of the genes were normalized using GAPDH.", "Transfection of in vitro-synthesized genomic RNA and generation of PRRSV mutants" ] },{ "paper_id": "a3f9d6933e737f7f0a7bd27a54a9bb4882eca041", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical and Epidemiologic Characteristics of RSV Infections PLOS ONE |", "In this study, we aimed to evaluate the epidemiology, clinical characteristics and management of ALRIs caused by RSV infection among hospitalized patients of all age groups in eastern China between 2009 and 2013 in a hospital-based surveillance study." ] },{ "paper_id": "a3ff62cdc7cd33bb6618950b28fe649bf95ef6de", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "None to report. Symptoms were collected by interview. Severity was ranked on a fourpoint scale ranging from none (0) to severe (3) . The number of people asked about particular symptoms is reported in parentheses.", "The study was funded by the National Institute of Allergy and Infectious Diseases, National Institute of Health, under Inter-Agency Agreement Y1-AI-5072, and the Armed Forces Health Surveillance Center, Global Emerging Infections Surveillance and Response System.", "Analyses were performed using SAS software, version 9\u00c13 (SAS Institute, Cary, North Carolina)." ] },{ "paper_id": "a401eee90cc270520c65bc001f31a617f4edb7df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ligand-based pharmacophore was previously made available: http://figshare.com/articles/Ebola_active_cpds_pharmacophore/ 1190902.", "The following PDB structures were used in this study (4IBB, 4IBC, 4IBD, 4IBE, 4IBF, 4IBG, 4IBI, 4IBJ, 4IBK).", "For models and advice please contact Sean Ekins (ekinssean@ yahoo.com)." ] },{ "paper_id": "a4097a2674eed241d6c9d0f0e98e86e037315cfc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a40f0baaa8d1450af8f21422d3623abe288f7cd8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The oil and components tested in here showed higher antibacterial activity against Gram (+) than Gram (\u2212) bacteria. Gram negative bacteria are, in general, more resistant than Gram positive ones [48] [49] [50] [51] [52] [53] [54] [55] . Overall, the oils and single compounds were more active vs. yeasts and Gram positive bacteria than Gram negatives, has reported in similar studies [43, 46, [56] [57] [58] .", "where A 0 is the absorbance of control sample (without essential oils), and A 1 is the absorbance of the samples with essential oils at different concentrations. Oil concentrations (mg/mL) providing 50% inhibition (IC 50 ) was calculated from a graph plotting scavenging activity against oil concentration.", "The " ] },{ "paper_id": "a413230495919e899e941fe5c2993c7cec504d4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NP was purified using the protocol described in 54, 55 . it. After air-drying, the samples were observed in a T12 FEI electron microscope and images were taken using an Orius SC1000 CCD camera (Gtan Inc., Pleasanton, CA)." ] },{ "paper_id": "a43db4dbbe6272ff71bcd5dc9cbf29bad9cd958e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HPV16 pseudoviruses were prepared as described earlier [66] . HCMV strain TB40/E was originally isolated from a throat wash specimen obtained from a bone marrow transplant patient and subsequently propagated in HUVECs [67] .", "If not stated otherwise, the experiments were repeated at least three times. Statistical analysis of all analyzable data points was assessed with two-tailed, unpaired t-tests using GraphPad Prism software and Microsoft Office Excel 2016. p-values smaller then 0.05 (p < 0.05) were considered as significant differences between groups. ", "(2) The cells were transfected with a mixture of C-terminal tetraspanin peptide and a PULSin (Polyplus-transfection, Illkirch, France) preincubated for 1 h in medium without supplements before PsVs addition and were further cultured in medium with FCS. PULSin was used according to manufacturer's instructions." ] },{ "paper_id": "a445e4cc0146046d191344e3b61cd8dd4f33eb83", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sequences of primers and probes for each assay are shown in Table 1 as described elsewhere [18, 29, 36] . All PCR's were performed using light cycler 480 II (Roche, Germany).", "The population of Techiman municipality based on the 2010 population census is 206,856 [33] . The projected population of Forikrom and Buoyem are 3,800 and 3,900 individuals respectively [34] . The Techiman municipality has a population density of 318 people per Km 2 with several ethnic groups [32] . The population of Sekyere Central district is 71,232 and the projected population of Kwamang is 8,000 [34] . The population density of the district is 64 people per Km 2 [35] ." ] },{ "paper_id": "a447f42b4f4ed16afea798513f8c1409ee2252fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hijacking of host lipids and their biosynthetic pathways is a common strategy for microbial infection. Human enveloped viruses including hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-1 use cholesterol-rich lipid rafts for entry [1, 2] , assembly [3] , and/or replication [2, 4] . Lipid droplets (LDs), once considered static storage vesicles for host lipids, are now appreciated as dynamic organelles [5] that are also utilized in the lifecycles of pathogenic human viruses including rotavirus (RV) [6] , dengue virus (DV) [7] , and HCV [8] . HCV in particular requires host LDs for assembly of nascent viral particles [9] [10] [11] .", "Cell viability was determined using CellTiter 96 AQueous One Solution Cell Proliferation Assay (Promega, Madison, WI, USA). This assay employs a tetrazolium compound [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; MTS], which is bio-reduced by cells into a colored formazan product that can be detected in tissue culture media at 490 nm wavelength [98] .", "(TIF)", "Protein engineering of the Spn4A scaffold and drug delivery strategy to target secretory pathway SKI-1/S1P" ] },{ "paper_id": "a462888bb4b9f31940fb166c07a8590406150575", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were plotted as mean\u00b1standard error (n=5) and the difference comparison was conducted by using an unpaired, two-tailored Student t-test. The difference was considered statistically significant when P values were \u2264 0.05.", "Female BALB/c mice (5 week-old) were obtained from Orient Bio (Seoul, Korea). All of the mice were maintained under specific pathogen-free conditions in the experimental facility at the Ewha Womans University. ", "The viral RNA from PR8 virus was acquired by using QIAamp MinElute virus spin kit (Qiagen, Valencia, CA) in accordance with the manufacturer's instructions. The cDNA corresponding to NP gene was generated by RT-PCR using forward primer (5'-GGGTACCGCCACCATGGCGTCCCAAGGCACC-3') which contains a KpnI restriction enzyme site and the Kozak sequence to enhance translation and the reverse primer (5'-TTCTAGATTAATTGTCGTACTCCTC-3') that contains a stop codon and an XbaI restriction enzyme site at 3' terminus. The whole open reading frame was then digested with Kpn I/Xba I double digestion and inserted into the pShuttle-CMV vector." ] },{ "paper_id": "a466d42cb39e44cacc9d9923ddf169e6a9dad838", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "which can be rewritten as", "Therefore, the total likelihood is calculated as the following product:", "4" ] },{ "paper_id": "a46d2cd0e65ba71e9d1ccf20762c9043ed3e67c2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical features and laboratory findings" ] },{ "paper_id": "a48482a6bd5e78f140777702151cffe852ea5f1e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The GC3s value is defined as the proportion of GC nucleotides at the third (variable) coding position of synonymous codons. It is a useful parameter for evaluating the degree of base composition bias.", "The GC content for the total 4870 genes varies from 46.43%\u02d85.80% (GC2) to 64.11%\u02d810.16% (GC3), with a mean value of 56.41%\u02d84.6% being distributed mainly between 24.80% and 73.00% (Table 1) , the GC12 being distributed mainly between 40.00% and 60.00% ( Figure 1 ). The greatest differences of GC content are found in GC2 (46.43%\u02d85.80%) and GC3 (64.11%\u02d810.16%), where most synoymous mutations occur [33] ." ] },{ "paper_id": "a4860aeadf8a51f4702262a58b808ea851eb4c27", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following assumptions were used given the lack of specific experimental data, but further efforts to produce the data can be done to address the issues listed here:", "Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. " ] },{ "paper_id": "a490933d0fb05e92f52ae3ef9f2d31d3384a9539", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a49651276ae7cd5bf402c1066944fb7cfc83ffaa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed from a total of 10-21 patches from 21 leaves and 5 different plants. Graphpad Prism One-way analysis of variance (1 way ANOVA) was used to assess the overall statistical differences between the means of different groups. Following 1 way ANOVA, Tukey's Multiple Comparison Test was also used to assess whether the mean of two particular groups were different from each other. P value summary (P,0.05) shows statistically significant differences between different treatments. Figure S2 (A-C) Repeated experiment as described for Fig. 2D , Fig. 3D and Fig. 4E , respectively. One-way analysis of variance calculation followed by Tukey's Multiple Comparison Test allowed analysis of differences between means: = NS, not significant, ***, 0.0001,P value,0.001, **, 0.001,P value,0.01, *, P,0.05. (TIF) Figure S3 (A-C) Repeated experiment as described for Fig. 6D , Fig. 7B and Fig. 8A , respectively. One-way analysis of variance calculation followed by Tukey's Multiple Comparison Test allowed analysis of differences between means: = NS, not significant, ***, 0.0001,P value,0.001, **, 0.001,P value,0.01, *, P,0.05.", "pTRV2 with myosin fragments was as described [22] . Virusinduced gene silencing (VIGS) studies were conducted as described previously [78, 79] . vTRV infections were established in N. benthamiana by co-agroinfiltration of pTRV1 and pTRV2. To confirm silencing of specific myosin transcripts, RNA was isolated from 20 day-old TRV-infected systemic leaves (two plants/ construct) using the RNeasy plant mini kit (Qiagen). DNasetreated RNA (4 mg) was used to generate cDNA with iScript cDNA synthesis kit (Bio-Rad). After a 15-fold dilution of the cDNA, 2 mL of solution was used for quantitative RT-PCR through a Rotor Gene 3000 real-time DNA detection system (Corbett Research). The following primers were used to detect N. ", "After acquisition, images were processed using Metamorph and/or ImageJ to quantify the average intensity of fluorescence, Carl Zeiss LSM Image Browser, and/or Adobe Photoshop software for post-capture imaging processes." ] },{ "paper_id": "a49923d05f7decbdc6f0d8a3825fd2cfb6711775", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a4995af42a012dd1b7f8da3936d79d78d0e24405", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protein samples were separated by electrophoresis on 8% (w/v) SDS-PAGE and transferred to PVDF membranes (Millipore, Bedford, MA). After blotting, the membranes were probed with appropriate antibodies. Subsequently, the membranes were washed ten times with 0.05% PBST and incubated with horseradish peroxidase (HRP) conjugated goat-anti-mouse or goat-anti-rabbit IgG (Beyotime, Nanjing, Jiangsu). The enhanced chemiluminescence (ECL) system (Vigorous, Beijing) was utilized to detect the blotted proteins.", "The animal use in this study was approved by ", "(XLS) " ] },{ "paper_id": "a4a1f5c5d5bb581f195dee744257396bbbe26dd6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In contrast to other viruses, such as HCV, EMCV, or poliovirus, for which translation relies exclusively on IRES-mediated initiation, the unspliced HIV-1 genomic RNA can use three different mechanisms of ribosomal recruitment:", "All eukaryotic mRNAs contain an N7-methylated guanosine linked to the first nucleotide of the RNA via a reverse 5 to 5 triphosphate linkage called the cap structure, which is required for mRNA processing and nuclear export, but also for stability and translation efficiency [6] .", "In conclusion, translational control of HIV-1 is a very complex process with multiple strategies to utilize or detour the cellular machinery. Although a lot of work has already been done to decipher some of the molecular mechanisms, some issues remain to be addressed and future work should clarify how the virus juggles with all these mechanisms during the course of viral replication. " ] },{ "paper_id": "a4ac0a556416712bc053f001c5bc6931c908bfd1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "COC was purchased from TOPAS Advanced Polymers (Frankfurt-H\u00f6chst, Germany). Unless otherwise stated, all chemicals were purchased from Sigma-Aldrich (St. Louis, MO, USA) and used without further purification steps. Rabbit anti-H1 polyclonal Ab was obtained from AbFrontier (Seoul, Korea).", "where I is the fluorescence intensity and C is the concentration (\u03bcg/mL) of Cy3-labeled-Ab with a correlation coefficient of 0.983.", "Swine-origin influenza virus, a high-risk human influenza A virus (H1N1), is a serious health threat and potential leading cause of death all around the World [1] . The World Health Organization (WHO) has reported that more than 16,000 cumulative deaths were reported from 213 countries due to H1N1 in February 2010 [2] . Several laboratory diagnostic methods have been developed to monitor the outbreaks of the virus as follows: (1) specific real-time polymerase chain reaction (PCR)-based detection method, (2) isolation of H1N1 influenza virus, (3) detection of 4-fold rise of neutralization antibodies to the virus [3, 4] . However, these methods require highly skilled-personnel and expensive laboratory instruments. In addition, they are not suitable for undeveloped countries because of the limited access to central laboratories and expensive costs." ] },{ "paper_id": "a4b16ad01125dda3a5dd4ae97fe8cb53c9538075", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author(s) declare that they have no competing interests." ] },{ "paper_id": "a4c0d3619ba273adce8a9d0df51eca6adaaf2f23", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The complete genome sequence of PEDV strain CH/JXJA/ 2017 has been deposited in GenBank under the accession number MF375374.", "The full-length genome sequence of a variant of porcine epidemic diarrhea virus (PEDV), that of strain CH/JXJA/2017, was highly homologous to CH/ ZMDZY/11, a highly virulent Chinese PEDV strain. CH/JXJA/2017 had a distant relationship with the attenuated CV777 vaccine strain, but the insertion sites of the S1 gene were similar to those of the recombinant strain of CH/ZMDZY/11.", "P orcine epidemic diarrhea (PED) is a devastating enteric disease (1) caused by PED virus (PEDV), an RNA virus in the genus Alphacoronavirus, family Coronaviridae (2) . Presently, PEDV is posing a threat to the swine industry worldwide (3) (4) (5) (6) (7) . PED was first reported in England in 1971 (8) and has since been identified in many pig-raising countries, including European, American, and Asian countries (9) . In 2010, the largescale outbreaks of PED with high morbidity and mortality occurred in swine farms in China, resulting in huge economic losses (10, 11) ." ] },{ "paper_id": "a4c922f362c4d59ebe0b890776670e406d9dc985", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To evaluate the genetic relationship among the virus-related sequences within the same species and/or family, phylogenetic trees were constructed using the neighbor-joining method with maximum composite likelihood nucleotide substitution model and pairwise deletion for missing data implemented in MEGA program (v5.2.2). Branch support and nodal confidence were assessed by bootstrap resampling with 1,000 replicates and bootstrap value of 70% was used as the cut-off for cluster analysis. Percent nucleotide and amino acid sequence identities from pairwise comparison were calculated using BioEdit Sequence Alignment Editor (v7.0.9.0).", "DNA for sequencing were prepared by using a ScriptSeq RNA-Seq library preparation kit (Epicentre, WI, USA) according the manufacturer's recommendation. Terminal-tagged oligomer were subsequently annealed at the 3 0 -end. The di-tagged single strand cDNAs were purified using 8x volume of Agencourt AMPure magnetic-bead (Beckmann Coulter, CA, USA) and used as starting templates for second-strand synthesis. The libraries were enriched by 15 cycles of PCR amplification. During the amplification, different tagged random primers containing short nucleotides signature at the 3 0 -end of the primers (barcodes) were used to assign sequences to the corresponding pool. Finally, amplified adaptor-tagged libraries were further cleaned up by using Agencourt AMPure magnetic bead purification followed by library quantification using KAPA library quantification kit (Kapa Biosystems, MA, USA). The purified products from the three pools were combined in equal concentrations and subjected to sequencing on the MiSeq Illumina platform (Illumina, CA, USA)", "The research protocol was approved by the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University. Since the samples were anonymized and could not be traced back to individual patients, the ethical board determined that the need for informed consent was waived. All clinical investigation was conducted according to the principles expressed in the Declaration of Helsinki." ] },{ "paper_id": "a4cfc3e2cc8c3a69d8a6384aa77b9a9ff7a51dd7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No new human samples were collected as part of this study. Serum samples were de-identified before being used in the research project.", "All titrations were performed by plaque assay on Vero cells as described previously [59] .", "ELISAs were performed using DuoSet ELISA Development kit (R&D systems) following manufacturer's instructions." ] },{ "paper_id": "a4d06a5b2f6f7b1071b36b9ba083e757d0f4ec97", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a4e2f812c3232e60ac1af78fed10d292e28906d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Effective responses to epidemics of infectious diseases hinge not only on early outbreak detection, but also on an ongoing assessment of disease severity. Indeed, the proportion of infected patients who develop severe illness often governs public perception and is a key factor in deciding whether or not to trigger interventions that can cause harm and exact significant social and financial costs." ] },{ "paper_id": "a4e41dcddb7c0eb538defbf19602371176f1f97c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mazumdar et al. [14] CFD simple object model a single inpatient ward tracer gas (sulfur hexafluoride, SF 6 )", "where L r p I;s " ] },{ "paper_id": "a4e72fc5914fe0e8387e5acce1aa3106705f7677", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition to the temperature, we collected information regarding age, gender, aircraft (i.e. place of embarkation), self-reporting (i.e. presence or absence of voluntary reporting of any symptoms) and information of the satellite where the surface temperature was measured by an infrared thermoscanner (i.e. alliances A, B or C). Since air-conditioning greatly influences room temperature variations within the airport, and because the room temperature also varies with arrival gates and satellites (e.g. depending on individual routes of entry), we were not able to measure the room temperature for each subject. History of medications prior to the screening was not collected systematically.", "Third, among the 1,049 screened passengers, we measured the associations of hyperthermia with age, gender, place of embarkation (categorized into six regions of the World Health Organization, but grouping Southeast-Asia and Western Pacific regions into one region owing to their geographic closeness), self-reporting (dichotomous) and satellite of measurement (categorized by three areas as shown in Figure 2 ). Except for the axillary temperature and the surface temperature measured by an infrared thermoscanner, only age was a continuous variable. We employed the Welch test to examine the association between hyperthermia and age. For all the remaining variables, we used Fisher's exact test or the c 2 test.", "The study conformed to the principles of the Helsinki Declaration. Eligible subjects were voluntarily enrolled, and informed consent was obtained before the enrollment. Simplified map of Narita International Airport. The airport has two discrete terminals. A total of four infrared thermoscanners were placed in each terminal. Terminal 2 is mostly used by alliance A, while Terminal 1 is roughly divided into two groups of satellites used by alliances B and C, respectively. The stationary infrared thermoscanners were set up near the quarantine station before immigration. The survey was conducted during the entry screening practice following the guideline of the Japan Pandemic Influenza Plan issued by the Government of Japan [11] . The fever screening, health examination and laboratory testing were conducted according to the Quarantine Act (Articles 12 and 13), and the use of the infrared thermoscanners and examination of axillary temperature adhered to the Health Service Bureau Notice issued by the Tuberculosis and Infectious Disease Control Division of the Ministry of Health, Labour and Welfare of Japan. The analysis of the data and its publication are permitted by Article 27-2 of the Quarantine Act. No names (only ID numbers) were assigned to each study participant and the data were anonymously analyzed." ] },{ "paper_id": "a4ee11dba58a0b0c6566a1fac060b4329bcdc8cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "associated with particular diseases (respiratory syncytial virus and bronchiolitis, parainfluenza virus 3 and laryngitis, rhinovirus and common cold, influenza virus and flu syndrome), there is no evidence for a clinical specificity, and only the virological diagnosis provides an accurate identification of the ARI [4, 5] .", "Virological tests allow for the establishment of accurate diagnosis of infection, assessment of evolving risks (bacterial infection, acute respiratory distress syndrome), and the establishment of measures to limit its spread (isolation, wearing gloves and masks).", "All the tests were two-tailed and their level of significance (p) was defined as p < 0.05. IBM\u00ae-SPSS\u00ae 22.0 for Windows\u00ae was the statistical software used.", "AdV, adenovirus; ARI, acute respiratory infection; CT, cycle threshold; DNA, deoxyribonucleic acid; EC, extraction control; ERV3, human endogenous retrovirus 3; Flu, influenzae virus; HBoV, human bocavirus; HCoV, human coronavirus; hMPV, human metapneumovirus; PCR, polymerase chain reaction; PIV, paraInfluenza virus; RhV/EV, rhino/entero virus; RNA, ribonucleic acid; ROC, receiver operating characteristic; RSV, human respiratory syncytial virus; SARS, severe acute respiratory syndrome; UTM, universal transport medium" ] },{ "paper_id": "a4ee99345c99a1f9806c8d17dc7e6accaf5309d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "liposomes to encapsulate and deliver chemotherapeutic drugs to tumor sites.", "One study found no cardiotoxicity in 40 patients receiving cumulative doses of 500-1500 mg/m 2 of doxorubicin [62] . Free doxorubicin, on the other hand, is limited to a maximum recommended cumulative dose of 450-550 mg/m 2 . Colbern et al. found that the activity of PEGylated liposomal doxorubicin 1-2 mg/kg was almost equivalent to that of free doxorubicin 9 mg/kg in mouse Lewis lung carcinoma [59] .", "organ or tumor [34, 35] . Endothelial cells of blood vessels within solid tumors express certain molecular structures that are absent or minimally detectable in normal blood vessels [13, 36, 37] . These structures can be used as molecular targets for antitumor treatment.", "In addition, we can take advantage of the differences between endothelial cell plasma membrane proteins (i.e., vascular zip codes) to develop drug delivery systems capable of guiding therapeutic or imaging agents to a particular [13, 14, 50] . The reaction was completed and confirmed by quantifying the remaining amino groups using TNBS (Trinitrobenzenesulfonate) reagent [51] . Peptidyl-PEG-DSPE was transferred to preformed liposomes after coincubation at a temperature above the transition temperature of the lipid bilayer [52] . There were 500 peptide molecules per liposome [53] . The mean diameter of the targeting liposome is approximately 75 nm [2, 13] ." ] },{ "paper_id": "a4efe5912760797318110dec69b255d743f0f0bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations BBB: blood-brain barrier; CNS: central nervous system; CXCL: chemokine (CXC motif) ligand; CXCR2: CXC chemokine receptor 2; ELISA: enzyme-linked immunosorbent assay; i.c.v.: intracerebroventricular; IL: interleukin; LPS: lipopolysaccharide; PCR: polymerase chain reaction; TNF-\u03b1: tumor necrosis factor-\u03b1; WT: wild-type; \u03b2 2 -MG: \u03b2 2 -macroglobulin.", "The authors declare that they have no competing interests.", "The data were analyzed using SPSS software (17.0 for Windows, IBM Inc., Chicago, IL, USA). Data shown represent the means \u00b1 standard error of the mean (SEM). Statistical significance was determined using Student's t tests for comparisons between two groups or by oneway ANOVA with Bonferroni correction for multiple groups of treatments. The differences were considered to be significant when P < 0.05." ] },{ "paper_id": "a4f120c79ea75052176f2c3d6a351485862a6ca8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dromedary camels exposed to MERS-CoV showed mild clinical signs but developed exceptionally potent neutralizing antibodies. Camelid species naturally produced heavy chain-only antibodies (HCAbs) [28] , which are dimeric and devoid of light chains, and their antigen recognition region is solely formed by the variable heavy chains (VHHs) (also called nanobodies, Nbs). VHHs or Nbs have long complementarity-determining region 3 (CDR3) loops and are capable of binding to unique epitopes not accessible to conventional antibodies [29] . Notably, camelid VHHs are relatively stable and can be produced with high yields in prokaryotic systems [30] . Because of their small size; good tissue permeability; and cost-effective production, storage, and transportation [31] [32] [33] , VHHs or Nbs have been gaining acceptance as antiviral agents.", "Vaccines are the most important approach against viral infections, but usually take a long time to develop. They are also unable to provide either immediate prophylactic protection or treat ongoing viral infections. Neutralizing monoclonal antibodies (mAbs) have recently emerged as a powerful tool to provide prophylactic and therapeutic protection against emerging viruses [5] . Potent neutralizing mAbs can be achieved by various technologies, such as hybridoma technology, humanized mouse, phage or yeast display, and single B cell isolation [5] .", "Middle East Respiratory Syndrome (MERS) emerged in 2012 in Saudi Arabia with the death of a man with pneumonia; the causative agent was subsequently identified as MERS-CoV, which belonged to lineage C betacoronaviruses [1] . With dromedary camels (Camelus dromedarius, also known as Arabian camel) as direct sources and bats as potential reservoirs [2] , MERS-CoV has been frequently introduced into human populations. Once MERS-CoV is introduced into a person, person-to-person transmission might occur, and is responsible for approximately 40% of MERS cases globally [3] . MERS-CoV has been a consistent threat to humans. As of October 2018, MERS-CoV has caused 2254 laboratory-confirmed human cases, including 800 deaths in 27 countries, with the fatality rate as high as 35% (http://www.who.int/emergencies/mers-cov/en/). Although MERS cases are primarily reported in the Middle East, facilitated by international travelling, MERS-CoV can also be a worldwide threat, which is well illustrated by the MERS outbreak in South Korea in 2015 [4] . Given the potential risk of causing worldwide public health emergencies and the absence of licensed vaccines and antiviral therapeutics, the World Health Organization has listed MERS-CoV in the \"List of Blueprint priority diseases\" (http://www.who.int/blueprint/priority-diseases/en/)." ] },{ "paper_id": "a4f3abb6d4a6463835878af8817389b825347d7b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The effect of left-censoring was accounted for in the multivariate model by including a dummy variable or by excluding the left-censored episodes.", "The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.", "For supplementary material accompanying this paper visit http://dx.doi.org/10.1017/S0950268814001393. ", "Cox proportional hazards models were used to identify factors influencing the rate of loss of virus detection (hereafter referred as the recovery rate).", "In conclusion, this study defines RSV shedding patterns in the natural setting with significant potential for improved understanding of the spread of this important virus and with relevance the design of control programmes." ] },{ "paper_id": "a4f3e08e12cadc025f14c7a3f0d6cf3241e0375c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ". " ] },{ "paper_id": "a4f95bc90ea589d614f0e2a70daf60fbd7d23c31", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflicts of interest." ] },{ "paper_id": "a4fe3ad28d82650b92cbbfe942f2714038e83ba3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clearly, the availability of extra levels above the family rank will facilitate the taxonomy development of other, currently less structured supergroups of ssRNA + viruses of plants and animals, and other classes of viruses, which have highly diverse monophyletic groups, e.g. Reoviridae, Mononegavirales, etc.", "Unlike currently recognized taxa, Baltimore classes were established using purely functional considerations concerning genome type and its expression. Its broad albeit informal use in taxonomy is due to overall (perceived) good agreement between these classes and taxa that are recognized phylogenetically. However, this correspondence is not universal, as, for instance, was demonstrated for the dsRNA Birnaviridae and the ssRNA + Permutotetraviridae, which form an inter-class monophyletic group [9, 30] . There are few other examples of complex relationship between Baltimore classes and phylogenetic groups.", "Handling Editor: Sead Sabanadzovic." ] },{ "paper_id": "a4ffcadecc4b60c30df8f699c480724523272e62", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The commercial plant virucide Ningnanmycin, perhaps the most successful registered anti-plant viral agent, Ribavirin and (R)antofine were used as the controls.", "Inhibition rate (%) = [(av local lesion no. of control 2 av local lesion no. of drug-treated)/av local lesion no. of control] 6 100%.", "Author Contributions" ] },{ "paper_id": "a50c402f6452315b8ee669802c6c96cc993586e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ability to fully interrogate the MBC response established after natural infection to viral antigens will allow researchers to durably and comprehensively interrogate vaccine responses to further understand the differences between natural and vaccine derived immunity.", "All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. ", "Neutralizing antibody responses play a critical role in anti-viral immunity-controlling and preventing infection, and are an important aim of vaccination. During initial infection, na\u00efve host B-cells, specific to the infecting antigen, proliferate and differentiate into short-lived plasmablasts that secrete antibodies at a high rate to combat the existing infection. Following viral clearance, two distinct layers of humoral immunity remain to protect against repeat infection with the same antigen-antibodies in the sera, constitutively produced by long lived plasma cells (LLPCs) and memory B-cells (MBC) primed to expand and secrete antibodies upon antigen re-exposure." ] },{ "paper_id": "a50f2af4833bd314b5664e5f30a6d39792a73f5c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethical approval for this research was granted by the NHS National Research Ethics Service, South East Research Ethics Committee. All data were analyzed anonymously.", "By default, when analysing both wards together, we assume minimal cross-infection between the wards (s~0:0001), though we also consider the opposite extreme (s~1), representing complete ward mixing. We report results here where q ijt is fixed at 0.005, though also describe results of sensitivity analyses with values of 0.001 and 0.025.", "where c is a constant and" ] },{ "paper_id": "a50f3a7514dd9363e42a1eff725a7eb3e49b6ed2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a50f42269649e20ec3580496c72923ef1c4abd6a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In silico analyses were performed using the ExPASy World Wide Web server (http://ca.expasy.org/tools/pi_tool.html) [37] .", "A Q-Exactive (Thermo, Fisher, Bremen, Germany) was operated in data dependent mode for mass spectrometric analysis. For each precursor scan, the top 12 most abundant ions were selected for tandem MS. For MS1 scans, a resolving power of 35000 at m/z 200 was used with an automatic gain control (AGC) of 1,000,000 charges and a max ion injection time (IT) of 10 ms. A resolving power of 17,500 at m/z 200 was set with an AGC of 200,000 charges and a max IT time of 55 ms for MS2 analysis. A 90 s exclusion window was used to avoid repeated selection of abundant ions. For selection of ions, peptide-like isotope distributions were preferred with the exclusion of unassigned and 1 + charge states.", "Aphids were allowed a 48 h acquisition access period (AAP) on leaves detached from BYDV-RPV-infected plants inoculated 4 to 5 weeks previously. Viruliferous aphids were transferred from the virus source leaves to 12 recipient noninfected 'Coast Black' oat plants and allowed a 5 day inoculation access period (IAP). Plants were observed for symptom development for 3 to 5 weeks. Virus transmission efficiency was calculated as the percentage of the total number of plants infested with viruliferous aphids that become infected." ] },{ "paper_id": "a51659a324f74a7cf16acd3b1180d203cab2b8d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following rabbit antibodies were used: Ribosomal Protein S4X Polyclonal Antibody (YT4135), Ribosomal Protein L17 Polyclonal Antibody (YT4098), QM Polyclonal Antibody (YT3916), Histone H3.1 Polyclonal Antibody (YT2163), Laminin \u03b3 -1 Polyclonal Antibody (YT2531), GNL3L Polyclonal Antibody (YT1938), Ribosomal Protein L7 Polyclonal Antibody (YT4118), and \u03b2 -Actin Polyclonal Antibody YT0099). All the rabbit antibodies were purchased from ImmunoWay Biotechnology Company. The Peroxidase AffiniPure goat Anti-Rabbit IgG was used as the secondary antibody (Jackson ImmunoResearch Lab.).", "Additionally, to reduce the complexity of the peptide mixtures, reverse-phase chromatography using a RIGOL L-3000 system was applied for separating the peptides. The labeled peptide mixtures were dissolved in 100 \u03bc L of mobile phase A [2% acetonitrile in ddH 2 O, pH 10] and centrifuged at 14,000 g for 20 min prior to loading onto the column. Samples were eluted by injection of stepwise gradients of mobile phase B [2% ddH 2 O in acetonitrile, pH 10], with a flow rate set at 700 \u03bc L/min. Each fraction was eluted for 1.5 min. Analysis by Q-Exactive mass spectrometry. The fractionated peptide mixtures were analysed by a Q-Exactive mass spectrometer equipped with an EASY-nLC 1000 System (Thermo Fisher Scientific). The spray voltage, capillary temperature, and declustering potential of the source ionisation parameters were set as 2.1 kV, 250 \u00b0C, and 100 V, respectively." ] },{ "paper_id": "a51a3f793ea6a59523eff2c0fe6555b729840084", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Infectious diseases have been emerging and reemerging over millennia [1] .", "NDV-vectored vaccines have been evaluated in several animal species (i.e., chicken, cattle, sheep, cat, mouse, pig, and dog) for veterinary use [35] (Table 2) . NDV is a natural vaccine vector for poultry pathogens. Live attenuated NDV vaccines are widely used all over the world. Therefore, an NDV vector carrying the protective antigen of another avian pathogen can be used as a bivalent vaccine. Such a vaccine will be economical for poultry farmers.", "Canine distemper virus (CDV), a morbillivirus, infects many carnivores and cause several high-mortality disease outbreaks [37] . The current CDV live vaccine cannot be safely used in some exotic species, such as mink and ferret. NDV strain LaSota expressing envelope glycoproteins, hemagglutinin (H, rLa-CDVH) and fusion protein (F, rLa-CDVF), were generated as vaccine candidates. In immunized minks, rLa-CDVH induced higher titers of neutralization antibodies against CDV than rLa-CDVF neutralizing antibodies. Further, rLa-CDVH provided complete protection against virulent CDV challenge during the four weeks of observation. In contrast, all animals immunized with rLa-CDVF developed clinical signs of distemper and virus shedding. This study suggested that recombinant NDV expressing the H protein of CDV is a safe and efficient candidate vaccine against CDV in mink. The efficacy of rLa-CDVH virus also needs to be evaluated in other host carnivore species." ] },{ "paper_id": "a523dca1cc7a585e2433acb959f3d396f35b9c79", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A cross-sectional survey was conducted to investigate rearing and biosecurity practices, and flock health history. A draft questionnaire was designed and pretested at thirteen farms. This draft was modified based on the results obtained from the pretest. The translated questionnaire is provided in the supporting information (Text S1).", "Flock health history data were acquired to design a casecontrol study. Univariate analysis was conducted to test for associations between presence of disease mortality and health history by using \u03c7 2 tests for categorical variables. To examine the independence of explanatory variables, multivariate logistic regression analysis was performed. Variables from univariate analyses with P values < 0.10 were included in the multivariate regression. The final model of potential risk factors was constructed by stepwise backward selection applying the iterative maximum-likelihood estimation procedure. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were ", "A total of 62 villages in Poyang Lake area were included in this study. Three hundred and nine backyard poultry owners completed their questionnaires." ] },{ "paper_id": "a5243628f77d40d5861c26212a3cc3102d9b2449", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total nucleic acids were extracted from archived NPA using a NucliSENS easyMAG platform (bioMerieux), and eluted in a final volume of 60 ml of elution buffer [25] . RNA was reverse transcribed with High Capacity cDNA Reverse Transcriptase (Invitrogen, Life Technologies) and primed with oligo-dT primers (Invitrogen, Life Technologies). Real-time PCR was done in an ABI 7500 RT-PCR system (Applied Biosystems, Life Technologies), reactions were performed in 20 ml using TaqMan Universal PCR Master Mix (Applied Biosystems, Life Technologies) and the primers and probes listed in Table S1 ." ] },{ "paper_id": "a52566f6d96ec5a9a371582766a992a4ac38bd64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In total, we secured simultaneous data on four male cheetah dyads ranging from 113 to 329 days per dyad. One individual (M01) was part of three of the four dyads, two individuals (M02 and M03) were part of two dyads and one individual (M04) was part of one dyad ( Table 2 ).", "Aggressive interactions with fatal consequences are not uncommon in cheetahs. Caro [22] reported three cases in Serengeti where singletons were killed by coalitions (all three-male coalitions). Similarly, Mills and Mills [27] found that 50% of male-male encounters recorded in the Kgalagadi Transfrontier Park in Botswana/South Africa resulted in death. To our knowledge, fatal interactions have not been observed between female cheetahs. This could explain why male mortality is higher and life expectancy lower for males compared to females [51, 52] resulting in a female biased sex ratio [52] . For some species, such as voles (Microtus oeconomus), lions and grizzly bear (Ursus arctos), the removal of males, through either displacement or mortality, has a negative effect on population growth as a result of increased infanticide [53] [54] [55] . Infanticide has however not been observed amongst cheetahs [56] possibly because it rarely occurs in predominantly solitary species [57] . The removal of males could however have other population-level consequences [58] but the impact of male mortality on population dynamics in cheetahs is unclear.", "Static and dynamic interactions can play a role in disease transmission [3, 4] . In the Mara-Serengeti ecosystem there is a relatively high prevalence of mange [59, 60] and in Southern Africa cheetahs have been positively tested for feline coronavirus (FCoV) and feline panleukopenia virus (FPV), which can be highly contagious and fatal [61, 62] . Pathogens such as these can easily spread through faeces and other bodily fluids, which are deposited and investigated by male cheetahs at marking posts. This could explain why in 2015 several males in the Maasai Mara, who overlapped spatially, died of a yet unknown disease within a short space of time [63] . We suggest that future epidemiological research should investigate the role of scent marking posts and movement in disease transmission [64] ." ] },{ "paper_id": "a5293bb4f17ad25a72133cdd9eee8748dd6a4b8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a52fd1386e8a463e46bde0e66125bfd826a64f56", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The management of critically ill EVD patients in a resource-constrained setting has historically been restricted to variable monitoring of daily clinical signs and symptoms without access to continuous assessment [8] .", "CRRT continuous renal replacement therapy; F female, IHD intermittent hemodialysis, LOS length of stay, M male, MV invasive mechanical ventilation, N/A not available, NIV non-invasive ventilation, TKM TKM-Ebola, small interfering ribonucleic acids (siRNA) produced by Tekmira", "While acute kidney injury can often be explained by under-resuscitated hypovolemia, it might also arise from viral or secondary bacterial sepsis, acute tubular necrosis, myoglobinuria, and microvascular renal thrombi associated with sepsis or disseminated intravascular coagulation [29, 30] . Adrenal gland viral infection has been shown in animal models and might contribute to hypotension, renal sodium loss, and hypovolemia [30] ." ] },{ "paper_id": "a533da998e4132f8192e41a197f5d8cd065df996", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a5360f18c21cf7f9a04e9b21663301b4548eadd9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "doi:10.1371/journal.pone.0135288.g006 siRNAs were effective against HIV-1 replication in PBMCs, although the protection was transient. However, when siRNAs targeting CCR5 and tat were expressed through lentiviral vectors, primary macrophages could be protected against HIV-1 infection in culture for longer periods [38] .", "Preclinical safety and efficacy testing of microbicide candidates involves a large number of in vitro, ex vivo, and in vivo assays and models. Here we demonstrated that chitosan-based nanoparticles showed no significant toxicity in rhesus monkeys, which is consistent with other modified chitosan nanoparticles for siRNA delivery [55, 56] . Thus, the siRNA-based chlipid microbicides described in this study were subjected to a very cautious and rigorous preclinical evaluation to assess their efficacy in models used for microbicide development.", "Water-soluble chitosan (1 mg/ml) was mixed with Lipofectamine 2000 (Invitrogen) in the ratio of 2:1 (2 \u03bcg of chitosan to 1 \u03bcg of Lipofectamine in a total volume of 20 \u03bcl) and vortexed for 15 min at room temperature. Later these chlipid nanocomplexes were mixed with the respective DNA (1 \u03bcg each or total psiRNAs) for in vitro studies. The mixtures containing CNs with DNA or psiRNAs were vortexed for 30 min at room temperature before administration." ] },{ "paper_id": "a53b809c3b22d019046ee761e05c464bd629079a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After inoculation for 24 h, mock-infected IECs and IECs infected with PEDV, at multiplicity of infection (MOI) of 0.1 were fixed with 4% paraformaldehyde at room temperature (20 \u2022 C-25 \u2022 C) for 15 min, permeabilized with 0.2% Triton X-100 in PBS at room temperature (RT) for 10 min, and blocked with 0.3% bovine serum albumin in PBS at 37 \u2022 C for 30 min. Next, mouse anti-PEDV S protein monoclonal antibody (developed in our laboratory) and fluorescein isothiocyanate (FITC)-conjugated goat anti-mouse immunoglobulin G (IgG) (ZSGB-BIO, Beijing, China) were incubated as first and second antibodies, respectively, followed by counterstaining with 4,6-diamidino-2-phenylindole (DAPI, Beyotime, Shanghai, China). The coverslips were mounted on microscope glass slides in mounting buffer and cell staining was examined using a fluorescence microscope (Leica, Wetzlar, Germany)." ] },{ "paper_id": "a53cae6e96975f86052ebaee23f1b83f8b90d175", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results: Among the lead transcripts identified were genes encoding for proteolytic enzymes including an A. ceylanicum APR-1, but the most common proteases were cysteine-, serine-, and metallo-proteases. Also in abundance were specific transporters of key breakdown metabolites, including amino acids, glucose, lipids, ions and water; detoxifying and heme-binding glutathione S-transferases; a family of cysteine-rich/antigen 5/pathogenesis-related 1 proteins (CAP) previously found in high abundance in parasitic nematodes; C-type lectins; and heat shock proteins. These candidates will be ranked for downstream antigen target selection based on key criteria including abundance, uniqueness in the parasite versus the vertebrate host, as well as solubility and yield of expression.", "We further explored various subcategories within the main gene ontologies and weighted those using FPKM values. Those protein categories with the highest expression levels in the intestine are analyzed below." ] },{ "paper_id": "a541d630fd5736ce515214386cf9642b1e3d02e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Brucellosis is a zoonotic granulomatous disease that can affect any organ. It is caused by Brucella species which are small, Gram-negative, and coccobacilli bacteria. Clinical presentation varies from an acute, nonspecific febrile illness to chronic, debilitating forms with features of osteoarticular and neuropsychiatric abnormalities [1] .", "The system is one of few classical virulence factors identified to date [33] . The type IV secretion system is a pumping system that selectively transports proteins or other macromolecules through membranes [34] . After Brucella is taken up by vesicles in macrophage, acidification is thought to induce VirB expression. The VirB system interacts with components of the endoplasmic reticulum, neutralising the pH and allowing the Brucella to undergo regulated cell division [34] . Other classics that further The oldest citation classic article was published in 1950 and was at position 29. It was by Harris who described the side effects associated with the use of aureomycin and chloramphenicol in treatment of brucellosis. Prior to the development of these treatments, chemotherapy of brucellosis yielded unsatisfactory results [37] .", "The authors declare that they have no conflicts of interest." ] },{ "paper_id": "a55fe997f40a68ed1e3169a8e6d8c5df4c91e34e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Retrospective study. From January 2001 to April 2010, we recruited 8696 pregnant women including 8258", "Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 1212 |" ] },{ "paper_id": "a562830d55b0d773e1e687e569bf2f5af6e55f0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Differences in the concordance rates of results for multipleinfection samples and single-infection samples were \u03c7 2 -tested. A p-value <0.05 was considered statistically significant.", "The study was performed in accordance with the recommendations of national ethics regulations and approved by the Institutional Review Board of the Institute of Pathogen Biology. All participants provided written informed consent in accordance with the Declaration of Helsinki. For children, written informed consent was obtained from parents or guardians.", "For CAP cases, multiple types of specimens should be used for microbial diagnosis (Johansson et al., 2010) . A positive result from blood or pleural fluid (e.g., for meningitis, cerebrospinal fluid) samples by molecular test is of great value for pathogen identification. However, some substances present in blood, body fluids, and sputum may affect polymerase activity and inhibit amplification (Burd, 2010) . Because of this, in the next stage of evaluation, various specimen types will be included." ] },{ "paper_id": "a56b804d0fb9dfe5c6e194c8a4e5b68d0c040adb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pneumonia was caused by bacteria, atypical bacteria and viruses in 75 (51.0%), 20 (13.6%) and 52 (35.4%) subjects, respectively.", "All data have been added to this manuscript and the Supplementary Material section." ] },{ "paper_id": "a56bc2a490d1558f0fceb37fe4375874dea4453c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The complete genome of the isolate HKD/JPN/2016 has been deposited in GenBank under the accession no. LC260045.", "In 2016, an outbreak of diarrhea with high mortality in piglets occurred on a swine farm in Hokkaido prefecture, Japan. The causative porcine deltacoronavirus HDK/JPN/2016 was isolated from intestinal samples of the dead piglets on LLC-PK1 cells. The complete genome of HKD/JPN/2016 was sequenced and analyzed by next-generation sequencing technology.", "RNA from the HKD/JPN/2016 isolate was reverse transcribed and PCR amplified by using originally designed primer sets against the PDCoV genome. The amplified genomes were sequenced using next-generation sequencing technology on an Ion PGM platform (Thermo Fisher Scientific, Carlsbad, CA, USA) according to the manufacturer's instructions. The data were assembled using Torrent Suite version 5.0 based on known complete genomes of PDCoV strains obtained in the United States, South Korea, China, Hong Kong, Thailand, and Laos (4-12)." ] },{ "paper_id": "a56fc47514bbcbeeab571a5d5cf6ae87dcab2a1e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The experimental animals were not anesthetized or euthanized in order to conduct this study [4] .", "Cattle genomes have an abundance of structural, repeat and indel variation [31, 32] . We expect that improvements in the reference genome assembly will soon lead to substantial benefits for variant calling and the physical ordering of loci within haplotypes. Assemblies created using long read technologies, chromatin capture and optical maps possess great improvements in contiguity [33] . As the cost of sequencing continues to decrease, genotyping will be enabled by long read or synthetic long read technologies which can detect structural variation, directly phase haplotypes, and also enable individual-specific sequence assembly [34] ." ] },{ "paper_id": "a5701c6fbac36d0fcac9dc32cd78288f3f27f24b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by the Ethics Committee of Niigata Graduate School of Medical and Dental Sciences. Informed written consent was obtained from all subjects." ] },{ "paper_id": "a57080f174e3ede5138af08070a2b9db8f9c36a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A549 cells (ATCC CCL-185) were cultured in Ham's F-12 Nutrient Mixture with GlutaMAX (F12; Gibco), supplemented with 10% (vol/ vol) FBS (Gibco). SFV_Zs-Green (a kind gift of Giuseppe Balistreri, University of Helsinki, described in reference 88) was expanded and titrated by plaque assay on BHK-21 cells (89) . Zika virus (ZIKV) was expanded and titrated by immunofocus assay on Vero cells. Influenza A/WSN/33 virus (IAV) (H1N1) was grown in eggs and titrated by plaque assay on MDCK cells.", "As our initial observations suggested mbIFITM3 P70W may be preferentially associated with Golgi compartments (Fig 4A) , we colabelled fixed and permeabilized cells with anti-HA mAb (to detect the HA-tagged IFITM3 protein) and markers of intracellular organelles.", "Supplementary Information is available at https://doi.org/10.26508/lsa. 201900542." ] },{ "paper_id": "a576b341e354b09d299d85220586219f18a9bef2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The disorder tendency and the secondary structure of hRID and mutant hRIDs were predicted using IUPred [44, 45] and GOR IV [46] , respectively.", "In addition to their conserved role in translation, some ARSs including LysRS have additional domains with unique structural characteristics that are neither part of the enzymatic core nor present in bacterial homologs [1, 7] . The newly evolved domains are not essential for tRNA charging, but rather are responsible for the non-canonical, moonlighting activities unrelated to aminoacylation [26] . Nevertheless, defects in either canonical or non-canonical ARS functions are associated with human diseases [27] .", "The pGE-hRID3 vector was constructed from the pGE-LysRS vector [15] . The pGE-LysRS and the PCR products of hRID were cleaved with NdeI/HindIII, and the PCR product was inserted into the cleaved pGE vector. Expression vectors for mutant hRID were constructed using the Dokdo\u2122 Site-Specific Mutagenesis Kit in accordance with the manufacturer's instructions (Elpis-biotech, Daejeon, South Korea; Cat. No. EBT-5001). To ensure high protein expression, 5 -proximal sequences of eLysRS (ATGTCTGAACAACACGCACAG-, corresponding to the amino acid sequence, MSEQHAQ) were added at the 5 -ends of all hRID genes as a translational enhancer [15, 43] .", "The hRID that had been purified by Ni-affinity chromatography was dialyzed against 10 mM phosphate (pH 7.5). Then, 8.8 \u00b5M hRID was mixed with or without 50 mM P100 polyphosphate (polyP) (Kerafast, Boston, MA, USA; Cat. No. EUI005), and the CD spectra of the hRID-polyP mixtures were recorded using 1-mm cells. For CD measurements, a Jasco 700 CD spectrophotometer was used under 10 psi nitrogen conditions with a step resolution of 1 nm and a scan speed of 50 nm/min. Here, 10 mM phosphate was used as a baseline, and all spectra were scanned three times and smoothed using Spectra Manager (Jasco, Easton, MD, USA)." ] },{ "paper_id": "a58c4de6acdb5e333840e07494c95b0e81b6e52e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The fly sampling was carried out in four wildlife reserves in Gabon (Figure 1a ", "Mammals Artiodactyla Table 4 continued on next page", "Unknown_host_819 KY631984 DOI: 10.7554/eLife.22069.008" ] },{ "paper_id": "a58e071a01535515949fdc00e6942e2e5ada7ad7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The procedures to determine the presence of a viral envelope by chloroform/ether treatment, type of nucleic acid employing 5-iodo-2-deoxyuridine (IUDR), acid stability (pH 3.0) and heat stability (MgCl 2 ) and size employing membranes of graded porosity are described elsewhere [10] ." ] },{ "paper_id": "a58e2554025589270e688199f55c97c719fe874d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a599eb2c6ca51522fa234d8059f989569f4fe298", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Similar to most polyomaviruses, JC encodes for early proteins, which constitute the small and large T antigens and their many splice variants, which engage with many host processes to ensure a cellular milieu is available that is conducive to virus replication. In addition to this, three late structural proteins are expressed. These include the major capsid protein, VP1, and the VP2/VP3 minor capsid proteins [33] . JC encodes for an additional late protein termed agnoprotein [44] . Agnoprotein is only expressed by a limited number of polyomaviruses including the related BK and SV40.", "The Papillomaviridae contains an extensive array of different papillomavirus (PV) types capable of infecting a variety of animal species, of which at least 170 have currently been isolated from humans [65] . Like Polyomavirus, they are small, non-enveloped double stranded DNA viruses around 55 nm in diameter [66] . Most PV encode six early (E1, E2, E4, E5, E6 and E7) and two late structural genes (L1 and L2). Approximately 12 HPV types, termed high-risk, are the causative agents of several ano-genital and oral malignancies [67] . Of these, HPV16 and HPV18 are the most important and are responsible for approximately 70% of the cervical cancer cases, and for the deaths of approximately 270,000 women in 2012 alone [66] . Low risk HPV are usually cleared by the body and vaccines are available for prophylactic treatment of high risk HPV, but there is as of yet no therapeutics for existing cases of HPV infection.", "The Polyomaviridae are small, non-enveloped, double-stranded DNA viruses that infect a wide range of species [33] . The family was named after the founding member, polyomavirus, which caused \"many tumors\" in mice [34] , followed by the prototypic primate polyomavirus, Simian Vacuolating agent 40 (SV40), from the rhesus monkey [35] . The first two human polyomaviruses discovered in 1971, JC and BK, were named after the index cases, and cause serious disease in the immunocompromised [36] . The last decade has seen the discovery of several novel human polyomaviruses, including Merkel cell polyomavirus, which causes an aggressive skin cancer [37, 38] . These discoveries have led to resurgence in interest in polyomavirus biology and to the roles of virus encoded proteins in pathogenesis. In this regard, two members of the family have recently been shown to encode proteins with viroporin characteristics.", "Modulation of ionic homeostasis within specific cellular compartments allows for viroporins to manipulate a wide range of cellular processes from autophagy [13] [14] [15] , trafficking [16, 17] , inflammation [18, 19] , transformation [3] to cell survival [20] . Due to these broad perturbations to host cell physiology, it is not surprising that viroporin function has been shown to assist in all stages of the virus life cycle including entry, membrane penetration, genome replication and virus egress [1, 2] ." ] },{ "paper_id": "a59fdbfef640d08b4729060ee005ff35f87c0a40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The primary endpoints were:", "( [25] .", "Not applicable." ] },{ "paper_id": "a5a3e3edfad63f20fc48ba5885fb9cc863411d2e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "The " ] },{ "paper_id": "a5add18a3b3f98e15c3afcc6186642140033d975", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a5b3f4df4b5b773e35f56703b5a653559e82b139", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Second, by the nature of a near elimination context our sample size is very small. The methods we use for estimating R c are well suited to small, well observed infection cascades, however this small sample size does provide a limitation for mapping, meaning our maps have relatively high levels of uncertainty outside of the areas of El Salvador where cases are seen principally around the pacific coast, Guatemalan border and in San Salvador. There is scope to incorporate expert knowledge to refine the map in areas where data are lacking.", "Here we aim to estimate individual reproduction numbers over time and space by adapting methods from the study of information diffusion processes. These methods address the general problem of reconstructing information transmission using known or inferred times of infection by a 'contagion' [33] [34] [35] [36] . They provide an adaptable framework to integrate multiple data types 37 , identify likely unobserved cases/external infection sources, and have been evaluated using real and simulated transmission processes at multiple scales and network structures 36 .", "Our data input consisted of a time series of symptom (fever) onset t 2 t 1 ;" ] },{ "paper_id": "a5bedf3a8d33e6b501c2203982eaaa5567011d86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Members of the Pestivirus genus, within the Flaviviridae family, account for a variety of diseases in farm animals, the most economically important of which are bovine viral diarrhoea virus (BVDV) and classical swine fever virus (CSFV). Classical swine fever virus (CSFV) is the etiological agent of a highly contagious viral disease of swine affecting domestic pigs and wild boars [1] , which has caused major losses in stock farming [2, 3] . CSFV is composed of a lipid envelope, a capsid and a single plus-strand RNA genome carrying a single, large open reading frame (ORF) flanked by two untranslated regions (UTRs). The ORF encodes a polyprotein of approximately 3900 amino acids, which are processed by cellular and viral proteases in the four structural proteins-C, E rns , E1, E2-and in the 8 non-structural proteins-N pro , P7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B [4] .", "PK-15 cells (ATCC CCL 33) and SK6 cells [26] were cultured in Dulbecco's Modified Eagle Medium (DMEM), supplemented with 10% foetal bovine serum (FBS), Pestivirus-free, at 37\u00b0C in 5% CO 2 . The cells were infected with 0.1 TCID 50 /cell in 2% FBS, and the virus was harvested 48 h later. Additionally, ST cells (ATCC CRL 1746) were cultured in DMEM, supplemented with L-glutamine (2%) and 10% foetal bovine serum (FBS), Pestivirus-free at 37\u00b0C in 5% CO 2. Peroxidase-linked assay (PLA) [27] was used for viral titration following the statistical methods described by Reed and Muench [28] .", "Previous reports have suggested that the availability of mammalian models for SIE in vivo is hampered by the interferon response generated against the infecting virus in these species [11, 24] . It is noteworthy that CSFV postnatally persistently infected swine have shown an immunosuppression state comprising a reduction in interferon responses (Types I and II) [5] [6] [7] . This immunological status might promote the maintenance of a high and constant CSFV load, as already described, preventing second viral entry [5] . Nevertheless, further studies would be needed to clarify the molecular mechanisms involved in this phenomenon." ] },{ "paper_id": "a5bfd762a4fb6bdef664818c4e82ca3c718c8862", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest. Western Reserve strain X-Gal 5-bromo-4-chloro-3-indolyl beta-D-galactopyranoside X-Gluc 5-bromo-4-chloro-3-indolyl beta-D-glucuronide YFP yellow fluorescent protein.", "Author Contributions: Sara Baldanta wrote the paper and created the figures, Saly al Ali and the rest of the authors also wrote the paper.", "VACV can replicate in different cell lines, primary cell cultures, and also grows in several animal species, such as mice, guinea pigs, rabbits, etc. [10] . This broad host range allows infection of cell lines with recombinant viruses for large-scale expression of heterologous proteins, which reduces its cost " ] },{ "paper_id": "a5cd1a73534959eff5332bcd3e5bc012f38c9137", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Neuroblastoma is a heterogeneous embryonal tumor [10, 11] that is accountable for 15% of deaths caused by malignant conditions in children [12] . The disease is associated with an exceptionally low median age of presentation of 17 months [13] and is often diagnosed in utero. Metastatic neuroblastoma has two biologically divergent subtypes. Stage 4S is characterized by an age of presentation between in utero and 18 months, metastases confined to liver, skin, lymph nodes and bone marrow, and its ability to regress spontaneously [14, 15] . In contrast, stage 4 tumors are presented at any age, demonstrate high infiltration rates in bone marrow and bone, and are most often progressive [10, 16] . While genes related to neuronal differentiation have been described to be upregulated in stage 4S in comparison to stage 4 neuroblastoma, thereby indicating distinct levels of neuronal differentiation [17] , little is currently known about the differences between molecular etiologies of stage 4 and stage 4S neuroblastoma.", "Sample panels containing neuroblastoma transcriptomes sequenced at 2|36 bp and 2|95 bp effective read lengths are denoted as NB1 and NB2, respectively. While the NB1 panel contains seven transcriptomes of neuroblastoma stages 4 and 4S each, the NB2 panel contains one sample of stages 4 and 4S each (see Table 1 ). Positive control panels of human cancer transcriptomes with known viral cofactors (BCL, HeLa, ceSCC, and HCC) are denoted as POS. The negative control panel consisting of a normal human brain transcriptome is denoted as NEG.", "processing. Quality of all neuroblastoma samples and related deep sequencing data was additionally confirmed by an orthogonal computational analysis focusing on human gene expression in the context of differential splicing [51] .", "Consensus sequences can be further processed by phylogenetic analyses. For generating phylogenies, Virana employs the software PhyML [64] following the maximum likelihood approach and using default parameters recommended by the HIV sequence database (http://hiv.lanl.gov, GTR model of nucleotide substitution, transition/transversion ratio: 4, gamma shape parameter: 1, number of substation rate categories: 4, approximate Likelihood Ratio Test (aLRT) using SH-like supports where applicable). We note that the topology of the phylogenetic trees constructed in this manner is stable with regard to the model choice; while more complex model parameters may yield better likelihoods in some instances, these differences do not influence interpretation of our results." ] },{ "paper_id": "a5d44eaf14b7ed5402af3501540147d36b314824", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 The door opens 90 degrees (3 s followed by 0.5 s wait).", "\u2022 The door closes (5.4 s).", "\u2022 The stem hits the side wall and continues along it." ] },{ "paper_id": "a5df67ac88dab77c50c138cec2944814000c859f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After adjusting for independent variables listed in Table 1 " ] },{ "paper_id": "a5e0a0ed5bd96d5d8bda79b3b77b68ade21eaee0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study is an important contribution to our scientific knowledge of RSV-induced illness because it provides candidates for future genetic analysis, haplotype determination, and functional studies to further define the contributing factors that are responsible for severe disease. In addition, the data reveal that genetic susceptibility to RSV bronchiolitis is a very complex trait with host response genes being strong contribution factors.", "SNPs were also discovered that were associated with severe RSV disease at the allele level [48] . Based on the function of the gene products, the investigators divided the SNPs into four subgroups: innate immunity (IFNA13, IL15, STAT1, and TLR8), chemotaxis (CCL8, ITGB2, and VCAM), adaptive immunity (CD28 and STAT1), and allergic asthma (MS3A2, ADAM33, IL4R, and IL9R). Those SNPs that had an association with RSV at the genotype level only were present in genes involved in innate immunity (TNF and NCF2) and adaptive immunity (IL10, IL4R, and IL17).", "PCR: polymerase chain reaction; RSV: respiratory syncytial virus; TLR: toll like receptor; TNF: tumor necrosis factor; IL: interleukin; SNP: single nucleotide polymorphism; VDR: vitamin D receptor; IFN: interferon, NOS2A: nitric oxide synthase; FEV1: forced expiratory volume in 1 second; PEF: peak expiratory flow; RV: rhinovirus." ] },{ "paper_id": "a5f1fd1f2782b89068dd76bde0acbffc35632895", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that they have no competing interests." ] },{ "paper_id": "a5f3efe99c8dbe988fef58595e7d6d502109a190", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Objectives of NHSII", "The following are available online at http://www.mdpi.com/1660-4601/16/7/1273/s1, Table S1 : List of keywords, terms, and text strings used for data searching. ", "(2) non-personal information; and (3) shared information. The shared information refers to information that is voluntarily shared on the platforms by users freely and instantly, thus providing a valuable perspective and opportunity to gather public opinions on healthcare services." ] },{ "paper_id": "a5fdb40f1b5bddf4ab24efaddedc40d441e3a130", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human host and pathogenic NTM relationship is still poorly understood, as NTM virulence is highly variable from one species to another. NTM lung disease is strongly associated with pre-existing pulmonary conditions such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, idiopathic bronchiectasis, prior active tuberculosis or pneumoconiosis [6] . It is also frequently associated with genetic or acquired systemic immune deficiency such as defects in the pathways of inflammatory cytokines interleukin (IL)-12, tumor necrosis factor (TNF)-\u03b1 or interferon (IFN)-\u03b3, immunosuppressive treatments (including anti-TNF-\u03b1 therapy or corticosteroids), solid-organ transplantation, or acquired immune deficiency syndrome (AIDS)/human immunodeficiency virus (HIV) infection [1] [2] [3] [4] [5] [6] [7] . However, it may also occur in individuals without recognized severe immune local or systemic deficiency. In the absence of patent predisposition, NTM diseases are overrepresented among the specific morphotype of slender women with a low body fat [8] .", "Descriptive data were used to estimate the frequencies of the study variables. There were expressed as count (percentage, %) for dichotomous variables and as medians (interquartile range [IQR]) for continuous values. The number of missing values was excluded from the denominator. Non-parametric statistical methods Fisher exact test, \u03c72 test and Mann-Whitney U test were used to compare groups, where appropriate. The probability of treatment initiation over time was evaluated by Kaplan-Meier survival curve analysis, with group comparison using the log-rank (Mantel-Cox) test. Stepwise binary logistic regression analysis was used to assess the determinants for treatment initiation, expressed as odd ratios (OR) with 95% confidence intervals (95% CI). After checking the variables for interactions, variables with medical meaning and with p-values obtained in the univariate analysis of < 0.15 were included in the final multivariate model. A value of p < 0.05 was considered significant. All analyses were performed using SPSS software version 24.0 (SPSS. Chicago. IL).", "An independent expert chest radiologist, blinded to the patient information, retrospectively reviewed the CT-scans performed without injection of intravenous contrast media, assigned in random order at diagnosis and six to 24 months after treatment or during the follow up of the untreated patients. The number and size of cavity(ies) and their wall thickness were evaluated in the lung window setting. Nodular opacity(ies) (\u2265 10 mm), cluster(s) of small nodules (\u2264 5 mm), the tree-in-bud pattern, the presence of bronchiectasis in any of the lobes or multifocal bronchiectasis were evaluated. Based on the number and size of the lesions, the expert classified the lesions as improved, stable or worsening." ] },{ "paper_id": "a600310d78ebe675d0d7bc5d9188a77d73e0e79a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were expressed as mean \u00b1 SEM. All samples were paired and differences between groups were analyzed by paired Student t test or the non-parametric equivalents using the Instat software (GraphPad Software, Inc. San Diego, CA, USA).", "Blood mononuclear cells were isolated from whole blood by centrifugation, using Ficoll-Hypaque gradients (Phar-macia Biotech, Uppsala, Sweden), washed, and labeled with immunomagnetic antibodies. Positive selection was performed according to manufacturer's specification (Miltenyi Biotec, Bergisch Gladbach, Germany) as in previous experiments [8] . Isolated CD14+ monocytes from the positive fraction were resuspended in RPMI 1640, supplemented with 50 IU/ml penicillin and 50 \u03bcg/ml streptomycin and 10% fetal bovine serum (Invitrogen, Grand Island, USA). Cell viability, as measured by trypan blue exclusion, was more than 95%. The purity of the isolated cells as measured by flow cytometry was consistantly between 90% to 95%." ] },{ "paper_id": "a6156979e95c44541bc7fe236a1285161b77794a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Raw data will be made available upon request. Authors also agree to share reagents used in this manuscript.", "Published: xx xx xxxx opeN www.nature.com/scientificreports/" ] },{ "paper_id": "a6176cded64c46ece2d4cef65ffdf638f4adceba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a62150169f3f45fa30e13124ba0ff6c1945f5c0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.ppat.1007284.g001", "Total RNA extraction was performed using the GTC extraction method [102] . Purified RNA (10-500 ng) was subjected to RT-qPCR using random hexamers and a Reverse Transcription Kit (Applied Biosystems). Quantitative PCR was performed using 2X Reaction Buffer from (Applied Biosystems) and specific oligonucleotides as previously described [99, 103] . Standard curves were prepared by serial dilution of a known copy number of the corresponding amplicon cloned in a plasmid vector." ] },{ "paper_id": "a62951116b1815c48334c0caae599e4d4f06e58f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CPE inhibition assay was performed to determine whether the extracts prevented viral replication by affecting one or more steps of their replication when viruses were already in the cells.", "In the present study we described in vitro cytotoxic and anti-RV properties of crude extracts of the A. kellalensis collected from Chaharmahal va Bakhtiari." ] },{ "paper_id": "a62bab2887ddd15979d7ef71e48ea7ae3596adf6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We thank the Laboratory of Molecular Technology of SAIC-Frederick, Inc., for providing Roche 454 sequencing service. We thank Tina Ju for critically reading the manuscript. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, the Intramural AIDS Targeted Antiviral Program (IATAP) of the NIH and by Federal funds from the NIH, National Cancer Institute, under Contract Nos. NO1-CO-12400 and HHSN261200800001E. The www.frontiersin.org", "Similarly, the maturation pathway of the potent V1V2-directed HIV-neutralizing antibody, CAP256-VRC26, has been described, in which a germline-like intermediate with a 35-amino acid residue long CDRH3 was shown to bind and neutralize the superinfecting virus weakly, but did not bind or neutralize heterologous viruses (30) . These results suggest that the CAP256-VRC26 lineage could be initiated by using a rare superinfecting-virus-like V1V2 Env.", "DNA isolation, amplification, and 454 sequencing of the human cord blood IgM library were previously described in detail (18, 19) . For quality control, we trimmed the 454 sequence reads and retained only sequences with lengths of more than 300 nucleotides, covering the entire antibody variable domains consisting of all three complementarity determining regions (CDRs) along with framework regions (FRs). We used IMGT/HighV-QUEST for immunogenetic and statistical analyses (20) . The output results from the IMGT/HighV-QUEST analysis were stored in a local PostgreSQL database, and structured query language (SQL) was used to retrieve the data for further analysis. Statistical calculations were carried out using JMP10\u00ae statistical software (SAS Institute, Cary, NC, USA)." ] },{ "paper_id": "a636cda3a52177d0c79927f54079b476b04b85b3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2018, 10, 600 2 of 17 RNA secondary structure or protein sequence. However, the large population sizes produced during the rapid population growth of RNA viruses are believed to result in an overall effective strategy for swift adaptation to changeable environments [14] .", "In fact, recent research has clearly demonstrated that the high fidelity G64S PV mutant has a significant growth defect [54] .", "Funding: Research reported in this publication was supported by NIAID of the National Institutes of Health under award numbers R01-AI095753-01A1 and R01-AI125902-01. TFK was supported by a predoctoral fellowship from the UTMB McLaughlin endowment as well as a predoctoral fellowship from the NIH/NIAID Emerging and Tropical Infectious Diseases Training Program (T32 AI007526)." ] },{ "paper_id": "a63d851872c31a91cf814a84fc2af7f4fb15ce3d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thus modifying the original screen data with additional correction factors by those proposed mathematical treatment may lead to more man-made artifacts.", "MAD \u00bc 1:4826 \u00c2 median x ij \u2212median x \u00f0 \u00de \u00c0 \u00c1 ;" ] },{ "paper_id": "a63e10c460821fd20aa9f58b6d7f4634b05b16ce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ", (e) 259 children (median age, 1.6 years) who had been hospitalized for acute expiratory wheezing", "The authors declare that they have no competing interests.", "Authors' contributions MD, FC, MC wrote the manuscript. ERC organized the table. All authors read and approved the final manuscript. ", "Nevertheless, despite the availability of novel diagnostic assays, data are still controversial regarding the role of coinfection in a more severe clinical outcome in comparison to single infections." ] },{ "paper_id": "a63e670d74fe754980355a4f59c770955914745d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Teleologically, this makes sense. Increased pro-inflammatory responses are needed for optimal protection against viral infection. However, they can also cause increased tissue damage, impaired respiratory function, and disease symptoms, and should not, therefore, be triggered unnecessarily. This is, in line with the emerging paradigm (schematically shown in Figure 1 ) placing type I IFNs as a second line of defense that only deal with respiratory infections that escape IFN\u03bb control, at the expense though of host fitness.", "Although neutrophils respond to both IFNs to augment antiviral defenses, they exhibit pro-inflammatory activation only in response to type I IFNs (32), a finding that awaits confirmation in humans. Also, IFN\u03bbs directly affect neutrophil pro-inflammatory function, in both mice and humans, by suppressing reactive oxygen species production and degranulation of neutrophils, thereby limiting their tissue damaging functions and preserving barrier integrity (59) .", "Pattern recognition receptors are abundant in the respiratory epithelium and immune cells lying beneath the epithelial layer, sampling the airway lumen or residing in the lung parenchyma such as conventional and plasmacytoid dendritic cells (DCs), alveolar and interstitial macrophages, and monocytes. Interestingly, although these cells broadly respond to PRR engagement, expression of IFN\u03bbs is selective to specific cell types, most prominently epithelial cells and DCs (19) (20) (21) (22) , suggesting the involvement of additional epigenetic, transcriptional, and posttranscriptional regulation, which determines the ability of cells to make IFN\u03bbs. Indeed, RIG-I-like receptor signaling via mitochrondrial antiviral signaling protein (16) in peroxisomes or presence of transcriptional repressors, such as ZEB1 and BLIMP-1 (23) , may provide such signals controlling IFN\u03bb expression." ] },{ "paper_id": "a63f9b0555e4ec19bb5a38d4e4f282ed9bbb8612", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LincRNAs identified from exploratory studies are a valuable resource for accumulating information about these relatively unknown transcripts. Information such as location, splice junction, and tissue specificity are important features. There are quite a few specialized databases that provide comprehensive annotations for lincRNAs or lncRNAs. These include The Broad Institute's Human Body Map project [4] , NONCODE [35] and Lncipedia [5] . Other large gene annotation sets such as GENCODE [36, 37] , UCSC's known genes [38] or Rfam [39] RNA family databases are not specific to non-coding RNAs, but nevertheless contain large sets of annotations and information on lincRNAs.", "In recent years, machine learning based classification approaches have been used to detect lincRNAs [17, 27, [32] [33] [34] . For example, iSeeRNA interrogated coding potential based on a variety of factors mentioned above, in addition to nucleotide composition. It was trained to differentiate protein coding genes and lncRNAs with an area under the curve (AUC) of 0.99 [27] . LncRNA-MFDL is another tool that uses a deep learning method and the fusion of multiple features to classify lincRNAs with an accuracy of 97.1 % [34] .", "More specialized lncRNA databases, such as NONCODE and Lncipedia, enumerate a much larger number of lncRNAs (Table 1 ). These databases have been created to facilitate functional analyses by integrating multiple data sources such as expression, chromatin markups, microRNA binding sites and mutational data with known lncRNAs. Not surprisingly, the overlap of those data sets can differ greatly, largely due to the selection criteria of particular lncRNAs or the tissue origins where lincRNAs were initially detected. ", "The UCSC ENCODE project provides a feature-rich resource to describe the transcriptional landscape in a variety of tissues from the GENCODE database [40] . The Ensembl Geneome Browser is another resource that identifies and annotates transcripts within their large database using transcriptional evidence as well as chromatin markups [36] . The Ensembl project uses the GENCODE database, and contributes multiple sources to GENCODE through an automated annotation pipeline in combination with the large Havana annotation by the Sanger Institute [36] . While GENCODE is one of the most comprehensive databases for mammalian species, it does not include lincRNAs found by RNA-Seq ab initio alignment methods, such as those in the Human Body Map. Neither is it as comprehensive as specialized databases." ] },{ "paper_id": "a64149dbac768a5fac5c4ca620c09c2dea2e2bf0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study shows that travel within and outside Europe has many implications for health and such data are key to prioritising pre-travel intervention strategies and post-travel decision making." ] },{ "paper_id": "a642d4021e92bf6974af05b20f17e6e8b25c368c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DNA and RNA were co-extracted from 200 ml sample supernatant using the QIAsymphony Virus/Bacteria Mini Kit (Pathogen Complex 200 protocol) according to manufacturers instructions (QIAGEN, Crawley, UK) prior to PCR analysis.", "For the purposes of analysis the following pathogens were grouped together: CoV OC43, CoV HKU1, CoV 229E and CoV NL63 (CoV); Influenza A and Influenza B (Flu); and PIV 1-4 (PIV)." ] },{ "paper_id": "a646c8ced739fd583e7e031a90e4936f2a764035", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In vector-matrix form, the differential equation is expressed as.", "The corresponding state transition matrix, W Dt \u00f0 \u00de, is,", "The mean vector,/, and covariance matrix, P(t), for an ensemble of multi-dimensional random variables, x(t), are.", "When the patients began to experience adverse side effects, clinicians treated the subjects with corticosteroids, chlorpheniramine, acetaminophen, ondansetron, metaraminol, methylprednisolene, and an anti-IL2 receptor antagonist antibody. All subjects received aggressive individualized treatment while in intensive care. Consequently, the recorded cytokine histories reflect not only the natural reactions of the subjects but their response to therapy." ] },{ "paper_id": "a64792baacb18e3bbfb88eee3a3592c85f04a627", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The bats were caught using harp traps and placed individually into cotton bags before subsequent investigation started. Once species, sex, age category (juvenile, subadult, adult), forearm length, and weight were determined, the bats were released at their capture site.", "The faeces were immediately collected when bats produced fresh bolus during handling and kept in 2 mL of RNAlater RNA stabilisation reagent (QIAGEN, Hilden, Germany) permitting RNA conservation during transport. The samples were then conserved at \u221280 \u2022 C before processing.", "Using 11FW-modified (5 -TGA TGA TGC CGT CGT GTG CTA CAA-3 ) and 13RV-modified (5 -TGT GAG CAA AAT TCG TGA GGT CC-3 ) primers, a 168 bp fragment located between the nt 15647-15814 (Coronavirus, SARS-CoV Tor2; NC 004718) was able to be detected.", "Forty-five greater horseshoe bat (Rhinolophus ferrumequinum) specimens were captured from different roosts in all of Italy, including caves, mines, and abandoned houses, over a 4-month period (from August to November 2009) ( Figure 1 and Table 1 ). All captures were authorised by the Italian Ministry of the Environment and were part of a Ph.D. project on Rhinolophus ferrumequinum conservation." ] },{ "paper_id": "a647ca891190fdc6954ebb1d68b2758a2c7d6f64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No potential conflict of interest was reported by the authors. ", "ARTICLE HISTORY" ] },{ "paper_id": "a648c37b99ce3b55b5a07125c086a958bbbf3c13", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a65111e0e1a8f26d4789ea6439cae1cfa5b391b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fnhum. 2016.00403", "and embryological features are in favor of our hypothesis, additional studies including animal models are warranted to validate our proposition. Such studies are likely to unfold ZIKV-microcephaly association and may help in devising methods to combat it.", "The immediate application of our study are immense. If it is established that ZIKV caused microcephaly in infected fetus is a developmental condition arising out of retinoic acid signaling dysregulation it would not only help to understand the ZIKVmicrocephaly pathogenesis but also may justify retinoic acid as a therapeutic target for preventing this condition. " ] },{ "paper_id": "a65b8907068dde79fb7cc6e885a745607ed1f371", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Oral vaccine inoculum was diluted to 10 3 cfu/ml in PBS and 200\u03bcl was administered using a 27 gauge needle into the tail vein.", "The effects of different vaccination techniques were examined in a series of three experiments (outlined below) that compared the performance of live S. Typhimurium oral and intravenous vaccines in their ability to colonise and elicit immune responses. A further two experiments were performed to asses the ability of these vaccination methods to provide protection from a virulent S. Typhimurium challenge.", "This study was carried out in strict accordance with the approval of The University of Melbourne Animal Ethics Committee (Permit number: 06222). All efforts were made to minimize animal suffering.", "Typhoid fever, caused by the bacterium Salmonella enterica serovar Typhi (S. Typhi) causes serious systemic disease in humans with an untreated case fatality rate of 10-20% [1] . The global burden of typhoid has been estimated at 21.7 million infections annually with 217,000 deaths [2] . While strategies for the control of typhoid are reliant primarily on improving sanitation in developing countries, the use of antibiotics and vaccines is becoming more common [3] . Development of resistance to currently available antibiotics has led to a push for increased vaccine usage [4, 5] . There are two vaccines currently on the market, first a live attenuated S. Typhi strain (Ty21a) that is administered orally, and secondly a Vi polysaccharide subunit vaccine administered parenterally. Both these vaccines are only partially effective with studies finding 16-96% efficacy at 3yrs post vaccination for orally administered vaccines and 55-72% at 1.4-3yrs for injectable vaccines [1, [6] [7] [8] [9] [10] [11] [12] [13] [14] ." ] },{ "paper_id": "a65d8f4193a3b03c5d20fac1972e0756ecf2d328", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two reviewers (M.E.S and S.A.A) independently screened the titles and abstracts. Potentially relevant full text articles were then screened independently for eligibility. Agreement was calculated using Cohen's kappa coefficient [6] . Disagreements were resolved by consensus discussion or third-party adjudication (A.M). Authors were contacted for additional information when required. Reviewers independently abstracted data using a standardized form.", "Checklist S1 PRISMA Checklist. (DOCX)" ] },{ "paper_id": "a65ed49e9217467923e8db733109be6e54b0bd09", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Spirometry measurements and flow-volume curves were obtained using a spirometer (MedGraphics, PF/DX 1085D, St. Paul, MN)." ] },{ "paper_id": "a672930b5dc73b6002ca4a697e2109b130dee042", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The PEDV genome is encapsulated by a single N protein, forming a long and helical coil structure that is wrapped in a lipid envelope containing 3 surfaceassociated structural proteins, S, M, and E (Fig. 1b) . Enveloped virions are roughly spherical and pleomorphic with a diameter ranging from 95 to 190 nm, including the widely spaced, club-shaped, trimerized S projections measuring 18-23 nm in length [4] . PEDV has a buoyant density of 1.18 g/ml in sucrose and is sensitive to ether and chloroform. The virus is stable at 4-50\u00b0C and is absolutely inactivated at pH values beyond pH 4-9 range [23] . Therefore, PEDV is inactivated by various acidic or alkaline disinfectants [24] .", "This paper is a brief review focusing on current understanding of the molecular biology, epidemiology, diagnosis, and pathogenesis of PEDV, as well as control strategies to prevent PEDV infection.", "PEDV infection among pigs occurs principally by a direct or indirect fecal-oral route. Airborne transmission may also play a role in PEDV dissemination under certain conditions [85] . PEDV can mainly enter farms by diarrheal feces or vomitus and contaminated environmental sources via clinically or subclinically infected pigs, trailers (transporting pigs, manures, or food), people (pig owners or visitors, such as swine practitioners or trailer drivers in contaminated work clothing and footwear), or wild animals and birds [6, 86] . Other contaminated fomites, such as sow milk, feed, food items, or food additives or ingredients, including spraydried porcine plasma, could all be potential sources of the virus [9, [87] [88] [89] ." ] },{ "paper_id": "a6761d94a9d2827b88e04a42b2e2ddd8036ba410", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HAE were rinsed three times with PBS, then placed on an inverted phase contrast microscope (TE 2000; Nikon) to record cilial movement with a 206 objective. High-speed (125 Hz) video images were captured with an eight-bit b/w camera (GS-310 Turbo; Megaplus). The analog signal was digitized via an analogto-digital converter board (A/D; National Instruments). A digital computerized CBF analysis system was used to analyze the acquired video images, using specialized software, based on Sisson-Ammons Video Analysis [57] .", "Apical and basolateral samples were collected 48 h pi by applying 0.2 ml of serum-free medium to apical surfaces and harvested 30 min later. Basolateral samples were harvested from the basolateral medium. Samples were stored at 280uC before cytokine analyses using 28-plex Beadlyte Assays (Upstate) with Luminex technology (see Text S1 for details).", "Western blot analyses of CFTR protein was performed on HAE lysed in M-PER buffer (Pierce). Equal amounts of total protein (850 mg) per sample were adjusted to 1 ml volume with lysis buffer and added to 2 ml of anti-CFTR Ab #596, followed by 50 ml of immobilized-protein G agarose bead slurry (Pierce). Proteins were released from beads with sample buffer, separated with a NuPAGE 3%-8% Tris-Acetate Gel (Invitrogen), and transferred to PVDF membranes. The membranes were then incubated with anti-CFTR Ab (#596) followed by goat anti-mouse IgG-HRP (Jackson ImmunoResearch), and CFTR were visualized with SuperSignal West Dura Substrate (Pierce)." ] },{ "paper_id": "a67a570efab57b9f2492a652c0c17f47546416c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells seeded and infected in 24-well clusters were lysed in 100 ml of passive lysis buffer (Promega) supplemented with 1% Nonidet P-40. Renilla luciferase luminescence was measured in a LB940 Mithras 'Research II' (Berthold) after addition of 20 ml of substrate as described by the manufacturer.", "SARS is a text-book example of a novel, emerging disease that resulted from the introduction of an animal virus into the human population. The natural reservoir of the SARS virus progenitor is most likely a bat species and from here the virus was transmitted to humans, probably by a route involving a mammalian amplification host [1] . SARS was first seen in the Guangdong province of China in late 2002 and spread rapidly to a further 30 countries with more than 8000 cases reported within only a few months. The outbreak was eventually brought under control by the implementation of classical infection control measures [2] .", "Peripheral blood mononuclear cells (PBMCs) were derived from the blood of healthy volunteers obtained from the Bloodbank Leiden (Sanquin). PBMCs were separated from human blood by gradient density centrifugation using Ficoll (GE Healthcare). Subsequently, CD14 + monocytes were isolated by MACS using CD14 MicroBeads (Miltenyi Biotec). To stimulate the formation of mdDCs, the enriched cells were cultured for six days at 37uC/5% CO 2 in RPMI 1640 medium containing 8% FCS, 2 mM Lglutamine, 800 U/ml GM-CSF (Invitrogen) and 500 U ml IL-4 (Invitrogen). Cells were analysed for the expression of iDC CD80, CD86, CD11c, CD40 and L243 (BD Biosciences) using flow cytometry.", "SARS is caused by a coronavirus, a group of positive strand RNA viruses that had previously only been associated with mild upper respiratory infections in humans [3] . However, SARS-CoV infection often resulted in severe atypical pneumonia and was associated with an overall case fatality ratio of about 10% [4] . The last reported case of the SARS outbreak was in April 2004 but the threat of SARS has not disappeared. There is a real risk that another SARS-CoV could re-emerge from its natural reservoir, either in its original form or as a more virulent or pathogenic strain; in which case, the virus would be difficult to control in the absence of any effective antiviral drugs or vaccines." ] },{ "paper_id": "a6943ae5bcdb965103926179b2a31a77312790e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "TSL-1-5-7 was dissolved in acetonitrile and analyzed by a gas chromatograph (Agilent Technologies model 6890) and an API III+ triple quadrupole mass spectrometer (Perkin-Elmer Sciex). A capillary GC column (60 m \u00d7 0.26 mm ID \u00d7 0.25 \u03bcm film thickness) was interfaced directly with the mass spectrometry (MS) source. The oven temperature was held at 50\u00b0C for three minutes, and subsequently programmed to rise to 350 \u00b0C at increments of 20 \u00b0C/min. MS conditions were ion source 180 \u00b0C and electron energy 70 eV. Helium served as the carrier gas. The MassLynx (Waters) matching algorithm and library of spectra from the National Institute of Science and Technology (NIST 05) were used to identify the compound.", "Molecules 2010, 15 8378" ] },{ "paper_id": "a699cfdfda9ccc5ccb41e946a63113106b39148d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analysis. Data analysis was performed using the \"SVY\" commands of Stata version 9.2 (Stata Corp, College Station, TX, USA), which allowed for adjustments for sampling weights.", "The five-point Likert-scale responses were dichotomised. The definitions of the variables used are as follows:", "All responses were coded on a five-point Likert scale. Response options for all questions were \"not at all\", \"a little\", \"moderately\", \"very\", and \"extremely\". In addition, \"do not know\" and \"refused\" responses were coded as missing.", "In total, 2081 state residents aged 16 and over completed the module on pandemic influenza. The overall response rate was 65%. The key demographics of the weighted survey were comparable to Australian Bureau of Statistics (ABS) 2006 Australian population census data [21] ." ] },{ "paper_id": "a69d1ee507dac9ef068764a5f6cec19be2fbc4a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Baicalein, a bioflavone present in the dry roots of Scutellaria baicalensis Georgi, is known to reduce eotaxin production in human fibroblasts. However, there are no reports of its anti-asthma activity or its effect on airway injury.", "8-isoprostane, a marker of lipid peroxidation, was measured in lung homogenates by competitive ELISA and results were expressed in pg/25 mg protein. 8-OHdG, a marker of oxidative DNA damage, was measured in BAL fluid supernatants by competitive ELISA and results were expressed in pg/100 ml BAL fluid supernatants.", "Data are expressed as mean 6 SEM. Unpaired student's 't' test and ANOVA with post-hoc correction were performed to calculate the statistical significance which was set at p#0.05." ] },{ "paper_id": "a69fd3fb91451692a0d45c306bd5c8c7dbc9debd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines (Moher et al., 2009 ).", "XC performed the conception and design of the work. XC and LZ drafted and revised the work critically. DL and JL analyzed data for work. FL and HM acquisited data for this work. All authors provide approval for publication of the content. " ] },{ "paper_id": "a6c379baf7fcba6a32b8fdadbcd9a85032dd4729", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The reference strains of influenza A H1N1, H5N1 and H3N2 used in this study had Genebank accession numbers: CY12306.1, DQ493076, CY016653, respectively.", "Overall, this technology may have wide ranging applications and may revolutionize molecular diagnostics and the use of multiplexing assays.", "During this process, the complementary sequences located at 3' end of the paired oligo would form a dimer and in the presence of DNA polymerase and dNTP, each oligo would extend its 3' end using the second oligo as a template (Figure 3 )." ] },{ "paper_id": "a6ce4ce12c7af1cfb4d71764b963285b687e6b51", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ".", "(2)" ] },{ "paper_id": "a6d2693a3c3bc48b290f231e8824be62c8f364ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Code (ISO3) in Figure 2 Research Effort by Search Terms *", "Country Code (ISO3) in Figure 2 Research Effort by Search Terms *", "Afghanistan" ] },{ "paper_id": "a6d3a67189b0d60da49032d2192a681dc06f5459", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As difficult as it may be to answer the question of what would have happened if the difficult decisions made had not been made, it is nevertheless possible to outline hypothetical scenarios.", "A moderate scenario, such as the 1968 pandemic, foresaw that without any mitigation and control measures, hospital admissions would have exceeded 30,000, deaths would have amounted to 8,600 and almost 4.6 million outpatient consultations would have occurred [9, 16] .", "In particular, the 1918-19 pandemic caused, according to estimates, between 40 and 100 million deaths at a time when the communications and means of transportation on earth were not as fast and efficient as they are now.", "A fund was created to provide economic incentives to the academic and researcher groups to participate in grants to further the knowledge on the virus, its virulence, transmissibility, affected groups, severity, etc.", "There are various useful approaches to model the potential impact of a pandemic. All of them are based on assumptions stemming from the documentation of previous influenza pandemics, particularly in the 20 th century. Since the purpose of models is to anticipate unknown situations, the former should therefore be taken with a grain of salt. Moreover, they include only a few of the impact indicators of this kind of pandemia [6, 14, 15] ." ] },{ "paper_id": "a6d3a75a05c35723193e5240b3ebd2a01a77f4d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Representative sections of small intestine were fixed in 2.5% glutaraldehyde and 2% paraformaldehyde in 0.1 M, pH 7.4 phosphate buffer (PBS) and post-fixed in 1% osmium tetroxide in PBS. After dehydration in an alcohol series, the fragments were embedded in epoxy resin, Quetol 812 (Nisshin EM Co., Ltd., Tokyo). Ultrathin sections were cut, double-stained with uranyl acetate-lead citrate, and observed under a JEM-1200EX (JEOL Co. Ltd., Tokyo).", "Clinical, pathological and etiological findings Case 1" ] },{ "paper_id": "a6d78920011473fe481d4fc46e9ba4535332b87c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Detection antibodies and printing of microarrays. Anti-huIgG (Cat: 309-005-008; Jackson ImmunoResearch Laboratories, West Grove, PA, USA) and anti-huIgA (Cat.: 555885; Becton Dickinson, Franklin Lakes, NJ) were labeled with DyLight 650 (Pierce, Thermo Fisher Scientific, Rockford, IL, USA). Customized printing of RV microarrays was done by Phadia-ThermoFisher using ImmunoCAP ISAC (Immuno Solid-phase Allergen Chip) technology 50, 51 . Spotting was performed by slow pin mode printing using the Aushon 2410 Printer (Aushon, Billerica, MA, USA). Stock solutions of peptides (5 mg/ml) were diluted 1:4 in a phosphate buffer, pH 8.4 and then used for spotting. Antigens were spotted in triplicates on a glass surface coated with an amino-reactive organic polymer, each spot containing 50-200 fg of microarray component, corresponding to 1-5 attomol. Allergens used for the calibration and other control proteins spotted on the microarray are listed in Supplementary Table 6 .", "In the present study funded by the European Union project \"PreDicta\" (https://cordis.europa.eu/project/rcn/96868_en.html), we investigated if it is possible to generate a microarray-based serological test which can discriminate RV-A, RV-B, and RV-C as culprit species involved in childhood asthma attacks.", "The reliable determination of the most common RV species involved in triggering severe respiratory illness will ultimately provide a rational basis for the development of RV vaccines and RV species-targeting therapeutic approaches [20] [21] [22] [23] [24] [25] [26] ." ] },{ "paper_id": "a6e5eab626d98db430e725caeec26c95ee086f86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a6f36e3233319626ec737895c1d52dedd7aac0bf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords: parvovirus; geminivirus; anellovirus; circovirus; nanovirus", "Genomic rearrangements and deletions frequently arise during anellovirus [49, 59, 133] , parvovirus [134] [135] [136] [137] [138] [139] [140] [141] and geminivirus [21, 123, 134, [141] [142] [143] [144] [145] infections.", "Sub-full length genome molecules (hereafter referred to as sub-genomics) and genomes with sequence duplications that arise during natural parvoviral infections are possibly the result of DNA secondary structure induced template switching of DNA polymerases at 5-10 nt long direct repeats [137, 140] during RHR. While the biological relevance of parvoviral sub-genomics and rearranged genomes are unknown, ultra-small sub-genomics retaining only the sequence elements required for trans-replication could potentially be harnessed for use as gene expression vectors [137] ." ] },{ "paper_id": "a6fc1b376a385d9f49f852a9f53e1e9149cb556a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results were plotted using R (www.R-project.org) and Graph-Pad Prism version 5.02. Multiple sequence alignments were generated with ClustalW (http://www.ebi.ac.uk/Tools/msa/ clustalw2/).", "All animal experiments were performed in accordance with Swiss federal legislation on animal protection and with the approval of the Animal Studies Committee of the Cantonal Veterinary Office (St. Gallen, Switzerland), license nr. SG 11/03.", "For data analysis from pulsed SILAC experiments, we used log-transformed heavy to light protein ratios. Only proteins with valid values were considered for analysis, and normalized by dividing by the row median. Profile plots were generated using LFQ intensities of log-transformed heavy-labelled protein intensities. We excluded proteins containing less than 10 valid values in all 12 measurements, and missing values were filled by imputation. LFQ intensities were then normalized by dividing by the row median." ] },{ "paper_id": "a7069f86aa3a4d5231c386f08dd28dc3a97b0e0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a70d334286efa96684bd35e383175063c285ab8b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Seventy-four serum samples containing genetic material of PRRS type 1 viruses confirmed by PRRSV genotype specific real-time TaqMan PCR targeting the ORF7 region of the PRRSV genome [26] were selected for further molecular characterization. The samples originated from fifty-four Dutch pig farms, predominantly located in the eastern part of the Netherlands and were collected from and including the years 2014 to 2016.", "Viral RNA was extracted from serum samples using the MagMAX pathogen DNA/RNA isolation kit as deposited in protocols.io [27] in combination with the semi-automated Mag-MAX TM Express-96 Deep Well Magnetic Particle Processor (Thermofisher Scientific) according to the manufacturer's protocol. First-strand cDNA synthesis was done with the SuperScript1 III kit (Invitrogen) using the 3'-end poly(dT) reverse transcription (RT)-primer (S1 Table) as described in protocols.io [28, 29] . Subsequently, a long range amplification PCR of ORF2-ORF7 was performed with the AccuPrimeTM Taq DNA Polymerase High Fidelity mix (Invitrogen) using a forward and reverse primer (S1 Table) as deposited in protocols.io [30] . Samples without visible product after PCR were re-tested using a second, and when necessary, a third forward primer. Subsequently, amplicons were sent to BaseClear (Leiden, the Netherlands) for purification and Sanger sequence analysis. PCR amplification primers and Sanger sequence primers are presented in S1 Table.", "Future research will be focusing on PRRSV-1 recombination and its implication on genetic analysis. It is of upmost importance that the variation of circulating PRRSV is being monitored and genetically analyzed, in order to improve diagnostics, increase vaccine efficacy and identification of found virus strains to support internal and external biosecurity measures on local farms." ] },{ "paper_id": "a70e7c4d8ee484ce956e91c8700d0c9310bbdbbc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In general, sensitivity depended on the device used, body area targeted and ambient temperature.", "We assume a low percentage, as no specific risk factors have been identified, and known times or sources of exposure are rarely reported in existing line lists.", "All code and source data used to perform analyses and generate figures is archived at https:// github.com/kgostic/traveller_screening/releases/tag/v2.1. (Gostic, 2020 ; copy archived at https:// github.com/elifesciences-publications/traveller_screening). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. " ] },{ "paper_id": "a71052d0d97adb979510b675275149d05cd7976e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Moreover, several groups are working on modifications of the basic antibody structure to generate monovalent and multispecific reagents that may have various therapeutic properties and even completely new structures. Examples of these new reagents include antibody alternative protein scaffolds based on leucine-rich repeat molecules of lamprey variable lymphocyte receptors (VLRs), libraries of fibronectin domains and designed ankryin repeat proteins (DARPs) [50] . With all these novel antibody formats, immunogenicity, stability and aggregation problems should be carefully considered.", "Soon after mAbs generation was reported in 1975, the potential of mAbs became clear and many companies showed interested in developing new reagents for diagnosis and designing new equipment, among other contributions. However, when it came to the field of human therapy, pharmaceutical companies did not initially show much interest in the development of monoclonal antibodies, although several research groups were showing promising results in preclinical and clinical studies. The reasons for their reluctance are many:" ] },{ "paper_id": "a714dc2983f4139a10c0222d8816654277e72965", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Installation of refrigerators and containers to preserve chilled products [extra expenses for installation covered by government subsidies]", "Sociodemographic characteristics of participants." ] },{ "paper_id": "a71b7e4060dbc1160df90e7bff684d05b2cbc089", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "L5Ba: 5\u2032-invddT-ACACrGrArCrGrCrUrCrUrUrCrCrGrA rUrCrUrNrNrNrArGrArGrCrN-OH-3\u2032. L5Bb: 5\u2032-invddT-ACACrGrArCrGrCrUrCrUrUrCrCrGrArUrCrUrNrNrNr GrUrGrArGrCrN-OH-3\u2032. L5Bc: 5\u2032-invddT-ACACrGrArC rGrCrUrCrUrUrCrCrGrArUrCrUrNrNrNrCrArCrUrArG rCrN-OH-3\u2032. L5Bd: 5\u2032-invddT-ACACrGrArCrGrCrUr CrUrUrCrCrGrArUrCrUrNrNrNrUrCrUrCrUrArGrCrN-OH-3\u2032. 3\u2032 adapter: 5\u2032App-NAGATCGGAAGAGCACAC GTCTG-ddC 3\u2032. RT Oligo: 5\u2032-CAGACGTGTGCTCTTC CGATCT-3\u2032.", "Funding GH was a recipient of a Wellcome Trust PhD studentship (105246). JR was supported by a Wellcome Trust Senior Research Fellowship (084229). JSN was a recipient of a Wellcome Trust PhD Studentship (096996). SG was supported by a Wellcome Trust Career Development Fellowship (091549). GM was a recipient of an MRC Career Development Award (G10000564). This work was also supported by two Wellcome Trust Centre Core Grants (077707 and 092076) and by a Wellcome Trust instrument Grant (091020). Next generation sequencing was carried out by Edinburgh Genomics (MiSeq), The University of Edinburgh. Edinburgh Genomics is partly supported through core grants from NERC (R8/H10/56), MRC (MR/K001744/1), and BBSRC (BB/ J004243/1).", "Ethics approval and consent to participate Not applicable" ] },{ "paper_id": "a71e4139dc4ba7ca03da5d99cac0781f092d5223", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sensitivity and specificity of these assays was higher than individual assays based on direct antigen detection and standard PCR against a range of control templates and in several hundred clinical specimens. The MT-PCR assays provided differential diagnoses as well as potentially useful quantitation of virus in clinical samples.", "Thirty-nine viral cell-culture extracts from stored clinical isolates (including isolates identified as INF-A n = 5, INF-B n = 2, RSV n = 1, RV n = 7, along with undifferentiated picornavirus n = 4, and one each of hPIV-1, hPIV-3, coronavirus 229E, coronavirus OC43, hMPV, enterovirus EV-68, adenovirus type 3 and adenovirus type 4) were tested ", "The Table 5 ). The set of INF-A/NONO ratios in Table 5 were derived from assays of serial samples of patients treated with oseltamivir for influenza A during the course of management of an institutional outbreak, demonstrating the potential for quantitation as a marker of sample quality (normalised NONO value) and perhaps of the course of infection (INF-A/NONO ratio). " ] },{ "paper_id": "a72473db86f1e26d0d1e6db3e7078a3536b9ba65", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells and viruses. Vero African green monkey kidney epithelial (ATCC, CCL-81) and human A549 (ATCC, CCL-185) cells were maintained at 37 \u00b0C with 5% CO 2 in Dulbecco's modified Eagle's medium (DMEM) supplemented with 5% fetal bovine serum (FBS), 2 mM L-glutamine, 100 units/ml penicillin and 100 \u03bcg/ml streptomycin (1x PSG)." ] },{ "paper_id": "a730b4d5a5a0353503a1cd46d458635f93618805", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 39 Cardiovirus genomes were used in this study, including 18 EMCV genomes and 21ThV genomes. The CDS of these viruses were obtained from NCBI http://www.ncbi.nlm.nih.gov/Genbank/ randomly in December 2010. And the serial number (SN), Gen-Bank number, genotype and other detail information are listed in Table 5 .", "Correlation analysis was used to identify the relationship between nucleotide composition and synonymous codon usage pattern [29] . This analysis was implemented based on the Spearman's rank correlation analysis way. All statistical processes were carried out by with statistical software SPSS 11.5 for windows." ] },{ "paper_id": "a7344a564121bf1e3f995911e78c17b1b2aee903", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The HSV-1 clone collection was cloned by recombinatorial (GATEWAY TM , Invitrogen) and conventional cloning into the bait vector pGBKT7, and screened against a library pooled from 12,381 MGC clones [35] in the pGADT7 prey vector using a semiautomated Y2H assay [77] . Interacting prey cDNAs were identified by sequential blasting of RefSeq, ENSEMBL and Unigene databases. BLAST hits with identical parameters (score, expectation value, length of alignment) were considered indistinguishable and counted separately. A high-confidence dataset was generated from interaction pairs isolated at least twice, or where the bait interacted with two highly related, non-promiscuous preys.", "To systematically identify host factors (HFs) required for viral replication, RNAi screens have been performed with a range of different RNA and DNA viruses including HIV-1 [7, 8, 9] , Influenza A virus [10, 11, 12] , Hepatitis C virus [13] , West Nile virus [14] , Dengue virus [15] , Enterovirus [16] and Vaccinia virus [17, 18] . The overlap between the results of these studies is generally very low [19] , reflecting either differences in biology, or different experimental set-ups, cutoff and selection criteria. In addition, microenvironmental effects might also play a role for the differences of the results [20] .", "Below lists the GeneID numbers for genes and proteins mentioned within the text of this manuscript: IFITM1 (8519) " ] },{ "paper_id": "a735cd10efb7df82d87da350bc33e3ca3acab6ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a73d97226cb958a94cd359666b35e092452818b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data represented the mean 6 standard error of n experiments. Statistical analysis was performed using the software program Instat. The significance between groups was determined by ANOVA. A p value less than 0.05 was considered to be statistically significant. ", "Chlamydia species are obligate intracellular pathogens that cause a wide range of diseases in humans, including sexually transmitted, ocular, and respiratory tract infections [1] . The capacity of Chlamydia infections to lead to infertility and blindness, their association with chronic diseases such as atherosclerosis, and the extraordinary prevalence and array of these infections make them public concerns of primary importance [1, 2] .", "We first examined inclusion morphology and progeny production in cells treated with increasing concentrations of HPA-12." ] },{ "paper_id": "a74504e83f52c1ed91c0e52adc5af8830d71ae5f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mp positive (N = 110) + + / 98", "Blood, serum, nasopharyngeal aspirates (NPAs) and BALF specimens were obtained for pathogen detection using multiple modalities.", "Mp negative (N = 4038) -" ] },{ "paper_id": "a748ccbe075d2bc2223dae088c6014428992718d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Five 1-day-old SPF White Leghorn chickens were intranasally inoculated with filtration sterilized allantoic fluid of each isolated virus strains, respectively. All of the chicks were examined and recorded daily for clinical signs of infection and mortality for 20 days post-inoculation, the dead birds were necrospied for lesions of respiratory tract or nephritis. Finally, all the survivors were sacrificed and necrospied." ] },{ "paper_id": "a760c40de63cc6df4ba38766deb3fbb54724ee44", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A P value less than 0.05 indicates statistical significance. SPSS software 15.0 was used to perform the statistical analyses." ] },{ "paper_id": "a762208186ddb3827966e6d7bec5a4fb8a0124cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data expressed as mean \u00b1 standard deviation (S.D.) are representative of at least two different experiments. Comparisons between individual data points for tumor sizes were made using a Student's t-test or repeated measure ANOVA (analysis of variance) test. Differences in survival between experimental groups were analyzed using the log-rank test. Tumor sizes were calculated using the following equation: (tumor length\u00d7width\u00d7height)/2. Death of mouse was arbitrarily defined as tumor diameter greater than 2 cm." ] },{ "paper_id": "a7655a74468e485dfd7f45390c5be4c4aa9361a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical spectrum. Table 2) .", "Supporting Information S1 " ] },{ "paper_id": "a765ae8d7eae55875cb832428c9082a6e4e4ae82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell cultured in 35-mm dishes were transiently transfected with the indicated plasmid DNAs using ProFection \u00ae Mammalian Transfection Systems (Promega, USA) according to the manual instruction. Briefly, transfected DNAs were first mixed with 37 \uf06dL of 2M CaCl 2 and brought to total 300 \uf06dL with sterile and deionized water. Then the DNA-CaCl 2 mixture was added into equal volume of 2\u00d7HBS drop by drop accompanying with gentle vortexing. After 15 minutes incubation, the reaction mixture was evenly distributed into the cell culture medium and incubated for 48 hours before harvesting.", "Overexpression of N protein in serum starved cell lines such as monkey kidney Cos-1 cells [17] or human pulmonary fibroblast HPF cells [18] induces apoptosis. More importantly, SARS-CoV N protein can function as an antagonist to counteract the host innate immune response by inhibiting the activity of IRF3 and NFkB, and subsequently blocking interferon \uf062 production [19] .", "The transfected cells were lysed with a lysis buffer containing 1% NP-40, 50 mM Tris-HCl (pH 7.5), 120 mM NaCl, 200 \u03bcM NaVO 4 , 1 \uf06dg/mL leupeptin, 1 \uf06dg/mL aprotinin, and 1 \uf06dM PMSF. About 15 \uf06dg of cell lysate for each sample was resolved onto 12% SDS-PAGE. After separation, the separated proteins were transferred onto Hybond nitrocellular membrane (Pharmacia). The transferred membrane was first probed with a primary antibody. Then, a secondary antibody labeled with horseradish peroxidase was added to the reaction and finally visualized with an ECL kit." ] },{ "paper_id": "a769fe3dd7a63ddec2a0180ddd8a004050eaddc1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The online version of this article (https ://doi.org/10.1007/s1126 2-019-01639 -1) contains supplementary material, which is available to authorized users.", "OpenAccess This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.", "Edited by William Dundon." ] },{ "paper_id": "a776acb66d26bc9ad550cb9909e0f1ef35b57fec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consequently, epidemiological programs should include not just virological diagnosis but genotype surveillance too.", "Dengue virus infection has been an important impact on humans over the last several years, with an estimated 50 million dengue infections and an average of 1 million cases reported annually in more than 100 countries in tropical and subtropical regions [1] [2] [3] [4] [5] . This mosquitoborne flavivirus causes a wide spectrum of clinical manifestations in humans, which include an acute self-limited flu-like illness known as dengue fever (DF). DF is characterized by headache, myalgia, arthralgia, retro-orbital pain and sometimes maculopapular rash. Dengue haemorrhagic fever (DHF) is a severe illness documented by haemoconcentration (haematocrit increase by 20%) and evidence of plasma leakage such as pleural effusion and ascites as the major pathophysiological features. In some patients, DHF may progress to hypovolemic shock (Dengue Shock Syndrome, DSS) with circulatory failure [2, [6] [7] [8] .", "Phylogenetic trees were constructed with the Maximum Parsimony and Maximum Likelihood (ML) methods incorporated in the PAUP* 4.0 program [56] . Phylogenetic analyses were performed by using the best model of nucleotide substitution based on Modeltest [57] (analyses are available upon request). Statistical significance of tree topology was assessed with a bootstrap with 1000 replicates. Obtained trees were visualized using the Tree View Program [58] ." ] },{ "paper_id": "a780aef42860533f02e613494ddb8283b9fbe83d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "S (i,j) (t) = 2 represents latent state, meaning that individuals have been infected, but they do not have infectivity;", "S (i,j) (t) = 3 represents infected state, meaning that individuals are infected and infectious; S (i,j) (t) = 4 represents recovered state, meaning that individuals have recovered and acquired immunity within a certain period of time;", "S (i,j) (t) = 0 represents dead state, meaning that individuals are dead and they do not have infectivity." ] },{ "paper_id": "a78fd1b34372e1e54bf2a192d04aa36670cea307", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In Japan, cancer has been recognized as a major component of the overall pattern of disease for decades. Thus, the importance of cancer prevention by lifestyle modification should now be strongly acknowledged." ] },{ "paper_id": "a792bbaa94e64b3e7e230718d114dfd5d8d174dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "While the year 2010 marked an important milestone in the EU's global health commitment, the foundation was laid already in the previous decade. The outbreak of severe acute respiratory syndrome (SARS) in 2003 formed the first global health threat in the new millennium.", "The lack of a concise and workable definition of global health also affects the policy stream. The policy stream Christoph Aluttis et al.", "O ur health is increasingly shaped by social, economic and environmental factors that are in turn influenced by globalization (1\u00c13). In a globalized and increasingly interdependent world, various European Union (EU) policies are likely to have consequences for health and well-being in other parts of the world (4, 5) . However, establishing links between the EU's policies and their health impacts at global scale is a fairly complex task, which has not been consistently taken into consideration in the EU's policies and actions with the third countries (5) ." ] },{ "paper_id": "a795b134187db133ca06a515ab1bec787916af2d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The efficacies of both strong anion exchange and weak cation exchange (WCX) protein chips (Ciphergen Biosystems, Inc., Fremont, CA, USA) for serum protein profiling were tested in this study. Results showed that the weak cationic exchange ProteinChip, CM10, had a higher capture ability and signal-tonoise ratio (S/N). Therefore, CM10 was selected for all subsequent experiments. Binding of proteins to the ProteinChip CM10 array can also be affected by pH dependent of the buffer and changing the ionic strength of the buffer.", "added into amniotic fluid sample, and immediately mixed. To equilibrate the chip, 200 ml binding buffer was applied to each chip spot, shaking at 250 rpm for 5 min and excess buffer was removed without contacting the active surface. The same procedure was repeated once. 100 ml prepared serum sample, or urine sample, or amniotic fluid sample, was then added into each Bioprocessor well, and chip was incubated in a humidity chamber for 1 h, shaking at 250 rpm at room temperature. Excess buffer was removed. 200 ml binding buffer was added into each well, shaking at room temperature for 5 min. The above procedure was repeated once. Each spot was washed with 200 ml deionized water. Then 0.5 ml saturated sinnapinic acid was applied to each spot and the chips were allowed to air dry. Chips were re-incubated with sinnapinic acid and air dried again. Captured proteins by the arrays were detected on a PBS-II C reader (Ciphergen Biosystems).", "Conceived and designed the experiments: ZL QZ. Performed the experiments: ZL ZY QZ. Analyzed the data: ZL QZ. Wrote the paper: ZL QZ. " ] },{ "paper_id": "a79847f406c9f694222cc18a1ffd04dbc0c06d08", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "AN is the principal investigator on a NIH R15 grant that was used to fund this work (R15AI123993).", "TL, FK, and AN wrote the article. TL was responsible for collation of information regarding nsP3 interaction partners. FK assisted with article preparation and formatting, and in addition to contributing to the written body. AN worked with TL and FK to compose the article and final review.", "Alphaviruses belong to the family Togaviridae and are divided into two categories: arthritogenic and encephalitic alphaviruses (Strauss and Strauss, 1994) . The classification is indicative of their geographic locale and differences in pathogenesis and symptoms, namely New World alphaviruses tend to be associated with encephalitic phenotypes in the affected host while Old World alphaviruses are more likely to cause arthritic outcomes (Fros and Pijlman, 2016) ." ] },{ "paper_id": "a799d4baa0f252468dcbeaa466fbed7736bf20c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed by Student's two-tailed t-test using the GraphPad Prism statistical software (San Diego, CA, USA). p values lower than 0.05 were considered statistically significant. *, **, and *** indicate p < 0.05, p < 0.01, and p < 0.001, respectively.", "Materials and Methods" ] },{ "paper_id": "a7ab989eb31d8d6dd0a09da2ee0cf5f6a5182885", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(5) Book and book chapters were qualified as books or selections involving the subject matter.", "(1) Peer-reviewed publications were classified as scientific journals and literature reviews of the pertinent subject matter (human, animal, and environmental health) that had been published in peer-reviewed journals.", "(3) Grants and funding allocations were characterized as proposals for funding research, policy development, and so forth in the collaborative subject matter of humans, animals, and the environment accessed from reviewing all professional publications available from the systematic search conducted.", "(4) WHO-related reporting included updates from the website that involved relevant health issues, specifically reflecting the one health approach." ] },{ "paper_id": "a7b1bcb7b1806dce219451f289d56b14434f7ac1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine epidemic diarrhea virus (PEDV) is an enveloped, positive-stranded RNA virus which readily infects pigs, resulting in highly contagious porcine epidemic diarrhea [1] . PEDV belongs to family Coronaviridae, subfamily Coronavirinae and genus Alphacoronavirus [2] . Some viruses of the Coronaviridae family cause severe disease in humans such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) [3, 4] . Coronaviruses of veterinary significance include avian infectious bronchitis virus infecting chickens, transmissible gastroenteritis virus (TGEV) infecting pigs, bovine coronavirus, feline coronaviruses, canine coronavirus and turkey coronavirus [5] .", "To deliver a recombinant protein orally, a live vector such as adenoviral vector might be used [27] .", "contr." ] },{ "paper_id": "a7bb5432ed9fc93c11b893bd499bb66becfc71f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analysis. Data were analyzed and figures were generated using GraphPad Prism 5.00 software (GraphPad Software, San Diego, USA). Significant differences between groups were determined by Mann-Whitney test at 90% confidence interval ( value < 0.05 was considered significant).", "In the aged subjects there were several subgroups based on comorbidities (Table 1 ). Subgroup analysis was performed for osteoarthritis, hypertension, and subjects taking vitamins and antioxidants as these subgroups had sufficient subject numbers. However, we did not observe any significant difference in any of the cytokine levels between the two groups ( > 0.5). Based on these subgroup analyses, we feel fairly confident that the comparisons between the young control and aged subject populations are yielding valid results across a general geriatric group.", "The objective of the present study was to compare the response to CPn of DCs obtained from both young and elderly subjects." ] },{ "paper_id": "a7c6ab514af0b9e5edc73e08e496ceb65111cfa9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "On June 11, 2009 , the World Health Organization (WHO) declared that infection with the Swine Origin Influenza A/H1N1 virus had reached pandemic proportions [1] . Cases were recorded in more than 180 countries and outbreaks that strained national resource capacities were documented in Canada, Australia, Chile, Argentina, and elsewhere.", "Initial Diagnostic Testing (assuming diagnosis not confirmed at ICU admission)", "A multi-national feasibility RCT involving adult ICUs in Canada, Saudi Arabia, Mexico, Argentina Australia/ New Zealand. An overview of the study design is provided in Figure 1 (see Figure 1 ).", "[6] Recruitment rates by approved consent model." ] },{ "paper_id": "a7c91b8fe16a943a9c53322b183bc2d867eef5cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at http://www.mdpi.com/1999-4915/11/6/516/s1, Table S1 . Information available on sera tested, by region and by species. ", "Here, we performed a large scale seroprevalence study of IDV in large and small domestic ruminants at a country level. As we aimed to detect IDV antibodies with an individual prevalence limit of 0.1% for cattle and 0.5% for small ruminants with 95% confidence, at least 3000 and 600 sera were needed, respectively.", "Five thousand three hundred and seventy-three animal sera (n = 33,181,430 and 625 sera coming from n = 92, 45, and 13 herds for cattle, sheep and goat respectively, Table S1) were collected in official veterinary laboratories and at the Veterinary School of Toulouse from five French regions. Most of these sera were initially collected for infectious bovine rhinotracheitis monitoring. The sampling plan was representative of the population taking into account the major cattle-rearing areas including Bretagne, Pays de la Loire, Bourgogne-Franche-Comt\u00e9, Hauts-de-France and Occitanie. In addition, sera from Occitanie were retrieved from the Veterinary School of Toulouse large animal clinics (n = 509). No data was available on history of respiratory diseases in the farms of each region. All the tested animals were older than 1-year-of age and the detection of maternally derived antibodies can therefore be ruled out. The type of sera, localization and years of collection are described in Table S1 . Three controls sera were used: an in-house polyclonal rabbit anti-IDV serum generated by inoculating rabbits with D/Bovine/Nebraska/9-2/2012 subcutaneously (as described in [11] ); IDV negative and positive French cattle sera generated during an experimental infection [16] . All sera were treated with receptor destroying enzyme (RDE, Seika) following the manufacturer's instructions and hemadsorbed on packed horse red blood cells. Hemagglutination Inhibition (HI) assays were performed as previously described [16] , with four hemagglutination units of D/bovine/France/5920/2014 and 1% horse red blood cells. Samples with antibody titers \u22651:20 were considered positive. Statistical analyses were carried out using Graph Pad Prism 5.0. A p value \u22640.05 was considered significant. A \u03c72 test was used to compare IDV seroprevalences between species and between French provinces." ] },{ "paper_id": "a7d6aeb7cd27e3f420ae9ca4711ad2ac77651089", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "were from a vulnerable population and all donors or next of kin provided written informed consent that was freely given.", "Induction immunosuppression consisted of basiliximab (20 mg on day of surgery and postoperative day 4) and methylprednisolone (1 g given during operative procedure, 125 mg on postoperative day 1 and 2). Maintenance immunosuppression included mycophenolate mofetil, prednisone and a calcineurin inhibitor, primarily cyclosporine [17] .", "For confirmation of identified virus hits, de-novo contigs were assembled with velvet (minimum contig length 200) [25] using only the virus specific reads reported by the VirMet pipeline and analyzed by BLAST. Enteroviruses were genotyped with an automated genotyping tool [26] ." ] },{ "paper_id": "a7da39018f8bac38c77086632a5ab80e8fe73516", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 7:41392 | DOI: 10.1038/srep41392" ] },{ "paper_id": "a7e3179a2dbf9f386ac702c0a6fc780889773829", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a7f21bc68611eecc7ea9f57f86ebd7541d77b632", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No association was found between PRRSV and HEV infections in the slaughter age pigs sampled. In addition, there was no difference in strain diversity of PRRSV sampled from clinically unaffected pigs in this study relative to those identified from clinical cases of disease in the UK.", "Sequencing of the ORF5 PRRSV gene was undertaken on 29 of the 31 tonsil samples from which PRRSV RNA was detected. Two PCR-positive tonsils were not suitable for sequencing as there was insufficient viral nucleic acid in the samples. Six samples did not yield useable sequence data. All of the sequences confirm that the viruses belong to PRRSV genotype 1. Only three of the sequences may be considered to possibly originate from the currently licensed attenuated vaccine, with greater than 99% similarity between the sample and vaccine strain ORF5 sequences (99.2%, 99.8%, and 100%).", "Hepatitis E virus (HEV) is the cause of hepatitis E in humans, typically a self-limiting hepatitis but more serious in those with pre-existing liver conditions and in the immunocompromised [1] . In pigs, HEV infection alone does not cause clinical disease. HEV genotypes HEV-3 and HEV-4 are the cause of sporadic cases of hepatitis E in developed countries, and are ubiquitous in the pig population worldwide [2] . Hepatitis E is a foodborne zoonosis, for which pork or pork products from infected pigs is one of the risks identified in Europe [1, 2] and consumption of processed pork products in the United Kingdom (UK) has been shown to be associated with an increased risk of acquiring HEV [3] . Hence, there is a need to better understand factors influencing HEV entering the food chain.", "The phylogenetic trees (Figure 1 ) illustrate the genetic diversity of the ORF5 genes from the 23 samples in this study in comparison to the vaccine virus licensed in the UK at the time and 48 published reference sequences representing the different genotypes and subtypes ( Figure 1A ) and in more detail, in the context of 431 previously sequenced viruses specifically from UK pigs between 1991 and 2014 (unpublished data) ( Figure 1B ). In the within-UK analysis, there is no clear association between geographic origin and the clade in which the PRRSV strains belong. All of the 23 sequences are found in clades where other UK strains were already identified, and no distinct clustering is observed. " ] },{ "paper_id": "a7f47a771ace5d75afbd36064bb1a843f9821f83", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples from named wLBMs in Shantou, China were taken between 2005 and 2006 and were collected reliably with a frequency of two to four weeks. Embryonated chicken eggs were used to isolate virus. Subtypes H1-H13 were tested for with monospecific antisera in haemagglutination inhibition (HI) tests. Further detail on the methods of data collection can be found in Pepin et al. [5] .", "Ethics. This study used secondary data and no human subjects were involved.", "Data accessibility. Data and code are available through Dryad (http:// dx.doi.org/10.5061/dryad.np4pm) [36] ." ] },{ "paper_id": "a7fa116862ab1522f6ccbe6c261e83722fca138b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "With several unqualified scenarios excluded, 1,744 scenarios were considered in the study. For efficient computations and accurate predictions, we ran simulations 1,000 times for each scenario.", "\u2022 Doctors and nurses were found to be the most possible to conduct their routine rounds following Pattern 5 (examining inpatients randomly in the clockwise direction).", "Supporting information S1 File. The following information is described in detail, e.g. details of the mathematical models, parameter selections for the mathematical models and supplemental figures." ] },{ "paper_id": "a80b756097aea945ba90510f7fa55cc84f849686", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Table S1", "(DOC)" ] },{ "paper_id": "a81118016cd86948665a49c7562f577f83cb87b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Response surface methodology is a statistical procedure used to understand, improve, and optimize a process. The objective is to model a response variable in terms of one or more independent predictor variables. Second order polynomial models (Equation 1)", "As Table 1 shows, there were three predictors, temperature (T), relative humidity (RH), and days (D). These were transformed to the coded variables, x 1 , x 2 , and x 3 in order to better determine the relative size of their effects. The codes were", "All B. thuringiensis Al Hakam test runs from Table 1 had complete inactivation except for runs one, three, six, nine, and twelve. Except for run one, a center point, these observations had temperature at the low setting." ] },{ "paper_id": "a8119ed9e9815a775ecff9c603542fe9ff7ae725", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HIV establishes a persistent infection in human hosts, with the depletion of CD4+ lymphocytes, the major target cells of viral infection in vivo, eventually resulting in defective cellular immunity, and thus leading to full-blown AIDS. The Joint United Nations Programme on HIV/AIDS (UN-AIDS) estimates that there were 35.3 million people living with HIV at the end of 2012 compared with 26.2 million in 1999 -a 35% increase. Although important progress has been achieved in preventing new HIV infections and prolonging HIV patients' life with antiretroviral therapy, the infection cannot be eradicated and therefore AIDS-related illnesses are projected to continue as a significant worldwide cause of premature mortality in the coming decades if a decisive cure is not found (40) .", "PDB ID: 2N4Y.", "Supplementary Data are available at NAR Online. " ] },{ "paper_id": "a81f08700b297b78c8f255c4a428f2675ca45ef9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chemicals. Asolectin (1,2-Diacyl-sn-glycero-2-phosphocholine Type II-S) was purchased from Sigma (Missouri, USA). All salts (KCl, MgCl 2 , CaCl 2 , BaCl 2 , NaCl), Hepes, MOPS, K-EDTA, and sucrose were also obtained from Sigma with at least >99.0% purity. Hexadecane was obtained at TCI (Oregon, USA) and pentane (high purity solvent grade) from Burdik & Jackson (New Jersey, USA). DMSO was obtained from EMD Millipore (Massachusetts, USA). For giant unilamellar liposomes, 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) and cholesterol were purchased from Avanti Polar Lipids (Alabama, USA)." ] },{ "paper_id": "a81fbdb3bc7956412cd686e72115f4cddf1090be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The strong cytotoxic effect of alphavirus-based vectors on host cells, holds drawbacks for their use as anticancer vaccine moieties. In contrast, this feature is highly appreciated for oncolytic vectors as reflected in the amount of ongoing studies with oncolytic alphavirus-based vectors (124) .", "Dendritic cells in both humans and mice represent a population of at least four different subtypes with distinct phenotypical and functional characteristics (4-7). These subsets are: plasmacytoid DCs (pDCs), two subsets of conventional DCs (cDC1 and cDC2), and inflammatory DCs. The latter represent a monocyte-derived subset that appears during inflammatory responses (Table 1) .", "Nature has fine-tuned viruses to highly efficient gene transmitters in a cell-specific fashion with intrinsic adjuvantlike features. Hence an abundant range of viral vectors has been explored and tweaked substantially to develop anticancer vaccines with specific features. As a result we believe it will not be a matter of finding the \"one-fits-all\" vector but the \"most appropriate combination\" for the cancer type and stage at issue. " ] },{ "paper_id": "a820465dbd9b10702c009445daa65b9bd48e0c72", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusions: There were positive associations between CO levels and childhood inpatient visits as well as NO 2 , CO and PM 10 and outpatient visits.", "Background: A nationwide asthma survey on the effects of air pollution is lacking in Taiwan. The purpose of this study was to evaluate the time trend and the relationship between air pollution and health care services for asthma in Taiwan.", "In conclusion, the present study provides evidence that exposure to the outdoor air pollutant, CO, exerted adverse effects on health and increases in the child admission. Our study also showed a linear association between NO 2 , CO, and PM 10 and outpatient visits. It is an important public health policy to monitor air quality and warn the public about atmospheric factors that could be associated with increased risks of asthma.", "Methods: Health care services for asthma and ambient air pollution data were obtained from the National Health Insurance Research database and Environmental Protection Administration from 2000 through 2009, respectively. Health care services, including those related to the outpatient and inpatient visits were compared according to the concentration of air pollutants." ] },{ "paper_id": "a825eb21bd4ff17296f2f289faa849d326472b73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a8557b122155d371bbf43c23abf059b526da6496", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To aid comparison across scenarios, we made several assumptions prior to evaluation to determine effectiveness of the different scenarios.", "Implementation of oral fluid testing for African swine fever, classical swine fever, or footand-mouth disease surveillance is not yet possible due to several limitations and information PLOS ", "OPEN ACCESS" ] },{ "paper_id": "a85684483483909019d84ebf3061582317fc841e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a85a6d90b479fd8547830827ec8898750794cdf3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Some of the open questions regarding autophagy regulation have accurately been discussed in a recent compendium [96] .", "The major amount of lipids, however, is required for the expansion of the phagophore into an autophagosome.", "The energy-sensing AMP-activated protein kinase (AMPK) and glucose-sensing protein kinase A (PKA) also regulate the Atg1/ULK1 complex by direct phosphorylation [90] [91] [92] . The molecular details of these regulations and the cross-talk between them remain to be elucidated." ] },{ "paper_id": "a85c514ecb1b99f55aafe306a5f3351d231a4de2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a87c83a672852a6d046357d68715f3c3c0cdf5b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Illegal bushmeat traffic is a problem for biodiversity conservation and is also a potential threat to human health when contaminated tissues are consumed [91] . Even legal bushmeat is a potential infectious hazard.", "Frugivorous, insectivorous or hematophagous bats worldwide have been studied for their role as reservoirs of infectious agents. Many viruses isolated from bats are able to cross the species barrier and infect humans, regularly causing severe diseases in humans (e.g., SARS, Ebola hemorrhagic fever, Nipah, rabies) (Table 2a) . Most metagenomic studies targeting wildlife have been conducted on bats (Table 2b) [59] . Because \"bat science\" is a large and well-studied area in infectious diseases, this review will not focus more on this topic.", "The end result of most of these PCR methods is amplified DNA that requires definitive identification by sequencing." ] },{ "paper_id": "a88ec297fe59d6c950ea8123ddda210a7b134032", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The E. coli strains used were either the ccdB resistant strain DB3.1 (Invitrogen) or the ccdB sensitive strain DH5\u03b1. Both were grown at 37\u00b0C in LB broth medium with appropriate antibiotics. Several different commonly used yeast lab-strains were grown at 30\u00b0C in synthetic defined medium (Clontech) lacking the appropriate amino acids.", "Competent yeast cells were transformed using the LiAc/SS carrier DNA/PEG method [39] .", "Total yeast protein extracts were obtained as described [41] and concentration quantified using the Bio-Rad Protein Assay (Bio-Rad). Samples were combined with 5x Laemmli loading buffer and denatured for 10 min at 95\u00b0C. Subsequently, 30 \u03bcg total protein was loaded on a 4-15% Mini-PROTEAN W TGX \u2122 Precast Gel (Bio-Rad) and transferred to a PVDF membrane using the Trans-Blot Turbo transfer system (Bio-Rad). Detection was performed using the following primary antibodies: anti-FLAG (Sigma), anti-c-myc-HRP (Invitrogen), anti-HA (Roche), and anti-V5 (Sigma)." ] },{ "paper_id": "a89a80a592e5af122545d57ff70bc683d28831e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a8a55f01d9e4a3e3b77512767ab78bb8d1d74a25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We should prepare for severer and longer infection pandemic as soon as possible.", "Historically, the professionalism of medical workers has been tested by various events such as HIV, Ebola hemorrhagic fever, the Tokyo sarin gas attack, SARS and so on. Among these events, SARS raised the question of how professionals should respond in public emergencies. SARS spread to 26 countries, where it infected 8096 people and killed 774 (mortality rate: 9.6%). Most hospitals continued to serve the public, but at least one hospital in China ceased to function because of mass absence of its workers [1] . Many people in the public were afraid of what would happen if infections like SARS occurred on a pandemic scale.", "Additional file 1: Questionnaire" ] },{ "paper_id": "a8a9aa42224ef1fe08733dda2169f2e18ce6e92d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In this review, we have used a classification that aims to combine the two classifications above: 1) The smuggling of large quantities for commercial intentions, including the illegal sale and usage of catering leftovers from planes, ships and trains; and 2) The informal import for personal consumption (in personal luggage or by post/mail).", "As globalization increases the interconnectedness between nations, economies, and industries,", "The following main exposure pathways can be considered: 1) Direct pig-to-pig contact; 2) Feeding on contaminated meat; 3) Fomite-pig contact, e.g. vehicles. Bellini et al. [10] described the preventive measures available to reduce such exposures, specifically for ASF." ] },{ "paper_id": "a8adfbfaece0694336909eceb6fa3ed7e737ae9e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IL-6 F: TGACCACTCCTGACCCAACC, R: TCCAGACTCCGCAGGATGAG; IL8F: ACTTCCAAGCTGGCTGTTGC, R: CTGGCATCGAAGTTCTGAACTG.", "Supporting Information Table. Representative data in different groups.", "(XLSX)" ] },{ "paper_id": "a8b614e1c39170f6cab8198aa119e71f28421669", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 5823 studies were retrieved, of which 678 duplicates and 4797 irrelevant studies were removed. After reading 311 abstracts, 201 full text studies were assessed for eligibility. This eventually resulted in 62 studies including references from snowballing (see Fig 1. PRISMA flowchart).", "(Continued) ", "Passive sampling: 78/110Active sampling: 12/14" ] },{ "paper_id": "a8b6b8608dfcb6b75a320c6a2661846bd152689c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a8b801f23efa409e89226176fec4c0517e330717", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Digestion 5%", "Apoptosis 5%", "Detoxification 1% Immune response 12%" ] },{ "paper_id": "a8c077a7cfb866ed4ad64e152568313e586ca77d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that they have no competing interest.", "Authors' contributions SS designed the study, wrote the review manuscript, and was involved in the discussion. DK made intellectual contributions. KK conceived of the project, provided intellectual contribution, and guided the manuscript writing and editing. All authors read and approved of the final manuscript. Fig. 5 Fibrosis of diabetic kidney. Diabetic kidney fibrosis is associated with suppression of microRNA29s, which targets both DPP-4 protein levels and TGF\u03b2-activating process", "In general, incretins are a group of metabolic hormones that stimulate a decrease in the blood glucose levels, by either increasing insulin release or reducing gastrointestinal absorption. The prototypical incretins are the intestinal GLP-1 and GIP hormones, and both GLP-1 and GIP are rapidly inactivated by the enzyme DPP-4. Therefore, DPP-4 is a well-documented drug target for the treatment of type 2 diabetes [33] [34] [35] . The pharmacological inhibition of DPP-4 results in GLP-1 accumulation, which stimulates insulin secretion and contributes to the reduction of postprandial hyperglycemia. Recently, the beneficial pleiotropic effects of DPP-4 inhibitors were reported in both clinical research and preclinical experiments." ] },{ "paper_id": "a8c1235bde8c7b6c2be395f062d100de29e658b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fluorescent images were obtained at \u00d710 or \u00d720 with a laser scanning confocal microscope (Zeiss, LSM710) equipped with 405, 488, 561, and 633 laser lines. For images taken for pixel-based quantification, identical settings were used for all images in a set. For images chosen for publication, distracting artifacts were removed in ImageJ (Schneider et al. 2012 ) and levels were adjusted in Photoshop to maximize the signal-to-noise ratio so that relevant features could be seen more clearly. For images chosen to highlight pixel-based quantification, sham and ZIKV group images were adjusted identically to enable equitable comparison.", "Male and female AG129 mice (van den Broek et al. 1995) were bred in-house in sterilized cages and maintained in a 12/ 12 light cycle. Mice were randomly assigned to treatment groups based on weight, gender, and baseline measurements.", "Data were graphed and analyzed with Prism (GraphPad Software, Inc.) for statistical significance using t tests or two-way ANOVAs with post hoc t tests. Linear regression was used for correlation analyses." ] },{ "paper_id": "a8cec4aaa782514ef42b320b845e9d2d1804b42d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two sets of blood cultures (BacT/Alert, BioMerieux) were drawn from each patient before initiation of intravenous antibiotic treatment.", "Conflict of interest The authors declare no conflicts of interest in relation to this study.", "Nasopharyngeal samples from the original tubes were prepipetted to 96-plates in a Microlab Starlet (Hamilton Robotics, Switzerland) before extraction. Total nucleic acid extraction was performed with the MagNA Pure 96 instrument (Roche Applied Science) using the DNA and Viral NA small volume kit, the protocol Pathogen Universal, sample volume 300 \u03bcL and elution volume 100 \u03bcL [20] . Samples of extracted nucleic acids were mixed into the PCR reagents with a Qiagility (Qiagen, Hilden, Germany).", "Informed consent Informed consent was waived because of the observational nature of the study." ] },{ "paper_id": "a8d63649b68d0dc86f49b474ef863ece99f915a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SPSS software package v21.0 was used for all statistical analyses. Categorical variables were expressed as frequencies and percentages. The chi-square and Fisher's exact tests were used to compare groups. Continuous variables are expressed as the mean and standard deviation. Student's t-test was used to assess the statistical significance between groups. p < 0.05 was considered to be statistically significant." ] },{ "paper_id": "a8d8faf148d930bc5d0b5908b0069c770123109e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NiV (Malaysia strain) was kindly provided by the Special Pathogens Branch of the Centers for Disease Control and Prevention, Atlanta, Georgia, United States. The virus were propagated on Vero cells in Dulbecco's minimal essential medium supplemented with 10% fetal calf serum (Hyclone, Logan, UT), Lglutamine, penicillin and streptomycin at 37uC in a humidified CO2 incubator (5%). All infectious work was performed in a class II biological safety cabinet in a biosafety level 4 laboratory (BSL4) at the Galveston National Laboratory.", "Approval for animal experiments was obtained from the Institutional Animal Care and Use Committee, University of Texas Medical Branch (protocol number 0905041). Animal work was performed by certified staff in an Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) approved facility. Animal housing, care and experimental protocols were in accordance with NIH guidelines of the Office of Laboratory Animal Welfare. Discarded tissue from deceased human fetuses was obtained via a non-profit partner (Advanced Bioscience Resources, Alameda, CA) as approved under exemption 4 in the HHS regulations (45 CFR Part 46). Need for informed consent was waived by the UTMB Institutional Review Board.", "Whole blood was tested for presence of infectious virus by 10fold diltutions as described below. Tissue samples were weighed and homogenized in 10 equivalent volumes of DMEM to generate a 10% solution. The solution was centrifuged at 10,000 rpm under aerosol containment in a table top centrifuge for 5 min to pellet insoluble parts. Virus titration was performed using a TCID50 assay on 96-well plates (1610 4 Vero cells per well) with 100 mL inocula (cleared homogenate or whole blood) from 10-fold serial dilutions. Plates were incubated for 3 days at 37uC, and wells were scored for cytopathic effect (CPE). Virus concentrations were calculated as TCID 50 per gram of tissue." ] },{ "paper_id": "a8dc7f137a340a631699a817a26b4b4d26136e7b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "5F7E, 5FA2, 5FEC, 5IGX, 5I90", "4JPK, 4JPI", "VRC03" ] },{ "paper_id": "a8e457ae28d8267ce76183b65b7ff026c346bec5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We quantified the changes in hospitalisation days empirically into various components, using a decomposition analysis. Ageing was found to make the strongest contribution to increasing inpatient demand, and will continue to do so. \u2022", "The methodology in this paper can readily be adopted in other settings, to assess the contribution of ageing, so that more focused and targeted measures can be developed.", "The five components in Equation ( Structural decomposition analysis, 31 which was developed in the field of economics, was thought to be suitable for this study. To measure the change of total hospitalisation days between two years, the decomposition formulation of the difference takes the form:" ] },{ "paper_id": "a8f484e668a71d016a40b1fd1de16fbf2e539ebe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a8f7ee410837cdbf7f974543e432d161fb70cd11", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total cell lysate was harvested at 0h, 8h and 10h post-infection and extraction was carried out using Total RNA Mini Kit (Blood/ Cultured Cell) (Qiagen). Extracted RNA was then subjected to Reverse-Transcription Real-Time Polymerase Chain Reaction (qRT-PCR).", "Cells were washed twice with PBS and lysed with 100\u03bcL of Passive Lysis Buffer (Promega) for 15 min at room temperature with shaking. After complete lysis, the lysate was transferred to an opaque white 96-well plate. Luciferase activity was quantified using GloMax-Multi Detection System (Promega) according to manufacturer's instructions." ] },{ "paper_id": "a8fb2e52e4545f4de90bc13e44ae914d9da6a8ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Isolation precautions (IPs) are used to minimize pathogen transmission and hospital-acquired infections. The three main indications are (i) microorganisms with antibiotic resistance (e.g., Methicillin-Resistant Staphylococcus aureus (MRSA), Vancomycin-Resistant Enterococcus (VRE), and Extended Spectrum Beta-Lactamase (ESBL) secreting organisms), (ii) microorganisms with high transmission (e.g., Clostridium difficile (C Diff), Mycobacterium tuberculosis (TB), norovirus, and influenza virus), and (iii) microorganisms with high virulence (e.g. severe acute respiratory syndrome (SARS) and Ebola virus disease (EVD)).", "We expend finite resources whenever we screen and isolate.", "Thomas Carlyle (1800s Scottish Philosopher)" ] },{ "paper_id": "a9075cf8e6853657941c799058d329b3e386fecd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Combination of different assemblies of the data can help to close potential gaps and confirm the sequences.", "Sequence assembly consists of searches of overlaps, alignment, and merging of sequences. Computational limitations however prohibit most assemblers to perform exhaustive overlap searches. In iterative assembly, the resulting contiguous sequences (contigs) and singletons of the initial assembly are subjected to assembly by the same or a different assembly algorithm. This process is repeated until no new contigs can be found. Iterative assembly disregards coverage information and is therefore well-suited for metagenomics samples where coverage biases might exist.", "Another method to link fragments is to extract all information obtained from an assembly by looking at the original contig graphs (Mulyukov and Pevzner, 2002) . Information on adjacency of contigs can be found in such graphs and extracted for genome finishing. This method has successfully been applied when sequencing the gram-negative bacteria Rickettsia prowazekii (Nagarajan et al., 2010) . Contig adjacency information is especially useful if repeats exist that are longer than the read length, and contigs were split at positions where the reconstruction was ambiguous.", "After linkage of fragments it can be necessary to determine the order of the fragments by generating overlaps between contigs. Order might be inferred from paired end data, if available, but can also be deduced from augmented assemblies, produced by applying different assembly and alignment parameters. Wrong assemblies at contig ends can be the reason that no further overlap has been found by an assembler. Editing of contig ends improves wrong assemblies and facilitates subsequent gap closing with a different assembler." ] },{ "paper_id": "a912f654028e787673b235c9ba2eb2d161e372aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data from only two groups were analyzed by the Student's t-test (Welch's t-test or Bartlett's test), and data from multiple groups were analyzed by one-way ANOVA followed by Tukey's test. ", "Cytotoxicity assay was performed to determine the non-toxic concentration of compounds against fcwf-4 cells ( Figure 1 ). The concentrations used in this study were selected because they had low cytotoxic effects (cell viability: >83-90%) on feline cells. ", "The fcwf-4 cells were seeded on 96-well plates. The compounds were added to the wells in triplicate. After incubation for defined periods, the culture supernatants were removed, WST-8 solution (Kishida Chemical, Osaka, Japan) was added, and the cells were returned to the incubator for 1 h. The absorbance of formazan produced was measured at 450 nm using a 96-well spectrophotometric plate reader, as described by the manufacturer. Percentage viability was calculated using the following formula: Cytotoxicity (%) = [(OD of compound-untreated cells\u2212compound-treated cells)/(OD of compound-untreated cells)] \u00d7 100." ] },{ "paper_id": "a918e4f69a765616d8708c2267fb54ddb8644409", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Other authors do not have any competing interests in the manuscript. ", "Not applicable.", "Co-author Kok Keng Tee is an Associate Editor for Virology Journal. This does not alter the authors' adherence to all the Virology Journal policies on sharing data and materials." ] },{ "paper_id": "a91c693865733755a406dbca884738a75b886455", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The bivariate analyses are shown in detail in Additional file 1." ] },{ "paper_id": "a92044661e4999b7f34275c0bf742cf6e03955b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To obtain mouse serum, whole blood was clotted on ice for 20 minutes before centrifugation (10,000 g610 min at 4uC). Fresh serum (15 ml, diluted 1/100) was mixed with an equal volume of 26 SDS-PAGE Sample Buffer containing b-mercaptoethanol (Sigma). After a 4 minute incubation at room temperature (RT) the samples were heated at 65uC for 4 minutes. The samples were subjected to 10% SDS-PAGE using Tris-Glycine running buffer and then transferred to nitrocellulose membranes. The membranes were blocked overnight with 5% nonfat dried milk in Trisborate saline (TBS) buffer. Primary goat anti-mouse C3 (1/10,000 dilution; MP Biomedicals) or goat anti-human factor B (1/5,000 dilution; Complement Technology, Inc.) antibodies were incubated with the membranes for 1.5 hours at RT. After three washes with TBS containing 0.05% Tween 20, HRP-conjugated rabbit anti-goat IgG (Sigma) was incubated for 1 h at 37uC. After three washes with TBS-Tween 20, membranes were visualized using a SuperSignal West Kit (Pierce).", "This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocols were approved by the Institutional Animal Care and Use Committee at the Washington University School of Medicine (Assurance Number: A3381-01). Dissections and footpad injections were performed under anesthesia that was induced and maintained with ketamine hydrochloride and xylazine, and all efforts were made to minimize suffering.", "Forty-eight hours after WNV infection, serum was obtained by intracardiac heart puncture, followed by intracardiac perfusion (20 ml of PBS), and organ recovery. Organs were weighed, homogenized using a bead-beater apparatus, and titrated by focusforming assay [83] on Vero cells. Infected cell foci were stained with a flavivirus-cross-reactive, chimeric mouse-human MAb (WNV E18, 1 mg/ml) [84] for one hour at 37uC and then washed. Foci were detected after the cells were incubated with a 1:2,000 dilution of horseradish peroxidase (HRP)-conjugated goat anti-human IgG (Sigma) for one hour. Staining was visualized by addition of TrueBlue detection reagent (KPL). Spots were analysis with a Biospot counter (Cellular Technology) using Immunocapture software." ] },{ "paper_id": "a92d2df5aae260091456d3a65800c01cca79d599", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical data collection. Clinical data were abstracted from the medical record onto a standardized form.", "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request." ] },{ "paper_id": "a9348f9a4519219e9f2adfab6e093b66f4ee3131", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "China lacks any state issued official guidelines to diagnose brain death.", "Additional file 1: Table S1 . ", "On 26 June 1945 in San Francisco, the Republic of China (ROC), first in suffering Axis aggression, was also first to sign the United Nations Charter and Statute for the International Court of Justice, which entered into force on 24 October, establishing the United Nations. The latter date followed the Double Tenth Agreement (10/10/1945) [43] .", "More recently, Mr. Wang, who currently lives in Canada, revealed that he was once a member of a team extracting organs from a still-living person. The incident happened in the 1990s when Wang was an intern doctor at the urology department of the Shenyang Military General Hospital in Liaoning Province [26] ." ] },{ "paper_id": "a945fe15ef46edadf3f4712668dfc7ee8e5c821d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We sampled key documents and people. We used theoretical sampling to determine which people and documents were 'key'. Included among the individuals sampled were senior administrators, managers, physicians, nurses, patients and family members.", "The data were analyzed concurrent with collection using a modified thematic approach in three phases: open coding, axial coding, and evaluation. In open coding, the data ", "There must be a mechanism for challenge, including the opportunity for revising decisions in light of considerations that stakeholders may raise." ] },{ "paper_id": "a9467bbfc6a67f8a76ac8242a14207676d03c041", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Writing -review & editing: GC SB MD LA BC LD LM." ] },{ "paper_id": "a94e4109b44346c490243c71fd533cd1a9fd047c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In little more than a decade, RNAi discovery has led to understanding the molecular processes responsible for small RNA biogenesis and function, as well as to developing reagents that utilize the power of the RNAi pathway. Notwithstanding the numerous hurdles for translating these technologies into therapy, such as important considerations for therapeutic RNAi that gene silencing approaches rarely remove 100% of a transcript, that off-target silencing can occur and that each target organ, cell type and target transcript presents unique challenges. Promising early clinical results warrant guarded optimism." ] },{ "paper_id": "a950b2355ef4a4ab294862a26fff70d090a81d6c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition to the above data, SKEMPI 2.0 also provides data on the location of the mutated residues, the homology between interactions in the dataset, and processed PDB files, which can be easily parsed.", "Motivation: Understanding the relationship between the sequence, structure, binding energy, binding kinetics and binding thermodynamics of protein-protein interactions is crucial to understanding cellular signaling, the assembly and regulation of molecular complexes, the mechanisms through which mutations lead to disease, and protein engineering. Results: We present SKEMPI 2.0, a major update to our database of binding free energy changes upon mutation for structurally resolved protein-protein interactions. This version now contains manually curated binding data for 7085 mutations, an increase of 133%, including changes in kinetics for 1844 mutations, enthalpy and entropy changes for 443 mutations, and 440 mutations, which abolish detectable binding.", "Defining homologous interactions: Each entry also specifies which other entries are mutations to homologous interactions. Two interactions are deemed homologous if they have a shared binding partner or homologous binding partner and at least 70% of the corresponding interface residues are common to both interactions. We determine the homology between proteins using the GAP4 program (Huang and Brutlag, 2007) , and define homologous proteins as those with a similarity score greater than 50 and at least 30% sequence identity. Interface residues are defined as those with a nonhydrogen atom within 10 \u00c5 of a non-hydrogen atom on the binding partner. Interactions falling within manually assigned clusters of homologous interactions are designated as pMHC/TCR, antibody/ antigen or protease/inhibitor. While the names of these clusters have been chosen to reflect the predominant function of their constituent interactions, they reflect the homologies within the dataset and are not functional assignments. Thus, for instance, some nanobodies are classified as antibodies as they bind to the same site as cetuximab, 14.3.d is classified as TCR, even though it is only the b chain, and its binding partner, enterotoxin C3, is classified as a pMHC." ] },{ "paper_id": "a95452bb03845776e74c5af3dd628cb5c25a02aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The search terms used are shown in Table 1 . Search terms for \"dog\", \"sentinel\", and \"disease\" were combined using the 'AND' Boolean operator.", "Of all the pathogens, thirteen (25%) were viral. Of these, eight were mosquito-borne (California serogroup viruses (CSGV), Chikungunya virus, equine encephalitis virus (EEV), Japanese encephalitis virus (JEV), Toscana virus, Usutu virus, Venezuelan equine encephalomyelitis (VEE), and West Nile virus (WNV)), two were sandfly-borne (Punique virus and sandfly fever Sicilian virus (SFSV)), and one was tick-borne (tick-borne encephalitis virus (TBEV)). Two were not vector-borne (Ebola and rabies).", "Of all the pathogens, eighteen (34%) were bacterial. Of these, one was flea-borne (Yersinia pestis), four were tick-borne (Anaplasma, Borrelia, Ehrlichia, and Rickettsia), one was rarely tick-borne (Coxiella), one was transmitted by trematodes (Neorickettsia), three were transmitted by various arthropods (Mycoplasma, Bartonella, and Wolbachia pepiens), and eight were not vector-borne (Bacillus anthracis, Bordetella, Brucella abortus, Brucella suis, Cryptococcus gatti, Helicobacter, Leptospira, and Mycobacterium goodii).", "When analyzed by World Bank global regions according to income (GDP), it was unsurprising to find that 69/142 (49%) results collected data from high-income economies, 57/142 (40%), from upper-middle-income economies, 10/142 (7%) from lower-middle-income economies, and five out of 142 (4%) from low-income economies. This bias against low-income countries supports concern for the lack of adequate systematic infrastructures and funding for surveillance and disease control in low-income countries, particularly regarding neglected zoonotic diseases, poverty alleviation, and emerging infectious diseases [10, [27] [28] [29] .", "Translating the theoretical idea of sentinel surveillance into a feasible and practical surveillance system requires examination of several factors. Firstly, the objective of the surveillance must be clear; for example, whether the objective is to measure frequency of disease or to provide a warning of disease emergence or expansion will determine which regions and dog populations will be most useful." ] },{ "paper_id": "a95e3a09d229a35ff2189682c618cff5add85e4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Eight main questions were asked, and individual responses were subsequently evaluated. The individual responses to each question were tabulated, and those that made the same points in common (coding) were written up. Other individual responses that were not proffered by other respondents were also evaluated for their pertinence in answering the question posed. Those that were pertinent were also included to provide a comprehensive response (collated answer) to each question (see Results).", "Collated answer -question 3:", "committee?", "AARONS within a country has to undergo preparations in order to function. We saw examples of this during the 2014 -2016 Ebola virus epidemic in parts of Africa, and the chikungunya virus infection that caused much morbidity in all countries of the Caribbean. We are now witnessing a wave of zika infection with its severe adverse neurological effects in some foetuses and neurotropic effects in some adults." ] },{ "paper_id": "a969190e8cae42cb65e639aee83d71d9f78c4dc0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Because conventional suckling pigs are the targets for future vaccine studies, PEDV-na\u00efve sow E was selected and the naturally delivered suckling piglets were inoculated orally with PC22A at 100 PDD 50 /pig at 4 days of age to verify the results from the CDCD pig experiments.", "Porcine epidemic diarrhea (PED) is a highly contagious enteric disease of swine characterized by acute watery diarrhea, vomiting, dehydration, and weight loss. It was first observed in farm pigs in England in 1971 [1] . The causative agent, PED virus (PEDV), was identified in 1978 [2] . Subsequently, PEDV caused epidemics with pig mortality in European countries until the late 1980s. Thereafter PEDV was more often associated with endemic cases in Europe. In Asia, epidemics with major losses in suckling pigs were first reported in 1982, continuing into the 1990s-2000s [3] [4] [5] . Since October 2010, severe PED epizootic outbreaks, affecting pigs of all ages but characterized by high mortality rates among suckling piglets, have been reported in China, causing significant economic losses [6] . In April 2013, PEDV emerged in US swine and spread rapidly throughout the country, leading to the death of 8 million pigs and economic losses between $900 million -$1.8 billion in 2013-2014 [7, 8] .", "To reduce the risk of cross contamination among pigs, PEDV PC22A-inoculated CDCD piglets were euthanized at onset of watery diarrhea and subjected to necropsy examination. Duodenum, jejunum, ileum, cecum, colon and mesenteric lymph nodes were collected and fixed in 10% neutral buffered formalin for histopathological examinations as described previously [9] . For each jejunum section, ten villi and crypts were measured using a computerized image system (PAX-it software, PAXcam, Villa Park, IL, USA) [9] . Villous height and crypt depth ratios (VH:CD) were calculated. Also, PEDV nucleocapsid (N) proteins were detected by immunohistochemistry (IHC) using mouse monoclonal antibody (SD6-29) (gift from Drs. Steven Lawson and Eric Nelson at South Dakota State University) [15] ." ] },{ "paper_id": "a977f44a0323a1017c2ba7e0ba03432fbf9aa822", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a986a6d115df1e271c89a765800aa931ac3f6833", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare they have no competing interests." ] },{ "paper_id": "a9a03b8e5d632fb01f973df42763da7fb0179629", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data used to support the findings of this study are included within the article.", "x ij represents the number of codons for the amino acid and ni represents the degenerate numbers of a specific synonymous codon that ranges from 1 to 61.", "The authors declare that they have no competing interests." ] },{ "paper_id": "a9af3598d5bb039283b8334f770488e6e8e6821c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nuclear, cytoplasmic, and whole cell lysates were quantified by Bradford assay and resolved by SDS-PAGE and western blotted with antibodies against PABPC (Cell Signaling, 1:1000), PABPC4 (Bethyl, 1:1000), LARP4 (Thermo Fisher, 1:1000), Gapdh (Abcam, 1:3000), Histone H3 (Cell Signaling, 1:2000), LYRIC (Abcam, 1:1000), RRBP1 (Bethyl, 1:1000), MSI1 (Abcam, 1:1000), Lin28b (Abcam, 1:1000), CHD3 (Cell Signaling, 1:1000), RPP20 (Novus, 1:1000), THOC6 (Life Technologies, 1:1000), PNN (Life Technologies, 1:1000), EXO4 (rabbit polyclonal produced using recombinant EXO4 with an MBP tag, 1:1000), NPM (Abcam, 1:1000), GW182 (Abcam, 1:1000), DDX6 (Bethyl, 1:1000), DCP2 (Bethyl, 1:1000), TRIM32 (Abcam, 1:1000), RNAPII Rpb1 (BioLegend, 1:2000), TBP (Abcam, 1:2000).", "Mass spectrometry proteomics data reported in this paper have been deposited at the ProteomeXchange Consortium via the PRIDE partner repository under accession number PXD009487.", "The following dataset was generated: " ] },{ "paper_id": "a9be3897c30e4a416d00398d86a623fc3d9faab5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a9cab864aceb9a873c6a049a8d7951ac80d993d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Monoclonal antibody (MAb) Ch/IBV 26.1 against the IBV S2 protein was obtained from Prionics (Thermo Fisher Scientific, Waltham, MA, USA) [37, 38] . The production of rabbit polyclonal antiserum k134 against MHV was described previously [39] . Chicken polyclonal antiserum was derived from a SPF chicken vaccinated with IBV strain H120 (BI, Ingelheim, Germany). Secondary fluorescently-labeled antibodies Alexa Fluor 488 goat anti-chicken IgY, Alexa Fluor 568 goat antirabbit IgG, and Alexa Fluor 488 goat anti-mouse IgG (Invitrogen by Thermo Fisher Scientific) were stored in 50% glycerol at \u221220\u00b0C.", "CAMs were collected from ECEs, washed in PBS, fixed in neutral buffered 10% formalin in PBS for 24 h, stored in 70% ethanol and finally paraffin-embedded. Four micrometer sections of CAM were mounted on glass slides and subsequently deparaffinized and rehydrated in alcohol series. Next, the sections were subjected to endogenous peroxidase inactivation and antigen retrieval as described before [40] . Sections were washed in phosphate buffered Normal Antibody Diluent (NAD, ScyTek Laboratories, Logan, USA) containing 0.1% Tween-20, and after primary antibody incubation with PBS 0.1% Tween-20. Sections were incubated for 60 min at room temperature with MAb Ch/IBV 26.1 diluted 1:100 in NAD. Antibody binding was detected by Dako Envision HRPO labeled polymer anti-mouse (Dako, by Agilent Technologies, Santa Clara, USA) diluted 1:1 in NAD, and visualized by 3-Amino-9-ethylcarbazole (AEC, Dako). Slides were counterstained with hematoxylin, mounted with Aquatex (Merck, Darmstadt, Germany), and viral antigen presence was assessed by light microscopy (BX60, Olympus, Tokyo, Japan).", "Avian coronavirus infectious bronchitis virus (IBV) primarily infects the upper respiratory epithelium of chickens, causing a respiratory disease that is frequently complicated by secondary bacterial pathogens [1] . In addition, some IBV strains affect the renal tubuli, oviduct and parts of the gastrointestinal tract, leading to pathological lesions in these organ systems, with subsequent reduced weight gain and a drop in egg production. The virus has a worldwide presence in both commercial and backyard chickens, appearing in a wide variety of geno-, sero-and protectotypes [2] . IBV is currently regarded as one of the economically most relevant viral pathogens in the poultry industry." ] },{ "paper_id": "a9e209c7a59e188267e27014ed46db5490b57543", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Overlapping PCR with canine pol1 promoter", "The vRNAs and cDNAs from wild type and blind passage reassortant viruses were prepared as previously described [22, 31] . Briefly, total RNAs were extracted by using the RNeasy kit (Qiagen, Valencia, CA) following manufacturer's instructions. Reverse transcription was carried out with the Uni12 primer (59-AGCAAAAGCAAGG-39) and avian myeloblastosis virus (AMV) reverse transcriptase (Promega, Madison, WI). The cDNAs were stored at 280uC until use.", "For sequencing the HA gene from plaque-purified viruses, the agarose was plucked from areas of the plate were plaques were observed. Viruses were eluted from the agarose pluck in tissue culture media and later expanded in MDCK cells for 72 h prior to RNA extraction, cDNA synthesis, PCR, and sequencing.", "The rescued viruses were examined by plaque assay in MDCK cells (30) . Briefly, confluent cell monolayers in 6-well plates were infected with 10-fold dilutions of virus in a total volume of 0.4 ml PBS for 1 h at 37uC. Cells were washed twice with PBS and covered with an overlay of modified Eagle's medium containing 0.9% agar, 0.02% BSA, 1% glutamine, and, when noted, 1 ug/ml TPCK treated-trypsin. The plates were then incubated at 37uC under 5% CO 2 . After 3 days of incubation the overlays were removed and the cells were stained with 0.1% crystal violet." ] },{ "paper_id": "a9e7f41215542f62723e5118535f51d7d0c5cdab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Informed consent was obtained from all participants after the nature and possible consequences of the studies were explained. ", "Flow cytometry data were analyzed using the FlowJo software (Tomy Digital Biology). Statistical analysis was performed using Prism (GraphPad Software). In addition, Wilcoxon signed rank test, Mann-Whitney U test, or one-way analysis of variance (ANOVA) post-hoc test was used when appropriate.", "(TIF) " ] },{ "paper_id": "a9eaa4a3217735fbc02153aeea3f34e9c763e5d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "a9f1cb393010b269321cb82a569379a5af380a89", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the protein sequences used in this study were downloaded from e National Center for Biotechnology ", "Our approach is first applied on two short segments of protein from \"yeast Saccharomyces cerevisiae\":", "Information encoded in the genome of any organism plays a central role in defining the life of that organism. e nucleotide sequence that forms any gene is translated into its corresponding amino acid sequence. is sequence of amino acids becomes functional only when it adopts its tertiary structure. Experimental methods such as X-ray diffraction and nuclear magnetic resonance are considered authoritative ways for obtaining proteins' structure and function. ese experimental methods are very expensive and time consuming. erefore, computational methods for predicting protein structure have become very useful. Proteins with similar sequences are usually homologous, typically displaying similar 3D structure and function." ] },{ "paper_id": "a9f21b4c08ef6cf4b7553c5666b4102d0c984243", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells are able to promptly repair damages, ranging from 0.2 to 10 \u03bcm, of cell membrane by cytoplasmic endomembrane;", "Host cellular defense is the first hurdle against viral infection. However, viruses are able to utilize cellular machineries for viral replication. Growing knowledge has helped identify broadspectrum antiviral agents by targeting the cellular machineries of defense, programmed cell death, and metabolism, as presented in the following subsections, and in Table 2 and Figure 1 .", "Current strategies of controlling viral infectivity focus on identification of agents capable of intervening in the essential steps for viral infection, including viral attachment, fusion/endocytosis, replication, assembly and budding in addition to drugs targeting viral envelope, as detailed in the following subsections, and in Table 1 and Figure 1." ] },{ "paper_id": "aa05b23cbdb62abd6dc349744370d9338a2f4e21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "aa080b8ad0bb2c4cd4e24f407b32f0e837c27432", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics statement. Our animal research was conducted under the guidance of the SCAU's Institutional Animal Care and Use Committee. The chicken sampling procedures were approved by the Animal Care and Use Committee of Guangdong Province, China." ] },{ "paper_id": "aa14d6de32495ec579e30a5c6f1ae21666c01c8a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The intranasal route of drug administration has been frequently used to treat local conditions such as nasal congestion and allergy. Intranasal administration is characterized by easy administration, rapid onset of action and avoidance of first-pass metabolism. The needle-free administration route is non-invasive and can avoid the risk of spreading blood-borne infections, which is a particular problem in developing countries. These desirable features lead to the exploration of the systemic delivery of polar drugs or biomolecules including vaccines that are not feasible in other administration routes.", "High versatility is one of the attractive features of polymer-based DNA delivery systems. Cationic polymers can form complexes (polyplexes) with nucleic acids through electrostatic interaction. Polymer synthesis is relatively cheap and is easy to scale-up. Particle size and surface properties of polymeric particles can be controlled by using different polymers and fabrication methods in order to optimize their cellular uptake and transfection efficiency. The polymeric particles can also be modified to include specific function groups or ligands to enhance immune responses.", "Overall, many recent preclinical studies and clinical trials have indicated that DNA vaccines are generally well tolerated with good safety profile, and no systemic inflammation was reported [11, 14, [51] [52] [53] [54] . Nonetheless, DNA vaccines are relatively new vaccination approaches and yet to be approved in human use, the long term safety of their uses must be thoroughly evaluated for routine prophylactic and therapeutic use in human, especially when new delivery systems or adjuvants are introduced into the formulation.", "Mankind has been haunted by respiratory infectious diseases for aeons. They have created public health concerns since ancient times. With the emergence of new or drug-resistant strains, it is becoming a challenge to protect the public from infections using conventional vaccine methods. DNA vaccines have huge potential for the prevention of respiratory infections due to their ability to offer broad immunity, the relatively rapid process of designing new DNA vaccine construct and the possibility of large-scale production in a short period of time. In this section, four pathogens that cause severe diseases in the airways are highlighted, including tuberculosis, coronavirus, influenza and respiratory syncytial virus, with a brief discussion of current DNA vaccine development against these infections.", "To evaluate the efficacy of DNA vaccine in humans, serum antibody titer or the enzyme-linked immunoSpot (ELISpot) assays are the commonly employed methods to measure the immunogenic response, although the induction of antigen-specific immune effectors by an immunization process does not imply that these antibodies or cytokines represent surrogates or correlates of vaccine efficacy. In early stage of vaccine development, in vitro serum antibodies and ELISpot assays are the direct detectable indicators of the clinical potential of a vaccine formulation. At later stage of development, morbidity and mortality (especially the improvement of survival rate after vaccination) in animals upon target pathogen challenge is a more certain way to confirm the protective efficacy of vaccines [28, 29] , as the ultimate goal of vaccine is to prevent the targeted disease. The efficacy of vaccine such as influenza vaccine could be monitored in human during subsequent influenza epidemic season [30, 31] or challenged with a controlled influenza virus [32] . However, some lethal virus challenge studies are difficult to conduct directly on human. Hence, the measurement of antibodies production and immune responses in humans remain the most direct way to assess vaccine efficacy. Longer study is required to investigate if the vaccine is indeed able to prevent disease.", "A number of studies have already demonstrated the potential of liposomal DNA vaccine system for intranasal administration, and some could offer considerable immune protection against respiratory infections in animals. However, the lipid composition of different liposomal systems varied greatly, and currently there is a lack of knowledge of how the composition may affect the immune response. To enable the utilization of liposomal DNA vaccine for clinical application and approval, a better understanding of how these factors govern the efficacy and immunity of the liposomal delivery system must first be sought." ] },{ "paper_id": "aa1eaad52d7a7827850cecf3d6b582e728e7e543", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Toxicological diagnostic screening of the liver tissue showed no evidence of anticoagulant poisons.", "Clinical data for cases 2 and 3 are present in Table 1 .", "Early in January the following year both dogs participated in a sled race resulting in a time track record, and medal placements in various championships were achieved the following season." ] },{ "paper_id": "aa1f783a1af8b14cdbee5ea50cc0a78c56d7442e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Crystal structure and thermostability of the H2Db-NP-N3A complex", "Na\u00efve precursor frequency and TCR repertoire for D b NPN3A", "Thermostability measurements of recombinant class I complexes using circular dichroism (CD) Circular Dichroism Spectra were measured on a Jasco 815 spectropolarimeter using a thermostatically controlled cuvette. A far-UV spectra was collected from 190nm to 250nm. The UV minimum was determined as 219 nm for H2Db-NP-N3A. The measurements for the thermal melting experiments was made at the minimum for H2Db-NP-N3A, at intervals of 0.1uC at a rate of 1uC/min from 20uC to 90uC. The Jasco Spectra Manager software was used to view and smooth the traces and then the GraphPad Prism software was used to plot Temperature versus % unfolded. The midpoint of thermal denaturation (Tm) for each protein was determined as the point at which 50% unfolding was achieved. The measurements were done in duplicate at two concentrations (4mM and 2.2mM) in a solution of 10mM Tris pH 8, 150mM NaCl." ] },{ "paper_id": "aa2d1de5f5f45ad793fffda7679200d35e971b4f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We observed that a reduced number of cells were irregular and smaller than average, with an area smaller than 30 mm 2 .These include partially attached cells, due to the semi-adherence of the S2R+ cell line, as well as a small number of unhealthy cells, and were not included in subsequent analysis.", "We observed that a reduced number (7.5%) of SGs were weakly stained and were not recognized by the above operations. This was compensated by the application of the imfilter function with the fspecial: unsharp filter thus allowing faint or blurry SGs to be detected. These newly acquired SGs were added to the SGs identified in the unfiltered image, so for each micrograph, 16 correlations (8 prototypes, 2 Cy3-micrographs with or without filter) were assessed.", "Cells in 384 MW plates were analyzed in an OPERA Autoscope at the DRSC and 636 micrographs were captured at 5126512 pixels. Cells in glass coverslips were analyzed after mounting. Images were acquired in a LSM510 Meta confocal microscope (Carl Zeiss, Oberkochen, Germany) using Zeiss LSM software at 25uC and EC 'Plan-Neofluor' 406/1.30 Oil or a Plan-Apochromat 636/1.4 Oil. Equipment adjustment was assessed using 1 mm FocalCheck fluorescent microspheres (Molecular Probes). Magnification and resolution were as follows: Figures 2A, 2B , 3A, 4 and 5B: 636, 102461024 pixels; Figure 3B : 406, 204862048 pixels; Figure 1A and 5A: 636, 5126512 pixels." ] },{ "paper_id": "aa2ed61346b7c005b96d661476a671b555b2a93a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Middle East Respiratory Syndrome (MERS) is a severe respiratory infection caused by a novel beta coronavirus (MERS-CoV) [1] [2] [3] . The symptoms of MERS include fever, chills, cough, shortness of breath, gastrointestinal symptoms, expectoration, wheezing, chest pain, hemoptysis, sore throat, headache, myalgia, abdominal pain, vomiting, and diarrhea; it can also cause death in severe cases [3] [4] [5] [6] .", "The causative pathogen of MERS is transmitted via 4 modes: animal-to-human, intra-familial, healthcare-associated, and travel-related [7, 8] . The 186 cases that occurred in South Korea (hereafter Korea) were predominantly caused by healthcare-associated", "The asymptomatic infection was acquired via healthcare-associated transmission. Thus, it is necessary to extend serologic studies to include inpatient contacts who have no symptoms.", "This study received approval from the bioethics committee of the KCDC (2015-08-EXP-03-P-A) and the institutional review board of the National Cancer Center (NCC 2016-0058). Informed consent was obtained from study participants or their parent or legal guardian for children under 14." ] },{ "paper_id": "aa34a2ba35c3daf0b882dfa8b96e65aa251b5ea8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Epigrass graphical user interface Figure 2 Epigrass graphical user interface.", "2. Edge-specification file: This is also a spreadsheet-like file with an edge per row. Columns contain flow variables.", "Cost in vaccines applied vs. benefit in cases avoided, for a simulated epidemic starting at a relatively low degree city(Salvador) Figure 7 Cost in vaccines applied vs. benefit in cases avoided, for a simulated epidemic starting at a relatively low degree city(Salvador)." ] },{ "paper_id": "aa5c3ba1a343c13446ce37073c2e03cf91032f28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus stocks were produced in transfected 293T cells. The Reverse Transcriptase (RT) activity present in virion particles in the culture medium was determined with a real-time PCR-based RT assay that used avian myeloblastosis virus (AMV) RT as standard [29] ." ] },{ "paper_id": "aa6297e7fd55345b1ef69a2cbbb9629d155580a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author details", "Steeper slopes indicate greater dose-dependency.", "To estimate differences in the dose-dependency of the virucidal effect of the tested compounds, we calculated the slope of a linear regression model fitted line for urea titration at each citric acid concentration and vice versa." ] },{ "paper_id": "aa69482e261bf1d6546491ba52991ea1ac3402a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PFCs were isolated by first lysing erythrocytes with an ammonium chloride solution and resuspending the pellet to a final concentration of 2610 6 cells/mL in complete RPMI 1640 medium (Invitrogen, Grand Island, NY) supplemented with 10% heat-inactivated fetal calf serum (FCS; HyClone, Logan, UT), 100 U/mL penicillin, 100 mg/mL streptomycin, 2 mM L-glutamine, and 50 mM 2-mercaptoethanol. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Hypaque gradient centrifugation of heparinized venous blood obtained from healthy individuals or TB patients.", "Wilcoxon matched pairs test (Two-tailed) was used to determine the statistical differences between the groups using GraphPad Prism software version 5. A value of p,0.05 was considered statistically significant.", "Conceived and designed the experiments: CW. Performed the experiments: LL DQ. Analyzed the data: LL. Contributed reagents/materials/ analysis tools: DQ XF. Wrote the paper: LL. Recruited all subjects: SL XZ." ] },{ "paper_id": "aa6d90b5eb890db486db2e09d3b28db343a7d48c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All questions about nonpharmaceutical preventive behavior required yes/no responses.", "The second survey assessed risk avoidance behaviors (June 23-25th) using the following questions:", "Adjusted odds ratios of nonpharmaceutical preventive behaviors according to political orientation." ] },{ "paper_id": "aa6fd0de59bb82e7c94b044d8145fbd50d7c9b9a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "aa7340d432336723e1ffd475cd2940170b33995c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "doi:10.1371/journal.pone.0142927.t001 contribution of each agent for the diarrhoeal morbidity and mortality estimates, and have taken a simplified approach to estimate uncertainty.", "Our results provide public health policy makers, including risk managers, and other stakeholders with information for advocacy for improved regulation and control of diseases commonly transmitted through foods. We highlight the most important diarrhoeal diseases in different regions and age groups, which will allow policy makers to define and improve control strategies targeted at different pathogens, settings and countries." ] },{ "paper_id": "aa80dd33eb3cc7ebcabeaee4b46635b8ddb64f4c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Synthesis of double-stranded cDNA. The concentration of RNA in the samples was measured with QUBIT RNA HS Kit in a Qubit 2.0 Flourometer (Invitrogen Thermo Fisher Scientific)). Using the SuperScript IV First-Strand Synthesis System (Invitrogen, Thermo Fisher Scientific) cDNA was synthesized with random hexamer on a Bio-Rad S1000 Thermal cycler according to the manufacturer's instructions. RNase H was added to each well and incubated for 20 min at 37\u02daC to destroy the template RNA. Ds-cDNA was synthesized by adding 0.5 \u03bcl of 3'-5' exo-Klenow DNA polymerase (Klenow Fragment, New England BioLabs) and incubating for 60 min at 37\u02daC followed by a 10-min enzyme inactivation step at 75\u02daC. The concentration of ds-cDNA was measured with QUBIT dsDNA HS Kit (Invitrogen, Thermo Fisher Scientific) and normalized to 0.2 ng/\u03bcl for further library preparation.", "Library preparation and sequencing. Libraries with dual indexing for each sample were generated with Nextera XT DNA Library Prep Kit (Illumina Inc, San Diego) according to the manufacturer 0 s instructions with the minor modifications that half the volumes were used for all reagents in the tagmentation and amplification steps. The libraries were cleaned up with AMPure XP beads (Beckman Coulter) and the size distribution and the concentration of each library were estimated using a High Sensitivity DNA Chip in an Agilent 2100 Bioanalyzer Instrument (Agilent). The libraries were diluted in Resuspension Buffer (Illumina) to 2 nM and pooled. After denaturation with 0.2 M NaOH, the pool of libraries was diluted in Hybridization Buffer (Illumina) to 10pM and combined with 1% denatured PhiX Control before sequencing on the Illumina MiSeq platform with MiSeq 600 Cycles Reagent Kit v3.", "In Fig 1 all figure. ). However, for the reads coming from diarrheic pools, there were also a significant number of reads assigned to Clostridia (light blue top), Escherichia-Shigella (orange) and Enterobacter (red).", "16S library preparation. Library preparation for sequencing of the variable V3 and V4 regions of the 16S ribosomal RNA gene was done according to the protocol 16S Metagenomic Sequencing Library Preparation (Rev.B) recommended and applied for the Illumina MiSeq System (Illumina Inc, San Diego). The amplicon libraries were combined at equimolar concentrations, spiked with 5% PhiX control, denatured and loaded on a MiSeq flow cell and sequenced with a 600 cycles reagent kit v3 (Illumina Inc, San Diego) in paired-end sequencing runs." ] },{ "paper_id": "aa833047a4b1e39dcdacffc2d5e219ffa4ddb06b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following Finkenst\u00e4dt & Grenfell [10] , we assume a general transmission model of", "License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.", "We then examined how variation in l and a 2 2 a 1 affected the left-hand side of equation (2.4) and likewise the critical proportion of the population to control in order to effect pathogen elimination, which, under our model, is p c \u00bc 1 2 (1/b)." ] },{ "paper_id": "aa8471e98490ab2c5a2dabea9a4d2f66c9427bfb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses are small, infectious, obligate intracellular parasites that are capable of replicating themselves within their host cells. They are even smaller than the smallest elementary biosystem, yet still possess some properties of living systems such as having a genome and the ability to adapt to changing environments. However, viruses cannot capture and store free energy and they are not functionally active outside their host cell [1] ." ] },{ "paper_id": "aa89136217edb205585668227efb1b0a976be854", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The isolated bacteria form (Table 1) . " ] },{ "paper_id": "aa89440c172e206c9cdd2f77373ed2b4d1a6b975", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated.", "This study was approved by the Institutional Review Board of Kyoto Prefectural University of Medicine and all procedures were conducted in accordance with the Declaration of Helsinki. All participants provided written informed consent after an explanation of the nature and possible consequences of the study." ] },{ "paper_id": "aa8a9f4a432fa52294b1fa674b3ffbeadeff563f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Prediction of protein topology and subcellular localization was done by NetNGlyc, NetOGlyc, TMHMM http://www.cbs.dtu.dk/services/, TMPred http://www.ch. embnet.org/software/TMPRED_form.html, and ProDiV/ TOPCONS http://topcons.cbr.su.se/index.php. The alignments and a sequence identity matrix were done by using BLAST and MEGA4 (BLOSUM; parameters p-distance and pair wise deletion).", "In addition to the S, E, M and N protein genes, the structural gene portion of CoV genomes contains a variable number of accessory ORFs. Because these accessory ORFs are not shared between different CoV groups, they are also referred to as group-specific ORFs [21] . Proteins encoded by group-specific ORFs of different CoV have been shown to influence pathogenesis, virus replication, or host immune response [21] [22] [23] [24] [25] [26] [27] . Others may be dispensable for virus replication in cultured cells of primate or rodent origin, as well as in rodent models [26, 28, 29] ." ] },{ "paper_id": "aa8c9ce5d6162a02fc51e0d95b27e63a709ca140", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using one-way ANOVA or 2way ANOVA with the Tukey multiple comparisons test as indicated in the Figure legends. The Wilcoxon matched-pairs signed rank test was also used where indicated. Correlation analyses were performed by non-parametric Spearman correlations. Statistics were generated using GraphPad Prism.", "All datasets generated for this study are included in the manuscript and/or the Supplementary Files.", "BAL samples were obtained using standard techniques (34) . Briefly, rhesus macaques were anesthetized, and an endotracheal tube was inserted through which sterile saline solution (10 ml/kg) was instilled. Suction was applied to recover the instilled fluid and the lung lavage was collected in sterile conical tubes. Cells were pelleted by centrifuging at 1600 RPM for 10 min at 4 \u2022 C and washed in 25 mL cold PBS. Centrifugation was repeated, and cells were resuspended for counting. Cells showed \u223c90% viability as determined by trypan blue staining." ] },{ "paper_id": "aa8d35501e36393df4a38d6c5ec187c7b1710a94", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "aa8fbab7c3255083bf78bcf8752b279ec210e684", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "aa92ab17aef0b2ef391bad5a3590956c72794948", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Text S1 Detailed study design and preliminary analyses." ] },{ "paper_id": "aa96296a83b9395223f9a9b1b116f50ae8bcdb11", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The identified intervention studies concerning single vs. multi-bedrooms provided sufficient data to allow the calculation of a risk ratio (RR). We used Review Manager (RevMan Version 5.0; The Cochrane Collaboration, 2008) to perform meta-analyses using a randomeffects model, if appropriate.", "We searched the databases Medline (assessed via Pubmed), EMBASE (assessed via OvidSP) and the Cochrane Central Register of Controlled Trials (CENTRAL). The detailed search strategy used for Medline (Pubmed) for each topic is shown in the Appendix (Tables 2-4) ." ] },{ "paper_id": "aa973f2833829b97ebdfd6ce2ac6a29b9100db3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mouse anti-FLAG (M2) and anti-\u03b2-actin antibodies were purchased from Sigma-Aldrich (St. Louis, MO, USA). Mouse anti-V5 and anti-HA (Y11) antibodies were purchased from Life Technologies (Grand Island, NY, USA) and Santa Cruz Biotechnology (Dallas, TX, USA), respectively. Rabbit anti-IRF3 and anti-phospho-IRF3 (Ser 386) antibodies were purchased from IBL-America (Minneapolis, MN, USA).", "Cell culture and Sendai virus HEK-293 human embryonic kidney cells were maintained in Dulbecco's modified Eagle's medium with 10% fetal bovine serum (Life Technologies) at 37\u00b0C in a humidified chamber supplemented with 5% carbon dioxide. Plasmid transfection was performed with GeneJuice (Merck Millipore; Billerica, MA, USA). poly(I:C) was purchased from Sigma-Aldrich and was transfected with Lipofectamine 2000 (Life Technologies). Sendai virus (Cantell strain) was purchased from American Type Culture Collection (Manassas, VA, USA).", "Dual-luciferase reporter assay, co-immunoprecipitation and western blotting were performed as previously described. 30, 38 Particularly, relative luciferase activity in arbitrary units was calculated by normalizing firefly luciferase activity to Renilla luciferase activity recovered from cell lysate. Non-denaturing native polyacrylamide gel electrophoresis (PAGE) was performed as previously described. 36, 39, 40 Bioinformatic analysis Sequence alignment was performed using Cluster Omega, an online tool based on the hidden Markov model, 41 and hosted by the EMBL-EBI server (http://www.ebi.ac.uk/Tools/msa/clustalo/). Transmembrane domain prediction was performed using TMFinder, which considers hydrophobicity and helicity of the amino-acid sequence (http://tmfinder.research.sickkids.ca/). 42 " ] },{ "paper_id": "aaa7d4e5136a4175368222cba1f76b0a33f5a688", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Various anti-inflammatory, blocking agents, and prophylactic stimulators targeting relevant signaling events, summarized in Figure 1 , have shown promising results in promoting survival and preventing injury in experimental bacterial meningitis.", "Keywords: microglia, bacterial meningitis, blood-brain barrier, experimental models, therapeutic strategies", "ST and FI wrote the literature study and wrote the manuscript. BH-N contributed in writing the manuscript. " ] },{ "paper_id": "aaaaf1da07387bece9bfca99582b31ebe33b1fbd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "aaaf05c5781726bd7c58cffa351a651580893257", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2. Surveys of animal reservoirs to support a specific human outbreak investigation.", "Intentional sentinels (captive chickens, cows, etc.) followed in a cohort fashion to gauge increase or decrease in human risk.", "Scenario 4 is similar to scenario 2, but is initiated by the discovery of unusual animal deaths, not human deaths." ] },{ "paper_id": "aab412e1a2fee75cf3e3fbc911d985ac004f866e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LGG feeding protects intestine physiology after virus infection" ] },{ "paper_id": "aac395d967bf4ce6affb506eb9cf5f1bf853e69f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The present study was approved by the National Medical Ethics Committee, Ljubljana, Slovenia (no. 60/02/09).", "Categorical data are summarized as frequencies (%) and numerical data as medians (range)." ] },{ "paper_id": "aac4ce5fe242548dc36346e402490ab79dbf1df2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Stool production/day (kg) mean \u00b1 SD 4.8 \u00b1 3.8 --", "Supporting information S1 Table. Rubric for the evaluation of appetite, mentation, fecal consistency, and hydration. " ] },{ "paper_id": "aac8b9ab0f36b70cdaf2e6c239d581d4b3737aed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "When building and operating the LIF detection system, laser protective goggles should be worn to avoid eye damage." ] },{ "paper_id": "aad82670f39f4f9731dfeab9064d1063d13c5cb8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The development and implementation of an open-source, electronic disease surveillance system in a resource limited setting faces many challenges. Assuring the smooth interoperability of all software components is sometimes difficult, as is balancing functionality with simplicity for sites with minimal infrastructure. Additionally, finding the appropriate person or group within a country to champion the implementation of a new surveillance system can be fraught with financial, political, territorial challenges. Finally, the open source nature of the software inherently has the consequence of a lack of control of modifications to the software after it is released, potentially leading to incompatible and unverified versions. Conversely, if these changes can be shared in a Wiki-like environment, the entire community using SAGES may benefit from novel improvements.", "Emerging and re-emerging infectious diseases are a serious threat to global public health. [1, 2] The World Health Organization (WHO) has identified more than 1100 epidemic events worldwide in the last five years alone. [3] Recently, the emergence of the novel 2009 influenza A (H1N1) virus and the SARS coronavirus have demonstrated how rapidly pathogens can spread worldwide. [4] This infectious disease threat, combined with a concern over man-made biological or chemical events, spurred WHO to update their International Health Regulations (IHR) in 2005. [5] The new 2005 IHR, a legally binding instrument for all 194 WHO member countries, significantly expanded the scope of reportable conditions and are intended to help prevent and respond to global public health threats. SAGES, an electronic biosurveillance initiative described herein, aims to improve local public health surveillance and IHR compliance with particular emphasis on resource-limited settings.", "Modeling/Simulation/Evaluation. JHU/APL has sponsored several electronic disease surveillance exercises to train users and test surveillance system features. [15] We have developed a number of methods for developing simulated outbreaks, both natural and man-made, which can then be 'injected' into a simulated database for exercise purposes. JHU/ APL has experience with agent-based infectious disease modeling for pandemic influenza as well as other techniques for predictive disease modeling. [16] It is our desire to explore possible collaborations between our disease modelers and users of electronic disease surveillance systems such as SAGES." ] },{ "paper_id": "aae1603af1bb84087248441716a5c0bd373603b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The protocol for this trial and supporting CONSORT checklist are available as supporting information; see Checklist S1 and Protocol S1.", "Nasopharyngeal Dacron-swab specimens were collected from participants displaying acute respiratory infection and placed onto transport medium (Hanks solution with 100 U/mL penicillin and 100 mg/mL streptomycin) [13] . The RNA from clinical samples was extracted (QIAmp Viral RNA mini kit, Qiagen, Germany) and tested for the presence of seasonal and H1N1pdm09 by the WHO/CDC-recommended rRT-PCR [14] . Real time RT-PCR was performed to detect the following agents: subtypes of Influenza A, Influenza B, coronavirus (229, 43 e 63), parainfluenza (1, 2, 3 and 4), metapneumovirus, parechovirus, rhinovirus, RSV A/B, bocavirus, adenovirus and enterovirus (Fast-Track diagnosis, Luxembourg, Luxembourg).", "Checklist S1 CONSORT Checklist.", "We followed the WHO-recommended protocol to perform HAI assays [11, 12] . In brief, serum samples were treated with receptordestroying enzyme (Denka-Seiken, Japan) and incubated with four hemagglutination units of H1N1pdm09 for 1 hour. After, guinea pig red blood cells were added to the well at final concentration of 0.5% and incubated for 1 hour, when the HAI was read. Results were expressed as the reciprocal of the highest dilution that inhibited hemagglutination. HAI titers ,1:8 were considered to have a value of 1:4 for calculation purposes [10] .", "Protocol S1 Trial Protocol. (PDF)" ] },{ "paper_id": "aae339db3ebacca2632136e51dac48f209a952f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A Taiwan AIV H 6 N 1 strain, 2838V (virulent), was obtained by serial inoculation of an original field isolate, H 6 N 1 2838, into specific pathogen free (SPF) chickens [36] . The virus was further amplified by passage into the amnion of SPF eggs. Cell debris in the collected fluid was clarified by centrifuging at 1000 rpm for 10 min and passing through a 0.45 mm filter. The viral titer (50% of the egg infectious dose, EID 50 ) of 2838V was 1610 8 /ml.", "The SAa2-6Gal expression of primary CTE cells", "The SAa2-3Gal expression of primary CTE cells", "Tracheas were obtained from one-day-old SPF chicks (Animal Health Research Institute, Tansui, Taipei, Taiwan) and rinsed in a DMEM medium (Invitrogen, Carlsbad, CA, USA) under a sterile condition. The procedure for removing epithelial sheets from the tracheas and the detailed culture conditions for the CTE cells have been described previously [21] . Briefly, tracheas were digested with dispase I solution (2.5 U/ml dispase I, Roche) for 2 h at 37uC. The detached cell sheets of tracheal epithelium from the tracheal lumen were harvested and further digested with collagenase I (1 mg/ml, Roche) for 5 min at 37uC. The disrupted tracheal epithelial sheets were gently pippeted and homogenized into small cell clumps. The cell pellets were resuspended in a CTE medium [21] and were seeded on 2% matrigel-coated 24-well plates (Corning). The cells were cultured at 37uC with 5% CO 2 for 3 days. The animal use protocol in this study had been reviewed and approved by Institutional Animal Care and Use Committee in National Chung Hsing University. The approval number is 99-09." ] },{ "paper_id": "aae5455daa4cc48f51eb989fac34252c045556b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "China's CDC has further standardized data management, including data collection, verification, and analysis. Daily reports, including analysis and real-time mapping of case distribution on the internet, monthly data collection of sentinel surveillance, quarterly video meeting for elimination progress, and, annual dissemination meeting and publications, will all be summarized and fedback to the NHC and all CDC levels.", "Once the sustained importance on elimination interventions has waned, malaria could be re-introduced in areas where it has been previously eliminated, because the Anopheles mosquito still exists. For instance, in Liaoning and Hainan, after malaria transmission was interrupted for 4 years, officials reported 2 local P. vivax and 6 local P. malariae cases, respectively, in 2015 [6] .", "The 24 provincial reference laboratories, established between 2011 and 2014, have achieved all of the requirements to be part of the network, including laboratory room, devices, organization, and technical demands. Qualitative assessment was conducted by 20 blood slides from external quality assessment programme for communicable diseases (malaria microscopy) in the WHO Western Pacific Region. PCR assessment was carried out using 3 different blood spots to each staff in a blind test for analysis [31] ." ] },{ "paper_id": "aae7699e079d2964df8078931cd0f94d4b1423d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HIV self-similarity (HLA-A2)", "where the length of the interval |I| = A max 2A min depends on references peptide x and matrix W. Two different intervals (I x , I y?x ) are not comparable per se. Thus, we define the normalized peptide similarity using the relation" ] },{ "paper_id": "aae9028bc39c23fd877b0059777933774b7bf2e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The structural determination will provide a molecular basis for explaining numerous physical phenomena and for future docking and molecular dynamics studies on BSA complexes with drugs and other bioactive small molecules.", "Int. J. Mol. Sci. 2012, 13 3783 " ] },{ "paper_id": "aaf71afd1d3f2d1ee34ba2fb720aca20c35a303b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To avoid confusion, commonly traded wildlife species were displayed on the website as shown in Table 1 , broken down into common names and broad categories instead of listed by scientific names. When possible, detailed scientific names of species were recorded in an internal database in order to determine each species' red list status (the conservation status determined by the International Union for Conservation of Nature). Transportation methods used were also recorded when information was available.", "CITES data showed that Elephas genera imports averaged 13,661 from 2008-2010, and were comprised of both live animals and animal products ranging from ivory carvings to meat and hair. The Loxodonta genera averaged 89,523 from 2008-2010 comprised of live animals in addition to products such as bone carvings, ears, feet, hair, ivory carvings, meat, skins, skulls, and teeth [18] . It should be noted that according to CITES, gross import data is often an overestimation of the quantity actually traded, as where different quantities have been reported by the importer and the exporter, the program selects the larger of the two quantities [17] .", "The International Union for the Conservation of Nature (IUCN) provides a list of species at risk of extinction called the Red List of Threatened Species. Threatened species may be poached or caught live and sold for a high value because of their novelty in the market. The system detected reports involving numerous species of concern including the near-threatened pangolin for its scales, the critically endangered black rhino for its horn, the endangered Javan slow loris for the exotic pet trade, the vulnerable mandrill for bushmeat, and many others [21] . The presence of IUCN Red List species in our digital surveillance underscores the need to prevent illegal trade." ] },{ "paper_id": "aaf76d77eb09c00e78926e76d0e9644a3d472161", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Given ( ) ,", "(2) Take", "with probability ( ( ) , ) ," ] },{ "paper_id": "aafce0ff10bc7077faedbbc334c60a1d7021409c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were managed in Excel 2013 (Microsoft Inc., USA). Statistical analyses were performed in Stata 14 (Stata Statistical Software: Release 14. StataCorp LP, College Station, TX, USA), and graphs were made in R [38] . T-tests were used for calculations of significance based on means, except for oocyst counts for which Mann-Whitney U-tests were used, due to lack of normality. Fisher's exact tests were used to evaluate correlations. P< 0.05 was considered significant." ] },{ "paper_id": "ab0550f67f34bd6484d7a24b253c8a3e12759b0f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All analyses were performed using R version 2.14." ] },{ "paper_id": "ab1216072d2b617ce819d2201747699262b5177d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, nucleic acid-based vaccines against CHIKV are under development. These vaccines have clear advantages, from ease of production, to safety, to the ability to induce both humoral and cell-mediated immunity; however many have shown a relatively low immunogenicity, requiring large doses, repeated boosters, and the use of adjuvants [12] . One RNA-based vaccine, VAL-181388, is recruiting for a Phase 1 clinical trial (Table 1) .", "PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd." ] },{ "paper_id": "ab15d5ebce1f5f7cf0e689d32a55701e9e8fcde3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An anti-influenza A antibody directed against the HA (H1N1 subtype), named RB62, and an anti-HCV E2 glycoprotein antibody, named e137, produced and purified with an identical procedure were used as controls in all experiments.", "Positive clones were then sequenced. An in silico analysis was performed, using Mimox and Pepitope servers, comparing the selected peptides to the available crystal structure of A/PR/8/34 and A/South Carolina/1918 haemagglutinins (1RU7.pdb and 1RD8.pdb).", "For sequences analysis the following software packages were used: SeqScape (Applied Biosystems), ClustalX (Toby Gibson), Bio Edit (Tom Hall, Ibis Therapeutics), and Treeview (GubuSoft). " ] },{ "paper_id": "ab179a2dc1b93e7d39b5b371760a3e59da2f2b7e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rotavirus (RV) is the most common cause of viral gastroenteritis in children, and 43-78% of asymptomatic neonatal infections have been described [1] . Despite being predominantly asymptomatic, neonatal RV infection has received considerable attention, because some studies have reported that natural infection in the neonatal period has been shown to confer protection against subsequent severe diseases [2] . Although it is known that jaundice occurs in premature infants due to RV infection, studies on whether RV infection causes jaundice in neonates are lacking [3, 4] .", "Jaundice itself is not a disease but rather a symptom or sign of a disease [5] . Many conditions may clinically present as prolonged neonatal jaundice, including neonatal hepatitis and extrahepatic biliary atresia. These conditions have numerous infectious, metabolic, and genetic causes [6] . Multiple studies have described patients with proven bacterial infections who developed jaundice during the course of their illness [7, 8] . In previous studies, urinary tract infection was observed in 12.5% of asymptomatic jaundiced neonates, with the onset of unconjugated hyperbilirubinemia in the first week of life [9] . Although studies on jaundice due to bacterial infections have progressed, there are limited studies on jaundice caused by viral infections. Therefore, we investigated the relationship between asymptomatic RV infection and jaundice in neonates.", "Jaundice is common and is associated with a variety of physiological and pathological conditions. It is the main reason for hospital readmission during the neonatal period and has long been recognized as a clinical manifestation of infection in the neonate and early infancy [7] . It is known that various infections such as neonatal sepsis, congenital infection, and hepatitis are risk factors for neonatal jaundice. Previous studies have demonstrated that urinary tract infections were associated with jaundice, but there is no such study on RV [8, 9, 20, 21] . In our study of the jaundice group, total bilirubin levels were less than 15 mg/dL in the rotavirus infection group." ] },{ "paper_id": "ab1ac4f7b9c57dad5e3d61f72e8e3d552059fa09", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HFFs (Viromed, Minneapolis, MN) were maintained in minimal essential medium (MEM) supplemented with 10% fetal bovine serum, penicillin G (100 U/ml), streptomycin (100 mg/ml), 2 mM L-glutamine, 1 mM sodium pyruvate and 100 \u00b5M non-essential amino acids at 37\u00b0C in 5% CO 2 . HCMV strain RVdlMwt-GFP was propagated in HFFs as previously described [52] . RVdlMwt-GFP, referred to as Towne-GFP throughout this manuscript, is a recombinant of HCMV strain Towne that expresses GFP under the control of the early promoter UL127. This virus was kindly donated by Mark F. Stinski and has been previously described [53] . " ] },{ "paper_id": "ab1dfbe0d723b54d14e414d732fbedcd40adb021", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ab1f467d067233119dcffc5c542a88cbd7794397", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The laboratory environment has changed considerably over the last decade as larger projects and broader scientific challenges have required scientists to cooperate and collaborate with peers around the globe. Thus, few research labs remain isolated, independent units. The internet has enabled these research teams to work in trans-disciplinary environments, with researchers from many disciplines, nations, time zones, and languages working together on large-scale research projects. While this new development enables researchers to address these new challenges, a new approach to conducting daily research is required.", "Allowing multiple participants to jointly create and edit web pages is known as a ''wiki,'' first developed and implemented by Ward Cunningham in 1995 (http://en.wikipedia.org/wiki/Wiki). The Wikipedia is perhaps the most widely known and used wiki and is essentially an encyclopedia collaboratively written by volunteers [10, 11] .", "Controlled access-Users are authenticated against an Active Directory to determine their level of access to projects and entities. Access can also be provided to accounts residing on external LDAP repositories via MOSS. Anonymous read-only access is also available." ] },{ "paper_id": "ab23c1ed37392d4e2dbbd809e62171775e75369b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animals were anesthetized and transcardially perfused with PBS followed by zinc formalin. Lungs were removed, fixed in zinc formalin, and paraffin embedded. Sections were stained with hematoxylin and eosin.", "In situ CFSE staining CFSE (Molecular Probes, Eugene, OR) was dissolved at 25 mM in DMSO stored at 220uC until use. The CFSE stock solution was diluted in DMEM media to a concentration of 8 mM and then administered i.n. (50 ml/mouse) following anesthesia with isoflurane [12] .", "The following monoclonal antibodies were used for these studies: rat anti-mouse CD3 (145-2C11), rat anti-mouse CD4 (RM4-5), rat anti-mouse CD8b (53-6.7), rat anti-mouse CD11b (M1/70), hamster anti-mouse CD11c (HL3), rat anti-mouse CD16/32 (2.4G2), rat anti-mouse Siglec F (E50-2440), mouse anti-mouse I-A d (AMS-32.1), all from BD Bioscience (San Diego, CA); rat anti-mouse IFN-c (XMG1.2), anti-mouse F4/80 (BM8), rat anti-mouse CD40 (1C10), all from eBioscience (San Diego, CA); rat anti-mouse CD43 (1B11, Biolegend, San Diego, CA); rat anti-mouse CD200R (OX-110, Serotec, Raleigh, NC)." ] },{ "paper_id": "ab26098d2e9876c05c8c1fd3d30d45a749b944e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Another well known mucosal vaccine in recent years is FluMist\u00ae, which is a live attenuated, trivalent cold-adapted influenza vaccine (CAIV-T) manufactured by MedImmune, Inc [10] [11] [12] . FluMist is given as a gentle nasal mist. This nasal vaccine has been proved to be safe, effective and well tolerated in adults including those infected with HIV-1. It was approved by the United States ", "Viruses 2010, 2 284" ] },{ "paper_id": "ab2859ea36cc85687a9caad282ffaca666bd0b64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nine surface accessible epitopes were predicted from the conserved peptide", "be conjugated with adjuvant [44] . Though this epitope based vaccine is designed by in silico analyses, the actual immunogenicity, stability, efficacy and their delivery strategy inside the recipients body can't be determined by this in silico analysis. To address these questions in vitro and in vivo experiments are essential.", "A total available 46 replicase polyprotein 1ab, 17 spike (S) protein, 18 envelope (E) protein, 18 membrane (M) and 18 nucleocapsid (N) protein sequence data were retrieved from NCBI GenBank sequence database [45] (Additional file 7: Table S1 )." ] },{ "paper_id": "ab2dc5037a08c6bab002949e27839054d0ff87bf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ab2e4c7ae023d55fde4ae3df32825484d00fcb3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conducting clinical trials to assess experimental treatments for potentially pandemic infectious diseases is challenging. Since many outbreaks of infectious diseases last only six to eight weeks, there is a need for trial designs that can be implemented rapidly in the face of uncertainty. Outbreaks are sudden and unpredictable and so it is essential that as much planning as possible takes place in advance. Statistical aspects of such trial designs should be evaluated and discussed in readiness for implementation.", "Citation: Whitehead J, Horby P (2017) GOST: A generic ordinal sequential trial design for a treatment trial in an emerging pandemic. PLoS Negl Trop Dis 11(3): e0005439. https://doi.org/ 10.", "It is important and feasible to pre-determine many of the statistical aspects of an efficient trial design in advance of a disease outbreak. The design can then be tailored to the specific disease under study once its nature is better understood. PLOS " ] },{ "paper_id": "ab371ed38caa53c720fd4c0333e1bf4de84550f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The presence of macroscopic observable changes that are computable from a large number of relatively smaller changes mean that it may be possible to find an objective mathematical formalism to infer the turning point at which these radical changes occur.", "We also eliminated all the probes with missing values, remaining 13,188 probes.", "Finally, one particular type of probes has also caught our attention, and we would like to refer to them before concluding this section." ] },{ "paper_id": "ab3c4f88e655875b72719f078f4e1e4fd4459445", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Single-use nasal cannulas were used in conjunction with Nomoline \u2122 Adapters connected to a Masimo Root \u00ae Patient Monitoring System with an ISA \u2122 CO 2 module to log the ETCO 2 , fractional inspired carbon dioxide (FICO 2 ) and respiratory rate (RR) information." ] },{ "paper_id": "ab3cd83b4fa77a65b99102d3d9afcfe861bdb2c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "With the option -genes 1, if any sequences have gi numbers, annotations which overlap predicted amplicons are automatically downloaded from NCBI Genbank with the efetch utility. Annotations reported are primary tag, product, gene, note, and protein id, for coding sequences (CDS), genes, mRNA, mature peptides, miscellaneous features, etc.", "For Coronaviridae primers, one amplicon from a glaucous-winged gull was predicted if a single mismatch in the forward primer was allowed, although there were no matching probes. This was the only predicted amplicon from nt outside Coronaviridae, besides synthetic RNA transcription vectors derived from coronaviruses (feline coronavirus and murine hepatitis virus vectors pBRDI1 and pBRDI2). The run took just over a minute against the Coronaviridae genomes database, 4.5 hrs or 3.5 hrs against nt with or without amplicon extraction and gene annotation, respectively." ] },{ "paper_id": "ab40400780c96601bae9d2f4d1c317dc3322f865", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus growth and purification. The TBE virus prototype strain Neudoerfl was grown in primary chicken embryo cells, harvested 48 h after infection, and purified by two cycles of sucrose density gradient centrifugation [59] . For membrane fusion assays, virions were metabolically labeled with 1-pyrenehexadecanoic acid as described previously [51] .", "Here, we show that it is possible to trigger the conforma- ", "envelope organization could therefore not be based on this experimental approach.", "The GenBank (http://www.ncbi.nlm.nih.gov/Genbank) accession number for the flavivirus TBE virus strain Neudoerfl is TEU27495." ] },{ "paper_id": "ab49a01b79f3623438ca5e7f5833d95ef1701a55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thirty years ago, a list of animal species, including humans, cattle, sheep, cats, dogs, deer, chickens, turkeys, and ducks, had been found susceptible to astrovirus infection [2, 10, 15, [27] [28] [29] [30] [31] . Recently, there has been a dramatic increase in astroviruses infected in animal species as the advent of advanced molecular assays and pathogen discovery tools [32] [33] [34] . Recombination between different strains of astroviruses aggravated the prevention of astrovirus infection [17, 35] .", "Sequences of the primers were DAstV-1 F (5\u2032-CAT CCA AAC CTC CAA ACA TCT TG-3\u2032) and DAstV-1 R (5\u2032-CTG TAC CCT CGA TCC TAC TCG G-3\u2032). Data are expressed as mean \u00b1 SD.", "Members of the Astroviridae family are non-enveloped, positive and single-stranded RNA viruses, typically 28 to 30 nm in diameter. This family is subdivided into two genera with Mamastrovirus and Avastrovirus, known to infect mammalian and avian species, respectively [1] . In 1975, astrovirus was first identified by electron microscopy as the cause of gastroenteritis in infants [2] . Astroviruses mainly infect the young populations of multiple species, including avian and mammalian species both in terrestrial and aquatic environments [3] . As a potential zoonotic virus, astroviruses spread quickly and are distributed globally, resulting in significant economic losses for the breeding industry and posing a threat to human health [4] [5] [6] ." ] },{ "paper_id": "ab4c508f4a6ff84276581ce0746b4a5768728d0f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis to assess significant differences of morbidity was performed using SPSS version 17.0 software. A p-value <0.05 was considered statistically significant.", "This study", "CCoV, canine coronavirus; CDV, canine distemper virus; CPV, canine parvovirus; FPV, feline panleukopenia virus; PCR, polymerase chain reaction" ] },{ "paper_id": "ab52aa56838160b5ec7a015a05ef76fc06129b5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bhargavaea cecembensis 8 0", "Leucobacter alluvii 1 0", "Microbacterium esteraromaticum 1 0" ] },{ "paper_id": "ab54f13666ed771c15684d73ff6bcc7c92b8ae05", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lower respiratory portions were selected from induced sputum samples and placed in an RNA lysis buffer (Buffer RLT-Qiagen, Hilden, Germany) as previously described [10] . Nasal swabs and throat swabs were also immersed in Buffer RLT. Extraction and purification of sputum, swab RNA was performed using the RNeasy kit (Qiagen) as per manufacturer's instructions. RNA was then reverse-transcribed to total cDNA using random primers and the Superscript II RT kit (Invitrogen, Carlsbad, USA)." ] },{ "paper_id": "ab5652086c345dbe360ca35b48b31e43f95507e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Signaling Molecules and Interaction ", "Cluster analysis showed clusters A -J contained 25 (11%), 14 (6. ", "Here, both y i and l are not comparable between statuses, because the library sizes can vary. We can however, compare m's among statuses (i.e., libraries) because they quantify the underlying ''true'' frequencies of SAGE expression.", "The animal use protocol was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of the National Animal Disease Center-USDA-Agricultural Research Service." ] },{ "paper_id": "ab5bba6cb4c6f9a00931f232ac3be14667c4f807", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "have been a popular field, especially since the SARS (Severe acute respiratory syndrome) outbreak in 2003. The continuation of growing numbers of infectious diseases in hospitals, [17] propagation of pathogens, and their resistance against conventional antibiotics [18] have significantly raised global concern. Therefore using nanomaterials as antibacterials complementary to antibiotics is highly promising and is gaining a large interest, as they may fill the gaps where antibiotics frequently fail [19] .", "Although, AMNP nanoparticles exhibit antimicrobial functions, their chemical and particle characterisations are not documented. Furthermore, how they interact with microbes has not been directly investigated. Most known antibacterial nanomaterials interact electrostatically with the bacterial membrane causing membrane disruption [19, 34] . Consequently, free radicals are produced and instigate secondary membrane damage causing protein malfunction and DNA destruction [3] . Other antimicrobial nanomaterials such as nitric oxide matrices involve photoactivation with RNS (Reactive oxygen and nitrogen species) [35] or polycationic nanomaterials induce signal secretion to promote programmed cell death [36] .", "Results and Discussion" ] },{ "paper_id": "ab70ed497469460f2ec13fcfe51611005fab867a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional Supporting Information may be found online in the supporting information tab for this article: ", "Prior to each collection, voltages were manually calibrated to a common template using Rainbow Beads (BD Biosciences, San Jose, CA, USA), to insure accurate MFI tracking over time. Fluorescent conjugated a-Mouse antibodies against CD3(SK7), CD4(MCD0430), CD8a(S3-6.7), CD62L (MEL-14), CD44(IM7), a-Ki-67(B56), CD127(A7R34), KLRG1(2FI), CD86 (GL-1), B220(RM2630), NK1.1(PK136), CD49b(DX5), CD19(RM7717), IgM(II/41), and MHC-ii(M5/114.15.2) were purchased from commercial sources. Tetramers against NS4b (H-2D(b) -SSVWNATTA) were obtained from the National Institutes of Health Tetramer Core Facility. Staining occurred at 4C followed by fixation and permeabilization (FoxP3 kit; eBioscience, San Diego, CA, USA). Blood and spleen counts were performed using a Hemavet cell counter (Drew Scientific, Dallas, TX, USA). Samples were run on a Fortessa Flow Cytometer equipped with four lasers and using DiVa software (BD Biosciences). Compensation and analysis were performed using FlowJo software (Tree Star, Ashland, OR, USA).", "Statistics were performed in Prism 6.0 (GraphPad Software, La Jolla, CA, USA). When data from multiple cohorts were combined for analysis, data from each cohort were normalized to the average of 0 Gy group from that cohort, to avoid cohort-specific biases. Significance is noted as follows throughout: ns = not significant, ****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05. All error bars shown are SEM." ] },{ "paper_id": "ab85c4fceac01205bc463599fa6263a6498528c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Patients who had received the first dose of DPT vaccine were excluded from the study.", "For RV detection samples were analyzed by reverse transcription and gene amplification with RT-PCR.", "The medical records of subjects were retrospectively reviewed. Information collected included age, gender, medical history, immunization status, clinical presentation, ongoing antibiotic therapy, admission diagnosis, length of illness, length of hospital stay, laboratory test results, concurrent infections and complications (requirement of oxygen therapy, pneumonia, death).", "The bacterial DNA was processed immediately on Taqman platform (Applied Biosystem) with Bordetella R-gene\u2122 assay (Argene, Biomerieux, Marcy l'Etoile, France), able to amplify a fragment of 191 bp of the target region IS481 for BP. The ready-to-use amplification mixture included primers, dNTPs, amplification buffer, Taq Polymerase, probes specific for Bordetella and for the IC. The target DNA was amplified through the Taq Polymerase activation at 95\u00b0C for 15 min, and 45 repeats of denaturation at 95\u00b0C for 10 s and hybridization/elongation at 60\u00b0C for 40 s." ] },{ "paper_id": "ab8c1e32b66b02cd703799df3d2ee37a1cb369b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Serum neutralizing activity was determined using a MERS-CoV pseudovirus system as reported previously 15, 18 . The neutralizing antibody efficiency was calculated as: (relative luciferase units of mock sera-relative luciferase units of immune serum for a given dilution) \u00f7 relative luciferase units of mock sera.", "Statistical analyses were conducted by one-way analysis of variance with Bonferroni post-test using SPSS for Windows software (ver. 17, SPSS, Inc., Chicago, IL, USA). Unpaired two-tailed Student's t-test was used to compare the means between the different groups. A value of P < 0.05 was taken to indicate statistical significance. The results are expressed as the means \u00b1 standard deviations (s.d.). All figures were rendered using Prism 5 software (GraphPad Software, La Jolla, CA, USA).", "After mice were euthanized, the lungs were collected for HE and IHC examination. Tissues were fixed using 10% neutral buffered formalin, embedded in paraffin, sectioned sequentially to a 4 \u03bcm thickness, and stained with HE prior to examination by light microscopy. For immunohistochemistry (IHC), the sections were then incubated with a rabbit-serum-derived polyclonal antibody against nucleoprotein (Sino Biological, Inc., Cat. No. 100213-RP02) or mouse-serum-derived monoclonal antibody against S protein (produced in our laboratory) at a 1:1000 dilution. The secondary antibodies were goat anti-rabbit (ZSGB-Bio, Beijing, China; Cat. No. pv-9001) and goat anti-mouse at 1:2000 dilutions. The results were evaluated by light microscopy. Multiple independent sites in the lung tissue samples were used for IHC analysis. Finally, four or five slides per animal were evaluated.", "Animal studies were conducted in strict accordance with the Guide for the Care and Use of Laboratory Animals of the People's Republic of China. The study protocol was approved by the Committee on the Ethics of Animal Experiments of the Chinese Centre for Disease Control and Prevention (China CDC)." ] },{ "paper_id": "ab8da309a4060c4f4a3774c3ec9e7ebdc5a3a74e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Replication competent VV Western Reserve strain (VV) was provided by B Moss (National Institutes of Health, Bethesda, MD). Recombinant viruses encoding enhanced green fluorescent protein (VV eGFP) or fulllength ovalbumin (VV-Ova) based on the Western Reserve strain were provided by JW Jewdell and JR Bennink (National Institutes of Health, Bethesda, MD). VV and replication deficient Modified Vaccinia Virus Ankara strain (MVA, cloned isolate IInew) used in this study were propagated and titered according to standard methodology [21] .", "For detection of VV-infected cells or macrophages, paraformaldehyde (PFA) (4%) fixed and paraffin embedded CNS tissue sections were incubated with Bond Primary Antibody Diluent (Leica) containing either polyclonal rabbit anti-VV serum (1:1000; Quartett Immunodiagnostika & Vertriebs-GmbH, Berlin) or monoclonal antibodies against Mac-3 (1:750; M3/84) purchased from BD Pharmingen. IHC staining was performed on an automated Leica BOND-MAX instrument using Bond Polymer Refine Detection Solution for DAB. For detection of GFAP, PFA-fixed and paraffin-embedded CNS sections were incubated with Dako polyclonal rabbit anti-GFAP antibodies (Z0034; 1:13000) in Ventana buffer and staining was performed on a Ventana NexES IHC Slide Stainer using iVIEW DAB Detection Kit (Ventana). Images were taken using the Leica SCN400 slide scanner analysis software or were acquired on an Olympus BX53 Microscope (DP72 camera) using the cellSens 1.8 digital imaging software (Olympus).", "CNS tissue was digested as described and single cell suspensions were obtained by passing digested CNS tissue through a 70-\u03bcm nylon filter. Pelleted cells were subjected to three freeze-thaw cycles (-80\u00b0C and 37\u00b0C) and sonicated three times for 1 min. Serial dilutions in RPMI-1640 medium containing 10% FCS were added in duplicates to 90% confluent RK-13 cells seeded in 6-well plates and incubated for 24 hours at 37\u00b0C. Plaques were counted after crystal violet staining.", "was responsible for the failure to clear intracerebral VV infection.", "Animals were kept in a specific pathogen-free facility at the Technische Universit\u00e4t M\u00fcnchen. All experimental protocols were approved by the standing committee for experimentation with laboratory animals of the Bavarian state authorities (\"Governmental Department of Upper Bavaria, Approved animal experimental proposals No 55.2-1-54-2531-88-08 and No 55.2.1-54-2532-29-13 according to \u00a78.1, German law for experimentation with laboratory animals\") and carried out in accordance with the corresponding guidelines." ] },{ "paper_id": "ab906d73fa3fecf440ed8c98ad852397bf7bee1f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are expressed as means \u00b1 SEM. Differences in RGC numbers, SIRT1 activity, and protein expression were assessed using one-way ANOVA followed by Student Neuman-Keuls post-hoc test. Statistical differences were considered significant at P < 0.05.", "Authors' contributions RSK helped design these studies, performed all experiments, analyzed the data, and prepared the manuscript. KD assisted with induction of MHV disease, prepared tissue sections, and performed histological studies. JDS helped with experimental design, data analysis and preparation of the manuscript. KSS oversaw all aspects of these studies and was involved in experimental design, data analysis and manuscript preparation. All authors read and approved the final manuscript.", "Competing interests SRTAW04 was provided at no cost by Sirtris, a GSK Company, to KSS for these studies. No funding was provided by Sirtris for the studies, and KSS has no financial interests or relationships with Sirtris or related to its SRTAW04 compound. The authors have no other competing interests to declare." ] },{ "paper_id": "ab9240ebae17608f688ebee1fea34fff47003ef0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two kinds of indicators were obtained:", "We calculated the following citation indicators by journal, country, and geographic region:" ] },{ "paper_id": "ab93177f9535fe5635e94d021785133011c87d93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ab98d1b125aa0704e63adef426b27abd32e935f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In total, 12 full genomes of mammalian viruses could be generated. Viruses belonged to the RNA and DNA viruses (cosavirus, adenovirus, hepatitis B virus, human papillomavirus, norovirus, and torque teno virus).", "Sequences mapping to an Enterococcus phage were identified in several samples, sufficient reads were present in sample 9 to assembly a genome-sized contig.", "All samples contained at least one plant virus and most contained sequences from several plant viruses. Complete genome-sized contigs related to Tobacco mild green mosaic virus (TMGMV), Paprika mild mottle virus, Cucumber green mottle mosaic virus, Tomato mosaic virus (TMV) and a partial genomes of Grapevine rupestris vein (GRV) feathering virus were assembled from the data. These plant viruses are not known to be associated with human disease and their presence may simply reflect recent dietary consumption.", "A virus associated with non-A, non-B hepatitis (NANB-1) was identified in patients in the early 1980s [38, 39, 40, 41] . The disease potential of NANB-1 is still controversial and the virus is likely to be a bacteriophage [13] . NANB-1 was detected in two of the fecal samples (sample 15, sample 20) and sufficient sequence was available to assemble a partial (80%, sample 15) or a complete (sample 20) genomes." ] },{ "paper_id": "ab9e34ee687f60a4de8ef675f307230e1b6c6f23", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The alternative therapeutic option is based on interferon-alpha (IFN), but an HBV cure is achieved in only 10-20% of IFN-treated patients and therapy is frequently associated with severe side effects [4, 8] .", "Therefore, there is a clinical need for safe, novel treatments to shorten the duration of NUC therapy by accelerating virus control, and to enhance the effect of current anti-viral therapies.", "Loss of HBsAg is observed in less than 10% of patients after five years of therapy, thus often requiring long-term administration to avoid virus reactivation at therapy discontinuation [5, 6] . This is due to the persistence of cccDNA in the nucleus of infected hepatocytes, which is not affected significantly by NUC therapies.", "Hepatitis B virus infection has been considered by the World Health Organization (WHO) to be a major public health burden because of the high rate of deaths and clinical sequelae, despite the availability of a prophylactic vaccine." ] },{ "paper_id": "aba0193185525dbd5c85f38245bcd05861ec4513", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The advice of health ministries of some Zika-countries for women to defer pregnancy for considerable periods to lessen the risk to their newborns is unprecedented and controversial. Apart from the attendant population planning risks of a distorted population profile resulting from a diminished birth cohort, some of these countries have high rates of unplanned pregnancies, strict abortion laws, a lack of sexuality education programs in schools, and poor access to contraception, leading to difficulties in implementation of this policy (Ahmed, 2016) .", "In countries that do not have Zika activity but harbor competent vectors of the disease, disinsection of arriving airplanes is an important consideration. The WHO recommends that these countries undertake a risk assessment, and if it concludes that a disinsection program is indicated, that it should be conducted according to standard WHO recommendations (WHO, 2016a).", "Maybe it is time to reconsider research horizons, and to pay attention to the integral circle of host, agent, environment and vector. Health promotion approaches are still valid, and can be an alternative for the global reality of health inequities and weakening of public services (Caprara and Ridde, 2016) .", "Two broad types of complementary vector control strategies can be applied. First, individuals must take personal responsibility for avoiding mosquito bites and, second, government and non-government organizations must implement vector surveillance and control programs at global, national and local levels.", "Disease control methods available for the fight against ZIKV are limited. There is neither an effective vaccine against the virus, nor anti-viral drugs to reduce the viremic period during which a competent vector with hematophagic behavior can amplify the disease. Vector control measures are, therefore, crucial and reduction of contact between hosts and vectors form the basis of disease control strategies worldwide." ] },{ "paper_id": "aba67455b71206b20d9b978e994cb571392dd404", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "calcein labeling buffer at 23\u00b0C and resuspended in the desired media.", "Normal peripheral blood neutrophils were prepared by a modification of the method of Boyum as previously described [56] , and were suspended at the indicated concentrations in Hanks' balanced salt solution (HBSS) with or without Ca 2+ (Gibco, Grand Island, NY), as indicated. Differential cell counts on Wright-stained cells routinely revealed greater than 95% neutrophils. Viability as assessed by trypan blue dye exclusion was greater than 98%.", "The PE-labeled CD11b mAb (Leu 15) was obtained from Becton Dickenson (Mountain View, CA). The source of mAbs was either hybridoma cell culture supernatants, purified antibody, or ascites fluid diluted in PBS containing 1 mg/ml BSA as indicated. All sera and ascites were heat inactivated at 56\u00b0C for 30 min and clarified by centrifugation at 13,000 \u00d7 g at 4\u00b0C for 15 min before use. Nformyl-met-leu-phe (FMLP) and normal mouse serum (NMS) were purchased from Sigma Chemical Co. (St. Louis, MO).", "Effects of mAbs on neutrophil adhesion to HUVECs was analyzed by the Mann Whitney U test when appropriate." ] },{ "paper_id": "abb5a68caf42d65dcb946056258028cccf87cd4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ELISA, neutralization assay and histopathology. The serum samples of PRV-specific gB antibodies were evaluated using commercial ELISA kits according to the manufacturer's directions (IDEXX, USA). The neutralizing antibody against PRV was tested as described previously 34 . The brain tissues were fixed with 4% paraformaldehyde solution at room temperature for 2 days and then processed by routine histopathological procedures as previously described 35 .", "DMEM with 10% FBS, and streptomycin/penicillin. DNA was transfected into HEK293T and PK15 cells using Lipofectamine. PRV infection was performed as previously described 26 . The culture medium was changed to DMEM with 2% FBS after transfection and viral infection. DNA synthesis, sequencing and analysis. The PCR primer synthesis and DNA sequencing were done by Shanghai Sangon Biotch, China. gB, gC, and gD gene sequences of PRV Ea strain obtained from NCBI were analyzed by BioEdit software.", "The aim of the present study is, therefore, to isolate the re-emerging PRV and use it as a model virus to establish a fast and cost-effective technology for express vaccine development." ] },{ "paper_id": "abb624287a5b93c29ec470b38dd4d03b21c8fc34", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ORF1B is predicted to encode nsp1B, which results from proteolytic cleavage of nsp1ab. Nsp1b is the RNAdependent RNA polymerase (RdRp), and this is the only domain identifiable by CDD or BLAST search. The nsp1B protein is the most conserved of the three polyproteins ( Figure 2) .", "In this study, we describe the identification and genomic characterization of a member of the Astroviridae family of viruses. Traditionally, astroviruses have been named after the host species from which they were identified, so we propose naming this virus species Astrovirus rabbit/TN/2009/USA.", "Fresh fecal samples were submitted to the Clinical Virology Laboratory (University of Tennessee Veterinary Medical Center) for electronmicroscopic examination. Samples were processed as described in [63] . Briefly, samples were centrifuged in distilled water at approximately 15,000\u00d7g for one hour. The supernatant was discarded and pellet resuspended in 2-3 ml distilled water. 100ul of the resuspended material was added to 1 ml distilled water containing 3% phosphotungstic acid. The solution was aerosolized onto a carbonate-coated copper grid and examined by EM at 30,000 and 300,000X." ] },{ "paper_id": "abb703e29b1ee7ddf60006b33de199828666d7b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "abcb3cbc5b6ed2707546a1a22fd81724104416ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the raw read files were submitted to the sequence reads archive (SRA), NCBI database (accession number-SRR5091816).", "Although virological and genetic characterizations of NNV have been reported, its infection mechanisms and disease outbreak mechanisms remain unclear. Therefore, systematic approaches are needed to determine its infection mechanisms." ] },{ "paper_id": "abd80dcf360dafb7c921416daedc2021908c3503", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "summarizes the most up-to-date findings on virushost interaction of MERS-CoV based on cellular and animal studies and their implications on disease pathogenesis [11] .", "Editorial" ] },{ "paper_id": "abf6f66d8e18b652d10944bb21e19debca5dc5e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2.6. Statistics. One-way analysis of variance (ANOVA) and Bonferroni's post hoc were used for data analysis. All results were expressed as mean \u00b1 SD. P < .05 were considered statistically significant. ", "All the isolated fractions were subjected to cytotoxic and apoptosis assays.", "Natural products have long been used to prevent and treat diseases including cancers and might be good candidates for the development of anticancer drugs." ] },{ "paper_id": "ac02f40071a3fc513d2d834ec0bdb3ce8dd16b51", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The basic reproduction number R 0 is given by", "(2:4)", "royalsocietypublishing.org/journal/rsif J. R. Soc. Interface 16: 20180670" ] },{ "paper_id": "ac04992c38f8d8bb758a7460e350827c390698a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ten (27%) of 37 patients with chest imaging performed had abnormalities noted, with alveolar infiltrates (n = 4; 40%) as the most common finding. Three (6%) patients required supplemental oxygen therapy, and no patients required mechanical ventilation. Eleven (20%) patients received antibiotic therapy; indications included febrile neutropenia, bacteremia, and pneumonia." ] },{ "paper_id": "ac0a277a70cf2e3e6e51ddb07ad06eae08cc7fef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Off " ] },{ "paper_id": "ac0ab279eea38eef425c76172c917fd896417d6c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the Uppsala Regional Ethics Committee, Sweden (2006/201)." ] },{ "paper_id": "ac0ed4e3ae92a0e194ea6808c289a0b6224ea054", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The spatial effectiveness of control strategies is also of interest, and thus a series of infection intensity maps are displayed in Figure 2 . The infection intensity represents the density of total infections as points occurring within every geographic unit (50 m650 m) during the entire 150-day epidemic. The intensity value at each cell location is also the average from 50 model realizations and is converted to a unit of infections per sq km 2 for the ease of comparison. An effective strategy is expected to reduce infection intensity at every location, and meanwhile confine the spatial extent of affected areas.", "(DOC)", "Conceived and designed the experiments: LM. Performed the experiments: LM. Analyzed the data: LM. Wrote the paper: LM." ] },{ "paper_id": "ac14252dbac614e01fef29b981cd841aa223f28e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by the Institutional Review Board at Queen Mary Hospital" ] },{ "paper_id": "ac14fff2effb225af96af173c6035a28b34fb507", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ac1e0c34f47a58c5d830bd63399b3400cab8375d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the previous study [16] , it was found that the poly ( ", "Interactions between consensus polyadenylation signal (PAS) hexamer AAUAAA or its variant (AGUAAA, AUUAAA or UAUAAA) located10-30 nts upstream of the poly(A) cleavage site [5, 10] and related proteins are integral aspects of eukaryotic mRNA polyadenylation [6, 50] .", "Determination of the minimum length of poly(A) tail required to initiate poly(A) tail lengthening of coronavirus defective interfering (DI) RNA" ] },{ "paper_id": "ac379a37c74e9e9ea13ad9813f46f53dbab62b66", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Model specification: District-specific intercepts and growth rates " ] },{ "paper_id": "ac37ba61c91bb6939a507dbf4efe2119ddafeb9c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ac433e9c802d7f78f6b05a4ac8aedf3aee005086", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In vitro antifungal susceptibility testing of a selection of C. auris isolates (n = 12) was performed using the M38-A2 broth microdilution method of CLSI (Clinical and Laboratory Standards Institute) [26] .", "Candida auris was isolated by routine microbiology procedures from clinical samples, such as blood, urine, surgical wounds, and catheters, as well as from screening samples (axilla, groin, nasal, throat, and perianal swabs).", "Descriptive statistics of the cases were presented as the mean, the median for continuous variables, and percentages for categorical variables. These analyses along with the chart for patient transfer within the hospital were constructed using Excel software." ] },{ "paper_id": "ac476cee9fb4aca11b589ea119a527db34398453", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the excess lung specimens and anonymous clinical data presented in this study were permitted and approved by the Hospital for Tropical Diseases and the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University, Thailand (approval number MUTM2014-049-1 and -2).", "https://doi.org/10.1371/journal.pone.0181674.g006", "Conceptualization: Natthanej Luplertlop, Georges E. R. Grau, Sumate Ampawong. " ] },{ "paper_id": "ac51af9995edb441f0ce4fdc384908daa6e83675", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The structure of full-length TREM2", "The structure and production of soluble TREM2", "Whether the production of sTREM2 in AD occurs by alternative splicing or ectodomain shedding is unclear. It may be cell-type and context dependent as different cell types showed either an up-(dendritic cells) or downregulation (microglia, monocytes) of the TREM2 splice transcript levels when stimulated by LPS [161, 228] . IL13 and IL4 were also shown to enhance sTREM2 production in bone marrow derived macrophages [149] . This is consistent with studies examining other members of the TREM family as TREM1 [233] [234] [235] and TREMlike transcript-1 [236] which also produce cell-specific protein products." ] },{ "paper_id": "ac52347e640db03cb8dfaf1f0228caf47570ddaa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Where G1\u2026Gn represents the aggregate measure of all the genes. A Z ratio of 6 1.96 is equivalent to the significant level of P value,0.05 [10] .", "Zratio~M ean\u00bdZscore(group1){Mean\u00bdZscore(group2) SD(ZscoredifferenceG1:::Gn)" ] },{ "paper_id": "ac5854f7ef4751d0a621fafd02e4cd05b08321cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DS conceived the study, designed the experiments and prepared the manuscript. SS designed, carried out the experiments performed the data analysis and drafted the manuscript. MC designed, carried out the insilco work and data analysis. All the authors reviewed the manuscript.", "This study was funded by Department of Science and Technology, India SERB grant EMR/2015/00107, PI: DS and NPDF-SERB grant PDF/2016/002887, PI: SS.", "All datasets generated for this study are included in the article/Supplementary Material." ] },{ "paper_id": "ac5b22cca25686b387a8ea806008de5d8e41bd55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The HMPV strain C85473, a clinical isolate, and the recombinant HMPV strain C85473 \u0394SH were grown in LLC-MK2 cells and concentrated as previously described [69] . Viruses were concentrated by ultracentrifugation and pellets resuspended in PBS. Viral stocks were sequenced and titers were determined by immunostaining [70] and expressed as plaque-forming units (PFU) per milliliter.", "To block NLRP3 inflammasome activation, MCC950 (5 mg/kg) [21, 71] was mixed and administered intranasally at the same time with the virus. However, MCC950 was also given 24 h post-infection in a single experiment. Equivalent dilutions of DMSO (Sigma Aldrich) served as control. This treatment was repeated once a day for two consecutive days. For IL-18 inhibition, immediately following inoculation of virus, mice underwent intraperitoneal injections of IL-18BP at a dose of 75 \u03bcg/kg (R&D Systems, Minneapolis, MN, USA) [72] . This treatment was repeated once a day for two consecutive days during infections. Control mice were given sterile saline in a similar manner.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "ac6a39a0545f0b00b01c5e6875632f9c0f8883f9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Moreover, the World Health Organization (WHO) and the European Centre for Disease Prevention and Control (ECDC) requested an increasing number of epidemiological data for multiple pathogens (such as Polio virus, Rabies virus, Clostridium botulinum, . . .) which should be collected by a recognized reference center [3, 4] .", "The partners or stakeholders of the project and their relationships are represented in Figure 1 .", "Thirty (30) pathogens were selected for a single species or for multiple species belonging to the same species group.", "Given the lack of financial incentives for the accomplished reference laboratory activities, the risk for reducing or even stopping the reference activities became a major issue for both patient care and public health.", "The implementation of the NRCs allows the development of an integrated surveillance and epidemic intelligence of antimicrobial resistance in human and zoonotic or emerging pathogens. The possibility to play a major role in technology innovation and research consolidating our capacity in diagnostic, surveillance and epidemic preparedness is reinforced." ] },{ "paper_id": "ac6b3fe26ffb1e6b3b34200c9053a724e81f2d7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/AAC .00383-17.", "enzymatic step is catalyzed by the dihydroorotate dehydrogenase (DHODH), which is bound to the inner membrane of mitochondria, where it converts dihydroorotate (DHO) to orotate (3) . Finally, the multifunctional UMP synthase uses orotate to produce UMP, a common precursor of all other pyrimidine nucleosides.", "SUPPLEMENTAL FILE 1, PDF file, 0.4 MB." ] },{ "paper_id": "ac6bfed80dfd9922eeb3124fe302d0a7b29997d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Specific signals were visualized by incubating membranes in dark with 3,3-diaminobenzidine (DAB, Thermo Scientific Pierce) in 0.05 M Tris-HCl and 0.04% hydrogen peroxide for 10 min.", "These results indicated a potential effect inherent to nanodiamond towards modulating immune systems, which should be further evaluated and broadly applied in nanovaccine development." ] },{ "paper_id": "ac793b3e925f08bf9fac41b70e5c9a61d1f37e39", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Stress Response Inventory (SRI). Participants' psychological response to stress was measured using the SRI [35] . The inventory consists of 39 items (score range: 0-156) categorized into 7 factors: fatigue, tension, frustration, anger, depression, somatization, and aggression.", "The Internet offers many advantages as a medium for easy participation in MBT and is not subject to the limitations of time and space that are inherent to traditional group training. There is evidence of the impact of online training in mind-body skills in terms of significant improvements related to stress, mindfulness, and participants' confidence in their ability to provide calm and compassionate care, with emphasis on the cost-effectiveness and convenience of online programs [7] . The same researchers have also reported effects of online mindbody skills training on resilience, mindfulness, and empathy [8] .", "Supporting Information S1 Appendix. Available raw data. (SAV)" ] },{ "paper_id": "ac7d8fb495888876f03df56a1d3a3faa1f05e770", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For each sample, approximately 200 nuclei per field were counted (20x magnification), and the mean fusion index of five fields was calculated (n = 3).", "A Student\u00b4s t-test was performed for statistical evaluation of n!3 independent epxeriments: \u00c3\u00c3\u00c3 , P < 0.00025; \u00c3\u00c3 , P < 0.0025; \u00c3 , P < 0.025.", "Supporting Information S1 Table. Prediction of hydropathy segments. " ] },{ "paper_id": "ac8b5e9b4a49a1062eddf4fc48a19778e66e9a78", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vaccines 2019, 7, 145 2 of 21 serotypes (1-4) in one given restricted geographic area [4, 5] . While there is an unmet medical need regarding strategies against dengue, the incidence of this disease is expected to geographically expand in the future considering that the arthropod vector is colonizing northern European and American territories with temperate climates.", "DENV RNA synthesis and capping are believed to occur within the VPs since the viral replication dsRNA intermediate localizes within this ER-derived ultrastructure as shown by imaging studies using immunogold labelling and electron microscopy [16] . This confined environment is most probably important not only to concentrate the metabolites and proteins required for replication but also to exclude potentially inhibitory host factors. Considering this, it is tempting to speculate that neo-synthesized uncapped DENV RNAs \"hide\" from RIG-I in VPs although this model remains to be experimentally validated." ] },{ "paper_id": "ac8d2e900ee0c6d713d153782a530ddee6d606aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In contrast during a low or non-pathogenic viral infection, the mixing of hosts may be more likely.", "Minimum lethal dose and minimum infectious dose assays.", "Statistical analysis. All statistics were performed using the statistical function on GraphPad Prism 7 (GraphPad Software). Statistical calculations included two-tailed paired Student's t-test and Mann-Whitney Utest. P-values <0.05 were considered significant.", "We assessed the ability of the isogenic H9N2 virus pair to undergo multiple cycles of replication from a low m.o.i. (0.0001 p.f.u.) in a range of avian cell substrates in vitro." ] },{ "paper_id": "ac8f8e404ca0e3a052340bf089d90474b38d2b2b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Expression of markers was measured by flow cytometer using specific antibodies and their corresponding isotype controls." ] },{ "paper_id": "ac99323189694e10b699a6c845bd15b86cc06d82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cycle threshold (C T ) analysis was conducted using ABI StepOne TM software according to protocols by Thiessen et al. (2016) . Spore concentrations were determined for field samples by identifying the average C T value for each triplicate reaction, and comparing this value to the standard curve described below. Average C T values of positive controls", "At the time this research was initiated the LAMP technology was the most advanced for inexpensive field application and thus selected for investigation over other potentially suitable technologies. However, other DNA amplification techniques have since become more accessible for field use (Marx, 2015) , including qPCR (BioMeme, Inc., Philadelphia, PA, USA), recombinase polymerase amplification (Piepenburg et al., 2006) , and helicase-dependent isothermal DNA amplification (Vincent, Xu & Kong, 2004) . These assays require minimal DNA preparation, are capable of real-time data, and may be easily adapted to the air samples used here but require evaluation. There are several reviews that discuss the advantages and disadvantages of these technologies (Craw & Balachandran, 2012; Gill & Ghaemi, 2008; Mahaffee, 2014; Niemz, Ferguson & Boyle, 2011; Yan et al., 2014) .", "The purpose of this research was to develop a quantitative molecular assay for commercial implementation that could be used by growers or vineyard consultants for the detection and quantification of airborne E. necator inoculum. The specific objectives of this project were to (1) develop a real-time, quantitative LAMP (qLAMP) assay that was sensitive and specific to E. necator, and (2) test field use of a mobile, qLAMP device by growers." ] },{ "paper_id": "ac99b803a90e235412c73efa91894e9a1ed3f019", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our study has several limitations. First, the accounting of disease funding in 2006 by NIH is not standardized nor is the reliability known [32] . However, no alternative source of information is publicly available and historical and new accounting methods yielded similarly poor correlations with burden." ] },{ "paper_id": "ac9e71b8ce45ac71f25abec56e4d60db6b68d703", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Quantitative Insights into Microbial Ecology (QIIME) version 1.9.1 was used to analyze the sequencing data generated from three replicate trials samples ( Table 1) . Raw data were demultiplexed, and quality filtered with QIIME default settings (22) . The 250-bp reads were truncated at any site of more than three sequential bases receiving a quality score \u03b1-thujone > 1,8-cineol > \u03b2-thujone;" ] },{ "paper_id": "ad4dc41b48d9f6024088cb6c65a51972d928d200", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A detailed derivation of the above formula is published elsewhere [31] .", "The first three equations of equation group Eq (1) can be transformed as follows:", "doi:10.1371/journal.pone.0152438.g006" ] },{ "paper_id": "ad4f830c6a0985b878a66d4e797232ccba91aedc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Compound 1 was prepared as previously described [49] and reacted overnight with a mixture of NaH and tert-butyl (2-bromoethyl) carbamate in DMF to produce compound 2. We reduced compound 2 with LiAlH 4 and AlCl 3 (at a 3:1 ratio) in THF at room temperature for 4 h to produce compound 3. The N-Boc-protected amine was deprotected with H 2 SO 4 in CH 2 Cl 2 at room temperature for 22 h to produce compound 4. Finally, Biotin-X-SSE (Invitrogen) was coupled to compound 4 using Et 3 N in DMF at room temperature for 22 h to produce compound 5, the biotinylated tylophorine, a tylophorine-based dibenzoquinoline derivative (Fig. 1A) ", "We performed western blotting as previously described [18, 20] with antibody listed in Supplemental Table 5 . See Supplemental Materials and Methods for co-immunoprecipitation using anti-caprin-1 antibody (ProteinTech Group).", "CAPRIN1-pCMV6-entry was obtained from Origene, and transfected in HEK-293 cells. Expressed caprin-1 was purified using anti-FLAG M2 affinity gel (Sigma-Aldrich). After washes with TBS buffer, the human caprin-1 protein was eluted with 3X Flag peptide (N-Met-Asp-Tyr-Lys-Asp-His-Asp-Gly-Asp-Tyr-Lys-Asp-His-Asp-Ile-Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Lys-C, Sigma-Aldrich)." ] },{ "paper_id": "ad552caeace5008fba0e156d30a5e6f8f6c2f420", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hydrogen Bonds ", "The results contained in this manuscript were integrated into a requested patent in Mexico." ] },{ "paper_id": "ad58a9c8fca5baf158c0c25aa68a08dc7265d3c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reads containing adapters, low quality reads, and rRNA reads were removed. The remaining reads of each sample were then mapped to Sus scrofa reference genome (Sus scrofa 10.2) by TopHat2 (version 2.0.3.12), respectively.", "To identify the novel transcripts, all of the reconstructed transcripts were aligned with reference genome and divided into twelve categories using Cuffcompare (V2.2.1). We used the following parameters to identify reliable novel transcripts: the length of transcript was longer than 200 bp and the exon number was more than 2.", "LncRNA abundance was quantified by RSEM (V1.2.8) and normalized to fragments per kilobase of transcript per million mapped reads (FPKM). The formula is shown as follow:" ] },{ "paper_id": "ad60294d191a68f9db374d7ec49f42c2303b3b00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total cellular RNA was extracted using the RNeasy kit (Qiagen). HCV RNA quantification was performed with a real-time RT-PCR assay, as previously described [25] .", "HCV RNA in supernatants was extracted using the QIAamp viral RNA mini kit (Qiagen). HCV genome sequences were determined by directly sequencing overlapping purified RT-PCR fragments, with the BigDye Terminator v1.1 kit (Applied Biosystems). The sequence of primers used for RT-PCR and sequencing reactions are available on request.", "Mann Whitney test was used as indicated, and values of p < 0.05 or p < 0.001 were considered as thresholds for significance." ] },{ "paper_id": "ad68e5f84b2feb5e50d799f3a1eedf293fb19961", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fcimb. 2019.00340/full#supplementary-material Figure S1 | Allelic discrimination plot for IFNL4 rs12979860. Example showing genotype clusters CC (circle), CT (triangle), TT (diamond) and no template controls (square). Figure S2 | Allelic discrimination plot for IFNL4 rs368234815. Example showing genotype clusters TT/TT (circle), G/TT (triangle), G/ G (diamond), and no template controls (square). For three cases in this plate the genotype was not possible to determine (cross) due to low concentrations of genomic DNA. Genotyping was repeated for such cases using higher DNA concentrations.", "Sociodemographic and clinical data were analyzed using the statistical package for social sciences (SPSS) version 25.0 (IBM Corporation, New York, USA). Graphs were generated by the GraphPrism 8 software (GraphPad Software, Inc., CA 92037, USA). The chi-square test for trend or logistic regression were employed to relate genotypes to binary responses. Genotypes were coded 0, 1, or 2 according to favorable allele count. Fisher's exact test was employed when genotypes were collapsed into two groups.", "The datasets for this manuscript are not publicly available. Requests to access datasets should be directed to Dr. Maria Andersson, maria.andersson.3@gu.se." ] },{ "paper_id": "ad6a3623db73b778bbfabb99c47116c30459e66d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A number of human pathogens, e.g., Borrelia, Streptoccocus, and Leptospira interrogans acquire plasminogen on their surfaces and use the proteolytically active plasmin to cleave and inactivate C3 and C5 in order to disarm the host immune defense (see, e.g., [40] and references therein).", "Proteolytic cleavage of key complement components by complement and non-complement proteases Complement component C3", "Chymotrypsin is the archetype serine protease, being able to cleave proteins on the carboxyl side of a large hydrophobic or aromatic amino acid. Its substrate preference has been demonstrated using a series of substrates, with increasingly hydrophobic amino acids giving higher and higher k cat /K m values, indicating that the most efficient cleavage is obtained for the aromatic amino acid Phe [6] .", "Proteases are expressed ubiquitously in all tissues of the human body. By definition, the word Bprotein-ase^derives from the Greek word Bprotelos^(\u03c0\u03c1\u03c9\u03c4\u03b5\u03bb\u03bf\u03c3) meaning Bfirst rank [ 1] in combination with the word Bdiastasis^(\u03b4\u03b9\u03ac\u03c3\u03c4\u03b1\u03c3\u03b9\u03c2) meaning Bcleavage^or Bseparation.^Proteases capable of cleaving Bfirst-rank^molecules seem to be excessively released and activated under local inflammatory conditions, resulting in local barrier breakdown, cellular dysfunction, and invasion of inflammatory cells and/or microorganisms. There is longstanding evidence that proteases are involved in many, if not all, acute diseases [2] ." ] },{ "paper_id": "ad71472308fc72f2b3fe0044ac4bc2f08c4481b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Feline coronavirus infection presents a virological and immunological conundrum. How does a relatively innocuous enteric pathogen that induces a modest immune response evolve into an ", "The following are available online at http://www.mdpi.com/1999-4915/11/10/906/s1, Table S1 : Serum Chemistry and Hematology Results. " ] },{ "paper_id": "ad724f7660b9d84da71a1855f411b5a450aa309e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results clearly indicate that all infectious gRNA is removed at the step of PCR (Fig. 3B ), likely resulting from the temperature cycling conditions. However, we cannot ", "Supplemental material for this article may be found at http://dx.doi.org/10.1128/ mSystems.00039-15. Figure S1 , EPS file, 1 MB. " ] },{ "paper_id": "ad7576ff127570ebd90067bd6707f02776b687e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animal domestication was a significant turning point for mankind.", "Working with primates also requires very well-trained staff (owing TA B L E 1 Schematic compilation of traits and possible challenges to consider when planning to use an animal model 2,6,11", "None. " ] },{ "paper_id": "ad79f4149f66651ceee0f251347fc5093294f68d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Foot-and-mouth disease (FMD) is a highly contagious disease caused by foot-and-mouth disease virus (FMDV). Outbreaks of FMD spread rapidly and usually cause devastating economic losses and trade embargoes. FMDV primarily infects cloven-hoofed animals including cattle, swine, sheep, and various ruminants. The virus belongs to the genus Aphthovirus in the Picornaviridae family and has seven serotypes: O, A, C, SAT1, SAT2, SAT3, and Asia1. There is poor cross-protection among these serotypes [1] .", "The genome of FMDV consists of a single-stranded positive-sense RNA with a length of about 8500 nucleotides. The genomic structure can be artificially divided into three parts: the 5\u2032 untranslated region (UTR), the open reading frame (ORF), and 3\u2032-UTR. The single long ORF of viral RNA encodes a polyprotein that is subsequently processed into four mature structural proteins (VP1, VP2, VP3, and VP4) which form the capsid, and about 12 non-structural proteins (L pro , 2A, 2B, 2C, 3A, 3B, 3C, 3D, 3AB or 3ABC, 2BC, and 3CD) ( Figure 1 ) [2] .", "influence the activity of L pro because its cleavage activity varies greatly in different pH ranges [34] ." ] },{ "paper_id": "ad7c54f9cbd1779ce878360e15699bebcbd80cd6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "First and second round amplicons were resolved in a 1.5% (w/v) molecular biology grade agarose gel, stained with 0.1 mg/ml ethidium bromide and viewed under ultraviolet light.", "EM was responsible for carrying out this study and was the main contributor to writing the manuscript." ] },{ "paper_id": "ad8462ee6be4cf7ab5b17b2b81c713879c599a73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell lines and cell culture. HeLa, U2OS, THP-1, HEK293, HEK293 Flp-In T-REx-GFP-Artd8-macro2-3" ] },{ "paper_id": "ad898b084d41c346f3da45e58960ae7925d52100", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ad9cec450f3304e01cb4b517de934ba18094ce43", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PCR that used to detect other pathogens including MDV (F: 5 0 -T GCGATGAAAGTGCTATGGAGG-3 0 ; R: ", "In total, 722 clinical specimens from suspected sick fowl or fowl embryos (mostly comprising livers, spleens, and thymuses) were collected from 2014 to 2015, covering many provinces of samples were not only collected from clinical dead chickens, but also from suspected sick ones (acting depressed; loss of appetite; emaciation; diarrheal; crippling or growth retardation).", "MDCC-MSB1 cell cultures are preferred for virus isolation. Freshly prepared cultures containing 2 \u00d7 10 5 cells/well were seeded in 6-well plate. Cells are inoculated with 400uL/well (1:5, v:v) of prepared clinical tissue homogenates. Cultures are split every four days for 10 passages or until cell death is observed [18] .", "The genus Gyrovirus, a diverse group of non-enveloped icosahedral viruses containing circular single-stranded DNA [1] , infects a wide range of hosts. They also trigger several serious diseases in animals as causative agents. In particular, chicken anaemia virus (CAV), a member of family Anelloviridae genus Gyrovirus, is the etiological agent of chicken infectious anaemia [2] . CAV infects several bone marrow-derived cells which results in severe anaemia and immunosuppression in young chickens. In terms of older birds, CAV can jeopardize the immune responses [3, 4] . Since its first reported in 1979 [2] , CAV infection has become epidemic among chicken populations on a global scale [5] [6] [7] . CAV also has dramatic financial impact in a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 areas of intensive chicken farming. Vaccination is generally used to contain the spread of the virus [8] . In a recent study, a novel human gyrovirus was isolated from a skin swab and designated as human Gyrovirus (HGyV) [9] . Since Circovirus shares partial homology to CAV, the identification of HGyV signals possible threats for human pathogenesis, further investigation is yet required.", "In 1996, CAV was first reported from young broilers in China [13] . 42% of overall seroprevalence was shown in farms of five Chinese provinces in a domestic poultry survey [14] . In addition, a high prevalence of 87% resulted in studies of the virus on live bird markets in Southeast China [15] ." ] },{ "paper_id": "ada981b0b99f2468f331107ff419b9aea9c9175e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "critical structures and developing understanding of their role in virus replication will provide insight into this central stage of the virus life cycle.", "Ethics statement. Primary chick kidney (CK) cells and ex vivo tracheal organ cultures (TOCs) were prepared by The Pirbright Institute microbiological services department from chickens produced in the Institute's poultry production unit. Sacrifice of chickens and embryos was performed by trained staff under a schedule 1 procedure, in accordance with local rules. This procedure does not fall under any UK Home Office licence requirements as procedures were not carried out on live animals. However, studies were carefully considered for animal welfare and ethical implications and were approved via institutional processes. The kidneys were removed from the sacrificed chickens for preparation of the primary CK cells and trachea were removed from the sacrificed chickens or embryos for preparation of ex vivo TOCs. All work was performed in a designated establishment, The Pirbright Institute, Compton Laboratory." ] },{ "paper_id": "adab31f0d8b09bc7d087969e7664b22ab584dc81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "adbb0a486cf43c474df8b8b86fa6eacd422b171c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The HMPV A2 stain NCL03-4/174 was used in the LLC-MK2 cell line in DMEM (BSA, 0.5 \u03bcgml TPCK-trypsin) at 37\u00b0C for 7 days." ] },{ "paper_id": "adbb693cc7e5436489cb3043cecc6f28a346c7ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics. This work was conducted with approval of the Noguchi Memorial Institute for Medical Research Institutional Review Board ( permit #005/12-13), the University of Cambridge Human Biology Research Ethics Committee ( permit #HBREC.2012.12) and the Zoological Society of London Ethics Committee (Human Impacts ref. WLE655).", "Emerging infectious diseases (EIDs) represent a major threat to global health. In recent years, re-emerging and newly emerging wildlife-associated zoonoses such as Ebola virus in West Africa, Severe Acute Respiratory Syndrome (SARS), Human Immunodeficiency Virus (HIV) and numerous novel strains of influenza have led to substantial economic and human losses [1] .", "This context places this study of how novel zoonoses may be diagnosed (or not) at the centre of real world One Health issues; if diseases are not diagnosed, they will remain neglected. The assumption is often made that important zoonoses can be detected and responded to 'at source', although the lack of reporting of single cases or isolated clusters of important human diseases like Ebola is evidence that primary cases that do not spread are almost invariably missed. It is of great concern that current systems must be missing a significant burden of disease." ] },{ "paper_id": "adbfd5297c83ec9c3bec89f2cf68b2715034c4d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Angiotensin type 1 receptor blockers (ARBs or \"sartans\") have been widely used as a successful and established therapy for the treatment of clinical hypertension [45] .", "MMCA, ER and CM all contributed to the review of the literature, critical analysis and drafting of the manuscript. MMCA prepared the figure and tables. All authors read and approved the final manuscript.", "Recombinant tissue plasminogen activator (rt-PA; Alteplase), is the only thrombolytic treatment currently available for acute ischaemic stroke (AIS). It acts by breaking down the clot or thrombus obstructing the cerebral vessel, thus, re-establishing blood flow. However, it has a narrow therapeutic time window of 4.5 h from stroke onset, resulting in only 2-5 % of ischaemic strokes being treated globally, and can have detrimental side effects, including haemorrhage [4] . Recent results from a number of randomised clinical trials of mechanical thrombectomy have demonstrated efficacy for this intervention up to 6 h after stroke onset [5] . The positive results from these trials have reinvigorated the stroke community and open up new possibilities for adjunctive protective strategies.", "Failure to translate effective therapeutic strategies from the 'bench to bedside' may partly be attributed to the use of animal models that do not incorporate non-modifiable risk factors such as gender and many of the stroke comorbidities observed in the clinical stroke population, such as hypertension, diabetes, obesity, etc. For instance, hypertension is the single most important modifiable risk factor for stroke, acting as a contributing factor in over 75 % of first time stroke patients [6] with hypertension during acute stroke is associated with poorer clinical outcome [7] ." ] },{ "paper_id": "adc882dda7e73073791ae83afee7affd0d3e3793", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hospital Research Ethics Committee. All study participants provided written informed consent upon admission for their information to be stored and used for research. The methods were carried out in accordance with the approved guidelines and regulations.", "HIV-1 infection does not only increase cytokine levels, but also reorganizes cytokine networks, establishes new strong correlations between various cytokines and thus imposes a high rigidity to the cytokine network 15,16 ." ] },{ "paper_id": "adca0aec2cb598e223c27174528cac36c4ae057f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A target-agnostic approach to identify functional antibodies", "The insertion of non-VDJ sequences encoding structured domain into Ig genes is a new and potentially general concept. Our finding was facilitated by the huge expansion of LAIR1-containing B cells and by the unique properties of the antibodies made. In an initial attempt to determine the generality of this phenomenon, we found frequent insertions in the switch region of memory B cells from European blood donors. Interestingly, the inserts largely originate from genes that are transcribed in B cells and are encoded in virtually all chromosomes and, in rare cases, comprised exons with frames compatible with expression ( Fig 2D) .", "A trove of antibodies M emory B cells represent the repository of the immune experience of an individual. They are selected in the germinal centres, where they undergo a process of somatic mutations and selection by antigen and T helper cells. Memory B cells persist for a life time and can rapidly respond to a booster immunization by generating large numbers of plasma cells that are transiently present in the blood and localize to surviving niches in the bone marrow as long-lived plasma cells that are the main source of serum antibodies.", "Malaria infection can cause chromosomal instability and translocations involving the switch region, suggesting that it may also play a causative role in the generation of templated insertions. However, the finding of frequent templated insertions in European blood donors is more consistent with a general mechanism that remains to be molecularly defined. The sites of insertion suggest a mechanism of patch-repair of DNA double-strand breaks induced by either RAG or AID during V-DJ recombination or class switch. The integrity of the genomic LAIR1 loci in B-cell clones producing LAIR1containing antibodies suggests a copy-andpaste mechanism. In view of the finding that the inserts contain intronic sequences and are derived from expressed genes, we favour the hypothesis that the templated DNA may originate from the resolution of stalled replication forks caused by a clash between transcription and DNA replication." ] },{ "paper_id": "add093424f4f1c1da746abb3227193fb2fefbefa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ade1a8f088544b34547d3f9608805c969c9f189f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The animal experiment (pig feeding trial) was approved by the local state office of occupational health and technical safety ''Landesamt f\u00fcr Gesundheit und Soziales Berlin'' (LaGeSo Reg. Nr. 0347/09). Animal Experiment and Sampling Scheme" ] },{ "paper_id": "ade5723fc8cfb81cb7bc212d21539f1fe53fe218", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bat A3 cDNAs were PCR amplified from parental vectors and subcloned into pET24(\u00fe) vectors (EMD Biosciences). Plasmids were transformed into calcium competent C43 (DE3) strain E. coli (gift from Dr. Do-Hyung Kim) and grown in LB plates with kanamycin. Single colonies were selected and grown in LB with kanamycin for 28 h to ensure stationary phase growth. Thereafter, cultures were spread on either rifampicin plates or serially diluted in M9 salt media and spread on kanamycin plates. Colony counts were obtained after 18 h. rpoB mutation frequency was obtained by dividing the number of viable colonies on rifampicin plates by colonies on kanamycin plates and correcting for the dilution factor. A portion of the rpoB gene was PCR amplified using primers: forward 5 0 -TTGGCGAAATGGCGGAAAACC and reverse 5 0 -CACCGACGGATACCACCTGCTG. PCR products were enzymatically purified using Exonuclease I and rSAP (NEB). Purified fragments were sequenced using the forward primer (GeneWiz, NJ).", "Human embryonic kidney cells (293 T cells) and human epithelial cervical adenocarcinoma cells modified to express constitutively high levels of HIV-1 receptors and coreceptors (TZM-bl cells), were utilized in the inhibition of infectivity assay. The TZM-bl cells were obtained through the NIH AIDS Research and Reference Reagent Program (Wei et al. 2002) . All cell cultures were maintained at 37 C, 5% CO 2 in Dulbecco's modified Eagle's medium (Thermo) supplemented with heat-inactivated fetal bovine serum (100 ml/l; Invitrogen), glutamine (292 lg/ml; Invitrogen), and the antibiotics penicillin (100 units/ml; Invitrogen) and streptomycin (100 units/ml; Invitrogen).", "Supplementary data are available at Molecular Biology and Evolution online.", "This study represents the first report of the differential evolution of an important antiviral gene family in bats relative to other mammals. The full account and explanation of the ability of bats to act as such effective hosts and transmitters of zoonotic viral pathogens will likely consist of many complex and interlinking factors beyond simple metrics such as gene numbers and amino acid sequence characteristics. Ongoing studies of this expanded gene family should further demystify the strategies and mechanisms utilized by bats that result in an impressive tolerance for viral infections. " ] },{ "paper_id": "adeb15fc330fe6710ad1c979d0a33035b52f3ba0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pneumonia is the third leading cause of death worldwide and the leading cause of death due to infectious disease in industrialized countries. In developing countries, approximately 2 million deaths (20% of all deaths) of children are due to pneumonia [1] . The majority of patients with community-acquired pneumonia (CAP) in industrialized countries are treated as outpatients with a low mortality rate usually less than 1%. In patients requiring inpatient management, the overall mortality rate increases up to approximately 12%. Of note, lethality rate in hospitalized patients differs significantly among different patient groups due to comorbidity (COPD, stroke, etc.) or risk factors (age, patients from nursing homes) [2] .", "NOD proteins share a tripartite domain structure: The carboxy-terminal LRR domain seems to mediate ligand recognition (Fig. 2) . The central NOD (NACHT) domain exhibits ATPase activity and facilitates self-oligomerization. An amino-terminal localized caspase-recruitment domain (CARD) (one CARD domain in NOD1, two in NOD2) mediates protein-protein interaction [44] [45] [46] .", "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "ae0144eb4ec61e7765eed001bc8a9c775cd31b67", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Taiwan had been free of indigenous human and animal rabies case since canine rabies was eliminated in 1961 [1, 2] , despite the lower than recommended 70% rabies vaccine coverage among dogs and cats. The successful maintenance of rabies-free status was attributed to Taiwan's relative geographic isolation as an island and strict animal importation control [2] .", "Specimen submitted by sentinel hospitals were collected previously for encephalitis surveillance and re-tested for rabies virus. Information collected from persons requiring rabies postexposure prophylaxis was for public health use. All specimen and information collection were done by the pronouncement of the Central Epidemic Command Center, and, in accordance with regulations of Taiwan, therefore did not require institutional review board approval. Only oral consent was obtained for specimens collected for surveillance purposes. The data was deidentified prior to analysis.", "As of December 28, 2013, no patients who received PEP had developed symptoms suspected to be associated with rabies." ] },{ "paper_id": "ae0547531bec47c718e9f48ebb2454d9fdf4e487", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There have been volumes written in recent years about virus populations within individual hosts (see for example [25, 26] ); for ssRNA viruses these populations are often called quasispecies, and the level of variation can be extreme. It seems likely that ssDNA viruses develop similar diverse populations [27] .", "Symbiogenesis is the process whereby symbiotic entities fuse and create a new species. This process was first recognized in the discovery of the relationship between mitochondria and bacteria, and is now recognized as an important evolutionary force that may be responsible for major leaps that cannot be explained by Darwinian natural selection [3] , and that has probably played a major role in the evolution of new viruses [4, 5] . The most extreme cases of virus mutualism are really symbiogenic relationships.", "Although there are a number of other examples of epigenomic mutualistic viruses [2] , there have been few reported studies on the population dynamics of these viruses." ] },{ "paper_id": "ae0700fe06361c6d9e2286332ba467940ec9f89e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After washing five times, target protein was detected by western blot.", "KG, LX, MW, and YZ designed the research. KG, MW, YH, YJ, JL, PX, ZF, and RZ performed the research. KG, LX, FX, and YZ analyzed the data. FX and YZ contributed to new reagents and analytic tools. KG, LX, MW, FX, and YZ wrote the manuscript. ", "The Supplementary Material for this article can be found online at:" ] },{ "paper_id": "ae072e0f04db143d038aa090e714f31e0c8c34bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bacterial/yeast diagnostic samples were processed immediately in a qualitative and semi-quantitative ways using standard microbiological methods [12, 13] . For all samples, macroscopically distinct colonies were isolated in pure culture and standard methods for identification, typing, and sensitivity patterns were used.", "Clinical data HBoV without bacteria detection (n = 10)", "Data on the descriptive characteristics of the patients were analyzed by x2, Fisher's exact test. Non-parametric tests and median values were used for those variables, because they were not normally distributed, such as cytokine/chemokine concentrations. Correlations were made with Spearman's two-tailed rank correlation in addition to Pearson's linear regression two-tailed analysis. For all outcomes and relations between variables, differences between groups were considered statistically significant at P,0.05. SPSS (version 17.0) was used for all analysis." ] },{ "paper_id": "ae098292360fde9d65ff12d2beef927dff6c6077", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Supporting material. Model details, additional results.", "The risk associated with the accidental laboratory escape of potential pandemic pathogens is under the magnifying lens of research and policy making communities [1, 2] . The recent debate on the genetic manipulation of highly virulent influenza viruses [3, 4] has made clear the necessity for quantitative risk/benefit assessment before starting research projects involving biosafety level (BSL) 3 and 4 agents. According to data collected in 2010 and 2011, the number of BSL 4 laboratories worldwide is 38 [5] , mostly concentrated in the US (10) and Europe (14) .", "The preventive immunization of laboratory workers (see for instance the Special Immunization Program in the US [51] ) is another option not considered in this work. Although for diseases for which a vaccine is available this is a measure to take into account (for instance, the incidence of hepatitis B virus (HBV) infection among laboratory workers in the UK has significantly dropped because of the availability of immunization [52] ), this measure is highly questionable for genetically modified influenza viruses, not to speak of influenza viruses for which no vaccine is currently available, for example, A(H7N9)." ] },{ "paper_id": "ae0b9375dd56b6338cb63a3b5857e4125f5edf41", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ae165f6805cbb0b5c688d4d5e5a89b6b7c16fae0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Paraffin-embedded sections (4 \u03bcm) on charged slides were used for IHC for detection of L. intracellularis using specific rabbit polyclonal antibodies and a previously described method [32] . Stained sections were evaluated by bright field microscopy.", "Lawsonia intracellularis is a Gram-negative bacterium that requires an intracellular culture system and a specific atmosphere to be propagated in vitro [5] .", "There was no difference in growth or morphology between enteroids maintained for 1 week in the microaerophilic atmosphere relative to those maintained under regular conditions, i.e., 5% CO 2 incubator (data not shown), indicating that growth conditions required for L. intracellularis do not impact enteroid viability or growth." ] },{ "paper_id": "ae19236936b05793ceac08ed5d58269c25486320", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "While there are several open source tools available [21] for developing ontologies, we selected Prot\u00e9g\u00e9 because of its extensibility to a variety of plug-ins that are readily available for integration. It also has the ability to export to different formats including the Ontology Web Language (OWL) (http://www.w3.org/TR/owl-features/), which allows interoperability with other ontologies." ] },{ "paper_id": "ae29a35ad6b9e4267e1d965b523a6b72cb2c088c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To further streamline haplotype definitions, only lineage level allele names were considered (commonly referred to as two-digit resolution in human HLA genotyping, e.g., all Mamu-A1 \u00c3 007 allelic variants were grouped with the designation Mamu-A1 \u00c3 007; Figure 1 ). Alleles are named by the nonhuman primate Immuno Polymorphism Database-MHC group based on similarity to other known macaque MHC class I alleles, such that alleles sharing a common lineage level designation are identical or nearly so within the peptide binding regions.", "Whole blood samples from 96 Indian rhesus macaques were obtained from the Wisconsin National Primate Research Center (WNPRC) and New England Primate Research Center (NEPRC) breeding colonies. The WNPRC cohort was selected to be unrelated based on pedigree records whereas the NEPRC cohort was taken from active adult breeding stock. Macaques at the WNPRC were cared for according to protocols approved by the University of Wisconsin-Madison Graduate School Animal Care and Use Committee, whereas macaques housed at the NEPRC were maintained in accordance with standards of the Association for Assessment and Accreditation of Laboratory Animal Care and the Harvard Medical School Animal Care and Use Committee.", "RNA isolation, cDNA synthesis, and polymerase chain reaction (PCR) amplification (normalization and pooling) RNA was isolated from whole blood or peripheral blood mononuclear cell samples using the Roche MagNA Pure instrument and RNA High Performance kit (Roche, Indianapolis, IN), following manufacturer's protocols (Supporting Information, File S1). Synthesis of cDNA and PCR amplification were performed as previously described, generating either a 248-bp or 638-bp genotyping amplicon (the shorter amplicon dates back to studies performed before Roche/454 sequencing technology advanced to~500-bp read lengths) (Wiseman et al. 2009; Fernandez et al. 2011 ). The amplicons for each sample were tagged during primary PCR with a multiplex identifier sequence, a unique 10-bp tag for each sample (File S1). Amplification was confirmed by running PCR products on a Flash Gel (Lonza Group Ltd, Basel, Switzerland), and bead-based purification was performed using AMPure XP SPRI beads (Agencourt Bioscience Corporation, Beverly, MA) to remove primer dimers. Quantification of purified products was performed using the Quant-iT dsDNA HS Assay kit and a Qubit fluorometer (Invitrogen, Carlsbad, CA). Products were then normalized to 0.3 ng/mL and pooled in equal volumes." ] },{ "paper_id": "ae3594fcd839554d0a4ea161dc9bbd3d1f6dbaa9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "for any X and Y.", "If we denote:", "The distance defined by 2 / )) ," ] },{ "paper_id": "ae36c3fc53af891f884df86ac68bcebd0ad37229", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The present study was funded by Natural Science Foundation of Jiangxi Province of China [grant number 20151BAB205043].", "The interactions between CLDN1 genotypes and various clinicopathological characteristics were summarized in Supplementary Table 1 . The distribution of rs10513846 genotypes was significantly associated with age and grade ( than CC genotype carriers, the 5-year DFS was 74.8 and 39.8%, respectively. However, the difference was not significant, P-values were 0.050 and 0.056 in univariant and multi-variant analyses, respectively. Since only ten patients carried rs9842214 TT genotype, the results need to be verified.", "Peripheral blood samples (5 ml) were collected from each patient upon recruitment and stored in \u221220 \u2022 C for DNA extraction. Genotype data from CLDN1 gene regions encompassing 5 kb of upstream and 5 kb of downstream flanking sequences were extracted from the HapMap Chinese Han population. Haploview 4.2 software was used to identify Tag single nucleotide polymorphisms (SNPs). The inclusion criteria were SNPs known in ethnic Han Chinese population and with a minor allele frequency (MAF) >0.05 and r 2 > 0.8. A total of five candidate SNPs were selected for genotyping (Table 1) . Primers and probes were designed by MassARRAY Typer 4.0 software. MassARRAY MALDI-TOF System (Sequenom Inc., San Diego, CA, U.S.A.) [18, 19] was used for genotyping by the method described in the Sequenom Genotyping Protocol." ] },{ "paper_id": "ae3d16cad153ad376ec5782d74688a6f93093c37", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2015, 7 3687" ] },{ "paper_id": "ae40184ce67c93d60f2d5d00f451b00017af16cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The experiment was performed in accordance with EU and French regulations on animal welfare in experimentation. The protocol was approved by the AFSSA/ ENVA/UPEC ethical committee.", "is omitted because it plays no role in the calculations. The different b parameters were estimated using maximization of the log-likelihood with nlm function in R software (Version 2.6.0., [25] ). Confidence intervals were determined using the inverse of the Hessian matrix (variance/covariance matrix) of parameter estimates, also provided by nlm function in R software.", "with S j and C j the number of susceptible animals and cases at each sampling interval j respectively, d j the duration of the interval between two sampling times, and where log" ] },{ "paper_id": "ae423f7ae98fa3e8a1249bd193df1c09bdeedf7c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conflict of interest The author of this study has no conflict of interest.", "Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://crea tivecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.", "Ethical approval The MERS patient was informed of an urgent clinical test. This study was approved by the Medical Ethics Committee of Southern Medical University on May 28 and is in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards." ] },{ "paper_id": "ae44f456afccca76e1eec1637ce1af6041956c64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fraction 1 (F1) capsular protein of 17.5 kDa and virulence (V) protein of 35 kDa are virulent subunits produced by Yesinia pestis which causes the plaque disease. Vaccines based on F1 and V protein display protective immunity in both bubonic and pneumonic animal models (Williamson and Oyston, 2013) .", "Bacterial second messengers such cyclic di-nucleotides (e.g. c-di-AMP and c-di-GMP) are suggested as promising Cytokines IL-1, IL-12**, TNF and mutants Regarded as less toxic since they are human innate substances.", "Synthetic small organic molecules (imidazoquinoline, compound 48/80, vitamin E TPGS, glycolipid \u03b1-galactosylceramide)" ] },{ "paper_id": "ae4c5ad260f38772c10120bb77062912dcce189e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "On admission, his white blood cell (WBC) count was 30.6 \u00d7 10 3 /\u03bcL with 66.9% of granulocytes (in absolute numbers 20.6 \u00d7 10 3 /\u03bcL), hemoglobin 12.4 g/dL, and platelet count 321 \u00d7 10 3 /\u03bcL. His C-reactive protein (CRP) was 5.09 mg/L. A chest radiograph showed infiltration of the upper lobe of his right lung ( Fig. 1 ).", "After 46 days of hospitalization he recovered completely from HBoV1-associated acute bilateral bronchiolitis with right-side pneumonia and a subsequent hospital-acquired upper and LRTI and was discharged.", "On admission, his respiratory rate was 44 breaths/minute (reference 20-30), heart rate 146 beats/minute (reference 80-130), oxygen saturation 99% (with an oxygen flow of 5 liters/minute via face mask), and axillary temperature 38.7\u00b0C. Auscultation of his lungs revealed bilateral wheezing and crepitation with severe intercostal and subcostal recessions. The other organ systems were without pathology. Due to the severe respiratory distress, tracheal intubation was performed.", "At the time of admission, a nasopharyngeal swab (NPS) tested negative by direct immunofluorescence (IMAGEN\u2122 OXOID, UK) for antigens of RSV, influenza virus A and B, parainfluenza virus types 1-3, and adenovirus. Bacterial blood cultures were negative. NPA, blood, and stool samples were collected for HBoV1 molecular diagnostics and serology." ] },{ "paper_id": "ae7835c99d1391c53fec8da5b13783ebdd195223", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "with v = v s or v f depending on the type of transportation. To account for travel time, a link from node i to node j is divided into \u03c4 ij segments, with \u03c4 ij = t ij if mod(r ij ,v) = 0 and \u03c4 ij = int(t ij ) + 1 if mod(r ij ,v) \u2260 0 (lower Fig. 3) , where mod(x,y) represents the modulo operation and int(x) taking the integral part of x.", "Next, we set \u03b2 1 = 10 \u22124 > \u03b2 1c and Fig. 6 (a) shows that \u03c1 I (\u03b2 2 ) increases monotonically with \u03b2 2 , for v f = 250 and 500. Here, \u03c1 I \u2260 0 for all \u03b2 2 . There exists a value \u03b2 2c\u2032 (\u03b2 2c\u2032 = 0.0025 for the case in Fig. 6 (a) below (above) which \u03c1 I for v f = 250 is lower (higher) than that for v f = 500." ] },{ "paper_id": "ae79fbbd7e6130c0d5b451617260a7e63bda79e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total Symptom Score (TSS)" ] },{ "paper_id": "ae88cd3f2ac21948c74fd7b15b62cc03e9bac235", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sf21 cells [16] were maintained at 27uC in TC-100 media (Sigma) supplemented with 10% fetal bovine serum (Atlanta Biologicals). Wild-type AcMNPV strain L1 virus [17] used in this study and titrated by plaque assay followed standard procedures [18] to calculate the plaque forming unit (pfu)/ml. Plaque assays were performed in duplicate on three independent samples. All infections were carried out at multiplicity of infection (moi) of 10.", "RNA levels were determined as the number of cycles needed for the amplification to reach a fixed threshold in the exponential phase of the PCR reaction. The overall cycle threshold values (Ct) were compared for the different genes. Each of the seven candidate reference genes displayed a narrow range of mean Ct values across all experimental samples (Fig. 1A) . However they exhibited a wide range of RNA levels ( Table 2 ). The fluorescence peak after 5.54 cycles showed that 28S was the most abundant RNA, whereas myosin was the least abundant RNA with a Ct value of 33.5.", "It is well documented that due to experimental limitations of the PCR reaction, its DNA product is not amplified exponentially and the DNA synthesis will be saturated after 30 to 35 cycles [29] . Ribosomal protein L35, exhibited an expression pattern that was similar to tubulin, actin, and GAPDH in qRT-PCR analysis, declining rapidly after 6 hpi (Fig. 3) , inconsistent RNA levels were also observed on microarrays (unpublished data) indicating that L35 is not a good choice for normalizing qRT-PCR in AcMNPVinfected Sf21 cells." ] },{ "paper_id": "ae8b139ede9460926a290fbae525b59fbe0e5c53", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ae8c759fe82750edd66adb5e87e2ee44cb73c419", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The full complement of cellular factors that are sufficient for HSV entry is not clear. Receptor-negative cells that normally support entry by endocytosis are excellent tools to screen for factors that trigger HSV-cell fusion.", "HSV is able to traverse a pH-dependent, endocytic pathway [9] . The endosomal route is utilized in many cell lines including the model cell lines, CHO-nectin-1 and B78nectin-1 [9, 10, 12, [22] [23] [24] [25] . HSV entry into several human epithelial lines including epidermal keratinocytes occurs via a low pH-dependent pathway similar to CHO-receptor cells [9, 10, 21, [25] [26] [27] . Entry into human neuronal SY5Y cells and human epidermal cell line A431 proceeds via a pathway similar to that in B78-receptor cells [10, 24] . In addition, HSV enters several human neuronal cell types and model Vero cells by direct, pH-independent penetration at the plasma membrane [10, [28] [29] [30] [31] . An emerging theme for herpesvirus entry is the utilization of endocytic and non-endocytic routes in a cell typedependent manner [9, 10, [32] [33] [34] [35] [36] [37] .", "To accomplish entry via virus-cell membrane fusion, viruses depend on one or more cellular triggers such as endosomal pH, receptor engagement, and/or enzymatic cleavage [1] [2] [3] [4] [5] [6] . The host requirements for herpesviral fusion and entry are incompletely defined. Herpes simplex virus (HSV) binds to a cellular receptor such as nectin-1 or HVEM. This interaction is essential, but it is not clear if it is sufficient for fusion and entry [7, 8] . There is mounting evidence for additional cellular cues for HSV entry such as intracellular low pH [9] [10] [11] [12] [13] [14] and receptors that bind either gB [15] [16] [17] or gH [18] [19] [20] [21] ." ] },{ "paper_id": "ae918e83ef815351c2c0e47a337ec78954f5cec0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The original typing module was implemented in Borland Delphi 7 running on a 32 bit Windows environment. The software was recompiled using a 64 bit Windows environment with a Delphi compiler (RAD Studio XE5; Embarcadero, Austin, Texas, USA) and actual components for data access (MyDAC, CoreLab software development) and web frontend (intraweb components from Atozed-Software). The module was embedded into the maintaining PHP web frontend on the web server but running on a separate computer to speed up computing time. Additional code optimization of the implemented algorithms (Needleman-Wunsch, Smith-Waterman, Neighbor-Joining) was achieved by loop unrolling, via dead code elimination, via the deletion of unused variables, and by restructuring the code.", "CSFV nucleotide sequences were determined as described previously [11] . E2 encoding sequences of the CSF-DB catalogue numbers CSF0088, CSF0183, CSF0605, CSF0631, CSF0804, CSF0818, CSF0819, CSF0869, CSF0934, and CSF1040 were included in the CSF-DB and deposited in GenBank under Acc. Nos. KX687712-KX687721.", "The CSF-DB runs on a Linux server using a MySQL-Server (Version 5.5.50). The Web frontend for maintaining, searching, and accessing the separately running genetic typing module and the new \"CSF Maps\" tool is written in PHP (Version 5.4.45). The PHP scripts run on an Apache web server (Version 2.2.22). The CSF-DB is available online via http://viro60.tiho-hannover.de/eg/csf/; access is permitted after a password request at csf.eurl@tiho-hannover.de." ] },{ "paper_id": "ae94601843c7f14fc95e723c9bce16232b0bfd70", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Primer 5\u2032-3\u2032", "chloromethyl ketone (TPCK)-treated trypsin (Sigma, USA) and 0.3% bovine serum albumin (BSA; Sangon, China). After 1 h, cells were incubated with fresh infection medium at 37\u00b0C for the indicated times.", "The animal study was reviewed and approved by Academy of Military Medical Sciences (AMMS; ID: SYXK2012-05).", "ChZ and GL contributed to conceptualization. ChZ, GL, and LZ contributed to methodology. LZ, CaZ, and YS contributed to investigation. RW and ChZ contributed to writing the original draft. RW and ChZ contributed to writing, reviewing, and editing. ChZ contributed to funding acquisition. LZ, DD, and MB contributed to resources. RW, GL, and ChZ helped in supervision. " ] },{ "paper_id": "ae94b6a3da2521778ce8af0fe653a30a14f74c6a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ae99d270c1b2d2307c4375fecde1a037c263b507", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "aea331cddd5eef46512ecea34503ed02af95d23e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Substrate specificity of AtSBT1.1", "Phytosulfokines (PSKs) are a class of plant peptides discovered through the study of growth factors that mediate density-dependent growth in cell culture . isolated and identified growth factors from conditioned medium that promoted the growth at low density of asparagus mesophyll cells in tissue culture. They identified a sulfated pentapeptide [H-Tyr(SO 3 H)-Ile-Tyr(SO 3 H)-Thr-Gln-OH, abbreviated sYIsYTQ], named PSK-a, and a sulfated tetrapeptide [H-Tyr(SO 3 H)-Ile-Tyr(SO 3 H)-Thr-OH], named PSK-b, that were active in the asparagus cell system.", "Root segments (5 mm) incubated on CIM were harvested and further incubated for 6 h in GUS staining solution [100 mM Tris/ NaCl buffer, pH 7, 2 mM ferricyanide, 2 mM X-gluc (5-bromo-4-chloro-3-indolyl-D-glucuronide), 2 mM ferrocyanide, 10 mM EDTA and 0.1% Triton X-100] at 37\u00b0C in the dark. The staining solution was removed, and the tissues were dehydrated in an ethanol series from 70% v/v to absolute ethanol. Samples were visualized under the light microscope.", "Six genes encoding PSKs (AtPSK1-6) have been identified in Arabidopsis. Each encodes a preproprotein precursor of approximately 80 residues, with the YIYTQ peptide near their C-termini . generated transgenic Arabidopsis plants (AtPSK4ox) over-expressing one of the AtPSKs, and found that root growth and callus formation were slightly enhanced in over-expression lines, but otherwise the seedlings were phenotypically indistinguishable from wild-type." ] },{ "paper_id": "aea827ad6b4888677fad2702e41ef2b6d65e8141", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The intracellular RNA was isolated using peqGOLD Trifast (peqlab Biotechnologie GmbH) according to the manufacturer's instructions.", "Materials and Methods", "Primary human hepatocytes (PHHs) were isolated and cultivated as described [23, 24] . Infection and treatment of the PHHs were performed in accordance with the A549 experiments.", "Results are presented as means \u00b1 standard errors of the means (SEMs) from at least three independent experiments. The significance of the results was analyzed by unpaired two-tailed Student's t test, using GraphPad Prism, version 6.07 for Windows (GraphPad Software, San Diego, CA, USA). In all figures the statistical significance is compared to the DMSO control group. Statistical significance is represented in figures as follows: ns = not significant = p > 0.05; * = p \u2264 0.05; ** = p \u2264 0.01; *** = p \u2264 0.001; **** = p \u2264 0.0001." ] },{ "paper_id": "aeac4c993813c60687acf54e7a35957830c7b727", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Proposed additional countries to expand or to initiate environmental surveillance in 2017 includes Uganda, South Sudan, Burundi, Ethiopia, Algeria, Guinea Bissau, Guinea, Equatorial Guinea, Gabon, DR Congo, Sierra Leone, Liberia, Cote d'Ivoire, Mali, Tanzania, Zambia, Mozambique, South Africa and the Central African Republic.", "The country must have a capacity for initial processing of the samples and for transporting them rapidly to the laboratory. The laboratory capacity must first be sufficiently increased to be able to cope with the high workload. When sites are selected, consideration should be made for households that are equipped with water closets connected to a converging sewer network allowing collection of downstream samples that represent a large number of people living in the catchment area. Also, when selecting sites, consideration should be made to select areas without chemicals from industrial wastes that may be detrimental to poliovirus stability or be toxic to cell cultures and interfere with poliovirus replication. Lastly selected sites should represent selected high-risk populations." ] },{ "paper_id": "aeaf5bd4725051f6926d06450566673d1cc4a639", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "TEM was utilized to obtain more detailed pathological information responsible for the major symptoms. The tissue samples were fixed in 2.5% (vol/vol) dialdehyde for 2 h, postfixed in 1% (vol/vol) osmium tetroxide for 1 h, dehydrated in graded ethanol, and embedded in Epon-812 epoxy resin. Then, 70 nm ultrathin sections were produced and quickly stained in aqueous uranyl acetate and Reynolds' lead citrate. Finally, the generated tissue sections were examined using a JEM-1200 TEM (Jeol Ltd. Tokyo, Japan).", "Coronaviruses (CoVs) are a family of RNA viruses belonging to the Coronaviridae family and the Coronavirinae subfamily and are the largest group of positive-sense single-stranded RNA viruses. From an academic perspective, CoV can be divided into four genera, namely Alphacoronaviruses, Betacoronaviruses, Gammacoronaviruses, and Deltacoronaviruses. The alphacoronaviruses and betacoronaviruses are usually found in mammals, while the gammacoronaviruses and deltacoronaviruses are mainly associated with birds 1,2 .", "All 440-bp-long amplicons were aligned with their closest phylogenetic neighbors in GenBank using Clus-talW v.2.0. Representatives of different species in the genera of Alphacoronavirus and Betacoronavirus as well as some unapproved species were included in the alignment. Phylogenetic trees based on nucleotide sequences were constructed using the neighbor-joining method using MEGA v.7 with the Maximum Composite Likelihood model and a bootstrap value of 1000 37 .", "To test the pathogenicity of the ZC45 agent, infection experiments were performed in suckling rats. 3-day-old suckling BALB/c rats (SLAC, China) were intracerebrally inoculated with 20 \u03bcl of volume grinding supernatant of ZC45 intestinal tissue. Animal housing care and all animal experiments were performed in a biosafety level 3 (BSL-3) facility and were approved by the local ethics committee. After 14 days, the brain, lungs, intestine, and liver tissues from infected rats were selected to prepare pathological sections. Briefly, the tissues were fixed in 10% (vol/vol) neutral-buffered formalin. After routine tissue processing, including dehydration by graded alcohol solutions, washing, and incubation in paraffin, 4 \u00b5m thick sections were cut and stained with hematoxylin and eosin (H&E). Approximately 2 h later, the prepared tissue sections were imaged using optical microscopy (Olympus, Japan)." ] },{ "paper_id": "aeb63d391feee1b548adf8d5a208d70c3ee5c802", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using the two-tailed student's t-test, by using SPSS 18.0 (SPSS for Windows Release 18.0, SPSS Inc., Chicago, IL, USA). Statistical significance: * p < 0.05, ** p < 0.01.", "Viruses 2017, 9, 235 9 of 17" ] },{ "paper_id": "aeba70238bd0c68d3995b9a241da7cb9d2bf73dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "aebf3e6b69b0563ab38d9d973db9a7795f75f47e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In brief, sterile beads were added to the samples, vortexed and processed routinely followed by centrifuged at 2000 rpm for 7 min. Specimens were then decontaminated by adding a 10% antibiotic mixture (Gibco, N.Y.USA) and incubating for 1 h at 4\u00b0C. A volume of 200 \u03bcL of sample was inoculated into each of the following cell lines: MRC-5, HEp2, RD, MDCK, and LLCMK2 (ATCC, Manassas, VA, USA). One \u03bc\u039b of maintenance medium (minimal essential medium with 1% fetal bovine serum) (Gibco, N.Y.USA) was added to each cell line and incubated at 37\u00b0C for 14 days. The CPE was observed every other working day by inverted light microscopy (Olympus, Japan). After CPE appeared, cell smears were prepared and fixed in chilled acetone at \u221220\u00b0C for 10 min and then tested by fluorescein-conjugated monoclonal antibody in a direct immunofluorescence assay (D 3 Ultra 8 TM DFA Respiratory Virus Screening & ID Kit, Diagnostic Hybrids, USA). Stained cell smears were examined in a fluorescence microscope at 400\u00d7 magnification (Olympus, Japan). Un-inoculated cell smear was used as negative control." ] },{ "paper_id": "aec276f9c340e5be5f9db9264727cbc8606203e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reads were first assembled by metagenomics assemblers, and output contigs were then aligned to NT and NR.", "Supplementary tables and figures are available with the online version of this paper.", "Unlike bat CoVs which are grouped into various evolutionary clades of the genera Alphacoronavirus and Betacoronavirus [32, [52] [53] [54] [55] , CoVs identified in various rodent species from various regions can only be classified into two lineages: lineage A of Betacoronavirus and a separate lineage of Alphacoronavirus. Human CoV OC43, human CoV HKU1, and bovine CoV under lineage A of Betacoronavirus are human or animal pathogens that cause mild-to-severe diseases [28] . The identification of diverse lineage-A rodent \u03b2-CoVs confirms the hypothesis that rodents may be an important reservoir for ancestors of lineage-A \u03b2-CoVs [28, 29] . The identification of \u03b1-CoVs under separate lineage from diverse provinces suggests a broader geographical distribution of these rodent-specific viruses." ] },{ "paper_id": "aec5514aada77bb18c23a36f314ce949ba0ff846", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The \u03c72 or Fisher exact test was used to assess the statistical significance of categorical variables. We considered results to be statistically significant with p < 0.05 via the Fisher's exact test. All analyses were performed using the OpenEpi 2.2 statistical package [9] . The survey was supported by the National Centre for Immunization Research and Surveillance, Children's Hospital at Westmead. Ethical approval was sought and granted from both of the hospitals.", "Methods: Cross-sectional investigation of a convenience sample of clinical and non-clinical HCWs from two tertiary-referral teaching hospitals in Sydney, Australia was conducted between June 4 and October 19, 2007. The self-administered questionnaire was distributed to hospital personal from 40 different wards and departments. The main outcome measures were intentions regarding work attendance and quarantine, antiviral use and perceived preparation.", "Despite these issues, the large sample size of our study, broad spectrum of HCWs represented, and representative age/gender demographics provide a general indication of what responses to a pandemic may occur and provide information on differences between health care worker groups. In addition, much research focusing on behavioural intentions indicates the potential for these to be reasonable in predicting actual behaviour [27] ." ] },{ "paper_id": "aec923adf0e16d218315a3083aaa71fb9ddb8b39", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accumulated TNF-a protein was measured in 24 h culture supernatants by ELISA (R&D, DY410) as previously described [18] , except that all samples were analysed in triplicate wells.", "An estimator of body condition was produced by taking residuals (BW resid ) from a regression of body weight (BW) on SVL, incorporating different slopes for males and females and quadratic terms to allow for a curvilinear association.", "It was not possible to identify a candidate infectious aetiological agent for the extreme immunological expression syndrome described above amongst the microparasites (Eimeria spp., Babesia microti and Bartonella spp.) and macroparasites whose presence we " ] },{ "paper_id": "aecb440fc8c84846d96359ffd450f3e24a00cdca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Yersinia sp. utilizes a type III secretion system for translocation of virulence effectors into the host cell [3] . All three Yersinia species contain a 70kb plasmid that encodes a type III complex system and effectors (Yops).", "\u0394G bind = G Complex \u2212 G Receptor \u2212 G Ligand Where G stands for free energy.", "The experiments were performed at least three times. The data were applied and analyzed with GraphPad Prism (GraphPad Software v.4). Statistical analyses were performed using ANOVA combined with Tukey's test or T test combined with Wilcoxon test. The data were expressed as means \u00b1 SD. Differences between means were considered significant for P < 0.05." ] },{ "paper_id": "aecd12a815bf5fd6486b92bc8fb631d00fef541f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A two-hour training session proceeded as follows:", "2. The group then observed two educators describing and demonstrating the dress-up and the dress-down method for the PPS.", "6. All physicians trained with their peers concurrently on call. There were six anesthesia residents and six medical residents, but many more nurses and respiratory therapists, to be trained. Hence, once we had trained the residents, we modified the simulation for the remaining nurses and respiratory therapists. Subsequent simulations involved only basic cardiopulmonary resuscitation and intubation because hospital policy mandates defibrillation by physicians only.", "To expedite dressing we put up wall posters demonstrating the dress-up procedure and we used one dressing assistant per two team members. This represented a realistic number of people probably available to help at an actual arrest. It was also an acceptable total number of people (six) that could fit around the equipment cart.", "We also proposed having all SARS patients on cardiac telemetry, so that a defibrillator could be brought into the room by the first responder. Available resources did not permit a defibrillator in each room." ] },{ "paper_id": "aed0e70359bffd12f9748dc4d900d9ec3a170422", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "K48 chain-CTD binding stimulates the Cdc48 ATPase activity.", "The S498R or A494F mutation hardly affected the affinity for K63-or M1-Ub 4 , in contrast to that for K48-Ub 4 , and thereby 3.78 \u00b1 0.14 Q554M", "1.11 \u00b1 0.09" ] },{ "paper_id": "aed3656733b0b5c6f2ad8a14ef5e864d468d66da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Commentary", "The authors' findings are consistent with recent releases of a US Presidential Policy Directive [5] , and related guidance from the US Department of Health and Human Services [6, 7] , which shift the focus of preparedness planning in the US toward an all-hazards, capabilities-based approach.", "This paper does not address another critical issuemeasuring the preparedness of the public health system. As public health and medical care are so interdependent, we hope that similarly rigorous work regarding the public health system is ongoing." ] },{ "paper_id": "aed44d8b5c29a7cdf02ed56dc2cbac07dd1d6eed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Falcipain-2 (50 nM) and falcipain-3 (300 nM) were assayed in triplicate at 25uC in 100 mM sodium acetate, 100 mM NaCl, 1 mM DTT, 1 mM EDTA, 0.01% Brij-35, 1% v/v DMSO, pH 5.5. Aliquots of 25 nmol (in 1 ml) from each of 20 sub-libraries of the P 1 -, P 2 -, P 3 -, and P 4 -libraries were added to the wells of a 96-well Microfluor-1 U-bottom plate (Dynex Technologies). The final concentration of each compound was 31.25 nM in 100 ml final reaction volume. The assays were initiated by addition of preactivated enzyme and monitored fluorometrically for 30 min with a SpectraMax Gemini fluorescence spectrometer (Molecular Devices) with excitation at 380 nm, emission at 460 nm, and cutoff at 435 nm.", "Malaria, especially that caused by Plasmodium falciparum, is responsible for hundreds of millions of episodes of disease, and probably at least one million deaths each year [1, 2] . Among impediments to effective control of this disease is increasing resistance to most available drugs [3] . New artemisinin-based combination therapies offer excellent efficacy, but resistance to most artemisinin partner drugs has already been seen [4] , and resistance to artemisinins may be emerging [5] . The pipeline for development of other classes of effective antimalarials, especially compounds that act against novel biochemical targets, is limited. To facilitate development of such compounds, it is important to characterize the biochemical features and biological roles of new drug targets.", "It is of interest that two common polymorphisms leading to alterations in the sequence of hemoglobin, HbS and HbC, offer protection against severe malaria [57, 58, 59, 60, 61] , and many other polymorphisms in hemoglobin may offer protection against malaria. It is possible that this protection is mediated, in part, by altered susceptibility of mutant hemoglobins to hydrolysis by parasite proteases, including falcipains. This will be an interesting area for future study.", "The extent of 18 O incorporation for each peptide was determined by linear regression analysis of the raw spectra using least squares fitting with a model consisting of a linear combination of four components, the theoretical average in isotope clusters positioned at m/z, (m+2)/z and (m+4)/z, and a constant term. Linear regression computed four multipliers, the amplitude of the unlabeled, singly-labeled, and doubly-labeled peaks, and the baseline. It was thereby possible to measure the unlabeled, singly labeled, and doubly labeled contributions for each peptide identified in the mass spectrum." ] },{ "paper_id": "aee43bea8ff949773e7d22ebbfd6304c20c2a76d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A respiratory disease syndrome has been observed in large numbers of wild shingleback lizards (Tiliqua rugosa)", "The 335 amino acid sequence encoded by ORF 3 (termed putative accessory protein) did not return any hits on BLASTp analysis. Attempts to predict function using ITASSER [42] and Phyre2 [43] were unsuccessful, with no significant templates found using either system. The protein is predicted to encode an N-terminal signalling region, a long non-cytoplasmic domain and a C-terminal transmembrane region, perhaps indicating that it is also a structural protein.", "We describe here, for the first time, the systematic investigation of respiratory disease in shingleback lizards using next generation sequencing (NGS) technologies, and the discovery and partial characterisation of an associated nidovirus." ] },{ "paper_id": "aef400eac72623d01820a1b2ca11e49a81917416", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "aef63bcba33e2bc1d7a7f1c3e71d7313e2769d98", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "except for a distinct HLA-A*1101 AVFDRKSDAK tetramer positive population (0.046% of total CD8 + T cells).", "CD107 surface expression upon peptide stimulation, confirmed the HLA-tetramer results (Fig. 6C )." ] },{ "paper_id": "aef63beff452ee2eee54c7d60770dccf59890568", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chain Reaction (qRT-PCR) Analysis. Total cellular RNA was isolated by lysis of cells in a guanidinium isothiocyanate buffer, followed by single step phenol-chloroform-isoamyl alcohol extraction procedure modified from that previously described [21] . Briefly, untreated or treated cells with TSL-1 . Then the membrane was exposed to Fuji medical X-ray film (Fuji Ltd, Tokyo, Japan) for 3 minutes.", "All statistical analyses were performed using SigmaStat statistical software (version 2.0, Jandel Scientific, CA, USA). Results were represented as means \u00b1 standard deviation (SD). ANOVA was carried out when multiple comparisons were evaluated. Values were considered to be significant at less than 0.05. All experiments were repeated at least three times independently. The estimated CC50 of TSL-1 extracts was higher than 300 g/mL (Figure 1 ).", "The tender leaves of Toona sinensis (TS) have been traditionally regarded as a nutritional supplement or vegetable in both Mainland China and Taiwan. In a recent report [6] , 2 Evidence-Based Complementary and Alternative Medicine there were no significant toxic effects on the biochemical and histopathological parameters of female mice treated with the extract of TS. The extracts from TS leaves have a wide range of biologic functions, including glycemic control, anti-LDL glycative activity [7] , and improving cognitive function [8] . TS extracts have also been demonstrated to inhibit cancer cell growth in human ovarian cancer, human premyelocytic leukemia, human lung adenocarcinoma, and prostate cancer [9] [10] [11] [12] [13] . The mechanism of anticancer activity by TS could be due to the generation of reactive oxygen species and mitochondria-mediated apoptosis [11, 14] . Moreover, TS possesses antiangiogenic activity through suppressing VEGFinduced expression of metalloproteinase-(MMP-) 9 and MMP-2 on endothelial cells [15] .", "To follow the treatment procedures of attachment assay or penetration assay, the cell culture supernatant was collected. One hundred microliter of the supernatant with further fresh preparation 0.5% guinea pig erythrocytes suspension was added into the U-shaped 96-well microtitre plates and mixed thoroughly. The plate was incubated for 3 hours at 4 \u2218 C. The RBC agglutination was observed. The experiments were repeated three times independently." ] },{ "paper_id": "aef8022f38dee0b0eadc00eb8a955384b87f3626", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Providing population-wide coverage across diverse HLA profiles and ethnicities.", "-Requires local (i.e., intranasal) administration of antigen. -Further work needed to determine the lifespan and stability of human lung and airway Trm, and their potential to provide durable vaccine memory.", "The authors declare no conflict of interest." ] },{ "paper_id": "aefd3e6661ed4befc6dd11d15cb80a66e025102e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For factors related to severity, a bivariate analysis was performed using Student's t-test for independent samples, when the variable was quantitative and parametric. Otherwise, a Wilcoxon rank-sum test was used. For categorical variables, tests of independence were performed using Chi-Square. If this was not possible, due to the number of observations, Fischer's exact test was performed.", "The most frequent diagnoses for both groups were pneumonia (50%), bronchiolitis (18.3%), and rhinopharyngitis (14.1%). Altogether, 77.3% of metapneumovirus infections were community-acquired, as well as 69.4% of other respiratory infections ( Table 1) .", "For seasonality analysis, the monthly number of infections due to human metapneumovirus was calculated, as well as the number of respiratory syncytial virus and rhinovirus/enterovirus infections, using a Spearman's correlation analysis for non-parametric variables.", "Statistical analyses were performed using STATA 14.0 (StataCorp LP, College Station, TX), using descriptive statistics for the demographic variables and central tendency and dispersion measure for continuous variables, according to the distribution of the variable defined by the Shapiro Wilk normality test. Absolute and relative frequencies were described for qualitative variables. The prevalence was estimated for the described observation period." ] },{ "paper_id": "aefd921eef67855fd84f460502e9e7277aeb92a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "From a funding perspective, the increasingly embraced philosophy of open source [43] and creative commons licensing [44] assures that these tools are available without charge. Key however, will be the extent to which local (and national) colleagues are indeed comfortable in using the tools and promoting their use locally. Also, in the case of information technology that requires maintenance and periodic updating, commitment from authorities (either government or external funders/partners) is needed. The \"business model\" of using revenue from distribution in high-income countries to fund maintenance and updates globally, is one way that LMICs can have their systems maintained and updated without strain on their resources, and assist high income countries to assume their global responsibilities [35] .", "Our first real challenge was in sustaining engagement of politically active workplace stakeholders, specifically the trade unions. We have had decades of successful experience in this regard [29, 39, 40] , but may have taken for granted that labour union trust would be there. While this was not problematic in our Latin American work, a communications breakdown occurred in the South African work, creating a setback. The lesson learned was that trust can never be assumed, and it is well worth taking the time to ensure that all key stakeholders are indeed engaged before the project moves ahead too far. Getting process issues right is paramount to success.", "Finally, it should be stressed that the success of this work has been, and will continue to be, based on frontline support and active engagement of the decisionmakers. This can never be taken for granted." ] },{ "paper_id": "aefeb0e9f2d0db1868113232cdb87597e7614068", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "[37]", "Combining traditional SELEX with a microfluidic system. This system contains reagent-loaded micro-lines, a pressurized reagent reservoir manifold, a PCR thermocycler, and actuatable valves for selection and sample routing. [43] High-Throughput Sequencing SELEX (HTS-SELEX)", "Molecules 2018, 23, x FOR PEER REVIEW 9 of 57" ] },{ "paper_id": "af000c5a8e181550fd16291e5d4f0f70ca9161a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "af06f5132b3178795ba440ec4f4949e9008c1737", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Further studies are needed to quantify the roles that each host species plays in amplifying and transmitting the pathogen among species and to humans.", "Third, in vector-borne zoonoses, the presence of a variety of species can act to regulate the abundance of the vector itself, thereby modulating pathogen transmission. For example, some hosts for the tick vector of the Lyme disease bacterium, Borrelia burgdorferi, are poor quality hosts for ticks, killing the majority that attempt to take a bloodmeal. The result is a strong reduction in vector abundance compared with host communities in which species of low quality for ticks are rare or absent [53] .", "In some cases, emerging zoonoses can be traced to a single-reservoir host species. For example, a recent outbreak of the Sin Nombre virus, a deadly member of the New World Hantavirus family, caused severe morbidity, mortality, and widespread panic in the Southwestern US in the early 1990s. Nearly all cases can be traced back to contact with contaminated urine or feces from the deer mouse (Peromyscus maniculatus), the primary reservoir species of the Sin Nombre virus. Sin Nombre virus and other related Hantavirus species tend to specialize and coevolve with a specific species of mouse [4] [5] [6] ." ] },{ "paper_id": "af10fafcbc7f54b2c2cf780db5ccf5a2b4a1c985", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Secreted IFN-\u03b1 and -\u03b2 bind to a distinct IFNAR receptor (IFNAR1/IFNAR2) expressed on the surface of most nucleated cells. Ligand binding induces receptor oligomerization followed by phosphorylation of STAT1 and STAT2 by IFNAR associated kinases, JAK1 and TYK2, respectively. STAT1 and STAT2 dimerize and associate with the transcription factor IRF9 to form the ISGF3 heterotrimer. Formation of this complex drives ISGF3 nuclear transport and binding to the IFNstimulated response element (ISRE), found in promoters of most IFN-stimulated genes (ISGs), which enhances transcription (reviewed in [40] ).", "Coronaviruses are a family of large positive-sense RNA viruses that cause a wide range of veterinary and human diseases. Coronaviruses are divided into three groups, with group I and II viruses infecting mammals and group III viruses infecting avian species [1] . Human coronaviruses (HCoV), HCoV-229E (group I) and HCoV-OC43 (group II), cause approximately 5-30% of all human respiratory infections [1, 2] . In late 2002, Severe Acute Respiratory Syndrome associated coronavirus (SARS-CoV) infected more than 8,000 people resulting in approximately 750 deaths [3] [4] [5] , demonstrating that human coronaviruses can also cause more serious disease in humans. Although SARS-CoV has not re-emerged in humans since the initial outbreak, other than a few remote incidents, isolation of SARS-related viruses in civets and several other animals [6] [7] [8] and more recently in bats [9, 10] suggests that an animal reservoir of the virus exists. The identification of two new human coronaviruses since the SARS epidemic, the group I HCoV-NL63 [11, 12] and the group II HCoV-HKU1 [2, 13] , associated with respiratory illnesses have also added to the need to further our understanding of coronavirus pathogenesis." ] },{ "paper_id": "af28c7f2e54f09c2ee5ea579d8646768a3be25c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The virome of insectivorous bat feces has been shown to consist largely of insect viruses, followed by plant viruses, reflecting the insect-based diet of these bats, and plant-based diet of these insects [1-3].", "Conversely, our study, based on the analysis of tissue samples, led to the detection of only a few new insect viruses, and even fewer new plant viruses.", "Based on BLASTx and BLASTn analyses, numerous read and contig sequences from pooled bat samples were identified as taxonomically related to families of viruses infecting invertebrates, mostly the Polydnaviridae, Baculoviridae, Dicistroviridae and Nodaviridae. For the last two of these families, we were able to identify and confirm the presence of putative new insect viruses, in bat specimens b2 (Pipistrellus pipistrellus) and b7 (Eptesicus serotinus), respectively." ] },{ "paper_id": "af2a0da4beb166ca0b189ee6282120c9b664ea79", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Citation: Tongaonkar P, Golji AE, Tran P, Ouellette AJ, Selsted ME (2012) High Fidelity Processing and Activation of the Human a-Defensin HNP1 Precursor by Neutrophil Elastase and Proteinase 3. PLoS ONE 7(3): e32469.", "To study the processing of human myeloid a-defensins, we established an in vitro assay utilizing recombinant proHNP1.", "Analytical HPLC HNP1 preparations derived by enzymatic or CNBr treatment were analyzed on an Alliance 2690 Separations Module using a C18 column (3 mm particle, 180 \u00c5 pore, 2.0 mm6150 mm, Varian Polaris 5A) with a flow rate of 0.2 ml/min using a 0-to-60% ACN linear gradient in 0.1% aqueous TFA at 1% per minute. Eluting peaks were detected at 210 nm and 280 nm using a Waters 2487 Dual l absorbance detector using Clarity software. Natural (human neutrophil-derived) HNP1 was used as standard in these analyses." ] },{ "paper_id": "af2d96a09d1d6fcfef38c823fac66da0dcbb299e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "If the postulation is indeed correct, the woman with fever in the Bible is among one of the very early description of human influenza disease.", "The Bible has many examples of descriptions of medical diseases. For instance, the first pediatric case of mouth-to-mouth cardiopulmonary resuscitation is vividly described in the Old Testament when the prophet Elisha pressed upon an apparently dead child and breathed into him seven times, and the child was revived (Kings 4:34-35) [1] .", "Influenza and respiratory viral infections have been documented throughout human history [3] . The current 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus, often referred to colloquially as \"swine flu\" which began in the state of Veracruz, Mexico in April 2009 and the virus continued to spread globally. The World Health Organization (WHO) and US Centers for Disease Control (CDC) in June escalated the global alert level to phase 6 and declared the outbreak to be a global pandemic since the 1968 Hong Kong flu [4] ." ] },{ "paper_id": "af2e81683f4a37a0ada4acd6fbc495550306c86f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by the Ethics Committee of the Institute of Clinical Pharmacology, Central South University of China. Written informed consent was obtained from the participants." ] },{ "paper_id": "af400a711649c6703b915e8a935dfe778bc42132", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "af4389942bc90f030be76a193485be1b0c138cc0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Global Assessment Functioning (GAF) scale describes the current psychological, social and occupational functional status of a patient in a single measure ranging from 0 to 100 [43] with higher scores reflecting better functioning and low symptomatology.", "Baseline assessments (T0) were computed within 12.12 days on average (SD = 11.22) after intake the initial appointment with the psychiatrist and the nurse." ] },{ "paper_id": "af475b1445628312443de29d85bff40825d411e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The samples were cultured in nutrient broth (Merck, Darmstadt, Germany) overnight at 37 \u2022 C. Thereafter, a 10 \u00b5l of the broth was cultured on mannitol salt agar (37 \u2022 C, 48 h).", "No ethical clearance was necessary as animals were not captured and no invasive samples were taken. The authors complied with all of the legal requirements pertaining to the locations in which the work was done.", "This study was supported by institutional funds." ] },{ "paper_id": "af547c43638857c71c035fa4217e167f681f837c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the data supporting our findings is contained within the manuscript.", "The authors declare that they have no competing interest. " ] },{ "paper_id": "af59bab3c82817cf0ebe456cf3283a3d8217cabf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "af5ac6d8e177f588034d75237f65dc8d6c0deb2f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed by SigmaPlot 11.0 software. Significant differences between groups were assessed by the Kruskal-Wallis One Way Analysis of Variance (ANOVA on Ranks) and Dunn's Method pairwise multiple comparison (P < 0.05 was considered significant). For significance of cytokine-enhancement experiment, the Mann-Whitney Rank Sum test was employed (P < 0.02).", "Type I interferons (IFN), mainly IFN-\u03b1/\u03b2, are essential to the innate immune system for direct antiviral activity as well as efficient induction of adaptive immune responses [1, 2] . This critical role is underlined by the fact that seemingly all viral pathogens have evolved strategies to counteract this innate defense system [3] .", "PRRSV infects macrophages, MoDC, and monocytederived macrophages in vitro [6, 8, 9] . However, sorted CD172a + cell populations of pDC were not permissive to infection. Flow cytometric three-colour analysis did not reveal the presence PRRSV nucleocapsid in gated pDC or monocytes even after prolonged incubation with PRRSV for three days ( Figure 5A ). These results are consistent with a previous report employing GFP tagged PRRSV [26] , indicating that pDC are not permissive to PRRSV. High levels of IFN-\u03b1 were detected in these cultures, confirming that productive infection is not required for pDC sensing of PRRSV ( Figure 5B )." ] },{ "paper_id": "af5dfacb6eac020ef858b5223fa8cdc3893f709d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "af5f5cae93582ca713bbc2abaea17d7898b63f72", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All viruses initiate infection by binding to specific receptor (s) on the surface of susceptible host cells (Neu et al., 2011) .", "Virus purification by caesium chloride gradient centrifugation." ] },{ "paper_id": "af678e8cd31d74cdb2d690addc19d59dca331f2b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where l 1,2 represents two time boundaries separating a period of high exposure from a period of low exposure (1 l 1,2 52) . We expected that a \u00fe . a 2 .", "where u \u00bc fa + , q, l 1,2 g is a set of model parameters.", "a w\u00c0k (a + , l 1,2 ) \u00c2 g k 1 \u00c0 r :", "One contribution of 15 to a theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'." ] },{ "paper_id": "af6cc29d9bc7f9d84ded3d7ad30509a945e425d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "af6dacec0a1ba933a47d7451ef69ea06f7029882", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Written informed consent was obtained by all participants through Institutional Review Board Protocol #000-2492 approved by Georgia Institute of Technology, Emory University, and US Centers for Disease Control and Prevention.", "Supported by internal grants from US Centers for Disease Control and Prevention and Emory University Hospital.", "I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard." ] },{ "paper_id": "af728043c4fdbde717229134e2cd8bada6760176", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine epidemic diarrhea (PED) is an acute, highly contagious and devastating enteric disease characterized by severe enteritis, vomiting and watery diarrhea in swine [1] . PED is caused by porcine epidemic diarrhea virus (PEDV), which was firstly identified in Belgium in 1978 [2] . PEDV is an enveloped, single-strand, and positivesense RNA virus, which belongs to the Coronaviridae family [3] . The PEDV genome is~28 kb in length and comprised of a 5\u2032 untranslated region (UTR), a 3\u2032 UTR, and at least seven open reading frames (ORFs) that encode four structural proteins [spike (S),envelope (E), membrane (M),and nucleocapsid (N)] and three nonstructural proteins(replicase 1a and 1b, and ORF3) [4] .", "We have developed an efficient approach to rapidly detect PEDV. This method holds great promises not only in laboratory detection and discrimination of PEDV but also in large scale field and clinical studies." ] },{ "paper_id": "af7e42cdc9fa098ffcfdbf92ebfb9dbd4dbde545", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pros Cons Viruses/Ref.", "High image contrast and temporal resolution Limited availability of labels respiratory syncytial virus (RSV) [111] Total internal reflection microscopy (TIRFM) [195] Illumination of a few 100nm thin layer reduces background signal", "Only cover glass attached basal membrane is accessible" ] },{ "paper_id": "af92c6b29f579151999d766c4208146088aa12c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chickens are used only for blood collection in this study. All animal research protocols were approved by South China Agriculture University's Institutional Animal Care and Use Committee. (Permit Number: 2017003).", "In order to identify differentially expressed genes (DEGs) across groups (ALV-J vs NC, IFN-\u03b1 vs NC), the edgeR package was used. Genes with fold change of |log 2 FC | > 1 (FC: fold change) and a false discovery rate (FDR) < 0.05 was considered as DEGs.", "All experiments were performed independently at least two times and each experiment was performed in triplicate. Statistical comparisons were performed using GraphPad Prism 5 (GraphPad Software Inc., San Diego, CA, USA). Results are presented as means \u00b1 SEM, and statistical significance was assessed at P values of < 0.05, 0.01, or 0.001." ] },{ "paper_id": "af95b3932b07aabf277276810797aebe765c8859", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 1213 |", "We chose a study area extent, occurrence data, and environmental variables, following the previous publication 20 , but excluding the Piedmont area in Italy, as those occurrences were not made available (Fig. 4) . Occurrences were resampled to one occurrence point per grid cell at 2.5\u2032 resolution. The area across which models are calibrated affects performance of ecological niche models based on correlative algorithms requiring background data or pseudo-absence data for calibration 34 . Thus, for a replicate experiment our M was based on previous evaluations for the Americas and Europe 20 : we included the area from Central America (Nicaragua, Honduras, El Salvador) and the Greater Antilles (Jamaica, Cuba, Dominican Republic, Haiti) north to northern Canada and Alaska; in Europe, we focused on Ireland and the United Kingdom." ] },{ "paper_id": "af987eff63f3d7ee36dc7631807d9aac7c165d2d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, the precision was computed to measure the reproducibility of the results, in eq. (8):" ] },{ "paper_id": "af989f3b3f8bf8e0b3d8da323e3443a3f50ca2ce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Permission to search patient records including medical folders and contact information was obtained from the hospital management. The lead researcher reviewed medical records of eligible patients and extracted relevant clinical data. Data were captured electronically, anonymized, and recorded in a standard case report form. The study radiologist and pathologist independently reviewed and entered data related to chest radiography, CT findings, BAL, and lung biopsy findings.", "Oil administration may be a common practice that is not recognized to be potentially dangerous by caregivers or medical professionals. This history may not be forthcoming from caregivers unless health workers probe for it explicitly, leading to misdiagnosis, treatment delay, and a missed opportunity to prevent ongoing oil aspiration [2] . The aim of our study was to describe the clinical-radiological-pathological pattern of ELP in children in the South African context.", "This study was approved by the University of Cape Town Human Research Ethics Committee (548/2017). ", "Exogenous lipoid pneumonia (ELP) is considered a rare disorder caused by inhalation or aspiration of mineral, plant-based, or animal oils [1, 2] . It results from a foreign body type of inflammatory reaction due to the presence of lipid material in the lung parenchyma initiating cellular and humoral defence mechanisms [3, 4] . Populations at risk include the elderly, children, and those with an underlying swallowing dysfunction or neurological disorder resulting in an unprotected airway. In addition, forced ingestion in the recumbent position in infants and young children who actively refuse oil may result in gagging and aspiration of the oil [5] . Common ailments for which oil has been used medically or culturally include constipation, colic, and nasal stuffiness [6] ." ] },{ "paper_id": "afa0cf3bd7286376ed6c62033c05a5b6d9e4211f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "afa67c34e52aa31421d540d1ea7484f52b3318e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although there are various ways to measure interorganizational collaboration, we used two survey items asking the following question to measure collaboration:", "The response on each item is rating of each dimension and ranges from 0 (not at all) to 10 (very much helpful). The response categories are ratings of the responses and are summed as one index variable (Cronbach's alpha = 0.9102). As shown by the descriptive statistics in Table 2 , the average value is 21.44 and the standard error is 6.65.", "Network hierarchy measured as the extent which total constraints are located at the focal node's single other [33] . When an actor has a high hierarchy score, the actor has an alter that interact with multiple partners and can help the actor to access new information efficiently [39] . We calculated the hierarchy score using UCINET 6 [64] .", "Sending information: \"To which organization did your organization send information regarding MERS during the outbreak directly (information about high risk patient, hospital, or response information).\"" ] },{ "paper_id": "afac5482c4fb73ba67db7127e3d0c9ed19882c35", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tissue samples. In Japan, the capture and handling of a bat were approved by the Japanese Ministry of Environment (license No. 21-27-0213 to 21-27-0215), and conducted in accordance with the approved protocol. An E. nilssonii was captured in Hokkaido, Japan and euthanized; then, the liver was removed. The liver sample was stored in RNAlater (Thermo Fisher Scientific, Waltham, MA, USA) prior to the isolation of genomic DNA. Bat muscle tissue (E. serotinus) and cell cultures from E. serotinus, M. daubentonii (MyDauNi/2), M. nattereri (MyLu/2), Nyctalus noctula (NyNoNi/2) and Pipistrellus pipistrellus (PipNi/1) were available from previous studies and originated from animals found dead in Germany and delivered to centres for bat protection 34, 35, 36, 37 .", "Because all German bats are protected through the European Commission (http://ec.europa.eu/environment/ nature/legislation/habitatsdirective) and the Agreement on the Conservation of Populations of European Bats (www.eurobats.org), investigative research requires special permission by local government bodies. As part of a study on diseases in European bats 38 Table 3 ). The PCR conditions were as follows: denaturation at 94 \u00b0C for 2 min, 40 cycles of 94 \u00b0C for 30 sec, 60 \u00b0C for 30 sec, and 72 \u00b0C for 30 sec, followed by a final extension at 72 \u00b0C for 3 min. Amplified DNA was analysed by agarose gel electrophoresis.", "We developed a pol II-driven firefly luciferase-based minireplicon assay for BDV (the construct is available upon request). For transfection, 2 \u00d7 10 5 293T cells were seeded into each well of a 12-well plate. The next day, plasmids expressing the BDV N, P and L proteins, the minigenome and Renilla luciferase (as a normalization control) with or without a plasmid expressing esEBLL-1 were transfected using Lipofectamine 2000 (Life Technologies). After 24 hours, the cells were lysed with Passive Lysis Buffer (Promega), and the luciferase activities were measured using the Dual-Luciferase Reporter Assay System (Promega). The values of firefly luciferase were normalized by the Renilla luciferase activity." ] },{ "paper_id": "afc03cd8197cd7aa9e0ca665ebe6626c2a56ac4b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "afc498abcb287239b8ea84ff535adf09158b0cfe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "[ , ]", "Project name: ANDES Project home page: http://andestools.sourceforge.net/ Download web site: https://sourceforge.net/projects/ andestools", "Operating system: Tested and in production on Linux." ] },{ "paper_id": "afd61adb91428007558db20c6234a77695c8851c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Male sex (%) 41 ", "We would like to express our special appreciation for administrative staff and professors in Leading Program at Nagasaki University, Graduate School of Biomedical Sciences for their kind support during the research. This study was conducted in part at the Joint Usage/Research Center on Tropical Disease, Institute of Tropical Medicine, Nagasaki University, Japan.", "The authors have declared that no competing interests exist. " ] },{ "paper_id": "afd83a90943b4d9103daaf9507267b65e257c85c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "The following MRI sequences were obtained with a 3.0-T scanner (Achieva, Philips Medical Systems, Best, The Netherlands): T2w and T1w pre-and post-contrast administration (0.5 ml/ kg i.v., Dotarem, medithek GmbH, Oststeinbek, Germany) each in sagittal, transversal and dorsal section as well as transversal section of FLAIR." ] },{ "paper_id": "afe59f82672ff792a00e11e74e4ff6d9e560dc0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consequently, we modified the model reported previously 24 , and the expected value of daily cases ( \uf0b5 I t E( ( )) i ) was estimated by equations (2) and (3):", "A national census data was available from \"https://www.e-stat.go.jp/stat-search/database?page=1&layout=\u2212 datalist&toukei=00200521&tstat=000001080615&cycle=0&tclass1=000001101935&survey=%E5%9B%B-D%E5%8B%A2%E8%AA%BF%E6%9F%BB&result_page=1&second=1&second2=1\". NESID data in Miyazaki Prefecture was available from \"https://www.pref.miyazaki.lg.jp/contents/org/fukushi/eikanken/ center/infectious/2010/index.html\" and \"https://www.pref.miyazaki.lg.jp/contents/org/fukushi/eikanken/ center/infectious/2011/index.html\"; those in other prefectures were available from https://idsc.niid.go.jp/ idwr/CDROM/Kako/H22/SyuList.html\" and \"https://www.niid.go.jp/niid/ja/all-surveillance/2270-idwr/ nenpou/3359-syulist2011.html\". Data regarding the number of medical institutions were available from \"https://www.e-stat.go.jp/stat-search/files?page=1&layout=datalist&tstat=000001030908&cycle=7&tc-lass1=000001038857&tclass2=000001038860&second2=1\". However, the Kyushu Okinawa hospital data were not available free of cost and had to be purchased. Furthermore, the total number of clinics in each jurisdiction in the Miyazaki Prefecture has been shown in the Methods section.", "The goodness of fit to Weekly CPS. Weekly CPS, estimated value obtained by spline, and expected value obtained from the mathematical model were used to compare the weekly reported number of influenza cases per sentinel, as shown in Fig. 1 . When a chi-square test of goodness of fit was conducted 8, 9 , the deviation between Weekly CPS and estimated value was not significant (P < 0.05) at all jurisdictions. The estimated value and expected value were in good agreement in any jurisdiction." ] },{ "paper_id": "aff7baf924af877c824d6c9c1132caa094342636", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The chicken embryo fibroblast cell line (DF1, ATCC, Manassas, VA, USA) was grown in Dulbecco's minimal essential medium (DMEM) with 10% fetal bovine serum (FBS) and maintained in DMEM with 5% FBS. The African green monkey kidney Vero cell line (ATCC, Manassas, VA, USA) was grown in Eagle's minimum essential medium (EMEM) containing 10% FBS and maintained in EMEM with 5% FBS. Primary chicken neuronal cells were grown in Neurobasal medium with B-27 supplement (Invitrogen).", "Virus titers for in vitro and in vivo replication were quantified by immunoperoxidase staining with N-specific antibodies on DF1 cells (APMV-1, -2, -3, -4, -6, and -9) or Vero cells (APMV-5, -7, and -8) [3-10].", "From the experiments described above, brain tissue harvested 3 dpi from 1-day-old chicks infected by intracerebral route and various tissue samples harvested 4 dpi from 2-week-old chickens infected by the intranasal route were fixed in phosphate-buffered formalin (10%). Fixed tissues were embedded in paraffin and sectioned (Histoserv, Inc., Germantown, MD). Sections from mock-infected birds were used as controls. The tissues were deparaffinized, rehydrated, and subsequently, immunostained to detect viral N protein using the following protocol. Briefly, the sections were blocked with 1% BSA in PBS for 1 h at room temperature, incubated with a polyclonal antibody (1:200 dilution) against the respective N protein (29, 30) followed by horseradish peroxidase-conjugated goat anti-rabbit antibodies for 30 min, and then stained with AEC (3-amino-9-ethylcarbazole) substratechromogen." ] },{ "paper_id": "b0022167496e4388b198ab691103ffe066e0c9cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession numbers. Nucleotide sequences for BTV-16 ITL2002 have been deposited in GenBank with the accession numbers KF387521 to KF387530.", "The complete genome sequence of a reassortant field strain of bluetongue virus serotype 16 (BTV-16), isolated from cattle in the Apulia region of Italy in 2002, has been determined by Illumina sequencing. Sequence comparisons of segment 1 (Seg-1) to Seg-10, except Seg-5, show that BTV-16 strain ITL2002 belongs to the major eastern topotype of BTV.", "ment/recombination events in RNA viruses means that each infected host is likely to carry viral populations with potentially high genetic diversity. Rapid retrieval of complete and accurate genomic data is fundamental in order to elucidate the emergence and molecular epidemiology of these viruses. A full-genome approach becomes crucial when dealing with segmented RNA viruses, such as influenza A virus (1, 2) or bluetongue virus (BTV) (3), or with viruses with extraordinarily plastic genomes, such as coronaviruses (4, 5, 6) . BTV is the prototype of the genus Orbivirus, within the family Reoviridae (7), and causes bluetongue, a disease affecting wild and domestic ruminants (8) . BTV includes 26 distinct serotypes (7, 9, 10) and its genome is composed of 10 segments (Seg-1 to Seg-10) of linear double-stranded RNA (dsRNA) (11) . Total dsRNA (12) was used as input for library preparation using the Illumina TruSeq RNA library preparation kit (Illumina) with modifications. dsRNA was fragmented and subjected to first-strand cDNA synthesis (13) . After secondstrand synthesis, bar-coded DNA adapters were ligated to both ends of the double-stranded cDNA, and the ligated product was size selected and subjected to PCR amplification. The resultant library was checked on a Bioanalyzer (Agilent) and quantified. The libraries were multiplexed, clustered, and sequenced on an Illumina HiSeq 2500 genome analyzer with a paired-end protocol. The sequencing run was analyzed with the Illumina CASAVA pipeline (v 1.8.3), with demultiplexing based on sample-specific bar codes, obtaining 260 Mb of sequence data. The quality of the sequences was enhanced by trimming off low-quality bases using the CLC Genomics Workbench. The quality-filtered sequence reads were aligned against the reference sequences by use of the CLC Genomics Workbench. The 10 segments of BTV serotype 16 (BTV-16) strain ITL2002 were amplified successfully for their entire length (14) . Sizes in base pairs for Seg-1 to Seg-10 of BTV-16 ITL2002 were 3,944, 2,935, 2,272, 1,981, 1,776, 1,637, 1,156, 1,125, 1 ,052, and 822, respectively. BTV-16 was isolated for the first time in 1960 in Pakistan, supplied to the Onderstepoort Veterinary Research Institute, and named RSArrrr/16 (South Africa). It was recently fully sequenced at Pirbright, United Kingdom (14) . All segments except Seg-5 showed \u03fe99% sequence identity with RSArrrr/16 and the corresponding vaccine strain RSAvvvv/16. Equal levels of identity were demonstrated with the Chinese BTV-16 (strain BN96/16) isolated from a sheep in 1996. Seg-5 of BTV-16 ITL2002 is identical to that of the BTV-2 vaccine strain (RSAvvvv/02). Indeed, BTV-16 ITL2002 Seg-5 shows only~82% to 83% nucleotide identity with the other BTV-16 strains, suggesting that this segment is likely derived from genomic reassortment between RSAvvvv/16 and RSAvvvv/02, widely used in the Mediterranean basin in the past (15) . Multiple BTV serotypes are currently circulating in the southern Mediterranean basin (4), thus potentially leading to the spreading of novel reassortant viruses with unpredictable biological features. Full-genome sequencing and sharing of genomic data are therefore highly recommended in order to promptly identify the emergence of viruses with novel genome segment constellation." ] },{ "paper_id": "b00ed3b8efc4531b84e5035419418056eea0799b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b010b3bb7db4f358b0ec2829523ccbfd6d52afbc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "That is, we have", "where \u03b5(t) may be modelled as", "Thus, the contact matrix M is given by" ] },{ "paper_id": "b0218dd5c965f2c92348a50f46ea2e271a56c7c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RT-PCR amplification, cloning, and sequencing of CTV genome fragments", "Sequence fragments and the associated quality scores generated by GDAS were converted into fasta-format files and used to assemble full and partial CTV genomic contigs using the Phrap program [32] implemented in the CodonCode Aligner (CodonCode, Dedham, MA).", "Text S1 Online Supplemental Materials and Methods for Persistent infection and promiscuous recombination of multiple genotypes of an RNA virus within a single host generate extensive diversity Found at: doi:10.1371/journal.pone.0000917.s001 (0.05 MB PDF)", "Equimolar amounts of each PCR fragment were pooled, and labeled with biotin-dNTP by terminal deoxynucleotidyl transferase. Hybridization of the labeled target DNA to the microarrays, washing, and subsequent staining in GeneChip Fluidics Station 450 were performed in strict accordance with the instructions provided by Affymetrix. The stained microarray was then scanned at a resolution of 1.563 mm/pixel using a GeneChip Scanner 3000 (Affymetrix, Santa Clara, CA). The final probe intensity data were analyzed with the Affymetrix GeneChip Sequence Analysis Software (GSEQ) to extract sequencing information. Base calls were made using the ABACUS (adaptive background genotype calling scheme) algorithm [31] ." ] },{ "paper_id": "b02612aa65049060e0a24064db96105458ac083b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2015, 7 7", "Interferon-induced transmembrane proteins (IFITMs) encoded by a variety of vertebrates, including pigs, chickens, bats, fish, mice, and humans, have been shown to restrict cellular infection by specific viruses [1] [2] [3] [4] [5] [6] . IFITMs inhibit viruses that fuse within cellular endosomes [7, 8] by preventing the formation of the viral fusion pore [9, 10] . As a result of the block to viral entry through endosomes, virus is subsequently degraded in cathepsin-positive endolysosomes [6, 11] . However, the molecular mechanisms by which IFITMs exert their antiviral functions and the precise evolutionary history of vertebrate IFITMs remain unknown [12, 13] .", "immunofluorescence microscopy ( Figure 5B) . Thus, the ability to interact may be a conserved aspect contributing to the functional homology between mycobacterial IFITMs and IFITM3. " ] },{ "paper_id": "b0321c49afd322bf426b0dfb3eca1152a69ed168", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Heart tissues were fixed with 4% formalin and embedded in paraffin. Five \u00b5m-thick sections were prepared and stained with hematoxylin and eosin, or Masson's trichrome." ] },{ "paper_id": "b04c8cddba2dfb4f953daac916d936924976392d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The chi-squared test was used to compare categorical variable in subgroups. And for those continuous variables with normal and non-normal distributions, mean or median values were compared using the t test or Mann-Whitney U test. SPSS 19.0 statistics package (SPSS Inc., Chicago, USA) software was used for all statistical analysis. p < 0.05 was considered statistically significant.", "Abbreviations CAP: Community acquired pneumonia; GeXP assay: GenomeLab Genetic Analysis System; MP or M. pneumoniae: Mycoplasma pneumoniae; RT-PCR: Reverse transcription polymerase chain reaction", "The GeXP assay (GenomeLab GeXP Genetic Analysis System) was performed on all specimens for the 13 type/ subtypes of common respiratory pathogens including M. pneumoniae. The multiplex-PCR was performed as previously described elsewhere [18] . The bacteria infection was examined by standard culture methods from sputum specimens [19] . The determination of MP-specific antibody was performed using a commercially available micro-particle agglutination test Serodia-MycoII kit (Fujirebio, Tokyo, Japan) [14] . Diagnosis criteria were defined as \u22654-found rising for paired sera or single serum of titer \u22651:160 [15] ." ] },{ "paper_id": "b04df94d885c540b1a5adba12f6fb402e9a09b0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LR7 mouse fibroblast cells [27] were maintained in Dulbecco's Modified Eagle's Medium (DMEM) (Cambrex Bio Science) containing 10% (v/v) fetal calf serum (Bodinco B.V.), 100 U/ml Penicillin, and 100 \u03bcg/ml Streptomycin, supplemented with Geneticin G418 (250 \u03bcg/ml). MHV strain A59 was grown in and titrated on LR7 cells." ] },{ "paper_id": "b061aea11013896c5d3a9c7c0c4f884397ad38d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Classes IV, V, and VI mutations are relatively less severe than the first three classes because they still retain residual CFTR function at the cell surface. As a result of these mutations, Cl \u2212 conductance may be reduced (Class IV), CFTR splicing may reduce protein function at the cell surface (Class V), or accelerated protein turnover may reduce CFTR halflife at the cell surface [12, 31, 32] (Figure 2 ).", "Aside from the CFTR modulator approach, ENaC channel antagonists are also being investigated using the -ENaC mouse model for their efficacy in restoring normal Na + flux and their downstream effects on mucus clearance and inflammation [86] .", "Cook et al. demonstrated, using pig epithelial cells, that ivacaftor therapy functions to potentiate the CFTR channel, similar to human epithelial cells [108] . This provides researchers with the opportunity to study the longevity of ivacaftor therapy on pig models and further opens the research to other potentiators and correctors.", "The treatment of CF involves therapeutics for management of the symptoms and potential correction of the CFTR protein." ] },{ "paper_id": "b0691ba288acf449186c899b08788d6b4a2ecdeb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supernatant was removed from transfected cell monolayers, cells were briefly washed with PBS and lysed using 200 l 1\u00d7 Glo Lysis Buffer (Promega R ) per well in a 12-well plate. The oxidation reaction was catalysed by the addition of 50 l cell lysate to 50 l room temperature Bright-GloTM Luciferase Assay System (Promega R ) substrate and shielded from the light for 5 mins. Luciferase activity was measured using a luminometer with values normalised to mock transfection controls.", "Plasmids encoding type 1 and type 3 poliovirus genomes (full length or sub-genomic) were linearized with Sal I and Apa I respectively, transcribed in vitro using T7 RNA Polymerase (Fermentas), treated with 2 U DNAse Turbo (Ambion) to remove residual DNA template and the RNA transcripts purified using RNeasy Mini Kit (Qiagen) before spectrophotometric quantification. Unless otherwise specified 1g of RNA was transfected into near-confluent T25 flasks using Lipofectamine 2000 (Invitrogen).", "Supplementary Data are available at NAR Online. " ] },{ "paper_id": "b0718d5c8888216c95fa19d7a79fd709da2c3ff4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ICU-acquired infections were recorded. The diagnosis of infection was confirmed if patients met both the following criteria: microbiological identification of a pathogen and administration of related antibiotic treatment.", "Conclusions: Severe VZV-CAP is responsible for an acute pulmonary involvement associated with a significant morbidity and mortality. Steroid therapy did not influence mortality, but increased the risk of superinfection." ] },{ "paper_id": "b07bcd8179099f8a5e49b8a7a2530590da99403b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition to their direct antimicrobial and antiviral effects, AMPs have important modulatory effects on responses of many immune cells (see Table 1 ). ", "Fragments of other host defense molecules or peptides not commonly known to serve host defense functions have been showed to have AMP like activity with regard to bacteria and viruses.", "A 27 amino acid N-terminal fragment of human BPI was recently shown to inhibit various IAV strains (including H1N1, H3N2 and H5N1 strains) in vitro through a direct action on the virus [89] . Of interest, the murine homolog of this peptide lacked anti-IAV activity. In addition, the human peptide inhibited IL-6 and TNF responses of monocytes triggered by IAV.", "HD5 and HD6 have been found to promote infection by human immunodeficiency virus (HIV) in vitro by increasing viral entry [20] . These defensins also counteract anti-HIV effects of polyanion microbicides [21] . HNP1 was also reported to increase HIV infectivity by facilitating transfer of the virus across epithelial barriers [22] . Note that other studies show an ability of these defensins to inhibit HIV [23] [24] [25] . No studies have indicated promotion of infection of IAV by defensins." ] },{ "paper_id": "b07ebfcd149b785998d9a32a9b151e83e9f46c67", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022immunocompromised condition 5 (2.1)", "\u2022congenital abnormality b 17 (7.3)", "\u2022chronic respiratory illness 9 (3.9)" ] },{ "paper_id": "b08591a37f6db5d579f4e875e8326ae408a257bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "T RM s are a distinct class of memory CD8 + T-cells that are self-renewing, highly protective against subsequent infections, and permanently reside at sites of infection, disconnected from circulation [37] .", "The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.", "The programmed death (PD)-1/PD-L1 pathway is a well-recognized negative immune checkpoint that results in functional inhibition of T-cells. Microglia, the brain-resident immune cells are vital for pathogen detection and initiation of neuroimmune responses. Moreover, microglial cells and astrocytes govern the activity of brain-infiltrating antiviral T-cells through upregulation of PD-L1" ] },{ "paper_id": "b0889b0058183e21ed81e8b41414fd4cc450ce84", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data analysis was performed with SPSS 16.0 software. One-Way ANOVA with Duncan's post hoc test was used for multiple comparisons between groups. Values were expressed as the mean \u00b1 standard deviation (SD). The results of the comparisons between groups were considered significantly different if p < 0.05.", "(2) unknown components of the SPP may contain a type of cytokine that binds to cell surface receptors to promote T and B cell differentiation and proliferation; (3) a number of small lipid-soluble polysaccharides from SPP may directly enter T and B lymphocyte and affect cell metabolism or the secretion of cytokines, among other factors [31] .", "The effects of SPP against the combined ND-IB-AI inactivated vaccines on the immune responses of chicken have been studied. From this study, the following conclusions are derived:" ] },{ "paper_id": "b09362a1f23af2b6603e7b92b58003b7f9719840", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Multiple sequence alignments were performed using Muscle in MEGA 5.0 [64] and were refined manually in Bioedit (http:// www.mbio.ncsu.edu/BioEdit/BioEdit.html).", "Conserved motifs in the complete amino acid sequences of the mammalian IFITM proteins were analyzed by MEME/MAST software (http://meme.sdsc.edu/meme/website/intro.html). The secondary structure of IFITM proteins was predicted using SMART (http://smart.embl-heidelberg.de/smart). The logo pictures were generated by Weblogo (http://weblogo.berkeley.edu).", "In this study, we demonstrated the evolutionary dynamics of IFITM genes that diversifies in different sub-clades, probably in accordance with their distinct functions. Future studies on immunology, developmental biology and comparative biology to determine IFITM functions would better clarify the relationship between divergence and functions and likewise extend our knowledge on IFITM function and evolutionary mechanisms." ] },{ "paper_id": "b0988e41e28d6f9269e7198ec419142d0a81c7a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Avian leukosis virus (ALV) is a major infectious disease that impacts the poultry industry worldwide. Despite intensive efforts, no effective vaccine has been developed against ALV because of mutations that lead to resistant forms. Therefore, there is a dire need to develop antiviral agents for the treatment of ALV infections and RNA interference (RNAi) is considered an effective antiviral strategy.", "Experiments were repeated three times and values were expressed as means \u00b1 standard deviation (SD). The ttest was performed using the SPSS 13.0 statistical software (version 13.0; SPSS, USA). Differences were considered statistically significant when p < 0.05.", "RNA interference (RNAi) is a simple and effective tool for silencing target genes that involves endogenous or exogenous double-stranded RNA (dsRNA)-mediated degradation of the specific mRNA sequences. The main nucleic acid molecules that induce gene silencing are small interfering RNA (siRNA) and microRNA (miRNA), where the siRNAs mediate specific mRNA degradation, whereas miRNA inhibits specific mRNA at the translational level. Both of these biological processes are considered key methods of modulating host gene expression, and these two molecules are also involved in antiviral and transposon silencing pathways." ] },{ "paper_id": "b0a17b1f4447f0a81d2e93f2e23720feadee96cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where r~N{(1{h)(IzI m ) and N is the total population ", "Using the transfer diagrams in Figure 1 we obtain the following system of differential equations:", "where t is the threshold number of infected individuals at which masks start to be used.", "The rate coefficients are modeled by step-functions of the number of infectious individuals:" ] },{ "paper_id": "b0ad001bf30a7e66883a682031b9847028664e3d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where Ao and Ai are the signal of total antibody incubated in the absence and presence of a given concentration of antigen, respectively, and a o is the total concentration of antigen in the antigen-antibody mixture.", "Conclusions: Our technology eliminates the need for both cell propagation and screening processes, offering a significant advantage over hybridoma and display strategies." ] },{ "paper_id": "b0ae17e124d5aff160a564dd700ff9d5ee31578a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "JL and DJ conceived the review. JL wrote the manuscript. DJ revised the manuscript. All authors have read and approved the final version of the manuscript. ", "Liver fibrosis is a pathogenic result of chronic liver diseases, such as ASH and NASH, and characterized by deposition of extracellular matrix (ECM) (89) . Hepatic stellate cells (HSCs) are the primary cells for the storage of ECM, and multiple functional changes of HSCs can be caused by NLRP3 inflammasome, including suppression of chemotaxis, upregulation of collagen and transforming growth factor-\u03b2 (90, 91) . These functions are confirmed by the study that knocking in NLRP3 induces the activation of HSCs and subsequent accumulation of ECM proteins, while fibrogenesis is not reversed by IL-1Ra therapy, indicating that some other regulators of NLRP3 inflammasome pathway instead of IL-1\u03b2 promote fibrogenesis (20).", "Frontiers in Immunology | www.frontiersin.org inflammation responses and perpetuating liver fibrosis driven by NLRP3 inflammasome activation (92) . Collectively, NLRP3 inflammasome pathway appears to be central to the pathogenesis of liver fibrosis, and this uncovered link may open avenues for novel therapeutics for liver fibrosis." ] },{ "paper_id": "b0bb72323af0b1a945243ed46769e00f6d9ceca2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b0cf5fb3ba91c15b0f93c584949fbc235f5b2d1a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "General procedure. The Jolly-Seber model with POPAN parametrization served as the starting structure for model fitting [34] . We estimated the following three parameters using his approach:" ] },{ "paper_id": "b0da552a101206a82845a47dc3ee9f0a64ed2bac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that they have no competing interests. ", "Nevertheless, the prevalence and transmission of influenza and other respiratory viruses among homeless populations are currently poorly studied [4, 5] .", "The 2 snapshots were positioned temporally at different periods of local peaks of influenza virus circulation as assessed by the diagnostic laboratory of the University Hospital of Marseille ( Figure 1) ." ] },{ "paper_id": "b0db6a5fa1ab9115d590c33a7934a6fbab65558e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b0dcc756c7f2641a8319b96355ec871ba2922f90", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2012, 4 2755 (230/373, 56%) across all age groups. The proportion of mixed-infection vs. mono-infection was highest for ADV (46%), followed by CRV 229E (32%), CRV HKU1 (31%), CRV NL63 (28%), CRV OC43 (23%), PIV (20%), RSV (17%), hMPV (15%) and ERV (13%). hMPV was significantly more likely to be identified in mono infection as compared with ADV, CRV, PIV, and RSV with the exception of ERV [p<0.05].", "The age distribution of virus found in mixed infection with hMPV is summarized in Table 3 . ERV was the most commonly found virus in hMPV mixed infection across all age groups." ] },{ "paper_id": "b0e519e2224e5ee8dd2303ed3f347e049cb599a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Also against influenza viruses, a universal epitope-based vaccine (Multimeric-001) was developed containing nine conserved B and T cell epitopes of influenza A and B viruses. This vaccine has recently entered clinical phase IIb [35] , and phase III studies are planned by the producer company BiondVax. All epitopes are being expressed as a single recombinant protein of 50 kDa in E. coli.", "In general, synthetic peptides-as compared to recombinantly generated peptides and proteins-are useful tools for the mimicry of protein sites, including epitopes for antibodies, since they can present natural protein fragments, and also allow for diverse chemical modifications, including the incorporation of a large range of non-proteinogenic amino acids [90] . Apart from extending the chemical and structural diversity presented by peptides, such modifications also increase the proteolytic stability of the molecules, enhancing their potential as drug candidates.", "Finally, the trimeric Env spike does not have a fixed conformation, but is characterized by tremendous flexibility with a native closed form shifting towards more open conformations [48] . In addition, sequential binding to two different receptors is necessary to activate the fusion event between viral and cellular membranes, whereby binding to the first receptor, CD4, triggers conformational changes leading to the exposure of co-receptor binding epitopes, either binding to CCR5 or CXCR4 [49] . However, in this period the virus is already very close to the cellular membrane, so that many antibodies, in particular those against the membrane-proximal external region (MPER), can hardly interfere with infection.", "The corresponding antigens are processed by antigen-presenting cells (APC) to expose pathogen-specific peptides on major histocompatibility complexes (MHC) types I and II for activation of cytotoxic CD8 + and CD4 + helper T-cells, respectively ( Figure 2 ). This natural immune response also includes the generation of long-lived memory B and T cells, which are rapidly activated and expanded upon the next encounter with the pathogen. In contrast, passive immunization consists of the direct administration of protective antibodies from external sources providing immediate, but short-lived, protection due to the limited half-life of antibodies (about three weeks). Passive immunizations can also occur naturally, i.e., by transfering antibodies from mother to child via the placenta or breast milk, or occur artificially by transfering purified natural or recombinantly expressed antibodies directly to the patients. Examples of infections prevented by passive vaccinations are rabies, tetanus and hepatitis A. " ] },{ "paper_id": "b0e52525fd4deb91e0fc1fd94e9453fddce62905", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b0e5a700bc9e8fe25e5c3f2c10976314cb30c150", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were presented as means 6 standard deviations (Tables 2-4) , and all data processing, data management, and statistical analysis were performed using SPSS version 18 software (SPSS, Chicago, IL)." ] },{ "paper_id": "b0eabdda18ddcbe7d2c1ed0932ee123d7eb6dbbf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A supplementary figure and two supplementary tables are available with the online version of this paper.", "The dilution of virus that resulted in infection of 50 % of replicates could then be calculated.", "Sensitivity of the neutralization assay using a CVS-11 pseudotype" ] },{ "paper_id": "b0ece8ef777c5e15e41c4140cb6be2a8944af191", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DJ and K-PK discussed and developed the concept of the review. DJ, SH, and K-PK edited the manuscript. DJ and K-PK wrote the manuscript.", "This work was supported by a grant from the Deutsche Forschungsgemeinschaft KN 590/7-1 and BMBF (BacVirISG15).", "It was shown that ISGylation can occur in a cotranslational process favoring modification of newly synthesized proteins. As in infected cells mainly viral proteins are translated, ISGylation can interfere with pathogen protein function as shown for capsid assembly of the papilloma virus (Durfee et al., 2010) . Furthermore, cellular proteins involved in antiviral defense or export of viral particles were shown to be ISGylated (Perng and Lenschow, 2018) ." ] },{ "paper_id": "b11cf879da2036d92fbdbbca07fd8cb7f0416e5f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The CD spectra (195-250 nm) were recorded on JASCO J-815 in 1-mm quartz cell at 25\u00b0C. Protein concentrations were 0.230 mg/ml.", "Sera were diluted 4-fold and the concentration of cytokines (IL-1\u03b2, IL-6, IFN-\u03b3, IL-10, IL-17 and TNF-\u03b1) were measured using Luminex multiplex technology (Bio-Rad Laboratories) according to manufacturer's instruction.", "The means \u00b1 SEM or means \u00b1 SE were calculated in Prism 6.0 (GraphPad) from three to ten replicates. Statistical comparisons were performed using t-test, where \u00c3 P 0.05, \u00c3\u00c3 P 0.01, or \u00c3\u00c3\u00c3 P 0.001 was considered significant." ] },{ "paper_id": "b11f198de26a3035fb312becd5eeac9a25d5f2c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus discovery combining sequence unbiased amplification with next generation sequencing is now state-of-the-art. We have previously determined that the performance of the unbiased amplification technique which is operational at our institute,", "Viruses 2012, 4 1329 VIDISCA-454, is efficient when respiratory samples are used as input. The performance of the assay is, however, not known for other clinical materials like blood or stool samples. Here, we investigated the sensitivity of VIDISCA-454 with feces-suspensions and serum samples that are positive and that have been quantified for norovirus and human immunodeficiency virus type 1, respectively. The performance of VIDISCA-454 in serum samples was equal to its performance in respiratory material, with an estimated lower threshold of 1,000 viral genome copies. The estimated threshold in feces-suspension is around 200,000 viral genome copies. The decreased sensitivity in feces suspension is mainly due to sequences that share no recognizable identity with known sequences. Most likely these sequences originate from bacteria and phages which are not completely sequenced.", "Every clinical sample has its own background of VIDISCA-interfering non-viral nucleic acid. For respiratory swabs, we determined that the background mainly consists of rRNA, and we have introduced several adjustments to the VIDISCA protocol to select and enhance sequencing of everything that is different from rRNA [6] . The background of other kinds of materials is unknown therefore we determined the performance and the background in feces suspensions and serum. In general, the VIDISCA-454-performance in serum and respiratory material is comparable with the same detection limit of approximately 10,000 copies/mL. Remarkably, the background in serum is quite different from respiratory material. In respiratory material, the amount of ribosomal RNA is 35%, while it is only 9.5% in serum samples. Careful inspection of the non-viral sequences showed that a substantial amount of the sequences is unassigned, so without any homology with known sequences. In serum, the percentage no-hits is about 10% and in fecal material 80%. This high amount of no-hits in feces could be attributed to the high number of bacteria and phages in this material, many of which have not been fully sequenced and thus the reads remain unassigned." ] },{ "paper_id": "b121a4b1dc6d8e513631edeb11421f20aad79106", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Inactivation kinetics data on virus survival were analyzed using the Weibull model [14] . The fitting of the model to the experimental data was performed by using the GINAFiT add-in software on Microsoft excel [15] . Assuming that the temperature resistance for PEDV follows a Weibull distribution, an equation was used to predict the log concentration of surviving virus after the thermal treatment (Eq. 1):", "The NVSL strain of PEDV was grown in Vero-81 cells, which were grown in Dulbecco's Modified Eagle Medium (Mediatech, Herndon, VA), 8% fetal bovine serum (FBS; HyClone, South Logan, UT), 50 \u03bcg/mL gentamicin (Mediatech, Herndon, VA), 150 \u03bcg/mL neomycin sulfate (Sigma, St. Louis, MO), 1.5 \u03bcg/mL fungizone (Sigma, St. Louis, MO), and 455 \u03bcg/mL streptomycin (Sigma, St. Louis, MO). Before inoculation, the cells were washed 3 times with phosphate buffered Saline solution (pH 7.2). After inoculation, the cells were incubated at 37\u00b0C allowing virus absorption using maintenance medium (DMEM, antibiotics, and 10.0 \u03bcg/mL trypsin; Gibco, Life Technologies, Grand Island, NY). After 1 h, new media were added to the flask and the cells were placed in an incubator at 37\u00b0C under 5% CO 2 . The cells were examined daily for the appearance of cytopathic effects (CPE), usually appearing 4 to 5 days post-infection. After CPE was observed, the cells underwent 3 freeze-thaw cycles (\u221280\u00b0C to 25\u00b0C) and were then centrifuged at 2500\u00d7g for 15 min at 4\u00b0C. After centrifugation, the supernatant was collected, aliquoted in 25 mL tubes, and stored at \u221280\u00b0C until used.", "During the 10-day incubation period, PEDV titer was reduced by 1.3 log on all surfaces except for stainless steel, in which only a 0.83 log reduction was observed. The PEDV remained viable (10 2 TCID 50 /g) on each of the four surfaces after 10 days of incubation. When delta values were compared, there were no differences among all 4 surfaces ranging from 0.7 and 7.7 days (Table 4 ).", "Upon infection with Porcine Epidemic Diarrhea Virus (PEDV), pigs experience vomiting, diarrhea, and dehydration leading to high mortality in suckling pigs [1] . The virus is excreted in large amounts in the feces of infected pigs, making it highly contagious and difficult to control [2] . After the virus was identified in Belgium in 1978, it slowly spread to multiple countries including Canada, Korea, and China [3] . In the United States, the virus was first detected in May of 2013, and while the mode of introduction has not yet been confirmed, contaminated feed has been suspected as the cause of transmission [4] .", "A total of 4 surface materials were evaluated including stainless steel, aluminum, plastic, and galvanized steel. Stainless steel and aluminum sheets were purchased from Hardware Hank (St. Paul, MN). For the plastic surface, 6-well plastic plates (Nunc, New York, NY) were used, and galvanized steel (28 gal. Silver Galvanized Steel Hobby Sheet Sleeved; Model # 57321) was obtained from Home Depot (Roseville, MN)." ] },{ "paper_id": "b128c844332f52b348e2d35863b3d0cfcbc78bf9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conflict of Interest The authors declare that they have no conflict of interest.", "Prior to each flight, we prepared an ordered list of seven randomly selected seats, of which the first two occupied seats, as confirmed by the gate agent prior to boarding, were sampled. We also randomly chose a rear lavatory door (port or starboard) for sampling.", "Each of five round-trips, on non-stop flights, targeted a different west coast destination to provide data representative of transcontinental flights. We flew to San Diego, Los Angeles, San Francisco, and Portland, OR, between November 2012 and March 2013. We flew to Seattle, WA, in May 2013. We flew on narrow-body twin-engine aircraft, with all but one flight on a specific model. Our movement data are representative of passenger and crew movements in a single aisle B3 + 3^economy cabin configuration.", "The two air sampling pumps used were model SKC AirChek XR5000. These were located in a seat at the back of the economy class cabin. Both pumps sampled at 3.5 liters per second, the NIOSH protocol for stationary sampling and approximately the normal breathing rate of adults." ] },{ "paper_id": "b147a9e7654ef4257a7c45cae6606543a7864c80", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "the CNS of FTY720-treated mice, surviving mice were able to reduce the amount of virus below the level of detection and this lasted to day 28 p.i., arguing that viral recrudescence does not occur in this model." ] },{ "paper_id": "b15e513ac2f5696b1e51324fb0a3118c44a6a9e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "gives R 0,rep as a function of R 0,ran , n and \u03c4 (see also figure 3a ; details for equation 1 are given in additional file 4):", "Orange circles stand for \u03b2\u00b7n\u00b7\u03c4 = 1.2, red squares for \u03b2\u00b7n\u00b7\u03c4 = 1.8, blue triangles for \u03b2\u00b7n\u00b7\u03c4 = 2.4 and green rhombi for \u03b2\u00b7n\u00b7\u03c4 = 3.0." ] },{ "paper_id": "b16129cfc36efc5d85192fbaa31d96799c98f8c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b16b23aad25d88c3af9ccd50b754cd4d9e8762fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where the computation of q varies with interventions.", "Let p H,t \u00f0 \u00debe the probability that individual is in class H at time t. Assume that the above mentioned process is Markovian on the relevant time scales, the dynamics of this probability is governed by the following master equations:", "\u00f0 \u00dezV ? \u00f0 \u00de. This definition follows the minimum affected principle and assigns equal weights to class R individuals and class V individuals [11] . Other more complex definitions could be obtained by weighting the two quantities." ] },{ "paper_id": "b16e9ad986a7b19e35e008a79293bba8fb2c6787", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In (4a) and (4b)", "where once again ( ) = (0) exp[\u2212(", "In (10) " ] },{ "paper_id": "b1734efe5e012f983218c7155fc434cada1a35ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b187316c24eb26f96af6ebbc243e90cfc504d94b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Administration of FGF21 resulted in a dose-dependent reduction in circulating levels of glucose.", "Values are expressed as means \u00b1 S.E.M. Mean Value Comparisons between two groups were performed using the Student t test. Significant differences were considered at P < 0.05." ] },{ "paper_id": "b18ff7b65ed56a87c0c0de1ee312b8a0ddb51e4c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:28950 | DOI: 10.1038/srep28950" ] },{ "paper_id": "b190452f13e95ef0af0c07243e44a98371fe00eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses (CoVs) have a global distribution and infect a variety of human and animal hosts, causing illnesses that range from mostly upper respiratory tract infections in humans to gastrointestinal tract infections, encephalitis and demyelination in animals; and can be fatal [1, 2] . The International Committee for Taxonomy of Viruses (ICTV) reports four coronavirus genera, namely Alphacoronaviruses, Betacoronaviruses, Gammacoronaviruses and Deltacoronaviruses [3] . CoVs are enveloped single-stranded, positive-sense RNA viruses with genomes ranging between 26.2-31.7 kb, the largest among known RNA viruses [4] . This large, capped and polyadenylated genome contains seven OPEN ACCESS common coronavirus genes in the following conserved order: 5'-ORF1a-ORF1b-S-ORF3-E-M-N-3' [5] . ORF1a/b encompasses two-thirds of the genome and produces a genome-length mRNA (mRNA1) that encodes two overlapping viral replicase proteins in the form of polyproteins 1a (pp1a) and pp1ab [6] .", "These polyproteins are formed as a result of a -1 ribosomal frame shift that involves a complex pseudoknott RNA structure [7] and are then proteolytically processed by virally encoded proteases into mature nonstructural proteins (nsp1 to nsp16), which assemble to form a membrane-associated viral replicase-transcriptase complex (RTC) [6, 8, 9] . The last third of the genome produces subgenomic (sg) mRNAs that encode the four structural proteins, spike (S), envelope (E), membrane (M), and nucleocapsid (N), as well as a number of accessory proteins [10, 11] .", "Cape 7535, South Africa; E-Mails: rmcbride@uwc.ac.za (R.M.); 2917799@myuwc.ac.za (M.Z.) \u2020 These authors contributed equally to this work." ] },{ "paper_id": "b19a29c5c29055c01ee2e63ec63a395c0f7ddb17", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LOMA is implemented in java and is available at http:// www.comp.nus.edu.sg/~bioinfo/AES_LOMA/" ] },{ "paper_id": "b1b2eb98641f5fbf2b51cb26566196ae59a7ad96", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Methods: Seven web-based surveys were conducted including 3,840 respondents over a one-year period. Time trends were analyzed with linear regression analyses. Multivariate analysis was used to study determinants of precautionary behaviour.", "Infectious diseases are once again among the major public health challenges. The SARS epidemic of 2003 showed not only that there are new unknown viruses which can have severe health consequences, but also made clear how fast a disease can spread globally, what the societal and economic impact can be, as well as how the media may contribute to awareness and public concerns [1, 2] . While SARS came as a surprise, since April 2009 the world is confronted with a new influenza H1N1 pandemic.", "-To study precautionary behaviour related to avian influenza and its potential determinants." ] },{ "paper_id": "b1b9699bbe9b36657ae6aa66628dc06e232da95b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "From 2006-2009, 843 bats were trapped within their natural habitat from several provinces in mainland China in accordance with animal ethics protocols approved by the Wuhan Institute of Virology, Chinese Academy of Sciences. Serum, pharyngeal and fecal swab samples were collected and stored as described previously [8] . Most animals were released back into their habitat. Those did not survive underwent necropsy.", "A surrogate virus neutralization test was conducted using a recombinant env -HIV-1 virus containing the luciferase reporter gene pseudotyped with spike glycoprotein proteins (GP) of EBOV (Zaire-GP) or RESTV (Reston-GP [11] ). The plasmid encoding Zaire-GP (L11365) was kindly provided by Prof. Lijun Rong (University of Illinois at Chicago, USA). The Reston-GP gene was synthesized based on the RESTV genome sequence (FJ621583). Serum was serially diluted at 1:20 to 1:640 in 30 \u03bcl of medium and mixed with 30 \u03bcl of pseudovirus solution. The mixture was incubated for 1 h at 37\u00b0C and subsequently added, in triplicate, to 293T cells grown in a 96-well plate. The plate was incubated for 1 h at 37\u00b0C before being replenished with fresh medium and incubated for 48 h. Cells were lysed in 30 \u03bcl of lysis reagent (Progema) and luciferase activity was measured using a Luciferase assay kit (Promega). None of the positive bat serum inhibited entry of Reston-GP or Zaire-GP pseudotyped virus." ] },{ "paper_id": "b1bc4e62b880ab407cb7af2514847a38f76df2c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Laboratory technicians conducting biomarker tests were blinded to clinical data and comparator method outcomes.", "Data on demographics, medical history, physical examination, complete blood count, and chemistry panel were obtained at enrollment. Data were also collected relating to additional diagnostic tests and imaging studies performed on a clinical basis, such as blood culture, throat culture, and serological testing for cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, and Coxiella burnetii.", "A nasal swab was obtained for microbiological investigation. Nasal swabs were stored at 4\u00b0C for up to 72 h before transport to a central laboratory, where two multiplex polymerase chain reaction analyses were conducted to detect common respiratory viral (Seeplex RV15) and bacterial (Seeplex PB6) pathogens: parainfluenza virus 1, 2, 3, and 4, coronavirus 229E/NL63, adenovirus A/B/C/D/E, bocavirus 1/2/3/4, influenza A, influenza B, metapneumovirus, coronavirus OC43, rhinovirus A/B/C, respiratory syncytial virus A and B, enterovirus, Streptococcus pneumoniae, Haemophilus influenzae, Chlamydophila pneumoniae, Legionella pneumophila, Bordetella pertussis, and Mycoplasma pneumoniae." ] },{ "paper_id": "b1be7d31c3101fa5b0c803ee2d354eb7d3943526", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Copyright: Lee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.", "The authors declare no conflicts of interest." ] },{ "paper_id": "b1c01e51053266154ff1cf59628c2cb92a8184ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b1c3b2b1c4cf2f4e3cb4ac316dc9ad8d33946c77", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our firm conducted a risk/benefit assessment of \"gain-of-function\" research, as part of the deliberative process following a U.S. moratorium on the research (U.S.", "The combination of prospective human reliability primary data gathering to assess what might go wrong and historical incident record keeping to assess what did go wrong provides a powerful path to reducing biosafety risk. Using these data, laboratory safety practices can be improved, lowering the risk to the researchers and to their surrounding communities. In addition, training, equipment, and safety systems can be redesigned to prevent common mistakes before they happen.", "Not only is scholarship lacking on how mistakes may be made, data are not collected on how mistakes have been made either. Despite a clear need for keeping these records, the United States has no standardized or comprehensive system for tracking laboratory incidents or near misses in high-containment laboratories. Astoundingly, we appear to lack even the most basic knowledge of how many high-containment laboratories are currently in operation (12) . Although some partial reporting systems exist (13, 14) , none of these systems are sufficiently standardized, complete, or of high-enough quality and detail to provide usable statistics about the type, magnitude, and kind of incidents that occur in biological laboratories. This lack of centralization and standardization hinders the spread of lessons learned and best practices between laboratories, which likely results in us suffering the same mistakes in multiple laboratories." ] },{ "paper_id": "b1cb9713cb3f669a5f4b63e04395fb4669312d5b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For serum isolation, blood was sampled from the caudal veins (N = 3) at days 28 and 35 post-inoculation, and clotted at 4 \u2022 C overnight. The serum was obtained by centrifugation at 3,000 \u00d7 g for 10 min and stored at \u221220 \u2022 C before use.", "V. anguillarum was isolated and stored in our laboratory (18) . The bacteria were cultured at 37 \u2022 C with Luria Bertani (LB) medium for 12 h, harvested by centrifugation at 8,000 \u00d7 g for 5 min, and the concentration measured using an Accuri C6 cytometer (BD Biosciences, Piscataway, NJ, USA). Bacteria were subsequently used for challenge and in ELISA at a concentration of 1.0 \u00d7 10 7 CFU/ml.", "The underlined letters represent the restriction enzyme sites." ] },{ "paper_id": "b1d31bf64148c3dabdd5b8a288b78c0c6d3a7cea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Almost all other curated articles were published in the late 1990's.", "Interaction Evidence -which journals are curated?" ] },{ "paper_id": "b1d4318370f0bf32b2c6afded3ef07c1a37abe7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Throughout the study, node support was estimated by nonparametric bootstrap (BS, bootstrap support) in ML and with multiple samples from the posterior distribution (PP, posterior probability) in BI.", "Figures S1 a-b RDP3 analyses results. The x axis shows genome length in nucleotides, numbered form the start of ORFs after alignment with Neudoerfl (U27495) as reference. The y axis represents the metric used by each method for detecting recombination. Detected recombination signals appear as colored rectangles.", "(TIF) " ] },{ "paper_id": "b1d5a591bff2740b3b81dce8659fec2470ac9dfb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results are presented as mean \u00b1 SEM of the three independent replicates of commonly used fomite materials on a farm. Virus sample eluted from each fomite replicate was processed independently by TCID 50 assay, immunoplaque assay, and real-time quantitative RT-PCR. An ANOVA was used to determine statistical significance between data sets using GraphPad Prism 7 software (Graphpad Software Inc., San Diego, CA, USA).", "On the other hand, PEDV survival decreased precipitously at room temperature within 1 to 2-days post application, losing 2 to 4 log titers within 24 h (Figure 1 ).", "In conclusion, our findings provide a new perspective on how fomite material and temperature impact viral stability over time, indicating the significance of understanding the nuances of indirect transmission in the epidemiology of PEDV." ] },{ "paper_id": "b1d62ed79fe0391283061a488e3d43be2c03807a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "cDNA synthesis process was performed using cDNA synthesis premix (Seegene Inc., Seoul, South Korea) with 8 l of RNA, 2 l random hexamer primer, and 10 l mix of transcriptase, MgCl 2 , dNTP, and buffer. The multiplex reaction was performed using Biorad CFX 96 Real Time Thermal Cycler. The reaction mixture was first denatured at 95 \u2218 C for 15 min, followed by 50 cycles of denaturation at 95 \u2218 C for 30 s, annealing at 60 \u2218 C for 60 s, extension at 72 \u2218 C for 30 s, and a final extension step at 55 \u2218 C for 30 s. The melting curve temperature from 55 \u2218 C to 85 \u2218 C (5 s/0, 5 \u2218 C) was used to read the amplification. Any positive result was detected as a peak in electropherogram, compared to positive control. ", "This present study is the first study reporting respiratory viruses' detection in ILI patients in Indonesia. During 2012, 1692 patients that meet ILI case definition criteria were enrolled. From 334 cases randomly selected, 175 (52.3%) were male and 159 (47.6%) were female. The median age was nine years with a range from 1 month to 79 years. Most of the cases selected were patients with age > 5 years old (60.7%).", "Influenza-like illness (ILI) surveillance was conducted in thirteen sentinels' public health center across 13 Indonesia provinces in 2012 in Figure 1. The WHO case definitions were used to determine the ILI cases: fever \u2265 38 \u2218 C and a cough or a sore throat [25] . Demographic and clinical data were obtained from questionnaires that are filled out by trained staff. Throat swab and nasal swabs from 1,692 patients were collected in viral transport medium (VTM), which were then sent to the Virology Laboratory, National Institute of Health Research and Development (NIHRD) in Jakarta. The VTM consists of bovine serum albumin, penicillin, streptomycin, and amphotericin B, according to WHO surveillance manual [6] . Only specimens were received by the laboratory within three days after the collection was processed for molecular examinations. Specimens were stored in a \u221280 freezer prior to the laboratory tests. For this multiplex study, a total of three hundred thirty-four specimens were randomly selected." ] },{ "paper_id": "b1d65769b15ff7bd395ae21186fd09642f69571f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Positive controls for ZIKV and DENV were obtained by virus isolation from Brazilian patients' sera in C6/36 or Vero E6 cells.", "Placentas were fixed in 10% buffered formalin immediately after delivery.", "For both, statistical analyses were performed using GraphPad Prism 6.01 software. Differences were considered to be statistically significant at p < 0.05." ] },{ "paper_id": "b1d8740e2366dfb7237e416b257905c5bb06f349", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b1ebb695b7eb5d98f551f2c3ffd027cc0bab2016", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Equine viral pathogens belonging to diverse viral families have been described including, but not limited to, equid herpesviruses, equine arteritis virus, African horse sickness virus, equine infectious anemia virus, equine coronavirus, Hendra virus, vesicular stomatitis virus, equine influenza virus, West Nile virus, Eastern Equine Encephalitis, Venezuelan Equine Encephalitis, Western Equine Encephalitis, and most recently equine parvovirus-H causing hepatitis [2] [3] [4] [5] [6] [7] [8] [9] .", "The use of horse samples adhered to the animal use guidelines set by UC Davis' Institutional Animal Care and Use Committee (AICUC Protocol # 19988, approval date 5/31/2018).", "The United States has the largest horse population with 9.5 million horses, followed by those of China, Mexico, Brazil, and Argentina with an estimated 2006 world population of 68 million [1] .", "The expected NS1 ATP-or GTP-binding Walker A loop motif (GxxxxGKT/S; GPPSVGKS) and Walker B motif (EE) were all found [27, 28] . The phospholipase A2 (PLA2) catalytic residues (HDLGY) and its highly conserved calcium-binding site (YTGPG) were also found at the N-terminus of the capsid protein [29] ." ] },{ "paper_id": "b1ec83bddfe11fc5f176972ca4ae358b4f46c79f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sudden emergence of SARS-CoV shocked the world and impacted the public health seriously. The pandemic was contained under high level quarantines, but its disappearance also raised numerous mysteries to the research community. Even today we know little about its severe pathogenesis and have no effective treatment protocols. In preparedness, we also need effective diagnostic approaches and preventive vaccines.", "The global outbreak of severe acute respiratory syndrome (SARS), caused by a novel coronavirus (SARS-CoV), resulted in more than 8,000 cases with a fatality rate of about 10%. Impressively, the rapid spread of SARS-CoV made a great impact on public health and social-economic stability. It is thought that SARS-CoV might originate from its natural reservoir bats and transmit to humans through an intermediate such as palm civets and raccoon dogs, and no one can exclude the possibility of its recurrence [1] .", "Micro-neutralization assays SARS pseudovirus system was developed in our laboratory as previously described. In brief, HEK293T cells were co-transfected with a plasmid encoding codonoptimized SARS-CoV S protein (Tor2) and a plasmid encoding Env-defective, luciferase expressing HIV-1 genome (pNL4-3.luc.RE) using Lipofectamine\u2122 2000 reagents (Invitrogen) according to the manufacturer's protocol. Supernatants containing pseudovirus bearing the S protein were harvested 48 h post-transfection and used for single-cycle infection of ACE2-expressing 293T cells (293T/ACE2). Briefly, 293T/ACE2 cells were plated (10 4 cells/well) in 96-well tissue culture plates and grown overnight. The pseudovirus was preincubated with serially diluted purified anti-RBD at 37\u00b0C for 1 h before addition to cells. The culture was re-fed with fresh medium 12 h later and incubated for an additional 48 h. Cells were washed with PBS and lysed using lysis reagent included in the luciferase kit (Promega, Madison, WI). Aliquots of cell lysates were transferred to 96well Costar flat-bottom luminometer plates (Corning Costar, Corning, NY), followed by addition of luciferase substrate (Promega). Relative light units (RLU) were determined immediately on the Modulus\u2122 II Microplate Multimode Reader (Turner Biosystems, Sunnyvale, CA)." ] },{ "paper_id": "b1f385c02a27a04b941f53de42b53c1ecc1a7c94", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Models of representative sequences of the S proteins from each clade were built with the structure of MERS-CoV S protein (5X59) using homology modeling (SWISS-MODEL) with default parameters. The models were then superimposed and analyzed using Discovery Studio visualizer (Accelrys) (BIOVIA, San Diego, CA, USA).", "The number of synonymous substitutions per synonymous site, dS, and non-synonymous substitutions per non-synonymous site, dN, in S were calculated. Sites under positive selection were inferred using different methods as described in previous publications [21] [22] [23] [24] . First, single-likelihood ancestor counting (SLAC) and fixed effects likelihood (FEL) methods were used as implemented in DataMonkey server (Available online: http://www.datamonkey.org). The overall \u03c9 (dN/dS) value was calculated according to NJ trees under the custom (010121 with AIC of 16604.47594182065) substitution model. The \u03c9 (dN/dS) values for different clades and lineages were calculated according to NJ trees under either the F81 model or the custom substitution model (010121, 010011, 001020, or 000010 with various AIC). Positive selection for a site was considered to be statistically significant if p-value was <0.1. A mixed-effects model of evolution (MEME) was further used to identify positively selected sites under episodic diversifying selection in particular positions among different clades within a phylogenetic tree, even when positive selection was not evident across the entire tree.", "To assess adaptive evolution of MERS-CoV, dN/dS ratios (\u03c9) in S gene across the 219 strains were calculated on codon-by-codon basis. The overall \u03c9 was 0.424737 (0.392404 and 0.439492 for clade A and B strains, respectively), with most codons having \u03c9 < 1, indicating purifying selection (Table 2) . Nevertheless, four codons were predicted to have \u03c9 > 1 by different methods with statistical significance, including codons 26 and 312 by fixed effects likelihood (FEL) method, codon 1250 by mixed-effects model of evolution (MEME) method, and codon 1224 by both FEL and MEME methods, indicating possible functional constraints at these positions during evolution. Among them, codons ", "Among all known CoVs, the largest numbers of complete/near-complete genomes are available for SARS-CoV and MERS-CoV, of which >300 and >200 genomes, respectively, are available for analysis. Such large number of genomes has given us a good opportunity to improve our " ] },{ "paper_id": "b1f86a8d26afcb49621b2b3aba8eaf1851b95315", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Female BALB/c mice, 4-6 weeks of age were obtained from Charles River and housed under pathogen-free conditions at the University of South Florida Vivarium. All treatment protocols were approved by the USF Institutional Animal Care and Use Committee (IACUC)." ] },{ "paper_id": "b1f90c0a862d8dc3485d61deb8c87c0b53b798b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and GraphPad Prism5 software. The statistical significance was determined using One-way ANOVA. The Spearman correlation test was used to test the correlation between CXCL10 concentrations and clinical parameters. A value less than 0.05 was considered to be statistically significant.", "Hantaan virus (HTNV) is a member of the enveloped Bunyaviridae family characterized by a tripartite single-stranded RNA genome of negative polarity. The large (L) segment encodes the viral RNA-dependent RNA polymerase (RdRp), the medium (M) segment encodes two surface glycoproteins (Gn and Gc), and the small (S) segment encodes the nucleocapsid protein (NP) [1] . HTNV could cause a severe lethal hemorrhagic fever with renal syndrome (HFRS) in human [2, 3] .", "Human umbilical vein endothelial cells (HUVECs) were prepared by the method described before [22] . Cultures of HUVECs were grown on fibronectin-coated plates (Millipore, USA), were maintained in EGM (Lonza, USA) supplemented with 10% fetal bovine serum (PAA, Austria), 100 IU of penicillin/mL, and 100 g of streptomycin/mL, and were used before the 10th passage.", "The study was approved by the Institutional Review Board of the Fourth Military Medical University. Written informed consent was obtained directly from each adult subject, and all the children had informed consent given from their guardians for the collection of samples and subsequent analysis." ] },{ "paper_id": "b1fa74682266ab3d64275b8f738e8e9a37732efe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b20a6cf878e90b22d10ce2ddbd4c566a9b86fba2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "C ell membranes function as platforms to coordinate numerous steps in viral replication (1, 2) . Mitochondria, lysosomes, phagosomes, Golgi complex, peroxisomes, and endoplasmic reticulum (ER) are subverted and remodeled by viruses (3, 4) , many of which use the ER as a preferred membranous compartment to build replication organelles (5) .", "Cells, viruses, and plasmids. HeLa CCL2 cells were grown in Dulbecco's modified Eagle's medium (DMEM; D6429; Sigma) supplemented to contain 10% fetal bovine serum, 100 U/ml penicillin G, 100 g/ml streptomycin (Gibco), 0.25 g/ml amphotericin B, nonessential amino acids, 2 mM L-glutamine, and 1 mM sodium pyruvate (Sigma).", "Engineered mCherry-T1LM3 230MT-HeLa CCL2 cells stably expressing viral NS protein fused to mCherry and a metallothionein (MT) tag were generated by transducing cells with replicationincompetent retrovirus. Cells were then cultured in the same medium supplemented with 1 g/ml puromycin (Sigma). L929 cells and MEFs were grown in Dulbecco's modified Eagle's medium (D6429; Sigma) supplemented to contain 10% fetal bovine serum, 100 U/ml penicillin G, 100 g/ml streptomycin (Gibco), nonessential amino acids (Sigma), and 2 mM L-glutamine.", "Mammalian reoviruses are nonenveloped, double-stranded RNA (dsRNA) viruses that replicate in a wide range of cells and tissues (18) . These viruses infect humans throughout their lifetime (19) and have been implicated in the pathogenesis of celiac disease (20) . Reovirus replication, transcription, and assembly occur in large cytoplasmic structures termed viral inclusions (VIs) (21) . Inclusions were generally thought to be membrane-free structures, but they contain smooth membranes attached to mitochondria (22) . ER cisternae surround reovirus inclusions, and ribosomes are distributed within these structures (21, 22) . These findings point to the potential participation of the ER in VI formation and architecture." ] },{ "paper_id": "b2126ad45f5a952f27851ec2ef42245a3d8f09c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human embryonic kidney (HEK) 293T ((ATCC CRL-3216) and African green monkey (VeroE6) cells (ATCC CRL-1586) stably expressing porcine aminopeptidase N (VeroE6-APN) [13] were grown and maintained in Opti-MEM TM (Gibco TM , Thermo Scientific, Waltham, MA, USA) supplemented with 10% heat-inactivated fetal bovine serum (FBS). Cells were cultured in humidified air containing 5% CO 2 at 37 \u2022 C.", "1 -a-flag :======::::: ", "Supplementary Materials: The following are available online at http://www.mdpi.com/1999-4915/11/4/382/s1, Table S1 : Pathway analysis of interacted host proteins by using PANTHER data base. " ] },{ "paper_id": "b23a403b1daf18cd8a06665ad3111e92453bd61b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Peptone was obtained form Bacto (Sparks, USA). Yeast Extract and nutrient agar were obtained from Difco (Sparks, USA). MSTFA was obtained form Macherey-Nagel (D\u00fcren, Germany). All other chemicals used were of analytical grade and obtained either from Sigma-Aldrich (St. Louis, USA) or Fluka (Buchs, Switzerland). Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "b2511d6e6a5faa918701cd2bf6e2641ba7f4c9cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Transactivator of viral latent genes and host genes; responsible for episome replication, segregation and persistence of viral genome; involved in p53 degradation and oncogenesis.", "A co-activator of EBNA-2; dispensable for B-cell transformation; viral tumor suppressor; and up regulates CXCL10. EBNA-3Bknockout induces DLBCL-like tumors.", "The various factors controlling EBV-associated oncogenesis can be categorized and summarized in the following:" ] },{ "paper_id": "b263c0ae8e08257b2d46468d7561dbb7d7d6b6e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NP swabs were collected using flocked-tip swabs and transported to the laboratory in the Copan universal transport medium (UTM-RT) system (Copan Italia, Brescia, Italy).", "Stool samples were diluted in sterile phosphate-buffered saline (PBS) to a 10% suspension. Aliquots of 180 \u03bcL of MagNA Pure bacteria lysis buffer (Roche Applied Science, Mannheim, Germany) and 20 \u03bcL of proteinase K (Qiagen, Hilden, Germany) were added to 190 \u03bcL of stool suspension.", "Before the extraction procedure, 5 \u03bcL of Equine herpesvirus 1 and 5 \u03bcL of Equine arthritis virus isolates were added to all samples. Specific target sequences of these viruses were subsequently amplified in separate real time reverse transcription polymerase chain reactions (RT-PCRs) as an internal control to ensure that negative results were not caused by poor nucleic acid extraction or inhibition of the RT-PCR assay [15, 16] .", "None of the 38 samples from 33 children positive for HCoVs in NP swabs and/or stool sample had viruses detected in blood sample taken simultaneously." ] },{ "paper_id": "b272687e1bbab9fefce2b87887609a88e6ecd860", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MBs have a hairpin structure that can undergo spontaneous conformational changes upon hybridization to complementary nucleic acids or protein targets, activating fluorescence resonance energy transfer (FRET) [61, 62] . For example, the dye molecule does not emit lights when it is near a quencher, and it emits when it is distant from quencher.", "PDA-based biosensors have attracted considerable attention due to their unique color change from blue to red in response to a variety of stimuli such as applied stress, changes in temperature or pH, and ligand-receptor binding. Thus, PDA-based biosensors have been applied to a wide range of analytes, including proteins, viruses, antibacterial peptides, antibodies, and pharmacologically active compounds.", "Fluorescence images of layer-by-layer fluorescence dye particles (reproduced with permission from reference [35] . Copyright 2010, Elsevier B.V.)." ] },{ "paper_id": "b27d654e2342664a7dc5ea9442bde90b11b0cefd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The developments of specific, potent and accessible antiviral treatments that restrain rotavirus infection remain important to control rotavirus disease.", "Hyperimmune colostrum (Gastrogard-R W )" ] },{ "paper_id": "b281ffd13e1ca8492cc60ae608b6b24a7be46a1f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b285ac5faca47fd0d835d385a193bb169447015f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:32154 | DOI: 10.1038/srep32154", "Affinity-purified rabbit anti-cytoplasmic tail of porcine FcRn (anti-pFcRn-CT) polyclonal antibody was prepared in our laboratory. Horseradish peroxidase (HRP)-conjugated goat anti-rabbit and rabbit anti-mouse IgG were purchased from Thermo Scientific Pierce (USA). Mouse anti-GAPDH monoclonal antibody was purchased from BOSTER (China)." ] },{ "paper_id": "b287ba995f0d86627890bf70c5d6aad88deff2c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was conducted in accordance with the Guide for the Care and Use of Laboratory Animals of Hubei Province, China. All animal experiments were performed according to the protocols approved by the Laboratory Animal Monitoring Committee of Huazhong Agricultural University, China. ", "The genome sequence of phage PHB09 and partial genome sequence of B. bronchiseptica Bb01 have been deposited in GenBank under accession numbers MN103401 and MN660071, respectively. The authors confirm all supporting data and protocols have been provided within the article or through Supplementary Data Files.", "One hundred microliters B. bronchiseptica cells (1.5 \u00d7 10 4 CFU/ml) were mixed with 100 \u00b5l of mouse serum (Yisheng, Shanghai, China), inactivated mouse serum, and PBS, respectively. After 1 or 2 h incubation at 37 \u2022 C, the titers of B. bronchiseptica were determined as described above." ] },{ "paper_id": "b28a8c489742fd2227e6e4049d777febfd4051cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords: nanoparticles, HPV, WT1, survivin, CD8 T cell epitopes, vaccine, immunogenicity, HLA-A2. 1 ", "Frontiers in Immunology | www.frontiersin.org the matching amount of each antigens across each experimental groups were used for immunogenicity studies.", "All statistical analyses were performed using Graph Pad Prism v6.04 software (Graph Pad Software, Inc., La Jolla, CA, United States) and Microsoft Excel (Microsoft Corporation, Redmond, WA, United States). Comparisons were performed using one or two-way ANOVA analysis as appropriate. Differences were considered statistically significant when p < 0.05. Values are expressed as mean \u00b1 standard deviation (SD)." ] },{ "paper_id": "b293146d54c66eef361bc16cc69f793f46f88f1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "While oblique lines indicate movement in space, straight segments should represent stays over a period of time." ] },{ "paper_id": "b293192e82a70515cb199bca870a9fe2ca9b081d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Microbiota profiling with 16S rRNA PhyloChip (version G3) which can detect up to 60,000 bacterial and archeal taxa was performed as previously described [32, 33] .", "Upper respiratory infection (URI) is one of the most common reasons for children in the USA to seek medical care [1] . URIs frequently lead to bacterial complications, resulting in billions of dollars in health care expenditures [2] ; 30 % of URIs are complicated by acute otitis media and 8 % by rhinosinusitis [2] . The presence of Streptococcus pneumoniae, Haemophilus influenzae, and/or Moraxalla catarrhalis in nasopharyngeal (NP) cultures from children with URIs is predictive of increased likelihood of progression to acute otitis media [2] , and these species are also known to potentiate the effect of rhinovirus infection on the likelihood of asthma exacerbation [3] ." ] },{ "paper_id": "b298992d7feb9dd3d23192572f975abdf2cebc0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As indicated in the figure legends, fold changes and associated standard errors (SEs) were estimated by linear mixed effects models with a fixed effect (treatment time or group) and a random effect (experiment date or hepatocyte donor), allowing for treatment time/group-specific variation, similar to what has been published previously [10, 29] . In the case of multiple comparisons, p-values were adjusted based on the Bonferroni's method within the linear mixed effects models. A two-sided p-value of <0.05 defines statistical significance. SAS software (version 9.3, Cary, NC) was used for statistical analyses.", "Experiments were conducted similar to those published previously [38] . After treatment with bortezomib or vehicle control, the cell culture media was assayed for lactate dehydrogenase (LDH) activity with a cytotoxicity detection kit (Roche Diagnostics GmbH, Mannheim, Germany), according to the manufacturer's instructions. Triton-X (2%)-treated and non-treated cells served as the 100% cytotoxicity positive control and negative control, respectively.", "The proteasome inhibitor bortezomib is currently the front-line therapy for the treatment of newly diagnosed multiple myeloma patients and for patients with mantle cell lymphoma who have received at least one prior therapy [18] . The interaction of bortezomib with metabolizing enzymes has been characterized in the past decade. Bortezomib is a substrate of several cytochrome P450 isoenzymes [19] , but only mildly inhibits CYP2C19 and CYP2C9; therefore, no major metabolism-mediated DDIs are anticipated [20] . Statins are widely prescribed for the treatment of hypercholesterolemia and hypertension, and are also reported to have beneficial effects in cancers, including multiple myeloma [21] [22] [23] . Since elevated systemic exposure to statins due to DDIs may cause severe side effects, determining the DDI potential and myopathy risk associated with bortezomib upon concurrent administration with OATP substrate statins has significant clinical relevance. To date, the potential of bortezomib to cause OATPmediated DDIs has not been assessed." ] },{ "paper_id": "b29aec7c51b6c428e566fa6e092797fc4da21b29", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b2a382ff964250dde3c7387b87bd244b27e4f81d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Whole blood was collected in an EDTA-containing tube within a maximum of 24 hours after hospital admission. The peripheral blood mononuclear cells (PBMC) were immediately separated by gradient centrifugation using Ficoll-Paque Plus (GE Heathcare, cat. no. 17144002). After cell separation, the PBMC were collected, preserved in RNAlater (Qiagen, cat. no. 76106) " ] },{ "paper_id": "b2b5a490834c8b80177d322022e6c5c0828a5eaa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There is no specific viral life cycle pathway within the KEGG dataset. However, viruses use adhesion molecules as receptors, endocytosis for cellular entry and the intracellular actin and tubulin networks for migration to and from the nucleus, mediated via dynein and kinesin motors. They also subjugate intracellular vesicular trafficking pathways, and are able to subvert both lysosomal and phagosomal pathways. Their exit may depend upon exocytosis, or by apoptotic or other means of killing their host cell [122] . These pathways are heavily represented within the schizophrenia gene analysis.", "Autoimmunity, involving several key schizophreniarelated proteins may well be a consequence of pathogen infection, and related to viral/human protein homology. Antigen and antibody removal by immunoadsorption techniques might therefore also be if clinical benefit.", "Antigenicity (B-cell epitope prediction) was estimated using the BepiPred server http://www.cbs.dtu.dk/services/ BepiPred/ [32] (Table 4) ." ] },{ "paper_id": "b2b90b3519bdcdd02d17595b01c3bb30cb8be63a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The p15A origin was amplified from plasmid pACYC177 using primers p15A-F and p15A-R, and an EGFP expression cassette was amplified from pHP using primers NotI-prosseA-F and XhoI-Ter-EGFP-R. Both fragments were directly ligated together to creat pLP.", "Abbreviations EGFP: Enhanced green fluorescent protein; HA: A fragment of the hemagglutinin protein from the H5N1 influenza virus; HAOP: A synthetic codon-optimized HA epitope gene; IFN-\u03b3: Interferon-gamma; CFU: Colony forming unit; ELISA: Enzyme-linked immunosorbent assays; HIA: Hemagglutination Inhibition Assays; APCs: Antigen-presenting cells.", "Differences between the means of two experimental groups were analyzed by the Student's t-test. One-Way ANOVA (SPSS 16.0, SPSS Inc., Chicago, USA) was performed to compare the differences of multiple groups. Results are presented as mean values \u00b1 standard error, and at least three independent replicates were performed for each condition.", "Background: Despite the development of various systems to generate live recombinant Salmonella Typhimurium vaccine strains, little work has been performed to systematically evaluate and compare their relative immunogenicity. Such information would provide invaluable guidance for the future rational design of live recombinant Salmonella oral vaccines.", "In vivo immune response to recombinant Salmonella-HA strains Humoral immune response" ] },{ "paper_id": "b2c1c0ce4885d8a926e9ff2b97aeb3ea220286b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At the genomic level, bats appear to have a much larger repertoire of germline genes encoding immunoglobulin variable (V), diversity (D) and joining (J) segments than humans, which could potentially provide a larger number of antigen specificities in their naive B cell receptor (BCR) repertoire. In little brown bats (Myotis lucifugus), there is less evidence of somatic hypermutation, indicating that bats may rely more on their germline repertoire to respond to infections (107, 119) .", "Nucleotide-binding oligomerization domain (NOD)-like receptors are intracellular PRRs that can recognize nucleic acids from invading viruses (104) . Genes encoding the NOD-like receptors NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) and NOD-, LRR-and CARD-containing 5 (NLRC5) have been identified in the transcriptome of P. alecto (37) but only NLRP3 has been functionally characterized in bats (17) .", "AB, MB, KK, and KM wrote the first draft. All authors edited and contributed to subsequent drafts.", "Following ligand sensing, PRRs signal through adaptor proteins to express antiviral and pro-inflammatory cytokines. Regulation of such inflammatory responses is crucial in order to limit tissue damage. Many severe virus infections are associated with excessive inflammation-associated pathology in humans (51, 52) . Bats have evolved novel mechanisms to limit virus-induced proinflammatory responses while maintaining type I IFN responses to limit virus propagation (Figure 1) . Understanding how bats limit virus-induced pro-inflammatory processes may enable researchers to adapt these strategies to counteract inflammation in humans." ] },{ "paper_id": "b2c35edb017ca3e5f0d14a0155034e02851f814a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords: M2 channel inhibitors; adamantane-based drugs; virtual screening; pharmacophore modeling", "OPEN ACCESS" ] },{ "paper_id": "b2ca7959b768af6c0ac1f5e347a31dacf9fcfd2f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The EGFP gene was amplified by polymerase chain reaction (PCR) using a forward primer (5'-CCGGGGATCCG GTGAGCAAGGGCGAGGAG-3') and a reverse primer (5'-CCGGAAGCTTTCTTGTACAGCTCGTCCAT-3'). PCR was performed under the following conditions: 5 min at 95\u00b0C denaturation, 30 cycles: 30s at 95\u00b0C, 30s at 55\u00b0C, 1 min at 72\u00b0C; 10 min at 72\u00b0C additional extension. The PCR products were loaded on 1% agarose gel." ] },{ "paper_id": "b2d1fbbdf2e7ff09c09119e4d49f3f60e9091101", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "From STEM data logger, number of effected districts, exposed individuals, infectious persons, and deaths at different time point is shown in Table 2 .", "After developing the model, the programme was run and simulation result in map view was represented at 4-month interval up to 2 years. Then, predicted numbers of exposed individuals, infectious patients, and deaths were logged in data logger.", "There is no conflict of interests regarding the publication of this paper.", "(i) At the very beginning of the epidemic there was ( ) = ( ); that is, total population of India is susceptible as there was no previous incidence of Ebola case." ] },{ "paper_id": "b2d2050a4b62e13a5c78e23190f61a7895ca33e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(II) The second major group comprises the remaining 20 species, including the Pteriomorphia groups Mytilida, Arcida and Pinnoidea (represented by the lone species A. rigida), together with various Imparidentia species classified as Cardioidea, Cyamiidae, Mactroidea, Sphaeriidae and Venerida, implying that this well-defined group of bivalves with high CUB (ENC \u223c40-52) and low GC 3 (30-40%, with the outlier M. chinensis reaching \u223c23%) comprises phylogenetically distant species." ] },{ "paper_id": "b2d3a11928e26fbdd71764c358950fca41199fe5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Copyright: He et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.", "The statistical significance between experimental groups and controls was determined by one-way ANOVA and Fisher's least significant difference (LSD) posttest. Differences were considered significant at p<0.05. p<0.05 was denoted by *." ] },{ "paper_id": "b2d7e294cc9cffc5de442aef23ef615f70e3c746", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "YL performed the systematic literature review and wrote the manuscript. MG, XY, BZ, and S-HC edited the manuscript. J-LC organized and provided the frame for the manuscript and critically revised the manuscript. All authors read and approved the final manuscript.", "Recent studies proved that IFITM proteins are associated with the transduction efficiency of lentiviral vector. Human and pig IFITM proteins partially limited the transduction of VSV-GFIV and GP64-FIV, thereby limiting the transfer of genes based on lentiviral vectors to airway epithelial cells (Hornick et al., 2016) . It was observed that H37Rv-mCherry signal was weaker in IFITM3overexpressing cell lines compared to cells transduced with empty lentiviral vector and IFITM1 and IFITM2 overexpression vector. Moreover, IFITM3 overexpression can significantly inhibit the growth of Mycobacterium tuberculosis in monocytes (Ranjbar et al., 2015) , indicating its clinical potential for treatment of the disease caused by Mycobacterium tuberculosis.", "Recently, a novel mechanism by which IFITM proteins restrict viral infection has been identified. It shows that IFITM suppresses HIV-1 protein synthesis by excluding viral mRNA transcripts from polysomes, which can be rescued through expression of the viral accessory protein Nef. The observation indicates that IFITM-mediated HIV-1 restriction takes place at the translational level (Lee et al., 2018) ." ] },{ "paper_id": "b2e781c81e340e91a0f27009b29d0c8a3635c5e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Representativeness: Age and sex distribution of total cases detected reflect the general distribution of Ghana's population. The median age of cases was 30 years (range: 3 weeks to 90 years). Females constituted 60% (1775/2948) of cases." ] },{ "paper_id": "b2eef726fe46a8ddef327c78e7d5affbfd2fe69c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The complete genome sequences of the two nasopharyngeal Coronavirus HKU15 strains were deposited into the International Nucleotide Sequence Databases with accession numbers LC216914 and LC216915.", "Pairwise alignment was performed using BioEdit 7.2.5 (optimal GLOBAL alignment) 29 or EMBOSS Stretcher (Nucleotide Alignment); 30 whereas multiple sequence alignment was performed using MUSCLE 3.8, 31 where the aligned sequences were further manually inspected and edited. Tests for substitution models and phylogenetic analysis by the maximum likelihood method were performed using MEGA 6.0.6. 32", "Divergence times for the Coronavirus HKU15 strains were calculated based on the complete genome sequence data, utilizing the Bayesian Markov chain Monte Carlo method using BEAST 1.8.0 33 with the substitution model GTR (general time-reversible model)+G (gammadistributed rate variation)+I (estimated proportion of invariable sites), a strict molecular clock, and a constant coalescent. Fifty million generations were run with trees sampled every 1000th generation to yield 50 000 trees. Convergence was assessed based on the effective sampling size after a 10% burn-in using Tracer 1.6.0. The mean time to the most recent common ancestor (tMRCA) and the highest posterior density (HPD) regions at 95% were calculated. The trees, after a 10% burn-in, were summarized as a single tree using TreeAnnotator 1.8.0 by choosing the tree with the maximum sum of posterior probabilities (maximum clade credibility) and viewed using FigTree 1.4.0." ] },{ "paper_id": "b2f39f20e4e523aab2915f1d22d29d6a29110a20", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The negative controls included in these tests were supernatant of culture medium MRSC without inoculation (C1) and the same supernatant incubated for 2 h at 37 \u2022 C (QC3). Control with noninactivated proteinase K supernatant could not be tested due to post-incubation cell lysis. As a negative control of inhibition, a non-fermented freeze-dried sample was used (C1). As positive control of infection, a solution containing cells and viruses was used.", "FIGURE 1 | MALDI mass spectrum of the common peptide among functional fractions obtained following purification by cationic exchange chromatography.", "Frontiers in Microbiology | www.frontiersin.org ", "Data are the average of at least two independent experiments. n.d., not detected. Control has no mineral addition. Data are the average of at least two independent experiments. SD, standard deviation; a P-value < 0.01; b P-value < 0.001." ] },{ "paper_id": "b2fde3b77f54db50b124bca17aaba10069e4424b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "File S1 This file contains Statistical (MCMC) details; Sensitivity analysis of the full model; Full inference while holding b fixed; and, Some analytic results. (PDF)", "Infection is assumed to be frequency dependent (but densitydependent transmission is no obstacle to the methodology we outline, and will be discussed later) with transmission parameter b [15, 24] . The transition rates for this model are given in Table 1 .", "The serial interval probability mass function is formed by binning into days, as detailed in the next section.", "The model is specified by the matrix Q, which encodes the transition rates between different possible states of the household [6, 18] . For the SE(j)I(k)R model we consider, the total number of possible states is" ] },{ "paper_id": "b2ffe7f0bedb7b3ab6d0181ec70ece3e4e2dabea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The family Flaviviridae contains many member viruses which are highly pathogenic to humans and/or have high outbreak potential. West Nile fever, Dengue fever, Yellow fever, Japanese encephalitis, and Zika fever are all mosquito-borne diseases, caused by West Nile virus (WNV), Dengue virus (DENV), Yellow fever virus (YFV), Japanese encephalitis virus (JEV) and Zika virus (ZIKV), respectively.", "Due to their inability to generate a complete immune response, mice knockout for type I interferon (IFN) receptors (Ifnar -/-) are more susceptible to viral infections, and are thus commonly used for pathogenesis studies. This mouse model has been used to study many diseases caused by highly pathogenic viruses from many families, including the Flaviviridae, Filoviridae, Arenaviridae, Bunyaviridae, Henipaviridae, and Togaviridae. In this review, we summarize the findings from these animal studies, and discuss the pros and cons of using this model versus other known methods for studying pathogenesis in animals.", "YFV is endemic in tropical areas of Africa and South America (WHO, 2016b), when the virus was introduced via the slave trade during the 17 th century. Many infections are symptomatic, but if clinical symptoms appear, they include fever, chills, appetite loss, nausea, muscle pains, and headaches. A small percentage (~15%) of cases will go on to develop more severe disease including jaundice, dark urine, vomiting and abdominal pain. Hemorrhage from the mouth, nose, eyes or stomach may occur and 50% of patients with these symptoms succumb to disease (WHO, 2016b). YFV was responsible for ~127 000 severe infections and 45 000 deaths in 2013 (WHO, 2016b), with increased incidence over the past decades, and the risk of an outbreak in urban centers is a serious public health threat (Barrett & Higgs, 2007) .", "DENV is widespread in the temperate and tropical regions of the world, and each year approximately 50-150 million people are infected (Bhatt et al., 2013) , with over 10 000 deaths (Stanaway et al., 2016) . Symptoms of Dengue fever include a high fever, headache, vomiting, muscle and joint pains, and skin rash. Severe cases of disease is usually associated with secondary infection with heterologous types of DENV (Halstead, 1988) , and can develop into Dengue hemorrhagic fever (with hemorrhage, thrombocytopenia and blood plasma leakage), or into Dengue shock syndrome, both of which are potentially fatal (Kularatne, 2015) ." ] },{ "paper_id": "b30770ae30b35cdfaf0a173863e74e93edbb0329", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b313d134237c1d12ea832bcad736937d908a6c25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). Raw microarray data for these studies were deposited in publicly available databases in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (41) and are accessible through GEO accession no. GSE65574 (http://www.ncbi.nlm.nih.gov/geo/query/acc .cgi?acc\u03edGSE65574).", "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .00665-17.", "FIG S1, DOCX file, 0.1 MB. ", "Research was supported by grants from NIAID of the NIH (U19AI100625, U19AI106772, and HHSN272201000019I-HHSN27200003 to R.S.B. and K99AG049092 to V.D.M.). Pacific Northwest National Laboratory is operated by the Battelle Memorial Institute for the DOE under contract no. DE-AC05-76RLO1830." ] },{ "paper_id": "b314e4a20b1f0a2f4a49afb65c17859ad7d50c4d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Spinal cords from 30% sucrose solutions were cut into 16 ?ere cut intusing a cryostat microtome (Leica CM 1850; Leica Microsystems, Seoul, Korea) and stained with LFB/Crystal Violet (LFB, IHC World, Ellicott City, MD) and H&E for identification of intact myelin and infiltrating cells, respectively. Sections were evaluated via light microscopy (Olympus, Tokyo, Japan) ( 50 or 200).", "-\u0394 \u0394 CT = (C T,target -C T,beta-actin ) experimental sample -(C T,target -C T,beta-actin ) control sample.", "The authors declare that they have no competing interests. " ] },{ "paper_id": "b31d9e4a450071584fa87e054414be87264def22", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results were considered statistically significant with p < 0.05. Statistical analyses were conducted using IBM SPSS statistical software version 20.0 (IBM SPSS Inc., Chicago, IL, USA).", "Six hundred ninety-eight prospective participants provided written consent. Of these, 600 completed the baseline survey, provided a nasal swab and were randomized into the study. Four hundred seventy one (78.5%) completed all weekly surveys, 86 (14.3%) completed at least one but not all, and 43 (7.2%) completed none ( Figure 1 ). The median age of the participants was 19 years (interquartile range 18-20), 60% were first or second year undergraduate students, and 64% were female. Baseline characteristics were similar across the intervention arms (Table 1) .", "Upper respiratory tract infection (URTI), which presents clinically as the common cold, is the most common human illness [1, 2] . Multiple respiratory viruses are known to cause episodes of URTI, however rhinovirus has consistently been identified as the most common cause of the common cold [2, 3] . While the majority of infections are mild and self-limiting, URTI can exacerbate existing medical conditions and can cause severe illness which may result in hospitalization or death [1, 2, 4] ." ] },{ "paper_id": "b31dc72ffc01a849e4f2fce7ddd09067cfc82770", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The most commonly detected respiratory viruses were hRV (range, 2-35%; median, 16%), IFV (range, 0-62%; median, 2%), ADV (range, 2-28%; median, 6%), RSV (range, 0-24; median, 2%), and hCoV (range, 0-19%; median, 2%) (Fig. 2b) .", "The average DID of the total antibiotic prescriptions during the study period was 26.2 (range, 20.3-31.2). For primary clinics, the prescribing rate was 25.2 (range, 20.6-31. 2) DID in 2010 and 26.9 (range, 20.4-30.1) in 2015 with a tendency to increase (p < 0.01) (Fig. 1a) .", "The statistical package R, version 3.2.4 (R Foundation for Statistical Computing, Vienna, Austria) was used for all statistical analysis. All p-values were 2sided and considered significant at p < 0.05." ] },{ "paper_id": "b33f78304f8fdb97631ad4b5b5ed9d8d85d0622f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusions: Acclimatization to mild hypoxia incites a number of endogenous adaptations that induces an anti-inflammatory milieu. Further understanding of these mechanisms system may pinpoint possible new therapeutic targets to treat neurodegenerative disease.", "All histological and immunocytochemical analyses are conducted using four to six sections per animal with three to six areas of analysis per section and four to six animals per group (see the \"Materials and methods\" section). Data is expressed as an average of each area of analysis. Between-group analysis was accomplished using one-way analysis of variance (ANOVA) with least significant difference post hoc testing. Significance is set at p value <0.05. Based on the variability in these data from our previous studies [25] , we can distinguish a difference in individual proteins and in capillary density with 95 % power.", "To determine whether exposing immunized mice to hypoxia influenced the influx of immune cells, T cells, polymorphonuclear leukocytes (PMNs), macrophages, and microglia were quantitated by fluorescence-activated cell sorting (FACS) analysis, as previously described [26] . Briefly, mice were perfused to eliminate leukocytes from the vasculature, whereupon the brain and spinal cord were collected to recover infiltrating cells. Following vascular perfusion, tissues were minced in HBSS (HyClone, S. Logan, UT) and digested filtered through a 70-\u03bcm nylon mesh cell strainer using a rubber policeman. The resulting slurry was digested for 30 min at 37\u00b0C in HBSS supplemented with 0.2 mg/ml collagenase type I (Sigma-Aldrich, St Luis, MO), 5000 U/ml DNase I (Invitrogen, NY), 1 mg/ ml dispase (Invitrogen), and 0.025 % trypsin to obtain a single-cell suspension. Following enzyme neutralization, cells were layered onto a discontinuous OptiPrep (Fisher) gradient and centrifuged at 2000 rpm for 15 min at room temperature in a swinging bucket rotor. After centrifugation, myelin debris was carefully aspirated and the cell interface was collected. Following extensive washes and incubation in Fc block (BD Biosciences, CA) to minimize nonspecific Ab binding to FcRs, cells were stained with directly conjugated Abs for the four-color FACS to detect PMNs and macrophages (CD11b+, CD45 high ) and microglia (CD11b+, CD45 low-intermediate )." ] },{ "paper_id": "b34cc3d570e41a80c01088f73600357cf071a4da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The inclusion criteria are:", "Exclusion criteria: admission into intensive care, macrolide therapy contraindicated (e.g. liver dysfunction, hypersensitivity), presence of diarrhoea (stools of increased watery consistency and more than two stools above usual stooling frequency), received macrolides (in last 7-days), or clinical and radiological features consistent with a primary diagnosis of pneumonia, [33] at time of randomisation.", "The ", "At each site, the site-specific study nurse visits the wards twice daily to screen all newly admitted infants. A standardised collection form is used to collect clinical data (see below) and hospital outcomes associated with the bronchiolitis episode. All infants are managed according to a standardised protocol. This has been used at the Royal Darwin Hospital since 2008. The protocol outlines when supplementary oxygen is prescribed (Sp0 2 <94%) and reduced, and when nasogastric feeds or intravenous fluids are used. Enrolled infants may receive additional therapies (other than macrolides) at the discretion of the attending paediatrician." ] },{ "paper_id": "b35188139844b656464c0727fa39ec03d970c443", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Genomic DNA was extracted from peripheral blood with Qiagen kit (QIAamp DNA Blood Midi/Maxi; Qiagen, Hilden, Germany). DNA samples were sent at the Spanish National Genotyping Center (CeGen; http:// www.cegen.org/) for DNA genotyping by using GoldenGate assay with VeraCode Technology (Illumina Inc., San Diego, California, USA). Moreover, for healthy subjects, the frequencies of alleles and genotypes for studied polymorphisms were obtained using the 1000 Genomes Project website (http://www.1000genomes.org/home), which provide a broad representation of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations 35 . We select the IBS (Iberian populations in Spain) population that included 107 individuals.", "Hardy-Weinberg equilibrium (HWE) for all SNPs was assessed by a Chi-square test, considering equilibrium when p > 0.05. In addition, pair-wise linkage disequilibrium (LD) analysis was computed to detect the inter-marker relationship using the standardized D\u2032 and r 2 values by Haploview 4.2 software. Haplotype-based association testing was performed using Plink software (http://pngu.mgh.harvard.edu/~purcell/plink/) comparing each haplotype with the rest of haplotypes (there was no reference category). All p-values were two-tailed and statistical significance was defined as p < 0.05.", "Each diagonal represents a different SNP, with each square representing a pairwise comparison between two SNPs. Abbreviations: OAS, 2\u2032 5\u2032 oligoadenylate synthetase; Mx1, myxovirus resistance proteins." ] },{ "paper_id": "b3574701bdaf6c4d408e9abe2d4176e058fc5208", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b35c5f90e09d90f6fd6cff9dab355755e4c33fe4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Because data were collected using telephone interviews we had to adapt measures to suit a brief format in order to avoid people hanging up mid-way or providing invalid answers to hurry the interview, a problem encountered with this data collection method. We therefore used parsimonious measure to minimize assessment fatigue and low response rates which threaten representativeness.", "Structural Equation Modeling (SEM) is a method for simulating and testing multiple and interrelated causal relationships simultaneously in statistical data, making it suitable for theory development and testing [40] . SEM was applied to test the hypothesized model. SEM is usually performed when a model contains latent variables assessed with specified measurement models. Despite including estimations of a series of multiple regression equations, SEM differs from regression analysis in several ways, which make it advantageous for this kind of analysis.", "A simple version of our findings can be found it the supporting file (Text S1)." ] },{ "paper_id": "b360dd33baf9170084ca4b452e13e92d3bbdefee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b3751edcd573ad46664235ecd8b63e9db99d4c09", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(DOC) paper: GZ JI RLM. Edited the manuscript: GZ JI WAD RLM. Contributed equally in all aspects: GZ JI." ] },{ "paper_id": "b37857f5ea12c3dadcd0929c3c38720fc8c7d028", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "TCGAGGATGCGAAATTTACATATG Probe-qPCR-S10 c ACTATCCTAATGGCGGCGACGCGCA F-qPCR-S10 CAAGGAGTATCGCGAAGGGC R-qPCR-S10 ATTTGGATCGCACGTGGCTT Probe-qPCR-egfp c AGGCTACGTCCAGGAGCGCACCATCTT F-qPCR-egfp CCACATGAAGCAGCACGACT R-qPCR-egfp GGGTCTTGTAGTTGCCGTCG a Restriction sites are underlined; b Homologous fragments are indicated with italics; c The probe primers were flanked with 5 -FAM and 3 BHQ1 moieties.", "All recombinant vectors were confirmed by PCR and DNA sequencing at Sangon Biotech (Shanghai) Co., Ltd.", "Author Contributions: Conceptualization, G.Z., J.H. and X.S.; methodology, G.Z. and X.S.; software, G.Z., J.Y. and X.S.; validation, G.Z., F.Q. and X.S.; formal analysis, G.Z., J.Y., C.X., J.W. and C.L; investigation, G.Z. and X.S.; resources, G.Z., F.Q. and X.S.; data curation, G.Z., C.L. and X.S.; writing-original draft preparation, G.Z.; writing-review and editing, G.Z., C.X., J.Y., F.Q., J.H. and X.S.; visualization, G.Z. and X.S.; supervision, X.S; project administration, G.Z., X.S; funding acquisition, X.S." ] },{ "paper_id": "b386f0bbf59b80952e0320feacb36572c6c3b9ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b3873c777b754d108ce93d5feca0c3dff4a74564", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Written informed consent was obtained from the patient's guardian/parent/next of kin for the publication of this report and any accompanying images. quality, (3) final approval of the version to be submitted. All authors read and approved the final manuscript.", "Measles is a severe respiratory infectious disease caused by measles virus [1] . Measles has been statutorily notifiable since the earlier National Notifiable Diseases Reporting System (NNDRS) was established in 1950. Hospitals reported cases by posting a card to the county Center for Disease Control (CDC). Every month county CDC aggregated data that were then submitted through prefecture and provincial CDC to reach the national level [2] . In 1987 NNDRS was further improved, which reported basic epidemiologic data including age, sex, date of disease onset and residence by electronic document each month [3] . Since 2004 after severe acute respiratory syndrome (SARS), NNDRS was upgraded to direct reporting through network to improve timeliness, completeness of case reporting [4] .", "For each suspected case, the local CDC is required to carry out an epidemiological investigation, including obtaining specimens for laboratory confirmation since 2000." ] },{ "paper_id": "b38901ead62c88fd24f7d28ca738711e13fb79ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lags were longest for studies with phylogenetic and clinical trials applications (median = 125 and 108 days, respectively), although there were fewer publications with these models. ", "Of the 125 models reported across the studies, 74% included mechanistic assumptions about disease transmission (e.g., compartmental, agent-based, or phylogenetic models), while 26% were purely phenomenological (Supplementary file 2).", "An important caveat of our review is that it only captures published results. We are aware of additional EVD epidemiological investigations and modeling not yet published. Some modelers providing direct support to operational response efforts have not published results, possibly because of operational demands." ] },{ "paper_id": "b39cfc766778529c14cb69cc1b12e016fb9581d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SAFV RNA concentration of the positive tissues ranged between <10 and 1x 10 4 copies/ reaction. Three specimens showed values over 1,000 copies/reaction.", "The GenBank accession numbers for the three SAFV nucleotide sequences were as follows: MK182597, MK182598, and MK182599.", "Supporting information S1 ", "A total of 70 children (41 males and 29 females), ranging from 0.8 to 12 years of age, were included in the prospective study. The median age at adenoidectomy was 3 years (IQR 2.5 years). All parents gave written informed consent. The study was approved by the ethics committee of the University of Bonn (044/11) in written form." ] },{ "paper_id": "b3ad716630b356b1399e9df08cad73b1e92f317d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To ensure the validity of our results, basic model-fitting techniques for (1) variable selection, (2) goodness-of-fit (GOF) assessment, and (3) regression diagnostics were all used in our regression analyses. The statistical analysis was performed using SAS 9.1.3 (SAS Institute, Cary, NC, U.S.A.). Variables with p-value less than 0.05 were considered statistically significant. Cox & Snell R-square and Nagelkerke R-square were applied and the results listed in Additional file 3: Appendix 3.", "Among all the factors associated with RAP related to human infection of AIVs, the pathogenicity of AI virus is crucially important, particularly in those areas or countries with no prior experience of HPAI outbreaks." ] },{ "paper_id": "b3b492aee17ce67199d458de9b98bc219c2cbf3c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lungs were perfused with cold PBS containing 0.5mM EDTA and immediately ground in Hank's Buffered Saline Solution containing 0.5mM EDTA and 0.5% FBS using the gentleMACS Tissue Dissociator (Miltenyi Biotec). Mediastinal lymph nodes were mechanically disrupted. Both tissues were then incubated with 0.25mg/mL collagenase (Liberase type III, Roche) and 8000U/mL DNAse I (Invitrogen) for 20 min at 37uC. Collagenase was inactivated with sterile HBSS containing 2% FBS and the suspension was passed through a 70mm strainer. Suspensions were then treated with red blood cell lysis buffer (BD Biosciences), and resuspended in HBSS containing 10mg/mL Fc-receptor Block (BD Biosciences). Total cell counts were then attained by hemocytometer. Cells were then stained with antibodies for multiple surface antigens: CD8 (53-6.7), CD3 (17A2), CD11c (HL3), MHCII (M5/ 114.15.2), CD86 (GL-1), NK1.1 (PK136), Ly6G (1A8). For intracellular cytokine staining, total lung was digested and a single cell suspension was incubated with Brefeldin A-containing GolgiPlug (BD Biosciences) for six hours, according to manufacturer's instructions. Following staining of extracellular antigens, intracellular cytokine staining was performed using the Cytofix/ Cytoperm system (BD Biosciences). Intracellular antigens Granzyme B (GB11), and IFN-c (XMG1.2) were stained following permeabilization. Antibodies were purchased from BD Bioscience, eBiosciences, and Biolegend. Kb/SIINFEKL pentamer was purchased from ProImmune. Influenza NP-specific tetramers were kindly provided by Dr. David Woodland (Trudeau Institute). Samples were acquired using Cytomic FC500 Coulter Station (Beckman Coulter) and analyzed using Flow Jo software (Treestar Corp).", "All mice were infected using an Inhalation Exposure System A42X (Glass-Col, USA). Virus was diluted in PBS to obtain a solution of 10 7.9 TCID50 in12mL. This solution was placed in a glass nebulizer and aerosolized for a total exposure of 30 min. This leads to 100% infection rate as described previously [36, 71] . We estimate between 10 and 100 infectious particles are passively inhaled during this period [72] . Mock infected animals are exposed to aerosolized PBS.", "a-Tubulin " ] },{ "paper_id": "b3d50623bac3bd61b8af9c6dc65fa73e6086e645", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recalling sPLA 2 -IIA and sPLA 2 -X: a matter of species difference", "Healthy skin depends on a unique lipid profile to form a barrier that confers protection and prevents excessive water loss, aids cell-cell communication, and regulates cutaneous homoeostasis and inflammation. Alterations in the cutaneous lipid profile often have severe consequences for skin health and have been implicated in various skin diseases. Recent developments in lipidomics technologies now allow in-depth qualitative and quantitative investigation of a wide variety of cutaneous lipids, providing insight into their roles and mechanistic actions [63] . Cross-communication between various types of bioactive lipids suggests that their cutaneous activities should be considered as part of a wider metabolic network that can be targeted to maintain skin health, control inflammation, and improve skin pathologies [64] .", "Of additional note, PLA2G15 (also known as lysosomal PLA 2 or LPLA2) has the capacity to catalyze the biosynthesis of 1-O-acylceramide through transacylation of fatty acid from the sn-2 position of phospholipid to the 1-hydroxy group of ceramide [61] . 1-O-acylceramide is a natural component of human and mouse epidermis [62] . However, the biological importance of this unique lipid and the contribution of PLA2G15 to its biosynthesis in vivo are unclear." ] },{ "paper_id": "b3d7fd02de63c9e801c668f9784a1f31be59cc97", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral DNA was extracted from the clinical samples (either feces or rectal swab) and screened for CPV-2 by real-time PCR, as described by Lin et al. [43] . Samples showing positive results for either type of specimen were included in this study. The partial VP2 gene of CPV-2 was amplified by PCR, as described by Buonavoglia et al. [1] , and the DNA fragments were purified and sequenced as described by Lin et al. [41] .", "Clinical specimens (feces and/or rectal swab) were collected from 99 dogs with suspected CPV-2 infection from northern, central, southern, and eastern Taiwan from January 2014 to April 2016. These samples were mainly acquired from dogs with diarrhea and/or bloody diarrhea. The year of sampling and the age, clinical history, and CPV-2 types of the sampled dogs are summarized in Additional file 1.", "This is the first report to identify a novel CPV-2c variant in Taiwan. The novel CPV-2c variant was found to be ", "The substitution of Gln370Arg is unique to the Taiwanese CPV-2c strains, and this mutation is also observed in Chinese panda parvovirus [52] and Chinese CPV-2c strains [26, 27] . Residue 359 and 375 constitute a flexible surface loop of the capsid protein that is adjacent to a double Ca 2+ -binding site; this region is essential for virus infectivity, and changes are correlated with the ability of the virus to cause erythrocyte hemagglutination [53] . Therefore, it remains to be investigated whether Gln370Arg substitution causes antigenic alterations." ] },{ "paper_id": "b3d980d9df2556687fc5d6bf3b18c95215da600c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and F i are calculated in a self-consistent manner using the above equations.", "where F i is a constant for window i. There are several approaches for determining F i , of which the most popular is the weighted histogram analysis method (WHAM) [57] [58] [59] . It calculates the unbiased global distribution P u (z) using the relation", "The free energy along the reaction coordinate is then given by" ] },{ "paper_id": "b3deae058a2e470aac4ba8f9425c6150575f1522", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Neutropenia was defined as an absolute neutrophil count #500/mm 3 . Fever was defined as a single temperature reading $38.5uC or .38.0uC that persisted for 1 hour. Upper respiratory tract symptoms (URTS) were defined as onset of rhinorrhea, sneezing, nasal congestion, cough, or hoarseness. For a diagnosis of coagulase-negative staphylococci bacteremia, at least two positive blood cultures were required." ] },{ "paper_id": "b3e1d993fd5eb9e538a5acb4f5933d4bb6209878", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where \u03b8 is the exponential growth rate. The date of pH1N1 seeding can be calculated as", "We also developed a bootstrap method to calculate 95% confidence intervals (CIs). Supposing pairs of resample (T i *, m i *) were randomly drawn from the original pairs of T i and m i with replacement, the bootstrapped RSE for the jth iteration of bootstrapping was:", "Parameter distributions were drawn from 1000 simulations." ] },{ "paper_id": "b3e5d96ea8379f9890861c6a1c0246f2b93e833a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data used in these secondary analyses were de-identified data obtained from WHO or datasets from peer-reviewed literature. As such, these data were deemed exempt from institutional review board assessment. (2019) 9:7385 | https://doi.org/10.1038/s41598-019-43586-9 www.nature.com/scientificreports www.nature.com/scientificreports/", "Year of outbreak Period of time* www.nature.com/scientificreports www.nature.com/scientificreports/" ] },{ "paper_id": "b3e679d6e37ba367e165971515663ecd71ea522c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Complete genome sequences from 41 TTSuV2 isolates were downloaded from the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/Genbank/). Each TTSuV2 CDS was analyzed using DNAStar version 7.1 (DNAStar, Madison, WI). Table 1 summarizes relevant details about these viral sequences.", "Recently, Torque teno sus virus (TTSuV) infection of pigs has become widespread in many countries, including the USA, Canada, Spain, Germany, China, Japan, Korea and Brazil [21] . Despite the fact that TTV infection in humans is not yet directly associated with any disease [22] , TTSuVs have been shown to be involved in co-infection with other diseases, including the experimental induction of porcine dermatitis and nephropathy syndrome in combination with porcine reproductive and respiratory syndrome virus infection [23] and post-weaning multisystemic wasting syndrome (PMWS) in combination with porcine circovirus type 2 (PCV2) infection in a gnotobiotic pig model [24] . Moreover, Kekarainen et al. (2006) found that TTSuV2 was detected at a significantly higher rate in PMWS pigs than in healthy pigs [25] . Other research comfirmed that the replication of TTSuV2, but not of TTSuV1, was upregulated in the pigs with PMWS [26, 27] . This result was supported by Taira et al (2009) , who examined animals suspected of infection with PMWS and porcine respiratory disease complex [28] . However, due to the limited number of animal species examined and the lack of information about viral cell and tissue tropism, the characteristics and evolution of TTSuV are not fully understood.", "Torque teno virus (TTV) is a small, single-stranded, negative-sense non-enveloped, circular DNA virus [15] , which has been classified as a member of the recently discovered Anelloviridae family [16] . It was first identified in a Japanese patient with post-transfusion hepatitis of unknown aetiology in 1997 [17] . Subsequently, TTV has been detected in humans, chimpanzees, poultry, swine, cattle, sheep, cats and dogs [18, 19] . TTV was first detected in swine in 1999 and two genetically distinct species, Torque teno sus virus 1 (TTSuV1) and 2 (TTSuV2), have been identified based on the low sequence identity between the two variants [20] ." ] },{ "paper_id": "b3e7a3736c037ca082235e695e686cce2a4790a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b3e94bce63878a41d45d22c012a9492d079b3b7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Host-targeting antivirals are generally expected to have significant advantages, including a much lower frequency drug resistance, universal antiviral effects beyond viral genotypes and complementary mechanisms of action that might act in a synergistic manner with currently available antiviral agents [48] . More importantly, they offer an additional therapeutic choice, given that only IFNs and nucleoside analogs are currently available as anti-HBV agents.", "Int. J. Mol. Sci. 2014, 15 2893 " ] },{ "paper_id": "b3ecc8a7254be2774d6b64e0793dd38b035ad7bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sequence data of the two PDCoV strains will facilitate future research on the epidemiology and evolutionary biology of PDCoV in China.", "Data availability. The complete genome sequences of the two PDCoV strains (HNZK-02 and CH-01) have been deposited in GenBank under the accession numbers MH708123 and KX443143.", "This study was supported by funds from the National Key Research and Development Program of China (2016YFD0500102-1 and 2018YFD0500100) and the National Natural Science Foundation of China (31772773 and U1704231). " ] },{ "paper_id": "b3f4cd3e21b32b677d50fda144e8eed9ee44df8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Formalin-fixed tissue sections were stained with hematoxylin and eosin (H&E) using standard staining protocols and analyzed using the freehand line selection tool of Image J (Rasband, ImageJ, NIH, Bethesda, Maryland; http://rsb.info.nih.gov/ij/).", "Images were taken with an inverted Zeiss LSM 510 META confocal laser-scanning microscope (Carl Zeiss, Jena, Germany). Digital images were processed using Fiji imaging software [46] and Zeiss LSM 510 META software. " ] },{ "paper_id": "b3fc1f4cd16b65fb6454b7c2705a95aee4419c46", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was a part of GBG's research work during his M.V.Sc. program. GBG carried out the experiment. DPB and SKD designed the experiment and provided necessary guidelines. MB and BB assisted in laboratory works. DPB drafted the final manuscript. All authors have read and approved the final manuscript.", "Ethical approval for the study was obtained from IAEC, Assam Agricultural University (AAU), Khanapara campus vide approval No.770/ac/CPCSEA/ FVSc/AAU/IAEC/14-15/263 dtd. 20.6.2014." ] },{ "paper_id": "b3fe63ea9f4794d58f37083f3430c6e5238449c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Guinea pigs were bled through the jugular vein at various time points from Day 0 through Day 168. Blood was collected and serum isolated in serum separator tubes. Serum was diluted twofold starting at 1:10.", "All animal procedures were conducted in a facility (USF) that is fully accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC) and the Public Health Service (PHS). Research was conducted under a protocol approved by the Institutional Animal Care and Use Committee (IACUC) at the University of South Florida, College of Medicine (protocol # 2879). All animals were housed, handled and utilizing following guidelines of the United States National Institutes of Health.", "The enzyme linked immunosorbant assay (ELISA) was used to assess the production of antibodies from treatment and performed per manufacturer's protocol (Aldevron). Briefly, a 96-well plate (Nunc) was coated with 10 mg/ml of Hepatitis B surface antigen (Aldevron) and allowed to coat overnight at 4uC. The plate was blocked with 3% BSA in PBST for 2 hours at 37uC. Serum samples were two-fold diluted in blocking buffer and added to the plate for 2 hours at 37uC. Goat anti-Guinea pig-AP antibody was added at a 1:10000 dilution in blocking buffer. AP substrate, pNPP, (Sigma) was added to colorize and the plate was read at 405 nm." ] },{ "paper_id": "b406fb73bb91dd7aed57b8187b69a5db7e83bd85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Relationship between G and R (Scenario 1)", "The likelihood is:" ] },{ "paper_id": "b40b2c7a9a57323d18e7b564d0dec8ee330d3d01", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cloning, expression and purification of proteins used for in vitro studies", "BST2 specifically binds \u03bc1 of AP1, but not \u03bc2 of AP2 or \u03bc3 of AP3", "Conceivably, subtype C Vpu hijacks AP complexes using residues distinct or partly overlapping with those used by subtype B Vpu.", "A novel open conformation is observed for the BST2/Vpu-activated AP1", "Source, Argonne National Laboratory, and beamline X29 at the National Synchrotron Light Source, Brookhaven National Laboratory. The crystals were in the P43 space group and diffracted to a highest resolution of 3.0 \u00c5. The data collection statistics are summarized in Table 1 ." ] },{ "paper_id": "b41f3634a764bf08cbc4588f37d7d422a02fa541", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Various training methods were used, including case studies, workshops, tutorials, seminars, group discussions, role-playing, drilling, and fieldwork. Formal lecturing was the method least used. The training center was equipped with modern audiovisual aids designed for training purpose. The training logistics and general services, such as transportation and housing, were provided free of charge to the participants.", "Through an anonymous questionnaire, the following outcomes were measured and investigated: individual basic information, knowledge levels, and self-assessment of skills regarding emergency preparedness. The questionnaire was designed by experts in the field of training pro-" ] },{ "paper_id": "b420e61b7bad7118736507f69d3a255d5d171dea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b4236b54e869414c7cb19814dc2e6216a9573c0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "-Single nucleotide polymorphism (SNP) analysis to determine the phylogenetic group of bacteria, -Multi-locus VNTR analysis (MLVA) to distinguish similar groups of partially shared sequences among the obtained isolates, -Single nucleotide repeat analysis (SRA) if the above methods were not able to differentiate the tested strains (Table 3) .", "Marek's disease", "1-2 C 1-2 . CG 3 and plasmids pX0 1-2 . together with drug susceptibility to selected antibiotics a b-lactam resistance strains including ASC70 and 183; for more details see the text" ] },{ "paper_id": "b42f394d5ea15733d96063ffabef231a98ce5429", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b4523d37bd98ceef10d57d2e5a11abb5cd068832", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In vivo [90] Turpentine-induced fever rabbits Decreases body temperature", "In vivo [91] Turpentine-induced fever rabbits and rats", "Fude Yang and Xiaoxv Dong contributed equally to this work and share first authorship." ] },{ "paper_id": "b453be7df859d451667f709fbb0c843cf0b9f25c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The history of a classical protease substrate: Benzoyl-L-arginine amide", "Abbreviations" ] },{ "paper_id": "b454887997af026ed0589fcb18e59aed44473e1d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The structure and organization of cellular membranes play important roles in a wide range of biological processes. Caveolae are specialized membrane nanodomains with a distinct V-shaped morphology in the membrane. Caveolae may act as signaling platforms by allowing signaling molecules to cluster together within their ordered domains, facilitating interactions among the components [1] . Critical cellular processes associated with caveolae include signal transduction, cholesterol homeostasis, and adaptive immune signaling [2, 3, 4, 5, 6, 7] .", "Cell culture. EPC (epithelioma papulosum cyprinid) cells originated from carp epidermal herpes virus-induced hyperplastic lesions [62] . EPC cells have a broad sensitivity for fish viruses and are commonly used for isolation, propagation, and diagnostic assays for fish viruses. EPC cells were maintained at 28uC, 4% CO 2 in Minimum Essential Medium (MEM) (GIBCO-Invitrogen, Carlsbad, CA) supplemented with 10% heat-inactivated fetal bovine serum (GIBCO-Invitrogen, Carlsbad, CA) and antibiotics.", "The camera was controlled using Solis software (Andor). Additional achromatic lenses (f = +60 mm and f = +200 mm, Newport Corporation, Irvine, CA), arranged as a telescope, were mounted in the detection path to provide additional magnification and to produce an effective camera pixel size of ,136 nm. A motorized filter wheel (FW102, Thorlabs, Newton, NJ) containing neutral density filters provided control over the activation intensity to maintain a density of visible molecules of ,1 per mm 2 or less." ] },{ "paper_id": "b45e94d7cf1a4ac89b45053ce5a24f03984f8e24", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Images were obtained with both mediastinal (width 350-450 HU; level 20-40 HU) and parenchymal (width 1200-1600 HU; level 2500 to2700 HU) window settings." ] },{ "paper_id": "b4609f3760031ac126473d8438bdebc4df596be0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These studies were approved by the Animal Care and Use Committee of Colorado State University (approval number 13-4384A) and were conducted in an Association for the Assessment and Accreditation of Laboratory Animal Care, International (AAALAC) approved facility.", "<10", "The authors declare no conflict of interest." ] },{ "paper_id": "b460e5b511b4e2c3233f9476cd4e0616d6f405ac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus stocks were generated by 24 h of growth from a low dose inoculum in the cell lines described below. Supernatant medium from infected cells was centrifuged to remove cell debris, aliquoted, flash frozen and stored at -80\u02daC. PR8 (A/Puerto Rico/8/1934 (H1N1)), obtained from BEI Resources (NR-3169), was grown and titrated by plaque assay in MDCK cells from ATCC (CCL-34) [18] . MHV, obtained from ATCC (VR-261), was grown and titrated by plaque assay in 17Cl.1 cells [19] (provided by Dr. Kathryn Holmes, University of Colorado Denver School of Medicine). RV, obtained from ATCC (VR-1645), was grown and titrated by tissue culture infectious dose 50% (TCID 50 ) assay in HeLa (ATCC: CCL-2) cells [17] . LA4, a murine lung epithelial cell line from ATCC (CCl-196), was cultured in Ham's F12K medium (Mediatech) with 10% FBS (Atlanta Biologicals) and 1X antibiotic/antimycotic (Gibco).", "Gene expression responses to RV1B were compared between our data from mouse cells and published data using human cells [24] using the MGI vertebrate homology database provided by The Jackson Laboratory [25] as well as the annotate package in R.", "NimbleScan v2.5 software (NibleGen, Madison, WI) was used to extract raw intensity data for each probe on each array. Intensity data were read into the R statistical computing environment and checked for quality [20] . Data were prepared for processing using the pdInfoBuilder package and then normalized using the robust multichip average (RMA) function in the oligo package [21] ." ] },{ "paper_id": "b46170b59d879a53ec59e8a24a0c01b16df08e3d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "While the HBV therapeutic landscape is vast, few approaches are being developed to disable cccDNA directly. Targeted mutagenesis by sequence-specific RNA-guided nucleases (RGNs) and proteins has thus generated considerable interest, as the technology potentially provides the means to cure HBV infection by permanently disabling cccDNA [33, 34] .", "Several novel anti-HBV therapeutics are in preclinical development or early clinical trial (reviewed by [15, 16] ). Most candidate drugs are small molecule drugs designed to impede various stages of HBV replication. Affordable next-generation NAs, which inhibit the viral polymerase with reduced toxicity and higher barriers to HBV resistance are currently the preferred first-line of therapy. Other direct-acting antivirals include HBV core protein allosteric modulators [17, 18] , HBV surface antigen (HBsAg) release inhibitors [19, 20] and nucleic acid polymers which also inhibit viral entry [21] . With the discovery that the sodium taurocholate co-transporting polypeptide (NTCP) facilitates HBV entry into hepatocytes [22] , peptide inhibitors such as Myrcludex-B (NCT02881008 and NCT02888106) are also being developed for therapeutic application [23] . Another popular host-related strategy has been to recondition the immune system using interferons, cytokines, and peptides as immune modulators which are discussed in more detail below (Section 3.3).", "Administration of recombinant IFN-\u03b1 or its pegylated derivatives remains the only immunomodulatory drugs licensed for management of chronic HBV infection. IFN-\u03b1 is therefore the only licensed anti-HBV therapy capable of eliminating cccDNA. Immunomodulation has been shown to augment innate and adaptive immune responses against the virus. Stimulating T-cell-mediated elimination of infected hepatocytes, and indirectly cccDNA, is thus a promising immune-based strategy to achieve functional cure from HBV infection. However, the success rate of IFN therapy remains low and side effects represent a major shortcoming of this therapy. Gene therapy to enable durable expression of immune modulators may be useful to attenuate cccDNA." ] },{ "paper_id": "b4625acf19fca7b49e058b46f640125fa4e367f5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster.", "The authors declare that they have no conflicts of interest." ] },{ "paper_id": "b4662fd83b035e7eb06014924a4a03c854ad797f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "D espite remarkable progress in its control, diarrhoea remains a leading infectious cause of morbidity and mortality in low-income and middle-income countries, especially for children ,5 years [1] [2] [3] [4] . It is estimated that in 2010, worldwide, there were more than 1.7 billion episodes of diarrhoea in children ,5 years, resulting in 700, 000 deaths in 2011 3 . China, together with other 14 countries, shoulder the heaviest burden of diarrhoea, accounting for 53% of total diarrhoea episodes and 56% of severe diarrhoea episodes in children aged ,5 years 3 .", "www.nature.com/scientificreports SCIENTIFIC REPORTS | 5 : 8241 | DOI: 10.1038/srep08241 peak time in persons .55 years, and relative humidity was linked to diarrhoea amplitude in children ,5 years.", "Demographic, economic, geographic and climate information in all 31 provinces from 2005 to 2012, including population, per capita gross regional product (PGRP), latitude, longitude, monthly average mean temperature, monthly average relative humidity, and monthly average rainfall, were collected from China Statistical Yearbook 27 to identify the putative drivers of diarrhoea seasonality." ] },{ "paper_id": "b470eec84fd5bb0a9a7079506df05c3cdf398832", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following primers were used: m36F, 5'-TGG TTT CGC TAC CGT GGC CCA GCC GGC CCA GGT GCA GCT GGTG-3' (sense); m19FcR: 5'-GTG AGT TTT GTC GGG CCC TAG GAC GGT CAG CTT GG-3' (antisense).", "Binding and competition ELISAs were performed as described previously [17] ." ] },{ "paper_id": "b47b54d0d0a92245735b5b88ed1c3634574772d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human lung epithelial cell line A549, human embryonic kidney cell line 239T, and Hela cell line were cultured in DMEM (Cellgro, Manassas, VA, USA) supplemented with 10% fetal bovine serum (FBS, Gibco, Carlsbad, CA, USA), 100 \u00b5g/mL of streptomycin, and 100 units of penicillin (Invitrogen, Carlsbad, CA, USA) at 37 \u2022 C and 5% CO 2 .", "The hit extract was two-fold serially that was diluted for dose-response titration, and the IC 50 and CC 50 values were determined by fitting dose-response curves with four-parameter logistic regression to the data in GraphPad Prism software (version 5.02, La Jolla, CA, USA).", "Ebola virus (EBOV) and Marburg virus (MARV) belong to the Filoviridae family and are enveloped, single-stranded, negative-sense RNA viruses with filamentous morphology. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with mortality rates up to 90% [1] . The recent 2014-2016 Ebola epidemic led to more than 11,500 reported deaths, demonstrating the urgent medical need for effective anti-EBOV vaccines and therapeutics for humans [2] ." ] },{ "paper_id": "b48c4779aeb4c5d68971cc74ac6e6974d39d9195", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The combined operations of Union and Intersection are defined as", "Pr~T P TPzFP", ":" ] },{ "paper_id": "b4977e3f26125c15ddb66fbfc8515e08ad166bf0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. ", "The genome sequences of four economically important shrimp viruses, Penaeus stylirostris densovirus 1, hepatopancreatic parvovirus, yellow head virus, and gill-associated virus, are reported here. Genome data are fundamental for epidemiological studies in determining the origins of these viruses detected for the first time in Egypt and in developing disease management strategies.", "P enaeus semisulcatus and Marsupenaeus japonicas are the two native shrimp species in Egypt cultured since the 1980s. With the introduction of Fenneropenaeus indicus, a nonnative species, shrimp farmers started experiencing disease outbreaks. Laboratory diagnosis revealed the presence of Penaeus stylirostris densovirus 1 (PstDNV1), hepatopancreatic parvovirus (HPV), yellow head virus (YHV), and gill-associated virus (GAV). The genome sequences of these viruses are presented here." ] },{ "paper_id": "b4a0898920270c599908b3efbf4f7342a8b56c8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animals were age matched (8-12 weeks) , maintained in specific pathogen free conditions, individually tracked and monitored daily for clinical signs of stress or illness, including but not limited to changes in skin and hair, eyes and mucous membranes, respiratory system, circulatory system, central nervous system, salivation, diarrhea, or lethargy. Upon arrival, animals were housed socially (2) (3) (4) (5) in commercially available, individually ventilated caging systems with a 12 h light/12 h dark cycle. Animals were provided ad libitum commercial irradiated rodent chow (Teklad Global) and tap water filtered via reverse osmosis in autoclaved water bottles; all bedding and enrichment materials was autoclaved prior to use and changed regularly.", "In vitro co-culture data were analyzed using two-and three-factor repeated measures models: mouse-type, bacterial treatment, and bacterial uptake (bacteria + or bacteria -/exposed). Means were compared within and across time points and response variables were modeled with the PROC MIXED statement in SAS software version 4.3 (Cary, NC) using restricted maximum likelihood (ReML) parameter estimation with Sattherthwaite approximation for degrees of freedom. Means between treatments were assessed using the \"slice\" statement with a Tukey-Kramer adjustment, whereas means compared to controls used the Dunnett's adjustment.", "https://doi.org/10.1371/journal.pone.0196950.g002 respectively). The lack of SlpB/X or LTA expression by NCFM did not alter IL-1\u03b2, TNF-\u03b1, or KC production by WT BMDM.", "Harnessing the power of the mucosal immune network for durable and anamnestic vaccination responses requires an understanding of the mucosal innate and adaptive immune systems [2] . Although more studies are required to understand the mechanism by which antigenspecific humoral responses are achieved by the mucosal NCFM vaccine platform, we have identified NOD2 as an essential regulating factor. Thus, with numerous tools available for the genetic manipulation of lactobacilli, these studies provide insight into pathways that can be exploited to enhance vaccine efficacy across model systems [26, 67, 68] ." ] },{ "paper_id": "b4a97db27c8eaeb487a83a37c4bf05cd31abebf8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b4b8196a56fe00d653d288226f12952824c5b7cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Altogether, the results suggest that in cuprizone-induced deand remyelination activated microglia play a crucial role creating a repair promoting environment due to myelin debris clearance proceeding in a highly controlled manner, as well as by production of cytokines/growth factors essential for oligodendrocyte lineage cells.", "There is increasing evidence that astrocytes are key players in complex interactions with OPC, mature oligodendrocytes, and microglia supporting remyelination at least in the cuprizone model.", "A close relation between the presence of astrocytes and the efficiency of remyelination has already been recognized for a long time (Ludwin, 1980; Blakemore, 1981) . However, the exact role of astrocytes in de-and remyelination is still not fully understood.", "In addition, in this model microglia seem not to be assigned to a certain phenotype characteristic either for de-or remyelination since most of the genes that were regulated showed an unidirectional up-regulation or down-regulation throughout the deand remyelination processes (Olah et al., 2012) In respect to the M1/M2 classification it seems that the microglia population in the cuprizone model is either heterogeneously composed of both M1 and M2 phenotypes or microglia display an intermediate status." ] },{ "paper_id": "b4c05b7cdc0a9a75d52f42db2151988cc1724194", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal procedures were performed on a protocol approved by the Wake Forest University Institutional Animal Care and Use Committee according to recommendations in the Guide for Care and Use of Laboratory Animals (Institute for Laboratory Animal Research) and in compliance with the USDA Animal Welfare Act and Animal Welfare Regulations (Animal Welfare Act as Amended; Animal Welfare Regulations)." ] },{ "paper_id": "b4ced0e08f5b03e84a5addaaf3557b3cdc1ef277", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Neural progenitor cells can be infected by this virus, leading to attenuation of their growth [12] .", "Viral RNA genome sequences were obtained from GenBank. The MR-766 prototype ZIKV strain originates from the index case: a monkey infected in 1947 in Uganda (Genbank entry NC_012532). Other ZIKV ", "Several members of the Flavivirus genus are the causative agents of significant diseases in humans, livestock and wildlife. These include dengue virus that affects more than 50 million people worldwide each year, West Nile virus and Japanese encephalitis virus that caused outbreaks in North America and Asia, respectively [1] . Zika virus (ZIKV) is an emerging pathogen in the family Flaviviridae that was first isolated in 1947 from a sentinel rhesus monkey placed in the Zika Forest near Lake Victoria in Uganda [2] . ZIKV is transmitted by mosquitoes, especially Aedes africanus, but the virus was also isolated from other Aedes species (reviewed in [3] ).", "Base composition along the complete RNA genome length and the accompanying ss and ds fasta files was analyzed by cumulative skew diagrams using overlapping windows [19, 20] . Overlapping windows were defined around 1 % of the sequence length with a step size of 20 % of the window size, which generated about 500 data points per analysis irrespective of sequence length. A skew between nts N1 and N2 is defined as (N1 \u2212 N2)/ (N1 + N2). A positive value indicates that N1 exceeds N2." ] },{ "paper_id": "b4d499844440e3aacd1644715092e8d170e39517", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A third hurdle concerns funding requirements. Introducing flu vaccine into an NIP requires evidence of cost-effectiveness involving high vaccine efficacy; reasonable cost (with drawbacks including the need for two-dose priming and/or annual revaccination); and negligible AEFI costs. Currently, 29 countries in Latin American but only seven in Europe have routine influenza childhood immunization programs, and vaccine uptake in developed countries does not surpass 30%.", "Funding. Novartis Vaccines (Cambridge, Massachusetts) provided financial support for the meeting.", "Expertos en influenza de Argentina y Brasil reunidos en un grupo de trabajo evaluaron la carga de enfermedad de influenza en ni\u00f1os, analizaron las coberturas vacunales, la efectividad de las vacunas y discutieron estrategias para mejorar la prevenci\u00f3n. En ambos pa\u00edses se realiza vigilancia de virus respiratorios en todo el territorio. Las \u00faltimas temporadas de gripe fueron leves, con predominio de influenza A H3N2, influenza B represent\u00f3 menos del 30% de los aislamientos (con co-circulaci\u00f3n de ambos linajes). La vacuna de influenza inactivada trivalente est\u00e1 incluida en el Programa Nacional de Inmunizaciones en ni\u00f1os entre 6 meses-2 a\u00f1os en Argentina y hasta los 5 a\u00f1os en Brasil, y en ni\u00f1os mayores con factores de riesgo. Las coberturas alcanzan 80% (menor para la segunda dosis). Las estrategias propuestas incluyen incrementar la vigilancia de la enfermedad y estimar la tasa de letalidad (Argentina), realizar vigilancia de efectividad y seguridad de las vacunas, fortalecer los programas para aumentar las coberturas y considerar incorporar nuevas vacunas m\u00e1s eficaces. Tambi\u00e9n se discutieron acciones de educaci\u00f3n, tanto en la comunidad como en los trabajadores de la salud, y de comunicaci\u00f3n para concientizar sobre el impacto de influenza en la poblaci\u00f3n y la importancia de su prevenci\u00f3n.", "Orthomyxoviridae; pediatr\u00eda; vacunas contra la influenza; Argentina; Brasil; Am\u00e9rica del Sur." ] },{ "paper_id": "b4d5ebb1c574e7ecf75864238a2bedcac860b5bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total DNA was extracted using a Genomic DNA Mini Kit (Geneaid Biotech, Ltd., Taipei, Taiwan) following the manufacturer's protocol. All of the clinical specimens were confirmed to be infected with parvovirus by real-time PCR, as described by Lin et al. [25] .", "Canine parvovirus type 2 (CPV-2) is one of the most dangerous enteropathogens, causing fatal disease in dogs and puppies worldwide [1] . CPV-2 is a nonenveloped, small DNA virus with a diameter of approximately 25 nm and a single-stranded DNA genome of approximately 5 kb [2] . CPV-2 belongs to the genus Parvovirus in the family Parvoviridae, which includes feline panleukopenia virus (FPV), mink enteritis virus, raccoon parvovirus, and porcine parvovirus [3] . Clinical manifestations of CPV-2 infection are characterized by intestinal hemorrhage with severe bloody diarrhea; other clinical signs include anorexia, depression and vomiting [1, 3, 4] .", "Parvovirus-positive samples were further characterized by a SimpleProbe\u00ae real-time PCR assay, following the method developed by Hoang et al. [26] . First, the reaction was carried out in a final volume of 10 \u03bcl containing 3 mM MgCl 2, 3 pM SimpleProbe\u00ae (TIB MOLBIOLGmbH, Berlin, Germany), 5 pM and 2 pM each of primers Parvo-F (5\u2032-ACA CCT gAg AgA TTT ACA TAT ATA gCA CA-3\u2032) and Parvo-A (5\u2032-ATT AgT ATA gTT AAT TCC TgT TTT ACC TCC-3\u2032) , 1 \u03bcl 10x Light Cycler 480 Genotyping master mix and 1 \u03bcl 10x diluted template DNA. Real-time PCR was cycled under the same thermal conditions as those previously described for the SimpleProbe\u00ae assay [26] .", "To clone full length VP2, we performed PCR amplification using the primer pair VP2F (5\u2032-CGGTGCAGG ACAAGTAAAA -3\u2032)/VP2R (5\u2032-GGTGCTAGTTGATA TGTAATA -3\u2032) that amplified a 1755 bp fragment of the gene encoding the capsid protein. The PCR conditions were as follows: denaturation at 94\u00b0C for 2 min; 40 cycles of denaturation at 94\u00b0C for 30 s, annealing at 50\u00b0C for 1 min, and extension at 72\u00b0C for 2 min; and a final extension step at 72\u00b0C for 5 min. PCR products were electrophoresed, followed by the purification of electrophoresis products by a Wizard\u00ae SV Gel and PCR clean-up system (Promega Corporation, USA). The PCR products obtained from the previous step were cloned by a T&A\u00ae Cloning kit before being sent for automated sequencing (MB mission biotech, Inc., Taiwan). The resulting sequences were compared with reference FPV (M38246), CPV-2 (M38245), CPV-2a (M24003, and M24000), new CPV-2a (AY742953, AB054213, EU009200, JQ686671, KF676668, and KR611488), CPV-2b (M74852 and M74849), new CPV-2b (AB120720, AB120721, AB120722, AB120723, AB120724, AB120725, AB120726, AY742955, AY869724, JQ268284, KR611459, and KR611461), CPV-2c (FJ222821, AB120727, FJ005235, KM236569, KR611522, KT156832, KT162005, KY937650, MF467229, and KU244254), CPV-2a vaccine strain (FJ197847) and previous Vietnamese strains (AB120720, AB120721, AB120722, AB120723, AB120724, AB120725, AB120726). The Clustal W method and MegAlign program (DNASTAR, Madison, WI, USA) were used for multiple alignments of the nucleic acid and amino acid sequences. Phylogenetic analyses were conducted by the maximum likelihood methods using MEGA 6 based on the Tamura-Nei model [27] ." ] },{ "paper_id": "b4e24eaf67301135a909892450e011eaaa27f780", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vero cells or PaKi cells in 35-mm dishes were transiently transfected with Hendra virus F or PIV5 F alone or in combination with the homotypic attachment protein (G or HN). The F:G/ HN ratio used was 1:3 for Hendra virus and 1:1 for PIV5. Twenty-four to 48 hours post transfection, syncytia formation was examined and photographs were taken using a Nikon digital camera mounted atop a Nikon TS100 microscope with 10x objective.", "Multiple sequence alignment of mammalian furin and cathepsin L Sequences of P. alecto furin and cathepsin L were identified using BLAST searches of the P. alecto genome and transcriptome databases generated previously [71, 72] . Sequences of other mammalian proteases were obtained from GenBank. Multiple sequence alignment of mammalian proteases was generated using ClustalW [73] . P. alecto bat furin or P. alecto cathepsin L was used as a standard reference for amino acid numbering.", "In conclusion, our results show that bats have cathepsin-like and furin-like proteases analogous to their counterparts in other mammalian species, suggesting that the utilization of cathepsins for viral glycoprotein processing in a number of bat-resident viruses is not due to a lack of furin-like enzymes in the bat reservoir host. However, potential alterations in furin localization or activity in the bat host may affect virus replication. Newly emerging viruses can be major threats to public health, so further investigation of virus biology in bat reservoirs is needed to provide a global perspective on the changes that occur in viruses within their natural hosts that contribute to the emergence of the virus and transmission to other species." ] },{ "paper_id": "b4e276ce333eefee623e9d425f5c538c64b567cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "can become a cornerstone of pandemic influenza preparedness.", "Chikungunya is a mosquito-borne viral disease, endemic in Africa and", "West Nile fever is a flavivirus that causes a viral infection typically spread by mosquitoes. To date, no vaccine is available to prevent the West Nile infection. Partially purified virus-like particles were resolved by SDS-PAGE, and the Coomassie blue-stained band corresponding to Env protein was excised from the gel, destained, and analyzed by MS.", "Mass spectrometric characterization of the glycosylation pattern. Of HIV-1 gp120.", "Reversed phase HPLC of the tryptic digest. Peptides collected from RP-HPLC were further identified by amino acid analysis (AAA) or Nterminal sequencing analysis." ] },{ "paper_id": "b4e5ee4be574a65dee1c7fca178580f9db58087f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Neither study attempted to perform a comparative approach using animal models with their human tissue that would add validity to any prior or future reports into this topic. On the other hand, the study by Becker et ", "Quantification of sequences is possible as MPSS generates a digital output. Differential expression comparisons can be formed with ease between samples with detection levels for statistical significance possible even with low abundance genes expressed at 30 to 40 copies per million. In contrast, hybridization techniques require replication of experiments, high abundance genes and large differences to provide adequate quantification (83) .", "The unique cerebral responses in different individuals must be kept in mind in all laboratory and translational research studies.", "SAGE as originally described is based on two basic assumptions: (i) that a short nucleotide sequence tag (9-10 base pairs) contains sufficient information to uniquely identify a given transcript; and (ii) concatenation or linking of the so-identified short sequence tags allows the efficient analysis of transcripts in a serial manner by the sequencing of multiple tags within a single clone (103) ." ] },{ "paper_id": "b4e98770894089e276f91c1d00e58c8885708e11", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Urine samples were collected and assayed for Streptococcal pneumoniae and Legionella pneumophila antigen. Immunochromatographic membrane tests (Alere BinaxNOW S. pneumoniae and BinaxNOW Legionella, Waltham, MA) were performed on urine samples for detection of S. pneumoniae and L. pneumophila antigens. Identification of L. pneumophila by PCR also confirmed the diagnosis of Legionella.", "Serum CRP is not usually elevated above 10 mg/L in viral infection (17) ; however, invasive adenovirus and influenza can raise CRP to 10\u00c180 mg/L (18) . A metaanalysis of 10 studies that looked at a single value for serum CRP to be used as a cutoff for bacterial disease, including both gram-positive and gram-negative bacteria, resulted in a bimodal outcome, with three studies recommending that the CRP cutoff value be set between 6 and 20 mg/L and seven studies recommending a cutoff of 60\u00c1100 mg/L (19) .", "According to Korppi, CRP measurement is recommended as the first-line method of screening suspected bacterial inflammation (43) . Several studies have indicated that CRP is feasible and accurate at differentiating pneumonia from acute bronchitis (6, 44\u00c146). Pneumonia is associated with elevated serum CRP levels greater than 10 mg/L, whereas severe pneumonia has serum CRP typically greater than 100 mg/L (11, 47) . In Scandinavia, POC CRP testing is part of the routine evaluation of patients with LRTI, and its use has proved cost-effective (48, 49) ." ] },{ "paper_id": "b4f6baab270ef953349d05c6f2936803c92bf4b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Capybaras (Hydrochoerus hydrochaeris, Linnaeus 1766) are the world's largest rodent and have a wide distribution throughout South America. They are herbivores with a generalist diet, and their semi-aquatic habit requires the presence of water bodies such as lakes, rivers, and lagoons [1] . Capybaras are wild animals but also well adapted to human-modified landscapes [2, 3] . Due to their high reproductive rates, capybaras can expand their population rapidly, especially in areas with few predators such as urban environments and agricultural farms [4, 5] . The proximity of capybara habitats to humans and domestic animals in urban areas can facilitate the zoonotic spread of pathogens such as Rickettsia rickettsii [6] .", "Two capybara faecal samples were collected in Brasilia and Planaltina, Distrito Federal, Brazil, in 2016. The fresh faecal pellet samples were picked off the ground from a grass field where wild capybaras were feeding, and were placed into a 50 mL tube. The faecal pellets were homogenised in an SM buffer (0.1 M NaCl, 50 mM Tris/HCl-pH 7.4, and 10 mM MgSO 4 ) and subsequently centrifuged for 10 min at 4300 rpm. The supernatant was sequentially filtered through a 0.45 \u00b5m and 0.2 \u00b5m syringe filter and PEG-precipitated (15% w/v) overnight. The precipitated filtrate was centrifuged, and the pellet was resuspended in 1 mL of SM buffer. A measure of 200 \u00b5L of this suspension was used for viral DNA extraction using the Zymo viral purification kit (Zymo Research, Irvine, CA, USA). The extracted viral DNA was enriched for circular viral DNA using rolling circle amplification (RCA) with the Illustra TempliPhi amplification kit (GE Healthcare, Chicago, IL, USA).", "The family Circoviridae is composed of animal-infecting ssDNA viruses with genomes of~1.8-2.4 kb. Currently, the family is divided into two genera: Circovirus and Cyclovirus. Cycloviruses have been associated with both vertebrates and invertebrates, whereas circoviruses seem to be restricted to vertebrates [45] .", "All genome-wide and protein pairwise identities were determined using SDT v1.2 [32] . BLASTp [25] analysis of the MCP of the microviruses was undertaken to determine the closest related protein sequences using the complete MCP (MCP_all) dataset." ] },{ "paper_id": "b50c31a428792413355bec3fe2f5eaa30e73fefe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Adenoviruses (Adv) are nonenveloped, double-stranded DNA viruses that can cause upper and lower respiratory tract infections either in sporadic fashion or as epidemics. Currently, 49 distinct Adv serotypes have been isolated from humans. Adv typically cause mild self-limited respiratory infections. Although Adv can cause a variety of clinical manifestations, in immunocompromised patients, adenovirus infection often leads to fatal outcomes. For example, in immunodeficiency states such as a solid organ or stem cell transplantation, severe adenovirus infection may occur, with mortality up to 80% [1] [2] [3] [4] .", "The data are presented as the means \u00b1 standard deviation or as the median [interquartile range] for continuous variables and as numbers and percentages for categorical variables. The data were analyzed using Kolmogorov-Smirnov tests for normal distribution. The data were compared using the Mann-Whitney U-test or Student's t-test for continuous variables and the \u03c7 2 or Fisher's exact test for categorical variables. Statistical analyses were performed using SPSS version 23.0 (SPSS Inc., Chicago, IL, USA), and a two-sided P-value < 0.05 was considered to indicate significance.", "Initial antibiotic agents were intravenously administered to all of the patients. Initial antibiotic regimens were followed by adherence to the \"Treatment Guidelines for Community-acquired Pneumonia in Korea: An Evidence-based Approach to Appropriate Antimicrobial Therapy\" from The Korean Academy of Tuberculosis and Respiratory Diseases [21] . The antipyretic agents and regimens used in this study were as follows. Propacetamol was intravenously administered at a dose of 1 to 2 g as needed to a maximum of 8 g per day. Acetaminophen was given orally at a dose of 2 tablets (650 mg per tablet) every 8 h to a maximum of 6 tablets per day. Physical cooling methods applied to all febrile patients included external air, ice bag, or water blanket techniques." ] },{ "paper_id": "b50ee1febe5e4b252cbc70678de7272524377ca1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1)", "Using (5) in (4) we get", "Computational By taking the inverse of both sides of (8) we get" ] },{ "paper_id": "b514652703a631715ca85e65499c66016fb994d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ln[E(Counts)] = \u03b2 0 + \u03b2 1 sin(2\u03c0 t) + \u03b2 2 cos(2\u03c0 t) + \u03b2 3 (t) + \u03b2 4 (t 2 ), where ln[E(Counts)] are hospitalization counts modelled with Poisson distribution, \u03c0 is the constant, \u03c9 is the frequency, and t is the day in a time series ranging from 1 st to 5884 th day. The terms \u03b2 3 (t) and \u03b2 4 (t 2 ) control for longterm linear and quadratic trends. The coefficients \u03b2 1 and \u03b2 2 are needed to derive peak timing in days. Detailed methods can be found elsewhere [18] . SAS version 9.0 (Cary, NC) and S-PLUS version 8 (Palo Alto, CA) were used for the data abstraction and analysis, respectively. ArcGIS version 9.3 (Redlands, CA) was used for mapping. The Tufts Medical Center Institutional Review Board approved the study protocol for this analysis of the CMS data.", "Accurate monitoring and estimation of influenza activity require understanding not only influenza dynamics, but also population characteristics and their changes. Important dynamic factors such as the transmissibility of influenza strains, the accuracy of contact rate assessment, and the movement of populations within and between geographical units, if not clearly understood and properly modelled, may compromise the precision and accuracy of the estimation. The SARS epidemic of 2003 [10] illustrates these complexities by demonstrating the potential of global travel patterns to impact the spread of a virulent infectious agent, the coronavirus, necessitating a systematic investigation on how travel and migration patterns affect disease epidemics." ] },{ "paper_id": "b515cc5df8df49a37037106bfe3d94a2370e30bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A HPLC analysis was conducted with an Agilent Series 1260 liquid chromatograph equipped with a quaternary gradient pump system and variable-wavelength detector system connected to a reversed-phase (RP) SB-C 18 column (5 \u00b5m, 4.6 \u00d7 250 mm, Agilent, USA). Data collection was performed using ChemStation software (Agilent, USA). Chromatograph-grade methanol and acetonitrile were purchased from Sigma-Aldrich Co. Ltd (St. Louis, Missouri, USA).", "Folin-Ciocalteus's phenol reagent (Beijing Solarbio Co. Ltd, PR China), 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2-azino-bis (3-ethyl-benzothiazoline-6-sulphonic acid) diammonium salt (ABTS), 2,4,6-Tripyridyl-s-triazine (TPTZ), and 6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox, Sigma-Aldrich Co., St. Louis, Missouri, USA), gallic acid, quercetin, and acetic acid (Tianjin Bodi Chemical Holding Co. Ltd, PR China) were used. All solutions were filtered through 0.22 mm nylon filters before use. Reagents were of analytical grade and dissolved in deionized water (18 M cm).", "Antimicrobial activity was tested against nine bacterial strains provided by the Microbial Culture Collection Center of Guangdong Institute of Microbiology, China. Tests against four gram-positive bacteria (Staphylococcus aurous Rosen Bach ATCC6538, Pseudomonas aeruginosa ATCC29212, Bacillus subtilis ATCC6633, and Listeria monocytogenes ATCC19115) and five gram-negative bacteria (Klebsiella pneumoniae ATCC46117, Salmonella enteritidis ATCC14028, Salmonella typhimurium CMCC50115, Salmonella paratyphi CMCC50093, and Escherichia coli ATCC25922) were conducted. All strains were cultured at 37 \u2022 C on Mueller-Hinton medium. " ] },{ "paper_id": "b516e53a03a6dc4df9eb13c85d0a57ef71452125", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The components of population, exposure, comparator, and outcome (PECO) are as follows:", "The research report exceeds 500 words The research report is less than 500 words", "The study presents unique results which have not been previously published, or is the most recent and comprehensive analysis of the data." ] },{ "paper_id": "b51c5f53980e0118362f26862e1243aac186a4ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2015, 7 12", "The virulent nephropathogenic IBV strain, B1648 has been isolated in 1984 [17] . Virus stocks were prepared in 10-day-old embryonated SPF chicken eggs by allantoic route inoculation. Then, virus was propagated in embryos for 48 h at 37\u02ddC. Finally, the allantoic fluid was harvested, clarified by low speed centrifugation and frozen at\u00b470\u02ddC until use.", "Comparison of Spike Protein (1166 aa) and Partial S1 Gene (727 nt)", "Fragments ranging from 350-600 bp were selected using the BluePippin (Sage Science, Beverly, MA, USA) according to the manufacturer's instructions. Sequencing of the samples was performed on a HiSeq 2500 platform (Illumina, San Diego, CA, USA) for 300 cycles (150 bp paired ends). Raw reads were trimmed for quality and adapters, and were de novo assembled into contigs using SPAdes [25] . Scaffolds were classified using a tBLASTx search against all complete viral genomes in GenBank using an e-value cut-off of 10\u00b41 0 . Scaffolds with a significant tBLASTx hit were retained and used for a second tBlastx search against the GenBank nucleotide database using an E-value of 10\u00b44 [26] ." ] },{ "paper_id": "b51c9ebdbe84eed97f99e5aebbc0e5e7c4fba9b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following abbreviations are used in this manuscript:", "Leucine-rich repeat-containing G-protein coupled receptor 5 Bmi1", "Proto ", "The evolution of the enteroid/organoid models to include sub-epithelial myofibroblasts, smooth muscle cells, enteric nerves, immune cells, microbiome, and endothelial cells is expected to help facilitate our understanding of complex intestinal organ development. In addition, methods have been established to alter gene expression either by overexpression or shRNA-mediated knockdown using lipophilic transfection reagents and virus mediated transduction [40, 41] .", "These new models may provide valuable insight into developing methodologies for intestinal regeneration that lead to therapeutic options including repair of the damaged epithelium that occurs in ulcerative colitis, microvillus inclusion disease, or intestinal transplantation to treat short bowel syndrome [42] . Despite these evolutions in therapeutic possibilities, the in vivo transplantation in humans remains a challenge [43] .", "In the future, organoid technologies will undoubtedly provide a methodological window, allowing us to understand development in all species, including companion animals, and disease in depth, and will enabling new therapeutic options and a better understanding of the pathophysiological processes of various diseases." ] },{ "paper_id": "b5215808485ffba5aa16d95577bd6344ede9d45c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The VIPS web service has been built in Linux platform in IBM server X3400. The automatic batch system will execute the customers' requests and run through all programs ( Figure 1 ) to compare four individual IRES type plus pseudoknot parameters and create a plain text file will be sent back through email to the user due to long CPU running time.", "To examine the prediction ability of IRES elements for viral genomes by VIPS, the sequence information of the four genera, Cripavirus, Hepacivirus, Cardiovirus and Enterovirus, and randomly selected 500 viral genomes without redundancy sequences (447861 records in total that are included 330728 ", "The VIPS has been implanted with known IRES elements as standard structures. For example, twelve IRES models were built upon the consensus sequences in Rfam database. consensus secondary sequences are the major templates for RNA fold program, a part of VIPS. In VIPS, if the RNAL fold program predicted an IRES element that cannot match any IRES models of Rfam or fetch at least two homolog IRESs from related species, the input data will be discarded." ] },{ "paper_id": "b53f3fa13a84fed43c6314ae35e98f59eb54c9e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hygiene barriers, separating clean area from dirty area to avoid recontamination (f) 22", "Always keep up good routines; clean clothing and good hygiene (own) 19", "Hand disinfectant (f) 11" ] },{ "paper_id": "b5421a028a9ff8b2f36ad9be3c51d3d0cb78ddd6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data thus far suggest that Nullbasic can alter the localizations of nucleolar proteins in a Rev-dependent manner.", "Trafficking of Rev in cells has been studied extensively ( Fig. 1 ) [3, 4] . In the nucleolus, Rev promotes the nuclear export of various HIV-1 mRNAs by directly binding to singly-spliced and unspliced viral transcripts via the RRE contained therein (Fig. 1, step 1 ).", "HEK293T and HeLa cells were cultured in RPMI 1640 medium supplemented with 10% (v/v) newborn bovine serum (Invitrogen) and 1% (v/v) penicillin-streptomycin. All cells were typically incubated at 37uC in a humidified 5% CO 2 atmosphere. When 50% -80% confluent, cells were transfected with desired plasmids using FuGENE 6 transfection reagent (Roche Applied Science) according to the manufacturer's instructions. At 24 h post-transfection, cells were harvested for further analysis. In certain experiments where Rev nuclear export was blocked, Leptomycin B (Sigma-Aldrich) was added to growth medium at a final concentration of 20 nM and incubated for 2 h before cell fixation." ] },{ "paper_id": "b5464879315d206d3053d3cfbba9b3d914e8b709", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nuclear extracts of uninfected and infected cells were prepared using hypotonic/nonionic detergent lysis according to Schaffner's protocol [33] . To prevent contamination with cytoplasmic proteins, isolated nuclei were purified by centrifugation through 1.7 M sucrose buffer A for 30 min at 12,000 rpm before nuclear protein extraction, as previously described [12] .", "The culturing of LLC-MK2 and A549 cells, hMPV stock preparation, and virus titration were done as previously described [13, 17, 32] . Confluent cells were infected with hMPV in serum-free media with 1.0 \u00b5g trypsin/mL at a multiplicity of infection (MOI) of 2. Mock-infected cells, defined as control or uninfected cells throughout the manuscript, were treated with the same concentration of sucrose and the same viral infection media.", "Quantitative differential proteomic analysis of experimental and clinical samples using isobaric tags for relative and absolute quantification (iTRAQ) or tandem mass tagging TMT multiplex labeling, one of the stable isotope labeling-based proteomic methods using LC-MS/MS, and bioinformatics analysis, are powerful methodologies for identifying novel networks and/or pathways important in biological processes/events and diseases [23] [24] [25] [26] . These proteomic approaches are also currently becoming important tools for identifying biomarkers and host proteins involved in the pathogenicity and immune responses following viral infections [27] [28] [29] [30] . The significance of using these proteomic approaches to evaluate the safety of virus vaccines is emerging as well [31] ." ] },{ "paper_id": "b54932936d9dd6f8a399f23e19d0a1d0aeabd954", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CD34 is a transmembrane phosphoglycoprotein, first identified on hematopoietic stem and progenitor cells." ] },{ "paper_id": "b54ab920006bd7dceb8851d37e0eef82d3711534", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total nucleic acids were extracted with standard protocols using a commercial platform (Corbett XTractor-Gene, Qiagen, Valencia, CA, USA). A housekeeping gene (18S rRNA) was used to determine the amounts of genomic DNA and cDNA after reverse transcription and to confirm DNA integrity.", "A fecal flotation procedure was performed with zinc sulfate [29] and saturated sodium chloride [30] flotation solutions, as described previously. The parasitological test was performed with light microscopy by identifying the parasite eggs, larvae, cysts, and oocysts, according to their morphological characteristics [30, 31] .", "The authors declare that they have no competing interests." ] },{ "paper_id": "b54f08610e08f2cb15fa8bb649bfe09658843416", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Given a DNA sequence \u03b1 (e.g., \u03b1 = ATTCGCAT ...) we can employ the Voss representation to compute its corresponding fourth-dimensional DNA signalX \u03b1 by applying Eq. (1)", "ndr r ri icht thy hy ye e y yes es y ( ( ( ( (1) ) ) ) Ascidiacea (1)", "on ondr d dr dric icht hthy hye e y yes es ( ( ( (1 1) )" ] },{ "paper_id": "b55320e1004341c20c8b61cca6a2bb47c0dc4d59", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The CRPAb-T2 was synthesized by the reaction of CRPAb with the slfo-SMCC activated oligonucleotide target probe T2, following the reported method [32] .", "The SAM of ssDNA on chip surfaces are obtained by DNA immobilization techniques such as physical adsorption [11] , covalent immobilization [12, 13] , and streptavidin-biotin immobilization [14] . The common disadvantage of these methods is the low sensitivity and specificity due to the random arrangement of the high surface density of immobilized DNAs, leading to low hybridization yield, and non-specific interactions. The ability to routinely measure protein targets at femtomolar concentrations and lower would be extremely valuable for early disease diagnosis [15, 16] . However, conventional microarray methods involving the single fluorophore labeling of either the protein target or a secondary probe molecule typically have a detection limit in the low-to mid-picomolar range [17, 18] .", "The discovery of protein biomarkers whose change in expression level or state correlates with the progression of a disease is becoming increasingly important. Once validated, the proposed biomarkers can be involved in achieving an earlier diagnosis, differentiating between disease types with greater accuracy, and assessing response to treatment. Therefore, protein detection with high specificity and sensitivity is required [1] . Unfortunately, the most widely used techniques for detection of biomarkers OPEN ACCESS such as mass spectrometry [2] , 2-D western blotting [3] , 2-D gel electrophoresis [4] , enzyme-linked immunosorbent assay (ELISA) [5, 6] are not suitable for the analysis of large numbers of samples or the multiplexed detection of many targets within an individual sample. The protein microarrays produced by direct immobilization methods are known to suffer from drawbacks like instability of the immobilized proteins, thus resulting in low sensitivity [7, 8] ." ] },{ "paper_id": "b5535ddf603f7b3b78897553296917cad0c0a789", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To inhibit cervicovaginal infections, an ideal drug should inhibit:", "\u2022 microbial growth;", "aUTHOR CONTRibUTiONS PM, RP, and PV conceived the topic concept and wrote and revised the final manuscript; LR, AC, ML, DC, and ES provided figures and contributed to manuscript preparation and editing. All authors read and approved the final version." ] },{ "paper_id": "b562f1a519bc6a12df5e62930bdf4345cf0f7ce9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "to access the ED.", "The study instrument is a pretested and validated questionnaire (Porro et al., 2013) . It was modified for use in this research, and it has been endorsed by experts.", "All cases were categorized as urgent and non-urgent according to the Canadian classification for ED attendance.", "The data were analyzed using the Statistical Package for the Social Sciences (SSPS Inc., Chicago, IL, USA), version 20.0. Descriptive statistics were performed for all variables. The chi-square was used to assess the relationship between categorical variables, while the independent t-test was used to compare group means for continuous variables. Statistical significance was set at the 0.05 alpha level." ] },{ "paper_id": "b56324b4de371913188d3eae4437eaaeda3b814b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where D 1 z t = differenced series, that is, z t \u2212 z t\u22121 , z t = set of possible observations of the time-sequenced random variable, a t = random shock term at time t, F 1 \u00b7 \u00b7 \u00b7 F P = autoregressive parameters of order p, q 1 . . . q p = moving average parameters of order q.", "Overcrowding in emergency departments (EDs) reflects dysfunction in healthcare systems [1] . Contributing factors including mismatch between ED capacity and various input, throughput, and output factors as well as insufficient capacity [2] . During the 12-year period from 1995 to 2006, annual ED visits in Taiwan increased 40%, from 4,664,209 to 6,569,247 per year [3] . Therefore, higher than expected admissions of critical patients to inpatient units is an important hospital administration issue [4] .", "To reflect changes in real dollar value, ED revenue data were adjusted by the consumer price index (CPI) for each year of 2005-2009 (95.16, 95.72, 97.44, 100.88, and 100.00, resp.). The ED revenues were then converted from Taiwan dollars to US dollars at an exchange rate of 30.5 : 1, which was the average exchange rate during 2005-2009. All tests were two-sided, and P values less than 0.05 were considered statistically significant. Statistical analysis was performed with SPSS software for Windows, version 15 (SPSS, Inc, Chicago, Ill, USA)." ] },{ "paper_id": "b56db50e2116c867bbc86aefcdfec72c74e971ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "either \"droplet\" 11 or \"contact\" spread 12 in different guidelines, we performed a sensitivity analysis by including RSV into the droplet transmission category instead of contact.", "Ethics approvals of two clinical trials were obtained from the Institutional Review Board and Human Research Ethics Committee of the Beijing Center for Disease Prevention and Control.", "Clinical efficacy data are a higher level of evidence than theoretical paradigms of transmission, and show better protection afforded by respirators." ] },{ "paper_id": "b58b4809e706401c8f5851d5b0d2be93b8f431cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animals were handled in strict accordance with good animal practices, as defined by current European legislation. Bat capture and blood-sampling were authorized by permit from the Spanish Regional Committee for Scientific Capture.", "repetitions. Samples were considered positive when the number of fluorescent foci was reduced by 50% at the 1:27 dilution (starting dilution). This cut-off value is similar to that applied in other studies [17] , [19] , [24] .", "Determining whether these differences are a consequence of ecological, immunological or phylogenetic factors is very difficult. Perhaps the phylogenetic distance between the Rhinolophidae and Vespertilionidae contributes to these differences [27] , as was shown in studies on Coronavirus in bats [48] . However, further studies are needed to investigate this hypothesis." ] },{ "paper_id": "b59b58c13370a390a58c6cd79e61f97bf9bee37d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "V E~Vm |t d where V E is the exposure volume and t d is exposure time.", "Cryptococcosis is an opportunistic fungal infection caused by Cryptococcus and which is a predominant cause of morbidity and mortality in immunocompromised and HIV-positive hosts [1] . Cryptococcus is responsible for approximately one-third of all AIDS related deaths and a more prevalent cause of HIV-related mortality in sub-Saharan Africa than tuberculosis [1] . In other developing countries infections as a result of Cryptococcus are second only to tuberculosis and frequently co-occur together [1] . The development of new antifungals, highly active antiviral treatment (HAART), and combination therapy regimens has increased longterm survival rates, but infections remain difficult to treat and frequently reoccur. Cryptococcus is now increasingly associated with a rising number of infections in seemingly healthy humans and animals worldwide [2] [3] [4] [5] [6] [7] [8] [9] .", "Spray factor was calculated as F S~C a Cs where C a is viable aerosol concentration and C S is nebulizer sample concentration." ] },{ "paper_id": "b59f1ed9272403216c276badc217b78b39251098", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Whole cellular extracts were prepared by lysing 3610 6 of cells in a NP-40-based lysis buffer containing phosphatase inhibitors, proteinase inhibitors (Roche and Thermo Scientific), and 0.5 M EDTA. The concentration of protein was measured by Bradford assay (Themo Scientific). Samples (25 mg) were boiled for 5 min and resolved on 10% Bis-Tris pre-cast gels (Bio-rad). Resolved proteins were transferred to a polyvinylidene fluoride (PVDF) membrane (Millipore). The membrane was blocked with 5% nonfat milk and immunoblotted with the indicated antibodies. Antirabbit IRF3, anti-rabbit phospho-IRF3 (Ser396), anti-mouse IkBa, anti-mouse phospho-IkBa (Ser32/36), and anti-rabbit IgG (HRP-conjugated) were purchased from Cell Signaling. Antimouse GAPDH was purchased from Sigma. Anti-mouse IgG and anti-mouse IgG 1 (HRP-conjugated) were purchased from Jackson Immunologicals. Lumi-Light western blotting substrate was used for HRP detection (Roche).", "LLC-MK2 cells were transfected with 250 ng or indicated doses of DVG and genomic RNA using lipofectamin 2000 (invitrogen). At 4 hours post transfection, the cells were harvested and total RNA was isolated using TRIzol according to the manufacturer's specifications.", "Statistical analyses were performed as indicated in each figure. GraphPad Prism version 5.00 for Windows, GraphPad Software, San Diego California USA, www.graphpad.com, was used for analysis." ] },{ "paper_id": "b5a7acc938d3d05c5ef67cb6b1dd090805e487e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Duck viral hepatitis (DVH) is an acute, contagious, and highly fatal disease of young ducklings [1] that is mainly caused by duck hepatitis virus 1 (DHV-1) belonging to the Picornaviridae family [2] . There are currently very few drugs to treat this disease. Some antiviral drugs, especially some traditional Chinese medicines, still need to be comprehensively evaluated before they can be introduced into veterinary medicine, although some compounds are effective in some cases.", "One-day-old cherry valley ducks were purchased from Nanjing Tangquan Poultry Farm (Nanjing, China). Ducks were housed in wire cages (60 cm \u00d7 100 cm) in airconditioned rooms at 37\u00b0C with lights on for 24 h before the study. The temperature was gradually reduced to room temperature and 12-h light/12-h dark phases, which were kept constant for the remainder of the study. Ducks were fed a commercial starter diet provided by the feed factory of Jiangsu Academy of Agricultural Science (Nanjing, China).", "Animal experiments conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication, Eighth edition, 2011) and was approved by the Nanjing Agricultural University Animal Care Committee. To ameliorate suffering, animals that were not expected to survive were humanely euthanized. All steps were complied with AVMA Guidelines for the Euthanasia of Animals (2013 Edition). " ] },{ "paper_id": "b5ac1d6f75cea098965bf8e6cfe492b1fab346c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PK-15 cells infected with TGEV were harvested by freezing and thawing three times. One mL of cell culture was centrifuged for 5 min at 800 \u00d7 g. The supernatant was transferred into a new microfuge tube and centrifuged for 10 min at 13,400 \u00d7 g. Then, the pellet was negatively stained with 2% phosphotungstic acid and analyzed on a transmission electron microscope (H-7650, Hitachi, Tokyo, Japan) [13] .", "Pigs used in this study were approved by the Institutional Animal Care and Use Committee (IACUC) of the Harbin Veterinary Research Institute (HVRI), the Chinese Academy of Agricultural Sciences. No animals were sacrificed specifically for this study. Feces samples were collected at the farm." ] },{ "paper_id": "b5af7319ee1fd5e9cc3cf8c5836b19a408ac519b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Expression and purification of a putative dihydropyrimidinase from P. aeruginosa PAO1" ] },{ "paper_id": "b5b3d491ce72ba843d589539a807b0cf32946849", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All analyses were performed in SAS Version 9.4 (Cary, NC) or R [18] .", "Overall " ] },{ "paper_id": "b5b87074a3f33c0a1408a01218e1776ae85f5b31", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest.", "Results" ] },{ "paper_id": "b5c6a1c48730f12db7c74e51ca05a54fb4a9d202", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2) assessing the impact of public health campaigns on behaviour change through evaluation of community participation to reduce mosquito breeding sites; (3) monitoring the perceived risk of the exposed population with longitudinal surveys when the outbreak shows signs of becoming endemic; (4) connecting and integrating the data collected in these surveys with serological, entomological, and geographical data, which would then be entered into models aiming to forecast the course of an epidemic.", "We must note that there is a strong interdependency among socio-demographic and psycho-cognitive dimensions in risk perception and behavioural changes. Although much research in the past has shown the impact of social factors on health, the associations found here between the risk of infection and certain socio-demographic variables such as sex, age or education would more likely be seen as markers of infection or confounding factors than as causal factors.", "Despite a good understanding of the disease and a consensus on the efficacy of the main protective tools available, people do not use them enough to be protected. Thus, endemic disease can be viewed as a particularly challenging context for successfully implementing risk-reduction strategies because of the difficulty of ensuring sustainable protection. The challenge is to translate this finding into relevant risk management and communication approaches." ] },{ "paper_id": "b5d836ef3f064ed0bf47d2fa690786815ad26659", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b5e5be4a7ee27bb1faa29832b5b20c36a903433a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b5e8c704bc997577cfb950adffa06c7019aacf4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To summarize, four completely separate computational analyses -conservation of an ORF, conservation of a potential translation mechanism, positive MLOGD coding signature and a greatly suppressed frequency of substitutions at ORF5-frame synonymous sites -all pointed to the existence of a novel coding sequence, ORF5a.", "Computational analysis reveals the presence of a small ORF overlapping the arterivirus GP5 gene", "The unification of the previously unclassified members of the arterivirus family was the direct result of sequence" ] },{ "paper_id": "b5e924927b31aface620ada453f904e6e9ebb203", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rabbit antisera raised against T1L and T3D have been described [87] . Rabbit antiserum specific for procaspase-9 was purchased from Cell Signaling. Goat antiserum specific for Bid was purchased from R & D systems, and goat antiserum specific for actin was purchased from Santa Cruz Biotechnology. HRP-conjugated antirabbit and anti-goat secondary antibodies were purchased from Amersham GE Biosciences. Alexa Fluor-conjugated anti-mouse immunoglobulin (Ig) G, anti-rabbit IgG, and anti-goat IgG secondary antibodies were purchased from Invitrogen.", "Murine L929 cells were maintained in Joklik's minimal essential medium supplemented to contain 10% fetal bovine serum (FBS), 2 mM L-glutamine, 100 U/ml penicillin, 100 mg/ml streptomycin, and 25 ng/ml amphotericin B (Invitrogen). Wild-type and Biddeficient MEFs were maintained in Dulbecco's minimal essential medium (DMEM) supplemented to contain 10% FBS, 2 mM Lglutamine, 100 U/ml penicillin, 100 mg/ml streptomycin, and 25 ng/ml amphotericin B. TRAIL-R-deficient MEFs, prepared from D13 embryos, were maintained in DMEM supplemented to contain 10% FBS, 2 mM L-glutamine, 16 MEM nonessential amino acids, 0.1 mM 2-mercaptoethanol, 20 mM HEPES, 100 U/ ml penicillin, 100 mg/ml streptomycin, and 25 ng/ml amphotericin B. Reovirus strain T3D is a laboratory stock. T3SA+ was generated by reassortment of reovirus strains T1L and type 3 clone 44-MA as described [84] . Purified reovirus virions were generated from second-or third-passage L-cell lysate stocks of twice-plaque-purified reovirus [85] . Viral particles were Freon-extracted from infected cell lysates, layered onto 1. ", "Plasmids pRenilla-Luc and pNF-kB-Luc [88] were obtained from Dr. Dean Ballard (Vanderbilt University)." ] },{ "paper_id": "b5f778aafd8e2a94701f7398641519a2041ab303", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Severe Acute Respiratory Syndrome (SARS) is a viral respiratory disease caused by a coronavirus (SARS-CoV). SARS has caused a significant impact on psychosocial and legislative regulation [1] [2] [3] [4] . SARS brought about not only relatively discernable economic losses [5] , but also observable damage to healthcare organizations, and this has resulted in a lower healthcare utilization rate [6, 7] ." ] },{ "paper_id": "b6019e4fafd2bf05e5f46bef590141a2f115c4c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Phyllostomid bat microbiome composition is associated to host phylogeny and feeding strategies", "Other questions about the possible excretion of viable bacteria through bat guano and the ability to infect plants remain unknown ( Figure 1F ). Seeds could be part of bat guano, but phytoplasma transmission through seeds has not been confirmed or disproved yet. Alongside birds, bats are capable of true flight. The possibility to deposit phytoplasma-contaminated guano from one area to another and within the same area is high. Aryan et al. showed that phytoplasmas are transmissible through graft (Aryan et al., 2016) . Thus, mechanical transmission is another possibility. This form of transmission occurs when feeding animals cause tissue damage in plants, aiding the spread of microorganisms.", "AB and EP-L wrote the commentary. KM edited the commentary." ] },{ "paper_id": "b603913495d3cbce15eff09e645007cdf42a6e1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b60f35d40ea356d450ec485223083150e662b10f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Funding was provided by the University of Minnesota Veterinary Diagnostic Laboratory.", "Nucleotide sequence accession number. The genome sequence of the swine Deltacoronavirus strain SDCV/USA/Illi-nois121/2014 was deposited in GenBank with the accession no. KJ481931.", "To investigate the causative agent of swine diarrhea, next-generation sequencing (NGS) was performed on a porcine fecal sample. The NGS reads were assembled, which generated a complete swine Deltacoronavirus genome sequence, that of strain SDCV/ USA/Illinois121/2014." ] },{ "paper_id": "b61d4d87ea3b4fa2ff058ee867bdac4f15c0cf11", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral genomes do not code for all of the components that viruses require in order to complete their replication cycle. Thus, viruses are dependent on diverse factors and conditions in the host cell. However, the process of replication is not easy, because the viral presence within the cell represents a threat that triggers a complex and integrated antiviral response. Interestingly, some viruses have OPEN ACCESS developed strategies that enable them to counteract, tolerate, or even take advantage of this antiviral response, thereby allowing efficient replication.", "The SGs are not aggregated permanently. They disassemble when the cell recovers from a sublethal stress and consequently protein synthesis is restored [21, 24, 29, 34] . The mechanism of disassembly of SGs is also poorly understood, but proteins such as Staufen-1, which binds to dsRNA [35] and microtubules [36] , have been described as being important to the disassembly of these aggregates.", "Given that SGs are constituted by preinitiation complexes, it could be expected that the majority of mRNAs are recruited into the SGs. However, mechanisms that determine which mRNAs will be included exist. In two different studies, it was observed that heat shock mRNAs are not found in SGs but were predominantly associated with polysomes [31, 32] . Even though the reasons of inclusion or exclusion of mRNAs into SGs have not been established, recent studies show that mRNAs bound to endoplasmic reticulum are not aggregated to the SGs and that the 5\u2032-UTR (5\u2032-untranslated region) plays an important role in their exclusion [33] ." ] },{ "paper_id": "b6277684930fa5819fe101a39441601ab89da85a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ProteinPilot Software (version 4.5, Applied Biosystems, MDS Sciex) was applied to analyze the raw MS/MS file data by searching against UniProt database containing 20,240 sequences (uniprot-swissprot-Homo.fasta) with parameters as followings: the instrument was TripleTOF 5600; cysteine was adjusted with iodoacetamide for iTRAQ quantification; biological qualifications contained ID focus and trypsin digestion; the Quantitate, Bias Correction and Background Correction was examined for protein quantification and normalization. Only proteins with at least one unique peptide and unused value \ufffd 1.3 (credibility \ufffd 95%) were used for further analysis.", "Proteomic data of iTRAQ were quantified using Proteinpilot software (version 4.5, Applied Biosystems, MDS Sciex). The means of pairwise comparisons between biological or technical replicates were first normalized as the ratios, and the minimum ratio was used as p-values to screen the differential expressed proteins (DEPs) by student's t test (two-tailed or unpaired). DEPs were accounted to be significant using p < 0.05 and fold changes > 1.5 (upregulated) or < 0.67 (downregulated) as cutoff criteria.", "which together are a significant worldwide contributor to morbidity and mortality in children up to age 5 [4, 5] . Since HBoV was first detected in 2005 in children with respiratory infections [1], four different subtypes have been identified (HBoV 1, 2, 3, and 4) [6-8]. HBoV-1 was predominantly detected in the respiratory tract, whereas the three other types (HBoV-2, HBoV-3, and HBoV-4) were mainly identified in stool and associated with gastroenteritis [8]. However, HBoV can also found in asymptomatic people [9] . A genomic study of HBoV suggested a rearrangement of the HBoV group into two classes: human bocaparvovirus 1 (including the previous HBoV-1 and HBoV-3) and human bocaparvovirus 2 (including the previous HBoV-2 and HBoV-4) [10] ." ] },{ "paper_id": "b62ce73d8d2c9e794c96ce0be7d52ed55b87fa52", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Yamaguchi strain of SFTSV (GenBank accession no. AB817995, AB817987, and AB817979) that was isolated in 2013 from a patient in Yamaguchi Prefecture, Japan was inoculated to confluent monolayer of Vero-E6 cells. These cells were then maintained at 37\u00b0C in Eagle's Minimum Essential Medium supplemented with 2 % fetal calf serum and 0.2 mM of each non-essential amino acids for 5 days. The infected culture fluid (ICF) was harvested and from a 140 \u03bcl of this ICF, viral RNA was extracted using the QIAamp viral RNA mini kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. The extracted RNA was eluted in 60 \u03bcl of elution buffer and then used as template for RT-PCR.", "Severe fever with thrombocytopenia syndrome virus (SFTSV), also named as fever, thrombocytopenia and leukopenia syndrome virus (FTLSV) or Huaiyangshan virus, is an emergent virus that was first reported in 2011 [1] [2] [3] . The sources of serum samples where the virus was identified were from patients infected in 2009 and 2010 in China. Severe fever with thrombocytopenia syndrome (SFTS), the disease caused by the virus has a major clinical presentations that include fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, neurological symptoms, bleeding tendency, as well as less specific clinical manifestations [1, 2] . This disease has a case-fatality rate ranging from 2.5 to 30 % in different areas of endemicity [4] . Human-to-human transmission of SFTSV was reported to occur through close contact with the blood and/or body secretions of infected patients [5] [6] [7] [8] [9] .", "This research was approved by the Institutional Review Board at the Center for Disease Control and Prevention of Henan Province. All participants gave written informed consent for the use of their serum samples for research purposes. " ] },{ "paper_id": "b6353f8b0fcd86c2fd1e6f27c9b18a3ccc07980b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Anti-Ebola Antibody Activity In Vivo", "The investigators adhered to the Guide for the Care and Use of Laboratory Animals when conducting research, using animals [28] . The United States Army Medical Research Institute of Infectious Diseases (USAMRIID) animal facilities and animal care and use program are accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International. All infectious material and animals were handled in a maximum-containment biosafety level 4 facility at USAMRIID under standard operating conditions. Antibody purification. IgGl KZ52 was produced and purified as described by Parren et al. [29] and was .98% pure, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and contained ,1 IU of endotoxin/ml, as determined in a quantitative chromagenic Limulus amoebecyte lysate assay (BioWhittaker, Cambrex, http://www.cambrex.com).", "PLoS Pathogens | www.plospathogens.org January 2007 | Volume 3 | Issue 1 | e9 0063" ] },{ "paper_id": "b6365c84be3efb9b6845cf8f664ae3e5b913c4a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Western blotting. Cells were lysed in 2\u03eb Laemmli sample buffer (50 mM Tris-HCl, pH 6.8, 20% [vol/vol] glycerol, 4% [wt/vol] sodium dodecyl sulfate [SDS], 20 mM dithiothreitol, 0.02 mg/ml bromophenol blue) and separated by electrophoresis on SDS-polyacrylamide gels. Proteins were transferred to polyvinylidene fluoride membranes (Amersham) using a Trans-Blot Turbo transfer system (Bio-Rad). Blots were blocked with 5% (wt/vol) ELK skimmed milk powder (Campina) in phosphate-buffered saline (PBS) supplemented with 0.05% (vol/vol) Tween 20. Secondary horseradish peroxidase (HRP)-conjugated antibodies (Dako) and ECL Plus Western blotting substrate (Thermo Fisher) were used to visualize protein signal.", "Cells, viruses, and antibodies. HuH-7 cells (kindly provided by Ralf Bartenschlager, Heidelberg University) were grown in Dulbecco's modified Eagle's medium (DMEM; Lonza) supplemented with 8% (vol/vol) fetal calf serum (FCS; Bodinco), 2 mM L-glutamine (PAA Laboratories), and nonessential amino acids (PAA Laboratories). 293T cells (kindly provided by the Virgin lab, Washington University School of Medicine in St. Louis, MO) were cultured in DMEM with 10% (vol/vol) FCS. All cell culture media contained 100 U/ml penicillin and 100 g/ml streptomycin. Infection of HuH-7 cells with MERS-CoV (EMC/2012 strain kindly provided by Ron Fouchier, Erasmus Medical Center, The Netherlands [3, 4] ) was performed as previously described (21) .", "Immunofluorescence microscopy. After electroporation, HuH-7 cells were seeded on coverslips and fixed 24 h later with 3% (wt/vol) paraformaldehyde in PBS. Samples were permeabilized with 0.2% (vol/vol) Triton X-100 and incubated with antibodies, including fluorescent conjugates, diluted in 5% (wt/vol) bovine serum albumin (BSA) in PBS. Nuclei were stained with 1 g/ml Hoechst 33258. After embedding with Prolong Gold (Thermo Fisher), samples were analyzed with a Leica TCS SP8 confocal laser scanning microscope, which was equipped with a 63\u03eb objective (numerical aperture [NA] 1.40; 1 Airy unit) and a Leica HyD hybrid detector. and incubated with antibody overnight. Antibody-protein complexes were then pulled down using protein A and protein G Sepharose beads (GE Healthcare), which were first blocked with 2% (wt/vol) BSA in PBS, and incubated for several hours. After repeated washing of the beads with IP buffer, proteins were eluted by heating in 2\u03eb Laemmli sample buffer. After separation on large 10% polyacrylamide gels and gel drying, signal was visualized using an Imaging Screen-K (Bio-Rad) and a Typhoon 9410 scanner (GE Healthcare).", "Electron tomography. Sections of 150-nm thickness were cut from the resin-embedded blocks of transfected HuH-7 or 293T cells prepared as described above. Prior to poststaining, colloidal gold particles of 10 nm were applied to both sides of the EM grid to serve later as fiducial markers for alignment. Tomography data were recorded on an Eagle CCD camera (FEI) in an FEI Tecnai 12 BioTwin (HuH-7 samples) or a Twin (293T samples) electron microscope operated at 120 kV, with the grids mounted on a 2040 Fischione tomography holder. Dual-axis tilt series of the regions of interest were collected using Xplore3D software (FEI) at magnifications that resulted in a pixel size of 1.7 nm (BioTwin data) or 1.4 nm (Twin data). The angular coverage for each single-axis tilt series was 130\u00b0sampled in" ] },{ "paper_id": "b65730c8b239180dd62a079fd2a40f2325a86a78", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Oligomers were dissolved in binding buffer (100 mM KCl, 20 mM HEPES, pH 7.4), heated to 85\u00b0C for 10 min, and allowed to cool slowly. The oligomers were then added to serial dilutions of protein solution in triplicate, and FP was measured on a Corning black 96-well, half-area assay plate (Corning, NY) using a Hidex Sense Microplate Reader (Turku, Finland).", "Supplemental material for this article may be found at https://doi.org/10.1128/ JVI.01606-16.", "TEXT S1, PDF file, 0.09 MB." ] },{ "paper_id": "b6682adfe5026c78e3d59b165126abfa8945eb5f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We modeled human DCIR structure using the SWISS MODEL homology modeling program via their website interface [40, 41] , run in automatic mode after submitting the DCIR sequence (UniProtKB/Swiss-Prot accession number: Q9UMR7). The resulting model was examined using the PDB viewer program [42] .", "The free public database ZINC 8 compiles over two million compounds [45] . A subset of 128,000 compounds with drug-like properties and satisfying the Lipinski Rule of Five [46] were selected for further analysis. The database was used for virtual screening for the selected docking sites of DCIR and compounds were ranked according to their ChemScore [44] and hydrogen bonding potential.", "Docking sites for inhibitors of HIV-1 binding were selected from a number of potential sites identified by the Site Finder utility of the Molecular Application Environment (MOE) program (cf.", "The 3D model of DCIR served as a receptor for the docking studies. Hydrophobic pockets on the DCIR extracellular domain structure (residues 103-233) were evaluated with the Site Finder application under the MOE program (Chemical Computing Group, Montreal, QC, Canada) and ranked according to their hydrophobic contacts and locations. The protein model was inspected visually for accuracy of the x 2 dihedral angles of Asn and His residues and the x 3 angle of Gln, and was rotated 180u as needed to maximize hydrogen bonding. The proper histidinyl tautomer was selected manually to maximize hydrogen bonding. Finally, all aspartyl, glutamyl, arginyl and lysyl residues were treated usually as charged species." ] },{ "paper_id": "b66c037ebfee8059dd47d2614cf5d55618d8260f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the detection of Jun\u00edn virus, rabbit polyclonal antibody against JUNV N protein [30] or " ] },{ "paper_id": "b6761b66c1494299587710188e9a371713d88450", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Frozen tissues were cut in 4 mm sections, fixed in acetone for 20 minutes at room temperature, and stained with murine monoclonal antibodies to adenovirus 2 hexon (Diagnostic Hybrids, Athens, OH) conjugated to FITC at 37uC for 30 minutes. These antibodies have previously been shown to broadly detect a variety of mammalian adenoviruses [31] . Staining was visualized using an epifluorescence microscope.", "Table S1", "(PDF) " ] },{ "paper_id": "b676de09cf12905dea5d204930150599d5256cde", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "P\u00f0f#f m gj#U; fy B;f g\u00de \u00bc P\u00f0f#f m gj#B \u00bc N \u00c0 #U; #U; fy B;f g\u00de \u00f011\u00de", "The research protocol was approved by both institutional IRBs (University of Pittsburgh PRO08030129 and Intermountain Healthcare 1024664). All the research patient data were deidentified.", "Supporting information S1 Appendix. Derivation of Eqs 9 and 10. (PDF)" ] },{ "paper_id": "b67b75854801b20d8d89d71adf85199ec70c3daa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. The standard power as I(0, 0).", "Takahashi and Tango [26] also proposed the profile of the extended power as Q(r | s*) = I(1/s*, r/s*), (0 \u2264 r \u2264 1)" ] },{ "paper_id": "b68d33bbec8af949490bf52a5b8dd215c2b37590", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "case, its phenotypic classification was changed from control to a case and two new matched control and case calves were enrolled.", "The estimated odds ratio for BRDC pathogens and case status (inclusive of the 95% confidence intervals for the estimated odds ratio) were calculated in R. A two-tailed Fisher's exact test was used to determine if the odds ratios differed significantly from 1, with a significance threshold of P = 0.05." ] },{ "paper_id": "b691523206f8c2fc150e5939b3136d361d193815", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Inclusion criteria to determine which studies would be reviewed were developed using the PICOS acronym (Participants, Intervention, Comparator, Outcome Measures, Study Design) as recommended by The Centre for Research and Dissemination (2009) . Only studies published in English were included. No date restrictions were set." ] },{ "paper_id": "b6ad9d6a39c2a67b36e8d058d2e57ba08423afc3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "First-strand cDNA was synthesized using AMV reverse transcriptase (TaKaRa Biotechnology, China). Briefly, the following reagents were added and mixed: 4 \u03bcL of 5\u00d7 reverse transcriptase buffer, 2 \u03bcL of dNTP mixture (10 mmol/L), 1 \u03bcL of random primer (50 mmol/ L), 2 \u03bcL of AMV reverse transcriptase, 0.5 \u03bcL of RNAase inhibitor (40 U/\u03bcL), 5 \u03bcL of RNA, and 5.5 \u03bcL of RNAase-free water. The reaction mixture was sequentially incubated at 42\u00b0C for 60 min and then at 72\u00b0C for 15 min. The cDNA was subsequently stored at \u2212 20\u00b0C.", "These viruses, in association with bacterial agents or independently, can lead to diseases [9, 10] . In addition, the clinical symptoms caused by single-or multipleviruses are similar, which makes it difficult for veterinarians to distinguish these viruses in the field. Therefore, sensitive and rapid detection techniques that can distinguish these respiratory viral infections are needed for the surveillance of the emergence of new viruses, outbreak management, and disease control.", "Microarray was prepared in a 100,000 grade clean room. Probes were diluted with printing buffer (0.3 M phosphate buffer, 0.2% glycerin, 0.01% Triton X-100, and 1.5% mannitol) for further printing. Each dilution of probes was printed on initiator-integrated poly(dimethylsiloxane) (iPDMS), a novel solid supporting material. The oligonucleotide microarray was completed using a contact printer SmartArrayer 48 (CapitalBio, China) with approximately 0.6 nL of printing solution for each sample. Each well has positive control with biotin and negative control with printing buffer.", "Before detecting the specimens, the co-infection models, which included various arrangements, were designed and tested to determine the detection efficiency of the oligonucleotide microarray." ] },{ "paper_id": "b6b06d62a3af9c36824d3c674f4d43d6d78d9073", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In baby-suckling mice", "Mice still alive mean complete virus inactivation but death indicates incomplete inactivation. Complement fixation test (CFT)", "Thirty calves free from FMD were divided into six groups (five calves/group). Five groups were inoculated I/M by the inactivated prepared vaccines, and one group was kept as a control without vaccination. Serum samples were obtained from all groups of vaccinated calves every month for 9 months.", "Foot and mouth disease (FMD) is a contagious viral disease affecting cloven-hoofed animal that causes highly significant losses. Therefore; using safer and high potent vaccines are required [1] . Decrease in milk production, weight gain, reproductive inefficiencies, and death in young ruminants is the main economic losses caused by FMD [2, 3] . The virus inactivation process is the most safety and critical steps in the production of FMD vaccines. For FMD vaccines, in particular, guaranteed safety is essential because any occurrence of the disease will have great economic consequences [4] .", "Inactivation can be performed using chemical or physical methods or a combination of the two. A wide range of well-established and novel inactivation methods have been described to successfully inactivate viruses for vaccine purposes. Examples are formaldehyde [6, 7] , binary ethyleneimine (BEI) derivatives [8] , sodium chloride or phosphate [9] , psoralens [10] , hydrogen peroxide [11] , heat [12] [13] [14] , Available at www.veterinaryworld.org/Vol.8/September-2015/11.pdf ultraviolet (UV) irradiation [13] [14] [15] [16] , and gamma radiation [17] [18] [19] [20] .", "The experiment was as per the protocol of Institutional Animal Ethics Committee, the authors had taken permission of animal owners of the private farm." ] },{ "paper_id": "b6b083c197d1f01a9fe29b40ad10f893db7a263f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b6b73f121cfd9d486f77bae744fa2a7e09df51f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To reveal cytotoxicity of pDNA/CyDs/AFliposomes, we examined the WST-1 method (Figure 8 ).", "The principle of somatic gene therapy is that genes can be introduced into selected cells in the body in order to treat genetic or acquired diseases. The liver may be potentially an important target for gene therapy, because crucial diseases such as amyloidosis, primary biliary cirrhosis, familial hypercholesteremia, phenyl ketonuria, and virus hepatitis occur in this organ [1] . In addition, the liver has the ability to synthesize a wide variety of proteins, to perform various posttranslational modifications, and to secrete them into the blood.", "Asialofetuin (AF) is a glycoprotein that possesses three asparagine-linked triantennary complex carbohydrate chains with terminal N-acetylgalactosamine residues. The protein displays affinity to asialoglycoprotein receptor (ASGP-R) on hepatocytes and enters the cells through the receptor [7, 8] . Thus, AF has been used as a ligand to deliver drugs to hepatocytes and a competitive inhibitor to ASGP-R [9, 10] . In fact, the widespread use of AF-appended liposomes (AFliposomes) as a hepatocyte-selective gene transfer carrier has been reported [11, 12] ." ] },{ "paper_id": "b6c38211730ff7826aa6a52aff9e3be848f8e738", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Using the TRIzol method, the total RNA was extracted in strict accordance with the manufacturer's protocol. RNA degradation and contamination was monitored on 1% agarose electrophoresis and NanoDrop ND-1000 nucleic acid/protein concentration meter (GE, USA), followed by storage at \u221280 \u2022 C until further use.", "The 20 \u00b5L reaction system included 10 \u00b5L SYBR Premix ExTapTM II (2\u00d7), 0.4 \u00b5L for upstream and downstream primers (10 \u00b5mol/L), 0.4 \u00b5L ROX Reference Dye II (50\u00d7), 2 \u00b5L cDNA, and 6.8 \u00b5L RNase-free ddH 2 O with a thermocycling program of 40 cycles of 95 \u2022 C for 30 s, 95 \u2022 C for 5 s, and 60 \u2022 C for 34 s. To analyze the specificity of the amplified products, a melting curve analysis was executed after amplification as follows: 95 \u2022 C for 15 s, 60 \u2022 C for 1 min; 95 \u2022 C for 15 s, and 60 \u2022 C for 15 s.", "According to Figures S2A,B , the PCR products had only one specific peak, without primer dimers and non-specific products, which indicated that all of the target genes had been successfully amplified." ] },{ "paper_id": "b6c62ca4653ef469da8a131bcd9fe168e439e3a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the cytoplasmic region, consensus ITAM and ITIM were identified, where the tyrosine residue is invariant ( fig. 4) .", "Phosphorylation of ITAM/ITIM initiates of terminates, respectively, signal transduction pathways implicated in cellular proliferation (Beauchemin et al. 1997) or regulation of immune response.", "CEACAM genes are expressed in a wide variety of cell types including epithelial, endothelial, and immune cells such as leukocytes and dendritic cells, whereas PSGs are expressed exclusively in the placental trophoblasts (Hammarstrom 1999) ." ] },{ "paper_id": "b6c747316db8f591a729c4ed060a6df0e3a18fc8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Asthma classification of subjects and medication use. ", "PBMCs were isolated using Ficoll density gradient, incubated with Fc block (eBiosciences, San Diego, CA) and then stained in media with the following antibodies: CD3-Pacific Blue (clone UCHT1, eBiosciences), CD4-PerCP (clone RPA-T4), CD25-APC (clone 2A3), CD127-PE (clone hIL-7R-M21) (BD Biosciences, San Jose, CA) and FoxP3-Alexa Fluor 488, (clone 206D, BioLegend, San Diego, CA, USA) according to manufacturer's protocol within 24 hours of blood draw. Cells were acquired on a LSR II (BD Biosciences). Positive staining and gating strategy was determined by comparison to isotype or Fluorescence Minus One (FMO) control. Data were analyzed using Flowjo software (Treestar, San Carlos, CA)." ] },{ "paper_id": "b6ccfd5dcb8970df391aeaed0992cb00251fc7f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A 45-year-old female patient presented to the emergency department with dry cough, headache, and fever up to 39.5\u00b0C lasting a few hours. Her past medical history was unremarkable, and she did not take any medication regularly. She has never smoked, worked as a teacher at a local high school, and has not recently travelled.", "e initially described coronavirus strain 229E has been previously identified as the second most frequent cause of common cold after rhinoviruses in healthy adults. Predominant symptoms were acute rhinorrhea, nasal congestion, and/or sore throat [9, 10] . Nasal discharge was the hallmark of all symptoms after inoculation of HuCoV-229E to healthy volunteers, and further observed symptoms were malaise, headache, chills, and cough [6] .", "e authors declare that they have no conflicts of interest." ] },{ "paper_id": "b6d7e94615aea8a7a591d68cea8c6710ce86df13", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The analytical balance (Model: AL204) and electronic balance (Model: PL602S) were purchased from Shanghai Mettler-Toledo Instruments Co., Ltd. The -80\u00b0C ultralow temperature freezer was purchased from Haier, China. The low temperature refrigerated centrifuge (Model: FRESCO 17) ", "A total of 48 healthy Kunming mice (24 male, 24 female) weighing 20 \u00b1 2 g, were provided by the Xinjiang Medical University Experimental Animal Center (license number: SCXK (Xin) 2011-0004). The U27 cervical cancer cell lines were purchased from Wuhan University.", "All of the data was tested for normality and homogeneity of variance before further analysis. Statistic analysis was performed with SPSS17.0 One-way analysis of variance ANOVA and chi-square tests where experimental data was indicated as mean \u00b1 SD. The mean difference is considered significant at the p-value < 0.05 level." ] },{ "paper_id": "b6deb91c6796184b969f10b262910634eeff4a33", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Other enzymes and protein effectors, either engineered into virus expression cassettes or provided exogenously, include hyaluronidase, decorin, various other MMPs, and notably relaxin-a peptide hormone normally expressed during particular phase of pregnancy that does not possess tissue-degrading activity itself, but instead induces a number of key collagen-degrading proteases seemingly in a tumor-specific manner [26] . Beyer showed that relaxin expressed by murine stem cells improved trastuzumab penetrance and therapy outcome in syngeneic tumor models [27] . In another study, chimeric adenovirus Ad5/35 expressing relaxin showed increased tumor transduction and virus dissemination [28] .", "Tumors are invariably fenestrated by host fibroblasts, myeloid cells and other non-transformed cells, which driven by cancer-induced cues can adopt various reprogrammed phenotypes to promote tumor angiogenesis and growth and to alter tumor responses to therapies [1, 55] . As most of them normally play a role in immune homeostasis and pathogen sensing, they also respond to and influence oncolytic virus infection of tumors.", "Some other strategies to alleviate matrix-imposed restrictions to oncolytic viruses have been discussed elsewhere [26, 29] ." ] },{ "paper_id": "b6e8f6a447550c5a8d3581adfffb225e8b59fe43", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hundred microlitres of the processed supernatant was used for template DNA preparation by boiling at 96\u00b0C for 10 min and chilling immediately in crushed ice [42, 43] . The supernatants were diluted 1:10 in distilled water to reduce residual inhibitors of DNA polymerase activity [12] .", "Conclusions: These findings extend the knowledge on CPV molecular epidemiology of particular relevance to wild carnivores." ] },{ "paper_id": "b6eed04e43ad653c06247b10ab05d03bdccf04bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and", "Assuming that all individuals mix homogeneously, then the transmission model defined earlier by equation (1) is generalised to", "I can now substitute (17) into (14) to obtain" ] },{ "paper_id": "b6f1dc149af87fc1daff699b8b599dae61773ebd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GBD 2010 covered 20 age and sex groups.", "The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility to submit the paper." ] },{ "paper_id": "b6f6aee927db36fcefbc96af78e21ac7d0059b4f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antibodies. An anti-human FITC-labeled anti-CD147 monoclonal antibody (clone MEM 6/1, mouse IgG1; Immunotools, Friesoythe, Germany) and an allophycyanin (APC)-labeled anti-CD14 monoclonal antibody (M\u0278P9, IgG2b; Becton Dickinson, San Jose, CA) were used for flow cytometry. The anti-CD147 monoclonal antibody (MEM 6/1, IgG1; Immunotools) was also used for immunoblotting.", "Where applicable, Student's T-test was performed for statistical analysis. A p-value of < 0.05 was accepted to be significant.", "To this end, in all experimental setups, the following scenarios were investigated:" ] },{ "paper_id": "b6fa578aa0397c1d6e2e0340b8581eb2c318974a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Positive-sense RNA viruses are responsible for frequent and often devastating diseases in humans, animals, and plants. However, the development of effective vaccines and anti-viral therapies targeted towards these pathogens has been hindered by an incomplete understanding of the molecular mechanisms involved in viral replication. One common feature of all positive-sense RNA viruses is the manipulation of host intracellular membranes for the assembly of functional viral RNA replication complexes. This review will discuss the interplay between cellular membranes and positive-sense RNA virus replication, and will focus specifically on the potential structural and functional roles for cellular lipids in this process.", "Despite the axiom that cellular membranes are essential host factors for positive-sense RNA virus replication, the specific role of individual membrane components, and in particular lipids, represents a vastly understudied area of virus biology and pathogenesis. We have discussed three potential structural or functional roles that cellular membrane-resident lipids may play in the assembly and function of positive-sense RNA virus replication complexes. These roles are not mutually exclusive, and it is possible that lipids contribute to several steps in the virus life cycle via multiple mechanisms, some of which we currently recognize, and others that remain to be discovered. The recent increase in targeted and genome-wide screens to identify host factors that impact positive-sense RNA virus replication [54] [55] [56] [57] [58] [59] [60] [61] [62] [63] , several of which have highlighted the importance of lipid metabolism-associated genes, provides an exciting foundation for these discoveries.", "The virosphere is large, complex, and continually expanding. One group of viruses responsible for a wide range of diseases in humans, animals, and plants are classified as positive-sense RNA viruses OPEN ACCESS due to their genome structure, which consists of one or more single-stranded RNA molecules that in many respects resemble cellular mRNAs. Clinically important members of this group cause significant morbidity and mortality, include viruses from the Picornaviridae, Flaviviridae, Caliciviridae, Coronaviridae, and Togaviridae families, and represent a prominent component of the growing list of emerging and potentially devastating health threats [1, 2] . Currently approved therapies for infections with these pathogens are limited, and the development of specific viral enzyme-targeted inhibitors is frequently complicated by the inherently high mutation rate of viral RNA polymerases and the rapid development of resistance [3, 4] . An alternative approach that has been advocated in the development of novel and potential broadly active antivirals is the targeting of host processes, which range from blockade of cell surface receptors to altering cellular metabolism [5] [6] [7] [8] [9] . However, the cell-centric approach to antiviral development requires substantial knowledge and understanding of the hostpathogen interactions that control virus replication." ] },{ "paper_id": "b70653608d4d8838aaf1dae4e710fa03a858df43", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HIV-1 sequences were downloaded from the Los Alamos National Laboratory (http://www. hiv.lanl.gov/) sequence database and aligned with MAFFT (v. 6.903b) [36] . Only sequences that encoded an intact, aligned slippery sequence (TTTTTTA) and that passed quality control checks used by the Los Alamos National Laboratory (i.e. were free of additional frameshift mutations, premature stop codons, and apparent hypermutation) were analysed. Sequences with ambiguous base calls in the intercodon were excluded. In total, 3534 of 4675 total sequences met these criteria and were used for further analysis. The BioPython (v. 1.59) toolset was used for further sequence analysis [37] . WebLogo (v. 2.8.2) was used to generate sequence logos [38] .", "[test] /RLuc [test] )/(Luc + [control] /RLuc [control] ) \u00d7 100. The Student's two-tailed t-test, assuming equal variance, was used to determine statistical significance, with an a priori \u03b1 value of 0.05.", "For the fluorophore assay, whole cell lysates were transferred to black 96-well plates (Greiner Bio-One) and relative fluorescence units were measured using a BMG POLARstar OPTI-MA (BMG Labtech). EGFP (5\u00b4reporter) and DsRed.T4 (3\u00b4reporter) fluorescence was detected using 485 nm excitation/520 nm emission and 525 nm excitation/600 nm emission spectra, respectively. Relative frameshift efficiency was calculated as above. . Expression levels were calculated using the comparative C T method of relative quantification, after confirming that amplification efficiency of the target gene was within 5% of the reference gene efficiency." ] },{ "paper_id": "b708da1945a7a42cd61526e043d527592d4d9518", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Western blotting was carried out using standard methods; bmercaptoethanol was used in sample preparation. BLV and HTLV-1 envelope was detected using supernatant from murine hybridoma cell lines expressing monoclonal antibodies raised against recombinant antigen derived from BLV or HTLV-1 envelope, and anti-mouse horseradish peroxidase conjugated secondary antibody at a dilution of 1:10,000 in PBS containing 5% (w/v) marvel and 0.025% Triton X-100.", "The plasmids pCMV-BLVenv-RRE and pRSV-Rev have been described [17, 47] . To construct pCMV-HTLVenv-RRE the BLV env sequences in pCMV-BLVenv-RRE were replaced by a HTLV-1 env coding region amplified by PCR from pHTE-1 [48] . To construct the plasmid pMAL-gp30hairpin (MBP-BLV-hairpin), a modified fragment of the MBP open reading frame from pMAL-c2 (New England Biolabs) with a 59 BglII site and a 39 PvuII site replacing a SacI site was PCR amplified. A fragment of BLV env encoding amino acid residues 326 to 418 was PCR amplified with a 59 PvuII site and a 39 PstI site. The PCR fragments were ligated into a pMAL-c2 backbone digested with BglII and PstI. The Quikchange mutagenesis kit (Stratagene) was used to introduce point mutations into pCMV-BLVenv-RRE and pMAL-gp30hairpin following the manufacturer's instructions.", "The trimeric recombinant MBP-BLV-hairpin protein was purified by Superdex 75 gel filtration, and the required fractions pooled and concentrated to 12 mg ml 21 . Tris [2-carboxyethyl]phosphine hydrochloride (TCEP-HCl) was then added to a final concentration of 5 mM. Protein concentration was estimated by absorbance measured at 280 nm. Crystallization conditions were identified using the sitting drop vapour diffusion technique, with crystal screens from Hampton Research and Emerald Biostructures. Optimal crystallization was achieved by streak seeding with a reservoir solution composed of 24.5% (v/v) isopropanol, 13.5% (v/v) PEG-4000 and 0.1 M sodium citrate pH 5.6, and optimal diffraction was achieved using a cryoprotectant composed of mother liquor supplemented with 20% (v/v) glycerol. Diffraction data was collected at beamline BM14 at the European Synchrotron Radiation Facility (ESRF) in Grenoble. The structure was solved by molecular replacement using a truncated model of MBP-HTLV Hairpin (PDB ID 1MG1). Refinement proceeded through cycles of model building using Coot and O [50, 51] and refinement using REFMAC5 [52] . Data and refinement statistics are given in Table 1 Peptides Peptides were synthesised using standard solid-phase Fmoc chemistry and unless stated otherwise have acetylated N-termini and amidated C-termini. The peptides were purified by reversephase high-pressure liquid chromatography and verified for purity by MALDI-TOF mass spectrometry. All peptides were dissolved in dimethyl sulfoxide (DMSO), the concentration of peptide stock solutions was confirmed by absorbance at 280 nm in 6M guanidine hydrochloride and peptides were used at the final concentrations indicated." ] },{ "paper_id": "b710adc78b56eb091aa40bc4cf5bc015e3f567e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "C8166 and CEMx174 cells, expressing secreted alkaline phosphatase (SEAP), were a kind gift of Dr. R. Desrosiers [26] . Raji-DC-SIGN cells have been previously described as B-THP-1 cells [27] . All non-adherent cell lines were maintained in RPMI 1640 medium (Invitrogen) supplemented with 7% bovine growth serum, 2 mM L-glutamine, 100 U/ml penicillin and 100 mg/ml streptomycin. Human 293T cells (ATCC) were maintained in DMEM medium (Invitrogen) supplemented with 7% bovine growth serum and antibiotics. Human peripheral blood mononuclear cells (PBMCs) were isolated from healthy donors using Ficoll gradient and maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 2 mM L-glutamine and antibiotics. PBMCs were activated prior to infection by phytohemeagglutinin A (10 ug/ml) and interleukin-2 (10 U/ml) for 3 days.", "estimated variance, to which we refer here as V total , was significantly higher than V ideal for all population sizes ( Figure 3A ).", "Because HIV populations in culture are growing exponentially, N 1 %N 2 %\u2026%N n . Therefore, the majority of the variance is contributed by the first generation and" ] },{ "paper_id": "b7240857da81a0bee7cfb964a7e838f7f1120b46", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An ethics board or IRB approval from Mayo Clinic is not needed since we have not conducted direct research involving human participants. We have used cloned plasmid derived from deceased patients obtained at autopsy. None of these deceased patients were from a vulnerable population and all donors or next of kin provided written informed consent that was freely given. The sequences encoded in the aforementioned plasmids have already been published and they are referenced throughout the manuscript.", "To harvest protein lysates, cells were washed with phosphate-buffered saline (PBS) before they were lysed on ice for 15 min with 0.5 mL RIPA buffer (Abcam) containing Halt protease inhibitor cocktail (ThermoFisher). The supernatant containing the cleared lysate was collected after centrifugation at 13,000 rpm at 4\u02daC for 15 min; aliquots were kept at \u221220\u02daC if not used immediately.", "Recombinant soluble MeV-Hs were prepared as previously described [15] . ", "Fusion activity was evaluated 24 h later after Hema-Quik staining (Fisher Scientific). The size of the syncytia was quantitated using NIS-Elements microscope imaging software (Nikon). Alternatively, the number of nuclei in randomly chosen syncytia was counted." ] },{ "paper_id": "b72e220b6500d2251e103f23d64b2f96f6e082f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each component of the coordinates is a function of distribution difference between the assigned two base-types, reflecting the distribution bias between them. We speculate that a certain continuous distribution bias along with a given sequence should yield a line along an axis. A line along the X axis illustrates a continuous distribution bias of purine (A plus G) over pyridine (C plus T); a line along the Y axis indicates a continuous distribution bias of amino-nucleotides (A plus C) over keto-nucleotides(G plus T); and a line along the Z axis demonstrates a continuous distribution bias of weak hydrogen bonds (A plus T) over strong hydrogen bonds (C plus G).", "centromeres in the human reference genome becomes an urgent interest, which intrigues the field to create new methods.", "given sequence, we searched it against RepeatMasker/Repbase database (at http://www.girinst.org/censor/index. php) to retrieve the registered repeats 27 . We used LTR-FINDER software 28 and TFR software 29 to conduct de novo predictions from the given sequence in order to predict LTR retrotransposons and tandem repeats, respectively. The parameters for LTR-FINDER were default, while for TFR were (2/7/7/80/10/50/500)." ] },{ "paper_id": "b72fc0df422070e077cfd05d8db51dfb059b9fd7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b73ed47108764542fff45d065e68ec160f10432a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thermo RAW files were imported into Progenesis QI for Proteomics (version 4.1, Nonlinear Dynamics, Newcastle upon Tyne, UK). Peaks were picked by the software using default settings and filtered to include only peaks with a charge state between +2 and +7. Spectral data were converted into .mgf files with Progenesis LC-MS and exported for peptide identification using the Mascot (version 2.3.02, Matrix Science, London, UK) search engine. Tandem MS data were searched against human and HRSV (A and B) databases (Uniprot, Feb 2015, 20,389 sequences; 11,407,585 residues). The search parameters were as follows: precursor mass tolerance was set to 10 ppm and fragment mass tolerance was set as 0.05 Da. Two missed tryptic cleavages were permitted. Carbamidomethylation (cysteine) was set as a fixed modification and oxidation (methionine) set as variable modification. Mascot search results were further validated using the machine learning algorithm Percolator embedded within Mascot. The Mascot decoy database function was utilized and the false discovery rate was < 1%, while individual percolator ion scores >13 indicated identity or extensive homology (p < 0.05). Mascot search results were imported into Progenesis LC-MS as XML files. Relative protein abundance was calculated by the Hi-3 default method within Progenesis.", "Viruses 2019, 11, x FOR PEER REVIEW 6 of 17 abundance than the F, M2-1 and L transcripts, and the G protein is present in virions. The major identified viral proteins are consistent with the presence of virus particles in the nasopharyngeal aspirates rather than proteins from intracellular material, where for example, the NS1 protein has been identified [17] . ", "Gene Low Medium High " ] },{ "paper_id": "b7430273f21b3a172f7f6e796636e376c2053fd8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results are expressed as means \u00b1 standard deviation. Statistical analyses were performed using Student's t-test. Differences were considered significant at * 0.01 < p < 0.05, ** p < 0.01." ] },{ "paper_id": "b747413330a7699f64ee1acbc773808fba975fb3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Patients' demographics, clinical presentation, treatments, and outcome data were entered into an SPSS database. The ILI-score, treatment, disposition, and virology results of triaged patients were compared by Pearson's X 2 , Fisher's Exact, Student t-tests, and Wilcoxon rank-sum tests." ] },{ "paper_id": "b75e7f3f923023185daed6f29e5beca4eddfc109", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LASV belongs to the Mammarenavirus genus (member of the Arenaviridae family) (8), a genus of enveloped, negative-strand RNA viruses that can be divided into two groups: Old World (OW) and New World (NW) (9) . The OW family of arenaviruses includes LASV and lymphocytic choriomeningitis virus (LCMV), a neglected human pathogen distributed worldwide (10, 11) , while the NW family of arenaviruses includes Jun\u00edn virus (JUNV) and Machupo virus (MACV), the causative agents of Argentine hemorrhagic fever and Bolivian hemorrhagic fever, respectively (9) .", "Supplemental material for this article may be found at https://doi.org/10.1128/JVI .01443-19.", "SUPPLEMENTAL FILE 1, XLSX file, 0.1 MB." ] },{ "paper_id": "b75f738ed440a2a6bd3f129238c0e661024577cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "When analyzing the monthly sequence data from patients infected with 2009 H1N1, by May 2010, 54", "Both of these example viruses, 2009 H1N1 and SARS, were identified and characterized based on sequence data, but targeted, rapid treatments were not readily produced using this sequence information. For example, the main treatment and control measures implemented for SARS were simply isolation of infected individuals. This included quarantining infected individuals, quarantining any patients presenting an upper-respiratory disease in hospitals, limiting travel, avoidance of public places, and implementing strict hygiene practices in hospitals [17, 18] . Not to disparage good hygiene as an effective means to combat infection, but given current medical advancements a more targeted treatment should be sought to combat these outbreaks.", "We propose the harnessing of rapid DNA synthesis to develop targeted treatments based on emerging sequences as an approach for swift clearance of newly emergent pandemic strains [23] . Rapid DNA synthesis may allow for an adaptable response and treatment that can change along with the mutating pathogen. Granted regulatory bodies could prove to be a hindrance in the quick development and dissemination of a novel therapeutic agent based on synthetic DNA; however, these policies may change if or when we are faced with a true pandemic threat such as the 1918 flu, which resulted in 50 to 80 million of deaths.", "Aside from the influenza pandemics, an entirely unrelated coronavirus was responsible for a significant emergent outbreak in 2002 that spread to numerous locations across the globe [12] . This was the well-publicized SARS virus which initially began in the Guangdong province of China and spread globally to 37 countries [13] . Initially, the exact viral cause of SARS was unknown until the implementation of the virus chip by Wang et al. allowed for its identification as a coronavirus [14, 15] . This virus was estimated to be the causative agent in the morbidity of 8,000 individuals, with a resulting mortality rate of 10% [12] . Despite having extremely different genetic compositions (i.e., influenza is a (\u2212) RNA virus and coronaviruses are (+) RNA viruses), they share the characteristic of cross-transmission. These viruses are capable of infecting a range of mammalian and avian hosts. Infection of humans usually manifests as a severe upper respiratory disease [16] ." ] },{ "paper_id": "b76a42e03efa0717d687c09551b0fb2a3cf116b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2.6. Statistical Analysis. The SPSS program version 16.0 was used for the calculation of unpaired -test and the Fisher's exact test, respectively.", "Of the 520 patients, 369 (71%) were hospitalized, 106 (20%) suffered from bronchopneumonia, 73 (14%) from acute bronchitis, and other furthers from different diseases of the lung (Table 1) ." ] },{ "paper_id": "b7737ffbdfa3d743dc16b4f99b0a85646529af3d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b77ed891047029cda65117192670f81edf87f1dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The S2 Subunit Determines IBV Tropism Journal of Virology", "Although live attenuated and inactivated vaccines are universally used in the control of IBV, they do not offer cross-protection between the different circulating serotypes of IBV. The advent of a reverse genetics system for IBV (75) (76) (77) creates the opportunity for generating rationally designed and more effective vaccines. The prospect of swapping spike genes from emerging strains of IBV into an attenuated backbone, such as Beau-R, is promising (8, 78) ." ] },{ "paper_id": "b786e66932955124f073e42aec53ea4a0f0cbb9b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 79 000 deaths estimated to be caused by EPEC represent different sub-types of this type of pathogenic E. coli, a group that requires further epidemiological studies in different parts of the world to further characterize them since some sub-types are isolated with the same frequency in diarrhea and control children [26] , new ''typical'' and ''atypical'' EPEC strains have been identified [27] , and in some regions have been identified to cause more persistent than acute diarrhea [28] .", "The following enteropathogens were considered: Rotavirus, enteropathogenic Escherichia coli (EPEC), enterotoxigenic Escherichia coli (ETEC), Salmonella spp. (excluding Salmonella typhi), Shigella spp., Campylobacter spp., Vibrio cholerae O1 and O139, Giardia lamblia, Cryptosporidium spp., Entamoeba hystolitica, human Caliciviruses (genogroup I and II norovirus and sapovirus) or astrovirus, coronavirus, and enteric adenovirus. We extracted data for all children less than five years of age for each pathogen. Data from more than one hospital in a country were treated as separate studies if the presentation of data permitted. Papers that published different etiological data from the same study site were grouped into one study. If co-infections were reported, they were not treated separately so each pathogen was counted as present if isolated alone or in combination. Three reviewers (CO, CXT, and CFL) did the primary extraction and all selected papers were reviewed by CFL and CFW independently. Disagreements were resolved by CFL and/or REB.", "Checklist S1 PRISMA Checklist (DOC)" ] },{ "paper_id": "b788a8861367f5eefe81794e3c77c4a15a872b03", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hendra virus (HeV) and Nipah virus (NiV) are both highly pathogenic zoonotic members of the Henipavirus genus and represent important emerging viruses discovered in the late 1990s in Australia and southern Asia. They are the etiological agents of acute and severe respiratory disease in humans, including pneumonia, pulmonary edema and necrotizing alveolitis with hemorrhage [135] [136] [137] [138] .", "The 2002-2003 SARS pandemic was caused by a coronavirus that emerged from bats (first reservoir) [25] to infect palm civets (intermediary reservoir) and then humans [215] . A total of 8096 probable cases were reported and almost 10% (774 cases in more than 30 countries) of these resulted in death [216] [217] [218] . The clinical portrait was described as an initial flu-like syndrome, followed by a respiratory syndrome associated with cough and dyspnea, complicated with the \"real\" severe acute respiratory syndrome (SARS) in about 20% of the patients [31,219]. In addition, multiple organ failure was observed in several SARS-CoV-infected patients [220] .", "HCoV-OC43 structural and accessory proteins are important for infection and some clearly represent virulence factors [38, [266] [267] [268] [269] 289, 295, 296] . Using neuronal cell cultures and our murine model, we gathered data indicating that some of these proteins also play a significant role in viral dissemination [269, 296] and now aim to exploit these promising leads to fully understand the course and determinants of propagation to and through the CNS and complete the neurologic portrait of short term HCoV neuropathogenesis." ] },{ "paper_id": "b79088a023db89b12d5630e426661985aba3921e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For example, the HAs from avian H1N1 or H3N2 virus had less glycosites than those of the seasonal human H1N1 or H3N2 virus (e.g., 286NAS in A/Memphis/28/1983 (H1N1). Figure 2A and File 5S).", "The IVs have an innate capacity for high mutation rates because they are RNA viruses. Humans are under continuous attacks by newly emerging IVs which constantly undergo ''antigenic drift'' and ''antigenic shift''. Accumulation of substantial sequences and 3D coordinates of IV proteins have provided the ideal tools for the investigation of how mutations affect transfaunation, vaccine design and drug-resistance [74, 75] .", "Most coordinate files of envelope glycoproteins are obtained from X-ray crystallography or NMR. Furthermore, complete larger glycans are too exible to yield sufficient electron density [46] . Isolation and purification of membrane glycoproteins by particular enzyme treatments lead to the lack of partial domains ", "It can be observed from Figure 1B that N10 is highly divergent from other subtypes [4] . The remainder of the current 9 NA subtypes are concentrated into two evolutionary groups: one group was represented by N2 and contains N3, N6, N7, and N9; and another group contains N1, N4, N5, and N8." ] },{ "paper_id": "b79e0dae232a80e5e92f12110cc4df835c171518", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Constructing and using GO terms for inter-species interactions presented a number of challenges and resulting ontology design decisions, which we describe below.", "One of the key terms we created in this project was 'symbiosis, encompassing mutualism through parasitism' (GO:0044403). Here, the usage of symbiosis is not synonymous with mutualism (an interaction from which both organisms benefit). Instead it is used in its broad sense, to mean any intimate association between two organisms of different species, regardless of whether the outcome of the interaction is beneficial to both species (mutualism) or detrimental to one species (parasitism).", "With this project, we provide an integrated, comprehensive ontology to describe multi-species interactions and microbial biology, with mappings to relevant external resources, where possible. The advantage of housing these data in GO is that the Gene Ontology is a well-known and respected, sustainable, open-source resource, for which a battery of annotation and analysis tools have been built. Thus microbial annotations can reach a wide audience for analysis, and microbial researchers have a wide range of tools and services available for analysing and interpreting their data." ] },{ "paper_id": "b7a6a987030c52cc7ecdf49c3933b6cfda488210", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All calculations were performed using the R software (R Development Core Team, 2013). All figures were made using the ggplot2 package (Wickham, 2010) implemented in the R programming environment.", "DAEC are defined by their diffuse adherence (DA) pattern on HEp-2 or HeLa cells (Servin, 2005) . DAEC express fimbriae like Dr and F1845 and/or afimbrial adhesins (Afa) which are responsible for adhesion to the epithelium and which are considered as the main VAFs for this pathotype. Adhesion results in an effacement of microvilli and a disruption of enzymes involved in intestinal secretion, which contribute to diarrhea.", "(2) For EPEC, STEC, and EHEC we analyzed and presented the prevalence of single VAFs and affiliation of all isolates to possible VAF patterns (e.g., one isolate was eaeA-positive = EPEC, one isolate was Stx-positive = STEC, one isolate was eaeA-and Stx-positive = EHEC). This was possible due to a large number of relevant publications.", "The methods used for VAF detection in E. coli are summarized in Supplementary Table 3 . PCR was used most often for VAF detection. More than a half of papers contained information about serotypes. Clonal relationship assays and antimicrobial susceptibility tests were analyzed in nearly one-fifth of all publications under review." ] },{ "paper_id": "b7b122d6d4cc409f7a22bec63936640b4cd0f334", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The one-way ANOVA method was used to analyze the significant difference between the indicated sample and the respective control sample. Significance levels were presented by the p-value (ns, non-significant; * p < 0.05; * * p < 0.01; * * * * p < 0.0001).", "The datasets generated for this study are available on request to the corresponding author.", "Coronaviruses (CoVs) are a group of enveloped viruses with non-segmented, single-stranded, and positive-sense RNA genomes (Masters, 2006) . Besides infecting a wide range of domesticated and laboratory vertebrates, six human CoVs have been identified, causing respiratory diseases with mild to severe outcomes. Among these, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are both zoonotic and highly pathogenic CoVs that have emerged in recent epidemic and/or pandemic outbreaks (Li et al., 2005; de Groot et al., 2013) ." ] },{ "paper_id": "b7b6bf20c919a0b200c528e76f76f508d5554700", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PLpro ridge mutants in the SUb2 subsite are impaired in their ability to deubiquitinate proteins and antagonize the NFkB pathway in the host cell", "In cellular deubiquitination assays HEK293T cells in 12-well Cell-Bind plate (Corning) were transfected (LT1, Mirus) with 300 ng FLAG-Ub and either 125 ng, 250 ng, or 500 ng of pcDNA3.1-SARS-PLpro per well. Cells were incubated for 18 hours then lysed with IkBa lysis buffer (20 mM Tris (pH 7.5), 150 mM NaCl, 1 mM EGTA, 1 mM EDTA, 1% Triton X-100, 2.5 mM Na pyro-phosphate, 1 mM Beta-glycerophosphate, 1 mM Na ortho-vanadate, 1 ug/ml Leupeptin) and incubated for 20 min on ice. Lysates were subjected to centrifugation at 4C and the cytoplasmic contents added to 26 sample buffer and separated by SDS-PAGE on a 4-20% gradient gel (BioRad). Gel was transferred to PVDF using semi-dry apparatus (BioRad) and immunoblotted with anti-FLAG (Sigma), anti-V5 (Invitrogen), and anti-calnexin (BD).", "Ubiquitin acetal was generated by reacting 10 mL of ubiquitin thioester with 2 mL of 4M aminoacetaldehyde diethyl acetal, pH 8.5 (Sigma-Aldrich) and 50 mL of freshly prepared 2M Nhydroxy-succinimide (Sigma-Aldrich) and incubated at room temperature. Upon full conversion (,1 hr), the ubiquitin acetal was dialyzed against 50 mM sodium acetate, pH 4.5, overnight at 4uC. The acetal was deprotected with 0.15 M HCl to produce ubiquitin aldehyde, then quenched with 0.15 M Tris base, and subsequently desalted into 20 mM HEPES, pH 7.5. Conversions from thiol ester to acetal and from acetal to aldehyde were monitored by HPLC on a C8 column as previously described [61] . The concentrations of the ubiquitin species throughout the purification were determined by HPLC, using unmodified ubiquitin (Boston Biochem) as a standard." ] },{ "paper_id": "b7bd823d7175ee551d3ba8508e5457d650056fd6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were maintained in DMEM supplemented with 10% newborn calf serum. The Vero-adapted IBV and recombinant vaccinia/T7 virus was propagated and titrated on Vero cells. Virus stocks were kept at 280uC until use.", "Viral RNA was extracted from the culture supernatants or infected cells using the RNeasy Mini Kit (Qiagen) according to the manufacturer's instructions. RT-PCR was performed using the Expand Reverse Transcription and High Fidelity PCR Kits (Roche). The PCR products were cloned into PCRH-XL-TOPOH vector (Invitrogen) and sequenced by automated sequencing.", "Conceived and designed the experiments: DXL. Performed the experiments: YY XBL SF FPT. Analyzed the data: YY XBL SF DXL. Wrote the paper: XBL DXL.", "The Beaudette strain of IBV was previously adapted to embryonated chicken eggs. This embryo-adapted IBV strain was subsequently adapted to cultured cells originated from chicken and monkey. For example, the virus was adapted by serial passages to primary chicken kidney (CK) cells [8, 9] and the African green monkey kidney cell line Vero cell [8] [9] [10] [11] [12] [13] . Furthermore, the Veroadapted IBV is able to infect cultured human and animal cell lines [14, 15] ." ] },{ "paper_id": "b7c8e73cf095e30552a32cea04a398331c55ab41", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "it has been estimated that 7.4 million deaths may result worldwide [7] .", "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "b7cf054fd2a9f9366458e8c251a37bda87fca328", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An aliquot of approximately 100 mg of grounded tissue was taken and mixed with 200 mL of extraction buffer (0.2 M Tris, 0.2 M NaCl, 50 mM EDTA, 2% SDS; pH 8). An equal volume of phenol:chloroform:isoamylic alcohol (25:25:1) was added, thoroughly vortexed and centrifuged at 14000 g for 5 min at 25uC. Ca. 160 mL of the upper aqueous phase were mixed with 80 mL of a solution containing 7.5 M LiCl and 50 mM EDTA and incubated overnight on ice at 4uC for RNA precipitation. The precipitated RNAs were centrifuged at 14000 g for 15 min at 4uC, washed once with 70% ice-cold ethanol, dried in a SpeedVac (Thermo) and resuspended in 30 mL of DEPC-treated ultrapure water. RNA concentration was measured spectrophotometrically and the samples were diluted to a final concentration of 50 ng/mL. Within-plant virus accumulation was measured by absolute RT-qPCR using external standard [47] . Standard curves were constructed using five serial dilutions of TEV RNA produced by in vitro transcription and diluted in RNA obtained from the corresponding healthy host plant species. Samples were grouped by hosts and quantity of viral RNA was calculated using the corresponding standard curve.", "RT-qPCR reactions were performed in 20 mL volume using One Step SYBR PrimeScript RT-PCR Kit II (TaKaRa) following the instructions provided by the manufacturer. The primers forward TEV-CP 59-TTGGTCTTGATGGCAACGTG and reverse TEV-CP 59-TGTGCCGTTCAGTGTCTTCCT amplify a 71 nt fragment within the TEV CP cistron. CP was chosen because it locates in the 39 end of TEV genome and hence would only quantify complete genomes but not partial incomplete amplicons. Each RNA sample was quantified three times in independent experiments. Amplifications were done using the ABI PRISM Sequence Analyzer 7000 (Applied Biosystems). The thermal profile was as follows: RT phase consisted of 5 min. at 42uC followed by 10 s at 95uC; and PCR phase of 40 cycles of 5 s at 95uC and 31 s at 60uC. Quantification results were examined using SDS7000 software v. 1.2.3 (Applied Biosystems).", "Ten days post-inoculation (dpi), the whole infected plant, except the inoculated leaf, was collected. The whole tissue was frozen in liquid nitrogen and ground with mortar and pestle.", "Infectious RNA of each genotype was obtained by in vitro transcription after BglII linearization of the corresponding plasmid as described in [45] . The infectivity of each RNA genotype was tested by inoculating five N. tabacum plants. All TEV genotypes were confirmed to be infectious on N. tabacum." ] },{ "paper_id": "b7de4f4a99e8da86891ed28bca52afcbcbdabfa1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b7e0b1aeadb98920f56a14043d2f170833a31ef5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antibodies in the whey preparation remained functional when added to milk that had been treated via ultra-high temperature pasteurization or milk that was fermented to extend shelf-life [75] .", "In the small intestine, immunoglobulins are further digested by pancreatic enzymes. One of them, trypsin, preferentially digests bovine IgG1 over IgM, whereas another enzyme, chymotrypsin, preferentially hydrolyzes IgM over IgG [199] . Bovine IgG1 is more susceptible to hydrolysis by pepsin than IgG2, while IgG2 is more susceptible to trypsin [200] .", "Flash-heat treatment of human breast milk, a method recommended by WHO to reduce vertical transmission of HIV in resource-poor regions, has minimal effects on milk IgA and antimicrobial activity of the milk [218, 219] . This method involves placing a jar of milk into a water bath, the water bath is heated to boiling, and then the jar of milk is removed and allowed to cool. The milk reaches a maximum temperature of 72-73 \u00b0C and is above 56 \u00b0C for over 6 min [218, 219] .", "Consumed colostrum also may impact immunological development of the neonate [1] . These maternal antibodies may then inhibit infant responses to vaccine administration and impact development of the infant's immunity [183] ." ] },{ "paper_id": "b7e0f3776f44e29508da3d6150d63790e7f38d9e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A recent study has shown that abortive herpes herpesvirus (HHV)-1 (herpes simplex virus-1) infection of mature MDDC is able to modulate their inhibition of T-cell stimulatory function [27] . Endocytosis in mature DCs is slowed somewhat relative to immature DCs, potentially the result of changes to their endocytic mechanism or receptor expression [28] . Similarly, virus was disseminated systemically in a patient with MERS [29].", "Cytotoxicity assays were performed in parallel to measure drug toxicity. One black opaque cell plate for each cell type was mock infected using R-10 medium under the same conditions ", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "To quantify the antiviral activity of the candidate compounds, a cell based immunofluorescence enzyme-linked immunosorbent assay was used as described previously [13] . The fixed plates, as described above, were stained with a rabbit polyclonal antibody to the MERS-CoV--EMC/2012 S protein (Sino Biological) at 1:1000 followed by staining with Alexa Fluor 594-conjugated goat anti-Rabbit IgG (H+L) antibody (Thermo Fisher Scientific) at 1:2500. Fluorescence was quantified on a plate reader (Infinite M1000 Pro; Tecan US, Morrisville, NC) with an excitation wavelength of 590 nm and an emission wavelength of 617 nm." ] },{ "paper_id": "b7e7ff011d768680bee745105bd24389068a5a1f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For subject 185F, V1V5 domain backbone, forward primer 59-Phos-atgagggacaattggagaagtg-39 (HXB2 nt 7647 to 7668) and reverse primer 59-Phos-gctttaagctttgatcccataaac-39 (HXB2 nt 6576 to 6553); V1V2 domain backbone, forward primer 59-Phoscaagcctgtccaaaggtctct-39 (HXB2 nt 6831 to 6851) and reverse primer 59-Phos-gctttaagctttgatcccataaac-39 (HXB2 nt 6576 to 6553); V3V5 domain backbone, forward primer 59-Phos-atgagggacaattggagaagtg-39 (HXB2 nt 7647 to 7668) and reverse primer 59-Phos-ccttacacacacaatttctac-39 (HXB2 nt 7118 to 7098); ectodomain backbone, forward primer 59-Phos-aagatatttataatgatagta-39 (HXB2 nt 8271 to 8291) and reverse primer 59-Phostttttctctctccaccactctcc-39 (HXB2 nt 7754 to 7732); V5 domain backbone, forward primer 59-Phos-atgagggacaattggagaagtg-39 (HXB2 nt 7647 to 7668) and reverse primer 59-Phos-catgttatgtttcctgcaatg-39 (HXB2 nt 4527 to 4507).", "University of Zambia School of Medicine Research Ethics Committee. Written Informed consent was obtained from human subjects.", "185F " ] },{ "paper_id": "b7f090aebd3ca0c64361662b87a6134c0afacb1a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The unpaired t test (Student, 1908; Welch, 1947) was used to assess the statistical significance of differences between groups. In all analyses, p < 0.05 was taken to indicate statistical significance.", "Further studies will be necessary to fully elucidate the pathogenicity of African MERS-CoV isolates.", "All datasets generated for this study are included in the manuscript and/or the Supplementary Files.", "This work was supported by a Grant-in-Aid for Scientific Research (B: 17H04642) from the Japan Society for the Promotion of Science.", "All authors participated in the planning of the project. KS, SM, TT, and HS collected specimens in Ethiopia. KS and NN performed next generation sequencing analysis. KS, KK, and WK constructed and generated MERS recombinants. KS and MK performed viral infectivity experiments. KS, MK, and NI-Y performed neutralization experiments. SM led the project. KS wrote the manuscript. All authors read and approved the final manuscript." ] },{ "paper_id": "b7f529b58714037f09a19f78d9a06d68f1f15dd9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The experimental studies clearly support a physiological and pathophysiological role for ACE2 in arterial hypertension, and data is also available that increasing/activating ACE2 has beneficial effects to lower blood pressure. As therapeutic strategies that block the RAS using ACE inhibitors or Ang II receptor blockers are first line therapy in hypertension, experimental studies are needed that combine ACE2 activators/recombinant ACE2 with RAS blockers to determine if this approach offers incremental benefits.", "Although a potentially reversible cause of hypertension can be identified in less than 10% of patients with hypertension, the overall high prevalence of hypertension means that secondary forms can affect millions of patients worldwide. Dysregulation of ACE2 has been reported in experimental models of secondary hypertension, such as endocrine hypertension [deoxycorticosterone (DOCA)-salt, Ang II infusion], renal failure (subtotal nephrectomy), and renal artery stenosis (Goldblatt hypertension).", "The evidence of ACE2 gene associations in Caucasians is also inconsistent. In a small case-control study conducted in Anglo-Celtic Australian subjects with hypertension (n = 152) or normotension (n = 193), four ACE2 SNPs were not associated with hypertension (Benjafield et al., 2004) . In another study of healthy subjects participating in the MONICA Augsburg echocardiographic substudy, four ACE2 SNPs (rs4646156, rs879922, rs4240157, and rs233575) were investigated but none were associated with systolic blood pressure variation (Lieb et al., 2006) . However, in our own study of 503 Australian Caucasians with type 2 diabetes , the prevalence of hypertension was significantly higher in both men and women and was associated with the G allele of the ACE2 SNP rs4240157 ." ] },{ "paper_id": "b7f56c8f1b2b82f7eae3786d2e59963b2a9b6d85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "M.N.); halromaihi@moph.gov.qa (H.A.-R.); malthani@moph.gov.qa (M.A.T.); dralmarri@moph.gov.qa (S.A.-M.); malhajri1@moph.gov.qa (M.A.)", "The funder had no role in study design, data analysis, data interpretation, or writing of the review." ] },{ "paper_id": "b7f783ce7fc3715b718384a9295bd8afb24b93ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A two-step real-time RT-PCR was performed using the CFX96 Real-Time PCR Detection System (Bio-Rad)." ] },{ "paper_id": "b7ff247b83afad127e3d971006647d12ce097d56", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The performance of the test clearly varies depending on the group of patients tested.", "Polymicrobial infections were detected in both studies by conventional and/or molecular methods. The agreement between methods on these specimens was low, as most of the mixed infections were detected by only one of the two methods. However, the use of this molecular method in addition to blood culture would have resulted in additional detections of clinically relevant microorganisms in some cases, which could have influenced patient outcome.", "[25] and 37.5% ( = 75) [26] ; specificities were 100% [25] and 86.6% [26] ." ] },{ "paper_id": "b817c40ff2740be4fb203fbef15d27aa6e25c299", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b81a921bc4d2223e69b7fddf4f1d2a3ba7622f92", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chemokines are a family of cytokines that induce chemotaxis of target cells. Though they were originally discovered for their ability to induce leukocyte migration into the infected or injured sites, more recently, it became clear that they could also promote cancer progression [1] [2] [3] [4] [5] [6] [7] [8] [9] . In addition to inducing tumor cell proliferation, angiogenesis and metastasis, chemokines and their receptors regulate tumor cell differentiation and survival. Currently, the human chemokine network includes more than OPEN ACCESS 45 known chemokines and 20 chemokine receptors. Based on the number and spacing of conserved N-terminal cysteine residues that form disulfide bonds, chemokines are divided into four groups: (X)C, CC, CXC, and CX3C [10] [11] [12] .", "In addition to the positive regulation by p65 NF\u021bB, AP-2 and SP-1, studies using human melanocytes have indicated that the CXCL1 expression is negatively controlled by the transcriptional repressors CDP and the poly(ADPribose) polymerase-1 (PARP-1) [113, 114] . The exact mechanisms of how CDP and PARP-1 inhibit the CXCL1 expression are not fully understood; however, they likely involve displacement of trans-activating factors that bind to CXCL1 promoter, resulting in transcriptional repression. ", "While hyperglycemia and obesity are thought to be contributing factors to cancer development and progression, caloric restriction has been associated with reduced cancer incidence [74] [75] [76] [77] . During reduced calorie intake or exercise, the body switches to obtaining energy from fatty acid oxidation, which results in ketone bodies production. Intriguingly, the recent study by Shimazu et al. [78] has demonstrated that the ketone body \u0215-hydroxybutyrate (\u0215OHB) is an endogenous and specific inhibitor of HDACs, and that administration of exogenous \u0215OHB increases histone acetylation, correlating with changes in transcription. Since HDACs regulate chemokine transcription by both deacetylating histones and p65 NF\u021bB [53] [54] [55] [56] [57] [58] , it will be important to analyze whether \u0215OHB and other HDAC inhibitors regulate chemokine expression in ovarian cancer cells, and whether this is modulated by the metabolic state." ] },{ "paper_id": "b82539a18c6aea935321822f2de5937fd7fef769", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations ARDS: acute respiratory distress syndrome; COPD: chronic obstructive pulmonary disease; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; RT-PCR: reverse transcriptase -polymerase chain reaction.", "The authors declare that they have no competing interest." ] },{ "paper_id": "b83417aceefa21bf06ba89462781ebe07142a259", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting information S1 Table. CDV strains with evidence for potential recombination in RDP analysis. ", "The gene sequences mentioned above were trimmed by MEGA V5.0 [10] . Seven transversional models with a proportion of invariable sites and a substitution model comprised of gammashaped distribution of rates across these sites (CDV genome = GTR+G+I, H = GTR+G, N = GTR+G, P = TrN+G, F = TIM+G, M = TrN+G, L = GTR+G+I) s were assessed by Mod-elTest v3.7 [11] , PAUP \u00c3 v4b10 (Swofford, 2003), and MrBayes v3.1.1 that explored the distance (neighbor-joining) and characteristics [Bayesian, maximum likelihood (ML)-based phylogenetic methods] of the nucleotides sequences [12] . The results of the analysis were confirmed using Bayesian and ML approaches with the MEGA 5.0 software package [10] . The phylogenetic tree was tested by bootstrapping with 1000 replicates. The phocine distemper virus (PDV) (GenBank accession number KC802221) was indicated as an outgroup in the seven models.", "The complete sequences of the CDV genome and its six genes (N, P, L, M, H, and F) were retrieved from GenBank. All sequences were aligned using ClustalW [8] and BioEdit [9] , followed by visual confirmation. The virus name, GenBank accession number, isolation time, and place are summarized in Table 1 .", "In conclusion, six phylogroups and homologous recombination events, occurring in the CDVs, were identified based on the CDV genome and their gene segments. The majority of CDVs underwent a negative selection pressure. This information provides a valuable reference for the study of molecular epidemiology of CDVs." ] },{ "paper_id": "b8423ebcd07e62c48ca7205a06fee753f9199e58", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Note that u(t) is now described on a daily basis; thus, u t represents the daily probability on day t.", "https://doi.org/10.1371/journal.pntd.0007468.t002" ] },{ "paper_id": "b84e5b51b40b345b68445d68483cc478e9ce5beb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Previous biochemical and structural studies with purified proteins of Bat09 hemagglutinin (HA) and neuraminidase (NA) ", "Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g.", "Human embryonic kidney 293T (HEK-293T) cells, mouse rectum epithelial carcinoma (CMT-93) cells, and African green monkey kidney (Vero) cells were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS). Madin-Darby canine kidney (MDCK) cells were maintained in minimum essential medium (MEM) supplemented with 5% FBS. Human lung epithelial (A549) cells, bat lung epithelial (Tb1Lu) cells, mink lung epithelial (Mv1Lu) cells and swine testis (ST) cells were maintained in MEM supplemented with 10% FBS. Human lung epithelial (Calu-3) cells were maintained in MEM supplemented with 10% FBS, 1% nonessential amino acids, and 1 mM sodium pyruvate." ] },{ "paper_id": "b85671451a6132068f92e5da9590cbc9ee5867d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The TEER of the airway epithelial cell cultures was measured by using a ''chop stick'' epithelial ohmmeter (World Precision Instruments, Sarasota, FL), as described previously [25, 26] .", "Data presented represent mean of multiple experiments and error bars indicate standard deviation from the mean. Where indicated, the data points were analyzed by Student's t-test or One-way ANOVA test. The P values smaller than 0.05 were considered statistically significant.", "No human subjects or animals were used in this study." ] },{ "paper_id": "b8567708fbc399167a11ae6ac3d9482f68bd7b24", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The characteristics of OH presented here resulted from a NEOH workshop held in June 2015. Twenty-five experts from 14 countries representing public, human, veterinary, wildlife and 1 http://neoh.onehealthglobal.net. environmental health, food safety, agriculture, agro-economics, geography and development aid, research, government, and international organizations attended. The notion evolved that there are specific conditions that demand integrated approaches, which we named drivers. At the other end, specific outcomes are expected to be produced as a result of these integrated OH approaches. The principal OH approach as such was considered to consist of a specific operational paradigm requiring a supporting infrastructure to become effective. Figure 1 illustrates the relations between drivers, operations, supporting infrastructure and outcomes of OH.", "Consequently, \"OH working\" relies on transdisciplinary collaboration that embraces contributions from the biological, natural and social sciences, and actively includes stakeholders in the process, from problem definitions to resolution. To operate as conceived, OH must rely on adequate information infrastructure and foster learning across all scales and fields (19) . A learning framework allows for stakeholders and institutions to evolve and improve autonomously, and requires mechanisms for knowledge exchange, institutional memory, feedback, and regulation. This relies on sharing of knowledge, data, resources, and staff across sectors and disciplines. This working paradigm will often lead to complex, polycentric organizational structures that support development toward sustainability and resilience (20) . To succeed, they rely on multiple, strong connections and coordinated activities across sectors, for example, joint health services for humans and animals (21, 22) , and/or for the environment (23).", "The purpose of this paper is to identify and describe evaluable characteristics of OH approaches, and to present what they can encompass and achieve. This provides a basis for evaluation of OH initiatives and their outcomes, which could not be achieved using standard, sectoral approaches." ] },{ "paper_id": "b85794a3749932e7585c864b7fbb766f38dd97f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Expression data were obtained from SymAtlas (http://symatlas. gnf.org/). The location of genomic elements that are highly conserved among vertebrates was derived from UCSC annotation tables (http://genome.ucsc.edu/; ''PhastCons Conserved Elements, 44-way Vertebrate Multiz Alignment'' track).", "All correlations were calculated by Kendall's rank correlation coefficient (t), a non-parametric statistic used to measure the degree of correspondence between two rankings. The reason for using this test is that even in the presence of ties, the sampling distribution of t satisfactorily converges to a normal distribution for values of n larger than 10 [76] .", "All calculation were performed in the R environment [78] (http://www.r-project.org/)." ] },{ "paper_id": "b85bcfe513307afbac6c3bd5866dc0c0aecd28a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HJ16, HK20 and HGN194 Abs were obtained as part of the Collaboration for AIDS Vaccine Discovery program from Dr. D. Corti (Institute for Research in Biomedicine, Bellinzona, Switzerland).", "In order to link the present and previous studies, plasma were tested in TZMbl assays against a sub-panel of PV included in supplementary table 2 of reference 7.", "The study was approved by the Institutional Review Board of the Institute of Tropical Medicine and the Ethical Committee of the University Hospital of Antwerp. All participants understood and signed an informed consent." ] },{ "paper_id": "b8660d5f12c9a6a85b73207bc61291535c2700ce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cinnamon is a popular spice around the world and is one of the oldest medicinal herbs. There is increasing evidence showing that cinnamon has anti-inflammatory, anti-viral, immunomodulating, anti-diabetic, and antiangiogenic effects [1] [2] [3] [4] [5] [6] [7] [8] .", "Statistical analysis was performed using student t test or one-way analysis of variances followed by Dunnet's test for multiple comparison. Calculations were carried out using the SPSS version 20. P values less than 0.05 were considered significant." ] },{ "paper_id": "b86c0b353d21e4ada6c8cd36da8c433123b23f8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Burtram C. Fielding receives funding from the National Research Foundation, South Africa. Any opinion, findings and conclusions or recommendations expressed in this material are those of the author and therefore the NRF does not accept any liability in regard thereto.", "Interestingly, hBoV appears to be more than just a respiratory or gastrointestinal virus. In a recent study, hBoV was identified in 18.3% of lung (n = 11/60) and 20.5% of colorectal (n = 9/44) tumors screened. Unfortunately, the study did not investigate whether the hBoV genomes were in fact incorporated into the host genome as reported for other known Parvoviruses. Therefore, based on their observations as well as previous studies on other parvoviruses, the authors speculate that hBoV could contribute to the development of some lung and colorectal tumors. However, they do also acknowledge that these tumors could simply be providing an optimal environment for hBoV replication and more conclusive studies are required to resolve this issue [171] .", "The authors declare no conflict of interest.", "Seroepidemiological studies have shown that 40% of wild animal traders and 20% of people responsible for the slaughtering of animals in the region where human SARS was thought to originate, were seropositive for SARS-CoV, although all cases were asymptomatic. This indicates that these people were previously exposed to a SARS-like-CoV, which resulted in asymptomatic infection [38] .", "Viral coinfections between hMPV and RSV have been reported, but remain a contentious issue. The typical seasonal overlap of the two viruses has been suggested to promote viral coinfection. One study reported a 10-fold increase in risk of admission to an intensive care unit in pediatric patients coinfected with RSV and hMPV and associated the dual infection as capable of augmenting severe bronchiolitis [118] . Other studies do not support this finding and further report a decreased correlation between hMPV-RSV coinfections and hospitalization and additionally lists dual infection, along with breastfeeding, as having protective effects [119] ." ] },{ "paper_id": "b87033ed15a4d9f337f37d67516b49992fd923c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Wild-type C. albicans SC5314 was maintained as previously described (Leonhardt et al., 2015) . For experiments, colonies were transferred to M199 medium (PAA), pH 4 and cultured at 30 \u2022 C to stationary phase. Germ tubes were induced by culturing in M199 medium, pH 8 for 1 h at 37 \u2022 C. Germ tubes were inactivated by washing them in phosphate-buffered saline (PBS) and followed by incubation in PBS containing 0.1% thimerosal (Sigma-Aldrich) for 1 h at 37 \u2022 C with shaking. Afterwards, germ tubes were washed five times and then re-suspended in RPMI-1640. Killing was confirmed by plate counts on YPD (2% Dglucose, 1% peptone, 5% yeast extract, Roth) agar plates.", "Cells were re-suspended in lysis buffer (6.65 M Urea (Sigma), 10% Glycerin, 1% SDS, 10 mM Tris (Carl Roth GmbH), pH 6.8), sonicated for 15 s (UP50H, Hielscher) and proteins quantified using the DC Protein Assay (BioRad). Cell lysates were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to nitrocellulose membranes. Membranes were incubated with rabbit anti-KLF4, anti-IFITM2 (Cell Signaling), goat anti-SPN and anti-FKBP1B (R&D systems) and mouse anti-\u03b2-Actin (Sigma Aldrich) antibodies over night at 4 \u2022 C or for 2 h at room temperature, respectively. Horseradishconjugated anti-rabbit, anti-mouse (Cell Signaling) and antigoat (R&D systems) IgG antibodies were used as secondary antibodies. Signals were visualized by ECL reaction with Clarity TM ECL Western Substrate (BioRad) or Pierce TM ECL Western Blotting substrate (Thermo Scientific) and analyzed using ImageJ software (ImageJ version 1.47, National Institutes of Health).", "The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fmicb. 2017.00270/full#supplementary-material", "This study, using whole blood specimens obtained from human healthy volunteer donors, was approved by the Ethics Committee of the University of W\u00fcrzburg (approval 302/12). Data analysis was conducted anonymously." ] },{ "paper_id": "b8797e77d9c91dd2cab19ba2e67cf32b6dd97bf6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b87dbfb99e667d88cda4e153340b44404f7b4c98", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We identified four broad approaches to entry screening. First, temperature checks were performed onboard aircraft prior to disembarkation. Second, health declaration forms were collected from every traveler or all travelers from countries identified with confirmed H1N1 cases. Third, arriving travelers were observed by alert staff for influenza symptoms (e.g. cough). Fourth, travelers were scanned for elevated body temperature by thermal scanners. In the majority of countries screening was implemented by May 1, 2009 although we were unable to determine whether there were any substantial changes in screening protocols after commencement of screening but before confirmation of the first local case.", "Additional file 1: Use of entry screening* and interval between confirmation of first imported pandemic influenza A (H1N1) case and confirmation of first untraceable local case", "For entry screening to be successfully employed, substantial resources are required to identify the small fraction of travelers who may have H1N1 infection [16] . Further resources may be needed to isolate identified cases, and trace and quarantine close contacts. An important caveat is that a delay in inevitable local transmission of a pandemic virus may not be desirable if it would defer local transmission into a season associated with higher transmissibility such as the winter in temperate regions [12] , or if it led to importation and local transmission of antiviral resistant strains [17] ." ] },{ "paper_id": "b87ddf92d90fd58bbdf08981116cd7841d75d483", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "On the contrary, Ficolls and dextrans of different sizes (in a variety of sizes ranging from 15 to 500 kDa, in a concentration range 0%-30% w/w) were shown to reduce the rate of the hydrolysis of p-nitrophenyl phosphate by alkaline phosphatase (which is a homodimeric enzyme from bovine intestinal mucosa, EC 3.1.3.1) in a crowder molecular mass-dependent manner, with crowding agents with greater molecular weight possessing high rate reducing capacities [61] .", "It is recognized now that not all crowders are made equal. This inequality is very protein-specific (i.e., crowders that efficiently act on some proteins would be less efficient on some other proteins), suggesting that there is a clear deviation from the simple excluded volume model, and that in addition to hard non-specific steric interactions some protein-specific \"soft\" interactions between proteins and crowders might be present.", "Irina M. Kuznetsova collected and analyzed literature data and helped with the manuscript preparation. Konstantin K. Turoverov collected and analyzed literature data and helped with the manuscript preparation. Vladimir N. Uversky conceived the idea, collected and analyzed literature data and wrote the review." ] },{ "paper_id": "b880cad36f03039d17617ae8be7e885caa54b7fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Purified proteins were applied to glow-discharged carbon-coated grids and negatively stained with 1% uranyl formate, as described . Images were recorded on a Gatan ES1000W CCD camera in a JEOL JEM-1011 microscope operated at 100 kV.", "For testing mouse serum reactivity, the microtiter plates were coated with 80 ng/well of purified protein in 50 mM Na 2 HPO 4 , pH 8.0, 300 mM NaCl, and non-specific binding was blocked as above. Then, serial dilutions of sera in blocking solution were added, and bound antibodies were detected with peroxidase-labeled goat antimouse Ig and OPD.", "Expanded View for this article is available online." ] },{ "paper_id": "b890aa8cb8a15fec0f4bb8e970f5a21fd2dfda33", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DNA was extracted from bacterial cultures using QIAamp \u00ae DNA mini kit (QIAGEN, Hilden, Germany). Bacterial cells were harvested in a microcentrifuge tube by centrifugation at 5000 \u00d7 g for 10 min. Cell pellets were re-suspended in 180 \u03bcl lysis buffer (20 mg/ml lysozym; 20 mM Tris-HCl, pH 8.0; 2 mM EDETA; 1.2% Triton) and incubated at 37\u00b0C for 30 min. Proteinase K and Buffer AL were then added and mixed by vortexing. After 30 min incubation at 56\u00b0C, ethanol was added and thoroughly mixed to yield a homogenous solution. DNA was then extracted as per manufacturer's instructions. DNA was extracted from tissue samples (liver, kidney, spleen) by QIAamp \u00ae DNA mini kit (QIAGEN, Hilden, Germany) according to the manufacturer's instructions following the animal tissues protocol.", "water bath and is hence suitable as a routine diagnostic tool in private clinics and field applications where equipment such as thermal cycling machines and electrophoresis apparatus are not available." ] },{ "paper_id": "b8915fde10e62d4b033a9141910e5639590f0bae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At weaning, lactogenic protection disappears, making the young animals highly susceptible to infections with enteropathogens. Most pathogens either colonize the mucosa or invade the host at a mucosal surface. Optimal protection against these pathogens most often involves the induction of pathogen-specific SIgA at the infection site [12] . As such, an optimal vaccine should induce robust mucosal SIgA immune responses.", "The authors declare that they have no competing interests. " ] },{ "paper_id": "b894fde1276ea66d0eef9ecf55b025adc58f105d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antibodies. The UV-inactivated anti-HCV human serum 42, 43 and rabbit antisera against FLUAV 21 , SeV 48 , HSV-1 49 and MERS-CoV 55 were described previously. A mouse monoclonal antibody against HCV NS3 (Millipore), rabbit polyclonal antibodies against DENV PrM (GeneTex), JEV NS3 (GeneTex) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH; Millipore), rabbit antisera against CV-B3 (Denka Seiken) and horseradish peroxidase (HRP)-conjugated goat anti-mouse IgG and goat anti-rabbit IgG (Life Technologies) were purchased.", "by qRT-PCR, as described previously 53 . The amounts of DENV RNA were determined by TaqMan qRT-PCR, according to the protocol reported by Ito et al. 56 ." ] },{ "paper_id": "b8a1d1bdea4cc683b11719ab5e20e2b85f7cb08e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For Salmonella detection, samples were inoculated into specifics Rappaport-Vassiliadis and Tetrathionate broth. Each broth culture was plated in xylose-lysine-deoxycholate agar and in bismuth sulfite agar and was then incubated. Suspected Salmonella sp. colonies were inoculated in triple sugar iron and lysine iron agar and classified using conventional biochemical tests [24] . A commercial agglutination test using polyvalent anti-Salmonella serum (Probac6) and serotype identification were also carried out [22] .", "2.8. Virulence of R. equi. Plasmid DNA was isolated using the alkaline lysis method with several modifications [29] . The target DNA for PCR amplification was based on reported vapA (15-to 17-kDa antigen) and vapB (20-kDa antigen) gene sequences (GenBank accession numbers D212361 and D44469). Plasmid DNA was digested with the restriction endonucleases EcoRI, EcoT22I, and HindIII [30, 31] . Then, the plasmid samples were separated by electrophoresis and examined under UV light. PCR amplification was performed as previously described [30] .", "Foals. Blood counts were performed using a hematological counter (Poch 100iV Diff, Roche5). Hematocrit (Htc) was measured using the microhematocrit method. Leukocyte counts were performed using 100 cells, along with evaluations of erythrocyte, leukocyte, and platelet morphologies, in blood smears stained using quick Panotic dye (LaborClin5). Analysis of venous blood [blood pH, Htc, hemoglobin (Hb), partial pressure of CO 2 (PCO 2 ), partial pressure of O 2 (PO 2 ), total CO 2 concentration (tCO 2 ), oxygen saturation (SO 2 ), base excess, and HCO 3 , Na, K, and ionized calcium (iCa) concentrations] was performed with I-STAT EG7+ Cartridges (Abbott6, East Windsor, NJ, USA).", "2.6. Identification of Escherichia coli, Rhodococcus equi, Clostridium perfringens, Clostridium difficile, and Salmonella spp. For the culturing of Escherichia coli, fecal material was plated on defibrinated sheep blood agar and MacConkey agar and evaluated at 24, 48, and 72 hours [22] . In addition, microbiological culturing of the feces was performed using CAZ-NB selective media for Rhodococcus equi isolation [23] .", "For the isolation of C. perfringens and C. difficile, fecal material was diluted. Aliquots were plated in sulfite polymyxin sulfadiazine agar and in taurocholate cycloserine cefoxitin fructose agar and incubated anaerobically. Suspected Clostridium colonies were classified using conventional phenotypic methods [24] and were then analyzed by PCR for detection of the major C. perfringens toxin genes (alpha, epsilon, beta, and iota) and beta-2, NetB-, and enterotoxinencoding genes [25, 26] . For C. difficile, a multiplex PCR for a housekeeping gene (tpi), toxins A (tcdA) and B (tcdB), and a binary toxin gene (cdtB) was performed on all suspected colonies [27] ." ] },{ "paper_id": "b8a27d9cc6b79620fefffaf23778c2d799248682", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Where", "X n j\u00bc1 w i w j C\u00f0y i ; y j \u00de:", "PLOS Computational Biology |" ] },{ "paper_id": "b8a55c284d17093b3d9c033f5c74633f47aaabe3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Culture and quantification of microbial stocks. Microbial stocks were obtained from ATCC (Manassas, VA) or clinical laboratories, grown on appropriate media and quantified by standard dilution and colony-count methods [31] at Ibis Biosciences (Carlsbad, California) or Zeptometrix (Buffalo, New York). Stocks were stored frozen in 15% glycerol at -70\u00b0C, thawed and diluted into test matrices, and again stored at -70\u00b0C or tested immediately.", "Carryover testing was performed by testing adjacent negative and high positive samples. Positives were spiked with 10 7 CFU/sample of either KPC, VRE, or both MRSA and Candida albicans. The test configuration provided 104 independent opportunities to observe carryover events between adjacent high titer and negative samples. No carryover events were observed.", "Cross-reactivity was characterized with samples containing 10 5 CFU/ml, copies/ml, or TCID 50 /ml of a variety of fungi, bacteria, and viruses which the assay was not designed to report. These included Aspergillus flavus, Aspergillus niger, Clavispora lusitaniae, Candida kefyr, Caulobacter segnis, Pedobacter heparinus, Shewanella oneidensis, Streptomyces griseus, influenza, parainfluenza, adenovirus, parvovirus, coronavirus, and herpesvirus. No cross-reactivity was observed." ] },{ "paper_id": "b8a836a0c73faa4072e986d99664f892cef7a579", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Whole-blood PCR [6, 7] Hantavirus Serum PCR [8] Japanese encephalitis virus CSF ELISA [9] Mumps ", "Running title: Metagenomic NGS of sepsis patients of unknown cause Supplementary Figure 3: Viral detection by mNGS, which were then confirmed by viral specific PCR, in different clinical entities", "Scrub typhus Whole-blood PCR IFA of paired sera [3, 4] Rickettsiosis and murine typhus Whole-blood PCR [4, 5] Murine typhus IFA of paired sera [3] Bacteraemia" ] },{ "paper_id": "b8aeb68acc940bb4f4d68bb6e7bb89da81c5d12f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Feline Calicivirus (FCV), a member of the genus Vesivirus within this family, is a major agent of respiratory disease in cats, which replication originates also membranous rearrangements and vesicles [98] .", "Brome Mosaic Virus (BMV, family Bromoviridae) generates its replication factory by hijacking ER membranes, similar to what has been described for other plant viruses like Tobacco Mosaic Virus (TMV, family Virgaviridae) [99] , Tobacco Echt Virus (TEV, family Potyviridae) [100] and Red Clover Necrosis Mosaic Virus (family Tombusviridae) [101] . However, other plant viruses such as Alfalfa Mosaic Virus (AMV) [102] and Cucumber Mosaic Virus (CMV), both belonging to the family Bromoviridae, and Turnip Yellow Mosaic Virus (TYMV, family Tymoviridae) [103] anchor their replication sites on chloroplasts. Cucumber Necrosis Virus (CNV), family Tombusviridae, utilizes peroxisomal membranes as replication platforms [104] , while other plant viruses replicate on the surface of mitochondria [105] .", "Viral replication complexes are targeted to the respective membranous organelle primarily by nonstructural (NS) proteins rather than viral RNA [140] . These NS proteins seem to have some specificity in recognizing organelle subpopulations and often contain multiple hydrophobic domains implicated in membrane targeting and rearrangement. The molecular mechanisms orchestrating the formation of these complex structures are still poorly understood, but it is clear that NS proteins, often working in a concerted action, are key players in replication factory biogenesis." ] },{ "paper_id": "b8b5d71242ee50c531cab2c04176241bc48fc468", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cytokines released into the blood before and after IBDV challenge were analyzed by using chicken IFN-\u03b3, IL-2, IL-4, and IL-6 commercial kits (AndyGene, Beijing, China).", "The negative control, pPG612, did not express a corresponding immunoreactive band.", "accelerate the production of antibodies. However, the difference was not permanent and usually appeared at an early stage after immunization." ] },{ "paper_id": "b8e80e078c91d674918e69168da4085a9e176053", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nurses n = 264 Administrators n = 147" ] },{ "paper_id": "b8e929a5f023a12cfe584678c9dc89cf2b8afc6e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The genome of a PBV consists of two segments: segment 1 and segment 2. Segment 1 contains the capsid gene and another open reading frame which encodes a putative protein of an unknown function, 1 Throat swab 52 3 (5.8%) 0 (0%) Dog Nasopharyngeal swab 50 0 (0%) 0 (0%) Cat Nasopharyngeal swab 50 0 (0%) 0 (0%) Bat 2 Mouth swab 157 0 (0%) 0 (0%) Horse 3 Nasopharyngeal swab 116 0 (0%) 0 (0%) Poultry Chicken" ] },{ "paper_id": "b8e9c45dda9cb8c9c4321a55704ab2a66fb34f7d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This was a prospective, cross sectional, observational study using a convenience sample of febrile patients with clinical signs and symptoms of a URI. Children and adults were enrolled between January and November 2014 at 10 clinical sites in the US, including 7 academic emergency departments, 2 community urgent care centers, and 1 ambulatory clinical research site. Major inclusion criteria included: age >1 year, new fever \u2265 100.5 \u2022 F within the past 3 days, and new onset of cough or sore throat within the past 7 days. Major exclusion criteria included recent history of trauma or surgery, use of antibiotics, antiviral agents, interferon therapy, immunosuppressive therapy or a live viral immunization within the past 30 days. Full eligibility is listed in Supplemental Table S1 . The study was approved by the governing institutional review board for each enrolling center. Written informed consent was obtained from each participant or their legal authorized representative, as appropriate.", "Study personnel at the site obtained a whole blood sample by finger stick, performed FebriDx testing according to the manufacturer's instructions [6] , and interpreted the results as bacterial, viral or negative. Personnel performing FebriDx testing were blinded to all reference testing outlined below. FebriDx results were not used for clinical care.", "Confidence intervals for sensitivity, specificity, and predictive values were calculated using the binomial exact method. Confidence intervals for kappa statistics were calculated by bootstrap with 1000 replications [28] . Statistical analyses were conducted with Stata 12 (StataCorp, College Station, TX, USA)." ] },{ "paper_id": "b8e9fcc34571f9c29e04f9feb34197250556cb9a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SAPN were synthesized and assembled as previously described [11] . Gold-encapsulating SAPN were synthesized [17] by first denaturing PfCSP-SAPN overnight in 9 M urea, 20 mM HEPES, pH 7.5, 50 mM NaCl, 5% glycerol. Next, the protein monomers were concentrated to 1 mg/ml using Amicon MWCO 3000. After concentration the monomers were diluted 20-fold into 20 mM HEPES, pH 7.5, 50 mM NaCl, 5% glycerol containing 10 nm citrate-coated gold nanoparticles (Nanocs, Inc via Thermo Fisher Scientific, Inc, Pittsburgh, PA, USA). The final molar ratio of protein chains per gold nanoparticle was 420:1. Dialysis was performed overnight in 20 mM HEPES, pH 7.5, 50 mM NaCl, 5% glycerol to remove the remaining urea. The gold-encapsulating SAPN were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS).", "Female C57BL/6 mice five to six weeks of age, sex-and age-matched from the Jackson Laboratory (Bar Harbor, ME, USA) were injected ip or im with 10 \u03bcg/mouse PfCSP-SAPN or sterile saline, for a total of three immunizations administered two weeks apart. Blood was drawn for antibody analysis one day prior to each immunization and two weeks post final immunization via tail vein nick. All animal protocols were conducted following review and approval by the WRAIR IACUC.", "Serum antibody levels were determined following PfCSP-SAPN immunization by ELISA. Anti-PfCSP antibody isotype profiles were determined using IgG1, IgG2c, IgG3 and IgE isotype-specific goat anti-mouse horseradish peroxidase-tagged secondary antibodies (Southern Biotech, Birmingham, AL, USA). Color change was initiated with ABTS Peroxidase Solution (KPL, Gaithersburg, MD, USA) and analysed by absorbance OD 405 =1." ] },{ "paper_id": "b8ee195be637c05754e714310c9d0d5ba715d683", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b8efd7ebd2057d44c6544e918c3631ac395c7fb2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. Graphpad Prism 6.0 software was used to calculate P values using the Log-rank Mantel Cox test. Each treatment group was compared to the corresponding PBS control for either Study #1 or #2. P values > 0.05 are considered non-significant (ns).", "Purified filovirus GP antigen preparation. All filovirus ectodomains for ELISA, western blot, EM, or DXMS were produced at TSRI in Drosophila S2 cells [16] , with the exception of Musoke GP, which was produced by IBT in Sf9 cells (as described above for Musoke GP\u0394muc). Briefly, Effectene Reagent (Qiagen) was used to transfect S2 cells with pMTpuro plasmids containing a strep-tagged filovirus GP gene of interest, followed by stable selection of transfected cells with 6 \u03bcg/ml puromycin in Insect XPRESS protein free medium (Lonza). Secreted GP ectodomain expression was induced with 0.5mM CuSO4 and supernatants harvested after 4 days. Proteins were affinity purified using Streptactin resin (Qiagen), followed by purification via Superdex 200 SEC in 1x TBS. The cleaved \"core\" ectodomain for MARV (MARV GPcl) was produced by incubating 1mg Ravn GPe\u0394muc with 0.01 mg trypsin (Sigma) at 37\u00b0C for 1 hour in TBS pH 7.5, followed by S200 SEC purification. The cleaved \"core\" ectodomain of EBOV (EBOV GPcl) was produced by incubating 1mg EBOV GPe\u0394muc with 0.02mg thermolysin (Sigma) overnight at room temperature (RT) in TBS buffer plus 1mM CaCl 2, followed by S200 SEC purification. SDS-PAGE gels comparing purity and molecular weight of several antigens in shown in S1 panel B.", "Purified Ravn GPcl was evaluated by Deuterium Exchange Mass Spectrometry (DXMS) as previously described [24] .", "This study was approved and carried out in accordance with protocols provided by the Institutional Animal Care and Use Committee (IACUC) at TSRI, Emergent Biosolutions, NIAID, and USAMRIID. Research at USAMRIID was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals, and adhered to principles stated in the Guide for the Care and Use of Laboratory Animals, National Research Council, 1996." ] },{ "paper_id": "b8fecbc5515e46b4dd16b9e11b4b1ce9a576e6d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A previously developed questionnaire used by Jazieh AR et al. (2012) , which was based in Jazieh AR et al. (2004) , was modified to include patients with hematological malignancies and those undergoing hematopoietic stemcell transplantation (HSCT), translated into Arabic and translated back to English for consistency [17, 19] . The questionnaire was administered to 15 participants and was subsequently adjusted to overcome inconsistency and to ensure reliability.", "The research coordinators collected demographic and disease profile data from medical records and used the validated questionnaire in a face-to-face interview with the participants (Additional file 1).", "Responses to all questions were reviewed to avoid missing data before the end of each participant's interview. Data were entered into a Microsoft Access database and peer reviewed for quality checking. Validity constraints were applied to the database to ensure accuracy and consistency. The data were then exported to IBM SPSS Statistics for Windows, version 22.0 (Armonk, NY, USA) for analysis." ] },{ "paper_id": "b90bc6d84f996cb85c97b94b98f976c7d93367a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ovine aortic endothelial (ovEC) cells were isolated by collagenase treatment using a method adapted from Gillespie et al. [50] . Aortas were harvested from recently euthanized animals and washed twice in sterile PBS. The aortas were then incubated at room temperature for 1 h in DMEM supplemented with 5% FBS, 25 mg/ml penicillin/streptomycin and 50 ng/ml amphotericin B. After incubation, the aortas were placed into collagenase in a Petri dish (2 mg/ml in DMEM) for 1 h at 37uC. After incubation, the endothelial cells were removed by scraping and seeded in 6-well plates. Cells were maintained at 37uC and 5% CO 2 in large vessel endothelial cell basal medium (TCS cellworks) supplemented with 20% FBS, human large vessel endothelial cell growth supplement (TCS cellworks), 25 mg/ml penicillin/streptomycin and 50 ng/ml amphotericin B. Cells were confirmed as endothelial cells by assessing their morphology using light microscopy and by immunofluorescence using antibodies against endothelial and smooth muscle cell markers. Cells used for this study were only passaged once.", "Approximately 30 percent of all infectious diseases that emerged between 1990 and 2000 were caused by arthropod-borne viruses (arbovirus) [1] . This is probably the result of a combination of factors including a dramatic increase in travelling and commercial exchanges, climate and ecological changes and increased livestock production. In addition, changes in trading and commercial policies have created optimal conditions for the movement of infected vertebrate hosts and invertebrate vectors over wide geographical areas.", "The 293T, 2fTGH, BHK-21, BSR and MDCK cell lines were grown in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS). BSR-T7/5 (provided by Karl Conzelmann) cells stably expressing the T7 polymerase were grown in Glasgow modified Eagle's medium supplemented with 10% FBS, 10% of tryptose phosphate broth and G418 at a final concentration of 1 mg/ml. Sheep choroid plexus cells (CPT-Tert) were grown in Iscove's modified Dulbecco's medium supplemented with 10% FBS (provided by David Griffiths) [48] . Bovine fetal aorta endothelial cells (BFAE, Health Protection Agency collection number 87022601) were cultured in Ham's F12 medium supplemented with 20% FBS. Ovine trophoblast cells, oTr-1, (provided by Thomas Spencer) [49] were cultured in DMEM/F12 media supplemented with 15% FBS, 1 mM pyruvate, 700 nM of human recombinant insulin and 0.1 mM of nonessential amino acids. All cell lines were cultured at 37uC in a 5% CO 2 and 95% humidified atmosphere and were supplemented with 10,000 U/ml of penicillin and 10 mg/ml of streptomycin." ] },{ "paper_id": "b92029ab36511c3072b0a3cba99c6dbca29097cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells containing more than two ATG8-speific puncta were defined as autophagy-positive cells. The number or the percentage of the cells showing the ATG8-positive signs were counted under a fluorescence microscope [50] .", "All relevant data are within the paper and its Supporting Information files.", "All data were analysed with SPSS, version 17.0. Percentage data were arcsine square-root transformed before analysis. Multiple comparisons of the means were conducted based on Tukey's honest significant difference (HSD) test using a one-way analysis of variance (ANOVA). The data were back-transformed after analysis for presentation in the text and figures." ] },{ "paper_id": "b92be96a5b5d040400b1eed4feff463fd3505b3b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All analyses were performed using the ESRI\u2122 suite of ArcGIS 10.3 software and Stata/SE Software version 12.1 for Windows\u2122.", "Predictors Coefficient (95% C.I.)", "Descriptive statistics were reported as frequency and percent for categorical variables and as mean and standard deviation or medians and interquartile range (IQR) as appropriate for continuous variables. Thereafter, social, environmental and clinical variables were compared by sex, by mild/severe genotype, and by rural/urban residence of participants. Mean, medians and frequencies were compared using two-sample t-test, the Wilcoxon rank sum test, and the chi-squared test as applicable." ] },{ "paper_id": "b936109e0b0de2cb59b2ed271614bb710e8e04af", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ambient temperature in the arrivals hall was a consistent 20.5uC at all times during data collection.", "Influenza-positive participants reported that the first of their symptoms started between 12 hours and 24 days prior to answering the questionnaire, with symptom duration of 2 days or less in 11 participants, more than 2 and up to 5 days in 7 participants, and more than 5 days in 8 participants (3 were asymptomatic and 1 did not respond to this question).", "Can thermal scanning predict core temperature?", "Background: Infrared thermal image scanners (ITIS) appear an attractive option for the mass screening of travellers for influenza, but there are no published data on their performance in airports." ] },{ "paper_id": "b94abc8c5e511d49e02cc4175cccc27629f5ee76", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One-day-old specific pathogen-free (SPF) chickens were obtained from the Laboratory Animal Center, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences (Harbin, China). All animal experimental procedures were approved by the Ethical and Animal Welfare Committee of Heilongjiang Province, China.", "Microarray data were subjected to bioinformatic analysis to identify statistically significant changes in gene expression between samples using GeneSpring GX 11.0 software (Agilent Technologies). Annotations for the microarray genes were downloaded from the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/), the Gene Ontology (GO) (http://www.geneontology.org/), and UniProt (http://www.uniprot.org/) databases. The GO category (http://www.geneontology.org) based on biological process and KEGG (http://www.genome.jp/ kegg/) pathway analysis was determined for differentially expressed genes and a probability (p)-value < 0.05 and a false discovery rate (FDR) < 0.05 was used as a threshold. Gene interaction networks were analyzed using the STRING (http://string-db.org/) database of known and predicted protein interactions, which included direct (physical) and indirect (functional) associations." ] },{ "paper_id": "b94bee4f159369de60f7d9e7cc5733676dfa15b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In this review, we have attempted to summarize examples of novel drug delivery systems. These systems share two main properties: they target a specific cell or tissue and their structure carries a CPP.", "For instance, Laakkonen and Ruoslahti have addressed new homing peptides that specifically recognize tumoral vasculature, tumoral cells or that are even able to distinguish between different stages of cancer [17] . For this purpose, they have worked extensively with phage display peptide libraries for in vivo screening, and have described several peptides of interest. Table 1 summarizes some examples within the lymphatic vasculature of several tumors. Combinations of targeting peptides and a CPP may provide a new approach to design specific drug delivery vectors. The level of specificity achieved would be selected by the type of tumor-homing peptide, which could be customdesign for each patient before the treatment.", "Bieker et al. [40] recently generated the fusion protein tTNF-NGR (the extracellular domain of tissue factor (truncated tissue factor, tTNF) and the peptide GNGRAHA, that contains the NGR motif), which targets tumor endothelial cells. tTNF-NGR inhibits tumor growth in mice by thrombotic occlusion of tumor vessels without any major side effects. It has also been reported to inhibit tumor perfusion in the first patients treated with this molecule [40] . With all these examples, NGR-containing peptides provide a good tool for tumor targeting of drugs and drug delivery systems.", "This mitochondrial cytotoxic peptide, D-(KLAKLAK) 2, was also coupled to the heptapeptide SMSIARL [53] , isolated from an in vivo phage display peptide library, and specific target for the prostate vasculature. When this peptide was coupled to D-(KLAKLAK) 2, only prostate tissue was destroyed. In prostate-cancer-prone transgenic TRAMP (transgenic adenocarcinoma of the mouse prostate model, [54] ) this chimeric peptide postponed cancer development, thereby suggesting a potential alternative to the surgical approach used to treat this disease [53] ." ] },{ "paper_id": "b94f30c95a54f9daa2912c96c63520d8e80c7146", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "b950247dbac25ce91de13806e102102a757c16ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human coronaviruses constitute a grave threat to public health, a situation exemplified by the outbreaks of SARS-CoV in 2003 and MERS-CoV in 2012. To date, however, there is still no specific antiviral treatment or vaccine available for human CoV infection 2, 22 , and the current standard of care for affected individuals focuses on symptom relief and, in severe cases, support for vital organ function 2, 22 .", "treatment at 6 h.p.i. was harvested and diluted to proper concentrations to determine the amount of IL-6 secreted using enzyme-linked immunosorbent assay kit for porcine IL-6 (R&D Systems, Inc.), per the manufacturer's recommendations.", "Coronaviruses are animal viruses containing an enveloped, positive-sense, single-stranded RNA genome; and include the common cold human coronavirus (CoV)-229E & CoV-OC43, severe acute respiratory syndrome (SARS) CoV, Middle East respiratory syndrome (MERS) CoV, porcine transmissible gastroenteritis virus (TGEV), and murine hepatitis virus (MHV) etc 1-3 . Since the 2003 SARS outbreak (which had a mortality rate of ~10%), novel anti-SARS-CoV treatments have been vigorously pursued. No new cases of SARS have been reported since the 2003 outbreak, but another novel coronavirus (MERS-CoV), this time with a mortality rate of ~35%, came to light in 2012 4 . To date, neither a commercially available vaccine for human coronaviruses nor a specific treatment for SARS-CoV or MERS-CoV is available." ] },{ "paper_id": "b952307f004f6feab9b3ae2cbee6d14f28ef9b4d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We thank all the lab members from LY's lab for discussing this manuscript. This study was supported by grants from the National Key ", "All of our studies were specifically reviewed and approved by the Institutional Animal Care and Use Committees of the Third Military Medical University.", "QH, JH, and JT wrote and edited the manuscript with LX and LY." ] },{ "paper_id": "b95e82e0343a470f5b39c97eae9f8541e218b76d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The virus exits the cell via exocytosis. Research on coronaviruses has greatly increased since 2003 due to the emergence of severe acute respiratory syndrome (SARS) caused by a zoonotic transmission of an animal coronavirus into the human population [10] .", "CCoV-II viruses (such as 1-71) typically grow readily in cell culture, with A-72 cells (canine tumor fibroblast cells derived from unknown tissue type) widely used for virus propagation. 1-71 also grows well in a variety of feline cell lines (e.g., CRFK), but, interestingly, not in many other canine cell lines [29] .", "CCoV is generally thought of as a mild, but highly contagious, enteritis of young dogs, most often under 12 weeks of age [2, 60, 61] . In some cases, CCoV infection can be fatal, particularly in puppies co-infected with other pathogens such as canine parvovirus [62, 63] . Therefore, the range of clinical signs from loose stools to severe watery diarrhea with high morbidity and variable mortality is mainly determined by the age at the onset of infection, the level and type of pathogen exposure, and the degree of maternal transfer of immunity.", "The receptor determinants for the serotype I FCoV/CCoV group are much less certain. While there is some evidence for fAPN as an FCoV type I receptor [43] , other studies have concluded that there is a distinct receptor for FCoV type I [48, 49] . Overall, receptor determinants for CCoV type I viruses remain essentially unknown." ] },{ "paper_id": "b9642bbf29d039de465c0b9cd7ab98ba0b81cd09", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinicians should review immunization records, if available, to determine if the vaccine doses and intervals are consistent with the age-appropriate immunization recommendations of the U.S. Advisory Committee on Immunization Practices (ACIP) and other national guidelines [23, 31, [110] [111] [112] .", "According to the U.S. Immigration and Nationality Act of 1996, for refugees with absent records or incomplete immunization status, a single vaccine dose in a series recommended by the U.S. Advisory Committee on Immunization Practices (ACIP) suffices for the immigration process, with a plan to complete the remaining doses in a series and catch-up vaccinations [23, 31, 113] .", "Any child with a positive TST or IGRA warrants further evaluation by performing a physical examination and obtaining a chest radiograph to exclude TB disease. Given the high prevalence of drug-resistant TB in many countries, efforts to isolate the pathogen via obtaining sputum samples (via early morning gastric aspirates or sputum induction) for drug susceptibility testing is crucial [12, 23] . Applicants diagnosed with active TB must complete treatment via directly observed therapy prior to arrival in the U.S. [29] .", "Public health programs are crucial for implementation of the screening and evaluation of migrants for infectious diseases. Historically, screening and quarantine procedures were performed utilizing port-of-entry strategies at the time of arrival of ships [114] . However, given the different routes of travel and dramatic increase of newly arriving migrants, the effectiveness of this strategy is limited [115] . For more than two decades, the U.S. Centers for Disease Control and Prevention's Division of Global Migration and Quarantine has implemented a health assessment framework (overseas screening, treatment, and immunization programs) to improve health for US-bound immigrants and refugees [29] . This program has had many successes, including decreased TB rates in the U.S., decreased transmission and importation of VPDs, reduction in morbidity from parasitic diseases, and reduced domestic healthcare costs [116] .", "The reported outbreak of measles among Somali children in Minnesota who were not up to date on measles-mumps-rubella (MMR) vaccinations due to safety concerns (erroneous link to autism) highlights the need to develop enhanced community outreach and education with families and Somali community leaders to address vaccine hesitancy, provide health education, and improve vaccination rates [86] . Studies with a rigorous study design must be conducted to assess interventions to successfully implement vaccination programs for migrant populations [125, 126] . In conflict zones and complex humanitarian emergency settings, the implementation of mass immunization campaigns has resulted in controlling the outbreaks of wild polio virus and circulating vaccine-derived poliovirus infections, suggesting that innovative approaches to vaccinate children on the move are needed [127, 128] . Cost-effective interventions to address health care disparities and provide high-quality primary and secondary health care for large numbers of recently arrived migrants remains a major priority for many high-income countries [10, 11, 28, [129] [130] [131] [132] ." ] },{ "paper_id": "b973a418c19776904cffc71357c7119485bf2b3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(H1): if ( ) \u2208 , then rank 1 < 2 < \u22c5 \u22c5 \u22c5 < ; The algorithm starts from (H1). If ( ) is full or ( ) is closed, then ( ) will be removed from and the algorithm returns to (H1). (H4) illustrates that individuals would choose the feasible location with the minimal travel time.", "The main characteristics of EVD include short incubation, high mortality, and fluid shift. In this section, the course model along with propagation model will be established.", "Let \u27e8 , \u0394 , \u27e9 be an activity of individual ( ); then its behavior schedules ( ) are formalized as" ] },{ "paper_id": "b9774fe2b5e6e752ff1e59bd6b2e46d7815b4a49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that they have no competing interests. ", "Differences were assessed for significance using chi-square goodness of fit and non-parametric binomial tests, where appropriate. Statistical analyses were performed using SPSS, version 21 software (IBM Corp., Armonk, NY, USA). P < 0.05 was considered statistically significant.", "Authors' contributions FA carried out the study design, data management, and data analysis, and helped to draft the manuscript. NM, FAl, RM analyzed the data and drafted the manuscript. All authors read and approved the final manuscript." ] },{ "paper_id": "b9795ebc63bc667ed27545d63f287cacf8604d62", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "4These authors are co-senior authors of this paper.", "Four supplementary tables are available with the online Supplementary Material." ] },{ "paper_id": "b97ac8d30646b2d3cc9ab2f7447534e9ecefbeee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Interferon-induced transmembrane protein 6", "Iqgap2 IQ motif-containing GTPase activating protein 2" ] },{ "paper_id": "b9881ca556b8d6e74c2fe3b9c2195429fcb0d09d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Blood samples were routinely sent for bacterial culturing, as were tracheal aspirates if the patient was intubated." ] },{ "paper_id": "b98f753cf246353e2ffff6822aeff4f2f3c5a7b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics statement. All mice experiments were approved and performed in accordance to the guidelines provided by Institutional Animal Care and Use Committee of National University of Singapore (Protocol No. 023/12).", "administration of 15 \u03bc g/g CPMO1v strongly protects against CHIKV disease in our murine model during the acute phase.", "Scientific RepoRts | 5:12727 | DOi: 10 .1038/srep12727" ] },{ "paper_id": "b9a74f1f03a9b75351badb02e13448d1f65f7ed8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "S. pyogenes, an external Streptococcus also known as Group A streptococcus (GAS), causes many diseases, ranging from mild superficial skin infections to life-threatening systemic diseases 30 . It also causes post infectious non-pyogenic syndromes, including rheumatic fever and acute post infectious glomerulonephritis 31 . Its pathogenicity is associated with several GASs common (e.g., Streptolysin O and S) and specific (e.g., Streptococcal pyrogenic exotoxin A and C 32 , and Streptococcal chemokine protease 33 ) virulence factors that enable the bacterium to attach to host tissues, evade immune responses, and spread by penetrating into tissue layers.", "Scientific RepoRts | 5:15820 | DOi: 10.1038/srep15820", "Generating PRLs. Each pair of samples containing one infection sample and one corresponding control sample was considered an instance. We paired infection samples and control samples in accordance with five principles:" ] },{ "paper_id": "b9a8782661a61d1562b8d6a2098fd35c76b35349", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "August 2012 | Volume 3 | Article 277 | 4 most (red) and least (blue) abundant VDJ types existing in the germline-lineaged repertoire for the corresponding IGHV genes used in association with different IGHD and IGHJ genes. The IGHV genes V1-69 and V1-2 were frequently found to recombine with IGHJ genes J4 and J6, and IGHD genes D3 and D6.", "Translated heavy and light chain variable sequences from the 454 sequencing that shared the IGHV genes of selected antiviral antibodies and associated immunogenetics data including the details of germlines, HCDR3 lengths, and mutations were retrieved from the database by using SQL. Sequence identities between the 454 sequence data and germlines were calculated based on the pairwise alignment using local BLAST as implemented in BioEdit v7.0.9 (Hall, 1999) . Phylogenetic analysis was carried out using the Archaeopteryx software (Han and Zmasek, 2009 ).", "For quality control of antibody sequences, we trimmed the 454 sequence data and retained only sequences of length more than 300 nucleotides (nt), covering the entire antibody variable domains consisting of the three complementarity determining regions (CDR) along with framework regions (FR). We used IMGT/HighV-QUEST (Alamyar et al., 2012) , a high-throughput version for deep sequencing NGS data analysis resource for the immunogenetic analysis. The output results from the IMGT/HighV-QUEST analysis in CSV files were stored at PostgreSQL database, and Structured Query Language (SQL) was used to retrieve the data for the further analysis. Heatmap generation and statistical calculations involving distributions of antibody HCDR3 lengths and mutations were carried out using SAS JMP10\u00ae statistical software (SAS Institute, Cary, NC)." ] },{ "paper_id": "b9ac24a16dd729a1db737ead634eaa577b00febd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A sociodemographic inventory and a medical history were taken, and a routine physical and laboratory examination (i.e., blood pressure, ECG, clinical chemistry and hematology tests, and urinalysis) was performed by the investigators as a baseline for future toxicology screening.", "Interventions. All patients received 12 g packages of granulated XTJYF or placebo twice a day for eight weeks [39] and were instructed to drink the contents dissolved in warm, boiled water.", "During the trial, patients were closely monitored for adverse events (AEs) and worsening of symptoms. The time of onset of any observed or spontaneously reported AE, its duration and severity, any action taken, and the outcome were recorded.", "Gan-Cao (Radix Glycyrrhizae preparata), and Sheng-Jiang (Rhizoma Zingiberis recens). Our modification, XTJYF, contains all the herbs of the original formula, except Sheng-Jiang, plus additional seven herbs, including Fa Ban-Xia (Rhizoma Pinelliae preparatae) and Chen-Pi (Pericarpium Citri reticulatae), that are commonly used for psychological disorders (see Table 1 )." ] },{ "paper_id": "b9b2738ea98d39ed9c2080bc308e1f57dcc512d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Emergency Response Level (a) viral strain capable of rapid and effective human-to-human transmission. (b) Influenza pandemic declared by WHO.", "Evanson Z. Sambala http://orcid.org/0000-0002-0363-0812 Lenore Manderson http://orcid.org/0000-0002-7883-1790", "ARTICLE HISTORY", "-To contain the disease as soon as possible, identify foci of infection, prevent local transmission and exportation of disease to other places." ] },{ "paper_id": "b9b85a4893f9ed75881adcedbf142098bd7edc93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Hepatitis C virus (HCV) is a blood-borne flavivirus that infects many millions of people worldwide. Relatively little is known, however, concerning the stability of HCV and reliable procedures for inactivating this virus.", ", and 65\u00b0C, respectively. At designated time points, aliquots were removed, transferred immediately into icewater bath to stop the effect of heat, and then subjected to FFU assay for virus titration." ] },{ "paper_id": "b9c267b7dcc9a8348248c04a8bf604aa52926101", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data generated or analyzed during this study are included in this article and its Supplementary Information files.", "The diagnostic code (i.e., relapsing-remitting MS [RRMS], SPMS and primary-progressive MS [PPMS], HV, NIND, and OIND) was broken only after the functional data were acquired." ] },{ "paper_id": "b9eaf7c97ff51c43bbcf3ed0605c2a040fe8c588", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics. All animal methods and care described in the present study were carried out in accordance with national guide. They were approved by the Institutional Animal Care and Use Committee of National Cheng Kung University (IACUC No. 100-135)." ] },{ "paper_id": "b9f063ab66715b75706b11ab3b0a2af52294cd5b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The MYSQL relational database version 5.0.45 (http:// www.mysql.com) was used in the current study to design and construct the SheddomeDB database and the interactive web interface. A JAVA-based model-view-controller (MVC) framework was utilized for the web interface to separate the logic, application, and the presentation into three distinct layers. All the interactions between the web client requests and the server side were handled by Apache web server. The dynamic web pages were designed using JavaServer Pages (JSP) and Cascading Style Sheets (CSS), and the user-interactive pages were supported by JavaScript and its library jQuery for client-side scripting." ] },{ "paper_id": "b9fb16bb3df1fc1af7dd479e06c120f376362880", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For other viruses, nucleotide identities with the closest sequences deposited were low: AstV3 (91%), AstV4 (89%), SAV (87%), EntVG (82%) and PasiV (86%) except for PosaV (96%), AstV5 (97%) and PEDV (99%) which were very similar to other European sequences reported. Figures 7 and 8 show the phylogenetic trees for SAV and AstV3, respectively.", "Additional file 1: Summary of the 51 samples analyzed: name, origin, RNA viruses detected and number of reads indexed.", "Supplementary information accompanies this paper at https://doi.org/10. 1186/s12917-019-2204-2." ] },{ "paper_id": "b9fe40055b01585084db291401c57f26d25fe478", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2) ", "The next generation matrix, G, is given as follows.", "Then, we derive R eff from G." ] },{ "paper_id": "ba03011c4b23d19642ea33554a6789895558ad97", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza A viruses of the H5N1 A/HongKong/483/97 (H5N1), A/Viet Nam/1203/04 (H5N1), A/Anhui/1/2005 (H5N1), and A/ Indonesia/5/2005 (H5N1) were grown in the allantoic cavity of 10day-old embryonated hen eggs at 37uC for 26 to 40 h. Allantoic fluid pooled from multiple eggs was clarified by centrifugation and frozen in aliquots at 270uC. The 50% egg infectious dose (EID50) for each virus stock was calculated by the method of Reed and Muench following serial titration in eggs. All experiments with HPAI viruses were conducted under Biosafety Level 3 containment.", "Cross-protection by a polyvalent DNA vaccine formulation expressing HA antigens from three representative H5N1 viral isolates", "This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the University of Massachusetts Medical School's Institutional Animal Use and Care Committee (IACUC) (Protocol: A-1674). All surgery was performed under sodium pentobarbital anaesthesia, and all efforts were made to minimize suffering.", "Hemagglutination-inhibition (HI) assay HI assays were performed by standard methods [50] . Briefly, the assay was performed using, 0.5% v/v fowl or horse [30] red blood cells, 4 HA unit of reference H5N1 virus (A/HongKong/ 483/97, A/VietNam/1203/04, A/Anhui/1/2005, A/Indonesia/ 5/2005) and specific sera treated with receptor destroying enzyme. The HI titer was defined as the highest dilution of the serum able to inhibit hemagglutination." ] },{ "paper_id": "ba1a34ae67fb2dcd9ad6cdf6d5b5e1fc32202839", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNAs were extracted using TRIzol reagent (Invitrogen). Real-time RT-qPCR was performed using SYBR Green Real-Time PCR Master Mix (Toyobo Biologics, Osaka, Japan) in the ABI PRISM 7000 sequence detection system (Applied Biosystems). Individual transcripts in each sample were assayed three times. The fold change in gene expression relative to normal was calculated using the delta-delta cycles to threshold (\u0394\u0394CT) method. Primers ( Table 2) were designed using Primer Express software (version 3.0; Applied Biosystems, Carlsbad, CA, USA).", "All animal experiments were approved by the Hubei Administrative Committee for Laboratory Animals (permission number 00024534) and complied with the guidelines of Hubei laboratory animal welfare and ethics of Hubei Administrative Committee of Laboratory Animals.", "acKnOWleDgMenTs" ] },{ "paper_id": "ba2009991ed471ace18c92633780cd180404c4a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analyses were performed using the paired onetailed Student's t test as previously described [29] . P values less than 0.05 were considered statistically significant. Results were presented as mean values 6 the standard deviation (SD) of at least three independent experiments.", "Cell Line, Virus and Monoclonal Antibodies 293 T cells were used for infection and cultured in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% heatinactivated fetal bovine serum (FBS, Hyclone) in a humidified incubator at 37uC under an atmosphere of 5% CO 2 . Genotype VII NDV strain (isolated in our lab) was propagated in the allantoic cavities of 9-to 10-day old specific pathogen free (SPF) embryonated chicken eggs and kept at 220uC for RNA extraction and neutralization assay. Monoclonal antibodies (mAbs) against HN and F were a kind gift from Dr. Shunlin Hu (the University of Yang Zhou).", "Newcastle disease virus (NDV) belongs to the Paramyxoviridae family. It has been found worldwide since its first report among poultry in the areas of Java, Indonesia, and England in 1926. This virus has an extensive range of susceptible hosts, with 27 of the 50 orders of birds reported to be capable of infection by NDV [1] , making Newcastle disease (ND) a global animal health concern. Although the vaccination of chickens is performed throughout the world, this disease still remains endemic in poultry in many regions. According to the severity of disease in chickens, isolates of NDV can be categorized into three pathotypes: the lentogenic (avirulent), mesogenic (intermediate virulence), and velogenic (highly virulent) strains. Infections with velogenic strains have had devastating effects on the poultry industry due to the high rates of morbidity and mortality. Thus, virulent NDV isolates are notifiable to the Office of International Epizootes (OIE) with obligatory control measures upon the occurrence of outbreaks of the disease." ] },{ "paper_id": "ba24b8b4f656dd857e9b151c22c0619b88c63f65", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses are unique organisms that have various effects on living things, such as microorganisms, plants, animals, and human beings [1, 2] . Since the beginning of the history of living things, viruses and living things have affected each other, leading to the evolution of advanced organisms, such as the immune system and population [3] . Nowadays, various local virus mutants are arising because of globalization and the development of worldwide transportation systems [4, 5] . Humans can visit anywhere in the world very conveniently by airplane and can be easily infected by endemic viruses. When the infected human returns to their home country, the endemic virus from another place can easily settle down in their home and spread to new hosts [6] . Influenza virus is one of the general viruses in human life that can be easily infected from human to human [7] . The influenza virus can be ", "antibody-immobilized FET (>50 pM) [51] . The smaller sizes of glycans (~2 nm) compared to those of antibodies (4-12 nm) allows for sensitive detection based on FET sensors because of the densely immobilized receptors and the proximity of target biomolecules to the sensor.", "Lin et al. developed a Si nanowire FET for the detection of high pathogenic strain virus (H5 and H7) DNA of AI, down to an LOD of 1 fM [47] . The ultrahigh sensitive detection of DNA is attributed to the high surface-to-volume ratio of Si nanowires, resulting in a high current change due to a field effect. Poly-crystalline Si nanowires were fabricated through the sidewall spacer technique, which enables the definition of the nanosized patterns without needing to employ an expensive lithography process. AIV H5-and H7-captured DNA probes were immobilized on the Si nanowires. The increased negative charges due to hybridization between target DNA and the captured DNA probes resulted in a current change of the Si nanowire FET biosensor. They confirmed the selectivity of the sensor with control experiments in which the transfer curves of the unmodified Si nanowire FETs remained unchanged in PBS buffer as well as in the presence of H5 and H7 target DNA. Ahn et al. developed a silicon nanowire FET-based biosensor to detect anti-AI in real-time [48] . The drain current of the FET changed upon injection of an anti-AI solution onto the device functionalized with the antigen of AI." ] },{ "paper_id": "ba29366173f97f54a22e5c410b3d05e9a9649d28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2) = 42.39, p < 0.001) and sampling week (X 2 (1) = 38.43, p < 0.001), including their interaction term (X 2", "The deformed wing virus (DWV) is a prevalent virus in honeybees with a broad host range spanning at least eight insect orders and three orders of Arachnida [17] [18] [19] [20] [21] . This virus is a positive sense single-stranded RNA virus and a harmful honeybee pathogen [22] , of which at least three distinct genotypes or master variants-type A, B, and C-are known [21] . DWV can cause clinical symptoms such as crippled wings, a shortened abdomen, and a reduced host lifespan [22] [23] [24] . Driven by efficient vector transmission via ectoparasitic mites Varroa destructor, DWV has become ubiquitous [25] [26] [27] [28] ." ] },{ "paper_id": "ba2d0f6467116c99ad6bc4df52b616cc683aecb5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Once collected, brushes and swabs were immediately stored at -80\u02daC prior to further processing.", "DNA was extracted from both swabs and brushes using the MPBio FastDNA\u2122 spin kit for soil as per the manufacturer's instructions." ] },{ "paper_id": "ba2d3601f5ae3bb5964c8515431abe352bad9437", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pone.0199579.g004", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Temperature " ] },{ "paper_id": "ba2f1457928b26ae7f4ad64983bac74a4e383378", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thus, the overall number of clones required for screening is substantially reduced.", "Finally, the intrinsic properties of each protein, if available, were closely scrutinized.", "Therefore, proteins with hypothetical character were predominantly chosen, as information on them is confined. In addition, all types of membrane-associated proteins deserved a better look, as these type of proteins offer a more direct route and accessibility, which might be of utmost importance in a future rapid point-ofcare device detecting whole organisms." ] },{ "paper_id": "ba2fc738765a5e090d04ad70d972bb35724d927a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animal migrations have the potential to enhance the global spread of pathogens and facilitate cross-species transmission [1] . Infectious diseases associated with wild birds have been particularly studied as these hosts can disperse infectious agents over long distances (e.g. avian influenza virus, West-Nile virus, Borrelia burgdorferi, or Plasmodium parasites); however, current knowledge on the role of seabirds in the transmission and dispersal of infectious agents remains limited.", "Of the 209 collected blood samples (Table 1) hippoboscid flies tested positive for the presence of Haemoproteus.", "Partial Cytochrome b (for parasites) and Cytochrome Oxidase I (for Hippoboscid flies) gene sequences were aligned using CLC 6.0.1. (CLC bio, Aarhus, Denmark). Maximum likelihood analyses were performed with the software PhyML 3.0 [16] . Nucleotide substitution models were selected with Model Generator 0.85 [17] and nodal supports assessed with 1000 bootstrap replicates. Nucleotide sequences generated in this study were deposited in Genbank under accession numbers KF725664 to KF725686.", "Blood films were collected for the 30 frigatebirds we sampled in 2012 on Europa (Table 1) . These films were fixed in absolute methanol in the field, stained with Giemsa back in the laboratory, and examined at high magnification (x1000) in order to assess the number of parasites per at least 10000 red blood cells [5, 18] . A Euromex Oxion microscope (Euromex Microscopen BV, Arnhem, The Netherlands) was used to examine slides." ] },{ "paper_id": "ba3179ae7ea6877b7b76e048959e97cc0012f5fc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DNA from each process was amplified with Platinum Taq DNA Polymerase High Fidelity (Thermo Scientific) using m13 primers and the following program: 2 min 95\u02daC, 30 cycles of 15 sec at 95\u02daC, 30 sec at 50\u02daC, 3 min at 68\u02daC and a final step of 5 min at 68\u02daC. DNA was quantified by Qubit dsDNA HS Assay Kit (Thermo Scientific), and length fragment was evaluated with Agilent High Sensitivity DNA Kit (Agilent Technologies).", "Four representative viruses were used to compare the genome coverage and depth. Contigs were ensembled to generate partial consensus genomes of RV-C (97% coverage, 6,824 bp) (S1 ", "One hundred and twenty respiratory samples were grouped into seven pools: asthma 2014 (A2014), asthma 2015 (A2015), pneumonia 2014 (P2014) and pneumonia 2015 (P2015) each one with qPCR positive (qPCR+) and qPCR negative (qPCR-) results, except qPCR-for A2015 season since we did not have enough samples to analyze (S1 Table) . The average amount of sequences obtained from each group after quality filtering was 2,247193 within a range of 3,634,710 to 519,470 reads. From those reads, 0.18 to 0.35% belonged to viral or bacterial sequences, and as much as 28.08% belonged to endogenous retrovirus and sequences without certain identification." ] },{ "paper_id": "ba3471e86d6880f42f1df67c9a381e83216d1b45", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were taken from MACiE (Mechanism, Annotation and Classification in Enzymes database) [3] version 3.0, EzCatDb (Enzyme Catalytic-mechanism Database) [14] , SFLD (Structure Function Linkage Database) [15] , UniProtKB [16] , InterPro [4] and Expasy Enzyme [17] in September 2013.", "Background: In this work we predict enzyme function at the level of chemical mechanism, providing a finer granularity of annotation than traditional Enzyme Commission (EC) classes. Hence we can predict not only whether a putative enzyme in a newly sequenced organism has the potential to perform a certain reaction, but how the reaction is performed, using which cofactors and with susceptibility to which drugs or inhibitors, details with important consequences for drug and enzyme design. Work that predicts enzyme catalytic activity based on 3D protein structure features limits the prediction of mechanism to proteins already having either a solved structure or a close relative suitable for homology modelling.", "In this context micro averaging (averaging over the entire confusion matrix) favours more frequent mechanisms, while macro averaging gives equal relevance to both rare and frequent mechanism classes. Hence a protein will affect the macro-averaged metrics more if it belongs to a rare mechanism. Micro and macro specificity are not presented because these metrics never fall below 99.7%. For binary classification, Specificity = TN FP + TN , hence, because of the hundreds of possible mechanism labels, most prediction methods provide a very high proportion of true negatives in comparison with false positives, making specificity very close to 100% for any reasonable method and thus not particularly informative. All metrics are further defined and discussed in [46, 49, 54] . The best achievable value of all these measures is 100% when all instances are correctly classified." ] },{ "paper_id": "ba3522d00ecebd159c5b5dc90119df8642993c49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell types expressing TMPRSS2, ACE2, HAT, 2,6-linked sialic acid are marked+, while those that do not express these molecules are marked2. ''weakly'' refers to a low level of staining. doi:10.1371/journal.pone.0035876.t001", "(TIF) Figure S2 The amino acid sequences of TMPRSS2 of human (NCBI Reference SequenceNP_001128571.1), chicken (XM_416737.3), swine (BAF76737.1) and mouse origin (AAF97867.1) were aligned using VectorNTI. Identical amino acids are marked in black, similar amino acids are marked in grey. ", "Oesophagus, stomach, intestine, bronchus" ] },{ "paper_id": "ba394664ad45d9f543519112dcd3dc4b3a213413", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SISPA-Sequence independent single primer amplification (sample S1 and S2)", "A variant of the SISPA protocol was followed [14] . Ten \u03bcl RNA was reverse transcribed and tagged using 10 \u03bcM primer FRoV26-N (GCC GGA GCT CTG CAG ATA TCN NNN NN) [15] and Superscript III (Invitrogen, MA, USA) according to manufacturer's instructions. Second strand was made by adding 0.5 \u03bcl of Klenow fragment (3' -> 5' exo-) (New England Biolabs, England) to the cDNA and incubation at 37\u02daC for 60 min and 75\u02daC for 10 min. Double stranded (ds) DNA was kept at -20\u02daC prior to PCR amplification.", "Raw data from the MiSeq run were quality checked and trimmed (Q!30; max number of ambiguities = 2) using CLC Genomic workbench (v7.5.3) (Qiagen) in order to remove poor data. Reads that passed the quality criteria were mapped against a reference BCoV genome available in GenBank (strain Mebus, accession number U00735.2) using the reference mapping tool (default values) in the CLC Genomic workbench. Sequences not mapping to BCoV were annotated through blastx analysis using Diamond [17] . The Diamond was run in sensitive mode and the blastx was performed against the nr-database (NCBI) using an e-value cutoff at 0.0001. SortMeRNA [18] was used to characterise the ribosomal RNA (rRNA) composition of each dataset and was run against the following databases: rfam 5.8s, rfam 5s, silva arc 16s, silva arc 23s, silva bac 16s, silva bac 23s, silva euk 18s and silva euk 28s." ] },{ "paper_id": "ba3f5979fe991711ff096116b05cdb182ef3aeab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step Description", "Samples collection Collection of blood sample by venipuncture. Inactivation of separated sera at 56uC for 30 min." ] },{ "paper_id": "ba3f924cd173278664082b760dccd4c6ae738436", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ba44a0c7d9af83e5fe417c92353af491ce4dc035", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2019, 11, x FOR PEER REVIEW 13 of 15 Figure 6 . Structure of the S protein was predicted. We used homologous modeling to predict the structure of original and mutant S proteins according to the Cryo-EM structure of IBV S protein." ] },{ "paper_id": "ba4cb142734825c7a8f759f10edfbc58ff798f9c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Diagnosis of fulminant lupus pneumonitis is a real challenge. As presented above several patogens should be taken into consideration in a case of interstitial pneumonitis including but not limited to viruses [7] , Pneumocystis carinii [8] and Mycobacterium sp [9] . In the case we present diagnosis has been made basing on a data from several negative cultures and striking history of sudden reduction, not increase in the dosis of the immunosuppressive agents. Intensive immunosuppressive treatment including glucocorticosteroids, cyclophosphamide, methotrexate, cyclosporin and in selected cases plasmapheresis should be introduced. A close cooperation between ICU, pulmonology and rheumatology departments is required in such a case to minimalize the risk of fatal outcome.", "Systemic lupus erythematosus (SLE) is an autoimmune chronic systemic disease which can involve several organs such as skin, lungs, brain and heart. Pulmonary manifestations of SLE can include a wide spectrum of diseases such as pleuritis, pneumonia, pulmonary embolism, pneumothorax and pulmonary haemorrhage [1, 2] . As the basic treatment of SLE include several drugs inducing immunosuppression pneumonia and acute respiratory distress syndrome (ARDS) followed by sepsis are the most common causes of admission to the ICU and fatal outcome in these patients. Only few cases of non-infectious fulminant lupus pneumonitis mimicking, by its interstitial pattern, atypical pneumonia has been presented in literature to date. Differential diagnosis and treatment of this condition represent a real challenge but only early introduction of intensive immunosuppressive treatment and close cooperation between ICU, pulmonology and rheumatology departments reduce the risk of fatal outcome.", "We report a case of systemic lupus erythematosus (SLE) in a 44-year old Caucasian woman complicated with pneumonia and severe respiratory failure requiring ICU treatment and mechanical ventilation. Symptoms developed in a generally well controlled SLE course after sudden stop in immunosupresant therapy (methotrexate, cyclosporin and methylprednisolone). A fulminant course of the disease, an interstitial pattern in a high resolution computed tomography (HRCT) and negative repeated sputum, blood and bronchoaspirate cultures enabled diagnosis of fulminant lupus pneumonitis. The response to pulses of cyclophosphamide and methylprednisolone was good but complicated with a significant leukopenia. HRCT confirmed significant remission of pulmonary changes. Fulminant lupus pneumonitis is a rare but potentially life threatening complication of SLE. Differential diagnosis requires exclusion of pneumonia induced by pathogens such as Pneumocystis jirovevecii (carinii) and Mycobacterium sp. Intensive immunosuppressive therapy and close cooperation between ICU, pulmonology and rheumatology departments is necessary in such a case to minimalize the risk of fatal outcome." ] },{ "paper_id": "ba502a88e3f83aa9e3d5edd649970db6da85c5bf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were analyzed using GraphPad Prism software (GraphPad Software, San Diego, CA, USA). Data from multiple group experiments were analyzed using oneway analysis of variance (ANOVA) followed post hoc by the Tukey multi-comparison test. Comparison of data from experiments using two groups of subjects was achieved using the unpaired t-test. For measurements of bacterial colony-forming units (CFU), groups were compared using the nonparametric Kruskal-Wallis test, followed post hoc by Dunn's test. Survival data were analyzed using the log rank test. A value of P <0.05 was considered statistically significant for all experiments. All values are presented as the mean \u00b1 standard error of the mean (SEM), except for bacterial counts, for which median values are designated.", "Lung Bacteria", "The authors declare that they have no competing interest." ] },{ "paper_id": "ba56c984234f222a42689dc2830c757add96b345", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequencing was performed on a MiSeq using a 300 cycle kit (Illumina MS-102-2002). Cutadapt [13] and Prinseq-lite [14] were used to trim primers and remove poor quality reads, respectively. Reads were assembled into contigs using Ray Meta [15] and annotation was done by BLAST in combination with custom scripts.", "While studying respiratory infections of unknown etiology we detected Saffold virus in an oropharyngeal swab collected from a two-year-old female suffering from diarrhea and respiratory illness. The full viral genome recovered by deep sequencing showed 98% identity to a previously described Saffold strain isolated in Japan. Phylogenetic analysis confirmed the Peruvian Saffold strain belongs to genotype 3 and is most closely related to strains that have circulated in Asia. This is the first documented case report of Saffold virus in Peru and the only complete genomic characterization of a Saffold-3 isolate from the Americas.", "CPE-positive culture supernatants were extracted using the QIAamp cador pathogen mini kit (QIAGEN, 54104. QIAGEN: Valencia, CA, USA) according to the manufacturer's instructions and nucleic acids were analyzed by MassTag PCR essentially as described [10, 11] . Briefly, RNAs were reverse-transcribed using SuperScript II (Thermo Fisher, 18064-014) and random primers (Thermo Fisher, 48190-011). Reverse transcription products were amplified using a panel of primers labeled with photocleavable mass codes (Agilent, custom. Agilent Technologies: Santa Clara, CA, USA) targeting Influenza viruses A and B, respiratory syncytial viruses A and B, human parainfluenza viruses 1-4, human metapneumovirus; coronavirus OC43 and 229E, enterovirus, rhinovirus, and adenovirus. Upon removal of unincorporated primers, tags were released by UV irradiation and analyzed using a 6100 Series Single Quadrupole LC/MS System (Agilent Technologies)." ] },{ "paper_id": "ba619ea88290fb57c91eaa57424ff64b0e811f0b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "doi:10.1371/journal.pone.0148986.t001", "doi:10.1371/journal.pone.0148986.g004", "Supporting Information " ] },{ "paper_id": "ba755009e5f7330a8344f1b2dd8e65d54b8488e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sampling and testing of diarrhea-associated viruses Table 1 ). The intestinal samples used in this study were obtained from the dead piglets and the fecal samples were non-invasively collected immediately after excretion from diarrheal pigs from premises by veterinarians in these farms and then submitted to our laboratory.", "Background: In China, large-scale outbreaks of severe diarrhea caused by viruses have occurred in pigs since late 2010. To investigate the prevalence and genetic evolution of diarrhea-associated viruses responsible for the outbreaks, a total of 2987 field diarrheal samples collected from 168 pig farms in five provinces in Southern China during 2012-2018 were tested." ] },{ "paper_id": "ba7a60024505cd93efc22344fc0c956bad66d6e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA was quantified on a NanoDrop spectrophotometer, followed by RNA quality assessment on an Agilent 2100 bioanalyzer (Agilent, Palo Alto, CA, USA). Amplification of cDNA was performed using the Ovation Pico WTA-system V2 RNA amplification system (NuGen Technologies, Inc.). Briefly, 50 ng of total RNA was reverse transcribed using a chimeric cDNA/mRNA primer, and a second complementary cDNA strand was synthesized. Purified cDNA was then amplified with ribo-SPIA enzyme and SPIA DNA/RNA primers (NuGEN Technologies, Inc.). Amplified ST-cDNA was purified with Qiagen MinElute reaction cleanup kit. The concentration of Purified ST-cDNA was measured using the Nanodrop. ST-cDNAs were fragmented and chemically labeled with biotin to generate biotinylated ST-cDNA using FL-Ovation cDNA biotin module V2 (NuGen Technologies, Inc.).", "Briefly, Affymetrix gene chips, Mouse gene 1.0 ST array comprised of over 750,000 unique 25-mer oligonucleotide features constituting over 28000 gene-level probe sets (Affymetrix, Santa Clara, CA), were hybridized with fragmented and biotin-labeled target (2.5 mg) in 110 ml of hybridization cocktail. Target denaturation was performed at 99uC for 2 min and then 45uC for 5 min, followed by hybridization at 45uC for 18 h with 60 rpm in hybridization oven 645. Arrays were then washed and stained with the GeneChip hybridization, wash and stain kit using Gene chip Fluidic Station 450 according to Affymetrix standard protocol (www.affymetrix.com). Chips were scanned on an Affymetrix Gene Chip Scanner 3000 7G, using Command Console Software.", "Use of animals and all experimental procedures were reviewed and approved by the Institutional Animal Care and Use Committee at the University of Pennsylvania, Philadelphia. Animal protocols adhered to the guidelines of the United States National Institutes of Health Office of Laboratory Animal Welfare Guide for the Care and Use of Laboratory Animals, 8 th Edition." ] },{ "paper_id": "ba7a8a3ea4005fb471ec2ff975634765f729c32f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest. " ] },{ "paper_id": "baa22aecb85ba7258afa2c07891ea8f08acdefa7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This mapping was built as a model in RapidMiner 5.0 (Copyright 2001-2010 by Rapid-I and contributors), an open source data mining package, which provides tools for data integration, analytical ETL (extract, transform, load), data analysis and reporting. RapidMiner includes an option to code any learned model in XML format, which can subsequently be directly manipulated.", "The results of automated classification using different algorithms are shown in Table 4 and described in detail below." ] },{ "paper_id": "baa419d7be9ab01f85ff19c108df77103b29cb50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Steroids are indicated for serious infectious diseases such as Severe Acute Respiratory Syndrome (SARS) and Acquired Immure Deficiency Syndrome, or for chronic autoimmune disease such as Systemic Lupus Erythematosus and Rheumatoid Arthritis. However, steroid-associated osteonecrosis (ON) frequently occurs. It is highly desirable to develop agents which could prevent ON occurrence due to its generally poor surgical prognosis [1] [2] [3] .", "Serum Examination for either Prototype or Metabolite of EF: Serum was obtained by centrifugation at 4500 revolutions per minute (rpm) for 15 min and stored at 280uC before analysis. All serum samples were thawed at room temperature. Analytes were extracted from 1 ml serum aliquots by liquid-liquid partition using water-saturated ethyl acetate. The ethyl acetate partitions were dried by gently blowing with nitrogen (N 2 ) gas at room temperature. The residues were re-dissolved in 60% MeOH-H 2 O for injection into performance liquid chromatographytandem mass spectrometry (HPLC-MS/MS) analysis, using an HPLC system coupled with a UV-DAD (Ultra-Violet) system and an ESI ion trap mass spectrometry. LC separation was conducted using an Agilent Series 1100HPLC system and a C18 reversedphase (RP) column (5 mm, 4.6 mm6250 mm; Shimadzu, Japan) and 75% MeOH-H 2 O as mobile phase at a flow rate of 1.0 ml/ min. MS analysis was performed using an Esquire 2000 ESI ion trap mass spectrometer (Bruker, USA) equipped with Esquire control software. Mass spectra were acquired and processed using the software provided by the manufacturer. The positive ion mode and MS/MS analysis were selected, working under the following conditions: Capillary Voltage = 4 kV; Capillary Temperature = 300uC; Nebulizer Gas Pressure = 30 psi; Drying Gas Flow Rate = 10 L/min. The scan range was m/z 50-1500, the maximum injection time was 50 ms, and two scan events were prescribed to run sequentially in the mass spectrometer.", "Statistics. The ON Incidence was compared using Fisher's exact probability test. The cross-sectional quantificational data were expressed as Mean6SD, which were examined using Analysis of Covariance (ANCOVA) with body weight as covariant variable for eliminating its influence on the measurement results, using LSD' s post hoc multiple comparisons. The longitudinal quantification data were analyzed using 'ANOVA of Repeated Measures' with body weight as a covariant variable for eliminating its influence on the measurement results, using LSD' s post hoc multiple comparisons. The in vitro data was evaluated by ANOVA, using LSD' s post hoc multiple comparisons. All statistical analysis was performed using SPSS 10.0. Statistical significance for compaison was set at P,0.05." ] },{ "paper_id": "baa8420ed8f9d0dc7ba81b519eda2c3fe91291b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HeLa cells were cultured in Dulbecco's modified Eagle medium containing 10% fetal bovine serum (Thermo scientific), 1 mM glutamine, 1 mM sodium pyruvate (Invitrogen). Cells were incubated in 5% CO 2 humidified incubator at 37uC. Anti-GM130 mouse mAb was purchased from BD Biosciences (catalog number: 610822). Anti-GRASP65 rabbit polyclonal serum was purchased from Novus Biological (catalog number: NBP1-57592). Anti-Sec61b polyclonal IgG was obtained from Santa Cruz (catalog number: SC-27695). Anti-flag M2 mouse mAb was purchased from Sigma (catalog number: F1804). Alexa Fluor 488conjugated goat anti-rabbit IgG and Alexa Fluor 546-conjugated goat anti-mouse IgG were purchased from Molecular Probes (catalog numbers: A-11008 and A-21143). Fluorescently labeled wheat germ agglutinate, WGA647, was obtained from Invitrogen (catalog number; W32466).", "In summary, we have identified two specific regions in human SAC1 that are independently involved in Golgi targeting.", "The Golgi apparatus is a central sorting organelle guiding soluble and membrane-bound proteins arriving from the ER to their different endomembrane compartments. Passage through the Golgi is also required for post-translational processing of secretory proteins [9] . The mechanisms responsible for the characteristic intra-Golgi distribution of resident enzymes that are required for glycosylation and other modifications are not well established. Unlike the classic retrieval motifs that control steady state localization of ER proteins, no common Golgi sorting sequence has been found [9] , [10] . Two mechanisms have been proposed for Golgi retention, commonly referred to as the oligomerization and the bilayer-thickness model [9] , [11] . The former proposes that retention of Golgi enzymes is achieved by forming large oligomers, which prevent sorting into anterograde transport vesicles [12] , [13] . The latter postulates that retention relies on the length of membrane-spanning domains and the membrane bilayer thickness of the individual Golgi sections [12] ." ] },{ "paper_id": "baae1b488b6763192f01d394138315d92f75c426", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the Ethical Committee of Hospital Universitario 12 de Octubre (EC number CEIC: 17/379).", "The samples included in the study belonged to a total of 862 patients ( ", "All NAATs were performed in a manner blinded to the results of the other NAATs." ] },{ "paper_id": "bab3d2a212eaf7740a45ee8efeec3db99bf94589", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These data may be useful for analyses of the epidemiology and evolutionary characteristics of PEDVs in southern China.", "oped, positive-sense, single-stranded RNA virus, is classified as a member of the genus Alphacoronavirus, the family Coronaviridae, and the order Nidovirales (1, 2) .", "Nucleotide sequence accession number. The complete genome sequence of PEDV CH/GDGZ/2012 strain has been deposited in GenBank under the accession no. KF384500." ] },{ "paper_id": "bab3e74b5db5b2e04b521d1172b9df7726871aaa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Positive traits, such as life satisfaction, optimism, and core self-evaluation (CSE), have garnered increasing attention from researchers and professionals. However, the trilateral relationship among them remains unclear.", "The findings extended prior studies and shed light on how dispositional optimism influences life satisfaction. This study provides valuable evidence on how to promote the life satisfaction of human beings in positive psychology. A further study can fully explore the relationship among them in multi-cultural follow-up studies.", "Objective: This study examines the effect of dispositional optimism on life satisfaction and primarily verified the mediator role of CSEs." ] },{ "paper_id": "bab6dd24b41528b0a321874ef4827c873846e335", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "T&CM methods and remedies are considered natural and organic as opposed to conventional medicine, which is often thought of as artificial and/or synthetic [24] .", "The assumption that T&CM treatments are natural and therefore non-toxic have been found to be associated with people's decisions to use T&CM in multiple studies in multiple conditions [4, 24, 39] .", "To further understand T&CM safety, it is also important for researchers to take into consideration the fact that the risk of T&CM needs to be viewed through a wider lens of missed opportunity for known safe and effective treatments, or following advice from poorly trained health professionals in an unregulated environment [43] . Findings from studies such as ours can inform regulatory and policy frameworks, the designing of public health messages and the nature of provider-patient communication regarding T&CM use; all geared towards ensuring safe and informed care for Ebola survivors." ] },{ "paper_id": "babad3896fca8ed7c89d9b785c08e7c42a48a6a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "COPD -Chronic Obstructive Pulmonary Disease " ] },{ "paper_id": "bad0e9f737316570c33138d5cc95cc233cd937ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Stata version 14.2 (StataCorp, College Station, Texas, USA) was used for the analysis.", "The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials." ] },{ "paper_id": "bad87b7effc9c6f6a9ef4ca024f7fe86daff4f45", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "bae589aad9c7fe95e859487dc9185968c54d584e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "3.2. The labile disulfide bond in CD132 is exposed to solvent", "The data were submitted to the in-house Central Proteomics Facilities Pipeline (CPFP) [39] and the datasets were searched with variable peptide modifications including carbamidomethyl cysteine, oxidized methionine, deamidated asparagine/ glutamine, and hydrolysed and non-hydrolysed versions of the appropriate cysteine-modifying label (NEM, MPM or MPB). The resulting peptide identifications from each search engine were validated with PEPTIDEPROPHET and PROTEINPROPHET and lists compiled at the peptide and protein level [40] . IPROPHET was used to combine the identifications from three search engines and further refine identifications and probabilities [41] . Normalized spectral index quantitation (SINQ) was applied to the grouped meta-searches to give protein-level quantitation between reduced samples and controls [42] . All lists of peptide and protein identifications were generated with a probability cut-off corresponding to a 1 per cent false discovery rate (FDR) relative to a target decoy database. Quantitated datasets were uploaded to ProteinCenter (Proxion, Thermofisher) for analysis. The dataset was reduced by removing single-peptide identifications and proteins of interest (cell surface, secreted and extracellular) were mined using gene ontology (GO) flags. Resultant protein and peptide lists were exported as tables.", "To test whether the decrease in STAT-5 tyrosine phosphorylation after reduction of CD132 is a pathway-specific process and that the reducing agent is not inhibiting all tyrosine phosphorylation in the cell, lysates from non-reduced and reduced HT-2 cells were Western blotted with an anti-phosphotyrosine antibody (figure 5c). This showed there was no significant decrease in global phosphorylation upon reduction, and that inhibition of phosphorylation of tyrosines in STAT-5 and cell proliferation is pathway-specific through CD132." ] },{ "paper_id": "bae5b0168a883973407af7229c5f3b59020cdfa4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A. salmonicida subsp. salmonicida (wild type strain JF 2267) was used for experimental infection of trout. The bacteria were cultivated from cryoconserved batches (Microbank, PRO-LAB Diagnostics, Cheshire, UK) in LB broth (SIFIN) at 15 \u2218 C for 72 h. The initial cultures were checked for purity by Gram-staining and observation of cell morphology. The bacterial suspension was concentrated by centrifugation (4300 rpm, 10 min, 4 \u2218 C). The bacterial pellet was washed once in sterile 0.9% sodium chloride solution and diluted to 1\u00d710 8 bacteria/mL." ] },{ "paper_id": "baf2944b65112b4b45b0c0f6aeb16e3e90a4f61e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Some species are considered synanthropic because they associate with humans. In urban and rural environments with economic activity, commensal synanthropic species are predominant, as well as some wild species that occasionally invade human dwellings.", "Hantaviruses cause persistent infections in rodents marked by a relatively short initial acute phase lasting two to three weeks, during which the concentration of infectious virus is high. Subsequently, the infection is marked by a prolonged chronic phase during which the infection is productive, but the virus is normally present at low levels that can vary cyclically, even in the presence of high levels of neutralizing antibodies [100, 104, [110] [111] [112] .", "Necromys lasiurus (hairy-tailed bolo mouse)-this species harbors the Araraquara virus. Its geographical distribution in Brazil includes the Cerrado, the Atlantic Forest-Cerrado ecotone and Caatinga areas. N. lasiurus can adapt to anthropic environments, especially grasses (Brachiaria) and sugarcane crops. These rodents are generally abundant but do not colonies human dwellings; however, they may occasionally invade homes [48, 78, 208] (Figure 4) .", "Calomys callidus-this rodent harbors the Laguna Negra-like hantavirus and inhabits Cerrado transition and Amazon areas in the States of Mato Grosso and Rond\u00f4nia [47, 174] . This region has suffered intense deforestation for the planting of soy and other cereals (Figure 4) .", "Taxonomic studies on sigmodontinae have led to ongoing descriptions of novel species [62] . Taxonomic revisions and large compilations include the restructuring of the systematic knowledge on this group [62] [63] [64] [65] [66] [67] [68] .", "Bats (order Chiroptera) are sources of a broad range of emerging pathogens, including coronavirus, filovirus, Hendra and Nipah paramyxoviruses and lyssavirus [228] . With fossil origins from the Eocene epoch approximately 50 million years ago, bats occur on all continents except Antarctica and are one of the most species-rich mammalian orders, totaling over 1100 [229] .", "These five factors are important in the biology and ecology of the virus-host ecosystem and may ultimately reflect the risk of human transmission." ] },{ "paper_id": "bafab6b3dd88dcdefe111698d02f81998c9accdb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "bafbd40e253b24fc6b10b66bf68fe838e0a6a313", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The total bacterial load of the samples was established by quantitative PCR. Real-time PCR for viruses One 200 ml aliquot of swab ''rinse'' solution was used to extract viral nucleic acids using the MagNA Pure LC total nucleic acid isolation kit (Roche Diagnostics, catalogue 03 038 505 001, Basel, Switzerland) as described previously [22] . Detection of viral pathogens was performed in parallel, using real-time PCR assays for bocavirus (HBoV), polyomaviruses (WUPyV and KIPyV), respiratory syncytial virus (RSV) A and B, influenzavirus (IV) A and B, para-influenzavirus (PIV) 1-4, human rhinoviruses (HRV), adenoviruses, human coronavirus OC43, NL63, HKU and 229E, and human metapneumovirus (hMPV). Real-time PCR procedures were performed as described previously [22] Briefly, samples were assayed in duplicate in a 25 ml reaction mixture containing 10 ml (c)DNA, 12. ", "The nasopharyngeal swabs were plated onto a 5% sheep blood agar plate, a 5% sheep blood agar plate with 5 mg/L gentamicin, a chocolate agar plate and a Haemophilus chocolate agar plate. Agar plates were incubated at 35uC for 48 h; the blood agar plate aerobically, the blood agar plate with gentamicin and the chocolate agar plates with raised CO2. Identification of S. pneumoniae, H. influenzae, M. catarrhalis and S. aureus was based on colony morphology and conventional methods of determination. ", "We randomly selected 150 NP samples from a cohort of 330 healthy children 18 months of age who had participated in a randomised controlled trial studying the effect of reduced-dose schedules of 7-valent pneumococcal conjugate vaccine (PCV-7) performed in a general community in the Western part of The Netherlands where the control children received PCV-7 only after the trial was finished at the age of 24 months [21] . An Table 1 . Thirty most common OTUs or 'species-level' phylotypes (ranked by predominance, i.e. absolute presence among the approx. 1 100 000 reads). " ] },{ "paper_id": "bafffaf17be4302a4a6e79b3f65b9238ab00c258", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using GraphPad Prism 6 on logtransformed data using multiple comparison analysis of the final mouse sera in one-way analysis of variance with Tukey's post-test. Significance was considered at p values \u22640.05.", "After multiple-step purification we observed similar in vivo stability for xenogenic rabbit IgG and homologous mouse IgG preparations in recipient mice, while rabbit F(ab\u2032) 2 was only detectable for 1 day after transfer. This short half-life of F(ab\u2032) 2 preparations was also observed in earlier studies where a single dose of antisera resulted in better protection over a longer period compared to repeated treatment with F(ab\u2032) 2 fragments. 29 Until processes to stabilize F(ab\u2032) 2 preparations have been developed, full IgG with its known and controllable risks for adverse events may be a valuable addition to the toolbox against newly emerging infectious diseases.", "The data reported in this paper are available from the corresponding author upon request.", "All experiments with infectious EBOV or NiV were performed in the BSL4 facility of the Institute of Virology, Philipps-University Marburg, in compliance with German regulations." ] },{ "paper_id": "bb01f3bd0a1b61ef92b556330b94f59c947ea1a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The toxicity of siRNA treatment was measured by aCella-Tox bioluminescence Cytotoxicity Assay (Cell Technology Inc, Mountain View, CA), which detects secreted Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) in cells with diminished membrane integrity. Values for released GAPDH were normalized to cellular GAPDH levels.", "All statistics were performed using a two-tailed, paired Student's T-Test (*P < 0.05, **P < 0.01)." ] },{ "paper_id": "bb11206963e831f1652775d26e3e5e48634a4545", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Considering the low frequency of PToV in diarrheic pigs, pre-selection by IAEM or pre-screening by diagnostic RT-PCR of ToV-positive fecal specimens could allow detailed studies of the genetic diversity among ToVs [22] .", "PEDV is a coronavirus that can infect and cause enteritis having typical clinical symptoms, including vomiting, diarrhea and dehydration, in pigs of all ages, but it is usually only fatal in piglets.", "Negative staining electron microscopy methods can" ] },{ "paper_id": "bb3716d66667c66f6f79b37c765388cd334f2cad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "While vaccines such as RataTeq and Rotatrix have been made available for prevention of RV infections [15, 16] , their effectiveness remains to be verified [17] . Use of a few synthetic compounds against simian RV, such as ribavirin [18] and isoprinosine [19] , and natural products against human and bovine RV [20] , such as theaflavins, has been reported. Unfortunately, these compounds are not available for human use, which necessitates alternative methods to control RV infection [21] . A promising alternative strategy to reducing the burden of diarrhoea caused by RV may lie in identifying and developing costeffective nutritional or phytomedical solutions; which can be applicable especially in children and immunocompromised persons.", "Below are the yields of each extract (mg) per g of T. esculentum bean and tuber material used.", "Correlation coefficients for data obtained on level of protection, nitric oxide release, and transepithelial resistance (TER) were calculated using Statsoft Statistica version 7 software." ] },{ "paper_id": "bb40bca4ee06eacfdf5f055cbaf09a54a2f54aff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Population immunity may contribute to the variability of ICV. Substantial antigenic and genetic diversity exists among ICV isolates; there are six genetic lineages representing six antigenic groups of HEF, with two major genetic lineages of the internal genes [56-60,87, [105] [106] [107] [108] [109] [110] [111] . Elegant longitudinal studies in Japan that compared the antigenic and genetic character of circulating isolates with concurrent serology showed periodic epidemics of ICV every few years. While multiple strains co-circulated, there was a dominant antigenic group that was replaced every few years, driven by herd immunity [56,60]. However, there was very little antigenic drift over time [56].", "Studies conducted in India, Jamaica, Japan, the Philippines, and other countries corroborate the widespread nature of ICV and general age distribution already described [77] [78] [79] [80] [81] [82] [83] . Collectively, these data indicate that ICV infection is widespread globally with most infections occurring in young children. ICV is uncommon in hospitalized adults but has caused outbreaks in military recruits [84] [85] [86] [87] [88] . ICV has been reported among travelers on the Hajj pilgrimage [89] .", "Seasonality of ICV is poorly understood, although outbreaks and cases of familial transmission have been described [74, 101] . Matsuzaki [103] . A single-year study performed by Pabbaraju et al. also identified a winter-spring seasonality in ICV detection [70] . In most studies, winter-spring seasonality remained consistent, though Anton et al. report year-round detection of ICV in Spain with highest numbers observed in the summer [104] ." ] },{ "paper_id": "bb5d7caba7ff8afec3c1fde62cadf65db745ce35", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A piece of tissue (40 mg) was homogenized in 1 mL of cold PBS using a Pro200 Power homogenizer (Diamed, Mississauga, ON, Canada) on ice. The tissue homogenates were centrifuged at 1000\u00d7 g at 4 \u2022 C for 10 min and the supernatant was stored at \u221280 \u2022 C until further processing.", "Serum anti-IBV antibody titers were determined using the IDEXX IBV antibody test kit (IDEXX Laboratories, Westbrook, ME, USA) following the manufacturer's instructions. The plates were read at 650 nm absorbance using SpectraMax M2 microplate reader (Molecular Devices, Sunnyvale, NS, Canada).", "Viruses 2018, 10, x 10 of 15", "Formalin-fixed terminal tissue samples (21 dpi) were processed at the Diagnostic Services Unit of the University of Calgary's Faculty of Veterinary Medicine including staining of sections with stained hematoxylin and eosin (H & E). Sections were examined under the light microscope and photomicrographs were taken under 40\u00d7 magnification." ] },{ "paper_id": "bb61dcfd20c7d56e90a52779d3f51a1f68c46362", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Primary mouse hepatocytes were isolated according to retrograde perfusion approach [23] . Briefly, anesthetized C57/BL6 mice were perfused through the inferior vena cava with Hepes buffer added with Liberase (2.3 mg/ml Roche\u00ae) and CaCl 2 to start in vivo hepatocyte dissociation. The liver was then transferred to the petri dish with Leibovitz medium, and liver capsule was broken to release hepatocytes before filtration, washed with Hepes buffer, and transferred to Williams' E medium. Alive hepatocytes were isolated on 35% gradient percoll before seeding on a collagen-covered dish in Williams' E medium added with 2 mM glutamine, 10 IU/ml penicillin, 10 \u03bcg/ml streptomycin, 10% SVF, and 5 \u03bcg/ml insulin. After 6 h, attached hepatocytes were cultured in maintenance medium and Williams' E medium in which SVF was replaced by 1 mg/ml bovine serum albumin (Eurobio) and 0.1 \u03bcM dexamethasone (Sigma).", "2.6. Western Blot. A piece of fast-frozen mouse liver was homogenized in RIPA buffer by Ultra-Turrax\u00ae and left on the ice during 40 min, vortexed regularly before a centrifugation of 10000g at 4\u00b0C. The supernatant was then recovered before Bradford dosage. 50 \u03bcg of total protein extract was then loaded on polyacrylamide gel, transferred to a nitrocellulose membrane before incubation overnight in IL-33 antibody (goat Ab, R&D) in TBS 5% milk and 1 hour in secondary HRP-conjugated rabbit anti-goat antibody (Dako, USA), and followed by a revelation with ECL (Pierce)." ] },{ "paper_id": "bb6a9f522a87a780723faca7cde002ece6dbfb48", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The four serotypes of dengue virus (DENV) belong to the genus Flavivirus within the family Flaviviridae [1] . The clinical manifestations of DENV infections cover a wide range of symptoms, from mild dengue fever (DF) to severe life threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) [2] . Commonly, DHF/DSS is associated with sequential DENV infection by different serotypes [3, 4] . Annually, 50 to 100 million people in over 100 countries are infected with DENV and DHF/DSS can be fatal in up to 5% of affected individuals. No vaccine or specific antiviral drugs is currently available.", "All statistical analyses were performed using SPSS 13.0. Graphs were performed using the Prism software (GraphPadPrism5, San Diego, CA). The data were presented as means plus standard deviations from there independent experiments. A P value < 0.05 was considered statistically significant." ] },{ "paper_id": "bb6be6d67dbc92ee528f4c09ca1643eeda4316bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The comparisons between percentages and two means were tested by chi-squared test and Student's t test respectively. A p value ,0.05 was considered statistically significant. Proportions, means and all statistical analyses were performed using STATA 9.0 (StataCorp., College Station, TX, Texas).", "The Table S6 and Figure S4 ).", "The [49, 50] ." ] },{ "paper_id": "bb6d4ff2bd0aa48e1d8b2b18f937a244cd806212", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Clinical specimen information and PCR results.", "Additional file 2: Multiple sequence alignment of hexon genes of human adenovirus species A to G and primer and probe sequences. (PDF 406 kb)", "(XLSX 18 kb)" ] },{ "paper_id": "bb6e40ae1720fa7008aa90c2c35d9d7e75c4611e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Please see Additional file 1 for translations of the abstract into the six official working languages of the United Nations.", "Background: H7N9 continues to cause human infections and remains a pandemic concern. Understanding the economic impacts of this novel disease is important for making decisions on health resource allocation, including infectious disease prevention and control investment. However, there are limited data on such impacts." ] },{ "paper_id": "bb76fcd0194eeda7dc70702dacad97492a497bea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Kingdom. HuNoVs have recently been isolated from pet dogs in Europe (M. Summa, C.-H. von Bonsdorff, and L. Maunula, J Clin Virol 53:244 -247, 2012, http://dx.doi.org/10.1016/j.jcv.2011.12.014), raising concerns about potential zoonotic infections.", "RNA extraction and reverse transcription-quantitative PCR (qRT-PCR). Stools were diluted 10% (wt/vol) in phosphate-buffered saline (PBS) (pH 7.2), and solids were removed by centrifugation at 8,000 \u03eb g for 5 min. Viral nucleic acid was extracted from 140l of each clarified stool suspension with the GenElute mammalian total RNA miniprep kit (Sigma-Aldrich) according to the manufacturer's instructions." ] },{ "paper_id": "bb7718e2a9a390578e8d3f5ea081f08d3fd17185", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In summary, it is plausible that microbial interactions are multifactorial and involve a complex interplay between multiple host factors and bacterial characteristics that may have important consequences for both the composition and stability of the microbial community itself and susceptibility to disease [37] .", "The mechanisms by which viruses influence bacterial colonization and invasion are very diverse. We have summarized the known mechanisms in Figure 2a and 2b and will discuss each of these mechanisms below.", "Text S1 Supporting information, including Table S1 (Bacterialbacterial interaction) and Figure S1 ", "Differences between studies are likely to be explained by inclusion criteria and heterogeneity of populations due to differences in age, sample size, genetic background, season of sampling, lifestyle, and environmental circumstances, as well as health status and registration of respiratory symptoms prior to or following sampling." ] },{ "paper_id": "bb7cd48a85b72f8d73e57d655c6d8a034fce3778", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "bb8030d58fcf70a3f77b3edb702ed8801f56cc0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To obtain virus-infected plants, clones of TYLCV isolate SH2 (GenBank accession no. AM282874.1) were inoculated into tomato (Solanum lycopersicom L.cv. Hezuo903) at 3-4 true-leaf stage as previously described [62] , TYLCVinfected and uninfected tomato plants were cultivated to 6-7 true-leaf stage when used in experiments. All plants were grown in a greenhouse at 20-30\u00b0C, LD14:10 h and 50-70% relative humidity. ", "Our results reveal the complex insect-virus relationship in whitefly gut and provide substantial molecular information for the role of insect midguts in virus transmission.", "Plant viral diseases have received great attention worldwide because of their tremendous economic impact [1] . The majority of plant viruses are transmitted by insects of hemipteran families, such as aphids, whiteflies, leafhoppers, planthoppers, and thrips [2] . As a consequence, vector control is currently the only practical and effective strategy for disease prevention. Over the past few decades, a number of research have investigated the interactions between plant viruses and insect vectors because of its importance in viral epidemiology and disease management [2] [3] [4] . A detailed understanding of the genetic and molecular basis of insectvirus interaction will lead the discovery of novel and specific molecular targets for whitefly and whitefly-transmitted virus control.", "Methods: We investigated the transcriptional response of the gut of B. tabaci Middle East-Asia Minor 1 species to TYLCV infection using Illumina sequencing." ] },{ "paper_id": "bb89ed5e7ed332cbc8565262db8a04d55e2869ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 1 H frequency scale is given in terms of chemical shift relative to the acetone signal used as an external reference (2.218 ppm).", "A second possibility regarding Arb activity is that Arb might interact with key motifs present in viral proteins, thereby impeding their structural reorganization at the onset of fusion and thus leading to fusion inhibition.", "This study aimed at further investigating the molecular mechanism of action by which arbidol (Arb) inhibits virus cell entry and membrane fusion, using HCVpp as a model of an enveloped virus.", "Huh-7 cells [19] were maintained in DMEM containing 4.5 g/ L d-glucose and 4 mM L-glutamine (Invitrogen, Cergy-Pontoise, France), supplemented with 100 U/ml penicillin, 100 mg/ml streptomycin and 10% FCS (Lonza). Productions of pseudotyped viruses were obtained by the transient transfection of 293T cells by the calcium-phosphate method. For the genotype study, HCVpp of genotypes 1a (H77; AF011752), 1b (Con1; AJ238799), 2a (JFH1; AB047639), 2b (UKN2B 2.8, AY734983), 3a (UKN3A 1.28, AY734984), 4a (UKN4 21.16, AY734987), 5a (UKN5.14.4, AY785283) and 6a (UKN6.5.340, AY736194) were produced as described previously [20] from 293T cells co-transfected with a murine leukemia virus (MLV) Gag-Pol packaging construct, an MLV-based transfer vector encoding GFP as a marker protein, and the E1-E2 expression constructs.", "Phosphatidylcholine from egg yolk (PC, 99% pure), dimyristoylphosphatidylcholine (DMPC, 99% pure), cholesterol (chol, 99% pure), lyso-phosphatidylcholine (lysoPC), dodecyl-phosphocholine (DPC), Triton X-100, tryptophan octyl ester hydrochloride (TOE) and N-acetyl-L-tryptophanamide (NATA) were purchased from Sigma. Octadecyl rhodamine B chloride (R 18 ) was from Molecular Probes. The peptides used were part of the sequence of structural or non structural (NS) proteins of HCV and of the bovine viral diarrheal virus (BVDV). The amphiphilic helix of BVDV NS5A [15] and the transmembrane domain of HCV NS4A [16] were obtained as described previously. The peptides identified as important for HCV fusion [17] were purchased from Clonstar Biotech (90% purity) or Sigma Genosys (70% purity), respectively, and dissolved in DMSO before preparation of lipid:peptide mixtures. Arbidol [Arb, 1H-indole-3-carboxylic acid, 6-bromo-4-[(dimethylamino)methyl]-5-hydroxy-1-methyl-2-[(phenylthio)methyl]-, ethyl ester, monohydrochloride ( Figure 1 )] was a kind gift from Stephen J. Polyak." ] },{ "paper_id": "bb8a05062237c64d231f3ba922b8ec26c7f32eaa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Romaric Larcher (speaker) 1 ", "Introduction: Nangibotide peptide is a specific TREM-1 inhibitor.", "Eric Thebault (speaker) 1 " ] },{ "paper_id": "bb8a9e29bc65471177f470285c32d879c2cb7263", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Onset-to-hospitalization 5 (WHO Ebola Response Team, 2014)", "Detailed model formulation", "(1 \u2212 f )(1 \u2212 g); fg. See Table 2 and Figure 2 for parameter estimates.", "Even so, Gostic et al. point out that in all of these scenarios airport screening will still miss many infected passengers. Thus, a challenge for future outbreaks will be to identify situations in which screening is worthwhile, and obtain better measurements of the factors that influence detection rates." ] },{ "paper_id": "bb99b6dde050807939930f078e0eed8a4693a710", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. Inter-isoform conservancy: the percent of conservancy between all isoforms of each E5, E6, or E7 oncoprotein.", "High prevalence and mortality of oncogenic infectious pathogens such as HPV and Helicobacter pylori have caused serious problems for humans. Currently, people who are infected with hrHPVs but show normal cytology or precancerous lesions do not have any treatment option, causing the disease progress toward invasive carcinoma in some cases. Unfortunately, no FDA-approved immunotherapy exists for pre-existing HPV infections or their related cancers to date. Immunotherapy of HPV-associated cancers by DNA or peptide-based vaccines, depends on the recognition of highly immunogenic epitopes, inducing robust and specific immune responses, particularly cell-mediated responses against the malignant cells.", "Several factors could clarify the difference between epitope and non-epitope peptides; An essential factor is epitope immunogenicity, i.e., it could be recognized by T cells. Some amino acids, particularly those with large and aromatic side chains (especially tryptophan, phenylalanine, and Isoleucine), are associated with immunogenicity. Moreover, the positions P4-6 of a peptide are more critical for immunogenicity [85] .", "Regarding the studies, different peptides usually get different scores/ranks in different analyses. This inconsistency indicates that these results needed to be analyzed with an integrated approach. Indeed, integrated approach is more practical and efficient in such conditions in comparison with analysis by analysis filtering approach, in which those epitopes are chosen for the next analysis that have gotten an acceptable score in the previous analysis. Herein, the integrated approach was applied in both steps of epitope selection." ] },{ "paper_id": "bba54a43464e4fda9280139894c5467524ef2faf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Peptide synthesis. A panel of peptides (Fig. 1A) , including T20, CP, CP-SM, CP-SW, CP-IDL were synthesized with a standard solid-phase FMOC method, as described previously 5 . The peptides were found to be about 95% pure by HPLC and were identified by mass spectrometry (Perseptive Biosystems, Framingham, MA, USA). Concentrations of the peptides were determined by UV absorbance and a theoretically calculated molar-extinction coefficient based on tryptophan and tyrosine residues.", "Scientific RepoRts | 6:31983 | DOI: 10 .1038/srep31983 antiviral activity of CHR-derived inhibitors by approximately 10-fold 15, 16 . Moreover, structural studies revealed that the hydrophobic side chain of the methionine residue in MT hook participates in hydrophobic interactions with both the NHR trimer and the CHR-derived inhibitor.", "Simulation analysis. Visualization and extraction of raw trajectory data for analysis were performed using VMD. To assess the stability of the interactions between IDL tail and its combined NHR trimer, the average C\u03b1 -C\u03b1 distance between each C-terminal residue of CP-IDL and all NHR residues was calculated. Then, the variance of the distance during simulation runs was monitored and plotted. In addition, the contribution of IDL tails to the buried areas were also calculated and monitored during simulation runs, where the buried area was simply considered as one half of the solvent accessible surface area difference between complex A:B and the sum of A and B. When calculating the solvent accessible surface, a typical probe radius of 1.4 \u00c5 was employed. Two Tcl scripts were coded and performed in VMD Tk console to realize the calculations described above." ] },{ "paper_id": "bbb4038e28cab7e031d4a60ee4501989aef467aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All consecutive patients, younger than 20 years old, diagnosed with high-risk hematological malignancies, in need of an allogeneic transplantation, and in good clinical condition who lacked either a matched related donor or a matched unrelated donor, were included. Indications for allogeneic hematopoietic transplantation for children with acute lymphoblastic leukemia (ALL) included: poor cytogenetics, induction failure (defined as no remission at 1 month following induction treatment), persistent minimal residual disease tested by PCR before transplant with a cutoff point of 10 \u22123 and 2nd complete remission (CR) or beyond. For acute myeloid leukemia (AML) patients transplant criteria included intermediate or poor risk characteristics at diagnosis and also 2nd CR or beyond. Primary refractory AML was defined as the failure to achieve a response after one or two cycles of induction. Refractory ALL was defined as the failure to achieve a cytological remission response after induction chemotherapy and secondline rescue chemotherapy. The only exclusion criterion was a poor clinical condition, defined as a Lansky score lower than 60%.", "Patients, parents, and/or their legal guardians gave written informed consent in accordance with the Helsinki Declaration.", "At the end of the procedure, quality control by flow cytometry was carried out in the final product, such as cell counts, viability studies, and aerobic and anaerobic cultures before and after immunomagnetic depletion.", "Myeloid recovery was defined as the first of 3 consecutive days on which the absolute neutrophil count was \u2265 0.5 \u00d7 10 9 /L. Platelet recovery time was considered the first of 3 consecutive days on which a platelet count above 20 \u00d7 10 9 /L was achieved, with no transfusion requirements." ] },{ "paper_id": "bbbac6572458c12b598b642d848b3852f2999573", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, to cope with future challenges in global health security, the following aspects require strengthening. First, preventive governance is necessary. The recovery stage capabilities were the weakest, which is far from achieving the standard of full recovery including sustainability, resilience after crisis and feedback to preparationstage. The prediction, communication, and social services during and after emergencies require improvement." ] },{ "paper_id": "bbbeb27419905cbacf36b6932302650784570099", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "African green monkey kidney (Vero E6) cells, baby hamster kidney (BHK21) cells and 293T cells were grown and maintained in Dulbecco's modified Eagle medium and modified Eagle medium (Gibco Invitrogen), respectively, supplemented with 10% heat-inactivated fetal bovine serum and 100 U/ml of penicillin and 100 mg/ml of streptomycin (Gibco Invitrogen). Viral cDNAs encoding individual SARS-CoV ORFs were generated and described in our previous work [39, 66] .", "The primers for individual ORFs were designed according to the genome sequence of SARS coronavirus strain WHU (GenBank accession number: AY394850) with restriction sites which were compatible for the downstream subclonings. The reagents for PCR were 0.2 mM dNTPs, 0.4 mM forward and reverse primers, ,10 ng template DNA and 1 U of KOD DNA polymerase (TOYOBO) in 50 ml reaction system. The amplification conditions were 94uC for 2 min and 30 cycles of 94uC for 15 sec, 52uC for 15 sec and 68uC for 3 min, followed by 68uC for 10 min and 4uC for 10 min.", "Trans-activation activity of N protein at the early stage of genome replication or transcription of SARS-CoV" ] },{ "paper_id": "bbc0322ac1427ea61ca213645a219daf5bd9d5ac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Local clustering coefficient C i is defined as:", "Results: The findings were as follows." ] },{ "paper_id": "bbc2824ce7dff3d23d060b7abbe96cba28095fb8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Children are important vectors for HRV transmission to family members particularly siblings [47, 48] . HRV shedding peaks two to four days after infection and decreases sharply thereafter, although nasal samples can be positive for rhinovirus for up to five weeks after a symptomatic infection [49] .", "Author's contribution HA and PDS conceived and designed the review. All authors reviewed the articles, abstracted data, and participated in the data synthesis. HA, PDS, YSC drafted the current manuscript, with critical review by PDS and CMJ. All authors contributed, read and approved the final manuscript.", "The authors declare they have no competing interests." ] },{ "paper_id": "bbc89603600968ee09dd4b38c91616f83f7e0bba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CACO-2, MDCK and HEK293T cells were cultured in Dulbecco's modified Eagle's medium (DMEM) containing 10% heat-inactivated FBS, 4.5 g/liter D-glucose, 2 mM glutamine, 25 mM HEPES, 110 mg/liter sodium pyruvate, 1% penicillinstreptomycin. HUVECs were cultured in M199 containing Earle's salts, 10% heat-inactivated FBS, L-glutamine, NaHCO3, 1% penicillin-streptomycin plus 1% of endothelial cell growth supplement.", "One-step reactions were performed in 25 ml volumes using qScript One-Step SYBR Green qRT-PCR Kit (Quanta Biosciences, Gaithersville, MD) starting with 100 ng of total RNA. Primer concentration was 10 pmol. Reaction conditions were: 50uC for 10 min, 95uC for 5 min, followed by 40 cycles of 95uC for 10 sec, 55-60uC for 20 sec and 72uC for 30 sec.", "The following reagents were purchased from the respective suppliers: protein A-sepharose, protein G-sepharose from GE Healthcare Bio-Sciences AB (Piscataway, NJ); general lab chemicals, DMSO, Nocodazole, Dynasore, Paclitaxel and Latrunculin the American Type Culture Collection (Manassas, VA). Human umbilical vein endothelial cells (HUVECs) isolated from individual umbilical cords as described [30] were obtained from Dr. Denise Hemmings (Obstetrics & Gynaecology, University of Alberta). These primary cells were used for experiments between passages 2-6." ] },{ "paper_id": "bbc8c0fb749a7bac1030cf1301654f7063c612dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Atomic coordinates and structure factors for the reported crystal structures have been deposited with the Protein Data bank under accession numbers 6KWQ and 6KWR.", "The EC crystals were grown by sitting-drop vapor diffusion at 16 \u2022 C using a 12.5 mg/ml EC sample. Rhombohedronshape crystals grew to their final size within 1-2 weeks in a precipitant solution containing 0.17 M sodium acetate, 0.085 M Tris (pH 8.5), 25.5% (wt./vol.) PEG4000 and 15% (vol./vol.) glycerol. Crystal soaking trials were done for 10 h using the precipitant solution supplemented with 5 mM ddCTP and 10 mM MgCl 2 . Crystals were directly cooled and stored in liquid nitrogen prior to data collection.", "Crystallographic data processing and structure determination X-ray diffraction data was collected at Shanghai Synchrotron Radiation Facility (SSRF) beamline BL17U1 (wavelength: 0.9792\u00c5, temperature: 100 K). Data of at least 180 \u2022 were typically collected in 1 \u2022 oscillation steps. Reflections were integrated, merged and scaled using D*Trek (32) . The initial structure solution was obtained using the molecular replacement program PHASER (33) with coordinates derived from EV-B EC structure (PDB entry: 5F8G, chains A-C) as the search model (10) . Manual model building and structure refinement were done using Coot and Phenix, respectively (34, 35) . The 3500-K composite simulated-annealing (SA) omit 2F o -F c electron density maps were generated using CNS (36) . Unless otherwise indicated, protein structure superpositioning was done using the maximum likelihood-based structure superpositioning program THESEUS (37) ." ] },{ "paper_id": "bbcb78719cba8e781ca99c3069823e9270053ac3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at www.mdpi.com/1999-4915/10/2/59/s1, Video S1: Spatial Arrangement of RdRp Motifs; Video S2: RdRp Motifs in the Mechanism of NTP Incorporation.", "In infected cells, viral RdRps have evolved to perform RNA synthesis under fine-tuned conditions. They must synthesize a faithful copy of the viral RNA genome, yet, they have to be able to generate a", "Alternatively, if reaction is slowed down, a slowed-down translocation of the primer may allow more time for occurrence of a nucleotide-excision repair such as the one described for HCV RdRp [30] ." ] },{ "paper_id": "bbcba5769c3aef1594790aa0d845ba112a0e1ab1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ochratoxin A (OTA) is a critical mycotoxin that causes various harmful effects in animals and humans. This mycotoxin is produced by filamentous fungi, such as Aspergillus spp., mainly A. carbonarius and Penicillium spp. A. ochraceus was the first fungus found to produce OTA [1, 2] .", "Serum samples collected from birds in each group at the end of the experiment were used to determine concentrations of serum total protein. The measurements were carried out with a spectrophotometer using commercially available kits (Diasys Diagnostic system GmbH, Holzheim, Germany).", "Before statistical analysis, all data were evaluated for homogeneity (Levin's tests) and normality (Kolmogorov tests). All data were subjected to one-way analysis of variance. Means of different groups were compared by Bonferroni tests using GraphPad Prism statistical package 5.01. Data were considered significantly different when p values were less than 0.05. " ] },{ "paper_id": "bbd8195f35ba4648be5eb649a3038f7485b7a71e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1) What is current knowledge:", "2) What is new here:" ] },{ "paper_id": "bbe42ce008a9dd9e25c03c36113d763dba358cbb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 12 different PLD isoforms encoded in the Arabidopsis thaliana genome are classified into six groups (\u03b1, \u03b2, \u03b3, \u03b4, \u03b5, and z) based on sequence similarity and in vitro activity [20] . PLDz1 and z2 have N-terminal phox homology (PX) and pleckstrin homology (PH) domains and share high sequence similarities to two PX/PH-PLDs in mammals. The remaining PLDs contain the Ca 2+ -dependent phospholipid-binding C2 domain and are unique to plants.", "Lipid overlay assays were conducted as recommended by the manufacture's protocol. Briefly, the membrane (PIP Strips or Membrane Lipid Arrays; Echelon Bioscience Inc) was incubated in 3% fatty acid free BSA (Sigma-Aldrich) in a mixture of phosphate-buffered saline and 0.1% Tween 20 (PBST) for 1 h at room temperature (RT) and then incubated in the same solution containing 500 ng of purified recombinant protein for 1 h at RT. After washing three times with PBST, the membrane was incubated with a mouse anti-FLAG antibody (1:10000; Sigma-Aldrich) for 1 h at RT, followed by three washes with PBST. An anti-mouse IgG conjugated with horseradish peroxidase (1:10000; KPL) was used as a secondary antibody. Binding of proteins to phospholipids was visualized by incubation with a chemiluminescent substrate.", "Positive-strand RNA [(+)RNA] viruses are the most abundant plant viruses, and include many viruses economically important in agriculture. (+)RNA plant viruses have a limited coding capacity. To replicate and achieve successful infection in their hosts, they need to use host proteins, membranes, lipids, and metabolites. All characterized eukaryotic (+)RNA viruses replicate their genomes using viral replication complexes (VRCs), which contain multiple viral and host components on intracellular membranes [1-6]. A growing number of studies have suggested that plant viruses have evolved ways to hijack plant host factors and reprogram host cell metabolism for their successful infection [6, 7] . Conversely, plants have evolved the ability to recognize viruses through specific interaction with viral proteins or viral double-stranded RNA intermediates for restricting virus infection [8, 9] . Viruses must circumvent or suppress such surveillance systems and host defense mechanisms. Thus, viruses must be evolved to achieve a good balance between hijacking/reprogramming host factors for efficient viral replication and avoiding the danger of stimulating antiviral defense responses." ] },{ "paper_id": "bbe74d62d65366418b61cb33a4ffe5ffcd3a8fce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All procedures using animals were approved by the Animal Care and Use Committees of Centre for Disease Control and Prevention, Chengdu Military Region and were in compliance with the China Animal Welfare Act. We state clearly that no specific permissions were required for these locations/activities and confirm that the field studies did not involve endangered or protected species.", "The Reoviridae (respiratory enteric orphan viruses) comprise a large and diverse group of nonenveloped viruses containing a genome of segmented double-stranded RNA, and are taxonomically classified into 10 genera [9] [10] [11] [12] [13] . Orthoreoviruses are divided into two subgroups, fusogenic and nonfusogenic, depending on their ability to cause syncytium formation in cell culture, and have been isolated from a broad range of mammalian, avian, and reptilian hosts [10] [11] [12] [13] [14] . Members of the genus Orthoreovirus contain a genome with 10 segments of dsRNA; 3 large (L1-L3), 3 medium (M1-M3), and 4 small (S1 to S4) [15] .", "To refer the Chua's report [9] , Serum samples from each bat were screened for anti-Cangyuan virus neutralizing antibody. Serum, the negative control (fetal calf serum, FCS), virus, and cell controls were included in the assay.", "Negative-staining EM of particles in the supernatant recovered from Vero E6 cells infected with Cangyuan virus revealed non-enveloped icosahedral virus-like particles, approximately 70-80 nm in diameter, possessing a double capsid with conspicuous \"spikes\" or \"turrets\" situated on the inner core; features characteristic of the family Reoviridae, genus Orthoreovirus ( Figure 1D ) [9] ." ] },{ "paper_id": "bbed3cc036065a43e9da69ad09ce74d487b31c6b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "bbf36eb3250211e0c223d0c2a9c41abcaa32d11a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "bbf555548912f929c3413cf6ee3314f9783cbb18", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "bbffb6a287ece187b7ad9ceb9f703854b0ea8e1d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Notably, viral mRNA transcription escapes from decay-induced repression, and this escape also relies on XrnI. However, the mechanisms that allow viral mRNAs, unlike cellular mRNAs, to escape from XrnI cleavage are unknown." ] },{ "paper_id": "bc00727fee1ac89ccac1843a04427ff7a504be41", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "bc01fae970a5c27f2213ac75db374170444545f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The homologous mammalian sequences of GSTM1 was identified using CdGSTM1 (accession number XP_010974221.1) amino acid sequence in PSI-BLAST. Ten homologous sequences of CdGSTM1 were retrieved from database. Multiple sequence alignment was done using MAFFT Multiple Sequence Alignment and Jalview [40, 66] . The output of aligned sequences was color-coded. Three-dimentional structure CdGSTM1 was modelled using Swiss-model server [67] using human glutathione S-transferase hGSTM1a-1a (PDB: 1GTU) as a template. The 3D structure of GSTM1 was analyzed using PyMOL software [68] .", "where Fo and F are the fluorescence intensities at maximum wavelength in the absence and presence of the quencher, respectively, Ksv is the Stern-Volmer quenching constant, and [Q] is the concentration of the quencher.", "Active fractions were pooled and subjected to size-exclusion chromatography to eliminate minor impurities and reduced glutathione. Superdex 75 16/600 GL prepacked column was equilibrated with 50 mM phosphate buffer containing 150 mM NaCl at pH 7.5. The active fraction of GSH-agarose elute was pooled and loaded on a column using a 5 mL superloop on an AKTA purification system. The purity of the gel filtration peak was analysed with a 4-15% mini-PROTEAN pre-casted TGX gel (Bio-rad) and stained with Coomassie Brilliant Blue G-250. The concentration of purified CdGSTM1was estimated at spectrophotometrically at 280 nm, with a molar extinction coefficient of 39,880 M \u22121 cm \u22121 ." ] },{ "paper_id": "bc04647c4db146a7078e6de38873824a95e99314", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Purified DNA was quantified for PCV2 against a standard curve using the Primer Probe Energy Transfer qPCR (PriProEt-RT-PCR) assay as previously described [30] .", "Conclusions: Our detailed analyses of piglets from NNPDS-affected herds demonstrated that viruses did not pose a significant contribution to NNPDS. However, further investigations are needed to investigate if a systemic virus infection plays a role in the pathogenesis of NNPDS." ] },{ "paper_id": "bc1beba35495c40001df667b4612b7cb9bb67185", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: The recent emergence of zoonotic diseases such as Highly Pathogenic Avian Influenza (HPAI) and Severe Acute Respiratory Syndrome (SARS) have contributed to dominant Global Health narratives around health securitisation and pandemic preparedness, calling for greater co-operation between the health, veterinary and environmental sectors in the ever-evolving One Health movement. A decade later, One Health advocates face increasing pressure to translate the approach from theory into action.", "One Health acknowledges the close relationships between humans, animals and ecosystems, promoting the potential added benefits to each sector or species that emerge as a result of its operationalisation ( Figure 1 ). Whilst attempts to categorically define One Health are many and varied, the general consensus that it promotes a transdisciplinary, collaborative ''whole of society'' approach towards global health in the 21 st century remains key [1] - [4] ." ] },{ "paper_id": "bc1d2578b23ef87c23e94bb11bf4986606483527", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(with a similar equation for , , and for , , ). We denote the transmission coefficient by , so that we have", "where", ", , = , , 12 + , , 21 \u2212 , , ( 13 + 23 ) , , , = ( , , ( 13 + 23 ) + , , ( 12 + 32 )" ] },{ "paper_id": "bc343b504f04146857602c5800c99ab7d08162d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "bc381e908d987cbecf5fb3df2640a7c878886405", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal care and experimental procedures were performed according to the guidelines established by the Tokyo Metropolitan ", "Madin-Darby canine kidney cells (MDCK cells; American Type Culture Collection, ATCC, VA, USA) were maintained in Dulbecco's modified Eagle's medium (D-MEM) supplemented with 10% fetal calf serum (FCS) and penicillin-streptomycin solution. RK-13 cells (ATCC) were maintained in modified Eagle's medium (MEM) supplemented with 5% FCS and penicillin-streptomycin solution. Cells were grown in an incubator at 37uC under 5% CO 2 .", "All rHAs except QH1A rHA were obtained from Sino Biological Inc. (Beijing, China).", "Sample solutions (10 ml) were suspended in 90 mL of FLIC dilution buffer (50 mM Tris-HCl (pH = 7.2), 150 mM NaCl, 1% Trition X-100), and dropped on the sample pad of the IC strip (Fig. 1a) . The fluorescence was detected with Konica Minolta immunochromatography reader (Konica Minolta, Inc., Tokyo, Japan) at excitation wavelength 660 nm and emission wavelength 710 nm (Fig. 2b) ." ] },{ "paper_id": "bc403b497ddc13f1a5352d7eef9d0fdaeccbc028", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "bc489624c814eedf1d191c84f7ca9efce0c98e1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The single and dual P-PMO conjugates were purified on a high-resolution (HR)-16 cation-exchange column (GE Healthcare, USA) using 25 mM sodium phosphate buffer (pH 7.2) containing 25% acetonitrile. The conjugates were eluted using a 1 M NaCl solution in the same buffer at a flow rate of 6 ml min \u22121 . The excess salts were removed by centrifugation using an Amicon R Ultra-15 3K centrifugal filter device. The conjugates were characterized using MALDI-TOF MS as mentioned above. They were dissolved in ster- ile water and filtered through a 0.22 m cellulose acetate membrane (Costar) before use.", "Mouse H2K/mdx myoblasts were plated at a density of 5 \u00d7 10 5 cells per well in a gelatin (0.01%) pre-coated 24well plate. H2K/mdx myoblasts were grown in high-glucose Dulbecco's modified Eagle's medium (DMEM) supplemented with 20% foetal calf serum (FCS), 2% CEE and 0.002% of interferon-\u2425 at 33 \u2022 C. The myoblast cells were differentiated into myotubes for the exon-skipping assay. Myoblasts were differentiated for 4 days in DMEM supplemented with 5% HS at 37 \u2022 C prior to transfection of P-PMOs in serum-free Opti-MEM for 4 h at 37 \u2022 C. The transfection medium was then replaced with DMEM/5% HS and cells incubated for a further 20 h at 37 \u2022 C.", "The levels of cytotoxicity of P-PMOs were assessed in human hepatocytes ", "Peptides were synthesized by standard Fmoc chemistry (34) using a CEM Liberty TM microwave peptide synthesizer (Buckingham, UK). Peptides were assembled on Fmoc-\u2424-Ala-OH preloaded Wang resin on a 0.1 mmol scale with excess of Fmoc-protected amino acids, PyBOP and DIPEA (5:5:10). The N\u2423-Fmoc protecting groups were removed by treating the resin with piperidine in DMF (20% v/v) at 75 \u2022 C twice, once for 30 s and then for 3 min. The coupling reactions were carried out at 75 \u2022 C for 5 min. In order to prevent racemization, Fmoc-cysteine (Trt)-OH was coupled at 50 \u2022 C for 10 min at 60 W microwave power. All amino acids were single coupled except for the arginines, which were double coupled. The Fmoc-L-bis-homopropargylglycine-OH was coupled manually using a 2-fold excess and the coupling success was checked using a TNBS test (35) . After completion of peptide assembly, the resin bound peptide was cleaved off by treating the resin with a cocktail of TFA:DoDt:H 2 O:TIPS (94:2.5:2.5:" ] },{ "paper_id": "bc4e3f1afdbc64641df9ffa7707910d13014d529", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vimentin is a type III intermediate filament and a major component of the cytoskeleton. Expressed in cells of mesenchymal origin, vimentin plays a key role in intracellular dynamics and architecture [26] . Vimentin encodes head, rod, and tail domains, and these domains are identified based on sequence and function [26] . Although it has long been considered a cytosolic protein, surface-expressed forms of vimentin have recently been discovered", "Other roles for vimentin during the picornavirus replication cycle include reorganization of cytosolic vimentin into cages that enclose autophagic vesicles at intracellular replication centers by TMEV and poliovirus [43] [44] [45] . The picornavirus encephalomyocarditis virus (EMCV) further induces an autoimmune response against vimentin after infection [46] .", "In addition to its role as a plant pathogen, CPMV has received recent attention as a nanoscale scaffold for the design of vaccines and therapeutics [4] [5] [6] [7] . The ability to generate nanoscale materials that can specifically target and image sites of disease is an important goal in biomedicine. A variety of nanoparticle strategies have been developed for targeting and imaging in vivo including antibodies [8] , dendrimers [9] , liposomes [10] , nanoshells [11] , quantum dots [12] , and viruses [13, 14] . Viruses are particularly suited for these applications because they are naturally designed for efficient circulation and specific ligand-binding and cellular internalization. Recently interest has turned toward self-assembling plant viruses, bacteriophages [4] , and protein cage [15] architectures that can be adapted for in vivo targeting purposes without the pathogenic properties of animal viruses. However these viruses must generally be tailored to recognize their targets using specific ligands.", "Cowpea mosaic virus (CPMV) is a member of the comoviridae family of plant viruses. The 31 nm-diameter capsid has a pseudo T = 3 symmetry composed of 3 beta-barrel domains formed from 2 capsid proteins, and is structurally related to animal picornaviruses that include such viruses as poliovirus, coxsackievirus, and Theiler's murine encephalomyelitis virus (TMEV) [1] . Within the picornavirus-like superfamily these viruses also share a similar genetic organization and along with CPMV are thought to derive from a common ancestor [2, 3] . The mechanisms of evolution of the picorna-like viruses within the kingdoms of life, and possible cross-kingdom transmission during evolution, are unknown." ] },{ "paper_id": "bc50818627fbe2bfdbd0b471da603d88ca9e54f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bat guano was collected from three sites in Turkestan Oblast from 11 April to 16 May 2017. These sites were the Kepterkhan tunnel and Qaraungir cave in Tulkibas Rayon District, with additional guano collected in the Ungirli cave in Altyntau, Sozak Rayon ( Figure 1 ). Bat feces were collected from plastic sheets placed underneath bat roosts. Multiple fecal pellets were placed into cryovials with viral transport media using polyester swabs, which were subsequently placed into a liquid-nitrogen dry shipper and then transferred back to the Research Institute for Biological Safety Problems (RIBSP) in Gvardeiskiy, Kazakhstan, where all samples were stored at \u221280 \u2022 C.", "The following are available online at http://www.mdpi.com/1999-4915/11/4/356/ s1: Figure S1 . Phylogenetic relationships of the RdRp gene sequences of coronavirus, inferred using the maximum-likelihood method with the GTR + GAMMA model in RAxML. Representative virus isolates from Alpha-, Beta-, and Gamma-coronavirus were included in the analysis. Colored branches and symbols denote viruses collected from different hosts. New CoV sequences generated from this study are marked by red branches. Bootstrap support values greater than 50% are displayed at major nodes. The scale bar indicates the number of nucleotide substitutions per site. ", "Bats are mammals in the order Chiroptera that possess a range of unique ecological, immunological, and behavioral attributes. Bats are exceptionally speciose, comprising 20% of all mammalian species, and they are the only mammals that are capable of true flight [1] . Most bat species are gregarious and roost in large colonies, which can number over one million individuals [2] . They are relatively long-lived for their body size, and temperate species often undergo torpor or hibernation [3] . Bats also act as rich reservoirs of virus diversity with at least 23 families of viruses detected, including double-stranded DNA viruses, single-stranded DNA viruses, and positive-and negative-sense single-stranded RNA viruses [4] . Bats are incriminated as the source of several medically important virus families, including filoviruses, coronaviruses, paramyxoviruses, and reoviruses [5, 6] . Several recent zoonotic spillover events and outbreaks directly or indirectly originated from bats [1] ." ] },{ "paper_id": "bc5761e9d769b9fb1e723e1932ee3c5d4e21bd0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mean c:p:m:of ODN \u00c0 treated cultures Mean c:p:m of PBS \u00c0 treated cultures", "Mean optical density OD \u00f0 \u00devalues of duplicate wells treated with plasma from timepoint 0h Mean OD values of duplicate wells treated with plasma from timepoint Xh", "Feline PBMC isolation, cell lines, ODNs, cell culture and cell viability assay Feline PBMCs were isolated from EDTA-anticoagulated whole blood by Ficoll-Hypaque density gradient centrifugation using a standard protocol [56] . Purified cells were counted prior to their utilization in the different experiments using the Sysmex XT 2000iV (Sysmex, Norderstedt, Germany) as described previously [57] , and cultured in RPMI 1640 with Glutamax I (Gibco \u00ae , Invitrogen, Basel, Switzerland). Adherent CRFK (ATCC no. CCL-94) and FEA cells were maintained in RPMI 1640 with Glutamax I, while adherent fcwf-4 cells (ATCC no. CRL-2787) were cultured in EMEM (ATCC " ] },{ "paper_id": "bc589336315df8e93a0fcd4fda5442bf982e9b6d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pilot work: novel methods of AE detection", "Prior studies have shown that the CDC/NNSH definitions have limited accuracy for identifying cases of AEs [51] [52] [53] ." ] },{ "paper_id": "bc64088b806d6f43c4888ddb00a0479c8e57d33e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mean \u00b1 SD (PCN/\u00b5g DNA)" ] },{ "paper_id": "bc67c021d6e189215a0101f6e5de32daa8e4ccee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Seven CoVs in clade 7 from S. kuhlii, S. heathii and C. sphinx were clustered in an independent lineage. These viruses (from 5 bats) had 99.15-100% identity of 119 amino acids and differed from HKU9 by 16.11-16.95% ( Figure 2 ). Further analyses using longer gene fragments and other genes from greater number of bats are required for confirmation of this novel group.", "In addition, this is the first report describing the presence of CoV RNA in 6 bat species including C. sphinx, T. melanopogon, H. lekaguli, R. shameli, S. heathii and Megaderma lyra, where the latter is the newly reported bat family (Megadermatidae) found to harbor CoV.", "Interestingly, co-infection of divergent CoV lineages was found in one bat (M. magnater, BFE55593), which was infected with 2 different CoV species, clustered in clades 1 (CoV 1A/B) and 2 (HKU7) (Figure 2 ). This finding is similar to a previous report from China, where coinfection of bat CoV 1B and HKU8 were detected in M. pusillus using species-specific RT-PCR assays [29] . Coinfection with different CoVs in the same host may facilitate recombination between these CoVs. Further studies of co-infection and CoV recombination within a given bat host could improve our understanding on the evolution of CoVs, including specific mutations or recombination events (e.g. involving the Spike gene), that could facilitate spillover to novel species." ] },{ "paper_id": "bc763a4c1cb0175d61d1332af8d137d0482df73b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Filoviral trans-infection from DCs to CD4 + T cells is improbable as lymphocytes are largely resistant to EBOV infection [135] . Nonetheless, filoviruses display a broad cell tropism, infecting hepatocytes, adrenal cortical cells, and endothelial cells, among other cellular targets [136] [137] [138] [139] . Thus, aside from lymphocytes, other cellular targets could be transinfected (Figure 3 , bottom right), as it was previously shown for a human cell line binding EBOV that transinfected HeLa cells [140] . However, further research will be required to determine in which anatomical context DCs trapping EBOV via Siglec-1 could transfer that infectivity to susceptible cellular targets in vivo.", "Yet, how these findings correlate with the pathogenesis of different Siglec-1-interacting human viruses, such as HIV-1 or EBOV, remains largely unexplored. HIV-1 is the causative agent of acquired immunodeficiency syndrome (AIDS), a pandemic that has affected more than 70 million people worldwide [36] , while EBOV is responsible for the intermittent outbreaks that produce a filovirus-associated disease (FVD) with high fatality rates [37] . In this review, we discuss how Siglec-1 is induced on human DCs upon viral infection, to what degree that impacts different viral antigen presentation routes, and in which ways distant enveloped viruses have evolved to exploit Siglec-1 function as a dissemination strategy in distinct anatomical compartments.", "While HIV-1 replication on DCs remains hard to identify in vivo, it has been known for more than a decade that DCs are among the first target cells encountering EBOV [11] . DCs are highly susceptible to EBOV infection [11, 103] , and this is a complex process that involves several host factors whose function is still being identified [104] . Indeed, Siglec-1 expressed on activated DCs has recently emerged as a new host factor implicated in EBOV attachment, a mechanism that facilitates subsequent cytoplasmic viral entry [22] ( Figure 2B ).", "Siglec-1 is a type I transmembrane lectin with an amino-terminal V-set domain that interacts with sialylated ligands, preferentially N-acetylneuraminic acid (Neu5Ac) in an \u03b12-3 linkage [19, 23] . Several enveloped viruses including human immunodeficiency virus (HIV)-1 [24] [25] [26] and Ebola virus (EBOV) [22, [27] [28] [29] incorporate such sialylated ligands within their membranes as an integral part of the gangliosides that are dragged from the plasma membrane when viruses bud from infected cells. Although Siglec-1 affinity for sialylated ligands is in the micromolar range, high-avidity binding can be achieved upon clustering of thousands of gangliosides in the viral membrane with their receptors on the cellular membrane [19, 30] . Moreover, as Siglec-1 contains 16 Ig-like C2-type extracellular domains that separate the ligand-binding site from the cell surface, it is available for interaction with external ligands and not bound in cis to cell-surface molecules, which is what usually happens with shorter Siglecs that are also expressed by DCs [19, 23, 31] .", "Initial EBOV attachment to the DC surface is mediated by several receptors that recognize different elements on the viral membrane and often have a redundant activity [105] . C-type lectin receptors (CLRs) such as the dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and the liver/lymph node sinusoidal endothelial C-type lectin (LSECtin) mediate viral attachment through binding to viral glycoproteins [106, 107] , while receptors of the TIM/TAM families (comprising the T cell immunoglobulin and mucin domain receptor along with Tyro-Axl-Mer receptors) recognize phosphatidylserine lipids present on the viral envelope [108] (Figure 2B ). EBOV incorporates sialylated gangliosides on their membrane [27] , and we have recently shown that these viruses are effectively recognized by the Siglec-1 receptor [22] (Figure 2B )." ] },{ "paper_id": "bc7b16d381d2acf67eb97db19f1686c90d72ecf1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. Only one of the four DENV serotypes was examined. 2. Cytotoxic effects limited the concentration test range of compounds.", "All data were analyzed using the GraphPad Prism program (GrapPad Software Inc., San Diego, CA). Statistical analysis of significance was undertaken by One-Way ANOVA on raw data reads using SPSS (SPSS Inc., Chicago, IL). EC 50 values were calculated using the freeware ED50plus (v1.0) software (http://scien cegat eway.org/ proto cols/cellb io/drug/data/ed50v 10.xls).", "These results suggest that some commonly taken natural compounds may have beneficial effects on DENV infection, but that others may potentially add to the disease burden." ] },{ "paper_id": "bc7b2271acba0248f021e9e11cb91cec6358d924", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "bc7c67f8bf777ec11fcdfdbd36ed0c3fb55f2c72", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The r.h.s. of equation (5) are not yet infected, as indicated by the probability", "Countries characterized by particularly low values of \u03b7, for cultural, behavioral, and/or social reasons, would be at a lower risk of invasion. Therefore control measures aimed at reducing the contacts ratio \u03b7 of a specific country may represent an effective policy option to consider. This could be achieved through the application of workplace interventions, including for instance working at home, reducing or avoiding work meetings, and shifting the working timing to reduce overlap at workplaces and at break hours, as well as crowding on transports [62] .", "Background: Confirmed H1N1 cases during late spring and summer 2009 in various countries showed a substantial age shift between importations and local transmission cases, with adults mainly responsible for seeding unaffected regions and children most frequently driving community outbreaks." ] },{ "paper_id": "bc91f45d3fb7fbedebffb850dbf2dc3d3c7c2142", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LC-MS/MS-The samples were fractionated by high pH reversephase High Performance Liquid Chromatography (HPLC). Briefly, peptides were dried by vacuum centrifugation. Then the Peptides were dissolved in 0.1% formic acid and directly loaded onto a reversed-phase precolumn (Acclaim PepMap 100, Thermo Scientific). Peptides were separated using a reversed-phase analytical column (Acclaim PepMap RSLC, Thermo Scientific) and analyzed by Q Exactive TM hybrid quadrupole-Orbitrap mass spectrometer (Thermo Fisher Scientific).", "samples. For each protein, we set the average ratio calculated from two duplicate samples as the final quantitation of protein. Student's test was explored to calculate differential significance degree of protein relative abundance changes. t test p value less than 0.05 was considered significantly differentially. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD008174 (http://www.ebi.ac.uk/pride/archive/) (18) .", "represents gene neighborhood; represents gene fusions; gene co-occurrence. Others: represents textmining; represents co-expression; represents protein homology." ] },{ "paper_id": "bca258b97648522c7513be8ef70fdfd2ba5e3240", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Similar to the approach in the previous study [31] , the association between the state rainfall level and LASV transmissibility are modelled by a linear mixed-effect regression (LMER) model in Eqn (3),", "Lassa fever (LF), caused by Lassa virus (LASV), is increasingly recognised as an important rodent-borne viral haemorrhagic fever presenting a severe public health threat to some of the communities in sub-Saharan West Africa [1] . Discovered in 1969 [2] , LF is endemic to much of rural Nigeria and regions in the Mano River Union [3] . LASV transmits from human to human, as well as via the zoonotic cycle [1, 3, 4] . LF has a high case fatality rate ranging from 1% in the community to over 60% in hospital settings [1, 4, 5] . The common reservoir of LASV is Mastomys natalensis, one of the most widespread rodent species in sub-Saharan Africa [1, 3] , which exhibits sensitive population dynamics to the water level, e.g. rainfall, flooded agricultural activities [6, 7] . Previous studies have recognised the ecological association between the population levels of rodents and rainfall [8] [9] [10] .", "Data. All data used for analysis are freely available via online public domains [12, 15] ." ] },{ "paper_id": "bca82a8723c167333ef1d73d5bf0fd900f30b695", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In recent years bats have been recognized as important reservoirs of highly pathogenic viruses for human and other animals such as SARS coronavirus, Hendra, and Nipah viruses 1,2 . Bats have also been proposed as potential reservoir for Ebola 3 and MERS 4 , although direct evidence is still lacking. How do bats cope with viruses that have a high mortality rate in humans without getting sick? How have they evolved to co-exist with such viruses? Understanding the bats immune system should help address this question and might open a door to new therapeutic interventions for humans.", "Among the MHCII + T cells, majority were Eomes + single positive whereas majority of MHCII \u2212 T cells were Eomes + Tbet + (CD8+ T cells) (Fig. 4c) . However, these percentages varied between bats and between organs (data not shown).", "Together, these results demonstrate for the first time that the main lymphocyte populations in bats are able to produce effector molecules such as cytokines and cytolytic factors in response to mitogenic stimulation.", "In conclusion, this study represents a landmark in the field of bat immunology being the first to describe a strategy for phenotypic and functional characterization of the main lymphocyte populations in bats." ] },{ "paper_id": "bca9f4ffe445882f2de559b938d83a69e90d2224", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "bcb10d6f9d4c95cfcd762fe6297dcb46bc15ec3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sialic acid (SA) as a natural ligand combines with both of the glycoproteins (HA and NA) and located at the membrane of host cell, which is the basis of heme-agglutination when viruses are mixed with blood cells and entry of the virus into cells of the upper respiratory tract [11, 12] . According to the mutagenic analysis the residues of both HA1 and NA binding sites are quite conserved for most influenza A strains [13, 14] .", "Owing to its deep active site cleft, the NA has been an attractive target for drug design. Both zanamivir and oseltamivir were designed by modifying the sialic acid (SA) structure. The two FDA-approved clinical drugs were once successfully used to inhibit the spread of influenza viral progeny [15] by binding to viral surface glycoprotein of neuraminidase (NA) [15] . However, it has also been found from several clinical cases [16, 17, 18] that oseltamivir failed to treat avian influenza virus. It is both antigenic drift (sequence base mutations) and antigenic shift (genetic recombination) of segmented RNA genome of influenza viruses that have caused the NA inhibitor being resistant [19, 20] .", "The drug-like database and the fragment database derived from ZINC [38] were used for virtual screening and core hopping searching, respectively.", "In recent years, severe flu-like human cases were reported around the world and subsequently the causative virus was identified as the influenza A virus [1, 2] . The virus was spreading rapidly around the world and had been identified as a new reassortant with three genetic lineages, mainly with a swine origin. Therefore, it was called swine-origin influenza virus (S-OIV). Owing to its extremely rapid human-to-human transmission rate, within only two months the 2009 S-OIV had been detected throughout the entire world. On June 11th, 2009 the World Health Organization (WHO) declared an official pandemic, the first pandemic in the 21st century [3] ." ] },{ "paper_id": "bcb21b0dcaf5456200446cd3e1c6ad1990253dbf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sweden is, by European standards, a large country, with a small population. Just over 9 million people share 450000 square kilometers. The population is, however, largely urbanized, and in that respect similar to other industrialized nations with large areas.", "The intermunicipal travel network Figure 1 The intermunicipal travel network. The intermunicipal travel network with travel intensities indicated by color lines. The scale is logarithmic in trips per day. SIM shows the complete dataset. In SIM50 and SIM20, all journeys > 50 km and 20 km, respectively, have been removed. The lines are drawn between the population centers of each municipality, so in many cases the trips are shorter than the lines representing them.", "The results for all nine scenarios were plotted geographically and color-coded according to the mean incidence ( Figure 2 ).", "Knowledge of the speed at which a contagious disease travels between geographical regions is vital for making decisions about the most effective intervention strategies. The actual routes a disease will take are strongly determined by how individuals travel within and between regions [1] [2] [3] [4] . As was shown during the outbreak of severe acute respiratory syndrome (SARS) [5] , current travel patterns enable contagious diseases to spread to far corners of the globe at alarming rates. This demonstrates the need for a new type of model that incorporates travel networks." ] },{ "paper_id": "bcd61a98bcf6ab96b5e65dd3f7bfe288e6f9153a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments were performed three times unless otherwise specified, and data are expressed as the mean \u00b1 SD of the values from all experiments. Statistical significance was assessed using a two-tailed unpaired Mann-Whitney t-test with a threshold set at p < 0 05.", "The simplified illustration summarizing differences between CLR agonists in Th polarization and mucosal IgA production is presented in Figure 8 .", "The authors declare that there is no conflict of interest regarding the publication of this article." ] },{ "paper_id": "bcd9208e1cff6a9d5e3af17745299ceea1479529", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bats represent approximately one fifth of the world's mammalian species and are among the most diverse and geographically dispersed mammals. Frugivorous and nectivorous pteropid bats (family Pteropodidae, suborder Megachiroptera) constitute approximately 170 species and are known colloquially as fruit bats or flying foxes. Their capacity for long-distance dispersal through flight has undoubtedly contributed to their widespread distribution throughout tropical and sub-tropical Asia and Australia, and on islands of the Indian and western Pacific Oceans. The black flying fox, Pteropus alecto, is distributed mainly across the northern and eastern coasts of Australia [1] . Since 1994, this species has gained particular attention after it was identified as the natural host of Hendra virus (HeV) [2, 3] .", "Total RNA was extracted from lymph node, spleen, liver, lung, heart, kidney, small intestine, brain and salivary gland as previously described [47] . For each sample, 500 ng total RNA was used as template in a 20 ml cDNA synthesis reaction. Quantitative PCR primers were designed using Primer Express 3.0 (Applied Biosystems) with default parameter settings. . qPCR reactions were preformed in triplicate as described previously [47] . Copy numbers of target sequences were calculated using standard curves and normalised relative to 18 s ribosomal RNA.", "A body of evidence exists implicating bats as a major source of zoonotic viruses [4] [5] [6] . Bats have been shown to harbour and disseminate highly pathogenic viruses including Ebola, SARS-like coronavirus and the henipaviruses (HeV and Nipah) [4] . Spillover events from bats to other species -including humans -have increased. In 1998, a spillover event of Nipah virus from pteropid bats to farmed pigs caused a major disease outbreak in Malaysia. More than 1 million pigs were culled, and of the 265 reported human cases, 105 were fatal [7, 8] . While the incidence of HeV in Australia has been more sporadic, an increase in spillover events from pteropid bats to horses has occurred. Between 1994 and 2010, 14 HeV outbreaks occurred in Australia involving 48 confirmed equine cases (75% fatality rate) and seven human cases (60% fatality rate). In contrast, between June 2011 and January 2012, 19 HeV outbreaks occurred [9] . The increasing incidence of HeV, combined with its high fatality rate, means HeV has the potential to cause further significant disease outbreaks in Australia and abroad. Recently, a novel paramyxovirus that is closely related to the henipaviruses, named Cedar virus, was isolated from fruit bats in Australia [10] . However unlike HeV, Cedar virus caused no clinical disease in experimentally infected ferrets and guinea pigs [10] . Evidence of henipavirus infection in multiple bat species has also been identified in continental Africa [11] ." ] },{ "paper_id": "bcdceb50d70afda0d8615859b356484af61aab04", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Optimized temperature of LAMP assay for PCV2", "One hundred and ten serum samples were analyzed using the LAMP method to determine whether they were infected by PCV2. PCV2 was detected in 95 clinical samples." ] },{ "paper_id": "bce65fb977ab27efae9992d88884173851877570", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hoetjes [28] e Impact of Armed Conflict on Health in Al-Raqqah Governate, Syria e study examined medical data to determine the effects of war on health of vulnerable groups of people in Al-Raqqah governorate in Syria.", "It was reported that, after a 15-year gap, Syria faced a polio outbreak.", "e authors declare that they have no conflicts of interest." ] },{ "paper_id": "bcfa3dbb3fadcb51bd684e07b654328d2bf4e0db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are presented as mean \u00b1 SD or median (range) and n = 8 unless indicated. Haematology results are presented in Table 1 .", "Analysis (Sigma Plot, Systat Software Inc.) over time was performed with one-way ANOVA for repeated measures (continuous data, normally distributed by test of Shapiro-Wilk) or Friedman repeated measures ANOVA on ranks (discontinuous data or non-normally distributed data) with Holm-Sidak's or Dunn's posthoc tests, respectively (multiple comparisons versus pre-induction). Pre-induction values were recorded 30 min after SC injection with medetomidine. For ETCO 2 , the first value used for the comparison over time was recorded 5 min after induction. A P-value < 0.05 was considered significant. Continuous and normally distributed data are presented as mean \u00b1 SD and discontinuous or non-normal distributed data as median (range).", "Medetomidine is known for its adverse cardiovascular effects [30] , even in very low doses [31] . In human anaesthesiology, alpha-2-adrenergic agonists are increasingly used in low doses to improve cardiovascular stability and prevent tachycardia [32] .", "The study was approved by Uppsala, Sweden, Experimental Animal Ethics Committee (C368/9)." ] },{ "paper_id": "bd05c37d7f0fe6c8ba93e2a5cbc52ac371a8fbce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .00869-18.", "FIG S1, TIF file, 0.2 MB. TABLE S1, DOCX file, 0.01 MB.", "The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of the NIH." ] },{ "paper_id": "bd067c850dd16252d8c195caeb129a3e304e5700", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results are presented as mean \u00b1 standard deviation (SD). All the statistical analyses were performed using the GraphPad Prism software.", "Micronucleus tests were conducted as previously described [30] . Briefly, 25 male Kunming mice (6-weeks old, 18-20 g) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd., Beijing, China. Animals were acclimated for a week and randomly allocated into the following groups with five mice each: vehicle control (normal saline), 200 mg/kg PT-1 (low-dose), 600 mg/kg PT-1 (mid-dose), 1800 mg/kg PT-1 (high-dose) and positive control (cyclophosphamide, CP, 40 mg/kg). Mice were administrated intragastrically with PT-1/normal saline or intraperitoneally with CP once a day for three days. Mice were sacrificed 48 h post the last administration, then the bilateral femur was separated, bone marrow cells were collected from the aforementioned femur in fetal bovine serum, centrifuged at 1000\u00d7 g for 5 min, and smeared onto slides. Slides were air-dried and fixed by submerging in methanol for 15 min, followed by Giemsa staining for 15 min. Slides were then randomly coded and counted under \u00d71000 magnification. Data were expressed as the ratio of immature erythrocytes (polychromatic erythrocytes, PCE) to total erythrocytes (PCE + normochromatic erythrocytes, NCE) by counting at least 200 erythrocytes and the number of micronucleated (MN) PCE in 1000 PCEs. The study was carried out with approval of the Animal Ethical Committee of China Academy of Chinese Medical Sciences (approval code: 2014059).", "Peripheral blood mononuclear cells were isolated from three healthy blood donors using a Ficoll gradient (GE Healthcare, Chicago, IL, USA). PBMC were pre-stimulated with ConA (5 \u00b5g/mL; Sigma) at a density of 1 \u00d7 10 6 cells/mL for 2 days, then the activated PBMC were washed twice with PBS and maintained in a culture medium containing human recombinant IL-2 (25 ng/mL; PeproTech Inc., Suzhou, China) during viral infection. PBMC (1 \u00d7 10 5 /well) were incubated with HIV-1 NL4-3" ] },{ "paper_id": "bd0a970593b33e212262cce0e5a9be28b555f18e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "bd0d94a4452f2b55cfab53adecb84ce5f2c91fe3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell viability was obtained using the following equation.", "Percent cell viability = Test 570 nm \u2212 650 nm/Control 570 nm \u2212 620 nm \u00d7 100", "All statistical analysis was done using SPSS software (version 16.0, SPSS Inc). Data are presented as mean \u00b1 SD. Numerical data were analyzed using student's t-test and ANOVA. P value < 0.05 was considered statistically significant." ] },{ "paper_id": "bd108a54d3d8e9f2a2389a2ee26798259273fd3b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The association of ACE activity with ARDS outcomes is far from linear. Multiple factors, like the heterogeneity of ARDS and the variability of RAS activation in patient subgroups, could be implicated in this complex interplay [1]. Even though increased levels of ACE and Ang II have been detected in patients with ARDS, the pathophysiological role of RAS in ARDS development remains unclear. Additional factors such as, for example, the variable substrates of ACE and ACE2 apart from Ang (namely bradykinin and apelin), the protective effects against lung injury which Ang II receptor type 2 exerts, and the effect", "Abbreviations ACE: Angiotensin-converting enzyme; ACE2: Angiotensin-converting enzyme 2; Ang II: Angiotensin II; ARDS: Acute respiratory distress syndrome; RAS: Renin-angiotensin system", "[1], are essential." ] },{ "paper_id": "bd18832006ef03fab74bf51388034b7e9605e14a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In terms of IAV antivirals, the recent progress in determining the structures and mechanisms of the viral polymerase should significantly aid in the current development of drugs aimed at inhibiting different aspects of IAV transcription (249) . Through continued progress in defining the fundamental mechanisms that are necessary for IAV infections, replication and intercellular movement, it should become possible to minimize the annual burden caused by IAVs.", "2", "RD wrote the review with input from DD, RR, H\u00d6, and HW. DD, RR, H\u00d6, and HW put together the figures and wrote the figure legends. ", "The movement of IAVs from cell to cell in the respiratory epithelium is significantly different from that in immortalized cell lines grown in liquid culture due to the presence of different cell types and a mucus layer. The mucus layer provides a protective barrier for the epithelium and is rich in heavily glycosylated mucins that can interact with IAVs and limit cell binding (226, 227) . Studies measuring viral movement through mucus and respiratory epithelial cells have shown that NA-mediated cleavage of SAs from mucins enhances IAV movement through the mucus layer and infectivity ( Figure 6C and step viii) (226, 228, 229) . Recent work showed that this function may also apply to transmission, as IAVs that possess low NA activity, and are inhibited by mucus, are deficient in aerosol and contact transmission (230) ." ] },{ "paper_id": "bd1d9c526a0194d356d7a65ebcebc322dd872a36", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Immunoglobulin deficiencies (ID) are congenital or inherited disorders of humoral immunity characterized by low immunoglobulin titers. They could account for a part of submerged celiac iceberg, since they contribute to a lower CD detection rate, in particular for potential, latent or SNCD.", "Such secondary forms of sIgMD, occurring concomitantly to CD, could be linked to a decreased immunoglobulin synthesis by a dysfunctional lymphoreticular tissue stimulated by gluten antigen exposure [85, 87] .", "CVID may show a wide range of immunological manifestations, including autoimmune phenomena, such as cytopenias, megaloblastic anemia/atrophic gastritis, immune thrombocytopenic purpura, autoimmune hemolytic anemia, sarcoidosis-like granulomatous infiltrative disorders, inflammatory bowel disease, autoimmune hepatitis and CD [61] ." ] },{ "paper_id": "bd246a6d199cb961f7c4c3421d22324aface4ff4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "bd44d72a9c41b1c382bd180da10a1f7ef38d2d56", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In conclusion, transductionally targeted viruses may provide a much needed tumor-specific therapy, but researchers will have to face, besides the technological challenges, a delicate balance between safety and effectiveness during development of such new viruses for clinical use. Yet, despite all problems and concerns, the importance of the ultimate goal of winning the fight against cancer warrants the sacrifice of all the energy and creativity needed for its realization.", "Replication-competent retroviruses have gained interest as oncolytic agents, in particular because of their high transduction efficiency (reviewed in [26, 27] ). Of MuLV different classes can be distinguished, of which the host range is based on the interaction between the envelope glycoprotein and a particular cell surface receptor. While the ecotropic MuLVs are particularly capable of infecting mouse and rat cells, amphotropic MuLV infects a range of mammalian, including human cells via the widely expressed Pit-2 receptor.", "Using Bispecific Adapters", "Another strategy successfully employed for the same purpose made use of pseudoreceptors. In this approach, bispecific proteins were generated by fusion of a soluble form of CAR (sCAR) to EGF [67, 68] , to the Fc region of human IgG1 [69] , and to scFvs against ErbB2 [70] and CEA [71] .", "Sindbis virus has inherent oncolytic properties and has been studied quite extensively as an oncolytic virus (reviewed in [43] ). One of the surface proteins on mammalian cells to mediate the Sindbis virus infection is the laminin receptor, which is overexpressed on various human tumors. The envelope protein E2 of Sindbis virus is responsible for receptor binding." ] },{ "paper_id": "bd45834afc3184d92957993038c6889353797fc1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Stress was induced using 500 \u03bcM sodium Ars (NaAsO 2 ; Sigma-Aldrich) for " ] },{ "paper_id": "bd55c44a2d6e3ec7d067fd6c46d569e4cc869d70", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "r 1a (t) from 1: i.e.," ] },{ "paper_id": "bd57ac5cebeff6091e3ca6756a1efcf1c692b0f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As a country that does not vaccinate against IBV, Finland has been exempt from IBV clinical cases since the 1970s. However, several vaccine-like pathogenic strains, including the D274 and 4/91 strains, were found in a 2011 outbreak, indicating the variation of vaccine strains [90] . Finland is now considering improving their vaccination process with live attenuated vaccines.", "In India, Patel et al. [81] isolated a strain similar, but genetically distinct, to the Mass type vaccine M41 strain. The first 4/91 type strain in India was isolated by Sumi et al. [82] , which may be a new vaccine strain variant based on its genomic sequence.", "According to Krapez et al. [91] , the predominant IBV strains in Slovenia from 1990 to 2005 were 624/I type strains (9/15, 60%), which can be distinctly clustered with strains of earlier isolation periods and geographical origin, based on the S1 gene." ] },{ "paper_id": "bd592988022fb91de64e0d4c287d3b04d864f8ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All tests had either two (reference vs. abnormal) or three (low, normal, or high) possible response values. For tests with three values, we performed two separate rule searches: one for high vs. not high-i.e., grouping normal and low-and one for low vs. not low.", "CART generated rules for 60 tests. However, the AUC for most of these rules was low, with only five tests having AUC$0.75: free T3, alpha-macroglobulin, CA27-29, hyaluronic acid, and alpha fetoprotein (AUC 0.75-0.79).", "Data-processing was performed in Python (Enthought Canopy Python version 2.7.3. R (version 2.15.3) was used for statistical analysis and reports generation.", "As proof of principle for GLM, we first tested it on the anion gap, a result calculated by subtracting the serum concentrations of the anions chloride and bicarbonate from those of the cations sodium and potassium, and confirmed that our methods found a rule for elevated anion gap based on these four items." ] },{ "paper_id": "bd5e22fa122a78846797a754e1dcb12887036229", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1)", "where", "The authors declare that they have no conflicts of interest." ] },{ "paper_id": "bd6dd93085fa736cac9569090a8cb88324daf18f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2.8. Differentiated PC12 Cell and Microglial BV2 Cell Culture.", "The data used to support the findings of this study are available from the corresponding author upon request. ", "at 37\u00b0C for 30 min, after which the cells were washed and transferred to 96-well plates. The ratio of red (585/590 nm) and green (510/527 nm) fluorescence was determined using a fluorescence plate reader.", "All statistical parameters were calculated using the GraphPad Prism 7.0 software (GraphPad Software, San Diego, CA, USA). Values are expressed as means \u00b1 standard error of the mean (S.E.M.). Statistical comparisons between the different treatments were performed using one-way analysis of variance (ANOVA) with Tukey's multiple comparison posttest. A p value < 0.05 was considered to be statistically significant.", "According to the WHO, as much as 80% of the world's population relies primarily on animal-and plant-based medicines [43] [44] [45] . Animal-assisted therapy is known as zootherapy (ZT) [45] . The phenomenon of ZT is marked both by a broad geographical distribution and very deep historical origins [45] . Despite its importance, studies on ZT have been neglected, when compared to those on plant-based therapies. However, in modern societies, ZT constitutes an important alternative to other therapies practiced worldwide [45] . Wild and domestic animals and their by-products (e.g., hooves, skins, bones, feathers, and tusks) provide important ingredi-ents to curative, protective, and preventive medicine [46] [47] [48] ." ] },{ "paper_id": "bd78c67dd1bf9aea39f8fb3a1fe1761628dbe422", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chemicals and antibodies. Celecoxib, NS-398, SC-58125, SC-236, nimesulide, and SC-560 were purchased from Cayman Chemical (Ann Arbor, MI, USA). GCDCA, dimethyl sulfoxide (DMSO), L-NAME, MDL-12330A, and indomethacin were from Sigma-Aldrich (St. Louis, MO, USA). COX-1 siRNA, COX-2 siRNA, and scrambled siRNA were purchased from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA, USA). Monoclonal antibody (MAb) against mouse COX-1 and polyclonal antibody against rabbit COX-2 were obtained from Abcam (Cambridge, MA, USA). Mouse MAb against HA tag was purchased from OriGene (Rockville, MD, USA). Synthetic PGE 2 was purchased from Tocris Bioscience (Ellisville, MO, USA). The anti-PSaV capsid MAb and the anti-PSaV VPg polyclonal antibody were previously described (41) . The secondary antibodies used were horseradish peroxidase-conjugated goat immunoglobulin against rabbit IgG (Cell Signaling, Beverly, MA, USA) and mouse IgG (Santa Cruz) and fluorescein isothiocyanate (FITC)-conjugated goat immunoglobulin against rabbit IgG (Jackson Immuno Research Laboratory, West Grove, PA, USA).", "Cells and virus. LLC-PK porcine kidney cells obtained from the American Type Culture Collection (ATCC) were maintained in Eagle's minimal essential medium (EMEM) containing 10% fetal bovine serum (FBS), 100 U/ml penicillin, and 100 g/ml streptomycin. The tissue culture-adapted PSaV strain Cowden was recovered from the full-length infectious clone pCV4A and was propagated in LLC-PK cells supplemented with bile acid (15) .", "Cytotoxicity assay. The cytotoxicity of the chemicals used in this study was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay (42, 43) according to the manufacturer's instructions. Briefly, cells in 96-well plates were incubated with medium containing different concentrations of various chemicals for 24 h. After removal of the medium, 200 l of MTT solution was added to each well and incubated for 4 h at 37\u00b0C in a CO 2 incubator. Each well was supplemented with 150 l of DMSO and incubated at room temperature for 10 min. The absorbance as an optical density (OD) was read in an enzyme-linked immunosorbent assay (ELISA) reader at 570 nm. The percent cell viability was calculated using the following formula: [(OD sample \u03ea OD blank )/(OD control \u03ea OD blank )] \u03eb 100. Nontoxic concentrations of each chemical were used in the study." ] },{ "paper_id": "bd7f96581b36339bff8aca7e50e1b91f333fc00e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Endnotes a Contextual translation of press conference videos posted at: China.com (2012) Press conference of medical and health system leadership team. http://www.china. com.cn/zhibo/zhuanti/2013lianghui/content_28211342. htm. Accessed 29 March 2013. b An exchange rate of 6.25 RMB per 1 USD is used throughout the article, based on the average for calendar year 2012. c This estimate is based on cases compiled at: China Daily Forum (2012) . d Author's analysis of data from P.R. China, Statistical Yearbook; OECD iLibrary; ClinicalTrials.gov; and IMS health.", "Medical device firms also are enjoying growth from market dynamics that encourage hospitals to acquire new technologies and use them extensively. The device market was estimated at 146 billion RMB ($23 billion) in 2012 (Business Monitor International 2012). In some notable cases, early entrants have developed new imaging devices and diagnostic tests in China for Chinese patients (Johnson & Johnson 2011 ). Yet foreign firms often find it challenging to understand the hospital procurement system for devices and diagnostics. Consequently, some firms are switching from a strategy of globally branded product development to partnerships with local Chinese companies.", "When announcing the 2009 healthcare package, the Central Committee and State Council took note of mounting tensions:", "System integration also declined significantly, and patients fell into gaps between different components of the health system. For basic care, people had to wait in long queues at hospitals, with no possibility for scheduled appointments and little privacy during a brief physician consultation. Since patients did not have a regular primary care physician or clinic, they had to maintain and carry with them personal medical records. A lack of coordination among health facilities also contributed to a rise of communicable diseases in China in the 1990s and early 2000s (Liu 2004; Tang and Squire 2005) ." ] },{ "paper_id": "bd907eded401f2594ef37b2f448ebf71046bd1dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This is a case which was reported during our work in the hospital, and there are no direct financial, indirect financial, and career or personal belief conflicts.", "On 29/9/2015, he presented to the Emergency Department with complained of diplopia and nasal regurgitation.", "1.2. Lab. His baseline blood count results are as follows: white blood cells 11.6K/ml, neutrophils 8.4K/ml, hemoglobin (Hb) 12.6 g/dl, MCV 85 fl, MCH 30 pg, and platelets 202K/ml. His renal and liver function tests were within normal ranges. His baseline carcinoembryonic antigen was 309 ng/dl. Proctocolonoscopy showed a mass 4 cm from the anal canal extending proximally for 10 cm. When biopsied, histopathologic examination result confirmed a poorly differentiated adenocarcinoma with focal signet ring morphology arranged in sheets and cords with minimal acinar formation." ] },{ "paper_id": "bd9162d8379baef31b50aa17a7f553740aa28ba2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u202b\u0620\u202c Organization of genomic data in a structured fashion to facilitate navigation from family to strain/isolate \u202b\u0620\u202c Compilation of representative genomic entries for every viral species ", "sequence-based and structure-based algorithms developed in-house [50] [51] [52] .", "The models were built using Homology module of Insight II molecular modeling package. Amber-all atom force field [83] and distance dependent dielectric constant of 4rij was used. The models were refined using steepest descents and conjugate gradient methods, the detailed protocol of which is described previously [37, 38] . JEV DEN2 S2 H51 H51 D75 D75 G151 G151 N152 N152 G153 G153 S1" ] },{ "paper_id": "bd921a71bee40ea8cb9c3725c6dce6ad0ce5a560", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "bd92cbae7179f07d59d1ce4d7ca96e37ebb40ec9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Citation: Yang H, Xie W, Xue X, Yang K, Ma J, et al. (2005) Design of wide-spectrum inhibitors targeting coronavirus main proteases. PLoS Biol 3(10): e324.", "[I] is inhibitor concentration; [S] is substrate concentration; K m is the Michaelis-Menten constant for the substrate; k 3 is the rate constant of inactivation, and K i is the equilibrium constant.", "Cytotoxicity assay. DBT cells were suspended in growth medium in 96-well plates. The next day, appropriate concentrations of the inhibitor were added to the medium. Two days later, the relative numbers of surviving cells were measured by MTT (Sigma, St. Louis, Missouri, United States) assay in accordance with the manufacturer's instructions.", "DBT cells were suspended in growth medium in triplicate wells in 6-well plates and preincubated with appropriate concentrations of the inhibitor. The next day, the medium was aspirated, and MHV-A59 was added to each well at a titer of 100 PFU/well. After incubation for 1 h, the virus inoculum was aspirated, and 2 ml of a media-agar overlay with appropriate concentrations of inhibitor was added to each well. The plates were further incubated for 24 h and stained with neutral red to visualize plaques." ] },{ "paper_id": "bd96aabb0e4aa01c5310bf23827eb32168779a7c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .00535-18. ", "Citation Lane WC, Dunn MD, Gardner CL, Lam LKM, Watson AM, Hartman AL, Ryman KD, Klimstra WB. 2018. The efficacy of the interferon alpha/beta response versus arboviruses is temperature dependent. mBio 9:e00535-18. https://doi." ] },{ "paper_id": "bd9937d46e1e7947e28497ca098b76703981d2d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since the Middle East respiratory syndrome-coronavirus outbreak in 2015, the Korean government has been encouraging hospitals to employ infection control doctors by policy. Consequently, the Korean National Health Insurance Service now reimburses infection control costs on the condition that doctors and nurses be allocated for infection control in hospitals with more than 300 beds [13] . Accordingly, there has been a recent increase in the number of IDSs working as infection control doctors in NAC hospitals. These IDSs are expected to play a major role in ASPs; however, this has not yet been fully evaluated.", "Use of antimicrobial agents has reduced mortality in infectious diseases. However, excessive antibiotic use has caused development of antimicrobial resistance (AMR) in bacteria [1, 2] . Infection with an antimicrobial resistant organism has become a major public health concern due to its difficulty to treat, resulting in an increase in hospital stays, cost, and mortality [3] . While antimicrobial resistant organisms have been increasing rapidly, only a few new drugs for combating these pathogens have been developed [4] .", "Statistical analyses were performed using SAS version 9.4 (SAS Institute, Inc., Cary, NC, USA.) or R software version 3. Statistical significance was considered as p < 0.05." ] },{ "paper_id": "bda64532f4a16e2885868385170f8bc89ab8f789", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell staining kit from Cell Signaling Technologies was used for cell staining and photomicrographs of stained cells were obtained with Nikon TS100 Eclipse inverted microscope and Nikon DS camera.", "Unpaired Student t test or one sample t test after logarithmic transformation was employed for statistical analysis.", "p < 0.05 was considered statistically significant." ] },{ "paper_id": "bda897976d2a119dd7f4505065d769c3b93cddf7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SCIENTIfIC RePORts | (2018) 8:1860 | DOI:10.1038/s41598-018-20305-4 (Hyclone) supplemented with 10% Human serum (HS) (I-DNA Biotechnology). All cultures were incubated at 37 \u00b0C with 5% CO 2 supplied with the exception of C6/36 which was incubated at 28 \u00b0C with no CO 2 supplied. All media and reagents were tested negative for endotoxins." ] },{ "paper_id": "bdb16338832867fb4c294b2694e8e23da78f3597", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The slides were mounted with Vectashield mounting medium containing DAPI (H-1200, Vector Laboratories) and images were captured with a Zeiss LSM510 META confocal microscope and analyzed with the ImageJ 1.42q software (Wayne Rasband, National Institutes of Health, USA).", "Putative caspase cleavage sites were searched in the BPLF1 amino acid sequence using the GraBCas software [47] . Sites with the highest probability of cleavage were identified by setting the cut-off scores to .15.", "Akata-Bx1 cells that carries a recombinant EBV where the thymidine kinase gene was replaced by a CMV immediate early promoter driven GFP [44] " ] },{ "paper_id": "bdb2855fba379ffefbd1e4b49d0d5db65ee93852", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Biotic Conditions", "The authors declare that there are no conflicts of interest regarding the publication of this paper." ] },{ "paper_id": "bdb4a76b9add4907c177c780d8318e3256dce7ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rubella is an acute infectious viral disease characterized by low-grade fever, a short-lived morbilliform rash, and lymphadenopathy 1 . Additionally, arthritis often develops in rubella patients, particularly in adolescents and adult female patients, and encephalitis, while rare, is a severe complication of this disease. Most importantly, neonates born from mothers who suffered from rubella during the first trimester of pregnancy may develop congenital rubella syndrome (CRS) and multiple organ malformations. Congenital cataracts, sensorineural hearing loss, and cardiovascular defects are most common in CRS.", "Statistical analysis. Two-tailed t-tests were used to determine significant differences among pseudotype virus infectivity titers in various cell lines. Data Availability. The datasets analyzed during the current study are available from the corresponding author on reasonable request.", "Results" ] },{ "paper_id": "bdbfaa82df2210193903b96916ffe6fed13694b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Vero (ATCC CCL-81) cell line was obtained from the European Collection of Cell Cultures (ECACC) (Sigma-Aldrich, L'isle d' Abeau Chesnes, France).", "The poliovirus type 1 strain SABIN LSc-2ab was obtained from the Eurovir Hygiene-Institut (Luckenwalde, Germany).", "The poliovirus was spread in a flask of Vero cells cultured in DMEM (Dulbecco's Modified Eagle's Medium, Invitrogen, France) supplemented with 2% FBS (Fetal Bovine Serum), 1% Non Essential Amino Acids and 1% L-glutamine at 37\u00b0C in a 5% CO 2 atmosphere. When a cytopathic effect of at least 90% appeared, the cells were scratched off and the cell suspension was freezed (\u221280\u00b0C) and thawed three times and then centrifuged at 1000 g for 10 minutes. The resulting supernatant was aliquoted and stored at \u221280\u00b0C." ] },{ "paper_id": "bdcfff55eaabeaa26d71810113d717ef85e417d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Where the real epitope is unknown, we would suggest running MIMOX with a range of parameters and consensus sequence derived fragments to find overlapping or otherwise promising (high surface accessibility) candidate." ] },{ "paper_id": "bdd49a68f33046aa3a724721b7050c5f548f90de", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Proteases enable breakdown of proteins via catalytic hydrolysis of peptide bonds [1] . Malfunction in the control of protease activity leads to undesired and unregulated proteolysis which causes many diseases. Therefore, inhibitors of proteases have the potential to provide successful therapeutics for a wide range of diseases [2, 3] .", "Plakortide E, obtained from the marine sponge Plakortis halichondroides, was identified as a new protease inhibitor. Plakortide E showed selectivity towards the cathepsin-like cysteine proteases, with a non-competitive, reversible, and, in the case of rhodesain, a slow-binding inhibitory mode of action. The anti-protease activity of the compound may contribute to its anti-parasitic activity against Trypanosoma brucei, as rhodesain and also the cathepsin B like protease TbCatB [13] are known to be essential for the parasite's growth and pathogenicity.", "In this paper, we report new protease inhibitory activity of plakortide E towards cathepsins and cathepsin-like parasitic proteases. We further report on its anti-parasitic activity against Trypanosoma brucei with an IC 50 value of 5 \u03bcM and without cytotoxic effects against J774.1 macrophages at 100 \u03bcM concentration. Plakortide E was isolated from the sponge Plakortis halichondroides using enzyme assay-guided fractionation and identified by NMR spectroscopy and mass spectrometry. Furthermore, enzyme kinetic studies confirmed plakortide E as a non-competitive, slowly-binding, reversible inhibitor of rhodesain." ] },{ "paper_id": "bdd4a8a3507c4df13f06d8693ce8d6b4e9d6c3af", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Genotyping of SNP by tetra-primer amplification refractory mutation system PCR (ARMS-PCR) and restriction fragment length polymorphisms (RFLP)", "Feline infectious peritonitis (FIP) is an immune-mediated disease caused by feline coronavirus (FCoV) infection. Despite the vast number of studies conducted since the recognition of FIP [1] , neither effective vaccines nor therapeutic agents are available for the prevention or treatment of this often fatal disease. Therefore, it remains one of the most important feline infectious diseases.", "In several studies on human viral infections, i.e., human immunodeficiency virus [43] , hepatitis B and hepatitis C [44, 45] , a similar correlation between the magnitude of the IFN-\u03b3 response and disease manifestation was identified. The polymorphisms in IFNG were associated with the diseases caused by these viruses [46] [47] [48] ." ] },{ "paper_id": "bdfce208ef62424bc68fdb610364dab6416365e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MMCT was done with each HAC vector as described previously [12, 17, 20] .", "Array probe design, chip hybridization, and data analysis were performed by Roche NimbleGen (www.nimblegen.com).", "(XLSX)", "In summary, our improved Tc bovine system for the production of fully hpAbs has further advanced achieving the goal of producing large quantities of therapeutic hpAbs as an alternative for plasma derived hpAbs." ] },{ "paper_id": "be0098a38881944590f4d51d6e29bf4e616267e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All RRs (95%CIs) were presented after adjusting for age and sex ", "Background and purpose: \uac10\uc5fc\ubcd1 \uad00\ub9ac\ub85c \uc778\ud55c \uaca9\ub9ac\ub294 \uc815\uc2e0\uac74\uac15\uc5d0 \uc601\ud5a5\uc744 \uc904 \uac83\uc73c\ub85c \uc5ec\uaca8\uc9c0\ub098 \uc544\uc9c1\uae4c\uc9c0 \uadf8 \uc601\ud5a5\uc5d0 \ub300\ud574\uc11c \uc54c\ub824\uc9c4\ubc14 \uc5c6\ub2e4. \uba54\ub974\uc2a4 \uc720\ud589\uc73c\ub85c \uaca9\ub9ac\ub418\uc5c8\ub358 \uc0ac\ub78c\uc5d0\uc11c \uaca9\ub9ac \ub2f9\uc2dc\uc758 \ubd88\uc548\uc99d\uc0c1\uacfc \ubd84\ub178\uac10 \uc720\ubcd1\uc728\uc744 \uc54c\uc544\ubcf4\uace0 \uaca9\ub9ac\ud574\uc81c \ud6c4 4-6\uac1c\uc6d4 \uc2dc\uc810\uc5d0 \ubd88\uc548\uc99d\uc0c1\uacfc \ubd84\ub178\uac10 \uc720\ubcd1\uc728\uacfc \uadf8 \uc704\ud5d8\uc694\uc778\uc744 \ud30c\uc545\ud558\uace0\uc790 \ud558 \uc600\ub2e4. Methods: 2015 \ub144 \ud55c\uad6d\uc5d0 \uba54\ub974\uc2a4 \uc720\uc785\uc73c\ub85c \uba54\ub974\uc2a4 \ud658\uc790\uc640\uc758 \ubc00\ucc29\uc811\ucd09\uc73c\ub85c 2 \uc8fc\uac04 \uaca9\ub9ac\uc870\uce58 \ub41c 14,999 \uba85 \uc911 1,692 \uba85\uc744 \ub300\uc0c1\uc73c\ub85c \uba54\ub974\uc2a4 \uaca9\ub9ac\ud574\uc81c \ud6c4 4-6 \uac1c\uc6d4 \uc9c0\ub09c \uc2dc\uc810\uc5d0\uc11c GAD-7 \uc744 \uc774\uc6a9\ud558\uc5ec \ubd88\uc548\uc99d\uc0c1\uc744 \ud3c9\uac00\ud558\uc600\uace0 STAI \ub97c \uc774\uc6a9\ud558\uc5ec \ubd84\ub178\uac10\uc744 \ud3c9\uac00\ud558\uc600\ub2e4. \uaca9\ub9ac \ub2f9\uc2dc\uc758 \ubd88\uc548\uc99d\uc0c1\uacfc \ubd84\ub178\uac10, \uadf8\ub9ac\uace0 \uc704\ud5d8 \uc694\uc778\uc740 \ud6c4\ud5a5\uc801\uc73c\ub85c \ud3c9\uac00\ud558\uc600\ub2e4. Results: \ubc00\ucc29\uc811\ucd09\uc790 1,692\uba85 \uc911 1,656\uba85\uc740 \uba54\ub974\uc2a4\ub85c \uc9c4\ub2e8\ub418\uc9c0 \uc54a\uc558\ub2e4. \uaca9\ub9ac\uae30\uac04\ub3d9\uc548 \uaca9\ub9ac\uc790\uc758 7.6% (95%CI: 6.3-8.9)\uac00 \ubd88\uc548\uc99d\uc0c1\uc774 \uc788\uc5c8\uace0, 16.6% (95%CI: 14.8-18.4)\uac00 \ubd84\ub178\uac10\uc774 \uc788\uc5c8\ub2e4. \uaca9\ub9ac\ud574\uc81c \ud6c4 4-6\uac1c\uc6d4 \uc9c0\ub09c \uc2dc\uc810\uc5d0\uc11c \uaca9\ub9ac\uc790\uc758 3.0% (95%CI: 2.2-3.9)\uac00 \ubd88\uc548\uc99d\uc0c1\uc774 \uc788\uc5c8\uace0, 6.4% (95%CI: 5.2-7.6) \uac00 \ubd84\ub178\uac10\uc774 \uc788\uc5c8\ub2e4. \uaca9\ub9ac\ud574\uc81c \ud6c4 4-6\uac1c\uc6d4 \uc9c0\ub09c \uc2dc\uc810\uc5d0\uc11c \ubd88\uc548\uc99d\uc0c1 \ubc0f \ubd84\ub178\uac10\uc744 \uacbd\ud5d8\ud558\ub294 \uc704\ud5d8\uc694 \uc778\uc73c\ub85c\ub294 \uaca9\ub9ac \ub2f9\uc2dc \uba54\ub974\uc2a4 \uc99d\uc0c1\uc774 \uc788\uc5c8\uac70\ub098 \uad6c\ud638\ud488 \ubcf4\uae09\uc774 \ucda9\ubd84\ud558\uc9c0 \uc54a\uc558\uac70\ub098 \uc774\uba54\uc77c, \ubb38\uc790, \uc778 \ud130\ub137 \ub4f1\uc744 \uc0ac\uc6a9\ud558\uc600\uac70\ub098 \uc815\uc2e0\uacfc \uc9c8\ud658\uc758 \uacfc\uac70\ub825\uc774 \uc788\uc5c8\ub358 \uacbd\uc6b0, \uc7ac\uc815 \uc190\uc2e4\uc774 \uc788\uc5c8\ub358 \uc0ac\ub78c\uc774\uc5c8\ub2e4. Conclusion: \uaca9\ub9ac\ud574\uc81c \ud6c4 4-6\uac1c\uc6d4 \uc2dc\uc810\uc5d0 \uc815\uc2e0\uac74\uac15\ubb38\uc81c\ub294 \uc815\uc2e0\uac74\uac15\uc5d0 \ucde8\uc57d\ud55c \uc0ac\ub78c\uc5d0 \ub300\ud55c \uc2ec\ub9ac\uc9c0\uc6d0, \uaca9\ub9ac \uae30 \uac04 \ub3d9\uc548 \uc815\ud655\ud55c \uc815\ubcf4\uc81c\uacf5\uacfc \uc2dc\uc758 \uc801\uc808\ud55c \uad6c\ud638\ud488\uc744 \uc81c\uacf5\ud568\uc73c\ub85c\uc368 \uc608\ubc29 \ud560 \uc218 \uc788\uc744 \uac83\uc774\ub2e4. \uc11c\ub860 2015 \ub144 5 \uc6d4 20 \uc77c \ud55c\uad6d\uc5d0\uc11c \uc911\ub3d9\ud638\ud761\uae30\uc99d\ud6c4\uad70 (Middle East Respiratory Syndrome, MERS; \uba54\ub974\uc2a4) \uccab \ud655\uc9c4\uc790\uac00 \ubc1c\uc0dd\ud55c \uc774\ud6c4 \ud658\uc790\uac00 \uae09\uc18d\ub3c4\ub85c \uc99d\uac00\ud558\uc5ec 45 \uc77c\ub9cc\uc5d0 186 \uba85\uc758 \ud655\uc9c4 \ud658\uc790\uac00 \ubc1c\uc0dd\ud558\uc600\uace0 \uc774 \uc911 38 \uba85\uc774 \uc0ac\ub9dd\ud558\uc5ec \uce58\uc0ac\uc728\uc774 20%\ub77c\ub294 \uae30\ub85d\uc744 \ub0a8\uacbc\ub2e4. \uc608\ubc29 \ubc31\uc2e0\uacfc \uce58\ub8cc\uc81c\uac00 \ud655\ub9bd\ub418\uc9c0 \uc54a\uc740 \uc0c1\ud669\uc5d0\uc11c \uba54\ub974\uc2a4 \uac10\uc5fc\uc774 \ud655\uc0b0\ub418\uc5c8\uae30 \ub54c\ubb38\uc5d0 \ubd88\ud655\uc2e4\uc131\uc5d0 \uae30 \uc778\ud558\ub294 \uc0ac\ud68c\uc801\uc778 \ubd88\uc548\uc99d\uc0c1\uacfc \ub450\ub824\uc6c0\uc774 \ud575\uc2ec\uc774\uc288\uac00 \ub418\uc5c8\uace0, \uac80\uc99d\ub418\uc9c0 \uc54a\uc740 \uc720\uc5b8\ube44\uc5b4\uc640 \ub8e8\uba38\ub85c \uc778 \ud55c \uc798\ubabb\ub41c \uc815\ubcf4\ub4e4\uc774 \uacf5\uc720\ub418\uae30\ub3c4 \ud558\uc600\ub2e4. \uc0ac\ub78c\ub4e4\uc740 \uba54\ub974\uc2a4 \uac10\uc5fc \uac00\ub2a5\uc131\uc5d0 \ub300\ud574 \uac71\uc815\uc744 \ud558\uac8c \ub418\uc5c8\uace0, \uc77c\ubd80 \ubcd1\uc758\uc6d0 \ud3d0\uc1c4\uc870\uce58\uac00 \uc774\ub8e8\uc5b4\uc9c0\uae30\ub3c4 \ud558\uc600\uace0 \ud559\uad50\uc758 \ud734\uad50\uae4c\uc9c0 \uc774\uc5b4\uc9c0\uba74\uc11c \uc0ac\ud68c \uc77c\ubc18\uc5d0 \ubd88\uc548\uac10\uc774 \uc99d\uac00\ud588\ub2e4. \uc804\uc5fc\uc131 \uc9c8\ud658 \ud2b9\uc131 \ub54c\ubb38\uc5d0 \uc790\uac00\uaca9\ub9ac \ud574\uc81c\ub41c \ub300\uc0c1\uc790\ub97c \uae30\ud53c\ud558\uac70\ub098 \uba54\ub974\uc2a4 \ubc1c\uc0dd \ubcd1\uc758\uc6d0\uc5d0 \uc885\uc0ac\ud558\ub294 \uc758\ub8cc\uc778 \ubc0f \uac00\uc871\ub4e4\uc744 \uba40\ub9ac \ud558\ub294 \uacbd\ud5a5\uc740 \uc0ac\ud68c\ub099\uc778\uc73c\ub85c \ubc88\uc9c0\uac8c \ub418\uc5b4 \uba54\ub974\uc2a4 \ud655\uc9c4\uc790\ub098 \uaca9\ub9ac\uc790\uc5d0\uac8c \ubd84\ub178\uac10\uc744 \uc720\ubc1c\ud558\ub3c4\ub85d \ud558\uc600\ub2e4. 2003 \ub144 30 \uac1c\uad6d\uc5d0 \uac78\uccd0 \ub300 \uc720\ud589\ud558\uc600\ub358 SARS(severe acute respiratory syndrome) \ub85c \uc778\ud574 8,000 \uba85 \uc758 \uac10\uc5fc\uc790\uac00 \ubc1c\uc0dd\ud558\uc600\uace0, \uc774 \uc911 774 \uba85\uc774 \uc0ac\ub9dd\ud558\uc5ec \uc804 \uc138\uacc4\uc5d0 \ubd88\uc548\uac10\uc744 \uc8fc\uc5c8\uc5c8\ub2e4. \ub2f9\uc2dc SARS \uac10\uc5fc \uc790\ub294 \uc0ac\ud68c\uc801 \ub099\uc778\uc744 \uacbd\ud5d8\ud558\uc600\uace0 \ubd88\uc548\uc99d\uc0c1, \uc6b0\uc6b8\uc99d \ub4f1 \uc815\uc2e0\uac74\uac15 \ubb38\uc81c\ub97c \ud638\uc18c\ud558\uc600\ub2e4 [1]. 2005-2006 \ub144 \ud64d\ucf69\uc5d0\uc11c SARS \uc0dd\uc874\uc790 1,394 \uba85\uc744 \ub300\uc0c1\uc73c\ub85c \uc815\uc2e0\uac74\uac15\uc744 \ud3c9\uac00\ud55c \uacb0\uacfc, 47.8%\uac00 SARS \uc774\ud6c4\uc5d0 \uc678 \uc0c1 \ud6c4 \uc2a4\ud2b8\ub808\uc2a4\uc7a5\uc560 (PTSD)\ub97c \uacbd\ud5d8\ud558\uc600\uace0, \uc774 \uc911 25.6%\ub294 30 \uac1c\uc6d4\uc774 \uc9c0\ub09c \uc2dc\uc810\uc5d0\uc11c\ub3c4 \uc815\uc2e0\uac74\uac15\uc5d0 \ubb38\uc81c\ub97c \ud638\uc18c\ud558\uace0 \uc788\uc5b4\uc11c \uc815\uc2e0\uc801\uc778 \ud6c4\uc720\uc99d\uc774 \uc7a5\uae30\ud654 \ub418\ub294 \uac83\uc73c\ub85c \ub098\ud0c0\ub0ac\ub2e4 [2]. \uc790\uc5f0\uc7ac\ud574\uc5d0 \ub178\ucd9c\ub418\uc5c8\ub358 \uc0ac\ub78c\ub4e4\uc758 \uc815\uc2e0\uac74\uac15\ud3c9\uac00\uc5d0\uc11c \uc7ac\ub09c \uc0dd\uc874\uc790\ub4e4\uc740 \uc678\uc0c1 \ud6c4 \uc2a4\ud2b8\ub808\uc2a4\uc7a5\uc560\ub97c \ube44 \ub86f\ud558\uc5ec \uc6b0\uc6b8\uc99d, \ubc94\ubd88\uc548\uc7a5\uc560, \uacf5\ud669\uc7a5\uc560, \ubb3c\uc9c8\ub0a8\uc6a9 \ub4f1 \ub2e4\uc591\ud55c \uc815\uc2e0\uc9c8\ud658\uc744 \uacaa\ub294 \uac83\uc73c\ub85c \ub098\ud0c0\ub0ac\ub2e4 [3-5]. \uc7ac\ub09c\uc73c\ub85c \uc778\ud574 \uc815\uc2e0\uc801 \ucda9\uaca9\uc744 \uacbd\ud5d8\ud55c \uc0dd\uc874\uc790\ub4e4\uc5d0\uc11c \ubd84\ub178 \uac10\uc815\uc740 \uc77c\ubc18\uc801\uc73c\ub85c \uc0dd\uaca8\ub098\ub294 \uac83\uc73c\ub85c \uc678\uc0c1\ud6c4 \uc2a4\ud2b8\ub808\uc2a4\uc7a5\uc560\uc758 \ubc1c\ub2ec\uacfc \uc870\uc808\uc5d0 \uc788\uc5b4\uc11c \uc911\uc694\ud55c \uc694\uc778\uc73c\ub85c \uc8fc\ubaa9\ubc1b\uace0 \uc788\ub2e4 [6-8]. 2003 \ub144 \uad6d \ub0b4\uc5d0\uc11c \ubc1c\uc0dd\ud55c \ub300\uad6c\uc9c0\ud558\ucca0 \uc0ac\uace0 6 \ub144 \ud6c4 \uc870\uc0ac\ud55c \uc5f0\uad6c\uc5d0 \ub530\ub974\uba74 40%\uc5d0 \ub2ec\ud558\ub294 \ud53c\ud574\uc790\ub4e4\uc774 \uc678\uc0c1 \ud6c4 \uc2a4\ud2b8\ub808\uc2a4\uc7a5\uc560\ub97c \uacaa\uace0 \uc788\uc5c8\uace0 \uc0ac\ud68c\uc801 \uad00\uacc4\ub97c \ud68c\ud53c\ud558\uac70\ub098 \uae34\uc7a5\uac10, \ubd88\uc548\uac10, \uc218\uba74\ubb38\uc81c \ub4f1\uc758 \uc5b4\ub824\uc6c0 \uc744 \uacaa\uace0 \uc788\ub294 \uac83\uc73c\ub85c \ub098\ud0c0\ub0ac\ub2e4 [9]. \uc0dd\ud55c \uc11c\uc6b8, \uacbd\uae30, \ucda9\uccad, \uac15\uc6d0 \ub4f1 4 \uac1c \uc9c0\uc5ed\uc744 \uc120\uc815\ud558\uc600\ub2e4. \uac01 \uc9c0\uc5ed\ub0b4\uc5d0\uc11c \uc870\uc0ac \ub300\uc0c1\uc790 \uc120\uc815\uc740 \uaca9\ub9ac \uc790 \uc911\uc5d0\uc11c \ud655\uc9c4\uac00\ub2a5\uc131\uc774 \ub192\uc740 \uc21c\uc11c\ub85c \uc870\uc0ac\ub300\uc0c1\uc790\ub97c \uc120\uc815\ud558\uc600\ub2e4. \ud655\uc9c4\uac00\ub2a5\uc131\uc5d0 \ub530\ub978 \uc21c\uc704\ub294 0 \uc21c\uc704 \ub294 \ud655\uc9c4\ud658\uc790, 1 \uc21c\uc704\ub294 \uc288\ud37c\uc804\ud30c \ud655\uc9c4\ud658\uc790\uc758 \ub3d9\uac70\uc778, \uac19\uc740 \ubcd1\uc6d0\ud658\uc790, \uac04\ubcd1/\ubc29\ubb38\uac1d\uc73c\ub85c \uad6c\uc131\ub418\uc5b4 \uc788 \uc5c8\uace0, 2 \uc21c\uc704\ub294 \uac10\uc5fc\uc804\ud30c \ud655\uc9c4\ud658\uc790\uc758 \ub3d9\uac70\uc778, \uac19\uc740 \ubcd1\uc6d0\ud658\uc790, \uac04\ubcd1/\ubc29\ubb38\uac1d\uc774\uc5c8\uace0, 3 \uc21c\uc704\ub294 \uadf8 \uc678 \ud655 \uc9c4\ud658\uc790\uc758 \ub3d9\uac70\uc778, \uac19\uc740 \ubcd1\uc6d0\ud658\uc790, \uac04\ubcd1/\ubc29\ubb38\uac1d\uc774\uc5c8\uc73c\uba70 4 \uc21c\uc704\ub294 \ud655\uc9c4\ud658\uc790\uc758 \uc77c\ubc18\uc778 \uc811\ucd09\uc790\ub85c \uc815 \uc758\ud558\uc600\ub2e4. \uc81c\uacf5 \ubc1b\uc740 \uc790\ub8cc\uc5d0\uc11c \uc811\ucd09 \uad00\ub828 \uc815\ubcf4\uac00 \ubbf8\ud655\uc778\ub418\uc5b4 \uc21c\uc704\ub97c \ubd80\uc5ec\ud560 \uc218 \uc5c6\ub294 \uc0ac\ub78c\ub3c4 \uc788\uc5c8 \ub2e4. \ud655\uc9c4\ud658\uc790\uc758 \uc815\uc758\ub294 \uc2e4\ud5d8\uc2e4 \uc9c4\ub2e8\uac80\uc0ac\ub97c \ud1b5\ud574 \uba54\ub974\uc2a4 \ucf54\ub85c\ub098\ubc14\uc774\ub7ec\uc2a4 \uac10\uc5fc\uc774 \ud655\uc778\ub41c \uc0ac\ub78c\uc774\uc5c8\ub2e4. \uc811\ucd09\uc790\uc758 \uc815\uc758\ub294 \uc801\uc808\ud55c \uac1c\uc778\ubcf4\ud638\uc7a5\ube44\uc778 \uac00\uc6b4, \uc7a5\uac11, N95 \ub9c8\uc2a4\ud06c, \uace0\uae00 \ub610\ub294 \uc548\uba74\ubcf4\ud638\uad6c \ub4f1\uc744 \ucc29 \uc6a9\ud558\uc9c0 \uc54a\uace0 \uba54\ub974\uc2a4 \ud658\uc790\uc640 2 \ubbf8\ud130 \uc774\ub0b4\uc5d0 \uba38\ubb38 \uacbd\uc6b0, \uba54\ub974\uc2a4 \ud655\uc9c4\ud658\uc790\uc640 \uac19\uc740 \ubc29 \ub610\ub294 \uc9c4\ub8cc, \ucc98 \uce58, \ubcd1\uc2e4\uc5d0 \uba38\ubb38 \uacbd\uc6b0, \ud639\uc740 \ud658\uc790\uc758 \ud638\ud761\uae30 \ubd84\ube44\ubb3c\uacfc \uc9c1\uc811 \uc811\ucd09\ud55c \uacbd\uc6b0\ub85c \uc815\uc758\ud558\uc600\ub2e4 [11]. \uba54\ub974\uc2a4 \uc758 \uc7a0\ubcf5\uae30\ub294 2 \uc77c\uc5d0\uc11c 14 \uc77c\uc774\uae30 \ub54c\ubb38\uc5d0 \ubc00\ucc29\uc811\ucd09\uc790\uc758 \uacbd\uc6b0 14 \uc77c \ub3d9\uc548\uc740 \uc99d\uc0c1\uc774 \ub098\ud0c0\ub098\ub294\uc9c0 \uad00\ucc30 \uae30\uac04\uc744 \ub450\uc5b4\uc57c \ub41c\ub2e4. \uc774 \uae30\uac04\ub3d9\uc548 \ubc00\ucc29\uc811\ucd09\uc790\ub85c \ud655\uc778\ub41c \uc0ac\ub78c\uc740 \uc790\ud0dd, \uc9c1\uc7a5, \ubcd1\uc6d0 \ub4f1\uc5d0\uc11c 2 \uc8fc\uac04 \uaca9 \ub9ac\uc870\uce58\ub97c \ubc1b\uac8c \ub418\uc5c8\ub2e4. 2015 \ub144 5 \uc6d4 \ub9d0\ubd80\ud130 6 \uc6d4 \uc911\uc21c\uae4c\uc9c0 \uaca9\ub9ac\uc870\uce58 \ub418\uace0 \ubcf4\uace0\ub41c 14,999 \uba85\uc758 \uba85\ub2e8\uc744 \uc9c8\ubcd1\uad00\ub9ac\ubcf8\ubd80 \uc5ed\ud559 \uc870\uc0ac\uacfc\ub85c\ubd80\ud130 \uc81c\uacf5\ubc1b\uc558\ub2e4. \uc774 \uc911 \uc870\uc0ac\ub300\uc0c1\uc9c0\uc5ed\uc778 \uc11c\uc6b8, \uacbd\uae30, \ucda9\uccad, \uac15\uc6d0 \uc9c0\uc5ed \uac70\uc8fc\uc790 7,313 \uba85 \uc911 \uc6b0\uc120\uc21c\uc704 \ub300\uc0c1\uc790 3,371 \uba85\uc5d0\uac8c \uc804\ud654\ub97c \uac78\uc5b4 \uc5f0\uad6c\ucc38\uc5ec\uc758\uc0ac\ub97c \uc9c8\ubb38\ud558\uc600\ub2e4. \uc6b0\uc120\uc21c\uc704 \ub300\uc0c1\uc790 \uc120\uc815\uc740 \ud574\ub2f9\uc9c0\uc5ed\uc5d0 \uac70\uc8fc\ud558\ub294 \ud655\uc9c4\ud658\uc790\uc640 \ud655\uc9c4\ud658\uc790\uc758 \ub3d9\uac70\uc778, \uac19\uc740 \ubcd1\uc6d0\ud658\uc790, \uac04\ubcd1\uc778, \ubc29\ubb38\uac1d\uc73c\ub85c \uc120\uc815\ud558 \uc600\ub2e4. 1,694 \uba85(50%)\uc774 \uc870\uc0ac \ucc38\uc5ec\uc5d0 \ub3d9\uc758\ud558\uc600\uace0 1,679 \uba85\uc740 \ucc38\uc5ec\uc5d0 \ub3d9\uc758\ud558\uc9c0 \uc54a\uc558\ub2e4. \ucc38\uc5ec\ub97c \uac70\ubd80 \ud55c 1,679 \uba85 \uc911, 65 \uba85 (4.8%)\uc740 \uc695\uc124\uacfc \ud3ed\uc5b8\uc744 \ud558\uba70 \uac15\ud55c \uc870\uc0ac \ucc38\uc5ec \uac70\ubd80 \uc758\uc0ac\ub97c \ubcf4\uc600\uace0, 315 \uba85 (23.2%) \uc740 \ud3ed\uc5b8\uc744 \ud558\uba70 \uc870\uc0ac\ucc38\uc5ec \uac70\ubd80 \uc758\uc0ac\ub97c \ubcf4\uc600\uc73c\uba70 568 \uba85(41.9%)\uc740 \ub2e8\uc21c \uac70\ubd80 \uc758\uc0ac\ub97c \ud45c\ud604 \ud558\uc600\ub2e4. 409 \uba85 (30%)\uc740 \ucc38\uc5ec\uac00 \uc5b4\ub824\uc6e0\ub358 \uc0ac\ub78c\uc774\uc5c8\uc73c\uba70 \uc870\uc0ac \ucc38\uc5ec \uac70\ubd80\ud55c \uc774\uc720\ub85c\ub294 \uac00\uc871\uc758 \uc0ac\ub9dd, \uac04\ubcd1, \uc785\uc6d0 \ubc0f \uc218\uc220, \uadfc\ubb34, \uac00\uc871\uc758 \ubc18\ub300, \ub300\uc0c1\uc790\uac00 \uc544\ub2c8\ub77c\uace0 \uc8fc\uc7a5, \uc54c\ub824\uc9c0\uae38 \uaebc\ub824\ud558\ub294 \uacbd\uc6b0 \ub4f1\uc774 \uc788 \uc5c8\ub2e4. 314 \uba85\uc740 \uac1c\uc778\uc801\uc778 \uc774\uc720\ub85c \ucc38\uc5ec\ud558\uc9c0 \ubabb\ud588\uace0, 8 \uba85\uc740 \uc870\uc0ac\ub418\uc9c0 \uc54a\uc558\ub2e4. \uc870\uc0ac\uc5d0 \ucc38\uc5ec\ud55c 1,692 \uba85 \uc911 \uaca9\ub9ac \uc911\uc5d0 \uba54\ub974\uc2a4 \ud655\uc9c4 \ubc1b\uc740 \uc0ac\ub78c\uc740 36 \uba85\uc774\uc5c8\uace0, \uba54\ub974\uc2a4 \uac10\uc5fc\uc73c\ub85c \ucd5c\uc885 \uc9c4\ub2e8\ub418\uc9c0 \uc54a\uc740 \uc0ac \ub78c\uc740 1,656 \uba85\uc774\uc5c8\ub2e4 (Figure 1). Expression Inventory, STAXI) \uc911 \uc0c1\ud0dc\ubd84\ub178\uac10 (10 \ubb38\ud56d)\uc744 Chon \ub4f1\uc774 \ud55c\uad6d\ud310(STAXI-K)\uc73c\ub85c \uac1c\ubc1c\ud55c \uac83\uc744 \uc0ac\uc6a9\ud558\uc600\ub2e4 [12, 13]. \ubb38\ud56d \ud615\uc2dd\uc740 Likert 4 \uc810 \ucc99\ub3c4\ub85c '\uc804\ud600 \uadf8\ub807\uc9c0 \uc54a\ub2e4' 1 \uc810\uc5d0\uc11c '\uac70\uc758 \uc5b8\uc81c \ub098 \uadf8\ub807\ub2e4' 4 \uc810\uae4c\uc9c0\ub85c \uad6c\uc131\ub418\uc5c8\uace0, \uc810\uc218\uac00 \ub192\uc744\uc218\ub85d \uadf8 \ud2b9\uc131\uc774 \ub192\uc74c\uc744 \uc758\ubbf8\ud55c\ub2e4. \uc810\uc218\uc758 \ubc94\uc704\ub294 10 \uc810-40 \uc810\uc73c\ub85c \ubcf8 \uc5f0\uad6c\uc5d0\uc11c\ub294 \ubd84\ub178\uac10\uc758 cut-off \ub97c 14 \uc810\uc73c\ub85c \uc815\uc758\ud558\uc600\ub2e4. \ubcf8 \uc5f0\uad6c\uc5d0\uc11c \ub0b4\uc801\uc77c\uce58 \ub3c4\ub294 (Cronbach alpha)\ub294 0.94 \uc600\ub2e4. \ubd88\uc548\uc99d\uc0c1 \ubd88\uc548\uc99d\uc0c1\uc740 \ubc94\ubd88\uc548\uc99d\uc0c1\uc7a5\uc560 \ud3c9\uac00\ub3c4\uad6c\uc778 Generalized anxiety disorder 7-item scale (GAD-7)\uc744 \uc774\uc6a9 \ud558\uc600\ub2e4 GAD-7 \uc740 \uc815\uc2e0\uc7a5\uc560\uc9c4\ub2e8\ud3b8\ub78c 4 \ud310 (Diagnostic and statistical Manual of Mental disorder, 4 th edition) \uc5d0 \ud3ec\ud568\ub41c \ubc94\ubd88\uc548\uc99d\uc0c1\uc7a5\uc560 9 \uac1c \ubb38\ud56d\uacfc \ud604\uc874\ud558\ub294 \ubd88\uc548\uc99d\uc0c1\ucc99\ub3c4\uc5d0 \ud3ec\ud568\ub41c 4 \uac1c \ubb38\ud56d\uc744 \uc120 \uc815\ud558\uc5ec \ucd1d 13 \uac1c \ubb38\ud56d \uc911 \ubb38\ud56d\uc0c1\uad00\ub3c4\uac00 \ub192\uc740 7 \uac1c \ubb38\ud56d\uc744 \uc120\uc815\ud558\uc5ec \uac1c\ubc1c\ub41c \uc790\uac00\ubcf4\uace0 \ubc94\ubd88\uc548\uc99d\uc0c1 \uc7a5\uc560 \uc120\ubcc4\ub3c4\uad6c\uc774\ub2e4 [14]. \uba54\ub974\uc2a4 \uaca9\ub9ac \ub2f9\uc2dc\uc640 \uaca9\ub9ac\ud574\uc81c \ud6c4 4-6 \uac1c\uc6d4 \uc2dc\uc810\uc5d0\uc11c 7 \uac00\uc9c0 \ud56d\ubaa9\uc744 \uc5bc\ub9c8 \ub098 \uc790\uc8fc \ub290\uaf08\ub294\uc9c0\ub97c \uc9c8\ubb38\ud558\uc600\ub2e4. 4 \uc810 likert \ucc99\ub3c4\ub85c \uc804\ud600 \ubc29\ud574 \ubc1b\uc9c0 \uc54a\uc74c (0 \uc810), \uba70\uce60 \ub3d9\uc548 \ubc29\ud574 \ubc1b\uc74c, \uc808\ubc18 \uc774\uc0c1 \ubc29\ud574 \ubc1b\uc74c, \uac70\uc758 \ub9e4\uc77c \ubc29\ud574 \ubc1b\uc74c (3 \uc810)\uc73c\ub85c \uc810\uc218\uac00 \ub192\uc744\uc218\ub85d \ubd88\uc548\uc99d\uc0c1\uc774 \ub192\uc74c\uc744 \uc758\ubbf8\ud55c\ub2e4. \uc810\uc218\uc758 \ubc94\uc704\ub294 0-21 \uc810\uc73c\ub85c 5-9 \uc810\uc77c \uacbd\uc6b0 \uacbd\ub3c4\uc758 \ubd88\uc548\uc99d\uc0c1, 10-14 \uc810\uc77c \uacbd\uc6b0 \uc911\ub4f1\ub3c4\uc758 \ubd88\uc548\uc99d\uc0c1, 15 \uc810 \uc774\uc0c1\uc77c \uacbd\uc6b0 \uace0\ub3c4\uc758 \ubd88\uc548\uc99d\uc0c1\uc73c\ub85c \ud3c9\uac00\ud560 \uc218 \uc788\uace0, \ubcf8 \uc5f0\uad6c\uc5d0\uc11c\ub294 10 \uc810 \uc774\uc0c1\uc744 \uc808\ub2e8\uc810\uc73c\ub85c \ud558\uc5ec \uc911\ub4f1\ub3c4 \uc774\uc0c1\uc758 \ubd88\uc548\uc99d\uc0c1 \uc99d\uc0c1\uc774 \uc788\uc744 \uacbd\uc6b0 \ubd88\uc548\uc99d\uc0c1\uad70\uc73c\ub85c \ubd84\uc11d\ud558\uc600\ub2e4. \ubcf8 \uc5f0\uad6c \uc5d0\uc11c \ub0b4\uc801\uc77c\uce58\ub3c4\ub294 (Cronbach alpha)\ub294 0.95 \uc600\ub2e4. \uc790\ub8cc\ucc98\ub9ac \ubc0f \ud1b5\uacc4\ubd84\uc11d\ubc29\ubc95 \uaca9\ub9ac\uc790 \uc911 \uba54\ub974\uc2a4\ub85c \ud655\uc9c4 \ubc1b\uc740 \uc0ac\ub78c\ub4e4\uc740 \uba54\ub974\uc2a4 \ud655\uc9c4\uc790\ub85c \uba54\ub974\uc2a4 \uac10\uc5fc\uc73c\ub85c \ucd5c\uc885 \uc9c4\ub2e8\ub418\uc9c0 \uc54a\uc740 \uc0ac\ub78c\uc740 \uba54\ub974\uc2a4 \uaca9\ub9ac\uc790\ub85c \uba85\uba85\ud558\uc600\ub2e4. \uc5f0\uad6c\ub300\uc0c1\uc790\uc758 \uc77c\ubc18\uc801\uc778 \uc815\ubcf4\uc640 \uaca9\ub9ac\uae30\uac04 \uc911 \uaca9\ub9ac\uc0c1\ud0dc\uc640 \uc0dd \ud65c \ud658\uacbd\uc740 \uba54\ub974\uc2a4 \ud655\uc9c4\uc790\uc640 \uba54\ub974\uc2a4 \uaca9\ub9ac\uc790\ub85c \ub098\ub204\uc5b4 \ube48\ub3c4\uc640 \ubc31\ubd84\uc728\ub85c \uc81c\uc2dc\ud558\uc600\uace0, \ub450 \uad70\uac04\uc758 \ube48 \ub3c4\uc758 \ucc28\uc774\ub294 chi-square \ubd84\uc11d\uc744 \ud558\uc600\ub2e4. \uaca9\ub9ac \ub2f9\uc2dc\uc640 \uaca9\ub9ac\ud574\uc81c \ud6c4 4-6 \uac1c\uc6d4 \uc2dc\uc810\uc5d0\uc11c \ubd88\uc548\uc99d\uc0c1\uacfc \ubd84\ub178\uac10\uc740 \uba54\ub974\uc2a4 \ud655\uc9c4\uc790\uc640 \uba54\ub974\uc2a4 \uaca9\ub9ac\uc790\ub85c \ub098\ub204\uc5b4 \ube48\ub3c4\uc640 \ubc31\ubd84\uc728\uc744 \uc81c\uc2dc\ud558\uc600\uace0, \ub450 \uad70\uac04\uc758 \ube48\ub3c4 \uc758 \ucc28\uc774\ub294 chi-square \ubd84\uc11d\uc744 \ud558\uc600\ub2e4. \uaca9\ub9ac\ud574\uc81c \ud6c4 4-6 \uac1c\uc6d4 \uc2dc\uc810\uc758 \ubd88\uc548\uc99d\uc0c1 \ubc0f \ubd84\ub178\uac10 \uc99d\uc0c1 \uacbd \ud5d8\uc758 \uc704\ud5d8\uc694\uc778\uacfc \ubcf4\ud638\uc694\uc778\uc740 SAS \uc758 proc Genmod \ub97c \uc774\uc6a9\ud558\uc5ec \ubd84\uc11d\ud558\uc600\uace0, \uc131\ubcc4\uacfc \uc5f0\ub839\uc744 \ubcf4\uc815 \ud55c RR (95% CI)\ub97c \uc81c\uc2dc\ud558\uc600\ub2e4. \uc804\uccb4 \ub300\uc0c1\uc790 \uc911 \uc811\ucd09\uc758 \uac15\ub3c4\uac00 \ub192\uc740 \uc0ac\ub78c\uc744 \uc6b0\uc120\ud558\uc5ec \uc870\uc0ac\ud558\uc600\uae30 \ub54c\ubb38\uc5d0 \uaca9\ub9ac\uc790\uc5d0\uc11c \ubd88\uc548\uc99d\uc0c1, \ubd84\ub178\uac10 \uc720\ubcd1\ub960\uc774 \uc5b4\ub290 \uc815\ub3c4 \uacfc\ub300\ucd94\uc815 \ub418\uc5c8\ub294\uc9c0 \ud30c\uc545\ud558\uae30 \uc704\ud574 \uc6b0\uc120 \uc21c\uc704 \uc815\ubcf4\uac00 \ud655\uc778\ub41c 1032 \uba85 (60%) \uc790\ub8cc\ub97c \ud1a0\ub300\ub85c \ubc00\ucc29\uc811\ucd09\uc790 \uc6b0\uc120 \uc21c\uc704\uc5d0 \ub530\ub77c \ubd88\uc548\uc99d\uc0c1 \ubc0f \ubd84 \ub178\uac10\uc758 \uc720\ubcd1\ub960 \ucc28\uc774\uac00 \uc788\ub294\uc9c0 chi-square \ubd84\uc11d\uc744 \ud558\uc600\ub2e4. \uac15\ud55c \ubd84\ub178\uac10\uc73c\ub85c \uc778\ud558\uc5ec \uc5f0\uad6c\uc5d0 \ubbf8\ucc38\uc5ec \ud588\uc744 \uac00\ub2a5\uc131\uc774 \uc788\uc5b4\uc11c \ucc38\uc5ec\uc790\uc758 \ubd88\uc548\uc99d\uc0c1, \ubd84\ub178\uac10 \uc720\ubcd1\ub960\uc774 \uacfc\uc18c\ucd94\uc815\ub418\uc5c8\uc744 \uac00\ub2a5\uc131\uc744 \uc54c\uc544\ubcf4\uae30 \uc704\ud574 \ubbf8\ucc38\uc5ec\uc790 \uac70\ubd80\uc0ac\uc720\ub97c \ubd84\uc11d\ud558\uc600\ub2e4. \ubaa8\ub4e0 \ud1b5\uacc4\ubd84\uc11d\uc740 SAS 9.3 version (SAS inc. Cary, NC)\uc744 \uc774 \uc6a9\ud558\uc5ec \ubd84\uc11d\ud558\uc600\uace0, \uc591\uce21\uac80\uc815 \uc720\uc758\uc218\uc900 0.05 \uc774\ud558\uc77c \uacbd\uc6b0 \ud1b5\uacc4\uc801\uc73c\ub85c \uc720\uc758\ud55c \uac83\uc73c\ub85c \ud3c9\uac00\ud558\uc600\ub2e4. \uacb0\uacfc \uba54\ub974\uc2a4 \uaca9\ub9ac\uc790\uc758 \uacbd\uc6b0, 944 \uba85 (57%)\uc774 \uc5ec\uc131\uc774\uc5c8\uace0 795 \uba85 (48%)\uc774 \ubb34\uc9c1\uc774\uc5c8\ub2e4. 33 \uba85 (2.0%)\uc774 \uc815" ] },{ "paper_id": "be050658bf3b654ae5d9cbe62f6198e5c4932a95", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceptualization: JCW WY. Mean number for RPA is the average of the threshold time (min) from 5 independent RPA reactions; Mean number for real time PCR is the average of the Ct numbers from 5 independent reactions. SD: standard deviation; CV: co-efficient of variation.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "doi:10.1371/journal.pone.0166903.t001" ] },{ "paper_id": "be12dac627e0584817ed6fbb4a7b154cc6fb304a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One-dimensional or multi-dimensional?", "Demographics. Participants provided their demographic details consisting of sex, age, current marital status, highest educational qualifications, and ethnicity.", "doi:10.1371/journal.pone.0172617.g001" ] },{ "paper_id": "be1d63805272f9d58e200bf0a8b57e8136b30af4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequencing is becoming the most common and reliable technique to identify novel organisms. For instance, LUJO was identified as a novel, very distinct virus after the sequence of its genome was compared to other arenaviruses [1] . The genome of an organism is a unique fingerprint that reveals many of its properties and past history. For instance, arenaviruses are zoonotic agents usually transmitted from rodents.", "We can then define, for any possible k-mer b, the mapping w from the sequence s onto a count of the elements in b's mneighborhood as", "Adaboost learns a discriminative function f(x) by iteratively selecting the y that maximally decreases the exponential loss." ] },{ "paper_id": "be2fad939fdfc83bded3b06dee772e6479049f9e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "be314554a535360c674f8666efdefd43e38e5ccc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Toxoplasma gondii is an obligate intracellular protozoan parasite with a worldwide distribution, which can infect a wide variety of warm blooded animals and humans. Approximately one third of the world population and 7.9% of population in China are seropositive for T.", "This study was approved by the Ethics Committee of Military Veterinary Institute, Academy of Military Medical Sciences. Bats were handled in accordance with good animal practices required by the Animal Ethics Procedures and Guidelines of the People's Republic of China." ] },{ "paper_id": "be459dd25c7c6092a050c722c69ddd3d34ce0f94", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Infectious bronchitis virus (IBV), a member of genus Gammacoronavirus, subfamily Coronavirinae, family Coronaviridae, affects the performance of both meattype and egg-laying birds, causing tremendous economic losses in the poultry industry worldwide [1, 2] .", "An increasing number of new serotypes or variants of IBV caused by frequent gene mutation have become the major challenge of the prevention and control of IB [9] ." ] },{ "paper_id": "be45cd588caaa0d8e5cdcd0cb7a1a59ccfc85d51", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The accuracy retention (AR) is defined as:", "The overall results suggest that the best set of parameter values to achieve higher accuracy, performance, and efficiency depend on multiple aspects including the input sequence and the available resources. Driven by these two aspects, in future work we will integrate an automatic selection of these values into our MR framework.", "AC and AW are given by the percentage agreement of the predicted structure with the known real structure calculated as:" ] },{ "paper_id": "be464c3787cad446a8be522f9ed4793c16c81b49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One effect of protein insertion would be to push lipids aside, temporarily stretching one membrane face to create an inward bulge around the budding virus. The line tension that would be created around the inserted matrix proteins could then be resolved by squeezing the new virus particle outward, a mechanism explored mathematically to explain how vesicular transport proteins work [14] .", "For each virus a linear mixed-effects model was fitted by restricted maximum likelihood, assuming that the electron microscope signal intensity was determined by the membrane phosphate peaks (inner or outer) and particle type (virus, GP vesicle, or empty vesicle), including cross-effects. The sample region, particle and micrograph were included as nested random effects. Model fit was deemed acceptable by inspection of Q-Q plots. Significant differences in the mean signal value were subsequently evaluated using Tukey contrasts, to allow for multiple comparisons. ", "Similarly, GP vesicles were compared to vesicles to distinguish the effects of matrix proteins from other viral membrane proteins.", "The presence of transmembrane helixes the virus glycoproteins studied here would be expected to displace less than 10% of the membrane lipid, based on helix diameter, the number of helices per glycoprotein complex and the spacing between complexes.", "Micrographs were minimally processed using the ctfit module of EMAN before analysis to correct phase inversion effects [23] . The brightness of entire micrographs was normalized to a common mean value. Data was collected by selecting a rectangular region ,80 \u00c5 wide and extending ,100 \u00c5 above and below the lowdensity node of the membrane, with dimensions varying slightly depending on image pixel scale. Linear density traces (Fig. 1) were calculated by aligning images and averaging the signal from each ,80 \u00c5 image row. Small errors in transect centering were corrected by ten cycles in which density traces were shifted by up to one pixel (3-5 \u00c5 ) to find the alignment with the highest linear correlation to the group average for that round. Phosphate peak values were extracted from ,25 \u00c5 regions as indicated in Fig. 1 . A total of 27912 density traces were analyzed. " ] },{ "paper_id": "be57ba746b8fec268025df6afc68536fbd0188d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An added effect of chloroquine is its immunomodulatory activity [5] . This may have an added benefit for the treat-ment of influenza A (H5N1) infection since the pathology of avian influenza infection in humans appears to be mediated by pro-inflammatory cytokines [13] .", "In conclusion, chloroquine demonstrates an inhibitory effect against the replication of human influenza A virus H1N1 and H3N2, in vitro and further studies to explore its therapeutic and prophylactic potential against influenza epidemics and pandemics should be encouraged.", "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "be5a6b0a0bff9b130578c5ad71a6be32d16525d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by the National Natural Science Foundation of China (31572500 to ZL).", "All experiments were repeated a minimum of three times. Differences among groups were determined by one-way ANOVA using GraphPad Prism (version 5.0; GraphPad Software). The significance levels for all analyses were set as p < 0.05 ( * ) and p < 0.01 ( * * ).", "SQ wrote the manuscript. SQ and ZL conceived and initiated the study. SQ, ZG, RC, and KY extracted the dataset. SQ, YC, SL, XM, QH, and ZL performed the analysis. All authors reviewed the manuscript." ] },{ "paper_id": "be5bddac1b08e3f6c757bdbd6564255e6ee96f4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using Student's t-test on Graphpad Prism 7 for Windows. p-values < 0.05 were considered as significant.", "MHC class I genes and type I interferons. It has been hypothesized that these factors allows greater 247", "EDTA blood was obtained from bats pre-challenge (D-95 and D-2) and day of necropsy. The total white blood cell, lymphocyte, neutrophil, monocyte, eosinophil, and basophil count were determined with the IDEXX ProCyte DX analyzer (IDEXX Laboratories, Westbrook, ME, USA).", "We observed cleavage of MERS S glycoprotein in our pseudotypes, whereas neither SARS S or WIV1 S glycoprotein were cleaved. This matches closely to what has been reported on proteolytic activation of MERS S and SARS S glycoprotein and further supports the validity of the use of pseudotypes. Whereas MERS S glycoprotein is processed by host proprotein convertases in virus-producing cells before virus-cell entry [18] , SARS S glycoprotein processing by these convertases is absent or inefficient [19] . Our results suggest that like SARS S glycoprotein, WIV1 S glycoprotein does not get cleaved by host proprotein convertases." ] },{ "paper_id": "be5d1a017f86407c335f5c76eb69b85d3b81c110", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "be738f9bf3b9a980ffecede2db4d06ea3f2518bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the experiments were repeated three times, each with quintuplicate determinations. The data were expressed as mean \u00b1 SD. Student's -test was performed to compare between the control and treatments. A value of < 0.05 was considered as significant difference ( * ) and < 0.01 was considered very significant ( * * ).", "See [16] .", "Evidence-Based Complementary and Alternative Medicine 5 " ] },{ "paper_id": "be7d22507f45b2b2927f91d16d7b89c1bf2c35cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although the molecular mechanisms underlying de novo prion formation remains elusive, the aggregation of PrPs is an amino-acid sequence-dependent process. Most prions contain specific domains enriched in asparagine (Q) and glutamine (N), which, together with the average residue hydrophobicity and net sequence charge, allowed the development of algorithms for the identification of candidate prionogenic domains (PrDs) based on the hidden Markov model (HMM) 20,27-30 .", "The HMM is currently used in many bioinformatic approaches for the statistical representation of prion domains, which allow, using the probabilistic sequence model of maximum likelihood estimation, to evaluate the compositional similarity of proteins and prions. One of these approaches is prion-like amino acid composition (PLAAC) analysis, which allows the evaluation of proteins containing PrDs, defined as domains with the compositional similarity to yeast prion domains, based on amino-acid interactions 27,31 .", "To facilitate the interpretation of the results, we grouped the proteins based on their functions using the GO terms ( Supplementary Figs 1-10) ." ] },{ "paper_id": "be86d94be6483de622f67e0c098684e4982c0441", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Provisions are made for national stockpiling of antivirals, vaccines, and personnel protective equipment; and such provisions are sensitive to locale-specific competing demands [17, 23, 43] Ethics training for healthcare workers Plan adequately outlines pandemic-specific ethics training for various categories of people working in healthcare setting [23] Timelines for planned activities:", "[43]", "Plan adaptability/flexibility: Outlined actions are flexible and encourage evidence-informed modification as required. That is opportunities to revisit and revise decisions as new information emerges throughout the crisis as well as mechanisms to address disputes and complaints are there. [18, 43] Preventive ethics consideration Preparedness actions ably balances emergency ethics and preventive ethics [46] Budgeting considerations: Plan has a budget and sources of funding are indicated [23] Outbreak simulations: Outbreak simulations are incorporated into preparedness activities [23] Back up essential personnel The need for identification and recruitment of additional essential personnel during pandemic outbreak is acknowledged and planned for [23] Ethical framework for the plan:", "During the last century, the world's population experienced one devastating influenza pandemic and three less severe global outbreaks. First was the Spanish influenza in 1918 (A/H1N1); the Asian influenza occurred in 1957 (H2N2); and the Hong Kong influenza in 1968 (H3N2) [1, 2] . The Swine flu pandemic occurred in 2009 (HIN1/09) [3] . Even though no public health expert can predict with certainty the timing and severity of the next outbreak, there is general agreement that future pandemics are perhaps inevitable [4] .", "Furthermore, the overall cost of actions deemed necessary to prepare the health care delivery system to respond to human avian influenza was estimated to be about $11,000,000 [12] . The actual amount that was released to relevant ministries, departments and agencies (MDAs) is unknown but is guessed to be an insignificant fraction." ] },{ "paper_id": "be99996c561fe43928f9914548fcd3a49563ade0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No potential conflict of interest was reported by the authors. ", "The study was conducted at two acute-care teaching hospitals in Cleveland between October 2015 and May 2016. The hospitals provided training for medical students from three different medical schools, residents in internal medicine and surgery, and fellows from multiple subspecialties. The institutional review boards of both institutions approved the study protocol.", "In addition to protecting healthcare personnel, correct use of PPE is essential for patient safety. A significant proportion of healthcare delivery has moved from healthcare facilities to outpatient and homecare settings [19, 20] , and it is not uncommon for patients receiving homecare nursing to be colonized or infected with multidrug-resistant organisms [21] . Healthcare-associated infections have a significant financial impact on the U.S. healthcare system, and many of these infections are considered reasonably preventable [22] [23] [24] . Thus, correct use of PPE to prevent pathogen transmission is as important in community healthcare settings as in the hospital. Efforts to improve PPE education should include community nursing personnel.", "Medical students were interviewed to obtain information on year of training, number of clinical rotations, and prior training in use of PPE. Students donned and doffed contact isolation gowns and nitrile gloves using their usual technique. After donning gloves, fluorescent lotion was applied to gloved hands. After PPE removal, a black light was used to assess for contamination of the skin of the hands and wrists. Simulations were observed and deviations in technique from CDC recommendations were recorded using a standardized checklist ( Figure 1 )." ] },{ "paper_id": "be9cb78bf2453f68b260e9ed4f75d9ceccb77754", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations: ESRD = end-stage renal disease, TA-SUA = time-averaged serum uric acid.", "The primary outcome was all-cause mortality after enrollment. The dates on mortality and cause of death were reported within 1 month after the event. In patients who withdrew from the study, we ascertained the mortality data from Statistics Korea. [32] We combined all these data according to the unique identification number held by all Koreans who provided informed consent. It was assumed that patients who did not have a reported death did not meet the primary outcome at the time of data close-out. In addition, the causes of death were divided into 8 categories: cardiac, vascular, infection, liver disease, gastro-intestinal, metabolic, endocrine causes, and other. The causes of death were collected for 75% of those who died.", "In conclusion, our study demonstrated the impact of SUA on survival in ESRD patients. The TA-SUA <5.5 mg/dL is associated with a higher mortality in patients. This association was more prominent in aged, overweight, normoalbuminemic, wellnourished, and diabetic patients. The causal relationship is still obscure and further research should be warranted to clarify precise mechanism." ] },{ "paper_id": "bec70be6631ac68e731b98fed55d2c28af45dc3d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ", "Membranes were labelled with membraneembedded palmitoylated green fluorescent protein, coded by pCAG-GFP plasmid (Addgene, MA, USA). Transfection of cells was done one day in advance with Lipofectamine 2000 Reagent (Life Technologies), following the manufacturer's instructions." ] },{ "paper_id": "becb2b5961d536efc8f0a0b535aeaf7e78d3d273", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The final logistic model was also presented as a nomogram for direct clinical use. All statistical analyses were performed using the statistical software R v3.1.1 (R foundation for statistical computing, Vienna, Austria) and its companion packages c060 version 0.2-3 (for stability selection), randomForest version 4.6-7 (for random forest) and rpart version 4.1-8 (for CART)." ] },{ "paper_id": "bed1c9834dbd81a9e254940379f80c3447a122e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data accessibility. This article has no additional data.", "Authors' contributions. J.L.G. and E.C.H. jointly conceived and wrote the paper. Both authors gave final approval for publication." ] },{ "paper_id": "bede1530aa4f5b0fdc57cd2d582bc7e4f153c1e6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Most important pandemics in human history, such as cholera, plague, influenza, HIV/AIDS, malaria, or severe acute respiratory syndrome (SARS), have propagated across large territories following transportation, commercial and travelling networks 1-3 . Pathogen invasion of distant areas through air transportation networks is promoting the appearance of emerging infectious diseases in new, formerly disease-free territories, such as malaria in Brazil 4 and dengue in North America 5 . The transmission dynamics of infectious diseases have been investigated extensively using complex network theory in which nodes represent species, populations, individuals, etc., which are connected through sexual, social, or commercial contacts 3,6 .", "In this study we investigate how network centrality and transitivity influence vulnerability to diseases of human populations by examining one of the most devastating pandemic in human history, the fourteenth century plague pandemic called Black Death. This epidemic ravaged Europe between 1346 and 1353, killing between 30% and 50% of its population 2 . The causative agent and etiology of the medieval Black Death are still debated.", "When a city is recurrently invaded, the overall mortality will be higher due to several, non-exclusive reasons. A first factor increasing the mortality rate in a given city could be due to different infection waves affecting different parts of the city. In this case, the overall mortality rate will be the cumulative outcome of partial mortalities caused by each infection wave. In addition, a city invaded multiple times could receive different pathogen strains. Theoretical models suggest that multiple infections with different strains generally lead to the evolution of population-wide increased virulence 4,5 , magnifying even more the devastating effects of the epidemic in that city." ] },{ "paper_id": "bedec26c3620f77256b9abfba6f57bc7570297b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The proposal of this study was submitted to the Center for Global Health (CGH) of Centers for Disease Control and Prevention for project determination and approval. It was deemed as \"not human subjects research\" and \"does not require human subject research review beyond CGH\".", "In total, 145 eligible individuals were approached and 94 participants were recruited to this study." ] },{ "paper_id": "bee044e4101c6958db139f19f6dd751990c2ce85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rotaviruses (RVs) are major enteric pathogens causing severe dehydrating diarrhea mostly in juvenile humans and animals worldwide 1 . RVs belong to the family Reoviridae and the genus Rotavirus consists of eight species (A-H) 2 . Recently, a distinct canine RV species has been identified and tentatively named Rotavirus I (RVI), although ratification by the International Committee on Taxonomy of Viruses (ICTV) is pending 3 . Group A rotaviruses (RVAs) are the most common of all rotavirus species and infect a wide range of animals including humans 4 . The rotavirus genome consists of 11 double-stranded RNA segments encoding 6 structural viral proteins (VP1-VP4, VP6, and VP7) and 6 nonstructural proteins (NSP1-NSP6). In 2008, a uniform classification system was proposed for each of the 11 gene segments resulting in G-, P-, I-, R-, C-, M-, A-, N-, T-,", "Bats have been proven to harbor several human pathogenic viruses including SARS, MERS-related coronaviruses, as well as filoviruses, such as Marburgvirus, or Henipaviruses, such as Nipah and Hendra virus [13] [14] [15] , but bat RVAs [10] , were isolated from a lesser horseshoe bat, and a Stoliczka's trident bat in China, respectively 18, 19 ." ] },{ "paper_id": "bee209540848ded10add285c6a2d90906961baea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data are reported as mean values \u00b1 sem. Statistical differences between treatment and control groups were evaluated by Sigma Stat (Systat Software, London, UK). Both parametric and non-parametric analyses were applied, in which the Mann-Whitney rank sum test (Mann-Whitney U-test) was used for samples on a nonnormal distribution, whereas a two-tailed t-test was performed for samples with a normal distribution.", "Total RNA was extracted from cells by Trizol (Invitrogen) and 1 \u00b5g RNA as template was reverse transcribed into cDNA with Transcriptor first strand cDNA synthesis Kit (Roche, Switzerland) per the manufacturer's instructions. Semiquantitative PCR was performed with Taq polymerase. Quantitative real-time PCR (qPCR) was performed with SYBR Premix Ex Taq (TaKaRa, Japan) on ABI StepOnePlus real-time PCR system (Applied Biosystems, USA). Primers used for the study were listed in Supplementary Table S1. All qPCR data were performed with at least three repeats. The PCR products were confirmed by proper melting curves and an agarose gel electrophoresis.", "MHPCs contribute to bile duct proliferation in a 3, 5diethoxycarbonyl-1, 4-dihydrocollidine-induced liver injury model" ] },{ "paper_id": "bef152d3ffbf6d9d35ae91a54f1eb447e18d7543", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Univariate analyses were performed using GraphPad Prism 5 (GraphPad Software, San Diego, California, USA). Mann-Whitney test and Wilcoxon signed rank test were used for unmatched and matched comparisons, respectively. Spearman rank tests were used to test for correlations. values less than 0.05 were considered significant.", "A total of 6 cytokines were measured in paired CSF and plasma samples using human cytokine/chemokine MILLIplex kits (Millipore Corp, Billerica, MA, USA): IL-8, eotaxin, granulocyte colonystimulating factor (G-CSF), interferon-(IFN-) 2, IFN--induced protein-(IP-) 10, and monocyte chemotactic protein-(MCP-) 1. The lower levels of detection were ranged between 0.2 and 10.1 pg/mL for each of the cytokines measured. All samples were assayed concurrently in duplicate. Data were collected using a Bio-Plex Suspension Array Reader (Bio-Rad Laboratories Inc., Hercules, California, USA). Cytokine concentrations that were lower than the lower limits of detection were reported as undetectable (0).", "Thus, this study aimed to firstly determine whether CSF levels of the inflammatory cytokine or chemokine were elevated in HIV infected patients with neurocognitive impairment and secondly to examine relationships between the concentrations of these cytokines in the CSF and plasma." ] },{ "paper_id": "bef31fcf85c2a93a2eeae36e5574372c3aa1c8f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was supported by the Ministry of Research, Technology, and Higher Education, Republic of Indonesia, and the United States Agency for International Development (USAID) Emerging Pandemic Threats (EPT) PREDICT." ] },{ "paper_id": "befd47f9dd7e050dcd46f483ca8e7bd902f4707f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the King Fahad Medical City Institutional Review board. Given that this was an outbreak situation they waived the requirement for individual informed consent.", "The study was conducted at King Fahad Medical Centre (KFMC), a 1200-bed tertiary care hospital in Riyadh which comprises of four hospitals (Main, Women's Specialized, Childrens' and Rehabilitation); the main hospital houses four affiliated centres (National Neurosciences Institute, Comprehensive Cancer, Diabetes and Endocrine) in addition to the Medical and Surgical Specialty departments within the same campus. The intensive care unit (ICU) is located in the main hospital. The medical city serves as a tertiary referral centre for patients from throughout the Kingdom.", "Patient demographic and clinical data were retrieved from electronic health records and via retrospective chart review." ] },{ "paper_id": "bf001dd7a7e2e974fa974607ccbcd9a2de960d2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cytokine analysis. Serum samples were collected on day 38 and cytokines were analyzed using Quantibody Mouse Cytokine Array Q1 kits from RayBiotech (Norcross, GA) following manufacturer's instructions.", "Scientific RepoRts | 6:28672 | DOI: 10.1038/srep28672" ] },{ "paper_id": "bf0a836e3d8d863356950aa4a760e449e5129792", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "80 90 100 | | | FTLTISSLQPEDFATYYCLQHNSYP-------------", "Occurrence e \u2022 1-2 2 \u2022 2-4 4 \u2022 4-10 0 \u2022 10-29 9 \u2022 29-541", "cag gtg cag ctg gtg cag tct ggg gct ... gag gtg aag aag cct" ] },{ "paper_id": "bf0bd7e3007cf87a4907ecf1bbf819d28e5c3c63", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral stocks were prepared and maintained as previously described [31] . Recombinant mKate-RSV expressing prototypic subtype A (strain A2) F genes and the Katushka fluorescent protein were constructed as reported by Hotard et al. [32] . HEp-2 cells (ATCC, VA) were maintained in Eagle's minimal essential medium containing 10% fetal bovine serum (10% EMEM), supplemented with glutamine, penicillin and streptomycin.", "Antibodies were expressed by transient co-transfection of HEK 293-F cells (Thermo Fisher Scientific, MA) with heavy-and light-chain plasmids using 293fectin (Thermo Fisher Scientific, MA). Cell supernatants were harvested after 4-5 days and passed over Protein A agarose (GE Healthcare, PA). Bound antibodies were washed with PBS and eluted with IgG elution buffer (Pierce, IL) into 1/10th volume of 1 M Tris-HCl pH 8.0. Fabs were created by digesting the IgG with Lys-C or HRV3C protease [24] , and the cleaved Fc region was removed by passing the mixture over Protein A agarose. Fabs were further purified by SEC.", "All animal experiments were reviewed and approved by the Animal Care and Use Committee of the Vaccine Research Center, NIAID, NIH, under animal protocol identification number 13-454, and all animals were housed and cared for in accordance with local, state, federal, and institute policies in an American Association for Accreditation of Laboratory Animal Care (AAALAC)-accredited facility at the NIH." ] },{ "paper_id": "bf0c3f90978f7e4794dfe1dd2d90ddb592fc6549", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All procedures involving animals and their care were conducted in accordance with the United States Department of Agriculture Animal Welfare Act and the National Institute of Health policy on Humane Care and Use of Laboratory Animals. Tissue samples from uninfected and prion agent-infected mice and hamsters were obtained using protocols approved by the Institutional Animal Care and Use Committee of the SUNY Downstate Medical Center (protocol #'s 07-250-09 and 07-251-09).", "Cellulose membranes spotted with 99 overlapping 13-mer PrP peptides were produced as previously described [36] . The membranes were blocked with 5% non-fat dry milk/tris-buffered saline containing 0.1% Tween 20 (TBST) probed with antibody diluted 1:5000 in 1% normal goat serum/TBS at 4uC overnight, followed by horseradish peroxidase (HRP)-conjugated goat antimouse secondary (Cappel 55570) for 2 hours at room temperature, and detected using Millipore Immobilon Western chemiluminescent HRP substrate (Cat WBKLS0500). Membranes were regenerated for re-use by shaking with dimethylformamide for 30 minutes, then 8M urea/50mM Tris-HCl pH 8.0/1% b-mercaptoethanol (b-MC)/1%SDS overnight at 37uC, followed by a 30 min wash in the same buffer, and then twice for 30 minutes each in 50% methanol/glacial acetic acid, and finally three times for 5 minutes each in methanol. After air drying membranes were stored in a sealed container at room temperature.", "Conceived and designed the experiments: RR TW. Performed the experiments: BC RP TW RR. Analyzed the data: BC RP TW RR. Contributed reagents/materials/analysis tools: RP TW RR. Wrote the paper: RR." ] },{ "paper_id": "bf0d0a5f74db0e532f85d90285a96f7e70670c55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary tables can be found at http://www.mdpi.com/1422-0067/15/12/22011/s1." ] },{ "paper_id": "bf0e3ed6e8fa4adbfacbf76e9fa2f5aa1ccdef19", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We performed a literature search in PubMed, MEDLINE, Embase, Wanfang Database and Weipu Database for studies published through April 2011 to use in this meta-analysis. The key terms were ''DC-SIGNR or CLEC4M or CD209L or L-SIGN or CD299 or DC-SIGN2'', ''HIV-1'', and ''polymorphism'' in various combinations. The search was limited to articles published in English and Chinese. We also manually searched the references matching the above criteria to identify additional studies." ] },{ "paper_id": "bf114390000199ac4f7c1f1f07c3320f0cb38657", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ebolavirus is the etiologic agent of lethal hemorrhagic fever in humans and nonhuman primates. Since its discovery in 1976, Ebolavirus has caused frequent outbreaks across Central Africa with exceedingly high mortality rate up to 90% 1,2 . While the natural host is currently unknown, Ebolavirus has been exploring more species as hosts across broader geographic frontiers 3-5 . Most notable was the unprecedented outbreak in West Africa in 2014 where the number of affected people has surpassed all the previously recorded cases combined 1 , raising the concerns about its pandemic potential and posing a serious threat to global health. Genetically, Ebolavirus isolated so far represents a divergent and evolving cluster and can be broadly classified into 5 species: Zaire (EBOV), Sudan (SUDV), Bundibugyo (BDBV), Reston (RESTV), and Tai Forest (TAFV) viruses 6 . Multiple lineages of EBOV were identified with increasing phylogenetic and genetic diversity in the 2014 outbreak in West Africa 7-12 . While it is uncertain whether the observed genetic diversity is the cause or the consequence of the current epidemic, the high mortality rate associated with rapid human to human transmission strongly argue for more effective therapeutics and vaccines against EBOV infection.", "with Fab of the testing mAbs in a molar ratio of 1:4 at 4 \u00b0C for about 12 h and the formed complex was purified with size exclusion chromatography. Four microliters of each GPdM-Fab complex at a concentration of ~0.02 mg/ml was applied onto a glow discharged continuous carbon grid (Beijing Xinxing Braim Technology Co., Ltd.). Once enough materials were adsorbed, the grid was treated with filter paper to remove the excess sample, immediately washed twice and incubated with ~4 \u03bc l of 1% uranyl acetate (UA) solution for additional 30 s. The grid was then further treated with filter paper to remove the UA, air-dried at room temperature, and examined under an FEI Tecnai F20 electron microscope equipped with an FEG filament and operated at 200-kV acceleration voltage, using a nominal magnification of 50,000\u00d7 at a pixel size of 0.168 nm." ] },{ "paper_id": "bf1b9188ca2e3eb5e80b73dcf3c12799344a7199", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Singapore is an island state nation with land size of approximately 710 km 2 and population density of 7000 persons per km 2 [13] . The island experiences tropical climate with high temperature, humidity, and rainfall." ] },{ "paper_id": "bf20dda99538a594eafc258553634fd9195104cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: All authors conceived the study, carried out the analysis, discussed the results, drafted the first manuscript. All authors have read and agreed to the published version of the manuscript. ", "We were also interested in inferring the patterns of the daily number of cases, denoted by \u03b5 i for the i-th day, and thus it is obviously that C i = C i\u22121 + \u03b5 i . A simulation framework was developed for the iterative Poisson process such that E[", "The time series data of 2019-nCoV cases in mainland China were initially released by the Wuhan Municipal Health Commission from 10 to 20 January 2020 [8] , and later by the National Health Commission of China after 21 January 2020 [9] . The case time series data in December 2019 were obtained from a published study [3] . All cases were laboratory confirmed following the case definition by the national health commission of China [10] . We chose the data up to 24 January 2020 instead of to the present study completion date. Given the lag between timings of case confirmation and news release of new cases, the data of the most recent few days were most likely to be tentative, and thus they were excluded from the analysis to be consistent." ] },{ "paper_id": "bf256a0f8fd3ff2faa39f340180e7e19bfa4c295", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The identification of alternative splicing variants for ELR1", "The bDNA is a sandwich nucleic acid hybridization assay, in which target mRNA molecules are captured through cooperative hybridization of multiple probes. Unlike PCR, in which a region of the intended target is exponentially amplified in order to generate detectable signal, in bDNA assays only signals are amplified. bDNA assays are consequently not susceptible to contamination risks associated with PCR-based assays [20, 21] . Equine MDMs were cultured and ELR1-IN mRNA was extracted and quantified using bDNA assay as described previously [18] . Samples were read by a Luminex 200 (Molecular Devices, USA) and all data were analyzed using the Luminex IS2.3 program. An acquisition gate between 5000 and 20,000 was set to exclude any doublet events and ensure that only single microspheres were measured.", "Statistical analysis and data presentation were performed using Student's t-test (two-tailed, confidence intervals of 95%). and Graphpad Prism version 4.0 (GraphPad Software, USA) programs, respectively. A probability value less than 0.05 was considered statistically significant." ] },{ "paper_id": "bf2609459ed9b514ad4b6ee4b0eb3656c0d6542d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition to the in vitro role of IFN-I in senescence it may also play a role in vivo. Progeria is a disease of accelerated aging caused by defects in telomerase or other maintenance enzymes, and stem cells from progeria patients rapidly approach senescence. However, replication of stem cells from progeria patients can be rescued from senescence by treatment with anti-IFN-\u03b2 antibodies [63] . While mice lacking the telomerase component TERC show signs of accelerated aging, this phenotype is reversed in double knockouts additionally lacking the IFN-I receptor component IFNAR1 [63] .", "The two best-characterized DNA sensors upstream of IFN-I induction are cyclic GMP-AMP synthase (cGAS), which non-specifically recognizes DNA in the cytosol, and IFN-\u03b3 inducible protein 16 (IFI16), which is believed to recognize naked DNA in the nucleus [66, 67] . It is not clear whether either of these sensors is involved in recognition of DNA DSBs or shortened telomeres.", "As an obligate intracellular parasite, a virus's success depends on strategies evolved to exploit host cells and the suitability of these strategies to overcome cellular antiviral defenses. Intrinsic antiviral defenses include passive features that protect the host from infection. For example, the cell membrane separates the intracellular space from the environment and creates a barrier to invading pathogens. In addition to intrinsic barriers to infection, cells have innate immune defenses activated by pathogen recognition. Viruses must overcome both intrinsic and innate barriers to infection, interacting with the cell to avoid or impair the cell's defenses." ] },{ "paper_id": "bf2fca4f15e9e4d36ab0e8a8c2b5b8c4b1009c04", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reporting summary. Further information on research design is available in the Nature Research Reporting Summary linked to this article.", "A further limitation of this study is the fact that the interactions between the host, virus and resident microbiota were studied in the upper airway. Since the pathogenesis of pneumonia is limited to the lower respiratory tract, future studies should aim to examine these interactions using samples derived from the lung. Such studies may provide a unique opportunity to examine the mechanistic basis for serious respiratory infections such as RSV.", "Data underlying Figs. 1a, 1b, 1c, 1d, 2a, 2b, 2c " ] },{ "paper_id": "bf30ca226d68a47371af20b85605f7c8550d2dd4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "bf3ec9cb72885b43173311a92e237c5417a53883", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For clarity about the definition of w, where the network adjacency matrix is G~(G ij ), then", "We perform our analysis within the SIS paradigm, meaning that while some of our terminology will be general to all infectious disease epidemiology, other statements will be geared towards the modelling of sexually transmitted infections where recovery/ treatment does not confer lasting immunity.", "Creation of a homogeneous random network. In order to create a homogeneous random network, we firstly generate a onedimensional ring with k -th nearest neighbour links. Since we consider networks where n is even, we set k~n=2, and then make five cycles through every node i, and for each of that node's links \u00bdi{j, swap with a random link \u00bdk{l as below," ] },{ "paper_id": "bf4d08eb7675759c77b722b7509bea52906930da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Citation: Widjaja I, de Vries E, Rottier PJM, de Haan CAM (2012) Competition between Influenza A Virus Genome Segments. PLoS ONE 7(10): e47529.", "The protein expression plasmids encoding PB2, PB1, PA and NP (pcDNA-PB2, pcDNA-PB1, pcDNA-PA and pcDNA-NP) and transcription plasmids encoding eight IAV-WSN vRNA segments (pPOLI-PB2, pPOLI-PB1, pPOLI-PA, pPOLI-HA, pPOLI-NP, pPOLI-NA, pPOLI-M, and pPOLI-NS) were a kind gift of Dr. Ervin Fodor [37] ." ] },{ "paper_id": "bf5c0b8c4f555f2af2ff41bc32faeb9c991dcafa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA was extracted from different cell sample using TRIzol Reagent (Invitrogen, CA, USA), according to the manufacturer's protocol. The RNA was cleaned up with an RNasey Mini Kit (Qiagen, Boston, MA, USA) and then treated with DNase I (Invitrogen) to remove the genomic DNA. The RNA quality and quantity were assessed by denaturing agarose gel electrophoresis and a Du530 spectrophotometer (Beckman, Heidelberg, Germany).", "Statistical analyses were performed using SPSS 17.0 software package. All results were expressed as the mean with standard deviation (SD) from three independent biological replicates for each treatment. Student's t-test was applied to compare the difference between the two groups. Moreover, the FDR was calculated to correct the P-value. P < 0.05 was considered statistically significant.", "For knockdown studies, HFF and THP-1 monocytes were seeded at 1 \u00d7 10 6 cells per well in a 6-well plate, individually. The next day, the cells were infected with recombinant adenovirus expressing shNONHSAT022487 (sh-NON-HSAT022487), and cultured for 48 h. Infection efficiency was monitored by observing the number of GFP-positive cells under a fluorescence microscope. The cell samples were harvested for RT-qPCR and Western blotting. The adenovirus-expressing shRNA for GFP was taken as the control (sh-control)." ] },{ "paper_id": "bf63f2e34138691d31b1282fe9cf47423c5f5a8a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Data obtained from three independent experiments are presented as the mean \u00b1 standard deviation (SD). Two sets of data were analyzed by an unpaired Student's t test. Three or more sets of data were analyzed by one-way ANOVA with Tukey's multiple-comparison test. Statistical significance was set at P < 0.05." ] },{ "paper_id": "bf6534fa1d3e5b2c6c5be7382633d56c6b92dea5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Automatic nucleic acid extraction was carried out using a total nucleic acid kit on a MagNa Pure Compact instrument (Roche Applied Science, Mannheim, Germany), following the manufacturer's instruction.", "Amplifications of parts of the specific genes of InfV A/ B, adenovirus (AdV), parainfluenza viruses 1, 2, and 3 (PIV 1-3), hRV/EV, RSV, hMPV, hCoV (hCoV-229E, hCoV-NL63, hCoV-HKU1, and hCoV-OC43), and human bocavirus 1 (HBoV1) were performed using assays previously described [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] .", "PCR amplification of EV was conducted on a Light Cycler instrument 480 II (Roche, Applied Science, Mannheim, Germany) using an Enterovirus R-gene realtime PCR kit (ARGENE, Biomerieux, Verniolle, France) and performed following the manufacturer's instructions." ] },{ "paper_id": "bf78c49c0e8c888ffd4b8f800895263eeca69ae8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells from isotope labelled cultures were tested for correct incorporation of isotopic labelled amino acids into proteins. Equal quantity of 'Light' , 'Medium' and 'Heavy' cell lysates were analysed by SDS-PAGE in MOPS buffer (Life Technologies) and two randomly selected regions were excised from the gel for in-gel trypsin digestion and MS analysis." ] },{ "paper_id": "bf7d69e6d9d85c3870025ee9e51632ca44283441", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Synthetic phage peptide mimics RF2-1:ACTSYNEPLC GGGSAK-(C6-biotin) and RF2-5:ACGDDWPHECGGGS AK-(C6-biotin) were made by standard 9-fluorenylmethoxy carbonyl chemistry and purified by HPLC (Center for Biologics Evaluation and Research Facility for Biotechnology Resources, US Food and Drug Administration, Rockville, MD). Peptides were confirmed to have the expected molecular weight by matrix-assisted laser desorption ionization-time-of-flight mass spectroscopy.", "Confirming the MAb-1G10 epitope using an in vitro functional test", "Data was obtained from the NIAID Virus Pathogen Database and Analysis Resource (ViPR) online through the web site at http://www.viprbrc.org (www.viprbrc.org) and from the Viral Bioinformatics Resource Center (VBRC; www.vbrc.org) and was aligned and visualized using multiple sequence alignment tools available at these websites. Statistical analysis was performed using Prism 5 (GraphPad Software). All experiments were performed in duplicate unless otherwise noted." ] },{ "paper_id": "bf931c3fa287d161d951ce9545d253daaf8a14e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Frontiers in Plant Science | www.frontiersin.org", "Limited information is obtained from conventional TEM due to the small thickness of thin sections. Hence, serial sectioning is emerging as a method to overcome this problem. A long ribbon of serial sections is needed, and hundreds to thousands of micrographs are recorded from the serial sections. The micrographs are aligned and processed to a stack. 3D structures can be generated from the stack of images. Although it provides more information than conventional TEM, serial sectioning has several drawbacks. For example, this sectioning requires welltrained staff to obtain high-quality serial sections without losing a single section, and the discontinuities between two consecutive sections often create difficulties in the alignment of images.", "XJ, YZ, XC, XW, JJ, and JW wrote the manuscript. YZ and J-FL designed and revised the manuscript." ] },{ "paper_id": "bfaeecd7b15a7d6d0563cd323c40681e285d70e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cleaved protein was concentrated to \u223c1 ml using Amicon filter concentrator membrane cut off 30 kDa (EMD Millipore), then loaded onto a HiLoad Superdex S200 pg gel filtration column (GE Healthcare Life Sciences). Protein elutions were concentrated using an Amicon concentrator described above to 5 mg/ml and 25 l aliquots were snap frozen in liquid N 2 using nuclease-free 0.5 ml microfuge tubes (Ambion Life Technologies) and stored at -80 \u2022 C.", "Here, we sought to develop a biochemical system to address these questions.", "Target identification", "Viral infection dramatically reshapes the gene expression landscape of the host cell. By changing overall messenger RNA (mRNA) abundance or translation, viruses can redirect host machinery towards viral gene expression while si-multaneously dampening immune stimulatory signals (1) (2) (3) . Suppression of host gene expression, termed host shutoff, can occur via a variety of mechanisms, but one common strategy is to accelerate degradation of mRNA (1) (2) (3) . This occurs during infection with DNA viruses such as alphaherpesviruses, gammaherpesvirues, and vaccinia virus, as well as with RNA viruses such as influenza A virus and SARS and MERS coronaviruses (1, 4, 5) . In the majority of these cases, a viral factor promotes endonucleolytic cleavage of target mRNAs. This strategy bypasses the normally rate limiting steps of deadenylation and decapping to effect rapid mRNA degradation by host exonucleases (1) ." ] },{ "paper_id": "bfbb1dddd2a6d304edf8c9cf1086613210f4a8f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a Data were below the detection threshold.", "Statistical analysis. Two-tailed, unpaired Student's t tests were used to analyze the differences in mean values between groups. All results were expressed as means \u03ee standard deviations; P values of \u03fd0.1 were considered significant.", "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .02325-17. " ] },{ "paper_id": "bfbee300d5a290a823a6a06f268e8a02a7e47455", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All Singaporean males enter national service for 2 years after high school or equivalent. During this period, the majority spend most of their time in communal living and training quarters in military camps and return home on weekends, resulting in a semi-closed environment with community interaction." ] },{ "paper_id": "bfcb22212525a49970dc301582343e388fc5cfd6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All participating nursery schools provided written informed consent for the acquisition and research use of data. The governing board of the Fukuoka City Medical Association granted ethical approval, and we obtained anonymized datasets before beginning the study analyses.", "Fever is one of the most common symptoms of disease in childhood and results in psychological and economic burdens for patients and their families. The prevention of febrile diseases therefore plays an important role in child health. The most common cause of fever in childhood is respiratory infection. 1 However, the evidence for putative preventive approaches for such diseases in childhood is not yet conclusive.", "Conflicts of interest: None declared." ] },{ "paper_id": "bfcd50d713b8f61b51563ec3abc1afcedf01f931", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Host proteome. Proteome of S. mediterranea, Smed Unigene 2015.02.17 [20] , was obtained from http://smedgd.stowers.org/.", "Protein secondary structure retrieval and prediction. Secondary structure was retrieved from PDB structures using the DSSP database [21] via the MRS system [22] for the following proteins: TGEV 3CLpro, 1LVO [23] ; SARS-CoV ExoN and N-MT, 5C8T [24] ; SARS-CoV O-MT, 3R24 [25] ; POLG_BVDVC, 4DW3 [26] ; RNT2_HUMAN, 3T0O [27] ; MMP2_HUMAN, 1J7M [28] . In all other cases, secondary structure was predicted for individual sequences using Jpred4 [29] in the MSA mode." ] },{ "paper_id": "bfd8dbd39a258f0a769375e64f7bd8df0e757266", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, ONC also inhibits 90-99.9% of human immunodeficiency virus type 1 (HIV-1) replication in H9 leukemia cells over a four-day incubation at concentrations not toxic to uninfected H9 cells [25] . HIV-1 transactivator protein Tat uses CREB to promote IL10 production. Although the importance of this for HIV pathogenesis is not clear, IL10 can inhibit HIV-1 replication in monocytes and macrophages, suggesting that Tat/CREB-induced IL10 production provides a negative feedback signal to prevent excess HIV-1 replication [89] .", "Construction of plasmid expressing ONC (pONC) has been previously described [90] . Recombinant ONC was produced and purified from Escherichia coli BL21(DE3) cells transformed with pONC essentially as described in [91] . The molecular mass of ONC was confirmed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry at the Unitat cientificot\u00e8cnica de suport, Institut de Recerca, Hospital Universitari Vall d'Hebron (Barcelona, Spain). ONC concentration was determined by ultraviolet spectroscopy using an extinction coefficient at 280 nm of 10470 M -1 cm -1 , calculated as reported [92] .", "Onconase (ONC), a protein of amphibian origin, is a member of the vertebrate secreted ribonucleases (RNases) family that presents antitumor and antiviral activities. Its structure endows it with unusual high conformation stability [1] and with the ability to evade the cytoplasmic ribonuclease inhibitor (RI), a 50kDa protein that tightly binds to some RNases and inhibits their activity [2] . Both its conformational stability and its ability to evade the RI provide ONC with significant intracellular survival that is critical to its biological actions." ] },{ "paper_id": "bfdf1cc025285b3c20fdde66f5de3be60b46930e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ears were fixed in PLP fixative (periodate-lysine-paraformaldehyde) overnight as reported in [64] , cryoprotected in 15% sucrose, embedded in OCT medium (Electron Microscopy Sciences) and frozen in dry-ice cooled isopentane. Sixteen-micron sections were cut on a Leica cryostat (Leica Microsystems), blocked with 5% goat or donkey serum then stained with CD8 (53-6.7), anti-GFP (clone 5F12.4). Sections were incubated with secondary antibodies only as controls, and images were acquired using identical PMT (photomultiplier tube) and laser settings.", "Scans were taken of entire infected ears equaling a 7 mm 2 imaged area and individual fields (tiles) were merged into one image. Total image fluorescence was calculated using ImageJ software.", "Significances were calculated using GraphPad (Prism) using unpaired two-tailed Student's t test." ] },{ "paper_id": "bfe634ff1fa0e8f0a43c1bd5fa6e0b5bd17705ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using Origin Pro 8 (Northampton, MA, USA) and SPSS statistics 17.0 (Chicago, IL, USA) software. Differences between medians in each of the two groups were determined using a paired student t test. Two-sided probability values <0.01 were considered to indicate statistical significance.", "The full genome sequence of variant strains is about 28,038 nucleotides (nt) in length. The genome organization is 5 1 UTR-ORF1a/1b-S-ORF3-E-M-N-3 1 UTR. Their sizes are about 292 nt; 20,345 nt; 4161 nt; 675 nt; 231 nt; 681 nt; and 1326 nt and 334 nt, respectively [13, 14] .", "3.4. Sequence Homology and Variation Characteristic of strainsYN1, YN15, YN30, YN60, YN120, YN144 and YN200" ] },{ "paper_id": "bff6e0b359144d2d7f0a1911dc76443c979690b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusions: These new markers will provide a valuable tool to investigate genetic structure in the poorly understood Hipposideros caffer species complex.", "Background: Noack's leaf-nosed bat, Hipposideros ruber, is a cryptic species within the Hipposideros caffer species complex. Despite a widespread distribution in Africa and being host to potentially zoonotic viruses, the genetic structure and ecology of H. ruber is poorly known. Here we describe the development of 11 novel polymorphic microsatellite loci to facilitate the investigation of genetic structure.", "Findings: We selected 20 microsatellite sequences identified from high throughput sequence reads and PCR amplified these for 38 individuals, yielding 11 consistently amplifying and scorable loci. The number of alleles per locus ranged from two to 12, and observed heterozygosities from 0.00 to 0.865. No evidence of linkage disequilibrium was observed, and nine of the markers showed no departure from Hardy-Weinberg equilibrium. We demonstrate successful amplification in two closely related species and two divergent lineages of the H. caffer species complex." ] },{ "paper_id": "c0120b34fddaa312eed6bdbb706c233bd0d0794f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where bars are used to denote dimensionless quantities. We also introduce dimensionless parameters defined by", "and _ z w \u00bc kg w y w \u00c0 n w a w z w x \u00c0 z w z w : (2:4e)", "where A \u00bc g w k \u00c0 (m \u00fe g w )n w , B \u00bc \u00c0((n w \u00c0 k)a w \u00fe z w )g w \u00c0 m(a w n w \u00fe z w ) and" ] },{ "paper_id": "c03edc5c954ae36334ee52e5b60ef611d075d1ac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c047b0340f79e0d34787e5f3500605b8c20e827d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession numbers. The final set of RSV sequences was deposited in GenBank with the following accession numbers: KP317916 to KP317956.", "IMPORTANCE", "Protein changes. After sorting by virus group (RSV group A or B), the genomic region under investigation was translated, the protein sequence was aligned using MAFFT (31) , and protein differences from the consensus sequence of the group were visualized and quantitated using Python scripts." ] },{ "paper_id": "c04c85e7d1935bf71b5ccca3b9cb3fe3b68131d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conflicts of Interest: D.B.W. has received an SRA, has an ownership interest including IP, and performs Board service for Inovio, has received an SRA from and consulted for GeneOne; has received an SRA from and consulted with Geneos; and has served on advisory boards for AstraZeneca and Sanofi, among others. A.P.-P. is an employee at Inovio Pharmaceuticals. The other authors declare no conflicts of interest. " ] },{ "paper_id": "c04cea5393ee21d23a0d8257fc67fecb57899a38", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "funding FIND was funded for this work by UK aid from the UK Government.", "Competing interests None declared.", "Patient consent Not required.", "disclaimer The opinions expressed in this article are those of the authors and do not necessarily reflect those of the institutions or organisations with which they are affiliated." ] },{ "paper_id": "c05053ab5281d6f0329a0b2b124acf02fb5875b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Alphavirus endemic to regions of South America. Normally maintained in a rodent reservoir, VEEV can be transmitted by mosquitoes to horses and humans where it can cause debilitating and potentially fatal encephalitis. There are currently no vaccines for VEE licensed for use in humans.", "The enzymatic activities and functional roles of nsP1, nsP2, and nsP4 have been partially characterized. nsP1 has methyltransferase and guanylyltransferase activity [5, 6, 7, 8, 9] , required for capping RNA, and is necessary for synthesis of minus-strand RNA [10] . nsP2 has multiple functions in viral replication. It has RNA helicase activity [11] and NTPase activity [12, 13] , and the C-terminus of nsP2 functions as a cysteine protease that cleaves the non-structural polyproteins P123 and P1234 [14, 15, 16, 17] . nsP2 has been found to enter cell nuclei and to be an inhibitor of transcription of cellular messenger and ribosomal RNAs including those involved in innate immune responses [18, 19, 20] nsP4 is the RNA dependent RNA polymerase [21, 22, 23, 24] .", "Temperature-sensitive mutants have been used extensively to elucidate replication and virulence properties of alphaviruses. To demonstrate the utility of our functional mapping method for identifying useful ts VEEV mutants, we further studied two nsP3 ts mutants, ts3-1 and ts3-3 for replication, virulence, and immunogenicity in mice. The insert locations in these two mutants are shown in Figure 5 . In addition to these two mutants, we constructed a mutant with both the ts3-1 and ts3-3 insertions (double ts).", "As a verification that the ts mutants had actually infected the mice, we assayed their sera for the presence of neutralizing antibodies 28 days after infection. One mouse each in the low dose V3000, ts3-1, and ts3-3 groups had no detectable neutralizing antibodies, but all others did ( Table 2 and Table S3 ).", "BHK and Vero cells were cultured in Eagle's minimal essential medium (EMEM) supplemented with 10% fetal bovine serum (FBS). VEEV strain V3000 is derived from a molecular clone of the wild-type Trinidad donkey strain of VEEV." ] },{ "paper_id": "c056bf64c107109def04dd9488e05b83a7742139", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Faecal sample collection from farms in different locations. To examine the correlation between C.", "All data generated or analysed during this study are included in this published article (and its Supplementary Information Files) .", "Fusobacterium species are anaerobic, elongated, Gram-negative rods. While there are multiple species of Fusobacterium, the species most commonly associated with human and animal disease is F. necrophorum, an opportunistic pathogen that causes numerous necrotic conditions (necrobacillosis) and both specific and non-specific infections in a variety of animals. Bovine liver abscesses and foot rot caused by F. necrophorum are significant concerns in the cattle industry 27 ." ] },{ "paper_id": "c05da515acecfc66d0b0b7a46a51e557cb9bb08d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plaque growth was simulated using a one-dimensional, timedelayed, partial differential equation (PDE) model:", "with P I (t)~1{ d dt f I (t)", ", with fixed parameters t I~1 2h and s I~1 h." ] },{ "paper_id": "c0617473da97a9dd36b02d46fe80b144f2138f0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Murine H2k mdx myoblasts were cultured in gelatin (0.01%)-coated flasks at 33 C, under 10% CO 2 , in Dulbecco's modified Eagles medium (DMEM PAA laboratories) supplemented with 20% heat-inactivated fetal bovine serum (FBS Gold, PAA laboratories), 2% chicken embryo extract (Seralab), 1% penicillinstreptomycin-neomycin antibiotic mixture (PSN, Gibco) and 3 pg/ml g-interferon (PeproTech).Murine C2C12 myoblasts (ATCC: CRL-1772 TM ) were grown in DMEM supplemented with 10% heat inactivated FBS (PAA laboratories) and 1% PSN.", "Total RNA was extracted using a Nucleospin kit (Macherey-Nagel) from each single well for the 24 h treatment or by Trizol extraction (TRI Reagent \u00d5 RNA Isolation Reagent, Sigma-Aldrich) by pooling duplicates for the 4 h treatment as per manufacturers' instructions. Total RNA quantification was done using Nanodrop \u00d5 ND-1000 (Thermo Scientific).", "All values are expressed as means\u00b1SEM. Multiple comparisons between groups were assessed by one-way ANOVA with Newman-Keuls post hoc test or T test when appropriate. P values were noted as: ** for P<0.001 and *** for P<0.0001.", "Data were analyzed using GraphPad Prism GraphPad Software, San Diego California, USA.", "After incubation with 3 0 -fluorescein labelled Pip6a-PMO or 3 0 -fluorescein-labelled PMO, cells were washed twice with PBS and lysed with 300 ml GLB buffer (Promega). In all, 100 ml of the lysate were transferred into black non-binding 96-well plates (Greiner) and fluorescence was measured on a Tecan plate reader (Ex 485 nm/Em 520 nm). Protein concentration was measured by a BCA kit (Pierce) on a Tecan plate reader (Abs 560 nm)." ] },{ "paper_id": "c0713cd16ef0d30221483b314837bcf9e642a884", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c0789cc30e0766ccdea9e216da799f9cb41f853d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c07b96b0ac94d1403d44dff3bc6ad12a64d171c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IgA molecules that are transported into the intestinal lumen as SIgA [10, 16] .", "In conclusion, novel approaches eliciting a stronger mucosal response are showing promising results both in preclinical and clinical studies. Further studies are needed to implement and improve these delivery systems; however, mucosal delivery is becoming the most preferred mode of vaccination. ", "To date, vaccine antigens have been transformed into many edible species including lettuce, tomato, potato, papaya, carrot, quinoa, and tobacco [32] . Their proper folding and enhanced expression have also been tested in animal models, proving the immunogenicity of antigens produced in these systems [24, 33] .", "Several vaccine prototypes are currently under evaluation, and strong systemic immune protective responses support the use of silkworm as a mucosal vaccine vector, as shown, for example, by high immunogenicity in mice of the urease B subunit of Helicobacter pylori produced in silkworm [60, 62] . While the data collected so far support the possible use of baculovirus-silkworm vaccines as a promising edible vaccine platform, it is only approved for food ingestion in a few Asian countries." ] },{ "paper_id": "c07d89610bf10dbbc4124f1a65ffaab6855954ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HT and EK conceived and designed the experiment. HT and ZC conduced the experiment and analyzed the data. All authors drafted the manuscript. All authors carefully read and approved the final version of the manuscript.", "Data from the quantitative RT-PCR analysis, sampling date, different sample types and pathogen were consolidated in a spreadsheet (Microsoft EXCEL; Microsoft Corporation, Redmond, WA, USA) and organized for analysis. Means, standard deviations, and minimum and maximum values for quantitative variables, and positive samples counts and percentages for qualitative variables were calculated for descriptive analysis. Statistical analysis was performed ", "The research was funded by the Manitoba Livestock Manure Management Initiative (MLMMI) and the Manitoba Pork Council. MLMMI is funded by Canada and Manitoba governments through Growing Forward 2, a federal-provincialterritorial initiative.", "Before barns were depopulated, the status of active viral shedding was examined in fresh fecal and pit samples collected from each barn. Samplings from fresh fecal and pits were started late September for farm-1 and early October 2014 for farm-2. Sampling was terminated if animals showed high viral shedding, however, continued for another two consecutive weeks if samples were negative or showed low positivity. Farm-1 was completely depopulated on September 28, 2014, and farm-2 was depopulated on October 8, 2014." ] },{ "paper_id": "c08002cc1b2282d646514bf4f2abde54ac144994", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "rLa-EBOVGP is more resistant to NDV antiserum than vector NDV and partially sensitive to EBOV antiserum", "The present study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the Ministry of Science and Technology of the People's Republic of China. The protocol was approved by the Animal Research Ethics Committee of Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (approval numbers 20132085 for chickens and 20132138 for mice)." ] },{ "paper_id": "c08e4437d35ae6cdbeae2993e4a2264258f3431e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To construct shRNA-expressing lentiviral vectors for silencing of TPN, stable short hairpin RNA (shRNA) expression cassettes were cloned into the pLVTHm/si vector containing eGFP as reporter [6] .", "sHLA producing clones were grown in bioreactors CEL-Line (Integra, Fernwald, Germany) and protein levels were determined by sandwich ELISA using w6/32 (Serotec, Duesseldorf, Germany) [31, 32] monoclonal antibody (mAb) as capture antibody. The supernatants were affinity-purified using NHS-activated HiTrap columns coupled to mAb w6/32.", "Human B-LCL 721.220 is lacking functional TPN and both HLA-A and HLA-B genes [15] while 721.221 lacks functional HLA class I genes [30] ." ] },{ "paper_id": "c09a602a62f8976f5772470145fd98f2abfa1236", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lessons learned include:", "A poorly designed or executed exercise may do more harm than good if it leads to a false sense of security and results in poor performance during an actual emergency [30] . Planning, executing and reporting on exercises to improve emergency preparedness should be high on the agenda of public health departments in all countries.", "Emergency exercises are only valuable to the extent that we learn from them and implement our findings into day-to-day practice. The implications of this exercise for public health preparedness can be considered in the context of the Donabedian model [27] which contends that information about structure, process and outcomes can be collected to make inference about the quality of a service." ] },{ "paper_id": "c0a3fa45a3d4599c5d0ccd212e4bde23a4253717", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data used within this study were anonymised and were collected: (i) in the scope of epidemiological surveillance for which submission to an ethical committee is not required and (ii) specific projects including GP Sentinel Network and I-MOVE's Euro EVA, which had already been approved by the Health Ethic Committee of INSA.", "The human respiratory syncytial virus (RSV) is a major cause of morbidity and mortality worldwide since it is the predominant viral agent affecting the respiratory tract, causing acute, sometimes fatal lower respiratory tract infections in infants, young children and the elderly [1] . In fact, RSV has been associated with a substantial disease burden in adults, especially in the elderly, with an estimation of 1.5 million episodes of acute respiratory infection (ARI) in industrialised countries in 2015 [2] [3] [4] . Moreover, according to a study in the same year, the global burden of RSV-associated acute lower respiratory infection has been estimated at 33.1 million annually resulting in over 3.2 million severe illness that required hospitalisation in children younger than 5 years [5] .", "Although many studies regarding RSV have focused on children aged under 5 years and elderly adults, little is known regarding RSV among patients of all ages. This study evaluated the clinical characteristics and the performance of three different case definitions for the diagnosis of RSV infection based on epidemiological and laboratory data from 2010 to 2018 in Portugal." ] },{ "paper_id": "c0afcaab27d3532f3396316eb529468097bd6de7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical testing was performed with GraphPad Prism 5.0 or 6.0 (GraphPad, San Diego, CA, USA). Data sets were tested for normality using the D' Agostino and Pearson omnibus normality test, followed by statistical significance testing using the appropriate tests as indicated in figure legends. Data sets with n values <8 were tested non-parametrically. P values < 0.05 were considered statistically significant.", "IL-10 was measured in cell culture supernatants using the IL-10 ELISA MAX kit (BioLegend), according to manufacturer's instructions. IL-27 was measured in cell culture supernatants using the DuoSet Human IL-27 ELISA (eBioscience), according to manufacturer's instructions. Microwell absorbance was read at 450 nm using a Wallac 1420 microplate reader (Perkin Elmer, Waltham, MA, USA). Concentrations of the analytes were determined based on the standard curve included on each plate.", "Roberts et al." ] },{ "paper_id": "c0b11b19a87de55ec7803cad2e855942ce498d6b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2018, 10, x 9 of 14" ] },{ "paper_id": "c0bba2814eb6c6e6af25662fc57b78b04d471191", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\ub418\uc5c8\uace0, \ubcf8\uaca9\uc801\uc73c\ub85c \uc2dc\ud589\ub41c \uac83\uc740 1957 \ub144 2 \uc6d4 28 \uc77c \uc804\uc5fc\ubcd1\uc608\ubc29\ubc95 \uc2dc\ud589\ub839\uc774 \uc81c\uc815\ub41c \uc2dc\uc810\uc774\ub77c\uace0 \ubcfc \uc218 \uc788\ub2e4 [8] . \uc5ed\ud559\uc870\uc0ac\uad00 Central Internal medicine 2 2 2 3 1 3 1 2 16 Pediatrics 1 1 1 1 1 2 2 1 3 2 1 1 17 Family medicine 1 2 1 2 1 1 8 Preventive medicine 1 3 4 Neurology 1 1 2 1 2 1 2 10 Occupational and Environmental medicine ** 3 2 1 1 2 1 1 2 1 3 4 1 2 24 General practitioner 1 1 1 3 2 4 1 1 1 15 No information 7 7 4 1 19 Subtotal 14 15 7 18 11 11 15 13 11 10 10 11 6 8 11 9 9 189 Total 18 19 10 23 13 14 19 15 16 14 11 19 9 13 17 12 13 ", "\ubc30\uacbd : \ud55c\uad6d\uc758 \uc5ed\ud559\uc870\uc0ac\uad00 \uc81c\ub3c4\ub294 1999 \ub144 \uc774\ub294 \uc2e0\uc885 \ubc0f \uc7ac\ucd9c\ud604 \uac10\uc5fc\ubcd1\uc5d0 \ub300\ud55c \ud6a8\uacfc\uc801\uc778 \ub300\uc751\uc744 \uc704\ud55c \uc5ed\ud559\uc870\uc0ac \uc804\ubb38 \uc778\ub825\uc744 \ud655\ubcf4\ud558\uae30 \uc704\ud574 \ube44\uad50\uc801 \uc778\ub825 \uc218\uae09\uc774 \uc6a9\uc774\ud55c \uacf5\uc911\ubcf4\uac74\uc758\uc0ac \uc778\ub825\uc744 \uc774\uc6a9\ud55c \uc81c\ub3c4\ub85c \uc2e0\uc124\ub418\uc5b4 \uc2dc\ud589\ub418\uc5c8\ub2e4. \uadf8\ub7ec\ub098 2015 \ub144 \uc911\ub3d9\ud638\ud761\uae30\uc99d\ud6c4\uad70(\uba54\ub974\uc2a4) \ubc1c\uc0dd\uc744 \uacaa\uc73c\uba74\uc11c \uae30\uc874\uc758 \uc5ed\ud559\uc870\uc0ac\uad00 \ubc0f \uac10\uc5fc\ubcd1 \uad00\ub9ac \uc81c\ub3c4\uc758 \uc6b4\uc601\uc0c1 \ud55c\uacc4\uc810\uc774 \ub3c4\ucd9c\ub418\uc5c8\ub2e4. \uc5f0\uad6c\ubaa9\uc801 : \uc774 \uc5f0\uad6c\ub294 1999 \ub144 \uc774\ud6c4 16 \ub144\uac04 \ud55c\uad6d\uc5d0\uc11c \uc9c4\ud589\ub418\uc5b4\uc654\ub358 \uc5ed\ud559\uc870\uc0ac\uad00 \uc81c\ub3c4\uc758 \uc6b4\uc601 \ud604\ud669\uc790\ub8cc, \uac01\uc885 \ubb38\ud5cc, \ud589\uc815\ubcf4\uace0\uc11c \ub4f1\uc744 \ud3c9\uac00\ud558\uace0 \ubc14\ub78c\uc9c1\ud55c \ud5a5\ud6c4 \uc5ed\ud559\uc870\uc0ac\uad00\uc81c\ub3c4\uc758 \uac1c\uc120\ubc29\ud5a5\uc744 \uc81c\uc2dc\ud558\uace0\uc790 \ud558\uc600\ub2e4. \uacb0\uacfc : \uc774 \uc5f0\uad6c\ub97c \ud1b5\ud558\uc5ec \uc5ed\ud559\uc870\uc0ac\uad00 \uc81c\ub3c4 \ubc0f \uad50\uc721\ud504\ub85c\uadf8\ub7a8\uc758 \ud3c9\uac00 \ubc29\ubc95\uc744 \uc81c\uc2dc\ud558\uace0 \ud5a5\ud6c4 \uc9c8\ubcd1\uad00\ub9ac\ubcf8\ubd80\uc5d0\uc11c \uc790\uccb4\uc801 \ud3c9\uac00\uc758 \ubc29\ud5a5\uc744 \uc81c\uc548\ud568\uc73c\ub85c \uc5ed\ud559\uc870\uc0ac \uc804\ubb38\uc778\ub825 \uc591\uc131\uc744 \uc704\ud55c \uc81c\ub3c4\uac1c\uc120\uc744 \uc704\ud55c \uadfc\uac70 \uc790\ub8cc\ub97c \ub9c8\ub828\ud558\uc600\ub2e4. \ub610\ud55c \uc5f0\uad6c\uacb0\uacfc\ub97c \ud65c\uc6a9\ud558\uc5ec \ubcf4\ub2e4 \uccb4\uacc4\uc801\uc778 \uac10\uc5fc\ubcd1 \uad00\ub9ac \uc804\ubb38\uac00 \uc591\uc131\uc744 \uc704\ud55c \ubc29\uc548\uacfc \uc5ed\ud559\uc870\uc0ac\uad00 \uad50\uc721 \ud504\ub85c\uadf8\ub7a8\uc758 \uccb4\uacc4\uc801\uc778, \ub2e8\uacc4\uc801\uc778 \uc6b4\uc601 \uae30\ubc18\uc744 \uad6c\ucd95\ud558\uace0 \uc804\ub7b5 \uac1c\ubc1c\uc744 \uc704\ud55c \uc9c0\uc18d\uac00\ub2a5\ud55c \uc218\ud589\uccb4\uacc4\ub97c \uc81c\uc548\ud558\uc600\ub2e4. \uacb0\ub860 : \uac10\uc5fc\ubcd1\uc5d0\ub9cc \uad6d\ud55c\ub418\uc9c0 \uc54a\uace0 \uacf5\uc911\ubcf4\uac74 \uc804\ubb38\uc778\ub825 \uc591\uc131 \ubc0f \uc5ed\ub7c9 \uac15\ud654\uc758 \uac00\uc774\ub4dc\ub77c\uc778 \uac1c\uc815 \ubc0f \uc804\ubb38\uad50\uc721\uae30\uad00 \uc124\ub9bd\uc5d0 \ub300\ud55c \uac00\ub2a5\uc131\uc744 \uc81c\uc548\ud558\uc600\ub2e4." ] },{ "paper_id": "c0bd429ecee8c353025af075ab372a8a40874cec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HBE were obtained by protease digestion of dissected airways (main stem bronchus to 4th generation) as previously described [15] , and stored in aliquots in liquid nitrogen until used. Each \"n\" value for experimental data represents the use of cells from a different individual donor. ", "Histology HBE were fixed in 10% neutral buffered formalin, embedded in paraffin, and sectioned to 4 \u03bcm thickness onto Superfrost plus slides. Alcian blue and hematoxylin staining was performed by de-paraffinization in two changes of xylene and rehydrating through graded ethanol solutions (100, 95, 70% EtOH). Alcian blue 8GX (Sigma) in 3% acetic acid solution was added for 2 min and rinsed in water for 2 min. Hematoxylin Gills II (Leica Biosystems) staining was performed for 5 min and rinsed in warm tap water for 5 min. Slides were dehydrated through reverse graded ethanol solutions (95, 100% EtOH) and cleared in two changes of xylene before applying coverslip with Permount (ThermoFischer)." ] },{ "paper_id": "c0bec3dd80af76e0f60020b72ab8f6e1f14354fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A technique based on ultracentifugation (Step 1) followed by concentration using a commercial water-insoluble elastomeric polyelectrolyte specially engineered for the capture and recovery of viruses (Viraffinity\u2122;", "Denaturing polyacrylamide gel electrophoresis, Western blotting and silver-staining", "Alternatively, the gels were silver-stained after electrophoresis using the SilverXpress Kit (Life Technologies, Paisley, UK). Densitometry analysis was carried out using Quantity-One software (BioRad).", "Despite an incomplete understanding of the mechanisms of pathogenicity, several hypotheses have been formulated to explain the disease process in patients infected with DV. However, the lack of animal models capable of reproducing the features of human disease has hampered the identification of reliable parameters and indicators to explain or predict the development of SD." ] },{ "paper_id": "c0bf3eba76bbd23ffe7c259b7de7f7c66886f22c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bat Cells Non-Bat Cells ", "Vero 76 (African green monkey, kindly provided by Andrea Maisner), HEK 293T (Human, DSMZ no. ACC-635), BHK-21 (Human, DSMZ no. ACC-61), EidNi/41 (Straw-colored fruit bat, Eidolon helvum) [37] , and HypNi/1.1 (Hammer-headed fruit bat, Hypsignathus monstrosus) [38] cells were maintained in Dulbecco's modified Eagle's medium (DMEM; ThermoFisher Scientific, Waltham, MA, USA) supplemented with 5% or 10% fetal calf serum (FCS; PAN-Biotech, Aidenbach, Germany) and 1% penicillin/streptomycin (PAA Laboratories GmbH, Pasching, Austria). Cells were cultivated in 75 cm 2 tissue culture flasks (Greiner Bio-One, Frickenhausen, Germany) at 37 \u2022 C and 5% CO 2 .", "GhV G wt " ] },{ "paper_id": "c0bf910304f6b63067f1f28709b964272cd6c182", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "which is proportional to the desired probability distribution (compare to Eq. (4)).", "This model of the possible non-equilibrium dynamics of frameshifting leaves", "With transition rates given by Arrhenius's law" ] },{ "paper_id": "c0cf1c6377c3115aa80ff787332120d4ba1cd386", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Is nsp14-ExoN the Proofreading Component of a Multi-Subunit Polymerase Complex Containing nsp10 and nsp12-RdRp?", "Coronaviruses encode a proofreading exoribonuclease that is responsible for genome expansion, increased robustness to mutations, and resistance to mis-incorporations during RNA synthesis, as well as being required for virulence. The stability of the ExoN2 genotype and phenotype provides a powerful model for the study of additional CoV fidelity determinants and of the effects of altered fidelity on virus replication, fitness, host-species range, and response to environmental changes. Experiments testing the proposed multi-subunit fidelity complex will yield exciting new insights into how CoVs ignore the RNA virus playbook and instead seem to play by their own rules while dancing on the edge of genetic disaster.", "RNA viruses rely primarily on low-fidelity replication by RNAdependent RNA polymerases (RdRps) to facilitate viral adaptation to complex host environments [4] . Because of the lack of proofreading and repair functions, the average mutation rate of RNA viruses is estimated to be around one mutation per genome per round of replication [5, 6] . Much beyond this rate, RNA viruses risk crossing an ''error threshold,'' or the point at which there are too many deleterious mutations for the viral population to reproduce faithfully [4] . Thus, while allowing for enormous population diversity, the low-fidelity of RdRp-mediated replication imposes constraints on both viral genome size and maintenance of genomic integrity, theoretically limiting the size of RNA virus genomes to around ,15 kb (reviewed in [4] ). RNA viruses have evolved several mechanisms to partially circumvent these constraints, including large population sizes, rapid replication cycles, robustness to mutations, recombination, and compact genomes [7, 8] ." ] },{ "paper_id": "c0de9d0fcd1d7f778c11f42fd399f6c0cc5e7a4b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ELISA analysis, receiver-operator characteristics (ROC) analysis, and comparison to the IFA results were performed using GraphPad Prism software (Version 5.0a, GraphPad Software, Inc., La Jolla, CA).", "The UMN-VDL performed a diagnostic IFA test to detect anti-SVA antibodies present in serum. Briefly, human lung cancer NCI-H1299 cells were inoculated with an SVA strain isolated in 2015 from an outbreak in the U.S. Infected cells were washed with PBS, fixed with acetone and incubated using two-fold dilutions of serum from 1:20 to 1:320 at 37\u00b0C for 1 h. After fluorescein labeled goat anti-pig IgG diluted 1:50 in PBS was added into the wells and incubated at 37\u00b0C for 1 h, the cells were observed under fluorescence microscopy. A positive signal at a sample dilution of 1:20 was considered suspect and a 1:40 or higher dilution was considered to be positive.", "Cloning, expression and purification of SVA VP1, VP2, and VP3 protein" ] },{ "paper_id": "c0e284c9dd2ca500ae5f10d04d0639d0f8779a16", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There were 268 farms included in this study; the majority of participating farms were located in the swine dense regions of Minnesota and Iowa. Fig 1 shows Table 1 . Fig 2 depicts the prevalence, upper and lower 95% confidence intervals of farms containing animals actively shedding PRRS virus over the weeks examined in this study.", "The level of resolution used in this study was weeks because this was the finer level of resolution available from the MSHMP and avoided possible weekend or holiday effects. Counts of swine farms containing animals actively shedding PRRS virus was used as the main outcome of interest. Data from a total of 388 weeks were available for analysis (2009) (2010) (2011) (2012) (2013) (2014) (2015) (2016) . Data were stratified at the state level and separately analyzed. The five states examined included Minnesota (MN), Iowa (IA), North Carolina (NC), Nebraska (NE), and Illinois (IL).", "The source population for this project corresponded to breeding herds (herds that contain sows) that participated in the Dr. Morrison's Swine Health Monitoring Project from July 2009 (starting on the 26 th week of 2009) to October 2016 (finishing on the 41 st week of 2016). Even though the MSHMP source population includes over 1,000 participating sow farms, only swine herds that contributed with complete data from those previously mentioned years were enrolled in this study, so that a closed population could be examined.", "Sporadic cases have anecdotally been referred to as \"summer outbreaks\". Even though it has been reported that cold temperatures (winter season) and low relative humidity favor PRRS virus survival [14] , some factors might help explain these off-winter incidence of PRRS cases. First, during summer months there is larger commingling of animal producers in state fairs or animal shows [15] , which could facilitate disease transmission in the absence of adequate biosecurity practices [16, 17] . Second, lack of awareness of occurrence of other PRRS cases outside the neighborhood and system could contribute to a relaxed attitude towards some biosecurity measures during these months (e.g. less truck washing, drying and disinfecting events), allowing for virus spread [18] . Lastly, considering the volume of activities that occur in the current structure of the swine industry [19] , it is not surprising that there are a lot of opportunities for the pathogens to spread via non-obvious manner such as through feed trucks, fomite and personnel, therefore; even though the virus might be easily transmitted during winter months, the amount of activity is enough for these sporadic events to occur in considerable amounts.", "Data were aggregated retrospectively at the week level for the number of herds that were considered as having an active outbreak each week. Farms would be allocated to that category as soon as outbreaks were identified and reported by herd veterinarians and based on a number of features. Those features included one or a combination of the conditions of presence of PRRS-consistent clinical signs and identification of the virus via diagnostic testing, and/or isolation of a different PRRS virus strain as compared to previous existing strains in the herd; as described elsewhere [7] . Once herds reported an outbreak, they were considered 'status 1' or 'positive unstable' following AASV PRRS classification guidelines [11] until there was absence of clinical signs and no detectable viremia in weaned piglets for a minimum of 90 days (tested at least every 30 days) [11] ." ] },{ "paper_id": "c0f05769898b94c3e481a16c7fee9666037bbdab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples from feces and intestine tissues were subjected to virological investigations for common viral swine pathogens such as PEDV, transmissible gastroenteritis virus (TGEV), porcine rotavirus (PRV), porcine circovirus 2 (PCV2) [35] , porcine kobuvirus [36] , and porcine bocavirus (PBoV) [37] , using previously described methods.", "The authors declare that they have no competing interest.", "Sick or dead piglets aged 1-21 days were submitted for laboratory investigation. Necropsy examination of all piglets revealed that the small intestines were congested and filled with fluid, and were thin-walled as a result of severe mucosal atrophy. Microscopically, marked cytoplasmic vacuolation and exfoliation of enterocytes with subsequent shortening of villi were noted. Tissues and feces and/or blood were collected from live or dead animals submitted for polymerase chain reaction (PCR) detection to perform a surveillance." ] },{ "paper_id": "c0f496f49f4b2dea73cf8c184ff21275bf706908", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments were performed at least three times with reproducible results. Data were presented as means \u00b1 standard deviations (SD). The Student's t-test was used to determine statistical significance. P-values less than 0.05 were considered statistically significant, and P-values less than 0.01 were considered highly significant.", "modulate the inflammatory response by regulating the NF-\u03baB pathway. Understanding the relationships between PRRSV Nsp2 and the host inflammatory responses should help develop more effective strategies for the control of PRRS.", "In summary, our data clearly demonstrated that the PRRSV Nsp2 alone, in the absence of other PRRSV proteins, could significantly activate the NF-\u03baB pathway." ] },{ "paper_id": "c0f7f46699d0ecf0c7ead699d564d952508e6f81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An analysis of the intercorrelations between the three threat appraisal variables (perceived susceptibility, perceived severity and fear) demonstrated relatively low coefficients (between .10 and .27) thus suggesting that the four variables are indeed distinct aspects of threat appraisal.", "Regarding the urgency of information, 64% reported wanting to receive information on protective measures immediately (see Figure 5 ). Information on how to recognize an infection was considered most urgent by 40% while information on how to treat the infection and how the infection is transmitted was considered most urgent by 35% and 33%, respectively. In general, topics that inform risk appraisal, namely information about the severity of the infection, the likelihood of infection and places that pose the greatest risk were considered less urgent.", "Medication will be available soon (wishful thinking) I will just have to accept it (fatalism)" ] },{ "paper_id": "c0fcd483132e1e59571bae716303dc7d3977b7d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "G-quadruplexes (G4s) are unique four-stranded nucleic acid structures that may form in guanine-rich sequences. Based on the strand orientation, they can adopt three main topologies: parallel, antiparallel, and hybrid-type structures. G4s have been shown to be involved in key regulatory and pathological roles in eukaryotes, including transcriptional regulation of gene promoters and enhancers, translation, chromatin epigenetic regulation, DNA recombination 1-3 . Formation of G4 in vivo has been consolidated by the development of G4 specific antibodies 4,5 .", "In general, several proteins that modulate G4s and/or serve as a bridge to recruit additional protein regulators have been reported 23 . Besides the shelterin complex proteins that are involved in telomere homeostasis 24 , G4 interacting proteins either stabilize (e.g. nucleolin, MAZ and nucleophosmin) or unfold (the helicase and heterogeneous nuclear ribonucleoprotein (hnRNP) families) 25,26 the G4 conformation to allow for a tightly controlled modulation of the epigenetic G4 switch.", "The score is reported as \u2212 10x log10(P) where P is the absolute probability. The mass of the putative peptides and of the 50 most intense fragment ions were used for the data base search. Significant Mascot hits were accepted as positive matches and their ion score reported. The highest score obtained in the three experiments is reported." ] },{ "paper_id": "c10d2b72f8d450209946e805ba18154c9a6c5f7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Three-dimensional structural model of 3CLpro", "Random bred cats free of most common feline pathogens, including feline enteric coronavirus, were obtained from the feline nutrition breeding colony, School of Veterinary Medicine, UC Davis.", "All animal experiments were conducted in strict compliance with the Animal Welfare Act, PHS Policy and other federal statutes and regulations relating to animals and approved by the Institutional Animal Care and Use Committee at University of California, Davis (Protocol Number:17557)." ] },{ "paper_id": "c1111df73b989050bd7ffb92d274943ae5529777", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The full-length viral genomic sequence of DogPyV1 was deposited in GenBank under the accession number KY341899.", "The presence of a novel polyomavirus in both tested Dachshunds from the same outbreak raises the possibility that this virus may be a previously unrecognized canine respiratory pathogen. Further studies are under way to determine the virus's prevalence, cellular tropism, and association with canine respiratory disease.", "We report here the first canine polyomavirus genome, identified by metagenomics in respiratory secretions of two dogs with severe pneumonia, which tested negative for all canine respiratory pathogens except Mycoplasma cynos. The isolate, Canis familiaris polyomavirus 1 (DogPyV-1), is a beta polyomavirus whose closest known LT antigen relatives are primate polyomaviruses. Citation Delwart E, Kapusinszky B, Pesavento PA, Estrada M, Seguin MA, Leutenegger CM. 2017. Genome sequence of canine polyomavirus in respiratory secretions of dogs with pneumonia of unknown etiology." ] },{ "paper_id": "c11eac2f07f5ad430230013f3eba74ff74a5c8a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Molecules 2020, 25, 698 19 of 40" ] },{ "paper_id": "c121bff36744aaaa59d19e21bb04b7f776cbeb42", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The datasets analyzed in this manuscript are not publicly available. Requests to access the datasets should be directed to jiang@scripps.edu.", "Whole blood (10 \u00b5L) was collected in an RNase free Eppendorf tube containing lysis buffer (QIAGEN) and stored at \u221280 \u2022 C until use. Total RNA was extracted using RNeasy Mini Kits (74106, QIAGEN) and reverse-transcribed into cDNA using iScript cDNA Synthesis Kits (170-8890, Bio-Rad). Viral RNA copies were quantified through TaqMan qPCR amplification of ZIKV (GZ01) envelope gene. Measurements were expressed as log 10 viral RNA copies per millimeter calculated against a standard curve. Sequences for primers and probes were as follows: ZIKV-F CCGCTGCCCAACACAAG, ZIKV-R CCACTAACGTTCTTTTGCAGACAT, ZIKV-probe AGCCTA CCTTGACAAGCARTCAGACACTCAA (5 \u2032 FAM, 3 \u2032 TAMRA).", "All ZIKV GZ01 (KU820898), ZIKV MR766 (AY632535), and DENV2 43 (AF204178) viruses were grown in C6/36 Aedes Albopictus cells and titrated on Vero cells before use. For neutralization assay, serial dilutions of mAbs were mixed with virus at 4 \u2022 C for 1 h before being applied to Vero cells in the 6well culture plates. After 1-2 h of infection, the antibody-virus mixture was aspirated and Vero cells were washed with PBS and overlaid with DMEM containing 2% heat-inactivated FBS and 1% SeaPlaque Agarose (Lonza, 50501). After 4-6 days, plaques were stained by 1% crystal violet and counted manually.", "All data were analyzed using Prism6 software (GraphPad). The half-maximal effective concentrations (EC 50 ) were calculated using the dose-response stimulation model. The IC 50 value for each mAb was calculated using the dose-response inhibition model. For experiments involving AG6 mice, four animals were included in each assessment group to ensure equal representation and consistency of the data obtained. Statistical analysis was performed using Student's unpaired t test. Data were presented as mean \u00b1 SEM. * p < 0.05; * * p < 0.01; and * * * p < 0.001." ] },{ "paper_id": "c125f2b3071406f51b9b9aee860030b2f402ee77", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fncel. 2015.00423", "We thank Paul Anderson and Pavel Ivanov (Harvard Medical School, Boston) for reviewing the manuscript as well as Gene Yeo and Sebastian Markmiller (UCSD) for sharing information to improve Supplementary Table S1 .", "The origin and nature of pathological inclusions found in ALS/FTD patients remains poorly understood. Inclusion formation could be a mechanism by which the neuron sequesters non-functional protein that could otherwise perturb normal function. Alternatively, they could arise from defective removal of normal SGs, themselves a type of cytoplasmic aggregate, responding to cellular stress. Lastly, it is remains equally possible that inefficient clearance of non-specific aggregates composed of non-functional proteins which feature aggregation-prone domains could yield these cytoplasmic accumulations or \"primoaggregates\" of undefined composition. This is an interesting concept given the discovery of VCP-mediated autophagy as a mechanism to clear SGs post-heat shock (Buchan et al., 2013) . However, the role of VCP remains unclear given that oxidative stress or proteasome inhibition of VCP-depleted cells feature smaller SGs with atypical composition (Seguin et al., 2014) ." ] },{ "paper_id": "c12642f0762cb4888b417ce295044080ab9202a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lungs from mice were perfused with PBS containing EDTA, minced and digested in collagenase IV. Cells ", "HRV1B (ATCC, Manassas, VA) were grown in cultured HeLa cells, concentrated, partially purified and titered as described previously [7] . Similarly concentrated and purified HeLa cell lysates were used for sham infection.", "Authors' contributions JYH, JKB, US, and MBH designed research. JYH, YC, JS, QC, JL, ATC, AMG and JKB conducted experiments. JKB, US, and MBH provided help with data interpretation. JYH and MBH wrote the paper. All authors read and approved the final manuscript." ] },{ "paper_id": "c13377750d32446f66a4bcd0bb2da626e4b2a035", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There was no need to obtain ethics committee approval.", "Umrah. Understanding what the risk to pilgrims is, what the risks of pilgrims returning with MERS-CoV is, and whether human to human transmission on their return poses a public health threat, is vital. Surveillance and control measures in response to this threat may need to be adapted or developed.", "The risk of Middle East Respiratory Syndrome Coronavirus spreading globally is worrying, given the annual mass gathering of the Hajj and the year-long influx of pilgrims undertaking the Umrah. Based on the incidence in Saudi Arabia since June 2012, the most likely scenario given recent pilgrim numbers is estimated to be one case per Hajj, and three Umrah pilgrims per year, but which could plausibly reach seven and ten pilgrims respectively. In addition to the 2015 Hajj, national surveillance systems should be on the alert for the low but long-lasting risk of infected pilgrims returning from the Umrah throughout the year." ] },{ "paper_id": "c1431d7d5f795acaa4781ae85a6b7c6d51cb54ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In total, we analyzed 1092 samples collected from LRTI patients ", "Methods: Nasopharyngeal aspirates (NPAs) from children with LRTI were collected." ] },{ "paper_id": "c146ea9fadc16cfc9571f748391f3aa07f5acbd7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, a Mantel correlation test [33] was applied, by using GenAlEx 6, to a matrix of pairwise geographic and pairwise genetic distances, with 999 random permutations to determine significance.", "Genomic DNA was extracted from the leaves of each individual using CTAB protocol [21] , dissolved in double distilled water, and quantified using a spectrophotometer comparing band intensities with known standards of lambda DNA on 1.5% agarose gels. In a preliminary experiment, 100 ISSR primers (designed by the University of British Columbia (UBC), Vancouver, Canada) were tested on five random individuals from all the populations. Ten primers (USB #807(AG) 8 T, #808(AG) 8 A negative control reaction without template DNA was also included to verify the absence of contamination. PCR products were separated in 1.2% agarose gels buffered with 1\u00d7 TBE. Only bands reproducible in different PCR reactions were further analyzed. Bands with similar migration distance amplified from different individuals were considered homologous. A positive control (PCR products amplified from a standard individual) and a Gene Ruler DNA 100 bp ladder (Bio Basic Inc.) were run on each gel for homology assessments of PCR products on different gels.", "An unweighted pair group method using an arithmetic average (UPGMA) dendrogram was performed on the data matrix of mean character difference between pairs of samples with software MEGA version 2.1 (downloaded from the website at http://www.oup-usa.org/sc/0195135857). The relationship between latitude and longitude and the molecular indices was calculated as a two-polynomial regression. Correlations were calculated with software SAS version 6.12." ] },{ "paper_id": "c14ce2c27ca770924c1ca4a4fef0fa5b532f73c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c1590dca1224c338b4163beacf9a838e7caec9c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c16b3804d97765832da8ea7579a114e98844c0ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Five ml cDNA were amplified using HotStarTaq DNA Polymerase Kit (QIAGEN, Hamburg, Germany) in a 50 ml PCR. The primers used were s2m-p (0.5 mM) and Blend (0.25 mM). The concentration of Mg 2+ in the reaction was 1.5 mM. The amplification programme consisted of an initial 15 min step at 95uC, followed by 40 cycles with 94uC for 40 s, 55uC for 20 s and 72uC for 40 s. A final elongation step at 72uC for 5 min was performed, followed by chilling to 8uC.", "Permission to capture and euthanize pigeons for sampling was given by the Norwegian Directorate for Nature Management (ref:", "Software used for sequence analysis was Sequencher version 4.1.4 (Gene Codes Corporation; http://www.genecodes.com), and FASTA similarity search." ] },{ "paper_id": "c16c86f79a95eff0e99629650c962b25249281af", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Frozen OCT-embedded Med-LNswere cut to 10 \u03bcm thick sections using a cryostat. Tissue sections were placed on membrane-coated slides (PEN-Membrane 2.0 \u03bcm; Leica Microsystems, Germany). The cryostat was treated with RNAZap Solution (Life Technologies, UK) between each sample in order to avoid cross-contamination of RNA. Sections were air-dried and fixed in 70% ethanol for 5 min and stained with RNase free haematoxylin for 1 min. Two consecutive Med-LN tissue sections were used per animal. All observed F and peripheral IF were dissected and captured separately in RNase-free PCR tubes (Greiner bio-one, UK) using a laser microdissector (Leica LMD6500, Leica, Germany). The samples were immediately frozen and stored at \u221280\u00b0C until laboratory processing.", "Representative images of CD3, CD79a and MAC387 IHC staining in all the groups are shown in Figure 3 .", "Primers and TaqMan probe sets for porcine cytokines were synthesized by Sigma-Aldrich (Table 1 ). All cytokines primer pairs produced amplicons smaller than 150 base pairs (bp). All primer and probe sets were optimized for our laboratory conditions.", "Porcine reproductive and respiratory syndrome (PRRS) is characterized by respiratory disease in neonatal and growing pigs and reproductive failure in gilts and sows (increased number of abortions, mummified foetuses, stillbirth and weak-born piglets) [1] [2] [3] . PRRS is considered one of the most economically important swine infectious diseases around the world, with estimated losses of up to $664 million annually in the USA alone [4, 5] ." ] },{ "paper_id": "c16d19032f42486b997727ee0f732ab9fd5b9a84", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The rhIFITM3 gene was amplified from genomic DNA by PCR and screened for polymorphisms by re-sequencing. Primers for amplification were based on the Macaca mulatta chromosome 14 scaffold (Mmul_051212) [41] . We used this scaffold before to successfully amplify cDNAs of rhIFITM genes [6] . Amplification of genomic IFITM3 sequences (LOC697829) was performed using primers mamuIFITM3gen5-1forA (5'-TTTGTTCCGCCCTCATCTGG-3') and mamuIFITM3gen5-1rev (5'-TCTGAGATCCACGCTCAGGA-3'). Primers were designed using primer-BLAST [42] to specifically avoid amplification of rhIFITM3(2) (LOC697564) or rhIFITM3 pseudogenes. Reaction mixtures contained 100 ng genomic DNA, 50 pmol of each primer, 100\u03bcM dNTP mix, 10% betain, 1x HF synthesis buffer and 1 U Phusion DNA polymerase. PCR cycling started with an initial denaturation step at 95\u02daC for 5 min, followed by 40 cycles with denaturation at 95\u02daC for 30 s, annealing at 68\u02daC for 30s and elongation at 72\u02daC for 1:40 min followed by a post amplification step at 72\u02daC for 10 min. PCR products were gel purified and sequenced using ABI Big Dye chemistry and primers mamuIFITM3gen5-1forA, mamuIFITM3gen5-1rev, IF3gi-for (5'-GTGCCCACGTC AGTAGCTTTA-3') or IF3gi-for2 (5'-TGTGCCCACGTCAGTAGCTTT-3') and IF3gi-rev (5'-CTTCCTCACTCAGGCTCAGAC-3') or IF3gi-rev2 (5'-CAAACTCTGAGCC AGCCAGC-3'). Amplicons were assembled on a scaffold sequence using Vector NTI ContigExpress and polymorphisms identified by visual inspection.", "The antiviral activity of rhIFITM3 was analyzed as described previously [6] . In brief, 293T cells seeded at 10 4 cells per well in a 96-well plate were spin-oculated [38] at 4,000\u00d7g for 30 minutes with IFITM3 or CAT encoding vectors. After incubation for 48h at 37\u02daC, the medium was replaced by 50\u03bcl of fresh culture medium followed by the addition of 50\u03bcl of MLV vectors harboring the viral glycoproteins to be analyzed and normalized for equal luciferase activity upon transduction of control cells. After incubation for 8h, medium was replaced by fresh culture medium and luciferase activities in cell lysates were analyzed at 72h post infection, employing a microplate reader, Plate CHAMELEON V (Hidex, Turku, Finland), and a commercial luciferase assay system (Promega, Mannheim, Germany) or Beetle-Juice (PJK, Kleinblittersdorf, Germany) kits.", "AIDS-free survival analysis, including a log-rank test for rhIFITM3 genotype-related differences, was performed using the LIFETEST procedure of the SAS software version 9.4 (SAS Institute Inc., Cary, NC). The association between rhIFITM3 polymorphisms and virus load was assessed for statistical significance by means of either a Kruskal-Wallis test (three genotypes) or a Mann-Whitney test (two genotypes), as appropriate, using the GraphPad Prism software. All p-values were two-sided. The level of statistical significance was depicted as follows, \u00c3 , p<0.05; \u00c3\u00c3 , p<0.01; \u00c3\u00c3\u00c3 , p<0.001.", "Interferon-induced transmembrane proteins are encoded by a gene family of diverse function in vertebrates [1] [2] [3] . A subgroup of immunity-related IFITMs (IFITM1-3) has been recognized recently to inhibit multiplication of a broad range of viruses including, but not limited to, a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 influenza A viruses (FLUAV), flaviviruses, coronaviruses, filoviruses and lentiviruses [4] [5] [6] [7] [8] [9] [10] [11] . IFITM proteins are type II transmembrane proteins and consist of a variable cytoplasmic Nterminus followed by a conserved intramembrane domain, an intracellular loop, a transmembrane domain and a short variable and luminal C-terminus [12] [13] [14] . It is well established that IFITMs inhibit viral entry [11] . While the exact mechanism still has to be elucidated, IFITMs seem to act through the arrest of virus-host cell membrane fusion at the hemifusion step by altering membrane fluidity [15, 16] . Despite their broad antiviral activity, IFITMs can also promote entry or assembly of selected viruses [17, 18] , indicating that they belong to a pathway that can positively and negatively regulate viral infection." ] },{ "paper_id": "c16ef70e46b997661c4aef194fd79c1b902a3c39", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There are limitations to this study. First, the PubMed search strategies utilized were not perfectly sensitive, and they certainly missed some publications that would be relevant. Also, the search strategies likely included some irrelevant citations, but we believe that these sources of error are not likely to have a major impact on the observed citation trends. Finally, our comparative analysis was only qualitative, but because there are so many factors that contribute to citation rates that we felt such an approach would be the most informative.", "Background: A rapid rise in PubMed citations on methicillin-resistant", "The authors declare that they have no competing interests." ] },{ "paper_id": "c1722fc1da22b2ccf5565ccf81a1677c2994aeee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Where SASA is the solvent accessible surface area and, \u03b3 and b are constants." ] },{ "paper_id": "c179446abc96980232e34b4e910f2c184301c07f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The animal study proposal was approved by the Institutional Animal Care and Use Committee (IACUC) of the Yangzhou University Animal Experiments Ethics Committee (permit number: SYXK (Su) IACUC 2012-0029). All experimental methods were conducted in accordance with the related guidelines and regulations.", "The authors declare that there is no conflict of interest." ] },{ "paper_id": "c181d32e2efda26882425f6179dc5549a59a3504", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analysis. Principal components analysis (PCA) is a common technique for dimensionality reduction and pattern recognition in datasets of high dimension [41] . The main purposes of PCA are the analysis of data to identify patterns and finding patterns to reduce the dimensions of the dataset with minimal loss of information. The general steps of conducting PCA are as follows.", "(1)", ". . , } and \u2208 {1, 2, . . . , }." ] },{ "paper_id": "c182fa44ed42d3f4bce316dc78bec2ea3b6d31ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ENc-GC3s plot. A ENc-GC3s plot was used to investigate the influence of the GC3s content on codon usage [20] . The expected ENc values for each GC3s were calculated using the following formula:", "To determine the influence of the overall codon usage of hosts on that of ZIKV, the similarity index D(A,B) [26] was calculated as follows:", "The statistical analyses were performed using SPSS 13.0 software package (SPSS Inc., Chicago, USA). Correlation analyses were carried out using Spearman's rank correlation test. The P-values less than 0.05 were considered statistically significant." ] },{ "paper_id": "c1903895a3fc53a43a81d310f7567181bdee782f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The detailed experimental procedures for pharmacological evaluation of the synthesized compounds were provided as supplementary materials.", "All of the measurements were conducted in triplicate.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "c19b92f638a71bdf631c296aee8d9fbfd4202034", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Stage E14.5 pregnant female ICR mice were purchased from BioLASCO Taiwan Co., Ltd. (Taipei, Taiwan). Mouse care and handling procedures, and experimental protocols were approved by the National Taiwan University of Science Animal Care and Use Committee, and conducted in accordance with Directive 86/609/EEC for animal experiments.", "3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay" ] },{ "paper_id": "c1a54ec890c135c78fb0c2b0b9c1b96ac2b945eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RIPA lysis buffer contains 50 mM Tris\u00b7HCl pH 7.5, 150 mM sodium chloride, 0.1% sodium dodecyl sulphate, 0.5% sodium deoxycholate, and 1% NP40. Giordano lysis buffer contains 50 mM Tris\u00b7HCl pH 7.4, 250 mM sodium chloride, 0.1% Triton X-100, and 5 mM EDTA. Lysis buffers were supplemented with protease inhibitors (Complete mini tablets, Roche Diagnostics, Almere, The Netherlands). Western sample buffer has the following concentrations: 50 mM Tris\u00b7HCl pH 6.8, 10% glycerol, 2.5% \u03b2-mercaptoethanol, 2% SDS, and 0.025% bromophenol blue.", "For western blot analysis, the total protein concentrations were determined by a BCA assay kit (Thermo Scientific Pierce, Rockford, IL, USA). Equal amounts of protein (30 \u00b5g) were separated by gel electrophoresis on gels with the indicated percentage of polyacrylamide, and transferred onto Immobilon-P membranes (Millipore, Etten-Leur, The Netherlands). The proteins were visualized using standard protocols. Primary antibodies rabbit anti-Atg5 (ab108327), mouse anti-LC3B (ab129376), rabbit anti-Atg3 (EPR4801) (Abcam, Cambridge, UK), mouse anti-p62 (ab56416) (Abcam, Cambridge, UK) were purchased from Abcam, rabbit anti-LC3B (NB600-1384) from Novus Biologicals (Littleton, CO, USA), mouse anti-\u03b2actin from MP Biomedicals (Santa Ana, CA, USA) and rabbit anti-Atg13 from Sigma-Aldrich (St. Louis, MO, USA). Primary 4F2 mouse anti-reovirus \u03c33 was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the University of Iowa, Department of Biology (Iowa City, IA, USA) [20] .", "Rapamycin (Rapa) and Bafilomycin A1 (BafA1) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Stock solutions were stored at \u221220 \u2022 C. Rapa was reconstituted in pure ethanol at a concentration of 1 mM, and BafA1 in pure ethanol at a concentration of 50 \u00b5M. Acridine orange (Sigma-Aldrich) was reconstituted in milli-Q at a concentration of 2 mM." ] },{ "paper_id": "c1aff1d1cda60a3215266ed6d56288d5b3630c50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our models are numerical analyses of ordinary differential equations. The equations are given in supporting information (S1 Appendix). The were numerically evaluated and graphed in R (S1 File, a Markdown file), sometimes also evaluated in Mathematica (S2 File).", "https://doi.org/10.1371/journal.pcbi.1006857.g002", "https://doi.org/10.1371/journal.pcbi.1006857.g005" ] },{ "paper_id": "c1b41ee52ac37d6d0543d4e3ad9fd4df61dc2f07", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Figure 1. Activation of signaling pathways in respiratory epithelial cells upon viral infection.", "These data illustrate that DUSPs have fundamental roles in adaptive immunity, affecting the activation, proliferation and differentiation of T helper cells. Although many of these studies have examined T cells in isolation, they identify the DUSPs as important regulators and suggest essential roles for them in airway diseases. ", "epithelium [17, 18] , and altered lymphocyte responses [19, 20] . This review will discuss the roles of the MAPK pathways in these processes and their regulation by a group of proteins known as dualspecificity phosphatases (DUSPs) or MAPK phosphatases (MKPs)." ] },{ "paper_id": "c1c6a98c21304f3788b20870b34afd8a115fa38c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c1cd72dfc8c71714d7751a0b9820f8f8e0ee3756", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Detection of IgGs by SDS-PAGE-For protein detection, the samples were analyzed under reducing and non-reducing conditions using NuPAGE 4 -12% BisTris gels in NuPAGE MOPS SDS running buffer with the Novex XCell SureLock mini-cell system (Invitrogen) at 200 V for 35 min. The gels were stained using Instant Blue Coomassie-based solution (Expedeon, San Diego). Images of the gels were obtained using a CanoScan 9000F scanner.", "% of antigen-specific IgGs \u03ed experimental R max theoretical R max \u03eb 100", "expected. The limit of detection was determined to be 31 ng/l, indicating that this was the minimum IgG concentration required to yield a detectable amount of deuterium protection.", "Sample Preparation-To prepare samples for epitope mapping analysis by mass spectrometry, a diluted sample (\u03f32 ml) of each purified mouse IgG was concentrated using a 100,000 molecular weight cutoff centrifugal filter device (Millipore, Billerica, MA). The loaded filter devices were spun in a swinging bucket rotor at 4000 \u03eb g for 40 min at 4\u00b0C. Concentrates of \u03f350 l were collected and subsequently buffer-exchanged with PBS using Zeba spin desalting columns (ThermoFisher Scientific) to maintain a physiological pH for the binding interactions and to ensure consistent deuterium exchange." ] },{ "paper_id": "c1dc7422f1716cf0750c974a86d1c5ac0b48d810", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The located reads and contigs were used for reads-based PCR to identify partial genomes in positive individual samples (The primer sequences are available in Supplementary Table 1) . Based on partial genomic sequences of each virus, the remaining genomic sequences were determined with genome walking, and 5 and 3 rapid amplification of cDNA ends (RACE) by using genome walking kit (TaKaRa), 5 RACE kit (Invitrogen), and 3 full RACE core set, version 2.0 (TaKaRa).", "Bats and rodents were treated in accordance with the guidelines outlined in the Regulations for the Administration of Laboratory Animals ( ", "All genome sequences have been submitted to GenBank. The accession numbers for the four bat pestiviruses are MH282908-MH282911. The accession numbers for the five rodent pestiviruses are KY370099-KY370103. The GA II sequence data have been deposited into the NCBI sequence reads archive (SRA) under accession numbers SRA051252 and PRJNA375958." ] },{ "paper_id": "c1df508d29e27cafd7a54a39bc2e087caa3a6bc6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal procedures complied with USDA guidelines and were conducted at the AAALAC-accredited Laboratory Animal Research Center at Utah State University under protocol 1229, approved by the Utah State University Institutional Animal Care and Use Committee.", "Detection of ALT in serum is an indirect method for evaluating liver disease. Serum ALT levels were measured using the ALT (SGPT) Reagent Set purchased from Pointe Scientific, Inc. (Lincoln Park, MI) per the manufacturer's recommendations. The reagent volumes were adjusted for analysis on 96-well microplates.", "Virus titers were assayed using an infectious cell culture assay as previously described [22] . Briefly, a specific volume of liver or spleen homogenate or serum was serially diluted and added to triplicate wells of Vero (African green monkey kidney; American Type Culture Collection, Manassas, VA) cell monolayers in 96well microplates. The viral cytopathic effect (CPE) was determined 7 to 8 days post-virus inoculation, and the 50% endpoints were calculated as described [23] . The assay detection ranges were 2.8 to 9.5 log 10 50% cell culture infectious doses (CCID 50 )/g of liver or spleen and 1.8 to 8.5 log 10 CCID 50 /ml of serum. In samples presenting with undetectable liver or spleen virus, a value of ,2.8 was assigned (,1.8 for serum). Conversely, in cases wherein virus exceeded the detection range, a value of.9.5 (.8.5 for serum) was assigned. For statistical analysis, values of 2.8 or 9.5 log 10 (1.8 or 8.5 for serum) were assigned as needed for samples with undetectable or saturated virus levels, respectively.", "Kaplan-Meier survival plots and all statistical evaluations were done using Prism (GraphPad Software, CA). The log-rank test was used for survival analysis. For analyzing differences in viral titers, ALT levels, and weight change, a one-way analysis of variance (ANOVA) with Newman-Keuls post test or the Kruskal-Wallis (two-tailed) test with the Dunn's post test was performed based on Gaussian distribution of the data." ] },{ "paper_id": "c1e2ffff403bab75c973812b3bf2e8d5a2f07600", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No functional analysis has been performed for PMS2P genes to date.", "Further, core duplicon genes commonly exist in two versions of gene structure; for example, SPATA31A versus SPATA31C, NPIPA versus NPIPB, LRRC37A versus LRRC37B, GOLGA6 versus GOLGA8 and TBC1D3 (1st cluster, A-D) versus (2nd cluster, E-H).", "\u2022 They express proteins with domains that suggest that they could be modifiers of general cellular pathways." ] },{ "paper_id": "c1e4465687748c1d03b1c648b1558d1051859b5a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data sampling was from January 1, 2010 to December 31, 2010. Total study sample was 1300. Consecutive hospitalised records of children with paediatric pneumonia were collected from each hospital in February, May, August, and November, respectively, that is, first consecutive 25 cases each month, or 100 cases per hospital over the 1-year study period.", "Specific pathogens (one pathogen or more) were identified in 624 (48.1%) cases (Table 3) . Negative pathogen findings were identified in 524 (40.4%) cases. Eighty-five (6.5%) cases were not tested for pathogens. Data were missing in 65 (5.0%) cases. TCM hospitals performed significantly fewer pathogen tests as compared to WM hospitals (30.3% versus 69.7%, p < 0.01). In terms of pathogenic agent, Mycoplasma pneumoniae (M pneumoniae) was identified more frequently, followed by mixed pathogens.", "A limitation of our study is that this was a crosssectional study. Our data was extracted from medical records at 13 hospitals. Although we exercised quality control to the best of our ability during the extraction process, still the quality and scope of the study were dependent on these records." ] },{ "paper_id": "c1eb7483446895edd38acb64e683bfd905d54211", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequences for virus genes were obtained from Genbank (http://www.ncbi.nlm.nih.gov/genbank). Primers and probes were designed using Integrated DNA Technologies PrimerQuest primer and probe design tool (http://www.idtdna.com/PrimerQuest/Home/Index).", "AMT + UV- ", "Viruses 2015, 7, page-page " ] },{ "paper_id": "c1edf39ded74b76134cc304dd347a4eb20bae012", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Differences between two groups were assessed using Pearson's \u03c7 2 test, Student's t-test or Mann-Whitney's U test. Additional analysis was conducted by multiple logistic regression model. Data analyses were performed with SPSS statistics version 17.0.0 (IBM Japan, Tokyo, Japan)." ] },{ "paper_id": "c1f0aaec8b7529fdf5fc1db7fdf3791300bacb18", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c200af0e42a9aa8539b208d993015a75a2fe1151", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The current situation is extremely dynamic and since then some countries have instigated flight restrictions and closed borders (e.g. Russia). These decisions were relevant for these locations but not based on probabilities. WHO has not recommended a cessation of transportation to free countries but suggested preventive measures. This would seem appropriate for Africa and South America with the caveat that only one case is needed to initiate a local epidemic without proper biosecurity and quarantine measures, whilst other regions will need to decide on a case-by-case basis through appropriate risk assessment.", "The timing of this outbreak around the lunar new year widely celebrated in China coincides with a period of highest annual human movement patterns in the region and between China and globally [8] , increasing the potential for rapid geographic dispersal of the infection. Further, recent investment in the African continent by the Chinese state and private investors has led to an increasing Chinese diaspora [9] and a greater number of direct and indirect flight connections to the African continent from China [10] .", "We modelled 388 287 passengers travelling to 1297 airports in 168 countries or territories. The risk index of 2019-nCoV for these countries is presented in Figure 1 . A regularly updated risk map is hosted on PANDORA's website ( https://ncovdata.io/import/).", "China has four times as many air passengers now than it had during SARS outbreaks in 2003. A large number of workers now travel internationally where China is heavily investing in infrastructure development in Africa, parts of Asia and Latin America. A significant and mobile Chinese population live in Europe and North America alongside an increasing amount of Chinese tourism. This travel poses a high risk of 2019-nCoV travelling across international borders. Although acquiring a case is low for these countries, the consequences are likely to be higher because of the country's capacity to control such situations [15] . ", "On 31 December 2019, local hospitals in Wuhan, China reported that they had detected a series of cases of Novel Coronavirus-infected pneumonia to the World Health Organization (WHO) [1] . On 7 January, the causative agent was identified by the Chinese Centre for Disease Control and Prevention as a Novel Coronavirus and designated '2019-nCoV' and finally as \"SARS-COV-2\". Epidemiological investigations identified the local Huanan seafood wet market as the location of an initial exposure event [2] . The market was closed on 31 December 2019 [2, 3] and wildlife market activity was banned countrywide. Despite travel restrictions to and from the city imposed by Chinese authorities to limit the potential dispersion of the virus beyond the region [4, 5] , international cases continue to be reported." ] },{ "paper_id": "c21a1e8e2ba8c0faa92fede77b7976f6f1061716", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Funding: Work on FCoV in the author's lab is supported by research grants from the Cornell Feline Health Center and the Winn Feline Foundation. AES is supported by the NIH Comparative Medicine Training Program T32OD011000.", "From the diagram in Figure 1 , it is clear to see why previous classification schemes based solely on phylogenetic analyses that do not take into account the flow of S gene exchanges and modifications (deletions) would fail to capture the complex relationships, histories and distinctive characteristics of this group of coronaviruses. We believe that, much like the situation with TGEV and PRCV, and despite the fact that type I (clade A) and type II (clade B) FCoV are grouped within the same species, the distinct origins of their S genes and the significant functional differences between them is such that they can be considered as two separate biological entities.", "The Coronaviridae family comprises a diverse group of viruses that affects birds and mammals (including humans), resulting in a variety of disease manifestations spanning respiratory, gastrointestinal, neurological and other tissue tropisms [1] . The diversity of viruses is encompassed by four viral genera, namely the alpha-, beta-, gamma-, and delta-coronaviruses. Among the coronaviruses (CoVs), severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), both betacoronaviruses, have received special attention as emergent pathogens in humans, with the potential to create global epidemics [2] [3] [4] . However, CoVs are also well known as important pathogens in both domesticated and wild birds and mammals [5] . Felids are no exception to this, and feline coronavirus (FCoV) is known to be the cause of disease in both wild and domestic cats [6] [7] [8] . FCoV is grouped as a member of the Alphacoronavirus genus, along with a range of other coronaviruses causing disease in dogs, pigs, and humans, as well as other mammalian species." ] },{ "paper_id": "c21f187377f454dff39c726a947077a5c74ae016", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting information S1 (8) " ] },{ "paper_id": "c229a350536a9e087003fb14e9e52aab0245d2ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Equal amounts of total protein prepared from transfected BHK-21 transfected cells were resolved in 10% SDS-PAGE, transferred to a PVDF membrane (Biorad) using a semidry electrotransfer device. VP1 protein was detected using the SD6 mouse monoclonal antibody (1:1000) [67] followed by goat-anti-mouse secondary antibody coupled to horseradish peroxidase (1:2000) (Thermo Scientific), and enhanced chemiluminescence (GE Healthcare). After stripping using restore western blot stripping buffer (Thermo Scientific) the same membrane was used to detect a-tubulin as a loading control using anti-tubulin antibody (1:5000) (Sigma).", "The plasmid pMT28, encoding a cDNA copy of FMDV C-S8c1 genome inserted into pGEM-1 under the control of the SP6 promoter was described previously [42] . Following NdeI linearization FMDV RNA was transcribed in vitro using SP6 RNA polymerase, as described [8] .", "A striking result was noted in the lack of inhibition exerted by AONs complementary to domain 4, with values above 60% (Fig. 8A) . However, and in agreement with the inhibition observed in transfected cells (Fig. 6A) , the AONs 432 and 452 were strong inhibitors of protein synthesis. " ] },{ "paper_id": "c2302facc633f9dfaf8597ffe57ca929e5d08b78", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c235de11eceb5f9f55e0b361818e959d4482b621", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NUagA, a seedling yellows isolate from Japan (Accession No. AB046398); and Qaha, a T36-like isolate from Egypt (Accession No. AY340974). In addition, full-length sequences were included of CTV isolate T3 (unpublished) from Florida and H33 from Texas (T. E. Mirkov, personal communication) and a partial sequence (13,585 nt) of the CTV T68 isolate from Florida (unpublished).", "CTV isolate FS2-2 was collected from a citrus grove in Florida in 2004, and was maintained on Madam Vinous sweet orange in an insect-proof greenhouse. The isolate was associated with an unusual stem-pitting symptom in a Hamlin sweet orange tree in the field. Full-length genomic sequences of seven CTV isolates were retrieved from GenBank: T30, a mild isolate from Florida [1]; T36, a decline-inducing isolate from Florida [2]; SY568, a decline and sweet orange stem pitting isolate from California [3]; VT, a decline and seedling yellows isolate from Israel [4]; T385, an essentially symptomless isolate from Spain which is nearly identical to isolate T30 [5];", "Amplified PCR fragments were cleaned using the Qiagen MinElute PCR Purification Kit 4.0 to retrieve sequence information. Base calls were made using the ABACUS algorithm [10] with a haploid model. The ABACUS parameters were as follows: no signal threshold = 20, weak signal fold threshold = 20, maximum signal to noise ratio = 20, quality score threshold = 3.0, base reliability threshold across samples = 0, trace threshold = 1, and sequence profile threshold = -0.175." ] },{ "paper_id": "c23b18fc16e216774e32f7dde9eebc8756194626", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c23d0e5107a2764e299a147d41a8c76ce91c231d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consequently, consensus sequences were created for individual conserved fragments within Shannon entropy threshold 2 from corresponding aligned sequence datasets . The consensus sequences were further used for the identification of MHC binders.", "where Pi is the fraction of residues of amino acid type i and M is the number of amino acid types.", "For conservancy analysis, sequence datasets were first individually aligned using ClustalW software. The substitution model was set to BLOSUM, since the mentioned substitution matrix is based on amino acid pairs in blocks of aligned protein segments, hence performs better in alignments and homology searches compared to those based on accepted mutations in closely related groups (Henikoff and Henikoff 1992) . Conservancy of the amino acids of HPV strains among the aligned sequences of datasets was estimated by Shannon entropy function using protein variability server (PVS). Shannon entropy analysis (Shannon 1948 ) is one of the most sensitive tools to estimate the diversity of a system. For a multiple protein sequence alignment, the Shannon entropy (H) for every position is calculated as follows" ] },{ "paper_id": "c24060d084e314b214e061995b5528b2e0071e31", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data is presented as average 6 SEM. Statistically significant differences were assessed by one way ANOVA, and p values less than 0.05 were considered significant." ] },{ "paper_id": "c24570f542d59b0d17450b1bd83c708f9401ca9c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For immunohistochemical staining, unfixed frozen liver sections were fixed in 4% paraformaldehyde for 10 min and then incubated with blocking buffer (1% bovine serum albumin in PBS) for 30 min at room temperature. Subsequently, the sections were incubated with biotinylated mouse anti-HCV core mono-clonal antibody (5E3) for 2 h at room temperature. After being washed with PBS, the sections were incubated with streptavidin-Alexa Fluor 488 (Invitrogen). The nuclei were stained with 4',6diamidino-2-phenylindole (DAPI). Fluorescence was observed using a confocal laser microscope (Laser scanning microscope 510, Carl Zeiss).", "Tissue samples were fixed in 4% paraformaldehyde in PBS, embedded in paraffin, sectioned (4-mm thickness), and stained with hematoxylin and eosin (H&E). Staining with periodic acid-Schiff stain, Azan stain, silver, or Oil-red-O was also performed to visualize glycogen degeneration, fibrillization, reticular fiber degeneration, or lipid degeneration, respectively.", "Text S1 Supporting information including material and methods, and references. (DOCX)" ] },{ "paper_id": "c248b6eb16165b2b06281401eaeb99df0ba7f211", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The severity of a patient's asthma had a bearing on which method of treatment was used with 'mild' and 'moderate' patients receiving medication via MDI/spacer, and 'severe' patients receiving nebulisation. Of note, in some sites, physicians believed that there was a tendency towards overestimating the severity of the patient's condition at triage, resulting in a higher than necessary use of nebulisation." ] },{ "paper_id": "c24af6314214e7d2ef8b04419efccd6f7f900858", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All procedures involving animals were approved by the Institutional Animal Care and Use Committee of Kansas State University (IACUC#: 2613 and 2961).", "For immunocytochemistry, whole-mounts or sections were incubated overnight at 4uC with diluted primary antibody (1:200 rabbit anti-pendrin, a gift from Dr. S\u00f8ren Nielsen, Aarhus University, Denmark; 1:200 rabbit-anti-Cx26 (Invitrogen, Carlsbad, CA) or 1:200 rabbit anti-Na + /K + ATPase alpha1 subunit (Novus Biologicals, Littleton, CO). Primary antibodies were diluted with PBS-TX containing 1-3% BSA. Whole-mounts or sections were washed three times in PBS-TX and incubated for 1 hr at room temperature with secondary antibody (Alexa594 conjugated goat-anti-rabbit (Invitrogen) diluted 1:1,000 with PBS-TX containing 1-3% BSA. After washing three times in PBS-TX, whole-mounts or sections were incubated at room temperature for 20 min with phalloidin and 5 min with DAPI diluted with PBS-TX at 1:40 and 1:1,000, respectively. After staining, whole-mounts or sections were washed again three times with PBS-TX, coverslipped with FluorSave (Calbiochem, La Jolla, CA) and observed by confocal laser scanning microscopy (LSM 510 Meta, Carl Zeiss, G\u00f6ttingen, Germany).", "Calibration consisted of taking a reference value in the superfused bath solution and then obtaining the slope of the electrode in a perfused agar cup placed into the bath chamber. Agar cups holding ,100 ml were prepared with warm (37uC) weakly-buffered Ringer solution. This method was devised to minimize the contribution of electrode drift and differences between reference electrodes. pH sensitive electrodes had a slope of 5863 mV/pH unit (n = 40). Three calibration solutions with different pH values were used. Calibration solution contained (in mM): pH 6: 130 NaCl, 20 MES; pH 7: 130 NaCl, 20 HEPES; and pH 8: 130 NaCl, 20 tricine.", "Data are generally presented as average 6 sem with N being the number of animals. In some instances averages are presented with SD, as indicated. Data acquired in paired experiments using littermates were evaluated by paired t-test. Significance was assumed when p,0.05." ] },{ "paper_id": "c25889c8a5469237f3437394d9c595f9af0c7c4c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Aedes aegypti is a major vector of several viruses such as dengue and Zika viruses. Understanding the intricate interaction of viruses with mosquito vectors and the factors involved in virus replication are essential for developing effective arbovirus control strategies. In PLOS Neglected Tropical Diseases |", "Dengue and Zika viruses are related mosquito-borne viruses that have a common primary vector, Aedes aegypti and infect millions of people worldwide [1, 2] . Recent outbreaks of Dengue and Zika in South America pose a serious risk for other tropical regions in the world as Ae. aegypti is one of the most abundant mosquito species in these areas [2] . Although certain vaccines have been licensed in some countries, there are no efficient specific therapeutics available for either diseases, hence, the best protection against their global spreading is an efficient vector control program [3, 4] .", "Ae. aegypti infected with the wMelPop-CLA strain of Wolbachia (+Wol) and without Wolbachia (-Wol, tetracycline-cured line) were stocks produced previously [37] . For the experiments in this work, 4-day-old female mosquitoes were used from which total RNA was extracted with 6-10 adult mosquitoes for each biological replicates." ] },{ "paper_id": "c25e535e8cb1fa2ff9e24c6e582d261d09551632", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Table S1 . Primers used for quantitative reverse transcription polymerase chain reaction (qRT-PCR).", "Cross sections (3 mm thick) were cut from stems of viruliferous or nonviruliferous SBPH-inoculated rice plants, infiltrated with an NO fluorescent probe (10 \u03bcM 4amino-5-methyl-amino-2\u2032,7\u2032-di-fluorofluorescein diacetate [DAF-FM DA]) diluted in a 20 mM Hepes-NaOH buffer, pH 7.2, followed by 15 min incubation in the dark [27, 28] .", "Supplementary information accompanies this paper at https://doi.org/10. 1186/s12985-019-1228-3." ] },{ "paper_id": "c26196c940aab1a9c43e70d5428672644d1e0972", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c2676bad025d5a255889b8a699c86711223e3a63", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Preparative HPLC: Agilent 1100 Series with a normal phase column (250\u00d720 mm i.d.) packed with 5\u00b5m silica (YMC Co., Ltd., Kyoto, Japan) that was equipped with 515 Waters pump and UV-Vis detector. All solvents used were of HPLC grade (Caledon Laboratory Chemicals Ltd.", "The pmzNL4-3 plasmid encodes the HIV-1 fulllength RNA, with packaging ability containing the aforementioned deletion in the Pol region; the psPAX2 plasmid encodes HIV Gag and Gag-Pro-Pol polyproteins, besides all the HIV-1 accessory proteins; and the pMD2G plasmid encodes the vesicular stomatitis virus surface glycoprotein (VSVG), which is required for assembly and the budding process of virus. These pseudotyped virions have the ability of infecting a broad spectrum of cell, even without the CD4 receptor (including Hela cells).", "(4)" ] },{ "paper_id": "c2749a18c00e1668167a5f65d6d9ff7896f25465", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fourier and wavelets analysis were performed using Matlab (Mathworks Inc.) software EPIPOI\u00ae (Alonso & McCormick 2012) . Statistical analysis was performed using SPSS v. 13.0 (SPSS Inc., Chicago, IL) software, and the plots were constructed using Microsoft Office 2013 (Microsoft Corporation). The research was approved by Research Ethics Committee of the Faculty of Medical Sciences, University of Campinas (number 909/2013).", "Respiratory syncytial virus (RSV) is a non-segmented enveloped RNA virus of the family Paramyxoviridae, genus Pneumovirus. Although RSV causes upper respiratory tract diseases in patients of every age, more severe influenza-like illness occurs in children. Most children are infected during the first year of life, and almost all are infected before the age of 2 years (CDC 2014) .", "The most appropriate dates for starting immunoprophylaxis with palivizumab for each region of Brazil are compared with the recent indication by Brazilian Ministry of Health (Table III) . There are differences in the months suggested for the beginning of therapy with palivizumab in Southeast and Midwest region when compared with Brazilian official guidelines.", "The main factors associated with the severity of the infection in infants under 5 years old are prematurity, congenital heart disease, and chronic lung disease of prematurity (CID 2009 ). RSV reinfections throughout life are common, generally manifesting through influenza-like illness." ] },{ "paper_id": "c27741de244a87a624f556884b3d2ffffdf9b4ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Signatures of length two, as those selected by our method for inclusion in the short panel ( Fig 2B, red boxes) , are sufficient to correctly identify the control/affected status of each individual.", "https://doi.org/10.1371/journal.pone.0194225.g001 classification is illustrated in Fig 2. The heatmap of the measured protein levels shows that no single protein level highly correlates with a partition of the subjects in two groups (Fig 2A) .", "Supporting information S1 Table. Tissue-specificity of proteins in the long biomarker panel. The data were retrieved from Human Protein Atlas. (PDF) S2 " ] },{ "paper_id": "c27cd721cc62f4294aeb0159e587efb9391ce8ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Peroxynitrite is formed by phagocytes for killing invading microorganisms, nevertheless if in high concentrations can oxidise several host biomolecules by nitration with the consequent cellular damages being responsible for diverse diseases [26] .", "The first pathway leads to initiation of rapidly progressing, destructive chain reactions, generating hydroperoxides and volatile compounds, generally through a three-phase process: initiation, propagation and termination.", "These are stabilised via double-bond rearrangement (electron deslocalization), originating conjugated dienes and trienes. These intermediates decompose, originating alcohols, aldehydes, alkyl formates, ketones, hydrocarbons, alkoxyl radicals and formic acid. All of these compounds are considered secondary products of lipid oxidation [5] ." ] },{ "paper_id": "c280d46d6fa7e2c2938a5c09bd6b092e1058a9b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Expression of VP1 by L. plantarum ", "Data handling and analysis and graphic representation were performed using GraphPad Prism 6.0 software (San Diego, CA). The data were analyzed to express the mean \u00b1SD as the error value and one-tailed t test was used for comparison. Differences were considered to be statistically significant when P value was less than 0.05.", "Detection of antibodies using enzyme-linked immunosorbent assay (ELISA)" ] },{ "paper_id": "c28845dc44f29502a6012256075760eab1d62af0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ChAdOx1 MERS vaccination elicited neutralising antibodies with no statistically significant difference detected between immunisation routes (Mann Whitney U test, p = 0.49) (Fig. 1a) . No MERS-CoV neutralising antibody response was observed among the ChAdOx1 vaccine encoding enhanced green fluorescent protein (ChAdOx1 eGFP) vaccinees.", "To address whether or not the single dose of ChAdOx1 MERS vaccine truly resulted in sterile immunity, we analysed the pre and post challenge sera with a MERS-CoV nucleoprotein ELISA. Irrespective of the route of immunisation, relatively low levels of IgG antibodies against nucleoprotein were detected (Fig. 1e) , indicating that the animals were likely briefly infected during the first 1-2 days after inoculation but that this did not result in morbidity and mortality. No significant difference in the MERS-CoV nucleoprotein response was detected between the vaccinated groups (Mann Whitney U test, p = 0.6970; Fig. 1e ).", "All data generated or analysed during this study are included in this published article." ] },{ "paper_id": "c28b246499550a272954111f550f0c8d2ac750cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c290f9617c78697d527d8a58bdbd8ef9af47fcfc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In compliance with relevant laws and institutional guidelines, this project protocol was approved by the Division of Wildlife Conservation Institutional Animal Care and Use Committee (DWC ACUC 2012-031). All efforts were made to minimize animal suffering.", "This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication." ] },{ "paper_id": "c2952e4d56bd9bf5c6eee0aaa733557471e60a92", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. Viral genome data for new CoVs obtained from this study are available in GenBank under accession numbers MN611517 to MN611525.", "Supplemental material is available online only. ", "Sample preparation. Control viruses were cultured for RNA extraction. Porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis coronavirus (TGEV), MERS-CoV, SARSr-CoV, and mouse hepatitis virus (MHV) samples were cultured in Vero, swine testis (ST), Huh7, Vero E6, and DBT cells, respectively. All cells were maintained in Dulbecco modified Eagle medium (DMEM) containing 10% fetal bovine serum (FBS) and incubated at 37\u00b0C with 5% CO 2 . Once cytopathic effect (CPE) was observed, 140 l of supernatant was collected for RNA extraction." ] },{ "paper_id": "c296f6a98b4eb94a69e4caef2df38ccf6e498511", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lung tissue samples were analyzed to discard any infection with secondary bacterial pathogens, being subjected to microbiological routine cultures (Xylose lysine deoxycholate agar, MacConkey agar and Blood agar) by using standard procedures. No bacteria were isolated from these samples.", "Glutaraldehyde-fixed samples were post-fixed in 2% osmium tetroxide, dehydrated in acetone and embedded in Epon 812 W (Fluka Chemie AG, Buchs, Switzerland). Sections (50 nm) were counterstained with uranyl acetate and lead citrate, and examined with a Philips CM-10 transmission electron microscope.", "NO is a potent vasodilator, acting to maintain vascular tone and function within the vessel wall, generated from L-arginine by nitric oxide synthase (NOS) enzymes. There are three main isoforms of NOS with distinct functions and patterns of expression: endothelial NOS, neuronal NOS and inducible NOS (iNOS) highly expressed in M\u03a6s [10, 12] .", "The bovine respiratory disease complex (BRDC) is an important problem for the cattle industry, often resulting in severe economic losses [1, 2] . This fatal bovine respiratory infection is a multi-factorial disease associated with a primary viral infection followed by a secondary bacterial infection. It is frequently characterized by concurrent infections of several pathogens. The etiologic agents related to feedlot pneumonias include bovine viral diarrhea virus 1 and 2 (BVDV-1 and BVDV-2), bovine herpesvirus type 1 (BHV-1), bovine parainfluenza-3 virus, bovine respiratory syncytial virus, bovine adenovirus, bovine coronavirus, Mannheimia haemolytica, Pasteurella multocida, Histophilus somni and Mycoplasma spp. [3] [4] [5] [6] . Resistance to respiratory disease in cattle requires host defense mechanisms that protect against viral and bacterial pathogens that have also evolved sophisticated strategies to evade the host immune responses, including among others an altered pulmonary macrophages (M\u03a6s) function or the induction of profound inflammatory responses that cause lung injury and sepsis [6] ." ] },{ "paper_id": "c2986eb912dbecc9c8508361012392706955076e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 2B protein of the FMDV was analyzed using the TMpred (http://www.ch.embnet.org/ software/TMPRED_form.html), DAS-TMfilter (http://mendel.imp.univie.ac.at/sat/DAS/), and PredictProtein (https://www.predictprotein.org/) programs.", "Many studies on viroporins, including poliovirus 2B and coxsackie virus 2B, have found that these proteins induce Ca 2+ abnormalities [7] . The flow cytometry analysis indicated that the FMDV 2B protein damaged the membrane integrity and disrupted the Ca 2+ concentration in host cells, similar to the effects of other viroporins.", "Foot-and-mouth disease (FMD) is a highly contagious disease in animals and is on the Office International Des Epizooties (OIE) list of notifiable animal diseases [1] . The causative agent of FMD is the foot-and-mouth disease virus (FMDV), which is a non-enveloped virus with icosahedral symmetry. The FMDV belongs to the Aphthovirus genus of the Picornaviridae family. It has a single-stranded, plus-sense RNA genome that consists of approximately 8,500 bases. The genome is divided into 3 regions, a 5' non-coding region, a protein-coding region, and a 3' non-coding region [2] . The protein-coding region can be further divided into the P1, P2, and P3 regions. The P1 region encodes four capsid proteins, and the P2 and P3 regions encode non-structural proteins, including the 2B protein. The research on FMDV non-structural proteins has increased over the last few years, but additional efforts are needed to obtain more information, especially on the 2B protein, which may act as a viroporin." ] },{ "paper_id": "c29e836db0541b34ffaf6a75c8b7079fd98220d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Study population. We recruited a community cohort and inpatients from TTSH between April 2012 and December 2013.", "Scientific RepoRts | 7:42963 | DOI: 10.1038/srep42963", "Adjusted Non FLU Crude Non FLU (1 Adjusted FLU)/(1 Crude FLU) All analyses were conducted using R version 3.0.1 (R Foundation for Statistical Computing, Vienna, Austria).", "One hundred and thirty episodes were reported from 99 community participants (community-ARI) with 76, 16, 6 and 1 individuals reporting 1, 2, 3 and 4 episodes respectively. For the inpatients, there were 145 episodes with only 1 individual having 2 and another having 3 episodes (inpatient-ARI).", "\u2022 ARI: episode with acute onset with any key respiratory symptoms including cough, shortness of breath, sore throat, or runny nose. \u2022 Febrile respiratory illness (FRI): ARI with self-reported fever, regardless of body temperature (T) measurement. \u2022 Influenza-like illness defined by Centers for Disease Control and Prevention of the United States of America (ILI-U): fever \u2265 37.8 \u00b0C together with cough and \u2044or sore throat in the absence of a known cause other than influenza 31 . \u2022 Influenza-like illness defined by World Health Organization (ILI-W): fever of \u2265 38 \u00b0C plus cough with onset within the last 10 days 32 ." ] },{ "paper_id": "c2a4b60c4285348cbc44c501adc3dbdc4088870b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Metabolic reprogramming in immune cells is a recurrent phenomenon when exposed to proinflammatory stimulants in the form of pathogens or cytokines. Macrophages and dendritic cells in particular are well-equipped to sense and respond to impending danger by pathogens, thus establishing the frontline of host defenses. Recent studies have highlighted the extraordinary contribution that multiple host metabolic pathways confer toward the ability of innate immune cells to respond to infections (1) . Not surprisingly, some of the very same pathways that function to eradicate infection are often rewired by the invading pathogen.", "Addition of free cholesterol to SREBP2-knockout cells significantly decreased pTBK1, while blocking IFNAR had no effect on pTBK1 levels, reinforcing the idea that cholesterol directly influences STING-mediated activation of TBK1. These data support a model in which a lack of cholesterol in the cell makes STING more sensitive to cyclic dinucleotides, upregulating the STING-pTBK1-IRF3 signaling axis, and ultimately increasing expression of Ifnb1 and ISGs, conferring an intrinsic proinflammatory phenotype to cholesterol-deficient cells (77) . Admittedly, most of these experiments used MHV68; however, these conclusions may very well be relevant in other virus infections.", "JP and SS discussed and wrote the manuscript. " ] },{ "paper_id": "c2a69ec62b5553d158b04c9a91409e451f91e2ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bat sampling methods were approved by the Research Ethics ", "Bats were captured at 24 colonies in eight departments across Peru (Figure 1a ) between 2013 and 2016 ( (Anthony, 1988) , which differentiated bats into four age classes.", "Faecal samples were collected using 3-mm-diameter rayon-tipped aluminium swabs (Technical Service Consultants Ltd) dipped in sterile Dulbecco's phosphate buffered saline (Gibco). Swabs were stored in cryovials containing 1 ml RNALater (Ambion) overnight at 4\u00b0C before being transferred to dry ice and stored in \u221270\u00b0C freezers, following the manufacturer's instructions." ] },{ "paper_id": "c2b8b47dcfe70db8080da73d7a3941c94b31b025", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral particles per mL = (2)", "Xneg is the mean value of the negative control samples; \u03c3neg is the standard deviation of the negative control samples; and t99% is the t value for N-1 degrees of freedom at the 99% confidence level." ] },{ "paper_id": "c2dfec16dd4c29856ec78ecbe519d7ba387f01ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "TTCATATGCAACCTGGTG, reverse: CGGAATTCGCTGTGCTCTA), APN\u22062 (1-400 AA, forward: TTCATATGGCCAAGGGATTC, reverse: CGGAATTCGGTCACCAGGTTG), APN\u22063 (332-400 AA, forward: TTCATATGTGCCGGTGCCA, reverse: CGGAATTCAGGGTCACCAG), APN\u22064 (1-331 AA, forward: TTCATATGGCCAAGGGATTC, reverse: CGGAATTCAAGTCGGGCAAGG), and APN\u22065 (332-963 AA, forward: TTCATATGTGCCGGTGCCA, reversed: CGGAATTCGCTGTGCTCTA). We sequenced the resulting PCR products, cloned these into pET-28a (+), and then transformed them into E. coli BL21 (DE3) cells for protein expression [20] .", "We used the recombinant plasmid pET28a(+)-APN as a DNA template for subsequent PCR amplification [17] . Five pairs of primers specific to the porcine APN mRNA (GenBank Accession Number: KF280271) were designed to amplify five truncated APNs, including primers for APN\u22061 (401-963 amino acids (AA), forward:", "All data obtained in this study were shown as the means \u00b1 standard deviations of at least three independent samples. We statistically analyzed the relative value between the absorbance of samples and controls at a wavelength of 450 nm via GraphPad Prism \u00ae 5.0 Software (GraphPad Prism Inc., CA, USA) and followed with a student's t test using SPSS 16.0 software (SPSS Inc., USA). A p value of < 0.05 was regarded as significant (*), and p value of less than 0.01 was considered extremely significant (**).", "The point-mutant amino acid in FaeG peptides are marked in italic. amino acids of the GST-tag) as negative control. We recorded the absorbance at a wavelength of 450 nm, and ran all of the samples in triplicate." ] },{ "paper_id": "c2fa41c3b09393428d9f973feb22bee011015eee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Molecules 2018, 23, x FOR PEER REVIEW 6 of 25", "Ki values (\u00b5M) determined from Dixon plots or * IC50 values (\u00b5M) of compounds 21a-j with, k-pAPN from porcine kidney, l-P. falciparum rPfAM1. m-E. coli rEcPepN, n-human endoplasmic reticulum aminopeptidase 1 (rHsERAP1), o-human endoplasmic reticulum aminopeptidase 2 (rHsERAP2), p-human puromycine sensitive aminopeptidase (rHsPSA), q-human Leucyl-cystinyl aminopeptidase (rHsIRAP), s-human leukotriene A4 hydrolase (rHsLTA4H), t-P. falciparum rPfAM17 and u-aminopeptidase from A. proteolytica (AAP 21f ", "Reactants were purchased from usual provider. Usual solvents were freshly distilled, dry MeOH distilled over Mg/MgI 2 , dry DME over Na and benzophenone, dry Et 2 O was distilled and stored over Na, DCM was distilled over P 2 O 5 and stored over anhydrous K 2 CO 3 ." ] },{ "paper_id": "c2fb6867057dd0152657070fde0a4ab564d375c2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The K 3 EDTA blood samples were analysed immediately after collection using an ADVIA 2120 analyser (AV ADVIA 2120; Bayer Healthcare, Siemens, UK), containing software necessary for the analysis of bovine blood as described by Johnston et al. [14] . Zinc sulphate turbidity (ZST) test analysis was carried out at 520 nm using a spectrophotometer [22] . The haptoglobin concentration was measured using an automatic analyser (Olympus AU 400 Analyser; Beckman Coulter, Inc., Clare, Ireland) and a commercial assay kit (Tridelta Development Ltd., Maynooth, Ireland).", "Bovine respiratory disease (BRD) remains among the leading causes of death of dairy and beef cattle of all ages in Ireland [1] and internationally [2] . Dairy calf pneumonia (enzootic calf pneumonia) represents an epidemiologically distinct component of the BRD complex, typically affecting 2 to 6 month old calves; shipping fever of feedlot cattle and atypical interstitial pneumonia are other recognised syndromes [3] .", "The variance inflation factor was used to detect multicollinearity. A backward stepwise selection procedure based on a likelihood ratio test (p > 0.05) was used to eliminate terms from the model. Regression diagnostics (heteroskedasticity, skewness and kurtosis) and plots of the residuals versus the predicted values were used to assess the presence of outliers and to check the fit of the final model." ] },{ "paper_id": "c32c30f41c1f50f242b977297a8ff85eda1a2987", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Most DIPs can attach to cells unless a surface protein required for entry is absent, which prevents viruses from invading cells. After DIPs invade cells, deletion of genomic fragments affects the interaction between viruses and receptors on the cell membrane.", "WZ, BZ, QW, CS, and LZ were involved in the conception and writing of the manuscript. YY, TL, RZ, and XH wrote the manuscript. KY, TC, and QX prepared the figures and tables. WZ and BZ checked the manuscript. All authors read and approved the manuscript.", "Different types of DI genomes are depicted in Figure 1 .", "Although numerous studies indicate that DIPs can suppress different stages during the virus replication cycle, it still lacks data for this dynamic intracellular behavior." ] },{ "paper_id": "c32c7f59bd902e4b2ef9fbe78e87c1d683de2d42", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that they have no competing interests.", "Clinical monitoring and sample collection were performed by DGP, MV and TA; viral study, phylogenetic study and cell culture were analyzed by CRG, EN and MM; the manuscript was prepared and critically discussed by CRG, DGP, EN, JLC and JMSV and all the other authors made contributions of. All authors read and approved the final manuscript.", "In addition to their role in pathology, adenoviruses are very important vectors in the gene therapy of genetic disorders and cancer [6] , as they can accommodate a large DNA cargo, exhibit tropisms for multiple organs and can be engineered to decrease virulence. Nonetheless, they still present toxicity problems [7] , which has led to investigation of the potential of using animal adenoviruses as vectors for gene delivery to humans [8] [9] [10] . In line with this, the identification of new animal adenoviruses, in addition to being interesting from an animal health perspective may be promising for gene therapy." ] },{ "paper_id": "c32d0c0e6f09f6da1b8d9075733574b26bfec04a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceptualization: TPV. Tuberculosis [46] rs4844609 (4868T>A) Sl4/Sl5 T1610S Alzheimer disease [49] [50] [51] [52] Cognitive decline [53, 54] rs6691117 (4883A>G) KCAM +/-I1615V Erythrocyte Sedimentation Rate [55] Alzheimer Disease [56] Gastric cancer [57] Lung cancer [58] Glioblastoma multiforme [59] 21. Moulds ", "CR1 variants were genotyped by direct sequencing in a cohort of 441 healthy individuals from Brazil, Vietnam, India, Republic of Congo and Ghana." ] },{ "paper_id": "c3334a3ad6a9e88664342aff618229775fb3e31a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One \u03bcg of hybrid human IFN-\u03b1B/D [67] or mouse IFN-\u03bb2 (IL-28A; PeproTech) were subcutaneously injected in 100 \u03bcl of PBS. 100 \u03bcg of poly I:C was injected intraperitoneally in 200 \u03bcl of PBS.", "PLOS Pathogens |", "Briefly, tissue was homogenized in 800 \u03bcl of PBS and feces in 500 \u03bcl of PBS using the FastPrep apparatus (MP Biomedicals). The homogenates were treated with chloroform (10% final concentration), centrifuged briefly and serial dilutions of the aqueous supernatants were incubated on L929 cells at room temperature. After 1 h, the inoculum was removed and cells were covered with 1.5% AVICEL in 1x DMEM medium containing 0.1% BSA. After four days medium was removed, cells were fixed with 4% paraformaldehyde and plaques were visualized with 0.5% crystal violet." ] },{ "paper_id": "c337fa83ebb25e4600c0f9333ee0cb0fa938e947", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GP10: Doctors yes, nurses probably, reception staff", "********************************* A1/2: I kind of feel about it the same way as if I saw somebody get knocked over by a car, I'd go and help if I could.", "Many participants, in a variety of roles, felt that absenteeism if one was able to work (whatever one's employment, in or out of the health service) was generally wrong and not just wrong during a pandemic." ] },{ "paper_id": "c33d7d8d49ed2a2ea4c997f587e75b9723418226", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c3411ca577f8a7a81a4bc8a3caff019243d75af9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bats were anesthetized in the field with Rompun 2% (Xylazin 20mg/ml) and Ketamin 10% (100mg/ml) [40] . Animals were euthanized by bleeding them with cardiac puncture. Tissue samples of spleen, liver, kidney, lung and intestines were aseptically taken. Intestines were removed last to avoid contamination of organs with intestinal content. All samples were immediately preserved in liquid nitrogen and stored at -80\u02daC until further analyses.", "The 10 strains that were initially identified as copy strains by MLST and PFGE analysis also shared identical virulence gene profiles and were excluded from subsequent analyses to avoid any bias in the interpretation of data.", "Isolates belonging to group B2 harboured the highest number of VAGs (median 10.5), followed by group ABD (8.0), AxB1 (8.0), D (6.5), A and B1 (5.0).", "All new assigned STs are available from the MLST website (http://mlst.warwick.ac.uk/mlst/ dbs/Ecoli/Downloads_HTML). WGS of the ST131 is available from ncbi (accession number LYRV00000000)." ] },{ "paper_id": "c343dec852bdfd28c3b8d0f06482408ac5ce52bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We are grateful to Oleksi Petrenko, Stephen D'Amico, and Jean Rooney for all their help. We also thank members of the laboratories of James Konopka and Nick Carpino for their support." ] },{ "paper_id": "c3461b2484a2c1b0532e47afba87d235e350b9e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bats (order: Chiroptera) constitute an abundant and diverse mammalian lineage comprising approximately 20 % of all known mammalian diversity [1]. Bats have evolved apart from other mammals for more than 50 million years [2] and are divided into two major suborders; the Yinpterochiroptera (megachiroptera) and the Yangochiroptera (microchiroptera). Yinpterochiroptera includes the family Pteropodidae and genera Rousettes", "and Pteropus whereas Yangochiroptera includes the family Myotidae and genus Myotis [3] . Unlike most mammals, bats can fly and this ability enabled their wide geographical range and increased metabolism [2] . Interestingly, bats have recently come to the forefront of zoonotic disease research with vast number of pathogens identified in a wide variety of bat species [2] .", "We compared our assembly to the transcriptomes of three related bat species --M. davidii, P. alecto, and M. brandtii. Using BLAST, we recovered 90. " ] },{ "paper_id": "c34dcfec2a5e68f31f6a0401d2cd636021d984bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Genome Biology 2006, 7:R110 comment reviews reports deposited research refereed research interactions information", "Average distribution " ] },{ "paper_id": "c351ce11cb0157d1118dfcbb55cf9f8bab0ad35d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Supporting information S1 " ] },{ "paper_id": "c3617dc2a70b0046f95b857cb09cafeebf0a8ce4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was partially supported by grants R01AI093450 (ISL) and R56AI135770 (SP) from the National Institute of Allergy and Infectious Diseases.", "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.", "efficacy of the ML29 reassortant vaccine for Lassa fever in small non-human", "LASV has a bi-segmented single-strand negative-sense RNA genome 36 . The large (L) RNA encodes for the L protein, an RNA-dependent RNA polymerase, and for the matrix Z protein." ] },{ "paper_id": "c36f5134f23a74677ed9d3a39f2eb8b4b19ad6e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We report the complete genome sequence of the first Mexican human coronavirus (HCoV) OC43, obtained by new-generation sequencing and a metagenomic approach, isolated from a child hospitalized with pneumonia. The genome is closely related to the other OC43 genome sequences available, ranging from 99.8% to 98.2% nucleotide sequence identity.", "Nucleic acids from the sample were extracted with the PureLink Viral RNA/DNA kit. Before extraction, the sample was treated with Turbo DNase and RNase, and a random-primer amplification of the genetic material was performed as previously described (5) . The sequencing was carried out with the Illumina Genome Analyzer IIx single-end platform. A total of 12,330,418 reads were generated and 1,657,101 (13.44%) were mapped to the consensus sequence of HCoV OC43. Mapping was accomplished by SMALT v.0.7.6 (6) with default parameters (only \u03eay set to 0.8).", "The whole viral genome sequence was obtained with an average coverage of 3,368\u03eb. The same genome sequence was obtained by de novo assembly using Velvet (7) . The complete Mexican HCoV OC43 genome was composed of 30,712 nucleotides, with an average G\u03e9C content of 35.51%. The strain shows the typical OC43 organization, with the following 5= untranslated region (UTR) (nt 1 to 199), genes: orf1ab (nt 200 to Accession number(s). The complete genome sequence of the Mexican OC43 strain was deposited at GenBank under the accession number KX344031." ] },{ "paper_id": "c381a318060a8b093ebc7911198e0b7c509bf580", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.pntd.0005659.g005", "Matrix approach [87] .", "Discriminating between studies which build explanatory models versus create predictive models is particularly important in statistical modelling [10] . We however avoided this way of grouping. The dichotomy explanatory vs predictive models might be clear from an epistemological point of view [10] , nevertheless, we have found it really challenging to rigorously separate papers according to this classification. For most papers, a formal distinction is often impossible as the causal relationships are inferred/discussed from the patterns captured from predictive models, and vice versa the hypothetical-deductive models (e.g. driven by causal relationships), could both be able to predict a range of future scenarios." ] },{ "paper_id": "c383b8dedcefbf78e370b0152058176d9219330e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). Raw reads have been deposited into GenBank under GenBank accession no. GSE75771.", "RNA-Seq. Stranded Illumina libraries for each tissue were prepared from total RNA using the NEB Ultra Directional RNA library prep kit with poly(A) selection. Sequencing (paired-end 100 bp) was performed on the Illumina HiSeq-2000 platform at the UC Denver Genomics core.", "Immunoglobulin sequence analysis. Contigs for immunoglobulins were translated using the default translation table of MacVector software. MUSCLE alignments were made to identify leader, framework regions, and complementarity-determining regions of the V segments using a black flying fox sequence as a reference (NCBI GenBank accession no. ADD71702.1) (50) . Heavy chains and hinge regions were identified by BLAST against other Chiroptera." ] },{ "paper_id": "c3868e20a756883f97b18c851e9e6df7ad0cb11e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequences were proof read and assembled using SeqMan software v7.1.0 (DNASTAR Inc., WI, U.S.). For assignment of molecular identity and identification of the closest match, sequence alignment was performed using the Basic Local Alignment Search Tool (BLAST) against NCBI GenBank database (http://www.ncbi.nlm.nih.gov).", "Continuous variables were summarized as means \u00b1 standard deviations (SD) or medians. For categorical variables, percentages of patients in each category were calculated. Differences between groups were assessed using Pearson's Chi square test or Fisher's exact test for categorical variables and the one way ANOVA, Independent-Samples T test, Mann-Whitney U test, and Kruskal-Wallis test for continuous variables. All analyses were performed using SPSS software, version 19.0 (IBM Corporation, NY, U.S.). All tests were calculated in a two-tailed manner and a P value of <0.05 was considered statistically significant." ] },{ "paper_id": "c38bc4bdbec2199031430ac3813398806a13a0a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Temoporfin was tested in a viremia mouse model and a lethal mouse model, and it was able to inhibit viremia and protect 83% of the mice; the mice that survived did not present any signs of neurological disorder (Li et al., 2017d) . These compounds inhibit the interaction between NS3 and the NS2B N-terminal fragment. By using an e-pharmacophore-based virtual screening assay, BAS 19192837 was chosen as a potent Zika NS2B-NS3 protein inhibitor [Figure 3(32) ]. However, the experimental data of the IC 50 about this inhibitor was not shown (Table 3 ; Rohini et al., 2019) .", "The structure of ZIKV envelope protein (E protein) is similar to that of other flaviviruses, and it has three characteristic domains: a central \u03b2-barrel-shaped domain I, a Slender fingerlike domain II, and a C-terminal immunoglobulin-like domain III (Dai et al., 2016) . The recognition and binding of ZIKV E proteins to host cell receptors mark the beginning of ZIKV infection; therefore, some inhibitors designed for envelope proteins can effectively inhibit virus infection (Byrd et al., 2013) .", "LW, RL, YG, YL, XD, RX, YZ, and FY drafted the manuscript. TY, SJ, and FY revised and edited the manuscript. " ] },{ "paper_id": "c39dd28fc793a6826ea646a27b79cdf565a42cde", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. regions instead of countries were selected as discrete states for the phylogeographic analysis.", "The obtained chromatogram quality was evaluated by FinchTV (http://www.geospiza.com) and the consensus sequences were reconstructed using CromasPro (CromasPro Version 1.5).", "Interestingly, while the vast majority of variants remained confined in time and space, some viruses have managed to invade broader regions or even to emerge as a worldwide threat [4, 9, 10] .", "SpreaD3 [47] was used to display the spreading process over time and to calculate the BF associated to each migration route. The directional transition rates among countries were considered non-zero (i.e. significant) when the BF was greater than 20. Additional summary statistics were calculated for the different runs using home-made specific R scripts [48] .", "A constant size population model was selected to reduce the computational burden and improve the mixing. The plausibility of this assumption was evaluated by inspecting the results of the non-parametric Skigrid estimated during the previous runs (see point 2))." ] },{ "paper_id": "c3a82cf68990138f6cbbbfe60b5b80d3f6d2e260", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "positive bacteria, eleven were findings of Gram negative bacteria and two were findings of Candida species (Table 4) .", "At present, blood culture is considered the gold standard for aetiological diagnosis in sepsis. Although blood culture is associated with high specificity in species identification, it is limited by a substantial time delay and low sensitivity, especially for slow-growing and fastidious organisms [12, 13] ." ] },{ "paper_id": "c3b1f22e16b5f9f5961e135d3a79eaad57061aa2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver", "The second step is to incorporate an inequalities dimension to this form of visualization. This could be done on standardized measures of inequalities or stratifiers (e.g. across income or wealth or educational attainment, or geographic region) over a period or 10-20 years (see Fig. 1 ).", "A feature of a CAS is that it has emergent properties, i.e. it is almost impossible to predict precisely what it the larger system will evolve to, by using knowledge relating to the interactions among its components and sub-components [35] . Rather than mathematical modeling where equations are the basis of the model, some complexity scientists use simulations using computer-based programmes (e.g. Python) [36] . The building blocks of these simulation models are considered to be as fundamental and irreducible as mathematic equations, and are being hailed as a 'new kind of science' [37] ." ] },{ "paper_id": "c3b24e7070067eba2414138f7532d66ae829f9be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis -Statistical analysis was performed using SPSS 20.0 and Stata 12 statistical softwares and the statistical significance level for all tests was 5%. The existence of associations between two categorical variables was verified using the chi-square test or the Fisher's exact test depending on the sample size. The Student's t test was used to perform comparisons of averages between two groups of data in cases of independent samples. To compare more than two averages, the analysis of variances (ANOVA) was used. Normal distribution of data was previously verified using Kolmogorov-Smirnov test. Nonparametric Mann-Whitney U and Kruskal-Wallis tests were used to compare the averages of samples that did not meet the normality assumption. If differences were found between averages, multiple comparisons were performed to localise such differences. For the pairwise comparisons of groups, adjustments in the descriptive levels were made so that the overall significance was 5%.", "Laboratory tests -A sample of nasopharyngeal wash was obtained from each patient at the enrollment visit. The median time from the onset of symptoms to the collection of nasal washings was three days (1-5 days). Samples were collected and processed using previously published procedures ) and immediately transported to the laboratory for respiratory virus testing.", "This study was conducted at one primary care facility and it is not possible to generalise the results to all Brazilian primary health care services, however, these preliminary data will help us to better understand antibiotic misuse among children with common cold viral infections. We believe that continuing education on appropriate antibiotics and antivirals use as well as accessibility to influenza vaccination, sensitive and specific tests for the rapid diagnosis of respiratory viruses and antiviral medication are essential to improve primary healthcare quality." ] },{ "paper_id": "c3b36cbef6bc5cbbd9ca8a7ce0d8581a3f7788c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2. Relative entropy of superfamily (RelEntropySuper): Entropy was normalized against the distribution of all amino acids in the superfamily alignment:", "Table S1 -The detailed description of 133 features Features were grouped into mutation site features and neighborhood features*. The abbreviated feature name is inside the brackets following the full name. Mutation site, sequence features 1. Entropy of superfamily (EntropySuper): Superfamily alignment was obtained from the SAM-T02 web server [1]. Entropy was calculated as ! \"", "Pr(x b ) represents the overall probability of occurrence of each amino acid in the superfamily alignment." ] },{ "paper_id": "c3bcae4e00c1244d63784b678740cfe2545a0870", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c3bee2a4caca614b34f92c17b643b854dcdab28d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The incubation time varies from 2-14 days after infection. The clinical presentation of this infection resembles SARS-CoV characterized with fever, dry cough, and shortness of breath in most of the cases, whereas non-respiratory symptoms such as headache, muscle ache, dyspnoea, rhinorrhoea, sneezing, sore throat, diarrhea, nausea, and vomiting are also reported in few patients. The affected persons also develop acute respiratory distress syndrome. Cases with critical illness showed respiratory failure, septic shock, and organs failure, which require intensive care support [3, 13, 14] .", "Coronaviruses (CoVs) belongs to the family Coronaviridae, subfamily Coronavirinae, and the order Nidovirales. They are classified into four genera such as Alphacoronavirus and Betacoronavirus, both of which infect mammals, whereas Gammacoronavirus infect avian species, and Deltacoronavirus infect both mammalian and avian species. It is a large enveloped virus with a positive sense, single-stranded RNA genome of about 26 to 33 kb that is distributed broadly among birds, humans, and other mammals such as camels, bats, mice, dogs, and cats [5] . The genome is surrounded by a helical capsid and an envelope; the spike protein forms large protrusions in the envelope in the shape of a crown, which gives the virus a coronal appearance. The word 'corona' in Latin means crown [6, 7] .", "The transmission of 2019-nCoV is often spread from person to person through the respiratory droplets generated during coughs or sneezes from an infected person. Human-to-human transmission is reported in countries such as Germany, Japan, Vietnam, and the United States [12] . The confirmed cases through inter-human transmission have increased the fear and panic accompanying the 2019-nCoV outbreak. It is still unknown whether the virus spreads only through human contact or if there is possible transmission through oral-fecal contact as well." ] },{ "paper_id": "c3bef1c075c76c313a27542f3aa138c48b1c5d3d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c3c131a47ced4db370181524292fac5627fb6389", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vector-borne viruses and zoonotic viruses represent another important and challenging field for viral discovery. The feasibility of detecting arthropod-borne viruses was explored in Aedes aegypti mosquitoes experimentally infected with dengue virus and pooled with noninfected mosquitoes to simulate samples derived from ongoing arbovirus surveillance programs [36] . Total RNA was purified from mosquito pools, reverse-transcribed using random primers and subjected to 454 pyrosequencing, which led to the correct identification of infected mosquito pools [36] .", "Novel DNA sequencing techniques, referred to as \"next-generation\" sequencing (NGS), provide high speed and throughput that can produce an enormous volume of sequences. The most important advantage provided by these platforms is the determination of the sequence data from single DNA fragments of a library that are segregated in chips, avoiding the need for cloning in vectors prior to sequence acquisition.", "Additional sequence analysis showed that it was a new arenavirus related to lymphocytic choriomeningitis viruses. Further serological and immunohistochemical analyses documented that the virus was transmitted through organ transplantation [21] ." ] },{ "paper_id": "c3c25b9a548eebd5505b4f20d75fa99a08ab88dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus dilutions of rVSV were added to confluent Vero monolayers in 12-well plates. The plates were incubated for 1 h at 37 \u2022 C and rocked at 15-min intervals. Virus inoculum was then removed, and the cells were overlaid with 0.5% methylcellulose to allow the plaques to develop. Plaques were fixed with 4% formaldehyde and stained with crystal violet and counted.", "Bicistronic lentiviruses expressing tagRFP and IRF1were generated as described before (8) . A virus expressing fire fly luciferase and tagRFP was generated to be used as a control. Viruses were titrated in HEK293T cells and percent cells infected was calculated by fluorescence microscopy.", "We followed appropriate standard biosecurity and institutional safety procedures." ] },{ "paper_id": "c3d210df12dab3dfa4d9a51c0d0a722a667aa262", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The RT-qPCR assay was optimized for using a total volume of 12.5 \u00b5l. Briefly, for a single 90 well 1.75 \u00b5l RNase-free water, 6.25 \u00b5l 2x RT-PCR buffer, and 1.0 \u00b5l primer-probe-mix for 91 template detection as well as 1.0 \u00b5l primer-probe-mix for detection of the internal extraction 92 control RNA, were pooled as a master mix. Finally, 2.5 \u00b5l RNA template was added and the 93 reaction was run on an CFX96 machine. Genome copy numbers per \u00b5l were determined by ", "inoculated waterfowl and served as sentinels. Animals were monitored daily for clinical signs 25 for a period of up to 21 days. Animals the suffered severe disease like pronounced lethargy or 26 apathy were sacrificed before and considered dead on the subsequent day. The intramuscular 27 pathogenicity and clinical scoring indices (IMPI) were calculated based on the following tissues, three mice of each group were euthanized on 3 dpi, in addition three mice from the 53 groups 10 3 , 10 5 , 10 6 were euthanized on 6 dpi, and organs (i.e., lungs, conchae, heart, and 54 brains) were harvested for histopathological-and virological examinations. The primer and probe set of the generic PB1 assay (summarized in table S4) was used to 87 determine the quantification cycle (Cq) in swabs, nasal washes, and organs using the one-step 88 RT-qPCR Kit qScript\u2122 XLT One-Step RT-qPCR ToughMix\u00ae (Quantabio, Beverly USA)." ] },{ "paper_id": "c3d247dfd60d48b2dcbb5996371c80b01f99dd22", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations: CC = Chest compression, CPR = Cardiopulmonary resuscitation, MERS = Middle East Respiratory Syndrome, NIOSH = National Institute for Occupational Safety and Health.", "Twenty-eight participants (93.3%) preferred the fold-type or valve-type respirators, and only 2 participants (6.7%) preferred the cup-type respirator." ] },{ "paper_id": "c3d79e1b3bb0159b3c333de43cdff8988bcd459f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses were propagated in C6/36 Aedes albopictus cells grown in minimal essential medium (Gibco, Grand Island, NY) at 32\u02daC. U937 cells were transfected with a lentivirus vector expressing DC-SIGN, or passaged in parallel, and sorted by FACS. U937 and U937+DC-SIGN cells were maintained in RPMI-1640 (Gibco) at 37\u02daC. Growth media were supplemented with 5% fetal bovine serum (HyClone, Logan, UT), 0.1 mM nonessential amino acids (Gibco), 100 U/ml penicillin and 100 mg/ml streptomycin (Gibco). U937 and U937+DC-SIGN media was supplemented with 2 mM GlutaMAX (Gibco), 10mM HEPES (Cellgro, Manassas, VA). U937 +DC-SIGN media included 2-mercaptoethanol (Sigma, St Louis, MO). All infection media contained 2% fetal bovine serum. Cells were incubated in the presence of 5% CO2.", "Infectious clones of wild-type strains were constructed using a quadripartite cDNA clone. The DENV4 (Sri Lanka 92) strain was used in the present study. Full-length cDNA was transcribed into genome-length RNAs using T7 polymerase and recombinant viruses isolated in C6/36 cells as previously described. Virus was then passaged twice on C6/36 cells, centrifuged to remove cellular debris, and stored at \u221280\u02daC as a working stock.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Analysis consisted of reverse-phase LC-MS/MS using Waters nano-Acquity M-Class dual pumping UPLC system (Milford, MA) configured for online trapping and interfaced with a Q-Exactive Plus hybrid quadrupole/Orbitrap mass spectrometer (Thermo Scientific, San Jose, CA). Both trapping and analytical columns were packed in-house using 360 \u03bcm o.d. fused silica (Polymicro Technologies Inc., Phoenix, AZ) with 1-cm sol-gel frits for media retention and contained Jupiter C18 media (Phenomenex, Torrence, CA) in 5\u03bcm particle size for the trapping column (150 \u03bcm i.d. x 4 cm long) and 3 \u03bcm particle size for the analytical column " ] },{ "paper_id": "c3de717508f4b790f53e9e998ef61c5f27b00ce7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Frontiers in Chemistry | www.frontiersin.org", "Although not specific for a single E3, the synthetic approach is broadly applicable.", "JM and NT drafted and edited the manuscript." ] },{ "paper_id": "c3e58660ecf2f667fb13b113859dba3a87ef36fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c3e92ff23f71052b519afe647c6d69f0bf1b8e0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(\u2212PMT (interest rate, 120, initial value))/number of pre-weaned calves (3)", "The authors would like to thank Dannon for their continued support of this project." ] },{ "paper_id": "c3f83fef0e35a95a6ff12ffacf58969db6172761", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Primary Ciliary Dyskinesia (PCD, OMIM #242650) is an inherited disease mainly characterized by dysfunction of airways' motile cilia. The prevalence is approximately 1 in 12,000-20,000 [1] [2] [3] . About 50% of patients affected by PCD have a situs inversus which results from monocilia dysfunction at the embryonic node [4] . This association is referred to as Kartagener's syndrome (OMIM #244400) [5] . PCD causes chronic sinus and bronchial respiratory infections that begin early in life, leading to nasal polyps and bronchiectasis. Males are frequently sterile due to dysfunctional spermatozoa flagella [6] . Other symptoms can also be associated with PCD like hydrocephalus, anosmia, retinitis pigmentosa and congenital heart diseases [7] [8] [9] [10] .", "DNAI1 encodes an axonemal dynein intermediate chain, a component of the outer dynein arm (ODA). Dyneins are molecular motors which produce energy for microtubules doublets sliding in the axoneme. To date, no etiologic treatment of PCD is available and on the long range, PCD leads to respiratory insufficiency and lung transplant.", "Poly(A) + mRNA was isolated by the Dynabeads Oligo(dT) 25 purification kit, according to the manufacturer's protocol (Dynal Biotech, Norway)." ] },{ "paper_id": "c405097039f3cfefa4c6cf436925d3e3c8c3e013", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following cascade of predictions arise from the perturbation hypothesis and from previous findings:", "Badgers were captured at active setts using wire mesh cage traps, with a 2.5 cm mesh size, placed at or near to setts and baited using peanuts. Traps were set over two consecutive nights, following at least one week of pre-baiting. Trapping was carried out between September 2002 and August 2003, with study areas trapped during winter (January), spring/early summer (May/ June), summer (August) and autumn (September, October and November).", "Badger day-time sett locations were also established using radiotelemetery. Only badger presence could be determined, as failure to locate an animal at a particular sett did not necessarily demonstrate absence. Failure to locate a badger at either the sett at which it was captured or the sett to which it was last radio-tracked initiated a survey of all surrounding setts until either the badger had been located or no more setts remained to survey.", "Epidemiological patterns of directly transmitted infectious diseases are the product of contacts between individuals that permit disease transmission [8] , and heterogeneous mixing of individuals is of particular importance [9] . Also, management interventions to control infectious disease in wildlife populations may themselves influence individual behaviours, such as dispersal, which may in turn result in counter-productive outcomes such as further disease spread [5, 7, 10] . Predicting such outcomes in wild animal populations is enormously challenging, not least because the behavioural processes underlying disease transmission are notoriously difficult to study [11] ." ] },{ "paper_id": "c40606c62e96d3ea8313b67bf60e8148eeb45f05", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c4127920bfadc5eaa2ff7d2180f8e1de7e3a673a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Associations were calculated treating each hive sample at each time-point as a distinct event. P-values (Chi-square values) and odds ratios (OR) listed were calculated by the OpenEpi statistical package v2.3 (http://www.openepi.com/OE2.3/Menu/OpenE-piMenu.htm). Only seven microbes with incidences in the study set of at least 10% (20 incidences in 197 samples) were examined for association, resulting in 28 discrete association tests and the corresponding Bonferroni multiple testing correction. Microbes occurring infrequently were not used in association tests and so did not contribute to multiple testing correction.", "Design principles used for APM oligonucleotides (70 nt) were based on previous pan-viral microarrays using ArrayOligoSelector (AOS) [54] . Briefly, array oligonucleotides were selected for uniqueness against an insect nucleic acid background, for ,50% GC content to maintain high complexity, and for cross-reactivity of highly-conserved nucleic acid features with evolutionarily related targets (,250 kcal/mol predicted binding energy). Arthropod pathogen oligonucleotides (GEO GPL11490) were synthesized by Invitrogen, suspended at 40 pmol/mL in 36 SSC and 0.4 pmol/mL control oligo and printed on poly-L-lysine slides (Thermo) with silicon pins as previously described [100] . Each oligonucleotide and its reverse complement were printed twice for redundancy. Arrays were allowed to air-dry and stored and room temperature. Prior to use, oligonucelotides were cross-linked to slides via UV exposure (600 mJ), washed with 36SSC/0.2% SDS and blocked using a methylpyrrolidone solution (335 mL 1methyl-2-pyrrolidinone, 5.5 grams succinic anhydride, 15 mL 1 M sodium borate).", "Six pools of sequence data were downloaded from GenBank: Nosema ceranae (draft genome), Spiroplasma (S. citri draft genome and all sequences longer that 500 nt), DNA viruses of arthropods (all complete genomes), all small RNA viruses of arthropods except dicistroviridae and iflavirus (complete genomes), all members of dicistroviridae and iflavirus except those infecting honey-bees (complete genomes), and all known honey bee RNA viruses (complete genomes). Each pool was converted into a Blast library and queried against the entire Solexa dataset by BlastN and tBlastx. Hits with an e-value greater than 1610 23 were extracted along with their paired end, regardless of similarity. Each pool was assembled using the Geneious sequence analysis package [102] . Contigs greater than 250 nt were queried again against the dataset by tBlastx with an e-value threshold of 1610 25 . Any positive hits were then queried against the NR database with the same parameters to eliminate spurious hits." ] },{ "paper_id": "c417b7235950a6e64054e00d24f75e2e5c748349", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PRRSV genome is approximately 15kb in length with 12 overlapping open reading frames (ORFs) at least [11] . ORF1a and ORF1b occupied more than 70% of genome at the 5' end, encode the replication-related pp1a and pp1ab, together with two ribosomal frame-shift (RFS) products pp1a-nsp2N, pp1a-nsp2TF, which are autoproteolytically cleaved into at least 16 nonstructural proteins (nsps) associated with virus replication and transcription [5, 12] . Among them, three important virus proteases, nsp1 (papain-like cysteine protease), nsp2 (chymotrypsin-like cysteine protease) and nsp4 (3C-like serine protease) in pp1a are associated with PRRSV nsp cleavage. And four crucial enzymes for PRRSV RNA synthesis, including nsp9 (RNA-dependent RNA polymerase, RdRp), nsp10 (RNA helicase), nsp11 (endoribonuclease) and nsp12 (functions unclear) are encoded by ORF1b [13] . The viral structural proteins encoded by ORFs 2 to 7, which involve in receptor binding, virus entry and neutralizing antibody elicitation etc., are individually expressed by a set of subgenomic RNAs (sgRNA) [14] [15] [16] ." ] },{ "paper_id": "c41cd165529d51d5418e2628ceda43970f8ca399", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DRM: detergent resistant membrane; GM1: monosialotetrahexosylganglioside; GPI: glycosylphosphatidylinositol; GHOST: human osteosarcoma cells expressing CD4 and green fluorescent protein; CTxB: cholera toxin-b subunit.", "HIV-1 particle assembly mediated by viral Gag protein occurs predominantly at plasma membrane. While colocalization of HIV-1 envelope with lipid rich microenvironment have been shown in T cells, the significance of viral proteins modulating envelope association in such microdomains in plasma membrane enriched in glycosylphosphatidylinositol-anchored proteins in primary CD4 + T cells that are natural targets of HIV-1 is poorly understood. Here we show that in primary CD4 + T cells that are natural targets of HIV-1 in vivo, Gag modulates HIV-1 envelope association with GM1 ganglioside and CD59 rich cellular compartments as well as with detergent resistant membranes. Our data strengthen evidence that Gag-Env interaction is important in envelope association with lipid rafts containing GPI-anchored proteins for efficient assembly onto mature virions resulting in productive infection of primary CD4 + T cells.", "beads (Pierce Inc). Lysates were further washed with cold PBS and were resolved in 12% SDS-PAGE under denaturing conditions. Equal amounts of immunoprecipitated materials were subjected to 12% SDS-PAGE under denaturing conditions [32] , transferred onto PVDF membranes and subsequently Western blot assay done with anti-human CD59 antibody (at 1: 1000 dilution) to assess the ability of Env association with CD59enriched compartment. As shown in Figure 1A , due to L30E mutation in Gag, Env failed to recruit CD59 in contrast to pNL4.3 wild type. Our data indicate that the mutation in Gag MA region (L30E) restricts the interaction between Gag and Env resulting in down modulation of envelope trafficking to GPI-anchored membranes in primary CD4 + T cells such as CD59. Moreover, in order to assess the effect of L30E mutation in p17 gag on HIV-1 envelope incorporation on virions in primary CD4 + T cells, cell-free virus pellets were obtained by centrifugation as described previously [13] . Equal amounts of virus particles (p24) were resolved in SDS-PAGE under denaturing conditions followed by Western blotting using monoclonal antibodies to p24 (183-H12-5C) and gp41 (1:1 of 2F5 and 4E10). As shown in Figure 1B , L30E substitution in p17 Gag was found to drastically affect envelope incorporation onto virus particles in CD4 + T cells as expected." ] },{ "paper_id": "c4243eccc82c5b1f6a7cfe910e2167556feab414", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c42f08c1803b6a13e7ff20041f34d336e4b0c7e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. Student's t-test P value > 0.5 (in all experiments).", "Reverse transcription was performed using Superscript II reverse transcriptase (Invitrogen, Dorset, UK) according to the manufacturers instructions [31] . Initially 200 \u03bcg (10 \u03bcl) total RNA was pre-incubated with 0.5 \u03bcg (1 \u03bcl) oligo-dT [12] [13] [14] [15] [16] [17] [18] (Invitrogen, Paisley, UK) and 10 mM (1 \u03bcl) dNTP mix (Invitrogen, Paisley, UK) at 65\u00b0 for 5 minutes. After", "For all of the tissue samples total RNA was extracted using a phenol/guanidine hydrochloride reagent (Trizol, Invitrogen Ltd, UK) with a chloroform extraction and ethanol precipitation, as previously described [30] . An on column DNA digestion step was included (RNase-Free DNase Set, Qiagen Ltd, Crawley, UK). Final elution of the total RNA was performed using 30 \u03bcl of RNase free water, and repeated to maximize the amount of RNA eluted. Total RNA samples were stored at -80\u00b0C until use. The concentration of total RNA representing each sample was quantified by using a NanoDrop \u00ae ND -1000 UV/Visible Spectrophotometer (NanoDrop Technologies Ltd, Utah, USA)." ] },{ "paper_id": "c42f9e96fcbb25a8f456fb17af3d591c1300ae64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell lysates were collected 16 h post mock-or Poly(I:C)-LMW/ LyoVec (InvivoGen, San Diego, CA) transfection (4 mg/mL) per manufacturers' instructions.", "Romero (GenBank accession nos. AY619640 and AY619641) [44] and Candid#1 (GenBank accession no. U70801) strains of JUNV were obtained from Dr. Thomas G. Ksiazek (Centers for Disease Control and Prevention, Atlanta, GA) and Dr. Robert Tesh (The World Reference Center for Emerging Viruses and Arboviruses (WRCEVA), University of Texas Medical Branch, Galveston, TX), respectively. Virus stocks were prepared using Vero cells. Cell debris in supernatants were filtered out through 0.45 mm HV Durapore Membrane Stericup sterile vacuum filtration system (Millipore Corporation, Billerica, MA). Cleared supernatants were concentrated through 30 min centrifugation at 32206g using Amicon Ultra-15 Centrifugal Filter Unit PLHK Ultracel-PL Membrane, 100 kDa (Millipore Corporation, Billerica, MA). All work with JUNV Romero was performed at the University of Texas Medical Branch BSL-4 facilities (Robert E. Shope Laboratory or the Galveston National Laboratory) in accordance with institutional health and safety guidelines and federal regulations [45] .", "Data were analyzed by two-way or three-way ANOVA using SigmaPlot 12.0 (Systat Software, Inc., San Jose, CA)." ] },{ "paper_id": "c444840c3b5380002dea23e1e8598f545a3470a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The severe acute respiratory syndrome (SARS) epidemic in 2003 which resulted in 775 human deaths was caused by SARS coronavirus (CoV) [1] [2] . The ongoing Middle East respiratory syndrome (MERS) infections in recent years which have claimed hundreds of human lives were caused by MERS CoV [3] . The discovery of these two previously unknown CoVs and other CoVs related to them in animals has greatly broadened our knowledge about the distribution, diversity, and significance of CoVs in both humans and animals [3] [4] [5] [6] [7] .", "Potential sequence recombination was detected using the software Recombination Detection Program (RDP) v3.8, by the methods of RDP, Geneconv, MaxChi, Bootscan, and Chimaera [23] [24] [25] [26] [27] . Only the potential recombination events identified by all these five methods with greater than 99% certainty (99% bootstrap support in the case of Bootscan) were accepted. ", "Supporting Information S1 Table. The ", "In conclusion, this study shed novel insight into the genetic diversity, distribution, evolution, and taxonomy of the coronaviruses in poultry." ] },{ "paper_id": "c44a9d064faca56bd284971828e4db13e656365c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "AIDS deaths averted = (AIDS deaths during 100 years of epidemic without treatment) -(AIDS deaths during a 50 year epidemic followed by 50 years of treatment).", "Text S1 Full description of the multi-scale model used to predict the effects of a TIP intervention on HIV-1 infection dynamics among a population of host individuals, within host individuals, and within host cells. This report contains detailed descriptions of each model, tables of parameters and state variables, supporting", "All numerical simulations were performed in Mathematica 7.0." ] },{ "paper_id": "c44ca052440fbba971baea20540e107fc480e836", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that there are no conflicts of interest regarding the publication of this paper.", "The dataset was analyzed through the GEO database's integrated statistics utility, GEO2R, in addition to PRISM6 (v.6), GeneSpring (v.13.1), and Microsoft Excel. More specifically, GEO2R calculated values in order to identify significant differences in gene expression while GeneSpring extracted and normalized the raw expression data using provided algorithms to allow for further statistical calculations using PRISM (Graphpad Software), which was also used to generate graphs and other figures from tables of raw data created in Excel. One value for ANPEP in the tumor group was excluded based upon the criterion of being more than 5 standard deviations from the mean.", "Since the number of samples in this specific data set differed between the tumor ( = 57) and the normal tissue ( = 49) groups, comparisons were made using an unpaired Student's -test with Welch's correction for heterogeneity of variance. Data is presented with and without Sidak's correction for multiple comparisons: = 0.05, = 1 \u2212 (1 \u2212 0.05) (1/15) (15 genes were studied) to provide a relative estimate of significance ( Table 2) " ] },{ "paper_id": "c45763bd83a192ce8ead3a628b11dd71b6e9c08a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c457f06e9474f83c6451e8740c24aebe35428408", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A measure of precision should quantify the relative magnitude of deviations from an expected value. The", "Synthesis, a Center funded by the National Science Foundation (Grant #DEB-0072909), the University of California, and the Santa Barbara campus. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." ] },{ "paper_id": "c458f17d49c0b39b4ac6fece7f994fd9f6ede076", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors' declare that they have no competing interests. " ] },{ "paper_id": "c459e1a77d9256b02b2b9a5460fcfc8b420b753a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CS and CB contributed to the writing, editing of the manuscript and approved the final version for publication.", "Altogether, these data shed light on the individual in vivo contribution of glial cells in overall IFN\u03b1/\u03b2 mediated early protection against MHV CNS infection. More studies using conditional ablation of IFNAR and selected ISGs in various encephalitic virus models will be beneficial in unraveling the importance of autocrine and paracrine protective IFN\u03b1/\u03b2 effects on subsequent adaptive responses and potential establishment of cell type specific persistence.", "This work was supported by the National Institutes of Health grant NS091183.", "The central nervous system (CNS) is susceptible to various neurotropic viral infections associated with acute inflammation. Depending on the distinct anatomical regions infected, inflammation is referred to as meningitis (meninges), encephalitis (brain), myelitis (spinal cord), or meningoencephalitis and encephalomyelitis if multiple sites are afflicted (1) . Viral meningitis is overall more clinically benign, whereas encephalitis is associated with clinical evidence of neurological dysfunctions, which can range from behavioral changes to seizures and paralysis. Many encephalitic viruses such as insect borne viruses, enteroviruses, and nonendogenous retroviruses can rapidly invade the CNS early following peripheral infection. However, encephalitis caused by members of the herpes viruses, e.g., Herpes Simplex Virus (HSV)-2, cytomegalovirus (CMV), or the polyomavirus John Cunningham virus (JC virus) are more commonly caused by immune suppression allowing re-activation of otherwise controlled chronic or latent peripheral infections and invasion of, or reactivation within the brain, resulting in severe disability and death (2) . For example, premature death of multiple sclerosis patients treated with Natalizumab due to JC-virus mediated progressive multifocal leukoencephalopathy emphasizes the importance of CNS immune surveillance to prevent viral recrudescence (3, 4) .", "The imprinting of the innate immune response on subsequent adaptive immunity and its effects on bystander cells such as microglia and infiltrating myeloid cells make it difficult to tease apart critical checkpoints determining disease progression or resolution. However, the availability of numerous conditional knockout mice blocking cytokine responses in distinct cell types and in a temporal fashion promise to shed more light on pathways ameliorating pathology while preserving viral control. Confirmation of similar pathways in multiple viral encephalomyelitis models will ultimately enhance targeted treatment options at early stages of disease manifestation. Accumulating literature in both rodent models and human encephalitis implicate that manipulation of IL-10 and IFN\u03b3 may have broad implications to treat encephalitis more broadly." ] },{ "paper_id": "c45cc3b97767ed8a1da4014f453533d6e840a3b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Brains from mice perfused with cold phosphate-buffered saline (PBS) were homogenized in Dulbecco's PBS (DPBS) (pH 7.4) using Tenbroeck tissue homogenizers as described previously (84) . Homogenates were centrifuged at 450 \u03eb g for 10 min at 4\u00b0C. Cells were resuspended in RPMI containing 25 mM HEPES (pH 7.2), adjusted to 30% Percoll (Pharmacia, Uppsala, Sweden), underlaid with 1 ml 70% Percoll, and centrifuged at 850 \u03eb g for 30 min at 4\u00b0C. Cells were collected from the 30%/70% interface, washed with RPMI, counted, and suspended in fluorescence-activated cell sorting (FACS) buffer (0.1% bovine serum albumin in DPBS). Fc\u2425 receptors were blocked with 1% mouse serum and rat anti-mouse CD16/32 MAb (clone 2.4G2: BD Biosciences, San Diego, CA) for 20 min on ice prior to staining with fluorescein isothiocyanate (FITC)-, phycoerythrin (PE)-, peridinin chlorophyll protein (PerCP)-, or allophycocyanin (APC)-conjugated MAbs specific for CD45 (clone 30-F11), CD8 (clone 53-6.7), CD4 (clone GK1.5), Ly6G (clone 1A8), CD11b (clone M1/70), and MHC class II (clone M5/114.15.2) (all from BD Bioscience, Mountain View, CA) and F4/80 (Serotec, Raleigh, NC) in FACS buffer. Samples were analyzed on a BD Accuri C6 Plus instrument (BD Biosciences). Forward-and side-scatter signals obtained in linear mode were used to establish a gate containing live cells while excluding dead cells and tissue debris. Data were analyzed using FlowJo 9 software (Tress Star Inc., Ashland, OR).", "Overall, our data demonstrate a vital protective role of astrocyte-mediated IFN-\u2423/\u2424 signaling in host protection from neurotropic coronavirus-induced encephalomyelitis. Further, the link between sustained elevated IFN-\u2423/\u2424 and impaired responsiveness to IFN-\u2425 supports the novel concept that temporally limited early IFN-\u2423/\u2424 responses are critical for effective antiviral IFN-\u2425 function.", "Microglia and astrocyte isolation for gene expression analysis. Brains from 5 or 6 naive or MHV A59-infected GFAP-GFP mice at days 3, 5, and 7 p.i. were homogenized using a neural tissue dissociation kit (Papain, Miltenyi Auburn, CA) following the manufacturer's protocol. Brain homogenates were prepared for 30/70% Percoll gradients to isolate cells as described above. CNS cells were blocked with mouse serum and anti-CD16/32 MAb as described above prior to staining with CD45 and CD11b in FACS buffer. Microglia and astrocytes were sorted based on their CD45 int CD11b \u03e9 and CD45 neg GFP \u03e9 phenotypes, respectively, using a FACS Aria III (BD Biosciences) and FACS Diva software (BD Biosciences). Sorted cells were resuspended in TRIzol (Invitrogen, Carlsbad, CA) and stored at \u03ea80\u00b0C.", "V iral infections of the central nervous system (CNS) are rare but can lead to rapid mortality or long-term neurological disabilities even if acute encephalitis is resolved (1) . Early essential host defense mechanisms involve induction of alpha/beta interferon (IFN-\u2423/\u2424) and signaling through the IFN-\u2423/\u2424 receptor (IFNAR) to upregulate IFN-stimulated genes (ISGs). ISG expression is associated with numerous biological activities, including antiviral and immunomodulatory pathways, e.g., interference with translation, apoptosis, and enhanced major histocompatibility complex (MHC) class I antigen (Ag) presentation (2) (3) (4) . While the IFN-\u2423/\u2424 response is critical in stemming CNS viral replication and spread, it is rapidly downregulated and insufficient to eliminate virus in the absence of subsequent adaptive immune responses (5) (6) (7) . Moreover, the efficiency of the innate response in limiting viral spread sets the stage for the effectiveness of subsequent adaptive immunity (2) (3) (4) 8) ." ] },{ "paper_id": "c46224620e6c2f039588f57d5133dedd75941da5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We used 100 ng enriched mRNA with Illumina mRNA-Seq sample preparation kit (Illumina, San Diego, CA) for library construction following the manufacturer's protocols. Briefly, mRNA was fragmented chemically by divalent zinc cations and randomly primed for cDNA synthesis. After ligating paired-end sequence adaptors to cDNA, we isolated fragments of approximately 200 bp by gel electrophoresis and amplified. We ", "We propagated H. somni 2336 on three TSA-blood plates (with 5% sheep red blood cells) for 16 hr or until a fresh lawn of cells was visible. IBC approval was not required for acquiring the plates as they were purchased through a commercial vendor: Fisher Scientific (Pittsburgh, PA), and manufactured by Becton Dickinson Diagnostic Systems, (Franklin Lakes, NJ). We washed the plates with brain heart infusion (BHI) broth, adjusted the culture to an OD620 nm = 0.8, and supplemented with RNAprotect reagent. The cells were harvested by centrifugation and stored at 280uC. We extracted total RNA using the RNeasy mini kit (Qiagen, Valencia, CA) following the manufacturer's protocol. Total RNA was treated with RNase-free DNAse (Invitrogen, Carlsbad, CA). Using Bioanalyzer 2100 (Agilent Technologies, Santa Clara, CA), we determined the RNA integrity number (RIN) of total RNA to be greater than 8. MICROBExpress TM Kit (Ambion, TX, USA), which specifically removes rRNAs, was used for mRNA enrichment. Small RNAs (i.e., tRNA and 5S rRNA) are not removed with this enrichment step (confirmed by Bioanalyzer).", "Gene expression: expressed reads with coverage above background were mapped onto the annotated genes of H. somni 2336. Genes that had a significantly higher proportion of their length (.60%) covered by expressed reads were considered to be expressed." ] },{ "paper_id": "c46b51e5657b05d7af97e9006d2033353ccd9512", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rotavirus C (RVC) has been detected increasingly in humans and swine in different countries, including the US. It is associated with significant economic losses due to diarrheal disease in nursing piglets. In this study we aimed:", "RVs are triple-layered, icosahedral, non-enveloped viruses that belong to the family Reoviridae. Their genome consists of 11 segments of double-stranded RNA (dsRNA) encoding six structural proteins namely: VP1, VP2, VP3, VP4, VP6 and VP7 and six nonstructural proteins (NSP): NSP1, NSP2, NSP3, NSP4 and NSP5 or NSP6 depending on the translated open reading frame [6, 7] . Within the RV genus, ten genogroups/serogroups (A-J) have been identified to date based on the molecular and antigenic characteristics of VP6, the inner capsid protein. RVAs, RVBs and RVCs infect humans and a wide range of mammals, RVDs infect chickens and turkeys, RVEs infect pigs only, RVFs and RVGs infect chickens, and RVHs infect both humans and pigs [8, 9] . RVIs and RVJs were recently detected in dogs in Hungary and in bats in Serbia, respectively [10, 11] .", "Similar to RVAs, a complete genome classification system based on nucleotide sequences was established for RVCs [21] . The introduced system allocates a specific genotype to each of the 11 RV genome segments according to established 85% nucleotide cut-off where VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6 genes of RV strains are classified as Gx-Px-Ix-Rx-Cx-Mx-Ax-Nx-Tx-Ex-Hx where x is an integer starting from 1 onward." ] },{ "paper_id": "c47b1bf314263894ae9a5589303b7af810741267", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed in STATA version 12.0 and R version 1.40. Continuous data were analyzed using the Mann-Whitney U-test and categorical variables using Fisher exact test or chi-square test as appropriate. In order to address temporal variations and age coinfections were studied for every half-month and stratification for age (,1 year, 1 to 6 years and .6 years of age) was performed." ] },{ "paper_id": "c481fdcf995099e14997dabd9fe3b47ce8784020", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c482f885d7100665959d0e8a2e97d940cc4c6961", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.", "BSQ receives salary support from the Michael Smith Foundation for Health Research and from Cystic Fibrosis Canada.", "The authors declare that they have no competing interests." ] },{ "paper_id": "c48bb15af3fe47ce755d022245d64cc0df2537e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Among these positive clones, the sequences of eight clones produced no BLAST results, and 12 different BLAST results were obtained from the remaining clones. ", "Mitochondrial antiviral-signaling protein, as a central adaptor of RLRs, is negatively regulated by UBXN1." ] },{ "paper_id": "c4943b5cc55140da6a5bbf9e5ecb5d6729f0728d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DS conceived the study. SQ, DG, and JZ analyzed the data. DS and SQ wrote the manuscript. ", "CPV belongs to the genus Parvovirus, family Parvoviridae, and causes a highly contagious and fatal disease in dogs (1) . The original viral strain, designated as CPV-2 to distinguish it from CPV-1 which is also known as canine minute virus and was believed to be non-pathogenic until 1992 (13) . CPV-2 is a non-enveloped DNA virus with a linear single-stranded DNA genome (5.2 kb), containing two major open reading frames (ORFs). One ORF encodes the two non-structural proteins (NS1 and NS2), and the other encodes the two capsid proteins (VP1 and VP2) (14) . The VP2 protein of CPV-2 is known to affect antigenic properties, playing important roles in controlling viral host ranges and tissue tropisms (15) (16) (17) .", "Nevertheless, CPV-2a, 2b, and 2c are circulating in almost equal proportions in Tunisia (101) . CPV-2a, CPV-2b, and CPV-2c are currently spreading globally, and their relative frequencies may be related to the geographic region and time of the sample collection and different commercial flows of dogs imported from foreign countries (3, 77) " ] },{ "paper_id": "c49543f507a07bcef2a9568fa458fac552d51fcd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chromatography purified fractions containing M protein were analyzed using dynamic light scattering (DLS). Hydrodynamic particle size measurements were done in ZEN2112 microcuvettes at 25\u02daC using Zeta Sizer Nano S DLS instrument (Malvern Instruments, United Kingdom). Light scattering was measured 15 times at 10-second intervals for each sample. The data was analyzed using Zetasizer ver.7.11 software (Malvern Instruments, United Kingdom).", "Materials and methods", "The Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University is a beneficiary of the structural funds from the European Union (grant No: POIG.02.01.00-12-064/08-\"Molecular biotechnology for health\")." ] },{ "paper_id": "c498ea64810a8da9cb26c48e1f5e96973537338d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All analyses were performed using R (www.r-project.org) and SAS software." ] },{ "paper_id": "c49e3b42331dd3c65340f486f5b6067df16cbbd4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All patient samples were collected according to protocols approved by the University of California San Francisco Committee on Human Research.", "The E-Predict software is available for download by any interested party [52] .", "-12 -10 -8 -6 -4 -2 0 2 0.0 0.1 0.2 0.3 ln(s) Density | | | | | | | | | | | | | | | 0" ] },{ "paper_id": "c4a42dab0e3e471c7a54410c8ddfee13741df4aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c4a6612ba3d6a23317a85c42cedd5e6d2f317a9c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The in vivo immunogen expression feature of DNA vaccines offers a number of benefits.", "More studies are needed to further optimize the DNA immunization schedule to elicit high-quality mAbs. It is important to determine whether different DNA delivery approaches are optimal with certain delivery schedules and whether the same delivery schedule can be applied to different animal species.", "The recent successful use of protective monoclonal antibodies as a life-saving treatment in Ebola virus-infected humans 1 highlights the need for the development of new technologies that are fast and efficient in eliciting functional monoclonal antibodies (mAbs) to control emerging infectious diseases." ] },{ "paper_id": "c4a909da9b4ab2d9a0a9f4305e1cdc4bc66f9d03", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All sequences obtained in this study have been deposited in GenBank under accession numbers MN175552-MN175554 for complete genomes and MN175555-MN175568 for partial sequences.", "Among vertebrates, the class Aves (birds) is one of the most ubiquitous lineages on Earth and, with over 10,000 living species, is also one of the most diverse [1] . Birds occupy various habitats, from natural to urban environments, and serve diverse ecological roles in various ecosystems [2] . They have a global distribution and, thanks to their ability to fly long distances, are capable of migrating across biological and geographical borders and over broad spatial scales [1, 3] . Because of these characteristics, birds play an important role in the dispersal of microbes and, therefore, influence microbial dynamics, impacting the ecology and evolution of various viruses and bacteria [3] [4] [5] .", "We describe here the characterization and molecular epidemiology of three novel viruses belonging to three different viral families that were identified in four species of wild birds. Although follow-up studies are required to determine additional aspects of their ecology and distribution, the discovery of these viruses, divergent from currently known avian strains and representing novel taxa, increases our knowledge about avian virus diversity and host ranges. Each one of the viruses identified in this study was observed in different related bird species, indicating limited host-specificity. Our results highlight one more time the limited knowledge about avian and, more generally, animal virology and show how a multitude of yet unknown viruses exist, even in species that are frequently subjects of metagenomic investigations." ] },{ "paper_id": "c4aa9bb066a64db00b8bdd44d5c021c5603a09a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary materials are available at Clinical Infectious Diseases online (http://cid.oxfordjournals.org). Supplementary materials consist of data provided by the author that are published to benefit the reader. The posted materials are not copyedited. The contents of all supplementary data are the sole responsibility of the authors. Questions or messages regarding errors should be addressed to the author." ] },{ "paper_id": "c4b02808f112f00b4271fcd1eabdba3b7edcc1a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. Pandemic emergency preparedness 2. Airborne isolation 3. Staffing 4. Vaccines administration to healthcare workers (HCW's) 5. Stockpile of supplies.", "There should be national agreement on the use of a standardised internationally recognised tool to be used in all acute hospitals for this purpose.", "Overall these findings are evidence for the need for greater prioritisation of pandemic preparedness stockpiling." ] },{ "paper_id": "c4b7ab00946639c33eebee571e31d74e2543de95", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ND, WH designed the experiments, supervised the experiments, and analyzed the data. ND, KZ performed experiments and interpreted the data. YL, XL, ZL, JS, HL contributed reagents, materials, and analysis tools. ND, FG, WH drafted the article or revised it critically for important intellectual content. All authors agree with final approval of the version for submission.", "To mark the acidic late endosomal and lysosomal structures, LysoTracker Red (50 nM) was added to the treated, mock-or infected cells for 1 h. Following treatment or infection, cells were settled in 4% paraformaldehyde for 15 min and washed with PBS for three times, and then permeabilized using 0.1% Triton X-100 for 15 min at room temperature. Blocking was performed with 5% nonfat milk powder in PBS for 1 h prior to incubation with primary antibodies followed by incubation with the suitable secondary antibody. Images were visualized by confocal fluorescence microscopy.", "In subsequent experiments, the optimum concentration of the corresponding drug was used and the cell viability were determined by a WST-8 cell proliferation assay (Beyotime, China) according to the manufacturer's guidelines. The concentrations tested for rapamycin (Selleckchem, USA) were 100, 500, and 200 \u00b5M; for chloroquine (CQ) (Sigma, St. Louis, MO, USA) were 16, 32, 64, and 128 \u00b5M; and for 3-methyladenine (3-MA) (Selleckchem, USA) were 1, 2, 3, and 5 mM. According to existing experimental procedures, the medium was removed with 100 \u00b5l of fresh medium added with 10 \u00b5l of WST-8, the sample was further incubated at 37 \u2022 C for 1 h (Shao et al., 2014) . Cell viability was evaluated by measuring the absorbance at 450 nm against the background control." ] },{ "paper_id": "c4bddec0b339a9f5ea397a7390327d12c72159a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Table S1 Cost projections (in millions of \u00a3) for each two-stage intervention strategy for each kernel model.", "Step A: specify management objective. The primary objective of outbreak management in 2001 was to minimize the number of farms or livestock lost, either through the slaughter of animals on infected premises, or control culling of livestock on farms without reported infection in an effort to control further spread of disease [4, 13, 14] . For the purpose of this work, the objective is to minimize the cost of livestock lost through disease mortality and culling:", "Step B: identify possible management actions. We consider four nested management actions ( Figure 1A ): (1) culling of livestock on infected premises (farms with confirmed cases of disease) only (IP); (2) pre-emptive culling of dangerous contacts (defined either as premises in which animals had been in direct contact with infected livestock or as premises that had been exposed to infection in any other way) as well as infected premises culling (DC); (3) culling of livestock on infected premises, dangerous contacts, and contiguous premises (farms sharing a border with an IP) (CP); (4) ring culling in a 3 km radius of infected premises in addition to infected premises and dangerous contact culling (RC)." ] },{ "paper_id": "c4db01f9d02579bbc25384c6f72a5ce25a4dba0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In general, ISG15 and MxA are expressed only after IFN stimulation, whereas OAS-RNaseL and PKR are expressed constitutively at low levels but increased by type I IFN stimulation. Constitutive expressions of OAS and PKR suggest that these proteins act not only as effectors but also as dsRNAspecific PRRs that can trigger antiviral responses.", "Nsp2 also down-regulates type I IFN induction (Figure 2 ). Nsp2 is a membrane-anchored protein that contains a CP activity and a deconjugation activity associated with ovarian tumor (OTU) domaincontaining protease activity. While the deconjugation activity is suggested to function in ISGs and NF-\u03baB signaling, the CP activity inhibits IRF3 phosphorylation and nuclear translocation [81] . The mechanism for the CP mediated-IRF3 deactivation is unknown.", "OAS1: 2', 5'-oligoadenylate synthetase 1 (OAS1) is constitutively expressed in cells at low levels and upregulated by type I IFNs. OAS1 resides in the cytoplasm as an inactive monomer. Once activated by viral RNA, this enzyme oligomerizes and forms a tetramer which synthesizes 2\u2032-5\u2032 linked oligoadenylates (2-5A). The binding of 2-5A to RNase L triggers the dimerization of RNase L enabling it to cleave cellular and viral RNAs. The cleaved RNAs then activate cytoplasmic PRRs such as RIG-I and MDA5 [53, 61] .", "More than 300 ISGs have been identified so far but a relatively few of these ISGs have been implicated in instigating the antiviral state including catalysis of cytoskeletal remodeling for apoptosis, regulation of post-transcriptional events, and post-translational modifications. Many other ISGs function as pattern-recognition receptors (PRRs) to sense viral molecules or encode transcription factors that participate in the amplification loop increasing IFN production and preventing dissemination of virus [53] . Among all ISGs, ISG15, GTPase, myxovirus resistance A (MxA), ribonuclease L (RNaseL), and protein kinase K (PKR) are the most extensively studied, and function as antiviral effectors." ] },{ "paper_id": "c4e5c3ffe90100931729abab4aa1155d8c145816", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Enterovirus 71 (EV71) is a positive single-stranded RNA virus belonging to the Picornavirudae family. EV71 together with Coxsackievirus 16 (CVA16), CVA5, and CVA10, are known to be major causative agents that cause mild rash symptoms called hand-foot-and-mouth disease (HFMD) in infants and children [1] . Since 1997 a significant increase of EV71 epidemics has been observed throughout the Asian-Pacific region [2] . In the 1998 EV71 outbreak in Taiwan, over 100 000 young children were infected, and approximately 400 children were hospitalized with severe pulmonary and neurogenic complications that resulted in 78 deaths [3, 4] .", "The clinically isolated strains of EV71, genotype B4 of E59 (GenBank: GQ150746.1), was obtained from the Taiwan Centers for Diseases Control (CDC). Genotype C2 of 5746-TW98 (5746; GenBank: AF304457.1), B4 of N0781-TW-01, B5 of N2838-TW-03 (GenBank: DQ008993.1) and one strain of CVA16, 5079 (GenBank: AF177911.1) were provided by Professor Jen-Ren Wang, Department of Medical Technology, National Chen Kung University, Tainan, Taiwan. Viruses were propagated in Vero cells and purified as previously described [41, 42] .", "Immunhistochemistry (IHC) was performed on paraffin-embedded tissue sections as previously described [11] . EV71 viral particles were detected using a murine anti-EV71 monoclonal antibody (Chemicon International) followed by visualization using a DAB PLUS substrate kit (Zymed Laboratories). Histopathological H/E staining was conducted in the Pathology Core Facility of the National Health Research Institute, Taiwan. Specimens were observed using a Olympus BX51 Research Microscope (model BX51TRF, Olympus, Japan). Pictures were managed using a DP controller provided by the same company." ] },{ "paper_id": "c4e99c8b861f4457b4a0518860bc9e52f5348e87", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For each class C and metapopulation threshold m, we calculated the average ratio between probability p i,r,m and distance d r for radius r as", "where n i,k is the population size for species i in zoo k. At each cluster, we assigned the indicator", "We repeated this procedure for radii ranging from 0 to 10,000 km, using 100 km increments. We excluded species for which the minimum population size was never reached, even when including all ISIS zoos." ] },{ "paper_id": "c4f28354c6015236a080fc0d67b0fc9d193c70d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The total RNA was reversely transcribed by M-MLV reverse transcriptase (Invitrogen, US).", "Jejunum tissue were fixed in 4% paraformaldehyde for 48 h at room temperature, embedded in paraffin, and sliced. The morphological observation of porcine jejunum was conducted after hematoxylin-eosin (HE) staining using Aperio Digital Pathology Slide Scanners (Leica, GER).", "HK2 was searched against STRING database (version 10.0) for protein-protein interactions (https://string-db.org/cgi/input.pl)." ] },{ "paper_id": "c4f2c649c3390b0a84ae38733bcbb9dfd054ccfa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c4fc28f1a66e4664a3dc12f5b121ee97aa9f122d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "VTT and MVTT-S viral stocks were propagated in Vero cells and then purified by centrifugation through a 36% sucrose cushion. MVA-S stock was prepared and purified using chicken embryo fibroblast (CEF) cells according to a procedure described previously [14] . Both viral stocks were titrated simultaneously in CEF by a plaque forming assay using crystal violet staining or counting the plaques with GFP expression.", "MVTT-S induced at least over 100-fold higher Nab response than MVA-S via i.n. or i.o. inoculation", "To determine the viral virulence in vivo, two groups of six-week old mice were inoculated with 10 5 and 10 6 PFU of MVTT-S via the i.n. route, respectively. Each group had six mice. The viral virulence was subsequently determined by the daily measurement of animal body weight change for a period of 31 days." ] },{ "paper_id": "c5078be94c34f8a7357c2b4a9e5ea3c19ecb45e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Morphology of HAE cultures was visualized by means of standard haematoxylin and eosin method. For fluorescence microscopy, slides were incubated consecutively in 0.2% Tween 20 (20 min, room temperature) and 2% bovine serum albumin ", "For visualization of HAE structures, cultures on Transwell inserts were washed one time with 16 PBS and fixed with 400 ml of 4% paraformaldehyde in 16 PBS. Samples were incubated for 15 min at room temperature and membranes were detached from the plastic frame. Subsequently, membranes were washed with 16 PBS, dehydrated in a gradient of ethanol and xylene, paraffin embedded, sectioned (5 mm) and mounted on silanised glass slides. Prior to staining, slides were deparaffinized with xylene and rehydrated in ethanol.", "RNA from clinical samples and viral culture supernatants was extracted using RNA mini kit (A&A Biotechnology, Gdynia, Poland), according to manufacturer's protocol. DNA was isolated using Viral DNA/RNA mini kit (A&A Biotechnology, Gdynia, Poland), according to manufacturer's instructions. Isolated nucleic acids were stored at 280uC.", "Human tracheobronchial epithelial cells were obtained from airway specimens resected from patients undergoing surgery under Silesian Center for Heart Diseases -approved protocols. This study was approved by the bioethical committee of the Medical University of Silesia in Katowice, Poland (approval no: KNW/ 0022/KB1/17/10 dated on 16.02.2010). A written informed consent was obtained from all patients. Primary cells detached from human bronchi and trachea with pronase E were expanded on collagen-coated (collagen type IV, Sigma aldrich) plastic in bronchial epithelial growth media (BEGM) to generate passage 1 cells and plated at density of 3610 5 cells per well on permeable Transwell inserts (6.5-mm-diameter; Corning Transwell-Clear) supports in BEGM. Cells were cultured at 37uC in presence of 5% CO 2 until confluence. Human airway epithelium (HAE) cultures were generated by changing the media to Air Liquid Interface media (ALI) and provision of an air-liquid interface for 6 to 8 weeks to form well-differentiated, polarized cultures that resemble in vivo pseudostratified mucociliary epithelium. All procedures were performed as previously described [34] ." ] },{ "paper_id": "c50f579edefdb6e484469d95488c5a2cd3f03135", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ten (10) mL of peripheral venous blood was collected using pre-labeled vacuum EDTA blood collection tubes. All blood samples were chilled immediately at 4\u02daC, and transferred to participating CDC laboratories at surveillance sites within 2 hours after sampling. Upon arrival of blood samples into the laboratories, sera were isolated by 1,500 g centrifugation for 15 min. Serum was aliquoted, flash frozen in liquid nitrogen, and then stored at -80\u02daC.", "Supporting information S1 File. Study questionnaire for persons hunting, butchering, eating and/or keeping wild animals as pets. (PDF) S1 Table. Prevalence of seropositivity for tested viruses, by reported wildlife exposure. (PDF)", "A total of 1,267 individuals provided a baseline blood sample for serological testing and completed a behavioral risk factor survey. The demographics of these individuals are shown in Table 1 .", "The majority of human infectious diseases have an animal origin, therefore understanding the human-animal interface as it relates to disease emergence and risk is of upmost importance [1] . The increasing frequency and variety of human-wildlife interactions in China provide opportunities for the transmission of zoonotic pathogens from animals to humans [2] . a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "c5139e673b41fa64eb80936bc9d63e83bf3c7172", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 7:46557 | DOI: 10.1038/srep46557", "Statistical analysis. Statistical analysis was performed using the software Graphpad prism 5.0 for determination of ID 50 values through a dose-response curve fit with non-linear regression. Significance was calculated using t-test. P < 0.05 was considered statistically significant.", "Peptide -binding antibody ELISA. Fifteen amino acid long linear peptides with 11 amino acid overlap spanning the entire length of gp160 of the Indian subtype C virus 93IN101 were synthesized commercially (Infinity Biotech and Resource Inc., PA). The peptides were adsorbed onto 96-well ELISA immuno maxisorp plates (Thermo Fisher) at a concentration of 5 \u03bc g/ml in 100 mM NaHCO 3 , pH 9.6, by overnight incubation at 4 \u00b0C and ELISA was performed as described previously 55 to map the epitope specificity of samples demonstrating good breadth and potency of neutralization. Each experiment was repeated three times. Healthy Human Plasma pool (HHP) was included as the negative control in all experiments. The samples were subsequently tested in an ELISA with recombinant proteins RSC3 and RSC3\u2206 371I/P363N to look for the presence of CD4 binding site (CD4BS) antibodies." ] },{ "paper_id": "c513fb0abb1aa50c3323e4f6d311248701f0280b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All raw data and protocols used to generate datasets for this study will be made available by the authors upon request to any qualified researcher.", "For B cell analysis via flow cytometry, CLN cells or spinal cordderived mononuclear cells were isolated from individual TMEV infected or sham mice as previously described (23 ", "Data generated in the present study were analyzed via Prism (version 6.0) software (GraphPad, San Diego CA). Data sets were assessed using a Pearson normality test to determine significant deviations from a normal distribution. Based on the normality results, the parametric Student's t-test or non-parametric Mann-Whitney U test was utilized to compare groups. The exact test used to perform analyses for each data set are denoted within the corresponding figure legend. In all cases, a P < 0.05 was considered significant.", "This study was carried out in accordance with the recommendations of the Institutional Animal Care and Use Committee. The protocol was approved by the Institutional Animal Care and Use Committee. for their expert care of the mice used for this study. The authors also acknowledge the NCCC light microscopy shared resource (IPIM) supported in part by NCI Cancer Center Support Grant 5P30 CA023108-37 and also NIH S10 SIG award S10OD21616 funding the LSM800 confocal." ] },{ "paper_id": "c5157f9976942d166a600cb570a5a8fa9ab91e57", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To reduce the complexity of the peptide mixtures, iTRAQlabeled peptides were fractionated by SCX chromatography using the AKTA Purifier system (GE Healthcare). Briefly, the dried peptide mixture was reconstituted and acidified with buffer A (10 mM KH 2 PO 4 in 25% of ACN, pH 3.0) and loaded onto a PolySULFOETHYL 4.6 \u00d7 100 mm column (5 \u00b5m, 200 \u00c5, PolyLC Inc., U.S.A.). The peptides were eluted at a flow rate of 1 mL/min with a gradient of buffer B (500 mM KCl, 10 mM KH 2 PO 4 in 25% of ACN, pH 3.0). The elution was monitored by absorbance at 214 nm, and fractions were collected every 1 min. A total of 15 fractions were collected with screening, and then desalted on C18 Cartridges (Empore TM SPE Cartridges C18 (standard density), bed I.D. 7 mm, volume 3 mL) and concentrated by vacuum centrifugation.", "MT and SC designed the study; MT, LY, NS, and YC performed the experiments; ZC and JW analyzed the data; SL, PL, and YS prepared the figures and tables; MT wrote the manuscript.", "This study was supported by Agricultural Science and Technology Innovation Project (No. 20150201006NY) and Jilin Provincial Science and Technology Development Project (No. 20150520128JH)." ] },{ "paper_id": "c52ffa67fea523c74bd0c0f45033183f403692ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNAs were isolated using the RNeasy Mini kit (Qiagen, France) and 200 ng of total RNAs were reverse transcribed into cDNA using the iScript cDNA Synthesis kit (Bio-Rad, France). Specific primers for ovine GAPDH, BMI1, OCT4 and NANOG were designed as follows (from 5' to 3'): GAPDH FOR CCACCAACTGCTTG GCCCCC, GAPDH REV CCTCGGCCATCACGCCA CAG, SP-C FOR GCAACGCCTGGCCCTGAGT, SP-C REV CATAATGTAGCAGCAGGTTC, CCSP FOR GTCA CCCTGACTCTCTTCTG, CCSP REV CAGGGCTGAA AGGTTCCAGG, CD34 FOR GATTGCACTGGTCAC CTCG, CD34 REV CTCCACGTAATAAGGGTCTTC, OCT4 FOR CAAGAACATGTGTAAGCTGC, OCT4 REV CGATACTCGTCCGCTTTCTC, NANOG-for GGC AGAAAAACAACTGGCCGAGGAA, NANOG REV CCCCACATGGGCAGGTTTCCAG, BMI1 FOR GCCA CAACCATAATAGAATGTC and BMI1 REV CCCTGG AACTAATTTGTATAC. The PCR reactions were performed using 10 ng of cDNA with the KAPA SYBR FAST kit (Cliniscience, France) as recommended." ] },{ "paper_id": "c5375b07f72048d739efc376420a5cb5374392d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The relative risk at the current exposure level (E) was estimated from epidemiological relative risk (RR\u00b0) expressed per a standard exposure increment:", "Pollutant specific diseases and methodology are presented in Table 3 . PAFs for each country and pollutant can be found from supporting information Additional file 2: Table S2 .", "The disabilities caused by various types of diseases are calculated accounting for the duration of the disease (L) and scaled using a disease specific disability weight (DW) and number of cases (N):", "Exposures to environmental pollutants are associated with increased mortality and morbidity. Some of the widely used risk assessment methods estimate these separately as numbers of cases. The results from such incidence-based models are not comparable over different types of health endpoints and to improve comparability of impacts on various types of diseases and including mortality, disability adjusted life years (DALY) has been proposed as a common metric [19] . The following model and data used in this study and more details of calculations are presented in a technical report published earlier [20] ." ] },{ "paper_id": "c53d3d043454289602f4177bb5125ef3d9d0df38", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments were performed at least three times. The data are presented as means \u00b1 standard error of the mean (SEM) and were analysed using Student's t-test. Twotailed P-values < 0.05 were considered statistically significant.", "Supporting information S1 Appendix. ", "Viruses (1 \u00d7 10 2 genome copies) were propagated in human A549 cells cultured in 12-well plates and were collected 6, 9, 12, 18, 21, 24, 36, 48 , and 72 h after infection. The cultures were subjected to repeated freezing and thawing thrice and centrifuged at 12000\u00d7g for 10 min. Then, 200 \u03bcl of supernatants were used for DNA extraction using Pure Link Viral DNA Mini Kits and virus titres were determined by detecting the number of viral E1 gene copies by realtime PCR. The E1 gene fragment was cloned into the T vector (pEASY-T1 Simple Cloning Kit, CT111-02; TransGen Biotech, Beijing, China) and diluted to 0.5 \u00d7 10 2 -0.5 \u00d7 10 9 copies/\u03bcL as standard samples.", "According to case reports, patients presented typical respiratory infection symptoms, such as fever (92.3%), cough (83.4%), sore throat (62.1%), swelling of tonsils (47.9%), and a runny nose (26.0%). Among them, 92 patients (54.4%) were diagnosed with upper respiratory infection, 77 (45.6%) with pneumonia (Table 1) , and 121 (71.6%) presented fever above 39\u02daC. In addition, nearly half (n = 37) of the patients suffering from swollen tonsils (n = 81) presented severely enlarged tonsils. Finally, there were also 17 cases of acute bilateral pneumonia." ] },{ "paper_id": "c549c2bfbb9c30559757547bb42f2999cf286723", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ASGPR is a protein receptor present on the basolateral membrane of hepatocytes that binds glycoproteins that lack sialic acid modifications. A direct interaction has been shown between the ectodomain of both ASGR1 and ASGR2 and HEV ORF2 by coimmunoprecipitation, pull-down, and ELISA [48] . Ectopic expression of ASGRP in HeLa cells increased HEV binding, whereas depletion of ASGPR in PLC/PRF/5 cells lowered HEV binding but not virion release. Both anti-ASGPR antibody and purified ASGPR ectodomain also reduced HEV binding to PLC/PRF/5 cells.", "Funding: This work is supported by grants from the National Institute of Allergy and Infectious Diseases (AI137912 and AI139511), The Gilead Science Research Scholars Program in Liver Disease, and internal startup funds from the Nationwide Children's Hospital (to Z.F.).", "The authors declare no conflict of interest.", "The less specific cell binding by eHEV may provide an explanation for the detection of HEV beyond the liver [57] . In addition, the exosome-like nature could facilitate its penetration of immunologically privileged sites such as the central nervous system. Since HEV infection has been associated with various types of extrahepatic manifestations [12] , a better understanding of the tropism and replicative capacity of eHEV in relevant cells/tissues will help differentiate between virus-mediated and immune-mediated effects in these conditions and shed light on HEV pathogenesis." ] },{ "paper_id": "c54a28ed68b1d30d44a3bce4033fa3e74103a33b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The outcomes of this panel are described in Table 1 .", "\u2022 Promotion of functional integration between EPI and Maternal Neonatal and Child Health (MNCH) programs using all available means, with national governments driving the process. Ideally equipping ANC clinics with immunization facilitieslogistics and skills.", "\u2022 Resource requirements' implications, including human resources and funding, should be adequately assessed and made available. Early and timely availability of resources for program implementation and community awareness will be instrumental." ] },{ "paper_id": "c56d753d8b3c0fb68cb1bd22f0b7d10eb3c08e93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mouse monoclonal AA5H (Abcam) was used to detect influenza NP by immunofluorescence.", "Plaque assays were performed as previously described in MDCK cells using Avicell overlays [15, 16] , in duplicate or where possible in triplicate.", "Influenza transmission is well documented in households and other residential settings [1] [2] [3] [4] . Yet the underlying mechanisms of transmission remain poorly understood and hotly debated [5, 6] . Although transmission by aerosols (particles typically ,5 mm in diameter), larger droplets and contact transmission (direct and via fomites) probably all play some role, the relative importance of each is uncertain, which has led to difficulties regarding the provision of evidence-based infection control advice for both pandemic and seasonal influenza [7] . If virus can survive for meaningful periods on surfaces and objects, or alternatively, if surfaces are frequently re-inoculated (e.g. by toddlers), then it is feasible that transmission via fomites might occur." ] },{ "paper_id": "c56e3599cec6dd5161af736e9d9cbd0e58c86315", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at http://www.mdpi.com/2218-273X/9/12/886/s1, Figure S1 : Generation and Testing of recombinant ACE2 Protein Truncates; Figure S2 : Purification of short mouse ACE2 1-619; Figure S3 : Amino acid sequences and molecular weights of the mouse ACE2 truncates. Funding: This work was mainly supported by National Institute of Diabetes and Digestive Kidney Diseases grants R01DK080089 and R01DK104785 and discretionary funds to Daniel Batlle at Northwestern University.", "For comparison of two independent groups, a two-tailed t-test was used if data was normally distributed. The normality of the distribution was assessed using Shapiro-Wilk test. For not normally distributed data, a Mann-Whitney test was used. For comparison of more than two independent groups, one-way ANOVA was employed, followed by Tukey's multiple comparisons test. For comparisons of Ang (1-7) formation and SBP over time, 2-way Anova was used. A p-value < 0.05 was considered statistically significant. Results are presented as mean \u00b1 SE.", "To examine whether, after glomerular filtration, a tubular uptake of filtered rACE2s takes place, ACE2-deficient mice were infused with either rACE2-1-605, 1-619 or the native rACE2 1-740 as negative control. Subsequently, L-lysine (a blocker of proximal tubular protein reabsorption) was injected i.p. (Figure 9 )." ] },{ "paper_id": "c56ffdaf1cfbae5a6ed0abea495eaf7fa1cbc031", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c5745c2eaaf8e94e31a179ce4e8775a3cd0e6745", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accordingly, UCP2 upregulation was recently observed in isolated endothelial cells overexpressing ACE2 [49] .", "To collect the urine, mice were individually housed in metabolic cages (Tecniplast 1 S.p.A., Hohenpeissenberg, Germany) for up to 72h with food and water available ad libitum. After 48 hours of acclimatization, 24h urine was collected, volume was measured gravimetrically, and the samples were stored at -80\u00b0C until further analysis.", "Total nitrate and nitrite urinary excretion rate (NOx) was determined using a commercially available kit (Cayman Chemical 1 , Ann Arbor, MI, USA) and normalized to creatinine concentration (mg.dL -1 ) (Labtest 1 , Belo Horizonte, Brazil). The levels of nitrite in plasma were measured as described previously .", "Results are expressed as mean \u00b1 SEM, and \"n\" indicates the number of animals used in the experiment. The dose-response curves of the different groups were compared by two way ANOVA followed by Bonferroni's correction. For simple comparisons between 2 groups, an unpaired Student's t test was used where appropriate using GraphPad Prism 1 version 5.0 for Windows. A value of P<0.05 was considered significant." ] },{ "paper_id": "c57fb53010f62a669421b0f4894a26e22e0e496c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ", (n~1,2,:::,N) \u00f00\u00de", "::: :::", "8 > > > > > > < > > > > > > : , (n~1,2,:::,N) \u00f01\u00de" ] },{ "paper_id": "c590a12be43ec57a2dde2a473802c5e47e354434", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step 2: Models are refined by energy minimization and side-chain repacking of groove and peptide residues (gray).", "3 Toor et al.", "7" ] },{ "paper_id": "c59c9a2c6315ed5aa7c437d1943fd94518119fd8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The cell lysates of rPA63 recombinant bacteria and E. coli BL21 were separately run on a 10% SDS-PAGE gel and then transferred onto a nitrocellulose membrane (Bio-Rad).", "Survival data were analyzed using the GraphPad Prism version 4 statistical analysis software (San Diego, CA). A t-test was used to compare the mean survival time between groups. A two-tailed log rank test was used to determine the statistical significance of differences between groups. A P value of < 0.05 was considered statistically significant.", "No reaction was seen with the negative control.", "Immunoprecipitation. Immunoprecipitation was performed using PA83, which could be split to active PA63 using trypsin. A protein of about 63 kDa was detected on SDS-PAGE, and its sequence matched that of the B. anthracis protective antigen in the Swiss-Prot database (Fig. 3A,C,D) . A 63 kDa membrane protein was also detected using a commercial anti-PA antibody (Fig. 3B) , and this protein did not reaction with any other antibodies." ] },{ "paper_id": "c59d6e789176b928523129adb96ca495720a3b4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All procedures were conducted in accordance with animal protocols approved by the Institutional Animal Care and Use Committee.", "where CT represents the threshold cycle at which the fluorescent signal becomes significantly higher than that of the background.", "Results are expressed as the mean \u00b1 SEM for each group of mice. In all cases, P<0.05 was considered significant. Graphs were plotted and statistics assessed using Graph-Pad Prism software (version 3.0)." ] },{ "paper_id": "c59f056b663000ffe9a935dbc10fcd847dd67867", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c5b4fb9b393c9e5d24b075349fbb4601ea89c8f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c5b72b9084df4d6f9e471b0e320a6136a7db7f0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "diet analyses, ecological genetics, environmental DNA, mammals, predator-prey interactions, wildlife management", "have not yet reached a technical level that would make them costeffective and efficient for large-scale applications.", "However, identifications at the lowest taxonomic levels were to arthropod taxa that are ectoparasites on vertebrates or nematodes (Table 2) ." ] },{ "paper_id": "c5c188fe8bbf7f71f4f6f96dc52747deac68ee3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 5:10942 | DOi: 10 .1038/srep10942", "Coexisting conditions including coronary heart disease, chronic obstructive pulmonary disease, hypertension, diabetes, cerebrovascular disease and cancer.", "Hypercytokinemia in H7N9-infected patients. We have performed multiplex analyses of 48 cytokine and chemokine mediators using these plasma samples while only 17 of these 48 mediators have been previously examined and reported inpatients infected with avian influenza virus [7] [8] [9] ." ] },{ "paper_id": "c5c2bc7a07670d6fb970d84a59aab3832752a3f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasmid pCMV-T7pol expresses the bacteriophage T7 RNA polymerase under the control of the cytomegalovirus promoter [30] and was kindly provided by Martin A. Billeter (University of Zurich, Irchel, Switzerland).", "Western blot analysis was performed employing mouse anti JUNV N protein NA05-AG12 mAb [24] and rabbit anti phospho-ERK1/2 (p-ERK) (Cell Signaling), anti ERK1/2 (ERK) (Santa Cruz Biotechnology; Dallas, TX, USA) and anti phospho-eIF2\u03b1 (p-eIF2\u03b1) (Cell Signaling) antibodies. Peroxidase anti-rabbit IgG (Amersham; Little Chalfont, Buckinghamshire, UK) or peroxidase anti-mouse Ig G (Sigma-Aldrich) were used as secondary antibodies.", "Total RNA was extracted using TRI reagent (Genbiotech; Antibes, France) and the detection of JUNV genomic S RNA by PCR was performed as previously described [31] . Briefly, cDNA was synthesized using the primer N (+) ( ", "Statistical significance of the differences between untreated and drug-treated cultures was determined either by 2-tailed paired Student's t test, to compare the results between two groups, or ANOVA analysis. Three independent experiments were analyzed unless stated otherwise. A p value < 0.05 was considered to be statistically significant.", "Plasmid p5 wt/3 wt_2, which expresses a transcript that mimics the wild-type TCRV N mRNA; plasmid p\u03b2Glo/poly(A) expressing a cell-like mRNA (named \u03b2-Glo/poly(A)) that bears the 5 untranslated region (UTR) of the human \u03b2-globin mRNA and a poly(A) tract flanking the FLUC ORF, and plasmid pRLUC, used to generate a synthetic mRNA expressing Renilla reniformis luciferase enzyme (RLUC), have been previously constructed [29] ." ] },{ "paper_id": "c5dd9137d5d43d4d46606a219f3ecce6d22375c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To remedy the problems related to transportation of specimens and handling of samples a regulatory framework for sample transfers is needed (within and outside the country), including e.g., the organization of the transportation process, handling of specimens, and intergovernmental collaboration.", "Moreover, in a number of countries, business continuity is a problem for diagnostic services because of complex procurement processes or insufficient funding, and lack of appropriately trained staff. In particular, there is a lack of support for clinical and reference laboratories for enteric disease/diarrhea diagnostics, which jeopardizes recognition of outbreaks with foodborne pathogens.", "To implement the policies/strategies on microbiology laboratory systems including the necessary technical advancements it is essential to build professional and institutional partnerships and seek functional partners e.g., from EU Member States, while ensuring the national commitment for sustainability." ] },{ "paper_id": "c5df32e01e9583e1b4430418e8f8f58c8a85021c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical observations beginning in the 1950s have suggested that individuals exhibit differences in their responses to drugs and that these variations could be inherited 1 . The detection of DNA sequence variations provides valuable insight into the diagnosis of genetic-related diseases and conditions, especially for early-stage treatment and response monitoring 2 . Thus, it is critically important to select a method with high sensitivity and specificity to detect single or small numbers of nucleotide polymorphisms 3, 4 .", "Numerous lines of evidence have strongly suggested that genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors and other drug targets are associated with inter-individual differences in drug treatment response 17 . Sequence variations in drug target proteins, drug-metabolizing enzymes, and drug transporters can alter drug efficacy, drug side effects, or both to cause variable drug responses in individual patients 18 . For example, on March 12, 2010, the US Food and Drug Administration approved a black box warning regarding the diminished effectiveness of clopidogrel in patients who carry two loss-of-function alleles (poor metabolizers) 19 , i.e., CYP2C19*2 (G681A) and CYP2C19*3 (G636A) alleles, which account for 85% and 99% of the nonfunctional alleles in Whites and Asians, respectively 20, 21 . The warning addressed the need for polymorphism genotyping to identify altered clopidogrel metabolism in patients 22 .", "Peripheral blood and genomic DNA extraction. Peripheral blood samples were collected from 100 unrelated Chinese volunteers using EDTA-coated tubes at the Shaanxi Provincial People's Hospital (Xi'an, China) with informed consent. The study was approved by the ethics committee of the National Engineering Research Center for Miniaturized Detection Systems, Xi'an, China. All methods were performed in accordance with these approved guidelines. The genomic DNA from the volunteer was isolated from 200 \u03bc L of blood using a Whole Blood Genomic DNA Isolation Kit (Xi'an GoldMag Nanobiotech Co., Ltd., Xi'an, Shaanxi, China), according to the manufacturer's instructions. The final DNA quality and concentrations were measured using a NanoDrop 2000c/2000 UV-Vis spectrophotometer (Thermo Fisher Scientific, Wilmington, DE, USA), according to the manufacturer's instructions." ] },{ "paper_id": "c5e5ce1e093a5acef8221d3f5cd3926cd8f9a87f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c5f1d681eb128c9c044a7f5ced6e0e943b201e93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The experimental data obtained in this study were statistically analyzed using Microsoft Excel 2007 and Graph-Pad Prism7. The results were statistically analyzed by one-way analysis of variance, and multiple differences were analyzed by Duncan's test. The results are presented as mean \u00b1 standard deviation (SD), and P < 0.05 was considered statistically significance." ] },{ "paper_id": "c5f986ded9c2caf03ce509dffc7e53f93f41941c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To record current of the expressed KCNQ channels in CHO cells, standard whole-cell recording was used. Pipettes were pulled from borosilicate glass capillaries (TW150-4, World Precision Instruments). When filled with the intracellular solution, the pipettes have resistances of 3-5 megaohms. During the recording, constant perfusion of extracellular solution was maintained using a BPS perfusion system (ALA Scientific Instruments). Pipette solution contained (in mM): 145 KCl, 1 MgCl 2 , 5 EGTA, 10 HEPES and 5 MgATP (pH 7.3); extracellular solution contained (in mM): 140 NaCl, 3 KCl, 2 CaCl 2 , 1.5 MgCl 2 , 10 HEPES and 10 glucose (pH 7.4). Current and voltage were recorded using an Axopatch-200B amplifier, filtered at 2 kHz, and digitized using a DigiData 1440A with pClamp 10.2 software (Axon Instruments). Series resistance compensation was also used and set to 60-80%.", "All animal procedures were performed in accordance with the National Institute of Heath Guide for the Care and Use of Laboratory Animals, under protocols approved and strictly followed by the Institutional Animal Care and Use Committees (IACUC). The IACUC checked all protocols and approved this study. Single myocytes were isolated from the left ventricle of adult guinea pig in a Langerdorff perfusion system as previously described [18] . The hearts were removed quickly via midline thoracotomy and perfused with a Ca 2+ -free Tyrode's solution containing collagenase (6 mg/ml) and protease (0.1 mg/ml) for ", "Cell culture and transfection CHO cells were grown in 50/50 DMEM/F-12 (Gibco) with 10% fetal bovine serum (FBS), and 2 mM L-glutamine (Invitrogen). To express the channels and mutants, cells were split at 24 h before transfection, plated in 60-mm dishes, and transfected with Lipofectamine 2000 TM reagent (Invitrogen), according to the manufacturer's instructions. A GFP cDNA (Amaxa, Gaithersburg, MD) was cotransfected to identify the transfected cells by fluorescence microscopy. FluxOR thallium assay CHO cells stably expressing the rat KCNQ2 were routinely cultured in DMEM/F12 medium, supplemented with 10% FBS and 500 mg/mL G418. The FluxOR thallium assay protocol was the manufacturer's protocol. CHO-KCNQ2 cells were seeded in wells of 96-well plates at ,10,000 cells/well and grown until 80-90% confluence at 37uC in a 5% CO 2 incubator. The medium was removed the following day and 80 mL of FluxOR loading buffer was added to each well for 90 min at room temperature (RT) in darkness. After removing the loading buffer, 100 mL/well of assay buffer and 20 mL/well of 7X control/test compound were added to cells at RT in darkness. Compounds to be tested were prepared using assay buffer; controls were assay buffer (EC 0 ), EC 50 of Retigabine and EC 100 of ztz240. After 30 min, cell plates were loaded on FDSS. After 10 seconds of recording, 20 mL/well of stimulus buffer was added. The plates were read every second for 110 s. The stimulus buffer contained 1.30 mM K2SO4 and 9.80 mM Tl 2 SO 4 . The gpotentiation% ((R test -R control )/(R control -R buffer )*100%) was calculated for each well using the 35 second fluorescence ratio. To identify compounds with potentiation activity on KCNQ channels, a thallium flux assay was developed and used to screen a Microsource TM library of 1,280 compounds at 10 mM final concentration. In the pilot screening, HCP exhibited strong potentiation on the fluorescence signal of KCNQ2." ] },{ "paper_id": "c6008b68c8b16e3a6a48a2cb892bac5c9353df86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(3) having a ratio of arterial partial pressure of oxygen to inspired fractional oxygen concentration (PaO 2 /FiO 2 ) of less than 26.8 kPa and absence of clinical evidence of left heart failure." ] },{ "paper_id": "c601e38de42c9188e237fe848d26c4a7c07c3d58", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Confocal images were taken on a Leica LSM700 or 780 confocal microscope; widefield and stereromicroscope images were taken on a Zeiss Axiovert 200M and a Zeiss Stereo Discovery V12, respectively. Images were processed with ImageJ software.", "KEYWORDS" ] },{ "paper_id": "c6024a8ca787b4af96d36292b86479031416a0b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Iterative HFold runs in O(n 3 ) time, as it runs four methods sequentially, when each one is O(n 3 ).", "Method 1: Run HFold on S and G, and store the resulting G \u222a G . Motivation: This is the core HFold method, motivated by the hierarchical folding hypothesis. .) ))))) -14.67", "We represent an RNA molecule by a sequence, S, of its four bases, Adenine (A), Cytosine (C), Guanine (G) and Uracil (U). We denote the length of the RNA molecule by n and refer to each base by its index i, 1 \u2264 i \u2264 n." ] },{ "paper_id": "c60392b55a9acde4311257b1693ce0285a922aae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Zika virus (ZIKV) was first isolated in 1947 when three owl monkeys from the Zika Forest, Uganda, were found to have a fever [1, 2] . Even though the first human case was reported in 1952 and although this virus has been circulating in Asia and Africa, very few ZIKV cases were noticed and recorded before the 2015/2016 epidemic, since the symptoms were generally mild [1, 3] and fatality was" ] },{ "paper_id": "c60b9bd1c5edac3f1f4916571a10a6daf9b569a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mean score changes from baseline to a particular endpoint were also abstracted. If unavailable, we extracted mean scores of baseline and endpoint as well as the SDs [43, 46] . Consensus was obtained by discussion or by consulting the third reviewer (D-Y K).", "3.3.1. Recurrence Rate. Five RCTs", "Mesalamine (USAN), also known as mesalazine (INN, BAN) or 5-aminosalicylic acid (5-ASA), is most commonly used as a first-line therapy for mild to moderate UC [10] ." ] },{ "paper_id": "c615556cb238bad03d0538519159600fe727c903", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/ mSphere.00422-18. TABLE S1, XLSX file, 0.03 MB.", "The reduced susceptibility of SCV to antibiotics is associated with their auxotrophism to menadione, hemin, and/or thymidine, resulting in deficiencies in electron transport (menadione and hemin) and/or the thymidylate biosynthetic pathway (30) . The deficiencies in these metabolic pathways result in lower membrane potential and reduced metabolism, which explain SCV's ability to survive antibiotic treatment (31, 32) .", "Additionally, SCV have the ability to persist intracellularly within nonphagocytic cells such as bone, epithelial, and endothelial cells, hence avoiding host-immune response and antibiotic treatment (33, 34) . The ability of SCV to revert to normal colony phenotype (NCP) also adds evidence for their important role in the reoccurrence of infection and the restoration of virulence, leading to recurrent infection. Thus, there is a clinical need to prioritize current antibiotics, reposition drugs, and/or identify novel agents that are effective against SCV to prevent relapses in infection and to effectively treat chronic infections." ] },{ "paper_id": "c6183dfbaabc06881c70097745b3e646479ac9a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c61f5c4971f07156d3c1d9dd76de4b158855ecc1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lung homogenates were clarified by centrifugation and diluted 1:10 and 1:100 in EMEM. Confluent HEp-2 monolayers were infected in duplicates with 50 ml per well starting with undiluted (neat) samples followed by diluted homogenates in 24-well plates. After one hour incubation at 37uC in a 5% CO 2 incubator, the inocula were removed and wells were overlayed with 0.75% methylcellulose medium and plates restored into the 37uC incubator. After 4 days of incubation the overlay was removed and the cells were fixed with 0.1% crystal violet stain for one hour, then rinsed, and air dried. Plaques were counted and virus titers are expressed as pfu per gram of tissue. Viral titers were calculated as the geometric mean plus standard error for all animals in that group at a given time.", "Lung were dissected and inflated with 10% neutral buffered formalin to their normal volume, and then immersed in the same fixative solution. Following fixation, the lungs were embedded in paraffin, sectioned and stained with hematoxylin and eosin. Two parameters of pulmonary inflammation were evaluated: interstitial pneumonia, defined as inflammatory cell infiltration and thickening of alveolar walls, and alveolitis, defined as cells within the alveolar spaces. Slides were scored blind on a 0-4 severity scale. The scores were subsequently converted to a 0-100% histopathology scale.", "pCD5 expression vectors containing RSV F ectodomainencoding sequences were transfected into HEK293T cells using polyethyleneimine I (PEI) in a 1:5 w/w ratio (DNA/PEI). At 6 h post transfection, the transfection mixture was replaced by 293 SFMII expression medium (Invitrogen), supplemented with sodium bicarbonate (3.7 g/liter), glucose (2.0 g/liter), Primatone RL-UF (3.0 g/liter), penicillin (100 units/ml), Streptomycin (100 mg/ml), glutaMAX (Gibco), and 1.5% dimethyl sulfoxide.", "Animal experiments and study protocols were either approved by the Committee for Animal Experimentation of the University of Groningen (the Netherlands) or by Sigmovir Institutional Animal Care Utilization Committee. The study was carried out in strict accordance with the guidelines provided by the Dutch Animal Protection Act or National Institutes of Health, respectively. All efforts were made to minimize suffering." ] },{ "paper_id": "c6202f96bd4b2aea699d5fbe867f311498dca3aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c62b68c066ad9cbdee5244b9b97e06d7286b2364", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At present, the conventional therapeutic approaches in HF management include angiotensin-converting enzyme (ACE) inhibitors, \u03b2-blockers, and diuretics. Although several of them have led to an important effectiveness, HF remains the leading cardiovascular disease with an increasing hospitalization burden and an ongoing drain on health care expenditure [5] . Therefore, it remains necessary to search alternative and complementary treatment, in which Traditional Chinese Medicine takes a good proportion [6] .", "However, we should consider the following limitations before accepting the findings of this paper.", "Heart failure (HF) is a leading cause of death, hospitalization, and rehospitalization worldwide. Despite advances in the treatment of HF, including use of drugs, devices, and heart transplantation, the condition remains associated with substantial morbidity and mortality [1] .", "The above side effects might be related to higenamine, which is the active ingredient of prepared aconite root. In TCM books and papers, prepared aconite root is frequently mentioned with adverse effects as dry mouth, dryness heat, fullness of the head, and dysphoria due to its strong effect of strengthening yang." ] },{ "paper_id": "c63c4d58d170136b8d3b5a66424b5ac3f73a92d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data S1. ", "In this report, we have demonstrated the viability of detecting novel pathogens via cross-hybridization to highly conserved sequence motifs. With the recent sequencing of the complete SARS coronavirus genome (GenBank NC_004718) (Marra et al. 2003; Rota et al. 2003) , we were able to retrospectively determine the degree of nucleotide identity shared between the hybridizing oligonucleotides and the new coronavirus genome (see Table 1 ). Stretches of relatively uninterrupted nucleotide identity as short as 25 nucleotides yielded clearly detectable hybridization signal, confirming that novel viruses with only limited homology to known viruses can be successfully detected by this strategy.", "Shotgun sequencing. Primer-B-amplified nucleic acid (see above) was cloned in pCR2.1TOPO, plated on 2xYT/kan plates, and grown overnight at 378C. White colonies were picked into 384-well plates containing 2xYT/kan plus 8% glycerol and incubated overnight at 378C. DNA was purified by magnetic bead isolation. DNA sequencing involved adding 3 ll of water to each bead pellet, followed by 3 ll of Big Dye terminator (v3.1) sequencing cocktail, and incubation for 35 cycles of 958C for 5 s, 508C for 5 s, and 608C for 2 min. Reaction products were ethanol precipitated, resuspended in 25 ll of water, and loaded onto the ABI 3730xl sequencer. The resulting sequence reads were trimmed to remove primer sequences from the RT-PCR step and then assembled by Phrap (P. Green, unpublished data). Resulting contigs were screened by blast to remove any contigs with high human or monkey sequence similarity. The remaining contigs were edited to high quality, making any obvious joins. (Sequences are available as Data S1.)" ] },{ "paper_id": "c63e2bbb0915e7d4d40813d58286d51e80453507", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DNA recombination of the all-in-one plasmid in E. coli was evaluated as described previously [28] .", "The PfuUltra High-Fidelity DNA polymerase (Stratagene) was used to amplify the influenza genes and cassettes in the current study. Agarose gel containing 10 \u03bcg/mL of crystal violet was used to isolate large DNA fragments." ] },{ "paper_id": "c64a088496e159b12a097a0c22a795a656aad07a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "New compounds, 2-oxo-5-aryl-3-hydrazone pyrrolidines, which offer a large number of potential derivatizations have been prepared. The work on the biological activities on these compounds is currently investigated in our laboratory.", "Hydrazine functionalities are also important intermediates for the synthesis of some bioactive compounds such as \u03b2-lactams [6] . Furthermore, they have been reported to show a variety of interesting biological activities [7] [8] [9] . The synthetic versatility of hydrazine has led to the extensive use of this compound in organic synthesis. Although some chemistry of hydrazine and pyrrolidone reactions have been studied [10] , to our knowledge reactions of 2,3-dioxo-5-arylpyrrolidinone with different hydrazine salts have not been reported before in open literature. Consequently, new 2,3dioxo-5-arylpyrrolidinones have now been synthesized and their reactions with various hydrazines are currently being investigated.", "In connection with our ongoing studies towards the total synthesis of codonopsinine, we became interested in the three-component condensation reaction reported by Dehaen et al. [1] . This elegant one pot reaction furnished the important intermediate 2,3-dioxo-5-arypyrroles which are required in our work. Depending on the substitution groups on the aromatic aldehyde used, this reaction will provide different 2,3-dioxo-5-arylpyrroles in reasonable to moderate yields. Particular attention has been made to these classes of compounds since some of the 2,3-dioxo-5-arylpyrroles were successfully converted to their respective 2,3-dioxo-5-arylpyrrolidinones [2] . These pyrrolidinones could be promising intermediates for preparing various synthetically challenging and medicinally important alkaloids such as codonopsinine, anisomycin and preussin [3] [4] [5] ." ] },{ "paper_id": "c64f525d77bf8b2ae4439a875f1bd8eb197a0519", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To single out significant tests in a group, raw significance probabilities were corrected by the sequential Bonferroni method for multiple independent tests as indicated in [60] .", "The conditional probability of non-infection by any other pathogen given the presence of pathogen i is:", "ps ik~P j=i (1{P jk ), and the conditional probability for the observed multiple infections given the presence of i is:", "The average prevalence of pathogen i over hosts will be" ] },{ "paper_id": "c6518c58374cc315647f2873a234cfa983746bfd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All microarray (CEL files and CHP files), GSEQ and sPROFILER sequencing data outputs, and all sample information were uploaded to the series records (GSE29550) of Gene Expression Omnibus (GEO).", "Total DNA was extracted from 16 patient samples, comprising 8 peripheral blood/bone marrow samples and 8 fibroblasts cultures. Blood or bone marrow samples were from 7 patients with myelodyplastic syndrome (MDS) and one patient with chronic lymphoblastic leukemia (CLL), obtained from the Australasian Leukaemia and Lymphoma Group Tissue Bank, Princess Alexandra Hospital, Brisbane, Australia, and the Hematology Clinic at Mater Adult Hospital, Brisbane. Low passage fibroblast cultures from 8 pediatric patients with metabolic disorders indicative of mitochondrial dysfunction were obtained from the Department of Pathology (Cytogenetics), Mater Adult Hospital, Brisbane. This study was approved by the institutional Human Ethics Review Committees of The University of Queensland and the Mater and Princess Alexandra Hospitals, Brisbane, Australia.", "For mtDNA7, a total of 35 homoplasmic and heteroplasmic mutations were identified using MitoChip, with 30 of these mutations being confirmed by conventional sequencing: 2 new homoplasmic mutations were not detected by ", "With the significant increases of throughput applications for large targeted sequencing or whole mitochondrial genome resequencing the need for new approaches towards data analysis and variant identification, combined with higher sequencing accuracy, will become paramount for both accuracy and to minimise sequencing costs. This is particularly important for variation in mitochondrial DNA from different tissues of the same individual, because of the presence of sequence variants among the large numbers of mtDNA copies within a tissue or even in a single cell [17] . New techniques such as digital sequencing [17] or 'next generation sequencing' [18] may eventually provide more comprehensive sequencing but their use for screening will depend upon low cost and ease/speed of use." ] },{ "paper_id": "c657f35b61e4e8e4ba9c06f72da78131608a4a85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We argue that the underlying driving force for such systemic shifts in international relations was the 'sticky' nature of the issues themselves. Many CSOs, for example, brought public attention onto many emerging critical social issues for policy change well before a state policy response was initiated in addressing them. Most notably, communitylevel action prompted the exigency of a national response for HIV/AIDS issue well before any official state-level response was initiated in Africa (The Joint United Nations Programme on HIV/AIDS [UNAIDS], 1997).", "Similarly, the United States created numerous objections during the negotiation process of the FCTC drafting on the ground of their constitutional rights. Bernard (2012) wrote,", "That being said, though, the normative orientation offers considerable compensation, as revealed by some earlier successful campaigns by the CSOs such as the boycott of Nestle on breast milk substitutes. The CSOs are also learning fast by sharing their global network of expertise. Indeed, South Africa's Treatment Action Campaign's (TAC) legal collaboration in 2001 is a perfect example (Berger, 2002; Heywood, 2009) . TAC intervened as amicus curiae in the court proceedings between the South African government and the Pharmaceutical Manufacturers' Association (PMA) when the former wanted to regulate drug pricing for better access to healthcare. TAC was supported by a global and local network of CSOs with legal expertise and, as a result, won the case for South Africa.", "Still, there continue to be elements of resistance from the traditional state authorities to address the emerging agenda and to adapt to changes that an effective solutionsometimes radical in nature -in response may call for. As a result, issue-specific CSOs may be in direct conflict with traditional state authorities. Indeed the contrast in normative positions acts to 'push' state and non-state actors further away from each other (see Figure 1 ). The 'push' effect is a natural tendency for the diverging actors in claiming the opposite pole to differentiate themselves notably on the question of the extent to which sovereign rights are defended or bypassed." ] },{ "paper_id": "c65f0939cf35a0f04bf93bd6e8f771b8521563a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where", "We used the posterior mean deviance as a Bayesian measure of fit or model adequacy as defined by Spiegelhalter et al. [20] . The posterior density deviance is defined as:", "The total log likelihood of the model can be written as" ] },{ "paper_id": "c65fdbefc02d44dbadad79451a6253465f075837", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where \u03c1 XY is the dinucleotide bias, f XY is the frequency of dinucleotide XY, f X and f Y are the frequencies of nucleotide X and nucleotide Y 38 , respectively." ] },{ "paper_id": "c66b53fa3a31eb9fcc20c56830c89061b7caed49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data was analyzed using GraphPad Prism (GraphPad Prism Software, San Diego, California). The specific statistical test to determine significance is noted in each figure legend.", "This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University of North Carolina at Chapel Hill (Protocol Number: 17-097).", "To maximize the utility, impact and biological relevance of pathogenesis studies or therapeutic evaluation, the measurement of multiple complementary and translatable metrics over time is crucial." ] },{ "paper_id": "c66be1e891285a777b15ba49e685452fed6ee837", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Primary chicken embryo kidney cells were prepared from 20 day old SPF chicken embryos as described previously [9] .", "In a live and dead staining (LIVE/DEAD Viability/Cytotoxicity Kit, Invitrogen, Darmstadt, Germany) we tested the oviduct rings for viability. Living cells are stained in green, dead cells are stained in red. Additionally we analyzed the oviduct rings for ciliary activity under the light microscope.", "To concentrate the proteins in the supernatant, Amicon Ultra-15 Centrifuge Filter devices were used. Aliquots of the soluble proteins were stored at \u221220\u00b0C." ] },{ "paper_id": "c66d7cf6243be684d42751e19f4f9c27ca8a1f3b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Here, we present the biophysical characterization of the nanoparticles and an immunological profiling using chickens as test animals. The results suggest that the selfassembling polypeptide nanoparticle shows promise as a potential vaccine against AI.", "Peptide sequence", "Scattering. Dynamic light scattering experiments were carried out on a Zetasizer Nano S Instrument (Malvern, Worcestershire, UK), with a 633 nm He-Ne laser. All measurements were carried out at 25 \u2022 C in a buffer containing 20 mM Tris pH 7.5, 150 mM NaCl, and 5% glycerol.", "Samples were negatively stained with 1% uranyl acetate (SPI Supplies, Westchester, PA, USA) and observed with a FEI Tecnai T12 S/TEM at an accelerating voltage of 80 kV (FEI, Hillsboro, Oregon). The peptide concentration of the constructs was about 0.05 mg/mL." ] },{ "paper_id": "c67580a2c552483f02b5df1f297d110b4263c5c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 Database. Database of community-onset pneumonia cases. Table. Microbiological profiles of patients with community-onset pneumonia with and without aspiration-associated conditions. (DOCX) S2 ", "A multicenter prospective surveillance for COP was conducted from September 2011 to January 2013 in Japan. All pneumonia patients aged !15 years, including those with community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP), were enrolled at four community hospitals on four major islands. The COP burden was estimated based on the surveillance data and national statistics." ] },{ "paper_id": "c682f8e05b7363e2407b3055826f6c93b6c1f3ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c68a6448007a158321fd4b610a17e646d77fea95", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Of the 563 patients with a virus, 526 (93.4%) were tested either prior to, or within 2 days of hospital admission, indicating detection of possible nosocomial cases to be uncommon.", "Ethics approval was granted by SCGH and Curtin University Human Research Ethics Committees (Approval numbers 2016-058 and 10492 respectively).", "Supplementary material. The supplementary material for this article can be found at https://doi.org/10.1017/S095026881900195X." ] },{ "paper_id": "c6981b83471474649ada35c45fe43e091aab4553", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.pcbi.1006204.t003", "For both scenarios transmission is subcritical, with disease presence maintained by reintroduction from an external reservoir. For each parameter combination 1000 replicates of both scenarios are generated.", "Increasing \u03d5 reduces the overdispersion of the data, so that for large \u03d5 the distribution of reports is approximately Poisson." ] },{ "paper_id": "c6a56489ca7a8d317c3244f06f15cbbc95181fd4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Titanium aluminum vanadium alloy (Ti-6Al-4V) is commonly used in medical instruments. Although the created biomedical instruments may disperse aluminum and vanadium into the human body [8] , causing possible health threats, small amounts of these metals can efficiently improve the mechanical properties (e.g., mechanical strength and toughness) of the Ti alloy in devices. Since Ti-6Al-4V exhibits excellent biocompatibility, it is commonly used in medical implants and instruments. Currently, 20-30% of medical instruments are manufactured using mainly Ti-6Al-4V [9] .", "Anodization, plasma electrolytic oxidation, and high-temperature annealing (HTA) are the common techniques to generate an oxide layer on the surface and protect the metal beneath. The generated TiO 2 layer exhibits numerous advantages, including favorable mechanical properties, corrosion resistance, and biocompatibility. Despite anodization and plasma electrolytic oxidation being mature technologies which require short processing time, these methods entail using electrolytes that contain heavy metals and chemicals. If incorrectly disposed of, such electrolytes pose a critical threat to the environment. With the increasing prevalence of the green industry worldwide, environmentally friendly surface treatment methods are receiving increasing attention.", "In this study, Staphylococcus aureus (Gram-positive bacteria) was used to analyze the antibacterial properties of samples coated with Ti-V-O using HTA and LSTO. The longitudinal axis of Figures 10 and 11 is related to the amount of remaining bacteria, and a lower value represented greater antibacterial properties." ] },{ "paper_id": "c6b416e31cb51e4ecc6264f20bb37db28e9a4cef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cloning and purification of IFIT1. IFIT1 was amplified with primer IFIT1F/IFIT1Xho from the plasmid pGAC-HA-IFIT1, restricted with NcoI and XhoI, and ligated with a modified pLOU3, in which maltose binding protein (MPB) was replaced with SUMO, while SalI in the mutliple cloning site (MCS) was replaced with XhoI. The primers were as follows: IFIT1F, CCGCCATGGCTACAAATGGTGATGATCATCAGG; IFIT1Xho, GCGCCTCGAGCTAAGGACCTTGTCTCACAGAGTT.", "The fusion protein His-SUMO-(TEV)-IFIT1 was expressed in Escherichia coli strain Rosetta in 6 liters LB-ampicillin-chloramphenicol (LB/ Amp/CM). Isopropyl-\u2424-D-thiogalactopyranoside (IPTG; 0.2 mM) was added when an optical density (OD) of 0.8 was reached. The expression was carried out at 18\u00b0C overnight." ] },{ "paper_id": "c6b5bfea0defb38a81a9c9dd23b4d0f272ac05da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All extracts irrespective of solvent used showed significant (p < 0.05) dose-dependent Vero cell plaque inhibition." ] },{ "paper_id": "c6b7bfae68c5c25203f76616c028668feea39e8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, we were unable to demonstrate a direct interaction between CR1 and five members of PvRBPs which were thought to play essential roles during reticulocyte invasion 12 " ] },{ "paper_id": "c6ba4dc13c3222eec0dcb0ae56ca8f1261485e96", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thirteen antiviral compounds were selected based on the reported in vitro antiviral effects against other caliciviruses [33] and included NNIs, NAs, PIs, and the broad-spectrum nitazoxanide. The stock solutions for all compounds were prepared in 100% dimethyl sulfoxide (DMSO) and aliquoted before storage at \u221220 \u2022 C." ] },{ "paper_id": "c6bf372c094f035a514975c35a7f9c094abbe493", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Loop-mediated isothermal amplification (LAMP) is a unique gene amplification method in which DNA can be isothermally amplified using only one enzyme [1] [2] [3] ." ] },{ "paper_id": "c6bfe832f2dd36a5c86f548138c96883ce0f46b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Supporting information S1 ", "Conceptualization: GPB EA ET WTA-L FCPV." ] },{ "paper_id": "c6c0a0d35bdedb534df909619bd7f240f9d52ae6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All DNA manipulation was done using standard methods; plasmids were grown in Escherichia coli DH5a and DNA was purified using CsCl gradients. Plasmids pcDNA6-GV-N and pcDNA6-GV-La plasmids have been previously described [61] . Plasmid pCAGGS-MCSII was the gift of Professor Adolfo Garcia-Sastre, Mount Sinai School of Medicine, New York, USA. The pCAGGs_MCSII_V5 construct was generated by insertion of V5 tag sequence into the multiple cloning site (MCS) of pCAGGS-MCSII; pCAGGs_MCSII_V5 was further used to generate pCAGGs_MCSII_PreGn_V5, pCAGGs_MCSII_NS M _V5 and pCAGGs_MCSII_PreGc_V5. These constructs were generated by amplification of appropriate fragments of the GV (i. : TA-TCATATCGATGGCAACCTCTTTAACTGCTTTTC) and pcDNA-GV-M [62] as template. These fragments were then inserted upstream of, and in frame with, the V5-tag of pCAGGs_MCSII_V5. All PCRs were performed using proofreading polymerase (KOD; Novagen). All inserts were sequenced completely.", "At the indicated times, infected or transfected cells were harvested and lysed with 100 ml of 1x SDS sample buffer (New England Biolabs). SDS-PAGE and Western blots were carried out as previously described [65] .", "To analyse secreted proteins, cell were cultured in 12-well plates containing 0.5 ml of growth medium per well. The medium was collected, pre-cleared of cellular debris by centrifugation at 664 g for 10 min at 4uC, and supernatants were mixed with 5x SDS-PAGE loading buffer (4% SDS, 250 mM Tris/Cl pH 6.8, 0.6 mg/ml of bromophenol blue, 7.5 mM DTT, 30% (v/v) glycerol in water). Such prepared protein lysates were analysed by Western blotting as described above.", "NSDV is closely related to a human pathogen, Crimean-Congo haemorrhagic fever virus (CCHFV), which causes viral haemorrhagic fever with an average mortality rate of 30% (reviewed in [18, 19] ). After Dengue virus (DENV), CCHFV is the second most widespread of the arboviruses pathogenic to humans [20] [21] [22] [23] [24] [25] [26] [27] [28] . The disease caused by CCHFV in humans is similar to that caused in sheep and goats by NSDV infection [2, 29] , and is characterised by fever, myalgia, superficial and internal haemorrhage, abdominal pain and diarrhoea [30] [31] [32] [33] . While work on CCHFV is limited to biosafety level (BSL) 4 laboratories and restricted by lack of a natural animal model to study the disease, NSDV may act as a suitable model to study haemorrhagic nairoviruses." ] },{ "paper_id": "c6c8b82bc5a800425b075540eff41b0af719f80f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Editors of medical journals accept that published research should be open to comment and correction in published correspondence ( [1] ; Box 1). \"Post-publication peer review\" enables comments on, clarifi cations of, and corrections to published research. All journals should have a correspondence page for this purpose.", "I am disappointed that PLoS Medicine has imposed a time limit of four weeks on correspondence. As explained above, I believe that such a limit is mistaken. The word limit of 750 words is generous by comparison to established general medical journals, but even this should be open to fl exibility should the circumstances merit it.", "Cancer Research UK/NHS Centre for Statistics in Medicine Oxford, United Kingdom E-mail: doug.altman@cancer.org.uk" ] },{ "paper_id": "c6d8bc1c51f8962ffbeb497c413e3e5e225b9c3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although the molecular tools to conclusively identify these membranes as autophagosomes would not be available for years, the evidence for double-membraned vesicle formation during picornavirus infection has been accumulating for more than half a century. Many questions remained-first and foremost being what role these vesicles play in the virus life cycle and the interaction between the virus and its host.", "In 1962, Samuel Dales and Richard Franklin published a fine structure study of murine L cells infected with encephalomyocarditis virus (EMCV) [7] . The images demonstrate cytoplasmic regions filled with multi-lamellar structures, which we would now identify as autophagosomes. This study marks the first demonstration that we can find of autophagic induction in a picornavirus-infected cell. Although large crystalline arrays of virus are observed in the cytoplasm, it is difficult to tell if any are within the membrane-bound cytoplasmic bodies.", "The second hypothesis is that RNA replication takes place on small vesicles containing trans-Golgi markers, as observed for human parechovirus, Theiler's murine encephalomyelitis virus, and one strain of human rhinovirus (HRV), HRV-1A [20] [21] [22] [23] . It is presumed that these small vesicles derive from breakup of the Golgi apparatus during infection, and as yet there has been no follow-up work to elucidate the mechanism of their formation. There may be overlap between these vesicles and the COPII vesicles observed during PV infection." ] },{ "paper_id": "c6e2851ef1f6e35c2954eeaa913f2da2502842d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where F k (k = 2, 3, 4, 6) is the mean F k values for k-fold degenerate amino acids, which is estimated with the formulae:", "where n is the total number of occurrences of the codon for that amino acid and", "where s represents the given GC 3 %.", "The complete genome sequences and coding sequence annotations of 31 ZIKV strains available at the time of study were obtained from the National Center for Biotechnology (NCBI) GenBank database 16 and the Virus Pathogen Resource database, 17 accessed on 10 February 2016. The demographics of the selected strains are given in Supplementary Table S1 ." ] },{ "paper_id": "c6e40c6e9f16528e3a7495481311cff9a886d86e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Such dissemination, were it to occur, could have other benefits. Some have hope for its educative and potentially transformative nature:", "Even now, more than two decades after his lament, few health workers appear to have grasped the immense significance of humans' alteration of the planet, likely to unfold in the coming decades. ", "Biogeochemical flows (nitrogen and phosphate)" ] },{ "paper_id": "c6e4261e1a6aa596741c8af357661827bff2c468", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Text S1 Supporting information.", "SwissProt ID AAK1 Q2M2I8 ACTR2 P61160 ACTR3 P61158 CAV1 Q03135 CAV2 P51636 CLTC Q00610 DAB2 P98082 DNM1 Q05193 DNM2 P50570 DYNC1H1 Q14204 DYNC2H1 Q8NCM8 EPS15 P42566 FLOT1 O75955 FLOT2 Q14254 LAMP1 P11279 MYO6 Q9UM54 NSF P46459 PAK1 Q13153 RAB5A P20339 RAB5B P61020 RAB5C P51148 RAB7A P51149 RAB7B Q96AH8 SNX1 Q13596 VCL P18206 VPS11 Q9H270 VPS33A Q96AX1 VPS39 Q96JC1 VPS41 P49754", "(PDF)" ] },{ "paper_id": "c6e819e9d3fdfd19cafd2ddf160b9ed2cfd9a27a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Toronto experienced the largest outbreak of SARS in North America, with investigation of 2,132 potential cases and identification of 23,103 contacts of SARS patients who required quarantine [11] . Post-SARS investigations have detected myriad adverse effects among those quarantined: significant feelings of uncertainty, anxiety, and isolation [14] ; experience of stigma, fear, and frustration [15] ; symptoms of depression and post-traumatic stress disorder [16] ; and loss of anonymity [17] .", "iii.", "iv.", "Bi-variate and multivariate analyses were performed to investigate the inter-relationships among variables. All analyses were performed using SPSS 11.0 for Windows. No statistical weighting of the data was performed." ] },{ "paper_id": "c6ee9f876eedfbe7aa60473dcad1e8fcdc4c3a2d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c6fa41b3711b116f3c39583812a0088793388395", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2017, 9, 262 10 of 23", "A part of extracted cDNA was measured by a Q-PCR to quantify the expression level of specific genes. Reagents prepared for Q-PCR included forward and reverse primers (2.5 \u00b5M), 10 \u00b5L SYBR green supermix (Kapa Biosystems, Wilmington, MA, USA), 4 \u00b5L cDNA template and 5.2 \u00b5L ddH 2 O, making a final volume of 20 \u00b5L. The thermal cycles included 10 min of activation with AmpliTaq at 95 \u2022 C and 40 cycles of amplification consisting of 15 s for denaturation at 95 \u2022 C and 60 s for amplification at 60 \u2022 C, with an Applied Biosystems 7500 Real-Time PCR system (Applied Biosystems, Carlsbad, CA, USA). Primer pairs used in this experiment are listed as follows: 18S rRNA forward, 5 -ATTGACGGAAGGGCACCACCAG; 18S rRNA reverse, 5 -AGAACGGCCATGCACCACTACC (for the internal control); D2V2 forward, 5 -TGGACCGACAAAGACAGATTCTT; D2V2 reverse, 5 -CGYCCYTGCAGCATTCCAA (for DENV2).", "Each comparison between two means was analyzed by Student's t-test at a significance level of \u22640.1, 1 or 5%. For those more than two means, a one-way analysis of variance (ANOVA) was used for the statistical test at the same level of significance." ] },{ "paper_id": "c6fde7aab8fedbe212cac83d89064d4fb74089b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reverse-transcriptase polymerase chain reaction (RT-PCR)", "Classical RT-PCR assays proved to be a sensitive and specific tool for routine diagnostic purposes [19, 15] , particularly in decomposed samples [20, 21, 22] or archival specimens [23, 24] .", "The diagnosis of rabies is routinely based on" ] },{ "paper_id": "c71d6e115ba17a5b6263cf65de99c7c0fa7d487a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c726b09add3a385ad9b4fa87e54130d78194dcd2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In this study 7,455,180 reads with an average length of 146 bases were generated and these sequences were de novo assembled into 24,945 contigs and 100,880 reads remained as singletons.", "Background: Ducks (Anas platyrhynchos) an economically important waterfowl for meat, eggs and feathers; is also a natural reservoir for influenza A viruses. The emergence of novel viruses is attributed to the status of co-existence of multiple types and subtypes of viruses in the reservoir hosts. For effective prediction of future viral epidemic or pandemic an in-depth understanding of the virome status in the key reservoir species is highly essential." ] },{ "paper_id": "c736a6c9e4e639e9102e4b95136a53cd99ad2def", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c73992ad20d48db3c7d34e9c85bff5e541598691", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Norovirus|Norovirusses|Norwalk|\"smallround-structur\"|srsv animal|animals|reservoir|nonhuman| zoonosis|zoonoses|\"disease model\"", "1.", "Pathology; pathological examination results. 5." ] },{ "paper_id": "c73aa8452ccd63758df52737aae67450f078e76b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Titration curves with CaCl 2 , MnCl 2 , MgCl 2 and ZnCl 2 were performed at 1 mg/ml protein in gel filtration buffer using thermal shift assay. Technical details can be be found in [41] .", "The Endonuclease Activity is Essential for RNA Transcription, not Replication", "Crystals grew in LiSO 4 250 mM, citrate 50 mM, isopropanol 5.5%, using the hanging drop vapor diffusion method in Linbro plates by mixing 1 ml of protein solution with 1 ml of reservoir solution. Crystals were cryoprotected by dipping in a solution containing 65% of crystallization buffer and 35% of a buffer made of size exclusion chromatography buffer/glycerol (50/50) . Crystals were cryo-cooled in liquid N 2 . The crystals belong to space group C222 1 and have two molecules per asymmetric unit. Despite repeated attempts, crystal soaked into the above buffer supplemented with various concentrations of MnCl 2 yielded crystals diffracting to .4 \u00c5 .", "A standard CDD search from the sequence of Tensaw virus allows retrieving all the L of the Bunyaviridae family hitting the pfam 04196 [40] .", "7 mg of purified protein were incubated for 15 min at 25uC, with 0.5 ml of the various a-32 P NTP (0.4 mCi/ml) in 10 ml of reaction buffer containing 10 mM Imidazole, pH 8.0, 50 mM NaCl, 2 mM DTT. The reaction mixtures were then exposed to UV light (254 nm) for 6 min at 5 mm distance. The crosslinked species were separated in a 15% polyacrylamide denaturing gel and visualized by autoradiography using photo-stimulated plates and a Fujilmager (Fuji)." ] },{ "paper_id": "c73f20f4c23082587dce9f31bfd6f76d4a7ed6c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at www.mdpi.com/2076-0817/6/4/53/s1, Table S1 : The gene-wise (partial/complete) accession number details of avian rotavirus D.", "Rotaviruses constitute the genus Rotavirus, which is one among 15 genera within Reoviridae family. Reoviridae is further subdivided into two sub-families, Sedoreovirinae and Spinareovirinae [6] (Figure 2 ). ", "Rotaviruses constitute the genus Rotavirus, which is one among 15 genera within Reoviridae family. Reoviridae is further subdivided into two sub-families, Sedoreovirinae and Spinareovirinae [6] ( Figure 2 )." ] },{ "paper_id": "c74616a5ce5f794dde0644f4cb72bf8a196028a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Severe morbidity, mortality, and respiratory disease following influenza transmission from infant to mother", "doi:10.1371/journal.ppat.1005173.g009", "doi:10.1371/journal.ppat.1005173.g010" ] },{ "paper_id": "c751c8772ce889d767d8896227d82d3f8f5f3bab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "If n(k) = / 0 then stop iteration of k.", "(S18)", "." ] },{ "paper_id": "c754ce4a15d6efa184842b77848e34d04445e209", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c756b061cd3d68d5167d5f8bec332d2763fae0ac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2012 Nature Reviews Neuroscience 1204", "Gastroenterology 602", "Cell 525" ] },{ "paper_id": "c75994b5485339cdf4180bedab58e60366e49740", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In these experiments EBOV-specific IgG levels were substantially decreased among HPIV-3 pre-immune NHPs; however, this hindrance was overcome when the NHPs were vaccinated with two doses of recombinant vector which was previously shown to offer complete protection against EBOV challenge [77] .", "A recent report that screened 2,200 molecules demonstrated that chlorophyllide was able to decrease the section of HBV DNA in a HBV antiviral assay. These results were obtained at compound concentrations which exhibited no cytotoxic effects. This molecule is an alkylated porphyrin containing copper and as such this compound is carries a charge at neutral pHs [175] . During these screens, the chlorin e6 compound, a metal-free chlorophyllide-like molecule, was found to be the most potent and was subsequently tested against other viruses, including MARV. During testing, the chlorine e6 compound showed significant antiviral activity in vitro against MARV. This compound also inhibited Junin virus, DENV, HCV, and HIV-1 [175] .", "Filoviruses are named for their long, filamentous shape which can been seen on the order of micrometers in length, while their width is more narrow (usually around 80 nm) with little fluctuation [13] . Contained within this filamentous virus is a single, 19-kb negative-sense RNA genome that encodes seven proteins [14, 15] . The seven filoviral proteins are the glycoprotein (GP), the polymerase (L), the nucleoprotein (NP), a secondary matrix protein (VP24), the transcriptional activator (VP30), the polymerase cofactor (VP35), and the matrix protein (VP40) [16, 17] . Homotrimers of the viral GP cover the surface of the virion, and this viral GP is believed to be the sole host attachment factor for filoviruses [6, 18] . Candidates for filoviral receptor and co-factors include transferrin, DC-SIGN, TIM-1, and NPC1 [16, [19] [20] [21] [22] . After entry, filoviruses replicate their genomes and viral proteins in the cytoplasm using a RNA-dependent RNA-polymerase which is carried in with the virus.", "The current clinical standard for filoviral infection is supportive care as there are currently no FDA-approved treatment strategies. Supportive care consists of oral fluid rehydration, oral medication, nutritional supplementation, and psychosocial support [25] . Nasogastric feeding tubes and i.v. administration of both fluids and medication are increasingly considered supportive care where possible during outbreak scenarios to prevent dehydration and facilitate support of blood pressure [25, 26] . However, given the limited equipment and laboratory support during outbreaks, care must be taken to prevent overaggressive fluid administration [27] . Fluid replacement was evaluated briefly in rhesus macaques, and while there was no significant benefit to survival, a less severe renal compromise was observed [28] . While supportive care may (or may not) reduce the overall case fatality rate in humans, the true impact of simple interventions such as fluid management has yet to be fully evaluated and the potential for benefit in combination with direct antiviral measures has yet to be assessed [29] ." ] },{ "paper_id": "c75ed4c49d52ac5862313eb9d22cad197df1c138", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "V H gene products were amplified with primer sets to introduce NcoI/BamHI sites (forward: 5\u2032-ATG TCT CTA TCC ATG GCC GTG ACG TTG GAC GA-3\u2032; NcoI site in boldface; reverse:", "Soluble expression of His 6 -tagged-scFvs in E. coli BL21 (DE3)" ] },{ "paper_id": "c760ba658ba0d10b96cf738e04f83f22bd15f3a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ul4 gene was amplified using previously published primers [26] . The PCR reaction was carried out in a total volume of 50 \u03bcL using HotStarTaq Master Mix Kit (Qiagen; Hilden, Germany) and 0.4 \u03bcM concentration of primers. The thermal profile for the PCR was 95\u00b0C for 15 min, followed by 35 cycles of 95\u00b0C for 1 min, 60\u00b0C for 45 s and 72\u00b0C for 1 min. The final extension step was performed at 72\u00b0C for 5 min.", "Ninety-five per cent confidence intervals (CI) for the standard errors (SE) were estimated from the expression se95% CI = 1 \u00b7 96(p [1-p])/n1/2.", "Natural transmission of Suid Herpesvirus 1 requires close contact between animals such as during coitus, licking, or nuzzling. Although, in high density commercial farms, sneezing and short distance droplet spreads are major routes of transmission [20] .", "DNA was extracted from pools of spleen and kidney tissues respectively using QIAamp DNA Mini Kit (Qiagen; Hilden, Germany), following the recommended tissue protocol.", "The amplified products were analysed by electrophoresis through 1.5 % agarose gel containing 0.5 mg/mL ethidium bromide. Each PCR run included positive and negative controls.", "AD is also named pseudorabies (PR) and the virus Pseudorabies Virus (PRV), because carnivores and pigs may display neurological signs which can be similar to rabies." ] },{ "paper_id": "c77304ebab5efc8f6d8af8b9a04e8614882523e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, seasonal dynamics seemed to differ across different states, with Minnesota, North Carolina, and Nebraska having more consistent seasonality than Iowa, and Illinois. Furthermore, there seems to be a secular pattern in the southern and southeastern regions of the country, with large epidemics occurring every 2-4 years (18, 19) .", "For the last 10 years (2008-2018), PRRSv has maintained stable incidence levels on an annual basis, with an increase in the number of outbreaks, colloquially referred to as \"PRRS season, \" consistently starting between mid-October to mid-November (16) . The only period that showed a substantial different incidence, compared to other periods, was in 2013-2014, when PEDv was first detected in the US (17) .", "Since its inception in 2011, the MSHMP has played a critical role in providing data that scientists translated into science-driven solutions to help the US swine industry mitigating PRRSv impact. Here, we summarize some important swine disease features that the MSHMP has helped to elucidate and that promoted engagement and participation among producers." ] },{ "paper_id": "c77f37d083293f7461d47471caa670e765270948", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MGC45438 hypothetical protein MGC45438. Type I membrane protein (LOCATE).", "NIP hypothetical protein FLJ32334 (DUOXA1). Multi-pass membrane protein (Ensembl-Gene ENSG00000140254: inferred from electronic annotation).", "PERP PERP, TP53 apoptosis effector. This tetraspan protein localizes to the plasma membrane, rather than to mitochondria, and may stimulate apoptosis (Ihrie and Attardi, 2004) .", "Structure information: 1E4J Crystal structure of the soluble human FC-gamma receptor III (Sondermann et al. 2000) ." ] },{ "paper_id": "c798225c8b1b45e38fcd6163a711500c1f667b03", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A small membrane protein family called the interferon-inducible transmembrane (IFITM) was recently discovered and is under active exploration. This family restricts a wide range of pathogenic viral infections, with different inhibitory extents for different viruses 1-3 . For example, IFITMs inhibit the cellular entry and replication of human immunodeficiency virus (HIV), the influenza A virus, vesicular stomatitis virus, the rabies, the West Nile virus, the dengue virus, the SARS corona virus, the Marburg virus, the Ebola virus, the Semlikiforest virus and other viruses 3-9 . Five members of the IFITM family have been identified in human cells, including IFITM1, IFITM2, IFITM3, IFITM5 and IFITM10 10 . Among them, IFITM1, 2 and3 can be induced by both type-1 and type-2 interferons 2 . IFITM5 cannot be induced by interferons, but it is involved in bone mineralization 11 . The detailed function of IFITM10 remains unclear 12 . IFITM2 and 3 are typically concentrated in the endosomal membrane, the lysosomal membrane or other intracellular compartments. Their subcellular distributions depend on the cell or tissue type and their expression level, but IFITM1 is expressed mainly on the plasma membrane 13,14 .", "Scientific RepoRts | 6:24029 | DOI: 10.1038/srep24029" ] },{ "paper_id": "c79cfa0bb8017217a2626f1b4aafdfdab162a8ce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Monoisotopic peak lists were generated in flexAnalysis 3.3 (Bruker) by SNAP algorithm. Precursor spectra with signal-tonoise less than ten were removed, and the remaining masses were externally recalibrated. Fragment spectra were smoothed using Savitzky-Golay algorithm (three cycles with 0.15 m/z width), the baseline was subtracted with TopHat algorithm, and filtering was done on signal-to-noise level five.", "Data were acquired on ultrafleXtreme TOF mass spectrometer (Bruker) operated by flexControl 3.3 (Bruker) in positive reflector mode. For each position on the target 4000 laser shots were summed in 700-3500 m/z range. Next, we selected the 25 most intense precursor ions per sample for fragmentation with signalto-noise threshold 15. Tandem mass spectra were recorded by accumulation of 3000 shots in LIFT mode using LID (laserinduced dissociation) mechanism. Laser power was boosted by 50% without collision gas, and the detector voltage was increased by 80%.", "We would like to thank Dr. Gabriela Flores-Ramirez from the Department of Rickettsiology, Institute of Virology, BMC, for her technical assistance.", "Persistent viral infections are currently one of the most important global health problems in the world. Understanding how viral persistence is initiated and maintained, and the pathological consequences of ongoing virus replication, is therefore of high importance." ] },{ "paper_id": "c7b16abf574515b631f758dc51170ef757fd58b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.", "Conclusion: Results indicate that LDV-induced activation of lymphocytes is due to recognition of LDV nucleic acid by TLR7 pattern recognition receptors in pDC's that respond with a lymphocyte-inducing IFNa response.", "Background: Lactate dehydrogenase-elevating virus (LDV) is a natural infectious agent of mice. Like several other viruses, LDV causes widespread and very rapid but transient activation of both B cells and T cells in lymphoid tissues and the blood. The mechanism of this activation has not been fully described and is the focus of the current studies." ] },{ "paper_id": "c7b980605c4ba138f35378e5f56b95e677cc87c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Real-time quantitative reverse transcription (RT)-PCR and enzyme-linked immunosorbent assay (ELISA). Following the indicated treatment, total cellular RNA was extracted from HEK-293T cells using TRIzol reagent (Invitrogen), after reverse transcription with oligo (dT) primer using a Transcriptor First Strand cDNA Synthesis Kit (Roche), the products were subjected to SYBR green PCR assay (Applied Biosystems) using gene-specific primers designed with Primer Express software v.3.0 (Applied Biosystems). The supernatants from infected cells were collected and subjected to ELISA using a commercial human IFN-\u03b2 kit (TFB).", "Mouse monoclonal anti-HA, anti His, anti GST and anti-beta-actin antibodies and rabbit polyclonal anti-USP15, anti-ubiquitin, anti-IRF3, and anti-phosphor-IRF3 antibodies were purchased from ABclonal Biotechnology. Other antibodies used in this study included anti-Flag monoclonal antibody (Macgene, China), anti-Myc monoclonal antibody (Beyotime, China), and anti-NF-\u03ba B p65 and anti-phosphor-NF-\u03ba B p65 polyclonal antibodies (Cell Signaling Technology). Horseradish-peroxidase-conjugated anti-mouse and anti-rabbit I gG antibodies were purchased from the Beyotime Institute of Biotechnology (Jiangsu, China). SEV was obtained from the Centre of Virus Resource and Information, Wuhan Institute of Virology, Chinese Academy of Sciences. The recombinant VSV expressing GFP (VSV-GFP) was generously provided by Prof. Zhigao Bu, Harbin Veterinary Research Institute, P. R. China.", "GST pulldown assays. Purified GST or GST-RIG-I-N proteins expressed in E. coli (BL21 cells) were conjugated to glutathione beads (GE Biosciences) at 4 \u00b0C for 2 . These beads were washed 5 times with lysis buffer and incubated with purified USP15 C250 (expressed in E. coli BL21 cells) at 4 \u00b0C for 6 h. After washing 5 times with lysis buffer, the beads were boiled in sample loading buffer and subjected to immunoblotting with indicated antibodies." ] },{ "paper_id": "c7bbdf2417a1b37fd9c1886c186e7a1b6fedc6ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "University of Basel 9", "The Aga Khan University 8", "Fudan University 8 " ] },{ "paper_id": "c7bf679ec25305b15089e89885f393de974be10d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(iii)Measurement of assay sensitivity using sequential samples", "Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-stranded enveloped RNA virus which belongs to the genus Arterivirus, family Arteriviridae and order Nidovirales [1] . Recently, a new proposal has classified PRRSV isolates into two species in the genus Porartevirus, PRRSV-1 and PRRSV-2, that replace their previous designations of European-like and North American-like genotypes, respectively [2, 3] .", "(i) Cutoff determination, diagnostic sensitivity and diagnostic specificity" ] },{ "paper_id": "c7c6c6ff7580f79ffba12017575ac3ccca4bc9b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These molecular initiatives and their corresponding downstream effects are collectively known as the unfolded protein response (UPR). This evolutionarily conserved countermeasure induces pro-survival responses including global arrest of protein synthesis, upregulation of protein degradation factors, and enhanced protein folding capability [45] . However, under severe ER stress conditions, UPR will instead trigger apoptosis.", "ZIKV-infected patients typically present mild clinical symptoms such as fever, maculopapular rash, conjunctivitis, and arthralgia [2] . Nevertheless, the second ZIKV outbreak in French Polynesia in 2013 provided the first compelling relationship between ZIKV infection and a neurological complication, where a woman was diagnosed with Guillain-Barr\u00e9 syndrome (GBS), an autoimmune disease typically affecting motor neuron functions, a week following the onset of ZIKV-like symptoms [4] . This epidemic also recorded a 20-fold increase of GBS incidence, where 41 GBS-diagnosed patients (98%) were serologically positive for ZIKV [2, 5] .", "Reticulophagy, also known as ER-phagy, is mediated by ER-phagy receptors such as Family with Sequence Similarity 134 Member B (FAM134B) and reticulon-3 (RTN3) proteins that reside on the ER membrane. These autophagy receptors sequester ER fragments via its LC3-interacting-region (LIR) domain interaction with autophagosomal-presenting microtubuleassociated protein 1 light chain 3 (MAP 1LC3) [87] . Similar to other ER-shaping proteins, FAM134B also possesses a reticulon homology domain (RHD), a motif that promotes membrane curvature [87] ." ] },{ "paper_id": "c7c91a1ce95ce401750cb856d14d48683a0e4fb7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "minfDSD,DS'Dg :", "If v is a similarity metric, the the problem becomes a minimisation problem, v expresses distance the goal is maximisation.", "It turns out that even using the average cut, one cannot simultaneously minimise the inter-cluster similarity while maximizing the similarity within the groups." ] },{ "paper_id": "c7cd6b41d8526f865821abc06fc4bb17923f16f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c7d1c17055c7320e8d2a0cca313bddc7dcb3d401", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c7d52191db94d11ad1d56bb48ecc64656b44a613", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Who pays for the data collection and knowledge production?", "How are the data communicated, by whom, to whom?", "The balance of emphasis may vary by setting, because the different institutional imperatives of the various data producers and users are not going to disappear. However, we would argue that more inclusive engagement could turn a vicious into a virtuous circle, beginning with greater investment in local data production, interpretation and use.", "ARTICLE HISTORY" ] },{ "paper_id": "c7d60067e11331d3c5e1f9b1d79e70caacb13f25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c7d6dd30a24a63898307d3d9e1dd6ca13a6cf9bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mechanisms of redox-induced regulation of Na/K-ATPase activity include S-glutathionylation, S-nitrosylation, carbonylation, phosphorylation, and 4-hydroxynonenal exposure; oxygen-derived free radicals, H2O2, NO, and oxidized glutathione are the signaling messengers that make Na/K-ATPase \"redox sensitive\" in different cell types.", "Molecules 2016, 21, 1172 3 of 12 epitope and the disinhibition of the tyrosine kinase function of Src with attendant downstream signaling. Downstream activation of PLC, PI3K and PKC has also been established. This model is shown schematically in Figure 2 , and in our admittedly biased opinion, constitutes an important advance in our understanding of sodium pump signaling [1] .", "Adipocyte mitochondrial dysfunction is also proposed as one of the reasons there is increased ROS production in obesity [38, 46] . In mouse models of obesity, the mitochondrial population is approximately 50% lower in white adipocytes from obese mice, compared to control mice. Furthermore, about 50% of gene transcripts encoding mitochondrial proteins are decreased with the onset of obesity in white adipocytes from obese mice compared to control mice [49] ." ] },{ "paper_id": "c7d8100f9f9f799f495a0458c8f23dcc7bcec3ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Objective: Cineole has mucolytic, bronchodilating and anti-inflammatory properties and reduces the exacerbation rate in patients suffering from COPD, as well as ameliorates symptoms in patients suffering from asthma and rhinosinusitis. Based on these effects, we therefore postulated the hypothesis that patients with acute bronchitis would also benefit from therapy with Cineole.", "Randomisation was sequentially assigned in balanced blocks of 4 from a computer-generated list (random, idv Data-Analysis& Study Planning, Krailling, Germany). After the randomisation, the following patient details were recorded: height; weight; age; time from the first diagnosis of asthma symptoms; documentation of allergies; concomitant disease; prescribed medication; assessment of the current maintenance therapy. Control visits were carried out after 4 and 10 days, when adverse events were recorded and compliance with the treatment plan, as well as potential changes to therapy were addressed.", "Trial registration: ISRCTN: ISRCTN37784439" ] },{ "paper_id": "c7d86587837b09a6b722f78beac7bfedaa0333d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Coagulase-negative Staphylococcus epidermidis has become a major frequent cause of infections in relation to the use of implanted medical devices. The pathogenicity of S. epidermidis has been attributed to its capacity to form biofilms on surfaces of medical devices, which greatly increases its resistance to many conventional antibiotics and often results in chronic infection. It has an urgent need to design novel antibiotics against staphylococci infections, especially those can kill cells embedded in biofilm.", "The compounds were injected for 120 s, and dissociation was monitored for more than 150s (see Methods).", "play a certain degree of specificity dependent on the characteristics of the HATPase_c domain structure in the different HKs." ] },{ "paper_id": "c7d87ef17e8863714b7ccd091373777918e9131d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Middle East respiratory syndrome coronavirus (MERS-CoV) has caused several hospital outbreaks, including a major outbreak at King Abdulaziz Medical City, a 940-bed tertiary-care hospital in Riyadh, Saudi Arabia (August-September 2015). To learn from our experience, we described the critical care response to the outbreak.", "Our MERS-CoV hospital outbreak stressed our system to unprecedented limits. We learned many lessons from it ( Table 4 ). The successful management of outbreak required integrating ICU functions with the hospitalwide plans, having preparedness plans, implementing proper infection control practices and managing staffing and staff exposure.", "Descriptive data were presented as means and standard deviations or frequencies and percentages, as appropriate. The infection prevention and control consumables were compared in the 4 months before (April to July) and the 2 months during (August and September) the outbreak. " ] },{ "paper_id": "c7ddb36588a83decb4c6bcd033f9a0b208e66973", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recombinant human IFN-\u03b21a was purchased from PBL Interferon Source (Piscataway, NJ, USA), and recombinant human IFN-\u03b3 from PeproTech (Rocky Hill, NJ, USA). The mouse anti-actin monoclonal antibody (clone AC-40) and the mouse anti-FLAG (clone M2) were from Sigma-Aldrich (Saint-Louis, MO, USA). Polyclonal antibodies against STAT1 (06-501), phospho-STAT1 (Tyr701) (07-307) and phospho-STAT2 (Tyr 689) (07-224) were from Merck Millipore (Darmstadt, Germany). The rabbit polyclonal antibody against STAT2 (SC-476) was from Santa-Cruz Biotechnology (Dallas, TX, USA).", "An unpaired t-test or an unequal variance t-test were used to analyse the data. Differences were considered to be significant if the p value was <0.05." ] },{ "paper_id": "c7e5e64683c8dbf4d6585fd231d20a4d8ee3885e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study establishes the PS as a novel virulence factor for MHV, and likely other coronaviruses.", "Statistics. Student's unpaired t test or the Mann-Whitney U test was used to analyze differences in mean values between groups. All results are expressed as mean \u03ee range or \u03eestandard error of the mean where indicated. P values of \u05450.05 were considered statistically significant. Survival data were analyzed using Mantel-Cox tests (*, P \u03fd 0.05).", "Cell culture. 17Cl-1 cells, HeLa cells expressing MHV receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1a) (HeLa-MHVR), and baby hamster kidney cells expressing CEACAM1a (BHK-MHVR) were grown in Dulbecco's modified Eagle's medium (DMEM), with 10% fetal calf serum, 1% penicillin-streptomycin (Pen-Strep), 2% sodium bicarbonate, 2% L-glutamine, 1% nonessential amino acids, and 1% sodium pyruvate (D10). Low-serum medium is the same as D10 with 2% fetal calf serum (D2)." ] },{ "paper_id": "c7f5828ffb5dbc51bda8427bc64056b6eeb1afb0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was specifically approved by the Institutional Animal Care and Use Committee of the University of California at Davis with animal use protocol #16424.", "One milliliter of Trizol Reagent (Invitrogen, Carlsbad, CA) was added to 50-100 mg of frozen bronchial lymph node sample, which was immediately homogenized. Samples were centrifuged at 12,000 g for 10 min at 4\u00b0C and 200 \u03bcl of chloroform was added after transferring the aqueous layer to a fresh tube. After another centrifugation at 12,000 g for 10 min at 4\u00b0C, RNA from the aqueous layer was precipitated first with 500 \u03bcl of isopropanol and then washed with 1 mL of 75% ethanol. The pellet was dissolved in 100 \u03bcl DEPC water and placed at 4\u00b0C overnight. The following day, the RNA sample was DNase1 treated to remove potential contamination from genomic DNA. RNA purity and concentration was established using a NanoDrop 1000 v1.3.2 (Thermo Scientific, Wilmington, DE). The absence of RNA degradation was first assessed by electrophoresis of 1 \u03bcg of RNA on a 1.0% agarose gel. Finally, the quality of each RNA sample was evaluated using an Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA) with an RNA NanoChip.", "Since BRD is multifactorial and can be caused by a number of pathogens individually or as co-infections [26] , determination of disease etiology can be difficult. We found both common Table 3 . Differentially Expressed Genes with the Largest Expression Variances by Challenge Group.", "The sequence data were submitted to the National Center for Biotechnology Information Sequence Read Archive under accession number SRP052314. S1 Table contains the sample identification for the RNA-Seq data that corresponds to each of the experimentally challenged animals." ] },{ "paper_id": "c7f717457621e576d69c56b61d9ad9bd52a8a8b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total nucleic acid was extracted from respiratory specimens using QIAamp Viral RNA kit (Qiagen, Crawley, United Kingdom) according to the manufacturer's instructions." ] },{ "paper_id": "c7fbc3c2ef9549d8a6531237b2e9d09cf09a6567", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A variety of materials, including silicon, glass, soft or hard polymers and biomaterials (e.g., calcium alginate, cross-linked gelatine or hydrogels) have been used for microfabrication [24] . The choice of polymeric materials is often limited to solvent-resistant materials, such as Teflon, photopatternable silicon elastomers, thermoset polyesters, poly(methylmethacrylate) (PMMA) and patterned poly-(dimethylsiloxane) (PDMS), polyimide and SU-8 (negative photoresist) polymers [25, 26] .", "LOC-based pathogen sensors are competitive with laboratory-scale technologies in the analysis of complex biological samples. The analysis of a biological sample involves various processing steps, such as sample preparation, analyte enrichment, labelling, signal amplification and signal detection, that are performed on the chip. Therefore, only highly integrated micro-devices, or -micro total analysis systems\u2016 (\u03bcTAS), have real-world applications [23] .", "Environmental pathogens often exist in food and water; these pathogens include bacteria, viruses, parasites and toxins [64] . Prior to the advancement of nanotechnology, medical professionals had difficulty detecting any case of biopathogenic outbreak before a report of symptoms from an infected host (plant or animal). The infection of a host (i.e., a human) can lead to quarantine to limit further transmission of the disease, depending on the pathogen type. The pathogenic threat to humans and the environment has necessitated quick biopathogen detection and identification [65] for better monitoring. Microfluidics-based LOCs can serve this purpose." ] },{ "paper_id": "c819bee642ae0f97b4d9e85a8558ccc1537dab2f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total DNA was extracted using the PowerSoil DNA Isolation Kit (MoBio, Solana Beach, CA, USA) and used as template for polymerase chain reaction (PCR) amplification with primer set 341F (5'-CCTACGGGNGGCWGCAG-3' and 805R: 5'-GACTACHVGGGTATCTAATCC-3') targeting the V3-V4 region of the 16S rRNA gene. Amplifications were performed in a final volume of 50 \u03bcl containing 10X Taq buffer, dNTP mixture, 10 mM of each primer and 2 U of Taq polymerase (ExTaq, Takara, Japan). Cycling conditions in C1000 Touch thermal cycler (Bio-Rad, Hercules, CA, USA) were: initial denaturation at 95\u02daC for 3 min; followed by 25 cycles of 95\u02daC for 30 s, 55\u02daC for 30 s, 72\u02daC for 30 s; with final extension at 72\u02daC for 5 min [38] . The PCR products were confirmed using gel electrophoresis and purified using the Agencourt AMPure XP Reagents beads (Bechman Coulter, Brea, CA, USA). Equal amounts of purified product were pooled, and final product quality were assessed on a Bioanalyser 2100 (Agilent, Palo Alto, CA, USA) using a DNA 7500 chip. Sequencing was performed by Chunlab Inc. ", "Introduction Bats (Order: Chiroptera) are highly diverse and ecologically valuable comprising 25% of living mammalian species. The most abundant group of mammals based on the number of individuals, they evolved into an incredibly rich diversity that roost in foliages, caves, rock crevices even in man-made structures [1, 2] . They feed on insects, nectar, fruits, seeds, fish, frogs and small mammals [3, 4] .", "Data preprocessing and taxonomic classification of C1 and C2 sequence reads were carried out in Mothur pipeline [39] . Forward and reverse reads, after primer and barcodes removal, were aligned to form one continuous DNA sequence. Sequences that contained ambiguous bases less than 430 bp in length, or with homopolymers of greater than 8 bp were discarded. Chimeras were identified and removed using UCHIME [40] . SILVA reference database release 128 [41] was used for sequence alignments and classification. The microbial diversity was analyzed using QIIME software [42] . In addition, the upstream analyses of microbial sequences through Mothur pipeline were also complemented with QIIME tool.", "A combination of several approaches on bat survey, namely, live-trapping with mist nets, acoustic monitoring using bat detector and visual surveys, were used. Bats inside Cabalyorisa Cave were mainly insectivorous and identified as Miniopterus australis, little long-fingered bat or little bent-winged bat; M. schreibersii, a common bent wing bat and Rhinolophus amplixedectus, the horse shoe bat. Encinares (2016) documented that aside from macroarthropods, microarthropods observed included isotomid, sminthurid and an unidentified springtail, Geolaelaps, Oplitis, Deraiophorus, two uropodids and one oribatd mite, and an unidentified brown ant. Presence of these microarthropods confirmed the insect-feeding nature of the bats roosting in Cabalyorisa Cave [36] ." ] },{ "paper_id": "c82205e91bbd1135020b4fdf0d9df2654c66650a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ", with c~0:6213 : i.e. the normalized reactivity was set to = 1 if t was equal to the average of the top 10% non-outlier data. These preprocessing steps were carried out in MATLAB.", "Three hundred and sixty mL of the folded RNA was treated with 40 mL of 50 mM 1-methyl-7-nitroisatoic anhydride (1M7) in DMSO and another 360 mL aliquot of the folded RNA was treated with 40 mL neat DMSO. Both were subsequently incubated at 37uC for 4 min. 1M7-modified RNA (+), and DMSO control RNA (2) were recovered by ethanol precipitation (with 200 mM NaCl, 2 mM EDTA, and 800 mg glycogen) and resuspended in 400 mL of 0.56 TE.", "cDNA samples were separated in a 33 cm long (75 mm inner diameter) capillary using a Beckman CEQ800 DNA sequencer. Samples were denatured at 90uC for 120 seconds, injected at 2.0 kV for 6 to 15 sec, and separated at 4 kV for 80 min." ] },{ "paper_id": "c8233094deb36e03c7c73fd03f3bab601498e563", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RPL14 forward -5\u2032TTCATCCTCAAGTTTCCGC3\u2032 RPL14 reverse -5\u2032TTCAATCTTCTTGGCCCATC3\u2032 RPL10 forward -5\u2032TGAAGACATGGTTGCTGAGAAG3\u2032 RPL10 reverse -5\u2032GAACGATTTGGTAGGGTATAGGAG3\u2032.", "The MERS-CoV qPCR primer sequences used were: Forward primer for genomic RNA and mRNAs -5\u2032GAATAGCTTGGCTATCTCAC3\u2032 Genomic RNA reverse primer -5\u2032CACAATCCCACCAGACAA3\u2032 ORF2 reverse primer -5\u2032AGTGTATCATTGTCACGGATAAG3\u2032 ORF5 reverse primer -5\u2032ACTAGCTGGACGGGTTTA3\u2032", "The Influenza qPCR primers sequences used were: Genomic forward primer (VN1203, NL602 and CA04) -5\u2032GGCCGTCATGGTGGCGAAT3\u2032 Genomic reverse primer (VN1203) -5\u2032GTTCCCCACCAGTTTCCATC3\u2032 Genomic reverse primer (NL602 and CA04) -5\u2032GCTCCCCACCAGTCTCCATT3\u2032 Forward mRNA primer (VN1203, NL602 and CA04) -5\u2032CCAGATCGTTCGAGTCGT3\u2032 Reverse mRNA primer (VN1203, NL602 and CA04) -5\u2032CGAACCCGATCGTGCCTTCC3\u2032" ] },{ "paper_id": "c825a4d277f3300983a01b6961865b8377e87cf0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the authors contributed equally to the design, writing, and editing of the review article.", "This study was supported by a Grant-in-Aid for Scientific Research (B)(2) (24380146, 16H05019), Challenging Exploratory Research (23658216, 26660216, 16K15028), and Open Partnership Joint Projects of JSPS Bilateral Joint Research Projects from the Japan Society for the Promotion of Science (JSPS) to HK and by an ANPCyT-FONCyT Grant PICT-2013 (No. 3219) to JV. This work was also supported by JSPS Core-to-Core Program A (Advanced Research Networks) entitled: \"Establishment of international agricultural immunology research-core for a quantum improvement in food safety. \" This study was also supported by grants for \"Scientific Research on Innovative Areas\" from the Ministry of Education, Culture, Science, Sports and Technology (MEXT) of Japan (grant numbers: 16H06429, 16K21723, and 16H06435).", "Studies with the porcine IPEC-J2 cell line, demonstrated that L. rhamnosus GG reduced the mucin and IL-6 secretion response triggered by porcine rotavirus, diminishing the inflammatory damage (48) . Our own studies in PIE cells also demonstrated that selected immunobiotic strains were capable to upregulate IFN-\u03b2 expression in response to poly(I:C) stimulation (54, 55) .", "Keywords: immunobiotics, antiviral immunity, beneficial microbes, bovine rotavirus, toll-like receptor 3 pathway, inflammation, agricultural immunology iNTRODUCTiON Over the past decades, the global bovine production has been subjected to intensification, in order to improve efficiency of production because of the demand from a growing human population. The intensification of bovine production involved the application of confinement methods characterized by the concentration of animals in large outdoor feedlots or in specialized indoor environments. In confinement, the potential for transfer of pathogens among animals is higher, as there are more animals in a smaller space (1) (2) (3) ." ] },{ "paper_id": "c82d59add457527b2858fb5157a92634815d9387", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c831071c9229a681189522e08cfc3b64f84f95db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animals. Guinea ", "There is an urgent need for simple, portable and sensitive devices to collect, eliminate and identify viruses from air, to rapidly detect and prevent outbreaks and spread of infectious diseases 1 . Each year, infectious diseases cause millions of deaths around the world and many of the most common infectious pathogens are spread by droplets or aerosols caused by cough, sneeze, vomiting etc. 2-5 . Knowledge of aerosol transmission mechanisms are limited for most pathogens, although spread by air is an important transmission route for many pathogens including viruses 6 ." ] },{ "paper_id": "c8319e7c2950df8028c8b9d90581eff5e13df132", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The studies involving human participants were reviewed and approved by Human ", "MG and ZD conducted the survey and drafted the initial manuscript. NN, HH, NW-A, and WA designed and supervised the study. AB helped in statistical analysis, interpretation, and manuscript revision. All authors read and approved the final manuscript. ", "The datasets generated for this study are available on request to the corresponding author." ] },{ "paper_id": "c83a4991d36a6086da50b13968955329c5f07a6c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study received written approval from the Instituto Aragon\u00e9s de Ciencias de la Salud (IACS) review board.", "Nasopharyngeal aspirate was obtained and processed for viral antigens using the direct fluorescence antibody (DFA) assay, and two different polymerase chain reaction (PCR) viral tests. DFA was performed for influenza A and B, parainfluenza 1, 2 and 3, adenovirus (ADV), human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) (D3 Double Duet DFA Respiratory virus screening and ID Kit, Diagnostic Hybrids, Athens, USA). The first PCR was a multiplex RT-nested PCR assay for 14 respiratory viruses (influenza A, B and C, respiratory syncytial virus A and B, adenovirus, coronavirus 229E and OC43, enterovirus, parainfluenza 1, 2, 3 and 4, and rhinovirus) [21] ; the second test was a RT-PCR commercial kit, the ResPlex II Plus Panel (Qiagen LiquiChip System, Hamburg, Germany) [22] for detection of 18 viruses: influenza A and B, RSV A and B, parainfluenza 1, 2, 3 and 4, hMPV A and B, enterovirus (coxsackie/ echovirus), rhinovirus, adenovirus B and E, coronavirus NL63, HKU1, 229E and OC43, and bocavirus. Nucleic acids were extracted from nasopharyngeal aspirates immediately after their reception.", "Statistical analysis was performed using the SPSS statistical software package, version 15.0. The level of significance for all statistical tests was a 2-sided, p value of 0.05." ] },{ "paper_id": "c83b149dc7f5339bd3efa3128d991bb9b802b909", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results on sanitation practices ( ", "Industry are also acknowledged.", "The authors declare that they have no conflict of interest." ] },{ "paper_id": "c848bce30b9e60bccfd15a5534af1d0cea54c686", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Objectives: This study examined risk factors and biomarkers for ARDS development and mortality in two prospective cohort studies.", "This study was approved by the institutional review boards(IRBs) of the Peking university third hospital, Beijing Friendship Hospital, China-Japan Friendship Hospital, Beijing Chao-Yang Hospital, and Harvard School of Public Health and a written informed consent was obtained from each subject or an appropriateproxy of the patient." ] },{ "paper_id": "c850a9040414008da523d4ca13b8e61b36e0d98b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analyses of RNase L-mediated rRNA degradation. RNA was harvested with buffer RLT (Qiagen RNeasy no. 74106) and analyzed on an RNA chip with an Agilent Bioanalyzer using the Agilent RNA 6000 Nano kit and its prescribed protocol, as we have described previously (catalog no. 5067-1511) (19, 23) .", "Statistical analysis. Plotting of data and statistical analysis were performed using GraphPad Prism software (GraphPad Software, Inc.). Statistical significance was determined by two-way analysis of variance (ANOVA) for viral replication curves and by unpaired Student's t test for RT-qPCR.", "RESULTS" ] },{ "paper_id": "c851a889568efd469f724ebacfe3270946f3e04f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were pelleted (five minutes, 2086g), resuspended in 1 mL PBS, and pelleted again (five minutes, 2086g). Supernatant was removed and 2.5% glutaraldahyde solution (adjusted to pH 7.4 using HCl and to 400 mOsm using CaCl 2 ) added. Samples were processed and imaged by Dr. Gary Mierau, The Children's Hospital Department of Pathology/Laboratory Services, Aurora, CO. Briefly, samples were post-fixed in 2% cacodylate buffered osmium tetroxide (pH 7.4), dehydrated in a graded series of alcohols, and embedded in epoxy resin. Sections, approximately 80 nm in thickness, were stained with uranyl acetate and lead citrate prior to examination at 60 kV with a Zeiss EM-10 transmission electron microscope (Carl Zeiss Inc, Thornwood, NY).", "Limiting dilution nested PCR detection of cHV68 genome-positive cells", "cHV68 WUMS (ATCC VR-1465) and all recombinant viruses were grown and titered as previously described [72] . DK3TET 2 cHV68 (cHV68-GFP) containing a GFP cassette under the control of an immediate early CMV promoter was generated and characterized by Dr. Phillip Stevenson [73] . cHV68 containing a stop codon within ORF 72 (v-cyclin.STOP. cHV68) was previously described [18] ." ] },{ "paper_id": "c851e8a17951dc6f713c2a832e6a516f72154a79", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Brains and spinal cords from 4% paraformaldehyde perfused mice were removed and fixed overnight in 4% paraformaldehyde at 4uC. Tissues were embedded in paraffin and stained with hematoxylin and eosin to determine the extent of inflammation.", "Brains from PBS perfused mice were homogenized in 50 mM Tris-HCL 0.5% TritonX-100 pH 7.6 and clarified by centrifugation. 15 mg of homogenate were separated on polyacrylamide gels containing 1% gelatin (BioRad) in the absence of reducing agents. Gels were washed for 20 minutes and incubated in developing buffer (BioRad) for 2 days at 37uC. Gels were stained with Coomassie R-250 and destained in 10% acetic acid and 10% methanol. Quantification was performed with Image J software (v 1.42l, NIH) and expressed relative to sham activity.", "Brains and spinal cords from 4% paraformaldehyde perfused mice were removed and fixed overnight in 4% paraformaldehyde at 4uC and cryoprotected in 20% sucrose. Tissue sections (7 mm) were fixed in 4% paraformaldehyde and blocked in 10% normal donkey serum, 0.3% Triton X 100. Immunostaining for CXCL1 and GFAP was performed serially using polyclonal goat anti-CXCL1 (2 ug/ml, R&D Systems, MN) and polyclonal chicken anti-GFAP (1:500 Abcam, MA) overnight at 4uC. Cy-2 or Dylight 549 conjugated donkey secondary antibodies (1:200, Jackson ImmunoResearch, PA) were used for visualization. Hoechst 33342 (Invitrogen) was used to stain nuclei prior to mounting coverslips." ] },{ "paper_id": "c856a5583dad88feeb274cf1ba74ce99632d3d6c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protein samples were separated by SDS-PAGE and were electrically transferred onto a polyvinylidene fluoride (PVDF) membrane. After being blocked with 5% skim milk in phosphate-buffered saline (PBS), the membrane was incubated with proper antibodies and subsequently probed with appropriated horseradish peroxidase (HRP) conjugated goat anti-mouse secondary antibody. The protein bands were developed with the ECL western blotting system (Fisher Scientific) and exposed to a fluorchem E apparatus (Proteinsimple, Santa Clara, CA, USA). Western blotting bands are quantified according to intensity by using ImageJ software, normalized to \u03b2-actin and expressed relative to mock infection.", "These recombinant plasmids were identified by sequencing and fluorescence microscopy. The bright green fluorescence was observed from these recombinant plasmids-transfected cells, although the expression efficiency of each recombinant plasmid is different due to individual gene specificity (Additional file 2: Figure S1 and Additional file 3: Figure S2 ). This indicated that these PEDV structural and non-structural genes are correctly constructed and fused well with the EGFP gene.", "Porcine Epidemic Diarrhea (PED) is an acute and highly contagious enteric disease characterized by severe watery diarrhea, dehydration, and anorexia. Deceased piglets presented with thin and almost transparent small intestines containing undigested milk curdles. The etiological agent PED virus (PEDV) was first isolated and recognized from Europe in the 1970s [1, 2] , then it was spread and prevalent in Asian for decades [3, 4] . PEDV originally caused a relatively mild and sporadic disease. However, since more virulent variant strains appeared in 2010 [5] [6] [7] [8] , PEDV has been subsequently associated with severe outbreaks of diarrheal disease [9] in Asia and in North American [10] [11] [12] [13] . Acute PEDV outbreaks normally resulted in enormous economic losses to swine industries around the world, for instance, in 2013 to 2014 PEDV killed more than 7 million pigs in the North American [14] . Currently, PEDV poses a serious threat to the swine industry worldwide." ] },{ "paper_id": "c85ca5217f9051f83911569eed1eb52cf992f7dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GDH catalyzes the oxidative deamination of L-glutamate and its mutations cause hyperinsulinism or hyperammonemia syndrome in animals. GTCs, especially EGC, control dysregulated GDH by hijacking the ADP activation site [113] . XCA of the GDH-EGC complex has also been discussed in a previous paper [5] .", "XCA of certain features of EGCG complexes with Pin1 and transthyretin has also been described previously [5, 116, 117] .", "The authors declare no conflict of interest. " ] },{ "paper_id": "c86eba5cb05531b033922afbe3f9148d1cd3c5dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "with", "The Gibbs sampler alternates between sampling each Z i conditional on all other parameters and sampling each component of \u03b8 conditional on all other parameters. The Z i s are conditionally independent of each other, and each Z i is conditionally independent of (X 1 , . . . , X i\u22121 , X i+1 , X N ) given X i . Hence, the conditional distribution for Z i is given by:", "6 Gene expression 6 " ] },{ "paper_id": "c878b060760db3b59ae0129a5de677e56a30866e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Should WHO develop international recommendations?", "\u2022 How should recommendations be adapted?", "\u2022 The guideline should present key review criteria for monitoring and audit purposes.", "\u2022 WHO should provide detailed guidance for adaptation of international recommendations." ] },{ "paper_id": "c883fc2c4774529ce853012e339acf2aadc53454", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The HRV 5'UTR and VP4/VP2 PCR products were purified with a QIAquick PCR purification kit (Qiagen, Hilden, Germany) and sequenced on an ABI 310 sequencer with a fluorescent dye terminator kit (Applied Biosystems, Foster City, CA, USA). The nucleotide sequences were aligned with known HRV sequences from GenBank, including HRV Ca and Cc reference strains [27] , using CLUSTALX software. A neighbour-joining phylogenetic tree was constructed using the Treecon software program (version 1.3b) with 500 bootstrap resamplings [28] . GenBank accession numbers are HM623207-HM623277.", "Continuous variables were expressed as median and inter quartile ranges and compared using Kruskal-Wallis Test. Categorical characteristics were analysed using Fisher's Exact test. A p-value of < 0.05 was considered statistically significant." ] },{ "paper_id": "c890cb0b691543c29b35b5a1351ff8c990739fe2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Briefly, nasopharyngeal swab was collected and stored in a sterile EP tube with 5 mL viral transport medium in Shenzhen border. All the samples collected were immediately refrigerated at 2-8\u00b0C and transported to the central laboratory of health quarantine of Shenzhen Entry-exit Inspection and Quarantine Bureau (SZCIQ) within the same day and stored at \u221280\u00b0C until analysis.", "This was a cross-sectional study in molecular epidemiology for coronaviruses infection, and the minimum sample size of this study was 1683 as determined by Z distribution. A total of 3298(>1683) nasopharyngeal swabs samples were collected from children (<6 years) who passed Shenzhen border, linking Southern China and Hong Kong SAR, from 2014 to 2015 and showed symptoms of respiratory tract infection, such as fever (body temperature > 37.5\u00b0C) and cough. Written informed consent was obtained from the guardians of all participants before the sample and data collection.", "Males and females shared a common detection rate of all the HCoVs studied and no significant difference was found among the detection rate of the four strains. Also, the p values of Fisher's chi-square test showed no significant difference in detection rates among different origins. The first three clinical symptoms of HCoVs infection were fever (p = 0.08), throat congestion (p = 0.58) and antiadoncus (p = 0.09). Yet, there was no significant difference between HCoVs infected and noninfected patients. For the age group distribution of four HCoVs infections, the infant age group (<1 year old) with weaker respiratory immunity was showed with the highest infection rate in total types of HCoVs infection (p = 0.049) and OC43 infection (p = 0.068) (Fig. 1b) ." ] },{ "paper_id": "c8973a511fb65247ed8f08c777512f17d5c4e977", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Peptides from the SCX fractions were dissolved in 0.3 \u00b5l 100% formic acid and diluted to 5 \u00b5l in 0.05% trifluoroacetic acid (TFA). The peptides were loaded onto a micrOTOF-Q II-nano LC system (Bruker Daltonics, Inc., Billerica, MA, USA) and mass spectra were acquired in the 250-1,600 m/z range every second for 60 min.", "Protein digestion and peptide tagging. Protein solutions [100 \u00b5g; 5 mg/ml in 0.5 M triethyl ammonium bicarbonate (TEAB) containing 0.1% sodium dodecyl sulfate, pH 8.5]were digested for 24 h with 10 \u00b5g L-1-(4-tosylamido)-2-phenylethyl tosylphenylalanyl chloromethyl ketone (TPCK)-treated trypsin. Each peptide solution was labeled for 3 h at room temperature using an iTRAQ reagent that had been reconstituted in 70 liters of ethanol, in accordance with the iTRAQ Reagents Multiplex kit instructions (Applied Biosystems, Foster City, CA, USA). The reaction was terminated by adding MilliQ water, and the samples were labeled with 114, 115, 116 and 117 mass-tagged iTRAQ reagents.", "Database screening. Data were processed using BioTools software (Bruker Daltonics, Inc.). The files were subsequently submitted to an in-house Mascot server (Matrix Science Ltd., London, UK) for database screening. The data were screened against the human sequence database [National Center for Biotechnology Information non-redundant (NCBInr)]. The search was performed using trypsin as a specific enzyme. A maximum of one missed cleavage was permitted and oxidation (M), iTRAQ 4 plex (K) and iTRAQ 4 plex (N-term) were selected as variable modifications. The data obtained on the micrOTOF-Q were searched with a peptide mass tolerance of 10 ppm and a fragment mass tolerance of 0.8 Da. Protein ratios were normalized using the overall median ratio for all the peptides in the sample for each separate ratio in every individual experiment. The ratio for a given protein was calculated by taking the average of all the peptide ratios that Briefly, the protein lysates were separated by polyacrylamide gel electrophoresis, transferred to a polyvinylidene difluoride (PVDF) membrane and subjected to immunoblotting with the following antibodies: Anti-apolipoprotein J precursor antibody (ab16077; dilution, 1:2,000; Abcam, Cambridge, UK), anti-hemoglobin \u03b2 (sc-21757; dilution, 1:500; Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA), anti-CRP precursor (ab32412; dilution, 1:1,000; Abcam), anti-platelet factor 4 precursor (AB1488P; dilution, 1:5,000; Millipore, Billerica, MA, USA) and anti-VN (ab11591; dilution, 1:500; Abcam) at 4\u02daC overnight. After washing, the membranes were incubated with horseradish peroxidase-conjugated secondary antibodies and visualized using an enhanced chemiluminescence system (ECL; Forevergen, Guangzhou, China)." ] },{ "paper_id": "c8978a8074a9df4bf07e49393821886d0b80979f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c899a0907dc026208ece3df9c6d4b3c909c6dd46", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Respiratory system (58) Streptococcus pneumonia (14) , Legionella pneumonia (4) " ] },{ "paper_id": "c8a09ce3cbd5d88ceb3bb530003b2f4a46d92d3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For viral detection, DNA and RNA were extracted from 200 \u03bcL of RNAlater of each swab sample collected from Christmas Hills, Allansford and Naracoorte (January 2016) using VX Universal Liquid Sample DNA Extraction Kits (Qiagen, Melbourne, Australia) and a Corbett Xtractor Gene Robot (Corbett Robotics, Sydney, Australia). Negative extraction controls utilised distilled water (Milli-Q, Merck, USA) only. Positive extraction controls utilised laboratory stocks of cell cultures infected with the avian alphaherpesvirus, infectious laryngotracheitis virus (ILTV) or the avian paramyxovirus, Newcastle disease virus (NDV).", "Gammaherpesvirinae (purple) subfamilies. The tree was generated from the 45 amino acid long alignment using MrBayes v3.2.6 [47] with four heated chains, a chain length of 1,000,000, sampling every 10,000 iterations, and a burn in of 10%. GenBank accession numbers are located to the right of each virus.", "GenBank Taxonomy " ] },{ "paper_id": "c8a84384011fca6e1e24511d1b053eef4650fc04", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c8adc8df36e5301e6455b55be70e3164b9de66a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c8b1da52eeb1d7dc2ff2f2f20a44ef13160fd626", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The research protocol used for this study was approved by the Health & Biosafety Committee at Emory University (Biosafety File #: 08-2528-11). No human or animal subjects were used.", "Background: Infectious bronchitis virus (IBV) is a pathogenic chicken coronavirus. Currently, vaccination against IBV is only partially protective; therefore, better preventions and treatments are needed. Plants produce antimicrobial secondary compounds, which may be a source for novel anti-viral drugs. Non-cytotoxic, crude ethanol extracts of Rhodiola rosea roots, Nigella sativa seeds, and Sambucus nigra fruit were tested for anti-IBV activity, since these safe, widely used plant tissues contain polyphenol derivatives that inhibit other viruses." ] },{ "paper_id": "c8c7265b3435763dfb209e8895c83e3cf8717a0f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Encompasses alerting public healthcare practitioners during the early phases of an outbreak, enabling them to promptly institute control measures and case finding and to ensure adequate access to treatment, thereby reducing morbidity and mortality [19] .", "Strengths and future challenges of newly emerging surveillance systems", "Infoveillance Information surveillance; longitudinal tracking of infodemiology metrics for surveillance and trend analyses [16] [17] [18] ." ] },{ "paper_id": "c8ca3a5306db10a7842b853031404ecbc0a363ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics statement. The study was approved by the University Malaya Medical Centre (UMMC) Medical Ethics Committee. Standard, multilingual consent forms allowed by the Medical Ethics Committee were used and written consent was obtained from all study participants. All experiments were performed in accordance with approved guidelines and regulations." ] },{ "paper_id": "c8d2fa6e178d17b218df59b33cfcb5839af7dc7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c8d60caf44017989b3b9633350fc1d2efda570a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pone.0184015.g001", "Genomic DNA was extracted from ethanol-stored foot tissues using silica columns (QIAmp Tissue kit, QIAGEN) for the host genetics component of the study [27] .", "The liver concentration of eight anticoagulant compounds (brodifacoum, bromadiolone, chlorophacinone, flocoumafen, coumatetralyl, difenacoum, difethialone, and warfarin) was determined using liquid chromatography-mass spectrometry (LC-MS-MS) [29]." ] },{ "paper_id": "c8d7f93deaccea9d11f6713cc20368d236fc3d82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following are available online at www.mdpi.com/1999-4915/9/5/102/s1, Figure S1 : Maximum-likelihood phylogenetic tree of MAstV (a) capsid nucleotide and (b) capsid amino acid sequences, Figure S2 : Maximum-likelihood phylogenetic tree of MAstV RdRp, Figure S3 : Maximum-likelihood phylogenetic tree of AAstV (a) capsid nucleotide and (b) capsid amino acid sequences, Figure S4 : Maximum-likelihood phylogenetic tree of AAstV RdRp.", "Historically human astroviruses (HAstV) were classified into five serotypes in 1984 [32] . Subsequent molecular characterization based on viral reactivity to polyclonal antibodies and nucleotide sequence analysis led to the recognition of eight serotypes (HAstV-1-8), now termed \"classic\" HAstV [18, 33, 34] . The relatively recent advent of next generation sequencing (NGS) and metagenomic analysis has led to the identification of numerous novel strains considered \"non-classic\" HAstV [18] . Currently, HAstVs are classified within the species MAstV-1 (HAstV-1-8), MAstV-6 (MLB1-3), MAstV-8 (VA2/HMO-A, VA4, VA5, BF34), and MAstV-9 (VA1/HMO-C, VA3/HMO-B) [18] (Figure 1a ).", "The authors declare no conflict of interest." ] },{ "paper_id": "c8df0fd2c7d06947d2bb15ebed6ce0bad831b297", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sense:antisense nucleotides needed to produce pairs of aa classes sense class antisense (1\u20322\u20323\u2032) aa class", "of a hypothetical antisense polypeptide. A special case of this hypothesis is that peptide ligands might have arisen for some proteins from the antisense strand complementary to their coding region 11, 12 .", "is the i th amino acid of X (resp., Y, X\u2032, Y\u2032), and p i , q j are position-dependent weights that reflect sequence conservation among natural homologs of X and Y. They are chosen so that positions in X, Y that are highly conserved (respectively, variable) have high (low) weights (see below)." ] },{ "paper_id": "c8e11bd3e14d4e681675fd8063c2896692d9e674", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by intramural funds from the Robert Koch Institute.", "CP and SV wrote and edited the manuscript." ] },{ "paper_id": "c8eb13b64a5392a43ac16027e68b30573a9d0df0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were hand entered twice, with resolution of discrepancies by comparison to paper questionnaires. Missing data, disallowed values, and outliers were also handchecked, and corrected if appropriate. Overall, >98% of intended data was collected. Formal missingness analysis was done for each instrument separately, following the approach set forth by Potthoff [54] . Assumptions were met for missing at random (MAR+), [54] therefore imputation using multivariate techniques was deemed acceptable. Reliability coefficients were calculated using methods of Joreskog [51] and Bollen, [52] with significance tested following Wald [55, 56] ." ] },{ "paper_id": "c8f60c136e1ace8011a2ee3844510d862ff9053a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c8f6c26a8275c6cbbeb30dc984f058902455ed52", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was supported by NIH grants (R01AI139092 and R21AI137790) and intramural funds from the New York Blood Center (NYB000475, NYB000486, and NYB000552).", "W.T., Y.Z., F.L., and L.D. designed the study. W.T., J.C., G.Z., Q.G., L.H., and Y.C. conducted the experiments and analyzed the data. Q.G. and F.L. performed the structural analysis. W.T., Y.Z., F.L., and L.D. wrote, revised, and proofread the paper.", "We declare no competing interests." ] },{ "paper_id": "c8f9c5d7e30e601b4ea6e3c42696177c57aa1c47", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IVM has also shown potency against other flaviviruses like Zika virus (ZIKV), which currently has no approved vaccines or specific treatments [181] . A screen of FDA-approved drugs demonstrated IVM to be an effective inhibitor of ZIKV infection across multiple cell types with minimal toxicity [181] . Furthermore, these studies demonstrate that IVM can be effective against a genus of virus, like flavivirus, and potentially others, such as alphavirus, where IVM treatment of infected cells resulted in a 2-4 log reduction in viral titers from CHIKV, Semliki Forest virus, and Sindbis virus [175] .", "The authors apologize to colleagues whose work could not be cited because of space constraints.", "The authors declare no conflict of interest." ] },{ "paper_id": "c90c4e5ca7134a20586234aae4f4f8b6b42c05fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the ethics review board at Peking University Institute of Mental Health (PKUIMH). Patients and/or their family members/guardians consented to participate in a written form.", "In case that there is failure of preventing \"relocking\", the \"686\" teams would take immediate action to restart the \"unlocking and treatment\" intervention as far as possible." ] },{ "paper_id": "c916747a33f9b4a986dd0e4a4b853db6814b74f9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Therefore, in addition to being a viable strategy for known viruses, inhibition of viral fusion offers the opportunity for a rapid response to emerging viral pathogens, opening the possibility to develop a specific antiviral in very short timeframe.", "The assays to measure Peptide inhibition of viral entry or viral infectivity were performed as previously described [38, 43, 45] . A brief description of the assays is given below.", "Nipah virus (isolate UMMC1; GenBank AY029767) [62] was prepared on Vero-E6 cells as described previously [63] in biosafety level 4 (BSL-4) laboratory Jean Merieux in Lyon, France. " ] },{ "paper_id": "c91fac9f0e239fab524c4595ebf8d0d8a5385f1a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All samples were transported refrigerated and stored in refrigerator at approximately + 4\u00b0C for short-term storage (maximum 24 h), and then frozen at approximately \u2212 60\u00b0C for extended storage before nucleic acid extraction and virus detection.", "The continuous growth in air travel [1] increases the likelihood of rapid spread of infectious diseases between countries and continents. Air travel made possible the rapid spread of Severe Acute Respiratory Syndrome (SARS) from Hong Kong in 2003 to several countries in a very short time [2] , as was the case for the global spread of pandemic influenza A(H1N1)pdm09 from Mexico and the United States of America in 2009 [3] .", "Helsinki-Vantaa airport is the main airport in Finland, with a throughput of 18.9 million passengers in 2017. Approximately 12% of the traffic is to or from Eastern, South-Eastern and Southern Asia.", "The Ct-values of the real time PCR readouts ranged from 36.15 to 41.59." ] },{ "paper_id": "c92099607cfae94a24e03a111d12994535cc2eae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza is an acute infectious disease caused by influenza virus, with respiratory damage as main outcome. It is epidemiologically characterized as rapid prevalence, wide dissemination, acute incidence and huge hazard, and is one of diseases that seriously threaten human health. A report by World Health Organization shows that there are 3-5 million severe influenza cases and 250,000-500,000 mortality every year [1] . Influenza pandemias happened for four times in the 20 th century. The Spanish flu in 1918 was the most serious one. It claimed 50 million lives at least, even more than the mortality in Fist World War [2] . More than 10,000 people died of H1N1 flu in 2009 [3]. Influenza produces a large number of morbidity and mortality, and also results in great economic loss and social burden.", "Implications of the hypothesis: CR2 targeting complement inhibitors are expected to be ideal drugs for viral pneumonia.", "An effective CR2 targeting complement inhibitor can reduce the mortality, significantly improve clinical symptoms (decreased weight, lung index and hemagglutination titer) and lung tissue inflammatory injury of virusinfected model group. Therefore, CR2 targeting complement inhibitor is expected to be an ideal drug for viral pneumonia." ] },{ "paper_id": "c92206983f9523a96c8ea02210f70ee5640edd14", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We analysed the Dutch (n = 267) and Israeli (n = 249) cohorts separately (Supplemental Table 3 ", "We included data from two different countries, both with different healthcare systems, to make the results of this study more generalizable. We did not observe significant differences in overall antibiotic use between Dutch and Israeli children and adults. However, existing literature shows that antibiotic use is higher in Israel, compared with The Netherlands [25] . A relatively high rate of antibiotic use in The Netherlands may be related to the high proportion of severely ill patients (e.g. more bacterial infection, more ICU admissions) in the Dutch cohort.", "In conclusion, viral RTI is more common in children, whereas antibiotic overuse is more common in adult patients with RTI, supporting the need for better diagnostics to differentiate between viral and bacterial infection across all ages.", "Data collection of this TTT-study was described previously [13] . In short, all available clinical data (including biomarkers tested for routine care, a study specific nasal swab and information from a 28-day follow-up assessment) was recorded in an electronic Case Report Form (eCRF) [13] . A multiplex PCR-based assay of the 14 most common respiratory pathogens (nine viruses, five bacteria) was performed on all nasal swabs (MagnaPure LC total nucleic acid kit and MagnaPure 96 DNA, Roche Diagnostics, Mannheim, Germany) [15] . The PCR results were not available for the attending physician, since this assay was performed after completion of the recruitment process." ] },{ "paper_id": "c923009c37cf93d35e69ec161afaf3cc334e03a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study has potential limitations. First, it is a retrospective study at a single hospital. Another limitation is that data on concomitant bacterial infection, viral genomic load and palivizumab prophylaxis were not collected.", "This retrospective descriptive study took place at the paediatric wards of Hamad General Hospital (HGH), a 603-bed, tertiary-care facility in Doha, for two consecutive years, 2010 and 2011. The institutional review board at Hamad Medical Corporation approved the study, IRB number 12054.", "Conducting a prospective, multi site surveillance of viral bronchiolitis in the warm, desert climate of the Gulf Cooperation Council (GCC) countries will allow for proper timing of preventable measures. Future studies within the GCC countries should investigate the interplay between climate characteristics, population's factors and the most detectable circulating viruses." ] },{ "paper_id": "c92d4b764634f984f72efccaa63b365bebc10616", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At present, antiviral drugs are available in fighting influenza, such as the M2 inhibitors and the neuraminidase inhibitors. Nonetheless, the emergence of drug resistant influenza strains raises concern over their effectiveness. It has been reported that M2 inhibitors resistant H5N1 viruses are widespread [14] . The efficacy of the neuraminidase inhibitor, oseltamivir, appears to be very time dependant, where treatment started later than 24 hours post infection is much less effective [15] . Therefore other alternative antiviral drugs are required to fight H5N1 influenza. In vaccination, it is well known that influenza viruses are dynamic and are continuously evolving. Influenza type A viruses undergo antigenic drift and antigenic shift, resulting in new virus strains that may not be recognized by antibodies to earlier influenza strains. Therefore, rational design of vaccines against influenza vaccines still has a long way to go. Although there are difficulties of tackling influenza virus with drugs or vaccines, they are very useful in the prevention and therapy of influenza. At the same time, effective diagnostic tests for viruses screening prior to application of drugs and vaccines are widely accepted, due to their simplicity, rapidity and applicability.", "Madin-Darby canine kidney (MDCK) cells (ATCC, Manassas, VA) were grown in Dulbecco's MEM with 1 mM L-glutamine and 10% fetal bovine serum at 37uC and 5% CO 2 in air. HPAI H5N1 strain A/goose/Jilin/hb/2003 were propagated in the MDCK cells in the absence of serum and purified by differential centrifugation conventionally. The concentration of the purified viruses diluted in PBS was measured by Thermo Scientific NANODROP 2000 Spectrophotometer ((NanoDrop Technologies, Thermo Fisher Scientific, Wilmington, DE) and calculated by the molar absorbance coefficient A 260 /A 280 according to the manufacturer's instructions.", "Since the first evidence regarding direct transmission of highly pathogenic avian influenza A virus (HPAI), subtype H5N1 from poultry to human in 1997 and resulted in the death of 6 of the 18 infected individuals [1] [2] [3] . The HPAI H5N1 has become one of the most important public health concerns worldwide. At present, the virus has spread to many countries in Europe, Asia and Africa [4] . In 2009, an identified fatal influenza (H5N1) infection in a human was reported on January 17, 2009 [5] . Increased geographical distribution and continued evolution of H5N1 viruses as well as an immunologically na\u00efve human population has maintained the pandemic potential of these viruses [6] [7] [8] ." ] },{ "paper_id": "c92fafbeda15f8604281f06c7461dcec5288d303", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Unidentified RNA virus [25] [26] [27] Epstein-Barr virus 11, 12) Candida albicans* 81) Human parvovirus B19 127) Human corona virus HCoV-NL63 121, 122) Human vocavirus (HBoV) 125) Human immunodeficiency virus 124) Streptococcus pyrogenes 47) Staphyrococcus aureus 42, 43) Yersinia pseudotuberculosis 76) Mycobacterium ssp 67) Lactobacillus casei* 130) \u03b1-mannan 87, 132) \u03b2-glucan 128) Virus / Microbe dUTPase 15, 123) TSST-1 35) SPEC 48) Possible effector molecule lipoarabinomannan 131) YPMa 64) Bacillus cereus 79) Candida ssp 72) A variant of Torque teno virus 7 126) Mycoplasma pneumoniae 129) Adenovirus 18, 19) ", "It might be possible to validate phlogogenic activity of the wind-blown microbes / molecules with established animal models for KD.", "Another KD-like murine coronary arteritis model involves induction by Lactobacillus casei cell wall extract (LCWE). TLR2dependent signaling, IL\u03b2-dependent signaling, and CD8 + T cells (cytotoxic T cells) play a crucial role in its pathogenesis (91) (92) (93) .", "The manuscript was written by AN, and it was edited by KI and KH." ] },{ "paper_id": "c9306dcd544f76f65824fec6810b03d0c4dfe5a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Respiratory function continued to improve, and the patient was recommended for immune deficiency evaluation.", "With pneumonia being a leading cause of pediatric hospitalization in the United States [4] , multiple studies have investigated the etiology of pediatric pneumonia in varying ages and settings, with various microbiologic techniques. Studies continue to demonstrate that rhinovirus should not be ignored as a common microorganism associated with CAP." ] },{ "paper_id": "c933e09cb9262b2edc2394b1a7d86357da840493", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral RNA was extracted from rectal and cloacal swabs and fecal samples using EZ1 Virus Mini Kit v2.0 (Qiagen, Germany). RNA was eluted in 60 \u00b5l of AVE buffer (Qiagen, Germany) and about 200 ng of RNA was used as template for RT-PCR.", "PW conceived of the study, designed the study, contributed reagents and drafted the manuscript. JT conceived of the study, designed the study, participated in data analysis and drafted the manuscript; RB carried out the molecular lab work and participated in data analysis. AW and AT participated in data analysis; PM and S-WH contributed reagents; CCL, SA, CY, GC, KL, and CSL carried out the lab work. SL revised the manuscript and contributed reagents; K-YY conceived of the study, designed the study, contributed reagents and revised the manuscript. All authors gave final approval for publication. ", "The genome sequences of otarine PBVs obtained from the present study were deposited in GenBank with accession numbers KU729746-KU729769.", "Plasmids with the corresponding target sequences were used for generating the standard curve. At the end of the assay, PCR products were subjected to a melting curve analysis (65-95 \u2022 C, 0.1 \u2022 C/s) to confirm the specificity of the assay." ] },{ "paper_id": "c936ef4688d255c47855066ca55d95f4dfc227e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "mice of each group were sacrificed for the collection of lung samples. Lung virus titers were measured on six-well plates containing confluent MDCK cell monolayers. Inflammatory cytokines (IFN-\u03b3 ) were determined using BD OptEIA mouse IFN-\u03b3 ELISA kit (BD Biosciences, San Jose, CA) following the manufacturer's procedure.", "To confirm the formation of crystalline NaCl coating during drying process and its stability during storage at 37 \u00b0C and 70% RH, XRD analysis (BRU-1098; Bruker, Billerica, MA) was performed at different coating conditions. Filters (1 \u00d7 1 cm) were mounted on a slide glass for XRD analysis (\u03b8 -2\u03b8 mode) using a CuK\u03b1 radiation.", "(PR/34, H1N1) and A/Vietnam/1203/2004 (VN/04, H5N1) were grown in 10-day old embryonated hen eggs, in which H5N1 virus was derived by reverse genetics from HPAI A/Vietnam/1203/2004 36 . Influenza viruses were purified from allantoic fluid using discontinuous sucrose gradient (15%, 30% and 60%) layers following the previously reported procedure 37 ." ] },{ "paper_id": "c93e251c48b43dfc3e162039968b8ce59810c410", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords: interferon lambda, interferon, immunity, immune cells, infectious disease, virus", "\u2022 Mice lacking IFNAR have enhanced viral loads, increased tropism, and complete mortality (85) Zika virus (+ssRNA Flaviviridae)", "The authors would like to thank Drs. Alison Kell and Matthew Long for their critical evaluation of this manuscript.", "All authors contributed to the conceptualization, writing, and editing of the manuscript." ] },{ "paper_id": "c95771649886404cfec24c5c139e851c614e632b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The mean absolute error (MAE) is given by:", "We model each group sub-epidemic by a generalizedlogistic growth model (GLM) which has displayed promising performance for short-term forecasting the trajectory of emerging infectious disease outbreaks [20] [21] [22] . The GLM is given by the following differential equation:", "where the parameter a is a positive constant." ] },{ "paper_id": "c95aaaeafc4bea827a28f4f300ca76608fecd107", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bacterial isolates", "Two multi-drug resistant bacterial strains-one K. pneumaniae isolate and one E. agglomerans isolate were resistant not only to all first line of antibiotics but also to all tested second line of antibiotics (Table 2) .", "Streptococcus spp. n = 10" ] },{ "paper_id": "c9653d4f2d22837f98e2be157df9dd6516c1ec96", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Descriptive statistics was used to summarize the data generated from the study. Data were presented as mean \u00b1 SE to compare antibody titers between the infected and the control group on different days following inoculation.", "The virus isolate used in this study was IRFIBV32 (GenBank: HQ123359.1) [12] . It was obtained from Shiraz Veterinary University and was propagated two times in 9to 11-day-old embryonated chicken eggs. The embryo lethal dose (ELD50) was calculated according to the Reed and Muench [13] formula.", "All tissue samples were immediately stored at \u221270 \u2022 C until used. RNA of the samples was extracted using the Accuzol User\u015b Manual (BioNeer Corporation, Republic of Korea) according to the manufacturer's protocol. Briefly, appropriate tissue (50-100 mg of tissue) was homogenized with 1 mL of Accuzol, and then 200 \u00b5L chloroform was added into the mixture and the mixture was centrifuged at 12000 rpm at 4 \u2022 C for 15 min. The upper phase was added to an equal volume of isopropyl alcohol and stored at \u221220 \u2022 C for 10 min then centrifuged at 12000 rpm at 4 \u2022 C for 10 min. After the washing step, by using 80% ethanol and centrifuging at 12000 rpm at 4 \u2022 C for 5 min, the pellet was dissolved in a final volume of 50 \u00b5L distilled water (DW) and stored at \u221270 \u2022 C until used." ] },{ "paper_id": "c96d197b59d78b7d5dba68fb9a4e5ef67bd066d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pan troglodytes IFITM3", "Capra hircus IFITM3", "Xenopus laevis IFITM3", "Types I and II interferons (IFNs) are critical for establishing an antiviral state, which is mediated by downstream IFNstimulated genes (ISGs) [1] . Viruses have evolved diverse strategies to escape immune defenses [2] . However, virus evasion of the interferon-inducible transmembrane proteins (IFITMs) restriction is not apparent.", "TMUV was a kind gift of the Avian Diseases Research Center of Sichuan Agricultural University. The agonists R848 (InvivoGen, USA), Poly (I:C) (Sigma, USA), ODN2006 (InvivoGen, USA), and LPS (InvivoGen, USA) were used to mimic treatment with single-stranded RNA, double-stranded RNA, synthetic oligonucleotides, and lipopolysaccharides, respectively." ] },{ "paper_id": "c9708301ac6326b1214f31ab93fcd4b72485cf4b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data shown (including luciferase assays, qRT-PCR, and quantitative ChIP) were analyzed using Student's t test at 5% significance level (P<0.05).", "Oncotarget 272" ] },{ "paper_id": "c9895a5f0147dc50b66530f0ffa3a7264559c0a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All OTU and ISG15 protein concentrations were determined through UV-visible spectroscopy at 280 nm using molar extinction coefficients experimentally derived by the method of Gill and von Hippel [58] .", "The OTUs of CCHFV, DUGV, ERVEV, NSDV, GANV, TAGV, QYBV, FARV, HpTV-1, ISKV, LPHV, DGKV, HAZV, and KUPEV were constructed, expressed, and purified as previously described [38, 41, 44, 45] . For ISG15s, those in the pro form from human (Homo sapiens; Accession: AAH09507.1), mouse (Mus musculus; Accession: AAB02697.1), sheep (Ovis aries; Accession: AF152103.1), dromedary camel (Camelus dromedarius; Accession: XP_010997 700.1), northern tree shrew (Tupaia belangeri; Accession: AFH66859.1), vesper bat (Myotis davidii; Accession: ELK23605.1), and fish (Oplegnathus fasciatus; Accession: BAJ16365.1) were constructed, expressed and purified as previously described [38] .", "The OTU \u03b13 selectivity helix contributes to OTU specificity for human and sheep ISG15", "The observed trends in OTU-ISG15 preferences provide a strong foundation for assessing virus-host interactions, and could serve as a marker for viral host range. Virus-host interactions may be predicted from ISG15 sequence alone, possibly allowing for the identification of previously unknown hosts involved in the enzootic maintenance of nairoviruses. In addition, these new structures and biochemical data may provide insights into the direction in which a given nairovirus is adapting. Our data demonstrates that only a few changes are necessary for a virus to adapt to ISG15 of a different species, potentially affecting host range or disease manifestation/pathogenesis. Testing mutant variants of nairovirus OTUs may help anticipate the degree to which it would have to adapt to human hosts and provide insights into the potential threat posed by the virus.", "Nairoviruses possess a negative sense, single-stranded RNA ((-)ssRNA) genome consisting of three segments denoted as small (S), medium (M), and large (L), that encode the viral nucleoprotein, glycoproteins, and the multifunctional L protein, respectively. Beyond the RNAdependent RNA polymerase (RdRp), the L protein contains a viral homologue of the ovarian tumor domain protease (OTU) at the N-terminus (Fig 1B) . This OTU reverses posttranslational modifications by ubiquitin (Ub) and interferon (IFN) stimulated gene product 15 (ISG15). Ub and ISG15 are conjugated to proteins (ubiquitination/ISGylation) in a process involving activating (E1), conjugating (E2), and ligating (E3) enzymes. Ubiquitination plays a key role in activation of the innate immune response, while ISGylation primarily occurs on newly synthesized proteins in response to IFN induction, making viral proteins a predominant target [18] ." ] },{ "paper_id": "c98b61b984da63b53eeef9f81e31a5ee79396b1d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Genome Sequence BRAV1 strain Sd-1", "Fetal bovine kidneys, sourced from an abattoir, were purchased from Innovative Research. Primary embryonic bovine kidney (EBK) cells were cultured by treatment of finely minced kidneys with 0.25% trypsin at 37\u00b0C for 4 hours following transfer to cell culture flasks with MEM with L-glutamine and 100 units/mL penicillin, 100 \u03bcg/mL streptomycin and 0.25 \u03bcg/mL amphotericin B. Madin-Darby bovine kidney (MDBK) (ATCC CCL-22) were maintained in MEM with L-glutamine and 5% fetal calf serum at 37\u00b0C with 5% CO 2 . BRBV (ATCCVR-1806) was first passaged on EBKs before being expanded on MDBK cells. Virus was grown in MEM at 33\u00b0C with 5% CO 2 .", "Bovine clinical samples used in this study were submitted to KSVDL for routine diagnostic testing. The samples were obtained from naturally infected animals in the field by licensed veterinarians as a part of normal veterinary care and diagnostic investigations." ] },{ "paper_id": "c98f64c50d8a1c2d378db2e8da009c2dbc7936b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Disease elimination strategy with an emphasis on snails control (1950s to early 1980s)", "Additional file 1: Multilingual abstracts in the six official working languages of the United Nations.", "Lastly, we need to emphasise that schistosomiasis control requires joint policy-making work across organisational boundaries and systems. Policy-making needs to move beyond the confines of the health system, a point we now pick up under the heading of intersectoral action for health." ] },{ "paper_id": "c992817218f27eaa39a7bc3b90e9bd0538017eb0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In some instances, managers may want to influence population connectivity to mitigate the possibility of pathogen spread (Hess 1994) . Such an approach requires a fine-scale understanding of host movement. Using landscape genetics, one can evaluate the most parsimonious sets of factors affecting gene flow relative to one another to establish their effect on dispersal rates and functional connectivity (Taylor et al. 1993) . To do so, causal modelling is often used to test different alternative hypotheses of landscape connectivity (Cushman et al. 2006 ) and least-cost paths are integrated in these models using habitat-specific costs to choose the most parsimonious model to explain the genetic distances documented among clusters or individuals. Isolation-byresistance (IBR) models (McRae 2006) , based on circuit theory, are also used to assign a resistance values to each element of the landscape and then compute resistance distances between pairs of individuals on the surface (see Dudaniec et al. 2013) . Importantly, these analyses allow the construction of maps allowing to visualize for a given study area the most likely routes of dispersal of hosts and thus the potential spread of disease (Rioux-Paquette et al. 2014) .", "The host-pathogen evolutionary relationship is fundamentally affected by changes in environmental conditions (Fig. 2) . Through phenotypic plasticity, genotypes interact with environments (Nussey et al. 2007 ) to produce different phenotypes for both hosts and pathogens (Mitchell et al. 2005). As a result, changing habitats can have profound effects on host-pathogen evolutionary dynamics (Altizer et al. 2013; Echaubard et al. 2014) .", "An interesting recent development in molecular epidemiology is the emergence of the field of phylodynamics (Grenfell et al. 2004; Pybus and Rambaut 2009) . Several pathogens (most notably viruses, but also bacteria) are characterized by typically high evolutionary rates. Consequently, their evolutionary and ecological dynamics occur on similar timescales: genomic diversity and adaptation can emerge within a few days. Statistical models at the interface of phylogenetics and population genetics that incorporate notions such as coalescent theory and relaxed molecular clocks (e.g. BEAST software; Drummond and Rambaut 2007) can thus be applied on pathogen genetic or genomic data to jointly estimate evolutionary parameters such as the timing of emergence of a given lineage or the estimated population size of a pathogen. Because of the interaction of evolutionary and ecological processes in such organisms, these evolutionary trajectories also provide insights into infection and transmission dynamics. For instance, the topology of a pathogen phylogenetic tree is influenced by the contact structure within host populations (Leventhal et al. 2012) . While most phylodynamic studies have been applied to global human diseases (but see Biek et al. 2007 with wildlife), we expect emerging wildlife diseases to be the focus of such work in upcoming years." ] },{ "paper_id": "c9931d8718e491e3002bbf42aec7cde49e93bac5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c99be1ffda777de5b7f9e0ed6c04fd70ce0bc3e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Transient transfections and reporter gene assays. Subconfluent cell monolayers of 293 cells seeded in 12-well plates were transfected with 250 ng p125-Luc reporter plasmid, 50 ng pRL-SV40, and 1 lg of expression plasmid in 200 ll of OPTIMEM (Gibco-BRL) containing 3.9 ll of Fugene HD (Roche, http://www.roche.com). At 8 h post transfection, cells were induced with either 0.2 lg of viral ssRNA containing 59 triphosphates [54] (p125-Luc), 2.5 lg of poly(I:C) (Sigma), or 500 U/ml IFN-a (p(9-27)4tkD(\u00c039)lucter), or left uninduced. After an incubation period of 16 h, cells were harvested and lysed in 100 ll of Reporter Lysis Buffer (Promega). An aliquot of 10 ll lysate was used to measure luciferase activity as decribed by the manufacturer (Promega).", "MHV-nsp1D99 showed no significant growth defect in primary pAPCs ( Figure 2C-2E) , indicating that the deletion of nsp1 did not alter the pronounced tropism of MHV for cDCs and macrophages.", "Recombinant DNA and viruses. LCMV-WE strain, originally obtained from F. Lehmann-Grube (Hamburg, Germany), was propagated on L929 cells. MHV A59 was generated from a molecularly cloned cDNA [24] based on the Albany strain of MHV A59. Coronaviruses and recombinant vaccinia viruses were propagated, titrated, and purified as described [24, 50, 51] .", "The GenBank (http://www.ncbi.nlm.nih.gov/Genbank/) accession numbers for the viruses and sequences discussed in this paper are HCoV-229E (AF304460), MHV-A59 (AY700211), and SARS-CoV Frankfurt-1 (AY291315)." ] },{ "paper_id": "c9a6a3d79f58c4b3a62e2913aaa1d076e5abf7c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Roughly 400 infectious diseases have been identified since 1940. New pathogens are emerging at higher rates, despite the increase in awareness and vigilance. A grave public health concern is when and how the next outbreak will occur 1 ; threats of imminent global outbreaks are real 2 . The 1917 Spanish influenza, which killed 50 million people, was the worst-ever pandemic on record -and that was back at a time when travel by ship was the fastest means of transportation around the globe. In today's tightly connected world, an epidemic can potentially travel at jet-speed. Indeed, Swine flu was first detected in April of 2009 in Mexico and within a week it turned up in London.", "We now consider separately the two components in the notion of response capability \u03b5.", "Possessing the ability to isolate individuals with probability p > p c alone is not enough; one must be able to identify infectious hosts with sufficient speed. We prove that for each p > p c , there is a critical identification time", "In Results, we considered initial conditions \u03c6 representing the sudden appearance of a small group of infectious individuals. These initial conditions should be near (1, 0, 0, 0, 0), the disease-free equilibrium with constant coordinate functions. Two examples are" ] },{ "paper_id": "c9ac0a1d2dd861bfa590dc654ddadb324a993fa0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analyses were performed on a personal computer using the statistical package STATA for Windows (Version 11.0, College Station, TX). A P-value of .05 was considered to represent statistical significance.", "A score of 1 was added when the subjects had co-morbid myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, connective tissue disease, peptic ulcer disease, mild liver disease, or diabetes without end-organ damage. A score of 2 was added when the subjects had co-morbid hemiplegia, moderate or severe renal disease, diabetes with end-organ damage, tumor without metastases, leukemia, or lymphoma. A score of 3 was added when the subjects had co-morbid moderate or severe liver disease. A score of 6 was added when the subjects had co-morbid metastatic solid tumors or acquired immunodeficiency syndrome (AIDS). The total score was obtained by adding the relative weight of all co-morbidities. For each decade > 40 years of age, a score of 1 is added to the sum of the above-mentioned scores. [27] [28] [29] " ] },{ "paper_id": "c9b0389a55de2f9cbfe37049d1072e0984613923", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasma donor samples were fractionated using weak anion exchange (WAX) magnetic beads (Bruker Daltonics, Bremen, Germany) according to the manufacturer's recommendation (Text S1).", "To monitor alterations of the acute form (A-SAA) as well as the constitutively expressed form (C-SAA) of serum amyloid A, we", "Plasmapheresis samples from the US plasma donor cohort used in this study were purchased from Zeptometrix Corporation and SeraCare Life Sciences. Donors were recruited via the SeptaCare Special Donor Program and enrolled for plasma donation after a medical examination and an interview with medical staff, in which it was explained that the donated plasma will be used by dedicated drug and vaccine researchers to perform research to help others. This study was approved by the Oxford Tropical Research Ethics committee (OXTREC, University of Oxford) and the NIH Office of Extramural Research (Nr. 201029 to B.M.K)." ] },{ "paper_id": "c9b4c7691175724573497c35ff6ac960a3208104", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1 ml blood samples were drawn aseptically from all neonates with suspected sepsis, inoculated into a heart infusion broth, incubated at 37\u00b0C, and was daily checked for signs of bacterial growth up to 7 days. For a positive broth culture, sub-cultures were done on Mac Conkey agar, blood agar and chocolate agar then incubated at 37\u00b0C for 24 h. Blood culture broths with no bacterial growth after 7 days were sub-cultured and if no growth occurred, were reported as a negative. Bacterial isolates were identified by colony morphology, gram staining and standard biochemical tests.", "SPSS version 16 software was used for the statistical analysis. The Chi square test was used to determine the relationship between dependent and independent variable. P<0.05 was considered statistically significant.", "Neonatal sepsis is a disease process, which represents the systemic response of bacteria entering the bloodstream during the first 28 days of life, which was confirmed by positive blood cultures in the presence of clinical and laboratory findings. It is a very serious condition and if not diagnosed and treated quickly, can lead to shock, multiple organ dysfunction, permanent disability or death [1, 2] ." ] },{ "paper_id": "c9b696a38ac25d3289283045ac72c8af370dda7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a The primers were used/analyzed previously (62).", "Accession number(s). Gene expression data were deposited in ArrayExpress, EMBL/EBI, under accession number E-MTAB-5431.", "during outbreaks. Hitchner (4) refers to NDV as a \"sleeping giant\" that requires close monitoring because the large range of clinical signs of infection with NDV and the genomic diversity of NDV make NDV detection and diagnosis challenging (5, 6) , the worldwide distribution increases the potential danger of NDV (5) , and, although they are uncommon, viruses of low virulence have the ability to mutate and increase in virulence (7) .", "Virus. A live attenuated Newcastle disease vaccine, the type B1 La Sota lentogenic strain, was propagated once in 10-day-old embryonated specific-pathogen-free (SPF) chicken eggs inoculated via the allantoic sac (52) . The allantoic fluid was harvested after 2 days, tested for virus presence by determination of hemagglutinating activity (HA), and centrifuged at 8,000 rpm for 30 min to clear the debris. Virus titration was performed in SPF embryonated eggs as previously described (53) . The final titer of the undiluted virus suspension was 10 8 50% embryo infectious dose (EID 50 ) per ml. The virus suspension was aliquoted and stored at \u03ea80\u00b0C until its use." ] },{ "paper_id": "c9b6f3ff358477fe654fa5e92b3fb85ebd3fb8a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(i) ISG15 LRLRGG. Nucleotides 1 to 465 of murine ISG15", "were PCR amplified using a 59 primer that introduced an AscI restriction site and a 39 primer containing GGT GGG TAA sequence and a PmeI site. (ii) ISG15 LRLRAA. Nucleotides 1 to 465 of murine ISG15", "were PCR amplified using a 59 primer with an AscI restriction site and a 39 primer containing GCG GCG TAA sequence and a PmeI site." ] },{ "paper_id": "c9b76a5f0e49ab1510fa1161baf7d588656582f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "c9bcd70bf18a413b1af105124cc232f2fe0fd5b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our experimental protocols were approved by The Institutional Animal Care and Use Committee (IACUC) of the Chinese Academy of Military Medical Science, Beijing, China.", "Animal experiments to evaluate immune responses were repeated at least twice (n = 5 per group). The response of each mouse was counted as an individual data point for statistical analysis. Virus challenge studies were performed twice (n = 5 or 9 per group). Data obtained from animal studies and pseudotyped virus neutralization assays were examined by using one-way ANOVA. Differences were considered significant at P,0.05.", "To measure viral replication in vivo, tissue samples (brain and lung) were taken from two mice in each group for viral isolation on the 3 rd and 6 th day post infection, respectively. After tissue samples were weighed and homogenized, 0.1 ml of each supernatant was inoculated into the allantoic cavity of 10 day-old embryonated SPF chicken eggs. The allantoic fluids were subsequently harvested and the HA activity was tested for the detection of virus replication." ] },{ "paper_id": "c9c113247df3932d3dbbabc25b9b927efa03c115", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As discussed here, systems-based approaches to understanding the basis of adjuvanticity have been limited mostly to transcriptional data sets. This approach should be extended to proteomic and metabolomics data sets obtained from individuals vaccinated with or without adjuvants. Integration of this information can inform the optimal use of the existing vaccine adjuvants, as well as the development of rationally engineered adjuvants for human vaccines.", "In comparison to B cell antigens (mostly conformational), T cell epitopes (mostly linear) are relatively simpler to predict, as the parameters required for data mining are based on the properties of interaction between MHC proteins and the antigenic peptides. Although extensive diversity in MHC haplotypes at individual level presents a major challenge in identifying broadly protective T cell epitopes, it can be compensated to a significant degree by including most frequently present HLA alleles across various populations in the epitope prediction protocol. The simplicity of peptides makes them an attractive target for vaccine design; however, T cell-epitope based design has not been able to deliver any commercial vaccine yet. This is because a standalone exogenous recombinant T cell antigen-based vaccine will not elicit CD8 positive T cell response, unless cross-presentation is engaged. This limitation has been overcome significantly by vaccines based on viral vectors, DNA vaccines and use of adjuvants that facilitate cross-presenting dendritic cell recruitment. Furthermore, correlates of cell mediated protection are still not well defined, and a combination of B and T cell-mediated immunity might always be needed to counter most viral pathogens.", "Adverse reactions to vaccine candidates pose a major hurdle in regulatory approval. Although mild reaction such as transient fever and local swelling at the injection site are fairly common, severe adverse reactions have also been reported in a few rare instances. Fatal viscerotropic disease caused by yellow fever vaccination (1 in 250,000 cases) and cases of narcolepsy in 2009 H1N1 pandemic vaccinees are a few examples. Immunological characterization of patients with viscerotropic disease showed 200-fold elevated levels of CD14+CD16+ inflammatory monocytes [28] . Genetic background studies of narcoleptic patients showed association of symptoms with ethnic background including the HLA-DQB1*06:02 genotype [29] . These examples show that it is possible to identify clinical and genetic markers that may lead to adverse reaction to a specific vaccine. Since such cases are very rare, it is very important to have the appropriate clinical infrastructure and surveillance to identify such cases and follow them over time to collect samples for analysis in order to identify molecular mechanisms and predictive markers of severe adverse reactions.", "The rapid emergence of high-throughput technology platforms in biology and the use of systems-based approaches to analyze and integrate large and varied sets of Omics data holds the promise of providing broader and deeper understanding of these complex phenomena [4] . Systems biology involves (i) monitoring different components of the biological system in response to specific perturbations, (ii) integration of multiple types of data over time, and (iii) creation of mathematical models to predict the structure and behavior of the system in question." ] },{ "paper_id": "c9c34b0ef9eacdf1bce00a71e1ff612479c3f004", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Transmission electron microscopy. For examination of infected BMMs by electron microscopy, BMMs were harvested at the time points p.i. indicated above and immersed in Ito's fixative (2.5% formaldehyde, 0.1% glutaraldehyde, 0.03% CaCl 2 , and 0.03% trinitrophenol in 0.05 M cacodylate buffer, pH 7.3) at room temperature for 1 h and then overnight at 4\u00b0C. After washing, samples were processed further as described previously (45) . Ultrathin sections were cut on a Leica EM UC7 ultramicrotome (Leica Microsystems, Inc.) and examined in a Phillips 201 transmission electron microscope (Phillips Electron Optics) at 60 kV.", "Although rickettsial infections have been studied for more than 100 years, the underlying mechanisms involved in the pathogenesis of rickettsial diseases remain incompletely understood.", "In addition, further investigations should focus on whether the autophagosomes observed in R. australis-infected BMMs result from blockage of the maturation of autolysosomes, which will lead to a better understanding of the mechanisms by which rickettsiae subvert the active autophagic response.", "In conclusion, by employing conditional, autophagy-specific gene-knockout mice, our studies clearly indicated that macrophages play a critical role in the in vivo pathogenesis of rickettsioses via autophagy gene-mediated mechanisms. R. australis manipulates macrophages for the benefit of infection in association with dampening the host inflammatory response and modifying the autophagic pathway. Our findings provide novel insights into potential host-based therapeutic interventions against rickettsioses by targeting the autophagy gene-dependent pathways in myeloid cells." ] },{ "paper_id": "c9cd7adce6639f51a4ee3e4bc7904eff851de25f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These data are expected to facilitate analyses of the epidemiology and evolutionary characteristics of PEDVs in Japan.", "This work was supported by the Science and Technology Research Promotion Program for Agriculture, Forestry and Fisheries, and Food Industry.", "We thank Hideki Hanaoka and all of the technical support staff at Life Technologies Japan Ltd. for helpful advice during this study." ] },{ "paper_id": "c9cf89e7642b3da75a33d482d26a330212677479", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ubiquitin is a small globular protein with a \uf062-grasp superfold conformation [39, 40] . Ubiquitin is covalently conjugated by its terminal glycine (G76) onto a lysine residue of a substrate protein.", "Ubiquitin is a small globular protein with a \u03b2-grasp superfold conformation [39, 40] . Ubiquitin is covalently conjugated by its terminal glycine (G76) onto a lysine residue of a substrate protein." ] },{ "paper_id": "c9d84fcde35a82c200f779df24657558638bf40b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The KT literature, which has grown considerably since 2000, overlaps with older implementation literature. Both KT and implementation theory are about putting knowledge into practice, but KT is explicitly focused on research evidence and the relationship between researchers and knowledge users. The older implementation literature focuses more on implementing innovations, policies, and programs, and influences on that process. Both bodies of literature inform our analysis.", "Implementation has been generally studied as a component of a larger change process, such as the diffusion of innovations [8, 9] . Implementation refers to a process of translating intentions into action with many possible outcomes, including degrees of both successful and unsuccessful implementation [10, 11] . These intentions are reflected in policies, plans, technologies, programs, and innovations. In public health, like other areas of healthcare, there has been movement toward evidencebased practice, programs, and policies [12] , and several terms have emerged to describe the process by which evidence is translated into practice, such as knowledge translation (KT), knowledge transfer, and knowledge exchange [13] .", "When practitioners believe they are already engaged in best practices (but we're already doing that!), leadership may be important to push staff 'to break out of the convergent thinking and routines that are the norm in large organizations' [8, p. 13] . It may encourage staff to reflect critically on whether they are truly implementing best practices, or just engaged in business as usual." ] },{ "paper_id": "c9df58c92109a1057c10b24867cb3566ffb46408", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author declares that they have no competing interests.", "Ability to immunize against multiple antigens and/or pathogens " ] },{ "paper_id": "c9df636e3e64891968ab4052a6fb6d20e95b1a2b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The cDNA expression construct encoding YN144 N protein was PCR amplified and cloned into pCAGGS-FlagC, which encode a C-terminal flag.", "Sequences (5\u2032-3\u2032) SiRNA-1 GGAAGAGUUGUGGAACCAATT SiRNA-2 GGAUUUGGUAAUGAUGGAATT SiRNA-3 GCGGUGGAGGUCAAUACUUTT Negative control siRNA (NC) UUCUCCGAACGUGUCACGUTT ", "SiRNA-1 GGAAGAGUUGUGGAACCAATT SiRNA-2 GGAUUUGGUAAUGAUGGAATT SiRNA-3 GCGGUGGAGGUCAAUACUUTT Negative control siRNA (NC) UUCUCCGAACGUGUCACGUTT" ] },{ "paper_id": "c9e24b269c1f1772454a1e93cc72c85251aeda6b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Aluminium is one of the most common adjuvant in non-living vaccines, has a record of successful use in human vaccination where it promotes antibody-mediated protective immunity [13] . Another classic adjuvant is that based on a water-in-oil-emulsion formulation, such as incomplete Freund's adjuvant (IFA). Recently, researches have focused on adjuvants that signal through pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) [14] . Cysteine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), which activate B cells and plasmacytoid dendritic cells via TLR9 and induce both innate and adaptive immunity, are currently being developed as a vaccine adjuvant [15] . Another frequently used adjuvant is polyriboinosinic acid (poly(I:C)), a synthetic dsRNA that mimics the effects of naturally occurring dsRNA, a TLR3 agonist [16, 17] .", "Pseudovirus inhibition (PI) rate was calculated as:", "(Relative luciferase units of mock sera -relative luciferase units of immune serum for a given dilution)/Relative luciferase units of mock sera." ] },{ "paper_id": "c9e87f843b3cf7dc47881fa3d3ccb4693d7d9521", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Children and adults have differences in hematologic and physiologic characteristics", "The optimal transfusion threshold for critically ill children has been evaluated in a multicenter trial in pediatric intensive care units [32] . This study reported that a restrictive transfusion strategy, which transfused at a hemoglobin <7 g/dL, had mortality and outcomes comparable to a liberal strategy (maintain hemoglobin >10 g/dL). This study evaluated stable, critically ill children without acute blood loss; hence, its applicability to burn patients is limited. A recently completed randomized prospective trial in adult burn patients with burn size >20% TBSA demonstrated no outcome difference between different transfusion strategies (Palmieri, in press).", "2. Cardiac function, mean blood volume, and normal hemoglobin levels are age-dependent in children; hence, children have a higher blood transfusion/unit volume ratio." ] },{ "paper_id": "c9eb97be96131dee33d53b03c46dacecf63c02b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Restriction-modification (R-M) systems encode a DNA methyltransferase and an endonuclease. The methyltransferase (MTase) methylates specific bases within the DNA recognition sequence; the restriction endonuclease (ENase) cleaves DNA that is unmethylated at these sites, whilst host DNA is methylated and avoids restriction (1) . This defence mechanism prevents incorporation of foreign DNA into the host and thus acts as a primitive form of 'immune system'.", "To avoid the possibility of ENase activity occurring prior to methylation of the host DNA, the system must be temporally regulated and ENase expression delayed until such time as the MTase has modified all potential host target sites. It is found that many R-M systems contain an additional gene coding for a small protein (the controller, or C, protein) (2-12) that regulates ENase expression (and may also, in some cases, modulate expression of the MTase).", "Cloning of the C.AhdI-binding site into a pBend vector" ] },{ "paper_id": "c9f6aba70979afa9fe1c10df0bce3909b26bb678", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus and cells H7N9 A/Anhui/1/2013 was obtained from the Chinese National Influenza Center, and all experiments with this virus were performed in approved enhanced biosafety level 3 (BSL-3) laboratories. A549 cells were cultured in Dulbecco's modified Eagle medium (DMEM; Gibco, NY, USA) with 10% fetal bovine serum (Gibco).", "A recent study by Ilyushina and colleagues [34] showed that a combination of the NA inhibitor oseltamivir carboxylate and rhIFN-\u03bb1 had a strong synergistic interaction. This discovery suggests that rhIFN combined with NA inhibitors might be a more effective therapeutic strategy against H7N9 infection. Our future work will investigate this combination therapy in appropriate cell lines and animal models.", "In addition to the seasonal influenza virus, some avian influenza viruses, such as H7N9 and H5N1 avian influenza A, can also infect humans. Since the first human infection with a novel H7N9 influenza virus (H7N9) was confirmed in China in the spring of 2013 [1] , there have been five epidemic waves of human H7N9 infections through 2017 [2] ." ] },{ "paper_id": "c9fca01d18bac485ae1c5257a712c516aeea8408", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mass spectrometric analysis of tryptic peptides was performed using a Synapt HDMS mass spectrometer (Waters, Manchester, UK) or a 4700 Proteomics Analyzer (Applied Biosystems) as described in [78] and [77] , respectively.", "Table S1 Plant proteins that were identified in the sucrose gradient fractions from healthy oat plants.", "Table S2 Raw and normalized peak areas, T-test results, and retention time coefficient of variation for plant peptides detected using SRM in aphids fed on CRDV-RPV infected or healthy plants. (PDF) " ] },{ "paper_id": "c9fee561c2a3834645dbb61dc4ae6448051da492", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequence (5 -3 ) Amplicon", "ANOVA. The data reported are the mean \u00b1 SEM. Differences were considered statistically significant when p < 0.05.", "The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher." ] },{ "paper_id": "ca04ce1ec6ebeed591eeaefdf378fa6aaaf91afc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ca091dd5921084c9469553962a04f7a475893623", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We examined the effects of daily local meteorological data (temperature, relative humidity, \"humidity-", "The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request." ] },{ "paper_id": "ca0c911ee3620b7acdb37a5b5d0b500128205f32", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Comparison of mean virus concentrations was done using an ANOVA analysis with Scheff\u00e9 post-hoc tests in the SPSS V20 software package (IBM, Ehningen, Germany). Cross-tables were done using EpiInfo7 (www.cdc.gov/epiinfo).", "Serological investigations in wild rodents were complicated by the fact that the vast majority of animals from virus-positive species were not live-trapped, therefore yielding no blood samples. Only post mortem peritoneal lavage fluids were collected from carcasses, but these were not qualified for serology. However, a subset of 97 live-trapped M. glareolus with appropriate blood samples were ", "Myodes hepacivirus clade 1 antigen specificity was proven by counterstaining with a high-titered rabbit serum raised against the same recombinant NS3 antigen down to dilutions of .1:20,000." ] },{ "paper_id": "ca0cc9c9da1307a7f36276eea4d117d6f74c2d7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses are a family of large, positive-sense RNA viruses that are responsible for a wide range of important veterinary (e.g. bovine coronavirus) and human (e.g. SARS-CoV, HCoV-OC43, HCoV-229E) diseases [21] [22] [23] [24] . MHV is a group II coronavirus that has long been used as a tool for studying coronavirus biology and pathogenesis.", "Coronaviruses (CoV) are enveloped, positive-stranded RNA viruses of the order Nidovirales, family Coronaviridae, and subfamily Coronavirinae [1] . Coronaviruses infect many species of animal including humans, and can cause severe disease in livestock animals that results in high economic losses. In 2002-2003, the appearance of severe acute respiratory syndrome (SARS), caused by a formerly unknown coronavirus (SARS-CoV) [2] [3] [4] , renewed the interest in this group of viruses.", "All statistical analyses were performed using Prism 4.0 software (GraphPad Software, http://www.graphpad.com/). Data were analyzed using the paired Student's t-test, with the assumption that the values followed a Gaussian distribution. A p-value of ,0.05 was considered to be indicative of statistical significance." ] },{ "paper_id": "ca0eb068e5fa4d0bdb05c7d5d6a2a0e0fbd36e40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "A NP aspirate method was selected as the best procedure for reducing discomfort of infants and young children during sampling. NP specimens were collected using NPAK 1 kits (M-Pro, Michigan, US). They were processed into aliquots (obtained by injecting a small 2-3 mL amount of physiological saline, and then aspirating) and immediately frozen at -80\u02daC. Frozen samples were shipped to Hospital Sant Joan de D\u00e9u and Hospital Clinic, both in Barcelona (Spain), where pneumococcal and respiratory virus studies were conducted, respectively.", "(XLS)" ] },{ "paper_id": "ca0f03f52fc023762577857285184f9777dc9a27", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ca13097c0bc4ca9abed010fa69c56531749da4dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background Healthcare workers may be exposed to people with respiratory viral infections more often than other working adults. Understanding the risk and the effectiveness of different preventive measures is of great importance.", "Conclusions Breakthrough influenza infection occurred in both vaccinated participants and those receiving antiviral prophylaxis. Most adults were willing and able to comply with season-long prophylaxis. Report of recent exposure to family members and patients with an ARI increased the risk of developing an ARI in healthy adults.", "Methods Participants were randomized 1:2 to receive the 2008-2009 influenza vaccine or daily prophylaxis with 10 mg of zanamivir during the season. Web-based questionnaires collected information on demographics, symptoms, exposures, medication use and side effects." ] },{ "paper_id": "ca1f90fcd49058d95c081f507c5496b6b962c982", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Diatom composition was computed in a similar manner as atom composition. The diatomic composition provides information about the pairs of atoms in each residue (e.g., C-C, C-O, C-N, etc.) of the peptides. The diatomic composition was computed using formula 2 which provided us a fixed length of 64 (8 \u00d7 8) vectors.", "(1) where atom (a) is one out of all eight atoms.", "(2) where diatom (a) is one out of all 64 diatoms." ] },{ "paper_id": "ca2a9474b1355a82b175767d68aaba4995e60681", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ca34ce0dd508d0f8777cc259e1b2fd4a58b73491", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PLOS ONE | https://doi.", "Human parainfluenza viruses 2(4) 3(5.5)", "Other viruses b 3(6) 6(11)" ] },{ "paper_id": "ca3ae7aca20eaa088ea6ebc2a21c619f5181f5f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ca3b60057b15c70f89253eea29c89a187fbc0fdc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ca46ca49c4bf5dd684e066f5674cc980b7afb0a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As shown by our earlier study, the emergence of an Egypt H5N1 drift variant (circulating one year later from the first H5N1 outbreak) exhibited significantly decreased crossreactivity by haemagglutination inhibition (HI) and microneutralization (MN) assays against the Mexican vaccine seed strain [15] . This evidence, together with previous observations, has raised the important question of the mechanism of antigenic drift under vaccine pressure. Additionally, the key role of an active serological postvaccination surveillance for the assessment of vaccine efficacy and evaluation of crossneutralizing capability of the vaccine concurrent with incremental virus escape from neutralizing antibodies is important [16] .", "Furthermore, reactivity observed validates the reliability and the quality of OIE-FAO reference sera that represents a prerequisite for the improvement of sero-diagnosis and can help to evaluate the effectiveness of vaccine strategies bearing in mind that an extensive library of reference sera for all influenza strains is an essential aspect for pandemic influenza preparedness [54] . It is likely that a new panel of reference sera will need to be prepared for use with pseudotype-based assays as they become more widely used in the future.", "The pp-NT assay is a valid surrogate for the more complex and time-consuming MN and for HI. Influenza pseudotypes can be employed to screen antibody responses on the particle surface due to the fact that HA is the major antigen of the virus against which neutralizing antibodies are produced [55] . It will permit HA subtyping, antigenic tracking of virus evolution, and help to improve both the evaluation of vaccine effectiveness and vaccine virus strain selection." ] },{ "paper_id": "ca52af941437873b4122bb2e26d7e3fab81cd73f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Base excision repair (BER) corrects damage to single mismatched or modified bases and is the principle pathway used for the reversal of oxidative DNA damage [40] . During BER, base damage is detected by DNA glycosylases that excise the damaged base creating an apurinic-apyrimidinic (AP) site [41] . The AP endonuclease 1 (APE1) incises the AP site, generating a single-stranded nick [42] . DNA polymerases fill the damaged region which is then sealed by either DNA ligase I or ligase IV [43] .", "IBV is a highly infectious avian gamma-coronavirus that primarily targets cells of the respiratory tract [187] . Coronaviruses comprise a diverse group of enveloped positive-strand RNA viruses that are responsible for several human diseases, most notably the severe acute respiratory syndrome (SARS) epidemic in 2003. Coronaviruses form replication complexes in association with intracellular membranes and the 27.6 kb genome encodes replicase proteins and four major structural proteins [188] .", "Biomolecules 2016, 6, 2 9 of 29" ] },{ "paper_id": "ca5775b18f2a5c86fc3efd929ef997a189fd1705", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "is full rank, N. This means that the system can be manipulated to reach any desired combination of states within all of state space following the defined input, B.", "In classic control theory, controllability is the idea that a deterministic system can be driven to any final state in finite time given an external input [34] . This is commonly applied to linear, time invariant dynamic systems," ] },{ "paper_id": "ca57f284dbad5683f531ee130483ca080a1f2d98", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Infections were initiated on day 0 by intraperitoneal (i.p) injection of 5610 4 PFU of salivary gland-passaged MCMV Smith strain prepared as previously described [40, 66] . In vivo responses were examined at indicated times post infection. Viral titer quantification was done as described (66) . Briefly, duplicate samples of serially diluted homogenates were plated on bone marrow stromal cell (M2-10B4) (American Type Culture Collection, Manassas, VA) monolayers for one hour at 37uC, 5% CO 2 . After 1 h incubation, inocula were removed from monolayers. Monolayers were overlaid with 16 DMEM/0.5% low melt agarose solution and further incubated for 7 days. Infected monolayers were fixed with 10% buffered formalin and stained with crystal violet to allow for visualization of plaques. Plaques were counted to calculate viral titers as previously described [23, 39, 66] .", "This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal work was approved by the Brown University Institutional Animal Care and Use Committee (Protocol number: 0903035).", "(DOCX)" ] },{ "paper_id": "ca5a2024931abd516addf3c4007d9a5b64432275", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: All authors contributed to the writing of the manuscript and carefully evaluated the manuscript before submission. " ] },{ "paper_id": "ca5c35779ac657261ff729dd0f8509e1b14a6acd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We limited the search to articles published between April 2012 (i.e., after the first MERS case was reported) and June 2016. Additional studies reporting associated outcomes that were not identified by the abovementioned search strategy were manually retrieved by tracking the references of included articles (i.e., ancestry and discordancy approach). We restricted ourselves to publications written in English.", "1. \"MERS\" OR \"middle east respiratory syndrome\" OR \"novel coronavirus\" OR \"novel coronavirus 2012\" 2. \"sever*\"OR \"fatal*\"OR \"death\" OR \"mortalit*\" 3. \"hospitalization\" OR \"intensive care\" OR \"ICU\" 4. 1 AND 2 AND 3", "Additional file " ] },{ "paper_id": "ca678602a715c23201b3947824b05053b0f56c4d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ca6b85f95f1eca57c0601972938aa2b8878bc2f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Poor nosocomial infection control may play an important role in emerging infectious disease outbreaks, including MERS", "On May 27, 2015, a suspected human case of MERS with a fever of 39.7\u00b0C, who had travelled from South Korea to Huizhou city, Southern China, was notified by the World Health Organization (WHO). This suspected case was then quarantined in a negatively pressurized room and confirmed to be infected with MERS on May 29. Strict infection control measures were taken in the hospital where the case was treated to reduce the risk of further transmission. On June 10, serum samples were collected from 53 healthcare workers who used personal protective equipment when treating this patient, and all were confirmed to be MERS-CoV negative [5] .", "Which intervention and control measures should be immediately taken when suspected Middle East respiratory syndrome (MERS) case(s) are imported from abroad? High priority should be given to the prevention of nosocomial infections among the workers and inpatients in the healthcare settings. Since the first human case of MERS coronavirus (MERS-CoV) was reported in Saudi Arabia in 2012, 1684 laboratory-confirmed cases and 600 related deaths have been recorded (as of January, 2016) [1] . As a result, great concerns about a potential pandemic arose [2, 3] . Although the majority of cases occurred in countries in the Arabian Peninsula, international spread of MERS due to travel has been reported in at least 20 other countries, with many cases emerging in the healthcare settings [4] ." ] },{ "paper_id": "ca6f9746b47f8fe6e187a867ad37502d950a3fbd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Healthy participants or legal guardians of the participants provided informed consent for participation. The Ethical Review Committee of icddr,b reviewed and approved the protocol for NiV surveillance and outbreak investigation.", "The field team centrifuged blood and transported specimens to IEDCR on wet ice or liquid nitrogen. Before 2007, specimens were shipped to the US Centers for Disease Control and Prevention (CDC) to test for Nipah-specific IgM by enzyme immunoassay. Since 2007, IEDCR and icddr,b have tested specimens using a Nipah-specific IgM ELISA provided by CDC, which has a high sensitivity, specificity and concordance with other Nipah-specific ELISAs [16] . CDC retested all positive samples and every tenth negative sample for reconfirmation and quality control.", "Researchers have identified regions characterized as emerging disease 'hotspots' where pathogens are more likely to emerge [31] . Different stage III pathogens with different case-fatality rates and different sociocultural settings and health systems may require different approaches and integration. Integration of clusterbased surveillance with other surveillance strategies could be evaluated in other low-income settings in emerging disease hotspots. Resources for surveillance in the highest risk areas of emerging infections remain scarce. Strategies to reduce cost have the potential to widen the global surveillance net for identifying and monitoring pathogens at highest risk for causing a severe human pandemic.", "In 2006, the Institute of Epidemiology, Disease Control and Research (IEDCR) of the Government of Bangladesh, with the collaboration of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) introduced year-round surveillance focused on identification of encephalitis clusters in 10 government hospitals and subsequent investigation of identified clusters. The objective was to identify encephalitis outbreaks including NiV at an early stage, to understand the risk factors and transmission pathways, and to introduce timely public health interventions to contain the identified outbreaks." ] },{ "paper_id": "ca73d739c9c8c6ddb081d0badcea76f821ae147a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The sequence of the MR766 ZIKV genome with the additional C nucleotide in the 3= UTR was deposited in GenBank under accession number KX830960. The sequence for plasmid pCDNA6.2 ATCCMR766 Intron3127 HDVr has been deposited in GenBank under accession number KX830961.", "ZIKV was first identified nearly 70 years ago (2) and has been progressively circulating in various parts of the world, including Africa and Asia. ZIKV emergence in South America in the last 2 years marked the first observation of a link between infections and severe forms of pathogenesis, including microcephaly and Guillain-Barr\u00e9 syndrome (3) . It is not known if the diseases caused by recent infections are a result of changes to the virus that increase pathogenesis or are influenced by host polymorphisms and immune reactions. The African, Asian, and South American ZIKV isolates are closely related phylogenetically; the original 1947 strain, termed MR766 (accession no. HQ234498) (2) , and a recent isolate identified in Puerto Rico, termed PRV2015 (accession no. KU501215) (4), share 96.9% amino acid identity. Thus, the characterization of sequence changes between these isolates that impact replication and disease should be reasonably straightforward. Such studies would be greatly empowered by the availability of a simple system to assay the functional consequences of altering viral sequences (i.e., a \"reverse genetic\" system).", "Immunoblot analysis. Immunoblot analysis was performed as previously described (19) with primary antibodies against NS3 (rabbit polyclonal antiserum 459, raised against a peptide representing amino acids 456 to 469 of the GenBank AAV34151 MR766 sequence) and actin (AC-15; Sigma-Aldrich, St. Louis, MO), horseradish peroxidase (HRP)-conjugated anti-rabbit and anti-mouse secondary antibodies (Thermo Fisher Scientific, Waltham, MA), and Immobilon chemiluminescent HRP detection reagent (EMD Millipore, Billerica, MA)." ] },{ "paper_id": "ca7514c743f1cab0c939328f75ff231ba9d9079d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The five peptides were successfully synthesized on an Abimed AMS 422 synthesizer by Fmoc solid-phase peptide synthesis. The purities of all five peptides showed reliable quality of more than 95%. The molecule weights measured by mass spectrometry (MS) were completely matched with the calculated molecule weights of these peptides.", "Samples were collected at day 7, 12, 13, 14, 15, 16 , and 17 after infection. Supernatant and cell samples were separated by centrifuge 1000 rpm for 5 min (Thermo). Samples were detected for p24 by ELISA and measured for infectivity by TZM-bl detection systems as described above.", "Nearly 34 million people were living with human immunodeficiency virus (HIV) at the end of 2010 in the globe [1] and half of them were women. Unfortunately, there are still no effective vaccine or other countermeasure to eliminate HIV transmission [2] . The Merck STEP [3] and the Thai RV144 HIV vaccine [4] trials confirmed that we still have a long way to go before developing a prophylactic HIV vaccine. Meanwhile, HIV virus spreads fast and the HIV/AIDS pandemic still stands as a serious public health problem worldwide [1] . Current situation clearly indicates the necessity of developing new anti-HIV agents which can be used for prevention of HIV/AIDS dissemination." ] },{ "paper_id": "ca8476b6429d8fb8ea4d3e094c222fbd5a7f6304", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: S.P.A. and A.F. performed the literature review and wrote the manuscript.", "Funding: This work was supported by a CIHR foundation grant #352417 to Andr\u00e9s Finzi. Andr\u00e9s Finzi is the recipient of a Canada Research Chair on Retroviral Entry #RCHS0235 950-232424." ] },{ "paper_id": "ca866226d436ba4c39fe854f9cc568f08638868d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vesicle preparations were spotted onto a PVDF membrane, incubated with with specific primary antibodies and an HRPcoupled secondary antibody and developed with the ECL system (GE Healthcare). Ganglioside M1 was detected with colera toxin (Sigma Aldrich).", "Epstein-Barr virus (EBV) is an almost ubiquitous human gamma herpes virus that infects resting human B-lymphocytes, including B-CLL cells, with high efficacy [1, 2] . EBV's B-cell tropism is mainly due to gp350, the viral envelope glycoprotein that interacts with the cellular complement receptor 2 (CR2, CD21) [3] on B cells. In EBV seropositive individuals, gp350 mainly elicits CD4+ T-cell responses [4] .", "Next we wanted to elucidate the specificities and cytolytic activity of these T cells in more detail. As mentioned above, restimulated T cells form B-CLL patients efficiently lysed autologous PBMCs that were activated with CD154+/gp350-exosomes." ] },{ "paper_id": "ca8f30a35b564945dd2588c382a0e181a1e08662", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study protocol and consent form were approved in written from the Human Research and Ethics Committee of Beijing Anding Hospital, Capital Medical University.", "For further examples and details relating to each theme please see Additional file 2. For a summary of theme and sub-theme please see Fig. 1 .", "All participants were informed of the objective of the study and gave written consent before the investigation." ] },{ "paper_id": "ca96c55394d856036b970cb39c695ef3bb616454", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ca96f361ba8d99dedbd1421fe735d230e86f7797", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In order to assess statistical significance, an unpaired (for single representative experiments) or paired (for graphs showing the mean of three independent experiments) student's t-test was performed. For inhibitor studies, statistical significance was calculated for results differing at least 5-fold from control conditions, since smaller effects were considered to be within the variation inherent to the assay system.", "The impact of the following compounds on filovirus GP-driven entry was studied (for detailed information please refer to Table 2 ): Mannan, ammonium chloride, bafilomycin A1, E-64d, ", "doi:10.1371/journal.pone.0149651.g004" ] },{ "paper_id": "caacab8201dadba7c322aaebad07309ef12e3c93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "M.A.A.); Mobarak.Mraheil@mikrobio.med.uni-giessen.de (M.A.M.) \u2020 These authors contributed equally to this work.", "Outer membrane vesicles (OMVs) are natural, spherical nanoparticles (50-250 nm) derived from Gram-negative bacteria. OMVs are released from both pathogenic and non-pathogenic bacteria and are highly immunogenic due to their components, including lipopolysaccharides (LPS), bacterial outer membrane (OM) proteins, lipids, immunogenic toxins, DNA/RNA and other periplasmatic and cytoplasmatic proteins [17, 18] .", "Influenza" ] },{ "paper_id": "caadc408ff1144a53369c7e0f63634ff264be9ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was done using SPSS, version 11.0 (Statistical Package for Social Science (SPSS, 22\u00ae, IBM, NY, USA). The reliability of test items was tested by calculating Cronbach's alpha coefficients for the knowledge and practice items.", "We also sought to measure the third level of Kirkpatrick's evaluation, [25] which specifies for behavior changes after training and education, by contacting the students by email after one and half years. Those who did not respond to the email were contacted by phone whenever possible.", "All the learning activities are inter-related, and this creates a framework for effective disaster medicine training [34] . It has been demonstrated that participants in courses using different teaching methods are more confident in their knowledge for at least 6 months following the training [35] .", "Cronbach's alpha coefficients for the knowledge and practice items, calculated on the pretest, were 0.723 and 0.897, respectively, demonstrating the reliability of the test items." ] },{ "paper_id": "cab83150f6a2199249918297638108ce1c45e4e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The corporate movement and new tax reduction strategies" ] },{ "paper_id": "cabe6a81b684ef3c7b8febdc093f1aacbe06ced6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "With the modulation of cholesterol levels in host endosomal membrane as a mean to inhibit IAV host cell entry is still under debate, further studies are required before clear conclusions can be drawn.", "July 2018 | Volume 9 | Article 1547", "Innate lymphoid cells are cells of lymphoid lineages that do not express antigen-specific B-or T-cell receptors (166) . Similar to T-helper cells, they are classified into subsets by their ability to produce type 1 (Th1), type 2 (Th2), and type 3 (Th17 and Th22) cytokines.", "Recent history has seen the outbreak of IAV pandemics of varying severity takes place at the cost of millions of lives. One such example would be the deadly Spanish flu of 1918, which claimed the lives of 20-50 million of the 500 million people infected worldwide.", "Studies suggested that IAV strains could be associated with either over-activating (human infection by avian H5N1 and H7N9) (153, 154) or suppressing (H1N1, H3N2) (155) immune response." ] },{ "paper_id": "cabe96ceeaf4de3ad158c2579936a1ff3dfa352d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The trajectories of 292.2 K, 300 K and 308 K were used in the further analyses except that only the trajectory of 300 K was used in the chemical shifts calculations.", "For conventional ordered proteins, the binding conformation is unique which could be selected from pre-existing conformations (the conformational selection mechanism) or be induced (the induced fit mechanism) by particular ligands. The scenario of ligand clouds around protein clouds for IDPs indicates that multiple protein conformations are selected and/or induced by the binding of a ligand on IDPs. This may extend the conformational selection-induced fit continuum in a new dimension.", "MD simulations with the explicit solvent model were performed with the GROMACS 4.5.4 software package [61] and AM-BER99SB force field under particle mesh Ewald periodic boundary conditions. The TIP4P-EW water model [63] was used with AMBER99SB force field because of its previously reported good performance in other simulations of IDPs [36, 47, 65] . In the holo simulations, the small molecule 10074-A4 ligand involved was parameterized using a general amber force field (gaff) with ACPYPE software [66] . An AM1-BCC charge model [67] was used to assign charges to the ligand." ] },{ "paper_id": "cac106b063755a144ec1154f593d78d5a4f6f4c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The cells were washed with ice-cold PBS and treated with RIPA lysis buffer containing 1 mM PMSF (Beyotime, China). The cell lysates were sonicated and then centrifuged at 12,000 rpm at 4\u00b0C for 20 min. Protein concentrates were quantitated using a BCA protein assay kit (Beyotime, China). Protein samples were mixed with 5X SDS loading buffer and boiled for 10 min before being separated by SDS-PAGE. The electrophoretically resolved proteins were transferred onto PVDF membranes (Millipore, USA) and blocked with 5% nonfat dry milk at room temperature for 1 h, and the membranes were incubated with the indicated primary antibodies overnight at 4\u00b0C; they were then incubated with HRP-conjugated secondary antibodies at room temperature for 1 h. The ECL Reagent (Millipore, USA) was used for chemiluminescent detection of HRP-labeled proteins, according to the manufacturer's instructions.", "TGEV replication was not significantly affected by the NF-\u03baB signaling pathway", "All experiments were repeated a minimum of 3 times. The experimental data were statistically analyzed by two-way repeated measure ANOVA (RM-ANOVA) using Graphpad Prism software (version 5.0). P-values less than 0.05 were considered statistically significant, and those less than 0.01 were considered highly significant.", "Coronaviruses constitute a significant threat to both human and animal health. Pathogenic inflammation is activated by a coronavirus infection, which might result in the death of the host [17, 18] . NF-\u03baB is highly activated in diverse coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus, murine coronavirus, porcine epidemic diarrhea virus (PEDV), and infectious bronchitis virus (IBV) [6, [19] [20] [21] [22] . The NF-\u03baB-induced inflammation in these coronavirus infections plays an important role in pathogenesis and disease development." ] },{ "paper_id": "cac120abb934d9ce2974326a0f98eef4ec6dd07e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine epidemic diarrhea (PED) is an acute and highly contagious enteric disease of swine that results in severe enteritis, diarrhea, vomiting, and dehydration. Especially in suckling pigs, mortality can be very high [1] . The causative agent, Porcine epidemic diarrhea virus (PEDV), is an enveloped positive single-stranded RNA virus that belongs to genus Alphacoronavirus in the family Coronaviridae [2].", "After its first recognition in the 1970s in Europe [3] , the disease caused considerable economic losses, especially in Asia. Since the 1990s, Europe has reported only sporadic cases [4] .", "Supplementary Materials: The following are available online at www.mdpi.com/1999-4915/9/7/177/s1, Table S1 : Overview of the sequences used as references for phylogenetic analyses, Table S2 : Nucleotides minor variants of sequenced PEDV samples, Table S3 : Overview of metagenome analysis of selected PEDV samples.", "For an overview of the bacterial background of selected samples, we compared data sets of duplicates per farm. The most widespread bacteria that could be identified in these samples belonged to Bacteroidaceae, Clostridiaceae, Lactobacillaceae, Methanobacteriaceae, Methanomassiliicoccaceae, Porphyromonadaceae and Prevotellaceae (see Supplementary Table S3 )." ] },{ "paper_id": "cac8f96521f21bbd0a84861a98a5715d86b293f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 872 samples were selected. (S1 Table) Total nucleic acid extraction ", "Climatic factors may also indirectly favour the transmission efficiency because low temperatures induce a change in social behaviour that favours interior overcrowding and increases the likelihood of close contact and transmission of infections [63] . For this reason, it is a common suggestion to avoid going to school or work when you are undergoing an infectious process.", "Supporting information S1 " ] },{ "paper_id": "cad994637f061356cd5ea11a7570b2f5ad38ed47", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(ZIP)" ] },{ "paper_id": "cada5ab8069fa39139ce27d9568654e67993adbf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "and because HU AIR \u00bc \u00c01000 and HU WATER \u00bc 0;" ] },{ "paper_id": "cae0b002b145d21b55c8fdde52e28b269aa405f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations BRVA: bovine rotavirus A; DNA: deoxyribonucleic acid; dNTP: deoxynucleotide triphosphate; EMEM: Eagle's minimum essential medium; ERVA: equine rotavirus A; IVT: in vitro transcribed; LOD: limit of detection; RNA: ribonucleic acid; RT-qPCR: reverse transcription real-time polymerase chain reaction; RVA: rotavirus A; SRVA: simian rotavirus A; TCF: tissue culture fluid", "Analytical specificity of ERVA-specific singleplex and multiplex RT-qPCR assays", "To evaluate the precision of the multiplex RT-qPCR assay, within-run and between-run imprecision was determined as recommended [42] . In all cases, the coefficient of variation was less than 3%, indicating that the multiplex assay has a high repeatability (within-run) and reproducibility (between-run) within the range of detection (Table 5) ." ] },{ "paper_id": "caef06c4bfe01781e8efcb9d5d22a1f5d5b2efc0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Melioidosis is a", "Author Contributions: X.Z. conducted the data collection and wrote the first draft of the manuscript; Q.X. reviewed and revised the manuscript. L.X. and W.L. contributed to the writing of the manuscript. ", "The first event linking melioidosis to China occurred in France in the early 1970s when an outbreak of melioidosis at the Jardin des Plantes zoo was attributed to a giant panda from China [6] . Nevertheless, as pandas uniquely inhabit the high-altitude mountainous areas of Southwest China, where neither B. pseudomallei nor human or animal melioidosis has ever been reported, the panda might actually have been a victim of this outbreak rather than the source." ] },{ "paper_id": "caf95fa590e7cbb34e10314bfd93beb44e35caab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cafa25b00fd0b65e7d337fd03a204be2acb3243f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was a fragment of the integrated research work \"Improvement of diagnostic, medical and preventive measures at widespread viral and parasitic diseases\" (state registration number ", "Control Group", "Statistical analysis was performed with Statistica 10 software package. The data were presented as mean M \u00b1 m). A two-way analysis of Student's t-test, Spearman rank correlation analyses, Mann-Whitney-Wilcoxon and Wilcoxon signed-rank tests were used. The p < 0.05 was considered significant." ] },{ "paper_id": "cafc9ffe47534a504ae1036e5b7299d80f49beb5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Is it possible to correlate evidence for ancient viruses with any other major transitional events in the evolutionary history of animals or plants?", "What ancient viruses have caused selective pressure along the human lineage?", "Essays articulate a specific perspective on a topic of broad interest to scientists." ] },{ "paper_id": "cb04b7111c59c623bd68cf0441f18ccfcddb5b40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/ mSphere.00047-19. ", "Signaling pathways were obtained using KEGG Mapper on the KEGG database (62) (63) (64) . Statistical analysis. Group comparisons of data were performed by one-way or two-way analysis of variance (ANOVA) using GraphPad Prism 7 software.", "The neural progenitor cell line (NPC) used in this study carries a neuron differentiation Map2-Nluc marker and was provided by Jihwan Song (CHA Stem Cell Institute, CHA University). NPCs were cultured at a 1:1 ratio of N2 and B27 media with 20 ng/ml of basic fibroblast growth factor (bFGF). N2 medium consisted of DMEM/F12 plus GlutaMAX, 1\u03eb N2, 1\u03eb nonessential amino acids, 5 g/ml insulin (Sigma), 100 M \u2424-mercaptoethanol (Sigma), penicillin, and streptomycin. B27 medium consisted of Neurobasal medium, 1\u03eb B27 with or without vitamin A, 1\u03eb GlutaMAX, penicillin, and streptomycin (59) . NPCs were maintained on a poly-L-ornithine/laminin-coated dish or plate. All materials for media were supplied by Gibco unless mentioned otherwise." ] },{ "paper_id": "cb0831902de1f8a19992ff86bcc7e15fa2d7d687", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflicts of interest.", "Author Contributions: H.N. conceived the study, and all authors participated in the study design. H.N. collected the data and A.R.A. and H.N. analyzed the data. All authors jointly drafted the manuscript. All authors gave comments on the earlier versions of the manuscript. All authors have read and agreed to the published version of the manuscript. ", "Three important arguments are made here with respect to epidemiological interpretation of the epidemic dataset. First, Figure 1A shows the epidemic curve of cases in Wuhan, distinguishing case generations by color. The index case developed symptoms on 1 December 2019, with cases 2-4 having onset nine days later, and cases 5-6 five days after that. Together, these intervals indicate a possible serial interval (SI)-the time between illness onset in an earlier case to that in a secondary case-with a mean of 7.4 days, consistent with the mean SI of severe acute respiratory syndrome [2] . The latter is also consistent with the mean SI estimate of 7.5 days presented in the preliminary epidemiological study [3] ." ] },{ "paper_id": "cb0ba244ebf7524d9303edd3c52946f08560f597", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We conducted a descriptive cross-sectional assessment using the protocol developed by the World Health Organisation (WHO). The data collection tools were adapted locally and administered to a convenience sample of IHR(2005) stakeholders, and frequency analyses were performed.", "Th e Atomic Energy Act of 2008 (CAP 143) provided guidance on the utilization of atomic energy for socioeconomic development and ensured that safety standards were upheld through regular inspections of radio-nuclear facilities by the Atomic Energy Council. Th e legislation, however, did not provide for mandatory notifi cation of accidents, leakage or theft of radioactive sources at radionuclear facilities.", "Th e core capacities assessed for each of the fi ve IHR(2005) hazards (infectious, chemical, zoonoses, food safety, radio-nuclear) and points of entry included: national legislation and policy; coordination; surveillance; response; preparedness; risk communication; laboratory; and human resource capacity." ] },{ "paper_id": "cb2072b85cfa7e151150b5ecea189ea22134f4d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All PIV-infected patients were immunocompetent which was defined as the absence of organ transplantation, human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), autoimmune disease, leukemia, pancytopenia, lymphoma or under immunosuppressive drug therapy. All patients underwent a respiratory virus panel screening. Respiratory system samples (bronchoalveolar lavage or tracheal aspirate) were collected in disposable mucus extractors (Vygon SA, \u00c9couen, France). Samples were assayed by reverse transcriptase-polymerase chain reaction (RT-PCR) to detect 20 respiratory pathogen which include ", "The age of the patients ranged from 4 days to 71 years with a mean of 14.6 \u00b1 23.4 years and Median (Inter-Quartile) is 7 months (2 months-24.5 years) ( Table 2) . Table 1 shows age grouping of the study population according to sex. The male to female ratio was 1.2:1.", "Patient records from the Virology Unit (VU), Faculty of Medicine, Kuwait University Database, were retrospectively reviewed to identify patients with viral infections admitted to the PICU & ICU from January 2013 to December 2015. The VU is an academic institution serving five hospitals in Kuwait (Amiri Hospital, Mubarak Al-Kabir Hospital, Sabah Hospital, Farwaniya Hospital, and Adan Hospital)." ] },{ "paper_id": "cb2653d6bccc8ea8da3bb3abef1840d3ba2b9701", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chikungunya virus is an alphavirus, member of the Togaviridae family, which causes fever, skin rash and severe joint pain. The symptoms resolve within weeks, but the arthralgia is recurrent in 30-40% of the cases and can persist for months or years [89] . The virus is transmitted to humans by Aedes mosquitoes and currently mainly affects individuals in the Americas." ] },{ "paper_id": "cb43de0358c05aba59dfb4957432fc2cbe31b30e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vero (African green monkey kidney) cell lines ATCC CCL-81 (American Type Culture Collection, USA) and all stable cell lines produced in this study were maintained in Earle's Minimal Essential Medium (MEM) (Invitrogen, USA) supplemented with 5% of fetal calf serum (FCS) (Invitrogen, USA).", "Methods S1", "(DOC) Figure S1 (DOC) Figure S2 (DOC) Figure S3 (DOC) Figure S4 (DOC) Figure S5 (DOC)", "It is unclear to what extent the molecular structure of SLAM receptors of species belonging to different carnivore families alters the binding ability of CDV-H proteins of different strains." ] },{ "paper_id": "cb44482e84ab91364682dfbcdb7ee5c9dd394f74", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SUPPLEMENTAL FILE 1, PDF file, 10.5 MB." ] },{ "paper_id": "cb495813627c5daa898a901ef2c076fe8469ea66", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ZQ, YW, and TD designed this study and prepared the manuscript. GQ, YG, and WG collected the specimens. YW, TD, and YG conducted the epidemiological investigation. TD, LQ, WL, BQ, ZZ, LS, HG, XD, BL, ZL, HY, QC, XW, and YL performed the laboratory experiments. YW and TD analyze the data and made the figures and tables. All authors reviewed the manuscript. ", "Flu PIV RSV ADV Cases", "Total 189" ] },{ "paper_id": "cb55f63de6946c57d21275e45c94c79955bba977", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animal experiments can provide direct information on the relationship between carcinogenic agents and carcinomas: successful examples include Mongolian gerbils infected with H. pylori for studying gastric carcinoma [53] and HBV transgenic mice for studying liver cancer [54] . Appropriate animal models play an important role in the evaluation of infectious agents in carcinogenesis.", "Tumor initiation is usually a complex, multistep process involving environmental, biological, and genetic factors. Tumor viruses may play important roles in carcinogenesis; they might also contribute toward uncovering the cell growth pathways of cancer [68] .", "1. Epidemiological study should provide evidence of the proposed factor being an independent risk factor for the cancer's incidence; 2. Introduction of the proposed factor into animal models should produce the malignancy, mirroring the human disease;" ] },{ "paper_id": "cb56f2e5caa4992c01aedc47943146ee81cac007", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ") within the subarachnoid space or meninges giving rise to plasma blast (PB) and memory B cells (B mem ). (C) Migration of peripherally activated PB into the CNS that further differentiate into plasma cells (PC).", "Nevertheless, culture of MHV-infected cells in the presence of neutralizing Ab results in persistently infected cells, which only produce progeny virions following fusion with cell lines capable of supporting replication [95] .", "It is intriguing that astrocytes are rarely infected by MHV-JHM [127] suggesting their CXCL10 expression is driven by T cell-derived IFN-\u03b3 rather than infection itself. CXCL10 is also induced in primary astrocyte cultures infected with TMEV or treated with IFN-\u03b3 [128] . These findings support the notion that astrocytes are main CXCL10 producers under inflammatory conditions where IFN-\u03b3 levels are high, irrespective of virus tropism. On the other hand, in settings where local IFN-\u03b3 production is less prominent, the response of infected cells may regulate ASC recruitment and positioning, especially under conditions of potent pattern recognition receptor and/or IFN-\u03b1/\u03b2 signaling. For example, CXCL10 induction in infected neurons [129] can direct regional migration of T cells and possibly also ASC. Direct comparison of virus variants with distinct tropism, in conjunction with their associated pro-inflammatory responses, may address this question in the future." ] },{ "paper_id": "cb57d1d9d929477c14cabe401b967245c70b4715", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The HR1-L6-HR2 fusion protein was crystallized at 20 C using the hanging-drop vapour-diffusion method. Crystals were grown on a siliconized cover slip by equilibrating a mixture consisting of 1 ml protein solution (8 mg ml \u00c01 HR1-L6-HR2 trimer in 20 mM Tris-HCl pH 8.0, 150 mM NaCl) and 1 ml reservoir solution (0.03 M citric acid, 0.07 M bis-tris propane pH 7.6, 20% PEG 3350) against 400 ml reservoir solution. Single crystals grew after one week and were flashcooled in liquid nitrogen for data collection after adding 20% glycerol as a cryoprotectant.", "The deadly global outbreaks of SARS in 2002 and MERS in 2012 highlight the importance of developing vaccines or treatments for CoVs, for which there are still no effective drugs or vaccines available. Both SARS and MERS are zoonotic CoVs. Before inter-species jumping, humans rarely came into contact with zoonotic CoVs, and therefore lack neutralizing antibodies to zoonotic CoVs. As a consequence, zoonotic CoVs usually pose substantial health and pandemic threats to humans. Given the high genomic mutation rate of CoVs and ever-increasing global population shifts, future research papers outbreaks of CoV pandemics such as SARS or MERS are very likely to occur. To this end, structural and functional characterization of HCoVs takes on greater significance, especially for the structure-based design of future therapies or vaccines.", "potential. HCoV-229E, on the other hand, is endemic and is frequently associated with respiratory diseases ranging from the common cold to atypical pneumonia (van der Hoek, 2007) . In healthy adults, HCoV-229E infection usually causes mild symptoms, including headache, cough, fever and rhinitis (Greenberg, 2016) , but can lead to compromised productivity in infected individuals and result in a large impact on the economy. Moreover, HCoV-229E infection can result in severe or even lethal outcomes in infants, young children, seniors and those with weakened immune systems (Forgie & Marrie, 2009; Jartti et al., 2011) . Therefore, it is important to investigate the structure and function of HCoV-229E to aid in the development of preventative or therapeutic strategies." ] },{ "paper_id": "cb763a61411514366d16bb2571461b6df1361517", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The statistical analyses were accomplished using GraphPad Prism 5 (GraphPad Inc., La Jolla, CA, USA). Either t-test or one-way analysis of variance (ANOVA) of mean and median, followed by Tukey's post hoc test, was performed according to the data types. Statistical significance was designated as p 0.05.", "To study the cytopathology of H5N1-infected hNPCs, cells in 6-well microtiter plate were infected by a 1 MOI of H5N1 virus. At 24 hpi, cells were fixed in 2.5% glutaraldehyde for 48 hours, washed three times with phosphate buffer saline (PBS), and post fixed in 2% osmium tetroxide for 1 hour at RT. After being serially dehydrated in ethanol, the cells were incubated in propylene oxide and embedded in resin (EM-bed 812, Electron Microscope, Washington, USA). Semi-thin sections were cut and stained with toluidine blue for light microscope examination. Thereafter, ultra-thin sections were cut, mounted on copper grid, and electron contrasted with uranil acetate and lead citrate. The grids were examined and photos were taken under a JEM-2200FS transmission electron microscope (JEOL ltd., Tokyo, Japan).", "Upon virus infection on day 7, the hNPCs (differentiated from hESCs) displayed morphology of spindle, bi-to multi-branch processes (Fig 1A) . The mRNA expressions of Nestin, Pax6 and Sox1 genes indicated their neural progenitor phenotypes (Fig 1B) . Immunophenotypic characterization of the hNPCs revealed that more than 85% of the cells expressed characteristic markers specific for neural progenitor phenotypes, including Nestin (Fig 1C-1E) , Pax6 (Fig 1F-1H) and Sox1 (Fig 1I-1K )." ] },{ "paper_id": "cb76568fb12e6a9802c85a994def23156d29352b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ObjectInputStream input = new ObjectInputStream(con.getIn-putStream()); // create input stream; out.writeObject(agentId); // send agent ID to the host; String agentName = (String) input.readObject(); // obtain agent name;", "Agent migration can help agents: (1) approach data sources or service requests, and reduce network communication workload;", "String rmiiiopAddress = ''//''+address+''/preReceiveAgent''; Receiver receiver = (Receiver) Naming.lookup (rmiiiopAdddress); // look for preReceiveAgent() method; boolean migrate = receiver.preReceiveAgent (host, port, agentId); // invoke preReceiveAgent(); \u2026 ObjectOutputStream out = new ObjectOutputStream(con.get OutputStream()); // create output stream;", "String address = desAddress; // the address of the destination host;" ] },{ "paper_id": "cb820c7373e5c272cc31065db8579e927176be72", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cb98e2840f97f1b0425ac66e90784b5fe5fcecb7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Inclusivity and exclusivity testing. M. canis (ATCC 19525), M. cynos (ATCC 27544) and synthetic DNA (plasmids) from both targets were used to test the inclusivity of the assay. Assay exclusivity included 7 different species of Mycoplasma spp. and 12 strains of bacteria and viruses associated with respiratory diseases, including DNA extracted from Nobivac vaccine (Merck, Kenilworth, NJ, USA) ( Table 1) . Genus and species identification of strains isolated at AVDL were confirmed by Sanger sequencing as previously described [33] .", "Supporting information S1 Table. Primers and probes used to detect pathogens associated with canine infectious respiratory diseases. F: forward primer; R: reverse primer; P: probe. ", "This study has some limitations. First, the PCR-based assays could potentially yield falsepositive results in dogs that recently received modified live vaccines containing the specific pathogens of interest. This assumption is based on findings from a previous study showing that PCR assays may detect vaccine content within 28 days after vaccination with modified live vaccines against CAV, B. bronchiseptica and CPIV [45] . Since the time between vaccination and the onset of clinical CIRD was not documented in our submission forms, we cannot say with certainty whether positive PCR results corresponded to field or vaccine strains. Secondly, as with any pathogen detection test, the PCR assays may yield false-negative results if samples are collected at a point in the disease process when pathogens are not present at detectable levels [46] .", "Evaluation of PCR performance using synthetic DNA (plasmid). For the purpose of analytical validation, the assay sensitivity and the amplification efficiency were verified by testing 10-fold serial dilutions of synthetic positive amplification controls (plasmids), using a modified approach [32] . These contained the 16S rRNA target for either M. canis or M. cynos, which were inserted into plasmids pUC57 kanamycin and transformed into competent Escherichia coli cells (DH5\u03b1 strain). Synthetic DNA plasmids were purchased from GENEWIZ (South Plainfield, NJ, USA). Each E. coli colony-forming unit (CFU) contained one copy of the plasmid. E. coli was cultured overnight on Luria-Bertani agar with Kanamycin (Remel, San Diego, CA, USA) and isolated colonies were used to prepare a 10-fold serial dilution from a starting 0.5 McFarland concentration. Each dilution was plated on McConkey agar (Remel) in triplicate (100\u03bcl). Colony counting was performed after 24h of incubation at 37\u02daC. DNA was extracted from each dilution as described above. The limit of detection (LOD) was defined as the lowest concentration at which 95% of the positive samples were detected [30] . The concentration (plasmid copy number) in each dilution was calculated from the plate counts (CFU/ mL). The copy number in each PCR reaction was calculated based on the extraction volume (200\u03bcl), the final elution volume (120\u03bcl) and the volume per reaction (5\u03bcl); assuming error free conditions. Dilutions were repeated in triplicate runs for each targeted microorganism and standard curves were constructed from the Cq values. PCR efficiency was calculated according to MIQE guidelines [30, 31] ." ] },{ "paper_id": "cbabbd687725e949c99a0a6f53f033128ea1aaca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Yearly, over 300 million people are infected with DENV of which~100 million symptomatic and 500,000 to 1 million develop severe disease resulting in~25,000 deaths. Several groups are performing clinical trials with TV-live attenuated dengue vaccines. The leading candidate had lower efficacy against serotype 2 and also overall poor efficacy in young children [10] , highlighting the importance of exploring new vaccine platforms. The use of nanotechnology in vaccine development has taken a rise in recent decades. Instead of using whole or live virus formulations to induce immunological protection against infectious diseases, subunit or subviral particle based platforms provide elegant and safe alternatives that have been proven efficacious against a large variety of viral pathogens [42] [43] [44] [45] [46] [47] ." ] },{ "paper_id": "cbb02b21e4165b060929344f2f02ab6859016be3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study applied mixed methods to collect and analyze public health-related risk factors using a correlational research design.", "A series of data collection tools were used. These included:", "(3) A descriptive analysis was performed on completed questions. Comparisons between risk factors were made by chi-square and ANOVA analysis using SAS version 9.3. (Carry, NC, USA). A p value < 0.05 was considered statistically significant." ] },{ "paper_id": "cbb97774bf1adc0c1465970bcdabcd43ce0b365d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These studies show that these kinds of vaccines not only do not induce protective immunity but may lead to increased morbidity and mortality.", "JVW serves on a Scientific Advisory Board of Quidel and an Independent Data Monitoring Committee for GlaxoSmithKline. NS has no competing interests.", "JVW was supported by National Institutes of Health grant R01 AI-085062. NS was supported by National Institutes of Health grant T32 AI060525.", "There are two major genetic lineages, A and B, further divided into the sublineages (or clades) A1, A2, B1, and B2 32-35 . All HMPV genes fall into these four clades, suggesting that genome recombination is very rare 33 . Although both genotypes A and B can co-circulate, the dominant lineage may vary year by year 33,36 . Phylogenetic analyses of HMPV suggest that the human virus diverged from the avian type C 200-400 years ago [33] [34] [35] 37 . HMPV cannot productively infect birds; thus, if HMPV did arise in humans as a zoonotic infection, the virus is now adapted fully to humans 2 . Evidence suggests that the different genetic lineages of metapneumovirus do not represent distinct serotypes; studies in rodents and non-human primates show a high degree of cross-neutralization and cross-protection between subgroups 38-41 .", "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ", "Vectored vaccine approaches that have been effective in animal models include chimeric rHMPV containing the avian metapneumovirus P protein 128 , alphavirus-vectored HMPV F 129,130 , bovine PIV3 vectored F 39 , or Sendai virus vectored F 131 . The establishment of a human challenge model 132 and a successful test of a live-attenuated candidate in seropositive adults 133 provides a platform for future clinical trials." ] },{ "paper_id": "cbc100f9459ee41fa74a2ef65540097e420a461f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Creative Commons CC-BY 4.0", "In addition, Town Cats (TC) and Palo Alto Humane Society (PAHS) are two small privately run shelters that are not government entities, and perform no cruelty investigations.", "Friendly (passes behavior)", "Shelter data was provided to, and maintained by, the authors on an annual fiscal basis from program managers, shelter officials, or Board reports for each shelter listed. The calendar year annual shelter reports were generally not publicly available until 2007, when Asilomar Accords (Maddie's Fund, 2011) reporting standards were adopted by five of the six local shelters whose data is included in this report." ] },{ "paper_id": "cbc8e184157e7543e44f09f2be3999131db359e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lycorine, a pyrrolophenanthridine alkaloid, is one the major alkaloids found in H. littoralis [2, 7] . It displays strong antiviral effect against poliovirus, measles, and herpes simplex type 1 viruses [8] . Besides, lycorine also possesses potent antiretroviral [9] , antimitotic [10, 11] , and cytotoxic activities [2, 12] .", "All experiments were repeated thrice with three replicates for each extract. The data were analyzed using IBM SPSS Statistics 20 software. Analysis of variance (ANOVA) and the means which were compared using the Tukey HSD at 5% level of significance ( < 0.05) were used.", "The Scientific World Journal maritimum [2] and Sternbergia species [14] as well as tissue culture of Pancratium maritimum [15] , Narcissus confusus [10] , and Leucojum aestivum [16] .", "The standard lycorine was purchased from Sigma-Aldrich (USA). Analytical grade methanol used for the extraction and HPLC grade acetonitrile and methanol used for analysis were purchased from Merck (Darmstadt, Germany). 2,4-D and BAP were purchased from Sigma (St. Louis, USA)." ] },{ "paper_id": "cbc96926929c9fd4fe5e83928688041b3bdde491", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cbca4377d54d06b3758597c0e562f3cc39427810", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cbcbf427bdac380dfdd327ab0fb83567f20b1987", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plant viruses accounted for 0.51% (77/15012) of annotated tags, which included the following four viral families: Luteoviridae, Totiviridae, Virgaviridae, and Phycodnaviridae. Phycodnaviridae accounts for the largest proportion of plant viruses (77%). Phycodnaviridae virus infection is widely present in fresh water algae or seaweed across the world." ] },{ "paper_id": "cbd8eed5192247d945644651f0a9de6166992567", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sequences determined in this study have been deposited in the GenBank sequence database under accession numbers AY758276 to AY758301.", "Coronaviruses are large, enveloped, positive stranded RNA-viruses [1] . The viral RNA genome is 27-32 kb in size, capped, polyadenylated and encapsidated in a helical nucleocapsid. The envelope is studded with long, petal-shaped spikes, giving the virus particle a characteristic crown-like appearance. Three distinct groups of coronaviruses have been described based on serological affinity and genome sequence. Coronaviruses can infect humans and a variety of domestic animals and can cause highly prevalent diseases such as respiratory, enteric, cardiovascular and neurologic disorders [2, 3] ." ] },{ "paper_id": "cbdc601a2f84e6e9749f437d5f25758f145c9137", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Front of kennel Located between front of cage, and up to and including the midpoint of the visible kennel", "Orients towards tail repeatedly (more than 3 times) and continuously", "Repeatedly (more than 3 steps) locomoting around kennel in fixed route", "Not visible from the front of the cage, behavior cannot be defined" ] },{ "paper_id": "cbe56b09d64047cba4ee7875c4f55276a0cdf273", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Autophagy is a biological process involving the degradation of aggregated proteins and damaged organelles to maintain homeostasis [19] . Aberrant autophagy may lead to various pathogenic conditions, including diabetes, neuron degeneration, heart disease, and cancers [20, 21] .", "The possible reason that 3-MA treatment significantly reduced viral yields at 12 h; however, such treatment only resulted in a delayed onset of clinical illness by 2 days, compared to PBS-treated controls, without significantly affecting weight loss is the short half-life and instability of 3-MA in vivo." ] },{ "paper_id": "cbe57a2150ad229d69d2ea7154d9245620c846c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Funding: This research received no external funding.", "Author Contributions: L.C.J. was responsible for the initial conceptualization of this article, which was further developed by I.G.B. Both L.C.J. and I.G.B. wrote the original draft, and were responsible its review and editing.", "The anniversary of the 1918-1919 influenza pandemic has allowed a refocusing on the global burden of influenza and the importance of co-ordinated international surveillance for both seasonal influenza and the identification of control strategies for future pandemics.", "The World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS) is a worldwide network of laboratories that was established in 1952 to monitor changes in influenza viruses circulating in the human population, with the aim of reducing its impact through the use of vaccines, and more recently, antiviral medications [10] . The WHO Collaborating Centre for Reference and Research on Influenza in Melbourne is one of five such Collaborating Centres (CCs), with the others being located in Atlanta, Beijing, London, and Tokyo. Below these WHOCCs is a network of National Influenza Centres (NICs) (n = 143) in 113 countries [11] , which are supported by their respective governments, and these laboratories are also supplemented with samples provided through large public and private diagnostic laboratories. One of the main purposes of maintaining this network is to have comprehensive monitoring of the antigenic and genetic changes in circulating human influenza viruses, and to make bi-annual recommendations on which influenza strains should be included in the influenza vaccine for the upcoming winter season in either the northern or southern hemisphere. Outputs from this network can be seen online on the WHO website with WHO FluNet (https://www.who.int/influenza/gisrs_laboratory/flunet/en/), which graphs the number of laboratory cases for the various types of influenza over time by country, region, hemisphere, or globally, and the WHO Flu ID website (https://www.who.int/influenza/surveillance_monitoring/fluid/en/), which is a global platform for data sharing that links and displays regional influenza epidemiological data. Both Australia and New Zealand contribute to FluNet (Figure 2 ). " ] },{ "paper_id": "cbf67540b068488c423bd787d23143b5246a432d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fresh peripheral blood mononuclear cells (PBMCs) were obtained from whole blood by Ficoll-Hypaque density gradient. PBMCs were placed in a 96-well-plate at 3.0 \u00d7 10 5 cells per well in RMPI 1640 medium (Gibco, Gaithersburg, MD) with 10% normal human sera (Sigma, St. Louis, MO); 5 \u00b5g of concanavalin A (Sigma-Aldrich) was added, and cells were incubated at 37 \u2022 C and 5% CO 2 for 5 days. EdU Click-iT Alexa Fluor 488 (Invitrogen) was added for 6 h, and cells were acquired by flow cytometry using the FACSCanto II cytometer (Becton Dickinson); the lymphoproliferation was analyzed using the FacsDiva software (Becton Dickinson) determined by the difference in fluorescence intensity means (MiFID) of the control and ConA wells.", "PBMCs were placed in a 96-wells plate at 3.0 x 10 5 cells per well in RMPI 1640 medium (Gibco, Gaithersburg, MD) with 5% normal human sera (Sigma, St. Louis, MO); 3 \u00b5l of Cytostim (Myltenyi Biotec) or medium as negative control was added and incubated at 37 \u2022 C and 5% CO 2 for 6 h, and supernatants of the wells were collected. Cytokines were determined using the Cytometric Bead Array Human Th1/Th2 kit (Becton Dickinson) following the manufacturer's instructions, which includes IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma obtained by flow cytometry (FACSCanto II) and analyzed with the FCAP Array software (Becton Dickinson).", "This work was supported by a grant from the Consejo Nacional de Ciencia y Tecnolog\u00eda, Mexico (CONACYT182274), to RW-C, PI." ] },{ "paper_id": "cbf9753177215fea032ae9f8193ce6a0380876e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Blood samples were analyzed for energy metabolites [i.e., glucose, non-esterified fatty acids (NEFA), and \u03b2-hydroxybutyric acid (BHB)], muscle mass catabolism (i.e., urea and creatinine), liver function [i.e., albumin, cholesterol, total bilirubin,gamma-glutamyl transferase (GGT), paraoxonase (PON), glutamic-oxaloacetic transaminase (GOT)], inflammation [i.e., Serm Amyloid A (SAA), haptoglobin, ceruloplasmin, Interleukin (IL)-6, and IL-1\u03b2], and oxidative stress [i.e., myeloperoxidase, reactive oxygen metabolites (ROM), ferric reducing antioxidant power (FRAP)] using kits purchased from Instrumentation Laboratory (Lexington, MA) following the procedures described previously [16, 17] .", "Supporting information S1 Table. Gene ID, GenBank accession number, gene symbol, hybridization position, sequence and amplicon size of primers used to analyze gene expression. ", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "cc0396cb510d6413b537440d00ce0bf51abda136", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The normal human hepatocyte line LO2 was purchased from the Type Culture Collection of the Chinese Academy of Sciences, Shanghai, China. The human hepatocyte LO2 cell was maintained in an incubator at 37 \u2022 C, 5% CO 2 and saturated humidity in 1640 medium supplemented with 10% FBS (Guo et al., 2015a) .", "Following our previous steps , total RNA from liver tissues and cells were isolated using RNAiso Plus following the manufacturer's protocol. The cDNAs were produced with PrimeScript RT reagent kit and incubated at 37 \u2022 C for 15 min and 85 \u2022 C for 5 s. Real-time PCR reactions were done using a StepOne Plus device (Applied Biosystems) at 95 \u2022 C for 10 s followed by 40 cycles of 95 \u2022 C for 5 s and 60 \u2022 C for 20 s according to instruction of the SYBR Premix Ex Taq kit. Data were analyzed by 2 \u2212 Ct method. All primers were synthesized by TSINGKE (Wuhan, China). The sequences of all primers are listed in Table 1 .", "Frontiers in Pharmacology | www.frontiersin.org" ] },{ "paper_id": "cc03e915afeb7acfe93595b75a38f7b58bf2d752", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All isolates were propagated into three specific pathogen-free (SPF) embryonated chicken eggs. The swab suspension was mixed with antibiotics (penicillin 1000 IU/ml and streptomycin 10 mg/ml) in a 4:1 v/v ratio. A 0.2 ml swab suspension was inoculated through the allantoic route into a 9-day-old SPF embryonated chicken eggs and then incubated at 36\u00b0C for 4 days or until the embryo died. Allantoic fluid was harvested on day 4 post-inoculation and stored at \u221220\u00b0C until use.", "The methods performed in this research have been approved by the Ethical Committee of the Faculty of Veterinary Medicine, Bogor Agricultural University, Indonesia, which were validated with the certificate number 058/KEH/SKE/IV/2017." ] },{ "paper_id": "cc146665ee73fa1830b7c42a24cd5844346c0f39", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral nucleic acids were extracted using QIAamp Viral RNA Mini kit (Qiagen, Hilden, Germany) which extracts both DNA and RNA. The procedure was conducted according to the manufacturer's instruction. Elution volume was 60 \u03bcl.", "CSF specimens were inoculated onto African green monkey kidney Vero cells as previously described [18] . Cells were observed daily for cytopathic effect.", "Quantitative data differences between two groups were compared by Mann-Whitney test and categorical data were compared using Fisher's exact test. P-values less than 0.05 were considered significant." ] },{ "paper_id": "cc33658b1e2bfebb81adf4b6befe9cb37f6f6f16", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Coronaviruses (CoVs) can be classified into alphacoronavirus (group 1), betacoronavirus (group 2), and gammacoronavirus (group 3) based on diversity of the protein sequences. Their 3C-like protease (3CL pro ), which catalyzes the proteolytic processing of the polyproteins for viral replication, is a potential target for anti-coronaviral infection.", "Although it is generally accepted that substrate specificity provides insights into the design of peptidomimetic protease inhibitors, there are exceptions to the dogma that good peptidomimetic inhibitors should be derived from good substrate sequences. For example, Hilgenfeld and co-workers showed that the P2 position of peptide aldehyde inhibitors can accommodate aspartate or serine, which are poor substrates for SARS-CoV 3CL pro [38] ." ] },{ "paper_id": "cc43e3bf906ec492da56895a85e1a85d87bf59b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human AFP (NCBI: NM 001134) with a C-terminal 6\u00d7 His-tag was cloned into the pFastBac 1 vector (Invitrogen Inc, U.S.A.). After the fusion sequences and the reading frames were confirmed by sequencing, this pFastBac 1 vector construct was transformed into bacterial DH10 cells, and the extracted bacmid was then transfected into Sf9 cells using Cellfectin II Reagent (Invitrogen Inc, U.S.A.) to obtain passage 1 baculoviruses (P1 baculoviruses) [14] .", "Human cord blood AFP was precipitated by ammonium sulfate and passed through an anti-AFP affinity chromatography column. AFP-positive fractions were collected and concentrated. The purity of prepared AFP was 92.7% as determined by SDS/PAGE. The protein was stored at \u221280 \u2022 C until use [19] .", "The eluted R-AFP was analysed by SDS/PAGE. The reduced protein SDS/PAGE sample contained a reducing buffer, such as DTT, and was boiled for 3 min. The non-reduced protein sample did not contain a reducing buffer and was not heated [18] ." ] },{ "paper_id": "cc4677c77d61de96ba2873ecfc8faa4a2f393def", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At harvest time, cells were first counted and then pelleted by centrifugation at 200\u00d7g and washed 3 times with at least 5-pellet volumes of cold PBS. The washed cell pellet was either used immediately or frozen in liquid nitrogen and stored at \u2212 80\u00b0C for later use.", "HEK-293-EBNA1-6E (293-6E) cells were grown in suspension in Freestyle 17 (F17) medium (Invitrogen) supplemented with 4 mM glutamine, 0.1% pluronic acid and 25 \u03bcg/mL G418 at 37\u00b0C with 5% CO 2 . Tryptone N1 was added to some of the cell cultures at a weight/volume ratio of 0.5%, but was found to have minimal effect on cultures grown 72 hpt. Cultures were maintained under 2.0 \u00d7 10 6 cells/mL in Erlenmeyer flasks shaken at 100 RPM in a humidified incubator at 37\u00b0C with 5% CO 2 ." ] },{ "paper_id": "cc4ee2499ad533a2201243233dfbd178aa3b7185", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CEACAM1 (also referred to as C-CAM, biliary glycoprotein BGP, and CD66a) is a complex glycoprotein linked to the cell membrane by a carboxy-terminal transmembrane anchor; it belongs to the carcinoembryonic antigen (CEA) family of the immunoglobulin superfamily. So far, six other CEACAM glycoproteins have been described (CEACAM3-CEACAM8), all of them being characterized by several domains: an Ndomain, a membrane IgV-related domain, and one/multiple IgC2-related domains. CEACAM1 N-domain may bind homophilically with CEACAM1 and heterophillically with CEA or other CEACAMs, thus acting as cell-cell adhesion molecule [11, 12] .", "The new immune checkpoint inhibitors, anti CTLA4 and anti PD1, are not tumor-specific and are sometimes associated with severe immunologic side effects.", "anti-CTLA4: Anti-cytotoxic T-lymphocyte-associated antigen 4 anti-PD1:" ] },{ "paper_id": "cc563b84c16c4fe4fb1fbd3baa6ffd08dda70006", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The average time from symptom onset to outcome in ASF is 6-20 days; however, the pig farms were usually in rural areas or even in a mountainous area far away from the city laboratory, which required more time for sampling and transportation.", "The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.", "The p72 gene was first amplified in the RPA reaction system comprising the designed primers (labeled biotin) and a 5-Carboxyfluorescein (FITC) labeled-probe, and the expected amplicons were labeled with 5 -FITC and 3 -biotin at the ends. Then, the amplified products were recognized by anti-biotin and anti-FITC monoclonal antibodies on the test line, where gold nanoparticles were prefixed (Figure 1) .", "Frontiers in Microbiology | www.frontiersin.org pMD19-p72. TaqMan runs of the experimental samples involved at least three replicates with no-template or no-primer control and the combination of the primers. The PCR conditions were 95 \u2022 C for 2 min and 40 cycles of 95 \u2022 C for 15 s and 60 \u2022 C for 60 s. A standard curve was generated from serially diluted p72 recombinant plasmids of known copy numbers." ] },{ "paper_id": "cc5bd8ae2cac9621202c04c1ec25699f5b7c3a91", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study did not require ethical approval. An official waiver was granted from participating institutions.", "How would you feel about describing symptoms to your manager? As a manager how would you feel about staff describing their symptoms to you?", "(Greece) \"...we all have the tendency to come to work even if we don't feel well.\"" ] },{ "paper_id": "cc5d4948fd9cd097469fbd4a6ee3ca4da5c4593c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All microwave irradiation experiments were carried out in a RM 800 microwave reactor (Plazmatronika, Wroc\u0142aw, Poland). (7) A suspension of a compound 5 (1.00 mmol), propargyl amine (1.05 mmol) in ethanol (15 mL) was stirred at 78 \u2022 C for 3 h. The reaction mixture was cooled to room temperature and filtered to give pure ", "-2-yn-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione", "-2-(prop-2-yn-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione" ] },{ "paper_id": "cc5ffabf819570a8912666ecdb9de62cb48e0387", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Satisfaction and acceptability were assessed using a nine-item questionnaire. Participants rated each item on a five-point Likert scale with 1 indicating strong disagreement, 2 disagreement, 3 neither disagreement nor agreement, 4 agreement, and 5 strong agreement. Some of these items were reverse-phrased to reduce response bias.", "Eighty-four participants responded to the invitation e-mail, corresponding to a response rate of 18%. Seventy-two participants (86%) were women, the median age was 37 years (range, 28-46). About half of the respondents had a university degree (including university of applied sciences) and about 12% were born outside Germany." ] },{ "paper_id": "cc61245f0f1817ac5d96a0cf9bce41377d6e4978", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To isolate the coronavirus strains, CoV RNA-positive faecal and organ homogenates were inoculated in confluent monolayers of VERO cells (African green monkey kidney), MARC-145 (foetal monkey kidney), HRT-18 (human colorectal adenocarcinoma), FRhK 4 (foetal rhesus kidney), LLC-Mk2 (rhesus monkey kidney), and TB1 LU (lung, Mexican free-tailed bat, \"Tadarida brasiliensis mexicana\").", "In conclusion, the implementation of a continuous veterinary surveillance program for detecting CoVs in bat species and in numerous countries may aid our understanding of the ecology of novel CoV infections.", "Cells were incubated at 37 \u00b0C with 5% CO 2 and observed daily for seven days to observe the development of the CPE. In the absence of CPE, the cryolysates were sub-cultured into fresh monolayers and checked for CoVs by RT-PCR." ] },{ "paper_id": "cc65837c07beb5eedce242ab30fa377907f22546", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All analyses were conducted using Stata 12 software (Stata Corporation).", "Abbreviations PCR: Polymerase chain reactionURIUpper respiratory illnessILIInfluenza-like illnessFTDFast Track DiagnosticsCtCycle thresholdHi-BHaemophilus influenzae type BHi-nonBnon-type B Haemophilus influenzaeIQRInterquartile rangeHMPVHuman metapneumovirus", "Not applicable." ] },{ "paper_id": "cc65afbab3c952058f9261b012cdc4407a9d264c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bunyaviruses constitute the largest RNA virus family and infect a wide range of hosts, including humans, arthropods and plants. Several emerging bunyaviruses pose a considerable threat to human health as exemplified by Rift Valley fever virus (RVFV) [1] , Crimean Congo hemorrhagic fever virus (CCHFV) [2] and severe fever with thrombocytopenia syndrome virus (SFTSV) [3, 4] , which can cause severe disease in afflicted patients. SFTSV, a novel member of the phlebovirus genus, emerged in 2007 in Central and Eastern China [5, 6] . The virus is transmitted from ticks to humans, with human to human transmission occurring on rare instances [7] [8] [9] , and can induce a severe disease characterized by fever, gastrointestinal symptoms and thrombocytopenia. The case-fatality rate is approximately 10% in China, with the elderly being disproportionately affected, but higher rates have been observed upon SFTSV outbreaks in South Korea [10] and Japan [11] . Moreover, a virus closely related to SFTSV, Heartland virus, has been identified in the US and infection was associated with severe disease [12] . Thus, SFTSV and related viruses are important emerging agents against which at present neither specific antivirals nor vaccines are available.", "For Western blot analysis, cell lysates were separated by SDS polyacrylamide gel electrophoresis (PAGE) and blotted onto nitrocellulose membranes (GE Healthcare, Life Sciences, Freiburg, Germany). Prior to antibody staining, membranes were blocked with 5% milk in PBS with 0.1% Tween. Expression of viral glycoproteins was analyzed with mouse monoclonal antibodies directed against the V5 tag (Invitrogen, Karlsruhe, Germany) or the myc tag [29] . As loading control, \u03b2-actin expression was detected using a mouse monoclonal antibody (Sigma-Aldrich, Taufkirchen, Germany). A horseradish peroxidase-(HRP)-conjugated secondary antibody (Dianova, Hamburg, Germany) and a chemiluminescence-based commercially available kit (GE Healthcare Life Sciences, Freiburg, Germany) were used for visualization of bound antibodies. Signals were detected with Intas ChemoCam Image 3.2. Quantification of signal intensities was performed using Fiji/ImageJ 1.51g software. ", "The SFTSV-Gn/Gc precursor is efficiently processed into Gn and Gc" ] },{ "paper_id": "cc66ac23fd5a72e5bf95bad4be77eb93527562d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where f s was the Poisson density of serial interval.", "We note that the formulation used above may not be correct for offspring and serial interval distributions that are not Poisson.", "where p B was the probability mass function of a binomial distribution, and Y j is defined in Eq (3). Standard maximum likelihood were used to obtain point estimates and confidence intervals. We used the optim function in R [8] to find point estimates and the optimise function to find univariate confidence regions." ] },{ "paper_id": "cc6fc7b79884d2ba613637a7a206dfb47233cccb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical operations were performed in MS-Excel 2007. Statistical comparisons between different groups were made by analysis of variance (ANOVA) followed by post hoc Tukey test performed with Daniel's XL Toolbox v.6.53. Unless stated otherwise, all statistical inferences were drawn at p < 0.01.", "Pre-confirmed, CEF-adapted IBD virus of strain UA-Bz 1, passage 6, available in the department was used in this study. Unless stated otherwise, the CEF were infected with the virus at a multiplicity of infection of 0.1.", "Nine -Eleven days old, embryonated chicken eggs, were obtained from the Instructional Poultry Farm, G. B. Pant University of Agriculture and Technology, and used for obtaining primary monolayer cultures of CEF as described previously by Villegas [24] . The fibroblasts were resuspended in EMEM with 10% fetal bovine serum, and the cell concentration was adjusted to a final seeding rate of 1 \u00d7 10 7 cells/mL of the media. About 3 mL and 100 \u03bcL of the seed were added per well in 6-well and 96-well tissue culture plates, respectively. The plates were incubated at 37\u00b0C with 5% CO 2 tension for 24 h to obtain the monolayer.", "Infectious Bursal Disease (IBD) is an acute, highly contagious, and immunosuppressive disease of young chicken, caused by double-stranded RNA virus belonging to the genus Avibirnavirus of family Birnaviridae. It is characterized by the destruction of dividing lymphoid cells in the bursa of Fabricius causing cytolysis leading to immunosuppression in addition to severe economic losses due to impaired growth, death, and excessive condemnations of carcasses because of skeletal muscle hemorrhages [9] . The virus is evolutionarily related to rotaviruses (Reoviridae) and picornaviruses (Picornaviridae) (Dalton and Rodriguez, [8] ). The virus can be adapted to grow and produce cytopathic effects in chicken embryo fibroblasts (CEF) [25] ." ] },{ "paper_id": "cc724dd07268172a4d5b9d83df29fe32757dee98", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cc7d924053530c0856e59387595309b8b1ea918e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Figure S1: Diagrams of the ventilation settings considered, and corresponding ventilation matrices V (for \u03b2 0 = 9 m 3 \u00b7 min \u22121 ). Grey arrows: ventilation between zones (\u03b2 ij -m 3 \u00b7 min \u22121 -); Black arrows: ventilation supply and extract to the ward; Circled values: extract ventilation rates (Q o,j -m 3 \u00b7 min \u22121 -)", "It does this by directing the air from these overpopulated rooms toward rooms 1, 3 and 5, which contain only one patient each. On the other hand, ventilation settings leading to larger pathogen concentrations in rooms 2, 4 and 6 (settings SA, SB and SC) lead to larger outbreaks.", "Our results and comments above suggest that, while some of our conclusions in [1] might be valid in a general sense (i.e. for wide ranges of hospital ward structures), others might be highly dependent on hospital ward structure. The flexibility of our methodology, which can be implemented to any hospital ward by just adjusting the ventilation matrix V accordingly, can then allow one to carry out a detailed analysis of the infection spread dynamics for each particular hospital ward, and to study the potential impact on these dynamics of outbreak management, ventilation settings, detection (e.g. surveillance) policies and patients allocation." ] },{ "paper_id": "cc8dfecfa5e0494957bbb094ce7989400d549027", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ": Synthesis of JMN3-003, 35.4 mmol), 1-fluoro-2-nitrobenzene (3.8 ml, 36.0 mmol) and Et 3 N (4.93 ml, 35.4 mmol) were mixed in a microwave tube and heated at 150\u00b0C for one hour. The mixture was stirred in water, ether added and the precipitate filtered. The reddish brown solid was washed with hexanes and dried under vacuum to give 8.0 g of substance (3) in 94% yield. 1 H NMR (400 MHz, CDCl 3, \u03b4 = 7.24 ppm); \u03b4\uf020\uf020\uf020\uf020 87\uf020 \uf020s , 1H), 10.01 (s , 1H), 8.18 (dd, J = 8.0, 1.6 Hz, 1H), 7.33-6.68 (m, 7H), 3.83 (s, 3H). For synthesis of N-(4-methoxyphenyl)benzene-1,2diamine (substance (4) in supplement 1), 10% Pd/C (300.0 mg, 0.282 mmol) was added to a", "suspension of (3) (2.6g, 10.65 mmol) in methanol (40.0 ml) and the mixture exposed to hydrogen at 40 psi for three hours. The mixture was filtered through a pad of celite and the filtrate concentrated. The resultant reddish brown oil was dried under vacuum to give a brown solid in quantitative yield. 1 H NMR (400 MHz, CDCl 3, \u03b4 = 7.24 ppm); \u03b4 9\uf0203 9 \uf020\uf020s \uf020\uf020\uf020H\uf020\uf020\uf0208 \uf020\uf0209 \uf0208 \uf020\uf0206 \uf020m \uf020\uf020\uf020H\uf020\uf020\uf0207 \uf0203 3\uf0207\uf0202 8 \uf020\uf020m \uf020\uf020\uf020H\uf020\uf020\uf0207 \uf0202 \uf020\uf0207 \uf020\uf0206 \uf020\uf020m \uf020\uf0202 H\uf020\uf020\uf0207 \uf020\uf020\uf0206 \uf0209 2 \uf020\uf020m \uf020\uf020 3H\uf020\uf020\uf020 6 \uf0207 \uf020\uf020 \uf020t, J = 8.0 Hz, 1H), 3.83 (s, 3H). To synthesize 1-(4-methoxyphenyl)-1Hbenzoimidazole-2-thiol (substance (5) in supplement 1), a solution of substance (4) (7.0g, 32.7 mmol) in CH 2 Cl 2 (100.0 ml) at 0\u00b0C was combined with 1,1-thiocarbonyldiimidazole (5.83g, 35.9 mmol) and the mixture stirred for 30 minutes. The cold-bath was removed and the mixture stirred for a further two hours before adding water (50 ml). The organic layer was separated and washed with water (50.0 ml), dried over Na 2 SO 4 , filtered and concentrated. The residue was triturated with CH 2 Cl 2 and hexanes to give a grey solid (6.5 g 88% yield). 1 H NMR (400 MHz, CDCl 3, \u03b4 = 7.24 ppm); \u03b4 10.7 (s, 1H), 7.46-7.42 (m, 2H), 7.28-7.09 (m, 5H), 6.95(d, J = 7.6 Hz, 1H), 3.93 (s, 3H).", "To generate 2-bromo-N-(2-chloro-4-methylphenyl)propanamide (substance (6) in supplement 1), a solution of 2-chloro-4-methyl-aniline (3.0g, 24.8 mmol) in CH 2 Cl 2 (100.0 ml) at 0\u00b0C was treated with i-Pr 2 NEt (6.5 ml, 37.3 mmol) and 2-bromo propionyl bromide (3.3 ml, 29.6 mmol) and the mixture stirred for one hour. The organic layer was separated and washed with 1N NaOH (2 x 30.0 ml), dried over Na 2 SO 4 , filtered and concentrated to give a white solid (5.1g, 74% yield) that was dried under vacuum and used without further purification. 1 To synthesize 2-(1H-benzoimidazol-2-yl)thio-N-(2-chloro-4-methylphenyl) propanamide (substance (8) in supplement 1), a solution of 2-mercaptobenzimidazole (500.0 mg, 3.33 mmol) in tetrahydrofuran (30.0 ml) was treated with NaH (150.0 mg, 3.75 mmol) and the mixture stirred for 10 minutes. Substance (6) (supplement 1) (920.0 mg, 3.33 mmol) was added to the reaction and the mixture stirred for six hours. Water (15 ml) was added and the product extracted using ethylacetate, the organic layer then dried over Na 2 SO 4 , filtered and concentrated. The crude product was purified by silica column chromatography (hexanes/ethylacetate; 2:1) to give 740.0 mg of substance (8) in 64% yield. The product was used in consecutive steps without characterization. For synthesis of JMN5-165, a solution of substance (8) (supplement 1) (100.0 mg, 0.29 mmol) in CH 2 Cl 2 (3.0 ml) was mixed with benzenesulfonyl chloride (40.0 mL, 0.31 mmol) and i-Pr 2 NEt (80.0 mL, 0.46 mmol) and the reaction stirred for eight hours. NaHCO 3 (2.0 ml) was added to the reaction mixture, the organic layer separated and washed with brine (2.0 ml), then dried over Na 2 SO 4 and concentrated. The crude product was purified by silica column chromatrography (hexanes/ethylacetate) to give a white solid that was dried under vacuum. 1 H NMR (400 MHz, CDCl 3, \u03b4 = 7.24 ppm); " ] },{ "paper_id": "cc8e81f5fd3efda044a42e965278d17c58bb4ea6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following information was supplied regarding the deposition of DNA sequences:", "The following information was supplied regarding data availability:", "and MH744158-MH744346 for ORF3 and N genes.", "Feces (n \u00bc 509) and small intestinal content (intestinal mucosa of the duodenum and upper part of jejunum from tissues scraping, n \u00bc 260) from diarrheic pigs were prepared as 10% (w/v) suspension in sterile phosphate buffered saline. Clarified filtrates were collected after centrifugation at 3,000\u00c2g for 20 min. The Institutional Animal Care and Use Committee (IACUC number 1731020) and the Institutional Biosafety Committee (IBC number 1731008) of Chulalongkorn University approved this study." ] },{ "paper_id": "ccaafc13b2c1551dce74e1a7fe3e43cea5228732", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human airway epithelium cultures (HAE) were generated by provision of an air-liquid interface for 6 to 8 weeks to form welldifferentiated, polarized cultures that resemble in vivo pseudostratified mucociliary epithelium [35] .", "RNA isolation, array hybridization, signal processing, normalization and QC filtering was performed as described in [17] . Briefly, RNA was isolated from infected cells, quantified, and hybridized to Agilent 4644K human HG arrays. Raw data extracted from image analysis were background corrected and normalized with quantile normalization.", "z 1{ betw: rank #genes 2 A similar procedure was followed to combine three rankings into one composite ranking." ] },{ "paper_id": "ccb21efaed2edb86c05dd860b5f61beaf856e2a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Zika virus (ZIKV) is a unique Flavivirus that causes mild or subclinical disease in pregnant women, 111, 112 but can have devastating effects for the fetus and neonate. Infection during pregnancy is linked with spontaneous abortion and a variety of birth defects, including microcephaly and impaired neurocognitive function. 113 Since its initial discovery in African macaques in 1947, ZIKV has expanded its geographical range and evolved into separate virus lineages, with environmental pressures resulting in the emergence of virulent substrains, raising concerns about vaccine escape mutants once a vaccine is approved. 114 The combination of its unique pathogenesis, diverse modes of transmission, and rapid global spread has increased efforts toward development and licensing of a ZIKV vaccine.", "Beyond the direct modeling of human congenital infection in animals, information can also be gained from the study of related veterinary pathogens. For example, bovine viral diarrhea virus (BVDV) is an important reproductive pathogen that infects cattle worldwide, and infection during pregnancy causes congenital infection and disease. Persistently infected animals serve as reservoirs within a herd and can have a huge agricultural financial impact. 109 As a result, significant resources have been dedicated to the development and optimization of BVDV vaccines and vaccine protocols, considering variables such as the type and timing of vaccination on immune response and protection against challenge. 110 The information gleaned from these studies may inform vaccine development and optimization protocols for related pathogens in pregnant women, for which similar studies cannot ethically be performed.", "Vaccination is the mainstay of preventative medicine for many infectious diseases. Pregnant women, unborn fetuses, and neonates represent three at-risk populations that can be simultaneously protected by strategic vaccination protocols. Because the pathogenesis of different infectious microbes varies based on tissue tropism, timing of infection, and host susceptibility, the goals of immunization are not uniform across all vaccines. Mechanistic understanding of infectious disease pathogenesis and immune responses is therefore essential to inform vaccine design and the implementation of appropriate immunization protocols that optimize protection of pregnant women, fetuses, and neonates.", "The vaccination strategies employed differ for micobes within each of these categories and vary based on the at-risk individual (i.e., mother, fetus, and/or neonate/infant), the timing of the greatest risk of infection (i.e., early pregnancy, late pregnancy, or post-natal), and on the duration of protective immunity following vaccination. In this review, we discuss evidence to suggest that immunization strategies for pregnant women should be tailored to optimize protection for the mother, fetus, neonate, infant, or all individuals. We review vaccine-preventable infections during pregnancy and the current vaccination strategies employed to reduce the burden of infectious diseases, including influenza. Further, we examine novel vaccine platforms and consider how their application may provide safe alternatives for enhancing protection of pregnant women. Finally, we discuss vaccine development and prevention strategies for combatting emerging infectious diseases, including Zika, that pose a threat to pregnant women and their fetuses." ] },{ "paper_id": "ccc1cedafbb30ee3184f9fc7999f4aa457805cab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We declare no competing interests." ] },{ "paper_id": "ccc32d31656760db245b5cd683d144eb013624c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The GraphPad Prism 4.0 software was used for statistical analyses (Two-way ANOVA or student t-test). Values are expressed as mean \u00b1 SEM. Values of p 0.05 are considered statistically significant, where \u00c3 = p 0.05, \u00c3\u00c3 = p 0.01 and \u00c3\u00c3\u00c3 = p 0.001.", "96 well MicroWell MaxiSorp flat bottom plates (Sigma-Aldrich) were coated with 2\u03bcg/ml of antigen (CII, Sigma-Aldrich)) and incubated overnight at 4\u00b0C. The following day the plates were washed and blocked. Serial serum dilutions were added to the plates and incubated overnight at 4\u00b0C. The next day, plates were incubated with anti-mouse IgG1, IgG2a, IgG2b, IgG3 and IgM isotypes coupled to Horse Radish peroxydase (Lo-Imex, Louvain, BE), revealed using a TMB kit (BD Biosciences) and read at 450nm using a ELISA plate reader [15, 16] .", "All experiments complied with the ECPVA guidelines (CETS n\u00b0123) and were approved by the VUB Ethical Committee (Permit Number: 10-220-13). Breeding and experimental work with tsetse flies was approved by the Scientific Institute Public Health department Biosafety and Biotechnology (SBB 219.2007/1410). To minimize mouse suffering and distress during blood sampling, all animals were anaesthetized with isoflurane using a UNO-Univentor Anaesthesia Unit according to the manufacturer`s protocol. Mice were monitored on a daily basis and no unexpected deaths were observed. Humane endpoints were used during the study, based on weight loss-animals with >25% weight loss were sacrificed using carbon dioxide treatment." ] },{ "paper_id": "ccc8cfc07dd790364ca7968e3e057dbdff53c792", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "covering sites perceived to have medium to high level bat-human interaction. The objective of this surveillance study was to apply a non-invasive approach using fresh feces to detect viruses circulating within the diverse species of Kenyan bats. We screened for both DNA and RNA viruses; specifically, astroviruses (AstVs), adenoviruses (ADVs), caliciviruses (CalVs), coronaviruses (CoVs), flaviviruses, filoviruses, paramyxoviruses (PMVs), polyomaviruses (PYVs) and rotaviruses. We used family-specific primers, amplicon sequencing and further characterization by phylogenetic analysis. Except for filoviruses, eight virus families were detected with varying distributions and positive rates across the five regions (former provinces) studied. AstVs (12.83%), CoVs (3.97%), PMV (2.4%), ADV (2.26%), PYV (1.65%), CalVs (0.29%), rotavirus (0.19%) and flavivirus (0.", "This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.", "The samples were completely homogenized by vortexing for 15 seconds and then centrifuged at 12000g for 1 minute to obtain a clear supernatant. Viral nucleic acid was extracted from 200\u03bcL of the supernatant using the high pure Viral RNA kit (Roche, Germany) following manufacturer's instructions. Virus screening was performed by RT-PCR using the Invitrogen OneStep-RT PCR kit using gene specific primers (Supplementary Table S1 ). Virus families screened included Coronaviridae (CoV), Filoviridae, Reoviridae, Astroviridae (AstV), Adenoviridae (ADV), Polyomaviridae (PYV), Paramyxoviridae (PMV) and Caliciviridae (CalV). The RT-PCR was performed in a 25 \u03bcL reaction mix containing 12.5 \u03bcL PCR 2 \u00d7 reaction mix Buffer, 10pmol of each primer, 2.5 mol/L MgSO 4 , 20 U RNase Inhibitor, 1 \u03bcL SuperScript III/ Platinum Taq Enzyme Mix, and 5 \u03bcL RNA. A nested/ hemi-nested PCR was done using 1uL of the first-round PCR product as a template in a 25 \u03bcL reaction mix contained 2.5 \u03bcL PCR reaction buffer, 5 pmol of each primer, 50 mmol/L MgCl 2 , 0.5 mmol/L dNTP and 0.1 \u03bcL Platinum Taq Enzyme (Invitrogen). The PCR products were visualized on 1% agarose gel after electrophoresis. The amplicons were gel purified and sequenced directly using the ABI prism sequencer or cloned using pGEM-T Easy Vector System before sequencing." ] },{ "paper_id": "cccb1a743e85a745309415410b3101c2ab1b59bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since the numbers of patients taking calcineurin inhibitors (95/ 100 patients) were highly skewed (Table 1) , multivariate analysis was also performed with exclusion of this variable. This did not alter the significance levels for any parameters reported in Table 2 .", "Text S1 Detailed methods for enzyme activity assays, immunoblots, real-time PCR assays, and measurements of Ang II and Ang-(1-7). (DOC)", "This study involved recruitment of human subjects as described below, with written informed consent, and the study was conducted according to the principles expressed in the Declaration of Helsinki. The study protocols were approved by the Research " ] },{ "paper_id": "ccd537b92136e3c66ddb7b0abac70c4f7765fb8b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ccdad2ec94a4e7dfd973faea6ce2fb7854b6bde8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Until such time as the causes of the AFM epidemic are better understood, development of preventive vaccines will remain challenging. NPEV virus-specific diagnostics are needed, as are virus-specific serologic tests to support epidemiologic studies. Also needed are experimental animal models to study viral neurovirulence and neuroinvasiveness properties (32), genetic markers, and drug therapies (40) . These and other research challenges are daunting because the NPEVs have been neglected for decades. Watching healthy children become permanently paralyzed virtually overnight by a seemingly random, lightning-strike disease is as heartbreaking today as it was in the polio era. The trajectory of AFM over the past 5 years suggests that the problem is getting worse, and so it is critical that we galvanize our efforts to learn more about, and respond adequately to, this ubiquitous, often crippling, continually reemerging group of viruses.", "Research challenges. A major challenge in the study of this disease is that AFM is an uncommon, sporadically occurring complication of a common infection that is difficult to diagnose with viral specificity. Moreover, one cannot predict where or when it will strike next, and the site of devastating tissue damage is inaccessible to direct study. Research progress is greatly impeded by lack of understanding of the natural history and pathogenesis of AFM disease, including viral pathogenesis, and by lack of understanding of AFM epidemiology, including aspects of cross-reactive immunity associated with the many and rapidly evolving NPEVs, especially EV-D68 and EV-A71. Perhaps, as has long been predicted, there is a \"poliovirus niche\" into which one or more NPEVs will evolve as we approach the eradication of polio (24, 39) . It is conceivable that we may be seeing the early stages of such an evolution.", "NPEVs, AFM, and AFP. Sporadic AFM inevitably appears at low incidence during widespread seasonal circulation of almost any NPEV. Some NPEVs, e.g., EV-A70 and EV-A71, have been historically more frequent causes of AFM than have others (8) (9) (10) . Beginning in 1988, polio eradication efforts further clarified NPEV epidemiology via the global establishment of national surveillance systems to identify all cases of AFP. As many as 60,000 documented cases of nonpolio AFP are reported annually (16) ; cases are predominantly associated with NPEVs or Guillain-Barr\u00e9 syndrome, the latter of which is itself often associated with NPEVs (17, 18) . Thus, multiple NPEVs have been closely linked to thousands of AFP and AFM cases for more than 3 decades.", "Clinical conundrums. As important as determining the cause of AFM is the establishment of optimal interventions to prevent, limit, or reverse neurologic damage that is often advanced at the time of clinical presentation. Attempts at treatment with interventions such as intravenous immunoglobulin, glucocorticoids, plasma exchange, and antiviral drugs such as pleconaril have been largely unsuccessful (34) . Experimental nerve transfer to adjacent unaffected segments of the cord may offer improvement to some patients (35) . Of greater promise is mounting evidence that early intensive physical therapy (36, 37) , the value of which has been well documented for polio (37) , may benefit nonpolio AFM patients as well. Therapy for polio was developed to be aggressive and comprehensive in addressing each of the three conceptual stages of acute, convalescent, and chronic polio paralytic disease (36, 37) . Specific therapeutic goals targeted loss of flexibility, loss of muscle power, decreased vital capacity, potential for residual deformity, loss of skill, and loss of functional stamina. In recent decades, recognition of the postpolio syndrome, usually developing decades after initial paralysis, and with potential future implications for AFM patients, has led to additional physical therapy approaches (38) . Physicians should consider physical therapy consultation at the earliest possible time after AFM onset." ] },{ "paper_id": "ccde33bdca9b5c7f879f105a4596e5b1ad3f9408", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BtCoVs have been identified in many insectivorous and frugivorous (family Pteropodidae) bats on many continents: America, Europe, Africa, and Asia [4] . Different species of Pteropodidae have been identified as a major source of lineage D \u03b2CoV (HKU9) in Africa (Rousettus aegyptiacus, Kenya [11] , Pteropus rufus and Eidolon dupreanum, Madagascar [12] ), and Asia (R. leschenaulti, China [13] , Cynopterus brachyotis, Philippines [14] , Ptenochirus jagori, Philippines [15] , Pteropus giganteus, Bangladesh [16] , Cynopterus sphinx, Thailand [17] .", "The RdRp PCR products were gel purified using the NucleoSpin\u00ae Gel and PCR Clean-up kit (MACHEREY-NAGEL GmbH & Co. KG), and sequenced directly using an automated ABI PRISM 377 DNA sequencer. When multi peaks were shown in chromatogram at same position from direct sequencing, PCR products were cloned using the pGEM\u00ae-T Easy Vector System and the LigaFast\u2122 Rapid DNA Ligation System (Promega) before sequencing. Five colonies were picked up for sequencing. Sequences were cleaned using Bio-edit program and aligned with reference sequences collected from GenBank. Alignments were performed using Multiple Alignment using Fast Fourier Transform (MAFFT) [26] . Phylogenetic trees were created based on 357 and 299 bp RdRp gene sequence using the maximum likelihood method. Bootstrap values were determined using 1000 replicates via Raxml-GUI 1.3 with outgroup (Bulbul CoV/HKU11-934/Pycnonotus jocosus/CHN/2007/FJ376619) using the GTRI substitution model [27] . The phylogenetic tree was visualised using the FigTree program, version 1.4.2 [28] ." ] },{ "paper_id": "ccfba2653a0baee4d4a733902529dc5c96bc69d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Libraries for deep sequencing were prepared from amplified cDNA libraries using previously published protocols [50] . Briefly, libraries were cleaved with Type IIs restriction endonucleases (GsuI), and truncated adapters containing unique 3 or 6 bp molecular barcodes were ligated on the resulting strand ends. Fulllength adapters were subsequently added via an additional 15 to 25 cycles of PCR. Libraries were size-selected on a 4% polyacrylamide gel at approximately 350 bp average length, and then loaded at a final concentration of 10 pM on three lanes of a second-generation Genome Analyzer IIx (Illumina, San Diego, CA). Paired-end reads were sequenced for 67 cycles in each direction.", "Cases of influenza-like illness in Canada and Mexico were reported by providers and hospitals to the British Columbia Centre for Disease Control (BC-CDC), the University of Toronto/ Ontario Agency for Health Protection and Promotion (OAHPP), and the Veracruz Ministry of Health. Suspected or confirmed H1N1 cases were identified through routine laboratory surveillance under protocols approved by each individual state public health agency. For each case, non-identifying demographic and clinical data were reported on standardized forms. Cases in California were identified by infectious disease physicians at University of California at San Francisco (UCSF), and demographic/clinical data were abstracted from the medical record.", "Using deep sequencing, we were able to recover and assemble near full-length genome sequences of the 2009 H1N1 virus from two individual patient specimens. Since the molecular determinants of influenza pathogenesis have been well-studied, we were able to analyze the genomic sequence for single nucleotide polymorphisms (SNPs) that specifically correlate with antiviral resistance, enhanced transmission or increased virulence. For a novel virus, where such genotypic findings would not yet be correlated with phenotypic data, the overall sequence and structure of the genome may still yield valuable insights into viral transmission and mechanisms of pathogenesis." ] },{ "paper_id": "cd06185d94b38abd3c8209a45897a589da964bf2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It is well known that the generation of large-scale expressed sequenced tags (ESTs) is a very useful approach to describe the gene expression profile and sequence of mRNA from a specific organism and stage (especially in non-model species). ESTs represent a valuable sequence resource for research and breeding, as they provide comprehensive information regarding the transcriptome [26] . They have played significant roles in functional genomics research for discovery of novel genes together with identifying different protein groups (e.g. proteins with signal peptides) other than the whole genome [27] [28] [29] , developing SSRs and SNPs markers [30] [31] [32] [33] [34] , allowing large-scale expression analysis [35] , improving genome annotation [36] , and elucidating phylogenetic relationships [37] .", "KEGG pathway analysis and COG analysis are helpful for predicting potential genes and their functions at a whole transcriptome level. The predicted metabolic pathways, together with the COG analysis, are useful for further investigations of gene function in future studies.", "The Roche 454 reads of L. aurea were submitted to NCBI Sequence Read Archive under the accession number of SRP018374. " ] },{ "paper_id": "cd18b402ae6cf0913a3a12aef3a8819964d8057e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To confirm our functional analysis, we utilized an additional approach in which we performed co-expression analysis of only differentially expressed genes and these identified clusters were then analyzed separately by IPA.", "Probe sequences annotation and functional analysis." ] },{ "paper_id": "cd1b2d233dba9a6446e41588ecf62f7030b5c75d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cd1d0cb4b82d5479e2aa72ec3d3cde6aae4a4eaf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at http://dx.doi.org/10.1128/ mSphere.00334-16. Figure S1 , PDF file, 0.9 MB. Figure S2 , PDF file, 0.8 MB. Figure S3 , PDF file, 2.8 MB. Table S1 , PDF file, 0.1 MB. ", "Other than the 4 rats mentioned above, no rats within the colony displayed overt clinical symptoms. However, from a reproductive standpoint, female rats within this colony usually had 4 to 8 pups per litter, and the reproductive life span consisted of 2 litters per animal. Rarely, females had third litters with very poor survival rates, suggesting markedly reduced fecundity. Female rats were unable to maintain pregnancy after 6 months of age.", "Accession number(s). The RatPyV2 genome has been deposited in GenBank under accession number KX574453." ] },{ "paper_id": "cd21b40d05f66d9cc280d65928651c4552ad8fdd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The highest expression was obtained with ACTB, B2M and RPL19 with C t averages of 14.64, 15.82 and 15.95, respectively, whereas the lowest expressed gene was GYPC (mean C t , 27.50). For all analysed genes, the relative standard curve gave correlation coefficients greater than 0.985 and efficiencies between 90 and 110%.", "The mean total RNA concentration was 96 ng/\u00b5L while A260/A280 and A260/230 ratios ranged from 1.99 to 2.04 and 2.02 to 2.16, respectively. Therefore all samples were pure, free from protein and organic pollutants derived from RNA extraction. The RIN obtained for all samples ranged from 7.2 to 8.2 with a mean value of 7.6." ] },{ "paper_id": "cd22fe835feb95cc3cc02e08dd38f962d4f69185", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "3.0 [11] . Additionally, sequences for terminal untranslated regions (UTRs) were determined by 5'/3' rapid amplification of cDNA ends (RACE) sequencing (S1 Table) [12] .", "Nucleotide sequence accession number. The nucleotide sequence determined in this study have been deposited in GenBank under the accession number MG029269 to MG029292. ", "Viruses strains used in this study were propagated into VERO cells (ATCC 1 CCL-81\u2122), as previously described [10] . The infected cells were incubated for 3 to 5 days until visualization of viral cytopathic effect. Table 1 provides the names, strains, year, sources and local of isolation, as well as the GenBank accession numbers." ] },{ "paper_id": "cd3c7bc4656919fc9d8564bff6693b24631f97d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells. Madin-Darby canine kidney (MDCK) epithelial cells (ATCC CCL-34), human embryonic kidney cells (293T; ATCC CRL-11268), human lung epithelial carcinoma cells (A549; ATCC CCL-185), African green monkey kidney epithelial cells (Vero; ATCC CCL-81), and murine fibroblast cells (L929; ATCC CCL-1) were grown at 37\u00b0C in air enriched with 5% CO 2 using Dulbecco's modified Eagle's medium (DMEM; Gibco) supplemented with 10% fetal bovine serum (Gibco) and with 50 g/ml gentamicin (Gibco). Human HAP-1 haploid wild-type (WT) cells and HAP-1 IFI44 knockout (KO) cells produced using the CRISPR/Cas9 technology were obtained from Horizon Discovery, Inc. These cells were grown at 37\u00b0C in air enriched with 5% CO 2 using Iscove's modified Dulbecco's medium supplemented with 10% fetal bovine serum (Gibco) and with 50 g/ml gentamicin (Gibco).", "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .01839-19.", "FIG S1, PDF file, 0.01 MB. ", "pattern recognition receptors (PRRs) (1) . Different PRRs recognize different viruses. For example, influenza A virus (IAV), which is a member of the Orthomyxoviridae family and which contains an eight-segmented, negative-sense single-stranded RNA (ssRNA) segmented genome, is mainly recognized by the membrane-associated PRRs Toll-like receptor 3 (TLR-3) and TLR-7 and cellular PRR retinoic acid-inducible gene I (RIG-I) (1) . Lymphocytic choriomeningitis virus (LCMV), the prototype member of the Arenaviridae family, contains a negative-sense ssRNA bisegmented genome and is mainly recognized by TLR-2 and RIG-I (1). Sendai virus (SeV), a Paramyxoviridae member containing a negative-sense ssRNA, is sensed by TLR-7, RIG-I, and melanoma differentiationassociated (MDA) protein 5 (MDA5) (1) . Lastly, vesicular stomatitis virus (VSV), a Rhabdoviridae member, whose genome is composed of a negative-sense ssRNA, is recognized by TLR-7 and RIG-I (1) ." ] },{ "paper_id": "cd3eeb911617dd22ee6f0d1843e19ba1d255e133", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "J-jL and CX wrote the manuscript. YL helped to collect reference articles. J-sL and X-wZ helped with language editing support and provided helpful comments on the article.", "Selecting an appropriate DNA region is essential for successful analysis. The GC content, Tm value, secondary structure, and primer location in the region are the limiting factors for primer design. As a general principle, the DNA fragment must be conserved, and the sequence length should be sufficiently long to contain all of the regions adapted to design LAMP primers . For this reason, not all common fragments result in highly efficient LAMP primers. Therefore, we recommend designing several groups of LAMP primers based on different fragments.", "To design reliable species-specific LAMP primers, assurance about the identity of the source plants is vital. At least three duplicate collections per species should be used; each collection (uniquely numbered) must include a small plant sample for DNA extraction and voucher herbarium specimens of the entire plant (ideally flowering or fruiting) and must be sourced from the same plant or population of plants. The collections should be accompanied by photos and detailed field notes describing any identifying characteristics not evident from the herbarium specimens. The samples must be in good condition (e.g., devoid of contamination). A detailed guide to making herbarium specimens can be found in The Herbarium Handbook (Bridson and Forman, 1992) ." ] },{ "paper_id": "cd4889df1e36fd838d6835714cbf4fdfd7e7e32e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All calculations were performed using SPSS ver. 14.0 (SPSS Inc., Chicago, IL, USA). Continuous variables were expressed as mean \u00b1 standard deviation. Student's t-test for continuous variables was used for comparisons between the groups. The Pearson's Chi-square test was used for categorical variables. A P value less than 0.05 was considered statistically significant.", "This study was conducted in two university hospitals in Daejeon, Korea: Chungnam National University Hospital (CNUH) and The Catholic University of Korea Daejeon St. Mary's Hospital (DSMH). To evaluate the changes in clinical features more clearly, we divided the subjects into 2 groups according to their time of admission, a decade-interval apart." ] },{ "paper_id": "cd4c984e7afa08f850f9173578fbae31d92a64a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses are classified into three well-accepted genera; alpha-, beta-, and gamma-coronavirus whereas deltacoronavirus [1,2] is proposed as an additional group in the family. Alphacoronaviruses and betacoronaviruses have been isolated from mammals, whereas gammacoronaviruses, represented by the infectious bronchitis virus (IBV), are detected primarily in birds including poultry [2] .", "Viral RNA was extracted from the allantoic fluids using Trizol LS\u00aereagent kit (ThermoFisher, Life Technologies Corporation|Carlsbad, CA 92008, USA) according to the manufacturer's instructions. The eluted RNA in 30 \u00b5L of nuclease free water was stored at (\u221270 \u2022 C) until processing for the amplification. A single step RT-PCR was performed using the Verso One Step RT-PCR kit (ThermoFisher, Life Technologies Corporation|Carlsbad, California, USA) using previously reported primers for amplification of partial polymerase (RdRp) and full length S1 gene [6, 21] . PCR products were gel excised and purified individually using QIAEX \u00ae Gel Extraction Kit (Qiagen, Hilden, Germany). Gene sequencing was carried out using a BigDye Terminator v3.1 cycle sequencing kit (Qiagen, Hilden, Germany) in an ABI PRISM\u00ae300 using sequencing primers as described previously [22] .", "Viruses 2019, 11, x FOR PEER REVIEW 4 of 16" ] },{ "paper_id": "cd501145689fd4bbd377e57583363920e99b1b6f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "FHL wrote the manuscript. CCW, SLS participated in the design of the study, and helped to revise the manuscript. CCL Table 3 Rate ratio of covariables for primary total knee replacement rate. ", "The rate ratios of the risk factors for TKR are shown in Table 3 " ] },{ "paper_id": "cd50536bcd80b20330a1382bbcb0f895748e338a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The development of vaccines is important for controlling diseases such as reproductive failure caused by PPV.", "In group P-18, there was an increase in the number of positive spots (Fig. 1c) . This situation was similar to group N, but the mapped response was higher when P-18 was compared to groups P, V and NC. Group P-18 pigs showed positive antibody responses earlier than the other treatments and included sites 1, 3, 4, 6, 12, 18, 19 and 20 (Fig. 1c) . This group was the only in which sites 5 (aa 101-116; 109-124), 7 (aa 209-224) and 11 (aa 429-444) were activated on D72.", "PPV infects pregnant gilts and sows, causing reproductive failure characterized by embryonic and fetal death, mummification and stillbirths, with delayed return to oestrus [4] . The resulting reduction in reproductive capacity can significantly decrease pork production [5] .", "The NADL-2 strain of PPV was cultured in SK6 cells as previously described [15] . Supernatants of cell cultures were separated and purified by CaCl 2 precipitation followed by gradient ultracentrifugation [16] . Fractions with hemagglutinating activity were dialyzed for 16 h at 4\u00b0C against a Tris-EDTA buffer, pH 8.0 [17] . The virus was titrated in SK-6 cells by serial dilutions in 96 well-plates and the cells were then screened for a cytopathic effect at 72 h post-infection. The test was considered positive when cytopathic effects were observed in > 75% of the cells. Samples containing 1 \u00d7 10 4.5 TCID 50 / mL were aliquoted and subjected to HHP. Vaccine aliquots and viral preparations were normalized to avoid an antigen-concentration effect [18] ." ] },{ "paper_id": "cd59245a431a62e93a213ec343f168d77dcfc199", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cytokines related to the immunological response were measured in cell culture supernatants using Pig Transforming Growth Factor \u03b21 (TGF-\u03b21) (CSB-E06843p), Pig Interferon IFN-\u03b3 (CSB-E06794p), Pig Interleukin 6 (CSB-E06786p) and Pig interleukin 10 (CSB-E06779p) ELISA kits purchased from CUSABIO (Wuhan, China) according to manufacturer's instructions.", "Thirty days old crossbred pigs obtained from Swine Breeding Center in Beijing were housed in groups in a confined university facility under ethologically and hygienically ideal conditions and acclimatized for two weeks. Animal use and animal trials in this study were approved by Beijing Municipal Committee of Animal Management and Ethics Committee of China Agricultural University (approval number: CAU20140629-2). All experiments strictly followed the recommended guidelines by the Ethics Committee of China Agricultural University. Animal cadavers were disposed of in compliance with the Rules for Working in Experimental Animal Facilities and Valid Waste Regulations. Pigs were anaesthetized with atropine (0.05 mg/kg), ketamine (5 mg/kg) and propofol (3 mg/kg), which were provided by Veterinary Hospital of China Agricultural University before experiments. All efforts were used to reduce the pain and adverse effect of the animals.", "Preparation and enzyme activity of recombinant protein dx.doi.org/10.", "The significant differences of the in vivo experiment and animal trials were analyzed using ttest, two-way ANOVA in the GraphPad Prism (version 5.0) software. Differences were considered statistically significant at a value of P < 0.05 and extremely significant at a value of P<0.01 or P<0.001." ] },{ "paper_id": "cd67f336a7356dd88e971d3541829bdc290257f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 Appendix. Details of the Model. (DOCX)", "Previous authors have observed the non-identifiability of specific parameter sets for the Ebola process [16, 17] , and our model is not identifiable either. We assign values for all parameters except for the transmission coefficient \u03b2, and conduct the fitting algorithm (see Shaman [18] ). Of particular importance is the fraction of unconfirmed cases since an arbitrarily changing pattern of incomplete reporting is indistinguishable from changes in transmission. Note that if transmission increases or decreases over time, the resample/move procedure introduces perturbations in the parameters and provides the ability to track changes dynamically. Given the parameter choices, we then compute the instantaneous reproduction number (R) implied by the model, which for our simple model, is given by", "For this study, we used weekly country-and subcountry-specific confirmed case count data that were obtained from the WHO Global Health Observatory's patient database available on the Internet [8] . Since the research only involved unidentifiable summary data (i.e., case counts by week), the research did not require review by the Committee on Human Research at the University of California, San Francisco." ] },{ "paper_id": "cd9086c9edba2e717fab23027e7debb9c21c23e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The complete genome sequence of the PDCoV strain CH/Sichuan/S27/2012 has been deposited in GenBank under the accession number KT266822.", "We report the first complete genome sequence of porcine deltacoronavirus (PDCoV) strain CH/Sichuan/S27/2012 identified in feces of diarrheic piglets from mainland China in 2012. This strain has two unique in-frame deletions within the ORF1a gene and is phylogenetically between the prototype PDCoV (HKU15) and the 2014 U.S. strains.", "To our knowledge, this is the first complete genome sequence of PDCoV from mainland China since 2012. The sequence data of CH/Sichuan/S27/2012 fill the gap of PDCoV sequences between 2012 and 2013, right before the suspected introduction of PDCoV into North America, which should facilitate further studies on PDCoV evolution." ] },{ "paper_id": "cd97d6b4e0495ffd6543a25ac01e843b8efa6b6c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cd99b86063184108e06b3b9c0595416888623cec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The PCR amplification product was confirmed on a 1% agarose gel and purified using GFX PCR DNA and Gel Band Purification kit (GE Healthcare, Chicago, USA), according to the manufacturer's instructions.", "The antibody horseradish peroxidase (HRP) -rabbit anti-chicken IgY peroxidase conjugate (Sigma) (1:10000) was added to all membranes and the reaction was revealed using 3,3\u2032-diaminobenzidine (Sigma). All incubation steps were performed at 37\u00b0C for 1 h under slight agitation and were followed by three washes with PBS-T.", "A previously characterized Brazilian viral sample of IBV Strain Massachusetts 41 (M41-CNPSA -EMBRAPA -Conc\u00f3rdia, SC, Brazil) was propagated after 9 days of incubation in the chorioallantoic cavity of specific pathogen free (SPF) embryonated chicken eggs. The allantoic fluid was then collected and stored at \u2212 70\u00b0C. Viral RNA extraction was carried out with TRIzol\u00ae LS reagent (Invitrogen\u2122, EUA), according to the manufacturer's instructions." ] },{ "paper_id": "cd9b28a218d57ae7506637d96b2a396dca870e0f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study protocol was approved by the Naval Medical Research Center Institutional Review Board in compliance with all applicable federal regulations governing the protection of human subjects.", "The Sultanate of Oman has a population of 2.8 million. The country has an area of 309.5 thousand square kilometers and is located in the southeastern corner of the Arabian Peninsula with a hot dry interior, humid coastal strip, and a mountainous southern region with seasonal (May to September) monsoon rainfall [2] .", "Introduction" ] },{ "paper_id": "cda16c8657cf582952bfe3a8e6756acaa8449452", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2018, 10, x 4 of 11", "The raw HTS data were imported to CLC Genomics Workbench (version 11) (Hilden, Germany) and trimmed based on quality (Q = 20) and length (\u226550). De novo assembly using CLC Genomics Workbench was performed to find overlapping reads and create longer contigs. Both the contigs and the remaining reads were then annotated using BLASTx (E-value \u2264 0.0001) in Diamond (version 0.8.26) (https://ab.inf.uni-tuebingen.de/software/diamond/). The Diamond results were visualised using MEGAN (ver. 6.8.20) (http://ab.inf.uni-tuebingen.de/software/megan/). The datasets containing the raw data have been deposited in GenBank under the BioSample accession numbers (SAMN08969257-SAMN08969272).", "The tonsils were homogenised in sterile PBS using Precellys CK14 tubes (Bertin Technologies, Montigny-le-Bretonneux, France) prior to filtration (0.45 \u00b5M) and DNase I (50 U)/RNase (5 \u00b5g) treatment. The RNA was then extracted using GeneJET RNA extraction kit (Thermo Fisher, Waltham, MA, USA) and eluted in 40 \u00b5L EB. The DNA was extracted using the GeneJET DNA extraction kit (Thermo Fisher, Waltham, MA, USA) and eluted in 50 \u00b5L nuclease-free water." ] },{ "paper_id": "cda5efb9ec3966e7cd1df793ff55b51d9611eec3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The research protocol used for this study was approved by the Committee for the Protection of Human Subjects in Research at the University of Massachusetts Medical School, IRB Docket #H-10507.", "EBPPH research process steps Figure 1 EBPPH research process steps.", "Step 1 -Identify existing PH and medical information resources and features", "Step 2 -Develop individual interview script and interview participants from Communicable Disease Control" ] },{ "paper_id": "cdb117ad4ac490f1e48e3738d5ccdaafe8916086", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All secondary endpoints and the supportive analyses were considered as descriptive evidence of efficacy and were analysed without any procedures to account for multiple comparisons. Pair-wise differences between treatment groups in the proportion of patients reporting treatment-emergent adverse events were compared via chi-square tests. Questions with binary responses were analysed using a logistic regression model with factors for treatment group and centre and a covariate for baseline throat soreness severity." ] },{ "paper_id": "cdb5b561f1c883eb82375c9c62550de77bc8b51e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cdbdc0b6176729a11ba5e08c708408592d189657", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Falls are an issue of great public health concern. This study focuses on outdoor falls within an urban community in Hong Kong. Urban environmental hazards are often place-specific and dependent upon the built features, landscape characteristics, and habitual activities. Therefore, falls must be examined with respect to local situations.", "It is important to consider specific characteristics of the built environment to explain the clustering phenomenon in a particular area. In this regard, identifying hot spots makes targeting geographically specific prevention programs feasible." ] },{ "paper_id": "cdc7a84bccdf6a66bb0e2c902a818aa09ffabfc9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PCR primers specific for selected target genes were predesigned and validated (Table 1) . Gradient PCRs were used to determine the optimal annealing temperature and primer concentration. qPCR reactions had a final volume of 10 L and contained 1 L of cDNA, 0.5 L of each primer, 5 L Sso-Fast EvaGreen supermix (Bio-Rad Laboratories, Hercules, CA, USA), and 3 L DEPC-treated sterile distilled water. The relative expression levels of mRNA of studied cytokines were Table 1: The primer sequences. TNF--forward TGCTATCTCATACCAGGAGA TNF--reverse GACTCCGCAAAGTCTAAGTA IL-6-forward TCTTGGGACTGATGTTGTTG IL-6-reverse TAAGCCTCCGACTTGTGAA IL ", "Tanreqing injection (TRQ) is a widely used classical compound herbal recipe for several decades in China. It is composed of water soluble natural extractives from five crude herbal plants, namely, Radix Scutellariae Baicalensis, Fel Selenarcti, Cornu Naemorhedi, Flos Lonicerae, and Forsythiae Fructus [1] , and is a mixture of about 12 main active pharmaceutical ingredients including chlorogenic acid, caffeic acid, luteoloside, forsythiaside, forsythin, forsythigenol, baicalin, wogonoside, wogonin, salidroside, and ursodeoxycholic acid [2] . Clinical evidence has supported the minimal toxicity and side effects of TRQ [3, 4] . With its predominant antibacterial and antiviral actions being proved by modern pharmacologic studies [5, 6] , TRQ is predominately used for acute inflammatory lung diseases including acute upper respiratory tract infections [7] , pneumonia [3, 8, 9] , acute COPD [4, 10, 11] , SARS (Serious Acute Respiration Symptom) [12, 13] , A/H1N1 flu [14, 15] , A/H7N9 flu [16] , and the recently mentioned Middle East Respiratory Syndrome (National Health and Family Planning Commission of China, http://www.nhfpc.gov.cn/).", "Medicine 5 (a) (b) (c) (d) (e) (f) (g) (h) (i) (j) (k) (l)(a) (b) (c) (d) (e) (f) (g) (h) (i) (j) (k) (l)" ] },{ "paper_id": "cddbec166688aaf25aa6e2e6dc76a90668ba9e9d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA was extracted from a known number of cells (between 2.4610 5 and 5.9610 5 ) and quantitated (RNeasy minikit): 100 ng was used as a template in each qRT-PCR reaction.", "x g =\u00bdplasmid length | 660| 6:022 | 10 23~y molecules Using the standards for each transcript, the quantity of transcript was determined relative to the standard curve for 100 ng input RNA. The number of copies per cell was estimated by dividing the total number of cells by the total RNA extracted, multiplied by 100. This gave the equivalent number of cells that produced 100 ng of RNA and from this the RNA copy number per cell was inferred.", "Five standards from 10 7 -10 3 copies were made using plasmids encoding the transcripts of human IFITM1, 2, and 3, using the following formula:", "The potential for loss of the CTD or C-terminal tags will affect the interpretation of cell localisation studies that rely on CTD epitopes. IFITM3 has been localised to endosomal compartments that co-label with markers for early and late endosomes (transferrin, CD63, Rab proteins, LAMP1, LAMP2 and Lyso-Tracker Red (as a marker for acidic compartments) [4, 9, 12, 27, 28] ), but IFITM2 has proved harder to localise. Reliance on CTD epitope tags to determine the cellular distribution of the protein may not reveal the full cellular content of protein, and functionally important pools may be overlooked." ] },{ "paper_id": "cddc369300f073cb0ba20e276fee32112502f4f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It is well known that transfection efficiency of gene carrier depends upon its ability to condense DNA into nano-sized particles [13] . As expected, PEI condensed DNA into nano-sized particles, suggesting their endocytosis potential ( Figure 1A ).", "Statistical tests were performed by using Student's t test. P value less than 0.05 was considered significant. " ] },{ "paper_id": "cdde042300059d2b850f850b56dc8c02d50b07e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflicts of interest." ] },{ "paper_id": "cde537507323b28a413a559c934c435b24546c63", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bats were treated according to the guidelines of Regulations for the Administration of Laboratory Animals ( " ] },{ "paper_id": "cde903001c25e2e1da0870eb9e40573e9fd8c424", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animals used for collection of fresh brain tissue were transcardially perfused with 200 ml of 0.9% saline containing heparin (10,000 U/l). The brains were extracted and the HP was dissected and frozen on dry ice. For collection of fresh tissue for AnkG immunoblotting, animals were perfused for 5 min with saline containing heparin (\u03f360 mL). The extracted HPs were then immediately frozen in liquid nitrogen and stored in liquid nitrogen until processing for AnkG immunoblotting. To collect fixed tissue, the saline perfusion was followed by 200 ml phosphate buffered 4% paraformaldehyde. The brains were postfixed in 4% paraformaldehyde for 24 h. After postfixation, the brains were embedded into gelatin blocks for sectioning (Smiley and Bleiwas, 2012) . The gelatin block was equilibrated in 20% glycerol. The gelatin block was cut into 40-m-thick coronal sections on a freezing, sliding stage microtome. Sections were stored in cyroprotectant until processed for immunohistochemistry or immunofluorescence.", "For axonal tau intensity measurements, a 4x objective (0.13 numerical aperture) was used to capture two to three images of the dorsal HP in three serial tissue sections per animal. The entire visible regions of the fimbria, alveus, stratum lacunosum, and stratum moleculare were outlined in NIS Elements software. The average fluorescent intensity per area was measured for each axonal region.", "As a positive control for detection of age-related changes of protein, blots were probed for GFAP, a protein previously shown to change in HP lysates of aging rats (VanGuilder et al., 2011) . A significant increase in GFAP was found in the old rats compared with the young rats (F (2,16) \u03ed 4.529, p \u03ed 0.0276; Fig. 1K )." ] },{ "paper_id": "cdf3bcf39150a5ef5537651e90d93cbccd097f79", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "White cell count(610 9 /l) 7.9(6.2-9.7)(n = 64) 9.6(7.9-13.5)(n = 10) 9.0(6.0-11.5)(n = 158) 8. " ] },{ "paper_id": "cdf5579d820bb3154dc31e2d72bce2fe3f39b1bf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cdf75a14256bbd7d9cd72634c174cb4e63c06a25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In summary, a combination of all cues may dictate tissue-specific infection rates and dissemination routes emphasizing the importance of in vivo studies for infection research.", "Intravital imaging using multi-photon excitation has been introduced into the fields of neurobiology and immunology very early after the technique was established in the 1990s [102] [103] [104] .", "In summary, although MP-IVM comes close to study biological effects under natural conditions, researchers must be aware that the physiological status is inevitably influenced by the required procedures. Animal manipulation should always be kept at a minimum and alternative methods should be considered. The quality of acquired data depends strongly on the preparation and monitoring of the experimental animal. A careful and critical data interpretation is always crucial for in vivo imaging experiments." ] },{ "paper_id": "cdf9d4e00e66bd0c1751c1cc41ec13d0baed9749", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cdffc1eadb85e776433b6850a2dd40a350874622", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Horseradish peroxidase (HRP)-conjugated goat antimouse IgG (H+L), HRP-conjugated goat anti-mouse IgG (H+L) F(ab') 2 fragments, and FITC-conjugated goat antimouse IgG were purchased from Jackson ImmunoResearch Laboratories." ] },{ "paper_id": "ce0425b48e9b111a10f612fc562a2cd316633c15", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The device will enable multiplasmid vaccine preparation to provide multiplasmid vaccine preparation without interference (Mackow et al., 2014) .", "Similarly, all DNA vaccines developed against hantavirus target the M gene expressing the envelope GP (Gn and Gc) of hantaviruses ( Table 2 , part 1).", "Their studies have confirmed that these DNA vaccines produce neutralizing antibodies in multiple experimental animal species and protected hamsters from HFRS (Schmaljohn et al., 2014) ." ] },{ "paper_id": "ce05a808109c6307485aeda93945cd3b0e536623", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Three types of input are supported:", "3. An Entrez ID or a Genome Project ID.", "The workflow consists of the following steps: " ] },{ "paper_id": "ce07f8b5cfe254e66c5d9f174dd1f3208a459520", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A sputum sample was taken in the acute phases of each episode of infection, diagnosed on the basis of symptoms and clinical findings as described in detail previously [27] . The military conscripts having at least one infection episode during military service were included in this analysis. The specimen collection consisted of 386 sputum samples. The specimens were stored at -70\u00b0C prior to virological analysis. The viral RNA was isolated from 100 \u00b5L of sample with RNAeasy Mini Kit (Qiagen Gmbh, Hilden, Germany) using QIAcube automatic nucleic acid extractor. ", "This work is part of a larger CIAS (Cold, Infections and Asthma) study about risk factors for asthma and respiratory infections in Finnish military conscripts [27] . Briefly, 892 men from a total of 3,697 men making up two intakes of conscripts to the Kainuu Brigade in Kajaani, Northern Finland, in July 2004 and January 2005, were enrolled in the CIAS study. These included all 224 men with a diagnosis of asthma in previous health examinations or the call-up examination, and 668 randomly chosen men without asthma. Their ages ranged from 17.4 to 29.6 years (median 19.6). The enrollment procedure has been described in detail previously [27] . Each man was followed to the end of his service time lasting 6 to 12 months, according to military duties. The protocol was accepted by the Medical Ethics Committee of Kainuu Central Hospital, Kajaani, Finland, and all the participants signed a declaration of informed consent." ] },{ "paper_id": "ce1f762e478087400412172f30e184d92f17d976", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "The ", "Methods" ] },{ "paper_id": "ce2184a9344e5a044a8e307ec161cfd454b258e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ce248b901191d45f3e56f1e6664a0239738aa148", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We re-analyzed two samples previously reported to harbor alphacoronaviruses [11, 20, 25] and one sample positive for hantavirus [28] . These samples included a UK Microtus agrestis gut (UKMa1), a UK Microtus agrestis kidney (UKMa K4D) and a France-resident Oryctolagus cuniculus intestinal wash (L232) ( Table 1) .", "All the samples used in this study were sourced from existing pest controls programs and approved by the University of Nottingham School of Veterinary Science Ethical Panel, reference numbers 1602 151102 and 1786 160518. ", "All the virus sequences generated in this study have been deposited on GenBank under the accession numbers MN626413-MN626440.", "In sum, our results confirm that metagenomic next-generation sequencing is capable of discovering previously unknown and divergent RNA viruses. However, our data also highlight that definitive identification of the likely host species can be complicated because of dietary or environmental contamination. As a consequence, true assignment of host species requires wider prevalence studies together analysis of multiple tissue types.", "In this study, we generated and investigated RNA sequencing data from European rodents and rabbits that were previously found to be positive for novel alphacoronaviruses and hantaviruses [11, 20, 25, 28] . Our aim was to perform an unbiased discovery of additional viruses that were present in these samples, reveal their evolutionary history, and assess their prevalence in their host populations. Accordingly, we demonstrate the presence of novel and highly divergent RNA viruses and discuss the potential pitfalls of the use of enteric samples for virus discovery." ] },{ "paper_id": "ce2d071c2152f86f8f190bb30ea857f16050ae8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reporting summary. Further information on experimental design is available in the Nature Research Reporting Summary linked to this article.", "Code availability. All code associated with this study can be found here: https:// github.com/Emergent-Epidemics/infectious_disease_predictability.", "Our finding that horizons exist for infectious disease forecast accuracy and that aggregating over multiple outbreaks can actually decrease predictability is supported by five additional lines of evidence. First, Hufnagel 51 . Finally, using state-level data from Mexico on measles, mumps, rubella, varicella, scarlet fever, and pertussis, Mahmud et al. showed evidence that while short-term forecasts were often highly accurate, long-term forecast quality quickly degraded 52 ." ] },{ "paper_id": "ce2f322118541b9901f218ce6e49177e5d25dd6c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the study, we developed an HRM assay by taking advantages of the more conserved segment and one SNP detection and use it to distinguish CPV from FPV in clinical samples simultaneously.", "Virus isolation was performed on the clinical swab samples using F81 cells for parvovirus as described previously [32] . Isolated viruses were identified by PCR assays [5] , and genotyped based on sequencing and alignment using the MEGA7.0 software package. ", "To exclude cross-reactivities between CPV/FPV and other canine viral pathogens, the DNA or cDNA of CAV-2C, CCV HB16-2, FPV (Fel-O-Vax-PCT), CPV-2/ 2a/2b/2c and CDV3, were tested using HRM assay. The ddH 2 O was set as the negative control (NTC).", "FPV was first isolated from a sick cat in 1965 [4] . Thirteen years later, a variant of an FPV like virus named CPV was identified in the fecal samples of dogs with diarrhea and spread worldwide rapidly [5] . Since then, the original CPV-2, which cannot infect cats, was subsequently replaced by three different but closely related antigenic variants (CPV-2a, CPV-2b, and CPV-2c), which can infect cats [5, 6] . CPV has evolved more rapidly than FPV, the substitution rate for the CPV and FPV clade was 1.7 \u00d7 10 \u2212 4 and 9.4 \u00d7 10 \u2212 5 substitutions per site per year, respectively [7] ." ] },{ "paper_id": "ce387fc60565255c55785be208ae0b6b8fbb2ed3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bacteria. Studies suggest a role for pomegranate extracts in reducing and preventing pathogenic dental bacteria and reducing the risk of plaque, gingivitis, and periodontal disease. Many of these studies are human clinical trials.", "Konowalchuk and Speirs [76] found that <1% of 3 log PFU poliovirus/0.05 mL survived after storage at 4 \u2218 C for 24 hours in pomegranate juice, though the mechanism of action was unknown. Poliovirus is transmitted through the fecal-oral route in a manner similar to other enteroviruses, being a nonenveloped RNA virus. As preventive measures, poliovirus vaccines are available.", "Pomegranate extract had a beneficial effect on rumen bacterial populations in lactating cows [26] . The peel extract was fed at levels of 1, 2, or 4% on voluntary intake. The supplementation had a significant positive dose-dependent effect on the entire ruminal bacterial community, as determined by automated ribosomal intergenic spacer analysis. In cows fed at the 4% extract level, there were significant increases in digestibility of dry matter, crude protein, and neutral detergent fiber, as well as milk yields." ] },{ "paper_id": "ce4252922cce80f4284eae7607b1967b35596ef5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human airway epithelial cells (HAECs) from normal subjects were obtained from nasal turbinates which were removed and discarded in the process giving access to the ethmoidal sinus (from the department of Ear, Nose and Throat, H\u00f4pital de la Croix-Rousse, Lyon, France). Patients were operated for tumours located in the ethmoidal region and had no respiratory disease.", "When they reached 80-90% confluence, collagen was digested (J', 7-10 days post-seeding) and cells were suspended in flasks with rotation (inclination 10\u00b0, 80 rpm) at 37\u00b0C, to redifferentiate in the form of ciliated vesicles.", "Cells from control subjects and the patient were grown using the immerged cell culture previously described by Jorissen et al." ] },{ "paper_id": "ce43f8f05a5db366babc9a6bfa086219534de208", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In total, 10 \u03bcg of each cellular protein lysate sample was separated by 12 % SDS-PAGE and electro-blotted onto a nitrocellulose membrane (GE Healthcare) soaked with blotting buffer (25 mM Tris, 192 mM glycine, and 20 % methanol, pH 8.3). Subsequently, the membranes were incubated for 1 h at 25\u00b0C with rabbit anti-actin (ab8227, Abcam), mouse anti-BiP (ab96483, Abcam), rabbit anti-P-eIF2\u03b1 (ab4837, Abcam), rabbit anti-P-IRE1 (ab48187, Abcam), or mouse anti-ATF6 (ab11909, Abcam). The blots were then incubated with an HRP-conjugated antimouse or anti-rabbit total immunoglobulin (respectively, ab6728 or ab6721, Abcam) for 1 h at 25\u00b0C. The detection was performed using the ECL reagent (Pierce) and exposure to radiographic films (GE Healthcare), the development of which was performed using an automated SRX-101A processor (Konica Minolta).", "Quantitative analysis of the data obtained from the Western blotting experiments was performed by band densitometry using the software ImageJ (http://rsbweb.nih.gov/ij/)." ] },{ "paper_id": "ce48c5f903bc1435190dd7ddf21612cb0a8b0815", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All studies described here were approved by the Ethics Review Committee of Jiangsu Institute of Parasitic Diseases, China (Permission number: JIPDERC2007008). The field studies did not involve endangered or protected species." ] },{ "paper_id": "ce50fd91c0c1bbd6f3f9de6a231a9cd41700108b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. Where appropriate, p values were calculated using unpaired two-tailed t-test for unequal variances. p values < 0.05 are reported.", "The data generated in the study are available from the corresponding author on reasonable request.", "It is thought that viruses and their host cells co-evolved over millions of years 19 . Recently, 214 vertebrate-associated RNA viruses have been identified in fish, amphibians and reptiles adding to the body of evidence 20, 21 . If co-evolution is true, it stands to reason that cells would have evolved to fight viral infections at an early stage (i.e. when life began in the marine environment), and potentially used the most commonly available resource -chlorine 22 . White leg shrimp (Litopenaeus vannamei), a euryhaline shrimp that can adapt and survive in a wide range of salinities, is known to get infected with white spot syndrome virus. Outbreaks of white spot syndrome virus are common in shrimp farms during the rainy season, with a possible association with lower salinity and temperatures. It has recently been reported that shrimp are more susceptible to white spot syndrome virus when the water is at a lower salinity, suggesting that chloride ions may have an antiviral effect in marine organisms as well 23 . This potential relationship between virus, eukaryotic co-evolution and antiviral mechanism is interesting and needs further research." ] },{ "paper_id": "ce5e67e3d17645302f7a91d7d0c8bc3428884187", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Under certain circumstances, we can find a simple expression for R 0 from the next generation matrix. The derivation is similar to the simplification of R 0 for the multi-city epidemic model described in Ref. [1] . For this we need the following theorems:", "Our SIR meta-population model can be defined as a system of differential equations as follows:", "We divide dS i dt (Eqn. (S4)) by S i and integrate between 0 and \u221e, then we have:", "(S13)" ] },{ "paper_id": "ce6af0bb9b796bf3ddc44ddabdce04a7584957d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1 H and 13 C NMR spectra were recorded in DMSO-d 6 on a JNM-ECX 400 spectrometer (Jeol, Tokyo, Japan) at 400 and 100 MHz, respectively, using tetramethylsilane as an internal standard, and chemical shifts are given in \u03b4 (ppm). UV spectra were obtained in methanol on a BioMate 5 spectrophotometer (Thermo Spectronic, Rochester, NY), Fourier transform infrared (FT-IR) spectra on a Nicolet Magna 550 series II spectrometer (Midac, Atlanta, GA), and mass spectra on a Jeol GSX 400 spectrometer. Silica gel 60 (0.063-0.2 mm) (Merck, Darmstadt, Germany) was used for column chromatography. Merck precoated silica gel plates (Kieselgel 60 F 254 , 0.20 mm) were used for analytical thin-layer chromatography (TLC). A SCL-10 AVP high-performance liquid chromatograph (Shimadzu, Kyoto, Japan) was used for isolation of active principles.", "To evaluate the level of gene expression, quantitative real-time reverse transcription-PCR (RT-PCR) with SYBR Green dye was performed. HRV-4 infected and noninfected cultures of HeLa cells grown in Corning 25 cm 2 cell culture flasks (Corning, NY) were treated " ] },{ "paper_id": "ce6f81a5f2e09ff7a23ea939e3c3c062ef6130c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The hospital sector in Taiwan is organized into six regions, each with its own capped budget, under which hospitals within the same region compete for reimbursement. We also introduced year-specific number of hospitals and beds in the region to explore the role of market consolidation and mergers. Finally, our model also included region dummies to control for any effects from unobservable regional-level factors.", "We also examined the role of the facility characteristics of the treating hospitals, including ownership (public and private), accreditation (medical center, regional, or local hospital, according to facility capacity in terms of bed numbers, medical specialties, and staff densities), and teaching status.", "Patient characteristics assessed as predictors of intensity of care were age; sex; beneficiary's earnings, on the basis of which the payroll-based premium is calculated; and co-morbidities, as defined by the Charlson Comorbidity Index (CCI) [40] . We also considered whether the patient had ESRD requiring renal replacement therapy, because of the expansive nature of dialysis treatments. In addition, patients with ESRD in Taiwan are entitled to free medical services without any patient cost-sharing under NHI, which could affect their utilization of health services. Eligibility for such a medical fee waiver is indicated in the NHIRD.", "Background Support for reforming the delivery of end-of-life (EOL) care has been observed in recent years, exemplified by the 2014 Institute of Medicine Report \"Dying in America\" [1] . Several policy interventions have also been suggested, including the recently proposed regulations by the Centers for Medicare and Medicaid Services to reimburse physicians for holding advance care planning discussions with patients [2] . In Taiwan, the government launched a pilot program in 2011 and amended its Statute of Palliative Care in 2014 to promote hospice and palliative care [3] . However, the current practice of EOL care for these patients, including most of the well-intentioned programs and initiatives to improve quality or reduce costs, is not evidence-based [4] ." ] },{ "paper_id": "ce74ed47b12de8d1c70b2cac843b6953c57bd5de", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The complete genome sequence of HCoV-229E strain 229E/ Haiti-1/2016 has been deposited in the GenBank database under accession number MF542265.", "These studies were funded in part by internal funds from the University of Florida Emerging Pathogens Institute and by a grant to J.G.M. from DHHS (NIH R01 AI126357-01S1).", "Human coronavirus strain 229E (HCoV-229E) and human alphaherpesvirus 1 were isolated from the plasma of a Haitian child in 2016 with suspected arbovirus diseases. To our knowledge, this is the first description of HCoV-229E in human plasma, which is the focus of this article." ] },{ "paper_id": "ce75acf2c22c37fdd88ecf5ed40c6713443fef47", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "March 2016 | Volume 7 | Article 89 2", "March 2016 | Volume 7 | Article 89 6", "ND, SB, and J-P S wrote the review." ] },{ "paper_id": "ce7b8f00255cb989194bd19a730abd529c0d1f82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Exemption for review by the ethical committee system and for obtaining informed consent was obtained from the Committee on Biomedical Research Ethics for the Capital region in accordance with Danish law on quality control and assay development projects. [21] and Sapovirus [22] , and ClartH HPV2 microarray (Genomica) for HPV. PCR's were performed on Mx3005P (Stratagene) or ABI7900 (Applied Biosystems) thermal cyclers.", "Microarray data has been submitted to the Gene Expression Omnibus (GEO) database http://ncbi.nlm.nih.gov/geo/ with the accession number GSE28597. All microarray data used in this study is MIAME compliant.", "(DOC) " ] },{ "paper_id": "ce88c461bd735cb67a9a7f6dc4d3ec1418d7dffb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Outpatient providers were defined as all sources of healthcare that did not admit patients for overnight stays, and included government and private ambulatory clinics, pharmacies, drug shops, the IGSS and traditional healers. Inpatient providers included government and private hospitals.", "We approached 1200 households but residents could not be reached at 33 (3%) locations after three visits, and in 36 (3%), the household head declined to participate. We interviewed residents from 1131 (94%) households and gathered information on a total of 5449 persons of which 2806 (52%) were female and 586 (12%) were children <5 years old (Table 1) .", "The adult respondents from each household were read a consent statement and asked to give verbal consent for their household's participation. The protocol for this study was reviewed and approved by the institutional review boards of the Centers for Disease Control and Prevention (Atlanta, GA) and the Universidad del Valle de Guatemala (Guatemala City, Guatemala) and approved by the MSPAS (Guatemala City, Guatemala)." ] },{ "paper_id": "ce90f3248a2ef874c0d7cfe5926a3ca6e56a7f83", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fifty SFTS patients who were confirmed to be infected by SFTSV previously were enrolled in this study [11] .", "The statistical analysis was performed using SPSS software 18.0 for Windows. Means for continuous variables were compared using independent-group Student's t tests when the data were normally distributed; otherwise, the Wilcoxon rank sum test was used. The categorical variables were compared with \u03c7 2 test. A p-value <0.05 was considered statistically significant." ] },{ "paper_id": "ceab18d97f09ef0d9030f0c808f7ab5ab1c7d583", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RT-PCR analysis of selected genes RNA extraction was performed using a Qiagen RNeasy mini kit with QIAshredder and cDNA was synthesized using a Bioline Tetro cDNA synthesis kit, both according to the manufacturer's instructions. The cDNA was then quantitated by PCR using Maxima SYBR Green master mix (Thermo) and a StepOnePlus\u2122 Real Time PCR system (Applied Biosystems). Primers were obtained from Sigma and are listed in S1 Table. The 2 -\u0394\u0394Ct method was used to determine relative transcript levels using the housekeeping GAPDH gene to normalize the data [45] .", "modified Eagle medium (IMEM, Sigma) supplemented with 10% (v/v) Foetal Bovine Serum (Sigma), 2 mM L-glutamine (Sigma) and 100 \u03bcg mL -1 penicillin-streptomycin (Sigma).", "doi:10.1371/journal.pone.0154674.g008", "Cells (2 x 10 5 ) were seeded into 25 cm 2 flasks containing 7 mL of growth medium. Chemical agents were added as stated and cells grown for 96 h at 37\u00b0C after which cultures were centrifuged at 500 g for 5 min, cells resuspended in fresh medium, and counted using a haemocytometer. Average counts were normalized to the cell count of the untreated culture." ] },{ "paper_id": "ceba28d8304f3df8001164f8edeef545154289f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.ppat.1007365.g008" ] },{ "paper_id": "cec21bb25c57f0e17f672a7ed7b91a01bd371ee7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After each completed sampling occasion, the farmers were sent information on their herd's serological status and information about basic biosecurity measures. A lottery ticket (value approx. 3 euro) was enclosed to the letter.", "BRSV commonly cause respiratory disease, particularly in calves. Disease can be caused by BRSV only or in combination with other viruses (e.g. BoCV) or secondary bacterial infection [9] [10] [11] . BoCV also causes enteric disease, in particular calf diarrhoea [12] , and is the causative agent of Winter Dysentery, outbreak of diarrhoea, in adults [13] . There have been reports of BoCV as the single agent in outbreaks of respiratory disease as well [14, 15] . In addition to impaired animal welfare due to illness, these infections may cause losses to production by reduced weight gain [16, 17] , reduced milk yield [4, 18] , increased bulk tank [19] and individual [18] milk somatic cell counts.", "Although these viruses may spread during the warmer seasons, seroconversion with or without an outbreak of clinical disease is more frequent during the housing season (autumn and winter) [6, 23, 24] . There is however, still a knowledge gap concerning what the most important routes for virus transmission between herds are. A few studies from the Nordic countries have studied risk factors for herds to be and to become seropositive to BRSV and BoCV. Risk factors at herd level have included a short distance to nearest herd, not providing boots to visitors, large herd size and a high density of cattle in the area [5, 7, 25, 26] .", "Study herds were sent instructions, material and protocol for sampling in November 2011, May 2012, and May 2013. These occasions were chosen to include as many stall periods as possible during the project. At each sampling occasion, milk from four homebred primiparous cows and BTM were sampled into test tubes with 1.5 mg of the preservative agent Bronopol. Samples were returned to the National Veterinary Institute by prepaid mail where they were stored at \u221220\u00b0C until analysed." ] },{ "paper_id": "cecee9224f871415878f3787539095673d50ca8a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of ", "Human influenza virus A/PR/8 (H1N1) propagated in chicken eggs and sucrose gradient purified from allantoic fluid was obtained from Charles River Laboratories, aliquoted, and frozen. Titer was determined by standard plaque assay on Madin-Darby canine kidney cells.", "Flow cytometry 5610 5 NIH 3T3 or RAW 264.7 cells were stained with a panel of rat monoclonal IgG 2a antibodies against the OSM receptor (clone 30-1, MBL International Corporation), IL-6 receptor (clone 255821, R&D Systems), gp130 (clone 125623, R&D Systems), or an equal amount of an isotype control antibody (clone eBR2a, eBiosciences). Secondary labeling was performed with Alexa 488conjugated donkey anti-rat (Invitrogen) and fluorescence was measured on a BD Biosceinces FACSCalibur flow cytometer." ] },{ "paper_id": "ced400d9d754e83891f4bc5b6ea39845fe076c92", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Next-generation sequencing is transforming many fields of investigation, including diagnostic evaluations and novel pathogen discovery. The current limitations of NGS application for these purposes include (i) sensitivity of detection of minute pathogen genome nucleotide ratios within complex eukaryotic host samples, (ii) bioinformatics pipelines that can efficiently detect NGS output data for veterinary pathogens, (iii) expertise required to design and conduct pipelines for biological problems, and (iv) expense for high-throughput analysis.", "Supplemental material for this article may be found at https://doi.org/10.1128/JCM .01463-16.", "SUPPLEMENTAL FILE 1, PDF file, 0.4 MB. SUPPLEMENTAL FILE 2, PDF file, 0.1 MB." ] },{ "paper_id": "cee3dd6c1927b863e94e9493295d99213401f158", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Apart from testing all cells for lyssaviruses, 454 sequencing was used for broad pathogen screening. After lysis of cell pellets and purification of RNA and DNA, nucleic acid amplification was performed using degenerate primers targeting conserved regions of major virus families or genera ( Table S1 ). All sequences obtained were identified as host sequences; no sequences from viral or bacterial organisms were found.", "Table S1 Virus families and genera for which screening by nucleic acid amplification was performed. Details on assays available upon request.", "(AVI)" ] },{ "paper_id": "cee73a9e8367f60e1149b8db0b8a00a780c84d9d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LGKVIDTLTCGFADL [38] Homo sapiens P27 LFGPVDHEELTRDL [39] Homo sapiens Focal adhesion kinase LRSEEVHWLHVDM (NES1) [40] LDLASLIL (NES2) African swine fever virus P37 LTVEELGL (NES1) [41] IDSIQTVQQM (NES2)", "The binding pocket" ] },{ "paper_id": "cef34a0d6cfce0c84ac90fb01338bb2429693d9e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cefbe0e7441f96ec3d0a08e9d7f291dbcf44f4e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical differences were carried out using standard Student's t test (two-tailed, unpaired). The statistical difference was considered to be significant as p < 0.05 (*) or p < 0.01 (**).", "Mitochondria were isolated using Mitochondria Isolation Kit for Cultured Cells (Thermo Scientific Inc., Waltham, MA, USA) as described in the manual.", "Cell proliferation potential was evaluated by both MTT and CCK-8 assays. Briefly, equal amounts of cells were seeded into a 96-well plate and treated with IFN-\u03b1 for 24 or 48 h before testing. MTT solution or Cell-Counting Kit-8 (Dojindo Molecular Technologies, Ltd., Kumamoto, Japan) solution was added into each well. After 2.5-3 h incubation, the absorbance at 490 or 450 nm was measured using a microplate reader." ] },{ "paper_id": "cf06138d477edd309f439ae40bf555d5bf63b173", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ". This assumption is relaxed in \u00a75.", "l i!j \u00f0tjQ\u00de:", "Assume that at the beginning of iteration n, parameter vector is Q n21 : -expectation step:" ] },{ "paper_id": "cf08012c131b34b073bc10b82fcb6574b17d13b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pathogen shedding and load SIV titration (nasal swabs, lung tissue) in Madin-Darby canine kidney cells (MDCK) (ATCC) were performed in duplicate as described previously [17] .", "All sera were examined using HI assays (SIV) against challenge strain and ELISA test against Hps as directed by the manufacturer (Swinecheck\u00aeHPS, Biovet, Canada). The presence or absence of antibodies to investigated antigen (Ag) was determined by calculating the ELISA ratio. ELISA ratio (Er) was calculated according to the following formula:", "The virus used in experiment (avian-like H1N1 A/Poland/ Swine/14131/2014 (SIV)), had been isolated from the lung of pig suffering from acute swine influenza. This strain is representative H1N1 SIVs circulating recently in Poland. The stock used for nasal inoculation represented the third passage in eggs. The virus titre was evaluated in Madin-Darby canine kidney (MDCK) cells (ATCC).", "Strain of Hps, previously isolated in National Veterinary Research Institute was selected for the experimental infections (isolate PIWetHps192/2015). Strain originating from lung of pig from Polish herd and the analysis of the 16S rRNA gene sequences [33] revealed 99% similarity to Hps isolate CN9-2 described by Olvera et al. [34] (classified as moderate virulent serovar 15)." ] },{ "paper_id": "cf085fe7f16317b15dddc417b76252025fc80f61", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cf0d47062feee58725fffdbd8b91eec680237fc1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(ii) Class B (SR-B1) has 2 transmembrane regions and are identified as as ocLDL receptors. Members include SCARB1, SCARB2, and SCARB3 (CD36). (iii) Class C has a transmembrane region in which the N-terminus is located extracellularly. There are other receptors that have been reported to bind to oxLDL which include CD68 and its murine homolog macrosialin, mucins, and LOX-1.", "It is clear that antigen mannosylation is an effective approach to potentiate antigen immunogenicity, due to the enhanced antigen uptake and presentation by DCs and macrophages.", "Receptor Family" ] },{ "paper_id": "cf0dd4d9f9f906626d5bc4a01e1f1eb21806291c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Preventing the brain drain Support health workers from low and middle income countries to continue working in their countries by:", "Support collaborative endeavours by:", "\u2022 Encouraging broader inter-sectoral communication; for example, with the animal health sector, by creating short-term clerkships in other health-related sectors outside the ministry of health." ] },{ "paper_id": "cf12680358351109a975a23165bbb48620b578a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Mann-Whitney U test and log-rank test were used to compare viral growth and compare characteristics between fatal and nonfatal mice in the Kaplan-Meier curves, respectively. The Steel-Dwass nonparametric test was used for multiple comparisons of VNA titers. All p-values were two-sided, and a p < 0.05 was considered significant. All data were analyzed using ", "In this study, we used humane endpoints as early indicators of animal pain or distress that could be used to avoid or limit suffering by taking actions such as humane euthanasia. During the observation period, we monitored neurological symptoms daily and set up the humane endpoint when mice were considered to have reached a moribund stage [i.e., observation of rabies-associated clinical signs after infection (e.g., paralysis or seizure)]. Moribund mice were euthanized with isoflurane immediately after they reached endpoint criteria. All research staff were specially trained in animal care and treatment under the standard operation procedures of our laboratory.", "https://doi.org/10.1371/journal.pone.0223684.g003" ] },{ "paper_id": "cf27e2301131c5cb6d5b67e2dd29eff6f31ead18", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. Simulate a length N random sequence of node degrees {D u } from the distributionp(d).", "4. Form the network by connecting stubs to stubs and corners stubs to corner stubs.", "2. Use the steps above to create the node role sequence (S u , T U ), u = 1, . . . , N and create the network." ] },{ "paper_id": "cf3abd4ab4ea9d7d602482b62166463db3dffc02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The most commonly used epidemiological parameters are reproduction number (R), illness attack rate (IAR), Initial set of articles filtered from PubMed using keyword search (n = 640)", "Remaining articles (n = 28)", "Exclusion of articles that examine global pandemic spread (n = 6)" ] },{ "paper_id": "cf418ee0dbf748c0464bc42111a8fc79e00dab3c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Disability was assessed by the Katz index [39] that included six essential ADLs: bathing, transferring, dressing, eating, toileting, and continence. The Chinese version of the scale has been extensively tested and has been shown to yield reliable and valid responses [40, 41] . As described previously [39] [40] [41] , we defined disability as needing personal assistance in performing one or more of the five essential activities (bathing, transferring, dressing, eating, and toileting) or being incontinent." ] },{ "paper_id": "cf47b85324ae854a471893563d2156f4a47632e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cf4a58774b63c053feab8838400b5bb5f595d401", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bacteriology. The fecal swabs taken at 0 dpi and 2 dpi did not show any growths of pathogenic bacteria.", "Another important fact is the reliability of commercial ELISA assays. In this study three commercial ELISA assays were compared and variations in specificity and sensitivity were found as already shown in other studies 51 . Therefore, the combined use of different diagnostic tools to investigate the serological status of an animal should be taken into account.", "To detect PEDV genome in fecal swabs, a RT-qPCR system targeting the S-gene of PEDV was used as described previously 33 . Cq values above 40 were considered negative and the amount of PEDV genome copies was calculated by using a standard curve." ] },{ "paper_id": "cf4b53e86101ba9279f53b315f8aee6ecba9e0c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cf5227d38a667f9612804971951c05e55d9bda01", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "S\u00f0fq i a g\u00de \u00bc \u00c0ln", "ACDEFGHIKLMNPQRSTVWY.", "Supporting Information S1 File. Parameters optimization by Grid-research combined with 5-fold cross validation." ] },{ "paper_id": "cf533451f25297fe0d1a6006fc562568358cefb6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors confirm that all relevant data are included in the paper and /or its supplementary information files.", "were premixed in a 1:1 molar ratio at 4 \u00b0C overnight. The mixture was loaded onto the gel-filtration column (Superdex 200 prep-grade XK16/70, GE Healthcare), and the protein complex was eluted at a flow rate of 0.5 ml/ min at 4 \u00b0C in a buffer solution consisting of 50 mM Tris and 100 mM NaCl, pH 8.0. The optical absorbance at 280 nm was used to monitor the eluted protein complex.", "EBV for immortalizing human B lymphocytes was prepared from B95-8 cell line, as described 31 ", "Enzyme-linked immunosorbent assay (ELISA). ELISAs were performed to examine the H1N1-virusor HA-binding activities of sera, culture supernatant and purified antibodies. Briefly, inactivated whole H1N1, H5N1 and H7N9 virus were coated on a 96-well plate (Maxisorb, Nunc) at 4 \u00b0C overnight followed by blocking with 1% bovine serum albumin (BSA)/PBS (Invitrogen) at 37 \u00b0C for 2 h. The serial diluted samples were incubated in wells at 37 \u00b0C for 2 h. After a complete wash, the horseradish-peroxidase-labeled anti-human IgG (dilution of 1\u22365000) was added and incubated at 37 \u00b0C for 1 h. 3,3\u2032,5,5\u2032-tetramethylbenzidine/H 2 O 2 was added to develop color, and the reaction was stopped with 50 \u00b5l of H 2 SO 4 . The amount of chromogen produced was measured based on absorbance at 410 nm and 630 nm using an ELISA reader (SpectraMax, MD, US)." ] },{ "paper_id": "cf665ea806b5a1b271c377e3826bf9d8bd0ebf9f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine reproductive and respiratory syndrome (PRRS) is an economically important disease of swine throughout the world, characterized by severe reproductive problem with late term abortions in sows and severe respiratory ailment leading to increased mortality in young pigs [1, 2] . The disease was first reported in the United States in 1987 and subsequently in Europe in 1991, reaching Southeast Asia and Japan in 1995 [3, 4] . The disease is now pandemic in many swine-producing countries and has become one of the most serious threats to intensive swine industry. In June 2006, the outbreak of \"high fever\" in China, caused by highly pathogenic PRRSV infection, spread to more than 10 provinces and took a huge toll in swine industry [5] .", "Highly purified virus (3 \u03bcl) was adsorbed to Formavarsupported, carbon-coated nickel grids (230 mesh) for 2 min at room temperature (RT). The grids were then negatively stained with 3% phosphotungstic acid and examined under a JEM-1400 electron microscope (JEM-100CX-II, JEOLLTD, Japan) operated at 120 kV." ] },{ "paper_id": "cf66e218ffa8ed3d638c5ddff568753609aac808", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical comparisons were performed using the CHISS software (version 2001, Yuan YiTang Sci-Tech Co., Ltd., Beijing, China). Categorical data were expressed as percentages and calculated using a chi-square test, and p \u2264 0.05 was considered statistically significant.", "The World Health Organization has made the development of a safe and effective vaccine against S. flexneri [1, [6] [7] [8] , but the vaccine effectiveness depends on the distribution patterns of local species and serotypes, because only type-specific immunity has been demonstrated in humans [9] [10] [11] [12] and moreover cross-serotype protection is controversial [11, 13] .", "Samples were cultured for Shigella by streaking diarrheal stools directly onto Salmonella-Shigella agar (Tian Tan Biologic Technology Company, Beijing, China) and incubating for 24 h at 37\u00b0C. Shigella-like colonies were selected and subcultured on Kligler iron agar (Qingdao Hope Biol-Technology Co., Ltd., Shandong, China). Except for S. flexneri 6 and S. boydii 14, Shigella spp. produce an alkaline slant and an acid butt but do not produce gas or H 2 S. As a species, Shigella organisms are characteristically nonmotile and lack the enzyme lysine decarboxylase." ] },{ "paper_id": "cf6aa226d19188bcb5215d3d1cced4773a82b6f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data generated or analyzed in this study are included in this published article.", "Viruses of the genus Orthohepadnavirus, family Hepadnaviridae, are partially double-stranded DNA viruses that infect a variety of mammals. Chronic infections in humans of the prototype species, hepatitis B virus (HBV), increase the risk of liver diseases including cirrhosis and hepatocellular carcinoma 1 ." ] },{ "paper_id": "cf6c6fa2a4cf3fd624d4ef8291804a3fab3f1b2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Transfected cells were harvested after 48 hrs and lysed in the cell lysis buffer (Luciferase Assay Kit; Promega, Madison, WI, USA). Normalized cell lysates were analyzed for luciferase activity according to the supplier's protocol and readings were taken on a luminometer (Sirius, Berthold, Germany).", "Tranfections were done with the Fugene 6 reagent (Roche, Mannheim, Germany) according to the manufacturer's instructions. At the indicated times post-transfection, cells were scraped, lysed and processed as described previously [7] . The protein concentration of the lysate was estimated using Bradford regeant (Bio-Rad), and immunoblotting was carried out as described previously [69] .", "Transfected cells were lysed in a buffer containing 20 mM Tris-HCl, pH 7.5, 150 mM NaCl, 1 mM EDTA, 1 mM EGTA, 1% Triton X-100, 1 mM NaF, 1 mM sodium orthovandate and a protease inhibitor cocktail (Roche, Mannheim, Germany). The lysates were clarified by centrifugation at 16,0006g for 20 min at 4uC. Protein quantitation was done by Bradford assay (Bio-Rad Laboratories). For immunoprecipitation of phosphoprotein, 0.7 to 1 mg of total protein in 400-500 ml lysis buffer was first incubated with 20 ml of Protein G-agarose beads (GE Healthcare, Uppsala, Sweden) for 1 hr at 4uC. The pre-cleared lysate was then incubated with 2 mg of the antibody overnight at 4uC, followed by 20 ml of equilibrated Protein G-agarose beads for 3 hr at 4uC. After washing five times in lysis buffer, the beads were boiled in Laemmli buffer, the proteins were separated by SDS-PAGE, followed by immunoblotting as described previously [69] . " ] },{ "paper_id": "cf6dbaad6eab542c67cde5670d0fa0a2a65248f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was conducted with samples from 73 municipalities of S\u00e3o Paulo State, Southern Brazil, using 305 samples of enteric content of 29 bat species of three families (Molossidae, Phyllostomidae and Vespertilionidae). These animals were submitted to Instituto Pasteur (S\u00e3o Paulo, Brazil) from March/2013 to July/2014, as a part of rabies surveillance program, and were stored at \u221220\u00b0C. Each animal was necropsied, the entire intestine was removed from abdominal cavity and all intestinal content was extracted and stored at \u221220\u00b0C.", "G. soricina is a nectarivorous neotropical bat that might be found inside houses and has already been described as a host for Alphacoronaviruses [23] . Although 3 and 98.4 %, respectively) . G. soricina species does not migrate over long distances [24] , therefore it is unlikely that transmission has occurred among these specimens, suggesting a virus-host adaptation.", "Environmental changes caused by man have promoted a major impact on ecology, affecting the movement of several wild animals species from their natural habitat to urban or rural areas [27] , increasing the chances of contact between humans and domestic animals with wild animals. Furthermore approximately 75 % of emerging infectious diseases have zoonotic origin and wildlife as source of infection [28, 29] . Therefore, it is essential to survey and identify possible sources of infection, especially in relation to bats that are considered important reservoirs of viral agents [30, 31] ." ] },{ "paper_id": "cf750714decab335f8990db7d0ca100506fa99fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Wild birds are an important but to some extent under-studied reservoir for emerging pathogens. We used unbiased sequencing methods for virus discovery in shorebird samples from the Delaware Bay, USA; an important feeding ground for thousands of migratory birds.", "Conclusions: Our findings highlight shorebirds as a virus reservoir and the need to closely monitor wild bird populations for the emergence of novel virus variants.", "Assessment of phylogenetic relationships was performed using programs of the MEGA 5 software package (http://www. megasoftware.net). Multiple sequence alignments were generated with ClustalW, and phylogenetic trees constructed based on the neighbor joining method using a Poisson correction model to calculate distance; bootstrap values were calculated based on 1000 pseudoreplicates." ] },{ "paper_id": "cf7837069ab6a12d5663c6f3c715b73fe53493a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Some data were processed with the appropriate statistical analysis described in figure legends.", "The mink were fed the same diet and euthanized according to local standards of animal welfare issues. All excised tissues were flash frozen in liquid nitrogen and stored at 280uC. Experiments involving animals were approved by the animal ethics committee of China Agricultural University with approval number XK320.", "F81 cells obtained from the American Type Culture Collection (ATCC) were cultured in MEM (Gibco, CA) containing 10% FBS (Hyclone, Logan, UT), and 1% penicillin-streptomycin (Gibco) at 37uC in a 5% CO 2 atmosphere. MEV strain L was originally isolated from an infected farm animal, Liaoning province, China. The whole viral genome which is highly homologous with MEV strain Abashiri (GenBank accession, D00765.1) has been sequenced in our laboratory." ] },{ "paper_id": "cf85ce2e8400011f5119b0eb1a87ffb7933b84a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mice were anesthetized with a mixture of ketamine/ xylazine (67/27 mg/kg) and perfused with PBS. After dissection, half brain was immediately frozen on dry ice and the other half fixed overnight with 4% paraformaldehyde (for immunohistochemistry). Thereafter, fixed tissue was stored in PBS/0.02% Na azide at 4\u00b0C until use." ] },{ "paper_id": "cf8e39bf81b1e6e273adf55fb5db2245bd8bc885", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results of this research should help in the development of new control strategies to treat or prevent TGEV infection.", "TGEV is highly contagious and can spread through various channels; however, the main infection route this virus is fecal-oral. At present, the virus is distributed worldwide; the prevalence of TGEV in different regions of China has long been reported, and TGEV infection has caused huge economic losses to the swine industry.", "Overview of the Solexa high-throughput sequencing data ", "Transmissible gastroenteritis virus (TGEV), belonging to the Coronaviridae family, is the pathogen of transmissible gastroenteritis of swine (TGE). All ages and strains of pigs are susceptible to the virus. Mortality is more than 10% in 2-3-week-old infected pigs, but it is 100% for pigs less than 2 weeks old. Infected animals show clinical symptoms of watery diarrhea, dehydration and vomiting [1] .", "Pathway analysis is a functional analysis that maps genes to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The P-value (EASE-score, Fisher-Pvalue or Hypergeometric-Pvalue) denotes the significance of the pathway correlated to the conditions. The lower the P-value, the more significant the pathway (the recommended P-value cut-off is 0.05)." ] },{ "paper_id": "cf92667ce9f346dd79bc980fdb5d21a5cf6b334a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Florida panthers have undergone continued surveillance from 1978 -2001 and routinely tested for several pathogens, including FeLV [105] . However, for the first time in early 2001, 23 panthers were discovered to carry antibodies for FeLV by ELISA that was confirmed by Western Blot. Clinical symptoms including lymphadenopathy, anemia, septicemia and weight loss rapidly appeared. Five panthers shown to carry FeLV antigens in their sera subsequently died of diseases compatible with FeLV etiology [105, 107] .", "An alternative \"circulating avirulent and virulent FCoV hypothesis\" suggests that distinctive benign and pathogenic strains of FCoV circulate in a population, and those individuals exposed to the virulent strains, with the appropriate predisposition, develop disease sequelae. Virological precedence for this possibility has been reported for dengue fever virus and equine Venezuelan encephalitis virus, both of which demonstrate circulating virulent and avirulent forms [41, 42] .", "As most people infected with HIV do not actually die of HIV infection per se, rather from subsequent opportunistic infections (e.g., pneumocystis, CMV, Kaposi's sarcoma, candidiasis and other infections) it seemed fair to ask whether FIV in large cats might contribute to secondary infection pathogenesis. An opportunity to inspect this occurred during the mid-1990s in Tanzania when an outbreak of canine distemper virus (CDV; a morbillivirus) eliminated ~1000 lions from the large Serengeti populations in a 10 month interval [91] . Because FIV prevalence in East African and Botswana lions approaches 100% in adults, the potential influence of FIV on CDV pathology was to us an interesting question.", "Conventional wisdom accepts the \"in vivo mutation transition hypothesis\" also called the \"internal mutation hypothesis\" which postulates that viral mutations occur in healthy FCoV infected cats giving rise to virulent virions that spread systemically and lead to FIP pathogenesis [36, 37] . Although this hypothesis has been widely cited [9, 25, 27, 30, 31, [36] [37] [38] [39] the precise nature of the mutation responsible for pathogenesis has never been identified. Various studies have speculated that variants in the spike protein, membrane protein, or NSP 3c [40] allow infection of macrophages, systemic dissemination, and fatal disease manifestation [36, 37] .", "Lions harbor six genetically distinct strains, or subtypes, of lion FIV (FIV Ple ) resolved by phylogenetic analyses [57, 58] (Figure 2 ). These strains have distinct phylogeographic distributions, suggesting prolonged host association, perhaps predating the Late-Pleistocene expansions of lions roughly 325,000 years ago [57] . Two lion FIV Ple strains, FIV Ple E and FIV Ple A, circulate in Botswana; while three very divergent strains FIV Ple A, B, and C occur in the Serengeti [92, 93] . Perhaps consequent of the highly social nature of lions, FIV Ple infected lion populations have high prevalence of seropositive individuals, approaching 100% in adult animals [7, 57, 92] (Figure 3a) ." ] },{ "paper_id": "cf997a9d856f8c044b352dad4b62e6718fbe93d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cfacb72c36e1bb7fade469d8bf5ebc12143e0b3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cfafca2d4a79e684fdd5291ae3b69245ff13b61c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Interviews involved between 1 and 5 health department staff, such as preparedness and response coordinators or directors (63% of interviews), communicable disease staff, including directors, epidemiologists, and nurses (38% of interviews), health officers or directors (16%), and environmental health staff (10%) (see Table 1 ).", "This research uses a mixed-methods approach. Quantitative and qualitative data on urgent event and response characteristics were collected through structured telephone-based interviews with health department representatives using a retrospective crosssectional design.", "The protocols for this study were reviewed and approved by the Committee for the Protection of Human Subjects at the University of California, Berkeley, which determined that our research activities qualified for exempt status. Participants' provided verbal informed consent to participate and to have the research interview audiorecorded, which was documented in the written record by the interviewer. This consent process is consistent with our Institutional Review Board's requirements for research with exempt status and with our approved research protocols. At this time, interview data are not available in a public repository." ] },{ "paper_id": "cfb03431670da70ab0a1cac08df0d45d8f420ad2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1) IL-35 and autoimmune diseases.", "IL-35 mediates the inhibitory effect on T cells through the signal pathway of STAT1 and STAT4, but also lead to the pro-inflammatory effects by activating the STAT molecule of IFN-\u03b3 and IL-12, in which the key difference is that IL-35 induced STAT1-STAT4 heterodimer formation [20, 21] .", "While gp130 is fairly ubiquitously expressed, IL-12R\u03b22 is expressed mainly on the surfaces of activated T cells, natural killer cells, B cells, and dendritic cells [19] . IL-12R\u03b22 is undetectable on most resting T cells, but can be rapidly upregulated by exposure to IL-2, IFN-\u03b3, IL-12, IL-27, and TNF-\u03b1. Indeed, IL-2 or IL-27 pretreatment increases T cell sensitivity to IL-35 mediated suppression [9] ." ] },{ "paper_id": "cfb06153bd9db651c6c7c268aecf6e65113fe008", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA was extracted according to manufacturer's instruction with Trizol (Invitrogen). RT-PCR was performed using RT-PCR kit (Promega) according to manufacturer's manual with the following primers: mouse b-actin forward, 59-GTCCCTCACCCTCCCAAAAG-39; mouse b-actin reverse, 59-GCTGCCTCAACACCTCAACCC-39; SeV N gene forward, 59-GATCGTTGGGAACTACATCCGAG-39; SeV N gene reverse, 59-GACAGGTAGGTGTCTATGAGGC-39; MHV SM gene forward (CK4), 59-TCGAGAAGTTAAATGTTA-39; MHV SM gene reverse (PM147), 59-AGAAAATCCAAGATACAC-39 [47] ." ] },{ "paper_id": "cfd0dbf05b77b0d303aaa222ae0f4e8d77d6f61b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The articles in this special issue of Viruses were written by researchers working in the MERS-CoV field. The main aims of this issue are to (i) better understand MERS-CoV transmission, epidemiology, and pathogenesis; (ii) summarize current progress on MERS-CoV animal models, vaccines, and therapeutics; and (iii) discuss future prospects for MERS-CoV research. This issue includes seven review articles and nine original research papers, each providing detailed updates on current MERS-CoV studies.", "Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus that was first reported in humans in June 2012 [1] . To date, MERS-CoV continues to infect humans with a fatality rate of~35%. At least 27 countries have reported human infections with MERS-CoV (https://www.who.int/emergencies/mers-cov/en/). MERS-CoV is a zoonotic virus. Like severe acute respiratory syndrome coronavirus (SARS-CoV), MERS-CoV is believed to have originated from bats [2, 3] . However, whereas the bat-to-human transmission of SARS-CoV was likely mediated by palm civets as intermediate hosts, humans likely acquired MERS-CoV from dromedary camels [4] [5] [6] . Human-to-human transmission of MERS-CoV does occur, but it is limited mostly to health care environments [7, 8] . Moreover, whereas SARS-CoV recognizes angiotensin-converting enzyme 2 (ACE2) as a cellular receptor [9,10], MERS-CoV uses dipeptidyl peptidase 4 (DPP4) to enter target cells [11, 12] . Currently, no vaccines or antiviral therapeutics have been approved for the prevention or treatment of MERS-CoV infection, although a number of them have been developed preclinically and/or tested clinically [13] [14] [15] [16] .", "Animal models are essential tools for the preclinical evaluation of anti-MERS-CoV countermeasures. Dromedary camels, alpacas, and non-human primates are susceptible to MERS-CoV infection [21] [22] [23] ; however, the virus does not infect small animals such as mice, hamsters, and ferrets [24] [25] [26] . Several mouse models that express human DPP4 (hDPP4) have been established for MERS-CoV infection [27] [28] [29] . In this issue, Widagdo and colleagues examine rabbits as potential hosts for MERS-CoV, showing that MERS-CoV infects rabbits without causing symptoms; they also analyze the route of MERS-CoV" ] },{ "paper_id": "cfdac27f152143ecfce91f501ea6a992be428333", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Database was established by using an electronic form on Microsoft Excel 2003 (Microsoft Corp., Redmond, WA); the data set extracted contained two quality ratings for each review, yielding a total of four ratings per review. Data analysis was performed by SPSS 13.0 (SPSS, Chicago, IL). P < 0.05 was considered significant.", "In addition, we compared the total scores obtained by applying AMSTAR on Cochrane reviews (n = 6, 8.42 \u00b1 1.02) with that of non-Cochrane reviews (n = 35, 5.66 \u00b1 1.31), and the former had higher quality score than the latter (mean difference = 2.76, P < 0.001, 95% CI: 1.62, 3.90).", "As the assessment was undertaken by two assessors, one assessor was with expertise in clinical epidemiology and clinical research methods, and the other was a novice user to these quality assessment instruments, thus it could possibly result in underestimation of the reliability of AMSTAR. Another limitation in this study is lack of backward translation for the adapted tools, the translation into Chinese may produce a different measurement instrument with different properties. The current Chinese version should be translated back into English by a third party, and the back translations would be compared with the original tools to ensure the conceptual equivalence. However, the absence of back translation may offset somewhat in present study by a check of accuracy with a previous Chinese version of two instruments tools [10] ." ] },{ "paper_id": "cfdfb727440e1010a4189d0c9bee58330c0383dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A DI RNA-free stock of the Mebus strain of BCoV (GenBank accession no. U00735) at 3610 7 PFU/ml was used as a helper virus in human rectal tumor (HRT)-18 cell line as described previously [56, 57, 58] .", "Identification of cis-acting RNA elements within the 39terminal 55 nts for (2)-and (+)-strand DI RNA synthesis", "Ten micrograms of TRIzol-extracted total cellular RNA at 48 hpi of VP1 was used for electrophoresis in a formaldehydeagarose gel. RNA was transferred from the gel to Nytran membrane by vacuum blotting, and the blots were probed with oligonucleotide TGEV 8(+) (for DI RNA), BCVN(+) (for N sgmRNA) or 18SrRNA(+) (for 18S rRNA), which was tailed with digoxigenin (DIG)-ddUTP using a DIG Oligonucleotide 39-End Labeling kit (Roche Molecular Biochemicals). The RNA detected was visualized according to the manufacturer's recommended procedure." ] },{ "paper_id": "cfeab2d69cb124669b131e9e97c35dcb29e6ab28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "cff09cd72961bfaa2c50919e65b093c20937b137", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Citation Webb SR, Smith SE, Fried MG, Dutch RE. 2018. Transmembrane domains of highly pathogenic viral fusion proteins exhibit trimeric association in vitro. mSphere 3:e00047-18.", "Supplemental material for this article may be found at https://doi.org/10.1128/ mSphere.00047-18. " ] },{ "paper_id": "cffa9b1def2d5c6d7bae6fb1ea9fa07948885c05", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV), a lineage C beta-coronavirus, was reported to cause severe respiratory tract infection [1, 2] . To date, 2266 laboratory-confirmed cases of infection with MERS-CoV, including 804 MERS-CoV associated deaths, have been reported to the World Health Organization (WHO) from 27 countries. Currently, no effective therapeutics or vaccines are available to treat or prevent MERS-CoV infection." ] },{ "paper_id": "cfffac30aa716974333312a44475097d94c8f475", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results from our quantitative analysis of the networks are available in Appendix S1.", "Research and development of software that could automate the process of creating (and easily updating) customized citation networks would be a welcome addition to the field of data visualization and any scientific realm in which comprehensive literature reviews are conducted. If it were standard practice to maintain such ''evidential trees'' for scientific and medical facts it would be easier to assess the weight which these facts should actually be given in practice and to determine when systematic reviews are necessary.", "References S1 A complete bibliography of the sources found by the literature review. (PDF)", "Social factors may influence downstream citation patterns. For example, papers written by well-known authors or in high-impact journals may have a wider and faster circulation than others. Also, the accessibility of the publication (i.e. subscription required or available for free online) may also have an impact on how widely a particular publication is read and cited. Comprehensive reviews should ensure that all sources of data are brought to light, and help provide equal footing for publications that might otherwise receive less attention." ] },{ "paper_id": "d00648209ca5de4e196a97b0655de7bd181f518e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Every year, over 150 million people worldwide experience a UTI; for 25% of women, the infection regularly returns. Antibiotics usually treat the problem but bacteria are becoming resistant to these drugs. New treatments could be designed if scientists understand what roles pili play in the infection mechanisms.", "Animals were maintained in a single room in our vivarium. Prior to and after infection all animals received PicoLab Rodent Diet 20 (Purina) ad libitum. All animals were maintained under a strict light cycle (lights on at 0600 hr, off at 1800 hr). Mice were acquired from indicated vendors and randomly placed into cages (n = 5 mice/cage) by employees of Washington University's Division of Comparative Medicine (DCM); no additional methods for randomization were used to determine how animals were allocated to experimental groups. Investigators were not blinded to group allocation during experiments.", "Exclusion criteria for mice were pre-established; (i) both introduced strains in competitive infections became undetectable during the course of a 14 day experiment, and (ii) mice died or lost >20% of their body weight. No mice in this study met these criteria. Each experiment was conducted with both technical (i.e., a single inoculum of bacteria) and biological (i.e., separate bacterial cultures of the same strain) replicates.", "To prepare the pilus extracts, bacteria of the E. coli strain BW25113 (Datsenko and Wanner, 2000) were inoculated by dense streaking on eight M9 minimal agar plates containing 0.5% glycerol (vol/ vol). After a 72 hr incubation at 30\u02daC, bacteria were harvested in 30 mL of LB medium, vortexed vigorously for 5 min and passed eight times through a 26-Gauge needle, to detach pili from the cells. Bacteria were removed at 4\u02daC by three successive 10 min centrifugation steps at 16,000 x g. To collect the pili, cleared supernatants were centrifuged for 1 hr at 100,000 g in a cold Beckman Ti60 ultracentrifuge rotor. Pellet containing the crude pilus fraction was taken up in 200 mL of 50 mM HEPES, 50 mM NaCl pH 7.4, and maintained at 4\u02daC for further analysis." ] },{ "paper_id": "d009fdd48b7a8539c810eee5b108ca0fc6c5e6a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d00f2e117b4d930186ab62bb1a94f929435f9aaf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although in different groups, the coronaviruses severe acute respiratory syndrome-coronavirus (SARS-CoV) and NL63 use the same receptor, angiotensin converting enzyme (ACE)-2, for entry into the host cell. Despite this common receptor, the consequence of entry is very different; severe respiratory distress in the case of SARS-CoV but frequently only a mild respiratory infection for NL63. Using a wholly recombinant system, we have investigated the ability of each virus receptor-binding protein, spike or S protein, to bind to ACE-2 in solution and on the cell surface. In both assays, we find that the NL63 S protein has a weaker interaction with ACE-2 than the SARS-CoV S protein, particularly in solution binding, but the residues required for contact are similar. We also confirm that the ACE-2-binding site of NL63 S lies between residues 190 and 739. A lower-affinity interaction with ACE-2 might partly explain the different pathological consequences of infection by SARS-CoV and NL63.", "To investigate CoV S protein binding to ACE-2 in a unified format, we produced soluble and cell-bound versions of the two S proteins through the use of baculovirus expression vectors designed for secretion of proteins as Fc-tagged fusion proteins (Chen et al., 2007) or, separately, displayed on the insect cell surface following tagging with the VSV G protein transmembrane (TM) domain (Chapple & Jones, 2002 ) (see Supplementary Fig. S1 , available in JGV Online). The vectors are isogenic except for the tags employed and lead to the abundant expression of the target glycoproteins in the cells and supernatant for both the SARS-CoV and NL63 S proteins and subdomains thereof (Fig. 1 ). In addition, we produced a secreted form of ACE-2 fused to green fluorescent protein (GFP) to provide a ligand with an alternate tag for the detection of ligand binding. In order to validate the interaction assays used, we produced two variants of the SARS-CoV S1 domain with alanine substitutions at arginine 426 (R426A) or asparagine 473 (N473A), known to reduce the affinity of SARS-CoV S1 interaction with ACE-2 (Chakraborti et al., 2005) . In addition, we introduced two alanine substitutions in the ACE-2 sequence at tyrosine 41 (Y41A) and lysine 353 (K353A), both of which have been mapped as important for the interaction of ACE-2 with SARS-CoV S (Li et al., 2005b) . With these differentially tagged and mutated potential ligands, we assessed the interaction of the CoV S proteins with ACE-2 by ELISA, pull-down and flow cytometry assays.", "Preliminary ELISAs capturing ACE-2-GFP to the plate, followed by incubation with the various Fc-tagged forms of S protein and detection with an anti-human Ig conjugate showed detectable interaction with SARS-CoV S and S1, but no interaction with either S1 R426A or N473A as expected (data not shown). Ligand binding was equally demonstrable in the alternate format of S capture followed by ACE-2-GFP and an anti-GFP probe. However, at equivalent concentrations of S protein, no interaction with NL63 S or any of its derivatives was detected in either assay format, suggesting an affinity of interaction for NL63 S with ACE-2 in solution that is substantially lower than that of SARS-CoV S. Supernatants containing Fc-tagged CoV S proteins were concentrated by spin dialysis, the levels of S protein present were normalized by quantitative Western blot and equivalent amounts of Fc-tagged S proteins were incubated with ACE-2-GFP in solution for 1 h at 21 u C. Following pull-down of the Fc components with protein A conjugated to Sepharose beads, the recovered contents were resolved by SDS-PAGE and the presence of CoV S proteins and GFP-tagged ACE-2 was detected by Western blot using anti-human Ig and anti-GFP antibodies, respectively. We observed that while SARS-CoV S and S1 pulled down ACE-2 effectively, NL63 S proteins pulled down between 10-and 100-fold less ACE-2 on a weightfor-weight basis (Fig. 2a) . ACE-2 interaction was apparent for NL63 S, NL63 S 15-739 and NL63 S 196-739 but not for NL63 S 15-195 (subscript numbers indicate the residues contained within each fragment) confirming that the unique 180 residue amino terminus of NL63 does not bind ACE-2 (Hofmann et al., 2006; Li et al., 2007) (Fig. 2) . Using SARS-CoV S1 and the minimum NL63 binding construct, NL63 S 196-739 , we tested the relative pull-down of ACE-2 with substitutions at residues 41 and 353. SARS-CoV S1 failed to interact significantly with ACE-2 Y41A (~2 %), it had reduced but demonstrable binding with K353A (~10 %) and did not pull down the double mutant (Fig. 2b) . NL63 S 196-739 also failed to effectively pull down ACE-2 Y41A and did not pull down either ACE-2 K353A or the double mutant (Y41A+K353A) (Fig. 2b ). Together these data show that NL63 S has a lower innate affinity for ACE-2 when compared with SARS-CoV S, and confirm the results of Li et al. (2007) which show that NL63 S and SARS-CoV S bind an overlapping ACE-2 sequence. However, this study demonstrated that the role of ACE-2 residue 353 was noticeably different. Substitution of the resident lysine for alanine reduced, but did not abolish, SARS-CoV S binding, while it effectively abolished binding by NL63 S. In addition, as the end points in our constructs differed somewhat from those published by Li et al. (2007) , our data reduced the carboxy-terminal boundary of the NL63 S RBD in an analogous Fc-fusion protein configuration from residue 749 to 739; however, this boundary is not reduced as far as residue 616 as recently described by Lin et al. (2008) . An affinity of interaction with ACE-2 by NL63 S of 10-100-fold less than that of SARS-CoV S would explain our inability to obtain a sound K d for the interaction by surface plasmon resonance. The SARS-CoV S1 affinity with ACE-2 was 8.71610 28 M ( Supplementary Fig. S2 , available in JGV Online), which is similar to published values (Li et al., 2005b) . However, the same assay format failed to record an accurate K d for the interaction of NL63 S with ACE-2." ] },{ "paper_id": "d0146d4c8a05561b617e944b7f7c523c46612dc8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Acknowledgments: This work is financially supported by National Research Foundation, South Africa and Tshwane University of Technology, South Africa.", "The authors declare no conflict of interest.", "The following abbreviations are used in this manuscript: " ] },{ "paper_id": "d014a65d8069ebac6e33bc8bc4dba674151e07d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HBECs H5N1 tyTR05, USSR huH1N1 and swine H1N1.", "H5N1tyEng91, H5N1 tyTR05 and swine H1N1.", "After 2h, cells were rinsed three times with PBS and incubated in fresh medium until harvest at 24h postinfection (PI). Virus infection of cells was confirmed by immuno-chemical staining using a murine monoclonal antibody to influenza nucleoprotein (Abcam) with a DAKO Envision system as previously described [45] (Data not shown)." ] },{ "paper_id": "d018f86bb03f5462f6201a4a2b897df8e5564ca0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the lungs, the PVR is conventionally calculated as follows:", "The studies in Table 2 have reached different conclusions about the significance of PAP and PVR and their relationship to outcome in ARDS. What might account for these differences?", "Is PVD a marker of the severity of ARDS?", "The authors declare that they have no competing interests.", "Authors' contributions DR was responsible for writing, editing and reviewing the majority of the manuscript. SF wrote and reviewed the section on high-altitude pulmonary oedema. PMcL was responsible for the concept for the review, editing and final review of the manuscript. All authors read and approved the final manuscript." ] },{ "paper_id": "d04d63e56673f57ed326ebf2314e5b8192266a79", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where", "where the terms R VH 0 and R HV 0 are defined in Eq. (6) and (7)." ] },{ "paper_id": "d04f10a35adf7daa66ebda57b141ed79abac0a2c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BALB/c female mice, 6-8 weeks old, were kept in biosafety level 2 housing and given access to standard pellet feed and water ad libitum. All experimental protocols followed the standard operating procedures of the biosafety level 2 animal facilities and were approved by the Animal Ethics Committee in the University of Hong Kong (17) .", "Statistical comparison was performed by Student's t-test using GraphPad Prism 6. Differences were considered statistically significant when P < 0.05." ] },{ "paper_id": "d05ba19fb87837ac31ae8501669bb7f74fd5739f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.", "We report here the complete genome sequences of four human coronavirus (HCoV) OC43 isolates generated using targeted viral nucleic acid capture and next-generation sequencing; the isolates were collected in New", "Accession number(s). The whole-genome sequences of the isolates have been deposited in GenBank under the accession numbers MF314143 (HCoV-OC43/USA/ ACRI_0052/2016), MF374983 (TCNP_0070), MF374984 (TCNP_00204), and MF374985 (TCNP_00212)." ] },{ "paper_id": "d05db9cdccfa196d13b8eb58b09208937911d70e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Further, protein refinement using GalaxyRefine leads to the increase in a number of residues in the favored region 24 . Initially, 87% of residues were in the Rama-favored region while after refinement the number of residues in the Rama-favored region reached to 92.4%. The refinement output was also validated by plotting Ramachandran plot and found the same that 92.4% residue in Rama-favored region, 5.4% residues in allowed region and only 2.2% residues in outlier region (Fig. 2B ).", "increase the drug efficacy and kills the remaining parasites. The most widely used combination therapies are Artemether-lumefantrine (commercial name: Coartem) and amodiaquine-artesunate (commercial name: Coarsucam) 10 . While the recently approved combination therapies are artesunate-pyronaridine (commercial name: Pyramax) and dihydroartemisinin-piperaquine (Euartesim) 10 . The recent emerging resistance against artemisinin urges to develop some new strategy to prevent the malaria diseases condition 11 . Therefore, in this study, we applied a novel immunoinformatics approach to design multi-epitope based subunit vaccine that may prevent the disease by maintaining the host hemostasis by the inhibition of anticoagulant and anti-inflammatory proteins present in mosquito saliva. It will also inhibit the entry of parasite within the host body by a similar mechanism. Apart from this, if any way parasite enters into the host body, vaccine candidate will stop the salivary protein-mediated induction of parasitic growth.", "Tertiary structure prediction, refinement, and validation. The tertiary structure was predicted by using the RaptorX server and 3D model was obtained as described elsewhere 24 (Fig. 2A) . The best template used for the homology modeling was crystal structure of a Legionella phosphoinositide phosphatase (PDB ID: 4FYE). Total 541 amino acid residues were modeled as a single domain with 1% disorder. Secondary structure information resulting in the presence of 53% helix, 4% Beta sheet, and 41% coiled structure. P-value is a parameter of homology modeling where low P-value defines the good quality of modeled structure 23 . The P-value obtained for the modeled structure was 6.14e-04 which is low and significant." ] },{ "paper_id": "d0620683a194e739baca5c13917899ad7e5b2337", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A key feature of latest NGS platforms is their speed. It takes minimum turnaround times about 8 hours for sequencing 13 . Thus, it is critical that subsequent computational handling of the large amount of sequence", "Taken together, our results demonstrate that the proposed VIP combined with NGS has the advantages of simplicity, rapidity, universality and feasibility in the applications of virus detection and discovery. In addition to maintaining the software, we are currently upgrading VIP including development of a user-friendly graphical interface (GUI) based on stand-alone web interface. Therefore, VIP shows the great potential to be standardized and readily and freely accessible to a wider audience of scientists in routine laboratories. Bioinformatics analysis is no longer the weak link when applying NGS as a diagnostic tool for infectious diseases.", "The world contains a high diversity of human viral pathogens. There are approximately 300 recognized viral pathogen species, and additional species continue to be discovered. The identification of viral pathogens has a tremendous impact on infectious diseases, virology and public health. Nearly all of the outbreaks of public health issues over the last decade have been caused by viruses, including Severe Acute Respiratory Syndrome (SARS) coronavirus 1 , 2009 pandemic influenza H1N1 2 , H7N9 avian influenza viruses 3 and the recently described Ebola virus in West Africa 4 . Traditional diagnostic methods for viruses, such as cell culture, serodiagnosis, or nucleic acid-based testing are narrow in scope and require a priori knowledge of the potential infectious agents 5,6 . Accurate diagnosis and timely treatment for the infection dramatically reduced the risk of continued transmission and mortality in hospitalized patients 7 . Wild interest in comprehensive detection of these newly emerging and re-emerging viruses from clinical samples highlight the need for rapid, broad-spectrum diagnostic assays." ] },{ "paper_id": "d0631859c5008f863d1b288755b97bb0b6dea4d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The aging of society is progressing because of benefits such as the recent developments in medical technology. As society ages, the number of people who face joint discomfort because of aging is increasing. Therefore, studies on exoskeletons have been actively carried out to overcome these problems.", "Phase difference 0.13 ms 0.07 ms 0.33 ms" ] },{ "paper_id": "d06b1f07cc3e2f1ac0dbcd16995fc351a1bafe91", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An epidemic of EVD (EBOV) has been spreading in West Africa since December 2013 in Guinea, Liberia, and Sierra Leone [8] . A total of 18,603 cases, with 6,915 deaths, have been reported to the World Health Organization as of December 17, 2014 [9] . While the causative strain associated with this epidemic is closely related to that of past outbreaks in Central Africa [10] , three key factors have contributed disproportionately to this unprecedented epidemic: (1) substantial delays in detection and implementation of control efforts in a region characterized by porous borders; (2) limited public health infrastructure including epidemiological surveillance systems and diagnostic testing [11] , which are necessary for the timely diagnosis of symptomatic individuals, effective isolation of infectious individuals, contact tracing to rapidly identify new cases, and providing supportive care to increase the chances of survival to EVD infection; and (3) cultural practices that involve touching the body of the deceased and the association of illness with witchcraft or conspiracy theories. Congo (1976 Congo ( , 1995 Congo ( , 2014 [4] [5] [6] and Uganda (2000) [7] . Case incidence was normalized by the total number of cases reported for each outbreak.", "EBOV is transmitted by direct human-to-human contact via body fluids or indirect contact with contaminated surfaces, but it is not spread through the airborne route. Individuals become symptomatic after an average incubation period of 10 days (range 2-21 days) [12] , and infectiousness is increased during the later stages of disease [13] . The characteristic symptoms of EVD are nonspecific and include sudden onset of fever, weakness, vomiting, diarrhea, headache, and a sore throat, while only a fraction of the symptomatic individuals present with hemorrhagic manifestations [14] . The case fatality risk (CFR), calculated as the proportion of deaths among the total number of EVD cases with known outcomes, has been estimated from data of the first 9 months of the epidemic in West Africa at 70.8% (95% CI 68. 6-72.8) , in broad agreement with estimates from past outbreaks [12] .", "Drake and colleagues [26] employed their calibrated model to forecast the epidemic trajectory in Liberia from 3 September to 31 December 2014 under different scenarios that account for an increasing fraction of cases seeking hospitalization and a surge in the number of beds available to isolate and treat EVD patients. Their results indicate that allocating 1,700 additional beds (100 new beds every 4 days) in new Ebola treatment centers committed by US aid reduces the mean epidemic size to~51,000 (60% reduction with respect to the baseline scenario), while epidemic control by mid-March is only plausible through a 4-fold increase in the number of beds committed by US aid and enhancing the hospitalization rate from 60% to 99% for a final epidemic size of 12,285. Moreover, an additional epidemic forecast incorporating data up to 1 December 2014 indicated that containment could be achieved between March and June 2015." ] },{ "paper_id": "d06c36f9ef81b72f1bdad04a8fd4579d0016c2e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Flow cytometric data were analyzed with FlowJo (Tree Star Inc.) and an unpaired Student's t-test was used, with a p < 0.05 being considered as significant.", "Inflammatory leukocytes infiltrating into the CNS were isolated using an established protocol (3, 4) . In short, CNS tissue was minced and leukocytes were isolated using a two-step Percoll gradient (90% and 63%). The isolated cells were collected and then washed prior to staining. Cells were incubated in an anti-CD16/32 Fc Block (BD Biosciences, San Jose, CA) at a dilution of 1:200. Cells were stained with fluorescently tagged rat anti-mouse IgG for the following cell surface antibodies, Ly6G FITC (1A8), CD11b PE ( ", "Spinal Isolated spinal cord leukocytes that were isolated using a Percoll gradient as above, were stimulated with MOG 35-55 peptide or 50 ng/mL PMA (Sigma, St. Louis, MO) with 2 ug/mL Ionomycin (Sigma, St. Louis, MO) and BD Cytofix/Cytoperm Plus Fixation/Permeabilization Kit (with BD GolgiPlug protein transport inhibitor containing brefeldin A) (BD Biosciences, San Jose, CA) and incubated at 37\u00b0C for 6 hours or 5 hours, respectively. Cells were stained the surface marker CD4 (eBiosciences, San Diego, CA) and for intracellular cytokines including Rat anti-mouse IgG, IL-17A (eBiosciences, San Diego, CA) and IFN-\u03b3 (BD Biosciences)." ] },{ "paper_id": "d077e86d41dd4161565d2edf1446d8bc4ec5ed0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(DOC) " ] },{ "paper_id": "d07d6b58460992a4530b7b24d66e8b3861036a50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Immunofluorescence images were captured with LSM Zeiss 510 microscope with the confocal laser scanning set up (objectives 60 or 1006). Per experiment, 10-15 images were captured and processed by ImageJ. For the virus particles detection Imaris software was used set up to detect particles larger than 0.5 mm and quality greater than 15.", "The inhibitors used included: PI-103 (Alexis Biochemicals), dynasore, dyngo-4a,dynol-31-2, pitstop-2 (Ascent Scientific), pirl1 (Chembridge), wiskostatin (Enzo), CAS 879127-07-8, CAS 371942-96-7, dec-RVKR-CMK, LY294002, NSC23766, staur-osporine, taxol, wortmannin, Y27632, a-PDX (Calbiochem), bafilomycin A, blebbistatin, calphostin C, chlorpromazine, cytochalasin D, EIPA, genistein, IPA-3, jasplakinolide, latrunculin A, leupeptin, ML7, monensin, NH4Cl, nocodazole, and rottlerin (Sigma).", "Antibody and fluorescent dyes that were used comprised: anti-N monoclonal MAB858-3-5 and anti-RSV goat polyclonal AB1128 (Millipore), anti-F monoclonal ab43812 (abcam), anti-P rabbit polyclonal (3-V Biosciences, Menlo Park, USA), anti-ZO-1, goat anti-mouse, goat anti-rabbit, donkey anti-goat AF-conjugated, 10 kDa dextran-AF488, phalloidin AF-conjugated, R18, DiOC, and transferrin-AF488 (Molecular Probes), goat anti-mouse, goat anti-rabbit HRP-conjugated (Bio-Rad).", "Expression plasmids encoding GFP-tagged Rab5, Rab7 and its mutants were kindly provided by Dr. M. Zerial (Max Planck Institute, Dresden, Germany).", "Paramyxoviruses are generally thought to infect cells by fusing directly with the PM [32, 33] . That paramyxovirus particles can also be endocytosed is, however, also clear. This has most recently been documented for Sendai, Nipah, RSV, Newcastle Disease viruses and for a lentivirus vector pseudotyped with measles virus glycoproteins [9, 34, 35, 36, 37, 38] . Which of the two pathways -fusion at PM or fusion after endocytosis -leads to infection is not clear.", "While macropinosomes are still poorly characterized, there is evidence that they undergo a maturation process similar to that of endosomes involving acidification, association with Rab5 and Rab7, and fusion with late endosomes or endolysosomes [42] . We noted that some of the vacuoles containing RSV were in fact Rab5-and later Rab7-positive. Over-expression of a D/N Rab5 mutant inhibited infection suggesting that RSV penetration required passage through 'early' macropinosomes that contained Rab5. The lack of inhibition by Rab7 mutants, a PIKfyve inhibitor, and nocodazole, all known to inhibit vacuolar maturation, implied that macropinosome maturation beyond the Rab5 positive stages was not necessary.", "For RSV, it will now be important to analyze the molecular features of the entry process in more detail, to identify the protease(s), and to determine whether the intracellular route is relevant also in vivo. Being inducible and highly regulated, the macropinocytic process may prove more amenable to inhibition than other endocytic mechanisms, and therefore more easily targeted by therapeutics.", "To confirm the presence of the p27 peptide in the purified virus, we used a targeted mass spectrometry approach based on selected reaction monitoring (SRM) (Fig. 9E) . As a negative control, we analyzed HEp-2 cells extracts used to produce the virus. In trypsin digested virus preparations, we detected 2 peptides corresponding aa 113-131 and 109-123 of F protein both spanning p27 peptide (Fig. 9D) . Neither peptide was present in HEp-2 control samples. SRM transitions of the targeted peptides are included as supporting information in Table S1 ." ] },{ "paper_id": "d0812df257e4fb4f247f98f53298adea60585674", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1. The original online questionnaire in German, distributed to the farmers.", "Data were statistically analysed using PASW, version 20.0 (IBM Cooperation, New York, USA). Descriptive statistics were calculated for farm characteristics and management practices.", "Abbreviations OR: odds ratio; 95 % CI: 95 % confidence interval; p.n.: post natum." ] },{ "paper_id": "d088899449bf633659a0c6018571d0f6f7d58ec0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments performed at the Jilin University were reviewed and approved by the Jilin University Experimental Animal Care and Use Committee.", "One thousand nanograms of total RNA was reverse transcribed using Moloney murine leukemia virus reverse transcriptase (Promega, Fitchburg, MA, USA) for first strand cDNA synthesis with 5 \u00b5M random hexamer primer and 5 \u00b5g oligo-dT according to the manufacturer's instructions. Briefly, primer and RNA were mixed and incubated at 70\u00b0C for 5 min and then cooled on ice for 5 min and followed by room temperature for 5-10 min. Then cDNA synthesis was started after adding tran-scription mixture prepared previously at 42\u00b0C lasting 1 h for reverse transcription. Finally, the reverse transcription was stopped at 70\u00b0C for 15 min. All cDNA samples were diluted 1:5 with DNase/RNase-free water and stored at \u221220\u00b0C for further studies.", "PCR was conducted using the ABI StepOne Real-Time PCR system (Applied Biosystems, CA, USA), based on Fast Start Universal SYBR Green Master kit (Roche, Basel, Switzerland) and TransStart Probe qPCR SuperMix (TransGen, Beijing, China). The PCR mixture contained 1 \u00b5l cDNA (10 ng), 1 \u00b5l (5 \u00b5M) of each primer, 10 \u00b5l PCR mix, and DNase/RNase-free water up to a total volume of 20 \u00b5l. First, one cycle at 50\u00b0C for 2 min and 95\u00b0C for 10 min, followed by 40 cycles at 95\u00b0C for 15 s and 60\u00b0C for 90 s. PCR were performed in 48-well optical reaction plates (Sangon, Shanghai, China). To evaluate that the used primers produced only a single PCR product, a melt curve stage was added after thermocycling from 60 to 95\u00b0C by increasing 0.5\u00b0C per cycle in the SYBR Green qPCR. The primers and probe are listed in Table 1 ." ] },{ "paper_id": "d08ac6ac9dd268022b8cbe5cba116dd2bd12f757", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antigen. CEP-MSA was prepared from commercially available mouse serum albumin (Sigma-Aldrich), which was converted to CEP-modified MSA following previously published procedures [40] .", "A further complication involves the two different forms of AMD: macrophages could have different roles in dry versus wet AMD. It is important to stress that the laser-induced CNV model is a completely different system from our CEP model of dry AMD, and findings in one model will not necessarily be directly comparable to the other.", "Mice. BALB/c wild-type mice, C57BL/6 wild-type mice, and 2 \u2212/\u2212 and B6(Cg)-\u22122 /J (B6-albino) mice were obtained from The Jackson Laboratory. All mice were housed in a room exposed to 300 lux (outside the cage) in a 12 hr dark/light cycle. Protocols for use of experimental animals in this study adhered to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research and were approved by the Institutional Animal Care and Use Committee of the University of Miami Miller School of Medicine." ] },{ "paper_id": "d096bbd29d25374aa7fea667ac750e5739370dcf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A future challenge is to find out exactly how the Influenza A virus distinguishes between different cellular mRNAs. This knowledge may help to develop new treatments for flu.", "Forward primer Reverse primer", "Probe library constructions, hybridization procedures, and imaging conditions were described previously . In short, probe libraries consisted of 48 probes of length 20 bases, were coupled to cy5 (for MYC, and KIF18A) or Alexa594 (for CDKN1B, HA and CHML). Hybridizations were performed overnight in 30\u02daC. DAPI dye for nuclear staining was added during the washes. Images were taken with a Nikon Ti-E inverted fluorescence microscope equipped with a \u00c2100 oilimmersion objective and a Photometrics Pixis 1024 CCD camera using MetaMorph software (Molecular Devices, Downington, PA). Quantification was done on stacks of 10-15 optical sections, with Z spacing of 0.2 mm." ] },{ "paper_id": "d09827278115fad7feb41c47b6da245f54ba1453", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Such coronavirus interspecies jumps, from animal hosts to humans, are likely to reoccur in the future.", "Orientation of ETM determined using paramagnetic probes and residual dipolar couplings (RDCs)", "A36-R38 when 1.5 mM of the water soluble paramagnetic probe gadodiamide was added to a fresh sample (not shown)." ] },{ "paper_id": "d09b4a75ec07b2369281492d99c716bc3e0eba5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d0a5f35e229929f76c9c7fb1dcac16d5324c12e8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d0a6596fcbf8b76491fd4f2c4da8d9037170caf8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d0a7af58aa5e272f1c7aef4e6908dd3059d9173e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In vivo bioluminescence imaging", "Statistical analyses were performed by using GraphPad Prism software (version 5.0). Error bars represent standard error of the mean (s.e.m). P values were generated by ANOVA and denoted as follows: *p < 0.05, **p < 0.01 and ***p < 0.001.", "Material and methods" ] },{ "paper_id": "d0a8b7f4cb8c1c634db8716057ae04282f65687f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protocol S1", "HeLa cells were grown on a cover slip until ,50% confluence, and subsequently transfected with 1 mg of DNA for each of the fluorescent vectors analyzed, either alone or in combinations, by means of Effectene (Qiagen). Cells were incubated for 24 h, and fixed by incubating with 4% paraformaldehyde for 30 min at RT. Coverslips with fixed cells were mounted in Vectashield Mounting Medium (Vector Labs), and imaged on an OLYMPUS BX61 microscope.", "The distance metric used to construct the phylogenetic tree ( Figure 3E ) for the complete and core network, respectively was based on the relative interaction overlaps. Accordingly," ] },{ "paper_id": "d0acac75cb3d2c19abfe061a5b1530b1dbbc6922", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The drug target data was downloaded from DrugBank [70] .", "Results and Discussion" ] },{ "paper_id": "d0ad5a9116068caa5f78a95f8141a2a811662793", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To our knowledge this is the first modular VLP purification approach which provides virologists the information to adapt their procedures according to their particular needs. For virome studies in faecal samples we provide an overview and detailed explanation of NetoVIR ( Fig. 1 and Protocol S1), which is suitable for large-scale studies and provided the best obtainable viral/bacterial ratio.", "Although our optimisation was performed with mock communities containing high concentrations of viruses, NetoVIR has been successfully applied on a number of biological samples such as faeces (both of human and animal origin), clinical respiratory samples, serum samples and even homogenised insects. For all these samples a variety of known and unknown viruses could be identified.", "In our method, only a single nucleic acids extraction method was tested. The QIAamp Viral RNA mini kit is a rapid method to extract viral nucleic acids, and has shown consistently good performance in previous virome studies 19, 20 . Nevertheless, non-column based extraction methods might be considered to avoid silica contaminants 39 , but can be too time-consuming for large scale studies.", "Next generation sequencing (NGS) has revolutionised the discovery of novel viruses in humans and animals in various ecosystems [9] [10] [11] . In contrast, the role of the virome in complex human disease has been less well characterised, even though efforts have been made recently to study the role of viruses in Inflammatory Bowel Disease, diabetes, Acquired Immune Deficiency Syndrome and transplant patients [12] [13] [14] [15] . A major limitation in better understanding the role of the human gut virome in health and disease is the lack of validated methods allowing for high throughput and reproducible virome analyses." ] },{ "paper_id": "d0bace106b5562f5e1cf5b124331f9c526d46d21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Post-translational modifications (PTMs) of proteins regulate a wide variety of cellular processes, including several aspects of innate immunity against pathogens. As a result, pathogens have evolved mechanisms to block, reverse or usurp this machinery in order to successfully replicate within their hosts [1] . For example, numerous viruses subvert the dynamics of phosphorylation, employing kinases, substrate mimics and phosphatases to disrupt host signaling [1] . Likewise, addition and removal of acetyl groups by histone acetyltransferases (HATs) and deacetylases (HDACs) can have a dramatic effect on viruses such as HIV, herpesviruses, polyomaviruses and papillomaviruses. In response, several viral classes encode proteins to specifically disrupt host phosphorylation and acetylation [2] . Beyond small-molecule PTMs, conjugation and cleavage of ubiquitin and ubiquitin-like molecules has emerged as an important point of cellular regulation that several viruses target or subvert in order to replicate [3] .", "Frequent gene turnover of macro-PARP genes PARP14 and PARP15", "Macrodomains from PARP9 and 14 were aligned and mapped to the known structure of the first macrodomain of PARP14 complexed with ADP-ribose (PDB code 3Q6Z) [48] . Figures were generated using PyMol [72] ." ] },{ "paper_id": "d0c6b0c2d387baae89eb2898969913218b3bedff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses are subdivided into three groups based on genetic and serological markers [22] . Groups I, and II infect mammals while group III is specific for avian species. Group I members are the porcine transmissible gastroenteritis virus (TGEV) and epidemic diarrhea virus (PEDV), feline and canine coronavirus (FCoV and CCoV), and human coronavirus 229E (HCoV-229E). Group II includes porcine hemagglutinating encephalomyelitis virus (HEV), murine hepatitis virus (MHV), bovine, equine, and rat coronavirus (BCoV, ECoV, and RtCoV), and human coronavirus OC43 (HCoV-OC43). Group III includes the turkey coronavirus (TCoV), pheasant coronavirus and avian infectious bronchitis virus (IBV). Although most closely related to Group II coronaviruses, SARS-CoV, with some of its unique genetic features, represents a distinct phylogenetic group [22] [23] [24] .", "ral drugs [55] . Finally, since the functional details of most coronavirus replicase gene products are not known, random screening of potential antiviral compound libraries will be a key area of drug discovery for SARS virus in the near future [47] .", "The third possibility is a genetically engineered version of live SARS-CoV for traits such as attenuated phenotype, increased immunogenicity, and safe handling (out of BL3+ facility). A full-length SARS-CoV cDNA-containing plasmid has been developed from which synthetic infectious viral RNA can be produced [28] . This system allows for the functional analysis of each gene in the context of infection and can be used for making attenuated strains for vaccine development." ] },{ "paper_id": "d0cb4b695a1cddbc249dcc8cb517441dea0157d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a) to provide access to:", "\u2022 disinsect \u2022 derat \u2022 disinfect \u2022 decontaminate, or \u2022 otherwise treat baggage, cargo, containers, conveyances, goods or postal parcels including, when appropriate, at locations specially designated and equipped for this purpose; f ) to apply entry or exit controls for arriving and departing travellers; and g) to provide access to:", "\u2022 specially designated equipment, and \u2022 to trained personnel with appropriate personnel protection for the transfer of travellers who may carry infection or contamination.", "crown dependencies required further assessment. An extension of the deadline for IHR compliance to June 2014 was therefore obtained." ] },{ "paper_id": "d0cd9dce26de5d011fa364f5131d8e40630ead35", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The questionnaire was administered in Chinese and was translated into English for dataset building and data analysis purposes (see Additional file 1 for more information). Survey data were collected between Nov 27 and Nov 30, 2015, and a total of 407 respondents participated in the study. Of these, 386 completed the questionnaire, thus leading to a completion rate of 95%. During the days of data collection, the average AQI was 121.5 (respectively 85, 112, 110 and 179). For this average AQI level government indicates that slight irritations may occur; individuals with breathing or heart problems should reduce outdoor activities.", "This validates the analytical gains of putting behavioural change into a broader and more realistic context than merely knowledge exposure. It also signals the potential advantages of identifying a more effective mobilizational language to encourage a wider embracement of the proposed action. In the health promotion literature, there are several examples on how by slightly changing behavioural triggers, or by adding almost-invisible nudges, individuals are more likely going to adopt healthier behaviours [38] ." ] },{ "paper_id": "d0ce640c27c2c8ef5f83e71bec07d829327d69d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "mRNA Levels RNA was extracted with Trizol, precipitated, and dissolved in water. cDNA was produced from 3 \u03bcg of RNA. cDNA was amplified by polymerase chain reaction for \u03b2-actin as described previously [25] , and for COX-2. COX-2 primers were sense, 5'-CCG GAC TGG ATT CTA TGG TG, and antisense, 5'-AGG AGA GGT TGG AGA AGG CT from Genbank accession BC052900, producing a 263 base pair product. Half of each reaction was electrophoresed in 1% agarose. Gels were imaged and analyzed after ethidium bromide staining [25] ." ] },{ "paper_id": "d0d330fbfb644da246909905d6537021f7393661", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: P.Z. and Z.-L.S. designed the study. Y.F. and K.Z. analyzed the data. P.Z. and Y.F. prepared the manuscript. ", "It is generally believed that bat-borne CoVs will re-emerge to cause the next disease outbreak. In this regard, China is a likely hotspot. The challenge is to predict when and where, so that we can try our best to prevent such outbreaks. ", "In this review, we collected information from past epidemiology studies on bat coronaviruses in China, including the virus species identified, their host species, and their geographical distributions. We also discuss the future prospects of bat coronaviruses cross-species transmission and spread in China.", "Coronaviruses (CoVs) belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. CoVs have an enveloped, crown-like viral particle from which they were named after. The CoV genome is a positive-sense, single-strand RNA (+ssRNA), 27-32 kb in size, which is the second largest of all RNA virus genomes. Typically, two thirds of the genomic RNA encodes for two large overlapping polyproteins, ORF1a and ORF1b, that are processed into the viral Bat are the only mammals with the capability of powered flight, which enables them to have a longer range of migration compared to land mammals. Bats are also the second largest order of mammals, accounting for about a fifth of all mammalian species, and are distributed worldwide. Phylogenetic analysis classified bats into two large suborders-the Yinpterochiroptera, consisting of one Pteropodidae (megabat) and five Rhinolophoidea (microbat) families, and the Yangochiroptera comprising a total of thirteen microbat families [15] ." ] },{ "paper_id": "d0d47cee33a4e690e05f6277dd513682b7d35bdb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analysis. qPCR, ELISA, and virus neutralization assay data are presented as means and standard deviations; statistical analysis of the data was performed using Sigma plot version 11.0 (Systat Software, Inc., Germany). Differences between the means of the four experimental groups were determined using one-way analysis of variance (ANOVA) Tukey's test with the significance level of 1%.", "Restriction enzymes (RE) NotI and BamHI, T4 DNA ligase, Eagle's minimal essential medium (MEM), Hank's balanced salt solution (HBSS), fetal bovine serum (FBS), L-glutamine (100 mM), antibiotics, TrypLE6, 7aminoactinomycin D (7-AAD), Nucleofector6 electroporation kit for Cos-7 cells, TaqMan master mix 2x, real time probe, primers, superscript II reverse transcriptase, and RNase later solution were all obtained from Life Tech-nologies6 (Carlsbad, CA, USA). All DNA and RNA isolation kits were purchased from QIAGEN6 (Valencia, CA, USA). MEM was supplemented with 10% FBS (MEM-10), penicillin (45 g/mL), streptomycin (100 g/mL), kanamycin (75 g/mL), and L-glutamine (1 mM). Human epithelial type 2 (HEp-2) and monkey kidney (Vero and Cos-7) cells were obtained from American Type Culture Collection (ATC-CTM, Manassas, VA, USA).", "In addition to immunofluorescence and flow cytometry analyses, the transcription efficiencies of the PF and PFG clones were quantified by qPCR analysis in Cos-7 cells using RSV F specific primers (Figure 3 ). The RSV F mRNA copy numbers for both clones (PF and PFG) were significantly higher (4 \u00d7 10 7 ) compared to the RSV F mRNA copy number for the negative control (mock transfected cells, <10 1 ). Thus, we confirmed, using three different methods, that PF clones were expressing RSV F protein in vitro.", "Based on previous studies, distinct administration routes of the DNA vaccine evoke different types of immune responses. Our study was designed based on the previous DNA vaccine study where intramuscular injection of a DNA vaccine stimulated a moderate T cell response and antibody production compared to the oral administration, which induced a strong T cell response and weak antibody response [35] ." ] },{ "paper_id": "d0f140c55a5096788d681aa9ab115fba68e0e059", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d0f3b9b638c07e1becd5d360d890349f4ff6a8ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analysis. Data analysis was performed by using SPSS (version 22.0; IBM). Differences in the distribution of categorical variables were compared using chi-square or Fisher's exact tests. A P value of \u22640.05 was considered significant.", "This study aimed to determine the distribution of 16 different viruses causing respiratory infections in children, by using RV16, and to compare data on demographic characteristics, symptoms, and single infections or coinfections.", "The authors declare that there are no conflicts of interest regarding the publication of this paper. ", "Respiratory virus samples were collected from patients presenting to hospital for the first time with symptoms of respiratory infection or within 7 days of admission. The time frame included for the sampling criteria was based on the incubation periods of these viruses [26, 27] ." ] },{ "paper_id": "d0fd34148f90e726e4ae52896f0c37146a57cbfc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Findings from this study will provide a holistic picture on WNV-related research which serves as a useful reference for future studies. Furthermore, it gives a picture for authors and editorial journals about future research direction.", "This study sheds light on how the status of research regarding WNV has developed during the past 73 years.", "To the best of knowledge, this study is the first of its kind that assessed research productivity in the field of WNV during the period between 1943 and 2016 at global level. However, there were some limitations for this study and most of them were similar to previous bibliometric studies [17, 31, 33-35, 68, 69] . This study was limited because only publications that were contained and ranked within Scopus were analyzed. Furthermore, data in 2016 may be incomplete, because some of the latest data from 2016 may not have been uploaded to the database at the day of data extraction." ] },{ "paper_id": "d100ca657bd37c9878a08f7fcc3a9b8ad2d1830f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To the editor::", "Please cite this paper as: Chiu et al. (2014) Population-based hospitalization incidence of respiratory viruses in community-acquired pneumonia in children younger than 5 years of age. Influenza and Other Respiratory Viruses 8(6), 626-627.", "We delineate that the incidence of hospitalization for bacterial pneumonia with at least one virus identified to be 232\u00c17 (95% CI: 94\u00c11, 479\u00c16) and 528\u00c19 (95% CI: 342\u00c15, 780\u00c15) per 100 000 children <2 years and 2-<5 years, respectively. (Table 1) The rates were highest in association with RV and RSV with the population-based hospitalization incidence higher in the older children when compared to children <2 years of age." ] },{ "paper_id": "d107ccddb5e20fc5a311869da6760711f2f1f8e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Compounds 16a-k and 17a-k", "IR spectral data were measured on an Infinity MI-60 FT-IR spectrometer (ATI Instruments North America-Mattson, Madison, WI, USA). Melting points were determined on a Boetius apparatus (VEB Kombinat NAGEMA, Dresden, DDR-Currently Germany) and are uncorrected. Elemental analyses were performed by the Microanalytical Laboratory of this faculty on a Perkin Elmer PE 2400 CHNS analyzer (Perkin-Elmer Corp., Norwalk, CT, USA).", "Microwave irradiation experiments were carried out in 50-mL glass vials in a microwave reactor Plazmatronika RM 800 (Plazmatronika, Wroc\u0142aw, Poland)." ] },{ "paper_id": "d10f84b9e2232aef0a3d90771b3f861208456d2d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ljubin-Sternak et al.", "From May 2017 to April 2019, a total of 590 patients were included from hospitals located in north-western and central part of Croatia: Clinical Hospital Zagreb and General Hospital Karlovac, respectively. Inclusion criteria were: age lower than 18 years, a clinical diagnosis of acute respiratory tract infection (ARI), and need for hospitalization [on ward (\u22651 day) or day hospital (for more than 6 but less than 24 h)]. Exclusion criteria were presumed bacterial respiratory infection -including otitis, sinusitis and bacterial pneumonia, healthcare-associated infection, and ambulatory treated patients.", "Frontiers in Microbiology | www.frontiersin.org December 2019 | Volume 10 | Article 2737" ] },{ "paper_id": "d117c8256785f2ff80a40fba878aa4f022d8310b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were from three independent experiments; error bars represent the standard error of the mean. Chi-square and Student's t-test were used to analyze all data, with statistical significance between types of cells noted at p < 0.05.", "Toll-like receptor 7 (TLR7) is one of the well-known pattern recognition receptors [1] , sensing single-stranded RNA viruses via the recognition of the viral RNA genome [2] . Binding of the ligand to the TLR extracellular domain causes the homodimerization of TLRs via further interaction of the intracellular Toll/interleukin-1 receptor (TIR) domain, then activates myeloid differentiation factor 88 (MyD88)-dependent and/or TIR domain-containing adaptor-inducing IFN-\u03b2 (TRIF)-dependent pathways [1, 3] . In the MyD88-dependent pathway, the complex of MyD88 with activated TLR dimers, except for TLR3, recruits IL-1 receptor-associated kinase (IRAK)-4, then leads IRAK4 to activate other members of the IRAK, like IRAK1 and IRAK2. The activated IRAKs directly interact with TNF", "Cis-reporter plasmids pISRE-Luc, pAP-1-Luc and pNF-\u03baB-Luc were used to examine the firefly luciferase activity driven from each cis-acting transcriptional element. SARS-CoV PLPro-expressing and vector control cells were transfected with the indicated cis-reporter plasmid, plus internal control reporter pRluc-C1 (BioSignal Packard, Montr\u00e9al, QC, Canada) using GenePorter reagent. After 4 h of incubation with or without IMQ, the activity of experimental firefly luciferase and control Renilla luciferase was measured by the dual Luciferase Reporter Assay System (Promega, Madison, WI, USA) and the Clarity\u2122 Luminescence Microplate Reader (BioTek Instruments, Bad Friedrichshall, Germany) [27] ." ] },{ "paper_id": "d11eb07952f5a0fb076a49935508707abeecf8af", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following transient transfection of HEK293 cells with FLAGtagged URAT1 constructs, we demonstrate strong plasma membrane expression in wild-type URAT1 (Figure 2A) .", "United Kingdom Patients: Adult kidney stone formers attending for lithotripsy at the Newcastle upon Tyne NHS Foundation Trust Hospital, UK were recruited (following informed consent) and screened for serum and urinary biochemical abnormalities.", "Online in silico analyses were performed when sequence variants were identified. These included SIFT (http://sift.jcvi. org/), PolyPhen (http://genetics.bwh.harvard.edu/cgi-bin/ggi/ ggi.cgi) and SNPS3D (www.snps3d.org/)." ] },{ "paper_id": "d1232afc1f36390f6834e4627d99db439020be56", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We thank all volunteers who participated in this study. We acknowledge the Biomedical Research Centre Immune Monitoring Core Facility team at Guy's and St. Thomas' NHS Foundation Trust and the Nikon Imaging Centre at Kings College London for assistance.", "Human immune cells were isolated from venous blood of healthy volunteers and patients with malignant melanoma. Specimens were collected with informed written consent in accordance with the Declaration of Helsinki. The study was conducted at King's College London, King's College London, Guy's and St Thomas' NHS Foundation Trust (08/H0804/139 approved by London Bridge NRES committee; 16/LO/0366 approved by London-Central NRES Committee). Human peripheral blood mononuclear cells (PBMC) were isolated from 40 ml blood using Ficoll \u00ae Paque Plus density centrifugation (GE Healthcare).", "influence of Microsphere Diameter and Biotin length on specific recognition of antigen-expressing B cells", "Different avidin-or streptavidin-coated fluorescent beads of different sizes were used (Table S1 in " ] },{ "paper_id": "d12f82f17862869b5118dc55c63929adc6597dd4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Immunohistochemical (IHC) analysis was performed by using indirect streptavidin-peroxidase method with specific primary antibodies against influenza A antigen (Inf A/FITC (\"Abcam\")), TNF-(\"DBS\"), and IL-6 (\"Novocastra\") and lysosomal enzymes (Cathepsin D (\"DBS\"), Myeloperoxidase (\"DBS\"), and Lysozyme (\"DBS\")). For IHC studies sections were dewaxed and rehydrated. After antigen unmasking in a microwave oven at 700 W power for 20-25 minutes and washing with distilled water, phosphate buffer, endogenous peroxidase was blocked within 5 minutes. Exposure time to the primary antibodies was 30-45 minutes at 37 \u2218 C. Sections were incubated with streptavidin-peroxidase complex, DABsubstrate and further counterstained with Mayer's hematoxylin. To visualize the antibodies \"NovoLink\" detection system (\"Novocastra\") was used.", "High hydrolytic capacity of cells, being an early nonspecific protection factor, at the same time, can be a trigger point to initiate lysis of host cells (secondary alteration) with the development of spread destructive complications in the organs in case of phagolysosome membrane labilization after absorption of viral particles.", "Samples of liver of animals infected with A/H5N1 were obtained 1, 3, 6, and 10 days after infection, 10 animals in each experimental period. Control animals were withdrawn from the experiment on the 1st and 10th day. Specimens were fixed in 10% formalin, dehydrated in alcohols of increasing concentrations, and embedded in paraffin pouring mixture \"HISTAMIX\" (\"BioVitrum, \" Russia). Sections of 3 micron thickness were prepared on a rotary microtome HM355S (\"Microm, \" Germany) and stained with hematoxylin and eosin by standard procedure and by immunohistochemical (IHC) method.", "The study has been conducted on 240 6-8-week-old outbred white male mice from the laboratory animal nursery of FBRI SRC VB Vector. Animals were housed in standard conditions with free access to food and water. Period of animal adaptation to housing conditions before the experiment was two weeks. The investigation was conducted in accordance with the Declaration of Helsinki international principles. The mice were taken out of the experiment through the dislocation of the cervical spine vertebrae under ether narcosis.", "Morphometric study of tissue structural elements was conducted using closed test system consisting of 100 points, square 3.64 \u00d7 10 5 m 2 . There were registered volume density ( V ) of destructive changes (as the sum of dystrophy and necrosis) and inflammatory infiltrates in the liver and the numerical density ( ai ) of cells expressing studied IHC markers [20] . Statistical analysis of the results was performed using the statistical analysis package Microsoft Office Excel 2007 and standard software package STATISTICA v.6. The arithmetic mean value ( ) and standard error of the mean ( ) were determined. To identify the probability of significance of differences of compared average values we used Student's -test. Differences were considered statistically significant at the 5% significance level ( < 0.05)." ] },{ "paper_id": "d130fc09f47711585fbeec45605bb516380eb5c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Physical examination revealed a blood pressure of 154/66 mmHg, heart rate of 105/minute, a temperature of 98.3\u00b0F (36.8\u00b0C), a respiratory rate of 18/min, and an oxygen saturation of 99% on room air. The oral mucous membrane was dry, and there was no scleral icterus. Lung and abdominal examination were unremarkable, and he was alert and fully oriented.", "Laboratory results upon admission to the initial hospital were notable for the following: hemoglobin (Hb) 13.6 g/dL (12.5 -16.5), white blood cell (WBC) count 2.7 x 10\u2079/L (4.5 -11.5) (differential notable for lymphocyte count 0.11 x 10\u2079/L (1. , and urine toxicology screen only positive for cannabinoids. Respiratory virus film array was negative for influenza A and B, coronavirus, adenovirus, metapneumovirus, parainfluenza virus, respiratory syncythial virus (RSV), rhinovirus, Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae. Hepatitis viruses, human immunodeficiency virus 1 and 2, and urine and blood cultures were also negative.", "G6PD is expressed in all tissues where it catalyzes the first reaction in the pentose phosphate pathway which generates reduced nicotinamide adenine dinucleotide phosphate (NADPH). NADPH, in turn, produces reduced glutathione (GSH) which protects cells against oxidative stress [1] . Erythrocytes are particularly susceptible to oxidative damage in G6PD deficient individuals because, unlike other tissues, they lack mitochondria and therefore depend solely on G6PD to generate NADPH." ] },{ "paper_id": "d1312034ff2df8c47731d9519e2a4330e5cbc535", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 3I Tool aids ED providers who play an essential role in identifying and treating this vaccine-preventable disease.", "In addition to protective measures to avert disease transmission, the most important preventative measure is", "Information current as of November 9, 2018" ] },{ "paper_id": "d135acb9011d47a0f0d9e2b6542cb86539042fdf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Movements and herd composition were investigated using summary statistics. To assess the herd structure over time, the presence or absence of bovines recorded as present at 1st January were subsequently determined on the following reference dates.", "It can nonetheless help to choose farms for surveillance with a semi-quantitative framework using the available information and including experiences from other countries.", "Animal movements are an important driver for the spread of contagious diseases [1] [2] [3] [4] . Information about animal movements and the resulting contact network are therefore of great value for surveying and controlling animal diseases [5] [6] [7] .", "The shared alpine pastures constitute a risk for disease transmission because of the mixing of different herds over three to five months. The animal contacts occur at watering places or salt licks, providing a pathway for the spread of other diseases [31] .", "Data analysis was conducted using R (version 3.1.2), whilst the network analysis were performed using the R packages EpiContactTrace (version 0.8.8) [40, 41] and iGraph (version 0.7.1) [42] . To calculate the skewness of the metric distributions, the package e1701 (version 1.6-4) [43] was used.", "Additionally, all cattle farms are under surveillance for bovine viral diarrhoea (BVD) in the final stage of the national eradication programme. BVD is an important production disease in cattle, associated with fertility disorders and production loss. Bovine viral diarrhoea virus (BVDV) has a unique capacity to cause persistent infections of foetuses exposed within the first 150 days of gestation. Persistently infected (PI) calves shed large quantities of virus for life and are primarily responsible for sustaining disease transmission at the population level [24, 25] ." ] },{ "paper_id": "d13f5a5fa79315e120154fcac023f97ccfe8ad6f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, soluble sensors in the cytoplasm detect dsDNA in a sequence-independent manner, exhibit a broad expression spectrum including pDCs, cDCs, macrophages, and mouse embryonic fibroblasts (MEFs), and activate signaling pathways leading to type I IFN expression (47, 51) . These sensors include the cyclic GMP-AMP synthase (cGAS)/STING pathway, the RNA polymerase III/RIG-I/MAVS pathway, DNA-dependent activator of IRFs (DAI), IFN\u03b3-inducible protein 16 (IFI16), and the DDX family (47, (51) (52) (53) (54) (55) (56) (57) (58) .", "The cytokine family of type I IFNs fulfills key functions in anti-viral immunity but is also produced in the immune responses to other classes of pathogens covering viruses, bacteria, parasites, and fungi (1) . Additionally, these cytokines are functionally involved in the pathogenesis of inflammatory autoimmune diseases (2) .", "In an alternative reporter mouse system, a firefly luciferase reporter gene has been placed under the control of the Ifnb promoter (IFN-\u03b2 +/ \u03b2\u2212luc ). Rather than IFN\u03b2 expression on a single cell level, this model detects in vivo kinetics of IFN\u03b2 expression in the mouse paralleling the spread of pathogens through the organism under infectious conditions (60) . Additionally, in this mouse line the IFN\u03b2 coding sequence is flanked by loxP sites (IFN-\u03b2 flox\u03b2\u2212luc/flox\u03b2\u2212luc ) providing the possibility to characterize the impact of IFN\u03b2 production by a given cell type on the pathophysiology of various infections via tissue-or cell-specific Cre-mediated deletion of IFN\u03b2 (60).", "With the aim to specifically express the Cre recombinase in pDCs a BAC-tg \"pDCre\" mouse line was generated which expresses Cre under the control of the Siglech promoter (68). By crossing these mice with a reporter mouse line that indicates Cre activity via red fluorescent protein (RFP) expression the authors found \u223c30% of SiglecH + pDCs terminally labeled with RFP. Additionally, RFP expression was observed in a minor fraction of SiglecH \u2212 B-, T-, NK-, and NK-T cells and splenic cDCs and CD11c int BM cells suggesting that a small fraction of early lymphoid progenitors actively transcribes the SiglecH locus. Thus, the broader expression pattern of SiglecH should be considered when using SiglecH-DTR-tg mice to evaluate pDC functions in vivo." ] },{ "paper_id": "d140ef602b48eb4187ce679fc47ec4a2d8ca248d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses within the family Caliciviridae are small, nonenveloped, icosahedral viruses that possess single-stranded, positive-sense genomic RNA of 7 to 8 kb in size (10) . This family contains five established genera, Lagovirus, Nebovirus, Norovirus, Sapovirus, and Vesivirus (11) . Recently, six additional unclassified caliciviruses may represent new genera, tentatively named Bavovirus (12, 13) , Nacovirus (13) (14) (15) , Recovirus (16) , Salovirus (17) , Sanovirus (18) , and Valovirus (19) . Caliciviruses are important etiologic agents in humans and animals, causing a variety of diseases in their respective hosts, such as respiratory disease (feline calicivirus [FCV] ), hemorrhagic disease (rabbit hemorrhagic disease virus [RHDV]), and gastroenteritis (norovirus [NoV] , sapovirus [SaV] , and nebovirus [NeV] ).", "Coomassie blue staining and Western blot analysis.", "Statistical analyses and software. Statistical analyses were performed on triplicate experiments using GraphPad Prism software, version 5.03 (GraphPad Software Inc., La Jolla, CA, USA), and a one-way analysis of variance test. P values of less than 0.05 were considered statistically significant. Figures were generated using Adobe Photoshop CS3 and Prism 5, version 5.03." ] },{ "paper_id": "d1465b112750748b01edc7837f005803a6e87658", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The \u03b2-galactosidase activity from whole cells of KSK003 (\u03bbrpoS'-'lacZ), KSK004 [SG30013 (\u03bbRpoS750:: LacZ)] [31] , RS8872 (\u03bbpnp'-'lacZ in rnc+) [32] , or RS8942 (\u03bbpnp'-'lacZ in rnc14) [32] overexpressing YmdB from ASKA-ymdB (\u2212) was determined as described by Miller [33] . The results are expressed as the means of three independent experiments.", "The assay was adapted from Nakao et al. [30] with the following modifications: E. coli were grown in LB broth for 16 h at 37\u00b0C and diluted to 5 \u00d7 10 6 CFU/mL in fresh LB broth with or without IPTG. Aliquots (800 \u03bcL) dispensed into polystyrene tubes (Falcon 352058, BD Biosciences) and incubated for 24 h at 37\u00b0C without shaking. Each data point represents the mean \u00b1 standard deviation of ten independent cultures." ] },{ "paper_id": "d148bed5cf622c1a263907a3cbf8c6d533edded8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza A viruses are highly infectious pathogens responsible for seasonal epidemics and for pandemics. Worldwide, seasonal epidemics result in 3-5 million cases of severe illness, and 250,000-500,000 deaths yearly [1] , while pandemics such as the 1918 Spanish Flu, 1957 Asian Flu, 1968 Hong Kong Flu, and 2009 Swine Flu have resulted in millions of deaths [2, 3, 4] .", "Chemicals showing growth restoration were retested in triplicate at different concentrations against WT M2 and empty plasmid strains to confirm activity and determine EC 50 .", "Author Contributions" ] },{ "paper_id": "d14958c8c606c6abc9d79a20721582b07f1fd704", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Escherichia coli is gram-negative facultative bacteria that belongs to the family Enterobacteriaceae.", "Although it is normally commensal in nature and animals, many strains are food-and waterborne zoonotic pathogens. Some strains like O157 and other enterohemorrhagic E. coli (EHEC) cause no discernible disease in their animal reservoirs; however, diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome are not uncommon in humans [59] .", "Q fever is a zoonotic bacterial disease with public health implications. The disease is caused by Coxiella burnetii, a gram-negative bacteriumthat mostly affect ruminants. The bacterium causes abortion in sheep, goat and cattle and is excreted in infected animal feces, urine, milk, and birth products. People can get infected by inhalation of contaminated materials. C. burnetii causes febrile flu-like illness and pneumonia in poor hygiene settings. The epidemiology of Q fever in Africa is poorly understood [80, 81] ." ] },{ "paper_id": "d150551dd14158a4aee11fb6c2913a0d58c91163", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "KK concept, design, and major contribution to writing the manuscript. EK made figures and discussion. DK intellectual input in the projects.", "This study was essentially supported by a grant from the Japan Diabetes Foundation (2016). This work was partially supported by grants from the Japan Society for the Promotion of Science for KK (23790381 and 23790381) and DK (25282028 and 25670414). This work was partially supported by a Grant for Promoted Research awarded to KK (S2017-1) from Kanazawa Medical University. Boehringer Ingelheim, Mitsubishi Tanabe Pharma, and Ono Pharmaceutical contributed to establishing the Division of Anticipatory Molecular Food Science and Technology.", "The association between autophagy and glucagon was reported approximately 50 years ago. In 1955, Christian de Duve reported on acid phosphatase-positive sac-like particles in rat liver cytoplasm (De Duve et al., 1955) . Electron microscopy analysis revealed that such particles are surrounded by a lipoprotein membrane (Novikoff et al., 1956) and later showed acid hydrolases in these organelles, which were subsequently named lysosomes." ] },{ "paper_id": "d15737a61bc7a5c77a10ff81579ab5ffcaab4393", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since its discovery by Fire and Mello [1] in C. elegans in 1998, which gained them the Nobel prize in 2006, and by Tuschl et al. [2] in mammalian cells in 2001, RNAi was quickly adopted by the research community as a versatile tool with a wide range of applications, from reverse genetics to high throughput screening of drug targets. The key therapeutic advantage of using RNAi lies in its ability to specifically and potently knock-down the expression of disease-causing genes of known sequence.", "Unique among the replicating viruses being developed as oncolytic agents, retroviruses, in particular MLVbased viruses, replicate without immediate lysis of host cells and can maintain viral persistence through stable integration.", "The human genome project not only unraveled the human genetic code, but spin-off technical improvements also inspired genome sequencing of a multitude of other organisms. However, since sequence data alone are not sufficient to identify gene function, gene knockout or knock-in strategies have to replenish the results in order to analyze the resulting phenotypic changes defining gene functions.", "In principal, there are many different ways to trigger RNAi. Most of the proposed clinical applications of RNAi incorporate chemically synthesized 21 nt siRNA duplexes with 2 nt 3' overhangs. This mode of administration is transient, since intracellular concentrations of the siRNAs are diluted during cell division. Furthermore, duplex siRNAs are negatively charged polymers and therefore do not easily penetrate hydrophobic cellular membranes without assisting carriers. In addition, unprotected and unmodified siRNAs are generally rapidly degraded by serum RNases.", "We constructed split viral genomes and used fluorescent proteins to visually monitor viral replication of the resulting SRRVs [71] ." ] },{ "paper_id": "d15dcc8f6d6ca39f7d43a8673ba44b0f0c53e449", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d15dfd546e238b29cacf7f28b83eb1cdb98f6ca8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "role in the infection process, while the parasite deactivates the lectin complement pathway 16 , which ultimately could favor T. cruzi cell internalization mediated by receptors for both molecules, including CR1.", "Although most individuals infected with T. cruzi remain asymptomatic all lifelong, approximately 2-5% of infected individuals progress each year to a symptomatic form of the disease, developing either chronic chagasic cardiomyopathy (CCC) or digestive megasyndromes, or both 5 . About 10% of patients develop lethal cardiomyopathy, with heart transplantation remaining the ultimate treatment available 6 . CCC is an inflammatory condition characterized by intense Th1-type immune response 7 . After initial infection, Th1 proinflammatory cytokines are produced and this production continues along chronic phase, likely due to parasite persistence among others 6 . Persistent Th1-type response can lead to cardiac commitment, starting with myocarditis and then progressing to CCC 8 ." ] },{ "paper_id": "d16e1bd4c6cae1bb55dbc695c5e2ba5105a13921", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Despite the fact that this new virus most likely jumped to humans from wild animal species, it has remarkably well adapted to the human organism as shown by its high person-to-person transmissibility.", "In conclusion, research in the area of coronavirus gene expression is important to delineate components which directly affect SARS-CoV virulence.", "Rapid progress has been made in understanding the clinical presentation of SARS in adults and children [53] [54] [55] [56] .", "The structure of the SARS viral RNA is organized in [13] [14] [15] open reading frames (ORF) and contains a total of approximately 30,000 nucleotides [6, 16, 17] ." ] },{ "paper_id": "d16f97626aabd7b5350d85d8cb07498bf2386a7e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "posterior distribution.", "Supplemental Table 3 : Outcomes and associated probabilities for model outcome probability", "All incubation period observations were treated as single interval-censored data, which means that intervals of possible incubation periods were observed rather than exact values (1). The data used for these analyses are publicly available at https://github.com/reichlab/activemonitr (current version of code), or at https: //doi.org/10.5281/zenodo.260135 (static release as of 26 January 2017)." ] },{ "paper_id": "d171f82b892a2afafc2bc8a5458219dc04c8fd8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SARS-CoV seemed predominantly transmitted by respiratory droplets over a relatively close distance [62] . However, direct and indirect contact with respiratory secretions, feces or animal vectors could also lead to transmission, at least under some circumstances [59, 63] .", "This potency of coronaviruses may be responsible for new disastrous outbreaks and therefore should be kept in mind.", "Furthermore, some studies reported also some heart troubles associated with HCoVs infections [29, 48] .", "Some parameters have to be checked particularly carefully to ensure the validity of the results." ] },{ "paper_id": "d1757146383c42ebfb3f6318f2fd63dc1b43f1fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CEFs were prepared from 9-11 days old specific pathogen free (SPF) chicken eggs and maintained in cell culture flasks [21] . After 24 hours, CEFs were stimulated with chIFN-\u03bb and cells were harvested after 12 hours post treatment, snap frozen, and stored at \u221280 \u2022 C for further processing. All experiments were performed in triplicate.", "Bm5 cells (Bombyx mori-derived cell line) were cultured and maintained at 27 \u2022 C with 10% fetal bovine serum (FBS, Gibco, USA) in TC100 (insect cell culture medium) (Applichem, Darmstadt, Germany) as per the published literature [18] . For co-transfection, Bm5 cells were cultured at a constant density of 1 \u00d7 10 6 cells per well in six well plates for 12 hours with TC100 media containing FBS. TC100 media without FBS was used to wash the cells twice and a mixture of transfection and co-transfection was introduced to cells. Between 4-6 h post-transfection, FBS was introduced to the cell culture media. For viral amplification and expression, cells were infected with a multiplicity of infection (MOI) of 0.1 for 1-2 h.", "The authors declare no conflict of interest." ] },{ "paper_id": "d17a476d549a21be3e70932a10c6fef328f42ba6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Construction of plasmids p3mGRFT, p4mGRFT, and p2mGRFT long Primers 5'-ggaccggtgccgtactgttcatagtagatgtccaggctatc-3' and 5'-ggggtaccggcagctcgacccatcgcaag-3' were used with p2mGRFT as the template in a standard PCR reaction.", "the MCS in p420TG to 5'-ggtacaggt-3'. The resulting vector contained a single ORF expressing two 1GS-S domains preceded by a TEV protease cleavage site and linked by a GlyThrGly linker.", "The surface glycoproteins of enveloped viruses act as anchors for docking and fusion with the target cell's membrane [1] . These glycoproteins are the most prominent features of the viral surface that can be recognized within the host cellular background and are targeted for antibody neutralization. Consequently, viruses have evolved a number of strategies for shielding the spike structures formed by their surface glycoproteins. These strategies include restriction of access to conserved structural features through conformational occlusion and oligomerization [2, 3] , sequence hyper-variability, especially within loops that mask conserved epitopes [4] , and extensive posttranslational glycosylation [5] ." ] },{ "paper_id": "d17a83f05547d542975169b6d43912eae3afd17b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antibodies preparation and labelling. Monoclonal antibodies against VP16 (LP1; Abcam (Ab110226)), gD (LP2) and VP1/2 (CB4) were described previously 14, 62, 63 . To generate HSV-1 pUL37-specific monoclonal antibodies, female BALB/c mice were infected with HSV-1 (strain 17) by ear scarification followed by an intraperitoneal boost 1 month later. Spleens were harvested 3 days later, and B-cell hybridomas were generated as previously described 64 . Hybridoma supernatants were screened for reactivity in immunofluorescence assays by using cells transfected with an HSV-1 pUL37 expression plasmid. A cloned hybridoma line secreting antibodies with a strong reactivity to HSV-1 pUL37 was selected and named CB8. Secondary AF antibodies were purchased from Molecular Probes, anti-mouse IgG1 conjugated to ATTO 532 were from Rockland antibodies and assays. AF647 succinimidyl ester was from Molecular Probes. Monoclonal antibodies were purified from hybridoma supernatants using Protein A or G sepharose 4B fast flow from Sigma. Fab fragments were prepared using Pierce Mouse IgG1 Fab and F(ab 0 ) 2 preparation kit for LP1 (IgG1) and Pierce Fab Preparation Kit for LP2 (IgG2a), CB8 (IgG2a) and CB4 (IgG2b), following the manufacturer's instructions. Primary antibodies and Fab fragments were labelled with succinimidyl ester AF probe as follows. Probe was dissolved in dissolved in dimethylformamide to concentration 1 mg ml \u00c0 1 immediately prior reaction. Molecular ratio of probe to protein was set to 2.5. One hundred micrograms of antibody/Fab was incubated with probe in 50 mM NaHCO 3 for 1 h. Labelled antibody was purified from unbound dye directly after reaction using NAP5 Sephadex G-25 column from GE Healthcare. Average degree of labelling was between 1.0 and 1.5, as determined using instructions from Molecular Probes.", "Labelling viruses. Lab-Tek II chambers were first blocked with 2 M glycine and coated with poly-L-lysine. Viruses (4 \u00c2 10 6 PFU) was bound for 1 h and then fixed with 3% EM-grade formaldehyde. Blocking and permeabilization was performed with 0.1% Triton X-100, 2% FBS in PBS and followed by antibody binding. Typically, primary antibodies were used at 100 mg ml \u00c0 1 and secondary at a dilution of 1/500. An additional post-staining fixation step using 3% EM-grad formaldehyde was included to prevent antibodies detaching from antigens.", "Infection assay. HFF cells were seeded onto Lab-Tek II dish after glycine blocking the plate. The next day, cells were infected with KOS VP26-mTQ/gM-EYFP virus at 5 PFU per cell. After 12-h infection, cells were fixed, permeabilized and labelled with antibodies as described above." ] },{ "paper_id": "d17ba127439d63e04c399c19a06fa63998d65e6d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The statistical analysis was conducted using SPSS software version 12.0 (SPSS Inc, USA). Differences between two groups or among multiple groups were analyzed by the two-tailed unpaired Student's t test and one-way ANOVA with Tukey's multiple comparison tests, respectively. A P value ,0.05 was considered statistically significant.", "Female BALB/c mice at 6-8 weeks of age were purchased from the Centers for Disease Control, Hubei, China, and were kept under specific pathogen-free conditions in the Experimental Animal Centre of Tongji Medical College, Huazhong University of Science and Technology.", "The expression levels of CD molecules and cytokines in the liver.", "This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Institutional Animal Care and Use Committee at Tongji Medical College, Huazhong University of Science and Technology (Permit Number: IACUC-2010-268). All surgeries were performed under sodium pentobarbital anesthesia, and every effort was made to minimize suffering." ] },{ "paper_id": "d17d178051c8b4585dd66e5bd7133508b3bc2402", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sequences of the Hig genes in insects were obtained from the NCBI database. The unrooted phylogenetic tree was built with the Neighbor-joining method [72] using MEGA software v. 6.06 based on the alignment of the sequences determined using CLUSTAL W [73] . The bootstrap consensus tree was inferred from 5000 replicates. The functional modules of AaHig and DmHig were predicted using the SMART (http://smart.embl-heidelberg. de ", "doi:10.1371/journal.ppat.1004848.g005" ] },{ "paper_id": "d17d9c2e082583da2dba7cfc61995f5af37e6851", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Six to eight week-old female BALB/c mice, purchased from Harlan Winkelmann (Borchen, Germany), were kept at our breeding facilities in specific-pathogen-free conditions and used in all experiments.", "Mice experiments were done according to the requirements of Justus-Liebig University Giessen Animal Ethics Committees with ethics approval number: 63/2007. Animals were sacrificed using CO2 asphyxiation and the appropriate organs aseptically harvested.", "Somatic soluble antigen was prepared by culturing Lm in tryptic soy broth for 18 h, washing it in PBS, and subsequently subjecting it to ultrasonication.1 g (wet weight) of bacterial cells were suspended in 10 ml of PBS and sonicated five times for 1 min (87.5%, output, degree 7 on a sonifier model S-125; Branson Sonic Power, USA) on ice. The sonicated suspension was centrifuged at 39 000 U for 50 min, and the supernatant was filter sterilized (pore size,0.45 mm) and stored at 220uC at a dilution of 1:100 in PBS [42] .", "Lm is a facultative intracellular microorganism and many of the bacterial determinants necessary for pathogenesis, including intracellular growth and spread of Lm, have been identified and are clustered on a 10-kb region of the chromosome termed the virulence gene cluster (vgc) which encodes the prfA, plcA, hly, mpl, actA and plcB genes organized in three transcriptional units [6] ." ] },{ "paper_id": "d1861375d64fea0dd4e02843a049792058ce6140", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d18636f47e3c7dd93da309d556ba464d964fd24f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "FIG 1 NEAT1 expression is induced by HTNV in a time-and dose-dependent manner. (A)", "Journal of Virology", "MATERIALS AND METHODS" ] },{ "paper_id": "d18a705998ad871dad46aeabeeed0a20909c10df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A follow-up questionnaire was administrated to all ILI cases approximately 60 days following the disease onset in order to identify any sequelae, hospitalizations, and disease outcome.", "Data from the questionnaire surveys and laboratory analyses were double-entered into a File-Maker Pro (v14) relational database.", "All statistical analyses were carried out using R version 3.3.2." ] },{ "paper_id": "d18e10321c54248f5fdfdac2501f5368ac8052c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pregnant and 5-week-old female ddY mice, an outbred strain, and 5-week-old female BALB/c mice, an inbread strain, were purchased from Japan SLC (Shizuoka, Japan). The ddY strain was maintained as a closed colony and shows good reproductive performance and growth [45] .", "Data are expressed as the mean and standard error of the mean. Statistical analysis was performed using Graph Pad Prism 5 software (GraphPad Software Inc., La Jolla, CA). Intergroup comparisons were performed using unpaired t-tests or one-way analysis of variance (ANOVA), followed by Tukey's post test. A P-value <0.05 was considered statistically significant." ] },{ "paper_id": "d1913c3e3106846c33b96d7276edc1d2a62b1a1e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were presented as means 6 SDs (n = 10 rabbits/group). Significance was evaluated using one-way analysis of variance (ANOVA) (SPSS 21.0; SPSS Inc., Chicago, IL, USA) followed by Turkey's test for comparisons among groups. Statistical significance was set at P,0.05. Correlations between different variables were assessed by Pearson's or Kendall's coefficient." ] },{ "paper_id": "d1963d550043eb5a1d7c49a21530848025ac4eb2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported, in part, by grant awards (to NJK) from the NIH and National MS Society.", "Potential CD8 + T-Cell: B-Cell interactions in MS/eAe?", "Another report also described mice expressing neo-self antigen in oligodendrocytes (ODCs) targeted by transgenic CD8 + T-cells (27) . In this model, ovalbumin was expressed exclusively in the cytosol of ODCs and therefore ignored by CD4 + T-cells and B-cells. Following immunization, mild EAE was observed in some ODC-OVA mice. Studies using double transgenic ODC-OVA/OT-I mice demonstrate treatment with D1 mAb (specific for H-2K b /OVA) prevented the lethal EAE normally observed in these animals (28) . Double transgenic mice were also given D1 prophylactically, which in certain instances led to spontaneous disease remission." ] },{ "paper_id": "d1a0400f1b97c8f05e14aa43796802ccec11f506", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sneezing or breathing x-y coordinate data was analysed, where the maximum distance (max-X) and 2-D area (max-A) in each frame area of the cough plume was calculated and plotted using custom-written algorithms in C++ and Matlab codes (Matlab v.6.5, MathWorks, Natick, MA http://www.mathworks.com/ products/matlab/index.html).", "Apart from their positioning in front of the mirror, no other constraint was imposed on their body posture or head position.", "Ethics statement. All experiments in this study involving human volunteers were approved by the Domain Specific Review Board of the National University Hospital/National University Health System (DSRB ref no. E/09/024), and all participating volunteers gave both their written and verbal consent." ] },{ "paper_id": "d1a76cbc915984f693d508e9024c67d001aa20d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "What clinical evidence is there on comparative mask and respirator effectiveness?", "Abbreviations HCW: Healthcare worker; HEPA: High-efficiency particulate air; PARP: Powered air purifying respirator; DM: Dust-mist; DMF: Dust-mist-fume.", "Competing interests RM receives funding from influenza vaccine manufacturers GSK and CSL Biotherapies for investigator-driven research. She has also been on advisory boards for Wyeth, GSK and Merck." ] },{ "paper_id": "d1ab379487b829f2a3d3f78f27a427f2dd87deda", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Image and statistical analyses. All data are presented as means \u03ee SD for at least three independent experiments, as indicated. All statistical analyses and calculations were conducted using two-tailed Student's t tests or one-way analysis of variance (ANOVA) in GraphPad Prism, version 5, software (GraphPad Software Inc., La Jolla, CA). A P value of \u03fd0.05 was defined as the threshold for statistical significance (single asterisks), and results were considered very significant for P values of \u03fd0.01 (double asterisks). pulldown test and prepared figures and tables. F.G. interpreted the data. Z.L. drafted the article, and F.G. and W.H. revised it critically for important intellectual content." ] },{ "paper_id": "d1c3da8411eed001028326eb33acfb6bcdac877c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses play important roles in respiratory tract infections. [1] [2] [3] [4] Recently, several novel respiratory viruses have emerged, including the 2009 pandemic influenza virus A(H1N1)pdm09, 5 the avian influenza viruses A(H7N9) and A(H5N6), [6] [7] [8] and the Middle East Respiratory Syndrome (MERS) coronavirus. 9 The novel avian influenza viruses and the MERS coronavirus are associated with high mortality rates of over 30%.", "Prompt and accurate detection of respiratory viruses is important for guiding antiviral treatment. 10 For influenza virus infection, earlier administration of neuraminidase inhibitors is associated with faster resolution of symptoms in randomized clinical trials and improved survival in retrospective studies. 11, 12 Hyperimmune intravenous immunoglobulin confers survival benefit for severe influenza only if administered within 5 days after symptom onset. 13 Antibiotic usage can be reduced if a respiratory virus is detected without evidence of bacterial infection. 14 Early detection is also important for infection control and public health measures.", "In real-life clinical practice, testing both NPA and saliva simultaneously is too costly. A more cost-effective approach is to test saliva only if the NPA result is negative. Hence, in the current study, we mimic this situation by collecting saliva only when the NPA result is available. Our previous studies on influenza viruses showed that patients usually had higher viral loads in their NPA upon hospital admission. 33, 34, 42 Therefore, saliva collected later may have a lower viral load and may result in a lower sensitivity of detection." ] },{ "paper_id": "d1c89147e1f62ad58bc92990ab797375e3aefd98", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The aim of this study was to study and compare the phenotype and functionality of T-cells in patients with acute ZIKV and Dengue viral (DENV) infections." ] },{ "paper_id": "d1d1a8d96a13afa9c54ff26241095b55c0be7ff1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following primers were used:", "Hu GAPDH_F, 5'-GAACGGGAAGCTTGTCATCA-3' (position 291-310), and Hu GAPDH_R, 5'-TGACCTT GCCCACAGCCTTG-3' (position 744 -763); sequence reference NM_002046; amplicon 473 bp.", "CHIK E1_F, 5'-AAGCTYCGCGTCCTTTACCAAG-3' (position 10387-10400), and CHIK E1_R, 5' -CCAAATT GTCCYGGTCTTCCT-3' (position 10595-10575); sequence reference EU-037962.1; amplicon 209 bp." ] },{ "paper_id": "d1d4ae8dd542e752e472532a2509525e22168568", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The spike tip glycoprotein (S1) of virus particle has direct relation to induce virus neutralizing antibody, and determines the cross-protection [10, 11] Additionally, the effectiveness of vaccination program using the common field strains practically against IB was also verified.", "Blood samples were collected on day 5, 10, 17 and 24. Serum antibody titers of 10 randomly selected chickens from each group were diluted (1: 500) and evaluated with a commercial total antibody ELISA kit (IDEXX Corporation, Westbrook, Maine, USA) as described by Liu et al [15] . Optical density (OD) of each well was read in an ELISA plate reader at 650 nm. Serum-to-positive ratios were calculated, using the formula: SP ratio = (OD sample -OD negative control)/(OD positive control -OD negative control). From these SP ratios, individual serum titres were calculated according to the manufacturer's instructions.", "After the birds were vaccinated, sera were collected and identified by ELISA, the antibody titer was kept ascending slowly, on 10 days after the second immunization reached to a considerable level, even better before challenge, but none in the control group 4 (unvaccinated but challenged)." ] },{ "paper_id": "d1d7471ec350b7a5839863b90218a6c0b9596e85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 at least for subsequent pandemic waves, an appropriate vaccine may be available;", "Expanding such modelling to other parts of the health sector workforce is also desirable, along with exploring the extent that such research is generalisable to other threats (e.g., from other new emerging infectious threats, including those from bioterrorism)." ] },{ "paper_id": "d1ecd2ec6f1030c8e1ba1844e0fea59b19267a55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d1eecf25e925b3c331a75d38e687648718e2d4f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The FAST software used in our study was also limited in its ability to accommodate complex programs required for larger research studies. The numbers of branching options needed when designing a logical flow of questions are limited. This makes it difficult to display select questions for specific subpopulations. For example questions directed to women in the reproductive age group were displayed for all female patients regardless of age. This would suggest that smartphone based systems operated using FAST software may be more suitable for simple routine surveillance systems than for larger research platforms." ] },{ "paper_id": "d1f0b5426cd092d2418eebffd0f2146313ac4e11", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "with 0 \u2264 \u03b5 k,p \u2264 1 (Neumann, 1998) . Here, \u03b5 k,p = 0 describes no drug effect while \u03b5 k,p = 1 refers to the case of a 100% effective treatment-a perfect drug. Note that before treatment \u03b5 k,p = 0.", "with boundary and initial conditions I (0, t) = kVT, I (a, 0) = I 0 (a), R (0, a) = 1, and R (a, 0) = R 0 (a) .", "LK received funding from the BMBF through the ERASysAPP project SysVirDrug (031A602A)." ] },{ "paper_id": "d1f35ee252fdb019a824ad4778e8e220c27fc608", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data are presented as the mean6SD from at least three independent experiments. Statistical analyses were performed using Student's t-test. Differences with P,0.05 were considered significant.", "Severe acute respiratory syndrome (SARS) is an infectious disease that emerged in Guangdong Province, China in November 2002 [1] . This deadly disease rapidly spread to many countries around the world, with a mortality rate of approximately 10%. SARS presents as an atypical pneumonia that often leads to acute respiratory distress syndrome and respiratory failure, the main cause of death [2] . This unusual infectious disease has become a major threat to public health and social stability since its outbreak. To date, there is no effective therapeutic strategy or preventive vaccine available for the treatment of SARS.", "SARS pseudotyped viruses were produced as reported previously [22] . Briefly, HEK293T cells at 70% confluence in 10-cm dishes were co-transfected with 4 mg of pQCXIX, 2 mg of sh-2, and 4 mg of the gag/pol expression plasmid using Lipofectamine 2000 (Invitrogen). After a 48-hour transfection, viral supernatants were harvested and filtered through screens with 0.45-mm pore size. Viral particles without glycoprotein as negative control were prepared with pQCXIX and gag/pol plasmids by the same method as above. pQCXIX, gag/pol and VSV-G plasmids were used for VSV-G pseudotyped virus packaging in the same way.Viral stocks were aliquoted and frozen at 280uC for longterm storage. Short-term storage at 4uC did not dramatically affect viral titers. Viral titers were determined as previously described [24] ." ] },{ "paper_id": "d1f82bd6a621efe50dc1888f875c82c7d948a547", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nasal lavage samples of 181 illnesses from 26 infants with frequent respiratory illnesses were analyzed by Respiratory Multicode Assay [33] . HRV was detected in 108 samples (60%) ( Table 2) . Other viruses detected were enterovirus, RSV, adenovirus, coronavirus, influenza A virus, metapneumovirus and parainfluenza virus. Among the 108 HRV-positive samples, 80 had only HRV and 28 had coinfection with at least one other respiratory virus.", "This study was approved by the Human Subject Committee of the School of Medicine and Public Health, University of Wisconsin -Madison. Written informed consent was obtained from the parents.", "RMA is a new high-throughput, multiplex PCR-microsphere flow cytometry assay system for comprehensive detection of common respiratory viruses including rhinoviruses (HRV), enteroviruses, respiratory syncytial viruses (RSV), parainfluenza viruses, influenza viruses, metapneumoviruses, adenoviruses and coronaviruses. Details of the RMA assay have been previously described [33] . The output signal is expressed as MFI (median fluorescence intensity), and samples with an average signal .6 standard deviations of average negative control signals (typically 400 to 500 MFI) are regarded as positive. The RMA is capable of distinguishing closely related HRV and enteroviruses [33] ." ] },{ "paper_id": "d1fc5729ff932800c93dbe279b36ea3c53375708", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PCR detection of C. psittaci", "A case was defined as a staff member working at the NTNAMC who was hospitalized for respiratory tract infection between November 1 and November 30, 2012, and confirmed to have C. psittaci infection by polymerase chain reaction (PCR) and/or a four-fold rise in serum microimmunofluorescent antibody titer against C. psittaci (Focus Diagnostics, Cypress, California, USA).", "Open reading frames were located using the ORF Finder tool at NCBI (http://www.ncbi.nlm.nih.gov/projects/gorf/), the gene" ] },{ "paper_id": "d1fd1fafa75ee05827d3e7e916a03ddf159317ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In both studies, pigs had limited clinical signs of diarrhea. Diarrhea was mild and transient in about half of the pigs.", "In conclusion, these results indicate the indirect transmission of PEDV through contaminated personnel PPEs occurs rapidly under modeled conditions and to prevent transmission between groups of pigs, changing PPE and/ or taking a shower is recommended as an effective option to lower the risk of virus spread. ", "Forty-eight, 3-week-old crossbred pigs including both male and females were obtained from a farm with no history of PEDV infection and were housed at the St. Paul animal research isolation units at the University of Minnesota. After arrival (2 days before the start of the study), rectal swabs from all pigs were collected and tested by real-time reverse transcription polymerase chain reaction (rRT-PCR) for PEDV, transmissible gastroenteritis virus (TGEV) and porcine delta coronavirus (PDCoV) at the University of Minnesota Veterinary Diagnostic Laboratory (St. Paul, MN, USA).", "Results presented here should be considered carefully as many factors, including contact time, exposure time, viral dose, time after exposure to virus and other experimental conditions may influence the outcome of transmission studies. However, this experimental study highlights the main advantages of good biosecurity procedures in breaking the transmission cycle between rooms. The fact that PEDV transmission occurred under low biosecurity procedures indicated that the virus could spread easily through contaminated fomites worn by personnel. These results provide critical information to develop effective biosecurity procedures and will have potential applications for the development and implementation of transmission control policies in swine production systems. Our results are also relevant to design biosecurity measures to control the spread of other pathogens of similar characteristics and transmission routes than PEDV such as transmissible gastroenteritis virus and porcine deltacoronavirus." ] },{ "paper_id": "d1fd684938b2d4358d1fde27a474bf71df02287b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Categorical variables were analyzed with the Pearson chi-square test or the 2-tailed Fisher's exact test. Continuous and nearly normal distributed variables were analyzed with the Student's t-test or ANOVA-test, and non-parametric variables were compared by Mann-Whitney U tests. A two-sided P-value less than 0.05 was considered statistically significant. Normally distributed and continuous variables are presented as average\u00b1standard deviation and nonnormally distributed variables as median (range). Analyses were performed using the Statistical Package of Social Science (SPSS, version 19.0) and SigmaPlot (version 12.0).", "The negative sense single strand RNA virus human metapneumovirus (hMPV) has since its discovery in 2001 emerged as a commonly detected respiratory tract pathogen involved in The NPAs were tested using PCR for hMPV (A1, A2a/b, B1, B2), adenovirus, human bocavirus-1, coronavirus (OC43, 229E and NL63), enterovirus, influenza A and B virus, parainfluenza virus type 1-4, parechovirus, RSV, rhinovirus, Bordetella pertussis, Chlamydophila pneumoniae and Mycoplasma pneumoniae. Nucleic acid was extracted using NucliSENS easy-MAG according to the manufacturer's protocol (bioMerieux). All PCRs were in-house realtime assays based on TaqMan probes [16] . For hMPV detection, primers targeting the N-gene allowing detection of all four hMPV genotypes were used as described elsewhere [17] . Genotyping was performed by sequencing an amplified F-gene PCR product [18] using a 3130 Genetic Analyzer (Applied Biosystems) and comparing sequenced data with the nucleotide BLAST database (www.ncbi.nlm.nih.gov/BLAST/).", "Supporting Information S1 ", "The study was approved by the Regional Committee for Medical and Health Research Ethics (REK, Mid-Norway). Caregivers to all patients and controls received written information about the study. Written consent was obtained at the hospital from the caregivers of all controls and the majority of the patients included in the cohort. Due to practical challenges by enrolling patients 24 hours a day, 7 days a week, some patients were enrolled after discharge from the hospital. Their caregivers received written information after the hospital stay and children were included if the caregivers did not resist enrollment by taking contact to the hospital within 4 weeks." ] },{ "paper_id": "d2057831023248265b009ed7fb7710123c69feaa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The protein can be divided in four functional regions (Nt to Ct): 1. An extracellular unstructured short domain (residues 1-24) involved (in the case of influenza A) in the incorporation into the virion [85] . 2. A TM domain, residues 25-46. This region is responsible for both tetramerization and proton conductance [86] . 3. A cytoplasmic membrane proximal amphiphilic helix involved in budding, scission and membrane localization [84, 87] . 4. A Ct disordered tail necessary for M1-M2 interaction [88] .", "In the present review we use the two-stage model as a leading thread to analyze not only the mechanism and forces required for the membrane insertion and folding of viroporins from RNA viruses but also the cellular machinery involved in the process in vivo.", "Viroporin-induced membrane premeabilization depends on homo-oligomerization [8] . Therefore, viroporins must, first, reach and insert into the membrane and, second, interact with themselves to form higher ordered structures that will eventually be the functional units. This two-stage process resembles the original two-stage model proposed in 1990 by Engelman and Poppot for \u03b1-helical membrane protein folding [9] . In their original model the authors propose that folding of many integral \u03b1-helical membrane proteins can be envisioned in two subsequent stages. In the first stage, hydrophobic alpha-helices would be established across the lipid bilayer; and in a second stage, the already inserted helices would interact with each other to form higher order functional transmembrane (TM) structures.", "Despite all the work with the M2 viroporin there are still controversies on its tetramerization process. In a recent work, Kawano et al. [98] propose that monomeric M2 protein first dimerize through interactions between the amphipatic helix of two monomers. No implication of the TM domain is required at this point. According to the authors, once formed, the dimer is stabilized by a disulfide bond between Cys17 and Cys19. The dimer is stable at neutral pH, however at acidic pH (eg. endosome) cation-\u03c0 interactions between protonated His37 and Trp41 induce the formation of the tetramer." ] },{ "paper_id": "d211a9ffb15714958d46365027d61af18c17a269", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Swine influenza virus (SwIV) is any strain of the influenza family of viruses that is endemic in pigs, including influenza C and the subtypes of influenza A, known as H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3 [91, 92] ." ] },{ "paper_id": "d213253353b62aa454d0bb02a7651a0ef7c0d34f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "S. pneumoniae is a Gram-positive coccus that can survive under both aerobic and anaerobic conditions [59] . It causes mucosal and invasive infections in children and adults, most commonly acute otitis media (AOM), community-acquired pneumonia (CAP), and invasive pneumococcal diseases (IPD), such as bacteraemia and meningitis [60] [61] [62] [63] [64] .", "Bordetella pertussis is a Gram-negative coccobacillus that causes whooping cough and persistent cough, especially in neonates, school-aged children and adolescents [71, 72] .", "The authors declare no conflict of interest.", "Practically, for the prevention of pneumococcal infections in the paediatric population it is generally inferred that PCV10 and PCV13 are similarly effective and that only the cost of vaccine procurement can influence the choice to use one over the other [70] ." ] },{ "paper_id": "d215fd9c30298cb374b6c9cbec60269c91255fcf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A new website dedicated to this project, named Weibo-Health [25] , was created to share our updated results with public health researchers and practitioners.", "Second, content analysis of Weibo posts will enable us to analyze human attitudes or reactions toward health hazard [43] . The research can be extended to investigate anxiety or fear towards the infectious diseases themselves and towards the outbreak information transmitted via the Weibo social network. Similar research on influenza has been conducted using Twitter data [12, 14] . Data mining methods, like topic models [44] , may be attempted.", "Please see Additional file 1 for translations of the abstract into the six official working languages of the United Nations." ] },{ "paper_id": "d21eaa427bea34a60db8a4fec53ee3a5021a1eba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lung homogenates were freeze-thawed three times, centrifuged at 4000 g and supernatants titrated in doubling dilutions on Madine Darby canine kidney (MDCK) cell monolayers in flat bottomed 96 well plates. After incubation at 37\u00b0C for 3 hours, samples were over-laid with 1% methylcellulose and incubated for 72 hours at 37\u00b0C. Cell monolayers were fixed and washed, then stained with Crystal Violet solution to visualize plaques. Infectious units were then enumerated by light microscopy and total plaque forming units per lung quantified (number of plaques \u00d7 dilution factor \u00d7 total volume of lung homogenate).", "Cell culture suspensions or single cell organ homogenates were washed in RPMI/10% FBS first followed by FACS Buffer (PBS/2% FBS/0.1% sodium azide), then incubated with a titrated amount of these antibodies: CD3 FITC, CD11b AlexaFluor 700, CD11c APC, MHCII PECy5, F4/80 Pacific Blue, CD80 PerCP Cy5.5, Ly6C FITC, CD37APCCy7, CD44PerCP, TNF-\u03b1 PECy7 (BD BioSciences or eBioscience, San Diego, CA) at 4\u00b0C for an additional 30 minutes. Cells were fixed with BD Stabilizing Fixative\u2122 (BD Biosciences) for analysis. Data were collected on a BD FACSAria\u2122 equipped with Diva v7.0 and CS&T v2.0 software (BD Biosciences) and analyzed using FlowJo version 10.", "We used Graphpad Prism software to perform non-parametric statistical analysis across no more than 2 groups of interest. Significance \u00c3 was set as P<0.05" ] },{ "paper_id": "d2263b3300cd722dfbadc7c40008126d95ab4af6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A comparison of actual and expected dinucleotide frequencies of the 16 dinucleotides in coding region of PCV genomes was also undertaken using SPSS 17.0.", "Correlation analysis of PCV was used to identify the relationship between nucleotide composition and synonymous codon usage pattern [42] . All statistical processes were carried out by with statistical software SPSS17.0 for windows." ] },{ "paper_id": "d23a5e1b6a5c6036c3e45e7c6d9019a59ddfd6bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 3: Figure S2 . Same as Figure 1B except that stay-time was 1 day.", "The model results are calibrated with surveillance data for H9 subtypes in a major wLBM and nine rLBMs in Shantou, China [5] , showing that average prevalence in rLBM is roughly twice as high as prevalence in wLBM (means \u00b1 standard deviation (medians): 4.9% \u00b1 5.5% (3.3%) in rLBM versus 2.7% \u00b1 7.5% (0.5%) in wLBMs; Figure 2 ).", "A recent analysis of surveillance data from rLBMs in Shantou, China found that the prevalence of H5 and H9 in chickens could not be predicted from their corresponding prevalences in ducks and quail within those same markets [4] , suggesting that a substantial proportion of transmission may occur in contexts other than rLBMs. Also, AIVs can be isolated at high rates from other holdings that form the supply chain for rLBMs [5] ." ] },{ "paper_id": "d249845a31b0c4dac3b85502b7c8f9a3af5f0f31", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Structure visualisation and docking atomic resolution data. The 3D cryo-EM data, including docked atomic resolution structures 3CSY, 3X2D, and 2EBO were visualised with the Chimera software package 41 (Computer Graphics Laboratory, University of California, San Francisco, supported by NIH P41 RR-010810)." ] },{ "paper_id": "d24a70c5203617db24e9777727d824bcad5597c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SFK). Our results identify a new role for Csk in flavivirus replication, which further enhances our understanding of viral replication and provides a new drug target for antiviral development.", "following the manufacturer's protocol (Life Technologies). Briefly, plasmid DNA and L-2000 were mixed with optiMEM separately and incubated at room temperature for 5 min, and the two were mixed and incubated for 20 min at room temperature. This mixture of DNA and lipid was added to cells plated in antibiotic-free media. After 4 h, media was replaced with complete media. 24 h post-transfection, cells were either infected with DENV2 or further processed for immunofluorescence.", "Dengue virus (DENV) is a mosquito-borne flavivirus, which is estimated to infect 390 million people globally, with 25% of these infections exhibiting disease symptoms each year 1 . Dengue disease manifests wide spectrum of symptoms, from mild dengue fever to severe hemorrhagic form known as dengue hemorrhagic fever (DHF)/ dengue shock syndrome (DSS). In addition to antivirals targeting viral proteins directly, identifying host factors required for the virus life cycle provides additional targets for drug development and is an alternate plausible approach to counteract viral infections [2] [3] [4] . DENV is a single, positive strand, 11 kb, RNA virus, encoding a single polyprotein that undergoes cleavage by host and viral proteases to form three structural proteins-capsid (C), precursor-membrane/membrane (prM/M) and envelope (E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). The structural proteins constitute the virus particle while the NS proteins are involved in viral RNA replication, virus assembly and modulation of host cell responses 5 .", "Immunofluorescence. Cells grown on coverslips were infected with DENV-2 at 5 MOI. 24 h pi, cells were fixed in chilled methanol and processed for immunofluorescence as described previously 48 . Images were acquired using Olympus FLUOVIEW FV1000 confocal microscope with a 20 X or 100 X objective. Images were processed for background subtraction using Fluoview software and prepared for illustration using Image J software (NIH). For colocalization analysis, single slices from Z-stacks were used. A region of interest showing colocalization was marked and extracted. Pearson correlation coefficient of the extracted colocalized pixels was determined using Fluoview software (Olympus). For quantitation of transfection and infection efficiency in plasmid transfections, DENV-E positive and FLAG-positive cells in each image was manually counted in multiple images acquired from each sample." ] },{ "paper_id": "d259c80b55cb69486ef75e66d13fe60688a1e028", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HeLa-R19, Huh7 and BHK-21 cells were maintained in Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% (V/V) fetal calf serum (FCS). Vero cells (ATCC CCL-81) were grown in Eagle's minimum essential medium with 8% FCS, 100 units/ml penicillin and streptomycin, 2 mM L-glutamine and non-essential amino acids.", "RNA isolation, cDNA synthesis, and RT-qPCR were performed as described elsewhere [66, 63] . " ] },{ "paper_id": "d25e47796b1250f545c2b7e5b2dc191eaa3735f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our results proved to be reproducible, which we showed using several technical replicates.", "Positive clones were used to inoculate 5 ml of lysogeny broth containing ampicillin (LB-amp) and cultivated under shaking conditions (270 rpm) at 37\u00b0C, until an optical density of OD 600 = 0.6 was reached. The cell suspension was centrifuged (1000 g, 5 min). The supernatant was discarded and the pellet resuspended in 0.9 ml of fresh LB-amp. Subsequently 100 \u03bcl sterile DMSO (Roth) was added. Clones were stored in cryo tubes at -80\u00b0C.", "The cell lysates containing the expressed fusion proteins were spotted to HaloLink\u2122 Slides (Promega) by the QArray2 microarray spotter. For the spotting layout see Figure 5 .", "Agarose gel electrophoresis was carried out in a Per-fectBlue Gelsystem Mini (Peqlab) for 90 min at 80 V. The DNA was visualized by ethidium bromide staining and detected on a transilluminator. Hyper Ladder I (Bioline) served as a size reference.", "Furthermore we show the outstanding performance of this method by expressing and detecting several proteins from Campylobacter jejuni previously described as immunogenic. As controls of the screening process, we included proteins from Campylobacter which have not been described as immunogenic before.", "Most of the fusion proteins investigated fall into a range between 61 and 73 kDa, namely HaloTag \u00ae fused to argC (73 kDa), pyrC (72 kDa), pseB (71 kDa), gapA (70 kDa), cjaA (65 kDa), peb1 (62 kDa), hisJ (62 kDa) and flaC (61 kDa). Outside of this size range, only HaloTag \u00ae -flaA (93 kDa) and the small HaloTag \u00ae -pal (52 kDa) are found." ] },{ "paper_id": "d26fb6227fcc98e9e8f9fecbedfd47bc4c00e7ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The specific lysis was calculated as previously reported [35] :", "where Rc is the ratio of PBS control mice and Rimm is the ratio of immunized mice", "doi:10.1371/journal.pone.0161193.g003" ] },{ "paper_id": "d29ac40afbb28f3dff1d4923aae6c01299399334", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To our knowledge, the only genetic rescue of VSR-deficient viruses in RNAi-deficient mammalian host cells was achieved for NoV replication in ESCs [80] . Given that these cells lack the IFN response, this represents convincing evidence for a VSR function of the NoV B2 protein and an anti-viral role for RNAi in ESCs.", "DsRNA also plays an important role in activating anti-viral responses in vertebrates. In mammals these viral dsRNA products are recognized by several pattern recognition receptors (PRRs), such as RIG-I, MDA5, and TLR3. These receptors activate the interferon (IFN) response, which is a hallmark of vertebrates and comprises a series of cytokines that are released by the infected cell to activate antiviral responses in a paracrine manner. In vertebrates, intracellular dsRNA can also directly activate the RNA-dependent protein kinase (PKR) and 2'-5' oligoadenylate synthetase (OAS). The former phosphorylates the eukaryotic translation initiation factor 2\u03b1 (eIF2\u03b1), leading to the inhibition of translation of both viral and cellular transcripts. The latter stimulates RNA cleavage by RNase L, leading to mRNA and ribosomal RNA (rRNA) degradation [75] .", "Whether RNAi is an important anti-viral system in vertebrate somatic cells, where the interferon response predominates, is debated [76] . Mammals themselves express very few endogenously encoded siRNAs but instead express mostly microRNAs (miRNAs) (Figure 4) , since human Dicer processes pre-miRNA hairpins at a much higher rate than long dsRNA substrates [77] . SiRNAs of viral origin have been undetectable in most studies of infected mammalian somatic cells [78, 79] . However, when the picornavirus encephalomyocarditis virus (EMCV) infects embryonic stem cells (ESCs), it produces readily detectable levels of virally derived siRNAs and differentiation of the cells dramatically decreases their ability to produce virally derived siRNAs. These data suggest that there is an inherent difference in the ability of ESCs and somatic cells to produce virally derived siRNAs [80] . This is particularly interesting as the IFN response is not active in oocytes and embryonic stem cells (ES cells) [81] .", "Several aspects of host shut-off mechanisms are common among SOX, BGLF5, murine SOX (murine gamma herpesvirus 68), HSV-1 VHS, and SARS CoV NSP1. Most pathways target Pol II transcripts even if the target is not selected through the 5 1 cap or poly(A) tail [3] . VHS interacts with translation initiation factors eIF4H and eIF4A, while NSP1 interacts with the 40S ribosome. Both SOX and NSP1 stall translation after the 40S ribosome complex has bound mRNA, blocking formation of the 80S complex [33] . Table 2 summarizes several mRNA suppression strategies discussed here.", "Some other proposed VSRs in mammalian viruses are the human immunodeficiency virus type 1 (HIV-1) Tat protein [93] , Influenza virus NS1 protein, VACV E3L [94] , Ebola virus VP35 [95] , Nodamura virus B2, and primate foamy virus Tas [96] . Although, more recent studies do not find that HIV-1 Tat or influenza NS1 actually suppress RNAi [85, 97] . One of the problems with demonstrating that these proteins indeed function as VSRs, is that their VSR function has been ascribed to their dsRBDs. By binding dsRNA, they can also block the IFN response. The specificity of these proteins as VSRs is called into question, by the fact that overexpression of even a bacterial dsRBD containing protein could function as a VSR in plants [98] . Additionally, an influenza virus lacking NS1, its putative VSR, was still lethal in interferon defective mice, suggesting either that the RNAi response is not sufficient to suppress the virus or that other VSRs are yet to be found [99] ." ] },{ "paper_id": "d2ac1b9fae19dbf111222f50982b4ed38e2f8e28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. Experiments were performed independently at least three times, with different donors.", "Even though H9N2 infection is mainly confined to poultry, H9N2 viruses have been detected repeatedly in swine in China 5, 6 . Laboratory confirmed cases of H9N2 infection in humans have been reported in Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 6208 |" ] },{ "paper_id": "d2b714f43fa6302301a1aa7d282de555f71024b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Staining reagents were used as set out in Supplemental Table I . GL7 was chosen as a GC B cell marker.", "Inguinal lymph nodes were harvested, immersed in Optimum Cutting Temperature (OCT) compound (VWR Chemicals), and immediately frozen on dry ice. Thirty-five-micrometer sections were cut using a cryostat (Leica), mounted on Superfrost Ultra Plus slides (Thermo Scientific Gerhard Menzel), fixed in acetone for 10 min at 220\u02daC, air-dried for 30 min, and stored at 220\u02daC.", "Prior to staining, non-specific Ab binding was blocked using a solution of 1% v/v normal mouse serum, 2% w/v BSA (Sigma-Aldrich), and 0.3% v/v Triton X-100 (Sigma-Aldrich). Primary Abs and secondary reagent were used as detailed in Supplemental Table I . After final washing, Fluoromount G mounting medium (eBioscience) was applied, followed by a coverslip.", "Prism 5 software (GraphPad) was used for the production of figures and for statistical analyses. Statistical methods used for each analysis are set out in detail in the appropriate figure legends. All cell count and Ab titer data were log 10 transformed prior to analysis.", "Slides were visualized using a Zeiss LSM 710 confocal microscope. Images were acquired using Zen software (Zeiss). ImageJ (National Institutes of Health) was used for image processing. Images were analyzed in a manner allowing comparison of both overall GC area and proportion of the B cell area occupied by GCs: GC and B cell areas were identified using GL7 and B220 staining, respectively, manually defined, and their areas were calculated (44) ." ] },{ "paper_id": "d2c72e2daceccd9b61cb182d778661e29256527b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pfaender et al 6", "HCV is an enveloped, positive-stranded RNA virus belonging to the genus hepacivirus in the family of Flaviviridae. A second species" ] },{ "paper_id": "d2d1d6227304c56323303dc51509bf3217925dcb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The fundamental role of lipids in virus biology and infection is becoming increasingly clear. New technologies, such metabolomics, and advances in mass spectrometrybased lipidomics are allowing for systematic characterization of the alterations in host lipid metabolism, as well as cellular and viral lipid profiles induced by viral infection.", "trafficking, they also reprogram lipid synthesis, metabolism, and compartmentalization for assembly and egress. Here we review these various concepts and highlight recent progress in understanding viral interactions with host cell lipids during entry and assembly.", "Attachment to cellular receptors commonly activates signalling pathways that induce endocytosis of the virus. Regardless of the mechanism used for uptake, trafficking within the endosomal network is a highly co-ordinated process. After formation, endosomes go through maturation, a process that involves defined changes in cellular location, pH, protein and lipid composition ( Fig. 1 for details) ." ] },{ "paper_id": "d2d7428869cef29308728dd3a05f0facaf1d25da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses are enveloped viruses with 27-32 kb single-strand positive-sense RNA genomes encoding four structural proteins: nucleocapsid (N), spike (S), membrane (M) and envelope (E) [1, 2] . Translated on free polysomes, highly basic N interacts with newly synthesized viral genomic RNA to form helical nucleocapsids [3, 4] . The M, S and E viral membrane proteins are translated on membrane-bound polysomes, inserted into the endoplasmic reticulum (ER), and transported to the ER-Golgi intermediate compartment (ERGIC) , where E and M interact and trigger budding [5, 6] . N and S are incorporated into virions via interaction with M, with virions accumulating in large, smooth-walled vesicles that eventually fuse with the plasma membrane and release virions from cells [2, [7] [8] [9] [10] [11] .", "Supernatants from transfected 293 T cells were collected, filtered, and centrifuged through 2 ml 20% sucrose cushions as described above. Viral pellets were suspended in PBS buffer and laid on top of a pre-made 10-40% iodixanol (OptiPrep) gradient consisting of 1.25 ml layers of 10, 20, 30 and 40% iodixanol solution prepared according to the manufacturer's instructions (Axis-Shield, Norway). Gradients were centrifuged in a SW50.1 rotor at 40,000 rpm for 16 h at 4\u00b0C; 500 \u03bcl fractions were collected from top to bottom and densities were measured for each. Proteins in each fraction were precipitated with 10% trichloroacetic acid (TCA) and subjected to Western immunoblotting." ] },{ "paper_id": "d2d8597279c4e4503fbe1c11365fd154230add81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two hepatotropic viruses, hepatitis C virus (HCV) and hepatitis E virus (HEV) have proven difficult to propagate in vitro, and only in recent years have researchers been able to study these viruses in a conventional cell culture.", "Over 200,000 children under the age of five die every year from human norovirus (HuNoV) infections, with norovirus infection representing the second leading cause of diarrheal death in this age group [67] [68] [69] . An effective cell culture model for modeling HuNoV infections and interactions with intestinal epithelial cells has been elusive, slowing the development of urgently-needed interventions for this deadly illness [70] .", "The authors declare no conflict of interest." ] },{ "paper_id": "d2d8c1069a0dcff2c3426bd70b34dc41dc14ad55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequence reads were trimmed using Trimmomatic with a 4-bp sliding window quality score cutoff of Q30. 6 For both samples, we mapped the trimmed sequence reads against a vaccine strain HA reference ", "It is known that influenza remains under-detected by established surveillance systems, which rely on sentinel-based reporting of medically attended cases. 13 ", "The authors have no conflicts of interest to declare. ", "case reports, coinfection, H3N2 subtype, influenza, viral surveillance" ] },{ "paper_id": "d2f29c0bf8f5b9bf9d357001a62b42244698b298", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The EV71 virus (sub-genotype C4) was originated from an epidemic in Fuyang, China, 2008 (GenBank: EU812515.1) [15] . The virus was grown in Vero cells (ATCC, Manassas, VA, USA) and harvested for freezing at 220uC [3] . The Vero cells were maintained in DMEM (HyClone, Logan, UT, USA) with 10% FBS (Gibco, Grand Island, NY, USA).", "Various tissue samples from the organs were fixed in 10% formalin in PBS, dehydrated in ethanol gradients and embedded in paraffin for further H-E staining [3] . The histopathological detection was performed under a light microscope.", "Flow cytometry-based cytometric bead array analysis (CBA)", "The EV71 titer was analyzed by performing a microtitration assay using a standard protocol [24] . A mixture of diluted serum containing anti-EV71 antibodies and the virus at a titer of 500-1000 CCID 50 in 100 ml PBS was incubated at 37uC for 1 h. The cellular pathogenic effect (CPE) of the virus was examined by inoculating the mixture onto Vero cells grown in 96-well plates [25] .", "All live animals were monitored daily for clinical signs under anesthesia twice a day. Body temperature was measured by inserting a soft probe attached to an Omron electronic digital stick thermometer (MC-BOMR, Omron Co.) into the rectum 2 cm from the anal margin for one minute [18] . All clinical signs were monitored from day 2 p.i.. Venous blood of biological indicators such as blood cell count using the Veterinary Multi-species Hematology System (Hemavet 950FS, Drew Scientific Co.) and evaluation of the viral load were performed." ] },{ "paper_id": "d300bc4b7cec3731d56241c2de486cacdc23a37b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These results confirmed BTV replication in A. albopictus cells, although no CPE appeared." ] },{ "paper_id": "d30e8b7dea667b484ce677f10755c971beff8e17", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "GalT", "Statistical analyses. All data analyses were performed by SPSS 19.0 software using Student's t-test for the comparison of the differences between different groups. P-values of<0.05 were considered as statistically different and were represented with asterisk. P-values of<0.001 were represented with two asterisks. NS denotes not significant." ] },{ "paper_id": "d311746113fa03b25d129db6c7acc6182499d679", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Asthma exacerbation during ARI was defined a priori as either:", "Gene enrichment analysis (GEA) was performed using both MetaCore\u2122 (GeneGo\u2122, Thomson Reuters) and Gene Enrichment Profiler [31] . MetaCore\u2122 identifies enriched biological process and pathways within gene sets using the Gene Ontology\u2122 and GeneGo\u2122 Ontologies, the latter derived from curated databases of experimentally validated interactions. MetaCore\u2122 employs a hypergeometric model to determine significance of functional relationships. Gene Enrichment Profiler generates enrichment analysis of gene sets in various cell types to provide a cell/tissue perspective of large gene expression datasets.", "This report encompassed samples from the Naturally Acquired Upper Respiratory Illness study conducted at University of California, San Francisco (UCSF) from November 2001 to November 2004. The study design was approved by the UCSF Committee of Human Research. This study conformed to the Helsinki Declaration. Written informed consent was obtained for all participants prior to inclusion in the study." ] },{ "paper_id": "d31b2db65b2e8d40eee096d5e67185099c10c4d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antibodies. Anti-LC3 polyclonal antibodies were from Novus Biologicals (Catalog number NB100-2220). Anti-GAPDH and anti-SQSTM1/p62 polyclonal antibodies were purchased from Santa Cruz (Catalog number sc-25778 and sc-25575, respectively). Horseradish peroxidase-conjugated secondary (anti-rabbit) antibodies were purchased from Jackson Immunoresearch (Catalog number 111-005-144).", "Cell viability (MTT) assay. Cell viability was assessed using MTT (3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay. MTT was purchased from Sigma. The assay was performed as previously described 76 . Statistical analyses. Experiments were independently replicated for at least three times. Quantification figures show mean values, and error bars represent standard error of the mean. Statistical significance was determined via Student's t-test (minimum p-value for significance 0.05). Unless otherwise indicated, the data were statistically significant (p-values < 0.05)." ] },{ "paper_id": "d31b3d462fe4af4bac27a166ddfdf39b03c8e911", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "have caused major concerns due to the association of ZIKV infection with severe congenital abnormalities, including microcephaly in infants and an increased risk of Guillain-Barr\u00e9 syndrome in adults [15] [16] [17] [18] . ZIKV is mainly transmitted to people through the bite of an infected Aedes spp. mosquito (Ae. Aegypti and Ae. Albopictus) [19] , which carries a high risk for pregnant woman due to the ability to cross the placenta and infected fetal nervous tissues [20] . In addition to maternal-fetal transmission, ZIKV can also be transmitted from mother to child during pregnancy or spread through sexual contact, breastfeeding, blood transfusion and non-human primate bites [21-23].", "The generation of rZIKVs using reverse genetic approaches is currently well established and although is used by multiple laboratories worldwide, it is possible to find multiple variations between these approaches among different research groups. Moreover, the origin of the ZIKV strain used and the reverse genetic approach selected might require introducing modifications and/or optimization procedures for the successful rescue of rZIKVs.", "Because the very recent emergence of ZIKV, there are not currently approved vaccines or antivirals available to combat infection by this important human pathogen. Therefore, the generation of prophylactic (vaccines) and therapeutic (antivirals) options for the treatment of ZIKV are urgently required. The development of ZIKV reverse genetic systems provide investigators with a powerful tool for the development of vaccines and antivirals to counteract disease caused by this important human pathogen." ] },{ "paper_id": "d31c808b7108ee70653f288622745ce73ca14adf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d31c8c30c1aaad525d6a1714296376a091414e5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Continued annual monitoring is needed to determine the effects of vaccine supply, changes in influenza vaccination recommendations, changes in groups targeted for vaccination, and other factors, on vaccination coverage among adults and children [4] . Vaccine coverage rates constitute the basic measure for evaluation of public health programs designed to improve vaccination uptake and for estimation of how the vaccination program affects the rate of disease.", "No investigation was carried out in 2000/2001 season owing to lack of financing. All surveys used the same questionnaire. The questionnaire was presented to one individual (\u226518 years of age) in each household using CATI (Computer Assisted Telephone Interview) technology. This individual provided information on his/her vaccination status and information on the household. The terminology \"percent of vaccinated\" used in reporting results refers to individuals who reported being vaccinated or on which the respondent said they were vaccinated.", "The (Table 2) ." ] },{ "paper_id": "d33624f8b27d81d663f54d3e167aaf15968ff8a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "[i \u2212 1, j \u2212 1] , R[i, j \u2212 1] and R[i \u2212 1, j].", "(1)", "Here, c denotes the index of character A[i \u2212 1] in string C." ] },{ "paper_id": "d336ffee34085032c158363c77b69204c58ca85a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The isolation of fresh splenocytes from P. alecto bats has been described previously [21] . Briefly, cell suspensions were prepared by pressing spleen tissue through a cell strainer using a syringe plunger. Mononuclear splenocytes were isolated by density centrifugation over lymphoprep (Axis-Shield). Culture media for mononuclear splenocytes consisted of DMEM supplemented with 10% FCS, 15 mM Hepes, 15 mM L-glutamine, 100 mg/ml penicillin and 100 mg/ml streptomycin. All animal experiments were approved by the Australian Animal Health Laboratory (AAHL) animal ethics committee (protocol number 1389).", "The genomic organization of each locus was determined by aligning the complete cDNA sequences of IFNl1 and IL10R2 with the corresponding P. vampyrus genomic sequence (Fig. 1 ).", "Sequences were edited using SeqMan PRO (Lasergene) and assembled manually using Clone Manager 9.0 (Sci-Ed Software)." ] },{ "paper_id": "d33a044bbb52673f1eeeb792b0376b0987fe02f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The RNA was eluted in 200 \u00b5L of DNase/RNase-free water. Concentration and purity were determined by using UV absorbance.", "Bioinformatic and phylogentic analysis were done using BLAST (National Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD, USA), CLC Genomics workbench (CLC Bio., Cambridge, MA, USA), RetroTector \u00a9 (Uppsala Universitet, Uppsala, Sweden), and MEGA 5.1 (Molecular Evolutionary Genetics Analysis, Tempe, AZ, USA)." ] },{ "paper_id": "d33f858e29256297e9721a300f968f346aa81b0b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Images generated with PyMOL. ", "KVFinder. The flexible 891-998 loop was represented in cartoon and the key Phe896 residue involved 137 in S1 subsite modulation was represented in stick. ", "PDB 4FYR (cyan, cavity volume 811.87 \u00c5 3 ). In the \"Phe-In\" conformation, Phe896 is oriented into the 135 active site inducing a partial closing of the S1 subsite. The active site cavity was computed by" ] },{ "paper_id": "d359875ce36c09a5832bce1d508798496a5eae3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d3618a7956fc136c7183df5b9c665e96a3df8748", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2019, 11, x FOR PEER REVIEW 11 of 18 vesicles are indicated with black arrows, DMVs are indicated with white arrows, and regions of zippered ER with spherules are indicated with black brackets. Scale bars indicate 1 \u03bcm (A and B) or 500 nm (C-F).", "Materials and Methods", "RO formation and function are critical steps in the replication cycle of all +RNA viruses. The membrane origin, shape, and structure of ROs varies between different virus families, but there are common themes in the types of structure produced. Several viruses, including enteroviruses, arteriviruses, toroviruses, hepatitis C virus, and foot and mouth disease virus, induce the formation of double-membrane vesicles (DMVs), often along with single-membrane vesicles and tubules or paired membranes [5] [6] [7] [8] [9] [10] . The second type of structure which are commonly induced are spherules or invaginated vesicles, which are formed by alphaviruses, flaviviruses, bromoviruses, and nodaviruses [3, 4, [11] [12] [13] [14] [15] . These are small single-membrane vesicles which are pinched out from a cellular membrane, but they remain tethered to the membrane and possess a channel connecting the interior of the spherule with the cytoplasm." ] },{ "paper_id": "d3622e7ade6a1af92f1f239619932a3863c77e19", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare that there is no conflict of interests regarding the publication of this paper.", "This well-studied autoimmune model shows how IL-10 produced locally acts as a natural negative feedback mechanism that controls inflammation and maintains immune homeostasis in the periphery. Indeed, IL-10 deficiency aggravates several experimental autoimmune disorders [27] [28] [29] , illustrating the central role of this cytokine in immune regulation.", "Another immunomodulatory mechanism of action for cmvIL-10 resides in its ability to alter macrophage polarization. Depending on the signal they received, monocytes and macrophages become polarized to either M1 proinflammatory or M2 anti-inflammatory subsets [191] . M1 macrophages have a proinflammatory effect with a relevant role in defense against intracellular pathogens. By contrast, M2 macrophages show increased phagocytic activity and suppress proinflammatory cytokine production. cmvIL-10 modulates macrophage polarization and promotes an M2 phenotype [192] characterized by downregulation of MHC-II, upregulation of molecules associated with anti-inflammatory functions, and poor activation of CD4 + T cells." ] },{ "paper_id": "d3669fc36015db30aaecba5e7d608584d9a2cdfa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The datasets for this manuscript are not publicly available because they are currently private (GEO accession number: GSE80011) and scheduled to be released on Apr 30, 2021. Requests to access the datasets should be directed to J-LC.", "C57BL/6 mice were intranasally inoculated with WSN virus for 3 days, and then sacrificed. Mouse lung tissues were collected and fixed in 4% paraformaldehyde and embedded with paraffin. Then, 4-mm-thick sections were prepared and stained with hematoxylin and eosin (H&E). The slides were visualized under an Olympus BH-2 microscope (Tokyo, Japan).", "Data were presented as mean \u00b1 standard deviation (S.D.) from three independent experiments. Statistical analysis was performed by Student's t-test. P < 0.05 was considered to be significant.", "The data of the microarray have been deposited in NCBI's Gene Expression Omnibus under the accession number GSE80011." ] },{ "paper_id": "d3693cdb4860d66db90f3e6249f4da09033448b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Demographics. Participants provided their demographic details consisting of sex, age, current marital status, and highest educational qualifications.", "Supporting information S1 Data. CT_PLOS_ONE_2.sav.zip.", "(ZIP)" ] },{ "paper_id": "d37ad55db18a412c55ca07e3780ab65ec8040908", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords: protein disorder prediction; applications of disorder prediction; machine learning; deep networks", "OPEN ACCESS" ] },{ "paper_id": "d38f4068c4bf5d99a9f4fc20b1914a3332a42ead", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tissue samples from trachea, lungs, and kidneys were obtained from 10 birds from each flock, placed on ice, and transferred to the laboratory in sterile transport medium containing 5 % antibiotics (20,000 U/ml of penicillin, 10,000 \u03bcg/ml of streptomycin, and 5,000 \u03bcg/ml of kanamycin). These samples were used for virus isolation." ] },{ "paper_id": "d38f954f1b3937ead02257e75454dd9ad2ec0ce6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. Not currently living in Lagos.", "For this study we targeted 120 respondents", "A total of 120 interviews were conducted, of which three were disqualified because the interviews were not completed. The mean age of participants was 34 +/ -9.6 years, age range 16-62 years." ] },{ "paper_id": "d392fcba605d12d5f9b3b31f6d0c620b6a89cdcc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were estimated and made using a GraphPad Prism Program (GraphPad, San Diego, CA, USA). Data were expressed as the mean6S.E.M. and analyzed by one-way ANOVA followed with Tukey's post-hoc test. P,0.05 was considered significant.", "The human ICAM-1 (pIC-339/0)/firefly luciferase was kindly provided by Dr. P. T. van der Saag (Hubrecht Laboratory, Utrecht, The Netherlands). ICAM-1-luc activity was determined as previously described [4] using a luciferase assay system (Promega, Madison, WI, USA). Firefly luciferase activities were standardized for b-gal activity.", "Total RNA was isolated with Trizol according to the protocol of the manufacturer. The cDNA obtained from 0.5 mg total RNA was used as a template for PCR amplification as previously described (Lee et al., 2008) . The primers used were as follows: 59-TGACGGGGTCACCCACACTGTGCCCATCTA-39 (sense) and 59-CTAGAAGCATTTGCGGTGGACGATG-39 (antisense) for b-actin; 59-CAAGGGGAGGTCACCCGCGAGGTG-39 (sense) and 59-TGCAGTGCCCATTATGACTG-39 (antisense) for ICAM-1." ] },{ "paper_id": "d39a4fdb4c67a86c47496bef56c34f732817b4bf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells, viruses, and plasmids. A549, BHK-21, HEK293, HEK293T, Vero B4, and Vero E6 cells were cultured in Dulbecco's minimal essential medium (DMEM) and CCM34 medium (DMEM with addition of 17.8 mg/liter L-alanine, 0.7 g/liter glycine, 75 mg/liter L-glutamic acid, 25 mg/liter L-proline, 0.1 mg/liter biotin, 25 mg/liter hypoxanthine, and 3.7 g/liter sodium bicarbonate) supplemented with 10% fetal calf serum (FCS), 2 mM glutamine, 100 U/ml penicillin, and 100 g/ml streptomycin.", "We are grateful to Besim Berisha for excellent technical assistance. We are indebted to Patricia Aguilar and Robert Tesh from the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA) for providing the Sabin strain of SFSV along with mouse immune ascites fluid and to Alejandro Brun for providing anti-RVFV antiserum. Expression and luciferase reporter constructs were kind gifts from John Hiscott, Takashi Fujita, Luis Martinez-Sobrido, Adolfo Garcia-Sastre, and Shizuo Akira." ] },{ "paper_id": "d3a753e3847b2c8524486ee213fb614c3c52d8c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For each EQA, participants were asked to analyse the provided EQA samples using the procedures routinely used by them in suspected human cases. Assay details, such as the type of method used, suppliers of commercial kits, protocols and references were requested. The participants could have the choice of the diagnostic procedure employed.", "In order to achieve practical recommendations about the possible routinely use of the serologic tests described above please refer to Table 1 . ", "Currently, the laboratory methods for the diagnosis of infection by WNV belong to two main categories: serology and viral detection.", "Patients with suspected WNV neuroinvasive disease or WN fever. The viral load in biological specimens (blood, CSF, urine) from patients with suspected WNV infection is hypothesized to be higher than in asymptomatic infected subjects and consequently the diagnostic methods do not need the same high sensitivity that is required for the screening tests used for asymptomatic individuals." ] },{ "paper_id": "d3a809d8853624054040f382feb05893b9f6cb7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After washing a few times with PBS, the membranes were incubated with secondary antibodies for 2 h and then detected by a chemiluminescence Western blotting detection kit (Thermo Fisher Scientific., Rockford, IL, USA) using an Image Quant TM LAS4000 imaging system.", "Ecklonia cava, which is edible seaweed belonging to the Laminariaceae family, is found in Asian countries, such as Japan and Korea. E. cava is a nutrient-dense food and it contains many types of organic compounds, including fucoidan and phlorotannins [1] , which have various biological activities, such as antioxidant [2, 3] , anti-allergic [4] , anti-plasmin inhibitory [5] , anticancer [6] ,", "The authors declare no conflicts of interest." ] },{ "paper_id": "d3adf3be72d751812577d37b2f3db193b2b93cc2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Denaturing polyacrylamide gels (6, 8 , and 16% w/v), native polyacrylamide gels (15% w/v), and 0.7% agarose gels were prepared and run as described [65] .", "Analysis of fidelity by steady-state kinetics also demonstrates higher fidelity with Zn 2+", "Polymerase chain reaction (PCR) for the PCR-based lacZ\u03b1complementation fidelity assay" ] },{ "paper_id": "d3aee39816e64957bf5d940e787330f152e71efe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Values with different letters (a, b and c) differ significantly between groups (one-way ANOVA for means and Fisher's Exact test for diarrhea rates, respectively. p < 0.05).", "Fecal consistency scores 0, 1, 2 and 3 correspond to normal, pasty, semi-liquid, and liquid feces, respectively, with scores of \u2265 2 corresponding to diarrhea.", "SD: standard deviation, ND: not detectable." ] },{ "paper_id": "d3b9423ca41bdd129766dce07506a87b9eec22a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All Perl scripts, for processing genomes, calculating genome signatures, and running SOMs are available on request from the author (d.gatherer@mrcvu.gla. ac.uk).", "A Perl script was written to derive raw k-mer counts on FASTA-formatted databases of input sequences, using the SeqWords.pm module from BioPerl (http://www.bioperl.org/Pdoc-mirror/bioperl-live/ Bio/Tools/SeqWords.html). The raw k-mer frequencies were then symmetrized, as follows:", "The range within which weight vectors are trained at each iteration is calculated:", "where f \u03bd and f \u03bd-comp are the raw frequencies of a k-mer \u03bd and its complement \u03bd-comp. Symmetrization means that a sequence and its complement will generate the same answer. The symmetrized frequencies are then corrected for the 1-mer content. For instance for a 2-mer XY, where X and Y can each represent any nucleotide base {A, C, T, G}:" ] },{ "paper_id": "d3c04715d99a379da9cf526b7542f027cf0a04c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tumor type 0.14 0.04" ] },{ "paper_id": "d3c12db300a385a8668a0ee077a3b39c4e536c4e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d3ca5f2f620d495c747bac2a00b3446b392f7535", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This was a prospective observational study performed from Oct. 2011 to Oct 2012 at the Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada, a 165 bed tertiary care hospital serving a catchment area 1.5 million." ] },{ "paper_id": "d3cbb775040a7d1eac36c6615653b2d94f6c6c13", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There were no calls to the toll-free number reporting an incident with clinical signs or symptoms compatible with influenza infection.", "In the present study we initiated poultry and environmental surveillance for A/H5N1 and other AIVs in four LBMs in Cambodia to better ascertain virus circulation in this setting. A longitudinal human serosurvey was also conducted to investigate the risk of human avian influenza infections in exposed LBM workers.", "Laboratory data were entered using an Excel spreadsheet (Microsoft Excel, Microsoft, Redmond, WA, USA). A baseline assessment was documented using point prevalence for influenza antibodies, and incidence rates during follow-up were then computed using data on laboratory-confirmed seroconversions in LBM workers (numerator), and the number of days elapsed during the last serosurvey (denominator). Poisson confidence intervals for the incidence rates were computed using Stata 11 (Stata Corp., College Station, TX, USA) with the function cii for the binomial CI, and the functions cii and the option 'poisson' for the poisson CI.", "The longitudinal human serological study was approved by the National Ethics Committee for Human Research (approval NO. 267, 24 December 2012). Serum samples were collected, after obtaining informed consent, from LBM workers at the start of the study (January 2013) to form a baseline, and 8 weeks after the three major national festivals shown by previous work to be associated with increased A/H5N1 circulation in markets: 25 Lunar New Year, week 6; Khmer New Year, week 15; Pchum Ben, week 40. All adult-age LBM sellers or workers were exhaustively recruited in the four targeted livepoultry markets. The sample size could not be calculated as transmission to humans was unlikely and its probability in Cambodia is unknown. Participants were informed to report any acute febrile, respiratory or digestive signs, and were provided with a toll-free phone number." ] },{ "paper_id": "d3d29e7ae22aaff4cdc9769cbe97e57c438d5ef2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A s obligate intracellular parasites, viruses have to penetrate living cells in order to replicate. While viruses generally have one or more cell surface receptors or attachment factors, only a few virus types can enter the cells through direct fusion with the plasma membrane. Throughout evolution, most viruses have developed elegant strategies to hijack the endosomal network, a maze of tubular and vesicular structures in eukaryotic cells tasked with cellular trafficking, to penetrate the cell and deliver their genome. Endosomes pick up cargo at the plasma membrane and transport it through the cell with the goal of delivering it to the cytoplasm or to other organelles, routing it to the lysosomal graveyard, or recycling back to the plasma membrane. To do this, endosomes undergo a maturation process that is accompanied by morphological and physiochemical transformations, including acidification and acquisition of various functional molecules. Ebola virus (EBOV) utilizes this dynamic endosomal environment to regulate a complex set of transformations of its own envelope glycoprotein that are necessary for fusion of viral and endosomal membranes and delivery of the viral genome into host cells.", "Colocalization studies using fluorescently labeled endosomal markers Rab5, Rab7, and NPC1 demonstrated that all virions colocalized with NPC1 at the time of dequenching. This is consistent with two recent reports (2, 11) but is in disagreement with another study suggesting that membrane fusion occurs in endosomes lacking NPC1 but expressing the two-pore calcium channel (TPC) (12) . However, in this live-cell assay, the TPC inhibitor tetrandrine did inhibit lipid mixing, consistent with a role for TPC in EBOV entry (12) . The study also showed that viral lipid mixing occurs primarily in Rab7-positive (Rab7 \u03e9 ) late endosomes, consistent with previous reports (2, 11) , but that, unexpectedly, about 15% of lipid mixing events occurred in Rab5 \u03e9 endosomes. These Rab5 \u03e9 compartments likely represent maturing vesicles transitioning from early to late endosomes.", "An interesting feature of this assay is its ability to uncouple lipid mixing from complete membrane fusion. As mentioned above, the specific cathepsin inhibitor E-64 blocks the entry by rVSV bearing GP CL . Interestingly, the live-cell imaging performed by Spence et al. shows that E-64 has no impact on lipid mixing, while it completely blocks productive fusion. These data suggest that there may be an additional protease-dependent step between initial lipid mixing and productive fusion leading to content release. Future studies should reveal the specific target of this proteolytic step and how it relates to the mechanism of fusion." ] },{ "paper_id": "d3d998de1e3cb950c425decbadc73af2c26102fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Emerging zoonotic viruses have received tremendous interest within recent years and are perceived as a major health risk for humans [1, 2] . Among them are many RNA viruses from wildlife reservoirs, with recent examples including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) Coronavirus (CoV) as well as Old-and New World hantaviruses [3] [4] [5] [6] [7] [8] [9] [10] . In addition, recent -pathogen hunting\u2016 approaches resulted in the discovery of novel paramyxo-, hepe-, hepaci-and hepadnaviruses in bats and rodents [11] [12] [13] [14] [15] [16] [17] .", "The many similarities between bat-, insectivore-and rodent-borne viruses could stimulate a synergistic approach for reservoir host-derived in vitro models to study hantaviruses. ", "In conclusion, investing in a large range of reservoir-derived cell culture models will be a promising tool to reveal novel aspects of the hantavirus-host relationship. Further, experience and model systems from the field of bat-borne zoonosis can serve as a blueprint for the hantavirus research community." ] },{ "paper_id": "d3f515c47fec377ecc7f3961948916239e4e079f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data used to support the findings of this study are available from the corresponding author upon request. ", "The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmicb. 2019.02879/full#supplementary-material FIGURE S1 | The schematic diagram of the BiMC assay.", "Cyclosporin A (Dalian Meilun, China) is a type of immunosuppressive preparation that targets CYPA (Chatterji et al., 2009) . The drug was dissolved in dimethyl sulfoxide (DMSO). EBV-positive cells were cultured in medium containing 40 \u00b5M of CsA. After 48 h of treatment, the cellular proteins and total RNA were extracted and subjected to detection." ] },{ "paper_id": "d3f7afa8b4d0f21b23ccb1135dec12356375f5cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The therapeutic vaccine-based HBsAg complexed with human anti-HBs was proposed by the group of Wen et al.", "Previous results from therapeutic immunization trials on woodchucks, chimpanzees, and humans indicate that the licensed vaccines are not able to boost a functional antiviral T cell response. There is a need to use more potent strategies.", "Surface glycoproteins (large-L, medium-M, small-S), core protein, \"x\" protein, \"e\" antigen, DNA polymerase with reverse-transcriptase activity [22, 105] The corresponding proteins [91] Replication strategy" ] },{ "paper_id": "d3f7f0af7fceb8d73489863fca4c5ebb608f6fd4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "of current study may provide valuable information for the design of more effective siRNA against the M gene of SARS-CoV.", "Molecules 2010, 15 7198" ] },{ "paper_id": "d3faa41624a8a99e5f600923cbe61fc457fb76a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed by Student's t-test, and the differences were considered as statistical significance when P <0.05.", "MARC-145 cells, derived from a monkey fibroblast cell line MA-104 [11] , and 293T cells were grown in Dulbecco's Modified Eagle medium (Gibco) plus 10 % heatinactivated fetal bovine serum (Hyclone). PRRSV strain BJ-4 was a kind gift from Prof. Hanchun Yang (China Agricultural University).", "Background PRRSV, a positive sense and single-stranded RNA virus, is a member of family Arteriviridae [1] . Since it was emerged in the United States in 1987 and in Europe in 1990, PRRSV has rapidly spread in the swine producing regions and became one of the most important devastating diseases of swine worldwide. It can cause severe reproductive failure in sows and respiratory distress in young growing pigs [2] . Infection with PRRSV also made pigs easy to secondary infection by other pathogens [3] . Up to date, since there is no efficient method or drugs against PRRSV, it is very important and urgent to develop the effective therapeutic strategies to control PRRS." ] },{ "paper_id": "d3ffe6ae419677ea33f6217317c7876f104f806f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bat passive surveillance database", "Vespertilionidae 147 (42) 171 (49) 30 (9) 101 (29) 207 (59) 40 (12) 133 (38) 143 (41) 72 (21) 169 (49) 143 (41) 36 (10) 348", "Eptesicus brasiliensis 2 (67) " ] },{ "paper_id": "d400825a1ea10fb8d5bdbc96b2c00e866eb75f1d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The calibrator was calculated from the mean \u0394C of mock-infected samples for each individual gene.", "Total RNA was extracted using MagMAX-96 Total RNA Isolation kit (Ambion, Austin, TX) in a MagMAX Express-96 magnetic particle processor (Applied Biosystems, Foster City, CA). RNA from each culture was treated with DNase to remove any contaminating genomic DNA (gDNA). The RNA concentration was assessed at OD 260 nm and purity was verified by the OD 260 /OD 280 ratio using NanoDrop (Thermo Scientific, Wilmington, DE). The reverse transcription reaction was performed with 1 g of total RNA using RT random primers and a MultiScribe reverse transcriptase (High Capacity cDNA Reverse Transcription kit with RNase inhibitor (Applied Biosystems, Foster City, CA)) according to the manufacturer's instructions. The following IFNprimers and probe set were used for PCR amplification with an Applied Biosystems 7500 Fast Real-Time PCR System: EqIL-IFN-F: 5 -AATGGCCCTCCTGCTGTGT-3 , EqIL-IFN-R: 5 -CCGAAGCAAGTCATAGTTCACAGA-3 , and EqIL-IFN-: probe 5 -FAM-CTCCACCACGGCTC-NFQ-3 . For each sample, cDNA corresponding to theglucuronidase ( -GUS) gene was amplified and used as an endogenous control. All PCR efficiency values were determined using LinReg [50] . The relative concentration of target gene mRNA was equal to", "Equine arteritis virus (EAV) is the causative agent of equine viral arteritis, a respiratory and reproductive disease of horses [1, 2] . EAV is a small enveloped virus with a positive-sense, single-stranded RNA genome of \u223c12.7 kb. It belongs to the family Arteriviridae (genus Arterivirus, order Nidovirales), which also includes porcine reproductive and respiratory syndrome virus (PRRSV), simian hemorrhagic fever virus (SHFV), and lactate dehydrogenase-elevating virus (LDV) of mice [3] [4] [5] . The EAV genome includes at least ten known functional open reading frames (ORFs 1a, 1b, 2a, 2b, 3, 4, 5a, 5b, 6, and 7) [5] [6] [7] . ORFs 1a and 1b are located at the 5 -proximal three-quarters of the genome and are translated to produce replicase polyproteins pp1a and pp1ab (1,727 and 3,175 amino acids, resp.). Translation of ORF1b depends on a \u22121 ribosomal frameshift located just before termination of ORF1a translation [8] . The two replicase precursor polyproteins are cleaved by three ORF1a-encoded proteases that reside in nsp1, nsp2, and nsp4, yielding at least 13 end-products, namely, nonstructural proteins (nsps) 1 to 12, including a recently described nsp7 and 7 [5, 9, 10] . The remaining eight ORFs (2a, 2b, and 3, 4, 5a, 5b, and 6-7) are located in the 3 quarter of the genome and encode the structural proteins (E, GP2, GP3, GP4, ORF5a protein, GP5, M, and N, resp.) of the virus [5, 6, 11-13]." ] },{ "paper_id": "d408854267a5f3330fab52531265d9a38a91e60f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This was performed as proof of principle on a single FIP cat heart (Group 2.1) to confirm that cardiomyocytes are themselves responsible for the detected mRNA transcription, and was therefore not subject to any statistical analysis.", "Frozen RNAlater TM samples were embedded in Tissue-Tek \u00ae O.C.T. Compound (Sakura \u00ae Finetek USA Inc., Alphen aan den Rijn, The Netherlands) in a cryostat at \u221220 \u2022 C before sectioning at 8-10 \u00b5m onto PEN Membrane Glass Slides (Applied Biosystems\u2122, Waltham, MA, USA) and staining according to published protocols ( [38] ). The slides were completely air dried before LCM to allow for proper excision performance." ] },{ "paper_id": "d4090dff0fba51422afb6bf34f29c10f9a35caac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "based studies where both quality control and validation are essential criteria 11 . The major concern in qRT-PCR is a suitable endogenous control/reference gene to nullify variations that arise in the due course of experiment 14 .", "In the era of high throughput sequencing, RNA-Sequencing (RNA-Seq) has been widely applied to evaluate global gene expression levels and composition 1-3 . RNA-Seq produces reproducible results with little technical variation due to its immense power 4,5 . It offers a clear-cut measure of gene expression over a wide dynamic range 5,6 . Validation is an important part in a RNA-Seq experiment 7 . The differentially expressed genes identified are often validated using quantitative RT-PCR (qRT-PCR) 8,9 . qRT-PCR is the premier molecular biological technique to define accurate expression profiles of selected genes of interest 10,11 . It is highly sensitive, specific and reproducible 12,13 and acts as a key factor in the systems biology Published: xx xx xxxx OPEN www.nature.com/scientificreports/" ] },{ "paper_id": "d4190432c724cc90504db6a90053c0a61057eb7c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Madin-Darby canine kidney (MDCK) cells were cultured in Dulbecco's modified Eagle's medium (DMEM; GIBCO, Grand Island, NY) supplemented with 10% fetal bovine serum (FBS; Hyclone, Logan, Utah), 100 U/mL penicillin and 100 mg/mL streptomycin and were incubated at 37uC in 5% CO 2 [23] . Virus isolation was performed in either 9-day-old embryonated eggs or in MDCK cells, as previously described [23] . We confirmed viral isolation using hemagglutination, neuraminidase activity or realtime RT-PCR assays [23] [24] [25] . Viruses were passaged no more than three times.", "KC967083-KC967090, CY052046-CY052050, CY052346-CY052350, CY054283, CY060444, CY060450, CY072074, CY072076, CY072082, CY072085-CY072088 and KJ417954-KJ417961. The amplified RT-PCR products were purified using the QIAquick PCR Purification kit (QIAGEN, Valencia, CA) and sequenced using a BigDye Terminator v3.1 Cycle Sequencing kit (Life technologies, CA).", "Finally, our results could stimulate a debate among investigators working on the molecular epidemiology/surveillance of influenza about critical mutations in the A(H1N1)pdm09 strain and could be interesting for physicians working on BMT. " ] },{ "paper_id": "d43a73492744f56383a502fdd4fdc36eb160e09e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d44554968fffa118597a03b93a4a3fa6150d8895", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antibody-mediated immune detection is a popular approach due to its convenience. Nanobodies, also termed the variable domain of heavy-chain only antibody (VHH), were surprising discovered in the sera of camelids, such as llamas, dromedaries, camels, alpaca and vicuna [23, 24] . Nanobodies are also the smallest antibodies with complete antigen-binding sites [25] . The single-domain nature of nanobodies due to their lack of light chains confers many special properties not observed in conventional antibodies: including high affinity, thermal stability and high yield in microbial production systems [26, 27] . Moreover, because the molecular weights of nanobodies are only approximately 15 kDa and they are associated with concave epitopes, nanobodies might be better adapted to access hidden targets and cryptic sites than antibodies [22] . Based on these unique features, nanobodies hold great potential as candidates for diverse biomedical applications, such as disease diagnosis and therapeutics [28] .", "Statistical analysis and drawing were performed using GraphPad Prism software 5.0 (GraphPad Software, Inc. LA Jolla, CA, USA). The Kappa values were calculated to estimate the coincidence between bELISA and the commercial ELISA kit using SPSS software (Version 20, http://www.spss.com.cn).", "The newly developed blocking ELISA was evaluated in terms of its specificity, sensitivity and cross-reactivity and exhibited excellent specificity and sensitivity and no cross-reactivity with serum positive for TGEV, PPV, PRRSV, PRV, JEV, PCV2 and CSFV. An intra-assay comparison also revealed the good repeatability of this method.", "In brief, bELISA is a rapid, low-cost, reliable and useful nanobody-based tool for the serological evaluation of current PEDV vaccines efficacy and indirect diagnosis of PEDV infection.", "The repeatability of bELISA was evaluated with four PEDV-seropositive samples and two PEDV-seronegative by determining the intra-assay variability. To determine intra-assay variability, each sample was tested 4 times by different operators on different occasions. The results are presented as the standard deviation (SD) of the percentage inhibition of each group of samples." ] },{ "paper_id": "d44571bd848bc813e4cdd2fe8c36b922433ec4da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Overview of the Animal Models That are Used to Study Multiple Sclerosis", "In conclusion, a great deal of evidence supports a role for peripheral infection in driving MS relapse. This evidence stems from both indirect (seasonal influence) and direct Glial activation induces chemokine (2) and cytokine expression that upregulates endothelial adhesion molecules that promote the extravasation of encephalitogenic T-cell and monocyte/dendritic cell trafficking across the BBB (3) . T-cells initially encounter resident perivascular meningeal microglia/macrophages, which have been \"primed\" for optimal antigen presentation (i.e., upregulation of CD86/CD80 and MHCII). T-cell activation stimulates the recruitment of professional APCs (including CCR4 + dendritic cells) and the production of cytotoxic factors, culminating in demyelination and neurodegeneration (4) . Abbreviations: APC, antigen-presenting cell; AST, astrocyte; DC, dendritic cell; OL, oligodendrocyte.", "Multiple sclerosis is considered to be a T-cell-mediated autoimmune disease. As such, it is very likely that autoreactive T-cells become activated in response to peripheral infection and that this represents one of the initial events that contribute to relapse. Mechanisms for how autoreactive T-cells become activated in response to infection are described below and are summarized in Figure 1 ." ] },{ "paper_id": "d44ccd4da37549d25e916096ebd616c982af0422", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where Z* is the average quasivalence number (AQVN) determined by:", "( . \u03c0 )/ \u03c0 ( )", "The web tool for the calculation of informational spectra of proteins is available at: http://www.vin. bg.ac.rs/180/istree/ and sequences of the different HA versions can be found in the supplementary information." ] },{ "paper_id": "d4535a63a31f97c7564ddf87608bc8b116ba0df0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Information on the CRFs was entered into a database created in Microsoft Office Access 2003. The chi square and Fisher exact tests were used to compare means and associations using SPSS software version 10.0 (SPSS Inc.; Chicago, IL) and R version 2.8.0 (R Development Core Team; Vienna, Austria). ", "Each person with ILI was asked to enroll in the study. A person was defined as having ILI if he or she had a sudden onset of fever ($38uC) and either cough or sore throat for less than five days in duration, with or without general symptoms such as myalgias, prostration, headache, or malaise [13] .", "Phylogenetic trees were constructed by the neighbor-joining method and bootstrap analysis to determine the best-fitting tree for the gene using MEGA software (version 4). The statistical significance of the tree topology was tested by bootstrapping (1,000 replicas). Pairwise distances between and within the genotypes at the nucleotide level were calculated with Kimura 2 parameters and with Poisson correction at the amino acid level with MEGA software. Genbank accession numbers are listed in Table S1 ." ] },{ "paper_id": "d45434768bff438c55a2ec36d9821e40fe7ddc7d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although many types of environmental samples and diverse organisms have been examined for bioactive lectins [40] [41] [42] [43] , microorganisms and terrestrial tropical habitats are under-sampled [44, 45] . Our results indicate that there is a heretofore untapped reservoir of potentially useful lectins to be discovered in this fashion. Our approach is a notable departure from previous efforts as we used de novo transcriptome assembly, bioinformatic screening, and DNA synthesis to bypass constraints of protein purification or focal gene approaches [46] . Using such methods in combination with bioinformatic analyses, oligonucleotide synthesis, and recombinant protein production can greatly increase the ease of discovery and testing of novel lectins and other useful proteins.", "In a study described previously [17] , we isolated RNA from roots of seedlings from six different species of tropical trees and synthesized cDNA using a poly-A primer. This process produced almost exclusively eukaryotic genes (those with poly-A tails on RNA) from the plant root tissue and associated eukaryotic microbes. We performed de novo transcriptome assembly to construct gene models and used a Hidden Markov Matrix procedure to detect deep homology and identify gene models from plants by searching for similar genes in 22 representative high-quality plant genomes. Remaining sequences (N = 268,008 unique sequences) were retained as a heterogeneous collection of genes most likely originating from diverse root-associated eukaryotic microbes, most of which appear to be fungi.", "Lectin samples were diluted in CD buffer (7.5 mM sodium phosphate dibasic, 2.5 mM sodium phosphate monobasic, pH 7.4) to a final protein concentration of 20 \u03bcM. The sample solutions were then added to the 10 mm path length quartz cell before collecting CD spectra using a J-1500 Circular Dichroism Spectrometer (JASCO; Oklahoma City, OK). The ellipticity (mdeg) measurements were done at 25\u02daC with data collected over a wavelength range of 180 nm to 260 nm. Three experimental replicates were performed, with three intra-experimental replicates, for each sample.", "With this background in mind, we began to explore the biologic activity of a family of lectins, newly discovered during the course of functional genomic analyses of root specimens from a small sample of tropical rainforest tree seedlings (Fig 1) [17] . Using a recombinant lectin expressed from this library we determine how this protein interacts with and potently inhibits human cancer cell lines. These findings may shed light on the glycomic signature of human tumors, identify new vulnerabilities of cancer, and establish a foundation for the future development of novel carbohydrate-targeted lectin therapeutics and diagnostics in oncology." ] },{ "paper_id": "d469f2e82c820caea8ab2d4f92b7a5a93a23f569", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After data collection, questionnaires were assessed by supervisors to verify the consistency of information and the fulfillment of criteria to include patients in this study. Hospital and household questionnaires were input to the Sphynx database, version 5.", "All patients in the present study, whether cases or controls, had a laboratory-confirmed infection of influenza A/H1N1pdm09, which was [38] .", "Patients who died presented important laboratory changes when compared to controls, with lower levels of leukocytes and platelets and an increase in CPK, LDH, urea and creatinine. Studies revealed a similar trend for the laboratory results of leukocytes [23] , CPK [26, 27, 30] , LDH [26] , platelets [22] and creatinine [27, 30, 34] ." ] },{ "paper_id": "d46d1cea1f8f20ffee27303fc83fb2517e4c23fc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sixteen healthy llamas were purchased and housed at IRTA farm facilities at Alcarr\u00e0s (Catalonia, Spain) during the immunization period and transferred for challenge at the BSL-3 animal facilities of the Biocontainment Unit of IRTA-CReSA, in Barcelona (Spain).", "Several vaccine prototypes to control MERS-CoV have been tested using a wide variety of delivery systems, including DNA vaccines, protein-based vaccines, vector-based vaccines and live attenuated vaccines [15, 18] . Vector-based-vaccines have been developed using the orthopox modified virus Ankara (MVA) [19] , different host-origin adenovirus (AdV) [20] [21] [22] [23] , measles virus (MeV) [24] , rabies virus (RABV) [25] , and Venezuelan equine encephalitis replicons (VRP) [22, 26] , all expressing different lengths of the S protein.", "Vero cells were cultured in Dulbecco's modified Eagle medium, DMEM (Lonza) supplemented with 2% fetal calf serum (FCS; EuroClone), 100 U/ml penicillin (ThermoFisher Scientific, Life Technologies), 100 \u03bcg/ ml streptomycin (ThermoFisher Scientific, Life Technologies), and 2 mM glutamine (ThermoFisher Scientific, Life Technologies). A passage 2 MERS-CoV stock (Qatar15/2015 strain) was propagated in Vero cells at 37\u00b0C in a CO 2 incubator for 3 days. The infectious virus titre was determined in Vero cells and calculated by determining the dilution that caused cytopathic effect (CPE) in 50% of the inoculated cell cultures (50% tissue culture infectious dose endpoint, TCID 50 )." ] },{ "paper_id": "d4718ccc1c08a82371c1d7525aae8cc567ff2424", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2. Health education or information, as released by health authorities, news agencies, education institutions, etc., that conform to modern scientific medicine;", "Collection, transportation and testing specimens of Class A pathogens require approval from the provincial authorities or the central government [27] . \u2020 Influenza A(H1N1) was classified as a Class B infectious disease and was added to the list as a separate entity during the 2009 pandemic [29] . On October 28, 2013, it was announced by the Chinese government that starting from January 1, 2014, influenza A(H1N1) would cease to be listed separately and would be grouped with other influenza strains as an aggregated number listed in Class C [30] .", "The protocol of data processing and anonymization was approved by the Human Research Ethics Committee for Non-Clinical Faculties, The University of Hong Kong, and by the Institutional Review Board, Georgia Southern University (H14167). This paper is the report of a international concern, of which cholera and plague (listed in the law) are (or were) endemic in parts of China. The law specified that outbreaks of class A diseases require prompt infection control measures including immediate isolation of patients and quarantine (medical observation) of their contacts.", "In our study, we manually coded Chinese microblog posts to obtain a better understanding of the actual contents. While there are other studies that used computerized machine learning methods [35, 36] , or keyword search to analyze health-related Twitter contents [37] , there are others that manually coded Twitter data on: childhood obesity [38] , influenza A(H1N1) [39] , and antibiotics [40] ." ] },{ "paper_id": "d474315fbb8b2c284039f0caec40aaa334db068b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Western blotting. Cell lysates were prepared 48 h after transfection and were separated by SDS-12% PAGE, followed by transfer to nitrocellulose. Protein detection was carried out using standard protocols with anti-HA antibody (66006; Proteintech), anti-GFP (66002; Proteintech), anti-FLAG (F1804; Sigma), and anti-actin (sc-47778; Santa Cruz Biotechnology). Luminescent signals were detected with the ChemiDoc MP imaging system (Bio-Rad).", "The study was supported by the National Natural Science Foundation of China (31270208 to W.G.). The funders had no role in the design, interpretation, or submitting of this work for publishing.", "Southern blot analysis. Isolation of low-molecular-weight (Hirt) DNA and Southern analysis were performed as previously described (29, 48) with digoxigenin (DIG)-labeled DNA probes (Roche).", "We thank Zhi Ning for providing the B19V infectious clone PM20 and all of the members of the laboratory of W.G. for discussions and critical reading." ] },{ "paper_id": "d4766bca29ba8c705eed4b4a721476ccf300fa21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethical approval All applicable intuitional guidelines involving animals were preapproved in accordance with the local IACUCs.", "We first studied the editing ability of six ANPEP guide RNAs (gRNAs) in cultured primary porcine fetal fibroblast cells. The six target sequences, all located within exon 2, are listed in Online Resource Table S1 .", "Conflicts of interest Alan Mileham is employed by Genus plc, which provided funding for the project. Randall Prather, Kevin D. Wells, Kristin M. Whitworth are inventors on a patent related to the ANPEP-modified pigs. The remaining authors, Vlad Petrovan, Maureen Sheahan, G. Cino-Ozuna, Ying Fang, Richard Hesse, Melissa Samuel, Raymond Rowland declare no competing interests." ] },{ "paper_id": "d4771e9bbc00e3937638507817289579abc270bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Herpes simplex virus type-1 (HSV-1) virions consist of an inner core with linear, double-stranded DNA that is enclosed in a capsid; an outer envelope containing various glycoproteins covers tegument proteins, which are exterior to the viral capsid [1, 2] .", "A recombinant strain of HSV-1, GHSV-UL46, which contains the sequence for green fluorescent protein (GFP) fused to the tegument protein pUL46, was used for all experiments [18] (ATCC, Manassas, VA, USA)." ] },{ "paper_id": "d4798a48149f9f99e2140e596a4246b15d05fd50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antibodies are an important component in host immune responses to viral pathogens. Because of their unique maturation process, antibodies can evolve to be highly specific to viral antigens. Physicians and researchers have been relying on such high specificity in their quest to understand host-viral interaction and viral pathogenesis mechanisms and to find potential cures for viral infection and disease. With more than 60 recombinant monoclonal antibodies developed for human use in the last 20 years, monoclonal antibodies are now considered a viable therapeutic modality for infectious disease targets, including newly emerging viral pathogens such as Ebola representing heightened public health concerns, as well as pathogens that have long been known, such as human cytomegalovirus. Here, we summarize some recent advances in identification and characterization of monoclonal antibodies suitable as drug candidates for clinical evaluation, and review some promising candidates in the development pipeline.", "broadly neutralizing antibodies have the potential to be developed into therapeutics against dengue infections. [142] [143] [144] [145] [146] [147] [148] Dengue targeting antibodies at high concentration may enhance infection. Therefore, therapeutic antibodies need to be engineered to abolish the interaction of antibodies to the Fc\u03b3Rs on macrophages, thus preventing ADE. 149 For example, a N297A mutation in the Fc region of D23-1G7C2 IgG1 was engineered to reduce the affinity of the IgG1 Fc region for Fc\u03b3Rs, resulting in a marked reduction in ADE activity in in vitro cell studies. 150 In another study, dengue neutralizing mAbs targeting distinct epitopes on the four DENV serotypes were engineered to prevent Fc\u03b3R binding by introducing LALA (L234A-L235A) mutations in the IgG1 Fc region. The LALA variant did not enhance infection and neutralized DENV in vitro and in vivo as postexposure therapy in a mouse model of lethal DENV infection. 151 Perspective Only one mAb, specific to RSV, has been approved for prophylaxis use of viral infections. Several challenges impede the progress of the many antiviral mAbs in the pipeline. One key challenge is the relatively small market for antibody treatments of viral diseases, and potentially higher cost associated with production of recombinant antibodies, as compared to small molecule antivirals.", "As discussed above, Fc region engineering has been shown effective for increasing the half-life of therapeutic antibodies, for instance the RSV mAb motavizumab YTE, and for preventing ADE through reduced FcR binding, as for dengue antibodies. The interactions of the Fc domain with diverse other receptors provides additional opportunities for engineering to optimize therapeutic efficacy of antibodies. The advantages and disadvantages of engineering approaches was recently reviewed by Bournazos and Ravetch. 155 Passive transfer of antibodies for the prevention and treatment of viral infections is easy to manage, but the high cost associated with antibody therapies is prohibitive in prophylactic use of antibodies for intractable viruses such as HIV and influenza A virus for a large population, particularly in low-resource areas. 156 One alternative to passive administration of antibody therapies involves the delivery of transgenes encoding well characterized neutralizing antibodies by a vector. The transgenes direct the expression of antibodies in non-hematopoietic cells, which then secrete mAbs into circulation. It has been demonstrated that intramuscular delivery by electroporation of synthetic DNA plasmids engineered to express modified human mAbs against multiple DENV serotypes confers protection against DENV disease and prevents ADE of disease in mice. 157 More work is needed before clinical applications, but vector delivery of prophylactic or therapeutic antibodies against viral infections is a promising alternative to the current practice of passive transfer." ] },{ "paper_id": "d479fdff7406604cebef7b82284ab7a275e17925", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To conduct all statistical analyses and to visualize the results we used the R package [113] .", "Linear (null hypothesis) and splines (alternative hypothesis) regression models were compared using standard weighted Fstatistics and a specially designed permutation test (see below). To exclude overfitting as the cause of support of the more complex models, we utilized a more sophisticated framework (LV-Test) for the comparison of non-nested regression models (linear vs. doublelogistic and splines vs. double-logistic) as detailed in [112] . The test was further modified to include weighted residuals according to virus sequence weights that account for sequence dependence.", "The latter, as well as several domains encoded in ORF1a and ORF1b, were implicated in the control of virus-host interactions [44] [45] [46] [47] [48] ." ] },{ "paper_id": "d480419719edb5f4d35e01306133b919c1474f89", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Paired T-tests (tailed) were used to compare means between groups of mice. Mortality rates were compared using the Fisher's exact test. Blinded lesion pictures were measured qualitatively using a scoring system ranging 0-4 in severity. P values <0.05 were considered statistically significant.", "PLOS Neglected Tropical Diseases |" ] },{ "paper_id": "d486d51868e8d420880e5f21ae906a5150642763", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pcbi.1006930.g003", "and is defined as:", "and is calculated as:" ] },{ "paper_id": "d494b68c054d6058bce92529a6d9ef3f7302094f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d495854289e2ffd80ba9ac86688abe6c7577b545", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Only results from reactions that yielded unambiguous results were used for analysis.", "in conjunction with QuantiFast SYBR Green PCR Kit (Qiagen 204056). We quantified coronavirus with RNA primers MyCVF2 and MyCV R1 (Table S9) . For initial experiments data were normalized to two transcriptsglyceraldehyde-3-phosphate dehydrogenase (GAPDH) and beta-actin 43 . As there were no differences in results, all subsequent experiments used only GAPDH as a normalizer using primers GAPDH US and GAPDH DS (designed for use in humans but also amplify M. lucifugus transcripts - Table S9 ). As well, a no-template (negative) control was included with every set of primers. Each 25 \u03bcl reaction contained: 1 \u03bcM of each primer set, 12.5 \u03bcl SYBR Green Master Mix and 8.5 \u03bcl of diluted cDNA.", "To verify the RNAseq data, cDNA from ileum samples in which coronavirus RNA had been detected via RT-qPCR were analysed using the following primers, IL22RA1, IRF1, RERG and SRC (for sequence of primers see Table S9 ). Primers were designed by aligning primers described for quantitating human cytokines (PrimerBank) with annotated transcripts of M. lucifugus genes: c-jun (Accession number: XM_006096110.1), cyclin D1 (XM_006098046.1), IL10 (XM_006094865.1) and TNF alpha (XM_006104644.1). The interferon beta primers were designed using the annotated transcript for the E. fuscus gene (XM_008145044.1), which also amplify transcripts from M. lucifugus. Primer efficiencies were determined from cycle threshold (Ct) values of purified PCR products serially diluted and re-amplified. Primers amplified targets with an efficiency of about 100% and in all cases the identities of the PCR products were confirmed by their specific dissociation temperature, specific sizes on agarose gels and by sequencing.", "We observed primer-dimers in some reactions in addition to the PCR product. The dimers dissociated at 77 \u00b0C, while the specific coronavirus polymerase product dissociated at 83 \u00b0C. To avoid false positives due to primer-dimers, the thermocycler was programmed to read at 80 \u00b0C (in the cycle after the primer-dimer had dissociated, and before dissociation of the target product). The thermal profile used was 95 \u00b0C for 5 min followed by 40 cycles of 95 \u00b0C for 10 sec, 60 \u00b0C for 30 sec (readings taken at 80 \u00b0C), and a final cycle of dissociation of product 95 \u00b0C for 1 min, 55 \u00b0C for 30 sec and 95 \u00b0C for 30 sec (readings taken at every degree between 55 \u00b0C and 95 \u00b0C)." ] },{ "paper_id": "d49cee8c7a1dcbaf01f8b3126ba8bc7b9ead7a5a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There was a lot of discussion about communication at the lecture seminar, and it was quite surprising. Among several lessons left by the Middle East Respiratory Syndrome (MERS) epidemic last year, the most significant one is the realization of the importance of communication in a crisis situation.", "experts were not involved in the process until much later.", "But as an expert in health communication, I think the concept of communication is only superficially understood. There is a tendency to think of it only as determining \"what\" to say. However, communication is a complex process that requires not only consideration of content, but also consideration of how, to whom, at what point, and through which channel to deliver the content. Risk communication must also consider the nature of risk, people's characteristics affecting their risk perceptions, and the complex media environment. Thus, communication experts should be involved with health and medical professionals from the very beginning of the response to a public health crisis." ] },{ "paper_id": "d4ab193f58a20b66aba4237f8d5f33d023bca4fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mosquitoes are efficient samplers of human blood. We have previously described xenosurveillance, a surveillance technique that makes use of the hematophagous behavior of some arthropods to survey vertebrates for the presence of pathogens [29, 30] . These studies demonstrated that blood meals from Anopheles gambiae mosquitoes are sufficient samples from which to detect viruses, bacteria, and parasites using quantitative PCR (qPCR) and reverse transcription PCR (qRT-PCR) along with next generation sequencing (NGS) in laboratory and field experiments.", "Capturing blood fed mosquitoes from inside houses is less burdensome to the occupants as compared to other direct techniques (e.g. finger-stick blood collection), and presents less of a risk for health workers and researchers. While specialized equipment is necessary (e.g. Insectazookas) and training is required for xenosurveillance, needles, sharps containers, antiseptics, and bandages are not needed, the occupants can continue with their regular activities, and residents do not need to be present when sampling occurs. The non-invasive nature of this technique also facilitates more frequent sampling, resulting in more blood samples collected, thus increasing the possibility of sampling pathogens that occur transiently in the blood. Additionally, no specific training is required to collect and process the mosquitoes and IRB approval is not required, as human blood is not being sampled directly. Furthermore, storing blood spots on FTA cards with RNA Later allows for bypassing cold chain, ensures deactivation of potential pathogens in samples [50] , and results in nucleic acid that is a high enough quality to sequence.", "While efforts to predict pathogen emergence in human populations have improved and become more robust, pathogen emergence remains unpredictable [12] . This highlights the need for vigilant infectious disease surveillance using cost effective, efficient methods for sample acquisition. Hematophagous arthropods have been used to survey wildlife populations for pathogen circulation [43, 44] , and human pathogens have been detected in blood meals of these arthropods [29, [45] [46] [47] . Using hematophagous arthropods as a sampling method in lieu of direct sampling techniques can be advantageous, but a comparison between the two has never been made. Accordingly, in this study, we sought to improve on existing xenosurveillance methodology while comparing this method to more traditional human blood collection approach, finger-stick blood." ] },{ "paper_id": "d4b5a78a1ab61e4e94bf8478c47e6f5e2ef33086", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Isatis indigotica, the source of the traditional Chinese medicine Radix isatidis (Ban-Lan-Gen), is an extremely important economical crop in China. To facilitate biological, biochemical and molecular research on the medicinal chemicals in I. indigotica, here we report the first I. indigotica transcriptome generated by RNA sequencing (RNA-seq).", "The unigenes were scanned for microsatellites using the MISA (MIcroSAtellite identification tool) software (http://pgrc.ipkgatersleben.de/misa/) with the default parameters. Perfect di-, tri-, tetra-, penta-, and hexa-nucleotide motifs were detected. The criteria for the SSRs are as following: mono-nucleotide type SSR requires a minimum of 10 repeats, di-nucleotide type SSR requires a minimum of 6 repeats, and the other type SSRs, including tri-, tetra-, penta-, and hexa-nucleotide, requires a minimum of 5 repeats." ] },{ "paper_id": "d4b76917de146cdbe4c922c15ac3d87d3d483446", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Feline coronaviruses are enveloped, positive sense RNA viruses that can be classified into two biotypes, namely low virulent Feline Enteric Coronavirus (FECV) and highly virulent Feline Infectious Peritonitis Virus (FIPV). FECV is very common in the cat population worldwide, and has been shown to have infected 20-60% pet cats and shed by 75-100% cats in multi-cat environments [1, 2] . Of those shedding the virus, 1-5% will develop Feline Infectious Peritonitis (FIP) disease [3] . Within the biotypes, the viruses are differentiated further into serotype I and serotype II, based on virus neutralizing antibodies. Type I FECV and FIPV strains are more ubiquitous worldwide and are more likely to cause clinical FIP, while type II strains are less common, but more adaptable to cell culture [2] .", "An RNeasy\u00ae Mini Kit (Qiagen\u00ae, USA) was used to extract and purify RNA samples as per the methods recommended by the manufacturer. The quality of the extracted RNA was determined by an Ultrospec 3000 Pro UV/Visible spectrophotometer (GE Healthcare, UK), where samples with an absorbance ratio value (A260/ A280) of 1.8 to 2.0 were considered for further analysis with an Agilent\u00ae 2100 Bioanalyzer. Samples with RNA Integrity Numbers (RIN) 9 to 10, and concentrations higher than 500 ng/\u03bcl per sample, were sent for Illumina GAII sequence analysis." ] },{ "paper_id": "d4c0c411fdb8d2389288d0389cf02121ae6d8a9c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Gene-neighborhoods and protein domain architectures suggest that HEPN domains function in multi-pronged defense jointly with prokaryotic restriction-modification systems", "Reviewers: This article was reviewed by Martijn Huynen, Igor Zhulin and Nick Grishin", "Ava_2192 -Bacterial with transfer to Naegleria, Dictyosteliida, Daphnia (expansion). All eukaryotes are solos." ] },{ "paper_id": "d4c35983add63a4f8eee72b1d8fa864de4147ead", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The human DPP4 ectodomain (residues 39-766) was expressed and purified as previously described for human ACE2 ectodomain [11] . Briefly, human DPP4 ectodomain containing an N-terminal honeybee melittin signal peptide and a C-terminal 66 His tag was expressed in insect cells using the Bac-to-Bac expression system (Invitrogen), secreted into cell culture medium, and subsequently purified by Ni-NTA affinity column and Superdex200 gel filtration column (GE Healthcare).", "Six-to eight-week-old female BALB/c mice were used in the study. The animal studies were carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Committee on the Ethics of Animal Experiments of the New York Blood Center (Permit Number: 194.14).", "The standard micro-neutralization assay was used to quantify the neutralizing potential of each specimen, as previously described [15] . Briefly, serum samples were diluted at serial 2fold in 96-well tissue culture plates and incubated at room temperature for an hour with ,100 infectious MERS-CoV/ EMC-2012 in each well before transferring the resultant mixtures to duplicate wells of confluent Vero E6 cells grown in 96-well tissue culture plates. After 72 h of incubation, when the virus control wells exhibited advanced virus-induced CPE, the neutralizing capacity of individual serum samples was assessed by determining the presence or absence of CPE. Neutralizing antibody titers were expressed as the reciprocal of the highest dilution of serum that completely (100%) inhibited virus-induced CPE in at least 50% of the wells." ] },{ "paper_id": "d4c687275097c11a1900e5f627c0c28c998e3d65", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The intestinal tissue was fixed in a 10 % neutral formalin solution. The fixed tissue was embedded in paraffin, sectioned to a 4-\u03bcm thickness, stained with hematoxylin and eosin, and subjected to measurement of the villus height (VH) and crypt depth (CD) under a microscopic field as previously described [26] .", "Detection of fecal shedding of PEDV RNA contained in the feces was extracted using RNasy Mini Kit\u00ae (QIAGN, Germany) after removal of contaminants by centrifugation for 10 min at 4000 \u00d7 g. Presence of PEDV in the sample was identified by the reverse transcription-polymerase chain reaction (RT-PCR) targeting a coding region of the membrane protein of the PEDV [14] . The base sequences of the forward and reverse primers were 5'-GGGCGCCTGTATAGAGTTTA-3' and 5'-AGACCACCAAGAATGTGTCC-3' , respectively. The PCR conditions were initial denaturation at 95\u00b0C for 2 min, 35 cycles of 95\u00b0C for 20 s, 56\u00b0C for 40 s, and 72\u00b0C for 1 min, and final extension at 72\u00b0C for 3 min. A 412bp PCR product was identified by the agarose gel electrophoresis.", "The porcine epidemic diarrhea virus (PEDV) or genus Alphacoronavirus causes an acute or sub-acute gastrointestinal disorder in pigs of all ages resulting in serious economic losses across Europe and Asia [1] [2] [3] . Primary clinical symptoms of the PEDV infection include acute diarrhea, vomiting, weight loss, and dehydration [4, 5] . Moreover, an increased mortality as well as higher morbidity in suckling piglets vs. older ones has also been reported as to the damage of PEDV infection [6] . Many attempts have been made to find effective prophylactic or therapeutic agents against PEDV infection, but no satisfactory agent has been reported to date [7, 8] ." ] },{ "paper_id": "d4c6f970018efbcc9df15a758f7ff2396f33225e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d4d0092e3e79f9d5ad3c48f23778317ad867d61c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.", "Information about the commensal and pathogenic microbial communities associated with host species, including humans, is limited. The endemic microbial community of a healthy host is important to characterize because its perturbation can be a cause of disease [1, 2] . Pathogenic microbes often escape detection if the clinical consequences of infection are similar to known pathogens or if they infect non-domestic species [3] . The maintenance of unknown pathogens in wildlife species is particularly problematic because many emerging human and livestock infections arise from contact with wild animals [4] [5] [6] [7] ." ] },{ "paper_id": "d4d15fb77f993153439d9ebd90c649962ee398e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d4d885e748fc8335d359da08f2ef0370103f98c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 293T cells were cultured in Dulbecco's Modified Eagle Medium (Gibco) supplemented with 10% fetal bovine serum (FBS) (Gibco) on 10-cm dishes to 90% confluency. Cells were then transferred to 15-cm dishes, incubated to 90% confluency and then washed with ice-cold phosphatebuffered saline (PBS) and detached by trypsinization using trypsin-EDTA (0.05% Trypsin with 2 mM EDTA, Gibco). After stopping trypsinization with medium containing 10% FBS (Corning), the detached cells were centrifuged at 1000 g at 4 \u2022 C to pellet the cells. The cell pellet was washed twice with PBS and re-suspended with hypotonic buffer (20 mM HEPES (pH7.5), 100 mM potassium acetate, 1 mM Magnesium acetate, 2 mM dithiothreiol (DTT) and proteinase inhibitor cocktail (Roche)). Re-suspended cell pellets were incubated on ice for 45 min and homogenized through a 1 ml syringe using 26 G, 3/4-inch needle (34) . After centrifugation at 14 000 g for 1 min at 4 \u2022 C, the supernatant containing cell lysate was collected with the contents of protein concentration measured by Bradford assay (Biorad), and stored at \u221280 \u2022 C.", "Supplementary Data are available at NAR Online.", "We thank Mr Daniel Flynn for reading the manuscript and comments. " ] },{ "paper_id": "d4ea57e72c426571255c1c45861db4c6b46b95d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results are representative of three independent experiments and expressed as means\u00b1SEM. Mann-Whitney U test was used for comparison of control group parameters with treatment group and multiple group analysis was evaluated by one-way ANOVA with post Mann-Whitney U test using GraphPad Prism5 software. For all statistical analyses, pvalues <0.05 were considered significant.", "The protocol and conditions for RNA extraction, RT-PCR and qPCR were similar as reported earlier by our laboratory using specific primers for 18S, IL-33, IL-6, IL-1\u03b2, IFN-\u03b2, IFN\u03b3, TNF\u03b1 and CXCL1 [10, 13] . For the quantification of viral nucleocapsid, the following primer set was used: 5'-TGGAAGGTCTGCACCTGCTA-3' (forward), 5'-TTTGGCCCACGGGATTG-3' (reverse). The relative gene expression was normalized against 18S gene expression. The control mice in each treatment group served as a reference for mRNA expression (control mRNA level was arbitrarily taken as 1).", "The C57BL/6 (Janvier, France) or CD1d KO mice (a gift of Maria Leite-de-Moraes, Paris) were intravenously injected with 30 \u00b5g/mouse of Poly(I:C) (Invivogen) alone or with Dgalactosamine (D-GalN) (SIGMA-G0264) pretreatment at a dose of 15 mg/mouse (i.p). The control mice received similar volume of vehicle in each treatment group. For NK cells depletion experiment, 35 \u00b5l of anti-asialo GM1 (anti-ASGM1) polyclonal antibody (Cerdalane, CL8955) was injected intraperitoneally (i.p) 48 h before D-GalN, Poly(I:C) or combination of both D-GalN Poly(I:C) injections, the control mice received or an equivalent amount of naive rabbit serum. The NK depletion in liver was confirmed by flow cytometry in isolated liver immune cells as described earlier [29] .", "Wild-type (WT) C57BL/6 mice were purchased from Charles River Laboratories (St-Constant, QC, Canada) or from Janvier (Le Genest-sur-isle, France). The animals, certified as MHVsfree by the manufacturer, were housed under HEPA-filtered air (Forma Scientific, Marietta, OH). The study was conducted in compliance with the regulations of the Comit\u00e9 institutionnel de la Protection des Animaux of the Universit\u00e9 du Qu\u00e9bec \u00e0 Montreal (UQAM agreement of L. Lamontagne, No. CIPA= 541), and French laws and the institution's guidelines for animal welfare (agreement of M. Samson #3596). The protocol was approved by the Committee on the Ethics of Animal Experiments of the French government (agreement of M. Samson #3596). All efforts were made to minimize suffering\"" ] },{ "paper_id": "d4f00f66c732c292fcfc28b19f44daa2fa620901", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pone.0188325.t004", "https://doi.org/10.1371/journal.pone.0188325.t006" ] },{ "paper_id": "d4f1ccfcf8b71a2828f39991e67142dd3a57fd1a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As demonstrated in recent epidemics of emerging viral infections, characterization of the viral genome may facilitate the identification of important virulence factors and diagnostic, therapeutic and vaccine targets. [21] [22] [23] In this study, we analyzed the available genomic data of ZIKV in GenBank to provide a quick search for possible virus mutations that may be associated with the rapidly expanding ZIKV epidemic.", "The genome sequences of 24 ZIKV isolates with complete genome or complete polyprotein sequences available in GenBank (accessed on 18 February 2016) were included in this study (Table 1) . These included strains collected from human, animals, and mosquitoes in Africa, Asia, the Pacific islands, and Latin America between 1947 and 2015. Representative genome sequences of other human-pathogenic flaviviruses, including Spondweni virus (SPOV, DQ859064.1), dengue virus serotype 2 (DENV-2, NC_001474.2), Japanese encephalitis virus (JEV, NC_001437.1), West Nile virus (WNV, NC_001563.2), yellow fever virus (YFV, NC_002031.1) and tick-borne encephalitis virus (TBEV, NC_001672.1) were also included.", "Phylogenetic tree construction by the maximum likelihood method was performed using MEGA 6.0 software, with bootstrap values being calculated from 500 trees. Protein family analysis was performed using the PFAM tool (http://pfam.xfam.org) Search for Conserved Domains server (http://www.ncbi.nlm.nih.gov/ Structure/cdd/wrpsb.cgi). Prediction of transmembrane domains was performed using the TMHMM 2.0 server (http://www.cbs.dtu. dk/services/TMHMM/). Prediction of signal peptides was performed by using signalP software 4.1 (http://www.cbs.dtu.dk/ services/SignalP/). The prediction of potential O-glycosylation and N-glycosylation sites in the polyprotein was performed using NetOGlyc 4.0 (http://www.cbs.dtu.dk/services/NetOGlyc/) and NetNGlyc 1.0 (http://www.cbs.dtu.dk/services/NetNGlyc/), respectively. Secondary structure prediction in the 5\u02b9-untranslated region (UTR) was performed using the RNAfold WebServer with default settings (http://rna.tbi.univie.ac.at/cgi-bin/RNAfold.cgi). The number of synonymous substitutions per synonymous site, Ks, and the number of nonsynonymous substitutions per nonsynonymous site, Ka, for each coding region was calculated using the Nei and Gojobori substitution model with Jukes-Cantor correction in MEGA 6.0. 16, 17 Bootscan analysis was performed using Simplot version 3.5.1 as described previously, 18 with the Asian lineage of ZIKV strains as the query. Multiple alignment of the amino acid sequence of each protein are performed by " ] },{ "paper_id": "d4f4ca21b787bb6a090b859a21aade4e7a0fb633", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The experimental procedures and animal handling procedures were conducted with the approval of the Local Ethics Committee for Animal Experiments in Olsztyn, Poland (approval number: 12/2015).", "Birds were raised till 21 dol in isolated units maintained at PCL 3 (physical containment level 3) facility. Water and feed were given to birds ad libitum.", "The authors declare that they have no competing interests. ", "Considering the fact that CMI associated mainly with cytotoxic T cells is protective against IBV we have performed flow cytometry analysis of both URT and systemic cellular immune response after different IB vaccination protocols." ] },{ "paper_id": "d4f6cfb312bae60aa35168d4a775bdb90c4bc39c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fundo de Incentivo a Pesquisa -SBPT; FIPE-HCPA; FAPERGS." ] },{ "paper_id": "d4f8fcc4360079a02215dd83c280e4ff2b2363be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In future work, false positive rates might be reduced by additional development of these algorithms and discard-ing single-probe clusters containing inverted repeats. Error analysis for development of improved algorithms or array designs should take into account whether errors occurred in the first \"mapping\" step or the second single bp resolution step of CGS." ] },{ "paper_id": "d503366d1b18e110431e5dc7cfe250414c60578f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Endogenous retroviruses were first discovered in pig kidney cell lines in 1971 (101) and are now known to be present in most, if not all, mammalians. The presence and potential reactivation of endogenous retroviruses has very important consequences in both allo-and xeno-transplantation.", "Perhaps the best known contribution of any farm animal to scientific progress was the somatic cell nuclear transfer that gave origin to Dolly, the sheep (89) . Although nuclear transfer itself is not a direct contribution to immunology, nuclear transfer technology has directly influenced many immunological concepts underpinned by technologies such as induced pluripotent stem (iPS) cells and CRISPR-Cas systems.", "By the early 1880s, William Smith Greenfield in the UK (8, 9) and Pasteur working with Henri Thullier, Charles Chamberland and Pierre Paul \u00c9mile Roux in France (10, 11) had begun developing and testing vaccines against anthrax in sheep and cattle. A decade later, the German scientists Friedrich Loffler and Paul Frosch identified the first ever filterable infectious agent in mammals: foot and mouth disease virus (FMDV) and developed a fully protective heat-inactivated vaccine against it (12, 13) ; however an effective long-lasting and broadly protective vaccine against FMDV remains elusive.", "Most circulating T cells in humans and mice are conventional T cells expressing the \u03b1\u03b2 T cell receptor (TCR) and either CD4 or CD8. Unlike mice, other species like cattle, pigs and chickens possess a substantial proportion of T cells expressing the \u03b3\u03b4 TCR cells in the circulation suggesting that circulating \u03b3\u03b4 TCR T cells have a more important role immunity than previously thought (54) .", "Another milestone in vaccine development was the generation in the 1970's of vaccines to control Marek's disease (MD), a naturally occurring neoplastic disease in chickens caused by an oncogenic herpesvirus (19) . MD vaccines are the first examples of the use of vaccination to protect against cancer (20, 21) .", "Engineers frequently look to nature for inspiration. Antibody engineers are no exception, modeling new therapeutics on molecules found in animals such as camels and cows. Indeed, 10% of bovine antibodies have unusually long heavy-chain CDR3s as part of their antigen-recognition sites. Stanfield et al. (45) have solved crystal structures of three new bovine Fab fragments and analyzed the five known structures to show that their ultra-long CDR H3s all adopt similar architectures composed of a knob domain containing a small conserved \u03b2-sheet connected by diverse disulfide-bonded loops that is separated from the antibody surface by a long conserved stalk. They propose that varying the length of the stalk and the positions and number of disulphide links in the knob may help drive antibody diversity. These structural insights could be leveraged to tailor antibody-based therapeutics." ] },{ "paper_id": "d5066cf95471ee885eb17e94e431fc5658cf1b1a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tissue sampling and cell preparation. Three mice from each group were euthanized at 0, 3, 7, and 14 dpi after secondary challenge. Lungs were collected, weighed, and homogenized in 1 ml of cold DMEM using an IKA T10 homogenizer under sterile conditions. Then, solid debris was pelleted by centrifugation at 5,000 \u03eb g for 10 min, and the homogenates were used for virus titrations in MDCK cells. Splenocytes were filtered through cell strainers and were lysed with 0.83% ammonium chloride lysis solution to remove erythrocytes (54) .", "Thermal stability assay. The stability of each HLA/peptide complex was tested using circular dichroism (CD) spectroscopy. All complexes were refolded and purified as described above and measured at 150 g/ml in a solution consisting of 20 mM Tris-HCl (pH 8.0) and 50 mM NaCl. CD spectra at 218 nm were measured on a Chirascan spectrometer (Applied Photophysics) using a thermostatically controlled cuvette at temperature intervals of 0.1\u00b0C at a rate of 1\u00b0C/min between 25 and 90\u00b0C. The denaturation curves were generated by nonlinear fitting with origin 8.0 software.", "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .01408-18. " ] },{ "paper_id": "d5076ff3eb3e96c862345fa109990f9a7b99b842", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal experiments are approved by the Ethics Committee of Northeast Agricultural University within the contract frame from Program for New Century Excellent Talents in University of Ministry of Education of P.R. China (NCET-10-0144).", "Statistical analysis of the data was performed using SPSS 11.5 software; p,0.05 and p,0.01 were defined as statistically significant and statistically very significant, respectively. ", "Serum IL-4 levels were similarly analyzed using an IL-4 detection kit (Excell Bio. China). Control IL-4 was serially-diluted two-fold in PBS between 500 pg/ml and 7.8 pg/ml then coated onto ELISA plates at 37uC overnight. The ELISA was performed as above and OD 490 values (pg/ml) were determined relative to an IL-4 standard curve." ] },{ "paper_id": "d508ee56bf2773ed13b19b85295c8e8709781bb7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Death certificate data for the years 2001, 2002, and 2003 were obtained from the provincial death registry. All deaths in Ontario are recorded in this registry. Data obtained from each death certificate included the decedent's date of birth, sex, place of death, and date of death. Because our goal was to examine the indirect effects of SARS through its impact on the health care system, we subtracted the 44 deaths in Ontario due to SARS from the death certificate database before performing further analyses. " ] },{ "paper_id": "d50946bee04acb73e91b3735ccb661a278b86685", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Because EBV-encoded DNase BGLF5 displays 40% homology to KSHV SOX at the amino acid level, EBV BGLF5 can also induce a robust and generalized host shutoff in productively infected cells [53] . BGLF5 can degrade mRNAs of both cellular and viral origin, irrespective of polyadenylation [54] .", "Similarly, EBV BGLF5 could also induce the nuclear relocation of PABP. Within the nucleus compartment, PABPC causes hyperadenylation and retention of nuclear mRNA molecules, thereby augmenting the shutoff phenotype initiated by BGLF5 [37] . In contrast, MHV68-encoded muSOX also induces both cellular and viral mRNA degradation upon productive infection [38] . However, the association between muSOX and PABP remains unknown.", "Viruses have evolved different abilities to exploit the cellular mRNA decay machinery to modulate host gene expression. The description below will address the subversion mechanisms about how viruses promote host mRNA turnover (Table 2) . " ] },{ "paper_id": "d51485f32ff85186571e9ec9de6d517f9180abe9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Timeliness: The software system a report and observer agreement when comparing the number of days from admission until diagnosis of URI was poor ( Figure 1 ). " ] },{ "paper_id": "d51a55b2f7c2277e6435f0ecf13569863cc3adf3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Double-strand RNA-dependent adenosine deaminases (ADARs) are another type of host enzymes that edit viral genomes by deaminating adenosines in long double-stranded RNA and converting them to inosines. The latter basepair with guanosines, resulting in A-to-G base substitutions [67] . ADARs also exhibit sequence context preferences, although less marked than in the case of APOBECs [68] . ADAR-driven hyper-mutation was first demonstrated in measles virus [69] and has since been suggested for a variety of RNA viruses including human parainfluenza virus [70] , respiratory syncytial virus [71] , lymphocytic choriomeningitis virus [72] , Rift Valley fever virus [73] , and noroviruses [74] .", "Elucidating the mutational mechanisms of small DNA viruses is a current challenge in virus molecular biology and evolution. Other exciting unresolved questions include unveiling the interplays between mutation and recombination, the roles played by viral accessory proteins in determining mutation rates, the effects of host-encoding enzymes on viral diversity and evolution, whether mutation accumulation can be evolutionary adjusted by modifying viral replication modes, and how template sequences regulate viral mutation rates. ", "Using a conceptually similar approach, we recently characterized the accumulation of mutations along the HCV genome under weak or no selection using a bicistronic replicon by cloning HCV sequences at a site commonly used for inserting reporter genes (Fig. 4b) . This revealed extreme mutation rate variations across individual nucleotide sites of the viral genome, with differences of orders of magnitude even between adjacent sites [105] . In that system, we found little or no effect of RNA structure on mutation rate, but a more significant effect of base identity, such that A and U bases were more prone to mutation than G and C." ] },{ "paper_id": "d51abe791f93cef40353f149feeb961a86ae90ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Infectious laryngotracheitis (ILT) is a highly contagious acute respiratory disease of chickens caused by the avian alphaherpesvirus, Gallid alpha herpesvirus 1 (GaHV-1), commonly known as infectious laryngotracheitis virus (ILTV). The disease has a worldwide distribution and is frequently ", "At 1, 3, 5, and 7 days post-ocular inoculation, conjunctiva tissues were collected and placed in 10% buffered natural formalin and fixed for 24 h at room temperature. Routine tissue processing, Viruses 2019, 11, 635 5 of 20 embedding and sectioning was performed. Four-micrometer sections stained with haematoxylin and eosin (H&E) were subjected to microscopic examination for the signs of ILTV lytic replication, indicated by the presence of syncytial cell formation and eosinophilic intranuclear inclusion bodies." ] },{ "paper_id": "d521a22ac03c5c56e1ca2aea0e90f322b348851b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LogP and pKa calculations. For the drug molecules listed in Table 1 , logP (partition parameter) and pKa values (strongest basic pKa) were estimated on the basis of their chemical structures by using the MarvinSketch program.", "Supplemental material for this article may be found at https://doi.org/10.1128/JVI .00941-17.", "SUPPLEMENTAL FILE 1, XLSX file, 0.2 MB." ] },{ "paper_id": "d52f0060c0eefc59aa2383d4951125726984fab3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In summary, we demonstrated that PEI, a mucosal stimulant for topical intranasal administration, is highly effective in preventing influenza virus infection. Compared to the bacteria-produced toxin CTB, the chemically synthesized polymer PEI is safer for mucosal application in humans. PEI has been tested in several clinical trials for gene delivery in vivo, demonstrating a good safety profile. 9 Moreover, its low cost of production and abundance makes PEI more suitable for urgent and widespread use during a time of influenza epidemic or pandemic.", "ACKNOWLEDGEMENTS" ] },{ "paper_id": "d5313a4142703e79978710a40320548a17eed201", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The structural proteins of arteriviruses include the nucleocapsid N and several membrane proteins, such as the Gp5/M dimer, the Gp2/3/4 complex, the small and hydrophobic E protein, and the ORF5a protein [5] . All structural proteins, in addition to ORF5a, are essential for EAV infectivity; however, only N along with viral RNA and Gp5/M dimer is required for budding. Note that Gp2, Gp3, Gp4, and E are minor viral components, and knocking them out individually from EAV does not prevent the", "Equine arteritis virus (EAV) is a prototype member of Arteriviridae, a family of enveloped positive-stranded RNA viruses comprising porcine reproductive and respiratory syndrome virus (PRRSV), a major pathogen in the swine industry [1] . EAV infects horses and donkeys and leads to abortions in pregnant mares and respiratory illness with flu-like symptoms, which can even lead to death in young animals. The virus is transmitted via the respiratory route and via the contaminated semen of previously infected stallions. Despite available vaccines, EAV remains an important pathogen in the horse industry [2] .", "The images were recorded using a Zeiss Cell Observer SD confocal microscope (Zeiss, Oberkochen, Germany) equipped with an EMCCD QImaging Rolera EM-C 2 camera and 40-63\u00d7 oil objectives (0.167 \u00b5m and 0.106 \u00b5m per pixel, respectively). The imaging was performed sequentially using 405 nm, 488 nm, and 561 nm laser lines with a quadruple dichroic mirror 405 + 488 + 561 + 640 and 450/50, 520/35, and 600/52 emission filters. Subsequently, the images were deconvoluted with Huygens software (SVI, Hilversum, The Netherlands)." ] },{ "paper_id": "d54725b7c8072e09a2498c8f2ce1e7ee7839eaf6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The complete genome sequence of PEDV strain HUA-14PED96 has been deposited in GenBank under accession no. KT941120. ", "In this study, we sequenced the complete genome of a Vietnamese strain of PEDV, HUA-14PED96, and analyzed it to understand the molecular characteristics and diversity of PEDVs in Vietnam.", "A highly virulent strain of Porcine epidemic diarrhea virus (PEDV) causing severe diarrhea has recently emerged in Vietnam. Genomic sequences from a novel strain, HUA-14PED96, isolated from a Vietnamese piglet with serious diarrhea show relatively high identity with U.S.-like PEDV strains, and have a 72-nt deletion in the open reading frame 1a (ORF1a) gene." ] },{ "paper_id": "d54f3fe4cf51fd80a04696c49d4fdc0455b8fe21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d55ee40e7898b693872356e1661f658732984bae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Preparation of RNA standard and RNA templates with various mutants. Various target gene fragments (human genes or virus genomic sequences) containing a T7 promoter were obtained by gene synthesis or RT-PCR amplification, and then cloned into pMD18-T plasmids (TaKaRa, Dalian China). A series of mutants were prepared using Fast Mutagenesis System (Transgene Biotech, Beijing, China). To obtain RNA template, in vitro transcription were performed using the recombinant plasmids or amplification products of the plasmids. RNA was quantified, serially diluted and used as RNA standard or templates." ] },{ "paper_id": "d55f09671ad483ed5c25dbff97c970e08c6be947", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As we have more samples to fit into four 96-well plates for genotyping (each plate holds 90 samples while the reminding wells were used for QC samples and negative control, i.e. 360 were genotyped in these four 96-well plates), we blindly pull out a block of 180 male and 180 female samples for genotyping. One additional male sample was used for reaction optimization and his genotype results was also included, which led to a total of 181 male genotyping results." ] },{ "paper_id": "d569871d337077bcb21c8c19fde422b0bca8e0c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d57066fb6b0be503b07e3d19f20166d06af60b18", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As an exception, one representative sequence was chosen for each virus genus for the Flaviviridae family, since very different RdRPs primary structure has been identified in this virus family. For simplicity, we used residues in the PV RdRP (also known as the 3D pol protein) to define conserved sites.", "Viral RdRPs represent a unique nucleic acid polymerase class of and is the only class that does not involve DNA in any stages of the synthesis. To preserve their RNA template and ribonucleotide triphosphate (rNTP) substrate specificity, the seven catalytic motifs are the central segments to preserve during virus evolution. While we have mainly focused on the diversity and variations beyond the catalytic modules, attentions may also be drawn to the variations within the catalytic module but excluding the catalytic motifs. For the representative RdRPs that we surveyed in this study, the spacing between certain catalytic motifs could vary to a great extent. For example, the residue distance between the conserved motif B serine and the motif C aspartic acid in these RdRPs ranges from 30 to 94, corresponding to a motif spacing of 12-76 residues (Figures 1, 2) . We hypothesize that such regions, if located at or near the RdRP protein surface, may have been utilized by the positive-strand RNA viruses as evolutionary \"hot spot, \" in particular in their host adaptation processes. Further investigations are needed to test this hypothesis.", "A large number of RdRPs from the positive-strand RNA viruses are proteolytic products of viral polyproteins (Palmenberg, 1990; Wimmer and Nomoto, 1993; Reed and Rice, 2000; Bartenschlager et al., 2010; Pietila et al., 2017) . Since not all related proteolytic cleavage sites have been reported for some of the virus families, we were only able to define N-and C-terminal boundaries for 33 RdRPs among the 49 representatives (Figure 1 and Table 1) . For the rest of the RdRPs, 7 of them only have a defined C-terminus, and 9 of them have both termini undefined based on our best knowledge. Hence, functional studies to identify polyprotein proteolytic sites are necessary to improve the global picture RdRP primary structure diversity, and our analyses are based on incomplete boundary assignments. The overall size of the RdRPs with clear boundaries ranges from \u223c460 to \u223c1930 residues, indicating that the primary structure of these RdRPs are quite diverse and potential functional regions are likely integrated into some of these RdRP proteins." ] },{ "paper_id": "d5794d9e687b1087383f2bca0c5beaf31ebc2955", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Epidemiological interventions aim to control the spread of infectious disease through various mechanisms, each carrying a different associated cost.", "Conclusions: Using simulation studies based on a classic influenza outbreak, we demonstrate the advantages of adaptive interventions over non-adaptive ones, in terms of cost and resource efficiency, and robustness to model misspecification.", "All statistical and computational methodology described here has been implemented in a freely available R package called amei (Adaptive Management of Epidemiological Interventions), which can be downloaded at http://cran.r-project.org/web/packages/ amei/index.html [11] ." ] },{ "paper_id": "d582ab2a736fc7555df7ad6512afbdcd74056201", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Several viral factors of VV utilize ATP and several steps in viral multiplication of VV require ATP [9] [10] [11] [12] [13] [14] . ATP is also required for DNA packaging and capsid maturation of herpes simplex virus, for capsid assembly and release of type D retrovirus, for capsid assembly of human immunodeficiency virus, and for budding of influenza virus [15] [16] [17] [18] . Therefore, it was expected that viral factors would modulate cellular energetics to benefit the virus, though this area is understudied [19] .", "Influenza A virus WSN33 was used to infect MDCK cells following previously published procedures for virus amplification and plaque assay [26] .", "RNAi experiments were performed using the lentiviral expressing system http://rnai.genmed.sinica.edu.tw, following the manufacturer's instructions. RNAi reagents were obtained from the National RNAi Core Facility located at the Institute of Molecular Biology/Genomic Research Center, Academia Sinica." ] },{ "paper_id": "d5878fe0a378d553186b212eeaadaa60257e933f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Written informed consent was obtained from all mothers who participated in the study. ", "Background: Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Dendritic cellspecific ICAM-3 grabbing-nonintegrin (DC-SIGN, also known as CD209) is an HIV-1 receptor that enhances its transmission to T cells and is expressed on placental macrophages.", "In 2010, UNAIDS estimates that 390,000 children acquired HIV-1-infection worldwide mostly through mother-to-child transmission (MTCT) [1] . Overall transmission rates in the absence of any intervention vary from 12 to 42%. Although antiretroviral therapy (ART) can reduce MTCT to as low as 2% [2] , limited access to timely diagnostics and drugs in resource-poor settings blunts the potential impact of this strategy. A better understanding of the mechanisms acting in MTCT of HIV-1 is crucial for the design of interventions other than ART for transmission prevention." ] },{ "paper_id": "d58edd47f5a609373fc4fbfd0b3cb4dfcec173c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the steps above will result in an ion-fragment peak table. Each row in the table corresponds with a sample. The first few columns will contain sample and patient data, such as sample data, age, gender and illnesses. The remaining columns will contain the abundances of the peaks or ion-fragments; typically there are a few thousand. This table will serve as input for extra quality checks and subsequent statistical analysis.", "The study will end when the required sample size is reached." ] },{ "paper_id": "d5a2557d0cb42ffcb93f693d7fa4e70fb817e20b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Twenty pancreatic primary tumors were purchased from Asterand, Inc (Detroit, MI). The panel included 13 adenocarcinomas (stage I-IV), 5 pancreatic endocrine tumors and 2 benign pancreatic adenomas. Four of the 20 pancreatic tumor tissue samples had matched normal adjacent pancreatic tissue samples. Patient age ranged from 23 to 77 years. All samples were freshly frozen and collected before the initiation of any cancer treatment. Tumor samples were macrodissected to remove normal tissue, and tumor purity in all samples was greater than 85%. Normal samples were macrodissected to remove non-glandular tissue.", "Cancer tissue cDNA arrays: HCRT101 (Colon Cancer), HGRT101 (Gastroesophageal Cancer), PNRT101 (Pancreatic Cancer), HLRT101 (lung cancer), and BCRT101 (breast cancer) were purchased from OriGene Technologies (Rockville, MD). Each array contains cDNAs from 5 to 8 normal tissues and 19 to 42 cancer tissues. The tumor stage ranged from stage I to IV and the tumor tissues were comprised of 50-90% tumor.", "The statistical significance of differences in affinity (apparent K D ) and cytotoxicity (EC 50 ) values was calculated using two-tailed, parametric t tests calculated in GraphPad Prism software version 5.01 for Windows (GraphPad Software).", "Carcinoembryonic antigen (CEA; CEACAM5; CD66e) is a glycosylated human oncofetal antigen that belongs to the CEArelated cell adhesion molecule (CEACAM) family of the immunoglobulin (Ig) gene superfamily [1, 2] . CEA is closely related to CEACAM1, CEACAM3, CEACAM4, CEACAM6, CEACAM7, and CEACAM8. Carcinoembryonic antigen has been suggested to mediate cell-cell adhesion, facilitate bacterial colonization of the intestine, and protect the colon from microbial infection by binding and trapping infectious microorganisms [3] ." ] },{ "paper_id": "d5a4d0cd6846bf609769f3274a5cbf22b11b14a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The WEF was prepared as described previously (Kim et al., 2014) . Dried EF was purchased from Yeongcheon Oriental Herbal Market (Yeongcheon, South Korea) and stored in the KM-Application Center herbarium (registration number, #354) Korea Institute of Oriental Medicine(KIOM), after verification of identity by Prof. Ki Hwan Bae (Chungnam National University, Daejeon, Korea). The WEF was filtered through standard sieves (150 \u00b5m, Retsch, Haan, Germany), concentrated by lyophilization, and stored at \u221220 \u2022 C until use .", "Fifteen authentic standards were used for the identification of phytochemicals in WEF. Psoralen (1), angelicin (2), rutin (3), quercitrin (4), isoquercitirin (5), syringin (9), caffeic acid (10), 1,3-dicaffeoylquinic acid (11), sweroside (15), and scopoletin (internal standard) were purchased from ChemFace (Wuhan, China). Quercetin (6), neochlorogenic acid (7), chlorogenic acid (8), p-coumaric acid (12), ferulic acid (13) ", "The genus Eupatorium (family Asteraceae) is known to include \u223c1,200 species in the world including Asia, America, Africa, and Europe and are known to have many biological activities including antinociceptive, anti-inflammatory, antibacterial, antifungal, anticancer, antiplasmodial, antioxidative, and anti-allergic activities and immunomodulating properties . The chemical composition of Eupatorium species include bioactive compounds such as flavonoids, monoterpene derivatives, sesquiterpenes, diterpenes, triterpenes, pyrrolizidine alkaloids, essential oil, and some other components .", "One-way ANOVA with Dunnett's test was used for the comparison of two groups. Treatment effects were evaluated via analysis. Statistical analysis was performed using GraphPad PRISM software (GraphPad PRISM software Inc., Version 5.02, CA, USA). * P < 0.01, * * P < 0.001, and * * * P < 0.0001 indicated statistical significance." ] },{ "paper_id": "d5b1fcbc43967a2f648462695d8c0a169aed6105", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Madin-Darby canine kidney (MDCK) strain II cells were maintained at 37\u00b0C in 5 % CO 2 in MEM (Gibco, Paisley, UK) supplemented with 10 % foetal bovine serum (FBS; Gibco) and MEM non-essential amino acids (Gibco). Experiments were performed on confluent or subconfluent cells cultured in 175 cm 2 culture flasks. McArdle cells (McA-RH7777, ATCC no. CRL-1601) were cultured in Dulbecco's modified Eagle's medium (Gibco) supplemented with 10 % FBS and 10 % horse serum (HS; Gibco) and maintained in 175 cm 2 culture flasks at 37\u00b0C, 5 % CO 2 under humidified atmosphere.", "Implications of the observed differences of DRM versus whole cell lipid composition, with respect to what this may imply for lipid raft composition in terms of membrane fluidity and membrane heterogeneity dynamics, are discussed including the role of cholesterol, cholesterol interacting proteins and glycolipids, with special reference to sperm physiology.", "Protein and phospholipid concentration in fraction 13 versus DRM containing fraction 5" ] },{ "paper_id": "d5bcb5d8c2edd7162e5f0fe6c189662b39eebfbe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal experiments and procedures were approved by the University of Wisconsin (UW)-Madison School of Veterinary Medicine Animal Care and Use Committee under relevant institutional and American Veterinary Association guidelines.", "Madin-Darby canine kidney (MDCK) cells were propagated in a minimum essential medium (MEM) containing 5% newborn calf serum and were maintained at 37 \u2022 C in an atmosphere of 5% CO 2 . Cell stocks are periodically restarted from early passage aliquots and routinely monitored for mycoplasma contamination.", "ML isolated a virus strain. AE, LG, RB, YK, and KW designed the experiments. AE, LG, and AS performed the experiments. HM, KS, JM, and KM conceived and designed the analysis. HM, KS, NH, and JW performed the analysis. HM and KW wrote the manuscript. All authors reviewed the manuscript." ] },{ "paper_id": "d5c3ab7d56a6d04ce4feb57a5dd9d0059abca0a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics approval and consent to participate Not applicable.", "The authors declare that they have no competing interests.", "Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. " ] },{ "paper_id": "d5cc1936183d8b73aa5006487dce09b3f8fe1d65", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Experimental shrimp (E. carincauda) were hatched in our lab. They were detected to be WSSV free through one-step PCR as described previously [22] . These shrimp were maintained in natural sea water with continuous aeration and were fed with commercial food pellet twice a day.", "WSSV was prepared and quantified as previously described [21] . The WSSV solution, serially diluted to 700 copies/ml with PBS, was used as inocula.", "Total RNA was extracted from cephalothorax samples with RNAisol reagent (Takara, Japan), assessed by electrophoresis in 1% agarose gel, quantified by NanoDrop 1000 spectrophotometer and treated with RNase free DNase I (Promega, USA) to remove the contaminating DNA. The cDNA synthesis were proceeded at 37uC for 2 hours with 4 mg RNA, 40 mM random primers (Sangon, China), 50 mM dNTP, 160 U RNasin (Promega, USA), 20 ml 56M-MLV buffer and 800 mM-MLV (Promega, USA) in a total volume of 100 ml." ] },{ "paper_id": "d5d29d1d48e1a4fe8f39d38639766c86dc976e5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Inclusion Criteria:", "1. Articles met initial screening criteria and were included if they met the following targeted requirements:", "Involved parties or entities played varied roles and represented diverse disciplines and sectors, as illustrated in Table 6 . " ] },{ "paper_id": "d5d68ccc9849f408aadaeb9c522469d610f323b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cordyceps fungi (i.e. Cordyceps sensu lato) are divided into four genera: Cordyceps sensu stricto (belonging to the family Cordycipitaceae), Ophiocordyceps (Ophiocordycipitaceae), Metacordyceps (Clavicipitaceae) and Elaphocordyceps (Ophiocordycipitaceae) ). Metacordyceps has partially to completely immersed perithecia and ascospores disarticulated or not. Elaphocordyceps is characterized by fibrous and darkly pigmented stromata, superficial to partially immersed perithecia and disarticulating ascospores, and parasitizes on either cicadas or the truffle genus Elaphomyces. Ophiocordyceps is composed of those former Cordyceps that give rise to darkly pigmented, fibrous and pliant stromata with superficial to partially immersed perithecia, disarticulating or non-disarticulating ascospores. Cordyceps species produce stromata with faint to bright pigmentation on the surface of leaf litter or soil and bear superficial to partially immersed perithecia, giving rise to ascospores that may or may not disarticulate .", "Although I. cicadae is a cosmopolitan species in many regions of the world, its natural resources is limited to satisfy the human demand. Large-scale cultivation of its mycelia and coremium has been successful. This fungus has not been approved by authority in China either as novel food or as medicine.", "G. roseum was isolated from Chinese cordyceps and has been developed to a medicinal product named Xinganbao capsule and cordyceps gliocladium oral solution based on the fermented mycelium. It could improve the liver function, reduce liver inflammation and fight against hepatic fibrosis (see the drug instruction of Xinganbao capsule). Hebei Changtian Pharmaceutical Co., Ltd. and Baoding Taifu Pharmaceutical Co., Ltd. are now manufacturing the products." ] },{ "paper_id": "d5d7c5ada2462aab2fa09789b1ef5ffe8e7f8d64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by the Institutional Review Board of Seoul St. Mary's Hospital, which waived the requirement for informed consent (No. KC15RISI0153)." ] },{ "paper_id": "d5dd18b98d06fac67015e3619c8e501ec02ad5a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To reduce possible batch effects, samples were processed in an inter-digitated manner using one sample from a wild macaque followed by one from a captive animal etc. until all samples were processed for sequencing. Swabs were stirred in VTM and removed from the collection tube. The fecal suspension was centrifuged at 8000\u00d7 g for 5 min at 4 \u2022 C and the supernatant (500 \u00b5L) was filtered through a 0.45 \u00b5m spin column filter (Millipore, Burlington, MA, USA) to remove bacteria and other large particulates. The flow-through was treated with a mixture of nuclease consisting of 400 \u00b5L of fecal filtrate, 14 U of Turbo DNase (Ambion, Thermo Fisher, Waltham, MA, USA), 3 U of Baseline-ZERO (Epicentre, Charlotte, USA), 30 U of Benzonase (Novagen, Darmstadt, Germany) and 30 U of RNase One (Promega, Madison, WI, USA) in 1\u00d7 Turbo DNase buffer (Ambion, Thermo Fisher, Waltham, MA, USA). The reaction was incubated at 37 \u2022 C for 1.5 h and then extracted immediately using the MagMAX TM Viral RNA Isolation kit (Applied Biosystems, Thermo Fisher, Waltham, MA, USA).", "As previously reported for other non-human primate species [69, 70] several adenoviruses were also detected including adenovirus G in one macaque. The species-crossing capacity of adenoviruses has been demonstrated [70] [71] [72] [73] [74] . Adenovirus G has also been reported in Macaca assamensis from Thailand [70] . Whether the adenovirus G virus detected here has the potential to infect human remains to be determined but represent the virus closest in sequence to one known to infect humans.", "Phages can contribute to the modulation of bacterial populations in the gut and regulation of intestinal physiology [2, 54] . The characterization of fecal swab viromes from 78 cynomolgus macaques showed that bacterial virus reads contributed the largest fraction of recognizable viral reads. Fecal virome composition may also be influenced by diet [55] [56] [57] . Changes in virome could affect the gut bacterial populations and contribute to digestive tract diseases such as inflammatory bowel disease [21, 58] . Here the most prevalent phage reads belonged to members of the Microviridae family, believed to infect mostly Bacteroidetes [59] . The Microviridae has experienced a large increase in its recognized diversity and specific member do not appear to be associated with particular mammals [44, 60, 61] ." ] },{ "paper_id": "d5f9caf3c407fae4690cd853b95d3c3e9b0a8b5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u00fe 0:191X 3 -0:080X 4 -0:220X 5 -0:083X 6 -0:147X 7 \u00fe 0:080X 8 F 2 \u00bc 0:030 X 1 -0:315 X 2 \u00fe 0:138 X 3 \u00fe 0:443 X 4 \u00fe 0:182 X 5 \u00fe 0:659 X 6 -0:214 X 7 -0:211X 8 F 3 \u00bc -0:253 X 1 -0:116 X 2 \u00fe 0:093 X 3 \u00fe 0:007 X 4 \u00fe 0:364 X 5 -0:318 X 6 \u00fe 0:936 X 7 -0:199X 8 F 4 \u00bc -0:144 X 1 \u00fe 0:288 X 2 -0:109 X 3 -0:119 X 4 \u00fe 0:148 X 5 -0:167 X 6 -0:148 X 7 \u00fe 0:972X 8 :" ] },{ "paper_id": "d603d8aa5b328d708683d754f224c1f9d170fc64", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reagents. LPS (serotype O55:B5) was obtained from Sigma-Aldrich (St. Louis, MO, USA). HW and hydrogen medium (HM) were prepared by dissolving H 2 gas as described previously 12, 75 . Both HW and HM had a concentration of >0.4 mM H 2 ." ] },{ "paper_id": "d604b2fa9328520de1cb77b550803b82b6bbbe87", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(ii) Analytical specificity. A panel of common respiratory pathogen culture supernatants ( Table 2 ) was used to validate the analytical specificity. All viruses tested negative by SAMBA.", "RNA preparation for quantification. For quantification of the culture stock, the diluted virus in UTM (1 in 100 dilution) was extracted using a QIAamp viral RNA minikit (Qiagen, Crawley, United Kingdom) according to the manufacturer's instructions (80-l elution volume).", "Clinical specimens collected from two sites (HPA Cambridge and WIV-ISP) were screened independently by qualified biomedical scientists for the presence of influenza virus according to their routine testing protocols." ] },{ "paper_id": "d617306cda56236d02117ae7a5fc5e7fcd015554", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Microscopy and deconvolution analysis. Microscopic analysis was carried out on an Olympus IX70 at 100X magnification. Images were captured and deconvolved using SoftWorx 2.50 on an SGI Octane workstation. MDC staining was detected at 360 nm excitation/457 nm emission. GFP-LC3 expression was detected at 490 nm excitation/ 528nm emission. Rhodamine was detected at 555 nm excitation/617 nm emission. Individual images from each stack were saved as TIFF files and processed in Adobe Photoshop 7.0.", "The SwissProt (http://us.expasy.org/sprot/) accession numbers for the gene products discussed in this article are 2BC and 3A (P03299), Atg12p (O94817), Atg8p (P38182), LAMP1 (P11279), LC3 (Q9GZQ8), mTor (P42345), Sec12p (P11615), Sec13p (P5573), Sec16p (P48415), Sec23p (P15303), Sec24p (P40482), and Sec31p (O94979).", "RNA interference to reduce intracellular concentrations of LC3 and ATG12. siRNA SMARTpools, consisting of four RNA duplexes targeting the gene of interest, and a control siRNA targeting firefly luciferase, were purchased from Dharmacon (Lafayette, Colorado, United States). For LC3, both LC3A and LC3B RNAs [93] were targeted, bringing the total number of transfected duplexes to eight. Pools consisted of an equal amount of each duplex. The siRNA sequences are given as sense/antisense pairs. The siRNA sequences for ATG12 were: GGGAAGGACUUACGGAUGUUU/59P-ACAUCC-GUAAGUCCUUCCCUU; GAACACCAAGUUUCACUGUUU/59P-ACAGUGAAACUUGGUGUUCUU; GCAGUAGAGCGAACAC-GAAUU/59P-UUCGUGUUCGCUCUACUGCUU; and UGUUGCAG-CUUCCUACUUCUU/59P-GAAGUAGGAAGCUGCAACAUU. The siRNA sequences for LC3A were: GGACGGCUUCCUCUAUAUGUU/ 59P-CAUAUAGAGGAAGCCGUCCUU; CGGUGAUCAUCGAGCG-CUAUU/59P-UAGCGCUCGAUGAUCACCGUU; ACAUGAGCGA-GUUGGUCAAUU/59P-UUGACCAACUCGCUCAUGUUU; and CGCCCAUCGCGGACAUCUAUU/59P-UAGAUGUCCGCGAUGGGC-GUU. The siRNA sequences for LC3B were: CAAAGUUCCUUGUAC-CUGAUU/59P-UCAGGUACAAGGAACUUUGUU; GAUAAUAGAAC-GAUACAAGUU/59P-CUUGUAUCGUUCUAUUAUCUU; GUAGAA-GAUGUCCGACUUAUU/59P-UAAGUCGGACAUCUUCUACUU; and AGGAGACGUUCGGGAUGAAUU/ 59P-UUCAUCCCGAACGUCUC-CUUU." ] },{ "paper_id": "d619c3ceec4db4f3f350c3d5fb3842bd83f04a80", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Furthermore, not only the physicians who may directly encounter with SARS patients need to be alert and better trained for this type of outbreak, obstetricians should also be aware and extremely cautious about suddenly substantial patient shift and strong demand of shorter length of maternity stay posed by the public's fear of such an outbreak. As these sudden changes in people's behaviors are likely to hinder patient's continuity of care and cause adverse maternal and neonatal health consequences, it is essential for obstetricians to be well prepared to deal with these consequences during an outbreak." ] },{ "paper_id": "d61d66e22524793eb025db202a84eaaae50da2bf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d62945f450e20fa12213b58d43cd1d0348de2e5b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "If sampling of i occurs before onwards infection:" ] },{ "paper_id": "d63201b4350a82c89280d64cf8a0fcbdffaaf40c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Milwaukee, WI) on Day 0 (baseline measure), Day 14 and Day 56 after LPS and MPS injection [19] . Four rabbits were randomly selected in each group for MRI on Day 0, 14, and 56.", "Nevertheless, there are some limitations to our study. Although the rabbit model of SAON has been widely utilized with a high incidence of necrosis [10, 19, 22] , no joint collapse caused by ON lesions occurs. This is attributed to differences in weightbearing, particularly at the hip, between quadrupedal animals and bipedal humans. Moreover, the exact mechanism by which the combination of PTH and CD improves treatment efficacy is still unclear, thus warranting further studies.", "Fifty-four adult male New Zealand White Rabbits (2.82\u00b10.16 kg) were used, including 40 for the osteonecrosis group (SAON) and 14 for the sham group (sham) (Fig 1) . Necrosis was induced by administration of steroids according to our previously reported protocol [19] ." ] },{ "paper_id": "d634751b77c1f304d9dc2a979806013710333b2f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All other enzymes (purchased from RD Systems, USA) were tested in concentration 2 \u00d7 10 \u22129 M in 20 mM Tris-Cl buffer supplemented by 150 mM NaCl (pH 7.4) at 37 \u00b0C for 30 min. Same conditions as above were applied to the assay.", "Kinetic parameters. The obtained substrate 1 displayed high affinity (expressed as K M reaching 7.6 \u00d7 10 \u22126 M) and moderate k cat value of 1 s \u22121 , and its specificity parameter value reached 1.3 \u00d7 10 5 M \u22121 \u00d7 s \u22121 (Fig. S7 ).", "A mass spectrometry quality check was performed at all stages of library deconvolution and all library components were identified within the HR MS spectra (Fig. S1 ). Similar analyses were performed for randomly selected sublibraries for each assayed position (X 4 , X 3 and X 2 ) identifying all signals corresponding to [MW+ H] + or its sodium/potassium adducts (Figs S9, S10 and S11)." ] },{ "paper_id": "d6398e61198491bab8f107952efe2bc30b9260b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d647c6b65ee08b38ecbd2bb85de064df41f7cf0f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "*PPM -Personal Protective Measures \u2020 Analytical method was not explicitly stated, however relevant reference was provided.", "Quotes are labelled with study reference, population, infection context and location.", "\".. .is he ill or is he dangerous something like that?" ] },{ "paper_id": "d64f2458851579ca8041d557f759eb0f8d515d6c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d65ee92563369f173d038fe15c6f066c4f134385", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "doi:10.1371/journal.ppat.1005501.g001" ] },{ "paper_id": "d65ef4b00759d797d28454625b4de2814675bb56", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Informed consent was obtained from all subjects according to an ethics protocol approved by The University of Western Ontario Research Ethics Board for Health Sciences Research Involving Human Subjects (HSREB).", "Additional file 1: Description of data: Table S1, Figure Legends , Figure S1 , Figure S2 , Figure S3 ." ] },{ "paper_id": "d660b285dc058ab74ce51cbd5179e01b9a6e8978", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thus, the network based index, I t , can quantitatively characterize the criticality of the state for each DNM member or node. Clearly, each node has an I t value, and hence those I t scores for all of nodes with the time evolution construct a landscape as shown in Figure 3 .", "As shown in Figure 1 " ] },{ "paper_id": "d6631a0f06bb98c73bfde3c98faf886c8be05522", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "can extrapolate from Peru. The number of missing cases was calculated as a Poisson random variable with mean given by AR*(2243*AR-615). We generate 1000 epidemic sizes for each attack rate.", "1. q t = 0.1, for all t, 2. q t = 0.5, for all t, 3. q 1 = 0.05, q 2 = 0.5, 4. q 1 = 0.4, q 2 = 0.9.", "ii. If q 1 > q 2 > 1 then SE R R SE ( ) ( ) 0 0 < \uf025 ." ] },{ "paper_id": "d665907080d2eae92859eab542dce90a57f11efb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Second, although the survey was well accepted, the quality of the resulting data is difficult to judge, as there are so few", "The early models of human immunodeficiency virus transmission tended to be very inaccurate, partly because of a lack of data on sexual behaviour. This stimulated a large number of detailed surveys of patterns of sexual mixing in many different countries (e.g. [15] [16] [17] ) that has lead to a deeper understanding of the spread of sexually-transmitted infections and improved model-based predictions.", "Of the 35 individuals asked to participate in the survey, 29 (83%) completed the questionnaire, 15 females and 14 males. One male was excluded from the analysis as he was not a full-time student (hereafter all results exclude this person). The ages of participants ranged from 18 to 24 years with a mean age of 20.5 years. Six first year undergraduates (aged 18-19 years) and 22 third year undergraduates (aged 20-24) participated in the survey." ] },{ "paper_id": "d66abf26034eafcdafdbcdac0b082a337ac2ffee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d672ce4063b2033261865d54cc7db91b9186beee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasma TNF-a concentrations were measured by enzyme-linked immunosorbent assay (rat TNF-a BMS622, Bender MedSystems, Vienna, Austria) [41] according to manufacturer's instruction.", "iNOS Immunohistochemistry (IHC)", "Protein concentrations were quantified with bicinchoninic acid (BCA) protein assay reagent (Pierce chemicals, Rockford, IL). Aliquots of the extracts were diluted in a 1:4 ratio with sample buffer (0.25 M Tris-Cl pH 6.8, 2% 2-mecaptoethanol, 8% sodium dodecyl sulfate [SDS], 0.02% bromophenol blue, and 40% glycerol) and boiled for 5 min at 100uC. All protein extracts were quantitated simultaneously to ensure subsequent equal protein loading. Protein extracts were separated on 10% SDS polyacrylamide gels (20 mg of protein per lane) and transferred onto a polyvinylidene difluoride membrane (Bio-Rad, Hercules, CA) by semidry electroblotting (Amersham Biosciences, Buckinghamshire, UK) for 45 min. Blots were blocked for 2 hrs at room temperature with 5% non-fat milk in Tris-buffered saline with 0.25% Tween 20, and then washed in TBS-T buffer solution. Membranes were hybridized with the mouse iNOS monoclonal IgG (1:500, BD Transduction, California, USA), mouse HMGB1 monoclonal IgG (1:1000, Abcam, Cambridge, UK), mouse IkB monoclonal IgG (1:1000, Santa Cruz Biotechnology, California, USA), and rabbit NF-kB monoclonal antibodies (1:500, Santa Cruz Biotechnology) in immunoreaction enhancer solution (Toyobo, Osaka, Japan) at 4uC for overnight. After wash, blots were exposed to horseradish peroxidase-conjugated anti-mouse IgG and anti-rabbit secondary antibodies (1:2000, KPL, Washington D.C, USA) for 1 hr at room temperature and immunoreactivities were visualized using an enhanced chemiluminescence (ELC) detection system (PerkinElmer life science, Massachusetts, USA). After stripping, blots were reporbed with a mouse anti-actin antibody (1:4000, Chemicon, Illinois, USA) and rabbit histone H2A polyclonal (1:2000, Cell Signaling technology, Beverly, CA) for normalization to equal protein loading. After scanning blots into computer, individual bands were analyzed by Image J software (National Institute of Mental Health)." ] },{ "paper_id": "d6750dff2734f993de45ffc3020428036b15ac21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Department of Livestock, Ministry of Agriculture Livestock and Fisheries of Kenya, County veterinary departments, and study area chiefs. This study was approved by the Kenyatta National Hospital/ University of Nairobi Ethics and Research Committee for conducting research on human subjects under permit reference number P210/04/ 2017. Informed consent was obtained from camel owners, handlers, and family members or their guardians (in case of underage children) from whom blood was collected. All institutional and National guidelines for care and handling use of animals were followed.", "For camel sampling, camel owners were informed about the study in a language that they understood. The camels were physically restrained, and 10 mL of blood from the jugular vein was drawn into anti-coagulant vacuum blood collection tubes. Additionally, 1163 nasal swabs samples were collected in RNAlater \u00d2 (Ambion, Foster City, CA, USA) and virus transport medium.", "Scale bar indicates nucleotide substitutions per site.", "Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creative commons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made." ] },{ "paper_id": "d68205dc527d5f0ee5a9ece74f3e7a7b22af8402", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Crystallization, structure determination of the N214A protease", "Severe acute respiratory syndrome (SARS) is the first emerging infectious disease of the 21st century and was caused by a novel coronavirus termed SARS-CoV. It suddenly broke out in China in 2002 and then rapidly spread to 32 countries, causing ,8500 infections and over 900 deaths (http://www.who.int/csr/sars/en/). So far neither a vaccine nor an efficacious therapy has been available. Therefore, it remains highly demanded to design the potential therapeutic agents against SARS.", "The structure overlay was done by LSQKAB from CCP4 suite [28] . All the figures were prepared using Pymol [31] ." ] },{ "paper_id": "d692faf09c38fc62f237f0ff9f2b3a2751ff76f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d69356747d4f5a940f9d2ee6e643d895b33f678e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d6941e8307d78b087937f9ee4324969ef7e1b623", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lamivudine (2R,cis-4-amino-l-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one, 3TC) is also an anti-HIV drug, approved in 1995 [40] .", "Adefovir (PMEA) yes [28] no [47] [48] [49] [50] [51] [52] effective in some cats, but relatively toxic I Tenofovir (PMPA) yes [25, 35, 45] nd possibly effective, but also likely relatively toxic IV", "Suramin no nd likely too toxic IV", "(1,1\u2032-(1,4-phenylenbismethylene)-bis(1,4,8,11-tetraazacyclotetradecane)-octachlo-ride dehydrate, AMD3100) is the bicyclam prototype compound. It is not marketed as an anti-HIV drug, but is used in humans for stem cell mobilization [84] ." ] },{ "paper_id": "d6a325260dac29bfe718f1e57160583cb23b5908", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This review describes the accumulating body of evidence suggesting that linagliptin may have protective effects against diabetic nephropathy, with a focus on preclinical studies and putative molecular mechanisms.", "Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors used to treat type 2 diabetes may have nephroprotective effects beyond the reduced renal risk conferred by glycemic control. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms.", "Other studies have also found a correlation between increased DPP-4 activity and diabetic and non-diabetic kidney disease [58] [59] [60] .", "Despite a common mechanism of action, DPP-4 inhibitors comprise a heterogeneous class of molecules with clinically relevant differences in pharmacology. Unlike other members of this drug class, linagliptin is non-renally excreted but capable of penetrating the various compartments of the kidney. Thus, based on its pharmacology and animal studies to date, linagliptin appears to offer the greatest potential for renoprotection." ] },{ "paper_id": "d6a34d159840a3895ac1768920a1c498d3c448c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.", "On admission, her highest recorded temperature was 39.2\u00b0C, and her oxygen saturation was maintained via room air (97 \u2212 99 %). Chest radiography showed diffuse bilateral lower lobe infiltrates (Fig. 1 ). Other laboratory findings included a leukocyte count of 6600/mm 3 comprised of 81 % polymorphonuclear cells, 13 % lymphocytes, and 5 % monocytes; a platelet count of 127,000/mm 3 ; alanine aminotransferase concentration of 254 U/L; and aspartate aminotransferase concentration of 258 U/L. The patient displayed normal renal function. A fetal ultrasound, performed upon admission, demonstrated a live intrauterine fetus of approximately 31 weeks of gestational age, and a posteriorly located placenta. MERS-CoV RNA was not detected in a nasal swab taken at that time.", "The male infant in the case reported herein was delivered by emergency cesarean under contact, droplet, and airborne transmission precautions. He was kept in the neonatal unit for observation, and was fed artificial " ] },{ "paper_id": "d6b52e3814a78239e5b5116dad2383b6faa327e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d6c06b168e38dd8418fbc697bb3cd5abbc7cdaa6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.", "All applicable international, national and/or institutional guidelines for the care and use of animals were followed.", "Exosomes, extracellular vesicles 30-120 nm in diameter, are released by various cells and have various physiological functions, as they transport proteins, messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs); facilitate intercellular communication; and elicit immune responses (10, 11) ." ] },{ "paper_id": "d6cbaee69496b4617b6032c4b82cfc7afe601fac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "FAST nitrocellulose slides (Schleicher & Schuell, Whatman) were printed at 20\u00b0C and 45% of humidity using a microarrayer (Omnigrid, GeneMachines) with 4 micro-spotting 70 \u03bcm diameter stealth pins with reservoir (TeleChem). Pins were fixed to dip once and prespot 10 times before printing approximately 3 nL of solution per spot. The separation between dots was 350 \u03bcm. Slides were kept overnight inside the arrayer at 20\u00b0C and 75% of humidity for immobilizing the antibodies. Nitrocellulose slides were stored at -20\u00b0C until use.", "List of Abbreviations scFvs: single-chain variable fragments; GFP: Green Fluorescent Protein; mAbs: monoclonal antibodies; MMP7: matrix metalloproteinase-7; pAbs: polyclonal antibodies; Trx: Thioredoxin." ] },{ "paper_id": "d6d7306eb3f303f7461ab6cab965ef0c5d179719", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nowadays, 69 countries worldwide are labeled as cholera-endemic, with 2.8 million cases each year leading to 91,000 deaths [37] . People in urban slums and refugee camps are at high risk of cholera because of limited or no access to clean water and adequate sanitation. CABM is an empirically and theoretically grounded model developed to study the 2005 cholera outbreak in Kumasi, Ghana [35] . The open-source code for the model code is available online.", "On a technical note, agent-based modeling software does not always include ML toolkits and libraries. This complicates the implementation of different types of social intelligence. Hence, better integration of ABM and ML in one software package or linkable libraries could eliminate this problem in the future.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Given the stochastic nature of ABMs, we ran each of the eight models 100 times. The average and standard deviations of the results of these runs for each output measure were listed in Table 3 ." ] },{ "paper_id": "d6d9d71d7a16885f268b86b5b8291bffa869ce43", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Headspace-solid phase microextraction -gas chromatographic mass spectrometry (HS-SPME -GC-MS) analysis" ] },{ "paper_id": "d6ea115f3fa7ea76715b04ee4a3f3a55add45397", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Picornaviridae family consists of 35 genera and 80 species, mainly including Enterovirus, Hepatovirus, Cardiovirus, Aphthovirus, and Rhinovirus [1] . To date, research on picornaviruses has mainly focused on enterovirus (EV) 71, coxsackievirus (CV), poliovirus (PV), encephalomyocarditis virus (EMCV), foot-and-mouth disease virus (FMDV), human rhinovirus (HRV), and hepatitis A virus (HAV). Picornavirus infections can cause enormous damage in humans and animals. The EV71, CVA16, and CVA10 cause hand, foot, and mouth disease in millions of children in Asia-Pacific region each year and can cause more serious clinical symptoms such as aseptic meningitis, acute flaccid paralysis, and neurological respiratory syndrome [1] [2] [3] .", "Author Contributions: Z.L., Z.Z. and Z.J. wrote the manuscript; Q.L. and X.H. revised for its integrity and accuracy; Q.L. approved the final version of this manuscript and takes responsibility for its contents. ", "The authors declare no conflicts of interest. " ] },{ "paper_id": "d6ea3039fed0942c355cabc8a67f7226cd05fc8c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HeLa cells cultured on glass coverslips were transfected with 1 \u03bcg of the indicated RNA samples prepared above, together with 0.5 \u03bcg of an empty pUC19 vector, using the FuGENE HD transfection reagent.", "defined as SGs based on the expression of related proteins such as G3BP1 and TIAR. G3BP1 and TIAR are well-established SG-associated proteins that are typically and diffusely present throughout the cytoplasm and dominantly present in the nucleus, respectively. However, treating cells with arsenite markedly changed the localization to form SGs containing these proteins in nearly all cells ( Figure 1A) .", "We first examined whether G3BP1-positive granular structures were formed during infections by a series of C knockedout and mutated SeV recombinants and the parental Z strain by immunofluorescence microscopy (Figure 1 ; Supplementary Figure S1 ).", "Translational arrest is one of the IFN responses of host cells triggered by viral infections. Various eukaryotic translation initiation factor 2 (eIF2) kinases such as protein kinase R (PKR) are activated in response to IFNs, and the accumulation of phosphorylated eIF2\u03b1 inhibits the translation of both cellular and viral mRNAs Kedersha and Anderson, 2002; Holcik and Sonenberg, 2005) . Cytoplasmic stress granules (SGs), which are the foci of concentrated 48S translation preinitiation complexes and defined by certain marker RNA binding proteins such as T-cell intracellular antigen-1 (TIA-1), TIA-1-related protein (TIAR), and Ras-Gap-SH3 domain-binding protein (G3BP1), are formed under these conditions Kedersha and Anderson, 2002) . Because they contain stable inert mRNA, SGs are believed to serve as temporary sites at which mRNAprotein complexes are stored to pause active translation or be decayed in adjacent processing bodies (Anderson and Kedersha, 2006; Balagopal and Parker, 2009; Buchan and Parker, 2009) ." ] },{ "paper_id": "d6ea8e153027d428bc443df40d70bfa2134a2deb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author(s) declare that they have not competing interest. " ] },{ "paper_id": "d6f1c9865c7d63536a77b8ba4e9bad1b507f9eb6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HAdV + HRV + Myco 0 (0.0%) 2 (0.06%) 1.000 " ] },{ "paper_id": "d6f350fa81730f8476614ffe7280454633d77f31", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Checklist S1 STROBE Statement-checklist of items that should be included in reports of observational studies. (DOC)" ] },{ "paper_id": "d708b6876813c3915edcbdda08c014d90ec694ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hospitals also seemed to favour innovation in health technologies providing perceived competitive advantage over other hospitals.", "(1) publicity, (2) relevance, (3) revisions and (4) enforcement (Daniels and Sabin 2002) ." ] },{ "paper_id": "d7101f63979fbbfbce1f7b9b1e6bd51f50adfd02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For protein expression analyses with western blots, PBL were first lysed in lysis buffer (9 M Urea, 2 M Thiourea, 65 mM Dithioerythritol, 4% CHAPS). Proteins were then separated by SDS-PAGE on 8% gels (7 \u00b5g protein/slot) and blotted semidry onto 8.5 \u00d7 6 cm PVDF membranes (GE Healthcare, Freiburg, Germany) and blocked with 4% BSA (1 h). Blots were incubated overnight with respective primary antibodies: rabbit anti-pSTAT1 Tyr701, rabbit anti-pSTAT3 Tyr705 (Cell Signaling, Darmstadt, Germany, 1:500) or mouse anti-beta actin (Sigma, Taufkirchen, Germany, 1:5000). As secondary antibodies, either HRP-coupled goat anti-rabbit IgG (H+L) antibody (Cell Signaling, Darmstadt, Germany, 1:5000) or goat anti-mouse IgG (H+L) antibody (Sigma-Aldrich, Taufkirchen, Germany, 1:5000) were used (1 h). Signals were detected by enhanced chemiluminescence on Xray film (SUPER-2000G ortho, Fuji; Christiansen, Planegg, Germany). Films were scanned on a transmission scanner and densitometric quantification of Western blot signals was performed using ImageJ software (open source: http:// imagej.nih.gov/ij/). Abundances of pSTAT1 and pSTAT3 were subsequently normalized to beta actin.", "Staining of 5 \u00d7 10 5 cells per well was performed with anti-bovine cluster of differentiation (CD) 4 (mouse IgG1 monoclonal, Bio-Rad AbD Serotec, Puchheim, Germany; 1:100), anti-bovine CD8 (mouse IgG2a monoclonal, Bio-Rad AbD Serotec; 1:50) and FITC-conjugated anti-bovine IgM (Bio-Rad AbD Serotec, Puchheim, Germany; 1:50) antibodies, diluted in staining buffer (1% BSA + 0,001% NaN 3 in PBS). Respective secondary antibodies anti-mouse IgG1 FITC and anti-mouse IgG2a FITC (both Santa Cruz Biotechnology; Heidelberg, Germany 1:200) were added. All antibodies were incubated for 30 min on ice. Cells were washed with staining buffer between primary and secondary antibody staining steps (200 \u00d7 g, 4 \u2022 C, 1 min). For all stainings with secondary antibodies respective isotype controls were used. Cells were fixed in 1% PFA diluted in staining buffer and stored at 4 \u2022 C until analysis. On FACS Canto II, measurement of cells was performed with FACS Diva Software (BD Biosciences). Lymphocytes were gated according to forward scatter (cell size) and side scatter (intercellular granularity) properties of cells. Per staining, between 5 \u00d7 10 3 and 1 \u00d7 10 4 cells were measured. ", "Bovine venous blood samples were collected in tubes with heparin sodium 25.000 I.U.. Blood was diluted with equal parts " ] },{ "paper_id": "d710e993d5c0aca81ed537d9462953a234309a1c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Griffithsia sp. griffithsin", "Molecular cartoons were drawn with Chimera [113] and YASARA.", "The authors declare no conflict of interest. " ] },{ "paper_id": "d71ba68f8d3e03e0a16d0ab59675786bae69b6ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Establishing the RPA-LFS assay", "Analytical sensitivity and specificity of the RPA-LFS assay", "We have developed an Ebolavirus assay that could be implemented in low-resource laboratories that do not have the capacity for RT-PCR, and this assay could potentially be helpful in the next outbreak. However, field evaluation of the assay in a typical clinical setting will help to determine clinical sensitivity and specificity respectively, and areas of improvement. " ] },{ "paper_id": "d71c2fa8fe1c3df75d031c50267993ede529b85c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Binding assays were performed with ten micrograms of whole cell extracts incubated in a total volume of 15 \u03bcL with buffer containing 50 mM HEPES (pH 7.9), 10% glycerol, 200 mM KCl, 5 mM EDTA (pH 8), 1 mM MgCl 2 , 5 mM DTT, and 1 \u03bcg of poly (deoxyinosine-deoxycytidylic) acid sodium salt (Sigma-Aldrich) to eliminate non-specific binding. Samples were incubated on ice for 10 min, followed by the addition of 150,000 CPU of 32 P-labeled DNA probe and 20 min of incubation at room temperature.", "Oligonucleotide probes corresponding to the ISREs of ISG15 and OAS were annealed to their complementary oligonucleoides using annealing buffer containing 100 mM NaCl and 50 mM HEPES (pH 7.6). Forward sequences for probes used:Oas1b ISRE: TTCCCGGGAAATGGAAACT GAAAGTCCCAT,ISG15 ISRE: GATCGGAAAGGGAAA CCGAAACTGAAGCC. T4 PNK (New England Biolabs) was used to end-label annealed probes with \u03b332ATP. Samples were electrophoresed at 180 Volts in 0.5% Trisborate-EDTA buffer on a 5% native polyacrylamide gel composed of 49:1 acrylamide to bis-acrylamide. Gels were dried on Whatman paper at 80\u00b0C for 1 h and exposed by autoradiogram.", "Expression plasmids were assayed for protein expression by Western blotting. Lysates were then run on SDS-PAGE gels (NuPage, Invitrogen) and blotted to PVDF membrane (Invitrogen). Proteins were visualized using anti-GFP antibody (G1544, Sigma Aldrich), anti-HA (Sigma H3663), anti-Flag (Sigma F7425), HRP-conjugated secondary antirabbit antibody (NA934, GE Life Sciences) and HRPconjugated secondary anti-rabbit antibody (NA931, GE Life Sciences)." ] },{ "paper_id": "d729eef3818cc854484ab0550aa245e5eaa2b72e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Heat shock proteins and solute carriers (HSPA2, HSPB1, HSPA8, SLC5A1) play a role in maintaining homeostasis and buffering the negative impacts of hyperthermic conditions as well as disease challenges [30, 31] . Heat shock proteins function in protein folding, intracellular trafficking, and managing proteins that are denatured by heat and other stresses, such as pathogens. Some heat shock proteins, such as HSPA2, are involved in binding antigens and presenting them to the immune system [32] .", "Genotyping was performed as single SNP assays using fluorescence-based allele specific detection with KASP chemistry [40] and analysis with Kraken software (LGC, Hoddeston, UK). The SNP data of each gene for each bird was used to identify the haplotypes segregating in the population and the specific haplotypes that were held by each individual. Haplotypes were defined by co-segregation patterns of SNPs (Tables S2-S12). Any haplotype occurring less than 10 times (0.5%) was excluded from the analysis.", "Heritabilities were estimated in ASReml 4 [42] using the following univariate animal model:", "Supplementary Materials: The following are available online at http://www.mdpi.com/2073-4425/9/11/560/s1, Table S1 : Genotyping details, SNP locations and impacts, Funding: K.R. was supported by a USDA National Needs Fellowship (2013-38420-20496). This work was supported by USAID Feed the Future Innovation Lab for the Genomics to Improve Poultry and Hatch project #5357. This study was made possible by the generous support of the American people through USAID. The contents are the responsibility of the Feed the Future Innovation Lab for Genomics to Improve Poultry and do not necessarily reflect the views of USAID or the United States Government." ] },{ "paper_id": "d73750cd7f032ab3f9fe5cf6f9a861c9e7567289", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The proteins encoded by the CoV genomic RNA (gRNA) can be divided into two major categories. The first entails the 15 or 16 nonstructural proteins (nsp1 to nsp15/16) 1, 2, 7 , which are synthesized in the host cell and assemble into the replicase-transcriptase complexes (RTCs). RTCs are associated with and/or are embedded into double-membrane vesicles (DMVs) and convoluted membranes, which are generated during CoV infection and very likely act as replication platforms 8 . The second category contains the structural and accessory proteins. A minimal set of 4 structural proteins is critically required for the efficient formation of infectious virions 1, 2, 7 . Those include the envelope (E), the membrane (M), the spike (S) and the nucleocapsid (N) proteins.", "Coronaviruses (CoV) are enveloped positive-stranded RNA viruses and Coronaviridae can be subdivided into four groups based on phylogenetic clustering: alpha-, beta-, gamma-and delta-CoV 1, 2 . Members of this virus family infect the mammalian respiratory and gastrointestinal tracts by incompletely understood mechanisms 2, 3 . The relevance of this virus family has considerably increased due to the recent emergence of the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which are caused by viruses belonging to the beta-CoV group 4, 5 . The Mouse Hepatitis Virus (MHV) is closely related to SARS-CoV and MERS-CoV, and considered the prototype for the investigation of the CoV life cycle 6 .", "MHV-infected LR7 cells were centrifuged at 15,000 \u00d7 g for 10 min (4 \u00b0C) to obtain a pellet (P13) and a supernatant (S13), which was further centrifuged at 110,000 \u00d7 g for 60 min (4 \u00b0C) to also get a pellet (P45) and a supernatant (S45). Proportional aliquots of Ext, P13, P45 and S45 fractions were examined by resolving them by SDS-PAGE and then by probing western blot membranes with monoclonal antibodies against MHV N protein and polyclonal antisera against GAPDH (Fitzgerald, North Acton, MA), tubulin (Sigma-Aldrich, St. Louis, MO) or VAPA (Santa Cruz, Dallas, TX)." ] },{ "paper_id": "d739cf97cba31e655d6c7438b864d94297f59ba3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BoHV-1 infection can cause conjunctivitis, pneumonia, genital disorders, abortions, and an upper respiratory infection known as bovine respiratory disease (BRD) or \"Shipping Fever\" [136] . BoHV-1 initiates BRD by immunosuppressing cattle [24, [48] [49] [50] 152] , which can lead to pneumonia as a result of secondary bacterial infections. BoHV-1 induced immune-suppression can result in secondary bacterial infections (Pasteurella haemolytica, Pasteurella multocida, and Haemophilus somnus for example) that cause life-threatening pneumonia [152] . BRDC and BoHV-1 infections costs the cattle industry at least $3 billion/year in the United States [1, 15, 24, [48] [49] [50] 71, 79, 122, 136] . Modified live vaccines are available, and in general, they prevent clinical disease in adults. However, the same vaccine strains are immunosuppressive and can cause serious disease in young calves or abortions in pregnant cows.", "Mice lacking type I and type II interferon receptors in combination with RAG-2 gene deletions die within a few days following BoHV-1 infection [3] . In contrast, BoHV-1 infection of wt mice does not lead to clinical symptoms or extensive viral replication highlighting the importance that IFN plays in controlling BoHV-1 replication and pathogenesis.", "BoHV-1, BoHV-5, and equine herpesvirus 1 encode a glycoprotein (gG) that is secreted from infected cells, and can bind to a broad range of chemokines [21] . Interactions between gG and chemokines block chemokine activity by preventing their interactions with specific receptors and GAGS. By preventing chemokine-GAG interactions, gG disrupts chemokine gradients, which controls the local environment surrounding an infected cell. A BoHV-1 gG deletion mutant was reported to have reduced virulence [78] suggesting gG is a viral immune evasion gene. However, the exact role of gG in virulence requires additional studies because the gG mutant that was examined was not rescued, and expression of surrounding genes was not examined." ] },{ "paper_id": "d73d189618e61f04c6dbabf3bbf8aa7adc65b156", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the present status of health care technologies, Veterinary Medicine will enter a phase of new and incredible transformations. Recently, nanotechnology offers great significant contributions for the ", "Nanosensors and MEMS technologies provide excellent opportunities as gas sensors for the agri-food sector and also to monitor temperature, pressure, and other processing parameters [238] . Applications of nanosensors opened a new avenue ranging from whole body monitoring to diagnosing various diseases due to their unprecedented sensitivity. Majorly, nanosensors are working based on two detection principles, such as catalytic and affinity sensing. Catalytic sensors utilize enzymes, cells, tissues/organelles and microorganisms as the recognition agent. Affinity sensors are those that utilize whole antibodies, antibody fragments, nucleic acid/aptamers, receptors, lectins, phages, novel engineered scaffold derived bonding proteins, molecular imprinted polymers, plastic antibodies, and synthetic protein binding agents as the recognition agent [239] . Nanosensors have major role in veterinary sciences, they use very small amount of a chemical contaminant, virus, or bacteria, which is helpful for agriculture and food systems that in return improves the feedstock [240, 241] ." ] },{ "paper_id": "d73eaecdf6e03c65d962791c98563c8a7d5cf79a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d7433f2be08b0e833cb270ee2ac736dce1e1a98e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ".2 shows the additional goodness-of-fit results arising from treating the network as multilevel. In particular, results for female-bipartite, male-bipartite, and female-bipartite-male network interactions are shown. All statistics are fit to an acceptable standard. Because the same-sex networks are fixed, graph statistics without bipartite edges show zero variation. The ability of this model specification to closely capture all these features of the empirical network, including ones not explicitly modelled, is strong evidence that a useful model has been specified. ", "Tables S4.1 and S4.2 show the goodness-of-fit results (burn-in 1,000,000 iterations, 1,000,000 iterations per graph, 1000 graphs) for the multilevel exponential random graph model (ERGM) for the relationships network. Results were generated using MPNet [1] [2] [3] . Table S4 .1 shows the results for just the bipartite network. Column 1 lists the various statistics that are evaluated. Column 2 shows the value of the statistic for the empirical network (\"Sample\"). Columns 3 and 4 show the mean (\"Mean\") and sample standard deviation (\"Std. Dev.\"), respectively, of the statistic over simulated networks. Column 5 shows the \"t-ratio\", defined as (observed value-mean value)/standard deviation. For each parameter, using standard methodology, the model is a good fit for the empirical network if the \"t-ratio\" has absolute value less than 0.1 for parameters explicitly in the model (shown in boldface) and less than 2 otherwise." ] },{ "paper_id": "d745e9cbecf81be30e9ffe290781acea84fbd9d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The classical ''gold standard'' diagnosis for HEV71 and CVA16 is by cell culture, followed by neutralization tests with serotypespecific antisera [4] . However, this requires 2-3 weeks of growth and neutralization of the viral isolates. Furthermore, antigenic typing could be hindered by nonneutralizable viruses because of aggregation, antigenic drifts, or the presence of multiple viruses in the specimens [11] . The development of PCR techniques has contributed significantly to laboratory diagnosis of viral infections in terms of sensitivity, specificity, and the rate of detection in comparison with the cell culture method.", "Hand, Foot, and Mouth Disease (HFMD) is a common illness of infants and children under 10 years of age, and is characterized by fever, sores in mouth, and rash with blisters. Epidemiological data show that HFMD had an increasing trend in Southeast Asia in the past 20 years. It is well known that a big outbreak of HFMD occurred in Taiwan in 1998 [1] . In China, the number of HFMD cases and fatal HFMD cases has been increasing every year, and multiple major HFMD outbreaks caused by Human enterovirus 71 (HEV71) had occurred in several provinces in China. HFMD affects more than one million children and is responsible for several hundred children deaths every year, causing widespread concern in society.", "The real-time PCR assays developed in recent years have many advantages, such as improved sensitivity, specificity, and reproducibility, and have been applied to the detection of a range of different respiratory viruses [12, 13] . An important aspect of this method is that the reaction and detection take place in a closed tube, which can effectively avoid contamination, and no post-PCR handling, such as agarose gel electrophoresis, is required." ] },{ "paper_id": "d7528a14c4876dbffb163105631a9dea22f20f83", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Project name: Glycosylator. Project home page: https://github.com/tlemmin/ glycosylator", "Operating system(s): Platform independent.", "Programming language: Python." ] },{ "paper_id": "d7531ccb3a8417e35a8a34badd9ae40ea731c7fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Investigation of the recently discovered tick-borne Jingmen virus has revealed that a segmented RNA virus has a genome derived in part from unsegmented viral ancestors 10 . However, the mechanism by which an unsegmented RNA virus undergoes genome segmentation into a segmented virus is unclear.", "Segmented RNA viruses are widespread in nature and include important human, animal and plant pathogens, such as influenza virus and tick-borne Jingmen virus. Viruses with segmented and unsegmented genomes typically belong to different viral families 8 . Unsegmented foot-and-mouth disease virus reportedly undergoes segmentation into two RNAs during prolonged cell culture 9 .", "Each fecal sample was re-suspended (1:10, wt/vol) in PBS buffer and vortexed thoroughly. The suspension was clarified by centrifugation at 15,000\u00d7g for 10 min. The total viral nucleic acids were extracted with a QIAamp viral RNA mini kit (Qiagen, China) according to the manufacturer's protocol. The concentration and quality of final RNA were examined using an ND-1000 UV spectrophotometer. These RNA were randomly merged into four pools for RNA-seq library construction and sequencing.", "For the confirmation of high-throughput sequencing results, we used nested RT-PCR to examine each potential viral sequence by specific primers. To obtain longer sequences or the complete genome, we used genome walking (Takara, Japan) and 5\u2032 and 3\u2032 rapid amplification of cDNA ends (Roche, USA) according to the manufacturer's protocol. All specific primers used are available on request." ] },{ "paper_id": "d75571144654e55a962409ab789839f59f7e772d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We further tested the target specificity of the MAVS and TRIF cleavage sites by analyzing a control mutant TRIF target site. A mutant TRIF cleavage site was constructed in which the C residue at the P1 position was substituted with a Y residue (Fig. 1 ). As shown in Fig. 3C , the mutant TRIF cleavage site prevented phage replication, indicating that TRIF processing was specifically mediated by CHV NS3/4A protease.", "Recent studies have identified viruses, in domestic dogs and horses, which are genetically very closely related to HCV [3, 4] . These findings suggest that HCV could have been introduced into the human population through contact with dogs and/or horses. Nevertheless, adaptation of CHV and NPHV to human cells would likely require these viruses to evade the human cellular innate immune response, which responds to viral pathogens by RNA composition-dependent activation of RIG-I and subsequent signalling via interferon regulatory factor (IRF)-3 [6] . The response to HCV infection is regulated by hepatic immune defences triggered by cellular RIG-I [14, 32] . In human liver cells, HCV interferes with RIG-I-dependent signalling to IRF-3 by NS3/4A-dependent cleavage of the crucial adaptor protein MAVS [14] . Likewise, TLR-3-dependent signalling to IRF-3 is ablated by cleavage of TRIF by the HCV NS3/4A protease [15] .", "The origin of hepatitis C virus (HCV) infections in humans has remained unknown, because related animal virus homologs had not been identified [1, 2] . Recently, a Flaviviridae RNA genome that was isolated from domestic dogs with respiratory illness was found to be the virus most closely related to HCV [3] . This Flaviviridae agent is known as canine hepacivirus (CHV). The discovery of CHV may shed light on the origin of HCV, and may also serve as a new model system with which to study this deadly human virus. CHV-like viruses (also known as nonprimate hepaciviruses [NPHV] ) were also recently identified in horses [4] . HCV belongs to the genus hepacivirus, one of the four genera in the family Flaviviridae [2] . HCV infects more than 170 million people worldwide (http://www.who.int/mediacentre/factsheets/fs164/ en/) and is one of the leading causes of liver cirrhosis and failure [5] . Although the discovery of the close homology between CHV and HCV is intriguing, there are barriers preventing viral transmission across species. Cross-species transmission of CHV to humans would most likely require evasion of the human cellular innate immune response, which leads to type I interferon production through RNA composition-dependent activation of retinoic acid inducible gene-I (RIG-I) and toll-like receptor (TLR) [6] ." ] },{ "paper_id": "d75b9ec5230fea9af4abc83383da97a102230cfd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RSV infection is one of the most common infections in children [2, 135] . In adult, RSV infection usually leads to self-limited upper respiratory illness [136] . However, severe RSV infection has been observed in elderly patients with lung diseases or in immunocompromised patients [137] . Current management of RSV includes bronchodilators, corticosteroids, antibiotics and supportive care [2] , but their efficacy is not satisfactory. To date, there is no licensed vaccine available to prevent this disease [138] . There is an unmet need to develop effective RSV therapeutics and vaccines in both the pediatric and adult population.", "Tuberculosis (TB) is a bacterial lung infection caused by Mycobacterium tuberculosis (Mtb). Because of the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB, the slow development of new anti-TB agents and the inefficiency of vaccination, TB is still a major global health problem. WHO reported that 9.6 million people suffered from TB in 2014 and 1.5 million die annually because of the disease [151] . A new and effective TB therapeutics is highly sought after.", "ALI is a severe form of diffuse lung disease that is commonly caused by acute systemic inflammatory disorders, such as sepsis, pneumonia, trauma and pancreatitis [11, 212] . It is a progressive disease, which can lead to acute respiratory distress syndrome (ARDS) or more critically, multiple organ failure and even death [175] . Its pathological changes include the release of pro-inflammatory cytokines and chemokines, and the destruction of the epithelium-capillary interface; the latter can facilitate the extravasation of protein-rich fluid and the infiltration of neutrophils, thereby exacerbating the condition [213, 214] . Since the molecular mechanism underlying the pathology of ALI is not well understood, there is no pathophysiologic-driven therapeutic approach available [162] ." ] },{ "paper_id": "d75d565a2c7f9bc13b6dbb4fa45eb85e2a1c72cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To construct a model capable of addressing these questions, the following data requirements were identified:", "It is instructive to compare our results with the qualitative risk assessment undertaken by WHO offices in September 2014, which focused on Pacific Island countries [14] . The assessment identified 3 scenarios:", "2. A localized cluster due to transmission in a health facility or social contacts. The assessment noted 'If an imported case occurs, the chance of limited secondary transmission would be moderate to high. Frontline health workers, patients, health facility visitors and social contacts would likely be exposed'; and", "The prospect of EID outbreaks in low and middle income countries raises particular concerns and challenges for global health agencies. The risk of emergence of novel pathogens in many of these countries is elevated [4] , and there may be limited capacity to mount an effective response [5] . Greater global connectivity increases both the risks and international consequences of EID outbreaks in these countries [6] . In consequence, there is a growing recognition that health security is a shared responsibility and that supporting health care systems capacity in low and middle income countries is a necessary step towards improving global health security." ] },{ "paper_id": "d760a0c49650a6c2a3d822bab4417057e6be1cd1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors wish to replace the introduction of [28] with the following:", "A number of sentences in the first paragraph of the introduction of [28] were copied verbatim from [21, 22, 25, 29] . Although [21, 22, 25] were cited in the text, [29] was omitted and it was not made sufficiently clear that direct quotations were used. The authors wish to apologize to the authors of [21, 22, 25, 29] and to the readers of the journal for any inconvenience.", "OPEN ACCESS" ] },{ "paper_id": "d766ab43735b3ae26606a19ef9ddbe46c77fb24e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The complete genome sequence of FAstV2 1637F has been submitted to GenBank under the accession no. KF499111.", "We report the first complete genome sequence of a feline astrovirus (FAstV), FAstV2 strain 1637F, identified from a domestic cat. The genome is 6,779 nucleotides (nt) in length and consists of three overlapping open reading frames (ORF1a-ORF1b-ORF2). Sequence analysis suggests that FAstV2 represents a new FAstV genotype that is closely related to human astroviruses.", "The complete genome of FAstV2 1637F was amplified and sequenced using published strategies for single-stranded positivesense RNA viruses (1, 10). RNA was extracted from the fecal sample with the EZ1 virus minikit (Qiagen, Germany) and used as a template. RNA was converted to cDNA by a combined randompriming and oligo(dT) priming strategy. The cDNA was amplified by degenerate primers designed by published strategies (10) . The 5= end of the viral genome was confirmed by rapid amplification of cDNA ends using the SMARTer RACE cDNA amplification kit (Clontech, USA). The sequences were assembled and manually edited to produce the final genome sequence." ] },{ "paper_id": "d76707259c99c13efac920c66169aa4560438499", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fitting time series using ARIMA models with trend and seasonality patterns", "AutoRegressive Integrated Moving Average (ARIMA) models have become popular tools for analyzing time-series data in both veterinary and public health disciplines [32] . ARIMA models can be used for short-term forecasting of acute infectious disease incidences like influenza and hence aid in disease intervention strategies [33] . Classically, ARIMA( p,q) models are defined in the following way:", "Week", "The Wilcoxon signed-rank test indicated no significant difference (P-values <0.05) between observed and reported cases with a median difference of approximately 1.2 weeks between the date of observation and reporting (8 days) . Therefore, we decided to use the reporting date series for all temporal analyses, in which the final count of cases matched those of both WHO and MoH databases for the GCC countries, because in 20.8% of cases the observation date information was missing." ] },{ "paper_id": "d7788ab137f05cf1c247c60dbe388b80fb5764a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The team concluded that the next step to improve predictive capabilities would be to fit a full multistrain model of influenza, but they questioned whether the available data were adequate to do so. 13 ", "Further work is needed to clarify the role of seasonality 31 and other stochastic factors such as demographics and environmental and climate changes. 34 ", "Zoonotic diseases are diseases that are passed from an animal reservoir to humans, many times through intermediate hosts such as horses, monkeys, and the like. Ebola virus disease (EVD) is one such disease. While the animal reservoir for EVD has still not been identified with certainty, spillover events that originate disease outbreaks have been linked to human contacts with bats. 39 Since the large 2014 West Africa outbreak, the dynamic of EVD has been thoroughly investigated. 38 ", "To evaluate the effectiveness of social distancing, the model was extended to automatically fit a window of variable duration at any start date, where the optimizer could amplify, attenuate, or leave unchanged the base transmission rate. 15 In searching for a start date, duration, and transmission rate scale factor that would minimize differences between the estimated and actual incidence, an arithmetic algorithm determined the window was optimally placed on April 24, the day schools were actually closed, and that the social distancing measure, controversial at the time it was implemented, was effective for a period of 6 days. Within the window, the reduction in reproductive number (and transmission rate) was *22%, a reduction close to that predicted earlier for the reduction in transmission expected among children. 17 " ] },{ "paper_id": "d77d46a447e665ddfcc2fe9a89a28b83f3050c5b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d77dcb77a4a620fd1de81f309bff0e04e2578272", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The web interface of Hotspot Hunter is intuitive, making use of a set of simple Graphical User Interface forms. Programs were built using a combination of Perl, CGI and C language. The implementation was carried out in SunOS 5.9 UNIX environment." ] },{ "paper_id": "d7803599fa57f39b06d7fd5bc8986420ae13fc2c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. Data were analyzed by unpaired t tests or ANOVA followed by Dunnett's multiple comparison tests using GraphPad Prism (GraphPad Software, San Diego, CA). The p values smaller than 0.05 were considered significant." ] },{ "paper_id": "d7817865765ddf7b0e1635e74b7a9393d0979a66", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coordinates and structural data have been deposited in the Protein Data Bank with accession codes 4k3u, 4k40, 4k7j and 4k9s.", "3.1. The overall structure and topology of Ape1", "The different stages in the catalytic cycle that we postulate are possibly because of crystal packing and accessibility." ] },{ "paper_id": "d78837afeedbb3c9dfa91a675aa03d34ef5a4387", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Confirmed in mice [23] and humans [24] TSP-1 CD36 (in complex with integrin \u03b1v\u03b23 or \u03b1v\u03b25) Confirmed in humans [21, 25] ", "Integrin \u03b1v\u03b23 or \u03b1v\u03b25 through MFG-E8 Low \u03b1v\u03b23 expression in humans [21, 22] ", "In any tissue, cell turnover is a natural homeostatic process and occurs predominantly by apoptosis before loss of plasma membrane integrity. Timely removal of these apoptotic cells is critical to prevent autoimmune reactions to cellular constituents. However, the speed of turnover determines the requirements for the local phagocytic system in terms of its capacity to clear the accumulating apoptotic cells and is often governed by the local microenvironment and past inflammation history." ] },{ "paper_id": "d78b99436685b3f545dedc32f1166776b916abd6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Validation methods for the determination of diagnostic sensitivity, specificity, repeatability and threshold cutoff level", "iELISA", "The genome is composed of a large~28 Kb molecule consisting of a 5\u2032 untranslated region (UTR), a 3\u2032 UTR, and at least seven open reading frames (ORFs) encoding three nonstructural proteins: ORF1ab (pp1a and pp1ab) and ORF3, an accessory protein. The four major structural proteins of the mature virion include the spike (S) glycoprotein (Mr 150-220 kDa), the nucleoprotein (NP) (Mr 45-57 kDa) that is associated with the positive stranded RNA providing integral support for its helical structure, the glycosylated membrane protein (M) (Mr 20-30 kDa), and the glycosylated envelope protein (E) (Mr 7 kDa) [5] [6] [7] .", "For time course studies, serum samples from experimentally infected animals were obtained courtesy of Dr. Richard Hesse (Kansas State University Veterinary Diagnostic Laboratory, National Pork Board Grant #13-228). Thirty-three PEDV na\u00efve 3-week-old feeder pigs were obtained from a private, high-health status swine production farm. . Of the 33 pigs, 23 were inoculated with PEDV at 4 weeks of age via intranasal and oral routes with a pool of gut derived intestinal contents that had been used as \"feedback\" inocula for controlled exposure of a sow herd. Serum was collected prior to challenge and at days 0, 6, 9, 14, 21, 28, 35 and 43 days post-infection (DPI). Multiple aliquots of all samples collected were shared with requesting laboratories to expand diagnostic testing and vaccine development capabilities." ] },{ "paper_id": "d78ca1eea9e94aa3dce73f05553d3ceb91f4c886", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total 200\u03bcL of each clinical sample was treated with Master Pure Complete DNA and RNA purification kit (Epicenter Technologies, Madison, WI) according to the manufacturer's instructions. The extracts were eluted in 50\u03bcL of DNase-and RNase-free water and stored at\u2212 80\u00b0C until use.", "HAdV-positive samples were also tested, and no positive results were obtained." ] },{ "paper_id": "d79628296e95343f9d5557983d7e19b66145b384", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An illustrative example is genome databases that are characterized by large amounts of data that are frequently updated from a variety of data sources. It is a highly time-consuming process to integrate \"new\" genome data especially because the processes that create keep changing and software tools must be continuously updated to reflect these changes. As a result, delayed software evolution may slow down scientific progress.", "A5 SET P2 P1 P2 P1 = +" ] },{ "paper_id": "d7a470f0dbe60172ed2a21ce65b9903b4825e3a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We typically use 1-5 \u00d7 10 5 Tissue Culture Infectious Dose-50 (TCID 50 ) per slice; variations are possible. 3.", "Incubate at 37 \u2022 C in 5% (v/v) CO 2 for 1 h.", "Harvest supernatants from slices (e.g., on day 2, 4 and 6 while replacing culture medium), transfer supernatant to tubes and centrifuge (5-10 min, 300\u00d7 g)." ] },{ "paper_id": "d7a55353f72476f71bb7437da54ee876acb7e0e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The primers used for PCR amplification of PpsbA, TpsbA, trnA and trnI DNA fragments are as follows: PpsbA-F, 5'-CCCGGGCAACCCACTAGCATATC-3\u2032; PpsbA-R, 5'-C CTCCTATAGACTAGGCCAGGATCTAGATTACATATG AAAATCTTGGTTTATTTAATCATCAGGG-3\u2032; TpsbA-F, 5'-CCCTGATGATTAAATAAACCAAGATTTTCATATG TAATCTAGATCCTGGCCTAGTCTATAGGAGG-3\u2032 and TpsbA-R, TCGAATATAGCTCTTCTTTCTTATTTCAATG ATATTATT-3\u2032. trnA-F, 5\u2032-GGGGAAGAATTCGGGGATA TAGCTCAGTTGGTAG-3\u2032; trnA-R, 5\u2032-GAAAAAGGT ACCTGGAGATAAGCGGACTCGAACC-3\u2032; trnI-F, 5\u2032-GG GGAAAAGCTTGGGCTATTAGCTCAGTGGTAG-3\u2032 and trnI-R, 5\u2032-GAAAAAGTCGACTGGGCCATCC TGGACTTGAAC-3\u2032." ] },{ "paper_id": "d7a80f6f56131be32a661d7604b38c6a893ded50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Six of ten tested bat cell lines are susceptible to MERS-CoV infection Figure 1A, 1B) .", "The reason for the observed differences in establishing persistent infection in these cell lines among the two different MERS-CoV isolates is unclear, but may have epizootiological significance and needs to be examined in future studies.", "Recently, CD26, also known as dipeptidyl peptidase 4 (DPP4) was identified as the human MERS-CoV cell entry receptor [19] and also as a receptor for Tylonycteris bat coronavirus HKU4 [20, 21] . CD26/DPP4 receptor is conserved among different mammals (e.g., bats, dromedaries, humans), and the possibly broad species tropism of MERS-CoV may partly be the result of this conservation [19, 22] ." ] },{ "paper_id": "d7a83aa4ab9b3fb17d6fbb6d7fb5e71f3939135f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. Paired t-test was used. Differences were defined as statistically significant when p < 0.05. All these tests were performed using GraphPad Prism 6.", "Bats serve as reservoir hosts for viruses that are related to many deadly emerging diseases in humans including Nipah virus, Hendra virus, SARS-like Coronavirus and Ebola virus 1-5 . Interestingly, bats carrying these viruses, which are pathogenic in humans and other mammals, show no clinical signs of diseases under natural or experimental infection conditions 3,6-9 . This unique ability may reflect an unknown interaction between these bat viruses and the bat immune system as a result of extensive co-evolution over a long period of time 10 ." ] },{ "paper_id": "d7b6798207f4093ed2187fc0d159bdb21a979f0b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), the most common cancer afflicting HIV-infected individuals 1 . KS is characterized by three histological features: angiogenesis, inflammation, and proliferation 2 . KSHV is also associated with two other B cell lymphoproliferative disorders: primary effusion lymphoma (PEL) and multicentric Castlesman disease (MCD) 3 . KSHV belongs to the \u03b3-herpesvirinae subfamily (genus Rhadinovirus) and was first described in 1994 4,5 .", "Over the past few years, several novel genes downstream of type I IFN signaling that inhibit infection by individual or multiple families of viruses have been described. There are two genetically and functionally distinct families of interferon stimulated genes (ISGs) that have antiviral properties, they are IFN-induced proteins with tetratricopeptide repeats (IFIT) and IFITMs. IFITs contribute to an antiviral state against some viruses by binding components of the eIF3 translation initiation complex and inhibiting protein translation 11 . In contrast, IFITMs block viral infection at the entry stage 12 . IFITMs are a double-edged sword when it comes to influencing viral entry; they can also enhance viral entry 13,14 . Interestingly, IFITM1 expression not only enhanced KSHV infection of cells, but also infection of cells with a closely related herpesvirus belonging to the \u03b3-herpesvirinae subfamily, Epstein-Barr virus (EBV) 10 .", "Cells. Human Burkitt lymphoma B cell line (BJAB) was used in this study. BJAB cells were propagated in phenol red-free RPMI medium (Invitrogen, Carlsbad, CA) containing 10% charcoal-stripped fetal bovine serum (FBS; Atlanta Biologicals, Lawrenceville, GA), L-glutamine, and antibiotics 40 . The cells used in this study were negative for mycoplasma as tested by Mycoplasma PCR ELISA (Roche Life Science, Indianapolis, IN)." ] },{ "paper_id": "d7b6ba6c543bcfd967c19fc3663abee090ed3a25", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Using serological studies to understand the dynamics of infectious agents in wildlife presents challenges. Few serological assays have been validated for wildlife species. Further, antibodies may cross react or cross-neutralize related viral antigens, which can limit the specificity of assays. There is also very little information available about maternal transfer of immunity in pteropid bats, including how long specific antibodies remain in the pup's blood. This makes it difficult, in studies of wild bats, to determine precisely when an animal was infected or whether a subadult may still have residual maternal immunity.", "Serum neutralization tests (SNTs) are considered the gold standard for detecting specific antibodies to Hendra and Nipah virus [20] . However, the use of SNTs have been limited, particularly in countries where henipaviruses are enzootic, because they are classified as select agents and require the highest level of biocontainment (Biosafety level (BSL) 4) in order to work with the live viral cultures required to conduct neutralization assays. As BSL 4 labs are not available in most countries where henipaviruses occur, IgG Enzyme-linked immunosorbant assays (ELISAs) and Luminex assays [21] have been used to test sera for anti-Nipah or anti-Hendra antibodies because they can be performed under standard biosafety conditions [4, 22] .", "This work was conducted at the CSIRO Australian Animal Health Laboratory (AAHL) in Geelong, Victoria and all work was approved by the AAHL animal ethics committee (protocols AEC1474 and AEC1532). Pteropus alecto were captured in the environs of Brisbane, Queensland using mist nets [17] . Bats were (DPI)Scientific permit #13909659; bats were imported to Victoria from Queensland under Victorian DPI Import permit #13894504. Thirteen adult female bats that were determined to be pregnant by abdominal palpation were brought into captivity at AAHL in August 2011. All thirteen bats gave birth to a single pup each between late October and early November 2011. Urine and oropharyngeal swab specimens from all adult and neonatal bats used in this experiment were screened and were negative for Hendra virus RNA using RT PCR (data not shown)." ] },{ "paper_id": "d7ccfdff2703c29904f679dc26fc8fd3f162e402", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The widespread and increasing use of molecular detection techniques has led to reports of multiple pathogenic agents detected in single samples [26] [27] [28] . This study supports those findings with two agents detected in 19 (16%) samples, and three or more agents detected in 10 (8%) samples ( Table 2) . No data was available to determine whether this may have altered the severity of illness. Some studies have reported more severe clinical presentation in the presence of mixed infection [9, 29, 30] while others have reported no significant greater disease severity in dual respiratory infection [31] .", "In recent years, improved nucleic acid amplification and detection technology has facilitated the identification of pathogens that had previously proved difficult or impossible to detect using traditional culture or immunofluorescent techniques. The increased use of molecular methods has also resulted in the discovery of novel respiratory pathogens including the human coronaviruses NL63 [1] , HKU1 [2] and the SARS coronavirus [3] , human metapneumovirus [4] , human bocavirus [5] and two human polyomaviruses, KI [6] and WU [7] . Despite these advances, there remain a significant proportion of respiratory disease episodes for which a pathogenic agent can not be identified [8, 9] .", "The technique may be used in the routine diagnostic setting or in an outbreak or pandemic situation, to facilitate testing for a range of common, exotic and emerging pathogens. Extra primers and probes for novel agents may be easily accommodated in this technique.", "No-template controls were included in the extraction process between every five samples and treated as samples for the completion of the assays. Since all PCR mixes were quality checked for all agents prior to use, and the internal controls cover the extraction, inhibitor removal and cDNA production processes, specific positive control materials were only included in the real-time Taqman PCR assays. Those control materials were well-characterized enrichment PCR products stored in aliquots at -20 \u00b0C.", "This technique facilitates the investigation of a comprehensive range of respiratory pathogens from a single nucleic acid extract and a single reverse transcription reaction. In addition, the ability to amplify multiple targets efficiently aids in the detection of mixed infections." ] },{ "paper_id": "d7e90855b317646bba5751946a9a5e675ea90fdc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were entered into a Microsoft Excel database (Microsoft, Seattle, Wash., USA) by a data manager (BD) under the supervision of the study steering committee (XM, YX, LJ, AL). Data were checked for inconsistencies and logical errors on entry, and queries were sent to the source hospital for resolution.", "All comparisons were unpaired and all tests of significance were two-tailed. A p value < 0.05 was considered as statistically significant." ] },{ "paper_id": "d7fa2195f292b4bd5cf3bce7670b11c254770923", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Under circumstances mentioned above, antiviral drugs may be used to treat patients infected with IAV and, alternatively, such drugs can be used prophylactically in outbreak situations.", "Clearly there is a need for novel drugs that can be used to treat IAV infection and that do not suffer from these disadvantages.", "Native pSP-D Native pSP-D (NpSP-D) was isolated from pig lungs as described previously [23] . For this purpose six months old surplus pigs were used that were euthanized for other purposes. In short, NpSP-D was isolated from lung lavage by affinity purification method using Mannan-sepharose beads. After elution from the beads with EDTA-containing buffer, NpSP-D was purified using gel filtration chromatography." ] },{ "paper_id": "d806b5203cfba5a87c9a39a25d953572eacf9ab9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Initially focused on Ebola virus disease, UMVE science policy was redirected since 2007 by expanding the main research themes to other emerging viral diseases that could threaten public health in the Congo basin (Table 1) [19] [20] [21] [22] .", "In order to facilitate national and international scientific exchanges including scientists, equipment, biological specimens, the capital of Gabon, Libreville, is part of CIRMF operational system. Hosted by the University of Health Sciences, Libreville, one laboratory is now operational. Tight connections with other scientific teams in Libreville are under development (i.e.,: Military Hospital, Libreville; General Hospital, Libreville; A. Schweitzer Lambarene Foundation).", "CIRMF is geographically isolated from the capital of Gabon, Libreville. The Libreville office is essential to the Franceville headquarters as it coordinates visits from staff on field missions, and forwards imported equipment to headquarters. The capital is accessible by a 12-hour ride in a four-wheel drive vehicle or in a train (three times/week schedule) covering 641 km. Due to tropical weather, four weekly domestic plane rotations often fly on an inconsistent schedule. Ultimately CIRMF needs to be largely autonomous in term of electrical power (i.e.,: unexpected fuel supply disruption), cold chain with the necessity to maintain in situ a unit of liquid nitrogen production (repository), and purified water supply. ", "CIRMF is uniquely suited to study infectious diseases of the Congolese tropical rain forest, the second world's largest rain forest. As a central point of a North-South transect of the rain forest, the Center is able to study the biodiversity of Africa including animal species, microbes, and parasites.", "As a National reference laboratory, CIRMF has the following roles: diagnosis of suspected cases during outbreaks of viral hemorrhagic fevers or severe clinical infectious syndromes; development of new methods for diagnosing such infections; surveillance of animal fatalities in reservoir or intermediate hosts; and intervention during outbreaks of unknown etiology. CIRMF diagnosed infections of more than 70 pathogens that could not be identified in other biology laboratories throughout the country. CIRMF maintains close ties to several components of the National Healthcare system, such as Amissa Bongo Regional Hospital in Franceville or the Sino-Gabonese Friendship Hospital." ] },{ "paper_id": "d80ebadc0c335da9a5c4fffa527690bf146e934d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The two RSV subtypes often co-circulate during epidemic seasons [6, 7] ." ] },{ "paper_id": "d8196519b0be213e70c77973a63cd4a13f5532c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "On 30 December 1969, person TS was admitted to ward A of Evangel Hospital in Jos, Nigeria due to a severe febrile illness (subsequently diagnosed as LF). TS was on the ward approximately 2 weeks. Both her new infant and a three year old daughter stayed with her during this period. Shortly after TS's discharge and return to Bassa, her mother and the two children became ill. The daughter died at home.", "In one respect, the illness of TS did di\u21b5er from most: there was severe pulmonary involvement." ] },{ "paper_id": "d819ba39c114acf69059a2d37f21246f30edaf56", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d8271398b9073fbb1ad449e72697e6ae8f71d3d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As influenza virus replication also impairs the mucociliary clearance, there is increased susceptibility to bacterial superinfections, which can often be fatal (reviewed in [9] ). In addition, immune dysfunction in those prone to respiratory disease with excessive cytokine stimulation in the airways during influenza virus infection can rapidly progress to pneumonia with fatal acute lung injury [10] [11] [12] . Thus effective strategies to combat influenza pandemics of catastrophic proportions involve both the generation of broad-spectrum immunity and protection from immunopathology, thereby lowering the risk of severe illness-associated complications and reducing both morbidity and mortality.", "IFNs have been used for clinical therapy of a variety of infections and diseases. Although IFN therapy predominantly utilizes IFN-2, other subtypes may be more or less effective, depending on the virus and cell type [39] . Differential efficacies have been found for individual IFN subtypes in mouse models of influenza, with IFN-5 and IFN-6 subtypes being more effective than IFN-1 in reducing lung H1N1 influenza virus titers [43] . The IFN-subtype has also been shown to protect against H1N1, driving a pulmonary Th1 type response beyond day 8, which normally switches to Th2 with eosinophilia/neutrophilia during natural infection [44] .", "The authors declare that there are no conflict of interests.", "Current influenza control requires effective vaccination. Updated vaccines with strain matching are developed on an annual basis requiring seed virus preparation generated by either reassortment or reverse genetics for propagation in eggs or cultured cells [13] . Recombinant DNA plasmidbased and virus-like particle vaccines are alternative options [14] to currently licensed inactivated and live attenuated vaccines (cold-adapted and temperature-sensitive viruses) [15] and recombinant proteins [16] . Heterosubtypic immunity is conferred by a variety of experimental vaccines including extracellular domain matrix (M2) protein [17] and formalininactivated whole virus [18] . Nonetheless, such contemporary vaccines would have narrow virus specificity, delayed availability, and restricted capacity to meet the global demand during a pandemic situation. Universal influenza vaccines that target invariant regions of the virus and induce effective broadly neutralizing immune responses could potentially provide more effective antiviral coverage but finding an appropriate immunogen is a major issue under intense investigation. A further limitation is efficacy as vaccine-induced B cell responses to conserved regions of the HA viral protein are generally low in frequency and generate poor antibody responses [19] .", "Neuraminidase inhibitors, although potent at inactivating virus replication, have been shown to display limited effectiveness when used beyond 48 hours after infection due to high viral titres and require regular dosing to those at risk of exposure during a virus outbreak. Other antivirals besides NA inhibitors (zanamivir and oseltamivir) that block the M2ion channel (adamantanes) have been used; however prepandemic stockpiling of such antivirals by governments has been reconsidered as a poor strategy against emerging virus resistance (reviewed in [20] ). Antiviral development has targeted specific oligosaccharide-comprised sites on enveloped viruses (cyanovirin) [21] , viral RNA dependent RNA polymerase (favipiravir) [22] , and their possible combination targeting different stages of the virus replication cycle in a synergistic therapeutic approach [23] . Innovative drugs may offer future clinical benefits including (DAS181) that mediates cleavage of sialic acid from host glycan receptors [24] ,defensins and antiviral peptides that prevent virion entry [25] , TLR3 ligand (PIKA) promotion of DC maturation [26] , TLR4 antagonists (eritoran) that block cytokine cascades [27] , nucleic acid-based drug (PolyIC, CpG) activation of innate immunity [28] , and siRNA that target conserved viral RNA sequences [29] . Furthermore, enveloped virus neutralizing compounds (polyphenols) found in pomegranate juice [30] and green tea [31] and even scorpion venom peptide [32] hold promise in their strain diversity-independence of antiviral activity." ] },{ "paper_id": "d82d6db1f132aa8d31e7b5afff09c1679e2dfe4e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Below, the varying anchoring strategies displayed in Fig. 1 are discussed in detail and references illustrating the use of these strategies are provided. All these strategies have to some extent been implemented in the pSIP system.", "Immunization strategies based on antigen delivery require a strong response from the host immune system. Alternatively, antibodies produced by LAB can be used to generate passive immunity, thus providing a more direct method, with fast response time.", "To date, several recombinant LAB have reached clinical studies [11] . The first clinical study was completed in 2006 using L. lactis for secretion of human IL-10 in patients with Crohn's disease [142] . Ten patients were included in a placebo-uncontrolled phase I trial." ] },{ "paper_id": "d83954775a8f0d595494ce00018ae409739f1062", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d8454139f839889cb542b3c91009e20ceded8625", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The simultaneous reading of both spectra is performed in purpose-designed readers ( Table 2) . They differ by their mechanisms of fluorescence capture and by the maximum number of samples that can be analyzed.", "xMAP immunoassays surpass the common enzyme immunoassays in the ability of multiple simultaneous detection, while requiring smaller amount of sample and lower cost. Moreover, these assay formats produce superior dynamic range and sensitivity.", "As we have descibed, the ISA represents an improved methodological alternative to current serological diagnostics, enabling multiplex detection of pathogenic agents with higher sensitivity.", "The analysis of beads is in general performed by two lasers. The red classification laser/LED (635 nm) excites the inner fluorescent dyes of the microspheres, thus identifying a specific microsphere set according to its spectral signature. If the analyte of interest is present, the green reporter laser/LED (525-532 nm) recognizes the fluorescent reporter bound to the captured analyte on the microsphere surface.", "Advanced detection instruments -the Luminex 100/200 (Bio-Plex 200) and FlexMAP (Bio-Plex) 3D -are based on flow cytometry principles. The microspheres with bound analyte are focused into a rapidly flowing fluid stream. Each microsphere is then individually detected and digitally processed as the stream passes through the imaging cuvette. Flow cytometrybased platforms are convenient for applications with samples of limited size. The reading of a 96-well-plate is faster than in the MAGPIX system and takes 45 min or less. The capacity of the 3D platform is further increased by the possibility of analyzing 384-well plates." ] },{ "paper_id": "d84ac9fd44932276ccfa7da5add9776e7d56595a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Blood was collected at the time of necropsy from the inferior vena cava and placed in heparinized tubes and centrifuged for 10 min. The plasma was stored at -80\u00baC until further analysis. Cytokines and chemokines", "PTX3 is an important inflammatory mediator and a critical component of the humoral arm of innate immunity [16, 17] . PTX3 is a soluble pattern recognition receptor with both immunostimulatory and immunoregulatory functions. It orchestrates clearance of pathogens through opsonization of damage-and pathogen-associated molecular patterns, regulates clearance of apoptotic and necrotic cells, and prevents autoimmune pathology [18, 19] . Elevation of PTX3 levels in the circulation following infection or tissue damage appears to predict poor patient outcome [19] , as seen in patients with sepsis and acute lung injury [20] [21] [22] .", "To determine whether the increased fibrosis was related to increased numbers of myofibroblasts, we performed immunofluorescent staining for \u03b1-SMA positive cells in the grafts. We excluded \u03b1-SMA positive smooth muscle cells around vessels and airways. Grafts in KO mice had more \u03b1-SMA positive staining (myofibroblasts) than grafts in WT mice ( Figure 4 )." ] },{ "paper_id": "d85a85112817de11b60dd2e8f8177a48c3015442", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d85ef5950a1be68a4dd4eebed557563bf88ba8ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One-step RT-PCR. FCoV-specific primers were used to reverse transcribe and amplify the viral RNA contained in 2 ml extracted total RNA using a SuperScript III One-Step RT-PCR System with Platinum Taq High Fidelity (Life Technologies) as described by the manufacturer. Briefly, a 50 ml reaction was set up on ice containing 2 ml RNA, 1 ml 10 mM forward and 1 ml 10 mM reverse primer, 25 ml 26 reaction mix (as supplied by the manufacturer), 2 ml SuperScript III RT/Platinum High Fidelity enzyme mix and water to a final volume of 50 ml. The reaction was incubated at 50 uC for 50 min to allow cDNA synthesis, and then raised to 94 uC for 2 min, followed by 41 cycles of 94 uC for 15 s, 50-66 uC (depending on the primer set) for 30 s and 68 uC for 1 min (kb of product size) 21 . The annealing temperature for individual reactions was determined by the melting temperature of the primers used. The reaction underwent a final extension phase at 68 uC for 7 min and was held at 4 uC. For each amplicon, 5 ml PCR product was separated on a 1 % agarose/TBE gel to confirm the PCR product size and to estimate the amount of DNA by comparison with standards. The PCR products were then pooled in approximately equimolar amounts and purified using Agencourt AmPure XP beads (Agencourt AMPure XP PCR Purification; Beckman Coulter), following the manufacturer's protocol, and eluted in nuclease-free water.", "Histology and immunohistochemistry. Formalin-fixed tissue samples (26M, 27C and 28O) were routinely paraffin wax embedded and examined histologically to confirm the presence of typical FIP lesions. The immunohistochemistry served to demonstrate FCoV antigen within the lesions, as described previously (Kipar et al., 1998) .", "FCoVs form two antigenically distinct serotypes: serotype 1, which is difficult to propagate in cell culture, and serotype 2, which is the consequence of a double recombination between type 1 FCoV and canine coronavirus (Herrewegh et al., 1998) and is relatively easy to propagate in cell culture. FCoV infections are endemic among cats worldwide, and serological and molecular studies confirm that serotype 1 FCoVs predominate (Pedersen, 2014b) . In the UK, about 40 % of domestic cats have been infected with FCoV, and in multi-cat households, this figure increases to almost 90 % (Addie, 2000; Addie & Jarrett, 1992) . The majority of FCoV infections are asymptomatic or result in only mild enteric disease. However, approximately 5 % of infected cats develop feline infectious peritonitis (FIP), a systemic inflammatory disease that is a frequent cause of death in young cats (Kipar & Meli, 2014) . Currently, there is no protective vaccine or effective treatment for FIP (Pedersen, 2009 (Pedersen, , 2014a ." ] },{ "paper_id": "d86146bbcb9ae18278150f4cb241ca1ce31fbf28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.", "\"A piece of bad news wrapped up in a protein,\" definition of a virus by Sir Peter Medawar.", "\"Two are better than one, because they have a good return for their labor\" Ecclesiastes 4:9-10.", "\"The most fruitful basis for the discovery of a new drug is to start with an old drug, \" famously stated the 1998 Nobel Prize in Physiology and Medicine Laureate, Sir James Black." ] },{ "paper_id": "d86a5350811ae89aa7878812f7e74944362dbf2b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We collected information in each news report on date of rescue or confiscation, number of individuals, location of rescue (e.g. field, market, residential area or transporting vehicles), physical condition of rescued individuals (e.g. healthy, unhealthy, injured or dead), and whereabouts of the individuals after being rescued (e.g. zoo, wildlife rescue centre, released into wild, or unreported) (Table 2; Fig. 1 ). China's primates are naturally distributed in 21 of 34 provincial-level administrative units (PLAUs), with four provinces in west and southwest China (Yunnan = 15 species, Guangxi = eight species, Tibet = eight species, Guizhou = six species), containing the highest diversity ( Fig. 2A) . We also recorded provinces where news was/had been reported to determine distribution of rescuing (Fig. 1) .", "The demand for pet primates, together with habitat loss and fragmentation, exerts a significant pressure on wild populations. In particular, slow lorises are perceived as suitable pets by both buyers and sellers due to their 'cute and cuddly' appeal, and have been one of the most popular primate taxa in wildlife markets (Nekaris, 2014) . The widespread illegal trade in China seems to be incompatible to their restricted distributions, high threat category, and poor public knowledge. Taking into account their small and declining wild population, it is urgent to take actions for conservation of this neglected and threatened primate taxon.", "We found that more than half (68.3%, 502 individuals) of the primate individuals were unhealthy, injured or dead when rescued. Of 105 individuals whose injuries were specified, most (40, 38.1%) were suffering from leg wounds. The proportion of healthy individuals rescued was significantly lower in 2006-2011 than the other two time periods (v 2 = 6.140, df = 2, p = 0.046)." ] },{ "paper_id": "d8714feba6d9a8670db5d8e4d998a3de95d16a3c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d876d3d89d579f47df9ac251a4139ab1051561f5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Paraffin tissue sections were prepared from whole left lung of ferrets for histo-pathology assessment at each scheduled sacrifice. Inflammation was graded on six indicators (bronchial/endobronchial, peribronchial, perivascular, interstitial, pleural and intraalveolar), each scored as: 0 (normal), 1 (mild), 2 (moderate) or 3 (marked) for a maximum combined score of 18 [28] . Vascular congestion and pulmonary edema were similarly scored.", "Lung immuno-histochemistry was undertaken to identify cells with virus antigen. Paraffin tissue sections were quenched for 10 minutes in aqueous 3% H 2 O 2 then pre-treated with proteinase K for 15 minutes. A 1:10,000 dilution of mouse monoclonal antibody to influenza A nucleoprotein (F26NP9; in-house) was applied for one hour. Sections were visualized using horseradish peroxidaselabelled polymer, EnvisionH+system (anti-mouse) (Dako, USA), reacted with the chromogen, diaminobenzidine and counterstained with Gill's hematoxylin.", "Change in lung cytokine mRNA gene expression was assessed by relative quantitative PCR (qPCR) with RNA extracted from 140 mL of right lung homogenate using the QIAamp viral RNA mini-kit. Reverse transcription was performed using the High Capacity RNA-to-cDNA Kit (Applied Biosystems) on 0.5 mg of the total RNA following manufacturer's protocol. qPCR was performed using the TaqManH Gene Expression Master Mix (ABI) with primers designed to target published cytokine sequences [29] [30] [31] from Mustela putorius furo mRNA sequences at a final concentration of 0.25 mM. Assays were run on the StepOne Plus (ABI) with the following conditions: 50uC-2 minutes; 95uC-10 minutes; followed by 40 cycles of 95uC-15 seconds; and 60uC-1 minute. Fold-change was calculated using the delta-delta Ct method [32] with uninfected ferrets as reference and GAPDH as endogenous control.", "Microneutralization methods. For MN assay, 50% tissue culture infectious dose (TCID50) viral titers were determined on MDCK cells. The sera were treated with receptor destroying enzyme (Accurate Chemical & Scientific, NY) and serially diluted in serum-free medium (MegaVir, HyClone, Utah) beginning at 1:10. To each 50 mL dilution, 100 infectious units of virus were added. The plates were incubated for 2 hours at 37uC to allow for virus antibody interaction. The contents of each well were then transferred onto microtiter plates with confluent monolayers of MDCK cells. After 3 hours of further incubation at 37uC, the medium in each well was removed and replaced with fresh MegaVir medium containing 2 mg/mL L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK)-treated trypsin. The plates were further incubated at 37uC and monitored for cytopathic effects on days 3 and 5. The MN titer was defined as the inverse of the serum dilution immediately preceding the wells with cytopathic effects." ] },{ "paper_id": "d87f44c7d76e4c51ed8e72103669c275e2db3e71", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Score Definition Table 3 . Cont.", "Cytoplasmic protein extracts for the analysis of caspase activity were prepared as described [24] . Briefly, tissue fragments were dounced on ice in a buffer containing 25 mM KPO 4 pH 7.8, 8 mM MgCl 2 , 1 mM EDTA, 1% Triton X-100 and 15% glycerol. The extracts were incubated on ice for 5 min. and then centrifuged at 4uC for 1 min. at 10000 g. The supernatants were then aliquoted and stored at 280uC.", "Horseradish peroxidise activity was detected using a diaminobenzidine dye-kit (Vector-Laboratories). The slides were incubated with substrate for 5 min. The reaction was stopped by washing the slides with distilled water.", "Milk proteins were separated on a 15% polyacrylamide gel and bands were excised manually. The proteins represented by these bands were trypsinised using a protocol of the Micromass MassPrep Station (Micromass Ltd, Manchester, UK) and analysed by electrospray LC-MS methods as described previously [26] ." ] },{ "paper_id": "d880151d3c6128788253389d87094b7cc1154837", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In order to study, prepare for, and intervene against disease outbreaks, infectious disease modellers and public health professionals need an extensive data analysis toolbox. Disease outbreak analytics involve a wide range of tasks that need to be linked together, from data collection and curation to exploratory analyses, and more advanced modelling techniques used for incidence forecasting 1, 2 or to predict the impact of specific interventions 3,4 . Recent outbreak responses suggest that for such analyses to be as informative as possible, they need to rely on a wealth of available data, including timing of symptoms, characterisation of key delay distributions (e.g. incubation period, serial interval), and data on contacts between patients 5-8 .", "The latter type of data is particularly important for outbreak analysis, not only because contacts between patients are useful for unravelling the drivers of an epidemic 9,10 , but also because identifying new cases early can reduce ongoing transmission via contact tracing, i.e. follow-up of individuals who reported contacts with known cases 11,12 . However, curating contact data and linking them to existing line lists of cases is often challenging, and tools for storing, handling, and visualising contact data are often missing 13,14 .", "vis_epicontacts(x, node_shape = \"sex\", shapes = c(F = \"female\", M = \"male\"), edge_label = \"exposure\")", "Operation epicontacts is released as an open-source R package. A stable release is available for Windows, Mac and Linux operating systems via the CRAN repository. The latest development version of the package is available through the RECON Github organization. At minimum users must have R installed. No other system dependencies are required." ] },{ "paper_id": "d882f79283751d6c7f2e48cb991ee8abbcd913ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "that is, a sum of Bernoulli random variables, which has expected value", "But as v is unobserved we sum over all possible infection trees to obtain the 'integrated likelihood'", "where S j = {1,\u2026,N}\\{j} is the set of all indices other than j. The integrated likelihood is a genuine likelihood (up to a multiplicative constant) permitting valid inferences about h conditional on outbreak size N." ] },{ "paper_id": "d887a0239eb93e1f9eed94d50126ba28157c4675", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Th1/Th2 balance Virus-specific Th1 and cytotoxic T cells are crucial to control viral replication, whereas B cells receive important growth signals from Th2 cytokines.", "The co-expression of type-I and -III IFNs is explained by common transcription factors and binding sites in the promoter regions.", "?, not known." ] },{ "paper_id": "d889f70c1e55668de7d33d59e76f3daf7cc8a28b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 Checklist. STARD checklist.", "(DOC)" ] },{ "paper_id": "d88b1e3e4d603dde6f344785e2371292e56f73a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the early stage of acute infection, when rectal temperature increased (\u226540\u00b0C) but without other CSF clinical symptoms, blood samples from each pig were collected and sera were separated. Serum albumin and immunoglobulin (IgG) were removed using a Proteo-Seek\u2122 Albumin/IgG Removal Kit (Pierce) according to the manufacturer's instructions. Samples were centrifuged at 12000 g in a YM-3 centrifugal filter (Millipore) to make protein concentration to 5-10 \u03bcg/\u03bcL as measured using Coomassie Plus-The Better Bradford\u2122 Assay kit (GE Healthcare).", "CSF caused by virulent strains of CSFV is a hemorrhagic disease of pigs, characterized by disseminated intravascular coagulation, thrombocytopenia and immunosuppression. Diseased animals show hemorrhages in the skin, mucosa and internal organs [2, 3] , and a general immunosuppression featuring a dramatic decrease of peripheral B-and T-cells early after infection of CSFV, due to bystander apoptosis in uninfected cells [4, 5] .", "In this study, a proteomic method of 2-D DIGE was used to compare serum protein profiles of CSFVinfected pigs and uninfected controls. 2-D DIGE is a fluorescence-based technique for protein visualization and quantification that circumvents the shortcomings of conventional two-dimension polyacrylamide gel electrophoresis (2D-PAGE) such as low sensitivity, reduced dynamic range and gel-to-gel variability [15] . Therefor, 2-D DIGE may present more reliable data with the accurate quantitation and the good reproducibility compared to conventional 2-DE." ] },{ "paper_id": "d897dfae4f3b4d98b4bb6fde108a29c253d87e50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Third, many plant and insect viruses encode viral suppressors of RNAi (VSRs) that interfere with distinct steps of the RNAi pathway, demonstrating the selection pressure imposed by this antiviral system (Pumplin & Voinnet, 2013; Bronkhorst & van Rij, 2014; Csorba et al, 2015) .", "LGP2 lacks CARDs and is unable to induce signalling via MAVS. It is thought to act by modulating responses by the other RLRs (Bruns & Horvath, 2014; Bruns et al, 2014; Parisien et al, 2018) .", "In line with other facets of immunity, it is likely that antiviral RNAi is highly tuneable and that it operates in conjunction with multiple other mechanisms of defence. Further studies are clearly needed to disentangle the complex web that regulates dsRNAi in mammals and to understand its ability to act as a cell-intrinsic mechanism of antiviral defence. " ] },{ "paper_id": "d8a0e6a4cc626dfe6090ea49ce8b920eee3f98e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Limitations worth highlighting include uncertain external validity (I) and possible threats to internal validity (II).", "In one paper, published in 2017, we investigated the relationship between diet and upper respiratory tract infections (URTI) [33] . Using data from the web-based food frequency questionnaire we found an inverse association between intake of vitamin C, vitamin E, docosahexaenoic (DHA) and arachidonic acid (AA) and risk of URTI among women, while intake of vitamin E and zinc was associated with an increased risk of URTI among men [33] .", "A more recent Swedish study showed that the proportion of workers who reported at least one day a year of absenteeism due to rhinitis and common cold was 37%, whereas 72% reported to have worked while sick with subsequent reductions in productivity [4] . The total annual costs for productivity loss in Sweden were estimated at \u20ac2.7 billion a year [4] ." ] },{ "paper_id": "d8a900446a0ac1e4d0096ab06f805c253a75523c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(DOCX)" ] },{ "paper_id": "d8af816aad9d7cfe8c158cefaa7f1de16bda7146", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "While operational research on dog vaccination provides grounds for optimism, awareness is growing about the challenges, complexities and time scales of moving from control to elimination (figure 3).", "rspb.royalsocietypublishing.org Proc. R. Soc. B 284: 20171880 these incursions to the persistence of rabies are not yet fully understood but will, undoubtedly prolong elimination efforts, and highlight the need for coordinated control at scale and across international boundaries as well as realistic projections of the investment required to eliminate rabies [94] .", "While human deaths and high PEP costs dominate in burden of disease studies, several other components of disease burden are also of concern, including livestock losses, which still remain poorly quantified but can have important impacts [22, 33] and wildlife conservation, with canine rabies threatening several endangered wildlife populations including the Ethiopian wolf (Canis simensis) and African wild dog (Lycaon pictus) [34] (figure 2).", "Pragmatic solutions are also being found to improve rabies diagnosis in settings with limited laboratory infrastructure, including techniques to support decentralized laboratory testing (e.g. direct rapid immunohistochemical test, dRIT) [73] [74] [75] [76] and field diagnosis (e.g. immunochromatographic tests) [77] [78] [79] . These have great potential for empowering field staff to engage in rabies surveillance and respond more effectively to surveillance data, but standardization and quality control of field diagnostic kits still needs improvement [80] . Given the rapid advances in metagenomic sequencing methods [81] , future approaches may include real-time genomic surveillance. However, even simple technologies such as mobile phones can serve as leapfrogging technology that can dramatically improve the extent and resolution of rabies surveillance data [82] ." ] },{ "paper_id": "d8d17ed0a635b0771ab27b88b15e868759b1dfb2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sample material from three deceased snakes was analyzed by a metagenomics workflow as described elsewhere [23, 24] .", "Our results show a nationwide distribution of nidoviruses in Germany with possible many existing strains." ] },{ "paper_id": "d8d257c7faebdd3d749b56befc9927d7d064e512", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The animal study was conducted under appropriate conditions with the approval of the Institutional Animal Care and Use Committee of Chungnam National University (Reference number CNU-00816).", "A reversed-phase high-performance liquid chromatography (HPLC) was performed using Agilent technologies 1200 series HPLC system equipped with a DAD detector (Agilent technologies, Santa Clara, CA, USA). The binary mobile phase consisted of water containing 1% formic acid (solvent A) and acetonitrile (solvent B). All solvents were filtered through a 0.45 \u00b5m filter prior to use. The mobile phase consisted of 1% Formic acid (Solvent A) and Acetonitrile (Solvent B) in the gradient mode as follows: 0-20 min 0-40% B; 20-22 min 40-100% B; 22-25 min 100-0% B at flow rate of 1.0 mL/min at 30 \u2022 C.", "Supplementary Materials: The following are available online at http://www.mdpi.com/1999-4915/11/7/604/s1, Figure S1 . Herb extract library screening results, Figure S2 . Selected herb extracts second round screening results. " ] },{ "paper_id": "d8e134d93a4666285518b7916316a97dcc258788", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Immunohistochemistry of tissues. Tissue sections were deparaffinized and rehydrated through xylene and graded ethanols. Slides went through heat antigen retrieval in a steamer at 95 \u00b0C for 20 mins in Sigma Citrate Buffer, pH6.0, 10\u00d7 (Sigma Aldrich, St. Louis, MO). To block endogenous peroxidase activity, slides were treated with a 3% hydrogen peroxide and rinsed in distilled water. The tissue sections were processed for IHC using the Thermo Autostainer 360 (ThermoFisher, Kalamazoo, MI). Sequential 15 min incubations with avidin D and biotin solutions (Vector, Burlingame, CA) were performed to block endogenous biotin reactivity. Specific anti-CCHFV immunoreactivity was detected using a primary polyclonal rabbit-\u03b1-CCHFV-NP antibody (IBT BioServices, Rockville, MD) at a 1:3200 dilution for 60 mins. A secondary biotinylated goat-\u03b1-rabbit-IgG (Vector Laboratories, Burlingame, CA) at 1:200 dilution for 30 mins followed by Vector Horseradish Peroxidase Streptavidin, R.T.U (Vector) for 30 mins. Slides were developed with Dako DAB chromagen (Dako, Carpenteria, CA) for 5 mins and counterstained with Harris hematoxylin for 30 seconds. Tissue sections from uninfected mice were used as negative controls." ] },{ "paper_id": "d8e9ba5b8657f01d92a6da7558aa323fa9ec5539", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HAstV stocks were inactivated by incubation for 1 h at room temperature in a class II biological safety cabinet under the UV light. Complete viral inactivation was confirmed by lack of capsid protein expression by immunofluorescence after infecting CaCo-2 cells.", "Comparisons between means were performed using the student t-test (unpaired) using the IBM SPSS Statistics version 20 software (SPSS Inc., Chicago, IL, USA). P values < 0.05 were considered statistically significant.", "An indirect enzyme-linked immunoassay was performed on serial 4-fold dilutions of samples. Astrovirus antigens in cell lysates were captured with mAb 8E7 and detected by using a rabbit polyclonal anti-HAstV antibody (Rab-3). Specifically bound antibodies were revealed by a peroxidase-conjugated anti-rabbit IgG antibody (Sigma Aldrich). Undiluted cell lysates from mock-infected cultures were used as negative controls to calculate a positivity cutoff value (mean + 3 standard deviations). Sample dilutions which had an OD value higher than the cutoff value were considered positive.", "Astroviruses were first identified by Appleton and Higgins in 1975, in association with an outbreak of infantile gastroenteritis in a maternity ward in England [1] and the Astroviridae family today contains viruses which infect more than 44 animal species [2] . Human astroviruses (HAstV) are recognized as common viral pathogens causing gastroenteritis in infants and young children, with very few reports of HAstV-mediated disease in normal healthy adults, and some reports of severe disease after dissemination to extra-intestinal tissues in immunocompromised patients [2, 3] . Astroviruses are non-enveloped positive-strand RNA viruses containing a 6.8 kb polyadenylated genome linked to a VPg protein on the 5'end [3, 4] . The genome contains three overlapping open reading frames (ORFs): ORF1a and ORF1b encode the viral protease and polymerase, respectively, and ORF2 encodes the capsid precursor [3] . The nonstructural proteins (nsPs) are translated from the genomic RNA as two large Knowledge of the host response to HAstV may provide keys for prevention and treatment of the human disease." ] },{ "paper_id": "d8eb14ca18661130fdaf099482d6cd5b46032efe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed by Mann-Whitney U-test with SPSS software, version 18.0 (SPSS Inc., Chicago, IL, USA). A P value <0.05 were considered significant." ] },{ "paper_id": "d8ec38752ec638efa9b55dffa8d0277ce889c976", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In conclusion, waterfowls have diverse innate immunity components, which possibly increase their resistance to the APMV-1 [42] .", "Recently, Yang et al. [45] have demonstrated that overexpression of 2\u2032-5\u2032-oligoadenylate synthetase-like gene lessens the replication of APMV-1 in goose cells.", "Additional file 1. Experimental infection studies of ducks and geese with Avian Avulavirus 1. Table summarizes " ] },{ "paper_id": "d8f8b6d50f16dfbdf817c36004a0424d44f35e93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d8ffe10c4c92236a38d1d27b1c0d7575b7672ed0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A child with severe malnutrition with cough or respiratory difficulty with the presence of end point consolidation or other infiltrates, or pleural effusion in chest X-ray defined by WHO, as assessed by a qualified radiologist [20] .", "Clinical characteristics of pneumonia: According to WHO, a child with a history of cough with respiratory difficulty or age-specific fast breathing or lower chest wall indrawing will be defined as pneumonia [18] .", "Normal 1 (3) 0 (0) 0 (0) 1 (1) 0 (0) 0 (0) 0 (0) 2(Consolidation 2 (6) 0 (0) 0 (0) 3 (4) 1 (6) 2 (13) 3 (5) 4 (4) Other 0 (0) 0 (0) 0 (0) 1 (1) 0 (0) 0 (0) 0 (0) 1 (1)" ] },{ "paper_id": "d9006d571ae04afb914b4bdd5c32f2090d409b4c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To initialize influenza transmission through the modeled network, five infectious individuals were randomly seeded into the study area at the first day of simulation.", "The socio-economic loss from work/school absenteeism is a potential problem for implementing weekend extension strategies. One solution is to encourage people to work at home during the extended weekend, complete business transactions through telecommunication, and take courses online. In such a manner, the face-to-face contacts for infection are reduced, while long-term interruptions on socio-economy could be minimized. If the long-distance working and learning are not feasible for certain occupations, an alternative is to grant these groups of people a higher priority for receiving pharmaceutical interventions.", "To construct such a contact network, three populations of daytime, nighttime and pastime were synthesized respectively and then linked together [13] . The census data was used to build the nighttime population of individuals and households that matched the real age and household structures. The nighttime population was assigned to business locations to create the daytime population, according to the travel time to work and industrial types of business locations. Next, the pastime population was generated based on the information of previous two populations and a regional travel survey [16] . Under the constraints of travel statistics, individuals were further allocated to service places and neighbor households. Detailed algorithms to generate these three populations can be referred to the work by Mao and Bian [13] .", "The modeled epidemic curve under R 0 = 1.4 matched well with the observed time course of a seasonal flu outbreak in year 2004-05 (Figure 2 ), although the magnitude of simulated curve was larger than the reported. This is because a large proportion of infected people may not manifest symptoms or seek health care, and thus the number of influenza cases was highly underreported by CDC. In this sense, the simulation model performed well in predicting the time trend, and at least allowed a representation of the worse case result. The pandemic flu (R 0 = 2.0) caused an earlier and higher epidemic peak with more influenza cases, because this virus strain is far more contagious and spreads faster." ] },{ "paper_id": "d90382cb2b05e6761cea35d274213ee4f5c0cd02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recently, between 2010-2014, an epidemiological survey showed the emergence of a novel strain of Italy02 serotype with a prevalence of 32 %, co-circulating with two serotypes; Massachusetts and 4/91, with a prevalence of 66 % and 2 % respectively, that are isolated from vaccinated and unvaccinated chicken flocks [15] .", "Finally, this current report justify that Italy 02 genotype isolated from different regions of Morocco is capable to induce a severe respiratory disease with a wide distribution of respiratory system. However, this genotype do not cause any kidney damage and without causing mortality. " ] },{ "paper_id": "d90b2c4decfc17d7349325f437a9ab6082742c24", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Biosafety and biosecurity. Reported studies were initiated after the NIH and the University of North Carolina Institutional Biosafety Committee approved the experimental protocol (project title, Generating Infectious Clones of Bat SARS-like CoVs; lab safety plan ID, 20167715; schedule G ID, 19982).", "Accession number(s). The near-complete genome sequence for PREDICT/PDF-2180 has been deposited in GenBank under accession number KX574227.", "Sampling and site characterization. A bat (identifier [ID] OTBA03-20130220) was trapped on 20 February 2013 in the Nkuringo area of Kisoro District, in southwestern Uganda (latitude \u03ea1.12, longitude 29.68) (Fig. 1) . This area is an established settlement of villages comprising approximately 15,000 inhabitants adjacent to the southwestern boundary of Bwindi Impenetrable National Park. Communities include subsistence farmers growing small crops, with some members working inside the national park or supporting tourism-related businesses. Livestock, including cattle, pigs, sheep, goats, and poultry, are present in the village and are raised on a small scale primarily for local consumption." ] },{ "paper_id": "d91c2ac8b93129970cedf7baaf3688e8026c2ca4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2.5, 5, 10, 20 and 30 \u00b5g/mL). Then, 10 \u00b5L 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT, Aladdin) was added to each concentration at different time (6, 12, 24, 36, 48 and 72 h), respectively. After incubation with MTT for 4 h, the supernatant was removed, and 150 \u00b5L dimethyl sulfoxide (DMSO, Sigma) was added. The UV absorbance was measured at 490 nm." ] },{ "paper_id": "d921cd2d71ffa5577a0d2c534da20f6780b3a564", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For annexin V/PI staining, treated cells (24 h) were stained with the Alexa Fluor 488 annexin V and PI flow cytometry kit (Invitrogen). Analysis of 10,000 stained cells was performed with a FACSAria 3 cytometer (BD Biosciences, USA).", "Western blot analysis. Western blotting was performed with anti-CHOP, anti-ATF4, anti-GRP94, and anti-GRP78/BiP antibodies (Abcam, USA) and anti-\u2424-actin (Santa Cruz Biotechnology, USA). Membranes were developed with a chemiluminescent reagent (Millipore). Caspase assay. The activity level of initiator caspase-8 was determined using the Caspase-Glo assay (Promega).", "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .01017-18. We declare no conflict of interest." ] },{ "paper_id": "d92ab60000f93cb3e6e10a1055b77224c8e9bae5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d92b7e913f313face4f704f326d15fca9a91183d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were lysed in RIPA buffer (150 mM NaCl, 0.5% sodium deoxycholate, 1% NP40, 0.1% SDS, 50 mM Tris-HCl [pH 8.0]) containing protease inhibitor and phosphatase inhibitor cocktails (Roche). Harvested cell extracts were separated by 10% SDS-PAGE and transferred to PVDF membranes, which were reacted with primary antibody, and then horseradish peroxidase-conjugated secondary antibody (Jackson ImmunoResearch Laboratory) and visualized with an enhance chemiluminescence system (Thermo). Images were acquired by a digital image system (UVP or Fujifilm)." ] },{ "paper_id": "d92d00ed95878f5a37061b76e848fda5b11d21da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For all capturing and sampling, permission was obtained from the Wildlife Division, Forestry Commission, Accra, Ghana. Samples were exported under a state contract between the Republic of Ghana and the Federal Republic of Germany, and under an additional export permission from the Veterinary Services of the Ghana Ministry of Food and Agriculture (permit no. CHRPE49/09; A04957).", "Protein analysis was essentially done as described elsewhere [33] . Generally, cells were lysed in RIPA lysis buffer (150 mM NaCl, 1% Igepal CA-630, 0.5% sodium deoxycholat, 0.1% SDS, 50 mM Tris (pH 8.0), protease inhibitor cocktail III, Benzonase 25 units/ml, 5 mM dithiothreitol (Merck, Darmstadt, Germany)) and separated on a 12% SDS-PAGE gel. Western blotting was performed by using mouse-anti-Mx1/2/3 (C-1, Santa Cruz, Heidelberg, Germany), goat-anti-IFIT/ISG56 (L-16, Santa Cruz), mouse-anti-actin (Sigma) immunoglobulins at dilutions 1:1000. Secondary detection was done with the help of horseradish peroxidase labeled goat-anti-mouse and rabbit-anti-goat antibody (1:20000, Dianova, Hamburg, Germany) and SuperSignalH West Femto Chemiluminescence Substrate (Thermo Fisher Scientific, Bonn, Germany).", "We thank Ute Winke and Stephan Kallies for excellent technical assistance, Antje Seebens (Noctalis) and Peter Vallo (Academy of Sciences of the Czech Republic) for field work in Ghana, and Beate K\u00fcmmerer for critical review of the data. We are grateful to Alexander Pfeifer, University of Bonn, for providing large T antigen lentiviruses, to Winfried Barchet, ", "For quantification of ONNV genome equivalents (GE) the dilution end-point was defined as one PCR unit. Log PCR units per ml for each experimental sample were calculated from the linear equations of the dilution series [26] . To determine the foldinduction of the different target genes (IFN, MxA, ISG56) the 2 2DDCt method was applied with TATA-box binding protein (TBP) as housekeeping gene [27] ." ] },{ "paper_id": "d92d26c41ab17c1cf0bea776233045118ffecb84", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2013, 5 1992 needs to be evaluated.", "There were few positives (5) by RT-PCR when 17 piglets with water diarrhea and dehydration were sampled. There may be two reasons for this phenomenon. Firstly, inability to amplify virus from all piglets might impact our results. Secondly, the piglets maybe have coinfections that might skew our results." ] },{ "paper_id": "d933299806fcd4e9e8a61e7760267154926c05ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d9367d8e090900c57b11a99848144bd83dcb80bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The bladder carcinoma cell line T24 (ATCC, Manassas, USA) was cultured in either DMEM or RPMI 1640 medium (Gibco, BRL, Life Technology Ltd. Paisley, Scotland) with 10% FBS (HyClone, Thermo Scientific).", "Results are presented as means with standard deviation. Statistical analysis was performed with the GraphPad Prism 6 program using the Mann-Whitney-U-test. Differences were considered statistically significant if p-values were less than 0.05." ] },{ "paper_id": "d940acd1f38f4b26cf2a7aeb4212f6854450ed0a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "doi:10.1371/journal.pone.0170577.g006", "Food allergies (FAs) represent an increasingly prevalent human health problem that affects a large proportion of the general population in developed countries [1] . Up to 8% of children and 5% of adults self-reported an allergy to at least 1 food [1, 2] . Despite the increasing prevalence of FA, therapeutic options remain limited [3, 4] . No treatments have been proven to a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 accelerate the development of oral tolerance or to provide effective protection from accidental exposure. The current standard management relies on antigen avoidance and emergency preparedness [4, 5] .", "The values are expressed as the mean \u00b1 SE of the respective test or control group (FA group). The statistical significance was evaluated using either a Mann-Whitney test or Bonferroni/ Dunn post-hoc tests for multiple comparisons. Probability values (P) of <0.05 were considered as statistically significant." ] },{ "paper_id": "d94115064a8168415d634f654869a4009e4c3c70", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The protocol for this trial and supporting CONSORT checklist are available as supporting information; see Protocol S1 and Checklist S1." ] },{ "paper_id": "d94872b6508c7d1b3bf580ff888aa862047ded07", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "anonymity and accommodate illiterate participants, and was documented by the interviewer electronically via personal digital assistants (PDA) prior to administering the survey. This method of obtaining informed consent was approved by CDC's IRB." ] },{ "paper_id": "d94c4d8b7d45f77cb6080edf6beae9d4bfb99fb2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ". Then Eq. (11) can be rewritten as,", "Therefore, from Eqs. (7) and (9) we obtain", "then, " ] },{ "paper_id": "d955f71fe354a87e671999a6a0a17b88376bcf8c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The NCBI database was used to obtain and compare reference genome predicted-protein sequences of CXCL16 for white rhinoceros (Ceratotherium simum; XM_004433427), horse (Equus caballus; XM_001504756), dog (Canis lupus familiaris; XM_844211), human (Homo sapiens; AY358909), domestic rat (Rattus norvegicus; DQ025528), cattle (Bos taurus; NM_001046095) and African elephant (Loxodonta Africana; XM_003416737).", "A total of 240 horses from four different breeds, Thoroughbred (TB; n = 67), American Saddlebred (ASB; n = 60), Standardbred (STB; n = 60), and Quarter Horses (QH; n = 53) were randomly selected for sequencing. These horses were a random subset of horses randomly selected from farms in Central Kentucky and previously tested for CD3 + T lymphocyte phenotyping [15] .", "doi:10.1371/journal.pgen.1006467.g003" ] },{ "paper_id": "d958168df85240e544a918d843a14e887dc41d2b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d9622ec04bc88f584cd280c9dccd177066960cf0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Overall, a GY94 model has eleven free parameters: j, x, and the nine nucleotide frequency parameters used to define U y .", "x \u00c2 ln p r;A\u00f0y\u00de =p r;A\u00f0x\u00de b 1 \u00c0 p r;A\u00f0x\u00de =p r;A\u00f0y\u00de b if A\u00f0x\u00de 6 \u00bc A\u00f0y\u00de;", "Supplementary data are available at Virus Evolution online.", "For the analysis in Fig. 2 , we fit models to the 'low divergence H1 subtree. This gave the parameter values in Supplementary Table S2 .", "All of the substitution models used in this paper have been described previously. However, here we briefly recap their exact mathematical implementations." ] },{ "paper_id": "d964ce1c8dd79290032b1b70d511f256b805e558", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ''accordion hypothesis'' of rapid evolution posits that gene amplification provides a replication benefit to the virus and those extra copies of a weak viral antagonist of host defenses provide additional templates to acquire potentially adaptive mutations.", "VVDEDK+RhTRS1 was constructed by homologous recombination of plasmid pEQ1233 [20] into the thymidine kinase (TK) locus of VVDEDK. Recombinant virus was plaque purified three times in BSC40 under G418 selection and subsequently propagated and titered on BSC40 cells.", "Library preparation and sequencing. From each viral pool, 75 ng of viral DNA was sheared and ligated to adaptors by transposition using the Nextera kit (Epicentre), following the manufacturer's direction with several modifications: transposition was performed in 20 ul volume using 0.1 ml Nextera transposase enzyme and ''HMW'' reaction buffer at final 1X. Transposition was carried out for 10 minutes at 55uC, after which sheared, adaptor-ligated templates were transferred directly to PCR reactions for amplification. In addition, PCR incorporated a sample-specific barcode tag on the reverse primer. Amplified libraries were pooled and cleaned using Ampure beads (Beckman Coulter) at a 1.8:1 ratio of beads to input. The pooled libraries were sequenced on an Illumina HiSeq 2000 instrument (Illumina) using 101-bp forward and reverse reads with a 9-bp index to read the per-sample barcode." ] },{ "paper_id": "d9664a611b4984ab4c6a6000a55ae8b495f7e997", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Doctors and patients often prefer newer and more expensive antibiotics, which are considered more \"powerful\" [62] \u2022 Physicians provide antibiotics to help individual patients; potential societal risks are not considered [86] ;", "\u2022 Doctors' prescribing habits is influenced by personal income generated and incentives provided by pharmaceutical companies [70, 86, 87] . In China, as in many other Western Pacific countries, drug prescriptions supplement a doctor's income [62] .", "Fear of poor patient outcome or litigation" ] },{ "paper_id": "d9830dd1a44317a284afc206daa20206fa6552bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).", "Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.", "Abstract P1" ] },{ "paper_id": "d986c44da50830e309f5d89cd81595edf1f05200", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.", "-Swiss Tropical and Public Health Institute, Switzerland -Animal and Plant Health Agency (APHA), United Kingdom -University of Ibadan, Nigeria -The Global Research Alliance for bovine Tuberculosis (GRAbTB)", "The Role of Media over the past 3 years, all efforts, activities, and events related to ZTB were highlighted by a considerable number of local, regional, national, and global media sources including Central News Network (CNN), the British Broadcasting Corporation (BBC), and Le Monde newspaper in France, to name a few." ] },{ "paper_id": "d98b22c96490966661c90f9c892c717545c5f8fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.ppat.1006778.g009", "https://doi.org/10.1371/journal.ppat.1006778.g010" ] },{ "paper_id": "d9a66cbdd96e0bce18bc370c96ef5e71c5a7a27d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The chemical structures of the separated diterpenes were established by UV, Mass, 1 H-NMR and 13 C-NMR spectrometry. The UV spectra were recorded using the DAD detector of the Agilent 1200 system. ESI-MS spectra were recorded on an API 2000 mass spectrometer in positive ion mode, whereas NMR spectra were recorded on a Bruker Avance III 600 MHz spectrometer.", "The HPLC analysis was carried out on an Agilent 1200 instrument (Agilent Technologies Co., Ltd., Santa Clara, CA, USA) consisting of a G1311A pump, a G1315D UV/Vis detector, a G1316A thermostat, an autosampler and an Agilent workstation. ESI-MS spectra were recorded on an API 2000 mass spectrometer (AB SCIEX, Milwaukee, WI, USA). The NMR spectra were recorded on Bruker Avance 600 MHz (Bruker, Karlsruhe, Germany) spectrometer using tetramethylsilane (TMS) as the internal standard.", "HPLC analysis of the separated diterpenes was carried out at 25 \u2022 C, on a XAqua C3-column (flow rate: 1.0 mL/min) and the chromatogram was recorded at 254 nm. Water and methanol were the mobile phases A and B, respectively. The gradient elution steps were as follows: 0-30 min, 75-85% B." ] },{ "paper_id": "d9b9b75ee4d554ad43e8a8531af0b6763a1d6652", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CD8 + T cell-intrinsic CEACAM1 is necessary for viral control.", "Histology. Histologic analyses of snap-frozen tissue were performed with a mAb to anti-CD45R (B220; RA3-6B2) and anti-CD90.2 (53-2.1) (both from eBioscience). Biotin anti-CD169/SIGLEC1 (MOMA-1) (Acris) antibody was used to stain CD169 macrophages. Sections were washed and stained with streptavidin antibody (eBioscience). In short, sections were fixed with acetone for 10 min, and nonspecific antigen binding was blocked in PBS containing 2% FCS for 15 min, followed by staining with various antibodies for 45 min. All antibodies were diluted 1:100 from their original concentration in blocking solution. Images of stained sections were acquired with a fluorescence microscope (KEYENCE BZ II analyzer; KEYENCE Corporation of America, Itasca, IL, USA).", "Alanine transaminase and aspartate transaminase. The activity of ALT and AST was measured at the Central Laboratory, University Hospital Essen, Germany." ] },{ "paper_id": "d9c174a11b8d2bd0a4df65b17e576934f3cce31c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Many different IBV serotypes and genotypes circulate worldwide [2, 6, 13] . These serotypes arise due to high frequency of mutations and/or recombination events [14, 15] . Cross-protection between different serotypes is variable or poor [16] .", "Viral vectored vaccines provide an alternative approach to live-attenuated IBV vaccines. A vectored vaccine expressing the protective antigen of IBV will not lead to creation of variant viruses. Attempts have been made to express S1 or S2 subunits of S protein using fowl pox virus, herpes virus and adenovirus vectors [31] [32] [33] [34] . However, none of these vaccines are effective in providing complete protection against IBV, suggesting the need for new vaccine vectors.", "Statistical significance between different groups were determined using one-way analysis of variance (ANOVA) followed by Tukey's multiple comparison test using Prism 7 (GraphPad Software Inc., San Diego, CA) with P value < 0.05.", "Infectious bronchitis (IB) is an acute, highly contagious viral disease of chickens. IB affects chickens of all ages and based on the organ system affected the disease is manifested in three major clinical forms-respiratory, renal and reproductive. IB causes great economic losses in the poultry industry worldwide [1, 2] . Infectious bronchitis virus (IBV) is a member of the genus Gammacoronavirus in the family Coronaviridae. The viral genome is a single-stranded, positive-sense RNA of about 27.6 Kb in length [3] . The 5\u2032-two-third of the viral genome codes for the non-structural proteins responsible for RNA replication and transcription. The 3\u2032-one-third of the viral genome codes for four structural proteins, namely, spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins, in addition to several non-structural proteins [3] ." ] },{ "paper_id": "d9c950cf19a2048596a6e143471fb2d0c009d8f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Of . The 124 people who received continuing services received an average of 4.7 consultations; 51 individuals in this group received more than one face-to-face service (41, 0.8 % of quarantined individuals) and CMHC staff evaluated five of these 51 individuals as facing a high-risk of mental illness and referred them to psychiatric treatment (Fig. 2) ." ] },{ "paper_id": "d9c9f9f03cb93fd7ddd3f409d8948f0ecf30445e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SCIeNtIfIC REPORTS | 7: 16652 | DOI:10.1038/s41598-017-16952-8", "Data availability statement. The datasets generated during the current study are available from the corresponding author on reasonable request." ] },{ "paper_id": "d9cd10250bab75a881cb23146ea83b8dee7bb302", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/ mSphere.00105-18. ", "Statistical analysis. All experiments were performed at least three times. Data were analyzed by either Student's t test for pairwise comparisons or by analysis of variance (ANOVA) with preplanned comparisons, using SAS (Cary, NC). Significance was set a priori at P \u03fd 0.05.", "Cells, viruses, and bacteria. The 293A cell line was obtained from Thermo Fisher Scientific (Waltham, MA) (R70507), and the A549 and Caco-2 (C2BBe1 clone) cell lines were obtained from ATCC (Manassas, VA) (ATCC CCL-185 and ATCC CRL-2102). Cell lines were tested for and verified as Mycoplasma negative. Escherichia coli strain K-12 (ATCC 10798) was purchased from ATCC. E. coli strain DH5\u2423 was a gift from Michael Gilmore at Massachusetts Eye and Ear Infirmary, Harvard Medical School. HAdV-D19 (ATCC VR-1096) and HAdV-D29 (ATCC VR-1107) were purchased from ATCC and verified by molecular typing of the major capsid genes. Viruses were purified using the cesium chloride gradient method, verified as endotoxin negative, and the titers of the virus were determined by the tissue culture infectious dose method." ] },{ "paper_id": "d9d1928e12dca038ff13cd0188d9fdc10a0f560d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These LMP1 features did not however co-segregate with EBV type I or type II, which are distinguished by the sequence of the EBV nuclear antigens (EBNA2 and EBNA3) [82, 86] .", "Several studies have tested for differences in LMP1 oncogenic signaling and biological properties, including the transformation of Rat-1 fibroblasts and increased motility in human foreskin keratinocytes [20] . All LMP1 strains have oncogenic properties and while there may be notable differences in regulators of NFKB signaling, there has been no consensus on a clear difference that distinguishes the oncogenic properties of the China1 strain or the closely related CAO variant [20, [108] [109] [110] [111] [112] . However, it remains possible that LMP1 sequence polymorphisms outside the regions defining LMP1 strains may indeed differ in biological properties.", "LMP1 is a six-pass transmembrane protein that is primarily characterized for its effects on cellular signaling pathways via protein-protein interactions in plasma and cytosolic membranes but is not known to possess intrinsic enzymatic activity [28] . The pleiotropic signaling properties of LMP1 have been extensively reviewed [6, 14, 15, 17, 28] . This review will focus on the latest developments on EBV epithelial infection models, discuss the implications of LMP1 sequence diversity, and summarize LMP1 effects on nuclear and extracellular processes." ] },{ "paper_id": "d9d2f8f421d0290a8dbf0ec92cbbe1ad2d93a694", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bats are a reservoir for a diverse range of viruses, including coronaviruses (CoVs).", "RdRp gene sequences were deposited in GenBank under accession number KT345294 to KT345296." ] },{ "paper_id": "d9e06d074df536664275030a32f54ff8d8bb0361", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The C 0 D 0 E 0 F 0 b-sheet (or ''top'' sheet) contains most of the determinants of CD81 binding (blue circles in Fig. 6A ", "A direct interaction of the HCV envelope protein E2 with CD81 and SR-B1 has been demonstrated, and these interactions were shown to be necessary but not sufficient for cell entry. The mode of interaction of HCV with the claudins and occludin is not understood at present.", "Because of the higher production yields, we pursued most of the biochemical characterization using E2e from genotype 2b, to which we will refer to as E2e in the rest of the manuscript, except when explicitly stated. Yet because the best functionally characterized HCV strain is H77 (genotype 1a), we use the amino acid numbering corresponding to the H77 polyprotein throughout the manuscript." ] },{ "paper_id": "d9eb8ffffee8147c850b00f613a1978c18505580", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses are characterized by a significant capacity for genetic change that enables them to adapt to new hosts and ecological niches, sometimes causing zoonotic outbreaks with disastrous consequences like the SARS epidemic in 2003 [103] . In this chapter, I shall discuss the possibility of heterospecific coronavirus infections in cats or dogs.", "Genotypes. FCoV and CCoV strains are classified into 2 main genotypes, which are schematized in Figure 1 , in which their phylogenetic relationships are highlighted.", "To date, only one pantropic CCoV strain (CB/05) has been sequenced and compared to avirulent CCoVs. Curiously, the S protein displayed the highest degree of identity to FCoV-II strain 79-1683. Only residues Pro-73, Asn-125, and Ala-407 were peculiar to strain CB/05. A substitution at position 125 (Asp to His instead of to Asn) was also found in the BGF10 strain, a hypervirulent enteric strain [87] .", "Investigation of recombinant coronaviruses, including MHV, TGEV, and IBV, has conclusively demonstrated that the spike is an essential determinant for the pathogenicity of these viruses [84] [85] [86] .", "Beyond the alphacoronaviruses, cats are also susceptible to SARS-CoV replication. After intratracheal inoculation, infected animals shed the virus from the pharynx from 2 to 10 days postinfection and transmitted the virus to animals with which they were in close contact [113] . Although none of the infected cats developed any symptoms, mild pulmonary histologic lesions were observed in these animals." ] },{ "paper_id": "d9ecb8e78616bebdb37e3b3b689ad60bafd922e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by a Midwestern University new investigator start-up grant.", "This work, including the efforts of Adeyemi O. Adedeji, was funded by Midwestern University New Investigator Start-Up Fund." ] },{ "paper_id": "d9f0fd49a89212c8d2089c84cd9a9d8573277288", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "d9fa99532407c6f68ffa719e321870586363c18a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The object of SVM is to identify an optimal decision boundary that is divided by maximizing the margin between the nearest samples of two different data groups [16] . SVM uses input-output pairs, such as D = {(x 1 , y 1 ), (x 2 , y 2 ), \u2026, (x \u2113 , y \u2113 )}, where i = 1, \u2026, \u2113 for classification, ", "where t means the order of the weeks and x t means the counted number at week t. For example, data for 'H1N1' can be expressed as", "(3) [18] :" ] },{ "paper_id": "da00316edfd01f02f8628c4e5740e0b825137634", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This review discusses in detail the NiV biology, its transmission and epidemiology, pathology, and advances in diagnosis, vaccine designing, and suitable prevention and control studies to be adopted to counter this emerging pathogen.", "An overview on different vaccine strategies available for Nipah virus (NiV) is presented in Table 1 and few important vaccine platforms are depicted in Figure 5 .", "ARTICLE HISTORY", "The phylogenetic analysis affirmed the circulation of two major clades of NiV, i.e. NiV-BD and NiV-MY, based on currently available complete N and G gene sequences ( Figure 3A ,B). The NiV isolates from Malaysia and Cambodia clustered together in NiV-MY clade, whereas isolates from Bangladesh and India clusterered within NiV-BD clade. Nonetheless, NiV isolates from Thailand harbored mixed population of sequences and distribution of the Thai isolates was seen in both NiV-MY and NiV-BD, based on N gene sequences. Notably, intra-clade (NiV-MY and NiV-BD) sequence similarity of G gene at nucleotide level was high between 98 and 100%, while inter-clade similarity was relatively less, i.e. 92.2-93.0%. Similar observation was recorded with N gene sequences where intra-nucleotide similarity in NiV-MY and NiV-BD isolates ranged between 99.1 and 100% and the inter-clade similarity was between 93.6 and 94.6%. The inference from analysis affirms circulation of two populations of NiVs currently." ] },{ "paper_id": "da030e57b186fc870eab92c4f1ac6be717ede6da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Singapore is an Asian city-state, situated near the equator with a tropical climate, comprising 5.40 million of people. Besides being exposed to daily ambient air pollution generated from domestic sources, Singapore is also exposed almost yearly to haze episodes of about a month long duration, whereby smoke from regional forest fires especially during the dry seasons is blown by winds from neighbouring countries [16] ." ] },{ "paper_id": "da2087c111ef9c8894c1dd1644d66a3aca35de9e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "da215867201d36fa409a1f64aa89dfe75d537784", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the different CHIKV virus strains ( ", "Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis." ] },{ "paper_id": "da263831b51c583027932f156c45463780ea35fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For Dr. Patcai -nil. Dr. Moldofsky is a consultant to, or is on the advisory boards of, or has received speakers honoraria, and/or research support from Eli Lilly, Jazz, Tonix (Krele), Lundbeck, Merck, Pfizer, Pierre Fabre, Sanofi Aventis, Schering Plough and Valeant." ] },{ "paper_id": "da26991502da97b746b148ad17cb2b435ef8e0cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were lysed in RIPA buffer (150 mM NaCl, 0.5% sodium deoxycholate, 1% NP40, 0.1% SDS, 50 mM Tris-HCl [pH 8.0]) containing protease inhibitor (Roche). Harvested cell extracts were separated by 10% SDS-PAGE and transferred to PVDF membranes, which were incubated with primary antibody, then horseradish peroxidase-conjugated secondary antibody (Jackson ImmunoResearch Laboratory) and visualized by an enhanced chemiluminescence system (Thermo). Images were acquired by use of BioSpectrum Image System (UVP, Upland, CA).", "TurboFect transfection reagent (Thermo Scientific) was used for transient transfection following the manufacturer's protocol. Cells cultured in 12-well plates were transfected with IFNstimulated response element (ISRE) Luc reporter plasmid before viral infection or IFN\u03b2 stimulation. pRL-TK (Promega), encoding Renilla luciferase under an HSV thymidine kinase promoter, was an internal control. Cell lysates were collected for dual-luciferase assay (Promega). Firefly luciferase activity was normalized to that of Renilla luciferase.", "The Pep VP0-21, a 21-amino-acid synthetic peptide, NLTQHPSAPTIPFTPDFRNVD, derived from the conserved VP0 caspid protein, was found highly antigenic for detection of HPeV [23] . New Zealand rabbits were vaccinated with Pep VP0-21 peptide in six boosts over 2 months. At 7 days after the last boost, immunized rabbit serum containing anti-HPeV1 VP0 antibody was harvested and peptide affinity-purified. The antibodies for phospho-IRF3 (pS386) (#2562-1, Epitomics), IRF3 (#sc-9082, Santa Cruz Biotechnology), phospho-STAT1 (phospho-Tyr701) (GTX50118, GeneTex), STAT1 (#9172, Cell Signaling) and \u03b2-actin (MAB1501, Millipore) were used for immunoblotting." ] },{ "paper_id": "da284bc0d5d74602b201a169fb7a0392eef5b6f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. The statistical package SPSS 11.5 was used for data analysis. P-value \u22640.05 was considered to indicate a statistically significant difference.", "It is estimated that approximately 180 million people have been infected with the hepatitis C virus (HCV) and approximately 130 million people are chronic HCV carriers (1).", "Plasmids and bacterial strains. The p90/HCVFLlongpU plasmid carrying full-length coding sequences of HCV was a generous gift from Professor Charles M. Rice from the Center for the Study of Hepatitis C, Rockefeller University, New York, NY, USA. The Escherichia coli (E. coli) strains, Jm109, DH5a and BL21 (DE3), were used as the cloning and expression hosts." ] },{ "paper_id": "da2b69c89152ddb6f2df6c836bd84aebba2a0b65", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations EST: expressed sequence tag; NT: non-redundant NCBI nucleotide database; HTGS: High Throughput Genomic Sequences database; PMT: Photomultiplier tube." ] },{ "paper_id": "da2bc204c003c35a7edb72cd61a721d51392f1da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mechanism of Inducing Autophagy (Activation/Inhibition)", "The authors declare no conflict of interest." ] },{ "paper_id": "da2e71598a773b197d08b2521a8fb1a2818bdd10", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The relationship between humans and viruses has a long history. Since the first identification of viruses in the 19th century, we have considered them to be 'pathogens' and have studied their mechanisms of replication and pathogenicity to combat the diseases that they cause. However, the relationships between hosts and viruses are various and virus infections do not necessarily cause diseases in their hosts. Rather, recent studies have shown that viral infections sometimes have beneficial effects on the biological functions and/or evolution of hosts. Here, we provide some insight into the positive side of viruses.", "Yet, these negative aspects of viruses do not tell the whole story since the relationships between hosts and viruses are multitudinous, and virus infections do not necessarily lead to disease symptoms in hosts. Rather, recent studies suggest that there are viruses that are beneficial to the biological functions and/or evolution of their hosts. Recently, we established a research consortium, designated as 'Neo-virology', which is supported by Grants-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Science, Sports, and Technology (MEXT) of Japan. In this consortium, we define a virus as a component of the global ecosystem. Our aim was to elucidate the roles of viruses in host organisms and the global ecosystem, in contrast to traditional virology research, which tends to focus on pathogenic viruses that cause diseases in their hosts. This research project is expected to develop into an important scientific field that examines the interactions between the global ecosystem and viruses. In this brief review, we give some insights into the positive side of viruses.", "Our world is made up of vastly different physical environments and the various organisms that have adapted to live in those environments. The complex interactions between the living and nonliving components of these environments are the basis of the global ecosystem. Various schemes have been proposed to classify living organisms: the one most often used currently defines all living organisms as archaea, bacteria or eukaryotes. Therefore, viruses are not considered living components of the global ecosystem. Given that approximately 10 31 virus particles exist on Earth 56,57 and all of them are parasitic in living organisms, it is not hard to imagine how virus infection might affect the physiological functions of both hosts and the ecosystem. Although 'traditional' virology research tends to focus on pathogenic viruses that cause diseases in their hosts, the recent progress in next-generation sequencing (NGS) technologies and data analyses has enabled us to discover a wide variety of new viruses, some of which do not cause diseases in their hosts. Some obstacles to comprehensive virome analyses remain, such as viral dark matter, which are sequences that originate during virus metagenomics but cannot be aligned to any reference sequences of viruses. 58 Nonetheless, recent viral metagenomic studies using NGS technologies and bioinformatic analyses have identified a large number of viruses in environmental samples, including plants and oceans. 59, 60 Characterisation of these newly identified viruses may provide new insight into the significance of viruses and virus-mediated processes within global ecosystems." ] },{ "paper_id": "da309b7481a117d1aad2212d42ad3b7c0c68abf3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coordinates and structure factor files have been deposited in the Protein Data Bank, with accession code 4K6M.", "The cells were resuspended in a Lysis buffer of 300 mM NaCl, 50 mM Tris pH 8.0, 10 mM imidazole, 0.02% (w/v) NaN 3 , 20% (v/v) glycerol, and were lysed by passage through an AH-2010 homogenizer at 14,500 psi (ATS Engineering Ltd.). IGEPAL CA-630 (Sigma-Aldrich) was then added to a final concentration of 0.1% (v/v), and polyethylenimine (PEI) was then added slowly to 0.05% (v/v) over a 20-min period to precipitate nucleic acid. The lysate was slowly stirred at 4uC for an additional 15 min and then centrifuged for 40 min at 17,000 rpm in a SS-34 rotor (Thermo Scientific). The clarified lysate was loaded onto a nickel-charged HisTrap HP column (GE Healthcare), followed by step elution with 300 mM imidazole in 50 mM Tris pH 8.0, 300 mM NaCl, 20% (v/v) glycerol, and 0.02% (w/v) NaN 3 . Fractions containing NS5 were pooled and diluted to reduce the NaCl concentration to approximately 90 mM prior to loading onto a HiTrap SP HP column (GE Healthcare) and eluting with a linear gradient to 1 M NaCl in 25 mM MES pH 6.0, 0.1 mM EDTA, 20% (v/v) glycerol, and 0.02% (w/v) NaN 3 . The pooled fractions were concentrated to approximately 0.9 ml and run over a Superdex 200 gel filtration column (GE Healthcare) equilibrated in a GF buffer of 300 mM NaCl, 5 mM MES (pH 5.8), 20% (v/v) glycerol and 0.02% (w/v) NaN 3 . Pooled fractions were supplemented with tris-(2-carboxyethyl)phosphine (TCEP) to a final concentration of 5 mM, concentrated to approximately 15 mg/mL, flash frozen with liquid nitrogen, and stored at 280uC in 10-20 ml aliquots. The extinction coefficient of 220,615 M 21 cm 21 was calculated based on protein sequence using the ExPASy ProtParam program (http://www.expasy.ch/tools/protparam.html). The typical yield is 3-5 mg of pure protein per liter of bacterial culture.", "general, RdRPs that initiates via de novo mechanism such as JEV NS5 have a bulkier thumb than those of primer-dependent RdRPs, carrying additional elements (either as insertions and/or C-terminal extensions) that facilitate de novo initiation [7] [8] [9] 21] ." ] },{ "paper_id": "da31b90321637cd3a3464969817540a35d6a597c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recently, many research groups have tried to improve the accuracy of ELISA by introducing monoclonal antibodies [16, 17] , synthesizing new ELISA polymer substitutes [15] , employing more sensitive biomarkers [18] and using nanomaterials [19] [20] [21] [22] [23] . However, these studies were optimized within the framework of traditional ELISA and still relied on ELISA plates. Thus, these problems remain largely unresolved. New techniques for immunosorbent assays call for quantitative surface sites for antigen-antibody binding and fewer steps or reagents in the process to avoid these limitations.", "Tau, tau-FITC, rabbit anti-human tau antibody and bovine serum albumin (BSA) were purchased from Sangon Biotech Co. Ltd (Shanghai, China). GO was purchased from XFNANO (Nanjing, China). N-(3-dimethylaminopropyl)-N-ethylcarbodiimde hydrochloride (EDC), 2-(N-Morpholino) ethane sulfonic acid (MES) and N-hydroxysuccinimide (NHS) were purchased from Tokyo Chemical Industry (Japan). All other reagents were purchased from J&K Scientific (China) and were of analytical reagent grade and used without further purification.", "Experiments under similar conditions were performed three times, and the data points in figure 4b were linear. The fitting function of the curve is I = 1.23c (tau concentration) with an R\u00b2 of 0.98888." ] },{ "paper_id": "da38234a5ddf7e9d8d468b64e942a50bf164e924", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These sequences are deposited in NCBI Genbank under the strain names SC677 day 15 (KY369909), SC379 day \u221212 (KY621348), and SC399 day \u22129 (KY674914). The non-human reads are deposited in the NCBI Short Read Archive under accessions SRR5809357-SRR5809372, SRR5809395, SRR5816371-SRR5816372.", "Attempts to culture each of the patient's specimens on MRC-5 cells proved unsuccessful. No CPE was visualized for any of the patient's four clinical samples and HCoV 229E RNA levels in the culture supernatant were undetectable by qRT-PCR after inoculation, while viral growth was apparent in the positive control HCoV 229E ATCC type strain ( Figure S3 ).", "In summary, we describe a large deletion in HCoV 229E encompassing almost an entire gene that was temporally associated with myeloblation. Little is known about the genome evolution of HCoV 229E as only 20 genomes are currently available in NCBI Genbank. Similarly sized (500-700 nucleotide) deletions have previously been found in hepatitis D virus in patients receiving antiviral therapy. 17 Our study is also the first demonstration of microbial evolution associated with cyclophosphamide treatment or irradiation. Further research into how chemotherapy and irradiation affect the microbiome is warranted. As mNGS is increasingly performed in the clinical lab, 18 much intriguing biology can be unlocked from clinical specimens, providing a continuing case for the sequencing clinical microbial genomes. [19] [20] [21] " ] },{ "paper_id": "da3dea36182741e1b3699e372f16e1f0bb2fd315", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "da412bad3772b82d1b3ab2d1aa1e00035869ac55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Briefly, as part of ORChID, families expecting a healthy term baby were recruited antenatally at either the publically funded Royal Brisbane and Women's Hospital or the North West Private Hospital, in Brisbane, Australia, a subtropical city of more than 2 million inhabitants [22] ." ] },{ "paper_id": "da5958b5a0d82961e2cef5f42fe1e3d9ce6a30cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mutant host strain required for propagation tRNA expression required for selection [36] Post-segregational killing (PSK) systems Sequence addition to miniplasmid is short Toxin is highly efficient for selection PSK genes can cause mild toxicity [55] [56] [57] RNA IN/RNA OUT RNA sequence is only transcribed in prokaryotes Mutant host strain required for propagation [58, 59] RNA I/RNA II No sequence addition to plasmid necessary Can be produced in gram quantities more easily than standard plasmids Mutant host strain required for propagation [60, 61] Overexpression systems No mutant host strain needed Not much shorter than plasmids Potential metabolic burden on host strain Possible antibiotic contamination of final product [62, 63] ", "Production process avoids bacterial contaminants such as endotoxin PCR amplification of product is potentially error prone [85] Ministring Chromosomal integration causes apoptotic cell death One-step in vivo production system This system can also create ccc vector topology", "Uses ampicillin resistance as a selection marker Residual ampicillin or endotoxin possible in final product [86] [87] [88] [89] Mini-intronic plasmid", "The authors were supported in part by the Baylor-University of Texas (UT) Houston Center for acquired immune deficiency syndrome (AIDS) Research Core Support Grant number P30 AI036211 (Butel, PI), and in part by the National Institutes of Health (NIH) grants R56 AI054830 and R01 GM115501 to L.Z. We thank our generous anonymous donors for the Research Support Fund. We thank Dr. Brian E. Gilbert (Baylor College of Medicine, Houston, TX, USA) and Christopher E. Coker (Twister Biotech, Inc., Houston, TX, USA) for critically reading the manuscript." ] },{ "paper_id": "da6d83da65e485c34b903968ae22da9efbd81628", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In 1992, the Institute of Medicine report Emerging Infections: Microbial Threats to Health in the United States correctly identified \"microbial adaptation and change\" and \"expanding international travel and commerce\" as two of the major factors contributing to disease emergence and re-emergence [1] . Severe Acute Respiratory Syndrome (SARS), in retrospect, epitomized this new model of disease outbreak. The previously unrecognized SARS-CoV coronavirus mysteriously surfaced in Guangdong Province, China, in November 2002, simmered there for three months, and arrived in Hong Kong on a jet plane. From that busy aviation hub, it quickly spread to Vietnam, Singapore, and Canada, eventually afflicting 27 countries and taking 813 lives [2].", "Air transportation has undoubtedly been a boon to humankind -bringing together peoples, cultures and values, and profoundly changing the way we live. But it has also greatly aided the global transmission of infectious disease. In the old days, geographical distance provided a measure of protection as signs and symptoms had time to develop and those afflicted could be screened at border entry points. Today, with hardly an airport unreachable within 36 hours from any point on our planet, the speed -and pattern -of microbial movements has altered dramatically.", "Take thermal scanners for instance -first deployed in Singapore's Changi Airport and enthusiastically adopted by other \"high-risk\" airports around the world, in answer to the International Civil Aviation Organization's (ICAO) call for mass-screening of arriving and departing passengers and crews for raised temperature [8] . It was an innovative application of military technology to address an urgent need. To date, however, we are none the wiser regarding the sensitivity, specificity, or cost effectiveness of this screening tool for SARS, much less its usefulness for influenza. About all we know is that Canadian officials reportedly screened 1 million passengers with thermal scanners at an estimated cost of Can$7.55 million, without detecting a single case of SARS [9, 10] ." ] },{ "paper_id": "da6eca2ce0887d1ac0cf592d964a42717bcaa33b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Upper respiratory tract infection (URTI)", "The detection of CRVs above and including the larynx (e.g., in samples from nose, pharynx, larynx, conjunctivae, or sinuses)", "The authors declare no conflict of interest. ", "A brief summary of parts of the above data can be found in Table 4 . " ] },{ "paper_id": "da77b57aa291d1174c30c2e07f56ec327564fb54", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "da7fb6a91b2595d009f5e9f60a45cc0a45fceac7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "YN and Y-JZ designed this manuscript. YN prepared the main body of the manuscript. Y-JZ prepared the figure and revised the manuscript. All authors approved it for publication.", "Frontiers in Microbiology | www.frontiersin.org April 2018 | Volume 9 | Article 750 Frontiers in Microbiology | www.frontiersin.org Disclaimer: Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement." ] },{ "paper_id": "da841082920197ef43a5d5bdb05b38ed7cccf9fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The concentration of drugs that caused 80% cellular cytotoxicity is referred to as CC 80 . Experiments were performed in triplicate. Data are represented as the mean \u00b1 standard deviation (SD). Statistical differences were determined using a paired t-test and a one-way ANOVA using the Prism 8.0 software (GraphPad Software,). A p-value <0.05 was selected to indicate significance.", "Total cellular RNA was extracted using the RNApure Tissue & Cell Kit (CWBIO, Nanjing, China). The primers for PDCoV M and \u03b2-actin genes were: PDCoV-F, 5 -ACAATCGACCACATGGCTCCAA-3 , PDCoV-R, 5 -CAGCTCTTGCCCATGTAGCTTCA-3 , \u03b2-actin-F, 5 -CTCCATCATGAAGTGCGACGT-3 , \u03b2-actin-R, 5 -GTGATCTCCTTCTGCATCCTGTC-3 [1] . The quantity of vRNA was determined using a LightCycler96 (Roche, Germany) and HiScript II One Step qRT-PCR SYBR Green Kit (Vazyme, Nanjing, China), according to the instructions of the manufacturer. The relative level of RNA expression was determined by the 2 \u2212\u2206\u2206CT method. \u03b2-actin mRNA level was used as a loading control. The mean RNA level of the mock-treated group was set at 100%.", "In conclusion, our results indicate that LiCl and DG have potential as effective anti-PDCoV drugs. During an outbreak of porcine epidemic diarrhea, LiCl and DG could be added to drinking water at the appropriate dose or be given as an intramuscular drug for treatment at the early onset of an epidemic. Further studies are required to explore their antiviral effect against other CoVs and their mechanism of action to control PDCoV infection in vivo." ] },{ "paper_id": "da867b3ea92b5191c4fbdc4d09c0712a73da7766", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "da8a9f50efb758be10b61ea4c5c51cd2fbd004b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at http://www.mdpi.com/2079-4991/7/1/2/s1." ] },{ "paper_id": "da9c223fd6f69816aca093a7d2ab333fe9b21ee1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ProteinChip arrays were read using a Ciphergen Protein-Chip Reader PCS4000 model and data were analyzed with Ciphergen Express Software (Ciphergen Biosystems).", "Porcine reproductive and respiratory syndrome (PRRS) is one of the most important infectious swine diseases throughout the world [1] [2] [3] and is still having, more than two decades after its emergence, major impacts on pig health and welfare (reviewed by [4] ). The responsible agent is an enveloped, ca. 15 kb long positive-stranded RNA virus (PRRSV) that belongs to the Arteriviridae family [5] and that can cause late-term abortions in sows and respiratory symptoms and mortality in young or growing pigs. Once this virus has entered a herd it tends to remain present and active indefinitely causing severe economic losses and marketing problems due to high direct medication costs and considerable animal health costs needed to control secondary pathogens [6, 7] .", "Veterinary inspections of the overall clinical status of the piglets at the day of serum collection did not evidence any clinical symptoms of PRRS, including respiratory distress or sneezing." ] },{ "paper_id": "da9c2a65da6499124bab5ad5754dddf47fe0baaf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In summary, we anticipate that this improved and updated version of IMG/VR along with the capability of downloading its data content will serve as an essential resource for researchers studying viral ecology and genomics from specific targeted environments to global scales.", "Viruses are ubiquitous, extremely abundant and diverse across all ecological niches (1) . Traditional cultivation ap-proaches remain challenging and have resulted in genomic characterization of only a small fraction of the virosphere (2) . Advances in sequencing technologies and approaches to reconstruct uncultivated viral genomes directly from the environment have provided new avenues to catalog and explore the vast viral sequence space (3, 4) .", "To complement iVGs and UViGs content, we incorporated a public set of 12 498 high-confidence viral genomes (prophages) detected in microbial host genomes (19) . This dataset was used to create additional vOTUs (see below), and to enhance host-virus predictions helping to connect 3017 genome fragments with their specific hosts.", "Viral-host specificity prediction. The prediction of putative host(s) for the UViGs has been split into two categories: specific host prediction and domain-level taxonomic assignment (prokaryotic and eukaryotic viruses)." ] },{ "paper_id": "daa3f7d4838adebf0aac1be3cda2924fc1d2106a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study conforms with the conventions outlined in the Declaration of Helsinki, it received internal ethics board approval at the Universities of Alberta and Calgary for use of human subjects, and all subjects gave written informed consent [15] ." ] },{ "paper_id": "daaa53a49dc0d23015e22a150495ac657aa993d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus isolates. A plaque-purified isolate of equine torovirus, Berne strain (isolate P138/72) (EToV), was kindly provided by Raoul de Groot (Utrecht University) and cultured in equine dermis (ED) cells. This virus was initially isolated from a symptomatic horse in 1972 (15) . ED cells were maintained in Dulbecco's modified Eagle's medium (Invitrogen) supplemented with 10% fetal calf serum, 100 IU/ml penicillin, 100 g/ml streptomycin, 1 mM nonessential amino acids, 25 mM HEPES, and 1% L-glutamine in a humidified incubator at 37\u00b0C with 5% CO 2 .", "To visualize TRS conservation, multiple-sequence alignments were generated using Clustal Omega with default parameters (67) . RNA structure was predicted using RNA-Alifold (68) and visualized using VARNA (69) .", "T he order Nidovirales currently contains four families of positive-sense, singlestranded RNA viruses: the Coronaviridae, Arteriviridae, Roniviridae, and Mesoniviridae (1). Their grouping into the one taxonomic order is based upon replicase protein conservation, genome organization, and replication strategy. However, these viral families are nonetheless very diverse with respect to their virion structure, host range, pathogenic potential, and genome size." ] },{ "paper_id": "dabb3cd242342b19aadc8f9eadd2677a18deac13", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "dacb58b5ac7adedfeb44dde5632c503c5d37548f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Glutamine plays a critical role during infection that can be partially substituted by addition of TCA cycle intermediates", "Global cellular metabolism is an intricate and tightly regulated network of pathways that generate building blocks and energy to sustain the life of the cell. Viral infection often leads to shifts in substrate utilization, dysregulation of metabolic pathways and changes in cellular energetics to facilitate maximal viral replication. This is exemplified by studies conducted on human cytomegalovirus (HCMV), in which infected cells display augmented cellular metabolism [1, 2] and an anaplerotic shift in which glucose is converted into precursors for nucleotide and lipid synthesis and glutamine is utilized to replenish the tricarboxylic acid (TCA) cycle [3] .", "We utilized electron microscopy to visualize the assembly process after synchronization with rifampicin for 12 h and release into vehicle alone or C75 for an additional 8 h (Fig. 9C) . When cells were released into vehicle alone, we saw the full spectrum of assembly intermediates including crescents (C), immature virions (IV), immature virions with nucleoids (IVN) and mature virions (MV). The images seen upon release into C75 were strikingly different. The flaccid membranes that accumulate in the presence of rifampicin were indeed ''chased'' into normal crescent membranes by their association with the D13 scaffold protein." ] },{ "paper_id": "dacc557b6e40bb69974e2e1a831aef665e524867", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For cell experiments, statistical analysis were conducted by one-way analysis of variance (ANOVA), followed by Tukey's post hoc test, or a t-test. For mice experiments, results were compared using two non-parametric statistical tests: Kruskal-Wallis and Mann-Whitney. Survival rates were plotted as Kaplan-Meier survival curves and were compared using the log rank (Mantel-Cox) test. Statistical significance was defined as p < 0.05.", "For the observation of viral particles by Transmission Electron Microscopy (TEM), 200 \u03bcL of the supernatant of infected mixed primary cultures of murine CNS were ultracentrifuged on a nickel grid at 50,000 rpm for 5 min. The grids were then dried with bibulous paper before negative staining of 1 min with a drop of 3% phosphotungstic acid (PTA).", "All animal experiments were approved by the Institutional Animal Care and Use Ethics Committee (IACUC) of the Institut National de la Recherche Scientifique (INRS) and conform to the Canadian Council on Animal Care (CCAC). Animal care and used protocols numbers 1304-02 and 1205-03 were issued by the IACUC of INRS for the animal experiments described herein." ] },{ "paper_id": "dad72c9c3422ef1c9b9149e8dd567de494d46a8a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed for statistical significance by performing unpaired T tests (two-tailed p value) or one-way analysis of variance (ANOVA) when appropriate. The differences in the mean or raw values among treatment groups were considered significant when p,0.05.", "B10.BR mice were immunized with 1610 10 particles of recombinant virus per mouse either by intramuscular injection (50 ml) in the right hindlimb, or by oral gavage (100 ml) using oral feeding needles (18G, 2.25 mm dia., Popper & Sons, Inc, New Hyde Park, NY). For nasal immunization, mice were anesthetized with isoflurane. Once anesthesia was achieved, 1610 10 particles of virus slowly delivered as a bolus into the nostrils using a standard micropipette (Gilson, Middleton, WI) as previously described [39] .", "B) Anti-ebola neutralizing antibody (mucosal). For the evaluation of the specific levels of IgG and IgA antibodies, bronchoalveolar lavage (BAL) fluid was collected in situ with a 20gauge catheter inserted into the proximal trachea, flushing the lower airways three times with 1 milliliter of L15 media (Sigma). BAL from each animal was incubated at 56uC for 45 minutes. Two-fold serial dilutions were added to 96 well plates pre-coated overnight with 30 ng of ZEBOV-like particles per well and incubated at 37uC for 1 hr. Goat anti-mouse secondary antibody conjugated to horseradish peroxidase (HRP) was then added and the plate was incubated for one additional hour at 37uC. The ABTS Peroxidase Substrate System (KPL) was used for detection and data collected using an ASYS UVM 340 ELISA plate reader (Isogen Life Science) at OD405. All infectious in vitro work was performed in the BSL4 laboratory at the NML, PHAC." ] },{ "paper_id": "dad72f4c1b14ead806c29f48ce276b06ffeb421a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "dadb8cce14cbf09b6fbaf927b0b2524899ac028d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses and cells. All virus stocks were propagated in Vero-E6 cells as described in 58 . All virus work was performed in a biological safety cabinet in a biosafety level 3 laboratory.", "Northern blot analysis. Intracellular RNA was isolated using RiboPure reagents (Ambion, Austin, TX) 12 h post-infection 13 . The mRNA was then isolated using a Qiagen Oligotex mRNA isolation kit, treated with glyoxal, and separated an agarose gel using NorthernMax-Gly (Ambion). The RNA was then transferred to BrightStar-Plus membrane (Ambion) for 5 h, cross-linked using UV light, prehybridized, and probed with an N gene-specific oligonucleotide probe (5\u2032-CTTGACTGCCGCCTCTGCT b T b CCCT b CT b GC b -3\u2032; biotinylated nucleotides are denoted with a superscripted \"b\"). The blot was hybridized overnight and washed with low-and high-stringency buffers and was then incubated with phosphataseconjugated streptavidin. The blot was then incubated with CDP-STAR, overlaid with film, and developed.", "Determination of virus titer in infected mouse lungs. Lungs harvested for virus titer were weighed and homogenized in 1.0 mL of PBS at 6000 rpm for 60 s in a MagnaLyser (Roche, Basel, Switzerland). Virus titers were determined by plaque assay on Vero cells." ] },{ "paper_id": "daeba3efafc5b3f9e71e38069aadf1e0178bac9d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Preparation. DNA extracts were prepared from 440 mg of porcine faeces. Faeces had been stored at \u221280 \u2218 C and thawed at room temperature for 1 hour before use. To homogenise the faeces, 2 mL of 1x PBS and 1 mL of 2% 2-mercaptoethanol were added to aid in dissolution of cells and samples were placed on a rotator for 2 hours.", "A reagent containing a mixed population of 25 known viruses [34] was stored at \u221280 \u2218 C in 100 L aliquots. All aliquots were centrifuged at 3,000 \u00d7g for 10 minutes and the supernatant was retained for generation of separate DNA and RNA libraries.", "Amplified products were quantified using the Qubit High sensitivity kit (Life Technologies), samples were diluted to 0.2 ng/ L, and DNA and cDNA libraries were prepared using the Nextera XT library preparation kit (Illumina)." ] },{ "paper_id": "daf2e3a8a879ec122b6d89903a43d18890638015", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plants have been used by humans since the start of mankind thousands of years ago as construction material [1] , clothing [2] , and obviously, as food and drugs [3] . Although scientific knowledge has permitted the development of medicine to today's standards based on herbal and traditional medicines, the oldest form of medicine known to man, they are still used around the world [4] . The use of plants themselves, their derived natural compounds and their biological and therapeutic properties have become a topic of increasing interest and investigation not only in modern medicine and pharmacology [5] , but also in food and cosmetics industries [6] .", "The Bajpai research group [58] reports also the potential of sugiol as antiviral once it inhibits the growth of H1N1 influenza virus in a cytopathogenic reduction assay using Madin-Darby canine kidney (MDCK) cell line. Severe cytopathic effect occurred in MDCK cells exposed to H1N1 influenza virus but in MDCK cells treated with sugiol (500 \u03bcg/mL) along with H1N1 influenza virus, cytopathic effect was absent. In fact, MDCK cells treated with sugiol showed similar morphology to control MDCK cells that were not exposed to H1N1 influenza virus.", "The Bajpai research group [58] reports also the potential of sugiol as antiviral once it inhibits the growth of H 1 N 1 influenza virus in a cytopathogenic reduction assay using Madin-Darby canine kidney (MDCK) cell line. Severe cytopathic effect occurred in MDCK cells exposed to H 1 N 1 influenza virus but in MDCK cells treated with sugiol (500 \u00b5g/mL) along with H 1 N 1 influenza virus, cytopathic effect was absent. In fact, MDCK cells treated with sugiol showed similar morphology to control MDCK cells that were not exposed to H 1 N 1 influenza virus." ] },{ "paper_id": "daf4eb5387fb452ec6b363fe7ed346df579535c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Duck embryo fibroblasts (DEFs) were obtained from 9-day-old specific pathogen free (SPF) duck embryos (purchased from Harbin Veterinary Research Institute, Harbin, China) according to the manufacturer's instructions [46] , cultured in Dulbecco's modified Eagle's medium (DMEM/F-12 1:1) (01-172-1ACS, BI, Kibbutz, Beit Haemek, Israel) at pH 7.2, supplemented with 10% fetal bovine serum (FBS) (04-001-1ACS, BI, Kibbutz, Beit Haemek, Israel), 100 U/mL penicillin and 100 mg/mL streptomycin (P1400, Solarbio Science & Technology Co., Ltd., Beijing, China), and grown in 25 cm 2 flask (07-8025, BIOLOGIX, Kennebunk, ME, USA) at 37 \u2022 C in a 5% CO 2 cell incubator.", "Moreover, all animal experiments were performed according to the guidelines of the Committee on Ethics of Animals of Shandong and the appropriate biosecurity, and the Animal Care and Use Committee of Shandong Agricultural University approved the protocol (No. SDAUA-2018-165).", "The RNA samples were treated with RNase-free DNase I to remove potential genomic DNA, purified using poly-T oligo-attached magnetic beads, and segregated into 200-300-bp fragments. The integrity and concentration of RNA samples were checked using an Agilent 2100 Bioanalyzer (Agilent, Palo Alto, CA, USA), high-quality samples (i.e., A260/A280 \u2265 1.5, A260/A280 \u2265 1.0, and RNA integrity \u2265 7) were used to synthesize first-strand cDNA using reverse transcriptase with 6-base random primers. Second-strand cDNA was synthesized using the first-strand cDNA as a template, and T bases were replaced with U to generate a chain-specific library. Further, library fragments were enriched by PCR amplification, and selection based on fragment size resulted in a 300-400-bp library. Next, 150 bp pair-end readers were performed on the library using an Illumina HiSeq 2000 sequencer at Personal Biotechnology Co., Ltd. (Personal Bio, Shanghai, China).", "Hemorrhagic ovarian inflammation, also termed egg-drop syndrome, is primarily caused by duck Tembusu virus (DTMUV), and has resulted in significant economic losses in the poultry industry in Southeast Asia since 2010 [1] . DTMUV, similar to other flaviviruses, is a single-stranded, positive-sense RNA virus with an approximately 11 kb genome. The virus belongs to the Ntaya antigenic group of the family Flavirviridae [2] . It infects ducks in addition to geese [3, 4] , chickens [5] , sparrows [6] , mice [7, 8] , and pigeons [9] . More importantly, a wide spectrum of mammalian cells exhibit cytopathic effects (CPEs) following Tembusu virus infection, such as A549, BHK21, Hela, Vero, and SH-SY5Y [10] , and also including HEK293 according to our recent study. These findings imply that the virus has expanded its host range and may pose a threat to mammals' health [11] ." ] },{ "paper_id": "daf5c921872ab27dc1a714408f626f49c71480e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results were analyzed using unpaired t tests for comparing two groups and using an ANOVA followed by a post-hoc test for comparing three groups in the GraphPad Prism 5.01 software (University of California San Diego, San Diego, California, USA) (***, p < 0.001; **, p < 0.01; *, p < 0.05; ns, p > 0.05).", "Thus, the coexistence of 13T and 49L on HA was a precondition to fully antagonize eqTHN. By contrast, 32T or 80V alone could help NA of SC09 work effectively.", "For assessing protein expression, cell lines were lysed using a RIPA Lysis Buffer (Solarbio, Beijing, China), and centrifuged at 13,000\u00d7 g and 4 \u2022 C for 10 min. Samples were taken from the supernatant, separated on 4-12% gels by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred onto nitrocellulose membranes. Membranes were blocked with 5% milk powder in Tris-buffered saline (TBS) for 2 h. Incubation with the first anti-mouse HA (Sigma, 1:10,000) and antibody-TBST (TBS plus 0.05% Tween20) was performed for 2 h at room temperature (RT), followed by washing three times with TBST. The secondary antibody (Sigma, 1:10,000) was then applied and samples were incubated at RT for 1 h. Subsequently, membranes were washed three times for 10 min with TBST. Signals were detected by a LI-COR Odyssey Imaging System (LI-COR, Lincoln, NE, USA).", "Viruses and their hosts undergo coevolution and adaptation over long time scales and most viruses have a defined range of hosts. For example, most retroviruses have strict host tropism and can rarely jump from one species to another. However, the influenza A virus (FLUAV) of the Orthomyxoviridae can infect different hosts and the virus can transmit between species [1, 2] . To successfully replicate in host cells, viruses need to counteract various host restriction factors at different replication steps. It is evident from several reports that host restriction factors, such as apolipoprotein B mRNA-editing enzyme catalytic subunit 3 proteins (APOBEC3) [3] [4] [5] , tripartite motif protein 5a (TRIM5a) [6] , SAM domain and HD domain-containing protein 1 (SAMHD1) [7, 8] , and tetherin [9] play important roles in blocking interspecies transmission of retroviruses. As with several other restriction factors, like interferon-induced transmembrane proteins (IFITMs), tetherin has been shown to have broad antiviral activity against different enveloped viruses from various virus families including human immunodeficiency virus 1 (HIV-1), Ebola virus and human herpes virus 8 (HHV8) [10] [11] [12] ." ] },{ "paper_id": "daf955dfd5f5ca4e6967e9c1a03904f441d4c319", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses mediate toxicity through focal necrosis of myocytes in the absence of inflammatory cell infiltrate within 3 ", "Here we report a case of a 52-year-old gentleman who presented with a clinical picture of acute myocardial ischemia versus dissection, which overlooked a rather less threatening etiology of myopericarditis." ] },{ "paper_id": "dafc5a833630d362e8ac97ce094a669204ef62e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2.5.2. ECoV S1 Dry Format ELISA (dELISA)", "Two different formats were developed employing ECoV S1 protein, a so-called wet format ELISA (wELISA) and a dry format ELISA (dELISA).", "ECoV strain NC99 was propagated and titrated in human rectal adenocarcinoma (HRT-18G) cells. HRT-18G cells and human embryonic kidney 293 cells stably expressing the SV40 large T antigen (HEK-293T) were maintained in Dulbecco modified Eagle medium (DMEM, Lonza, Basel, Switzerland) " ] },{ "paper_id": "daff41630d6cdd363db1971c2a7ebb0414c58a96", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Further details of experimental procedures used are given in the Supplemental Experimental Procedures.", "For electron tomography, 250-nm-thick sections were prepared. Counterstained and gold-labeled grids were placed in a high-tilt holder and digital images were recoded as single-axis tilt series over a \u00c053 to 53 tilt range (increment, 1 ) on an FEI Tecnai TF20 (Figure 4 ) or dual-axis tilt series over a \u00c060 to 60 tilt range on an FEI Tecnai TF30 microscope ( Figure 6 ). Tomograms were reconstructed using IMOD software (http://bio3d.colorado.edu/imod).", "Supplemental Information includes Supplemental Experimental Procedures, four figures, and five movies and can be found with this article online at http://dx.doi.org/10.1016/j.celrep.2017.02.014." ] },{ "paper_id": "daffb9a10450c4d9217cf3819a559c31cd49970c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CD spectra were measured on a Jasco 810 spectropolarimeter using a thermostatically controlled cuvette at temperatures between 30 and 90uC. Far-UV spectra were collected and analyzed as described [23] .", "Virus was inoculated onto confluent 17Cl-1 monolayers in a 12well plate at a multiplicity of infection (MOI) of 1.0. Groups of cells were harvested at the indicated time points and total virus (cellassociated and cell-free) was titered as previously described [27] .", "Total RNA was purified with TRIzol (Invitrogen, Carlsbad, CA) from the CNS of mice. The 1055 base pair region of the spike glycoprotein encompassing both S510 and S598 was amplified by RT-PCR and sequenced directly as previously described [19] ." ] },{ "paper_id": "db01b3a1badd793717ba425dc52f976f0212e763", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "db0761035838151a0b08a13888982ee36641b467", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "STATs were first discovered through their capacity to mediate signalling from interferon (IFN) and interleukin-6 (IL-6) receptors following binding of cytokines [3, 4, [6] [7] [8] . Each STAT family protein responds to a defined set of cytokines (Table 1) , and certain cytokines can activate more than one STAT protein [9] . Cytokine receptors on plasma membrane do not usually possess intrinsic tyrosine kinase activity and their engagement activates receptor-associated tyrosine kinases, prominent of which are Janus kinase (JAK) family kinases (JAK1, JAK2, JAK3, and TYK2) [3, 4, [8] [9] [10] .", "ND CCD DBD Linker SH2 TAD", "The author declares that there is no conflict of interests regarding the publication of this paper." ] },{ "paper_id": "db0b1c57b81cdb3facc4177cf7f6a208eab730b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ". As a member of the family of small integrin-binding ligand, N-linked glycophosphoproteins (SIBLINGs), OPN is highly conserved among mammals [3] .", "More recently, OPN was shown to exert an intracellular function which can affect diverse cellular processes such as tumor progression [13] and interferon-\u03b1 production in dendritic cells [14] . Here, too, these functions require the OPN protein to be appropriately cleaved, not by thrombin, but by various caspases [15] or produced as appropriate truncates from RNA splice variants [16] [17] [18] . Extracellularly, various metalloproteinases (MMPs) also cleave OPN into various types of fragments which have various tumorigenic or biological activities [19, 20] .", "The culture supernatant of HL60 (5 x 10 6 /mL) cells with or without treatment with PMA (ng/mL) for 72 hr was harvested and concentrated 1:10 the original volume by centrifugation at 13,000 rpm for 20 min at 4\u00b0C (Centricon YM-10, 10 kDa cutoff; Millipore, Billerica, MA). Samples were stored at -80\u00b0C before analysis.", "Microdissection of the tumor tissue, RNA extraction from the processed tissue, as well as reverse transcription and real-time PCR of the extracted RNA, were all performed as described [24] ." ] },{ "paper_id": "db0c5eb977ace3792bd9796c78e4d7e6bc243a7e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All medical institutions involved in the NFPCP in Shenzhen have been included in the G6PD enzyme activity screening program since 2013. In order to ensure reliability of the serology examinations, activities in all sites are implemented with standard operating procedures and subject to the annual national external quality assessment. The detailed study design and organization of this project were described elsewhere 23 .", "Participants and study design. The NFPCP is a nationwide, population-based cross-sectional study project aimed at providing free pre-pregnancy medical examinations for reproductive-age couples who have made their conception plan in 6 months 22 . The overall goal of the project is to reduce the incidence of adverse pregnancy outcomes throughout the country. Trained local health professionals use a questionnaire-based survey to complete a standardized family health file for each participating couple, and also complete medical examinations. Completed files are then converted into electronic records and transferred into the NFPCP medical service information system for storage. This information system was developed by the National Research Institute for Family Planning, and was built with logic checks and instrument interfaces to avoid human errors. Prior to the submission, the data would be rechecked thoroughly." ] },{ "paper_id": "db0f13123f5ba69c4a2b52b2d87fb2f5cd350c3c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Most chemicals, proteins, Protein G-Sepharose, and the Superdex 200 HR 10/30 column were from Sigma or GE Healthcare. We used purified human MBP containing 18.5 kDa form from RCMDT (Moscow; Russia). These preparations were free of lipids, oligosaccharides, nucleic acid, and other possible contaminations.", "The results are reported as mean 6S.E. of at least three independent experiments for each sample analyzed. Errors in the values were within 5-10%. The correlation coefficients (CC) between sets of different samples were analyzed. The differences between samples were analyzed by the Student's t-test, p,0.05 was considered statistically significant.", "Then, we estimated the relative concentration of IgGs containing kappa and lambda light chains in serum and CSF." ] },{ "paper_id": "db12f0dcf2d4d913668f70ce1848c37ae2f31c69", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Study subjects. This study was carried out at Children's Hospital, Zhejiang University School of Medicine and Hangzhou Children's Hospital between April and August 2013 and was approved by the Ethics Committees of both hospitals. All methods were conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from the children's parents or guardians prior to enrolment.", "Chemokines are a group of small secreted proteins that have been shown to induce directed chemotaxis in response to inflammation 5 . The most investigated chemokines belong to the CC and CXC families, which are classified by the relative position of the first consensus cysteines (either separated by a non-conserved amino acid or next to each other). CC chemokines include regulated upon activation normal T cell expressed and secreted (RANTES, also termed CCL5) and monocyte chemoattractant protein-1 (MCP-1, also termed CCL2), while interferon-\u03b3-inducible protein 10 (IP-10, also termed CXCL10), monokine induced by IFN-\u03b3 (MIG, also termed CXCL9) and interleukin-8 (IL-8, also termed CXCL8) belong to the CXC family 5 . Although they were initially characterized as being important in inflammation by targeting leukocytes, chemokines are now considered to" ] },{ "paper_id": "db20be21b59adb1bac603a79aeea4154fd703db1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Southern blot analysis was performed to verify a specific single integration into the genome. Genomic DNA was extracted using a Phenol-chloroform extraction [42] . Four mg of genomic DNA was digested with EcoRV enzyme and separated on a 0.8% agarose/0.5xTris-acetate-EDTA gel by electrophoresis. DNA was transferred onto a Hybond N+ filter (Amersham) in 10x saline sodium citrate (SSC) solution. The filter was washed in 2X SSC and baked at 80uC for 2 hours. Prehybridization of the filter was done for 2 hrs at 60uC in 5x SCC, 5x Denhart and 100 mg/ml of yeast tRNA. Probes specific for the group II intron (EBS2-tcdC623as/Sal-R1), ermB gene (oWKS1131/oWKS1132) and tcdC gene (tcdC5-tcdC6) were generated. Primers are listed in Table 2 . The generated probes (100 ng) were radiolabeled ( 32 P dATP) using Klenow enzyme (Roche) and overnight hybridized in 10 ml fresh pre-hybridization buffer at 60uC. The filter was washed for 30 min in 2x SCC, 0.5% SDS, 30 min in 1X SSC, 0.5% SDS and 30 min in 0.5X SSC, 0.5% SDS and analyzed using phosphorimage screen and a Typhoon 9410 scanner (GE healthcare).", "Total toxin amounts were quantified using 2 assays; a toxin end point titer assay and a commercial available ELISA (Ridascreen, Biopharma). The supernatants of culture samples (1 mL) were collected after centrifugation (30 min, 30006g, 4uC), filter sterilized (0.45 mM cellulose acetate membrane) and stored at 4uC.", "Statistical analysis was performed using the software package SPSS 18 (IBM). An independent sample t-test was employed to compare the strains at different time points.", "Clostridium difficile strain 630DErm is a derivative of the clinical isolate 630 [34, 35] , a PCR ribotype 012 strain. PCR ribotypes 012 strains constitute 4% of the clinically isolated toxinogenic isolates in Europe [7] . Clostridium difficile 630 (PCR ribotype 012)-derived strains are commonly used to investigate virulence of mutants [26, 36, 37] ." ] },{ "paper_id": "db2710799be5aaa4eacbc75a921c6d4cc9364538", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The nucleotide sequences obtained in this study are available from GenBank under accession numbers MF318497, MF318498, MF318499, MF318500, MF318501, MF318502, MF318503, and MF318504.", "DPP4 amino acid sequences of camels, sheep, goat, cattle, horse, and donkey (accession numbers AIG55259, AIG55264, AIG55261, NP776464, XP005601601, and XP014715582, respectively) were downloaded from GenBank and aligned using BioEdit." ] },{ "paper_id": "db2773bfab2b81fdcf13212b9c7b4fef0af57fcf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "db30c72b055266cbd06bb14d7f570f91d8e84e6e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cytokines and chemokines in mouse sera were quantified using a commercial Milliplex Mouse Cytokine/Chemokine Magnetic Panel kit (Merck Millipore, USA.). A panel of inflammatory cytokines and chemokines (IFN-\u03b3, IP-10, IL-1\u03b2, IL-17, IL-6, TNF-\u03b1, GM-CSF, KC, MCP-1, MIP-1\u0251, MIP-1\u03b2 and RANTES) was measured according to the manufacturer's protocols.", "Statistical analyses were performed using GraphPad Prism version 5.01. To compare the groups in terms of hDPP4 copies, inflammatory cytokine/chemokine levels, and tissue viral RNA copies, Student's t test with Welch's correction was used. The significance between survival curves was analyzed by Kaplan-Meier survival analysis with log-rank test. p values lower than 0.05 were considered statistically significant.", "The tissues of infected mice were harvested aseptically at indicated time points and homogenized in minimal essential medium (MEM) plus antibiotics to produce 10% (w/v) suspensions. Tissue homogenates were centrifuged and titered on the monolayer of Vero cells. The cytopathic effects (CPE) were daily observed under phase-contrast microscropy for 3 days. The viral titer was determined as TCID 50 by CPE-based assay, and calculated using the Reed and Muench method. The viral titer in tissue was expressed as Log 10 TCID 50 /g of tissue." ] },{ "paper_id": "db361f98f584f900325b649f3ffa0e8057d0f20c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All drugs and chemicals were obtained from Sigma Chemical Company (St. Louis, MO) except for darifenacin (which was a generous gift from Pfizer Limited, Sandwich, Kent).", "All data is presented as mean 6 SEM. For individual comparisons, statistical differences were determined by either Student's t-test or a nonparametric statistic (Wilcoxon Rank Sum/ Mann-Whitney U-test) when the variance between groups was non-homogenous. To determine statistical differences between multiple groups, analysis of variance with Newman-Keuls post-hoc comparisons was performed. However, if the variance between groups was non-homogenous, a non-parametric statistic (Wilcoxon Rank Sum/Mann-Whitney U-test) was used." ] },{ "paper_id": "db3824a1c673ce4d1bb41c065065598089c89578", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We also assessed whether selected polymorphisms correlated with mRNA expression in the publicly available eQTL IGV browser for primary cells (http://www.gtexportal.org/home/) or using the Haploreg data.", "The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fmicb.", "Supplementary Table 1 " ] },{ "paper_id": "db3f6cc774e724f7e9be22d7e76d489a1c131a46", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Published by Copernicus Publications on behalf of the Deutsches Primatenzentrum GmbH (DPZ).", "In the present study, 39 of 638 common marmosets (6.11 %) did not show any histological changes of the lungs. All spontaneous pulmonary lesions of the other animals are documented in Table 1 ." ] },{ "paper_id": "db459b8a4b49c8b1ad883d0824c6bffccefb525e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where s \u03c4 + 1 ", "Substituting these into equations 29 and 30 and re-arranging yields" ] },{ "paper_id": "db493d400b682be0385bd1ff034fa718d0c398cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was reviewed and approved by the Emory University Institutional Review Board and the Georgia Department of Human Resources Institutional Review Board." ] },{ "paper_id": "db4c8228189750c2de16f125ea1a96feefd63bda", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Live bird markets (LBM) are an important component of traditional poultry marketing systems in many developing countries. The characteristics of LBM have not been particularly well studied, but are known to vary from region to region depending upon the needs of the local customers 1,2 .", "Awareness of LBRS owners about susceptibility of different breeds to AIV could be useful in minimizing the spread." ] },{ "paper_id": "db5333b01a10f165ae516d30f9d1fbf96ab4b841", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Picornaviruses 2B are viroporins, a class of lowmolecular-weight hydrophobic transmembrane proteins encoded by a wide range of animal viruses. The transmembrane hydrophobic domains interact with the phospholipid bilayer to induce dispersion, increasing membrane permeability and promoting the release of viral particles. Thus, viroporins are crucial for viral pathogenicity [101, 102] .", "Foot-and-mouth disease (FMD), an acute highly contagious viral disease in susceptible cloven-hoofed animals, was described 100 years ago. The etiologic agent, FMD virus (FMDV), is a positive-sense, single-stranded RNA virus that belongs to the Aphthovirus genus, Picornaviridae family. FMDV is one of the most contagious viruses in cloven-hoofed animals and can cause both acute and prolonged, asymptomatic but persistent infection [1] . Upon infection of susceptible species, FMDV proliferates rapidly and causes vesicular disease in feet and mouth.", "As a consequence of in depth RNA-protein interaction studies performed with picornavirus IRES, the list of ITAFs is still growing incessantly [55] . The Glycil tRNA synthetase (GARS) emerges as a class of novel ITAFs stimulating picornavirus IRES activity [56] . Predictably, more ITAFs will be identified in the near future, which will help to provide more details about interactions of IRES-proteins within host cells.", "Following S-fragment is a poly(C) tract exhibiting a variable length of 150-200 nt in typical field strains. Investigations on genetically engineered viral genome revealed that a certain threshold length of poly(C) is required to rescue live virus, although no evidence has shown that poly(C) tract length is directly associated with virulence [17] . On the 3\u02b9 end of the poly(C) tract is a variable region folded as multiple pseudoknots (PKs) (2) (3) (4) [18, 19] . The function of this element remains unknown, but it is possibly associated with the poly(C) tract [16] .", "To sum up, FMDV L pro generally functions as a multifunctional protein that blocks IFN-mediated antiviral response via multiple distinct mechanisms (Fig. 4) : (1) L pro shuts off host cell translation through cleavage of the translation initiation factor eIF4G, suppressing IFN protein expression [93] ; (2) L pro represses IFN activity by inhibiting activation of central upstream regulatory factors, including NFkB and IRF-3/7 [82] ; and (3) L pro acts as a DUB and cleaves ubiquitin chains from RIG-I, TBK1, TRAF3, and TRAF6, thereby inhibiting type I IFN signaling [85] ." ] },{ "paper_id": "db5b99eac0c11848467c40af5744442e0b869870", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In recent years viruses have been isolated from regions outside their known geographic distribution. JEV was isolated in Australia for the first time in 1995. Until this time the closest location to report human JEV cases was Bali. The 1999 outbreak of WNV in New York reinforces the importance of accurate and rapid diagnosis of exotic viral agents, as the virus was originally mis-diagnosed in serological tests.", "Most current molecular assays for flaviviruses use highly specific primers, which may only amplify from one species, or a range of closely related species [1] [2] [3] [4] . In a clinical or quarantine setting the presentation and potential exposures, including relevant travel history, are required to generate a differential diagnosis which is required before testing with specific primers. There is a real need to develop broad range PCR assays that can detect all flaviviruses. Kuno [5] reviewed this subject and compared several diagnostic protocols. His recommendation was a two stage process: initially utilizing broad range group-reac-tive primers to narrow the range of targets, followed by species-specific primers [5] .", "novirus, Human bocavirus, Human rhinovirus 1, 2 or 3 (data not shown).", "The specificity of the primers was investigated by attempting amplification from cultures infected with viruses that are not flaviviruses, including Barmah Forest virus, Ross River virus, Influenza A virus, Human coronavirus NL, Human coronavirus OC43, Human adenovirus, Human bocavirus, Human rhinovirus 1, 2 or 3 and RNA from virus free cell cultures." ] },{ "paper_id": "db5d43606d70dcc0d0c32778aed4611d699b909d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The human medulloblastoma (DAOY HTB-186; ATCC), human lung adenocarcinoma (A549; a gift from R. Randall, University of St. Andrews, UK), and Vero (green monkey kidney; Biology Centre, CAS, CZ) cell lines were grown in low glucose DMEM medium supplemented with 10% foetal bovine serum (FBS), 1% antibiotics-antimycotics (amphotericin B 0.25 \u03bcg/ml, penicillin G 100 units/ml, streptomycin 100 \u03bcg/ml), and 1% L-alanyl-L-glutamine. DAOY HTB-186 cell line is derived from desmoplastic cerebellar medulloblastoma of a 4-year-old Caucasian male [36] . A549s are derived from a lung cancerous tissue (alveolar basal epithelial cells) of a 58-year-old Caucasian male [37] . Vero cells are derived from kidney epithelial cells from African green monkey (Cercopithecus aethiops). PS cells (porcine kidney stable) were grown in L15 medium with 3% new-born calf serum (NCS), 1% antibiotics-antimycotics, and 1% L-alanyl-L-glutamine [38] . The human osteosarcoma cell line MG-63 (Sigma-Aldrich) was grown in RPMI 1640 medium supplemented with 10% FBS, 1% antibiotics-antimycotics, 1% L-alanyl-L-glutamine, and 50 nM \u03b2-mercaptoethanol. These were explanted from a 14-yearold Caucasian male [39] .", "f \u00bc viability sample \u00bda:u:\ufffd viability control \u00bda:u:", "https://doi.org/10.1371/journal.pntd.0007745.g005" ] },{ "paper_id": "db5d4d312d002e6bdc87f433d1ad118681167016", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RT-PCR: a commercial cDNA synthesis kit (2-steps RT-PCR kit, RTPL12 W , vivantis, Malaysia) was used. The recommended procedures of manufacturer with some modifications were utilized. Briefly, 8 \u03bcl RNA, 1 \u03bcl of Random Hexamer primer and 1 \u03bcl dNTPs were added to a 0.2 ml microcentrifuge tube, boiled for 4 min and cooled on ice for 2 min. 2 \u03bcl of 10x RT buffer, 1 \u03bcl M-MULV reverse transcriptase enzyme (200 u/\u03bcl), and 7 \u03bcl nuclease free water were added. The tube incubated 10 min at 25\u00b0C, 60 min at 42\u00b0C and 5 min at 85\u00b0C. Finally cooled on ice and stored at \u221220\u00b0C.", "In the current research, eleven broiler flocks with age 5-7 weeks were selected for tracheal swab samples preparation. All broiler flocks were vaccinated against infectious bronchitis virus during the first week of life. Amplification of an expected DNA band (466 bp) from positive control as well as IBV positive swab samples indicated that the RT-PCR reaction has been performed correctly (Figure 1a) . The results showed that 4 out of 11 (36.36%) of the sampled flocks were positive to IBV by RT-PCR. Specific nested PCR were performed on RT-PCR positive flocks and the Massachusetts was specific serotype of infectious bronchitis virus in broiler flocks of Zabol ( Figure 1b ).", "Synthesized cDNA was amplified by PCR reaction. PCR was performed in a reaction volume of 25 \u03bcl containing: 2.5 \u03bcl PCR reaction buffer, 0.5 \u03bcl dNTPs, 0.75 \u03bcl of each of XCE2+ and XCE2-primers, 0.75 \u03bcl MgCl2, 0.2 \u03bcl Taq DNA polymerase, 3 \u03bcl cDNA and 17.25 \u03bcl H2O. Amplification was carried out in a thermocycler using 35 cycles consisting of denaturation for 30 s at 94\u00b0C, annealing for 1 min at 55\u00b0C, and extension for 1 min at 72\u00b0C, followed by a final extension for 7 min at 72\u00b0C. Electrophoresis of amplified products was carried out using 1.5% agarose gel. The amplified cDNA fragment were visualized and photographed under UV light. A pattern with 100 bp ladder was used (Figure 1a )." ] },{ "paper_id": "db62bc4bb76fa5755a43e79b6da62374886f2439", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Most plant viruses encode a capsid protein that gives them a flexuous, icosahedral, or tubular morphology (74) . Thus, SP24 is probably a new type of SP of plant and insect viruses. Its predicted topology is reminiscent of the Coronaviridae M protein, which contains three TM segments and a membrane-associated region (75) and forms spherical particles.", "Databases used. We ran BLAST (11) and PSI-BLAST (11) against the NCBI nonredundant (nr) database (1 April 2012 release). We ran HHsearch searches against version 26 of PFAM (21) and HHblits against its own database of UniProt sequence clusters, UniProt20 (22) (2 December 2011 release). We relied on the NCBI taxonomy (2/3 April 2012 release) to map UniProt identifiers (from the UniProt 21 March 2012 release) to the NCBI taxonomy.", "Putative glycosylation site (N-x-S/T)", "Implications for the study of ORFans. In conclusion, we suspect that our results are applicable to all organisms and not only viruses. BLAST can reliably identify ORFans in mammalian genomes (86) owing to their low rate of evolution. However, as the phylogenetic distance increases (for instance, when comparing vertebrates and invertebrates), homologs are expected to be increasingly difficult to detect. Tautz et al. wrote in a recent review \"we are still missing a systematic study that uses PSI-BLAST-based " ] },{ "paper_id": "db7abfe9ffd34b558951907efa3be430d7bbf28b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "NNDRS. In this study, we used SAS version 9.4 (SAS Institute, Cary, NC, USA) to analyze the data, and Po0.05 was considered statistically significant.", "AGWs is one of the non-notifiable diseases, and is monitored as one of the STDs according to the National Guidelines of Surveillance for Sexually Transmitted Diseases by the NNDRS in China. According to the guidelines, only the first episode patients were reported, whereas the return visit patients and recurrence patients were not reported. ", "1989-1996 6 (0.7) 1.0 - In addition, we checked whether the self-reported AGWs occurred from 2006 to 2015 and the observed AGWs in our prospective study were reported to the NNDRS, and we found that the percentage was only 17% (6/35).", "The prospective study. From May to July 2014, 2309 males and 2378 females aged 18-55 years were enrolled from the general population via media advertising, flyers, posters and educational presentations in Liuzhou City, Guangxi, China. The details of the selection criteria of the population and the methods of testing have been described elsewhere. 23 Volunteers were requested to attend three scheduled visits at 6-month intervals for 1 year to investigate the natural history of AGWs. At each visit, the volunteers underwent a clinical examination by trained clinicians to identify whether there were AGWs lesions in cervical, vaginal, vulvar, anal and perianal sites of women or in external genital, anal and perianal sites of men. For cases that were diagnosed with AGWs based on their clinical appearance, biopsy samples were obtained to be tested for HPV DNA and genotyped by PCR assay. The kits tested for 13 oncogenic HPV types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) and 3 non-oncogenic HPV types (HPV 6, 11 and 66). The study was approved by the Ethics Committee of Liuzhou Center for Disease Control and Prevention (CDC). Informed consent was given by all study volunteers." ] },{ "paper_id": "db7b306a406cd633344a193033ac15a798b1d1d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Introducci\u00f3n: La diplomacia en salud global (DSG) se ha convertido en un importante campo de investigaci\u00f3n debido a que los problemas de salud son cada vez m\u00e1s considerados en el \u00e1mbito de la pol\u00edtica exterior. Gran parte de la literatura existente se centra en la cooperaci\u00f3n Norte-Sur en salud global, y enfatiza el papel de la seguridad e intereses econ\u00f3micos por parte de los pa\u00edses del Norte como impulsores de la DSG. Chile presenta un escenario favorable para una mayor participaci\u00f3n en actividades de DSG. Sin embargo, existe poco conocimiento sobre lo que ha estado impulsando la integraci\u00f3n de la salud de Chile en la pol\u00edtica exterior, y pocos esfuerzos por usar los elementos de las relaciones internacionales y las teor\u00edas de la pol\u00edtica exterior para entender mejor el surgimiento de DSG. M\u00e9todo: Para llenar este vac\u00edo de conocimiento, realizamos una revisi\u00f3n narrativa de la literatura. Bas\u00e1ndonos en un popular marco anal\u00edtico utilizado en estudios sobre relaciones internacionales, identificamos las fuerzas que impulsan la integraci\u00f3n de la salud en la pol\u00edtica exterior de Chile en tres niveles de an\u00e1lisis. Resultados: En el nivel de an\u00e1lisis internacional / mundial, las principales fuerzas motrices se relacionaron con las preocupaciones de seguridad nacional y el cumplimiento de las reglamentaciones de las organizaciones internacionales. A nivel regional, la DSG se ha impulsado por: un compromiso con la solidaridad regional a trav\u00e9s de la mutua cooperaci\u00f3n en respuesta a las reformas neoliberales; una necesidad de coordinaci\u00f3n de salud en emergencias; y la protecci\u00f3n de pueblos ind\u00edgenas. Finalmente, a nivel dom\u00e9stico, los factores identificados incluyen los intereses econ\u00f3micos de varios sectores productivos (y c\u00f3mo las reglamentaciones sanitarias podr\u00edan afectarlos); el alto grado de inequidad social que impacta en el acceso a la atenci\u00f3n m\u00e9dica; y el manejo de desastres naturales. Conclusiones: Las acciones de salud en el contexto de las relaciones internacionales en Chile siguen estando motivadas principalmente por intereses de pol\u00edtica exterior tradicionales, m\u00e1s que por el deseo de satisfacer las necesidades de salud per se. Esto parece concordar con hallazgos previos, que enfatizan la importancia de la seguridad y los intereses econ\u00f3micos como fuerzas impulsoras de la DSG, y c\u00f3mo el tema de salud suele ser apropiado instrumentalmente dentro de la pol\u00edtica exterior para lograr otros objetivos. Sin embargo, la revisi\u00f3n tambi\u00e9n revela que, en el contexto de la cooperaci\u00f3n Sur-Sur (y la diplomacia regional de salud), la solidaridad y las consideraciones normativas tambi\u00e9n pueden ser importantes fuerzas impulsoras. Finalmente, ha existido una evoluci\u00f3n de las pol\u00edticas de salud centradas principalmente en el \u00e1mbito interno (p. Ej, el tratamiento de nutrici\u00f3n materno-infantil) hacia pol\u00edticas integradas inspiradas a nivel internacional (p. Ej., la promoci\u00f3n de la nutrici\u00f3n materno-infantil se alinea con las directrices internacionales).", "The review is part of a larger comparative research project to better understand GHD practices in Brazil, Canada, Chile, and Mexico and follows the study protocol of that larger research project, with a global literature review of GHD recently published elsewhere [3] .", "1 For the purpose of this article, we will not distinguish between different sub-strands of IR theories. However, we do acknowledge that, for example, within realism there are several sub-strands with significant differences in how each understands foreign policy choices (e.g. classical realism [based on theories of Hans Morgenthau and Reinhold Niebuhr] which emphasizes the role of individuals, structural (or neo-) realism which privileges international systemic factors [initiated by ideas of Kenneth Waltz], and neoclassical realism [concept developed by Gideon Rose] which opens up the black box of the state to domestic analysis)." ] },{ "paper_id": "db7b6440cfdfd2bbf71c22361d4ea606a16d4643", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "G-protein-coupled receptors (GPCRs), also known as G proteinlinked receptors (GPLR), serpentine receptor, seven-transmembrane domain receptors, and 7 TM (transmembrane), form the largest family of cell surface receptors. GPCRs share a common global topology that consists of seven transmembrane alpha helices, intracellular C-terminal, an extracellular N-terminal, three intracellular loops and three extracellular loops (Fig. 1) .", "w u{20 a u{20 P 20", "Substituting Eq. 21 into Eq. 20 and also noting Eqs. 18-19, we obtain." ] },{ "paper_id": "db7db8941a68a14e0b227ce42898ad4ecd40df62", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Three questions guided this literature review:", "terrorism \"preparedness message\"", "Additional file 1: Table S1 : Literature selected." ] },{ "paper_id": "db7ddc7b6e1689aed55b17716e2c2d3309b56f90", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "references Evolution, Medicine, and Public Health", "The crucial role these various mechanisms play in determining respiratory disease is demonstrated by contrasting M. catarrhalis with S. pneumoniae. Similar to S. pneumoniae, M. catarrhalis is a primary carriage species estimated to colonize between 31% and 50% of children <2 years in the USA [45] and frequently causes URT infections, such as acute otitis media. However, unlike S. pneumoniae, M. catarrhalis rarely causes pneumonia [46] , suggesting that differences in mechanisms of pathogenicity may be the explanation.", "Dr. Gordon has received consultancy fees from Abt Associates. All other authors report no potential conflicts of interest." ] },{ "paper_id": "db80870c75793687f024d74e11d6a6d49333b1b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Document S1 Specifies the PCR primer sets used in this study. (DOCX) ", "Deep sequencing viral detection methods rely upon alignment of the experimental sequences to known viral sequences. This work used the viral nucleotide sequences in GenBank. Using this approach, identification of a previously unknown virus in a sample is possible only if one or more related viruses are present in the database. The nonredundant viral database used here is comprehensive by current (2013) standards, but will need to be updated as new records are added to GenBank.", "In samples with high titers of virus, the coverage obtained from deep sequencing experiments is sometimes sufficient to elucidate many genomic features of the infectious agent. For example, in samples Co-A and Co-B, the signature genomic mutations associated with defective, SSPE-causing virus were easily observed." ] },{ "paper_id": "db864a0b9b9bddd9b5ea861011655f363d90b149", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ND production includes chemical vapor deposition, detonation [4, 10] , and high-pressure/hightemperature [20] methods (i.e., a bottom-up vs. top-down synthesis approach, respectively) [21] . Different treatment conditions, processing techniques, and production methods generate distinct surface properties resulting in diverse types of NDs that vary in surface chemistry, structure, shape, and size [21] [22] [23] [24] , which allows for their classification based on their primary particle or grain size from < 200 nm down to 2 nm [2, 21] .", "Nano-diamonds offer a novel approach to decrease the high levels of co-morbidity and mortality associated with antimicrobial resistance, as well as to decrease the costs of treatment, ultimately leading to the subsequent decrease in antimicrobial resistance. ", "An exciting ND-based matrix-assisted laser desorption/ionization coupled with time-of-flight mass spectrometry (ND-MALDI-TOF-MS) approach has also been used by Chang et al. [51] and Zhu et al. [52] to identify a carbapenem-resistant Acinetobacter baumannii and human papilomavirus (HPV), respectively." ] },{ "paper_id": "db97b6fadbd7b65de3e513beec8f3eca89bac377", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All diagnostic testing was conducted using protocols developed and validated by the South Dakota State University Animal Disease Research and Diagnostic Laboratory.", "Immunohistochemistry slides of porcine GI tracts were prepared using the standard SDSU ADRDL IHC procedure, with the following modification being the use of PEDV monoclonal antibody SD-6-29, of mouse ascites origin, courtesy of Steve Lawson, SDSU, at a 1:1000 dilution.", "The MagMAX\u2122 96 Viral Isolation Kit (Life Technologies, Waltham MA, USA) was used to obtain viral RNA from the samples, as described in the instructions provided (1836 M Revision F). A 175-\u03bcl volume of sample was used for the extraction. The magnetic bead extractions were completed on a Kingfisher96 instrument (Thermo Scientific, Waltham MA, USA)." ] },{ "paper_id": "dba0cdf3fbecdba11207ba0d7da322fc2a83b798", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After consulting various authorities, four criteria were taken into consideration while identifying designated Hsiao-Hsuan Chiu et al.", "A communication exercise might be necessary, especially for events with mass casualty or high profile event.", "Broader surveillance parameters may be considered to enable detection of non-respiratory diseases." ] },{ "paper_id": "dbaaa5a246123fee5013bba144f693f96e624988", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HeLa (Young) and Vero cells were maintained in DMEM medium with 10% newborn calf serum. Plasmid bearing the cDNA of Coxsackie virus B3 (Nancy) strain was a kind gift of F. van Kuppeveld (Radboud University, Nijmegen, Netherlands). Plasmids containing poliovirus cDNAs were previously described [17] . The following compounds were obtained from Sigma Aldrich:", "A confluent layer of HeLa cells was treated with 800 mM amiloride for 10 hours and incubated with PBS containing 100 mM Ethylene glycol-bis (b-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) for 15 min, to chelate Ca 2+ , before lysis in H2O-Tween 0.1%. The ratiometric magnesium indicator mag-fura-2 (Invitrogen) was added to a final concentration of 2 mM to 1 ml of sample and fluorescence was measured at 25uC using a Quanta-Master QM4CW spectrofluorometer (PTI) using a 1 cm path length quartz cuvette thermostated at 25uC. Excitation scans were performed from 250 to 490 nm with 1 nm steps, using 1 nm bandwidth; emission was monitored at 530 nm with 5 nm bandwidth. Continuous recordings of fluorescent intensities at 330 nm and 370 nm were transformed into 330/370 wavelength ratios.", "Ribavirin ", "All RNA oligonucleotides were from Dharmacon Research, Inc.; [c-32 P]-ATP (7000 Ci/mmol) was from MP Biomedical; T4 polynucleotide kinase was from USB; ATP and GTP were from GE Healthcare; all other reagents were of the highest grade available from Sigma, Fisher or VWR. RNA oligonucleotides were purified by denaturing PAGE and end-labeled by using [c-32 P]ATP and T4 polynucleotide kinase as described previously [21] . Concentrations were determined by measuring the absorbance at 260 nm using a Nanodrop spectrophotometer and using the appropriate calculated extinction coefficient." ] },{ "paper_id": "dbbb49ef360b3f97d6ecda042ef75186a78ddfa3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "dbbf1b6713b9819bbe78a272e728951afa62ef95", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The multifaceted challenges facing NAAT point-of-care testing in LMICs demand solutions that can reliably integrate the often challenging nucleic acid (NA) extraction procedure, together with a suitable NA amplification/detection method. This unified system must be simple to operate, environmentally robust, yield timely results, be affordable and have high diagnostic accuracy. NAAT-based diagnostic platforms that are developed for use in high-income countries typically cannot tolerate the environmental extremes (e.g. temperature, humidity and dust) encountered in RLS and are not designed for use by healthcare workers that have not received extensive training [7, 8] . These factors make most currently available sample-toanswer NAAT options unsuitable for implementation in peripheral facilities in LMICs [5, 9] . A rapid time to result is necessary to reduce loss to follow up wherein the client may have multiple constraints that prevent returning for test results and possible treatment; these include distances required for travel to the test site, time-off from work for the visit, limited financial resources and other competing needs [10, 11] . Currently, most NAAT test results for infectious diseases are not available on the same day [12] [13] [14] . Cost per test is a further barrier to adoption, as many LMICs cannot purchase these high-cost diagnostic tests without global donor support [15] . For example, the WHO published a target product profile for a simple and accurate diagnostic NAAT for Mycobacterium tuberculosis (MTB) to supplant smear microscopy with a targeted price of US $4-6 [16] . For such settings, there is a global need for innovators to design and develop low cost, fully integrated testing systems that meet required performance criteria, while being functional in austere environments and applicable for a variety of pathogenic agents.", "RNA-based microbe DNA-based microbe supposedly MTB negative sample. This sample was removed from the sputum panel and therefore the final SP panel was comprised of only nine samples, each of which were present in triplicate aliquots. The 10 panel members for the remaining blood and stool panels were each presented in triplicate.", "All developers completed the NA extractions using their respective technologies and shipped the extracts to the CDC. Two minor deviations were observed: Developer E shipped only two of the three ST3 and ST6 samples provided to them; and one extract of sample SP3 from developer C contained insufficient elution volume only allowing for influenza A screening and not MTB." ] },{ "paper_id": "dbd121bc5733e77f68826080a177fb8b0e8d3106", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The global MI was greater than zero (more (Table 2) .", "In this study, we looked at the ", "We thank DHS, ICF International for data access permission. We express our sincere gratitude to the Chinese Government and the teaching staff of the Department of Epidemiology and Biostatistics,School of Public Health, Cheeloo College of Medicine, Shandong University for study support and funding. We also thank Mr Alec Lasko Raymond for his advice and support throughout this study. " ] },{ "paper_id": "dbd27297be0609a02729bd99ac744b997d9e647f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SCientifiC REPORTS | 7: 8763 | DOI:10.1038/s41598-017-07824-2" ] },{ "paper_id": "dbd589ba5a6b57f60ccafcf475c57a88211ff95e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "dbd7344969972f79b75ee7553487633e645d9a3b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "dbe74afc075c179f7c6298934ce53e6e6bdae4ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ter City, CA). Amplification conditions are described in detail elsewhere [20] . The reactions were purified with the Performa DTR V3 system (Edge BioSystems, Gaithersburg, MD) and analyzed on an automated sequencer (ABI Prism 3100 Genetic Analyzer, Applied Biosystems, Foster City, CA). New variants (singletons) were verified by reamplification and resequencing." ] },{ "paper_id": "dbf76534e0b330bb0f155296e251c1e7031c90c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Healthcare personnel (HCP) are exposed to respiratory pathogens in many clinical settings [1] . Infected HCP may spread infection to their patients [2] [3] [4] [5] or coworkers [3] [4] [5] [6] , to family members [4, 7] , or to other community members [4, 8] . Respiratory viral infections among healthcare workers can negatively impact delivery of healthcare services [9] [10] [11] .", "(1) Precept 15320 or (2) Kimberly Clark Technol Fluidshield 47107.", "Power is estimated using an expected annual attack rate of 12 % {12 % = 0.35*0.2 + 0.65*(1-0.65)*0.2} [13] . This yearly attack rate translates into a 4-year attack rate of 39 % {39 % = 1-(1-(0.35*0.2 + 0.65*0.35*0.2)) 4 . Accounting for correlation of outcomes within clusters by assuming the correlation coefficient is 0.1, leads to a design effect of 2.5." ] },{ "paper_id": "dbf7ea2d45fff41a73853c26e5fca9862fd0edcc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral RNA was extracted from the anal swabs using a QIAamp Viral RNA mini kit (Qiagen). The RNA was eluted into 50 ml RNase-free water and was used as the template for RT-PCR.", "The study was approved by the Department of Agriculture, Fisheries and Conservation, HKSAR; and Committee on the Use of Live Animals in Teaching and Research, The University of Hong Kong. Bats from 14 different locations in rural areas of Hong Kong, including water tunnels, closed mines, sea caves and forested areas, were captured over a 36-month period. Anal swabs were collected by an experienced veterinary surgeon, and kept in viral transport medium at 4uC before processing.", "A total of 728 anal swabs from different bat species in Hong Kong were obtained. No obvious signs of enteric disease, like anorexia and diarrhoea, were observed in the bats during the brief period of captivity needed for sampling.", "Bats (order Chiroptera of class Mammalia) constitute a significant portion of biological diversity in many ecosystems and have a wide geographical distribution [28] . We have previously discovered novel viruses in several local bat species [29] [30] [31] [32] [33] [34] [35] , and there were many similar discoveries of novel bat viruses by researchers in other parts of the world. In particular, important human viral pathogens like the SARS virus, Nipah virus and Ebola virus were found to have originated from bats and contributed to substantial human morbidity and mortality in recent outbreaks. Taken together, these discoveries hint that these small mammals are important reservoirs of diverse and undiscovered animal viruses, with significant risk of zoonotic transmission to humans [36] ." ] },{ "paper_id": "dc014f8a66864512015686665ebbf01c92d8089e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The survey instrument consisted of questions about the following: A knowledge score was constructed from responses to questions about symptoms, mode of transmission, incubation period, precautions and vaccination. One mark was attributed to each correct answer to these questions (total of 28 marks)." ] },{ "paper_id": "dc173bac1ccb553dddf68b82320dfae5ff306f28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PocketMatch [24] function prediction [38] , polypharmacology [39] , evolutionary relationships [40] download (http://proline.physics.iisc.ernet.in/pocketmatch/)", "SiteEngine [51] protein-protein interactions [52] download (http://bioinfo3d.cs.tau.ac.il/SiteEngine/)", "SiteHopper [25] evolutionary relationships [53] OpenEye, available to academic users (https://www.eyesopen.com/sitehopper/)" ] },{ "paper_id": "dc180c51f54487e4bbbd129c1cc2e30deacd3181", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The purified MERS-5HB was loaded onto a Superdex 75 10/300 GL column (GE Healthcare, Uppsala, Sweden) connected to an \u00c4KTA purifier chromatography system (GE \u00c4KTA avant 25) (GE Healthcare) to evaluate its molecular weight (M.W.). PBS was used as the mobile phase with a flow rate of 0.8 mL/min. The ultraviolet absorbance at 280 nm was recorded. A gel-filtration of standard proteins consisting of Bovine serum albumin (67 kDa), \u03b2-lactoglobulin (35 kDa), Cytochrome C (13.6 kDa), Aprotinin (6.5 kDa), and Vitamin B12 (1.35 kDa) was used to define the standard curve.", "As reported previously [11] , the sequence of synthesized MERS-HR2P is Biotin-GGGSLTQINTTLLDLTYEMLSLQQVVKALNESYIDLKEL. An irrelevant peptide HIV-HR2P derived from HR2 in gp41 was used as control. We tested and compared the reactivity by ELISA in two ways which are described as follows.", "The secondary structure of MERS-5HB was determined by circular dichroism (CD) spectroscopy. Purified protein was diluted in PBS and adjusted to the final concentration of 1 mg/mL before data collection. The CD spectra from 190 nm to 260 nm were recorded on an Applied Photophysics Chirascan-SF.3 spectrophotometer (Applied Photophysics Ltd, Surrey, UK) at 25 \u2022 C in a 0.1 cm path length cuvette (Applied Photophysics Ltd). Thermo-induced unfolding was measured by recording the spectra at 222 nm in temperatures ranging from 25 \u2022 C to 95 \u2022 C at a ramp-rate of 1 \u2022 C/min for evaluation of the thermodynamic stability. The CD data were shown as mean residue ellipticity." ] },{ "paper_id": "dc1a1a0fec049e850789175fe06b1453c9114c62", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1." ] },{ "paper_id": "dc1e16996462dd1445f21c419b6e40dd0dd84c02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where" ] },{ "paper_id": "dc2451c2166ef31db7fc2ad93ade6bf4d18c55e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Acetylcholinesterase is the drug target for treating the neural degenerative disorder Alzheimer's disease (AD). AD in elderly individuals is characterized by memory loss, difficulty in storing new information, and behavioral and cognitive difficulties [7, 8] . The progressive nature of AD can require a high level of care since patients lose the ability to perform simple daily functions.", "Acetylcholinesterase (AChE) is a member of the \u03b1/\u03b2 hydrolase fold family of enzymes [1] . This enzyme degrades the excitatory neurotransmitter acetylcholine (ACh) in the synaptic junction at an extraordinarily fast catalytic rate, with a 2nd order rate constant almost as fast as a diffusion-controlled reaction [2, 3] . ACh is degraded to choline and acetate through a hydrolysis mechanism, resulting in decreased signal transmission in nerve synapses.", "Computational evaluation can delineate important interactions between the inhibitors and receptors, where mechanisms of inhibition and sites of interactions are unknown. Docking is a technique that has been performed for many biologically-important receptors [39, 40] . It is used here to predict the interactions between AChE and an inhibitor, suggesting the inhibitor's binding mode(s)." ] },{ "paper_id": "dc26c72d4373332c80c9cab18a7e3a8b41211333", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "dc320a349f137013cc728b319144588e3854cb20", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RIG-I-like receptors (RLRs) mainly include the cytosolic retinoic acid-induced gene I (RIG-I) and the melanoma differentiationassociated gene 5 (MDA5), both sharing the same molecular architecture consisting in a conserved \"helicase\" core connected to two caspase activation and recruitment domains (CARDs) at the N-terminus, and an RNA binding domain known as C-terminal domains (CTD) (Yoneyama et al., 2005) .", "During co-evolution with the cell host, viruses have evolved mechanisms to avoid cell responses against viral infections for their own success. Indeed, hiding dsRNA molecules represents a powerful tool to avoid a harsh cellular war against viruses' replication that initiates after TLR3 recognition and activation.", "Finally, and as a consequence, illustrating the virus-host cell co-evolution process once more, virus have evolved with weapons to be protected from innate immune response recognition irrespective of the origin of PAMPs generated during the course of infection.", "LD and MC together built up the idea and structure of the review. LD wrote the majority of the text. MC wrote a section of the review and helped performing the revision of the manuscript to its final version.", "However, a concern arises when observing that while +sRNA viruses build their replication niches associated to membranes, the host cells are still able to establish an antiviral response, mediated by the cellular receptors that the viruses are intended to hide from. Regarding this important question, a recent proposed mechanism will be included to clarify this intriguing crossroad, a paradigmatic scenario of virus-host cell co-evolution process." ] },{ "paper_id": "dc352893117f666477e7cf7c8c614bdf60592178", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Different from the Andersen six-stage sampler, the BioStage impactor collects all particles larger than 0.65 mm (its cutoff size), thus the enhancement observed was for all bacterial aerosols.", "The bioaerosol concentration levels obtained by mineral-oilspread agar plates and those regular ones were checked for normality by Shapiro-Wilk test and further analyzed using independent sample t-tests through the SPSS 16.0 Software. The equality of variances of the variable was also checked using Levene's Test. A p-value of less than 0.05 indicates a significant difference between groups (confidence level 95%).", "where N mineral-oil-spread is average particle concentration level for each specific size range when mineral-oil-spread agar plate is used, while N regular refers to the counterpart when the regular agar plate is used." ] },{ "paper_id": "dc38fa3321df5137294140ffe1a358399befb500", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using Prism 6 software (GraphPad).", "We obtained the approval of the Lille Hospital Ethic committee. All the participants provided their written or verbal conformed to participate on this study. The consent procedure was approved by the Ethic committee. The patients in this manuscript or their next of kin have given written informed consent or verbal consent, ", "Kruskall-Wallis test was used for all comparisons except when otherwise indicated. Significance was accepted at p,0.05." ] },{ "paper_id": "dc3d3e12aa6087b1141910cf58ac7f37c8cd0793", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ELISA for cytokines, chemokines, and hematopoietic factors. Sandwich ELISA was used to determine the serum levels of IL-6 and TNF-\u03b1 cytokines. Flt3-L level was determined by commercialized ELISA kit (R&D Systems, Minneapolis, MN, USA). GM-CSF, CCL2, and CXCL1 were measured by cytokine bead array (CBA) technique (eBioscience), according to the manufacturer's protocol.", "Scientific RepoRts | 5:17548 | DOI: 10.1038/srep17548", "Animals. C57BL/6 (H-2 b ) mice (4-6 weeks old) were purchased from Samtako (O-San, Korea).", "However, restraint of CNS infiltration is also required because hematogenous inflammation causes profound damage if the reaction is excessive or inappropriate. Therefore, peripheral innate immune cells are considered to be key players in maintaining functional homeostasis of the CNS under steady and/ or neuroinflammatory conditions. However, in-depth evidence for the role of peripheral innate immune cells in maintaining CNS immune privilege needs to be further accumulated." ] },{ "paper_id": "dc3df0a30a76ca925a5cc4466528ea0c4dab9638", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Utilizing bat's remarkable immunological functions, this novel model has a potential to be transformed into a powerful platform for basic and translational research.", "Data availability. All data generated or analyzed during this study are included in this published article (and its Supplementary Information files) .", "one of a kind advantage as an animal model because they are small, relatively inexpensive to maintain and most importantly, they have short generation times with an ability to produce a large number of offspring 22 . Inbred strains are almost genetically identical, and their environment can be controlled and manipulated easily 23, 24 ." ] },{ "paper_id": "dc4332792ad6c643b1142cef1d344755a64b9625", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Surfactant protein D (SP-D) is a pulmonary collectin involved in regulation of inflammation, innate immune defense, and surfactant homeostasis. It is expressed by Clara cells and alveolar type II cells in the lung. SP-D has a multimeric structure which gives it the ability to agglutinate pathogens, as well as aid in the clearance of apoptotic cells, cellular debris, and foreign particles in the lung [reviewed in [1] ].", "One factor that was found to differ between studies and could, therefore, be a source of variation of reported healthy population values, was the type of anticoagulant (or lack thereof) in the collection container. When blood was simultaneously collected in various vacutainers, serum and heparin plasma gave similar measurements of SP-D, while citrate plasma gave values significantly lower than serum values (Figure 3 ). EDTA plasma gave the most inconsistent results, and values were also significantly lower than serum values." ] },{ "paper_id": "dc45028785e8308de18df3a42fe11fe571da2cdc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Overall structural stability of the systems The overall stability analyses are considered important to note that the systems did not undergo any unusual changes during the time scale of simulation because of erratic system preparation. In this study, root mean square deviation (rmsd), root mean square fluctuation (rmsf), and intra-molecular hydrogen bonds were used in analyzing and comparing the stability of the systems under study (Figure 4) .", "In terms of preparing the enzyme-peptide complex to investigate the aminopeptidase function of LTA4H enzyme, 3D coordinates of the bound tripeptide Arg-Ala-Arg (RAR) in a solved X-ray structure of hLTA4H with a mutation E271Q (PDB ID: 3B7T) was utilized. The Superimpose Structures protocol as available in Accelrys Discovery Studio 3.0 (DS) was employed to copy the 3D coordinates of this tripeptide into the representative structure of LTA4H picked from the 5 ns MD simulation by superimposition. This complex was subjected to energy minimization using Energy Minimization protocol of DS before considered further in this study.", "Mutations of R563 to any other amino acid including a conservative replacement of R by K preserving the positive charge abolished the enzyme function but exhibited a significant residual aminopeptidase activity [27] . Crystal structure with R563A mutant could not reveal any structural changes explaining the complete loss of catalytic activity. It was also reported that esterified LTA4 cannot be the substrate of the enzyme and this phenomenon was explained with the steric hindrance [46] , which also proved that a free carboxylate group of LTA4 is critical for the hydrolase function. The other carboxylate recognition residue K565 located in a way that it can also involve in carboxylate recognition but its mutagenic replacements have not decreased the epoxide hydrolase activity [27] . The difference in observed aminopeptidase activities between the wild type and K565 mutants have suggested that K565 is a carboxylate binding site for peptide substrates also [27] . The information of a binding pocket for its ligand is very important for drug design, particularly for conducting mutagenesis studies [47] . In the literature, the binding pocket of a protein receptor to a ligand is usually defined by those residues that have at least one heavy atom (i.e., an atom other than hydrogen) with a distance from a heavy atom of the ligand. Such a criterion was originally used to define the binding pocket of ATP in the Cdk5-Nck5a* complex [48] that has later proved quite useful in identifying functional domains and stimulating the relevant truncation experiments [49] . The similar approach has also been used to define the binding pockets of many other receptor-ligand interactions important for drug design [50] [51] [52] [53] [54] ." ] },{ "paper_id": "dc46a9c2a3b3f5f7f3b6650c6fba4369a2793cd2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "dc4a3df470bfd502db850deec4219e39f7eadb63", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bacterial infections of the CNS are rare, but often life threatening, events (76) . Excluding direct inoculation following CNS trauma, bacteria typically gain CNS entry following hematogenous dissemination from distant sites (lungs and heart valves) or by direct extension from parameningeal foci of infection (inner ear and sinuses). Penetration of the BBB may occur via three potential mechanisms: (1) direct destruction of capillary ECs (77, 78), (2) disruption of intercellular TJ and migration in between ECs (79), and (3) transcytosis via intracellular vesicles directly through ECs (80) . Once inside, numerous innate immune receptors and pathways are activated (Figure 1 ).", "Blood-brain barrier EC forms a highly sophisticated barrier via a network of tight junctions (TJ) and adherens junctions (AJ) (8, 31, 32) . The EC of the CNS are unique in that the TJ restrict the paracellular passage of solutes, have no pinocytic activity, and have few if any fenestrations (33-39). This causes the BBB to have high endothelial electrical resistance (40, 41), some 50-100 times higher than peripheral microvessels (42-44). The TJ are composed of a parallel network of intramembranous protein strands, composed of claudins, occludin, and zonula occludin (ZO) proteins (37). Claudins, specifically claudin-3, -4, and -12, compose the TJ backbone (45-47). Occludin is not required for TJ formation (48); instead, it plays a role in \"sealing\" the junction thereby increasing electrical resistance (49, 50). CNS microvessel TJ are also abundant in ZO-2, and to a lesser extent, ZO-1, that are cytoplasmic accessory proteins that serve to anchor the transmembrane proteins of the TJ to the actin cytoskeleton of the ECs (51, 52).", "The choroid plexus (CP) is a villous structure located on the roof of the four cerebral ventricles where cerebrospinal fluid (CSF) is actively secreted. The CP is highly vascular and contains the blood-CSF barrier (BCSFB) (51). Unlike the BBB, however, the BCSFB arises from cuboidal choroid plexus epithelial cells (CPE) with a very different TJ structure. The CPE express ZO-1 and ZO-2 in different amounts (51), and have a different claudin signature, expressing claudin-1, -2, -3, and -11 (51, 53, 54). Furthermore, capillaries within the CP villi are fenestrated (51, 55, 56), reflected by a much lower endothelial electrical resistance than the BBB (57). For these reasons, the BBB is considered more of an absolute barrier, while the BCSFB may be where most normal immune surveillance of the CNS occurs (58)." ] },{ "paper_id": "dc502e4494d5ef1e5a2f54b5df88e7c391d9a763", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus genome segment" ] },{ "paper_id": "dc5164d2e228cba949bf1e085edef598e23ce967", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA from each intestine was extracted by TRIzol Reagent (Invitrogen Co. Ltd, San Diego, USA). RNA degradation and contamination were examined by electrophoresis on 1% agarose gels. RNA purity was checked by a NanoPhotometer\u00ae spectrophotometer (Implen, Westlake Village, CA, USA). RNA concentration was measured using a Qubit\u00ae RNA Assay Kit in a Qubit\u00ae 2.0 Fluorometer (Life Technologies, Carlsbad, CA, USA). RNA integrity was assessed using an RNA Nano 6000 Assay Kit and an Agilent Bioanalyzer 2100 system (Agilent Technologies, Santa Clara, CA, USA), demonstrating an RNA integrity number > 8." ] },{ "paper_id": "dc522664a7fd404e4e58448210812247a002e06f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was reviewed and approved by the Life Sciences and Ethics Committee of Zhengzhou University and the Ethics Committee of the Zhengzhou Children's Hospital. Written informed consent was obtained from each case's guardian before enrollment.", "The patients with congenital disease, acute or chronic hepatitis, cardiovascular disease, intestinal diseases, and other infectious diseases were excluded from this study.", "https://doi.org/10.1371/journal.pone.0197861.g005" ] },{ "paper_id": "dc55c16e1cfe2f794a9924f28d4b2c487316d4d2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For individual articles, semi-automated abstract screening was performed using a machine-learning algorithm, which was trained by four reviewers to prioritize abstracts for screening from highest to lowest relevance (http://abstrackr.cebm.brown.edu) [14] . Abstracts for individual articles were independently assessed for inclusion by at least two reviewers.", "Our search for existing systematic reviews yielded 46 results. For the search of individual articles, we screened 1451 citations (Fig. 1 ). Of those, 345 were selected for full-text review. No additional articles were identified for inclusion from Embase after searching PubMed.", "Additional file 1: Table S1 . PubMed Search Strategy. " ] },{ "paper_id": "dc55e7876326722cc7c5ad2a88a8d2217c296596", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PCR products were sized using QIAxcel DNA Screening gel cartridge (QIAGEN) on the QIAxcel system (QIAGEN, Switzerland), which enabled high-resolution capillary electrophoresis. A 50-800 bp QX DNA Size Marker (Qiagen) was included on QIAxcel runs, and the size of the products was determined using the QIAxcel ScreenGel software (Qiagen). The QIAxcel system produces a digital gel image and an electropherogram for fragment analysis. " ] },{ "paper_id": "dc6666eb8156bd4638809009f795ebd4a7843569", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HAI assays were performed as reported [38, 39, 45] . VLPs at 50 ng/reaction were pretreated with antibody as described above for the blockade assays before addition to O+ RBCs at 4uC, pH 5.5. An HAI titer was determined as the lowest antibody concentration that completely prevented NoV VLP-induced HA by visualization.", "In early 2009, following written consent, blood samples from 63 donors were collected from adult healthy donors at the Lugano and Basel Blood banks (Switzerland). Peripheral blood mononuclear cells (PBMCs) and plasma were isolated and cryopreserved. On the day of use, PBMCs from Donor 302898 (Figure 1 ), an individual born in 1948, were thawed and IgG + memory B cells were isolated using CD22 microbeads (Miltenyi) followed by cell sorting, as described [76] . Cells were immortalized at 5 cells/well in multiple cultures using EBV in the presence of CpG oligodeoxynucleotide 2006 (Microsynth) and irradiated allogeneic PBMC. After 2 weeks, culture supernatants were screened for the presence of norovirus-specific mAbs by EIA against VLPs and positive cultures were cloned by limiting dilution. Antibodies were recovered from supernatants and purified using protein A affinity chromatography and finally desalted against PBS using a HiTrap FastDesalting column.", "An additional measurement of antibody blockade ability uses RBCs as the VLP binding substrate. Previous work has demonstrated that Norwalk virus VLPs hemagglutinate (HA) O+ RBCs, that this interaction can be disrupted by antibodies found in polyclonal serum (hemagglutination inhibition; HAI), and that the HAI titer of serum correlates with antibody blockade of VLP-Bi-HBGA interaction [38, 39, 45] . To determine if these findings could be extended to study GII. 4 ", "The described mAbs indicate at least five unique or overlapping GII.4 blockade epitopes with different specificities: 1) early GII.4 strain specific, 2) contemporary GII.4 strain specific, 3) Minervavariant strain specific, 4) genogroup II strain specific, and 5) GII.4 strain specific. Using capsid sequences as a guide, mutant VLPs were designed to contain chimeric combinations of the predicted evolving GII.4 epitopes ( Figure 10) All epitope exchange VLPs were morphologically intact by electron microscopy visualization and retained the ability to bind PGM ( Figure 10A and B, [43] ), confirming chimeric VLP structural integrity." ] },{ "paper_id": "dc66ab3c756846482cc8d1d6abd41b623027fbf1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Real-time telemetry analysis was performed as detailed previous [32] . In brief, NHPs were implanted with radio telemetry devices (T2J; Konigsberg Instruments, Pasadena, CA) to monitor their temperature and activity throughout the experiment. Data were acquired and analyzed via Notocord-hem Evolution software (version 4.3.0.43; Notocord Inc., Newark, NJ).", "Serum separator tubes (Greiner Bio-One, Monroe, NC) were inverted after each phlebotomy and left to clot for approximately 30 minutes, at which time they were centrifuged at 1800 relative centrifugal force (rcf) for 10 minutes at RT. Serum was then pipetted into a Piccolo General Chemistry 13 disk and run on a Piccolo Point of Care Analyzer (Abaxis, Union City, CA).", "Methods. In this study, we deployed a platform to generate, test, and develop fully human antibodies to Zaire ebolavirus. We obtained specific anti-Ebola virus (EBOV) antibodies by immunizing VelocImmune mice that use human immunoglobulin variable regions in their humoral responses." ] },{ "paper_id": "dc69e220d40597887fac3851a1601408fe7bf568", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CCHFV Genome and Replication Cycle", "In transfected cells, the recently described CCHFV NS S localizes to the mitochondria and induces apoptosis by disrupting the mitochondrial membrane potential [28] . Although NS S has been detected in CCHFV-infected cells, the proposed apoptotic functions are based exclusively on the overexpression of NS S , and further investigations of NS S are warranted.", "Crimean-Congo hemorrhagic fever virus (CCHFV) causes a mild to severe hemorrhagic disease (CCHF) exclusively in humans, with case fatality rates of 5%-30%. Presently, efficacy of therapeutic options in controlled clinical trials remains unproven, and supportive care remains the mainstay of treatment. CCHF endemic foci are present over a wide geographic range, including areas in Western and Central Asia, the Middle East, South-Eastern Europe, and Africa [1] [2] [3] [4] . CCHFV exists in an enzootic cycle between ticks and mammals; and geographic distribution of the virus mirrors the distribution of the primary tick vector species that include members of the Hyalomma genus (H. marginatum, H. anatolicum, H. truncatum, H. impeltatum, and H. impressum) [5] . Viral transmission to humans can occur via tick bite, or via exposure to body fluids from viremic animals or humans [3] ." ] },{ "paper_id": "dc7809e3cbcc5bb53b481641f6796891f4ecedc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical specimens-Urine. Brisbane cohort. Urine specimens (226) that were submitted during 2003 to the diagnostic laboratory for routine investigation were collected. These represented a diverse mixture of donors, including those from (i) sexual health clinic (n \u00bc 50), (ii) pediatric clinic (n \u00bc 52), (iii) antenatal clinic (n \u00bc 33), (iv) indigenous health clinic (n \u00bc 36), and (v) bone marrow transplant patients (n \u00bc 55).", "Analysis of shotgun sequences. Sequences were assessed for quality using Phred [34] , and reads that contained less than 50 contiguous bases with a score of phred 20 or greater were rejected. The remaining reads were analyzed in the following steps: 1) reads were aligned to the human genome using BLASTn with an e \u00c010 cutoff; 2) remaining reads were aligned to a bacterial database using BLASTn with an e \u00c010 cutoff; and 3) remaining reads were aligned to the viral RefSeq protein database using BLASTx with an e \u00c02 cutoff [35] .", "Clinical specimens-Respiratory secretions. Brisbane cohort. A total of 1,245 specimens (predominantly NPAs) were collected between January 1, 2003, and December 22, 2003, from patients presenting to the Royal Children's Hospital in Brisbane, Queensland, Australia, with symptoms consistent with acute lower respiratory tract infection.", "In the literature, there is one animal polyomavirus that has been found extensively in lung tissue. Infection of suckling mice with the mouse pneumotropic polyomavirus (MPPV) causes interstitial pneumonia and significant mortality. MPPV also differs from other polyomaviruses in that besides the kidneys, it can also be detected in the lungs, liver, spleen, and blood of suckling mice [27] . Thus, there is precedence for an animal polyomavirus causing respiratory disease, suggesting at least the possibility that WU virus could be similarly pathogenic in humans." ] },{ "paper_id": "dc7de10933e811946c548cca7b1f3dbe61161d13", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All yeast plating assays were performed on selective media with either 2% glucose (for uninduced controls) or 2% galactose (for induction of IFIT and methyltransferase genes). A single yeast colony was picked from a freshly streaked plate of transformed yeast and grown overnight at 30 degrees in liquid media (SC -his GLU or SC -his/-leu GLU). Saturated overnight cultures were serially diluted 10fold from a starting OD 600 of 1 and spotted onto selective plates containing glucose or galactose. Plates were incubated at 30 degrees for 48-72 hr.", "The following commercially available primary antibodies were used: mouse M2 anti-Flag (Sigma-Aldrich, St. Louis, MO; F1804), rabbit anti-hCMTR1 (Sigma-Aldrich; HPA029979), mouse anti-PGK1 (Invitrogen, Carlsbad, CA; 459250), and rat anti-tubulin (Millipore, Temecula, CA; CBL270). Goat anti-mouse, anti-rat and anti-rabbit HRP-conjugated secondary antibodies were from Santa Cruz Biotechnology (Dallas, TX).", "For analysis of protein expression from stably transduced BSC40 cells,~200000 cells were harvested and lysed by boiling in 2x SDS sample buffer. For analysis of protein expression from yeast, a single yeast colony was picked from a freshly streaked plate of transformed yeast and grown overnight in liquid selective media containing 2% raffinose (SC -his/-leu RAF). Cultures were diluted in SC -his/-leu RAF to 0.5 OD 600 and grown 3 more hours at which point galactose was added to a final concentration of 2%. After 90 min, cultures were spun down and frozen. Cell pellets were resuspended in 2x SDS sample buffer containing protease inhibitors and bead beaten for 30 s. All cell lysates (yeast and mammalian) were run on 4-12% Bis-Tris gels (Invitrogen) and transferred onto nitrocellulose membrane. Blocking buffer and antibody dilution buffer for hCMTR1 blots was 5% bovine serum albumin in phosphate buffered saline (PBS) with 0.1% Tween-20. Blocking buffer and antibody dilution buffer for all other blots was 5% nonfat dried milk in PBS with 0.1% Tween-20." ] },{ "paper_id": "dc819c2ad69ad256a76b84efdf56063bc398fad5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Raw data sets not included in the manuscript or in the supplementary information are available from the corresponding author upon request." ] },{ "paper_id": "dc8b895c70dc5612cbe0efd328ca21624736c932", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "-Highly-pathogenic avian IAV (H7N9)", "HE, TG, GS, and GR conceptualized and composed the manuscript. GR and HE oversaw all aspects of the manuscript preparation.", "-Mouse-adapted laboratory IAV (H1N1)", "The continuous accumulation of adaptive mutations and the introduction of novel viruses in the human population continue to pose a threat to public health, especially to individuals at high risk to influenza. The emergence of strains resistant to existing classes of antiviral drugs and reduced vaccine effectiveness highlights the need for the development of alternative intervention strategies. Therefore, therapeutic approaches that can diminish the potential for drug-resistance while being effective against multiple IAV subtypes/strains are highly desirable. Targeting host cell factors meets these criteria and is more likely to avoid overtly robust immune responses thereby reducing disease severity and improve patient outcome (Figure 1) .", "IVs have segmented negative-sense single-stranded RNA genomes. The lack of proof-reading activity of the viral RNA-dependent RNA polymerase (RdRp) and successive replication can lead to the accumulation of nucleotide mutations which drive antigenic drift. In addition, the segmented nature of their genome allows genetic reassortment between IV's to take place, which can produce novel strains that have acquired alternative antigenically distinct hemagglutinin, also known as antigenic shift. Both antigenic drift and antigenic shift contribute to the IV's ability to evade pre-existing host immunity induced by previous infections." ] },{ "paper_id": "dca1ffcfcd6a2b7c8495e77c438d6b91d065bbf5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Extraction of total RNA was performed following manufacturers' protocol from QIAamp Viral RNA Mini Kit (Qia-gen, Germany) and TRIZOL (Invitrogen, USA) using all necessary safety precautions. The resultant RNA was dissolved in 20 \u03bcl of RNase-free water." ] },{ "paper_id": "dca48fcd1b8a28f470494d64ea3811707e28766b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dual Evolutionary Arms Races Shape TfR1 MMTV ERVs are thus reminiscent of the many ERV families found in the human genome, none of which currently circulate in infectious form [28] .", "Traditionally, TfR1 has been viewed as a housekeeping protein with an immensely important and conserved role in the cell. This study provides a much richer understanding of the multiple dynamic roles that this receptor is balancing in nature.", "The L212V SNP in human TFR1 (rs41301381) was identified in data deposited by the 1000 Genomes Project (http://browser. 1000genomes.org). As of Release 12, L212V had been found as a heterozygous SNP in 11 individuals, with no homozygous carriers identified. Three of these individuals were Han Chinese from the South (CHS population), six were Han Chinese from Beijing (CHB population), and two were Japanese individuals (JPT population). In total, 11 out of 286 Asian individuals surveyed were heterozygous at this position, yielding a genotypic frequency of 0.038 in Asia. This SNP has not been included in the HapMap Genotyping Project (as of Release 28)." ] },{ "paper_id": "dcb83fc0259abca0186d62b0b1d32eaf8607fcfc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Asthma is a disorder of the conducting airways that leads to variable airflow obstruction in association with airway hyperresponsiveness. It is characterized by inflammatory cell infiltration, mainly of eosinophils and lymphocytes, and reversible bronchoconstriction. As the disease becomes more severe, the airway acquire an altered repair response, and structural changes cause remodeling due to the secretion of factors and cytokines that induce mucous cell metaplasia, angiogenesis, and subepithelial fibrosis [1, 2] .", "Ovalbumin (OVA) grade V was purchased from Sigma-Aldrich (MO, USA). Antibodies against phospho-STAT3 (Ser 727 ), STAT3, SOCS3, and b-actin were obtained from Cell Signaling Technology (MA, USA); anti-mouse ROCK-2 was acquired from Sta Cruz Biotech (CA, USA), and anti-mouse RhoA was purchased from Cytoskeleton (CO, USA). Flow cytometry antibodies (anti-mouse CD49d PE, CD3 PE, and CD19 FITC) were all purchased from BD (NY, USA).", "Mice airway responsiveness was assessed in all animal groups 1 day before the animals were sacrificed. Four individual whole body plethysmography chambers, obtained from Buxco, were used as described previously [15] . Enhanced pause (Penh), a parameter that correlates with measurement of airway resistance, was used to perform the analysis." ] },{ "paper_id": "dcbb50e1f581ab72a3070c7639c8c1a23e031c27", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Table S1 GenBank accession numbers of representative parecho-, papilloma-, and anellovirus strains. (DOC)", "The genomes of identified viruses described in detail here were deposited in GenBank under the following accession numbers: ferret kobuviruses MpKoV38, KF006985; MpKoV32, KF006987; MpKoV39, KF006986; ferret parechovirus (MpPeV1), KF006989; ferret papillomavirus (MpPV1), KF006988; ferret anellovirus (MpfTTV1), KF006990. ", "Papillomaviruses (PVs) are a highly diverse family of viruses with double stranded circular DNA genomes of ,8 kb in size. They infect a wide variety of mammals, as well as birds and reptiles, and are highly species specific. Some papillomaviruses cause benign or malignant epithelial tumors of the skin and mucous membranes in their natural hosts [54] ." ] },{ "paper_id": "dcbe31a68ac67d38ccdae0615ebabd8461bd7095", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A rapidly accumulating body of evidence supports the concept that the tissue itself directs the differentiation pathway of CD8 T RM , leading to context-dependent differences in phenotype, master transcription factor regulators, metabolism, and requirements for maintenance. Superimposed on these tissue-specific effects are those involving viral infections, such as differences between viruses in cell tropism, whether infections are acutely resolved or persistent (and if so, whether persistence is latent or in a chronic infectious state), and variation in innate responses. Thus, there is a pressing need to fill many gaps in our understanding of the delicate balance CD8 bT RM must strike between controlling viral infections while minimizing pathology in the CNS. Funding: National Institutes of Health grants R01 NS088367 and R01 NS092662.", "The brain has long been considered an immune privileged organ. New research that shows that the brain has conventional lymphatic drainage, anatomical niches that harbor resident populations of macrophages and dendritic cells, and glia that operate as innate immune cells, runs counter to this concept [1] [2] [3] [4] . The immune privileged hypothesis of the brain arose, in part, from the unique cells that populate the central nervous system (CNS). Many cells in the brain, such as neurons and mature oligodendrocytes, are postmitotic and terminally differentiated, creating a fragile environment that is extremely sensitive to infection and infiltration. Despite this, many virus families, such as polyomaviruses (e.g., JC polyomavirus (JCPyV)), herpesviruses (e.g., varicella zoster virus (VZV) and herpes simplex virus (HSV)), enteroviruses (e.g., poliovirus), and flaviruses (e.g., Zika virus and West Nile Virus (WNV)) are neurotropic or gliatropic. The consequences of these viral brain infections-e.g., meningitis, myelitis, encephalitis, and demyelination-contribute to a significant health burden worldwide. Immune responses that can control these viral infections must negotiate a trade-off between viral control and immune-mediated damage.", "Despite its demonstrated role in CD8 T cell memory responses, the mechanisms underlying PD-1-regulated control of CD8 T RM differentiation remain unknown. Glial cells express PD-L1, which increases during inflammatory events and viral infections [77] . We have found that MuPyV-infected glial cells expressed high levels of PD-L1, suggesting that infected glial cells may directly affect the differentiation of CD8 bT RM through engagement of PD-1 [29] . However, no direct interaction between PD-L1 + glial cells and PD-1 + CD8 T cells has been reported. Thus, additional studies are warranted to clarify the importance and complexity of PD-1 signaling and CD8 bT RM differentiation." ] },{ "paper_id": "dcc14fe9ac1567bcde8412180b20c71162525235", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Despite considerable progress, there are many questions that remain to be addressed: How can we propagate infectious viruses in vitro for further studies? What is the receptor and is it specific for bats? Are there more influenza and influenza-like viruses circulating in bats or other hosts in Central and South America and other parts of the world? If so, do these viruses pose a risk for domestic animals and/or humans as observed in bat-derived severe acute respiratory syndrome (SARS), rabies, Nipah, and probably Ebola viruses?" ] },{ "paper_id": "dcc46888d647f293c6f9d136aaf7d3a708558372", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Overall, MERS-CoV vaccines have shown encouraging results in preclinical studies and we hope these vaccines stand up to safety considerations in order to proceed through clinical trials. While development of therapeutic treatment is critical, vaccination carries the promise of mitigating future outbreaks and alleviating disease burden from the most vulnerable populations including the aged, the immunosuppressed, healthcare workers, family members of infected patients, and those in endemic areas. ", "The authors declare no conflict of interest." ] },{ "paper_id": "dcc4db04a2a7001e0b9931be5648c7f0cc233620", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Eukaryotic pre-mRNA splicing is a process during which introns are removed and the flanking exons ligated to form the mature mRNA. Alternative splicing enables differential usage of splice sites, thus generating various transcript isoforms originating from one genetic template and increasing the proteomic diversity (for recent review see [31] ).", "Although the molecular mechanisms within the PI3K pathway leading to endocytotic uptake still remain elusive in many cases, the usage of this pathway for assisting viral uptake seems to be a widespread viral strategy [20, 21, 23, [25] [26] [27] 29, 30] (Figure 2 ).", "Expanding their coding potential, many viruses take advantage of the host splicing machinery to ensure the production of their own protein diversity and to regulate the different stages of infection by temporally expressing transcripts. Adenoviruses and HSV-1, both containing a double-stranded DNA genome, seem to manipulate mRNA splicing in favor of viral gene expression and replication. Both viruses do so via hypophosphorylation of particularly two SR proteins, SRSF1, SRSF9 (Adenovirus) and SRSF3, SRSF5 (HSV-1), by modifying either PP2A or SRPK1activity [46, 47] (Figure 3) .", "Taken together, the manipulation of cap-dependent protein synthesis-irrespective of the involvement of mTOR1-is a common mechanism of viruses to guarantee an efficient translation of viral proteins." ] },{ "paper_id": "dcceda0265e3540a12eef54836297a20d890c4a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The average charge number of charged particles was calculated as follows:", "Scientific RepoRts | 5:17462 | DOI: 10.1038/srep17462 used for bioaerosol detection 19, 20 . However, these methods need pre-treatments for binding antibody on a surface or particles.", "where W is the width of the nozzle width and E s is the electrostatic number; i.e.," ] },{ "paper_id": "dccf40912c6da39a0326cd025ae83d3933a1849a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceived and designed the experiments: RZ WKL. Performed the experiments: XHL WKL MXC SYQ HC. Analyzed the data: XHL ZBH. Contributed reagents/materials/analysis tools: DHC YL XHL ZQZ XGT. Wrote the paper: XHL ZBH WKL RZ.", "The statistical analysis was performed using SPSS 19.0. The \u03c72 test and Fisher's exact test were used where appropriate. All of the tests were two tailed, and a value of P < 0.05 represented statistical significance." ] },{ "paper_id": "dcd1759241f327b5235520cebe1f7432aa936c5d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(A) Dual-luciferase frameshift reporter plasmids (Grentzmann et al., 1998; Fixsen et al. 2010) harbouring the -1 PRF signals of human immunodeficiency virus gag/pol (HIV; stem-loop stimulatory RNA; SL), mouse mammary tumor virus gag/pro (MMTV; pseudoknot stimulatory RNA; PK) (Girnary et al., 2007), infectious bronchitis virus 1a/1b (IBV; PK) (Brierley et al., 1992) or the IBV slippery sequence (U_UUA_AAC) but lacking the PK (no structure) were transcribed in vitro and the resulting mRNAs translated in RRL in the absence or presence of nsp1\u03b2. The products were resolved by 15% SDS-PAGE and visualised by autoradiography. Molecular size markers were also run on the gel (M). Products derived from ribosomes that do not frameshift (stop) or that enter the \u22121 frame (-1 FS) are indicated. No specific inhibition or stimulation of frameshifting was seen, although some general inhibition of translation was FIGURE S1: related to Figure 1. Nsp1\u03b2 does not modulate PRF at established ribosomal frameshifting signals, nor stimulate programmed stop codon readthrough.", "To determine frameshifting efficiencies after siRNA-mediated knockdown of PCBP expression, 6x10 4 MARC-145 or 4.8 x 10 4 RK-13 cells were seeded per well in 12-well clusters in DMEM containing 8% FCS. MARC-145 cells were transfected with siGENOME Human siRNA SMARTpools (Dharmacon) targeting PCBP1, PCBP2, PCBP3, PCBP4, or hnRNPK (final concentration 10 nM) using 2 \u00b5l of Dharmafect1 lipofection reagent (Dharmacon) per well. RK-13 cells were transfected with siRNA pools targeting PCBP1 or PCBP2 (final concentration 25 nM) using 3 \u00b5l Lipofectamine 2000 (LifeTechnologies) per well. A non-targeting pool (NTP) of \"scrambled\" siRNAs (Dharmacon) was used as a negative control. At 24 h post transfection (p.t.), the transfection medium was replaced with DMEM containing 8% FCS. Possible cytotoxic effects of siRNA transfection were monitored at 48 h p.t., using the CellTiter 96\u00ae AQueous Non-Radioactive Cell Proliferation Assay (Promega). After 120 min, the reaction was stopped by the addition of 25 \u00b5l of 10% SDS and absorbance at 490 nm (A490) was measured using a 96-well plate reader (Berthold Using these values, -2 PRF efficiencies were calculated as (nsp2TF + nsp2TF\u2032)/(nsp2 + nsp2\u2032 + nsp2TF + nsp2TF\u2032 + nsp2N + nsp2N\u2032) and -1 PRF efficiencies were calculated as (nsp2N + nsp2N\u2032)/(nsp2 + nsp2\u2032 + nsp2TF + nsp2TF\u2032 + nsp2N + nsp2N\u2032). Quantification was performed in triplicate.", "(A) Left side. EMSA titration of binding of nsp1\u03b2 and PCBP2 to a short (58 nt) 32 P-labelled in vitro transcript containing the PRRSV PRF signal. After incubation at room temperature for 10 min, reactions were loaded onto a 4% non-denaturing polyacrylamide gel and following electrophoresis, the gel was fixed, dried and subjected to autoradiography. Nsp1\u03b2 was present throughout at 0.8 \u00b5M and the numbers below lanes show fold molar excess of PCBP2 with respect to the radiolabelled RNA (10 nM). BSB: RNA was incubated alone with band-shift buffer (BSB). Right side. Control EMSA showing similar RNA binding capacity of wild-type nsp1\u03b2/PCBP2 (NP2) and PR mutant nsp1\u03b2/PCBP2 (N PR P2) complexes. (B) RNA/protein complexes and free RNA were quantified by phosphorimagery and a binding curve plotted. From this, the Kd was estimated as 130 nM. (C) Control EMSA reveals that nsp1\u03b2 RBM mutant (at indicated molar excesses with respect to RNA) does not form stable RNA protein complexes in the absence (RBM, 1\u00b5M) or presence of PCBP2 (1 \u00b5M). Control lanes were nsp1\u03b2 (N, 1 \u00b5M) and PCBP2 (P2, 1 \u00b5M) alone, both proteins together (NP2, 1 \u00b5M each) and BSB. (D) Control EMSA confirms that RNA protein complexes do not form on the CC2 mRNA. Wild-type RNA (wt RNA) was used as a positive control. Figure S4 (A) Short, competitor RNAs containing the PRRSV PRF signal, the CC2 mutant or the poliovirus IRES stem-loop IV (P3/Leon/37; accession number K01392.1) were prepared by in vitro transcription. (B) An mRNA (0.25 \u00b5M) derived from FspI-cut pDluc PRRSV/wt was translated in RRL in the presence of increasing molar excesses of competitor RNAs (numbered above the relevant lanes). The products were resolved by 12% SDS-PAGE and visualised by autoradiography. Molecular size markers were also run on the gel (M). Products derived from ribosomes that do not frameshift (stop) or that enter the \u22121 or \u22122 frames are indicated. " ] },{ "paper_id": "dcd269e34e588ed3ce743184f98ed65229b84fdd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bromodeoxyuridine (BrdU) (10 mg/mL) (#550891, BS Pharmingen) was daily injected (150 \u03bcL) via i.p. into mice starting 1 day after MCAo until day 4. One-hour after the last BrdU administration mice were killed and processed for immunofluorescence. BrdU was detected in brain tissue sections using a rat monoclonal FITC-anti-BrdU antibody (1:50, #ab74545, Abcam, Cambridge, UK) [46] .", "Mouse blood and brain tissue were processed for flow cytometry as described [46] . Fc receptors were blocked by previous incubation for 10 min with CD16/CD32 (clone 2.4G2, BD Pharmingen) in FACS buffer (PBS, 2 mM EDTA, 2% FBS) at 4 \u00b0C. Live/dead Aqua cell stain (Molecular Probe, Invitrogen) was used to determine the viability of cells. Cells were incubated with the following mix of ", "To impair microglial function, mice received a daily oral administration by gavage of the CSF1R inhibitor GW2580 [12] (75 mg/kg body weight in a volume of 0.2 mL) (#S8042, Selleckchem) for 4 days, which is a dosing regimen that does not challenge microglial survival [54] . Treatment controls received the same volume of the vehicle (0.5% hydroxypropylcellulose, 0.1% Tween-80). Treatment started 2 h prior to induction of ischemia, it was randomly allocated, and was administered in a blinded fashion." ] },{ "paper_id": "dcd6d893dd1fcb8bd484691ccdb9043f3b2d9934", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ebola virus (EBOV) is an enveloped, single-stranded RNA (\u2212) virus known to cause severe hemorrhagic fever in both humans and non-human primates (NHPs). Historically associated with sporadic outbreaks in Central Africa, EBOV more recently gained notoriety during the largest outbreak to date in West Africa (focused in Sierra Leone, Guinea, and Liberia), where the virus was responsible for >11,000 cases and >28,000 deaths [1] . At the conclusion of this outbreak in 2016, EBOV once again faded from the public spotlight; however, outbreaks have continued to occur, particularly in the Democratic Republic of the Congo (DRC), where the virus is now considered endemic [2, 3] ." ] },{ "paper_id": "dcd7287d538d38848896654f8dd359f9adf94946", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Manytimes due to environmental stress, immunosuppression, and deficient managemental practices, secondary invaders more severely affect the diseased individuals; moreover, mixed infections with multiple aetiology are also common phenomena [5, 8, 13, 15] .", "(1) bacterial: Pasteurellosis, Ovine progressive pneumonia, mycoplasmosis, enzootic pneumonia, and caseous lymphadenitis,", "(1) acute: bluetongue, PPR, Pasteurellosis, and parainfluenza,", "Advances in diagnostic tools and assays help strengthening the surveillance and monitoring systems of animal diseases. The latest advances in molecular techniques have assisted in the rapid and confirmatory diagnosis of the diseases and epidemiological studies to formulate appropriate and timely prevention, treatment, and control measures, and alleviation of economic losses to animal producers [1, 7, 13, 22, 23] ." ] },{ "paper_id": "dcd7ba50d2dd32e9237d69e920ce1c4fa91f4df9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2019, 11, x FOR PEER REVIEW 4 of 11", "* N/A-Not available: was not analyzed because there was not enough RNA." ] },{ "paper_id": "dcde88584805e783b69565364975fc31053b6b4e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Associations between clinical manifestations and etiological agents were analyzed with Fisher Exact test, considering a P-value ,0.05 as significant value. Statistical analyses were calculated with EpiInfo software (version 3.5.1).", "This study was approved by the National Ethics Committee of the Malagasy Ministry of Health (CE/MINSAN nu 019). A briefing note explaining the purpose of the project and the informed consent form was given to each of the parents involved in the study who signed the consent forms to provide written informed consent.", "In this study, most pathogens were found distributed among the four groups representing the different clinical manifestations (Figure 1 ). Overall, HRV was detected in each group presenting a highest prevalence in ALRIs (26.8% and 22.1% in group I and II, respectively) compared to the others groups. HMPV A/B was mainly detected among ''CAP'' patients (17/71, P = 0.020) and most often single detected (15/17) . HPIV was associated with bronchiolitis, bronchitis and EVW ( " ] },{ "paper_id": "dce2c9d835e3ebbee3ff4e6868d5755ddec76b71", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A S A R G D L A H L T T C-S8c1 (5'-3',", "Microarrays containing 384 spots were printed by means of a GMS 417 DNA arrayer (Affymetrix) defining four grids per slide. Each oligonucleotide was spotted in duplicate dots 150 \u00b5m in diameter, with a center-to-center distance of 250 \u00b5m (Figure 3 )." ] },{ "paper_id": "dce34f36e8a1d8b4692c1e54852d6942da5d065a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antimicrobial peptides (AMPs) are important components of the nonspecific immune system of animals to eradicate invaders [6] , and the skin secretion of anuran amphibians are rich sources for collecting AMPs [7] [8] [9] . AMPs have a wide spectrum of antimicrobial activity against microorganisms such as bacteria, viruses, fungi, and parasites [10, 11] , but are very friendly to host cells [12] [13] [14] . Moreover, AMPs can work as growth and health promoters to improve the performance of pigs by enhancing the immune status, improving the intestinal health, and alleviating the toxic effects of deoxynivalenol in pigs [15] . There are also research findings that AMPs can modulate immune responses like chemokines, cytokine production, and pro-inflammatory responses [16, 17] .", "For this purpose, we investigated the inhibitory ability and antiviral mechanisms of Caerin1.1 against different PEDV strains in Vero cells, which will provide an insight into AMPs' antiviral mechanisms and its application as antiviral drugs or as drug loading compounds.", "The authors have declared that no competing financial interests exist.", "Alphacoronavirus of the family Coronaviridae with single-stranded positive-sense RNA [1] . It is the causative agent of an acute infectious enteric disease known as porcine epidemic diarrhea (PED) that is clinically manifested by severe watery diarrhea, vomiting, and dehydration in the suckling piglets [2] . With the high mortality in the piglets, PED infection finally caused enormous economic losses to the global swine industry, especially after its recent re-emergence caused by variant PEDV strain throughout the world [3, 4] . However, the classical PED vaccines could not provide appropriate protection against the variant PEDV infection. Considering this, relevant studies of new antiviral materials are needed to prevent and control emerging or re-emerging infectious diseases such as PED [5] ." ] },{ "paper_id": "dce4b37c7dd77b761ad89d62448183f4250d7266", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 Dataset. Study-level data used for analyses. ", "Zoonotic disease emergence is driven by a complex web of factors, including human behavior, modifications of natural habitats, changes in agricultural practices, and the underlying pathogen diversity found in animal populations [1] . With increasing environmental disruption and population growth, humans come into contact with bats and other wildlife at an increasing rate, leading to exposure to novel pathogens and disease emergence.", "We explored patterns of prevalence and calculated mean and median prevalence by specimen type at various viral and host taxonomic levels. All molecular data were aggregated to produce boxplots and heat maps. Heat maps were clustered by similarities in viral richness by row and column using the hclust 'complete linkage' method in R package pheatmap version 0.5.1. Other R packages used included: ggplot2, gplots, plyr, DTK, MASS, Hmisc, and RColorBrewer. All analyses were conducted using R software version 3.1.2 [27] . " ] },{ "paper_id": "dce8be353f8ed76957af86118e1b77fd82f54292", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Camelpox strain CP-19, CMV strain AD169, HHV-6 strain U1102, SARS coronavirus strain 6109 and YFV strain 17D were propagated according to standard procedures [8] [9] [10] .", "Primers, TaqMan probes and QPCR conditions for reference gene analysis were used as previously described [5] . PCR was performed in a Perkin Elmer 7700 Sequence Detection System in 96-well microtiter plates using a final volume of 25 \u00b5l.", "Total RNA from 1 \u00d7 10 6 cells was prepared using the QIAamp RNA Blood Mini Kit and RNase-free DNase set (Qiagen, Hilden, Germany) according to the manufacturer's recommendations for cultured cells. RNA solution was treated with DNA-free (Ambion, Huntingdon, United Kingdom).", "The best genes obtained from all three calculation tools were TBP and PPI. TBP seems to be a relative stable expressed gene during the course of virus replication of different viruses in different cells. However, as previously shown [5] TBP is not expressed in all tissues and therefore its use may be limited." ] },{ "paper_id": "dcef588534b114e24a8c93a3eeeba8c1d11dd8a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "U18666A was from Tocris Bioscience (Bristol, UK). Poly-Llysine, filipin, sulphorhodamine B Bafilomycin A1 and the Cholesterol Kit were from Sigma-Aldrich. AlexaFluor-488 amine-reactive carboxylic acid, vybrant-DiD (vDiD, 1,19-dioctadecyl-3,3,39,39-tetramethylindodicarbocyanine,4-chlorobenzenesulfonate salt), Hoechst-33342 and Live Cell Imaging buffer were purchased from Life Technologies (Grand Island, NY). CypHer5E Mono NHS Ester was from GE Healthcare (Pittsburgh, PA). Antibodies used were rabbit anti-IFITM3 (to N-terminus) from Abgent (San Diego, CA), mouse anti-IAV-NP and goat anti-IAVpolyclonal antibodies from Millipore (Billerica, MA), rat antimouse-IgG-FITC from eBioscience (San Diego, CA), and goat anti-rabbit-Cy5 from Jackson Immunoresearch (West Grove, PA).", "The pR8DEnv, BlaM-Vpr, pcRev, HIV-1 Gag-iCherryDEnv and pMDG VSV G expression vectors were described previously [37, 55] . The YFP-Vpr was a gift from Dr. T. Hope (Northwestern University). The pCAGGS vectors encoding influenza H1N1 WSN HA and NA were provided by Donna Tscerne and Peter Palese, and the pCAGGS BlaM1 (WSN) plasmid was a gift from Dr. A. Garcia-Sastre (Mount Sinai). Vectors expressing phCMV-GPc Lassa and pcDNA3.1-Ebola GP (Zaire) were gifts from Dr. F.-L. Cosset (Universit\u00e9 de Lyon, France) [56] and Dr. L. Rong (University of Illinois) [57] , respectively.", "Methods S1 Description of additional methods employed in this study." ] },{ "paper_id": "dcf12f1f76ae03b3107f00aadea540298105d312", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For", "the joint density f of Y, V, and of the vector h of unknown parameters is written as the following product:", "The date of death was V i~di . Finally, the professional category P i was acceptable if P i~ki . Hence:" ] },{ "paper_id": "dcf73eb12e0e246c75505f6723e6c10608963297", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are expressed as mean 6 SE. Experiments were conducted in triplicate with at least three independent cultures. Group differences were calculated using an Analysis of Variance (ANOVA) followed by a Bonferroni multiple comparison test. Differences were considered significant for p values less than 0.05.", "Influenza pneumonia remains a major cause of morbidity and mortality worldwide. Airway epithelial cells are the first line of defense against viral infections in the lung and are instrumental in coordinating the early inflammation leading to an adaptive immune response. CXCL10 (IFN gamma inducible 10 kDa protein, IP10) is a non-ELR CXC chemokine with potent biological effects including monocyte stimulation, natural killer and activated T cell migration, modulation of adhesion molecule expression, inhibition of angiogenesis [1] as well as antimicrobial effects at high concentrations [2] .", "The role of CXCL10 in viral pneumonia has not been thoroughly characterized but evidence suggests it is important for the migration of NK cells, macrophages, T cells, neutrophils and plasmacytoid dendritic cells into the lung [3, 4] . In a mouse model of RSV infection, antibody-mediated neutralization of CXCL10 resulted in a significant increase in disease symptoms including impaired viral clearance, reduced pulmonary dendritic cell numbers and maturation and a reduction in viral specific CD8(+) T cells [5] ." ] },{ "paper_id": "dcf9e10df84c4439f2fb380b472de9ef2a6e55b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Twenty amino acids are categorized into eight chemical groups according to their side chain shown in Table 1 .", "To validate our methods with other myosin family, we chose to study MYOI class of unconventional myosin (the second biggest sub-family of myosin). Myosin Is are single headed myosins that lack the heptapeptide motif responsible for coiled-coil association in the C-terminal like myosin II [29] . There are 8 myosin I isoforms found in vertebrates, and generally referred as MYO1A-H using nomenclature adopted from Human Genome organization [30, 31] . In Table 4 shows their names, length, accession number, protein names and remarks.", "doi:10.1371/journal.pone.0167651.g001 " ] },{ "paper_id": "dcfa47b076db144f586108d35f5d43e5100c02d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pa (serotype 10) LPS (1 \u00b5g/ml), MG-132, staurosporine, tobramycine, and DMSO were from Sigma-Aldrich (Saint-Quentin Fallavier, France). Purified Pa flagellin (50 ng/ml) was from InvivoGen (San Diego, CA, USA), and Tunicamycine (TM) and GSK2656157/PERK inhibitor were from Calbiochem (Merck Millipore, Molsheim, France).", "RNA was isolated using a NucleoSpin RNA/Protein kit (Macherey Nagel, Duren, Germany). RT was performed using a high-capacity cDNA kit (Applied Biosystems, Foster City, CA, USA). Real-time qPCR was performed with an ABI StepOnePlus, using TaqMan Fast Universal PCR Master Mix (Applied Biosystems), TaqMan probes for CHAC1 (Hs_00225520), IL-8 (Hs_174103), IL-6 (Hs_985639), CCL2 (Hs_00234140), GAPDH (Hs_2786624) and cDNA as a template. For relative quantification, the amount of target genes was normalized to the expression of GAPDH relative to control cells used as a calibrator and was calculated using the 2 \u2212 Ct method.", "LG, MC, and VB designed the study. " ] },{ "paper_id": "dcfbf04c5bf819de0d261d15a1936288f578d416", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All analyses were computed using Stata 14.1." ] },{ "paper_id": "dd12c39ca963dca8336d7f30c8842d892ec8236c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: In addition to seasonal influenza viruses recently circulating in humans, avian influenza viruses (AIVs) of H5N1, H5N6 and H7N9 subtypes have also emerged and demonstrated human infection abilities with high mortality rates. Although influenza viral infections are usually diagnosed using viral isolation and serological/ molecular analyses, the cost, accessibility, and availability of these methods may limit their utility in various settings.", "Vaccination and treatment with antiviral drugs (e.g., neuraminidase inhibitors (NAIs)) are primary interventions to prevent viral infections and their spread. However, vaccine production usually takes 6-12 months to prepare for newly emerging viruses. NAIs also should be taken within the first 48 h following an infection [5] . Thus, rapid and accurate diagnosis of viral infections is important for mitigating the spread of virus within a community, facilitating immediate treatment with NAIs, and controlling carriers of these pathogens. Methods to detect and identify influenza viruses have improved over the past decades, ranging from traditional virus culture [6] to introduction of serological and molecular diagnostic technology (e.g., real-time RT-PCR [7] and PCR [8] ) and more recently, rapid influenza detection tests (RIDT) [9] [10] [11] . With various influenza-specific diagnostic tools, selecting the most appropriate approach is based on a number of factors, including sensitivity, specificity, throughput, cost, and availability [12] .", "A total of 73 influenza-positive (confirmed using a qRT-PCR method) clinical nasopharyngeal aspirate samples collected from patients who demonstrated flu-like symptoms at Chungbuk National University Hospital, Republic of Korea were used for clinical evaluation of the RT-LAMP diagnostic assay developed in this study. In addition, 18 spiked samples in which 10 4 TCID 50 /ml of viruses (i.e., H1N1, H5N6, H5N8, and H7N9) were diluted into flu-negative human nasopharyngeal aspirate samples " ] },{ "paper_id": "dd2054667f5f1db92d4649fc420d0d86dc39dcd9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following this hypothesis, the possibility of a Cdc42-lead signalling pathway was investigated by our group in 2014 [35] . Two novel Cd42 inhibitors, ML141 [36] [37] [38] and ZCL278 [39] , were employed to investigate inhibition of infection of three different HIV-1 pseudo-type virus strains [40, 41] . The intersectin-specific ZCL278 was found to significantly inhibit the infectivity of all three pseudo-type viruses in a dose-dependent manner in both cell lines investigated (TZM-bl and PM1). At the highest doses used of 50 \u00b5M, the infectivity of X4 and R5 tropic pseudo-type viruses was reduced to 29.64% (X4) and 30.43% (R5) in TZM-bl cells, and to 22.96% for X4-tropic viruses in PM1 cells. The broader-acting ML141 showed almost no inhibitory effect on pseudo-type virus infectivity, and in fact increased the infectivity of X4-tropic virus in both TZM-bl and PM1 cells to a maximum effect of~175% of control (12.5 \u00b5M ML141 on PM1 cells producing 172.66% infectivity).", "Similarly to other members of the paramyxovirus family, RSV was originally believed to enter target cells in a fusogenic manner via the RSV fusion (RSV-F) glycoprotein found in the viral envelope. This theory was evidenced by initial dequenching assays, in which fluorescent lipid probes in target cell plasma membranes dequenched when incubated in RSV virions, indicating a mixing and dilution of the target cell plasma membranes that was attributed to RSV fusion [47] . It was then demonstrated in several studies that the RSV entry process is independent of endosomal acidification [48] [49] [50] , supporting fusogenic entry.", "Primary CD4+ T-cells exhibit a dichotomy of actin dynamics [15] : in activated T-cells there is a polarized migratory morphology brought about by an active and plastic cytoskeleton; in rounded resting T-cells, which include na\u00efve and memory subsets, a far more restricted cytoskeletal activity is observed, alongside a relative resistance to infection [16] [17] [18] [19] [20] . Although infection and subsequent depletion of activated T-cells is a leading process in the natural morbidity and mortality of HIV-1 infection, it is infection of resting T-cells that constitutes the principle barrier to cure. Activation of resting T-cells allows reestablishment of viremia when treatment is interrupted [21, 22] , therefore understanding viral entry into resting T-cells is of paramount interest and relevance." ] },{ "paper_id": "dd2a154b5fe59f997e47913b3a6da5d23bdb7556", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistics. Data were analyzed using GraphPad Prism v5.0a (GraphPad Software, Inc., SanDiego, USA). Data were presented as mean \u00b1 SEM. Statistical significance of the differences was determined using Student t test. Differences were considered significant when P < 0.05." ] },{ "paper_id": "dd3c5f3af25e4c6fe5395625ed96d9244cd467b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Informed consent was obtained from all participants before this study was conducted. The study and all procedures were approved by Jiaxing Municipal Center for Disease Control and Prevention (Jiaxing CDC), and carried out in accordance with biosafety and ethical standards of the institutional and national research committee and the relevant laws and regulations of People's Republic of China." ] },{ "paper_id": "dd40ad3eec9f455f6ab725f007eb32e852b3439c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To facilitate the real time PCR analysis, primers were either selected from the literature or designed using Primer Express 3.0 software (Applied Biosystem) with minimum amplicon size ranging between 50 and 115 bp and limited 3 G+C content. Primer details for all genes are given in Table 2 . To check the sequence specificity, primers were aligned against publicly available databases at NCBI and UCSC's Cow (Bos taurus) genome browser gateway using BLASTN. Prior to qPCR, primer specificity was further confirmed in a 20 L PCR reaction using the same protocol described for qPCR except for the final dissociation protocol. Five L of the PCR product was evaluated in 2% agarose gel stained with ethidium bromide. The accuracy of primer pairs was also ensured by the presence of a unique peak during the dissociation step at the end of qPCR.", "Mammary tissue was obtained from an adult riverine buffalo and was immediately transported to laboratory in Dulbecco's Modified Eagle's Medium/Ham's F12 media (DMEM/F12, 1 : 1 mix) (Hyclone, Logan, UT, USA) containing antibiotics 100 U/mL penicillin-streptomycin (Hyclone). Five grams of tissue was washed with PBS (Ca 2+ -, Mg 2+ -free) (Hyclone) for several times until the solution was pellucid and without milk. The tissue sample was cut into 1 mm 3 cubes and washed again. The smaller pieces of tissue were transferred to collagen-coated cell culture dishes (Corning, USA), containing DMEM/F12 supplemented with 10% fetal bovine serum (PAA), 100 U/mL penicillin-streptomycin (Hyclone), 5 L/mL insulin, 50 M hydrocortisone, 1 g/mL -estradiol, 5 g/mL holotransferrin, and 1 g/mL Progesterone. (Sigma-Aldrich) and incubated at 37 \u2218 C, 5% CO 2 . Initially, the basal media was replaced after every 12 h and then after every 48 h with fresh media until cells were visibly spread across the bottom of the culture dish. Cells were detached with 0.25% trypsin containing 0.02% EDTA (Sigma-Aldrich) and transferred to T75 culture flasks (Corning, USA). The process was repeated up to 10th passage, and pure mammary epithelial cells were obtained for further experimentation.", "The total RNA extracted from individual MECs samples exhibited high purity as determined by mean (\u00b1SEM) 260/280 ratio of 2.06 \u00b1 0.014. The bioanalyzer-based RQ value of >8 also indicated sufficiently good quality of each extracted RNA. The qPCR performance for each gene in 2 P\u00e9rez et al. [32] , and 3 Hernandez et al. [33] . 4 qPCR efficiencies for each primer pair were calculated from six-point standard curves using fivefold dilution series of pooled cDNA from control and heatstressed samples. terms of coefficient of determination, ( 2 ), and efficiency of amplification ( = 10 \u22121/slope ) on the basis of slope of six-point standard curve are summarized in Table 2 . The efficiency of PCR reactions ranged from 90.70% for ACTB to 131.37% for B2M. The characteristics of individual 16 genes based on their cycle threshold (Ct) values are shown as box whisker plot (Figure 1 )." ] },{ "paper_id": "dd40b192bbddb785dd3f6e42e45853cd4b14cdca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "dd41a45ccd8c4801ed131a349aa0ec0bc8f3895c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The data used for this analysis has been translated from Chinese sources such as provincial centres of disease control, and made publicly available [8] . We took the data as available on 29 January 2020 (Supplementary Material S1).", "The analysis yields the probability of being infected (dark pink), i.e. the cumulative density function of the estimated infection moments, using the Weibull distribution.", "Since the epidemic was developing during that time period, it is more likely that travellers were infected towards the end rather than the beginning of their stay. This might produce a slight bias towards longer incubation periods, so the estimated upper limit of 11.1 days could be considered conservative." ] },{ "paper_id": "dd46b3a35a8a6299b52a23022b0d5d9c23e24ae0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Acid hydrolysis was performed by a previously described method [28] . For this purpose, each compound (10 mg) was heated in an ampule with aqueous 12% HCl (5 mL) at 90 \u00b0C for 2h. The aglycone was extracted with chloroform, and each aqueous residue was adjusted to pH 7.0 with 12% NaOH and reduced with NaBH 4 (40 mg), followed by acidification with dilute CH 3 COOH, and then co-distilled with pure CH 3 OH to remove excess boric acid. The reduced sugars were acetylated with 1:1 pyridine-Ac 2 O in a boiling water bath for 2 h to give the corresponding alditol acetates, which were analyzed by GLC on a HP 6890 N gas chromatograph (Agilent) equipped with a flame ionization detector FID) using N 2 as carrier gas. The instrument was fitted with a HP-5 capillary column (30 m\u00d70.32mm\u00d70.25 \u03bcm). The injector temperature was set at 250 \u00b0C and the column temperature program was as follows: the initial temperature of 120 \u00b0C was increased by 3\u00b0/min to the final temperature of 210 \u00b0C, then was held 4 min. The detector temperature was set at 300 \u00b0C. The standard monosaccharides were subjected to the same reaction and GC analysis under the same conditions (D-galacose, t R , 30.8 min)", "According to the literature, the configuration of C-24 is R when C-16 chemical shift in the 13 C-NMR spectrum should be 102.9~103.7, while for S it appears to be 106.1~106.8 [19] In the case of 3, the C-16 chemical shift is 106.7. The 1 H-and 13 C-NMR spectrum of 3 were similar to those of 7,8didehydro-24S-O-acetylhydroshengmanol-3-O-xyloside [27] , respectively, except for the sugar moiety (Table 1) ", "Three new cycloartenol triterpene saponins, named shengmaxinsides A-C, have been isolated from the ethyl acetate soluble fraction of an ethanol extract of Cimicifuga simplex Wormsk roots. Their structures were established by chemical tests and detailed spectroscopic analysis as 25-O-acetyl-7,8-didehydrocimigenol-3-O-\u03b2-D-galactopyranoside (1), 7,8-didehydrocimigenol-3-O-\u03b2-D-galactopyranoside (2) and 7,8-didehydro-24S-Oacetylhydroshengmanol-3-O-\u03b2-D-galactopyranoside (3), respectively." ] },{ "paper_id": "dd48e5c738239c1d9b0497cbf4b5219bf252c0b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Urbanization rate signifies the level of urbanization, which indicates the level of economic development, infrastructure, existence of public services, and other related factors. A higher level of urbanization in one region generally indicates a comparative wealth of potential job opportunities and better healthcare, both of which appeal to potential migrants.", "These regression coefficients were determined using MATLAB programs developed by our group." ] },{ "paper_id": "dd4a3353ae21a249a81f30e23fc416a1d948887b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BSA stock solution (0.1 mM) was prepared in a physiological aqueous solution with 100 mM phosphate buffer, pH 7.2. The stock solution of warfarin (10 mM) was prepared in methanol. The preparation of ibuprofen and the tested components stock solutions (0.1 mM) were similar with BSA stock solution. All of the stock solutions were kept at 4\u00b0C in the dark.", "The fluorescence emission intensities of BSA can also be analyzed the modified Scatchard equation as follows:", "It is evident that several amino acids with hydrophobic and hydrophilic characteristics were in contact with SaB in these BSA and HSA complexes and, that hydrogen bonds play an important role in the binding system. In the SaB-BSA complexes (Fig 11b) . Lys-195, Arg-218, Arg-222, and Arg-257 formed hydrogen bonds with SaB, water molecules were also likely to serve as a bridge for producing hydrogen bonds." ] },{ "paper_id": "dd4c8ed4c8651c73d3d13a61cd7d14c9eb1fa745", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "dd5f8cf7e557b09094248fd8fbc59fbf7f01649e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "dd65db968a579c422c2fc4e43bbf0b265b5b3ea6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Authors' contributions Conceptualization, JYM; Data curation, ZHZ; Formal analysis, RTW; Funding acquisition, JYM; Investigation, XYT and YYZ; Project administration, TL and YS; Resources, JYM; Supervision, TL; Validation, YQC and XYT; Visualization, XYT; Writingoriginal draft, XYT. All authors read and approved the final manuscript.", "Consent for publication \"Not applicable\".", "LncRNAs are regulators of protein coding genes that lie near their genomic locations. We analyzed these RNAs for all protein coding genes within 100 kb of the lncRNA as potential cis-regulatory targets (Additional file 1)." ] },{ "paper_id": "dd673a8892d7431842f691147b9d4b1e6206b912", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No competing interests were disclosed.", "The author(s) declared that no grants were involved in supporting this work.", "1." ] },{ "paper_id": "dd74c8f2961dc716ec9d0c412206c88e0cb9b314", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The formula for information coefficient (I) calculation is as follows:" ] },{ "paper_id": "dd75883b3cd3c5b39b7cc9db85f682047961e1a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The lentogenic LaSota strain of NDV was kindly provided by Dr. Siba Samal at the University of Maryland, College of Veterinary Medicine (College Park, MD, United States). Titration of the virus was performed with the final titer of undiluted viral suspension of 10 7 50% egg infectious dose (EID 50 )/mL. The viral suspension was stored at \u221280 \u2022 C until further use.", "Animal use protocols were approved by the Pennsylvania State University IACUC committee (protocol numbers 46395 and 47175). Specific pathogen free (SPF) eggs from White Leghorn chickens were sourced through Charles River Laboratories International, Inc. (North Franklin, CT, United States). Tanzanian local ecotype and Kuroiler hatching eggs were sourced from Urio Cross and Pure Breeding LTD, a local farm, in Tanzania (Tengeru, Arusha, Tanzania). Embryonated eggs from two well-defined, inbred Leghorn sublines, Ghs6 and Ghs13, as well as two inbred Fayoumi sublines, M5.1 and M15.2, from Iowa State University Poultry Farm (Ames, IA, United States) were also included in this study. Eggs were incubated (37.5 \u2022 C, 55% humidity, rotating hourly) and only temporarily removed from incubation to candle for viability and perform inoculations with virus.", "Keywords: backyard poultry, chicken embryo, Newcastle disease virus, innate immune response, transcriptional response INTRODUCTION Newcastle disease virus (NDV) is one of the most important poultry pathogens worldwide, with over eighty countries in North and South America, Europe, Asia, and Africa reporting outbreaks each year (Diel et al., 2012) . NDV infections manifest through a wide range of strain dependent symptoms including those within the respiratory system (coughing, sneezing, and wheezing), the nervous system (such as twisted neck, tremors, and paralysis), and the reproductive system (loss in egg production). Mortality rates may reach as high as 100% in unvaccinated flocks (Ashraf and Shah, 2014) . Unsurprisingly then, NDV infections are responsible for considerable economic losses to poultry production in both developed and developing countries. For instance, the 2002-2003 NDV outbreak in California resulted in the destruction of 3 million birds and financial losses of over $160 million (Diel et al., 2012) ." ] },{ "paper_id": "dd8386559f84e8d56f399d577d4e97529e312db5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A secondary data analysis was performed from a previous cross-sectional study conducted from January 2010 to July 2012 in 5 Peruvian hospitals: Instituto Nacional de Salud Del Ni\u00f1o, Hospital Edgardo Rebagliati Martin, Hospital de Emergencias Pedi\u00e1tricas, Hospital Nacional Cayetano Heredia and Hospital Regional de Cajamarca.", "A database was generated in Microsoft Excel\u00ae 2015 (Microsoft Corporation, California, USA), all data was then exported to STATA\u00ae v13.0 (StataCorp, College Station, Texas, USA). Quantitative variables were described as frequencies and percentages for each group.", "Not applicable." ] },{ "paper_id": "dd916c3ebb297ef2b6a36f7d6f33bac8ed1198b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Of the 35 methods manuals previously identified on guideline development, only WHO, NICE and CDC provided guidance on RG development (Table 4 ) [1, 54, 55] .", "We found that timeframes were inconsistent with the organisations' methods manuals. While WHO recommends RGs be developed in a timeframe between 1 and 3 months, the median time required based on our systematic survey was 8.5 months. For the NICE guidelines, the results showed a median time of 21 months while the manual suggests a timeframe of between 11 and 13 months. We identify some reasons why the proposed timeframe is not followed by the RG developers.", "We present data narratively with descriptive statistics." ] },{ "paper_id": "dd94afcee3d0c4dbc80b40435ff4fb65487af3b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The protocol was approved by the Ethical Committee of Shandong Provincial Chest Hospital, written informed consent was not required because of the retrospective nature of the investigation.", "Cases were defined as \"definite\" according to the 2007 ATS/IDSA criteria for disease when they had clinical criteria and there were at least two separate positive cultures of sputum samples, or at least one positive culture from bronchial lavage or lung biopsy [1] . Patients with a positive NTM culture with a compatible clinical syndrome were termed as \"probable\". Cultures for mycobacteria were performed using L\u00f6wenstein-Jensen medium (L-J) method. The indirect proportion method with L-J medium was used for first-line drug susceptibility test (DST) [18] .", "Fifty-two (89.7%) patients were NTM lung disease, five (8.6%) were pleural disease, and one (1.7%) lymphadenitis. Thirty-seven (63.8%) patients had cough, 24 (41.4%) fever, 18 (31.0%) dyspnea and five (8.6%) hemoptysis. Eight (13.8%) patients were asymptomatic and admitted for abnormality of chest X-ray. Seven patients have contact history with a TB patient in the family." ] },{ "paper_id": "dd9a2b263b1b66db904ed8a18dd6eba55e64bfff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "cytotoxins to cancer cells 14 . One of these agents, a cyclic version of the NGR peptide complexed to the human tumor necrosis factor alpha, is currently undergoing Phase III clinical trials in mesothelioma 15 .", "Statistical analysis. Data were analyzed using the unpaired, two-tailed Student t test. Differences at the 95% confidence level (P < 0.05) were considered to be statistically significant." ] },{ "paper_id": "dd9f6d51d902c4493f797715278469d4c19bf65d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were analyzed using GraphPad Prism 4.03 software. An unpaired Student's t-test (two-tailed) was used to assess comparisons between two groups when the data met the assumptions of the t-test. Survival curves were generated by log-rank test. p<0.05 was considered a significant difference.", "Supporting Information S1 Text. Reagents and antibodies. (DOCX) S1 Table. The primer sequences for qPCR of the indicated genes. " ] },{ "paper_id": "dda497d889e111005663783d8ac3c1289e4a7f42", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The controls represent HCWs in their usual working conditions, without any interventions. This study is a post-hoc analysis of data collected during the primary trial on HRPs in the control arm. The prospective data collection and measurement of clinical endpoints in a group of HCWs working under usual conditions afforded the opportunity to measure the association of incident infection with HRPs.", "We prospectively studied 481 hospital HCWs from wards including emergency and respiratory wards from nine hospitals in Beijing, China over a 5-week period from 1 December 2008 to 15 January 2009. These 481 subjects were a control group in a larger study [27] .", "The hospital wards were selected as high-risk settings in which repeated and multiple exposures to respiratory infections are expected. Participants were hospital HCWs aged 518 years and who were provided with written information about the study. Staff who agreed to participate provided informed consent and a copy of the information sheet with the participants' initials was retained as documentation [27] . The study protocol was approved by the Institutional Review Board and Human Research Ethics Committee of the Beijing Ministry for Health." ] },{ "paper_id": "dda902a72728faf3f12e96b6765ed4beb0b57961", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Raw files were analyzed using Sequest HT in Proteome Discoverer (Thermo Fisher Scientific, San Jose, CS version 1.4.0.288) against a Uniprot Human database available at UniProtKB website (http://www.uniprot. org/taxonomy/9606) with the following parameters: trypsin as a digestion enzyme; maximum number of missed cleavages 2; fragment ion mass tolerance 0.60 Da; parent ion mass tolerance 10.0 ppm; fixed modification, carbamidomethylation of cysteine; variable modifications, methionine oxidation.", "Viruses can be inhaled or ingested as free viruses, be contained in droplets shed from an infected host, or be injected via arthropods. When they have overcome the first host barrier and enter the body, they get access to underlying permissive cells and can establish an infection (Figure 1) .", "Caco-2 monolayers grown on glass coverslips (thickness 0.17 \u00b1 0.01, 13 mm-diameter; Karl Hecht Assistent, Sondheim, Germany) were washed with PBS pH 7.3 and pretreated with 0.2% Triton X-100 (Sigma Aldrich) in PBS for 2 min on ice." ] },{ "paper_id": "ddba9808c2e5a41e0a27996ff5b59e4c09ae159a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "The antibodies against \u03b2-actin (clone AC-15, Sigma), CAPN5 (Abcam), CBLB (Invitrogen and clone C-20, Sant Cruz), CD81 (clone JS-81, DB Pharmigen), CLDN1 (R&D), EGFR (clone LA1, Merck), GAPDH (Sigma), HA (clone 16B12, Covance), NS5A (clone 9E10, kindly provided by Charles M. Rice), OCLN (clone OC-3F10, Invitrogen), SCARBI (Novus) and ZO-1 (clone 1/ZO-1, BD Biosciences) were used for immunoblot, flow cytometry and immunofluorescence staining. Horseradish peroxidase (HRP)-coupled anti-mouse and anti-rabbit antibodies were from Sigma and Jackson Lab Inc., respectively. Alexa 488-conjugated secondary antibodies were from lifeTechnologies, Alexa 647-conjugated secondary antibodies were from Invitrogen, APC-or FITC-conjugated secondary antibodies were from eBioscience. For immunoprecipitation, we used antibodies against CD81 (clone 1.3.3.22, Santa Cruz), HA (clone 16B12, Covance) and a mouse IgG 1\u03ba (clone MOPC-21, BD Pharmigen).", "For western blot analysis, equivalent volumes of cell lysates, IP flowthroughs or IP eluates were boiled 5 min with SDS sample buffer under non-reducing conditions, resolved by SDS-PAGE and transferred to PVDF membranes by electroblotting. Membranes were probed with primary antibodies o/n at 4\u02daC, then with secondary HRP conjugated antibodies for 1 h at room temperature and analyzed using a chemiluminescence (Intas) system." ] },{ "paper_id": "ddbf31002935c6a62e177e3085670455ec4121ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mention of trade names or commercial products in this paper is solely for the purpose of providing specific information and does not imply recommendation or endorsement by authors or their affiliated institute. The authors have no conflict of interests.", "Cytotoxic T lymphocytes MIP-1 : Macrophageinflammatoryprotein1 JAK/STAT: Janus kinase/signal transducers and activators of transcription MYD88: Myeloid differentiation primary response gene 88 IRF1:", "Interferon regulatory factor 1 NF B2:", "Nuclear factor NF-kappa-B p100." ] },{ "paper_id": "ddbf9291a1a1cd15d61bcb6cd1946813251ba5cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleic acids, particularly RNA, are extremely versatile molecules. Apart from their role as carriers of genetic information they can also express a phenotype, e.g., they may show a catalytic activity, have a specific binding function, or have the capacity to recruit specific molecules.", "In addition to these general steps, the amplified molecules may require additional manipulations prior to their introduction into the next round of selection When the selected molecule is ssDNA, both DNA strands must be separated and the positive one isolated, e.g., by incorporating a biotinylated residue into the unwanted strand [20, 21] via asymmetric PCR [22] .", "Variants that show the required phenotype need to be replicated to ensure their passage into the next generation and therefore their persistence in the population. Specific primer binding sites are used to amplify the selected molecules. When necessary a RNA polymerase promoter is incorporated at the 5' end of the PBS during the amplification step." ] },{ "paper_id": "ddcf8a29af29bdb7e62b35517fef0b0754e59f4f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The nucleotide sequence of the ITS region reported in this article was assigned the GenBank accession number KT164776.", "In 2015, viral pathogenesis became an intriguing hot topic among human society. This is exemplified by the recent Ebola virus outbreak in Western Africa and Middle East Respiratory Syndrome (MERS) in South Korea [1] . Meanwhile, influenza viruses are still a great threat to human health [2, 3] . So far, only two classes of antiviral drugs, which include amantadine and the neuraminidase inhibitors, are currently used as anti-influenza therapeutic drugs, but both of them have some adverse side effects in humans as well as the resistance of the virus towards this drug [4, 5] . Hence, a concerted effort is aimed at discovering new antiviral agents to treat and eradicate these infectious agents [6, 7] .", "Supplementary Materials: Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/ 21/1/34/s1." ] },{ "paper_id": "ddd0fb0cae99bad6466775c11b4d5a0c30be9219", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Overall, the results of this qualitative visualization study are not surprising and relatively intuitive, however being able to visualize these relative differences may emphasize the advantages and disadvantages of these different door designs in a more emphatic manner for consideration by hospital managers and administrators, infection control and hospital building design teams.", "For this baseline series of experiments, all of them were performed in a still water environment, with no pressure differential simulated across the doorway.", "It is difficult to make a direct comparison with contact transmission as to which route is more clinically significant for acquiring hospital-related infections. One recent observational study examined the number of viable bacteria found on hospital door handles of different designs in certain high traffic areas in a tertiary referral hospital in the UK. The authors found that the door handle's location, design and mode of use were all factors that affected their degree of contamination, with the traditional lever-style handles being the most highly contaminated [25] ." ] },{ "paper_id": "ddd24c570c13a2251edc4e4251a5545ce215e935", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since its establishment in 2005, the KPRC has become a highly-regarded NHP research and development center, serving as one of the major bases for biomedical research in China.", "Dr. Zhi-Wei Chen (AIDS Institute, University of Hong Kong) described his group's pioneering studies to elucidate the mucosal seeding of SARS-CoV infection using the Chinese macaque model .", "Dr. Jian-Qing Xu (Fudan University) presented work in the sequential immunization strategy of heterologous HIV immunogens .", "In summary, the organizers of the 4 th NHP symposium would like to take this opportunity to express our appreciation and gratitudes to all the attendees for their excellent lectures and active participation in discussions during the meeting. The organizers sincerely hope that the next symposium will continue to flourish both domestically and internationally and offer researchers many opportunities to collaborate and advance innovative research, from basic studies to translational medicine, using NHP resources." ] },{ "paper_id": "ddddc52ff6183d8092a992286fd64acb18cdf2bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In order to create consensus sequences, nucleotide sequences within each FASTA file specific to a genus were aligned using ClustalW [20] . If a minimum of two consensus subsequences with lengths of 20 bp and a maximum of four ambiguous positions with minor nucleotide frequency \u2265 10% were not identified, the original FASTA file was iteratively clustered using CD-HIT [21] , with decreasing threshold. The clusters obtained at each step were aligned independently using ClustalW to identify consensus subsequence(s) for all the subsets, which must collectively represent at least 90% of different species within the genus. Finally, at least one aligned FASTA file was obtained for every genus.", "(i) proportion of ambiguous positions (P AMB ) \u2264 20%;" ] },{ "paper_id": "dde2f725f681ca3d6af28e816b5b58db9fe56551", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, there are also reports that migrant populations have a higher support level than local groups, arguing that immigration enables people to obtain better job and better socioeconomic status, thus acting positively on them [31, 32] . However, although migrant women have risen in socioeconomic status in our scenario, this theory does not apply. Compared with the widelyfocused-on immigrants group (e.g., immigrant workers and merchants) whose migrating destination are developed districts, women in this study have several characteristics which may explain their worse social support conditions: (1) possible ethnic and language barriers makes them unable to smoothly adapt to new communities or pursue better socioeconomic status; (2) their origin and special way of migration (marriage) makes them susceptible to discrimination and hinders them from merging into new local societies, and additionally the conservative atmosphere in rural areas may intensify this discrimination; (3) low socioeconomic status of their husbands in local communities weakens their relative affection and living content.", "The means and standard deviations of social support score received by migrant and non-migrant women are detailed and compared in Table 2 . In most aspects immigrant group recorded a lower score, except that the dimension of utilization of support the difference was not statistically significant." ] },{ "paper_id": "ddf124684188ac29dba3b174f327bd0fd62155bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "China) according to the manufacturer's instructions. The extracted genomic DNAs were stored at \u221240\u00b0C. A commercial vaccine was used as a positive control, and distilled water was used as a negative control.", "Fecal samples that tested positive for CPV-2 were also screened for canine bocavirus (CBoV), canine coronavirus (CCoV), canine astrovirus (CaAstV), canine norovirus (CNoV), canine kobuvirus (CaKV), and group A-rotavirus (RV-A), by either PCR or reverse transcription-PCR (RT-PCR) and sequencing, as previously described [23] [24] [25] [26] [27] [28] .", "All animal experiments were conducted according to the Guide for the Care and Use of Laboratory Animals of Harbin Veterinary Research Institute (HVRI), Chinese Academy of Agricultural Sciences, China. Sampling and data publication also were approved by animal's owners. The field study did not involve endangered or protected species. No specific permissions were required for locations of samples because the samples were collected from public areas or nonprotection areas." ] },{ "paper_id": "ddf12f9e4ca7761aa1c1fd192e9bc9103ad8a642", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plates were coated with anti-human IgG (Dako) at 5 mg/ml in PBS or Tetanus vaccine (Dutch vaccine institute, The Netherlands) diluted 1:10 for 1 hr at 37uC or o/n at 4uC and washed in ELISA wash buffer (PBS, 0.5% Tween-20). 4% milk in PBS was used as blocking agent, before serial dilution of cell culture supernatants and enzyme-conjugated detection Abs were added (dilutions 1:2500 for HRP-conjugated anti-IgG (Jackson Immu-noResearch Laboratories) and 1:250 for AP conjugated anti-IgG (DAKO)). TMB substrate/stop solution (Biosource) or Alkaline Phosphatase Substrate (Sigma-Aldrich) was used for development of the ELISAs. To detect Tetanus Toxin we used the ELISA Ridascreen Tetanus (r-biopharm AG, Darmstadt, Germany)." ] },{ "paper_id": "ddfd6e95ebc735146d0f0d6ea7faacaf99d9613c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Materials. N-terminally acetylated and C-terminally amidated SARS FP ( 770 MWKTPTLKYFGGFNFSQIL 788 ) and SARS IFP ( 873 GAALQIPFAMQMAYRF 888 ) peptides were either purchased from GenScript (Piscataway Township, NJ) or manually synthesized according to the standard Fmoc solid-phase peptide synthesis method on a Rink-Amide resin 98 . The details of peptide synthesis are described in Vicente et al. 99 . Purification was performed as described in Supplementary section SI1." ] },{ "paper_id": "de01b5c28a44e4d80b38e389342275d0353673e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All HCoV-NL63-and HCoV-HKU1-positive samples were tested for ", "Studies of multiple respiratory viruses indicate that although single infections with HCoVs occur, coinfection with RSV and parainfluenza 3 viruses is common in both HCoV-HKU1-and HCoV-NL63-positive patients. This makes it difficult to clarify the role of coronaviruses in childhood pneumonia or bronchopneumonia. Future studies using real-time RT-PCR and sample collection over several consecutive years will be helpful in providing further insights into these etiologic agents of respiratory disease in China.", "The primers and probes for HCoV-HKU1 were as follows: HKU-1-N forward primer 5 -AGTTCCCATTGCTTT-CGGAGTA-3 ; reverse primer 5 -CCGGCTGTGTCTATA-CCAATATCC-3 ; TaqMan-MGB probe, 5 -FAM-CCCCTT-CTGAAGCAA-MGB-3 [8] ; HKU-1-1ab forward primer 5 -CCATTACAAGCCATAAGAGAACAAAC-3 ; reverse primer 5 -TATGTGTGGCGGTTGCTATTATGT-3 ; Taq-Man probe 5 -FAM-TTGCATCACCACTGCTAGTACCAC-CAGG-TAMRA-3 [9] ." ] },{ "paper_id": "de0bb38fe24062ae86287891a21a9851a0e6b7f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animal research at U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) was conducted under an Institutional Animal Care and Use Committee (IACUC) approved protocol in compliance with the Animal Welfare Act, PHS Policy, and other federal statutes and regulations relating to animals and experiments involving animals. The facility where this research was conducted is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care, International and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals, National Research Council, 2011 [24] .", "Blood chemistry profiles were determined using a Vitros 350 Chemistry system (Ortho Clinical Diagnostics) and coagulation analysis was performed using a Sysmex CA-560 (Siemens).", "Marburg virus (MARV) is a filovirus closely related to Ebola virus and similarly causes hemorrhagic fever in humans. MARV is endemic throughout parts of tropical Africa. Severe outbreaks of Marburg virus disease (MVD) have occurred involving hundreds of PLOS Neglected Tropical Diseases |", "Tissues collected for histopathology and IHC were immersion-fixed in 10% neutral buffered formalin for a minimum of 21 days before removal from BSL-4 containment. The tissue samples were trimmed, routinely processed, and embedded in paraffin. Sections of the paraffinembedded tissues 5 \u03bcm thick were cut for histology. The histology slides were deparaffinized and stained with hematoxylin and eosin.", "Replicate sets of the slides produced for routine histology were made for IHC. An immunoperoxidase assay using a cocktail of two mouse monoclonal antibodies against MARV as the primary antibodies was completed on unstained slides of all tissue sections. These slides were then counter-stained with hematoxylin." ] },{ "paper_id": "de15170cb79d459586be28d687e7d68117990644", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "de1c5a16a75d5c28d9e3a9be2e928406fee458e4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "de207527ab4b8826e6e8901d63e768c19691b178", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral epidemics can occur anywhere in today's \"global village\". MERS-CoV is a relatively new virus. Effective national and international preparedness plans are essential to predict and control outbreaks, improve patient management, and ensure global health security. ", "There has been a recent increase in reports of asymptomatic or mild MERS-CoV infection among women and children. However, there are no corresponding findings on contact tracing among healthcare workers or close contacts of infected patients in German, UK and US hospitals, or in serologic surveys of blood derived from donors and abattoir workers in endemic regions in 2012 [21] . Therefore, it is hard to estimate the proportion of asymptomatic patients among infected individuals.", "The origin of MERS-CoV has been widely discussed. Originally, a bat reservoir was posited based on the phylogenetic similarity of certain bat coronaviruses with MERS-CoV [4, 5] . However, the exact MERS-CoV strain found in humans has not been identified in any bat species [6, 7] . Furthermore, in almost none of the known cases to date was there a clear bat source of infection or a consistent history of contact with bats.", "Disaster and Military Medicine *Correspondence: fogelitay@gmail.com 3 Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petach Tikva 49202, Israel Full list of author information is available at the end of the article [9] . Camels are currently recognized as the main animal reservoir, with primary cases occurring in areas where they are an important part of life. Unpasteurized camel milk may be a route of transmission, but so far there are no data that MERS-CoV is excreted into camel milk [10] ." ] },{ "paper_id": "de22df7c68cc8f64265c0a26ef9f2acd53520ef6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "undertreating patients destined to relapse or overtreating patients who could be cured by surgery alone. Thus, new biomarkers pivotal to tumor biology are urgently needed to improve prognosis of the adjuvant treatment regimens." ] },{ "paper_id": "de2da69b84bad743d1e16d52a12d4ea8ca9f66d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine epidemic diarrhea (PED), caused by porcine epidemic diarrhea virus (PEDV), was first recorded in England in the early 1970s and has since spread to other European and Asian countries [1] . In North America, PEDV was detected for the first time in the United States (U.S.) in April 2013 [2] and subsequently PEDV was reported in Canada [3] and Mexico [4] . PEDV is an enveloped, single-stranded, positive-sense RNA virus belonging to the order Nidovirales, the family Coronaviridae, subfamily Coronavirinae, genus Alphacoronavirus [5] . The PEDV genome is approximately 28 kb in length and includes ORF1a and ORF1b encoding the replicase polyproteins and other opening reading frames (ORFs) encoding four structural proteins [spike (S), envelope (E), membrane (M), and nucleocapsid (N)] and one nonstructural protein NS3B (encoded by ORF3) [1] .", "The data set(s) supporting the results of this article is included within the article.", "Not applicable. " ] },{ "paper_id": "de33cc55be6bb27a8f52e33fe21836c670252e28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Multiple independent serodiagnostic antigens can dramatically improve the sensitivity and accuracy of serodiagnostic tests [37] .", "Detailed information for the genes/proteins from this study can be found at the Candida Genome ", "Human sera from candidemia patients and hospitalized patients were collected from SH-UF under protocols approved and created by the UF Institutional Review Board. Sera from healthy individuals were obtained from volunteers at the General Clinical Research Center at the University of California, Irvine. Written, informed consent was obtained from participants." ] },{ "paper_id": "de34db0d2ca85142ffadf43e8a6abec285608f9e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasmid and small interfering RNA (siRNA)" ] },{ "paper_id": "de4137cea11509b6caf359fd5c66a215a1e8390f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The clinical materials used in this study were discarded remains of specimen collected for routine diagnostic examination, all data was blinded with no links to enable identification of patients. As such, the study was exempt from ethical approval in accordance with US Code of Federal Regulations 45 CFR 46.101. Work in ", "In this study we have provided an evidence base for RPA as a tool for the rapid and sensitive detection of DNA from MTBC.", "Table S1 Culture, smear and RPA test results derived from clinical specimens. The scores for bacteria counted in the smear +ve specimens are shown in parenthesis, e.g. +ve (2+). Smear scores that were scanty are shown as +/2. Acronyms and other points. MTBC -Mycobacterium tuberculosis complex; NT -Not Tested; NTM = -Non Tuberculous Mycobacteria. MTBC. * Primary culture was contaminated; specimen was confirmed via a fresh specimen; # bronchoalveolar lavage (others not marked are sputum). (DOCX)", "To this aim, the Xpert MTB/RIF (Cepheid, USA) was endorsed by WHO in 2010 to detect pulmonary disease in settings with a high incidence of TB/HIV co-infection or with high rates of drug resistance [5] . This polymerase chain reaction (PCR) based test is fully integrated into a modular system and can detect both TB infection and indicate the presence of resistance to one of the key anti-tuberculosis drugs, rifampicin. The key attribute of the GeneXpert system is its ease of use, as the majority of key processes are integrated and automated from DNA extraction to interpretation of a test result [6] . However, the GeneXpert requires consistent electricity and laboratory temperatures maintained under 30uC, which poses logistical challenges [7] . Furthermore, the cost of cartridges, instrumentation and maintenance threaten its sustainability in the longer term in high TB burden countries that currently rely on global donor assistance to provide this technology. Therefore, to increase access to timely and accurate diagnosis for more TB suspected patients, rapid, high performance TB diagnostic tests that can meet the logistical challenges of unsupervised use in limited infrastructure settings are required and at a price that is more comparable to smear microscopy [3, [8] [9] [10] . Other technologies have been developed for TB diagnosis in microscopy centers in high burden countries and are currently undergoing evaluation. These include semi-modular systems (Epistem Genedrive and Molbio EASYNAT) or methods with manual specimen processing and test determination (Eiken LoopAMP TB and Ustar Biotechnologies Easy NAT) [9, [11] [12] [13] [14] [15] ." ] },{ "paper_id": "de452bf070bb2c100cab63901495507c492e6ada", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher. ", "( (Noris et al., 1994) . c Ts:Tv, transition:transversion ratio. d Na, not applicable.", "(2)" ] },{ "paper_id": "de4ab44a9e3ff11c0f831a0ab5a421191c78c6dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "National Taiwan University Hospital Research Ethics Committee.", "The pre-publication history for this paper can be accessed here:", "http://www.biomedcentral.com/1471-230X/9/63/pre pub" ] },{ "paper_id": "de5427785ad1385b62f0fbf18af129dc8cff303f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Preliminary work was done prior to the field surveys. We reviewed the Flora of China (Chinese vision) [30] and Flora of Hainan [31] and found the blue dye sources plant species distributed on Hainan Island. Then, we used photographs of them as a tool to assist the interview process [32] . During the field surveys, we asked the interpreters to help us translate the local language because none of the collectors could speak neither Hainan Miao nor Li language. Yet, the interpreters come from local villages. They spoke both Mandarin and local languages, so they could help to translate the local languages into Mandarin since some elder dyers could not speak fluent Mandarin.", "Abbreviations AI: Availability index; PR: Preference ranking; QI: Mention index", "Two field surveys were performed in April and August in 2018, each of roughly 14 days. The third visit of 5 days was conducted in November 2018. Snowball sampling methods and questionnaires were employed to collect primary data [28] . Questionnaires for the collectors were shown in Table 1 . Respondents, who were expert traditional dyers, were not forced to give their real names and answer all the questions. Prior informed consent [29] was taken verbally from all the respondents before documenting their traditional knowledge on various uses of indigo-yielding plant species. After getting permission, we took photos and videos of the main indigo extraction process." ] },{ "paper_id": "de562be49e01ca34319b504cbacad8d665d2d232", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Categorical data were compared between farm and nonfarm using the Chi squared test for association. Percentages were rounded to the nearest whole number.", "As outlined in Table 1 , in-person visits occur prenatally and when the infant is at 2, 9, 12, 18, and 24 months of age (with a permitted window of \u2212 1 to + 3 months for each study time point). All visits are led by a trained Research Coordinator and occur at participants' homes or coincide with a scheduled well child healthcare visit at their clinic. In addition, after the infant is born, mothers are contacted by telephone every 3 months to complete a study questionnaire. Prompts are sent by telephone or mail at monthly intervals to schedule study activities or remind about upcoming study procedures.", "Atopic dermatitis (incidence, cumulative prevalence, and resolution) is defined as parental report of chronic pruritic skin rash or doctor-diagnosed atopic dermatitis on the EHR.", "After the birth of the participant mother's child, a comprehensive birth record abstraction was conducted to rule out potential confounders due to complications from the pregnancy. Detailed study eligibility criteria are listed in Additional file 1: Table S1 . Exclusion criteria are: (1) maternal use of antibiotics (except Group B Strep prophylaxis) or corticosteroids in the last trimester of pregnancy; (2) delivery at \u2264 34 weeks gestation; (3) perinatal infections or prolonged rupture of membranes; (4) significant congenital anomalies; (5) significant respiratory distress after delivery." ] },{ "paper_id": "de64592c6c3786b48b73cac2debc515c642e31f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Snapshots of the code and further supporting data is available in the GigaScience repository GigaDB [40] .", "Project name: drVM Project home page: https://sourceforge.net/projects/sb2nhri/ files/drVM/ Operating system(s): OS X, Linux, Windows Programming language: Python Requirements: Amazon machine image, Docker, or Virtual machine; 8 GB RAM License: GNU General Public License, version 3.0 (GPL-3.0)", "AMI: Amazon machine image; HCV: hepatitis C virus; HIV: immunodeficiency virus; NGS: next-generation sequencing; RSV: respiratory syncytial virus; SRA: sequencing read archive; WNV: West Nile virus." ] },{ "paper_id": "de652a9f987a68568c425859c662ea8d2325631c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "for the purpose of providing specific information and does not imply recommendation or endorsement by the IZSAM.", "Porcine epidemic diarrhoea (PED) is an economically important and highly contagious enteric disease of swine, particularly in new born sucking piglets, in which strains of PED virus (PEDV) cause mortality up to 100% of infected individuals (Song et al. 2015) .", "Here we report and characterize a porcine epidemic diarrhea (PED) outbreak which occurred in a swine fattening farm in the province of Teramo, Abruzzi region (central Italy), in January 2016. PED virus (PEDV) identification was determined by real-time RT-PCR performed on RNAs purified from fecal samples collected from two symptomatic pigs. Whole genome sequence (PEDV 1842/2016) was also obtained by next generation sequencing straight from RNA purified from one fecal sample. Genome comparison with extant global PEDV strains revealed a high nucleotide identity with recently reported European and American S-INDEL PEDVs. Efficient sequencing, share of genomic data combined with the implementation of epidemiological tools would be the ideal approach for study and analysis of transboundary infectious diseases as PED." ] },{ "paper_id": "de6c34a97fa39dae81dd7f300648f1e6c21c67f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "for bringing the T84 cell line to our attention and Steeve Boulant (University of Heidelberg) for providing us T84 cells and a standard culturing protocol. O RCI D Oliver Schildgen", "Despite being frequently detected as a copathogen in respiratory infections, the human bocavirus has also been shown to be a major player in viral respiratory mono-infections in all age-groups. [1] [2] [3] [4] However, although known since more than a decade, cultivation of the virus remains a major challenge and was so far limited to some selected laboratories, which made either use of primary air-liquid interface cell cultures or not commercially available CuFi-8 cells. 5, 6 Recently, Ghietto and coworkers proposed that CaCo-2 cells, a cell line derived from a colorectal tumor, could be used to study parts of the HBoV replication cycle, as these cells could be infected with HBoV and shed the virus. 7 Without doubts, this is a major progress, as CaCo-2 cells are easily available and do not require extensive and expensive cell culturing efforts. Nevertheless, especially with respect to the pathogenesis of HBoV strains causing respiratory infections, the CaCo-2 model remains limited, although the study by Ghietto and coworkers unintendedly confirmed the previous assumption that HBoV displays a tropism to colorectal tumors. 8, 9 In search for alternative cell culture models, we became aware of the cell line T84 (ATCC \u00ae CCL-248\u2122), which originates from a colon metastasis of a bronchial tumor; the colorectal localization of the primary tumor from which T84 derived as well as the fact that the tumor was of bronchial origin made the cells thus an ideal candidate cell line to test, as two putative perquisites for HBoV growth; that is, tumor type(s) and target/organ tissue were fulfilled. T84 cells could be easily grown as monolayer cultures and by mounting them on filter membranes coated with rat or human collagen can be differentiated into a multilayer respiratory epithelium (detailed protocols on request). " ] },{ "paper_id": "de707f97b534ca340482600ed1f008b20d7b1b8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quantitative and qualitative data were expressed as means (+/-SD), or median [25%-75% interquartile range] and percentage (with their 95% CI), respectively. Categorical variables were compared using the chi-square or Fischer's exact test as appropriate. Quantitative variables were compared using the Student t-test or the Mann-Whitney non parametric test as appropriate. Confidence intervals of percentages were based on normal approximation. The level of significance was set at 0.05 and all tests were twosided. We used EPI-INFO version 6.04 dfr (EPI-INFO, CDC, Atlanta, GA) for data collection, and EPI-INFO and SAS version 9.1 (SAS Institute Inc, Cary, NC) for data analysis." ] },{ "paper_id": "de793a20bfe9029e76531469de1054c4d5ef37c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results of neutralizing antibodies levels were presented as the means \u00b1 SEM. The significance of the variability among the experimental groups was determined by twoway ANOVA. A probability value (P) of < 0.05 was considered significant.", "The porcine encephalomyocarditis virus (EMCV) is a member of the genus Cardiovirus of the family Picornaviridae, the genome is a single-stranded positive sense RNA of approximately 7.8 kb with a unique large open reading frame (ORF) [1] . Porcine EMCV infection, which is characterized by acute myocarditis and sudden death in preweaned piglets and severe reproductive failure in sows, results in severe economic losses for swine production [2] [3] [4] ." ] },{ "paper_id": "de79ddbf8cff4bf83533c1c991cf5640dab43ea5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hence, more precise cell manipulations are currently under investigation. Among them, gene editing of primary human T cells was recently demonstrated to be an efficient approach [137] .", "Finally, gene delivery by AAV has been reported to induce immune responses against the encoded protein.", "Although AAV usually maintains an episomal state, this vector still harbors an inherent risk of insertional mutagenesis. In patients with hepatocellular carcinomas integration of AAV2 into known cancer genes was observed [145] . Moreover, AAV-based immunotherapy faces various issues regarding immunogenicity [146] [147] [148] . A substantial percentage of the population has already been in contact with the used virus and consequently shows pre-existing immunity limiting the efficacy of treatment [149, 150] . The induction of anti-viral responses during immunotherapy may have similar consequences if a single virus serotype is used in repeated treatments [148] . Pre-existing or induced immunity could lead to clearance of the viral vector and/or AAVtransduced cells." ] },{ "paper_id": "de836dc0077e520bc97ba60c40fab7a6af4d8224", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Here we develop an experimental setup that attaches GB1, the soluble and small (56 amino acids) immunoglobulin-binding domain of streptococcal protein G to the C-terminus of the truncated polypeptides, to mimic a growing chain appended to a structured scaffold [24] -Sebastian Hiller, personal communication.", "CD experiments were carried out using a Chirascan TM , CD Spectrometer (Applied Photophysics) with a 0.1-cm path length quartz cuvette. CD spectra were recorded using 30 \u03bcM protein in Buffer C. Far-UV spectra were recorded from 190 to 260 nm, averaged over three scans at a speed of 0.5 nm/min, and collected in steps of 0.5 nm. The buffer baselines were automatically subtracted from the respective sample spectra. The raw data were processed using the software ProView, provided by the manufacturer. CD data was reported as mean residue molar ellipicity (deg\u00d7cm 2 \u00d7dmol -1 ).", "https://doi.org/10.1371/journal.pone.0182132.g008", "Protein folding is linked to one of the principles of life: most of the functions in a cell are carried out by proteins that have to fold properly. Incorrectly, folded proteins have to be directed to proteasomal degradation; otherwise, they can lead to misfolded protein diseases, also known as proteopathias, which can culminate in prion disease, Alzheimer's disease, Parkinson's disease, amyloidosis, or cancer." ] },{ "paper_id": "de876ac85313b4495ef6f7292ad5cc77cbd1880e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A129 mice used in this study were bred at the Department of Laboratory Animal Science of Shanghai Public Clinical Center under specific-pathogen-free conditions.", "Author Contributions: L.L. and P.Z. conceived and designed the experiments; X.W. performed the experiments and analyzed the data; S.X. assisted X.W. to analyze some data; X.W. wrote the original draft; L.L. and P.Z. reviewed and edited the paper." ] },{ "paper_id": "de8f4493515bdf7ed934509024d19a66dc57016f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The emergence of a novel avian-origin influenza virus subtype from patients with severe and fatal respiratory disease has received global attention since the first reported case of human infection with avian influenza A (H7N9) virus (A (H7N9)) on March 31, 2013. As of 8 April 2014, China has experienced two epidemic waves, and 402 A (H7N9) laboratory-confirmed cases and 146 deaths have been reported [1] .", "The sponsors of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication." ] },{ "paper_id": "de925d6c5bc669b0ada19aedaf299dfaed7445ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Migration has become one of the most important determinants of global health and social development (Carballo, Divino, & Zeric, 1998; Quinn, 1994) . People are moving in greater numbers and over larger distances than ever before, and migration has important implications for those who migrate, those who are left behind, and those communities that host migrants.", "Migrants may act as \"bridging\" populations as they are usually more at risk of infection both because of their working conditions and also because they are living in areas with higher background prevalence, increasing the chances that they are exposed to an infected individual (Coffee, Lurie, & Garnett, 2007; Lurie et al., 2003) . Thus migrants return with a higher prevalence of disease, thereby unwittingly exposing their partners, families and communities to an increasing risk of infection.", "These changes have resulted in an increase in labour and other migration as well as more frequent visits home by migrants. The impact of this movement if obvious in terms of TBmore frequent returns home render rural families more vulnerable since people with a higher likelihood of infection are spending more time in these rural communities and therefore exposing more people to potential infection. Little is known, however, about the impact of increased frequency of returning home on HIV transmission, and increased frequency of return in this example could potentially be protective: if migrants return home more frequently, they are perhaps less likely to take additional sexual partners while away; conversely, the increased frequency of return could result in more frequent exposure of uninfected partners." ] },{ "paper_id": "de95f39159534068d4a1aef3e5d6a884d1c39656", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Six to eight week old female BALB/c mice (Charles River, UK) were used in the studies. All experiments were carried out in compliance with the UK legislation and subject to local ethical review. Humane endpoints were strictly adhered to.", "Analysis was performed using FACS Diva. Frequencies are presented as a percentage of CD107a positive cells from total CD8+ cells with the irrelevant control frequencies subtracted.", "Vero cells were grown to confluence in 12 well plates. Samples were diluted in EMEM medium and added to the confluent monolayers followed by a one hour incubation period at 37 \u00b0C. The inoculum was then removed and 1 ml of overlay (4 % Carboxymethyl cellulose) solution was added and incubated for another 2 to 3 days at 37 \u00b0C. One hour prior to reading the plates, 1 mL of 2 % neutral red solution was added to enhance the visibility of the plaques." ] },{ "paper_id": "de9f765a9c35d3ea9c4423235277d69e6bab1823", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lectin purification. All the lectins used in this study have been well characterized by SDS-PAGE ( Fig. S1 and S2 \u2020), mass spectrometry (MS) and primary structure determination as described in the literature, and showed similar levels of purity as those reported.", "Finally, the activity of nine lectins against another set of 12 different viruses was determined, including Reovirus-1, Sindbis virus, Coxsackie B4 virus, Punta Toro virus, feline corona virus (FIPV), feline herpes virus, vesicular stomatitis virus, respiratory syncytial virus, herpes simplex virus 1 (KOS), herpes simplex virus 2 (G), herpes simplex virus 1 (TK-KOS ACV), vaccinia virus (Table 3 ). In these assays, the lectins did not show any promising activity towards most viruses such as reovirus-1, Sindbis virus, Coxsackie B4 virus, parainfluenza-3 virus, vaccinia virus and Punta Toro virus.", "The authors declare no competing financial interests." ] },{ "paper_id": "deaac80fa1b6ee6b493932b297496c8751c9ef1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mouse lethal dose 50 (MLD 50 ) was determined in 4week-old BALB/c mice (group assignment see table S3) inoculated intranasally (i.n.).", "July 2017 6 , in almost all cases as a result of zoonotic transmissions.", "In conclusion, as both H5N8 clades are derived from different ancestors 12 , this would suggest that duck pathogenicity evolved independently, presumably in Asia." ] },{ "paper_id": "dec1d801c2d5a971207df424ede4b1d65267b212", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "While this manuscript was under review, related studies were published by Garc\u00eda and colleagues [49] .", "Further details are given in Appendix Supplementary Materials and Methods.", "Leaf protein extracts were separated on 12% NuPAGE bis-tris gels, blotted to nitrocellulose membrane, probed with anti-V5 or anti-CP antibodies followed by IRdye680-or IRdye800-conjugated secondary antibodies and visualized with an Odyssey infrared scanner." ] },{ "paper_id": "dec25863e871c025ecfd92611e727196ae88cb5b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Text S2 Same as Text S1, but in Mathematica format. (ZIP)", "Modifications are needed to set a specific cutoff value or to capture host heterogeneity in transmission or incomplete sampling.", "When a pathogen is rare" ] },{ "paper_id": "deda9e69d8455166370e8bd96c2bdb630c4b97b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Molecules 2015, 20 2476 characterized in a quantitative manner using molecular dynamics simulation in conjunction with nuclear magnetic resonance spectroscopy. These complementary views provide new insights into glycoprotein recognition in quality control coupled with N-glycan processing.", "N-linked glycans as biological signal molecules are characterized by their intricate structures in comparison with other biosignal modifiers such as phosphate and sulfate. N-glycans have branched structures with extremely high-degrees of freedom in internal motions. This structural feature enables the glycans to embed and express multiple messages deciphered by various lectins, which are well exemplified by high-mannose-type oligosaccharides, as fate determinants of glycoproteins in the early secretory pathway." ] },{ "paper_id": "dedf310e36616461c82de98d9b0ceae75c30e5cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To test the methodology presented in our paper, we performed various sequence clusterings using different datasets previously tested in the literature (Hoang et al., 2015) . These include five genome datasets, i.e. mammal mitochondrion, influenza A virus, human rhinovirus, coronavirus and bacteria. Clustering results are shown below.", "Coronavirus complete genome dataset (D) resulted in accurate K5 clustering with the sole exception of SARS strain ZJ01. Most viruses clustered according to the species they affect. Murine hepatitis virus and Bovine coronavirus, two groups typically grouped together, clustered separately in C2 and C3 respectively, and C1 clustered most Human coronavirus." ] },{ "paper_id": "dedff395d93d8023667fc500d7c7c8451d581451", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, none of drugs scientifically demonstrated to exhibit a therapeutic effect on FIP are practically used. To solve these problems, it is desirable to identify a potent antiviral agent for FCoV infection among drugs generally used for cats.", "*Correspondence: hohdatsu@vmas.kitasato-u.ac.jp School of Veterinary Medicine, Kitasato University, Towada, Aomori, Japan percent cytotoxicity was calculated using the following formula: Cytotoxicity (%) = 100 \u2212 [(OD of ICZ (or solvent)-treated cells/OD of ICZ (or solvent)-untreated cells)] \u00d7 100. The final pH of all the diluents of ICZ and solvent was 7.5-7.6. The 50% cytotoxic concentration (CC 50 ) and 10% cytotoxic concentration (CC 10 ) values of ICZ were 208.0 \u00b1 22.9 (mean \u00b1 SE) \u03bcM and 1.1 \u00b1 0.4 (mean \u00b1 SE) \u03bcM, respectively ( Figure 1 ).", "We previously reported that type I FCoV is closely associated with cholesterol throughout the viral life cycle [7] . We also demonstrated that U18666A, the cholesterol transport inhibitor, strongly inhibits type I FCoV infection [8] . Based on these findings, U18666A may be applied as a therapeutic drug for FIP. However, to our knowledge, U18666A is not approved for veterinary practical use. To use U18666A to treat FIP, pharmacokinetic, pharmacodynamic, and safety studies must be performed for cats. As with U18666A, several candidate antiviral drugs targeting type I FCoV have been identified [9, 10] ." ] },{ "paper_id": "deeacb8558e3403c69cd8db9f4e8e5214fd85c46", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ACE, angiotensin converting enzyme; ADAM; a disintegrin and metalloprotease; EST, expressed sequence tag; RT-PCR, reverse transcription-PCR." ] },{ "paper_id": "deedf1e06ab3cae049c5326cab4e4a2771f54233", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "def1cf77e1ef84f4373a342e23145be05ec5e226", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "None declared. Amino acid changes in SARS-CoV's proteins are reflected as arrows on top of the protein bars (blue bars). Significant multiplenucleotide deletions (pink bar) and insertions (light-blue bar) were also observed (denoted as arrows under the genome) and appear to cluster around position 27000nt to 28000nt. ", "Sin849M", "Our assumption therefore is that this is a region of relative instability that is dispensable for viral replication.", "A number of single nucleotide variations (SNVs) were further confirmed using a sensitive Mass Spectrometry based genotyping assay that was developed within our institute [6] . The RNA of the virus was first isolated using QiAmp viral RNA mini kit and then reverse-transcribed into cDNA (using the RNA as template, SuperScript kit from Invitrogen, and sequence specific primers), which were further purified. Primer extension assays were carried out for the SNVs of interest. The extension products were then detected in the MassARRAY (from Sequenom) to determine the genotypes." ] },{ "paper_id": "def339c1e20c36c30ae665e0a4573ed30be45df7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Drugs. NFV and indinavir (IDV) were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH. NFV was solubilized in dimethyl sulfoxide (DMSO). IDV and acyclovir (Sigma-Aldrich) were solubilized in water.", "The primary antibodies used were as follows: mouse monoclonal anti-HSV gB (Virusys), mouse monoclonal anti-HSV1 gC clone 3G9 (Abcam), rabbit polyclonal anti-LC3B (Cell Signaling Technology), mouse monoclonal anti--actin, anti-FLAG M2 monoclonal, and anti-HA monoclonal antibody, clone HA-7 (Sigma-Aldrich). For Western blotting, the secondary antibodies used were peroxidaseconjugated AffiniPure F(ab )2 fragment of goat anti-mouse IgG(H + L) or peroxidase-conjugated AffiniPure F(ab )2 fragment of goat anti-rabbit IgG(H + L) (Jackson ImmunoResearch). Secondary antibodies for immunofluorescence were AlexaFluor 594 F(ab )2 fragment of goat anti-mouse IgG(H + L) or AlexaFluor 488 F(ab )2 fragment of goat anti-rabbit IgG(H + L) (Life Technologies).", "Human fibroblasts (HF) were cultivated in Dulbecco's modified Eagle's medium (DMEM; Gibco) containing 10% fetal bovine serum (FBS) and 100 units per mL penicillin G and 100 g per mL streptomycin (Pen-Strep) and maintained at 37 \u2218 C in a humidified 5% CO 2 atmosphere, as previously described [9] . HEK293-T cells were maintained in DMEM supplemented with 10% FBS and Pen-Strep. HSV-1 (strain F) was a gift from Keith Jerome (Fred Hutchinson Cancer Research Center)." ] },{ "paper_id": "df0310a74d62210e31be9fbe879085499825b14d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "df1017e24101a51f6b5ca30ae2cb8376d8756a61", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results were analyzed by a mixed model with fixed effects (time, diet, time*diet (ELISA and HI assay data); diet, vaccination, diet*vaccination (lesion score data); time, diet, vaccination, time*diet, time*vaccination, diet*vaccination, time*diet*vaccination (qRT-PCR, blood count, flow cytometry data)) and one random effect (animal). Post-hoc tests (LSD) were applied in case of significant effects. Calculations were performed with SPSSH Version 21 (IBM, Armonk, NY, USA) and GraphPad Prism 5 (GraphPad Software Inc., La Jolla, CA, USA).", "Swine influenza virus (SIV) is a major cause of acute respiratory infections of pig populations worldwide. The causative agents are type A influenza viruses, mainly of the H1N1, H3N2, or H1N2 subtypes. The main route of transmission is through direct contact between infected and uninfected animals, close contacts being particularly common during animal transport. Intensive farming may also increase the risk of transmission as pigs are raised in production units with high animal densities [1, 2] . SIV infections result in fever, sneezing, coughing, difficulty in breathing, decreased appetite resulting in weight loss and poor growth [1] . SIV can cause significant production losses, especially when complicated by secondary infections.", "(TIF) " ] },{ "paper_id": "df2491bf73b3224ca6018e8f7cb2242e633e636c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After retirement, field epidemiologists also act as educators in FETP, sharing information and their experiences with a sense of duty." ] },{ "paper_id": "df3fd6661b2d0bd3a51c54b4cdba7be250e52746", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A vaccine for cryptosporidiosis is not yet available, and immune protection of neonates is difficult to achieve because of their early-age immune status. However, various Cryptosporidium spp. proteins, particularly those considered to be virulence factors, have been proposed as possible vaccine candidates [13, 14] ." ] },{ "paper_id": "df4824b457c47934bafd828367bb0377132a903c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dataset S1 Phenotypes of Pre-CC animals. ", "MDCK cells were seeded into 96 well plates at a density of 1.5610 ' 5 cells/well in DMEM (10% FBS, 1% Pen-strep) and incubated at 37 degrees overnight. Cells were washed 2 times with PBS, before addition of 100 mL of DMEM to each well. Media was removed from all wells in the 1 st column of the plate, and 146 uL of lung homogenate in DMEM was added to these wells (each biological sample was added to 4 wells). Serial dilutions of 46 mL (0.5 log dilutions) were carried out across the plate. Plates were incubated at 37 degrees C for 1 hour, inoculum was removed and 150 mL of serum free DMEM with 1 mg/mL of trypsin was added to each well. Plates were then incubated at 37oC for 3 days. Media was then removed, and wells were stained with a 1% Crystal Violet solution. The stain was washed off with water. Titer is determined as follows:", "The right lung was removed and submerged in 10% buffered formalin (Fischer) without inflation for 1 week before being submitted to the UNC Linberger Comprehensive Cancer Center histopathology core for processing. Two 5 micron thick Hematoxylin and Eosin stained lung sections (step-separated by 100 microns) were blind-scored by microscopic evaluation performed by two independent scorers for a variety of metrics relating to the extent and severity of immune cell infiltration and pathological damage on a 0-3 (none, mild, moderate, severe) scale.", "Mouse studies were performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All mouse studies were performed at the University of North Carolina (Animal Welfare Assurance # A3410-01) using protocols approved by the UNC Institutional Animal Care and Use Committee (IACUC). All studies were performed in a manner designed to minimize pain and suffering in infected animals, and any animals that exhibited severe disease signs was euthanized immediately in accordance with IACUC approved endpoints. ", "Where Xp is the last dilution where all of the replicates of a given sample are positive, D is the serial dilution log and Sp is the sum of the proportion of replicates at all dilutions where positives are seen (starting with the Xp dilution)." ] },{ "paper_id": "df51bfb59565119816648b8f02f5a4f25ee4a76c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Most of the conducted simulation exercises focused on early containment (the early detection and control of outbreaks), but not on pandemic preparedness in later phases. There has been much less investment into preparing health systems for pandemic mitigation [12] . Nevertheless, the mitigation phase includes the peak period where the highest case number of infections is reached, and thus contains the peak demand for resources.", "In Indonesia, the first full-scale simulation exercise (of its kind in the world) was carried out, in which multiple ministries and agencies across central, provincial and district levels of the government participated. The exercise in Indonesia covered key areas for outbreak control, like surveillance (e.g. for early detection of human-tohuman transmission), pharmaceutical (e.g. antiviral drugs and vaccines) and non-pharmaceutical interventions (e.g. social distancing measures), medical response (case management and isolation of cases) and risk communication (to the population and media) [5] ." ] },{ "paper_id": "df5401bebedec1ea63a7afebb3b4166f775fbd82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Individual animal medical observations were recorded daily throughout the study. Observations included appetite, bowel movements, body weight, blood glucose (Accu-Chek Simplicity BG monitor and Chemstrips; maximum value of 600 mg/dL: Roche Diagnostics), urine glucose, and insulin therapy. ", "A total of six male devocalized Beagle dogs (Ridgelan Farms, Inc., Mount Horeb, WI) were received at approximately 20 weeks of age. The dogs were individually housed in stainless steel cages, 32 W \u00d7 42 L \u00d7 32 H, with rubber-coated mesh flooring and a stainless steel platform, 32 \u00d7 40 . Science Diet Growth (Hill's, 6730) was provided twice daily and clean municipal water provided ad libitum. Viokase (Henry Schein, 9758341) powder was added to food at a dose of 1 tsp/meal following pancreatectomy. Room temperature was maintained at 18-28 \u2218 C with relative humidity of 30-70%. A 12-hour light cycle was maintained throughout the study with lights on at 0700 hours. All study protocol procedures were approved by The Rogosin Institute Animal Care and Use Committee (IACUC). The Rogosin Institute-Xenia Division animal facility holds Full Accreditation status awarded by the Association for Assessment and Accreditation of Laboratory Animal Care, International (AAALAC, Int.).", "Standard radioimmunoassays from Linco Research, Inc. were used for the detection of porcine insulin (PI-12 K, sensitivity of 2 U/mL) and porcine C-peptide (PCP-22 K, sensitivity of 0.1 ng/mL). Assays were run according to the manufacturer's instructions with samples in duplicate and reference, standards, and controls in triplicate.", "for those patients already receiving immunosuppressive therapy for a kidney allograft [1] . Alternatively, the insulinproducing islets can be isolated from the majority of the pancreas and transplanted alone as free islets [2]. As noted above, a necessary component of the transplantation of an allogeneic pancreas or the islets alone is the need for lifelong immunosuppressive therapy. Because complications from such immunosuppressive therapy can include increased susceptibility to infections, malignancy, neurotoxicity, and nephrotoxicity, allotransplantation must be carefully considered and is often not suitable for young patients [3] . Further, the availability of human donor pancreas is extremely limited with only about 2,000 pancreas donors per year [4]. Worse," ] },{ "paper_id": "df605c7743673dade86350172a3c6513bc437c90", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In summary, emerging or re-emerging respiratory EVs have been highlighted in recent years and their circulation should be closely monitored, particularly EV-D68 and EV from species C exhibiting potential neurotropic features.", "Supplementary Materials: The following are available online at http://www.mdpi.com/1999-4915/8/1/16/s1, Table S1 : Genbank IDs of selected representatives of RV-A to -C , EV-A to -D and Simian Sapelovirus species that were included in the phylogenetic analysis in Figure 2 , Table S2 : References citing unusual symptoms or detection sites of respiratory EVs as listed in Figure 2 . ", "Adapted from [3] .", "The first line of defense against RV infection is the airway epithelium, which serves as a relatively resistant barrier against infection when undamaged and composed of well differentiated cells [69] . Early innate immune detection of RVs occurs very rapidly after infection of the epithelium and, most importantly, triggers the production and secretion of type 1 interferon (IFN), which will establish an antiviral state in the infected and surrounding cells." ] },{ "paper_id": "df61f934c991b4b4b08e1ec28804812ec0629ea1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "df63d7e1d02197e9dc6686976729bb00682f2ff8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "df6b70a2f62c9635377ece840d438d951d2558e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In North America, high risk cattle (e.g. non-vaccinated, low weight, unknown history, presence of BRD in cohort) frequently receive metaphylactic antimicrobials upon arrival to the feedlot to mitigate BRD and reduce colonization by bacterial pathogens [11] . It has previously been reported that 39.2% of high risk cattle receive an injectable antimicrobial following feedlot placement [7] . However, there are serious concerns regarding agricultural antimicrobial use and resistance in animal and human bacterial pathogens [12] . Consequently, new strategies through management or antimicrobial alternatives are required to reduce antimicrobial use in livestock, including the manipulation and supplementation of the various livestock microbiota.", "Nasopharyngeal swabs were suspended in 1.2 mL of brain heart infusion (BHI) broth with 20% glycerol and vortexed. For isolation of M. haemolytica and P. multocida, a 100 \u03bcl aliquot of the swab suspension was plated onto tryptic soy agar (TSA) plates containing 5% sheep blood, supplemented with 15 \u03bcg bacitracin ml \u22121 (Dalynn Biologicals, Inc., Calgary, AB, Canada), and incubated overnight at 37\u00b0C. For culturing of H. somni, a 100 \u03bcl aliquot of the swab suspension was plated onto TSA plates containing 5% sheep blood without the bacitracin supplement and incubated for 48 h in a 10% CO 2enriched environment at 37\u00b0C. Colonies displaying morphology of M. haemolytica (white-grey, round, medium-sized, non-mucoid, exhibiting \u03b2-haemolysis), P. multocida (translucent, greyish in colour, and mucoid in consistency) and H. somni (yellowish hue, haemolytic) were confirmed through polymerase chain reaction (PCR) analysis using HotStarTaq Plus Master Mix (Qiagen Canada Inc., Toronto, ON) according to manufacturer's specifications with primers and annealing conditions described in Table S1 (Additional file 2). Colonies were lysed in Tris-ethylenediaminetetraacetic acid (EDTA) buffer (10 mM Tris-HCl, pH 7.4, 1 mM EDTA, pH 8.0) at 95\u00b0C for 5 min and used as deoxyribonucleic acid (DNA) template (2 \u03bcl) in PCR. The swabs were placed in the remaining swab suspension and stored at \u221280\u00b0C until DNA extraction." ] },{ "paper_id": "df6c9f047f47069bc34b0b26c02aca2ab453f724", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For Western blot analysis, 20-50 \u03bcg of proteins from whole cell extracts were resolved on 7.5-12.5% ", "Briefly, 2 \u03bcg of anti-Flag M2 (F1804, Sigma-Aldrich) or anti-IKK\u03b5 (IMG-5571, Imgenex) antibodies were diluted in lysis buffer and incubated with Dynabeads \u00ae Protein G (Life Technologies) for 10 minutes at room temperature. After PBS washing, 350 \u03bcg of whole cell extract proteins in 200 \u03bcl lysis buffer were immunoprecipitated using the Dynabeads-antibody complexes overnight at 4\u00b0C under gentle agitation. After PBS washing, protein complexes were eluted using loading buffer (50 mM Tris pH6.8, 10% SDS, 10% glycerol, \u03b2-mercapto-ethanol and bromophenol blue) 5-10 minutes at 95\u00b0C. Protein complexes were loaded onto 10% polyacrylamide gels and transferred into PVDF membrane.", "pORF9-C/EBP-\u03b2 was obtained from InvivoGen (San Diego, CA). The pORF9-C/EBP-\u03b2-Flag 2 vector was derived from pORF9-C/EBP-\u03b2 by insertion of a labdesigned double-stranded oligonucleotide containing two Flag sequences (Flag 2 , Supplementary Table S1) and flanked by Sph I restriction sites for cloning. This doublestranded oligonucleotide was then cloned into the 3\u02b9 region of the C/EBP-\u03b2 gene of the pORF9-C/EBP-\u03b2 plasmid. Plasmids were verified by sequencing." ] },{ "paper_id": "df753ddb66629cfd0795d0ffa319caa0440de284", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "I H N E R G E M L D K G K S Y S G D E K I N T S D N A K S C S G D E K V I T S D N G K S Y D Y V K N E S E E Q E E K E N M L N N K K R S A S G S A K F V A A W T L K A A A S G S W E E W N A K W D E W R N D Q N D W R E D W Q A W R D D W A Y W T L T W R Y G E L Y S R L A R I E R R V E E L R R L L Q L I R H E N R M V L QFVRALSMQARRLESKLRNVEEELHSLRKNYNII sNEEIEEITKEFEKKQEQVDEMILQIKNKELE", "Protein expression was carried out in Luria-Bertani (LB) Broth (FisherBioReagents, Pittsburgh, PA). Briefly, starter cultures were grown for 16 h at 36 \u00b0C and inoculated at 1/100 into 1L of LB and grown at 37 \u00b0C. At an OD 600 of 0.8 cultures were induced with 1 mM Isopropyl-\u03b2-d-thiogalactopyranoside (IPTG) (FisherBioReagents, Pittsburgh, PA). Cultures were grown for 4 h, pelleted at 4000\u00d7 g and stored at \u221280 \u00baC until use.", "Cell pellets were thawed on ice and resuspended in Imidazole free buffer (8 M urea, 100 mM NaH 2 PO 4 , 20 mM Tris base, 5 mM tris(2-carboxyethyl)phosphine, pH 8.0), lysed by sonication, and centrifuged at 30,500\u00d7 g for 25 min to clarify the lysate. Purification was carried out on an \u00c4KTApurifier 100 (GE Healthcare, Piscataway, NJ) using a 5 mL HisTrap HP column (GE Healthcare, Piscataway, NJ). Briefly columns were equilibrated with Binding Buffer (8 M urea, 100 mM NaH 2 PO 4 , 20 mM Imidazole, 20 mM Tris base, 5 mM tris(2-carboxyethyl)phosphine, pH 8.0), lysate injected, and then washed with five column volumes of binding buffer. Columns were then washed with 5 column volumes of high phosphate buffer (8 M Urea, 500 mM NaH 2 PO 4 , 20 mM Tris base, 5 mM tris(2-carboxyethyl) phosphine, pH 8.0), binding buffer, isopropanol wash (60% isopropanol, 20 mM Tris base, pH 8.0) to remove LPS [25] , and finally Imidazole free buffer. Protein was eluted using a 1M Imidazole gradient. The resulting recovered protein was verified by a SDS-PAGE, and dialyzed overnight into pre-refolding buffer (8 M urea, 50 mM NaCl, 20 mM Tris, 5% Glycerol, tris(2-carboxyethyl)phosphine, pH 8.0)." ] },{ "paper_id": "df783d511b145a10e7f609a87392eb50799d2b2b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For indirect immunofluorescence staining, cells grown on coverslips were washed with PBS and fixed in cold acetone for 10 min at 220uC (anti-NOA36, anti-UBF and anti-Flag antibodies) or 4% paraformaldehyde before permeabilization with 0.1% Triton X-100 (eGFP transfected cells). Cells were then washed with PBS and incubated with primary antibodies diluted in PBS (1:100 of anti-NOA36; 1:100 of anti-UBF or 1:500 of anti-Flag M2 (SIGMA)) at 37uC for 45 min. Cells were then washed with PBS for 30 min at room temperature and incubated with Alexa fluor 488, 555 (Molecular Probes), or Cy3 (Jackson ImmunoResearch)-labelled secondary antibodies at 37uC for 45 min. Finally, cells were washed twice in PBS and mounted in PBS-glycerol containing DAPI at 0.1 mg/ml, for DNA staining. A Zeiss Axiophot microscope equipped with a 636NA 1.3 oilimmersion objective was routinely used. Images were taken using a SPOT Camera (Diagnostic Instruments Inc.) and processed using Adobe Photoshop software.", "Ref.", "Comparisons between groups were performed with Student's Ttest for paired samples (two-tailed) (n = 12) and significant differences (p,0.05) are denoted by an asterisk." ] },{ "paper_id": "df794557c0c0da0a84d28c5df7f3748560fde11f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "df7ce7b791dbb8848b6222b823622cc5866f681e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A laboratory-confirmed case was defined as an individual with influenza-like illness or severe respiratory illness who tested positive for pandemic H1N1 influenza A virus by real-time reverse-transcriptase PCR (RT-PCR) or viral culture. The first case of H1N1 infection in Manitoba was identified (tested positive) on May 2, 2009, and data were reported by the earliest date of symptom onset, initial care, specimen collection, hospital admission, and/ or intensive care unit admission. For the present study, data use was approved by the Human Research Ethics Board of the University of Manitoba (H2009:339) and Health Information Privacy Committee of Manitoba (2009/2010-40)." ] },{ "paper_id": "df82c611eb38c4c9dbef1a86da01ca432e61c8f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a ALD: Absolute lethal dose (the lowest dose causing 100% mortality). b MDT: Mean death time. * Significant difference of standard deviation (\u00b1SD) from K2 (p < 0.05).", "Infectious bronchitis virus (IBV) is a pathogenic gamma coronavirus that causes respiratory symptoms, egg drops, nephritis and proventriculitis in domestic fowls [1] . Due to the persistent infection IBVs are difficult to eradicate and easy to mutate into new recombinant viruses in infected flocks [2, 3] . The single-stranded, positive-sense RNA genome is approximately 27 kb and encodes RNA polymerase/transcriptase (1ab), spike (S), envelope (E), membrane (M), nonstructural (3a, 3b, 5a, 5b), and nucleocapsid (N) proteins [1] . Approximately 15 nonstructural proteins (nsp) are generated from the large 1a and 1ab proteins by viral proteases, and these nsp play roles in virus replication and pathogenicity [4, 5] . The spike protein is a protective antigen that is essential for virus infection in host cells [1] .", "The significance of growth kinetics and embryo pathogenicity were evaluated by two way analysis-of-variance (ANOVA) and a Man-Whitney test, respectively. The difference in virus frequency in tissues and lesions in the premature reproductive tract pathogenicity model was assessed using chi-squared distribution (95% confidence intervals).", "A primer set for real-time RT-PCR was designed based on the conserved region of the nsp 3 genes of 14 reference strains in the GenBank (Table 1 ). The reference strains used for the primer design are as follows: LX, Peafowl/GD/KQ6, KM91, QIA-03342, QIA-KR/D79/05, QIA-Q43, SNU-9106, SNU-10043, M41, Turkey coronavirus, SNU-8067, ITA/90254/2005, and ArkDPI11. Their accession numbers are available in Figure 3 . Primers for genome amplification and sequencing were described previously and additional new primers were summarized in Table 1 [6] ." ] },{ "paper_id": "df9b7b29b4b5a14245aea9cc707d52b732052a47", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reverse transcription (RT) and polymerase chain reaction (PCR) were performed separately. The synthesis of cDNA was carried out in a 20 \u03bcl reaction mixture using Rever-tAid Premium reverse transcriptase (ThermoScienfitic, USA) containing 5 \u03bcl of isolated RNA. The cDNA synthesis was performed according manufacturer's instructions.", "The size of PCR products was analyzed by 2% agarose gel electrophoresis and visualized by Gel Doc EZ imager (Bio-Rad Laboratories, USA) after staining with GelRed\u2122 (Biotum, USA).", "Statistical analyses of data were performed by chi-square (\u03c7 2 ) test with confidence limits of 95%, P < 0.05 or 99%, P < 0.01 using GraphPad Prism 5 for Windows (Graph-Pad Software, USA). " ] },{ "paper_id": "dfa781bcc4c907490ddfceebd374669983a98082", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical comparisons of nonparametric data were performed using the Mann-Whitney test or Wilcoxon signed-rank test. Comparisons of categorical data were made using Pearson Chi-squared test. All tests were 2-sided. A value of P < .05 was considered statistically significant. Data were analyzed using IBM SPSS version 20.0 software for Windows (SPSS, Chicago, IL).", "Inpatients (n = 49) Outpatients (n = 57) P " ] },{ "paper_id": "dfbb7bb506552b06794dbcefe56911e2a91a908b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results of this study revealed a good KAP score (56.0%) among the study participants towards RTIs. The median knowledge score was 18.0 (6.0) which also indicates a good level of knowledge.", "The Muslim pilgrimage to Mecca in Saudi Arabia is among the five pillars of the religion of Islam and is obligatory to each financially and able-bodied Muslim to perform it at least once in a lifetime. Umrah, also known as Lesser Hajj, can be performed at any time of the year and is not obligatory. This pilgrimage attracts millions of worshippers for Umrah and about two to three million people from various countries across the globe converge for the yearly Hajj rituals [1] . The official Hajj quota for Malaysian pilgrims stands at 30,200 based on the report from the Malaysian Hajj Fund [2] .", "Data entry and statistical analysis were performed using the Statistical Package for Social Sciences (SPSS) version 24.0 (SPSS, Inc., Chicago, IL, USA) and were presented by using mean and standard deviation. Categorical variables were presented by using frequency and percentage. Descriptive statistics were used to determine the socio-demographic factors and KAP scores. The KAP assessment was carried out by assigning scores to the variables. To assess the role of socio-demographic characteristics on KAP, differences in socio-demographic status were compared with the KAP scores using ANOVA or independent sample t-test as appropriate. Pearson correlation coefficient was used to describe the strength and direction of the relationship among knowledge, attitudes, and practices (KAP). Correlations were interpreted using the following criteria: 0-0.25 = weak correlation, 0.25-0.5 = fair correlation, 0.5-0.75 = good correlation and greater than 0.75 = excellent correlation [23] ." ] },{ "paper_id": "dfbdc96a5b50298935fd2f810339bdd055cb25fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The move of healthcare workers from lower to higher income countries (within Southern Africa and the Global North) has resulted in increased international migration, which creates further inequities (Gilson and Erasmus, 2005) .", "SADC health governance relates to basic principles of SADC's origins. SADC objectives are intended to 'promote sustainable and equitable economic growth and socioeconomic development' (SADC, 2014) through regional integration, effective governance and productive systems among the 15 member states.", "Findings from a study commissioned by the UN, African Union (AU) and the African Development Bank find that the primary use of the SDGs should be to inform their country's budgets and allocate more resources to SDGs that are not making progress. A secondary use would be to balance economic, social and environmental pillars in policymaking. The study emphasises the need for SADC to draw attention to the SDGs to define national policy priorities, review the influence of national policies and address pressures that lead to unsustainable development and guide development cooperation (Gandure and Kumwenda, 2013) ." ] },{ "paper_id": "dfc76bec0889529fc8cfd5075db5b638ee8cefbc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For lncRNAs microarray analysis, Agilent Array platform was employed." ] },{ "paper_id": "dfdeaf42e832860f70d1583ef54f9b319b5dd2a9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The intestinal porcine epithelial cell line J2 (IPEC-J2) (kindly provided by Prof. Jianxiong Xv) was maintained in DMEM/F12 medium supplemented with 10% FBS and incubated in an atmosphere of 5% CO 2 at 37 \u2022 C.", "Materials and Methods", "2.", "All the data were expressed as the means \u00b1 standard error of the mean (SEM). Data were compared for significance using a student's t test or one-way ANOVA with the SAS 9.0 software package (SAS institute Inc., Campus Drive Cary, NC, USA). A p-value <0.05 was considered statistically significant.", "PEDV is a member of the Alpha-coronavirus genus, within the family Coronaviridae in the order Nidovirales [3,10]. PEDV possesses an~28 kb single-stranded, positive-sense, RNA genome, which encodes seven open reading frames (ORF 1a/1b, and ORF 2-6) [11] . Among them, the first gene ORFs 1a/1b encode large replicase polyproteins, which are processed to generate 16 nonstructural proteins (nsp1-nsp16) [12] . ORF 2, -3, -4, -5, and -6 encode structural/accessory proteins, including spike (S) protein, nonstructural accessory protein, envelope (E) protein, membrane (M) protein, and nucleocapsid (N) protein, respectively [13] ." ] },{ "paper_id": "dff11250a455815390e0d3c8a6208f608aa681ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chip structure creates various advantages [2] . Users of this unique platform for nucleic acid analysis realize significant profits compared to other available conventional detection techniques.", "Although increased attention has been given recently to label-free chip detection systems causing significant progress in this area, many aspects crucial to specificity or detection limit remain unsolved. Thus, proper applications of these undoubtedly promising devices would still require a solid intellectual input.", "From another point of view, the trend in miniaturization seems to cope with the need of maintaining the statistical significance of the sample. For instance, when testing water supply it is clear that a drop of such sample would hardly have any cell of interest. Of course, possible solutions to these needs (i.e. related to analyte concentration) will appear and exciting developments for the detection systems will certainly be constructed in the future." ] },{ "paper_id": "e005630bf0183fb7a78efa065c0c545922d27009", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal procedures were approved by the Institutional Animal Care and Use Committee (IACUC).", "Using Cox proportional hazards to relate the survivorship to the continuous variable of bacterial loads, we find a significantly higher mortality of co-infected animals over the course of the experiment ( figure 4 ).", "Imaging bacterial infection models with the use of a bacterial lux operon allows for real-time monitoring and quantification of infection, without requiring administration of a substrate; an obviously useful tool for infectious disease ecology. BLI is in its infancy in infectious disease research, but where it has been used novel observations have occurred, mostly due to the increased temporal and spatial resolution available on the infections due to real-time and in vivo observations, including novel sites of pathogen replication [54, 55] . Here, we have observed high infection loads that may have been missed if the traditional techniques of observing infection every 2-7 days had been used [21, 56] ." ] },{ "paper_id": "e0111854ce52152339b685712b1a2843e3f1b839", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Several investigations, including ours, have revealed that IAV induce a strong remodeling of nuclear architecture with marked modifications of the nucleoli ultrastructure and compartments 3,17-20 . The nucleolus, known as the site of ribosome biogenesis, is also a sensor of cellular stresses and is involved in several cellular pathways, such as cell-cycle regulation or apoptosis 21-23 . Several DNA and RNA viruses, including cytoplasmic viruses are known to induce nucleolar alterations that contribute towards optimal infection 24-26 .", "Scientific RepoRts | 6:29006 | DOI: 10.1038/srep29006 Western blot analysis. The level of expression of viral or cellular proteins was assessed by western blotting." ] },{ "paper_id": "e01d6fcf286c7231445ac9db61237ac71ca26fec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses within the Picornaviridae family are small, nonenveloped viruses containing single-stranded, positive-sense RNA genomes. Picornaviruses can cause a range of infections, including intestinal, respiratory, neurological, cardiac, hepatic, mucocutaneous, and systemic diseases with various severities in humans and animals (13) . Porcine sapelovirus (PSV) appears to be most closely related to simian picornavirus type 2 (simian sapelovirus) and duck picornavirus TW90Ak (avian sapelovirus) (14, 15) . Simian, avian, and porcine picornaviruses have been recently assigned as members of a new picornavirus genus, Sapelovirus (14, 15) ." ] },{ "paper_id": "e021441c02baaade6b2b93427db4beb54b06ea92", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The comparative clinical analyses included 32 infants with a HRSV single infection (22 AON1 and 10 other genotypes) and showed no significant differences between these subgroups (Table 1 ).", "Of the 124 infants selected, 94 were studied after the exclusion of 30 cases (infants with clinical diagnoses or suspicion of infection by bacteria or other agents as well as those who received antibiotics).", "For clinical analysis, infants diagnosed with or suspected of having bacterial or fungal infections and those who received antibiotics, macrolides, or antifungals prior to or during hospitalization were excluded. Infants with codetection of respiratory viruses were also excluded from the clinical analysis.", "Nasal wash fluid was obtained after washing the nostrils with 3 ml of a saline solution and collecting the suctioned specimen in a cup within a maximum of 24 hours after admission. HRSV-positive samples were amplified by traditional PCR in two steps for DNA sequencing: cDNA was synthesized using the Super Script III kit (Applied Biosystems, Foster City, CA, USA) according to the manufacturer's instructions. The second hypervariable region of the G protein gene PCR was carried out with the primers Gr5_fwd (5 -CTGGCAATGATAATCTCAACTTC-3 ) and FV_rev (5 -GTTATGACACTGGTATACCAACC-3 ) in a 10 L mixture that contained 5 L of 10x PCR buffer, 25 mM of each dNTP, 25 pmol of each primer, and 1.5 U of Platinum Taq DNA Polymerase (Invitrogen, Carlsbad, CA, USA) for a final volume of 50 L. The amplification was performed in a GeneAmp PCR System 9700 thermocycler (Applied Biosystems, Foster City, CA, USA). A second step with Seminested PCR was carried out using the F1AB_rev (5 -CAACTCCATTGTTATTTGCC-3 ) primer corresponding to bases 3-22 of the F gene. The traditional PCR assays were performed with the following program: 95 \u2218 C for 5 minutes, followed by 35 cycles, each composed of 30 sec at 95 \u2218 C, 30 sec at 55 \u2218 C, and 45 sec at 72 \u2218 C, and finally 7 minutes of extension at 72 \u2218 C. The amplified products were analyzed by agarose gel electrophoresis and visualized under UV light after staining with ethidium bromide. The amplified products of gene G were \u2248490 bp, were purified by ExoSap-IT (Affymetrix, Inc., USA), and were submitted to a cycle sequencing reaction (Sanger) using the Bigdye terminator kit (Applied Biosystems, Foster City, CA, USA) and GR5, FV or F1AB primers in a 3100 DNA Sequencer (Applied Biosystems, Foster City, CA, USA). Both strands of each amplicon were sequenced at least twice. Sequence editing, alignments, and phylogenetic analyses were performed with MegAlign 5.03 v software (DNAStar, Inc., Madison, Wisconsin, USA). Standard published sequences from subgroups A (accession numbers from KY828387 to KY828428) and B (accession numbers from KY828374 to KY828386) were downloaded from GenBank as references of different lineages and genotypes." ] },{ "paper_id": "e023845ba693ca1f8667d37d40b02626a6c2ecd5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Despite the variety of modeling approaches and data sources, the impact of using different proxies for human commuting in epidemic models for rapidly disseminated infections is still poorly understood. Each approach or source of data clearly has its own intrinsic strengths and weaknesses, related to accuracy and availability of the dataset.", "Small-scale studies targeting specific populations (such as e.g. a city or a college town) with additional metadata accompanying the activity records may possibly shed more light in the identification of such biases.", "Our study was performed on three European countries, and we expect that our conclusions are applicable to other developed countries in the world characterized by similar cultural, social, and economic profiles." ] },{ "paper_id": "e035002c8135dab46801a3fc8a43b87240dbef8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The global spread of the severe acute respiratory syndrome (SARS) epidemic has clearly shown the importance of considering the long-range transportation networks in the understanding of emerging diseases outbreaks. The introduction of extensive transportation data sets is therefore an important step in order to develop epidemic models endowed with realism.", "This normalized measure is invariant under a rescaling of the vectors and by a constant factor. Therefore, we introduce also the similarity between the worldwide epidemic prevalence obtained in the two realizations: , where and a(t) = \u2211 j A j /\u2135, with \u2135 = \u2211 j N j being the world population. The overlap function \u0398(t) is thus defined as:" ] },{ "paper_id": "e0359b1b4c6d229299cb7b9f149bc9b943a2077f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The patients presented with high fever, headache, severe body aches, sore throat, dry cough, intense tearing, red eyes and posterior cervical lymphadenopathy over 3-5 days duration. Later they developed discrete maculopapular rash helping the diagnosis. They had a variable degree of leucopenia, lymphocytosis, thrombocytopenia and derangements in the liver functions mimicking any other acute febrile illnesses such as dengue, chikungunya, leptospirosis or Zika virus infection.", "Measles is an acute febrile illness caused by a virus that belongs to the family paramyxovirus in the genus Morbillivirus. It is characterized by fever (as high as 105 \u00b0F) malaise, cough, coryza, and conjunctivitis, followed by a maculopapular rash [1] . The rash usually appears 14 days after exposure and on the 3rd-5th day of clinical illness which spreads from head to trunk to lower extremities [2] . Measles is usually a mild or a moderately severe illness. However, measles can result in complications such as pneumonia, encephalitis and death. Post infectious encephalitis may occur in approximately one per 1000 reported measles cases. [3, 4] . In Childhood measles, approximately two to three deaths may occur for every 1000 reported measles cases [4] ." ] },{ "paper_id": "e0393328e9f59159671bff8a33e26edbdab28034", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The elevated sIgA and IgA in serum maintained for about 6 weeks." ] },{ "paper_id": "e0494e196f7f6d783c5c05ac339d19934c000c1f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We tested the differences between the detection rates of the two different methods using the \u03c7 2 test. A P < 0.05 was considered statistically significant.", "JP conceived the experiments, analyzed the results and wrote the manuscript. LX and CZ conducted the experiments and analyzed the results. ZW collected specimens. All authors reviewed the manuscript. ", "Potential biohazardous materials were handled in required levels of biosafety laboratories. All experiments (collection of samples, sample handing, operator training and protection, etc.) were carried out according to the approved biosafety standard guidelines set by The Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College." ] },{ "paper_id": "e0531f9c84005ac77b1bdb3075c486e6ac116760", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e05c7165987a9b706d1ab55ebb210bd571a59e5a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All spots on TLC were visualized by heating silica gel plates sprayed with 10% Phosphomolybdic acid hydrate in EtOH and 1% FeCl 3 in EtOH." ] },{ "paper_id": "e0668c4b793d0cad26639b070819334a94648123", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e066a2eab75d8d421fe141176355bcbabc52b4fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting information S1 Table. The Yassine." ] },{ "paper_id": "e077bb756a7a9e4df0cdcc18f2e1cd509e4a3993", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We will consider these two notable epidemiological characteristics in turn:" ] },{ "paper_id": "e08048659491371d0387ad99e9174a4c49c83872", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LigT was overexpressed in the BL21(DE3) strain using ZYM-5052 autoinduction medium [35] , supplemented with 100 \u03bcg/ml ampicillin and 0.01% Antifoam 204 (Sigma). The expression culture was incubated at +37\u02daC for 24 h. Overexpression did not lead to any obvious toxic effects. The dry cell weight was around 12 g for 1 liter of culture. Cells were harvested by centrifugation and resuspended in lysis buffer containing 50 mM Na-HEPES (pH 7.5), 500 mM NaCl, 20 mM imidazole, 0.5 mM TCEP, and 1x EDTA-free protease inhibitor (Roche). The suspension was flash-frozen in liquid nitrogen and stored at -70\u02daC until use.", "Structural sequence alignments were done with Swiss PDB Viewer [45] and Espript [46] . For structure analyses, PyMOL and UCSF Chimera [47] were used. Superpositions were done with the SSM algorithm [48] , and structural homologues were searched using Salami [49] . Modeling of the substrate complex and a complex with a 3-base RNA oligonucleotide was done in YASARA [50] . Electrostatic surfaces were calculated using PDB2PQR and ABPS [51] .", "Overall structure" ] },{ "paper_id": "e0833a1c57d22b36db54876afb2282e00148b691", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "La gestion du savoir en tant que domaine est un ensemble, qui inclut la gestion des processus de recherche dans ledit domaine. La th\u00e9orie de la gestion du savoir peut potentiellement \u00eatre utilis\u00e9e comme support \u00e0 la recherche concernant les probl\u00e8mes comme le VIH, la r\u00e9sistance aux antibiotiques et autres. Particuli\u00e8rement en termes de recherche scientifique li\u00e9e \u00e0 la science sociale. \u00c0 ce jour, malgr\u00e9 l'avanc\u00e9 de la science et des recherches, ces probl\u00e8mes persistent, et la contribution th\u00e9orique qui peut servir de compl\u00e9ment aux efforts des sciences naturelles pour \u00e9radiquer ces probl\u00e8mes est insuffisante. Cette \u00e9tude a pour but d'offrir une contribution th\u00e9orique bas\u00e9e sur la th\u00e9orie de paradigme d'innovation de Kuhn et le propos de Lakatos que la recherche scientifique peut \u00eatre fondamentalement non-innovatrice. Cela sugg\u00e8re que des aspects de la production du savoir dans le domaine des sciences sociales peuvent \u00eatre la cl\u00e9 d'une innovation biom\u00e9dicale efficace. Vu les cons\u00e9quences progressives des crises mondiales \u00e9mergeantes, et l'\u00e9chec des syst\u00e8mes de savoir des recherches scientifiques \u00e0 r\u00e9soudre ces probl\u00e8mes, cette \u00e9tude fournit une revue de la th\u00e9orie et de la litt\u00e9rature qui soutiennent un nouveau paradigme dans la recherche scientifique, bas\u00e9 sur le d\u00e9veloppement des syst\u00e8mes globaux pour maximiser et les collaborations scientifiques. Effectivement, l'approche de syst\u00e8mes globaux doit n\u00e9cessairement inclure la th\u00e9orie du d\u00e9veloppement des sciences sociales, ce qui est compl\u00e9mentaire aux processus de recherche des sciences naturelles. Mais, la technologie de l'information et la technologie des r\u00e9seaux sociaux sont d\u00e9j\u00e0 d\u00e9velopp\u00e9es au point o\u00f9 elles peuvent r\u00e9soudre des probl\u00e8mes du savoir \u00e0 une \u00e9chelle surprenante. Il est souvent accept\u00e9 que ces d\u00e9veloppements engendrent une nouvelle \u00e8re de recherche participative ou une d\u00e9mocratisation de recherche, qui offre de nouveaux espoirs pour la r\u00e9solution des probl\u00e8mes sociaux au plan mondiale. Cette \u00e9tude a pour but de contribuer de cette fa\u00e7on, et reconnait le r\u00f4le important de la th\u00e9orie sociale dans le processus de recherche scientifique.", "Motscl\u00e9s: Recherche sur le VIH/SIDA, collaboration de recherche et procedure de resolution, recherche en temps r\u00e9el, th\u00e9orie du d\u00e9veloppement", "Living in our connected world, pharmaceutical researchers can communicate in a variety of ways to leverage ideas from around the globe. These ideas do not have to come from within the walls of a single organisation. Taking this further: why limit access to just ideas? Open tools and data could feed an ecosystem. They could also breed a new class of researcher without affiliation, who has allegiance to neither company nor research organisation. They test their hypotheses with data from elsewhere, they do their experiments through a network of collaborations, they have no physical lab; while a shared cause may not be essential, confidentiality agreements and software may unite them as a loose cooperative." ] },{ "paper_id": "e08398305bb975e1eeb01ab0f93335347005297f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There are numerous different types of NC regarding material, size and shape, each having advantages and disadvantages in the field of nanomedicine. Inorganic nanomaterials have a rigid structure and a controllable synthesis allowing simple modification.", "Funding: DH and MB are funded by the Deutsche Forschungsgemeinschaft (SFB1066, project B05).", "The authors declare no conflict of interest. " ] },{ "paper_id": "e086d4275f9420065465a39f78c29bd36a5796d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where v j is one of a set of V classes and a i is one of n attributes describing an event.", "while the non-amyloidogenic probability is calculated as: ", "A direct implementation of the Naive Bayesian method results in prediction accuracies between 60.84% and 81.08%" ] },{ "paper_id": "e09ca57e55d73869520543f456019ee081d88a00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vero cells were cultured in minimal essential medium (Gibco, United States) supplemented with 5% fetal bovine serum (FBS, Gibco, United States) at 37 \u2022 C. C6/36 cells were cultured in RPMI-1640 medium (Gibco, United States) supplemented with 10% FBS at 28 \u2022 C. All cells were cultivated under a humidified atmosphere of 5% CO 2 .", "Female BALB/c mice (6-week-old) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.", "All antibodies and other staining reagents were purchased from BD Biosciences, United States. After red blood cell lysis, splenocytes were blocked with rat anti-mouse CD16/CD32 monoclonal antibody, and then stimulated at 1.5 \u00d7 10 6 /ml with 1 \u00b5g purified DENV2 particles for 6 h. The cells were ", "RW designed and performed the experiments, analyzed the data, and wrote the manuscript. XZ, JS, KF, NG, and DF helped the experimental design. XJ designed the codon-optimized sequence." ] },{ "paper_id": "e0a2b2bc691434ef31983736806d4e558b222c92", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Interestingly, M2 localizes at cell membranes and perinuclear autophagic vesicles, which was identified by fluorescence microscopy. M2 even accumulated in some autophagosomes for the blockade of their fusion with lysosomes [6] .", "The better understanding of pathogenesis caused by influenza A virus critically requires the analysis of autophagic mechanism in infected cells and the regulation of autophagy by influenza A virus. The parasitic characteristic of influenza viruses prompts them to evade the host cell defense and utilize cellular sources to accelerate their proliferation. However, molecular basis of these processes remains elusive.", "It is known that the autophagosome is an essential intermediate structure during autophagy. Thus, presence of autophagosomes in the cytoplasm indicates the induction of autophagy. Growing evidence suggests that infection by influenza A virus increases the generation of autophagosomes, which could be detected by electron microscopy, green fluorescent protein (GFP) labeled LC3, and biochemical analysis of LC3 [16] ." ] },{ "paper_id": "e0a44f822e93cacdd3a42102e77f6adfc0519c1a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral pathogen discovery is of critical importance to clinical microbiology, infectious diseases, and public health. Genomic approaches for pathogen discovery, including consensus polymerase chain reaction (PCR), microarrays, and unbiased next-generation sequencing (NGS), have the capacity to comprehensively identify novel microbes present in clinical samples. Although numerous challenges remain to be addressed, including the bioinformatics analysis and interpretation of large datasets, these technologies have been successful in rapidly identifying emerging outbreak threats, screening vaccines and other biological products for microbial contamination, and discovering novel viruses associated with both acute and chronic illnesses. Downstream studies such as genome assembly, epidemiologic screening, and a culture system or animal model of infection are necessary to establish an association of a candidate pathogen with disease.", "One advantage of using microarrays and NGS for pathogen discovery is that these same technologies can also be applied to evaluate the potential pathogenicity of newly identified novel agents. Host transcriptome analysis using gene expression microarrays [106] or RNA-Seq [107] can enable the characterization of associated host biomarkers in response to infection. Detailed NGS-based quasispecies analysis of novel pathogens that exhibit high mutation rates, such as RNA viruses [108, 109] , can also provide insights into how these agents infect and invade the host.", "Open access under CC BY license." ] },{ "paper_id": "e0af0e80af8fd724d1a23f90590617d72b452e1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Conceptualization: Audrey Dionne, Nagib Dahdah. " ] },{ "paper_id": "e0bf08186f4d0b6112d6f4b8535584739da35596", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Canine morbillivirus (canine distemper virus, CDV) causes canine distemper (CD) in a wide range of mammalian hosts, and may produce systemic, respiratory, cutaneous, bone, and/or neurological manifestations in these animals 1,2 . CDV produces immunosuppression 3 in susceptible hosts by targeting cells that express the signalling activation molecule (SLAM) 4 , which frequently results in opportunistic infectious diseases caused by agents such as Bordetella bronchiseptica 5,6 , Candida sp. 7 , Clostridium piliforme 8 , Toxoplasma gondii 9-11 , Dirofilaria immitis 11 , Mycoplasma cynos 12 , and Talaromyces marneffei 13 . Although the occurrence of CD is significantly reduced in domestic dog populations in developed countries due to the use of vaccination 14 , the disease is endemic and a", "Animal welfare issues. All methods used during this investigation were approved by and carried out in accordance with the guidelines and regulations of the Universidade Estadual de Londrina relative to the usage of animals submitted for autopsy evaluation. The owners of all animals used during this study give consent for their usage in diagnostic and scientific activities." ] },{ "paper_id": "e0cbbb6421bb2fb309021936921aaadadfe74844", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PEDV is a highly contagious virus easily spread by people, via transportation means, feed, aerosol and wild animals taking a faecal-oral route [4, 12, [15] [16] [17] . Therefore, strict biosecurity measures together with proper cleansing and adequate disinfection must be applied in order to block the entrance of PEDV into pig farms [4] .", "Serological workup unmasked a larger proportion of the PEDV spread than first assessed PEDV IgG ELISA test making use of a commercial IDVet ELISA kit resulted in 62 positive pigs (15.62%) and four positive agricultural holdings (9.09%) ( Table 1) .", "Croatia has been considered PED-free until the spring of 2016, when the suspicion on PED outbreak was first reported to the Croatian Veterinary Institute. This manuscript brings data on the very first PEDV outbreak in Croatia, together with the results of molecular characterization of the causative PEDV strain and postoutbreak serological workup.", "We attempted to grow the first Croatian PEDV strain in vitro, however the results were negative. The real-time S gene RT-PCR was positive for the inoculum (Ct = 27.25) and confirmed the first passage carryover (Ct = 35.53), but in the second passage the virus growth could not be detected (no Ct).", "Virus propagation in vitro was attempted on Vero cells (ATCC\u00ae CCL-81\u2122) in T 25 flasks using the cell culturing protocol that does not imply inoculum removal (0.2 \u03bcm filtered supernatant of 10% -intestinal content suspension), as described by US scientists [45] . Virus growth was monitored using a real-time RT-PCR suitable for the detection of PEDV S gene, as described above. The material used for RNA isolation was a cell culture supernatant obtained after a single freeze/thaw cycle." ] },{ "paper_id": "e0cc48136126e2cae2d7ac3eb10a9fc786124404", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The statistical analyses were performed by using a one-way or two-way RM ANOVA test in the GraphPad Prism 5 (CA, USA). The significance values were represented as follows: \u00c3 or # : P<0.05 (statistically significant); \u00c3\u00c3 or ## : P<0.01; \u00c3\u00c3\u00c3 or ### : P<0.001 (extremely significant).", "The animal experiments were performed according to the Chinese Regulations of Laboratory Animals-The Guidelines for the Care of Laboratory Animals (Ministry of Science and Technology of People's Republic of China) and Laboratory Animal-Requirements of Environment and Housing Facilities (GB 14925-2010, National Laboratory Animal Standardization Technical Committee). The license number associated with this research protocol was CAU20160520-1, which was approved by the Laboratory Animal Ethical Committee of China Agricultural University.", "Vero cells in 12-well plates were infected with the wild type or recombinant virus of PEDV at an MOI of 0.01. At different time points, the cell supernatants and the infected cells were collected, and the amount of total virus was quantified by the end-point dilution assay (TCID 50 ).", "We also investigated the virus shedding in the feces by real-time PCR. It was found that two piglets from the rBJ2011C group started the virus shedding at a high level within 24 h post challenge (Fig 5A) , and all four shed the virus within 36-48 h post challenge (Fig 5A) . In contrast, no detectable virus shedding could be found for the mock or rCHM2013 group (Fig 5A) . Consistently, the fecal score for rBJ2011C group is much higher than that for the rCHM2013 group ( Fig 5B) ." ] },{ "paper_id": "e0d0ceb2658c588ef2f3549f2b9a928b441d94a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In previous studies of various CoVs, pretreatment with antibody against receptor neutralized viral infectivity 32, 33 .", "The structure information of proteins evaluated in our study was obtained from the Protein Data Bank (PDB) library. pAPN (PDB ID 4F5C), TGEV S (PDB ID 4F2M), and PDCoV S (PDB ID 6B7N) were chosen for analysis of S1-CTD and pAPN using PyMOL software (https:// pymol.org/2/).", "To date, a series of cellular receptors for different genera of CoVs have been identified. For example, aminopeptidase N (APN, also called CD13) is the functional receptor for human coronavirus 229E (HCoV-229E) 28 , feline infectious peritonitis virus 29 , canine CoV 30 , and transmissible gastroenteritis virus (TGEV) 31 . Angiotensin-converting enzyme 2 is utilized by HCoV-NL63 and severe acute respiratory syndrome coronavirus (SARS-CoV) 24, 32 . Middle East respiratory syndrome coronavirus (MERS-CoV) S protein employs dipeptidyl peptidase 4 (also called CD26) as its receptor 33 . Carcinoembryonic antigen-related cell adhesion molecule 1 is reported to mediate viral infection by interacting with mouse hepatitis virus (MHV) S protein 34 . However, the relationship between hosts and members of genus Deltacoronavirus remains unknown." ] },{ "paper_id": "e0d2f1d5518c3f12943758f45d87e91ddf271c9a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e0d7ff094aad4031bc73a82ae7b4dd6e5f8723c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In total, 432 arthropods were collected inside Faucon and Zadi\u00e9 caves, including Culicidae (10 Uranotaenia nigromaculata and 320 Culex wigglesworthi), Nycteribiidae (51 Eucampsipoda africana, 26 Nycteribia schmidlii scotti and 21 Penicillidia fulvida) and Streblidea (Brachytarsina allaudi and 1 Raymondia huberi huberi) ( Table 1) . No arthropods tested were positive for Belinga Bat Virus (Table 1 ).", "Conceived and designed the experiments: GDM MB EML. Performed the experiments: GDM JON NN. Analyzed the data: GDM JFD. Contributed reagents/ materials/analysis tools: GDM MB CD CP JFD EML. Wrote the paper: GDM CP EML SM.", "performed in accordance with the guidelines of the American Society of Mammalogists (http://www.mammalsociety.org/committees/animal-care-anduse) [15] : bats were captured following recommendations by Kunz and Parsons [16] and identified by trained field biologist. Captured bats were removed carefully from nets as soon as possible to minimize injury, drowning, strangulation, or stress. Safe and humane euthanasia was achieved through the use of inhalant anaesthetic (halothane) prior to autopsy.", "This association between C. afra and BelPV could serve as an interesting model, (i) to evaluate modes of transmission within host populations, (ii) to study hostvirus interactions (pathogenesis and host specificity), and (iii) to evaluate the zoonotic risk of a newly identified virus." ] },{ "paper_id": "e0dbc66f68bc3baa8294c1fea46d8940f8a692db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "None." ] },{ "paper_id": "e0e0a545d003e79b46773517d09ac3e7af93ba3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2212 3\u2032 and reverse 5\u2032-GTAGCGTTGCCGGCCGAGAA-3\u2032, and the internal primers were forward 5\u2032-TTCC CCATGGCCCACAACAC-3\u2032 and reverse 5\u2032-GCCTCGAT GACGCC.", "Nested PCR targeting the HAdV hexon gene's hypervariable region was employed for genotyping. The outer primers used were forward 5\u2032-GCCACCTTCTTCCCC ATGGC.", "GCGGTG-3\u2032. Nested PCR was conducted in 25 \u03bcL volume comprising 2.5 \u03bcL of 10 \u00d7 EX Taq buffer, 1.0 \u03bcL (10 pM) of each primer, 2.0 \u03bcL of dNTP Mix, 0.5 \u03bcL of EX Taq DNA polymerase, 2.0 \u03bcL of viral nucleic acid extract or first nested-PCR product, and 16 \u03bcL of double-distilled water. The mixtures were amplified with an initial denaturation at 94\u00b0C for 10 min, followed by 36 cycles at 94\u00b0C for 1 min, 55\u00b0C for 1 min, and 72\u00b0C for 2 min, and a 7 min extension at 72\u00b0C. PCR products were analyzed on 1.50% agarose gels, purified, and then confirmed as authentic by sequencing. Samples that failed to amplify are defined herein as untyped." ] },{ "paper_id": "e0e1f657eb7a089f3a2fbb4beb3dc6a242a22b34", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Three Escherichia coli strains (O138, O149:F4 and F18) were isolated from faeces of piglets suffering from PWD and Yersinia ruckeri was isolated from Enteric Redmouth Disease affected Oncorhynchus mykiss. Salmonella enterica diarizonae was kindly provided by Gitte S\u00f8rensen at DTU Food.", "All animal procedures were approved by the Danish Animal Experiments Inspectorate under the Ministry of Justice (permit number: 2014-15-2934-01048) and animal experiments were conducted in strict accordance with their guidelines. Animals were acquired from a commercial farm near Roskilde, Denmark.", "qPCR data was fitted for each group with an equation of the form:", "At 28 days of age twenty-four piglets were randomly selected and weaned, and transported to the housing facility and distributed according to their experimental group A, B or C (Table 1) . Each pen of 8 piglets was provided with 2.5 kg of oat/wheat-feed each morning during the experiment, and group C was provided with oat/wheat-feed mixed with 160 ml (32 grams) of the IgG product. Water was provided ad libitum from water nibble, and animals were kept in 12/12 hour light/dark conditions with temperature controlled to 15\u00b0C and access to a heating lamp.", "The animals were inspected daily for signs of diarrhoea and general well-being. Faecal samples were collected on day 1, 3, 5, 7, 9 and 11 post infection. Four randomly selected weaners from each pen were killed at day 11 and the remaining half were killed at day 12 and inspected. Animals were sacrificed by an overdose of pentobarbital and jugular bleeding. The contents of the ileum were taken and stored at -20\u00b0C until further analysis." ] },{ "paper_id": "e0e5e7bee4a69a83d9cffeefcdcc26172d56f1a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Peripheral blood was obtained from healthy volunteer donors according to a protocol approved by the Emory University Institutional Review Board (IRB). Written informed consent was obtained from donors, and samples were de-identified prior to handling by laboratory personnel.", "HeLa and TZM-bl cells [57] ) were maintained in DMEM containing 10% FBS and antibiotics. The H9 T cell line (ATCC HTB-176) were cultured in RPMI medium 1640 supplemented with 10% FBS, 2 mM Glutamine, and antibiotics. MDMs were prepared from human peripheral blood as described previously [29] . HeLa T-REX cells for inducible expression of FIP1C and Rab14 were created using the T-REx system and vector pCDNA5/TO (Invitrogen). Cells were maintained in tetracycline-free media and induction carried out with 1 mg/ml doxycycline.", "Rabbit polyclonal antibody against FIP1C was obtained from Sigma. Goat polyclonal antibody against HIV-1 gp120 and gp160 (used in Western blotting) was AHP2204 from AbD Serotec (Oxford, UK). Human anti-gp120 antibody for immunofluorescence experiments was IgG1 b12; synthesized from recombinant cDNA by the laboratory of James Crowe (Vanderbilt University). Antibody used for immunoblotting of gp41 was murine monoclonal 5009 from BTI research reagents (Columbia, MD). HIV Gag detection was performed with either rabbit anti-p17 polyclonal, mouse anti-p24 monoclonal CA-183 (provided by Bruce Chesebro and Kathy Wehrly through the NIH AIDS Research and Reference Reagent Program), or mouse anti-p24-FITC (KC57-FITC) obtained from Beckman Coulter (Fullerton, CA, USA). Anti-VSV-G antibody was from Sigma (V5507), and antiamphotropic MLV goat antiserum (679) was obtained from Chris Aiken (Vanderbilt). Rabbit anti-Rab14 antibody was obtained from Aviva Systems Biology. Mouse monoclonal anti-Rab11a (8H10) was described previously by the Goldenring laboratory [60] , who also provided rabbit anti-Rab11b polyclonal antiserum (VU76). Alexa Fluor goat anti-mouse and Alexa Fluor goat antirabbit secondary antibodies, as well as the DAPI nucleic acid stain were obtained from Molecular Probes (Eugene, OR, USA). IRDye goat anti-mouse and IRDye goat anti-rabbit secondary antibodies used for Western blots were obtained from Li-cor Biosciences (Lincoln, NE, USA)." ] },{ "paper_id": "e0e8ee783d4c465b22a44cb27e7e0f1b0d073245", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasmid DNA was transformed into electrocompetent DH5\u03b1 Escherichia coli and purified with EndoFree Plasmid Maxi Kits (QIAGEN, Hilden, Germany)." ] },{ "paper_id": "e0ec066b46e51073a3ccfbc05fe626d0c93f8b29", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This research was approved by the Institutional Ethical Committee of the University of Santander and VECOL, Colombia." ] },{ "paper_id": "e0f1b5a380193e6ff0a4de4d44d74ad309a5dda3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mouse monoclonal anti-strep tag antibodies and mouse monoclonal anti-6x His tag antibodies were diluted at 1:5000, and mouse anti-CTD1 serum (provided by Panpan Zhou from Linqi Zhang's lab at Tsinghua University) was diluted at 1:1000." ] },{ "paper_id": "e0f36613dbfcdb38aee79337d0a011c8760acba0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All the authors declare that they have no competing interests." ] },{ "paper_id": "e0f39f2d61d66f276287f181454ae85cdafb7ffa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 File. " ] },{ "paper_id": "e10083014ab2d0c09bd8bed432e8ca883d8d3431", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2018, 10, x 11 of 24" ] },{ "paper_id": "e10af65e4c33f25a580260de1b277ca738dcc886", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Table S1 Summary of the E domains of epitope residues recognized by mAbs in this study. (DOC)" ] },{ "paper_id": "e10eb45af8825e380c4c7df28487b597f2b0402e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 1193 | the Gambian epauletted fruit bat (Epomophorus gambianus) and the Egyptian fruit bat (Rousettus aegyptiacus) 30,31 . These four bat species were chosen based on their interactions with humans as they roost and forage in the human habitat or serve as a human food source 28-31 . We show that DPP4 localization varies not only among MERS-CoV susceptible species 9,26 but also between bat species, which may imply variability in MERS-like-CoVs tropism, pathogenesis, and transmission route.", "Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in the human population in 2012 and has been causing multiple outbreaks of human disease, mainly in the Arabian Peninsula 1 . The dromedary camel (Camelus dromedarius) has been shown to be the reservoir host for primary human infections 2-8 , although other susceptible animals 9-11 , including bats 12,13 , are suspected also to be hosts for this virus. MERS-like-CoVs have been sequenced from bat samples, mainly from insectivorous bats, but they have not yet been successfully isolated 14-21 . Screening of over 5000 insectivorous bats from Ghana, Ukraine, Romania, Germany, and the Netherlands showed that MERS-CoV-like viruses were detected in 24.9% of Nycteris bats and 14.7% of Pipistrelle bats 17 .", "Our study aimed to understand the tropism of MERS-like-CoVs in bats by mapping the distribution of DPP4 expression in tissues from four bat species. DPP4 immunohistochemistry staining was performed on tissues collected from two widespread insectivorous bat species in Europe and Asia, the common pipistrelle bat (Pipistrellus pipistrellus) and the serotine bat (Eptesicus serotinus) 28,29 ; and two common frugivorous bat species in Africa, i.e." ] },{ "paper_id": "e11512bdc7871914c25d4ba5b098979d34123c34", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The intervention activities targeted MSM who were living in the project cities included distribution of health information and provision of free condoms, free HIV testing and counseling, STI referral service, and antiretroviral (ARV) treatment. Intervention was delivered by peers, public health staff and clinicians through multiple approaches, including clinic-based, community outreach, instant message, Internet-based (website, chat room).", "The China GF-5 project sought to prevent a new wave of HIV in 6 low-prevalence provinces (Heilongjiang, Jilin, Liaoning, Inner Mongolia, Ningxia, Gansu) and one municipality in China (Chongqing) (Figure 1 ). Sixteen cities were included with 2-3 cities from each province and three districts from Chongqing Municipality. Each province included one capital city and one or two prefectural-level cities. Prefectural-level cities were selected based on cooperation of local health departments and experience of access to MSM population. The target populations included the four HIV aforementioned populations: MSM, CSWs, IDUs and migrants, and interventions were implemented during 2006 and 2009.", "To examine the impacts of a multi-", "We analyzed yearly cross-sectional surveys among MSM performed on behalf of the China GF-5 project. All analyses used fully de-identified data and our protocol was reviewed and approved by the institutional review boards of the National Center for STD/AIDS Prevention and Control of China CDC and Vanderbilt University." ] },{ "paper_id": "e12e72939bfeb49c8865a15d0c1bc9a4f99c0ece", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All viral preparations were titrated by plaque assay on MA104 cells and expressed as plaque forming units per ml, as described [80] . Hemagglutination assays were performed to determine VP4 content of purified genome-containing and empty TLPs, unpurified RRV and 2/4/6/7 VLPs, as described [88] , and used to ensure that equal quantities of TLPs were added to pDC preparations. Additionally, DLPs were prepared by treating purified genome-containing TLPs with 20 nM of EDTA, thus removing the outer capsid from the virion and resulting in equal particle counts between the two preparations.", "Rotavirus, a dsRNA icosahedral virus in the Reoviridae family, is the leading cause of severe dehydrating diarrhea in young children worldwide, with 500,000 to 600,000 annual deaths attributed to rotavirus infections [26, 27, 28, 29] . Significant morbidity and economic impact are the main effects in the United States, accounting for approximately 50,000 to 60,000 hospitalizations a year and loss of time from work for caregivers [30] .", "Purified pDCs were incubated with 20 nM concanamycin A (Sigma-Aldrich, St Louis, MO) at 37 degrees for one hour prior to infection with live or inactivated RRV (moi 10).", "Supernatants of cultures .85% (mean 6 SEM: 90.84%60.7499) pure for pDCs were analyzed by Luminex using MILLIPLEX MAP (Millipore, Billerica, MA) per the manufacturer's instructions for the presence of IFNa, IFNc, TNFa, TNFb, IL1b, IL1RA, IL2, IL4, IL6, IL8, IL10, IL12p40, IL12p70, CXCL10 (IP10), CCL3 (MIP1a), CCL4 (MIP1b), CCL5 (RANTES) and sCD40L. Secreted IFNb was detected by ELISA, per the manufacturer's instructions (PBL Interferon Source, Piscataway, NJ)." ] },{ "paper_id": "e12fc1a31129f8aa683a597e3899199409cc67f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The UF IRB and the Haitian National IRB approved all protocols, and written informed consent was obtained from parents or guardians of all study participants.", "Whole blood (ca. 0.5-2 ml) was collected in K 2 EDTA tubes (BD Vacutainer, Becton, Dickinson and Company, Franklin Lakes, NJ). As part of the initial diagnostic evaluation, plasma was screened for CHIKV viral RNA (vRNA) by molecular methods [13, 14] . All virus isolations and RNA extractions on CHIKV-positive specimens were performed in a BSL-3 facility at the University of Florida (UF) Emerging Pathogens Institute in Gainesville, Florida." ] },{ "paper_id": "e1371bc7c700d3752ae645755967db504347d87f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2) selecting the most mutually compatible alignments and filtering out spurious alignments with the program EPIFILTER.", "The Tramontano lab from Italy might be the first team that tried to map discontinuous epitope computationally based on mimotopes and the antigen structure [26] . Their method includes four steps.", "Different from the tools described above, the RELIC server was particularly designed for the study of the interaction of small molecules with proteins [21] . By analyzing the sequence of a protein and the sequences of small molecule affinity-selected, phage-displayed peptides, RELIC can predict proteins or some residues on the protein that bind to drugs, drug candidates and small metabolites." ] },{ "paper_id": "e1400d2059ba0e337608df70a17351ee9c3caa17", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Haptoglobin concentrations were determined by a sandwich ELISA as described previously [38] . The detection limit was 66 \u03bcg/ml." ] },{ "paper_id": "e1406defdf36c0e9507a509d880dd7df0ed84f56", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The global airline network has brought the entire world closer together than ever before, creating an environment in which pathogens can readily spread to distant locations. Influenza viruses are perhaps the most widely recognized example of this phenomena [1, 2] , but by no means the only one [3, 4, 5] . Study of past spread and discussion about potential mitigation efforts has lead to a significant body of literature investigating the use of mathematical models to predict global pathogen spread and to assess the potential effectiveness of various interventions [3, 6, 7, 8, 9, 10, 11, 12, 13] .", "Text S1 Detailed description of the models and parameters used. (DOCX)", "General considerations." ] },{ "paper_id": "e141a069b6f6aef31ddf1a2ae592933db0b4a031", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The dataset analyzed in this study was generated as part of a previous analysis in our laboratory (10) and is publicly available at the NCBI Small Read Archive with the accession number SRP013296. These reads are 100-nt single reads generated on an Illumina HiSeq 2000 using standard cDNA library generation protocols and directional RNAseq.", "Ref:", "Briefly, authentic FHV particles were amplified in Drosophila S2 cells grown in suspension, harvested 2 days after infection and then purified over a series of centrifugation steps consisting of one 30% sucrose cushion and two 10-40% sucrose gradients in the presence of 50 mM Hepes, pH 7.0. An additional 2-h nuclease digestion was performed with 20 U DNase I and 0.5 ug RNase A in between the two sucrose gradient spins to remove any contaminating non-encapsidated RNA or DNA. After the final sucrose gradient, RNA was extracted using standard phenol/chloroform extraction, ethanol precipitated and re-suspended in pure water. In all, 400 ng RNA was used for cDNA library generation using standard TruSeq adaptors and barcodes, polymerase chain reaction amplified for 12 cycles and then purified by agarose gel electrophoresis to yield inserts of 200 nt. The cDNA library was loaded onto a HiSeq v3 single read flowcell and sequenced for 100 nt of the insert and 7 nt of the index sequence on an Illumina HiSeq 2000. Reads were processed using CASAVA 1.8.2." ] },{ "paper_id": "e142106dccc14c30910e705e1159d340c6a97832", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "EIAs. Mouse anti-Norwalk virus VLP polyclonal serum reactivity to Norwalk virus VLPs was determined by enzyme immunoassay (EIA) (45) . Briefly, plates were coated with decreasing concentrations of VLP in PBS before the addition of 0.2% serum. Primary antibody incubation was followed by anti-mouse IgG-horseradish peroxidase (HRP) (GE Healthcare) and color development with one-step ultra TMB ELISA HRP substrate solution (Thermo-Fisher). Each step was followed by washing with PBS-0.05% Tween 20, and all antibodies were diluted in 5% dry milk in PBS-0.05% Tween 20. The percent maximum binding was defined as the binding level (optical density at 450 nm) at a given VLP concentration divided by the binding level of 1 g/ml VLP multiplied by 100. Data were fit with sigmoidal dose-response curves in Prism 6 (GraphPad), and EC 50 s were calculated. EC 50 s between VLPs generated from different VRP coats were compared using a Student's t test. A difference was considered significant if the P value was \u03fd0.05.", "VLP-carbohydrate ligand-binding assays. Pig gastric mucin type III (PGM; Sigma Chemicals) was solvated in PBS at 5 mg/ml, coated onto EIA plates at 10 g/ml in PBS for 4 h, and blocked overnight at 4\u00b0C in 5% dry milk in PBS-0.05% Tween 20 before decreasing concentrations of Norwalk virus VLPs were added for 1 h. Bound VLPs were detected by a mouse anti-Norwalk VLP monoclonal antibody at 2 g/ml followed by anti-mouse IgG-HRP (GE Healthcare), and color was developed with one-step ultra TMB ELISA HRP substrate solution (Thermo-Fisher). All incubations were done at room temperature. Each step was followed by washing with PBS-0.05% Tween 20, and all reagents were diluted in 5% dry milk in PBS-0.05% Tween 20. Data were analyzed as described above for EIAs.", "We thank Victoria Madden of Microscopy Services Laboratory, Department of Pathology and Laboratory Medicine, University of North Carolina-Chapel Hill, for expert technical support.", "The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.", "and MERS-like CoVs circulating in bats further indicate the ongoing threat to human populations (5) (6) (7) . Design of a broadly cross-protective vaccine in such instances is dependent upon not only knowledge of the key antigenic determinants but also the availability of a rapid-response vaccine platform to easily generate, characterize, and successfully apply to vulnerable populations, like the aged (8, 9) ." ] },{ "paper_id": "e15c8f5664f0a614345b976780eeea291b282fd1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Categorical data were evaluated by \u03c7 2 or Fisher's exact tests, depending on the absolute numbers included in the analysis, quantitative data were analyzed by independent sample t test followed by Mann-Whitney U test. SPSS 16.0 software (SPSS, Inc., Chicago, IL) was used for all statistical analysis. Results were considered statistically significant at P < 0.05.", "Huh7, Hep3B, HL-7702, and 293T cell lines , which were purchased from American Type Culture Collection (Manassas, VA, USA), were cultured in Dulbecco's modified Eagle medium (Gibco BRL, Rockville, MD, USA) supplemented with heat-inactivated 10% fetal bovine serum (Gibco BRL). All cell lines were maintained in a 37\u00b0C incubator with 5% CO 2 .", "RNAi is a relatively new technology and shows promise for the development of therapeutic gene knockdown. Lentiviral vectors permit efficient delivery and stable transfection of a sequence of interest, and show minimal immunogenicity [31] and no adverse events [32] . Additionally, lentivirus can efficiently infect both dividing and non-dividing cells [33] . Thus, the combination of lentivirus and RNAi is a potential therapeutic strategy for cancer gene therapy." ] },{ "paper_id": "e164fa160155af75c4fc98397014ef055030950e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u00f02:1\u00de", "and for the null model is", "Monte Carlo sampling allows for the estimation of P(Q \u00bc y j R 0 \u00bc r). Through use of Bayes' theorem,", "ln P BDI (n t\u00fed j n t , R 0 (t)) \u00f04:2\u00de", "ln P BDI (n t\u00fed j n t , R 0 (0)): \u00f04:3\u00de" ] },{ "paper_id": "e1684d4ad73d5982451ae73e97542c2559c04038", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "algorithm implemented in the Image J plugin DeconvolutionLab was used for deconvolution 66 . Thirty-five positively-constrained iterations of deconvolution were performed with no early stopping criteria.", "Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen, causing a myriad of diseases that can impinge severely on female fertility and the health of neonates. Under permissive physiological conditions, these obligate intracellular bacteria can invade, replicate, and establish long-term infections in the columnar epithelium of the urogenital tract, indicating their capacity to evade host immune responses. C. trachomatis has evolved many evasive strategies to promote its long-term survival within its human host. These include inhibition of apoptosis 1-3 , modulation of NF\u03baB signaling 4,5 , downmodulation of CD1d 6 , and inhibition of transcription factors necessary for the expression of MHC classes I and II 7,8 ." ] },{ "paper_id": "e172007ec7885b58e7a14be7459e0250ac47ba52", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e172d0ebcbb5e8488f19e2193ac9a9ed96f60efb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since eIF2 is the substrate of PKR, the PKR binding domain located between amino acids residues 91-121 close to the C-terminus of Us11 contributes to physical association with PKR, resulting in a reduction of eIF2 phosphorylation [48] .", "HBV is a doublestrand DNA virus, a member of the hepadnavirus family. Its DNA genome contains four genes named S, C, P, and X, respectively. The HBx protein encoded by the X gene serves as a multifunctional regulatory protein since it is involved in regulating cell cycle, signaling transduction, and cellular apoptotic pathways [37] . HBV can enhance autophagic flux in cell culture and transgenic mouse liver and during natural infection. Enhancement of autophagy caused by HBV is now believed by the contribution of HBx [38] . In accordance with the results of coimmunoprecipitation assays performed by Sir et al., it was discovered that HBx can directly bind to Vps34, the catalytic subunit of PI3KC3, to promote the activity of PI3KC3. The HBx-induced autophagy benefits HBV DNA replication rather than RNA transcription. Furthermore, autolysosomes were not involved in HBV replication, since treatment of cells with bafilomycin to suppress formation of autolysosomes showed no effects on HBV DNA replication [38] .", ". Us11, a late 2 gene product, is a viral protein abundantly produced in the late stage of HSV-1 life cycle. Like ICP34.5, Us11 is involved in inhibition of eIF2 phosphorylation. Earlier studies have shown that Us11-null viruses grow normally in vitro and are slightly attenuated in vivo, suggesting that the function of Us11 may be compensated by the extant ICP34.5 [46, 47] . Nevertheless, Us11 acts in concert with ICP34.5 to inhibit autophagy through a mechanism totally different from that in which ICP34.5 is involved. Us11 blocks the kinase activity of protein kinase R (PKR) via directly binding to either PKR or upstream activators of PKR.", "2.5.1. The Unfolded Protein Response (UPR). UPR is an alarm system for cells in response to the accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER), triggering formation of autophagy to digest and clean these unwanted proteins. There are three main pathways activated upon UPR induction, including transcription factor 6 (ATF6), PKR-like ER kinase (PERK), and inositolrequiring kinase 1 (IRE-1) [76] . A number of viruses that have been characterized encode proteins modifying autophagy through UPR to their own advantages during infection. For example, severe acute respiratory syndrome coronavirus (SARS-CoV) modulates UPR by activating PERK protein kinase by its viral spike (S) protein [77, 78] , while the E protein encoded by the envelope gene downregulates the IRE-1 signaling pathway [79] . HCMV protein pUL38, like the small surface protein (HBs) of HBV, is capable of activating the key components of PERK pathway, including PERK, eIF2 , and transcription factor 4 (ATF4) [80, 81] . The latent membrane protein 1 (LMP-1) of EBV upregulates all three signaling pathways of UPR that have been described previously [76, 82] . Moreover, West Nile virus requires ATF6 signaling for its replication, and a viral protein responsible for regulating ATF6 signaling still remains to be determined [83] . On the contrary, HSV-1 glycoprotein B (gB), HCV cytosolic envelope protein E1, and CHIKV nonstructural protein 4 (nsP4) suppress the PERK pathway during infections [76, 84, 85] ." ] },{ "paper_id": "e178386cc3ca613c695540267c215754c02f2abe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Crystals of the NPD340/E391A-8bp dsRNA complex were grown in 0.1 M Bis-Tris pH 6.5, 0.2 M MgCl 2 hexahydrate and 25% PEG 3350. Crystals were cryoprotected with well solution containing 15% glycerol and flash-cooled in liquid nitrogen. Data were collected at the Advanced Photon Source, Beamline 19-ID.", "18 base DNA and RNA were purchased from IDT. Sequences of the oligonucleotides are as follows: RNA (sense) 59 CAGGAU-GUUGAUGCUGCU 39; RNA (anti-sense) 59 AGCAGCAU-CAACAUCCUG 39; DNA (anti-sense) 59 AGCAGCATCAA-CATCCTG 39. Oligonucleotides were labeled with P32 using protein nucleotide kinase according to the manufacturers directions (NEB). Standard reactions contained 50 nM wild-type or mutant NPD340 and 2 nM (labeled) and 10 nM (unlabeled) oligo(ribo)nucleotide. Sense and anti-sense RNA strands or, for hybrid experiments, sense RNA and anti-sense DNA were annealed at 65uC for 2 minutes and then cooled for 10 minutes at room temperature. Reactions were performed in 20 mM Tris pH 7.5, 150 mM NaCl, and 5 mM MgCl 2 . After incubation for 15 minutes, reactions were stopped with the addition of an equal volume of formamide loading buffer and boiled. The products were then analyzed in 18% polyacrylamide gels containing 8 M urea and buffered with 0.5x Tris-borate-EDTA. Gels were exposed overnight to a phosphorscreen and then imaged using a Typhoon phosphorimager.", "The Lassa (Josiah strain) NP-exonuclease domain (residues 341-569, termed NPD340) was produced as previously described for the unbound NPD340 crystal structure [3] . Point mutations were introduced via site-directed mutagenesis with Phusion Hot Start polymerase (NEB).", "Deprotected, desalted, 8-base RNA oligonucleotides were purchased from Integrated DNA Technologies and delivered as lyophilized powder. One strand of the RNA was designed to include all purine residues (59 GGAGGGAG 39) and the other to include all pyrimidine residues (59 CUCCCUCC 39). Oligos were resuspended in nuclease-free water to a final concentration of 1 mM. Equal parts of sense and anti-sense oligos were combined and annealed at 65uC for 10 minutes before slow cooling to room temperature to yield dsRNA. Tris pH 8.0 and NaCl were added to the dsRNA to achieve final concentrations of 10 mM and 300 mM, respectively." ] },{ "paper_id": "e18358325d65bee698980b7433a62923fcca051a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell culture media were purchased from Biochrom (Bioswisstec AG, Schaffhausen, Switzerland), and fetal calf serum (FCS) was obtained from PAA Laboratories (Lucerna-Chem AG, Lucerne, Switzerland). FCS was free of BVDV and antibodies to BVDV as tested by virus isolation and serum neutralisation assays, respectively." ] },{ "paper_id": "e18f75d74176ea6eff4a4e8ef6ad0a0836a92a5e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples positive after more than 35 Ct-cycles were re-evaluated to confirm a true positive result.", "Statistical analyses were performed in STATA 10.0, software packages SPSS version 22 and Microsoft Excell. Chi 2 -test, Fishers Exact test or Z-score test was used for categorical data analysis and two-sample T-test for numerical data. A p-value of < 0,05 was considered significant.", "Patient characteristics stratified by age group are presented in Table 1 .", "The Ethical Committee of Region Hovedstaden (protocolnumber: H-2-2012-132) as well as the Danish Data Protection Agency approved the study. This approval included acceptance of reviewing the medical records without informed consent of the patients." ] },{ "paper_id": "e192e65a6546583fe49086c4d3ac29a0620d5bd5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For ILTV, total DNA was extracted from the tracheal swabs using the MegaZorb \u00ae DNA extraction miniprep 96-well kit (Promega, Madison, WI, USA), as described previously [24] .", "The data were analyzed using Prism v.6.0 software (GraphPad Software, Inc., La Jolla, CA, USA; www.graphpad.com). For viral load data, a one-way analysis of variance (ANOVA) with Dunnet's posttest was used to compare treatment groups within each collection period. All other data were analyzed using a Kruskal-Wallis test with Dunn's posttest to compare treatment groups within each collection period. Significant differences were determined at p < 0.05.", "Clinical Signs ", "Each qRT-PCR reaction plate included a standard curve as an RNA extraction control and as a positive control. GA98 IBV isolated from allantoic fluid was used as the template for the standard curve. Negative controls were also included in each plate and consisted of PCR reagents with no RNA. " ] },{ "paper_id": "e197a8c2fc80727b35e38ea7aca28d8e6edfb27a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Interestingly, cat no. 1 had vascular changes in the cerebrum and cerebellum that were characterized by engorged blood vessels containing variable numbers of PAS-and Alcian blue-negative, eosinophilic, homogenous globular material and an expansion of the perivascular Robin-Virchow space ( Fig. 2i) with open spaces containing variable amounts of eosinophilic flocculent material intermixed with rare, small, proteinaceous droplets ( Fig. 2i, inset) . The affected blood vessels were lined by plump reactive or occasionally pyknotic endothelial cells.", "Clinical findings. In late December 2018, all ten cats kept at household A were brought to a veterinary hospital with reported acute depression, bloody diarrhea and bloody respiratory discharge. All 10 cats, aged from 1-3 y, had been up-to-date vaccinated for FPLV, feline calicivirus (FCV), FeLV and rabies virus (RV). Later, in the beginning of January 2019, four core-vaccinated cats, aged from 1-2 y, from household B showed clinical signs of depression, followed by diarrhea, acute hemoptysis and ataxia; while three 1-month-old non-vaccinated kittens in household C were carried to the hospital in late February 2019 due to the acute onset of depression, anorexia, bloody diarrhea, hemoptysis and seizure.", "Outbreaks of hemorrhagic enteritis were presented in three different household cat colonies under well-managed and environmental-closed systems. The disease spread to neighboring cats causing fatality in 13/17 symptomatic cats within a day. Initially, FPLV was thought to be the primary infectious agent in all cases. However, clinical presentations of hemorrhagic syndrome with multi-systemic involvement are atypical findings for simple FPLV infections. Thus, an unknown concurrent infectious etiology, highly likely viral, may have played an important role in these outbreaks. This prompted us to expand the search for other unknown pathogens. Interestingly, we identified a FBoV-1 co-infection in these cats, arguing the potential role of the both viruses in the outbreaks." ] },{ "paper_id": "e1a771476018079cd6dcb063ae78e04ca349ba08", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author(s) declare that they have no competing interests.", "The project described was in part supported by National Institutes of Health grant KL2RR025746 (MH), National Institute of Environmental Health Sciences ES013611 (IJ), and Nation Heart, Lung, and Blood Institute HL095163 (IJ).", "Authors' contributions MK designed and carried out the studies, analyzed the data, and drafted the manuscript; MH contributed in the clinical characterization and recruitment of the subject population; IJ contributed to the design, oversaw the coordination of the overall study, and finalized the manuscript. All authors read and approved the final manuscript." ] },{ "paper_id": "e1aadb0d868db77c282d5ce3f8f85508f8dabc4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In a soft Brexit [27] , it is likely that current arrangements may continue. Collaboration may stop with no legal framework to govern it in a failed Brexit; in a hard Brexit the external position is likely to undermine collaboration.", "The Epi-South project of 2010, involving Mediterranean EU MS e.g. Italy, Malta plus some African Mediterranean States e.g. Morocco, Algeria, is one model for addressing epidemic intelligence and interoperability with EWRS [30] .", "The IHR were transposed into national legislation in Ireland via the Infectious Disease (Shipping) Regulations S.I. 4/2008 [6] and the Infectious Disease (Aircraft) Regulations S.I. 411/2009 [7] . While both sets of Regulations outline a schedule of serious infectious diseases to which they apply, including existing, re-emerging (e.g. plague) and novel diseases, this schedule also provides for the inclusion of unspecified, novel threats of international importance, should they arise." ] },{ "paper_id": "e1ac05796a8f9ecfb55f2b105d4d1dc359a39fd4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Several research groups studied the antiviral properties of hinokinin against human hepatitis B virus (HBV) [97] , human immunodeficiency virus (HIV) [29] , SARS-virus (SARS-CoV) [98] , and in all cases 1 showed significant antiviral activity.", "Cytochrome P450 (CYP) enzymes play an important role in phase I oxidation metabolism of a widw range of xenobiotics. In humans, 57 isoforms of CYP were identified, CYP3A4, CYP1A2, CYP2A6, CYP2D6, CYP2C8 and CYP2E1 among others.", "M.C.M. conceived the work. M.C.M. and A.P. collected and organized bibliographic data. M.C.M. and M.C. wrote the manuscript.", "Lignans are important components of foods and medicines biosynthetically deriving from the radical coupling of two molecules of coniferyl alcohol at C-8/C-8\u2032 positions ( Figure 1 ). They are classified in different groups-dibenzylfuran, dihydroxybenzylbutane, dibenzylbutyrolactol, dibenzylbutyrolactone, aryltetraline lactone and arylnaphtalene derivatives-on the basis of the skeleton oxidation [1] and of the way in which oxygen is incorporated into the skeleton [2] (Figure 1 ). Podophyllotoxin and deoxypodophyllotoxin are, perhaps, the most important biologically active lignans, and their properties have been broadly reviewed [3, 4] ." ] },{ "paper_id": "e1ae1fce6ed744522728aef322c22b5f239b9157", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No specific permits were required for the described field studies. No specific permissions were required for these locations/ activities. No location is privately-owned or protected in any way. The field studies did not involve endangered or protected species.", "The 2,193 bp product was amplified and sequenced using a genomic template ( Figure 2B) , and its 219 bp intron was analyzed by NCBI. After a three-step PCR, the full encoding sequence was cloned. The results show that the open reading frame of this gene was 1,974 bp ( Figure 2B) , which encodes for 657 aa.", "In our previous work, A. terreus Li-20 was isolated and screened from a G. glabra planting field in Shihizi, Xinjiang. It was incubated in 100 ml liquid Czapek's medium in a 500 ml Erlenmeyer flask at 30uC and placed in a shaker incubator at 170 rpm.", "Far-UV Circular dichroism (CD) spectra were recorded at 25uC in the range from 190 to 260 nm with a spectral resolution of 0.2 nm using a Jasco J-715 spectropolarimeter. The scan speed was 100 nm/min and the response time was 0.125 s with a bandwidth of 1 nm. Quartz cells with an optical path of 0.1 cm were used. Typically, scans were accumulated and subsequently averaged. The spectra were corrected for the corresponding protein-free control." ] },{ "paper_id": "e1be06ec4d2cc4190334ac135f85090e6d3f380f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Determination of the optimal space window for spatial scanning" ] },{ "paper_id": "e1be35b4c835e9b982fe494d2d0b6e3fb1622d2e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To investigate the C3 cell interaction further, a His-tagged form ", "Synaptosomes were prepared at 4\u00b0C from postnatal (P2) mouse whole brains in the presence of protease inhibitors according to a modified standard procedure as described (96) . Briefly, after homogenization in 0.32 M sucrose (10 strokes at 900 rpm) and centrifugation at 1,300 \u03eb g for 10 min, the supernatants were centrifuged at 14,000 \u03eb g for 15 min. Crude syn-" ] },{ "paper_id": "e1c4d9cdea7ddbf8cad8a101da840b3394c5303b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\uf0b7 Mature pDCs can cross-present viral antigens for cognate CD8 T cell activation. ", "Viruses 2009, 1 384" ] },{ "paper_id": "e1c5d3a82f4296f2867ccca63989530f17a773d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accuracy and precision: The accuracy and precision of intra-day and inter-day determination were carried out in six replicates samples at three QC levels (low, medium and high) within the same day and on three consecutive days.", "Subsequently, sample pre-treatment procedures were also investigated. Protein precipitation by methanol, acetonitrile, ethanol, dimethyl sulfoxide and mixed organic reagent were employed, and " ] },{ "paper_id": "e1c6885ff3cb7eded9abdbbebc8e486459265c95", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "worldwide. As also shown in Figure 3 , these viruses could additionally be stored at +4 \u2218 C for up to 4 weeks (with a 50% reduction in infectivity) and at room temperature (23 \u2218 C) for 1 week (with a 50% reduction in infectivity).", "Subsequently, neutralizing antibody titres, obtained when standard and dual H5/H7 assays were undertaken (GMT reported in Table 3 ), revealed a strong correlation between the results of the standard and dual pp-NT assays (0.86; < 0.0001; Pearson's correlation; Figure 7) .", "As shown in Figure 5 (a), titres obtained via HI correlated strongly with titres obtained using HPAI H5 pseudotypes belonging to two different clades: clade 1 A/Vietnam/ 1194/2004 ( = 0.87, < 0.0001) and clade 2.1.3.2 A/Indonesia/5/2005 ( = 0.87, < 0.0002) despite the fact the HAs used in the two serological assays were not optimally matched. The percentage amino acid identities between the pseudotype antigens, the HI antigen, and the vaccine antigen are shown in Figure 4 .", "Serum samples (5 L) were twofold serially diluted in culture medium (DMEM GlutaMAX supplemented with 15% FBS and 1% Penicillin/Streptomycin) and mixed with pseudotype virus (500,000 RLU luciferase input) at a 1 : 1 v/v ratio. After incubation at 37 \u2218 C for 1 hour, 1 \u00d7 10 4 HEK 293T/17 cells were added to each well of a white 96-well flat-bottomed tissue culture plate. 48 hours later, pseudotype transduction titres obtained at each of a range of dilution points were expressed as RLU/mL, and an arithmetic mean was calculated. For each serum sample, RLUs were normalized and compared with the signal detected in the absence of pseudotype virus (equivalent to 100% neutralization) and the signal of the negative control (equivalent to 0% neutralization). The 50% inhibitory doses (IC 50 ) were determined as the reciprocal of serum dilution resulting in a 50% reduction of a single round of infection (reporter gene mediated signal)." ] },{ "paper_id": "e1c8f343e712b43a4cedc0a09731ceada6abc146", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In this review, current models of co-translational protein folding were reviewed for elucidating the generic molecular mechanism for its linkage to mRNA structure. Several preliminary studies that correlate computationally predicted mRNA structures with protein conformation shall be discussed. A major focus was placed upon regulatory signals in major mRNA coding sequences rather than a specific mRNA fragment such as translational ramp at 5' end (Tuller et al., 2010) . Furthermore, biologically relevant interpretations of this regulation were offered. 1", "Commonly known as \"the second half of genetic code\" (Kolata, 1986) , a vast pool of information is required for ensuring correct folding of polypeptide into its native structure. However, little is known about how information stored in nucleotide sequence is transmitted from genome into polypeptide chain. According to the Central Dogma, messenger RNA is frequently targeted for searching regulatory signals for protein folding. Indeed, as evidenced by unequal usage of synonymous codons and its correlation with efficiency and/or accuracy of translational elongation (Gingold & Pilpel, 2011) , mRNA molecule obviously contains more information than primary protein sequence. This logic and decades of genomic sequencing have elucidated the association between codon usage bias and protein structures (Spencer & Barral, 2012; Tsai et al., 2008) .", "With regards to the full contents of genetic information, the answer to this fundamental question in biology has been frequently updated as newly emerging techniques and growing data constantly challenge our existing understandings (Ramos & Laederach, 2014) . On one hand, novel functions of noncoding genome are uncovered (ENCODE Project Consortium, 2012) . On the other hand, our understandings of genetic information in coding regions have also extended beyond canonical schemes of how protein folding is regulated within cells." ] },{ "paper_id": "e1cb86642107f15ec6d854bebf9c8341d1416ef4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "supporting information. Sequences and reaction conditions for each figure were listed in Table S1 and Table S2 , respectively. Table S2 for convenient reading.", "Synthetic M. tuberculosis rpoB gene (RPOB) segment was generated from commercial genomic DNA of the virulent strain H37Rv (ATCC, Manassas, VA, USA) in the same protocol described above." ] },{ "paper_id": "e1d7e7883ad7d77a1c982c700f77e5ce09530fcf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e1e11bdec2d27ec0b9675e684fc2653513a029bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e1e50e72368b173717a1b7f886c65c61ce5ade59", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accession number(s). The rhinovirus C isolate described here has been deposited at DDBJ/EMBL/GenBank under the accession number MG148341.", "Here, we report the genome sequence of a divergent human rhinovirus C isolate identified from an infant with a severe community-acquired respiratory infection. RNA sequencing performed on an Illumina platform identified reads aligning to human rhinovirus species, which were de novo assembled to produce a coding-complete genome sequence.", "H uman rhinoviruses can induce a diverse spectrum of clinical outcomes, ranging from mild disease to fulminant pneumonia (1) (2) (3) . The factors governing the severity of rhinoviral infection are not well understood, but species-and type-specific differences are suspected to be influential (1) (2) (3) . The genomic study of rhinovirus isolates associated with distinctly severe clinical syndromes may illuminate such connections. As such, we report the coding-complete genome sequence of a divergent human rhinovirus species C isolate recovered in March 2015 from the tracheal aspirate of a 15-month-old infant with a severe community-acquired lower respiratory tract infection. The previously healthy infant developed progressively worsening cough and congestion that advanced to acute respiratory failure and septic shock. A clinical respiratory virus PCR assay returned positive for rhinovirus, but all other testing, including bacterial cultures from tracheal aspirate and blood, returned negative. Following 8 days of intensive care unit support involving mechanical ventilation, vasopressors, and empiric broad-spectrum antibiotics, he fully recovered." ] },{ "paper_id": "e1e619d488e5bde5fce5b538540333b0a9a69718", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e1ea07d20c6b64c1eae05319f1f66f729f2583d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Wogonin -cardioprotective [42] ; -anti-inflammatory [42] ; -antioxidative [42] ; -anti-hyperglycemic and lipid-lowering [43] -activating PPAR\u03b1 [43, 45] ; -decreasing ROS [42] ;", "The authors declare that there are no competing interests associated with the manuscript. ", "Correspondence: Panpan Hao (panda.how@126.com)" ] },{ "paper_id": "e1f2c0859f44eaf3e7a2110a5ca98ac0104815bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e1f6b17bdd06ae44978e5359fbe7df68ac5fa1cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e1f84229bcacd4ea32af6127963a174f888acb09", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:25133 | DOI: 10.1038/srep25133", "Hepatitis E virus (HEV) causes acute viral hepatitis, which is a major public health concern in developing and resource poor countries 1 . The disease is mostly self-limiting but chronic infection has been reported in immune-compromised patients 2,3 . Moreover, HEV infection significantly increases the mortality rate (~30%) in pregnant women 4 . The virus is zoonotic and transmitted predominantly through the feco-oral route (contaminated food and water), blood and vertical transfusion 5 ." ] },{ "paper_id": "e204da6f7d00469d696968ce521afce85abcb16d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 10-dimensional PCs were then used as input to a 5-fold cross-validation which used sparse logistic regression to predict outcomes. standard pipeline parameter settings were used for the algorithms, to guard against overfitting (i.e. no parameter tuning was performed using the current data set). From this sensitivity, specificity and receiver-operator-curves (with 95% confidence intervals) were calculated.", "A total of 48 of 71 patients (68%) had at least one microbiologic sample sent. The details of the samples sent and pathogens identified are shown in Table 3 ." ] },{ "paper_id": "e209784c9a22ca29bf423b8d77359142db053182", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Animals were euthanized by exsanguination through the abdominal aorta under xylazine and ketamine anesthesia following an approved IACUC protocol. Formaline-perfused lungs were embedded in paraffin wax. Sections 4 \u03bcm in thickness were cut and stained with hematoxylin and eosin (H&E). Histopathologic lesions were scored by a board-certified pathologist as described [48] : 1 = minimal damage to alveolar structures; 2 = mild; 3 = moderate; and 4 = marked/severe damage to lung tissue.", "Forward ", "Supporting information S1 File. Plos-one-human-endpoints-checklist.doc. (DOCX) " ] },{ "paper_id": "e20aef0065c509346a868a73020a7ba5862e1cd5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Madin-Darby Canine kidney (MDCK) epithelial cells and adenocarcinoma human alveolar basal epithelial cells (A549) obtained from ATCC were maintained in modified Eagle's Figure 4A . WT WSN and WSN PA-GFP viruses were rescued by transfection in 293T cells with TransIT transfection reagent (Mirus Bio Madison, WI) and then plaque purified on MDCK cells. GFP positive plaques were used to inoculate 10-day old embryonated chicken eggs. Infectivity titers for all virus stocks were calculated the 50% tissue culture infectious dose (TCID 50 ) per mL as described in [52] .", "Western blot analysis for GFP (mouse anti-GFP antibody, Living Colors, Invitrogen 1:1,000) or viral NP (mouse anti-Influenza A NP antibody, Millipore 1:5,000) was performed on purified viruses amplified in embryonated egg allantoic fluid.", "MDCK or A549 cells grown on circular coverslips (12Cir-1.5, Fisher Scientific Pittsburgh, PA) were infected with virus for the time and multiplicity of infection (MOI) specified in the figure legends. The cells were fixed with 4% paraformaldehyde (PFA) and probed with anti-Influenza A NP antibody (Millipore 1:2,000) for one hour followed by Alexa Fluor-594 goat anti-mouse Fab' fragment (Invitrogen 1:2,000) for visualization of viral NP protein." ] },{ "paper_id": "e20c3efee1c9653c22821eb34138d6138daefe40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e20efa446b9d31196d08c2a0cf51d2c851bfbbad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The starting point for this article is a concern that this enthusiasm is often based on optimistic assumptions about the innovation process (essentially that 'good' innovations will inevitably flourish), while the need is to identify specific health systems challenges and assess the extent to which ICTs might play a role in addressing these. Too often the focus is limited to defining an appropriate technical packagereporting formats, equipment, software, training, etc.which long experience in OECD countries suggests is a necessary but by no means sufficient requirement [10] . Failure may just as easily result from institutional or social constraints, and stakeholder analysis may be as important as traditional information systems analysis [11, 12] .", "This entails a recognition that often \"use and development are twin processes and that they unfold in real time, mutually shaping each other as learning by using expands or narrows the technology's scope of application\" (p302) [21] . Greenhalgh and Russell [12] , argue that so-called 'evidence based' health sector innovations are typically subjected to a convoluted series of negotiations between stakeholders which serve to mediate often highly contested understandings and perceptions. Consoli and Mina [21] suggest that innovations implemented to solve a given problem will typically result in a series of new problems necessitating appropriate adaptations. Implementation can thus be viewed as \"trajectories of problems and solutions\" (p309).", "Central to this issue is the fact that there is no real incentive to generate information that might be extremely useful to those concerned with health policy or planning, but has no obvious relevance for the operational activities of a specific facility. One interesting example relates to the use of record identifiers. Each Chinese citizen is in possession of a Resident Identity Card (RIC), which includes a unique identification number. This number will be included on an individual's IDRIMS entry which, in theory, should allow it to be linked to their facility medical records. However, while these records will typically include a field intended to capture the RIC number, in many cases it will not be completed because the facility has organised its data around an alternative, internal, reference code." ] },{ "paper_id": "e22140a30bea1676104edacd5240407c1f0d36a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Functional sites in eukaryotic proteins which fit the description \"linear motif\" are specified as patterns using regular expression rules. ELM server provides core functionality including filtering by cell compartment, phylogeny, globular domain class (using the SMART/Pfam databases) and structure [34] . Individual functions assigned to different sequence segments are combined to create a complex function for the whole protein.", "where J is the Jacobian matrix, which is a vector (the gradient) for scalar-valued functions. The full Hessian matrix can be difficult to compute in practice; in such", "A B find appropriate leads against different diseases, which can further be screened in vitro and in vivo." ] },{ "paper_id": "e2309c084ac694227f0411037944e3829c04c777", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were means \u00b1 SD from three independent experiments in triplicate. Results were analyzed by Student's t-test. A p-value less than 0.05 was considered to be statistically significant." ] },{ "paper_id": "e2445316a3475f25e869fa303d9ec90f8739d40f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "were previously reported as being active against multiple targets (i.e., whether or not they were promiscuous inhibitors). Results were only available for I01, which had been tested in 708 independent studies. In these prior works, I01 was reported as active in 14 studies to different targets, as an inconclusive inhibitor in 11 experiments, and as a nonspecific inhibitor of steroidogenic acute regulatory protein (BioAssay AID 651611; https://pubchem.ncbi.nlm.nih.gov/bioassay/651611) (66) . Due to its apparent promiscuity, I01 was not considered further.", "Cell lines and plasmids. The following reagents were obtained through the AIDS Reagent Program, Division of AIDS, NIAID, NIH: TZM-bl cells (number 8129; from J. C. Kappes and X. Wu) (100) and replication-defective HIV vector pNL4-3.Luc.R-E-(number 3418; from N. Landau) (101) . The following reagent was obtained through BEI Resources, NIAID, NIH: vector pcDNA3.1 containing Zaire ebolavirus glycoprotein NR-19814 (102) . Plasmid pCMV-VSV-G was a gift from E. Freed (NCI-Frederick). The EBOV trVLP transfection plasmids pCAGGS-VP30, pCAGGS-NP, pCAGGS-VP35, pCAGGS-L, pCAGGS-T7, p4cis-vRNA-Rluc, and pCAGGS-Tim1 were a gift from H. Feldmann (NIH) (57) .", "293T cells (ATCC CRL-11268) and TZM-bl cells were cultured in Dulbecco's modified Eagle's medium (DMEM; Corning) supplemented with 10% heat-inactivated fetal bovine serum (FBS; Gemini Bio-Products) containing 100 g/ml of streptomycin and 100 U/ml of penicillin (DMEM-PS-10% FBS) in a 37\u00b0C incubator with 5% CO 2 atmosphere." ] },{ "paper_id": "e24a0cd976fbe3f6a625425e6c9899d52af1067f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Primary chicken embryo kidney cells were prepared as described previously [7] and maintained in Medium 199 and 5% fetal calf serum.", "BHK-21 cells were transfected by calcium phosphate precipitation with expression plasmids containing the spike gene or with an empty vector as control. The supernatant of the transfected cells was collected at 24 and 48 hours post-transfection and pooled. The supernatant was either purified via FPLC by protein-A columns or concentrated by spinning through a 100 kilo Dalton filter device (Millipore). Both preparations worked well for binding tests.", "In the Gammacoronavirus genus, the infectious bronchitis virus is an important pathogen in the poultry industry. The spike protein of IBV binds to alpha 2,3 linked sialic acids. A protein receptor has not been identified so far. In contrast to BCoV and HCoV-OC43, the virus lacks a receptor-destroying enzyme. The presence of such an enzyme may be dispensable for IBV because of a relatively lower affinity to sialylated glycans [7] .", "Soluble spike proteins were generated by fusion of the S1 gene portion to the human IgG Fc gene and insertion into the vector pCG1. For TGEV, the cDNA of the strain Madrid (genbank accession number: M94101) was used and for IBV the cDNA of the B1648 strain (genbank accession number: X87238 )." ] },{ "paper_id": "e24bf8c23979d56fff33bd4ed96fb00a117f701b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We compared antibody prevalence between sampling locations using a log-likelihood ratio test (G-Test) [33] . A 95% confidence interval (CI) was constructed for the prevalence." ] },{ "paper_id": "e24e562b0fc39ee100724833115384f3c56ffd6d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e2500283a378472050282da03b7d5e9612e4e5ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethical clearance for collecting and using secondary data in this study was granted by the institutional review board of the University of Southampton, England (No. 18152). All data were supplied and analyzed in an anonymous format, without access to personal identifying information.", "Supporting information S1 Appendix. The appendix includes the materials and methods of data collation and analysis, tables A and B, and figs A-U. (PDF)", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "e26b6173b72a118e2b65869e3ba0cc176a3bb751", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We defined the probability q i as:", "We estimated \u03b8 = (\u03b2 0 , \u03b2 1 , \u03b2 2 , \u03b2 3 , \u03b2 4 , k, \u03b8, \u03c3 2 ) simultaneously using MCMC and the following likelihood:", "Scientific RepoRts | 6:35839 | DOI: 10.1038/srep35839", "Approach 1: exact likelihood approach. The equation (1) and consequently using equation (2) we can define the following pdf of the normal distribution:" ] },{ "paper_id": "e27b2ec189028052ab97b7b959087ac012222a98", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .01503-17.", "FIG S1, TIF file, 1.7 MB. " ] },{ "paper_id": "e27de1e584ddc112681240ed674464f524869e3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Loop-mediated isothermal amplification (LAMP) is a method that can amplify DNA under isothermal conditions. It was first developed by the Japanese researchers, the LAMP employs a DNA polymerase and a set of four specially designed primers that recognize a total of six distinct sequences on the target DNA [12] . Later, LAMP was supplemented by using additional primers, termed loop primers which prime strand displacement DNA synthesis. Moreover, LAMP has some advantages in comparison with PCR methods, including improved sensitivity and specificity, as well as time efficiency [13] .", "Conventional PCR reactions were performed to amplify the fiber gene for construction of pMD19T-fiber plasmid ", "Since LAMP was published, a range of LAMP methods have been developed. The RealAmp is one of them, which attempted to improve the method for diagnosis by using a simple and portable device capable of performing both the amplification and detection by fluorescence in one platform [14] . Currently, the LAMP assays are utilized to detect bacterial and viral pathogens including Mycobacterium tuberculosis, Acinetobacter baumannii, avian influenza virus, Middle East respiratory syndrome coronavirus and hemorrhagic enteritis virus [15] [16] [17] [18] [19] ." ] },{ "paper_id": "e283c964691d950836fd62790ff4c032b8b1a56a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All reagents and solvents were purchased from Sigma-Aldrich (Milwaukee, WI, USA) and Alfa Aesar (Ward Hill, MA, USA). All experiments involving moisture-sensitive compounds were carried out in an argon atmosphere. Analytical thin-layer chromatography was performed on precoated silica gel F 254 thin layer chromatography (TLC) plates (E, Merck, Kenilworth, NJ, USA) with visualization under UV light. The final products were purified by preparative medium-pressure liquid chromatography (MPLC) (Biotage Isolera One instrument) on a silica column (Biotage SNAP HP-Sil) spectrometer (Biotage, Uppsala, Sweden). Nuclear magnetic resonance (NMR) analyses were performed using a Bruker 400 (400 MHz for 1 H; 100 MHz for 13 C) spectrometer (Bruker, Rheinstetten, Germany). The chemical shifts are reported in parts per million (\u03b4). The deuterium lock signal of the sample solvent was used as a reference, and the coupling constants (J) are given in hertz (Hz). The splitting pattern abbreviations are as follows: s, singlet; d, doublet; t, triplet; q, quartet; dd, doublet of doublets; and m, multiplet. The purity of all tested compounds was confirmed to be higher than 95% by analytical high-performance liquid chromatography (HPLC) analysis performed with a dual-pump Shimadzu LC-6AD system equipped with a VP-ODS C18 column (4.6 mm \u00d7 250 mm, 5 \u00b5m, Shimadzu).", "A mixture of 2 ,4 ,6 -trihydroacetophenone hydrate (2.0 g, 11.89 mmol), potassium carbonate (3.62 g, 26.17 mmol) and dimethylsulfate (2.32 mL, 24.38 mmol) in acetone (30 mL) was stirred under argon at 66 \u2022 C for 2 h. The resulting mixture was cooled to room temperature, filtered, and washed with acetone. The filtrate was extracted with ethyl acetate. The organic layer was washed three times with saturated NaHCO 3 solution, dried over Na 2 SO 4 , and concentrated under reduced pressure to produce compound 2 with 100% yield (R f = 0.34 (1:9 ethyl acetate: hexane); 1 DiNap was synthesized following the procedure reported in the literature with slight modifications [46] . Briefly, a mixture of compound 2 (0.2 g, 1.02 mmol), 1-naphthaldehyde (0.14 mL, 1.02 mmol) and potassium hydroxide (1 g) in methanol (20 mL) was stirred at 50 \u2022 C for 3 days. The mixture was extracted with ethyl acetate. The organic layer was washed three times with water, dried over Na 2 SO 4 , concentrated under reduced pressure, and purified by MPLC to produce DiNap with 32% yield (R f = 0.27 (1:9 ethyl acetate: hexane); 1 ", "The authors declared that there are no conflicts of interest." ] },{ "paper_id": "e28eedb8b780c3b08fa6a3d7d4c617f9587adc9a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e2904c6e462291682dc4d65ce47a91bdc8509747", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The discovery of host microRNA (miRNA) targets in the genomes of many vertebrate viruses indicates that the corresponding miRNAs are a part of the host's innate antiviral defenses. miRNAs are post-transcriptional regulators that bind to complementary sequences on target messenger RNA transcripts (mRNAs), resulting in translational repression and gene silencing 1 . miRNAs are considered to be a major group of functional non-coding RNAs (ncRNAs) that bind to mRNAs, resulting in target-specific post-transcriptional repression 2 . Growing evidence indicates that miRNAs can directly modulate viral replication and modify host cell responses to viral infection in a proviral or antiviral manner 3, 4 .", "Sequenced sequences were processed using Illumina's Genome Analyzer Pipeline software and then subjected to a series of data filtration steps, using the mammalian miRNA data in miRBbase v16.0, to obtain mappable sequences with the ACGT101-miR program. The merged reference database of the pig genome (2.26 Bbp) (Sscrofa9 ftp://ftp.sanger.ac.uk/pub/S_scrofa/assemblies/) and non-redundant ESTs (0.5 billion nt) (ftp://ftp.ncbi. nih.gov/repository/dbEST) were constructed as an available complete sequence database for pig (named the pig genome and EST) and used for mapping.", "Statistical analysis. Data extracted from 3 independent experiments were expressed as the mean \u00b1 standard deviation. Statistical relationships were assessed using Student's t test, considering P values < 0.01 (**) and < 0.001 (***) as significant." ] },{ "paper_id": "e29425dbc37811e314513aed5880fbd088f52971", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results of the present study are valuable for informing further studies and health policy in preparation for MERS outbreaks.", "The 38 of total 58 included studies were classified as epidemiologic studies (Table 1) .", "MERS causes sporadic infection and intrafamilial and healthcare-associated infection. Its symptoms can vary from asymptomatic infection to death. Despite the infection's association with high mortality, specified antiviral therapy is lacking, especially for patients with concomitant diseases [2] ." ] },{ "paper_id": "e296fa71274bad6cabcf683a2ba47e58b1326877", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We also read the story of an anonymous Canadian girl whose death was associated with a prescribed acne drug. She was eventually identified by the media who compared the de-identified prescription data set against obituaries. The comparison helped in narrowing down the search to four possible girls, then by contacting all families the right one was found [6] .", "This 'best practice guide' should be circulated to all journals who publish maps, clearly stating the risks involved in accepting point level maps. At least this would enlighten editors [49] and hopefully force them to ask submitting authors about 'what steps have been taken to preserve confidentiality?'", "There is some good news though, as we have noticed more researchers referencing steps taken to preserve confidentiality during recent presentations.", "The issues of location privacy were also the subject of GeoPKDD (Geographic Privacy-Aware Knowledge Discovery and Delivery [43] ), a three-year EU-funded project that was recently completed in November 2008. GeoP-KDD's main research question was 'how to discover useful knowledge about human movement behaviour from mobility data (e.g., location data from mobile phones), while preserving the privacy of the people under observation?' The project attempted to develop new privacy-preserving methods for extracting knowledge from large amounts of raw data about individuals referenced in space and time. GeoPKDD organised the 'First Interdisciplinary Workshop on Mobility, Data Mining and Privacy: Preserv-ing anonymity in geographically referenced data' on 14 February 2008 in Rome, Italy [44] ." ] },{ "paper_id": "e2b354fb613a71ab7f449318fe0d8c20d535e9b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinical signs of failure to thrive were overt in piglets being diarrhoeic for >1 day, and in some cases even 1 day of diarrhoea resulted in hollow flanks, protruding ribs and signs of dehydration. These findings match experiences from swine practitioners, that NNPDs is a debilitating syndrome, significantly affecting the well-being of piglets (personal communication, S.E. Jorsal).", "The secondary objective was to describe the course of disease in herds suffering from NNPDS.", "Litters (approximately 20 litters from one farrowing batch per herd) were standardized to 11 or 12 piglets by simple random sampling among littermates with a minimum birth weight of 800 grams. No cross-fostering was allowed.", "The results of the microbiological study suggested that neither ETEC, C. perfringens type A/C, C. difficile, rotavirus A, coronavirus, Cystoisospora suis, Strongyloides ransomi, Giardia spp nor Cryptosporidium spp were associated with the syndrome [6] ." ] },{ "paper_id": "e2b3cf2cab4bdb3f5d357c987852c829cb4f6995", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This research received ethics approval from the London School of Hygiene & Tropical Medicine Ethics Committee.", "The literature review and interviews were used to construct a timeline of the key events ( Figure 1 ). Results are ordered according to the five key research questions.", "1. What are the motivations of the parties involved? 2. Who are the actors involved in the process? 3. What forums did negotiations take place in? 4. What were the processes undertaken?, and 5. What were the outcomes of these processes." ] },{ "paper_id": "e2b435104da658ed6518247430cff1d428aae830", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Allele T Allele C" ] },{ "paper_id": "e2b5298da8d9d86daf286304637a644139dc6dc1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ELISA kit for TNF-\u03b1 was purchased from R & D systems (Minneapolis, MN, USA). and all other chemicals were purchased from Sigma-Aldrich (St. Louis, MO, USA)." ] },{ "paper_id": "e2b6aa71fbb89c9a10e9b00f36313ba5be05b025", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sodium dodecyl sulphate-polyacrylamide gel electrophoresis and western blot analysis Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blot assays were performed as described previously (32) . The anti-MBP polyclonal antibody was purchased from New England BioLabs, and used at the dilutions of 1:10 000.", "As one of the three major CPV capsid proteins, VP5 is also named as clamp protein or large protrusion protein.", "The ratio of released single strands versus the total substrates was quantified with ImageQuant software.", "*To whom correspondence should be addressed. Tel: +86 27 68756654; Fax: +86 27 68754941; Email: zhouxi@whu.edu.cn Unlike other multishelled reoviruses, cypovirus is the simplest genus of the family Reoviridae because it has only a single-layered capsid (7) , and this characteristic makes it an ideal and simplified model for studying the mRNA/dsRNA synthesis and mRNA-capping mechanisms of reoviruses and probably other dsRNA viruses (8) . For this reason, extensive molecular and structural studies have focused on CPVs in recent years (8) (9) (10) (11) (12) . However, our knowledge about the molecular mechanisms that orchestrate the segmented dsRNA genome replication of CPVs and other reoviruses is still limited." ] },{ "paper_id": "e2cef67ca136f4b301736031caac1aa1085abcb6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lastly, the turn-around-time of several hours from tumor resection or biopsy to vaccine manufacture and subsequent administration significantly expedites treatment compared to other immunotherapy approaches.", "Additional patients at three Sydney (Australia) veterinarian practices were treated on compassionate grounds after owners gave informed consent. All vaccines were provided at no cost to the owners. Figure 1 demonstrates the vaccine production process. ", "Advax\u2122 adjuvants are covered by patents owned by Vaxine Pty Ltd." ] },{ "paper_id": "e2de7af2f055e3cf79556848d5b6aa2d27c4b97d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ribavirin (>98% purity) and MTT were purchased from Tokyo Chemical Industry (Tokyo, Japan) and Sigma-Aldrich (St. Louis, MO), respectively. Anitbiotic-antimycotic and minimum essential medium (MEM) were purchased from Invitrogen (Grand Island, NY). Fetal bovine serum (FBS) was supplied by PAA Laboratories (Etobicoke, Ontario, Canada). The protein molecular weight standards (Precision Plus Protein all blue standards) were purchased from Bio-Rad Life Sciences (Hercules, CA). RIPA buffer and 1% mammalian cell protease inhibitor cocktail were purchased from Sigma-Aldrich. The primary antibodies used in this study were as follows: anti-ICAM-1 antibody [rabbit polyclonal to intercellular adhesion molecule-1 (ICAM-1)], anti-low-density lipoprotein receptor (LDLR) antibody (rabbit polyclonal to LDLR), and anti-actin antibody (rabbit polyclonal to actin) purchased from Abcam (Cambridge, UK). The secondary antibody (horseradish peroxidase conjugated goat polyclonal to rabbit) was supplied by Abcam. All of the other chemicals and reagents used in this study were of analytical grade quality and available commercially.", "Effects of PA and PGG on HRV titers were compared with those of ribavirin (Table 5) ", "Instrumental analysis 1 Merck silica gel 60 RP-18 F 254S plates (for RP-TLC) and an Agilent 1200 series high-performance liquid chromatograph (HPLC) (Santa Clara, CA) were used for isolation of active principles." ] },{ "paper_id": "e2eb9193178fb904a4a5c884b692c82ffc1eca43", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Anti-CD200R1 and anti-CD200 for cell surface staining were purchased from AbD Serotec. Goat anti-CD200R1 intracellular domain-specific antibody was from Santa Cruz. Anti-IL-1b was goat polyclonal anti-mouse IL-1b (AF-401-NA; R&D Systems). The primary antibody used in immunohistochemical studies was rabbit polyclonal anti-HSV2 (B0116; Dako) and the secondary antibody used was biotin-conjugated goat anti-rabbit (H+L) IgG (656140; Invitrogen). The secondary anti-rabbit antibody used in blotting studies was rabbit anti-goat (H+L) IgG HRP conjugate (172-1034; Bio-Rad).", "pentamer was from ProImmune Inc., Bradenton, FL). Cells were incubated with CD3/CD11b/CD8/gB + 498-505 pentamer and monoclonal antibodies following the manufacturer's protocol. Stained cells were washed twice with FACS buffer and fixed with BD Cytofix/Cytoperm solution for 20 min at 4uC. Following fixation, the cells were washed twice in BD Perm/Wash buffer, resuspended in 4% paraformaldehyde, and analyzed using a multicolor five-laser LSR II instrument (BD Biosciences, San Diego, CA).", "An unpaired, two-tailed Student's t-test or a Kruskal Wallis test was used to determine statistical significance where indicated. Statistics were performed using GraphPad (Prism v5.0d) software. Values of P,0.05 were considered significant." ] },{ "paper_id": "e2fbe8d2a00bf0e7041a1b7c9e08c80ef87cb5cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The production system used depends on the need to retain more consistent original VLP formation and post translational modifications (PTMs, e.g., glycosylation and phosphorylation) while significantly reducing production times and costs. All production systems have advantages and drawbacks as discussed briefly.", "MM conceived the initial draft of the manuscript. DW, JT, EG, and BG-B revised many parts of the manuscript, and contributed to finalize the manuscript.", "The purity, potency and consistency of the particles and elimination of host cell and culture media contaminants are crucial for the downstream processing of VLP-based vaccines. In addition, the purification methods should be robust, costeffective, scalable and preferably applicable to a wide variety of VLPs." ] },{ "paper_id": "e3090e4e8baa6df559f0299519ad77821a09f873", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "pandemics. Public health measures such as travel restrictions then become essential in controlling pandemic spread.", "We denote bin(m, n) as a binomial distribution with probability m and number of total individuals n. The distributions of the classes are", "where \u03b2 is the disease transmission rate and 1/\u03b1 is the average latent period. The probability of a susceptible per-" ] },{ "paper_id": "e30e44f2eb7f2effe677e665ad14ad511ac17c3f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dating when viruses acquired the ability to infect human genomes is paramount to managing public health. Infections could occur directly and repeatedly via other animal hosts (e.g. Human Immunodefi ciency Virus, West Nile Virus). But, if infections were manifested secondarily, as a consequence from viral sequence substitutions that allowed sustained transmission among humans-as recent reports suggest for Avian Infl uenza Virus-a pandemic could ensue, with casualty numbers greatly exceeding those for infl uenza pandemics from the past century (Nicholls, 2006; Thomas and Noppenberger, 2007) .", "Researchers routinely adopt molecular clock assumptions in conducting sequence analyses to estimate dates for viral origins in humans. We used computational methods to examine the extent to which this practice can result in inaccurate 'retrodiction.' Failing to account for dynamic molecular evolution can affect greatly estimating index case dates, resulting in an overestimated age for the SARS-CoV-human infection, for instance.", "Pinpointing viral origins in humans enables researchers to extrapolate backward to estimate index case dates, calculate mutation and substitution rates, and document genetic events that permit effi cient interspecies transmission and enhanced virulence (Chen et al. 2004) . These data enable researchers to extrapolate forward to predict variability and develop vaccination or management programs to prevent or respond to potential global outbreaks. Herein, we show that adopting molecular clock assumptions can yield inaccurate estimated origin times, considering as an example data from the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) infection in humans." ] },{ "paper_id": "e30f5f76a403e0a60d32f941c32fb5e0cd08c458", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results are presented as mean 6 SEM of three experiments. One-way ANOVA with Tukey's post test was performed using GraphPad InStat Version 3.00 for Windows 95 (GraphPad Software, San Diego, CA, USA). P value ,0.05 was considered statistically significant.", "Densitometry and band quantization was performed using BioRad Quantity One software.", "To our knowledge, no investigation has so far been carried out about SIRT and FOXO families proteins involvement on other viral infection." ] },{ "paper_id": "e31625f324f8a44bca6c701f2c6e6d7c09a0830c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Diarrheic stool was collected on site using sterile containers. Wet mount microscopy, using direct saline and iodine smear, and modified acid-fast staining was performed for the detection of Cryptosporidium, Isospora and Cyclospora species. Stool microscopy was performed by two experienced laboratory technologists and discordant results were resolved by a local microbiology expert. After microscopy was performed, specimens were stored at 4\u00b0C for 1 month until further molecular testing was performed.", "Correlations between patient characteristics, symptoms, epidemiological risk factors and enteropathogen (s) were explored using STATA (Version 14.1). Categorical variables were analyzed using Pearson chi-squared or Fisher's exact test. Continuous variables were analyzed using two paired t-test for normally distributed variables, two-sample Wilcoxon rank-sum test for non-normally distributed variables and linear regression or Spearman rank test for two continuous variables.", "Out of the 100 specimens, 28 were positive for intestinal parasites using wet mounts and modified acid fast staining. C. parvum was the most common parasite at 28.6% followed by E. histolytica (17.9%), G. lamblia at (14.3%), C. cayetanensis (14.3%), S. stercoralis, (7.1%) and hookworm (3.6%)." ] },{ "paper_id": "e319e1968d1de70b511e1b51fa5a69b3c75e41d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Wild-type (WT) C57BL/6 male mice were purchased from Charles River Canada (St-Constant, Quebec, Canada) whereas CCR2 \u2212/\u2212 (B6.129S4-Ccr2tm1Ifc/J) male mice, which are maintained in a C57BL/6 background, were purchased from the Jackson Laboratory (Bar Harbor, ME). Animals were acclimated to standard laboratory conditions (12 h light/dark cycle; on at 7:15 and off at 19:15) and housed 3 to 4 per cage. All animals were used in accordance to the Canadian Council on Animal Care guidelines and the protocol was approved by the Animal Care Ethics Committee of Laval University (protocol no. 2013078).", "Differences in mouse survival rates were compared using a log-rank (Mantel-Cox) test. Differences in infectious viral titers, cytokine and chemokine levels and percentages of infiltrating cells in brain homogenates were evaluated using a one-way analysis of variance (ANOVA) with Tukey's multiple comparison post-test. All statistical analyses were carried out using the GraphPad Prism software program, version 5.00 (GraphPad Software, San Diego, CA). A P value 0.05 was considered statistically significant.", "doi:10.1371/journal.pone.0168034.g006" ] },{ "paper_id": "e31f9523d25a534a48452c6d78bd02b9c0222bca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pathogen-confirmed cases (by cultures or rarely ancillary antigenic/antibody testing) allow for direct comparisons to derive diagnostic thresholds of sequencing output (e.g., number of specific pathogen reads, community diversity indices) associated with bacterial culture positivity above clinically accepted thresholds (e.g. \u03fe10 \u03ea4 CFU). Culture-positive cases also offer the opportunity to refine predictive algorithms of antibiotic resistance gene detection versus clinical antibiograms (14) , so that real-time antibiotic recommendations would become feasible. Consequently, observational studies of culture-confirmed cases can help develop statistical models and/or train machinelearning algorithms for sequencing-based definitions of pneumonia (pneumonia index).", "The recent wave of human lung microbiome research was made possible by the development of next-generation sequencing (NGS) techniques. Without the need for ex vivo growth and isolation of microbial species, amplicon-based sequencing of the highly conserved 16S rRNA gene (16S sequencing) in bacteria has uncovered bacterial communities in respiratory health and disease that are low in biomass but complex in composition, debunking long-held dogmas of \"lung sterility\" (6) .", "Shotgun approaches are not ready for clinical prime time, not just due to technical challenges but also because we still lack the diagnostic test framework to utilize their output. Feeding sequencing reports to clinicians without the obligatory (but yet to be developed) interpretive decision support would stir more confusion and clinically inappropriate decision making. As a clinical investigator, I am looking at the future research needs and the type of clinical studies that will allow us to develop actionable diagnostic tests, with a primary focus on metagenomics for the diagnosis of bacterial pneumonias that mandate targeted antibiotic therapies." ] },{ "paper_id": "e332700e155cc5fdda4cb03b94d23df42647911b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bombyx mori, the domesticated silkworm, is an economically significant insect in silk production [1] . Farmers in many developing countries such as China, India, Brazil, Vietnam, and Thailand are evolving sericulture as a foremost income source. China, the biggest cocoon producer (almost 80%) worldwide, generated a sericulture-based income of 22.4 billion \u00a5 (Yuan) (approximately equal to USD 3.24 billion by March 2017) by producing 6.61 \u00d7 10 8 kg of cocoons in 2011 [2] . Moreover, this lepidopteran insect has become a model organism for several fundamental studies in biochemistry, molecular genetics, and genomics [3, 4] ." ] },{ "paper_id": "e33495040bf8950cd13d754656a31f9b9bdad01d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The planned subgroup analysis excluding patients who had infection proven elsewhere after enrolment e.g. urinary tract infection (n = 33) did not substantially alter any of the above results.", "(Continued on next page)" ] },{ "paper_id": "e33688801d9c88a6e02f0cd0775b31ad8d911c58", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pet dogs play an important role in humans' daily lives. Recently, the emergence of new pathogens and the continuous circulation of common etiological agents in dog populations have complicated canine diseases [1] . Among these diseases, canine infectious respiratory diseases (CIRD) and viral enteritis pose notable threats to dog health. a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "All procedures in the sample collection met the requirements and were approved by the Experimental Animal Welfare Ethics Committee of the South China Agricultural University.", "Viral respiratory and intestinal infections are the most common causes of canine viral illness." ] },{ "paper_id": "e344d21fb68d14bed65d7fbdc97164e61717a0f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The compounds were retrieved from public available database KEGG [14] (Kyoto Encyclopedia of Genes and Genomes) compound", "where m is the argument of j that maximize the value of S(C q [j).", "where", "For the j-th order prediction, the accuracy W j was calculated by " ] },{ "paper_id": "e35886a4c45a6f26a17e68185b4172fb32ceb452", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ", while H1N1 is known as a seasonal strain and caused pandemics such as the 1918 Spanish flu and the 2009 swine flu [5] .", "Competing Interests: The authors have declared that no competing interests exist.", "Materials and Methods", "Cells of the human embryonic kidney epithelial cell line HEK293T (ATCC, USA) were cultured in Dulbecco's modified minimal essential medium supplemented with 100 U penicillin and 10% fetal bovine serum at 37\u00b0C and 5% CO 2 ." ] },{ "paper_id": "e372562d7379dd73d838995bc9178634c865ba39", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although RNAi has many advantages over other genetic drug technologies, several problems, such as cellular delivery, stability against nuclease degradation, and side effects (off-target effects and interferon responses at high concentrations), must be solved before it can be applied in the clinic [14] [15] [16] [17] [18] [19] [20] .", "HeLa cells, which were obtained from the RIKEN Bioresource Center Cell Bank (Tsukuba, Japan), were cultured in Dulbecco's modified Eagle's medium (DMEM; Wako, Osaka, Japan), supplemented with 10% heat-inactivated FBS (Invitrogen, La Jolla, CA, USA), 100 U/mL penicillin, and 100 \u03bcg/mL streptomycin (Wako). The cells were cultured in a humidified atmosphere of 5% CO 2 in air at 37 \u00b0C.", "All of the siRNAs (20 pmols each) including the peptide conjugates were mixed with 1 U of recombinant Dicer (Gene Therapy Systems, San Diego, CA, USA) in 10 \u03bcL of 20 mM Tris-HCl (pH 8.0) containing 15 mM NaCl and 2.5 mM MgCl 2 . The mixtures were incubated at 37 \u00b0C for 12 h, and the reaction was stopped by adding 2 \u03bcL of stop solution (Gene Therapy Systems). The reaction products were electrophoresed on 20% PAGE (30 mA, 70 min) and visualized by silver staining (DNA Silver Stain Kit; GE Healthcare, Piscataway, NJ, USA). The signals of the reacted products were photographed by the LAS4000 imaging system (Fujifilm, Tokyo, Japan)." ] },{ "paper_id": "e3785336f334b853b3d269a8301dfc564f5fae74", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For " ] },{ "paper_id": "e37ede300a3a671cb392f6a06e5b5e0af6e34fd9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results suggest that these new NNRTIs may be used to treat patients against HIV-1 mutants resistant to the currently available RTIs. ", "CEMx174 5.25M7 cells, HIV-1 inhibitors AZT, TMC125, and NVP, laboratory-adapted HIV-1 strains IIIB and Bal, primary HIV-1 strains 94US_33931N and 93IN101, AZT-resistant strains 964 and 629, and the RTI-resistant strain RTMDR1 were all obtained from the National Institutes of Health AIDS Research and Reference Reagent Program. The small molecules NNRTI DAPA-2e, DAAN-14h, and DAAN-15h were synthesized as previously described [5] [6] [7] [8] .", "Author Contributions: S.J. conceived, designed, and supervised the project; F.Y., W.L., L.W., Y.D., X.L., and Q.W. performed the experiments, S.J., F.Y., W.L., and L.X. integrated all the data and wrote the paper." ] },{ "paper_id": "e38a8320180661475487156ee68de426868e6c45", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "3.2. The Role of Endolysosomal Ca 2+ Signaling in Cancer: Are Two-Pore Channels the Guilty Ones?" ] },{ "paper_id": "e39549d1d4e49cf191e2c743e6b82b738e3b21f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The approximate distribution of each detected RABV lineage was visualised using ArcGis (ESRI ArcGis version 10.0) at the highest spatial resolution available for virus locations (Fig. 4) .", "doi:10.1371/journal.pntd.0003569.g002 ", "No animals were used for this study. Brain samples were analysed that had previously been taken for diagnostic purposes, from animals that were already dead, with the permission of the local competent authority." ] },{ "paper_id": "e398a3cd7f7d75bc06f0f15103309511299bb653", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Biology (whole organism) Subject Areas: computational biology/health and disease and epidemiology/computer modelling and simulation", "MT, 0000-0001-7246-2341", "and", "2017 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited." ] },{ "paper_id": "e39c8a18a3d59b83951c4ebc331c17a54e6dacab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Variola virus caused a deadly human disease smallpox until its global eradication in 1977 [1, 4, 5] , in which VV was used as a vaccine. Other poxviruses causing human diseases are molluscum contagiosum virus and the zoonotic monkeypox virus [6, 7] . Notably, variola and monkeypox viruses are transmitted to humans by respiratory route, whereas molluscum contagiosum virus is mainly transmitted through the skin. Variola and monkeypox viruses cause systemic infections with high levels of lethality, but the details of their pathogenesis are not well-understood.", "Vaccinia virus (VV) is a member of the Poxviridae, which constitute a large family of enveloped DNA viruses and replicate entirely in the cytoplasm of the infected cells with a linear double-stranded DNA genome of 130-300 kilo base pairs [1] . Poxviruses have a broad range of eukaryotic hosts including mammals, birds, reptiles and insects [2, 3] and can grow in many cell lines in vitro. Some poxviruses are causative agents of human diseases." ] },{ "paper_id": "e3b40cc8e0e137c416b4a2273a4dca94ae8178cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bed rest, strengthen supportive treatment, ensure sufficient energy; pay attention to water-electrolytes balance and maintain the stability of the internal environment; closely monitor vital signs and finger oxygen saturation, and so on. B.", "In December 2019", "Antiviral treatment: no effective antiviral drug at present. Treat with IFN-\u03b1 aerosol inhalation (five million U per time for adults, two times per day), and/or Lopinavir/Ritonavir oral administration (two tablets per time, two times per day). E.", "Case detection and report, isolation, diagnosis, and treatment; clinical management and prevention and control of nosocomial infections; sample collection and detection, and training of medical staff in the institution." ] },{ "paper_id": "e3b748c735f2ba33e17ce4d92cfac9293b1c4866", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "development of autoimmune disease, and B-cell-targeted therapies are effective in the treatment of human autoimmune diseases 5 .", "After receiving a diagnosis of NSIP, all patients received a course of oral prednisone that began at 0.5 to 1.0 mg/kg/d for 1 month and was tapered every 3 weeks to 5.0 to 7.5 mg/d (the dose was decreased by 10% of the initial dose every 3 weeks); the dose was then maintained at 5.0 to 7.5 mg/d." ] },{ "paper_id": "e3c13df830390513f48908347eb132df3f2a773e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Where diseases were specifically mentioned, they were classified according to the relevant chapter in the British National Formulary (BNF), 63rd edition (British Medical Association and the Royal Pharmaceutical Society, 2012).", "Following data extraction, codes were entered into SPSS (version 19, SPSS Inc, USA) for analysis of trends and comparison of variables between countries. Descriptive statistics were used to summarise the data. The Mann-Whitney U test was used to test for differences between means of continuous variables. Differences in the reporting of categorical variables in UK and US articles were assessed using the Chi square test (\u03c7 2 ) or the Fisher's Exact test, as appropriate. Statistical significance was set at 0.05.", "The primary researcher (BMcC) used the final coding form to manually code the selected articles. A second coder coded a 10% random sub-sample blindly and Cohen's kappa (\u03ba) scores were calculated to assess interrater agreement for questions with mutually exclusive answers. Questions with more than two answers were dichotomised, for example, \"Type of benefits of healthrelated use of the Internet\" (nine options provided), was collapsed to \"Was a benefit stated?\" (yes/no).", "Initially, 749 newspaper articles were retrieved, of which 161 articles, 74 from UK papers and 87 from US newspapers remained following removal of duplicates and excluded articles (Figure 1 ). Inter-rater kappa values ranged from 0.5 to 1.0, indicating moderate to perfect agreement between coders [24] . The mean inter-rater kappa value across all of the coded variables was 0.65; this is similar to the level of inter-rater agreement reported in previous quantitative content analyses involving the newspaper media [19, 25] ." ] },{ "paper_id": "e3c22f7e1409db69c1be9a7ae76319405506aaea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Example files and tutorial related to the present study. (ZIP 36167 kb) ", "Step 2: Estimation of dispersal and epidemiological statistics", "Step 5: Significance testing using randomisation" ] },{ "paper_id": "e3c77bacc976ab718dae1e74bedb00219d701c3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In conclusion, there was an annual periodicity and seasonal variation of HFMD incidence in China, which could be predicted by a SARIMA (1, 1, 2) (0, 1, 1) 12 model. ", "The monthly incidence data of HFMD from May 2008 are released by the National Health and Family Planning Commission of the People's Republic of China (http://www.nhfpc.gov. cn/zwgk/rdts/ejlist.shtml, accessed on 12/8/2018). In China, all HFMD cases verified by the clinical diagnosis must be reported within 24 h via the Infectious Disease Information Management System. Duplicate cards from the same person must be checked and deleted by the end of each month. Ethical approval is not required for this study because these are secondary data for public access.", "China's self-developed inactivated monovalent EV-A71 vaccine was recently approved and is commercially available (http:// www.nhfpc.gov.cn/qjjys/s3594r/201512/fa403581683d4b619b-cee477aa15423e.shtml, accessed on 12/6/2018), and this is the first vaccine against EV-A71 in the world. The inactivated monovalent EV-A71 vaccine showed high efficacy (94.8-97.4%) against EV-A71-associated HFMD [8] . In addition, compared with no vaccination, routine paediatric EV-A71 vaccination would be very cost-effective in China [10] . Monovalent CV-A16 vaccine and bivalent EV-A71 and CV-A16 vaccine are under development. Therefore, with the inclusion of major circulating viruses in the development of multivalent HFMD vaccines, an increase in the success in HFMD control is anticipated." ] },{ "paper_id": "e3d75d7baf118918395a6950b724215ec2c8023c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ". For details, we refer the reader to [29] .", "It's worth noting that, if we change the parameter N and k, the frequency of different k-mers were consistent.", "Typing results by two methods " ] },{ "paper_id": "e3de6d6d50592102725cbe2ee5cb0fe02b851aac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although resveratrol was widely studied for its anti-proliferative mechanisms by inducing reactive oxygen species production and disrupting the release of cytochrome c from the mitochondrial membrane, which leads to cell death in various cancer cell lines [35] , references on the precise mechanisms of antiviral activities remain lacking.", "Natural medications are attracting increasing interest in the development of potential anti-viral drugs. We have been engaged in research on thistopic for a long period. Many herbs were investigated for their antiviral activities in our laboratory [8] . Resveratrol, a non-flavonoid polyphenol compound, is a naturally occurring phytoalexin produced by several higher plants such as mulberries, peanuts and grapes in response to stress or injury induced by environmental hazards [9] . This compound has been shown to possess high bioactivities against many diseases, such as cancers, cardiovascular diseases, inflammation, diabetes and viral diseases. In several studies, resveratrol was found to increase the potency of several antiretroviral drugs synergistically against human immunodeficiency virus (HIV) [10] and herpes simplex viruses (HSV) [11] . Resveratrol was also found to be effective in treating influenza virus and severe acute respiratory syndrome (SARA) [12] . In an in vivo study, 25% resveratrol cream could significantly inhibit the development of HSV-1 induced skin lesions on the abraded epidermis of SKH1 mice, and the therapeutical effect is the same as that of 5% acyclovir cream [13] .", "All data are representative of at least three independent experiments. Data are presented as mean 6 SD. Statistical significance was calculated using the SPSS 17.0 software.", "Duck enteritis virus (DEV), a member of the alphaherpesvirinae subfamily of the herpesviridae, is an acute, contagious virus infection that naturally occurs in ducks, geese and swans, which are all members of the family Anatidae of the order Anseriformes [1] . In susceptible flocks, this disease can be transmitted by direct contact or indirectly through environmental contamination [2] , [3] . It causes significant economic losses in domestic and wild waterfowl as a result of mortality, and decreased egg production [4] . As a major method for controlling this disease, the expanded use of vaccines could bring considerable benefit in reducing infected ducks morbidity and mortality, but sometimes infection could still not be prevented [5] , [6] , [7] ." ] },{ "paper_id": "e3f168287dc3669b48862c0e70e000fc49edf00a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Significant difference between two groups was determined by paired Student's t-test, with statistical significance set to p < 0.05. Each experiment was repeated at least three times on separate occasions. ", "TAPI-1 (1 \u00b5M) was pretreated for 60 min, and then were treated with TNF (100 ng/mL) in various durations. Supernatants were analyzed by ELISA according to manufacturer's recommendations.", "This study was performed to verify the hypothesis that EGFR-TKIs induce pneumonitis by blocking EGFR transactivation by TNF. The mechanisms of EGFR-TKI-induced pneumonitis have not been completely elucidated. However, this study provides evidence that EGFR tyrosine kinase activity prevents lung injury in a TNF-enriched environment. Furthermore, we have found that in lung epithelial cells BEAS-2B, TACE is required for TNF-induced EGFR activation and that PI3K/AKT is a target of EGFR transactivation. These findings show that transactivation of EGFR prevents TNF-induced lung epithelial cell apoptosis." ] },{ "paper_id": "e3f7e8c04762fc684f7ebfda560df8492e29929a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An UltraCleanTM DNA Blood Spin Kit (Mo Bio Laboratories, Carlsbad, USA) was employed for the DNA extraction from whole blood. Before the PCR amplification, DNA was evaluated for quality at 260/280 nm and quantified at 260/230 nm using a NanoDrop TM spectrophotometer (Thermo Scientific, Waltham, USA).", "It is still unknown how feline hemoplasmas are transmitted. Vector transmission through fleas [12] [13] [14] [15] [16] or ticks [17, 18] has been suggested, but direct transmission through aggressive interactions or blood transfusion have also been hypothesized as potential sources of infection.", "Purification of amplified DNA fragments obtained for the first PCR was obtained using the Speed Clean-Up kit (Biotools, Madrid, Spain) and subsequently sequenced in an automated 3730 DNA Analyzer using a Big Dye Terminator 3.1 (Applied Biosystems, Foster City, USA) in Secugen S.L. (Madrid, Spain). Data obtained were compared with reference sequences deposited in GenBank, using the Basic Local Alignment Search Tool (BLAST)." ] },{ "paper_id": "e3fe1b272c977754c55719ab93e90ecb0b9472d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Induces SG-like structures recruiting TIA-1, TIAR y PCBP2 [195] Paramyxoviridae", "TTP/BRF1 [117] hnRNP Q [124] Xrn1 [117] IPO8 [125] YB-1 [126] JNK [127] Lin28 [128] ", "Several viruses are known to disrupt P-bodies. Here, we will summarize the most up-to-date information known about the relationships between viruses and PBs (Table 3) ." ] },{ "paper_id": "e4007988dba3dcfa65314d50324bdff1ba7f55c2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "taneously ligated together. Transcription was driven using a T7 mMessage mMachine kit (Ambion), and RNA was electroporated into Vero cells. Virus viability was determined by CPE (cytopathic effect, in this case cell rounding and detachment), and progeny viruses were passaged at low multiplicity of infection (MOI). RNA was recovered from infected cell monolayers using TRIzol (Invitrogen) according to the manufacturer's instructions, and retention of introduced mutations was verified by RT-PCR and DNA sequencing.", "To measure the differences in nucleotide distributions between two samples, the root mean square deviation (RMSD) between them was calculated. Using the position profile that was generated for each sample based on the RazerS read mappings, positional nucleotide distributions were computed and then compared using a modified version of the standard RMSD formula [27] :", "Two-tailed Wilcoxon rank-sum tests and Pearson's chi-square tests were performed using STATA 9.1 software (StataCorp, College Station, TX). For all statistical tests a P value of ,0.05 was considered significant." ] },{ "paper_id": "e4065a39d9df47f5987404da83abbf7a10fa57db", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Amyloidogenic proteins are capable of misfolding and assembling into amyloid deposits which are considered to be important causative factors of amyloid diseases such as Alzheimer's disease, Parkinson's disease and type 2 diabetes mellitus 1-3 . In pathological situations, amyloidogenic proteins aggregate into oligomers, followed by forming extensive linear fibrils, which is accompanied with a structural transition into \u03b2 -sheet-rich structures 4-9 . Studies have shown that the oligomeric intermediates are the most toxic species during amyloid aggregation 10-13 , which induce cell apoptosis mostly by penetrating the lipid bilayer of the cell membrane 14-16 . Preventing amyloid proteins from aggregating into toxic conformers has thus become a strategy to prevent or treat amyloid diseases 17 .", "Human calcitonin (> 95%) was obtained from GL Chemicals Ltd. (Shanghai, China). Mag, Hon and EGCG were from Aladdin-reagent (Shanghai, China). Anti-oligomer antibody (OC), anti-fibril antibody (A11) and anti-rabbit IgG were obtained from Merck Millipore (Billerica, USA). Thioflavin-T (ThT), 2-Oleoyl-1-palmitoyl-snglycero-3-phospho-rac-(1-glycerol) sodium salt (POPG) and carboxyfluorescein were from Sigma-Aldrich (St. Louis, USA). SH-SY5Y cells were obtained from the China Center for Type Culture Collection (CCTCC). All other chemical reagents were of the highest grade available.", "Dynamic light scattering (DLS) analysis. Dynamic light scattering was performed on a zeta pals potential analyzer (Brookhaven Instruments, USA) as we described before 78 . Briefly, samples were measured with a scattering angle of 90 o . Each sample was scanned for three times (1 min/scan), and the data were analyzed by the multimodal size distribution (MSD)." ] },{ "paper_id": "e408e143da8a102c318c2d30be909628b96e1175", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step four: Conduct annealing reactions of PAGE-purified DNA fragments in pairs.", "3. Heat tubes up to 94\u02daC in an electric heating block, anneal for 5 min, and then allowed them to cool gradually to room temperature (RT).", "Three male New Zealand white rabbits purchased from SIPPR-BK Lab Animal Co., Ltd. (Shanghai, China) were caged at controlled temperature of 25\u02daC. All the performed experiments were in full compliance with standard laboratory animal care protocols approved by the Institutional Animal Care Committee of SIPPR. These rabbits were immunized intramuscularly with 1 mg of purified E. coli-expressed recombinant human zona pellucida glycoprotein-4 corresponding to amino acid residues from 227 to 463 (r-huZP4C 227-463 ) emulsified in 0.5 ml of complete Freund's adjuvant and 0.5 ml of PBS at multiple sites on rabbit's back. Three booster immunizations of 0.5 mg r-huZP4C 227-463 protein in incomplete Freund's adjuvant were administered at 3-week intervals. Sera were collected from each rabbit seven days after each vaccination and stored at -70\u02daC." ] },{ "paper_id": "e411c54208dfc5d918d46642a7f1694fcc681cf4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Few comprehensive data exist regarding the epidemiology of severe acute respiratory infections (SARI) in low income countries. This study aimed at identifying etiologies and describing clinical features of SARI-associated hospitalization in Madagascar.", "Nasopharyngeal, blood, and sputum specimens were collected for each patient enrolled from Monday to Friday and shipped the same day to laboratories located at the Pasteur Institute of Madagascar where they were immediately processed or stored at 4\u02daC until testing (test were performed within 48 hours post-sampling). All procedures for the biological analyses have been previously described [18, 19] . Briefly, nasopharyngeal swabs were screened for 14 respiratory viruses using in-house multiplex real-time PCR [19] . Sputum was collected for cytobacteriologic testing while blood samples were used for cell blood count." ] },{ "paper_id": "e42218bb9ddb954382e0db792ffeae988bf62545", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Purified recombinant proteins were separated by 12% SDS-PAGE and transferred onto a nitrocellulose membrane, as previously described [31] . The membrane was blocked for two hours in 5% non-fat milk. Mouse anti-His monoclonal antibody (Sigma, Munich, Germany) diluted 1:3000 in non-fat milk or serum samples diluted 1:50 in non-fat milk were added, and membranes were incubated for one hour at room temperature. Membranes were then washed three times with PBS-0.1% Tween and incubated for one hour at room temperature with the secondary antibody, IRDye 680 goat antimouse monoclonal antibody (Li-COR Biosciences, Nebraska, USA) or horseradish peroxidase-conjugated goat anti-human IgG monoclonal antibody (Sigma, Munich, Germany). Subsequently, membranes were washed three times with PBS-0.1% Tween, then developed using Odyssey (Li-COR Biosciences) or a tetramethylbenzidine (TMB) substrate (Thermo Scientific, Rockford, USA) according to the manufacturers' instructions.", "Seropositive rates were evaluated using \u03c72 tests. Mean antibody titers between children and adults positive for hMPV and hRSV exposure were analyzed using the Mann-Whitney U test. A P value \u2264 0.05 was considered statistically significant.", "Human metapneumovirus (hMPV), thought to belong to the Metapneumovirus genus of the Pneumovirinae subfamily, is a recently identified human respiratory pathogen first isolated from hospitalized children with acute respiratory infections (ARIs) in the Netherlands [1] . The viral genome, clinical manifestations, and epidemiology associated with hMPV are similar to those of human respiratory syncytial virus (hRSV), which was identified in 1956 and is the most important viral agent responsible for ARIs in children [2] [3] [4] ." ] },{ "paper_id": "e423977e8070a5037558ac9dfdd78a6db6a64d58", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ". . Flow Cytometry Analysis. Frozen PBMCs were thawed in a 37 \u2218 C water bath and then cultured overnight at 37 \u2218 C in RPMI-1640 (Gibco BRL) supplemented with 5% human AB type serum and labeled with FITC-, APC-, and/or PEconjugated murine anti-human monoclonal antibodies. The CD3, CD3CD4, CD3CD8, CD3CD16CD56, and CD4CD25 phenotype of lymphocytes were sequentially analyzed by flow cytometry (FACS caliber, 4 color system, BD Bioscience, CA, US).", ". . Sample Collection. All blood samples were collected before the hypothesis of this study was known. The blood samples were collected using Na-heparin plasma tubes from enrolled patients before IRE (preOP) and then on days 3 (D3) and 7 (D7) after IRE. Isolation of peripheral blood mononuclear cells (PBMCs) was processed immediately using Hypaque-Ficoll (Promega) and frozen in liquid nitrogen in 5% (v/v) plus 95% (v/v) autologous serum [20] .", "Here, immunomodulatory effect of IRE was examined by analyzing alterations of several immune cells and indexes in patients with LAPC. We aimed to evaluate the response to IRE therapy during the early treatment phase and identify their role in prognosis." ] },{ "paper_id": "e4281a03ae26dbf7a445f1697dde5b4352fec07b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thirty grams of S. baicalensis crude powder (Sun Ten Pharmaceutical Co., Ltd.) were dissolved in 200 mL ethyl acetate (EtOAc), methanol (MeOH), or chloroform and then gently sonicated 30 min at room temperature. Extract solutions centrifuged were filtered with Whatman No. 1 filter paper, then lyophilized by the freeze dryer (IWAKI FDR-50P). Each lyophilized extract powder was kept at \u221220 \u2218 C; stock solutions (1 mg/mL) dissolved in phosphate-buffered saline and sterilized using a 0.44 m syringe filter were stored at \u221280 \u2218 C until used.", "Of them, only baicalein showed therapeutic index greater than 2 (CC 50 /IC 50 plaque reduction) against both variants. Interestingly, virus yield assay with real-time PCR indicated these flavonoids with higher antiviral activity after infection than simultaneous treatment ( Figure 5 ).", "Su-Hua Huang is a cofirst author." ] },{ "paper_id": "e42c06c072d59a6eb0f4ae89f74cc4f4689644b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The animal experiment protocols were approved by the Animal Ethics Committee of Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences (CAAS), and the methods were conducted in accordance with the approved animal ethics guidelines. The Animal Ethics Committee approval number was SYXK (Hei) 2,015,042.", "Statistical analysis was performed using GraphPad Prism software (version 5.02 for Windows; GraphPad Software). Comparisons between groups were analyzed using the analysis of variance (ANOVA) test. A P-value less than 0.05 was considered to indicate statistical significance.", "Additional file 1: Figure S1 . " ] },{ "paper_id": "e42f45097fff6577e1ba2da76661b56f7bff299a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Badger [36] describes further practical considerations in crystal preparation, soaking, cryoprotection, structure refinement and electron density interpretation.", "In this review, we shall address practical considerations in FBS by crystallography and provide examples of its use in successful drug discovery programs, highlighting cases where complementary approaches have assisted the discovery process, and some potential pitfalls.", "Several commercial fragment libraries suitable for crystallographic screening are available. Zenobia Therapeutics (San Diego, CA, http://www.zenobiatherapeutics.com) distributes two sets of compounds \"Library 1\" (352 compounds) and \"Library 2\" (286 compounds). Maybridge (Cornwall, UK, http://www.maybridge.com) distributes the Ro3 (Rule of 3) 2500 Diversity Fragment Library consisting of a \"core set\" of 1000 compounds with a \"supplement set\" of 1500 compounds. Otava (Kyiv, Ukraine, http://www.otavachemicals.com) supplies fragment libraries from a set of 7129 compounds. ChemBridge (San Diego, CA, http://www.chembridge.com) distributes a >7000 compound fragment library. All libraries use the aforementioned \"rule of three\" criteria [21] and in several cases, additional (proprietary) filters for shape and chemistry in library development. Information supplied with the libraries varies with suppliers but will generally include chemical structures with SMILES strings [26] and three-dimensional structure files." ] },{ "paper_id": "e4387a9c18bca710c7fdc986a6b2f8df671e29b8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fresh L-glutamine was added to BGM in a 24 hr RPTEC culture and the cells observed every six hrs for one day to assess the effect on cell morphology, vacuolation, and viability.", "Plaque assays were performed following the procedures outlines in references 39 and 50. " ] },{ "paper_id": "e43ae4e86302c1a05c8a22675a192245626fa9ac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2) AMOC curves could be used to: a) adjust outbreak detection sensitivity according to a local jurisdiction's capacity to investigate alerts; or b) to estimate how much resources should be reallocated to surveillance activities during periods of increased threat [42] .", "conditions, SARIMA could reduce detection delay by 5-16 days. It also was more sensitive at detecting the summer wave of the 2009 influenza pandemic." ] },{ "paper_id": "e44632c9b598cac15ccda521e13c65ca9fcf7426", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For complete methods, please refer to Supplemental material." ] },{ "paper_id": "e4477a684773ddd26ed297e1dd0a5f297621db21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e447d139f1d046120a293f1219944e82c77bc829", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chinese Medical herbs are a great reservoir of active compounds against microbial infections [ 7 -14 ] . Plants generate a great deal of compounds to eliminate or limit microbe invasions. The family Guttiferae contains more than 450 species distributed over regions mostly in Asia, southern Africa and Western Polynesia. Many bioactive compounds, such as prenylated xanthenes, benzophenones, bifl avonoids, and polycyclic polyprenylated acylphloroglucinols, have been isolated from different family members [ 15 -23 ] . They exhibit various biological activities including antibacterial, antifungal, antioxidant, anti-infl ammatory and anticancer effects [ 15 -23 ] , despite the underlining mechanisms being poorly understood.", "Chemicals were purchased from Sigma (St. Louis, MO, USA). Oblongifolin M (OM) was previously identifi ed and isolated with purity over 98% [ 27 ] . Commercially available antibodies were purchased from different companies. Antibody against VP1 was from Abnova ", "Results were expressed as mean \u00b1 standard deviation (SD). All statistical analyses were carried out with SPSS, version 14.0 software (SPSS Inc.). Two-tailed Student's t test was applied for two group comparisons. A p value <0.05 was considered statistically signifi cant. " ] },{ "paper_id": "e458fadd59e9f9ac952f6c40f283b14071174259", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest.", "NIH grants R01AI072060 and R03 AI079444 supported this work. We thank Mardelle Susman for help in the preparation of this manuscript.", "NK cells are important for early immune reactions against viral infections and cancer. They are a subset of lymphocytes that provide innate effector mechanisms through secretion of cytokines and direct cytotoxic effects, which are triggered by releasing cytotoxic granules containing perforin and granzymes [22] ." ] },{ "paper_id": "e45d3e45dd952470cbbac928b949fc6339e3ec81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Yeast has been utilized in vaccine development. The classical example is the recombinantly expressed hepatitis B surface antigen that has become a safe and efficient prophylactic vaccine worldwide [73] . However, in this section we will focus on its use not as a mere production tool for recombinant antigens but as a vaccine vehicle itself.", "Stubbs et al. showed for the first time that recombinant yeasts expressing HIV-1 antigens and tumour antigens potently elicit antigen-specific CTL responses, including those mediating tumour protections in mice [80] . Further studies with the animal tumour challenge model could demonstrate that yeast-based immunotherapy using mutated Ras oncoprotein as target antigen caused a mutant-selective tumour remission in animals [77, 79] . This concept is now being tested in a Phase I clinical trial in patients with colorectal, pancreatic and non-small cell lung cancers [77] . Most recently, the same group has evaluated a recombinant yeast cell vaccine that expresses the HCV NS3-Core fusion protein as an immunotherapeutic vaccine in chronic HCV-infected individuals [84] .", "One advantage of using whole recombinant yeasts as antigen carriers is the oral application route. Feeding mice with S. cerevisiae expressing Actinobacillus pleuropneumoniae antigen led to the induction of protective systemic and mucosal immune responses [85] . The fission yeast Schizosaccharomyces pombe represents, like S. cerevisiae, a physiologically and genetically well characterized eukaryote that has been used in Africa for hundreds of years in brewing of millet beer, from which it was first isolated. Recombinant Sz. pombe cells expressing the human cytomegalovirus pp65 protein were able to stimulate CD4-and CD8-positive memory T cells in human blood [82] .", "Two yeast cell-based assays have been established to screen for viral inhibitors. The protein M2 of influenza virus has a fundamental role in the disassembly of the influenza virion. In fact, some of the commercially available drugs target this protein.", "The strategy to use yeast cells for vaccination could also be used to elicit protective immune responses against human pathogenic yeasts. For example, the genus Candida is able to cause a variety of infections from mucosal candidiasis to life-threatening disseminated and bloodstream infections, especially in immunocompromised individuals. Unfortunately, the interplay between protective and inhibitory antibodies dictates the outcome of experimentally disseminated Candidiasis in mice receiving a heatinactivated whole-cell C. albicans vaccine [87] . This observation may explain why subjects with elevated anti-Candida antibody titers remain nonetheless susceptible to invasive candidiasis [87] . However, Ibrahim and colleagues could show that vaccination with the recombinant N-terminal domain of the adhesin Als1p improves survival during murine disseminated candidiasis by enhancing cell-mediated, not humoral, immunity in both, immunocompetent and immunocompromised mice [88, 89] ." ] },{ "paper_id": "e45e16034a3ab42bfce64e2b6886604a57974091", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ubiquitin-proteasome pathway is responsible for proteolysis of eukaryotic cellular proteins related to cell cycle regulation, cell survival, and apoptosis [1] . Inhibition of proteasome activity is a novel therapeutic strategy against cancer cells. Bortezomib (formerly known as PS-341), a cell-permeable boronic acid dipeptide, is a specific inhibitor of the proteasome pathway [2] and received Food and Drug Administration (FDA) approval for the treatment of MM and mantle cell lymphoma [3] .", "Data S1", "Found at: doi:10.1371/journal.pone.0013095.s001 (0.03 MB DOC) Author Contributions", "All data are expressed as mean 6 standard deviation. Statistical significance was determined by Student's t-test (two-tailed), while the significance of the differences was determined using the twotailed Mann-Whitney test. Statistical significance was assigned if P,0.05." ] },{ "paper_id": "e466de47aa170d1f457c5fd9e1b01ae0ba0549cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral isolation was performed in Vero cells (ATCC # CCL-81) as described [32] . Supernatants were harvested when extensive cytopathic effect was observed, centrifuged to remove cell debris and frozen at -80 \u00b0C until further analysis. All specimens were subjected to a single passage in Vero cells.", "All isolates from this study with complete viral sequences shared 12 nucleotide mutations, including one non-silent mutation in the envelope gene E-T 1442 C. The number of deduced amino acid substitutions ranged from 3 to 8, most of which were conservative substitutions. In addition to the E-V 159 A amino acid substitution in the envelope protein common to all WN02 genotype viruses, all isolates except CO4-07 shared two substitutions common to the SW/WN03 genotype, NS4A-A 85 T and NS5-K 314 R.", "The overlapping amplicons covering the entire genomes of ARC13-06, ID21bd-07 and ID28bd-07, which we used for common Sanger sequencing, were re-sequenced using Illumina NGS technology. NGS generated more than 80 million 100 nt reads per genome. Base and paired-end read counts estimated using the Illumina pipeline software CASAVA v1.8 are shown in Supplemental Table S2 . Average quality scores per cycle ranged from 31.4-39.7. Since Phred quality scores are logarithmically linked to error probabilities, base call accuracy was in the range 99.9-99.99%.", "Multiplex PCR reactions for detection of deletions in 3\u2032UTR ( Figure 2 ) were performed using the One-Step RT-PCR kit (Qiagen, Valencia, CA, USA) and F10100 5\u2032-TCCATGCAGGAG GAGAGTGGATGAC; F10400 5\u2032-CTGTAGATATTTAATCAATTGTAAATAGACAA; R10630 5\u2032-GGGTCCTCCTTCCGAGACGGT primers to amplify fragments that allow visualization of the ID-\u039413 deletion. Amplification was performed under the following cycling conditions: cDNA synthesis at 50 \u00b0C, 30 min; denaturation at 94 \u00b0C, 15 min; PCR 30 cycles: 94 \u00b0C for 15 s, 55 \u00b0C for 30 s and 72 \u00b0C for 1 min; final extension 72 \u00b0C for 5 min. After amplification, 10 microliters of each reaction mixture were analyzed using 2% agarose gel in TAE buffer." ] },{ "paper_id": "e4722dbdd2d7a467fcfd82700a2493e5ee6efd9e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the research ethics board of Sunnybrook Health Sciences Centre.", "The cohort was derived from a linkage of well-validated, province-wide health care administrative databases housed at the Institute for Clinical Evaluative Sciences [15, 16] . The Registered Persons Database contains demographic data for all of Ontario's 12.2 million residents; the Ontario Health Insurance Plan database includes physician billing claims for all visits and procedures performed within Ontario's universal single-payer health care system; the Canadian Institute for Health Information Discharge Abstract Database details all hospitalization events; the Ontario Drug Benefit database contains comprehensive and accurate (.99% concordant with chart review) outpatient drug information for Ontario's 1.2 million elderly residents [16] .", "Analyses were performed using STATA procedure XTGEE. Patient confidentiality was maintained via encrypted health card numbers using Institute for Clinical Evaluative Sciences protocols." ] },{ "paper_id": "e47d1f361bc4007b3fd859fd80fda5b40cc4a684", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After the experiment, piglets was humanely euthanized after intravenous injection of 80 mg/kg body weight sodium pentobar-bital, and a complete necropsy was performed to collect tissues.", "GO analysis (http://www.geneontology.org) and KEGG pathway analysis (http://www.genome.jp/kegg/) were applied to determine the roles of differentially expressed mRNAs. A p-value< 0.05 and a false discovery rate of < 0.05 were used as thresholds." ] },{ "paper_id": "e47eb523372bb6d65a538c3678c78081dade7e9b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A viral metagenomic analysis of feces from an unexplained outbreak of feline diarrhea revealed the presence of Lyon-IARC polyomavirus (LIPyV) DNA. LIPyV, whose genome was originally sequenced from swabs of human skin, was fecally shed by three out of five diarrheic cats.", "Data availability. The complete genome sequence of this feline feces-associated LIPyV has been deposited in GenBank under the accession number MK898813. The raw data for both the Nugen and Nextera libraries are available under the accession number PRJNA541523.", "Random reverse transcription-PCR (RT-PCR) was then followed by use of the Nextera XT DNA library preparation kit (Illumina, San Diego, CA) (3). Sequencing was performed on a MiSeq platform (250-bp paired-end reads), generating 1,216,275 reads that were de novo assembled using the Ensemble program (4). Both contigs and singlets were then analyzed using translated protein sequence similarity search (BLASTx) to all annotated viral proteins available in GenBank." ] },{ "paper_id": "e47f91345fe98307b49fc5f39aa5f781ec37f893", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Respiratory syncytial virus (RSV) infection is a major cause of death in the first year of life, with especially high mortality rates in African and Asian countries [1, 2, 3] . Upper respiratory tract infections (URTI) with RSV generally cause relatively mild disease that does not require treatment. These infections can progress, however, into lower respiratory tract infections (LRTI) and cause severe disease, especially in pre-mature infants. RSV can also cause recurrent infection of the upper respiratory tract.", "Other common causes for respiratory tract infections are Haemophilus influenzae type b (Hib), parainfluenza virus, rhinovirus and influenza virus [9, 10, 11] .", "Table S1 Overview of donors used for various assays. (DOCX) " ] },{ "paper_id": "e4813a9f4fee2d74c954d90bed67e8738047a390", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mixture F-12 (DMEM/F12, Thermo Fisher Scientific, Waltham, MA, United States) supplemented with 5% Horse Serum and 2.5% FBS at 37 \u2022 C and 5% CO 2 .", "Peptides Z2 (MAVLGDTAWDFGSVGGALNSLGKGIHQIFG AAF), Z2-Cy5 and scrambled peptide (LDIIAGLSAGFQ GGATFVDAHGMVKASFLGGNW) were synthesized at Kangbei Bio, Co., Ltd. (Ningbo, China) with 95% purity. Peptides were solubilized in dimethyl sulfoxide (DMSO) at 10 mM and stored at \u221220 \u2022 C.", "The animal study was reviewed and approved by Shanghai Public Health Clinical Center Animal Welfare and Ethics Committee Institutional Laboratory Animal Care and Use Committee at Fudan University. " ] },{ "paper_id": "e488697a5a07d8a7077f4dae04f386ff038fba5b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Peripheral blood mononuclear cells (PBMC) were isolated using density centrifugation through a Ficoll gradient (LSM1077, PAA Laboratories). Samples were treated with erythrocyte lysis buffer for 5 min on ice, PBMC were washed with 10 ml of PBS with 0.2% BSA and centrifuged for 15 min at 700 \u00d7 g at 4\u00b0C. In all samples, PBMC viability was confirmed using standard procedures.", "Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine diseases worldwide [1] . Efficient PRRS virus (PRRSV) vaccines would be invaluable in minimizing the clinical and economic impact of PRRSV infections, but currently safe and effective vaccines which protect against a wide variety of strains are not available [2] .", "The data sets supporting the results of this article are included within the article (and its additional files)." ] },{ "paper_id": "e489f92a7fda5ea493642945b61c85b6bde8a76e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e48be328050790f8d642f93c224a2bf0d89c19bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There are two kinds of diagnostic methods; virological and serological, for PEDV infection in pigs. In virological methods, virus isolation, immunofluorescence assay, immunohistochemistry test, polymerase chain reaction based assays and isothermal amplification assays are used for detection of virus, its nucleic and viral protein.", "The neutralization test procedure was described previously. The cut off value for NT PEDV positive titer was described at \u22651:2, which follows the Japanese National Institute of Animal Health's guide-lines [17] .", "In serological methods, indirect immunofluorescence assay, viral neutralization assays, fluorescent microsphere immunoassay, blocking Enzyme-linked Immunosorbent Assay (ELISA) and indirect ELISA by using virus structural protein are used for detection of anti-PEDV specific antibodies [10] . Compared with virological methods, serological tests are cost-effective and can detect viral specific antibodies prior exposure in the absence of virus infection [11] ." ] },{ "paper_id": "e49106784cd05d905c10780cc5dbe2a10a6badb7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e495a03cd94f48b0ad88347e1b5c0680fab819b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e4bc8603739ef592b4ce5c2a3b92abd82a2a13ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Parenteral administration of PLGA NPs loaded phosphorothioate antisense oligonucleotide nanoparticles for HIV treatment was also found to be successful and protected oligonucleotides from degradation (13).", "Polymeric nanoparticles (NPs) have several advantages which make them distinctive among various nanoparticulate systems. These advantages include their structural stability, narrow size distribution and the possibility of their functionalization for targeted drug delivery (9). Various polymers may be utilized for polymeric NPs preparation, among which PLGA or poly (lactic-co-glycolic acid) has a special place. PLGA has received FDA approval as a biocompatible and also biodegradable polymer and is commonly used in pharmaceutical industry and research as a desirable drug carrier (10, 11).", "Surface morphology and shape of nanoparticles were investigated by scanning electron microscopy (SEM, Philips XL 30, Philips, the Netherlands). A small amount of freeze dried powder of NPs was fixed on a double-sided tape attached to a metallic sample stand, and was gold coated before SEM (9).", "To our best knowledge, there are currently liposomes, microemulsions and micro and nanoparticles are amongst the most important drug delivery systems which are utilized for the preparation of such targeted carriers (3, 4). For instance Lutwyche et al. achieved a higher intracellular antibiotic delivery by gentamicin encapsulation in a liposomal drug delivery system and an increased therapeutic activity against intracellular pathogens was achieved (5).", "The entire system was located at 37 \u00b0C in a beaker (250 rpm). After a predetermined period, the old medium was fully removed and fresh medium was replaced each time. 5 mL of the old medium was analyzed by UV spectrophotometry for its GLA content. The release profile of free GLA was also evaluated by a dialysis bag under the same conditions." ] },{ "paper_id": "e4c74e7b5b49aa74e2219f53fd0202f811cf85d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell lines and reagents. Vero E6 or BGM cells were cultured using Dulbecco's modified Eagle's medium (Gibco) supplemented with 10% fetal calf serum, penicillin, and streptomycin, and maintained at 37\u00b0C in 5% CO 2 . BGM(S1-10) cells, which express GFP(S1-10) and the puromycin resistance gene (Pac), have been described in reference 21. BGM(S1-10) cell culture medium was supplemented with an additional 30 g/ml puromycin as a selection agent.", "While the formation of ROs during infection is a hallmark of \u03e9RNA virus replication, the specific morphologies produced vary by virus. Some viruses (e.g., dengue virus [4] Citation Melia CE, Peddie CJ, de Jong AWM, Snijder EJ, Collinson LM, Koster AJ, van der Schaar HM, van Kuppeveld FJM, B\u00e1rcena M. 2019. Origins of enterovirus replication organelles established by whole-cell electron microscopy." ] },{ "paper_id": "e4d4fde9df50047757fa69030407e861748c0eb3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Avian infectious bronchitis virus (IBV) is a pathogen of domestic chickens that causes acute, highly contagious respiratory disease [1] . IBV is a member of the Coronaviridae, order Nidovirales [2] and its genome consists of a 27.6 kb single stranded positive-sense RNA molecule that encodes for four structural proteins; the spike (S) glycoprotein, the small envelope (E) protein, the membrane (M) glycoprotein, and the nucleocapsid (N) protein [3, 4] .", "Six subgenomic mRNAs are transcribed from the IBV genome in virus-infected cells. The mRNA 1 contains two large overlapping open reading frames, encoding two polyproteins 1a and 1b [5] , among which 1b is produced as 1ab polyprotein by ribosomal frame-shifting mechanism [6] . Many serotypes have been described for IBV, probably due to the frequent point mutations that occur in RNA viruses and also due to recombination events demonstrated for IBV [7] [8] [9] . For this reason, the characterization of virus isolates existing in the field is very important. The Ark DPI strain was first isolated from Delmarva Peninsula broiler flock [10, 11] and it is currently being used as a vaccine in the USA and Europe. In this study, we characterized the entire genome of virulent Ark DPI strain (embryo passage 11) and compared it with other IBV strains and coronaviruses from all over the world.", "The complete genome sequence analysis of Ark DPI strain shows striking similarity to the Conn, Gray, JMK, and Ark 99 IBV strains, which were circulating during that time period [1, [19] [20] [21] . The 5'UTR, PL pro , M pro and RdRp sequence analysis demonstrates that Ark DPI is 100% identical to Gray strain, except for PL pro which has 87% identity, as shown in Table 1 . It was suggested that PL pro gene has high genetic variation because of selection pressure [22] . From this analysis, it appears that genetic mutation may have occurred at PL pro gene level. The modern strain GA98 maintains 100% identity with Ark DPI in replicase proteins and because of unavailability of sequence information for rest of the genome; we speculate that GA98 may be a derivative of the Ark DPI strain." ] },{ "paper_id": "e4d53d6c63d62095343315894b1f882efe299f7d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e4d6c7b63c33ac798572f0e53ab6b53a2f71b452", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where k is a constant, and moreover, j(t \u2212 \uf074) = kexp(rt)exp(\u2212r\uf074). This simplifies (1) to the so-called Euler-Lotka equation:", "When j(t) follows an exponential growth path, it is easy to extract the integral of A(\uf074) from equation (1) . Supposing that the incidence grows exponentially at a rate r, we have j(t) = kexp(rt)", "where \uf047(\uf074) is the survivorship of infectiousness, or probability of being infectious, at infection-age \uf074." ] },{ "paper_id": "e4dedf2b46618a544180539e2a2943c3618b8fec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Restriction enzymes were purchased from New England Biolabs (Beverly, MA, USA). Agarose was from Cambrex BioScience Rockland (Rockland, ME, USA). 30% (w/v) acrylamide/bis solution and protein assay were purchased from Bio-Rad (Hercules, CA, USA). HBsAg PreS2 peptide (H 2 N-NSTTFHQALLDPRVRGLYFPAGG-COOH) was synthesized at Peptron (Daejeon, Korea). Ni-NTA affinity kit was from Qiagen (Hilden, Germany). Other chemicals and reagents were purchased from Sigma-Aldrich (St. Louis, MO, USA), unless otherwise stated. All oligonucleotides were synthesized at Bioneer (Daejeon, Korea).", "We have developed a simple electrochemical biosensing strategy for the label-free diagnosis of hepatitis B virus (HBV) on a gold electrode surface. Gold-binding polypeptide (GBP) fused with single-chain antibody (ScFv) against HBV surface antigen (HBsAg), in forms of genetically engineered protein, was utilized. This GBP-ScFv fusion" ] },{ "paper_id": "e4e1a4d2d3384d9abc48576bb31cdb9c497732fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To detect an odds ratio of 3.5 for control group exposures of 25 % or greater, with a confidence level of 95 % and a power of 80 %, the required sample size was 42 cases.", "The distribution of positive samples between cases and controls was statistically evaluated through Pearson's Chi square or Fisher's exact test, using the Minitab \u00ae 16.1.0 software.", "RT-PCR [12] Group A rotavirus RT-nested-PCR [13] " ] },{ "paper_id": "e4ea49d8e5168e27636315e248bad09766c31a2d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In a comprehensive report by WHO, 1841 laboratory cases were confirmed between 2012 and 2016 in which 80% of them were reported from Kingdom of Saudi Arabia. ", "Frontiers in Microbiology | www.frontiersin.org", "SS, SC, SP, SK, and VS collected data and prepared the complete manuscript. Further, SS reviewed, revised, and edited the manuscript." ] },{ "paper_id": "e50473adb66bac4a176d80051d63f415d2dbd5a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "6 Cells with shRNA1110 and shRNA1755 transiently transfected show moderate deficiency of integrin b3", "Classical swine fever virus (CSFV) causing the disease of ''classical swine fever (CSF)'', is a member of the Flaviviradea family which also contains Dengue fever virus, West Nile virus (WNV) and Hepatitis C virus. CSFV leads to huge economic loss in the swine industry as CSF causes problems characterized by high fever, alternating constipation, diarrhea and high mortality [1, 2] . Transmission of this virus mainly depends on contact spread, but recent investigations indicated that infected boars could transmit CSFV in semen as well [3, 4] . This disease was first identified in USA during a continuous major nationwide epizootics, and was subsequently found in many other countries [5, 6] . The last major CSF epidemic in European Union occurred mainly in Netherlands and to a lesser extent in Germany, Italy, Belgium and Spain [7, 8] . Considering its rapid speed in spreading across national borders, and the huge socio-economic damage to the porcine industry, CSF was classified as a notifiable disease by OIE [9] .", "To knockdown mRNA of integrin b3, four shRNA constructs (976, 1110, 1755 and nc, detailed sequence information can be found in Table 2 ) were synthesized by Gene Pharma (Shanghai, China). Nc construct generating none of any RNA hairpins was also designed as the negative control. All these constructs contain Neomycin and GFP genes, which are respectively responsible for G418-dependent cell selection and transfection-efficiency reporting." ] },{ "paper_id": "e50c8a016885a30fcf67cee1b1e70c56b5c27e2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e51146b66f1894acaf65626acab69810a1394a86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Any study design regarding aspects on timelines of sequence of events, environmental sampling and contamination, evaluation of hotel related interventions, modelling of interventions were included. Studies not meeting the above inclusion criteria or answering the research questions was excluded.", "The search identified 34 records from MEDLINE of which five were relevant (references [6, [12] [13] [14] [15] ), and an additional 13 records were identified through other sources and the grey literature.", "The " ] },{ "paper_id": "e5146a4b1c9ae4171d885efabc99ff1cc997aeec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "See http://severus.dbmi.pitt.edu/schizo-pi or http://severus.dbmi. pitt.edu/wiki-pi for annotations compiled from various databases for each of the individual proteins." ] },{ "paper_id": "e5230a23f4c70587a3cd4c19f54ae685125673a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "N.B. Cases are numbered chronologically, independently of the country of origin.", "The authors declare no conflict of interest.", "For each locus, sequences obtained were analyzed using the MLST database containing the sequences of alleles, allelic profiles, and information about the Burkholderia isolates, with analysis tools. This tool is stored on a publicly-available web-based database, allowing comparisons to be made between isolates from different laboratories (https://pubmlst.org/bpseudomallei/). MLST is the gold standard for comparison of isolates from different geographical locations due to high inter-laboratory reproducibility.", "Acknowledgments: Authors would like to address a special thank you to all the doctors and medical assistants from the CHU de Mahajanga. We also specially thank Jay Gee, CDC, USA for important information about the sequence types. A part of this work (which took place in Madagascar) was financed by Institut Pasteur \u00e0 Paris: ACIP2011. We also thank Le Dispositif Prioritaire de Recherche et d'Enseignement en partenariat One Health-Oc\u00e9an Indien for allowing some of the authors to meet and discuss this manuscript.", "A consecutive investigation to trace back the origin of the fertilizer identified its origins as the surrounds of the Amborovy airport (15 \u2022 40 56.59 S, 46 \u2022 22 20.50 E); however, none of four soil samples taken from this location were positive for B. pseudomallei, either by culture or PCR." ] },{ "paper_id": "e523533cb5df819c3354420da60b7c82f9f92485", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The huge variance in Figure 4B indicates the cluster transmissions.", "Results: R 0 ranged from 2.5 with 95% confidence interval (CI): [1.7, 3.1] (using the sequential Bayesian method) to 7.2 with 95% CI: [5.3, 9.4] (using the Nowcasting method). Estimates from transmission model were higher but overlapped with these.", "To reflect the huge dispersion in the daily number of cases, the nega- Assuming that the observed incidence x i (1), x i (2),\u2026, x i (T i ) are conditionally independent, the total likelihood given parameters \u0398 is where the starting points of the three series are t E = 3, t I = 1, t C = 10, respectively, and their end points are T E = 48, T I = 53, T C = 55." ] },{ "paper_id": "e52c04caa85880ec10ef5275a67cc3ea3a91a9c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We thank Keith Philibert for critically reading the manuscript. The authors apologize to all investigators whose work was not cited due to oversight or space constraints.", "Other cell types-Macrophages, platelets and dendritic cells.", "No potential conflicts of interest exist.", "We are grateful to funding from H. M. Bligh Cancer Research Laboratories and NIH-funded grant R01CA192970 to NSW. The funders had no role in design, decision to publish, or preparation of the manuscript. All authors have read the journal's policy on conflicts of interest. " ] },{ "paper_id": "e53306862eb2cab646ba36a1e685fdb5a392da42", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The present study is an attempt to elucidate more fully the nature of mutational change in this historically important human pathogen.", "Additional file 2: Relative Synonymous Codon Usage (RSCU) data, in .csv format.", "Additional file 3: H1N1 genomic variation data, in .csv format." ] },{ "paper_id": "e53455e72c6f41b5328175d2297717fbece5c6a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "With the patient's previous pericardial effusion, past laboratory workup demonstrated high titers for coxsackie B virus. Upon this admission, a viral panel was negative, including hepatitis B panel, influenza, respiratory syncytial virus, corona virus, metapneumovirus, parainfluenza virus types 1,3, and 4, Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, coxsackie, influenza A, myocoplasma pneumonia, Chlamydia pneumoniae, buccal virus, and rhinovirus. Rheumatologic workup was also negative, including antinuclear antibody, anti-double stranded deoxyribonucleic acid, antimicrosomal antibody, anticentromere antibody, Sjogren's syndrome A and B, Smith antibody, celiac screen, anti-Jo 1 antibody, and anti-SCL-70 antibody (antitopoisomerase I). Further testing for anti-21 alpha hydroxylase and anti-TPO antibodies were also negative." ] },{ "paper_id": "e53bab2c782aab7911dc57e4ecf3759a1755fb21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Proteins were harvested in RIPA buffer with PMSF and incubated overnight with polyclonal antibodies against APN. Blots were developed using enhanced chemiluminescence (ECL) (Pierce) reagents.", "Visible agglutination within 2 min incubation was considered as positive.", "F4ab +++ rF4ab ++++" ] },{ "paper_id": "e5407e15d4e044411687f36176bc9d27bb6a3fd4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coiled-coil (TRAF-N) domain TRAF-C domain Zn RING TRAF2 TRAF1 TRAF3 TRAF4 TRAF5 TRAF6 Nuclear localization signals TRAF7 WD40 repeats Figure 1 Domain structure of the seven TRAF proteins. Symbols for different domains are shown, including zinc RING (Zn RING), zinc fingers (Zn Fingers), coiled-coil (TRAF-N) domain, TRAF-C domain, nuclear localization signals, and WD40 repeats. [33] . The distinct TWEAK/Fn14 paradigm is covered in detail in a recent review by Silke and Brink [32] .", "Interestingly ", "The author declares that she has no competing financial interests." ] },{ "paper_id": "e545cfc731b5511fe89ef69e6d09cbc9bf428704", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics. All Bacteria. BCG strain Pasteur was a kind gift from Professor Juraj Ivanyi (King's College, London) and was grown according to previous reports 12 , using standard microbiological techniques. BCG expressing green fluorescent protein (GFP; also from the Ivanyi laboratory) was grown in identical conditions, but under selective media and agar containing 50 \u03bcg/mL hygromycin B (Sigma-Aldrich).", "For lymph node analysis, inguinal lymph nodes were excised from euthanised mice on the indicated day, followed by mechanical disruption, counting and immediate flow cytometric analysis.", "Prism software, using averaged technical replicates where possible. Each statistical test and post-test is detailed in the relevant figure legends. A p value less than 0.05 was considered significant." ] },{ "paper_id": "e546530d3c2507a91afb8ed59c87cac0c8b501da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses in the Coronaviridae family possess a positive (+) ssRNA genome and cluster into two subfamilies including Coronavirinae which includes the human coronaviruses, and six genera. The viruses of Arteriviridae family are also positive (+) ssRNA viruses and grouped into one genus, Arterivirus.", "The location of the nucleocapsid gene within the genome of selected viruses from the named families is shown in Figure 1 . The nucleocapsid [N, NC, or C (core or capsid)] gene is in the first position (3 end) in Paramyxovirus genomes and (5 end) in Flavivirus and Hepacivirus genomes. The nucleocapsid gene of Coronavirus and Arterivirus is in the last position (3 end) of these genomes, but the first gene to be copied into a negative sense subgenomic mRNA template for mRNA transcription.", "The nucleocapsid protein of RNA viruses is a structural protein found in a complex with the genomic RNA. The role of genome encapsidation varies across PSVs and NSVs, but usually comprises one or more of the following functions; [1] to protect the genome from cellular nucleases, [2] to form the ribonucleoprotein transcriptase complex, and [3] to package the genome into new infectious particles prior to budding." ] },{ "paper_id": "e54a9696e0da89388b8edef0dbe18a5f674a245b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Objective: The objective of this surveillance was to detect severe influenza cases, identify their epidemiological and virological characteristics and assess their impact on the healthcare system.", "Influenza B viruses were grouped as Victoria lineage or Yamagata lineage on the basis of the HA gene sequence (Fig. 6 [28] . Most of Yamagata strains were detected in severe cases (9/13; 69%). Inspite of lower mutation rate and lower pathogenicity than influenza A, influenza B infection contributes to significant proportion of acute respiratory infection among Tunisian people." ] },{ "paper_id": "e54d7c030edf8736b345a53ad17f7a7b00a74912", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Braymen, 1969 (13) / Experimental laboratorial Intentional contamination of the wall; automatic washer with pressurized jet, with water and disinfectant solutions. Air samples to determine the particle size (during and after the procedure).", "Other parameters shown in Figure 2 and creating air flow patterns (19) .", "Ventilation systems and air conditioning in various establishments promote comfort, and are useful in the prevention and treatment of diseases transmitted via aerosols. The use of these systems in health services (HS) requires special attention. The basic differences stem from the need to restrict the dispersion of air within an environment to adjacent areas; the specific requirements for ventilation and filtration aiming to dilute and eliminate contamination; the different requirements of temperature and humidity for each area; and sophistication that is demanded for the project (6) ." ] },{ "paper_id": "e5526afbb4d770dabb8c34da47c1267ee3342959", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reads from the noncoding regions were concatenated and consensus data from 454 and Illumina sequencing were compared (Fig. S7) Figure 5 ).", "Sequencing Center. Sequencing was performed as described previously [17, 18] . For all samples sequenced by Illumina (pairedend read technology), overlapping read pairs (ORPs), generated by combining short fragment libraries with long sequencing reads, was used to reduce sequencing errors and improve rare variant detection accuracy. Quality filtering procedure was also described in [17, 18] .", "(DOC)" ] },{ "paper_id": "e55459a4991dbc5ed150ee9174b48401b24517fc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples positive for ZIKV were selected to amplify genes encoding Envelope protein (E) and nonstructural protein 1 (NS1).", "Detection of ZIKV in saliva and urine from four hospitalized patients.", "Before RNA extraction, urine samples were concentrated with Amicon Ultra-0.5 Centrifugal Filter Units with Ultracel-10 membrane (Millipore, Shanghai, China). The QIAamp Viral RNA Mini Kit (Qiagen, Hilden, Germany) was used to extract viral RNA from urine and saliva according to the manufacturer's instructions. RNA was eluted in 50 \u03bcl of AVE buffer and stored at \u2212 80\u00b0C until use." ] },{ "paper_id": "e55df621c9df11f9127cdb8829686868bd2ec1cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mean number of viable bacteria (CFUs/ml) and standard errors of means were determined. Student's t-test was used to compare percentages of live and dead H. somni in control and NKlysin treated samples. The term significant indicates P value of less than 0.05.", "Bovine respiratory disease complex (BRDC), also known as shipping fever, is the most common infectious disease affecting older weanling, stocker, or feeder calves causing extensive economic losses to the North American beef and dairy cattle industry [15, 16] . BRDC develop as a complex interaction between environmental stress factors, host factors, and multiple viral and bacterial infectious agents [17] . Various viral pathogens such as bovine herpes virus-1, bovine viral diarrhea virus, bovine respiratory syncytial virus, bovine parainfluenza-3, bovine coronavirus and bovine adenoviruses have been implicated to predispose calves to secondary bacterial infections. The most important bacterial pathogens associated with BRDC are Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis [15, 17] . Each of these bacteria are commensals in the nasopharynx of cattle. H. somni is a Gram negative bacterium and is a commensal of the upper respiratory as well as genitourinary tracts of cattle [15] . H. somni can cause a wide variety of disorders in cattle in addition to respiratory disease, including septicemia, thrombotic meningoencephalitis, arthritis, myocarditis, and abortions [18] .", "As previously described [9, 10] " ] },{ "paper_id": "e56624da7d4f6a86a9cc0a91f3e5a8e98823cea5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The viral cell receptors and infection can be blocked by the expression of the viral receptor-binding protein.", "Preparation of membrane extracts. pcDNA-env_DF1 cells and DF1 cells in 100 mm dishes were harvested by scraping with a rubber policeman and homogenised with NP-40 lysis buffer containing 25 mM Tris, 150 mM NaCl, 1 mM EDTA, 1% NP-40, 5% glycerol (pH7.4) and a protease inhibitor cocktail (Roche). Intact cells and nuclei in the resulting extract were sedimented by centrifugation at 4uC for 5 min at 6000 g. The membrane proteins in the supernatant were sedimented by an additional spin at 13200 g for 1 h at 4uC and resuspended in 1% NP-40 lysis buffer. All extracts were stored at 280uC until use." ] },{ "paper_id": "e572a3a154399f2b500b0f547a7252c94580acf4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IF Rainfall is LARGE \u00f0 \u00de and Temperature is HOT \u00f0 \u00de", "For the disease prediction application, the rules of interest are called fuzzy class association rules (FCARs), meaning that they have only one consequent: the class. An example of a FCAR extracted by FARM is:", "Week is WEEK 30{33 \u00f0 \u00de ?", "where X and Y are variables, and A and B are membership functions that characterize X and Y respectively. X is called an antecedent and Y is called a consequent of the fuzzy association rule. An example of a fuzzy association rule (not used in dengue prediction) is:" ] },{ "paper_id": "e5746d8d6badecb0d0afc06192c540aed6479c83", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The datasets generated for this study are available on request to the corresponding author.", "The present work has been supported by the Italian Ministry of Health (Ricerca Corrente 2017-2018 to GDZ).", "GDZ and GDL have written the manuscript. GDZ, GZ, and AL have designed the study. GDZ, GDL, VC, and FM performed the experiments. All the authors have revised the manuscript and given the final approval for submission." ] },{ "paper_id": "e576c57618f99c0f5073d66ebedee4d80e910e0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sections of bone marrow examined were either hypocellular, characterised by increased numbers of, predominantly, adipocytes and extravasated erythrocytes interspersed with very low numbers of erythroid and myeloid precursors and megakaryocytes, or hypercellular, with increased numbers of myeloid and erythroid precursors. Some sections of the liver demonstrated hepatocellular atrophy and congestion, with minimal periportal mononuclear infiltrates. Among the sections of myocardium examined, there were no significant lesions.", "Mild-to-moderate multifocal lymphoid depletion was also apparent in splenic sections. Extramedullary haematopoiesis characterized by the presence of myeloid and erythroid precursors was variably present within spleen and lymph nodes.", "This study 2016-2018 ", "Feline panleukopenia (FPL) is a highly contagious and often fatal disease characterised by acute severe enteritis, severe dehydration and sepsis due to lymphoid depletion and pancytopenia [1] . FPL is usually associated with infection by feline parvovirus (FPV), a member of the genus Protoparvovirus (formerly Feline panleukopenia virus). Protoparovirus is one of eight genera of vertebrate viruses within the subfamily Parvovirinae of the family Parvoviridae. Collectively, FPV and canine parvovirus (CPV), along with associated variants found in various carnivore species such as mink and raccoons, constitute the species Carnivore protoparvovirus 1 [2] .", "DNA was extracted for sequencing of the Carnivore protoparvovirus 1 VP2 gene from tissue using the Qiagen DNeasy Blood and Tissue Kit (Qiagen, Hilden, Germany) or from faecal samples using the QIAamp Fast DNA Stool Mini Kit (Qiagen, Germany) or by homogenisation, boiling and centrifugation, as previously described [11] . The extracted DNA was amplified by conventional PCR using 5 u/\u00b5L of My Taq HS Red DNA polymerase (Bioline, USA), 1-90 ng of DNA, 1 x MyTaq Red reaction buffer and a final primer concentration of 0.2 \u00b5M in a final reaction volume of 25 \u00b5L. Three sets of overlapping primers were used to amplify the entire VP2 region (1931 bp) as described previously, with minor modifications (Table 1 ) [12] . An initial denaturation step at 94 \u2022 C for 1 min, followed by 35-40 cycles of denaturation at 94 \u2022 C for 30 s, annealing at 50 or 55 \u2022 C for 30 s and extension at 72 \u2022 C for 30 s, ending with a final extension at 72 \u2022 C for 1 min, was used for DNA amplification. The PCR products were separated by electrophoresis on a 1% agarose gel (Bio-Rad Laboratories, Hercules, CA, USA) in 1\u00d7 tris-acetate EDTA and visualized using SYBR Safe DNA (Invitrogen, Carlsbad, CA, USA). Sanger sequencing of positive PCR products was performed commercially (Macrogen, Seoul, Korea). " ] },{ "paper_id": "e57993034cb1196b96daff4505db38640782f4a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved through the University of Alberta Ethics Review Board and all patients provided written informed consent." ] },{ "paper_id": "e584b536fcbb3da70855c7f8d81c15319b0e9b7b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data management was performed at the Department of Pediatrics, University Hospital of W\u00fcrzburg. Data were entered twice into Microsoft Access databases and reconciled using Epi Info\u2122 (CDC, Atlanta, USA) Version 3.3.2. Statistical analyses were carried out using IBM SPSS Statistics version 24.0 (IBM Corporation, New York, USA).", "Additional file 1: Figure S1 " ] },{ "paper_id": "e58bb3ad5e35a2895353e82c3690e2dd33a8d86b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Libraries for 454 pyrosequencing were made using Rapid Library Preparation Method Manual (October 2009) GS FLX Titanium Series (Roche, Branford, CT) and Paired End Library Preparation Method Manual, 3kb Span (October 2009) GS FLX Titanium Series. Each library was processed using emPCR Method, Manual Lib-L MV (October 2009) in separate emulsion reactions. The paired-end sample was loaded on a single lane and the fragment sample was loaded in two lanes of an 8-region 454 GS FLX Titanium sequencing run. Genome assembly and gap closure was performed as previously described [44] . Sanger sequencing was used to correct errors due to runs of identical nucleotides. ", "(RPXV\u0394SPI-1-GFP). In panels B, D and E the cells were infected in triplicate for 48 h and titers were determined in duplicate on CEF. Error bars represent SEM and fold difference in titers are indicated.", "Rabbit antibody to VACV strain WR was described previously [45] ; c-Myc antibody (9E10) conjugated to horse radish peroxidase (HRP) (catalog number sc-40 HRP) was from Santa Cruz Biotechnology; and rabbit anti-actin (catalog number A2066) was from Sigma-Aldrich." ] },{ "paper_id": "e594dcc4d1864621d24cc6ffbc70a88a5ae1207d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Moderate concern (score = 35-45)", "Low concern (score = 5-34)", "A cross-sectional study design was used." ] },{ "paper_id": "e596bfbd1ba590f07fd2514040538bb5fb9ed166", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e5982e467e81a52787bc1c653fc65fa444501032", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Here, we summarize current knowledge on direct and indirect transmission routes of bat infectious agents of public health concern (Fig 1) . Although bats are recognized as major reservoir hosts of emerging infectious diseases, we highlight that a significant knowledge gap on transmission mechanisms remains and needs further exploration.", "In addition to wild animals, the role of livestock as intermediate and amplifying hosts between wild animals and humans has been clearly demonstrated in several outbreaks, such as for Filovirus and Henipavirus [15, 16] . Indeed, in Malaysia, the growth of commercial pig farms with fruit trees on the farm has created an environment where bats could drop partially eaten fruits contaminated with Nipah virus into pig stalls [4, 17] ." ] },{ "paper_id": "e59da8ad79490ad5270928bd54c9a4d0b417d1ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Age (mean, months) Gender", "Respiratory illness ( carried out using the IDseq pipeline, a cloud-based, open-source platform designed for detection of microbes from metagenomic data (https://github.com/chanzuckerberg/idseq-dag) that incorporates several features of previously developed pathogen detection pipelines [11] [12] [13] [14] [15] [16] [17] .", "https://doi.org/10.1371/journal.pone.0218318.g001" ] },{ "paper_id": "e5a10a7f2c9bb07f74fcce076a62f63f859cf3a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "the consequences of pandemics, and conflicts driving mass migration [25] [26] [27] can all reach far beyond local borders [28] [29] [30] [31] ." ] },{ "paper_id": "e5a309be751ae9e2575c3e35edd7f37fa0e99b3d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The \"ribosomal activity microbiome\" detection. Reads " ] },{ "paper_id": "e5a9130fe91644dc7bd9ef4f8d26e1d07faaca08", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e5b3fc64db01648fa06f51f1cde95ff3d0925607", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e5c06914d0daee6e881665b23adca340d0a6271a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting information S1 Table. Forward, reverse primers, SNPs and WT probes used in the study. (DOCX) ", "Trial registration: The study was registered following the WHO International Clinical Trials Registry Platform (WHO-ICTRP) on Thai Clinical Trials Registry (TCTR) website, registration number # TCTR20180720001" ] },{ "paper_id": "e5c0ca285de27831edf5b0306750cfa3f69eba8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest to report.", "Sibongile Walaza https://orcid.org/0000-0001-7588-2480", "Mitra Saadatian-Elahi https://orcid.org/0000-0003-1265-8806" ] },{ "paper_id": "e5c1960487379bc9bd2cdfef08fc1b6e515abf73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consecutive tissue sections, incubated with normal rabbit or rat serum or a non-reacting mouse monoclonal antibody, were used as negative controls for polyclonal and monoclonal antibodies respectively. For TUNEL, terminal deoxynucleotidyl transferase (TdT) was replaced by distilled water on negative control slides." ] },{ "paper_id": "e5ca488c67d3b9db4056f7fe900e10254d69f7ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Factors favouring a host shift", "Mutation rate High per nucleotide mutation rates increase the chance of specific mutations occurring, but can also slow rates of adaptation as many mutations are deleterious", "Finding tractable methods to monitor emerging diseases presents a significant challenge for the future. Studying the genetics of host shifts has the potential to uncover the evolutionary processes that pathogens undergo when they find themselves in a novel host, and may allow us to begin to address this challenge.", "Host shifts into humans have also involved parallel mutations ( Figure 2B ). In HIV-1, codon 30 of the gag gene has independently undergone the same change in all three human lineages of the virus that transferred from chimps [1] . This change increases viral replication rate in human cells [59] , and when a chimp was infected with HIV-1 it reverted to the residue seen in SIVcpz [59] . Similarly, five parallel mutations have been observed in two independent epidemics of SARs coronavirus following the shift from palm civets to humans [60] ." ] },{ "paper_id": "e5d1fd5c8ca1cb299a376d2b3109b4088b0c9ae5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GBM represents the most aggressive malignant primary brain tumor with a median survival of 16 months after radio-chemotherapy 1,2 . Importantly, GBMs were shown to be highly resistant to caspase-dependent apoptosis 3, 4 .", "Results are expressed as mean \u00b1 SEM. Statistical analysis was performed with SigmaPlot (v12.5). Statistical significance of two group data was analyzed by Student's t test (two-tailed). If samples did not pass either the Shapiro\u2212Wilk Normality Test or the Equal Variance test, statistical significance was analyzed by Mann\u2212Whitney Rank Sum Test. p values were interpreted as follows: *p < 0.05; **p \u2264 0.01; ***p \u2264 0.001.", "So far, there have been few studies on selective mediators of ACD. Recently, glucocerebrosidase (GBA1) has been identified by a signalome-wide shRNA-based cell viability screen as a critical mediator of autophagic selfconsumption and ACD 25 73 . Moreover, TP53 has previously been shown to regulate sphingosine kinase 1 (SPHK1)induced ACD in colon carcinoma cells 74 ." ] },{ "paper_id": "e5d7b78cf1acf78071a1b54e6f4fe6dd68ac9430", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e5db7954926b0072fa6bf086899e4faf42c15f3a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The lung tissues of challenged mice were immediately fixed in 10% neutral buffered formalin and embedded in paraffin wax. Sections were made at 4-6 \u03bcm thickness and mounted on slides. Histopathological changes were examined by H&E staining and observed under light microscopy as previously described [32] .", "Female BALB/c mice at 4-6 weeks were purchased from the Laboratory Animal Unit and housed in the animal facility of The University of Hong Kong following the approved animal care protocols. Mice were rested for 2 weeks before immunization. The animal study was approved by the Department of Health of Government of Hong Kong Special Administration Region, and University Animal Ethics Committee of The University of Hong Kong.", "The significance between survival curves was analyzed by Kaplan-Meier survival analysis with log-rank test. Other data were analyzed using the 2-tailed Student's t test. P < 0.0001 was considered significant. All analyses were performed in Graphpad Prism software. " ] },{ "paper_id": "e5ec3d4854fa2bfba10cae487ea5271ed00a24fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "http://www.biomedcentral.com/1471-2334/7/33/prepub" ] },{ "paper_id": "e5ee01ea0acff01da191ffff2d9fbef2f9aebff7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Peptides were synthesized by KareBay Biochem (Ningbo, China), using a standard solid-phase 9-flurorenylmethoxycarbonyl (FMOC) method. All peptides were tested by high-performance liquid chromatography (HPLC) with purity >95%. The peptides were stored at \u221220 \u2022 C and solubilized with dimethyl sulfoxide (DMSO) or PBS. The concentrations of the peptides were tested by UV absorbance (Nanodrop2000, Thermo Fisher Scientific Inc., Waltham, MA, USA), and molar-extinction coefficient was calculated based on tryptophan and tyrosine residues [46] .", "293T, Huh-7, A549 and MRC-5 cells were cultured in Dulbecco's modified Eagle's medium (DMEM, Invitrogen, Carlsbad, CA, USA). All cell culture media were supplemented with 10% fetal bovine serum (FBS, Biowest, Loire Valley, France) and the antibiotics penicillin and streptomycin (Cytogen, Wetzlar, Germany). Cells were maintained at 37 \u2022 C under a 5% CO 2 atmosphere. The American Type Culture Collection (ATCC) strain of HCoV-229E (VR-740) was propagated in MRC-5 cells. The viral titer (TCID 50 /mL) was determined on Huh-7 cells [30] .", "Coronaviruses (CoVs) are positive-sense RNA enveloped viruses with various hosts, including avian species and mammals [1] . Currently, six CoVs have been reported to infect humans, including human coronavirus 229E (HCoV-229E), OC43 (HCoV-OC43), NL63 (HCoV-NL63), HKU1 (HCoV-HKU1), severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) [2] [3] [4] [5] . During the 2002-2003 epidemic of SARS, approximately 8000 individuals were infected by SARS-CoV with a mortality rate of 10% [6] . During the 2012-2017 epidemic of MERS, 2121 laboratory-confirmed cases, including 740 related deaths (~35% mortality rate) in 27 countries, were reported to World Health Organization (WHO) [7] . Infection by other human coronaviruses, including HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, in healthy adults generally results in common cold with clinical manifestations that include discomfort, headache, sneezing, fever and cough. However, infection with these viruses in infants, elderly people, and immunocompromised patients may also cause severe diseases [2, [8] [9] [10] [11] ." ] },{ "paper_id": "e5f66769b3cbcb6b378257a7c83acdb1793a6803", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e5fe8631b7f7e99f1e71c0cffc582d135c7181a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Epitope mapping of antibodies to E2 antigenic regions (ARs) 1 to 3", "https://doi.org/10.1371/journal.ppat.1006735.g006" ] },{ "paper_id": "e6072267b50da2dfa7595ddd3e29fe99a96d4624", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Primers are listed in Table S1 . Comparative threshold cycle (C T ) values were used to evaluate fold change in transcripts using actin as an internal transcript control.", "Reagents and antibodies. Zymosan A (ZymA), DPI, luminol, horseradish peroxidase (HRP), lipopolysaccharide (LPS), and N-acetylcysteine (NAC) were obtained from Sigma (St. Louis, MO, USA). CellROX deep red, goat anti-mouse IgG, goat anti-rat IgG, goat anti-rabbit, or goat anti-guinea pig secondary antibodies conjugated to Alexa 594 or Alexa 488 were obtained from Life Technologies (Grand Island, NY, USA). Carboxyfluorescein succinimidyl ester (CFSE) was obtained from Thermo Fisher Scientific (Waltham, MA, USA). Rabbit polyclonal (Pc) anti-Gbp5 antibody was obtained from Proteintech Group (Rosemont, IL, USA). Cy5-labeled Gr1, fluorescein isothiocyanate (FITC)-labeled F4/80, and phycoerythrin (PE)-labeled B220 were obtained from BD Biosciences (San Jose, CA, USA). Mouse anti-actin (C4 clone) antibody was obtained from Millipore (MA, USA). Mouse monoclonal antibody (MAb) anti-caspase-1 (p20) was obtained from Adipogen Life Sciences (San Diego, CA). Goat anti-rabbit IgG IR800 and anti-mouse IgG IR700 were obtained from Li-Cor Biosciences (Lincoln, NE, USA). T. gondii parasites were stained with mouse MAb DG52 against the surface antigen SAG1 (69) . MAb DG52 was labeled with Pacific Blue (Pac Blue) dye using a protein labeling kit (Invitrogen) to generate Pac Blue-labeled antibody for parasite detection by flow cytometry. GRA7 was detected using a rabbit Pc serum described previously (60) . LAMP1 was localized with rat MAb ID4B, obtained from the Developmental Studies Hybridoma Bank (http://dshb .biology.uiowa.edu). Guinea pig polyclonal anti-p62 was obtained from Progen (Heidelberg, Germany). Mouse MAb FK2 against polyubiquitin and monoubiquitin was obtained from EMD Millipore Corporation (Billerica, MA). Anti-LAMP2 (rat MAb GL2A7) was obtained from Abcam. Fluorescein isothiocyanate (FITC)-conjugated Dolichos biflorus lectin (DBL) was obtained from Vector Laboratories (Burlingame, CA, USA).", "Supplemental material for this article may be found at https://doi.org/10.1128/mBio .01393-18. " ] },{ "paper_id": "e608f2a6b99e0e74c16aa9085128690e20b59ea0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Infection and age differences were evaluated using a 2way ANOVA with Bonferroni post-tests or two-tailed student T-tests, where appropriate. All data for statistical evaluation was log transformed and analyzed with GraphPad Prism 5.0 software (GraphPad, La Jolla, CA). A p value of 0.05 or less was considered statistically significant.", "monkeys whereas levels in the aged group showed no infection-induced increase.", "All procedures were conducted under protocols approved by the Institutional Animal Care and Use Committee (IACUC) at Lovelace Respiratory Research Institute (LRRI), all facilities were accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC), and guidelines for nonhuman primates described in the Guide for the Care and Use of Laboratory Animals, National Research Council, were strictly adhered to." ] },{ "paper_id": "e60dc2f814db6256844444e573ea98bc9a9b4a93", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total nucleic acids extraction was performed following RNA NOW\u2122 (BIOGENTEX, Seabrook, Texas, USA) isolation and purification protocol. Total nucleic acids were eluted in a final volume of 60 \u03bcl. cDNA were obtained following a previously published protocol [26, 27] . Briefly, reverse-transcription was performed on 20 \u03bcl of total nucleic acids, using 0.1 \u03bcl of random hexamers (Promega, Madison, Wisconsin, USA) and the GoScript\u2122 Reverse Transcriptase (Promega, Madison, Wisconsin, USA), under the following thermal conditions: 80\u02daC for 5 min, 25\u02daC for 5 min, 42\u02daC for 60 min and 70\u02daC for 5 min. The obtained cDNA (40 \u03bcl) were diluted 1:2 and stored at -20\u02daC until tested.", "The animal procedures used in this this study were reviewed and approved by the Comit\u00e9 de l'Environnement Polaire and by the French Ministry of Research (notification number 04939.03).", "The ABsolute Blue qPCR Low ROX Mix (Thermo Fisher Scientific, Surrey, UK) was used for Real-Time PCR detection (Coronavirus, Paramyxovirus and Influenza A virus), the ABsolute Blue qPCR SYBR Low ROX Mix (Thermo Scientific, Surrey, UK) for Real-Time SYBR PCR detection (Flavivirus), and GoTaq Hot Start Green Master Mix 2X (Promega, Madison, Wisconsin, USA) for end-point (P. multocida, E. rhusiopathiae, Rickettsia) or semi-nested quantitative PCR (Haemosporidia) in final volumes of 25 \u03bcl containing 5 \u03bcl of cDNA. PCRs were carried out in a BIO-RAD CFX96 Touch\u2122 thermocycler (BIO-RAD, Hercules, California, USA). Amplification products were analysed by electrophoresis on agarose gels stained with 2% GelRed\u2122 (Biotium, Hayward, California, USA).", "Introduction Infectious diseases are a major concern for wildlife conservation, with strong evidence for their influence in the decline and extinction risk in many populations [1] . Examples include amphibian chytridiomycosis, threatening several species with extinction at local and global scales [2] ; canine distemper virus epidemics, causing significant declines in wild canine populations in Serengeti [3] , or phocine distemper virus, killing 23,000 North Sea harbour seals Phoca vitulina in 1988 and 30,000 in 2002 [4] . Hence, examining the threat posed by such diseases may be particularly critical for the conservation of endangered species [5] [6] [7] [8] ." ] },{ "paper_id": "e6184d2db86268ba31e49b03a5aab475d5ce5ca6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "-AGAAGTATTTAAATTACG- " ] },{ "paper_id": "e620067ec156a1fc9e5b28aaf66b38dd08815df8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For all published primers, the PCR conditions were followed according to those previous studies [10, [43] [44] [45] [46] [47] . PCR conditions using newly designed primers were performed using 10\u00d7 PCR buffer, 25 mM MgCl 2 , 25 mM dNTPs, 25 pmol forward and reverse primers, 1 unit of Taq platinum polymerase (Invitrogen) and 50-200 nanograms of DNA in a total reaction volume of 50 \u00b5L. Amplicons from PCR-positive samples were purified using the PCR DNA Mini Kit (Real Genomics RBC, Banqiao, Taiwan) following the manufacturer's protocol and were sequenced in an ABI 3130xl platform (Thermo Scientific, Waltham, MA, USA). ", "Hemogram tests displaying blood cell counts of 35 animals were performed by a veterinarian diagnostic laboratory. Hemogram results were kindly provided by Dr. Carlos Gabriel Dias. Cats with low erythrocytes (below 5 milions/\u00b5L), hemoglobin (below 8 g/dL) or hematocrit (below 24%) levels were considered anemic.", "where the mass for each domestic cat cell genome was considered as six picograms DNA per cell [49] . The amount of DNA in nanograms was measured by spectrophotometry." ] },{ "paper_id": "e622c993d64e1bdcb0b7ec5505945ab5fbe3185e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Immunofluorescence studies. Immunofluorescence analysis was performed exactly as described previously (28) . Samples were collected at times indicated, washed with phosphate-buffered saline (PBS), and fixed either with paraformaldehyde (4%) followed by permeabilization with 0.5% Triton X-100 or by methanol (5 min at \u03ea20\u00b0C). Samples were blocked with PBS containing 10% NCS or a mix of 5% goat serum, 5% NCS, and 2% bovine serum albumin (BSA), for 1 h at room temperature. Primary antibodies for the antigens were anti-ICP4 antibody (Virusys) used at 1:400 and anti-ICP8 antibody used at 1:400. DNA was stained with 4=,6-diamidino-2-phenylindole (DAPI; Sigma), and coverslips were mounted in Mowiol supplemented with 2.5% 1,4-diazabicyclo(2,2,2) octane (DABCO). Images were taken using an Axiovert 135 TV microscope using Zeiss 10\u03eb, 40\u03eb LD, or 63\u03eb lenses (Plan-Apochromat, 1.4 numerical aperture) and captured using a Retiga 2000R camera with Image Pro Plus software or with a Zeiss laser scanning confocal microscope (Zeiss Pascal).", "IMPORTANCE" ] },{ "paper_id": "e62bebc2ecb5a648b06eb708f88a8024231a474d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Here " ] },{ "paper_id": "e62f6de9bc9588f663d52ae7d998bbe160485d48", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Categorical and continuous variables were analyzed using chi square, Fisher exact and Mann-Whitney-U tests. Statistical analyses were performed with the Statistical Package for the Social Sciences (SPSS, 18.0). After Bonferroni correction, p values \u22640.05 were considered statistically significant.", "This study was approved by the Ethics Committee of the Faculty of Medicine, University Heidelberg. Written consent was obtained from patients." ] },{ "paper_id": "e6338aaa400a0080f7189298a977daf80d91896c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e633cc8cbce07eacd478bb25aa824872ad55c59d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As a preliminary explorative test, taxonomic profiling was performed with MetaPhlAn2 [81] with default parameters. Additional profiling was performed by using the parameter \"-t rel_ab_w_read_stats\" in order to estimate the read mappability for each profiled species." ] },{ "paper_id": "e639223272807d9187847fb3a70c6026cb890d37", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell surface staining was performed using Becton Dickinson or eBioscience reagents. Following antibodies were used: anti-CD3, anti-CD4 (RM4-5), anti-CD8 (53-6.7), anti-CD43 (1B11), anti-CD45.1 (A20), CD80 (16-10A1), anti-PD-1(J43), and IgG fluorochrome-conjugates as isotype controlls. Dead cells were detected by Fixable Viability Dyes (FVD) (ThermoFisher).", "suggesting that proliferation and apoptosis of T cells might be affected by PD-L1.", "The FV stock used in these experiments was a FV complex containing B-tropic Friend murine leukemia helper virus (F-MuLV) and polycythemia-inducing spleen focus-forming virus free of lactate dehydrogenase-elevating virus (20, 21) . The stock was prepared as a 10% spleen cell homogenate from BALB/c mice infected 14 days previously with 3,000 spleen focus-forming units of non-cloned virus stock. Experimental mice were injected intravenously with 0.3 ml of PBS containing 20,000 spleen focusforming units of FV.", "Animal experiments were performed in strict accordance with the German regulations of the Society for Laboratory Animal Science (GV-SOLAS) and the European Health Law of the Federation of Laboratory Animal Science Associations (FELASA). The protocol was approved by the North Rhine-Westphalia State Agency for Nature, Environment, and Consumer Protection (LANUV). All efforts were made to minimize suffering." ] },{ "paper_id": "e63eaf2a9904a7212185d87824ddd187ab110272", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Publish with Bio Med Central and every scientist can read your work free of charge " ] },{ "paper_id": "e63edd41c1aca8fe732d5285a64fcbd45357cdfb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Elucidating the viral structure is regarded as a promising approach for antiviral drug design, and several crystal structures of NiV proteins have been reported. The crystal structure of the P protein is a tetramer with a parallel coiled coil (Fig. 5A) , while the N 0 -P complex, whose binding site is located in residues 1-50 (P 50 ) of the N-terminal domain of P, is characterized by an asymmetric pea-like form composed of three heterodimers. N 0 remains an open conformation in the complex due to P-mediated inhibition of the polymerization of N (Bruhn et al. 2014; Yabukarski et al. 2014) (Fig. 5B) .", "Belonging to the genus Henipavirus [the other pathogenic member of the genus is Hendra virus (HeV), reviewed in (Middleton 2014; Ench\u00e9ry and Horvat 2017) ] of the family Paramyxoviridae , NiV is classified as a Biosafety Level-4 (BSL-4) pathogen due to its high pathogenicity and the lack of any effective treatments or vaccines (Wit and Munster 2015; Angeletti et al. 2016) . The NiV genome consists of a negative-sense, single-stranded RNA of approximately 18.2 kb, encoding six structural proteins, nucleoprotein (N), phosphoprotein (P), matrix protein (M), fusion protein (F), attachment glycoprotein (G), and the large protein or RNA polymerase protein (L). In addition, the P gene encodes three nonstructural proteins by RNA editing (V and W proteins) or an alternative open reading frame (C protein) (Wang et al. 2001) (Fig. 1 ).", "Nipah virus (NiV), a zoonotic paramyxovirus belonging to the genus Henipavirus, is classified as a Biosafety Level-4 pathogen based on its high pathogenicity in humans and the lack of available vaccines or therapeutics. Since its initial emergence in 1998 in Malaysia, this virus has become a great threat to domestic animals and humans. Sporadic outbreaks and person-to-person transmission over the past two decades have resulted in hundreds of human fatalities. Epidemiological surveys have shown that NiV is distributed in Asia, Africa, and the South Pacific Ocean, and is transmitted by its natural reservoir, Pteropid bats. Numerous efforts have been made to analyze viral protein function and structure to develop feasible strategies for drug design. Increasing surveillance and preventative measures for the viral infectious disease are urgently needed.", "Genomic and amino acid differences may explain differences in viral pathogenicity and virulence between isolates in Bangladesh and Malaysia, particularly given the contributions of the N, P and L proteins to viral replication and transcription and the role of the nonstructural protein C in the virulence of NiV (see ''Viral Protein Function and Structure'' section). In sequence analyses (Harcourt et al. 2005) , nucleotide sequence identity between the genomes of NiV-Bangladesh and NiV-Malaysia was only 91.8%, with an uneven distribution of differences throughout the genome. The amino acid sequence identity between NiV-Bangladesh and NiV-Malaysia proteins were all greater than 92%." ] },{ "paper_id": "e63f49d69364214383bb4bd983e941816b11b8da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The particle size and polydispersity index of RV/MERS and MERS BLP were measured by a dynamic light scattering (DLS) device before immunization of mice. As shown in Figure 1 ", "All animal works were strictly in accordance with the welfare and ethical guidance on Chinese laboratory animals (GB 14925-2001). The agreement was approved by the Animal Welfare and Ethics Committee of the Institute of Veterinary Medicine of the Changchun Veterinary Research Institute (Laboratory Animal Care and Use Committee Authorization, permit number JSY-DW-2019-05).", "All statistical analysis was performed by using the Graphpad 8.0.2 software. The results are expressed as the mean \u00b1 SD, and significance in their differences between groups were analyzed using a Student's t-test." ] },{ "paper_id": "e642816c09dd07b7bdf515088670a72ee8698bd8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA). P < 0.05 was considered statistically significant. Numeration data were expressed as the incidence rate, a chi-square test was used, data were expressed as mean \u00b1 standard deviation, and parametric statistics was used.", "The experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of Jilin University, China. Written informed consent was obtained from individual participants." ] },{ "paper_id": "e64a2ab805fe19fae40eb382eccb7ea82a997a1d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Urine from each animal was collected weekly starting 7 days after post-challenge by placing the animals individually for 20-24 hrs in metabolic cages, and was captured into containers containing Roche Complete Protease Inhibitor, one tablet per 5 mL urine. Urines were separately centrifuged at 3000 x g for 30 min. The supernatant was withdrawn, the pH adjusted to 7, aliquoted and frozen at -70\u00b0C until further analysis.", "Genomic DNA was extracted from these weekly urines and qPCR was used to assess leptospiruria. In addition, at necropsy, kidneys were harvested, fixed in formalin, paraffin embedded, and infection confirmed by Warthin-Starry silver stain (S1 and S2 Figs.).", "Leptospirosis is a globally important tropical infectious disease that takes a disproportionate toll in tropical regions [1] . Important gaps remain in translating the know how to reduce the burden of this infectious disease and its pathogenic mechanisms remain poorly understood [4] .", "This work was approved by the Institutional Animal Care and Use Committee of the University of California, San Diego." ] },{ "paper_id": "e64c852725ef6bf2abf9071b522c10917b50ac6e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Anti-CD206-PE-Cy5, anti-mouse IgG1-PE-Cy5 and antimouse IgG1-FITC antibodies were from BD Biosciences. Anti-CD62P-FITC, anti-CD62P-PE, anti-mouse IgG1-PE and anti-DC-SIGN-FITC were from BioLegend. Anti LSECtin antibody was described elsewhere [26] . For neutralization of CXCL4 a neutralizing polyclonal antibody from Axxora was used. Recombinant human CXCL4 was purchased from R&D Systems.", "Statistical significance was determined using Student's t test for paired samples using Excel software." ] },{ "paper_id": "e6515195e0fdd7f1fb437a01b8737685d6d92765", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RNA was prepared directly from combined NTS or NPA using Roche High Pure RNA kits (Roche, Mannheim, Germany).", "The cDNA was reverse-transcribed from 10 \u03bcL of specimen RNA using 100 units of SuperScript III reverse transcriptase (Invitrogen, Carlsbad, CA, USA) and 4 \u03bcL used for real-time PCR as described previously. 19 Amplification was performed in glass capillaries on ", "CS07-7-A24 A A A CS09-5-A24 A A A CS09-22-A24 A A A CS09-3-A33 A A A CS09-12-A33 A A A \u2022CS09-2-A67 A branches with HRV89 A- A MS07-20-A57 A A A MS07-21-A57 A A A CS09-6-A21 A A A CS09-17-A21 A A A CS09-21-A21 A A A MS06-4-A61 A A A MS06-6-A61 A A A CS09-15-A41 A A A MS08-8-A55 A A A CS09-11-A58 A A A CS09-26-A58 A A A MS06-2-A89 A A A CS09-28-A8 A A A CS07-9-1B A A A CS07-12-1B A A A CS07-13-1B A A A CS07-14-1B A A A CS07-18-1B A A A MS08-6-A43 A A A CS09-4-A43 A A A MS07-16-A31 A A A CS09-13-A31 A A A CS09-20-A47 A A A CS07-24-A56 A A A CS09-23-A98 A A A MS08-2-A15 A A A MS08-3-A15 A A A CS07-6-A15 A A A CS09-27-A15 A A A CS07-4-A22 A A A CS09-1-A23 A A A CS09-8-A23 A A A (Continues)" ] },{ "paper_id": "e65736745475f7a3bab0f310edb593acc50528b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Effect of alanine mutations in nsp16 interface residues. Residues were identified using PISA (http://www.ebi. ac.uk/msd-srv/prot_int/pi_link.html). Same legend as Table S1 except that no BRET experiments were performed. (DOC)", "Overall, the chain traces are unambiguous, with clear electron density including for a single SAH residue bound to the nsp16 protein. Solvent accessible surfaces were calculated using program AREAIMOL [60] with a 1.7 \u00c5 radius sphere as the probe (Table 1) ", "AdoMet and cap analogs GpppA and 7Me GpppA were purchased from New England BioLabs, the[ 3 H]-AdoMet was purchased from Perkin Elmer and Sinefungin (adenosylornithine) from Sigma-Aldrich.", "Nsp16 adopts a canonical SAM-MT fold (Figs. 1B, 2A and B), as defined initially for the catechol O-MTase [25] . The sevenstranded b-sheet MTase fold has been described as having a secondary structure topology defining two binding domains, one for SAM and the other for the methyl acceptor substrate ( Fig. 2A) . The nsp16 topology matches those of dengue virus NS5 N-terminal domain and of vaccinia virus VP39 MTases [27, 31] . Nsp16 lacks several elements of the canonical MTase fold, such as helices B and C (Fig. 2B )." ] },{ "paper_id": "e657fc1a1df1ac7f0e7f45a43d405cfda6cda48d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The chemical reagents and standards for HPLC were prepared as previously described [15] . Briefly, HPLC-grade methanol, acetonitrile, chloroform, and isopropanol were purchased from Merck (Darmstadt, Germany). A Milli-Q water purification system (Millipore, Burlington, MA, USA) was used to prepare HPLC-grade water. Analytical grade formic acid, ammonium formate, and commercial standards used for biomarker identification were purchased from Sigma-Aldrich ( ", "In addition to their immunomodulatory roles, the omega-3 and omega-6 PUFAs can also directly regulate virus replication. We previously demonstrated that AA and linoleic acids (LA) could inhibit the replication of coronaviruses including the Middle East respiratory syndrome coronavirus (MERS-CoV) and human coronavirus 229E (HCoV-229E) [13] . Similarly, the PUFA-derived lipid mediator protectin D1 (PD1) was reported to markedly attenuate influenza virus replication via interference with the virus RNA export machinery [26] . On the other hand, inhibition of the PUFA synthesis pathway through depleting the delta 6-desaturase enzyme or by treatment with a small-molecule inhibitor impaired hepatitis C virus (HCV) production, indicating that PUFAs could also be required for virion morphogenesis [32] .", "Adjust p-value < 0.05, fold change >1.25 or <0.8 were used as the criteria for selecting significant features. For multivariate analysis, the features were first subjected to Pareto scaling, followed by orthogonal partial least squares discriminant analysis (OPLS-DA) to find important variables with discriminative power. Variable importance in projection (VIP) score >1 was used as a criterion for significant lipid features selection. The R2X/R2Y and Q2, which represented the X/Y variables explanation rate and the predicted ability of the OPLS-DA model, respectively, were calculated using the SIMCA-P software [41] ." ] },{ "paper_id": "e658837e4d77ef0bccdd849648e2db595f5ec65b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Approximately 4% of the ticks were infected with a microorganism with a base count signature consistent with a spotted fever group Rickettsia that was distinct from the characterized Rickettsia endosymbiont of I. pacificus. Further analysis is needed to determine whether this signature represents a novel spotted fever group Rickettsia or a genotypic variant of a known species.", "In our next generation DNA sequencing of the four ticks with Anaplasma we also determined the sequences of the Rickettsia endosymbiont 16S rRNA (GI: KP276589, KP276590 and KP276591), gltA (GI: KP276596, KP276597, KP276598, and KP276599), and rpoB (GI: KP276608, KP276609, KP276610, and KP276611) loci from four ticks. The groEL locus was not sequenced as it was not amplified due to primer design. No sequence variation was detected in the four tick specimens sequenced, and the sequences of the I. pacificus endosymbiont shared 100% identity with the recently published genome sequence. (Fig 1A-1D ).", "Tick collection and DNA extraction I. pacificus ticks were collected from 2007 to 2009 in thirteen counties throughout the state of California by flagging (S1 Fig). All ticks tested were adults with the exception of 126 nymphal ticks collected in Sonoma County. All ticks were visually pre-identified as I. pacificus, and the species was confirmed in 96.9% of the ticks tested by the detection of the Rickettsia endosymbiont of I. pacificus [10] . No ethical clearance was required to conduct research on invertebrate ectoparasites. All samples were submitted by private collectors or collected by county vector control agencies from locations that did not require specific permission. These studies did not involve endangered or protected species. Ticks were either alive, frozen, or ETOH preserved prior to DNA extraction using a modified Qiagen column-based protocol described previously [28] with the substitution of the Qiagen DNAeasy columns (Qiagen, Valencia, CA) for the Qiagen Virus MinElute columns (Qiagen, Valencia, CA). A negative extraction control consisting of lysis buffer was included with each set of extractions and carried through the analysis to monitor for potential contamination." ] },{ "paper_id": "e659993cca4cf1cc40900a6625576e8c63013602", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Laboratory data on admission revealed lymphopenia, elevated liver function tests, hypoalbuminemia, and elevated inflammatory markers (Table 1) . Chest radiography showed multiple bilateral patchy pulmonary infiltration (Fig. 1g) ." ] },{ "paper_id": "e666325d40e18c90c35e6a6eb9b5723a28cc15ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This controlled clinical trial was carried out in 2 phases in the Investigational Medicine Unit of National University Hospital (NUH), Singapore. Study procedures were approved by the National Healthcare Group Domain Specific Review Board in July 2010 (Reference Number: 2010/00226), and written informed consent was obtained from all participants." ] },{ "paper_id": "e67d66fb0773322520aa527d533c6cffb08016a2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The confirmed CMAH KO pigs (founders) were raised by following the husbandry practices for breeding stocks of SPF herd. When reached puberty and showed their second estrous cycle, the females were thereafter estrus synchronized by Regumate feeding and withholding. The female founders were then artificially inseminated with fresh extended semen collected from the male littermate founder to generate homozygous offspring for the study.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "e67eb3bd9090630fa37b601957ed1dcc088901cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DNA was first isolated 150 years ago and identified by James Watson and Francis Crick 65 years ago. Initially, the only function attributed to DNA was to carry and pass genetic information from one generation to another. However, with advancements in science, DNA molecules got recognition for having a new role in the field of materials science [85] .", "These chemical modifications of aptamers reduce selection time and increase their biostability in vivo. The early diagnosis and identification of subtypes, help target viral strains specifically and rationally.", "Antisense oligonucleotides have been studied extensively against several respiratory viruses with promising results.", "Aptamers have been developed against influenza for therapeutics purposes. Many of these aptamers developed against HA could prevent the entry of the virus to the cells by blocking " ] },{ "paper_id": "e6846e658261dafd5aff4d0433bafa8118d6fa7d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Blood samples were obtained from healthy volunteers at the Westmead Institute of Medical Research. Data points represent individual donors from a cohort of \u223c20 healthy individuals. Different cohorts of donors were used for individual experiments based on availability. Liver tissue was obtained at Westmead Hospital, Sydney, at the time of needle biopsy [chronic HBV/HCV infection, non-alcoholic fatty liver disease (NAFLD)/NASH, autoimmune hepatitis] or from patients undergoing liver resections (normal tissue). Ethics approval was obtained from the Sydney West Area Health Service and University of Sydney. Informed consent was obtained for all subjects [HREC2002/12/4.9(1564)].", "RNA sequencing data has been uploaded into the Figshare data repository: https://doi.org/10.6084/m9.figshare.10324511.v1.", "The studies involving human participants were reviewed and approved by Sydney West Area Health Service. The patients/participants provided their written informed consent to participate in this study." ] },{ "paper_id": "e68b0f3da8a02a8f0b86869e533eaf549f70ff9a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2018, 10, x FOR PEER REVIEW 5 of 12", "The authors declare no conflicts of interest. The funding sponsors had no role in the writing of the manuscript or the decision to publish this article." ] },{ "paper_id": "e68bb0f18492dc5645e027d5da3369ed17edbabd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As noted, a copy of the study questionnaire and codebook are appended." ] },{ "paper_id": "e69a0c654041707c6ffefca96f14c2f1fe05296c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.ppat.1006365.t003", "PLOS Pathogens | https://doi." ] },{ "paper_id": "e6a3a6591a7468ae5fdb3efcf43fa0dce1b0b00c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All NGS data and reference sequences are available in the NCBI SRA or RefSeq databases. Their accession numbers are provided in the method section.", "We also provided a novel view on cancer and virus-induced diseases. In one of our previous studies, we reported that U1 snRNA over-expression affected the expression of mammal genes on a genome-wide scale and that U1 snRNA could regulate cancer gene expression. This was explained by the fact that alternative splicing (AS) and alternative polyadenylation (APA) were deregulated and exploited by cancer cells to promote their growth and survival (Spraggon and Cartegni, 2013) . Our alternate explanation is that the over-expressed U1 snRNA in cancer cells recruits excess RNase III for RNAi, thereby causing RNase III to lose its abilities to function in the RNA degradation of other genes or in genome surveillance (Nicholson, 2013) . Viruses also recruit excess RNase III, prompting RNase III to lose its abilities to function in host defense as well as its regular functions.", "SG conceived the project and drafted the main manuscript. SG and ZeC supervised this project. SG, HJ, and XJ analyzed the data. XY, YL, and TZ curated the sequences and prepared all the figures, tables, and additional files. XX, ZhC, and QZ performed the experiments. JR and WB revised the manuscript. All authors have read and approved the manuscript. " ] },{ "paper_id": "e6a4aa79206219f2e1229c6ecc507078520466b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The antibody to gp160/41 (Chessie 8) and Vif (#319) were obtained through the NIH AIDS Research and Reference Reagent Program [41] . Polyclonal rabbit anti-Nef antibody was obtained from Thermo Fisher Scientific, Inc. Monoclonal mouse anti-\u03b2-actin antibody was obtained from Sigma. The antibody to p24 (EF7), has previously been described [42] . The secondary antibodies, HRP-conjugated polyclonal goat anti-rabbit immunoglobulins and HRPconjugated polyclonal rabbit anti-mouse immunoglobulins, were obtained from DAKO.", "HIV-1 gp41-derived monomeric peptides were custom synthesized by Synpeptide Co Ltd (Shanghai, China) and the dimeric peptides by Pepscan Presto BV (Amsterdam, Netherlands).", "HLtat (Cat. #1293) and TZM-bl (Cat. #8129) cell lines were obtained through NIH AIDS Research and Reference Reagent Program [43] [44] [45] [46] [47] and cultured in Dulbecco's Modified Eagle Medium (Life technologies) supplemented with 10% fetal bovine serum (Life technologies) and 1% Penicillin-Streptomycin (Life technologies). The expression plasmid for Env, Nef (negative regulator factor) and Vpu (virion protein U) from the HIV-1 strain NL4-3 (pNL1.5EU+) was kindly provided by Dr. Stefan Schwartz (Lund University, Lund, Sweden) [48] ." ] },{ "paper_id": "e6a9266f1f45099b19b5c4f3a4cf62de41786e54", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics Statement. All animal experiments were approved by the Institutional Animal Care and Use Committee of the Rocky Mountain Laboratories, and performed following the guidelines of the Association for Assessment and Accreditation of Laboratory Animal Care, International (AAALAC) by certified staff in an AAALAC-approved facility.", "Histopathology. Histopathology was performed on select hamster tissues. After fixation for 7 days in 10% neutralbuffered formalin and embedding in paraffin, tissue sections were stained with hematoxylin and eosin (H&E). For the histopathological analysis of the nasal turbinates whole hamster skulls were used. The skulls were decalcified using a 20% EDTA solution in sucrose (Newcomer Supply) and allowed to sit at room temperature for 3 weeks. The 20% EDTA/sucrose solution was changed once prior to mid-sagittal sectioning of the skull.", "The work with infectious MERS-CoV was approved under BSL3 conditions by the Institutional Biosafety Committee (IBC). Sample inactivation was performed according to standard operating procedures approved by the IBC for removal of specimens from high containment." ] },{ "paper_id": "e6a9cb9589ec2381d774a128189529fc2669f079", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at http://www.mdpi.com/2073-4425/10/5/332/s1, Table S1 : VIDISCA-NGS and qPCR data for all samples. ", "During the last two decades, conventional diagnostics for viral CNS infections have shifted from non-specific culturing techniques towards highly-specific viral nucleic acid amplification tests, like", "For patients with a suspected central nervous system (CNS) infection, rapid and accurate diagnosis is vital to determine treatment and improve prognosis [1] . The differential diagnosis of such patients includes infectious etiologies, of which viruses are the most common [2] , but also non-infectious etiologies, such as auto-immune diseases [3] . Nonetheless, in more than half of cases, the cause remains unknown [4] . Identification of a virus can aid in patient management as it may initiate specific antiviral treatment, or cease or prevent ineffective antiviral, antibiotic, and/or immunosuppressive treatments, which all have potential harmful side effects. For example, when differentiating between an auto-immune and viral origin, immune suppression could lead to deleterious outcomes when caused by an unidentified virus [5] ." ] },{ "paper_id": "e6b8ff26b423ef6507f006d69f9a183fb1147988", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition, access and availability of online information is differentially experienced in Canada. Despite the growing use of online media, Internet use is known to vary considerably by age group, level of education and income [35] . In 2009 only 41% of older Canadians (65 years and older) reported using the Internet at least once in the last 12 months, as opposed to 88% of those aged 35 to 54 years and 97% of those 34 years and younger. Although relatively low, this usage had increased from the mere 24% of older Canadians reporting Internet use in 2005. Internet use was also higher for Canadians with a university degree (95%) than for those with less than high school education (51%), and for those with annual incomes of greater than $50,000 (92%) than for those with annual incomes of less than $10,000 (76%).", "Greater breadth and channels of electronic information sources in recent years has further allowed people to engage in interactive online discussions through Web 2.0 platforms such as blogs, wikis and social networks. Social networking was thought to be widely used as an information source during the H1N1 outbreak and subsequent vaccination program [7] . However, as was noted for other types of Internet-based information, while some of the content available through social media was considered credible and valuable (particularly that generated through public health agencies), it was also demonstrated to be a source of misleading and bewildering information [33, 34] .", "Learning from past outbreaks, and trends between outbreaks, provides an invaluable opportunity to improve performance and mitigate impacts of future outbreaks. In this article, we report on public information use, together with assessed usefulness and credibility, in the province of Alberta, Canada during both the SARS epidemic and H1N1 pandemic. The lessons learned from these outbreaks will enable public health agencies to effect further improvement in risk communication efforts in subsequent infectious disease events.", "Participants were recruited using a Random-Digit Dialling (RDD) approach to ensure that residents had an equal chance to be contacted whether or not their household was listed in a telephone directory. A respondent within each household was selected on the basis of gender to ensure an equal selection of male and female participants. If contact was not made on the first call, a maximum of 10 call-back attempts were made before declaring a residential telephone number as \"no contact.\" Ten percent of the respondents were randomly selected and recontacted by the survey telephone supervisors for interviewing validation. The overall response rate was 47% for the SARS survey and 21% for the H1N1 survey." ] },{ "paper_id": "e6c10d7b9b6a71574918af6a89617962c6bbcf3d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e6d533faf65d64332697077b71aa71dfc78fc06a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Oil based veterinary vaccines have previously been reported to cause a prolonged chronic granulomatous reaction with sterile abscess formation [11] that may result in significant morbidity requiring multiple operations for debridement [11] .", "Calf diarrhoea is a contagious and often fatal disease of calves. Rotavirus, Coronavirus and E. Coli are three of the most important causal agents." ] },{ "paper_id": "e6d560c0ed2c420b3ca34de569c8a46d3722e2da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "During the first preschool visit, consent forms with information about the study were distributed to the children. Children were encouraged to bring back the signed consent forms the next morning. At the next school visit, examinations were performed on the children who brought back a signed consent.", "It was determined to choose the school as a unit of sample selection using a numbered list that was previously prepared. Preschools were randomly selected using Random Number Generator [33] . Two numbers representing a private and a public school were selected in each of Jeddah's main four districts (North, East, South, and West). Approval to visit the selected preschools and collect data from the children was obtained from the Ministry of Education in Jeddah, and approval of the school principal was obtained prior to the school visit.", "Ethical approval for the study was obtained from the Research Ethics Committee, Faculty of Dentistry King Abdulaziz University (#036-13). Informed consent was obtained from all participating caregivers." ] },{ "paper_id": "e6dcb411da6446850724d574d0e6bbb507a1f4ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Copy number = C DNA (ng/ml) 6 6.02 6 10 23 (Avogadro's number)/W.", "Knowing the number of plasmid molecules with the target viral gene in a ml, a series of dilutions was made to generate a PCR standard curve.", "1. Calculate the margin of error of the confidence interval (CI), W = t* 6 SD/!n, where: n -number of obtained C(t) values, SD-standard deviation, df = n21, and t* (for 95% confidence) is a ''critical value of the T distribution'' [14] . 2. One side CI covers this range: M-W, where M is sample mean.", "PCR multiplexing should be highly useful when both the volume of the samples and the time of testing are critical, as in the donor eligibility (DE) testing for tissue or organ transplantation [10] . Current regulation requires that DE testing be performed using assays approved and licensed by the U.S. Food and Drug Administration (FDA). However, the automated assay systems that are designed to screen large numbers of samples, without the strict limitation of sample volumes, may not be completely suitable or ideal for the needs of DE testing for tissue or organ transplantation." ] },{ "paper_id": "e6e00bfca850f42e1b2baa9ce190d37554f4a42e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "CapoNPV contains 12 replication associated genes, 12 transcription associated genes, 8 genes essential for oral infection, 34 structure related genes and 15 auxiliary genes ( Table 1 ). The rest are 45 of unknown function including 4 hypothetical unique genes of CapoNPV.", "Supporting Information S1 ", "Members of the family Baculoviridae are rod-shaped, insect-specific viruses with doublestranded large circular DNA genomes of 80-180 kb [1, 2] . Lepidopteran baculoviruses synthesize two progeny phenotypes, the budded virus (BV) and occlusion-derived virus (ODV). Virus particles of the latter phenotype are embedded into occlusion bodies (OBs) [3] , which offer some protection against environmental inactivating conditions such as UV light, heat and desiccation." ] },{ "paper_id": "e6e057796aa14fa1808ee7076da0109362acb7c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Multiple comparisons of the data were assessed by Bonferroni/Dunn analysis. A p value of <0.05 was considered statistically significant. All calculations were conducted using Excel for Mac (2011) with Statcel3C.", "According to a previously reported method [17] , the vinyl chloride material (1 \u00d7 1 cm) spotted with bacteria was washed with saline, fixed with 2.5% (v/v) glutaraldehyde in phosphate-buffered saline (pH 7.4) for 2 h at room temperature, then treated with 2% (w/v) osmium tetroxide for 1 h at 4\u02daC. The samples were then dehydrated in ethanol, freeze-dried, and coated with osmium using a plasma osmium coater, for analysis using a scanning electron microscope (Hitachi S-4800; Hitachi, Tokyo, Japan).", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "e6f54fcf3460165fb558903e975a526bc98e4eba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Fluorescent liposomes and p14-containing proteoliposomes were prepared exactly as previously described [28] . Liposomes (0.4-1.6 mM) were incubated with QM5 fibroblasts on ice for 1 h, then removed and cells were washed with Hank's balanced salt solution (HBSS). The cells were then resuspended in 10 mM EDTA in phosphate-buffered saline (PBS) and bound liposomes were quantified by fluorimetry as previously described [28] . The quantity of lipid molecules bound was calculated using a standard curve comparing fluorescence intensity to phospholipid concentrations.", "Cells grown on gelatin-coated glass coverslips were fixed with 3.7% formaldehyde (20 min) and permeabilized with 0.1% Triton X-100 in PBS (20 min). For surface immunofluorescence, cells were stained as below at 4uC in HBSS prior to fixation with 3.7% formaldehyde. Actin was stained (20 min) with Alexa Fluor 488or 555-conjugated phalloidin. N-and E-cadherin, HA, p14 and p14-2HAN were detected by incubating cells for 1 h with the appropriate primary antibody followed by fluorophore-conjugated secondary antibodies for 45 min. Cells were mounted with fluorescent mounting medium (Dako), images were acquired with LSM imaging software on a Zeiss LSM510 META laser scanning confocal microscope using the 488 nm argon laser for Alexa Fluor 488 or the 548 nm HeNe laser for Alexa Fluor 555. Images were captured with the 636 or 1006 Plan APOCHROMAT (1.4 NA) objective lenses and processed in Adobe Photoshop version 6.0 using only linear adjustments.", "Cadherin-mediated cell-cell contacts were disrupted by washing cells with PBS followed by a 1 min incubation with PBS +0.5 mM EDTA, just prior to the onset of syncytiogenesis in the transfected cells. Cells were then washed with PBS and incubated for the duration of the experiment with either MEM or S-MEM (calcium free MEM, Invitrogen) supplemented with 10% dialysed FBS.", "Coordinating the membrane attachment and membrane fusion stages of the fusion reaction using an autonomous fusion machine reflects the need for enveloped viruses to spatially and temporally regulate fusion of the virus envelope with a suitable target cell membrane." ] },{ "paper_id": "e703a33d5803f827c3d57a19385c0c2cbc2830e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As the study was conducted with the clinical cases (affected animals) ethical committee approval was not required. Available at www.veterinaryworld.org/Vol.10/August-2017/4.pdf", "The diagnostic methods based on PCR have the potential to be more sensitive and have a shorter turnover time, though they lack proper validation [21] . These molecular tests have been designed for the detection of many virulence genes and are often the most sensitive methods for detecting them [22] .", "How to cite this article: Priya AK, Balagangatharathilagar M, Chandrasekaran D, Parthiban M, Prathaban S (2017) Prevalence of enteropathogens and their antibiotic sensitivity pattern in puppies with hemorrhagic gastroenteritis, Veterinary World, 10(8): 859-863.", "The fecal antibiotic sensitivity results revealed gentamicin to be sensitive in 95% of the cases, azithromycin in 50%, enrofloxacin in 25%, cefotaxime in 20%, and tetracycline in 5% of the cases. The order of sensitivity was gentamicin > azithromycin > enrofloxacin > cefotaxime > tetracycline. Maximum resistance (100%) to amoxicillin and least resistance (5%) to gentamicin were observed." ] },{ "paper_id": "e7124df42078edba08ccba1b033dffb0a36f6305", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "doi:10.1371/journal.pntd.0005394.g007", "Many emerging viruses of public health concern are arthropod-borne, including tickborne encephalitis, dengue, Zika, chikungunya, and West Nile viruses. The arboviruses are maintained in nature via virus-specific transmission cycles, involving arthropod (e.g." ] },{ "paper_id": "e7188ee8f88af646369d7db34c99658cc80206c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rapidly replicating (+)RNA viruses, including mosquito-borne flaviviruses, are notorious for their ability to develop resistance to compounds targeting viral proteins [20, 21] . On the other hand, viruses rely on cellular metabolism for every step of their life cycle, providing an opportunity to control infections by manipulating host rather than viral factors. Cellular proteins do not change, thus targeting cellular factors critical for infection instead of easily adaptable viral proteins likely poses a higher barrier for development of resistance. Moreover, even distantly related viruses rely on highly conserved replication mechanisms and likely share the requirements for the same cellular factors, thus providing an opportunity for developing broadly effective therapeutics with high barrier of resistance [22] .", "virions, which also initiate their assembly on ER membranes. Assembled virions enter and then travel through the secretory pathway, undergoing maturation along the way, until their final release into the extracellular space. ", "Interestingly, BFA and GCA inhibit the development of infection when added early during the infection cycle but rapidly lose their effectiveness if added after~12 h, at the time of active virion maturation and release [96, 98] . This may suggest that GBF1 is involved not only in the early steps of virion assembly by regulating the availability of the capsid protein but also may support Zika RNA replication directly, as has been described for many diverse (+)RNA viruses [108] [109] [110] [111] [112] ." ] },{ "paper_id": "e725656b0cdd0f7e78279187e0c251cf8683f1e5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Text S1 Amino-acid sequences of MazF based zymoxins.", "The following Escherichia coli (E. coli) strains were used: XL-1 Blue and DH5a (Stratagene, USA) for plasmid propagation and BJ5183 (Stratagene, USA) for the generation of recombinant adenovirus plasmid DNA.", "Oligonucleotides. All the oligonucleotides that were used in this study were purchased from Hylabs, Israel. Oligonucleotides that were used in this study are listed in Table S1 .", "Table S1 Oligonucleotides that have been used in this study." ] },{ "paper_id": "e741dab28c2359000a1069189b3879c97f2f83ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There has yet to be any formal comparison between the RNA interactions identified in the new structure and the predictions made in previous studies. " ] },{ "paper_id": "e745a55d651d2f45443c39ed949185d8f968500a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Arabidopsis callus culture protoplasts were prepared and transfected using a polyethylene glycol-mediated transformation protocol as previously described (42) . Briefly, 20 g of PEMV gRNA transcripts were transfected into 5 \u00d7 10 6 protoplasts and incubated at 22 \u2022 C for 24 h in the dark. Total RNA was extracted using RNA extraction buffer (50 mM Tris-HCl [pH 7.5], 5 mM EDTA [pH 8.0], 100 mM NaCl, 1% SDS), followed by phenol-chloroform extraction and ethanol precipitation. Five micrograms of total RNA was subjected to electrophoresis through a 1.5% non-denaturing agarose gel and then denatured and transferred to nylon membrane by capillary transfer. [\u2423-32 P] dCTP labeled DNA probes complementary to the 3 UTR of the genome were used for hybridization. The blot was exposed to a phosphorimager screen, which was scanned by a FLA-5100 fluorescent image analyzer (Fujifilm). The viral gRNA accumulation was quantified using Quantity One software (Bio-Rad).", "Plasmid pUC19-PEMV, which contains the full-length wild type PEMV RNA2 genome downstream of a T7 promoter, was used as a template for polymerase chain reaction (PCR)-based site-directed mutagenesis. The desired mutations were introduced using custom designed oligonucleotide primers (Integrated DNA Technologies) using the QuikChange one-step site-directed mutagenesis procedure (46) . The resulting PCR products were subjected to DpnI digestion before introduction into competent DH5\u2423 E. coli cells. The presence of the desired mutations was confirmed by sequencing (Eurofins Genomics).", "SHAPE structural probing was performed essentially as previously described (40) . Briefly, PEMV gRNA was denatured at 95 \u2022 C for 3 min, snap-cooled on ice for 2 min and then incubated in SHAPE folding buffer (80 mM Tris-Cl, [pH 8.0], 11 mM Mg(CH 3 COO) 2 , 160 mM NH 4 Cl) at 37 \u2022 C for 20 min. Folded RNA was then treated either with 15 mM N-methylisatoic anhydride (NMIA) or with the same volume of dimethyl sulfoxide (DMSO) as a negative control at 37 \u2022 C for 40 min. RNA was recovered by ethanol precipitation and then re-suspended in 0.5x TE buffer. Primer extension reactions were performed using [\u2425 -32 P] ATP-labeled oligonucleotides and SuperScript III reverse transcriptase (Invitrogen) as previously described (47) . Primers complementary to PEMV positions 1052-1077 (5 -CCAAAATCTCCAAGAGGACGCACAAC-3 ) and 1165-1185 (5 -GAGGGGAAGGGAACCTTAGGC-3 ) were used for structural probing of the RSE/SLA and SLB, respectively. Reaction products along with ladders generated by Sanger sequencing were resolved on 8% ureabased polyacrylamide gels. Gels were then dried and exposed to a phosphorimager screen. The NMIA reactivity of each nucleotide was assigned none, low to moderate and moderately high to high by visually inspecting the intensities of individual bands. RNA secondary structures were generated from structure probing results and the best-fitting Mfold predictions (48) ." ] },{ "paper_id": "e7482377b6836c860bc4ea714ea5dd757a293ad0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Avian Infectious bronchitis (IB) is a highly contagious and economically important worldwide viral disease of chickens. It affects chickens of all ages with severe signs in younger birds and high mortality rates especially when a co-infection with a secondary bacterial or viral pathogen(s) (1) (2) (3) (4) . Infectious bronchitis virus (IBV) mainly causes respiratory disease and nephritis in chickens but can also result in poor weight gain and lost feed efficiency in broilers and reduced numbers and quality of eggs in layers (5) .", "(1) = 1 \u2212 mean ciliostsis score for vaccinated challenged mean ciliostsis score for challenged group \u00d7 100", "HS, WE, and AA: conceptualization. AA, WE, AB, and WK: methodology. AA, WK, AB, and MZ: investigation. AA, WK, AB, and MZ: data analysis. WE and WK: resources. AA, WK, AB, and MZ: data curation. AA, WK, and AB: writing-original draft preparation. HS, AA, WE, AB, WK, and MZ: writing-review and editing." ] },{ "paper_id": "e74b146de222afb1af191265d849fc86048712bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Scientific World Journal ", "The spectroscopic characterization data of (4a-f/5a-f) are given below. [2,3-d] [1 ,3 ] ", "4d 7 -Amino-2 2 -dimethyl-2,4 -dioxo-5-bromo-1,2-dihydro- spiro[indoline-3,5 -pyrano", "Heterocyclic chemistry is one of the most complex and intriguing branches of organic chemistry and heterocyclic compounds constitute the largest and most varied family of organic compounds. Among heterocyclic compounds, indole derivatives exhibit a number of biological activities [1] [2] [3] [4] [5] [6] [7] [8] , for example, antimicrobial, anticonvulsant, antineoplastic, antiviral, antihypertensive, anti-inflammatory, and enzymatic inhibition activities dopaminergic agonist and so forth. In addition to substituted and condensed heterocycles, spiroindoles, with C-3 as spiro atom, have received considerable interest due to their strong biological activities [9] [10] [11] ." ] },{ "paper_id": "e7742497150bd3dc1d60ff914d1c0fb05f747a1a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As all patients receiving medical treatment for their symptoms were children below the age of consent, informed consent for the testing of the swab and downstream sample processing was given by the child's parent or legal guardian. All methods and experimental protocols were approved by the Princess Margaret Hospital for Children Human Ethics Committee and the Research Governance Office (project numbers 1970/EP and 2014117EP).", "Data were not normally distributed and were therefore assessed non-parametrically. The Mann-Whitney U test was applied to compare two groups, and the Kruksall-Wallis test was applied when comparing three or more groups. Non-parametric Spearman's rank coefficient was used for correlations. Results in text and tables are presented as medians with the interquartile range. In all statistical analysis, a p-value <0.05 was considered statistically significant. All statistical analyses were carried out using SPSS statistical software version 16.0 (IBM Inc Chicago, USA).", "A univariate analysis was conducted to determine the influence of viral load on the cytokine responses. This was confined to inflammatory mediators that had shown a significant difference from the control group separately for asthma and non-asthma patient groups (Tables S2 and S3) . These showed weak, non-significant relationships between the selected cytokines and RV-C load for both groups. Moreover, none of the cytokines analysed showed any association with the likelihood of hospitalisation (Table S4) ." ] },{ "paper_id": "e782e045471faad6e0a63dae1f064e345d754493", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The AcMNPV recombinant bacmids were derived from the commercially available bacmid bMON14272 and propagated in Escherichia coli strain DH10B (Invitrogen Life Technologies). The bacmid-based recombinant viruses were propagated in Sf9 cells maintained in serum-supplemented TC100 medium at 27uC, as previously described [99] .", "Citation: Kikhno I (2014) Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis. PLoS ONE 9(4): e95322." ] },{ "paper_id": "e784769ed85685121bda82e89183d0b756686281", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Solving for q yields", "Therefore:", "doi:10.1371/journal.pone.0157450.g002" ] },{ "paper_id": "e788ce631ca8a7d0a0d0b48dfd06d343de282972", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e78cecafd32aeadea4fe12d0a7d3f7883d222b58", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The significance of differences in values of the measured parameters between the investigated groups was analyzed with the Kruskal-Wallis non-parametric test for independent samples using Statistica.pl v.10.0 software. Differences were considered significant at confidence levels of 95 and 99% (p< 0.05 and p<0.01, respectively).", "29 July 2005 on the National Committee for Animal Experimentation. The research protocol was approved by the Local Ethics Committee on Animal Experimentation at the University of Warmia and Mazury in Olsztyn (Authorization No. 64/2014). The birds were euthanized by intravenous administration of pentobarbital sodium at 70 mg/1 kg BW (Morbital, Biowet Pu\u0142awy, Poland) after premedication by intramuscular injection of butorphanol tartrate at 4 mg/1 kg BW (Torbugesic, Zoetis, USA). The researchers made every effort to minimize the suffering of birds.", "Mononuclear cells from the whole spleens collected from each bird were isolated with the method described previously [5] . Cell concentrations and the percentage of viable cells were determined in the Vi-cell XR analyzer (Beckman Coulter, USA).", "Each vaccination dose (20\u03bcg of PiCV rCP/ pigeon) was prepared individually by mixing a volume of protein equivalent for an immunization dose with PBS (phosphate-buffered saline) (Sigma Aldrich, Germany) up to the volume of 200 \u03bcL. Next, it was mixed with 200 \u03bcL of an oil-based adjuvant (Montanide ISA71 R VG) provided by Seppic (France). The mixed equal volumes of the adjuvant and PBS (400 \u03bcL in total) were used as a vaccination control." ] },{ "paper_id": "e7910acd7e2772df933ee8161c68baf67cc4991d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sections were post-fixed in 0.5% osmium tetroxide and 0.1 M Caco-buffer at room temperature, for 3 h and washed with 0.1 M Caco-buffer. Fixed sections were dehydrated by sequential incubation in ethanol 50-100% and propylene oxide, embedded in epoxy resin and polymerized at 62 \u2022 C for 72 h. Semi (500 nm) and ultra-thin (50-70 nm) sections, were obtained using a Leica EM UC7 ultramicrotome. Uultra-thin sections were collected onto plastic-coated nickel grids and immunochemically contraststained with uranium salts (uranyl acetate) and lead citrate to reveal cell ultrastructure. Finally, samples were analyzed using a transmission electron microscope EM902A Fa.Zeiss with the iTEM Soft Imaging System software (Olympus).", "Proteome profiling data has been deposited in the PeptideAtlas repository, identified as PASS00982.", "Untransduced, HCVcore-GFP and GFP transduced Jurkat cells were collected 48 h post-transduction, counted, washed with phosphate buffer saline (PBS) and fixed for 24 h using 4% paraformaldehyde (PFA) in PBS, pH 7.37. Subsequently, cell pellets were pre-embedded in agarose 1x, taken out of the tube with a needle and sliced into approximately 1 mm 3 pieces." ] },{ "paper_id": "e793ed5d6d883cd196795a4ca5d1ae0fbe632b34", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "that the problem with MABs is lack of complete coverage against the multitude of lyssavirus. The described MABs have very broad neutralizing activity and may therefore allow for their clinical development. The animal model is appropriate.", "Referee #3 (Remarks):", "Is there an estimate of variation within each group of data?" ] },{ "paper_id": "e7a4eae5bc97a5dc97189e3faa40ef9a91bb3207", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Agroastragaloside I-IV [30] 13", "Monghocoside I, II [30] 14", "Atramembrannin I,II [30] " ] },{ "paper_id": "e7a8dfcde06b70cb86b30074d9008635252d6301", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Likewise, when one looks not at a representative individual, but at the whole population, then the deletion of a single protein, within one host versus another, can render candidates previously valid and immunogenic as suddenly neither. Again, these are difficult issues; as yet, they remain unresolved.", "However, rather than look at nucleic acid sequences, or at protein sequences directly, a new approach, based upon alignment-free techniques, has been developed which shows significant potential; we examine this next.", "Vaccines are agentseither molecular or supramolecular -which can stimulate protective immunity against microbial pathogens and the diseases they cause. Protective immunity is a specific and enhanced adaptive immune response to subsequent re-infection or, when luck holds, infection by related organisms. Such augmented immunity is mediated by the exacerbation of immune memory, which militates against the effects of infectious organisms. The word vaccine itself is derived from vacca (Latin for cow). [1] [2] [3] .", "Traditionally, classification of VFs has categorised them as belonging to several thematic groups: adherence/colonization factors, invasions, exotoxins, transporters, iron-binding siderophores, and miscellaneous cell surface factors. A broader definition groups VFs into three classes: (1) \"true\" virulence factors; (2) VFs associated with the expression and regulation of class 1 VF genes; and (3) VFs required for the colonization of the host [74] .", "of the space, then straightforward methods drawn from, say, computer science -of which there are indeed very many -are now of satisfactory accuracy to build models of high predictive accuracy.", "Vaccines are a good thing; putting caveats and cavils to one side, no one sensible really doubts the truth of this statement. Vaccines have proved their worth time and again, but for them to continue to prove their worth we must find new ways of making them. Almost all present-day vaccines are mediated by antibodies, and the majority target viral diseases. Unfortunately, we are now running short of target diseases which fit this restrictive bill. Many of the pathogens responsible for current recalcitrant and emergent diseases are, and are set to prove, much more demanding and difficult to target. In many senses, the low hanging fruit has been cut down and now the fruit we most desire is well out of reach. Many diseases, including the WHO's big three diseases: HIV, TB, and Malaria, are much more complicated functionally and/or structurally, and cellular, as opposed to humoral, immunology is tasked with defence against these dark arts." ] },{ "paper_id": "e7b9c386495606981ed7a87be8a325c87c35fef9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Brackets indicate that CRISPR-Cas may be used or potential host factors could be targeted in the future. The \u2212ssRNA means negative-sense single-stranded RNA and +ssRNA means positive-sense single-strand RNA.", "In addition to the SAM system, Tanenbaum et al. developed another dCas9-SunTag-VP64 system that significantly improved the expression of endogenous genes. In the dCas9-SunTag-VP64 CRISPRa system, synthetic transcriptional activator VP64 is fused to green fluorescent protein (GFP) and single chain variable fragment (scFv) antibodies with binding specificity for peptides derived from the general control protein 4 (GCN4). The dCas9 fused to GCN4-containing peptide tags (Sun-Tag) can recruit up to 24 copies of GFP, leading to spatial recruitment of multiple VP64 domains to the gRNA-complementary target sites. Therefore, the dCas9-24xGCN4-v4, scFv-GCN4-sfGFP-VP64 and sgRNA constitutes the dCas9-SunTag-VP64 system provides a versatile toolset for gene activation [19] . 1.1.4 . Non Canonical CRISPR-Cas System-SaCas9, Cpf1, FnCas9, C2c1/2/3 and CRISPR-Cas13", "According to the WHO report, although two effective Human papillomavirus (HPV) vaccines are now available, HPV related cervical cancer remains the second most common cancer in women worldwide, classified by age-standardized incidence rate (ASR) (http://www.who.int/immunization/ topics/hpv/en/). HPV can also induce other types of anogenital cancer, head and neck cancers and genital warts in both men and women. The dsDNA genome of HPV may integrate into the host cell chromosome, which makes its genome an ideal target for CRISPR-Cas editing. Among the more than 200 identified genotypes of HPV [161] , the most commonly high-risk HPV types are HPV16 and HPV18, which are detected in cervical and penile cancers frequently [162] . HPV6 and HPV11 are the low-risk HPV types, which are associated with anogenital warts and laryngeal papillomatosis [163] . HPV-related tumorigenesis has been related to the deregulated expression of two oncogenic proteins HPV E6 and E7, which are important for both malignant transformation and maintenance of the malignant phenotype of cervical cancer [164, 165] . HPV invades host cells and expression of E6 and E7 can induce degradation of tumor-suppressive protein p53 (E6) and inactivation of retinoblastoma (Rb) protein (E7), thus blocking the cell cycle [165] . Therefore, these two viral oncogenes become the main targets to combat HPV infections." ] },{ "paper_id": "e7df6e6b00213948f60923cd0c111d58ffdfda00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e7e0c619c9f078101beffb8b3822c65e95995856", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e7e38adcd3016f0375633fd4d989c8016959484c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quality-adjusted life years (QALY) was the primary outcome. Willingness-to-pay (WTP) threshold was considered to be 30,000 Brazilian real (BRL) per QALY (Soarez and Novaes, 2017) . Prevented influenza A (H1N1) was also assessed, as a secondary outcome.", "Health expenditures were obtained from micro-costing of all inpatients admitted in 2016 for H1N1 treatment at the Clinics' Hospital of the University of Campinas, Campinas, S\u00e3o Pauloa 400-beds high complexity hospital.", "LV, TG and MS designed the work, LV collected the data, LV and TG did the analyses and drafted the work, MS, ES and MR interpreted the data and revised the work critically. All authors approved the version to be published and agree to be accountable for all aspects of the work." ] },{ "paper_id": "e7eab33081228b6405ecc7a3d97fb803aca119ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by National Institutes of Health grants ES016769 (TCL), ES014677 (TGR), HL081420 (MBH) and AI114220 (TCL and MBH), and Environmental Protection Agency grant EPA-G2008-STAR-B1 (SAB).", "Not applicable.", "The authors declare that they have no competing interests." ] },{ "paper_id": "e7ec7ae8528004b91b84a51d4752a0bd5b70d2f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e7f04672caa0b2d82df86553cdc266ff9ddda6fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u0420\u0438\u0441. 1. \u0420\u043e\u0441\u0441\u0438\u044f -\u0421\u0428\u0410. \u0420\u0438\u0441\u0443\u043d\u043e\u043a \u0441\u043e\u0437\u0434\u0430\u043d \u0441 \u0438\u0441\u043f\u043e\u043b\u044c\u0437\u043e\u0432\u0430\u043d\u0438\u0435\u043c \u0440\u0435\u0441\u0443\u0440\u0441\u0430 mapchart.net: https://mapchart.net/." ] },{ "paper_id": "e806597d3525be5b55b7bd8812217c2e53bced9f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Khetawat and Broder Virology Journal 2010, 7:312 http://www.virologyj.com/content/7/1/312", "Receptor positive cell lines, seeded into 48-well plates at a concentration of 10 5 cells per well, were infected (transduced) with pseudovirus, normalized for p24 antigen content using the HIV-1 p24 EIA Kit from Beckman-Coulter, and all infection experiments were carried out in triplicate wells. No DEAE-Dextran or polybrene was used to facilitate fusion/infection by the pseudovirions. After infecting for 2.5-3 hr, the cells were washed and incubated for additional 48-72 hr. For luciferase encoding particles, cells were lysed with 0.5% Triton X-100 in PBS and a 50 \u03bcl aliquot of the lysate was assayed for luciferase activity using luciferase substrate (Promega, Madison, WI) on a Mikrowin luminometer (Berthold Technologies Model: Centro LB 960). For the GFP-encoding particles, the efficiency of infection was evaluated by counting the number of green cells 48 h post-infection using Olympus IX81 fluorescent microscope.", "To measure the incorporation of the henipavirus F and G glycoproteins into pseudotyped HIV-1 particles, sucrose cushion purified particles were lysed in buffer containing 100 mM Tris-HCl (pH 8.0), 100 mM NaCl, 2% Triton X-100 and protease inhibitors at 4\u00b0C for 30 min. Samples were boiled in SDS-PAGE sample buffer with 2-mercaptoethanol and separated on a 4-20% Tris-Glycine gradient gels (Invitrogen), transferred to nitrocellulose, and probed with a cross-reactive polyclonal mouse antiserum to HeV G at a concentration of 1:25,000 or a rabbit polyclonal F 1 specific antiserum at a concentration of 1:25,000." ] },{ "paper_id": "e80ffcae95f83bc7e4353e746ec75187eb61281e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "= 0, 2 1 = 2 < \u221e, then { } is called autoregressive and moving average sequence.", "(1) Identify smooth sequence using scatter chart, autocorrelation function, partial autocorrelation function, and ADF unit root test." ] },{ "paper_id": "e8108cdb4654206b4d0e053ce95255aaf71f3303", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus abundance was estimated as the proportion of the total viral reads in each library (excluding rRNA). All ecological measures were calculated using the data set comprising viruses associated with \"higher\" vertebrates (i.e. birds and mammals), albeit with all retroviruses and retrotransposons removed (hereafter, \"avian virus data set\").", "Samples were collected as part of a long-term IAV surveillance study [26, 27] ", "Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.", "RNA was extracted and libraries constructed as per [28] (Table S1) and are described in the Supplemental Methods. Paired end sequencing (100 bp) of the RNA library was performed on an Illumina HiSeq 2500 platform at the Australian Genome Research Facility (AGRF, Melbourne). We used the bioinformatics pipeline reported in refs. [28] [29] [30] . All contigs were filtered to remove plant, invertebrate, fungal, bacterial, and host sequences. The virus list was further filtered to remove viruses with likely invertebrate [30] , lower vertebrate [29] , plant, or bacterial host associations using the Virus-Host database (http://www. genome.jp/virushostdb/). Hence, only those viruses that grouped within the previously defined vertebrate virus groups are identified as bird associated." ] },{ "paper_id": "e81fa612268526f1a649e7d5e70c90dc9c1c4cca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Given the range of species present in typical LBMs and the variety of detected influenza viruses [12, 13, 14, 15, 16, 17, 18, 19] , LBMs could potentially act as drivers of viral evolution, promoting the emergence of new variants. Identifying those LBMs that could act as viral reservoirs is, therefore, crucial for improving surveillance and control.", "Questionnaire data were entered in Microsoft Access 2007H (Microsoft Corp., Redmond, WA, USA) database. The accuracy of the data entry was verified by cross-checking each questionnaire with the recorded entry.", "Numerical variables were summarized as medians with interquartile ranges (IQR); binary and categorical variables as frequencies and percentages." ] },{ "paper_id": "e827d65c421e5a5ed761cc56cc2a5f06a3545a82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e835b6338e31398a5abaca8548b69da8e19b61d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "dose MERS 0 (3T3p0, CCL-81p2) (MERS-0 in ref. 2 ) was used for the challenge study. The ideal virus inoculum target was 6.7log 10 PFU/mL to conform to historical studies. Virus inoculum was used undiluted as the initial virus stock titer was quantified at 6.6log 10 PFU/mL average of two independent plaque assays on Vero cells (ATCC CCL-81).", "Gross and Histological Pathology. All animals underwent an extensive postmortem necropsy by a qualified pathologist. The animal's overall general condition and state of major organ systems was assessed. Tissues trimmed to 1 cubic centimeter, submerged and fixed in 10% neutral buffered formalin for 7 days. Paraffin embedded tissue sections were mounted on positively-charged slides and stained with hematoxylin and eosin prior to pathological examination.", "respiratory support for infected individuals experiencing severe pulmonary complications 1 . Anti-MERS therapeutic and vaccine countermeasures are gradually advancing toward the clinic (reviewed in 1 ); however, effective evaluation of anti-MERS countermeasures has been hampered, until recently, by the availability of animal models that reflect severe pulmonary complications observed during human infections 2, 3 .", "Virus inoculum was back-titrated using the standard Avicel RC591 \u00ae (FMC Biopolymer) semi-solid plaque assay method (CS-04-45). Briefly, virus inoculum was serially diluted by half-log increments in minimal essential medium alpha (Gibco) supplemented with Anti-Anti (Gibco) and heat-inactivated 5% fetal bovine serum (FBS, Gibco). Three-hundred microliters of sample was assayed on near-confluent 6-well plates of Vero cells (ATCC CCL-81) for 1 h at 37 \u00b0C and 5% CO 2 with gentle agitation every 15 minutes to prevent drying of the monolayer. Following adsorption, 2 mL of a mixture of 2X eagle's minimal essential medium (Gibco) and 2.5% Avicel RC591 \u00ae was added to each well and plates were returned to the incubator for 3 d. Plate counts were enumerated after removing the overlay, staining with 0.2% gentian violet solution prepared in 10% neutral buffered formalin for 30 minutes, rinsing and drying the plates." ] },{ "paper_id": "e8392d9561be82ded77c6e5d75f321d752776424", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We used chi-square tests to determine the between-site effects and the effect of bird group on the proportion of positive individuals. A value of P,0.001 was considered statistically significant.", "All animals were handled in strict accordance with good animal practice as defined by the Laboratory Animal of Swedish Board of Agriculture, and all animal work was approved by the Russian Academy of Medical Sciences and Russian Authorities.", "Due to their high mutation and recombination rate during replication, CoVs are able to generate extensive genotypic variation, which facilitates adaptation to new host species [12] . In animals, CoVs generally cause respiratory or intestinal infections, but they have also been associated with a wide spectrum of other clinical symptoms, including hepatic, renal, reproductive and neurological diseases [13] . The only exception is the notorious feline infectious peritonitis virus (FIPV), which causes a sporadic but fatal generalized disease in Felidae [14] .", "Coronaviruses (CoVs), members of the Coronaviridae family and sub family Coronavirinae within the order Nidovirales, are enveloped viruses with a positive-sense RNA genome of 27-31 kb [1] . Based on genetic and serological analyses, CoVs are divided into three genera [2] alpha-and beta-and gamma-coronaviruses." ] },{ "paper_id": "e840685d875ae1d0d6c08a0176f2151b2765a0d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One thousand newly emerging bees were painted and introduced into one typical host colony. Groups of 30 marked bees were collected directly from nest combs after 3, 6, 9, 12, and 16 days and immediately preserved in liquid nitrogen. Collections were performed from June 10th to June 29th, 2013. Individual bees were dissected using a binocular microscope that was chilled by dry ice. The tissues were transferred into liquid nitrogen and stored at \u221280\u00b0C for further use.", "All identified peptides were tested significance by the Mascot software under the threshold of 1% FDR. Proteins quantified with at least a 1.5-fold change were considered DEPs [31] .", "Next, the labeled samples were fractionated using a LC-20AB high-performance liquid chromatography (HPLC) system (Shimazu, Japan) using a 4.6 mm \u00d7 250 mm Ultremex strong cation exchange (SCX) column (Phenomenex Inc., USA). After reconstitution of the labeled peptide mixtures with 4 ml of buffer A (10 mM KH 2 PO 4 in 25% ACN, pH 2.6), SCX separation was performed at a flow rate of 1 mL/min using elution buffer A for 10 min, followed by a linear gradient of 5-35% buffer B (25 mM NaH 2 PO 4 , 1 M KCl in 25% ACN, pH 2.7) for 11 min and 35-80% buffer B for 1 min. The eluted fractions were monitored by measuring the absorbance at 214 nm, desalted with a Strata X C18 column (Phenomenex), and finally vacuum-dried." ] },{ "paper_id": "e854283ba0d428f16fb5eec6a1ba210ff7925125", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Expression of genes including surfactant protein A (SPA), SPB, SPC, SPD, CK-8, keratin-6 (KL-6), AQP-3, but AQP-5, was detected as described previously (Zhang, Zhang et al. 2013) . The sequences of primers are listed in Table 2 .", "Statistical analysis was performed with SPSS 12.0. Results are expressed as mean AE SE. Comparisons between two groups were made using ANOVA. P < 0.05 was considered statistically significant.", "Yield, purity, viability, and morphology" ] },{ "paper_id": "e8679d8c149ea6d25afb92e8a4f4b622dadcd872", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Enriched Gene Ontology groups were identified for the hit lists using a standard accumulative hyper-geometric P-value analysis. GO groups with P-value #0.01 were retained. Comparative microarray analyses were achieved by utilizing NextBio [18] . Transcription factor binding sites in gene promoters were predicted by SABiosciences Text Mining Application and the UCSC Genome Browser.", "Ames strain (pXO1 + , pXO2 + ) and Sterne strain (pXO1 + , pXO2 2 ) of B. anthracis were prepared as previously described [15] . The Green fluorescent protein (GFP) expressing Sterne spores [11, 16] and GFP expressing Ames spores (pXO1 + , pXO2 + ) (unpublished data) were kindly provided by Wilson Ribot (USAMRIID) and were used only for the imaging studies.", "Following engagement of ligands to TLR4, adaptor proteins MyD88 and TRIF are recruited to the receptor, resulting in the activation of transcription factors NF-kB and interferon regulatory factor-3 (IRF-3), respectively [4] . Mitogen-activated protein kinase (MAPK) pathway is also employed upon TLR activation to orchestrate the expression of pro-inflammatory and interferon stimulated genes (ISGs) [5] [6] [7] . However, B. anthracis has evolved ways to impair these host responses and thereby allowing growth of bacteria and establishment of infection. For instance, LF is a zinc-dependent bacterial protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 (MEK1 and MEK2) and this cleavage inactivates MEK1 and inhibits the MAPK signal transduction pathway [8] [9] [10] [11] . Also, EF is a highly active bacterial adenylyl cyclase that elevates intracellular concentrations of cyclic AMP and de-regulates cellular gene transcriptions." ] },{ "paper_id": "e86b3861c3d400a8a5baf860545af22254fc9c0b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: The 3C-like protease (3CL pro ) of severe acute respiratory syndrome-coronavirus is required for autoprocessing of the polyprotein, and is a potential target for treating coronaviral infection.", "The assay for each substrate was performed in triplicate." ] },{ "paper_id": "e87256ec4a079c0792106d6503eb78af24aebdb4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Third and maybe the most important, copper alloys compositions are probably very different from one study to another. Even if the percentage of copper is known, minor elements can have a huge importance in the antimicrobial efficiency of the alloy [23, 24] .", "First, those studies mainly focused on hospital wards, while our study focused on five long-term care facilities, where different types of peoples are moving and meeting (patients-residents/staff/visitors). Different human populations can convey different microbiomes and bacterial burdens, directly impacting bacterial contamination on touch surfaces.", "To release the collected bacteria from the swab to the resuspension medium, samples were placed in ultrasonic bath at 35 kHz for two minutes, and then vortexed for 30 s. Hundred \u00b5L of each sample were then inoculated onto tryptic soy agar plates (TSA, Biokar Diagnostics, Allonne, France). Plates were incubated aerobically at 37 \u2022 C. The number of bacterial colony-forming units (CFU) on each plate was determined after 24 h and confirmed after 48 h and 72 h. The lower detection limit was one CFU per cm 2 ." ] },{ "paper_id": "e88057a7b0014a7c9fc085a0e9d8b53b71886829", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "displaced by immunological and molecular methods such as rapid immunoassays and polymerase chain reaction (PCR) 11, 12 , these newer methods also suffer from limitations, for example: (i) an inability to detect organisms not represented in an immunoassay or PCR panel; (ii) an inability to discriminate between live and dead organisms in a specimen; and (iii) a tendency to detect low levels of virus that may not be clinically relevant 13 ." ] },{ "paper_id": "e8815ab60a5c49b74ba06d648c5e7c89c50668c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Unlike ICV that is typically cultured at 33 \u2022 C in experimental settings, the IDV shows optimal growth at both 33 \u2022 C and 37 \u2022 C further suggesting that IDV is not restricted to an elevated temperature for replication [36] .", "Although IDV genome structure is similar to ICV, they exhibit a broader cellular and host tropism than ICV [36] . The intensity and severity of the disease may become clearer with more number of relevant studies; however, the ability of influenza viruses to acquire frequent mutations makes IDV a potential threat to human health and warrants more comprehensive studies to understand its complexity and evolution.", "As the influenza viruses continue to evolve, there is a need of joint efforts from medical doctors, scientists, veterinarians, agricultural industry and policy makers across the world to closely monitor the circulating influenza viruses and prevent any future outbreaks.", "Although new studies have provided promising tools to manage IDV infections, yet more detailed investigations are needed to better understand this novel virus in terms of its epidemiological, pathological and biological characteristics specially when the capability of IDV to cause disease in humans have not been investigated in details and it's not clear if the virus can sustain human-to-human transmission.", "Advancements in several approaches to managing influenza infections have led to quick and efficient control measures that were best seen during the 2009-H1N1 pandemic when the vaccines were developed in record time. Several strategies utilizing nucleic acid-based therapeutics have also been in action against several respiratory viruses, including human influenza viruses [94] [95] [96] [97] [98] [99] [100] [101] . It would be interesting to have such strategies against IDV for timely management of the disease in cattle and other potential hosts." ] },{ "paper_id": "e88797458f110553b9418007d35401975dce1454", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experimental procedures were performed under isoflurane anesthesia, and all efforts were made to minimize suffering.", "PLOS Pathogens |" ] },{ "paper_id": "e88b28b3664d30889a0161ddee188c48897a3bee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell death was detected using cell-death-detection TUNEL assay kit (Roche Biochemicals), according to the manufacturer's instructions. Apoptotic cells were quantified by counting TUNEL-positive cells in each set of experiments. At least 200 cells from three separate images were inspected, and percentages were calculated." ] },{ "paper_id": "e88ddb14ceee73a1db00d2991c683b872e747b33", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Descriptive statistics of the responses were generated. Continuous variables were presented as mean values and standard deviations (SDs) and categorical variables as numbers and percentages. For categorical data, comparisons between groups were performed using a contingency table analysis with the \u03a7 2 or Fisher's exact test when appropriate. For ordered categorical data, a Cochran-Armitage test for trend was used to compare the groups. Continuous data were analysed using a two-sided Student's t-test after ensuring the data were normally distributed (based on the Shapiro-Wilk statistic) or using a two-sided Wilcoxon's rank-sum test if the data were non-normal. All analyses were two tailed, and p-values of 0.05 or less were considered to be statistically significant. All analyses were conducted using SAS version 9.2 (Cary, NC, USA).", "For genotyping, the viral VP-1/2 gene was amplified using a conventional PCR assay. Briefly, 4 sets of forward and reverse primers (5'-CACAGACAGAAGCAGACGAGAT-3' and 5'-GGTG AGAAGTGACAGCTGTATTG-3'; 5'-TTCAGAATGGTCACCTCTACA-3' and 5'-CTGTGC TTCCGTTTTGTCTTA-3'; 5'-AACTTTGACTGTGAATGGGTTA-3' and 5'-AAATAGTGCC TGGAGGATGAT-3'; 5'-CTATCACCAGAGAAAATCCAATC-3' and 5'-GAGACGGTAACA CCACTA-3') were used in PCR amplification and the Quantitect Probe Master Mix (QIA-GEN, Venlo, Netherlands) was used as the basis for the reaction mix. Viral products were analysed by electrophoresis on a 1.5% agarose gel and purified with the QIAquick Gel Extraction Kit (QIAGEN, Venlo, Netherlands). Sequencing reactions were set up with purified DNA, one of the specific primers used in the PCR and BigDye Terminator v3.1 Cycle Sequencing Kit (Applied Biosystems, California, USA) according to the protocol recommended by the manufacturer. Sequencing and sequence analysis were performed on a 3130 Genetic Analyser (Applied Biosystems, California, USA).", "Conceived and designed the experiments: NP SE. Performed the experiments: AP AZ AS. Analyzed the data: FB. Contributed reagents/materials/analysis tools: SBi GU AS SBo EF. Wrote the paper: NP AP SE." ] },{ "paper_id": "e8913cb59861302b5e0abb9eb28b1fdcdc2b71b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e8ae86b48db5e9860652f9c78c61f13c1b41c700", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For cluster generation, the library is loaded into a flow cell where fragments are captured on a lawn of surface-bound oligos complementary to the library adapters. Each fragment is then amplified into distinct, clonal clusters through bridge amplification. When cluster generation is complete, the templates are ready for sequencing. Illumina SBS technology utilizes a proprietary reversible terminator-based method that detects single bases as they are incorporated into DNA template strands. As all 4 reversible, terminator-bound dNTPs are present during each sequencing cycle, natural competition minimizes incorporation bias and greatly reduces raw error rates compared to other technologies. The result is highly accurate base-by-base sequencing that virtually eliminates sequencecontext-specific errors, even within repetitive sequence regions and homopolymers.", "The datasets generated for this study has been deposited in the Gene expression Omnibus (GEO) database with accession number GSE135873. ", "Data was analyzed and charts were prepared using GraphPad Prism software. All experiments were performed with two or more replicates and graphs have been prepared representing data from at least two independent experiments with n \u2265 6. Error bars represent mean \u00b1 SD. Statistical significance was estimated by t-test (unpaired, non-parametric) using Mann-Whitney test." ] },{ "paper_id": "e8ae9d6178f8322e2f9b2453ef13bb312427bd15", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022Travelers from the Arabian Peninsula (note that geographic regions of concern may change over time)", "MERS can be confirmed at a state or CDC laboratory via polymerase chain reaction (PCR) assays performed on respiratory samples. In addition, serum antibody titers can be measured for both acute infection as well as evidence of prior exposure and immunity. Serologic testing includes (1) enzyme-linked immunosorbent assay (ELISA) as a screening test, (2) immunofluorescent assay (IFA) for confirmation, and (3) neutralizing antibody assay as a definitive confirmatory test that takes longer to process.", "In May 2014, the Centers for Disease Control and Prevention (CDC) confirmed two unlinked imported cases of MERS in the U.S. states of Indiana and Florida. Both patients were believed to have been infected in Saudi Arabia where they worked as healthcare providers. They both required hospitalization and fully recovered.", "\u2022Close contacts of an ill traveler from the Arabian Peninsula \u2022People who have been in a healthcare facility in the Republic of Korea \u2022Close contacts of a confirmed case of MERS Elderly and immunocompromised patients are at higher risk of becoming infected with MERS than healthy hosts if they are exposed to the conditions described above." ] },{ "paper_id": "e8b3d7f86dd48b422693465d39ce72280df5527c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e8be80485fdee7344e970941c62ca23fb3eed4da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quantitative real-time PCR. Quantitative real-time PCR was performed using SsoFast TM EvaGreen \u00ae Supermix (Bio-Rad, Singapore) via a MyiQ TM 2 Two Color Real-Time PCR Detection System (Bio-Rad). Each reaction was performed in a 20 \u03bcl total volume with 10 \u03bcl SsoFast TM EvaGreen \u00ae Supermix, 1 \u03bcl of cDNA template, 1 \u03bcl of 10 \u03bcM of each primer and 7 \u03bcl of nuclease-free water in an iQ TM 96-well PCR plate (Bio-Rad). The program was set as follows: initial denaturation at 95 \u00b0C for 30 s, followed by 40 cycles of 95 \u00b0C for 5 s and 60 \u00b0C for 10 s. At the end of the reactions, a melting curve analysis from 65 \u00b0C to 95 \u00b0C was used to ensure amplified product consistency and specificity. All reactions were performed in triplicate.", "RNA extraction and cDNA synthesis. Total RNA was isolated according to the Trizol RNA isolation kit manufacturer's protocol. A total of 50 \u03bcl DEPC water was used to dissolve the RNA sediment. The A260/A280 ratio and A260/A230 ratio of the RNA were determined using a UV-1800 Spectrophotometer (SHIMADZU) and DU 730 nucleic acid/protein analyzer (BECKMAN COULTER). RNA samples with an A260/A280 ratio ranging from 1.8 to 2.0 and an A260/A230 ratio >2.0 were used for cDNA synthesis 29 . The first-strand complementary DNA was synthesized from 1 \u03bcg of total RNA with a PrimeScript RT reagent kit with gDNA Eraser (TaKaRa, Dalian, China) in a total volume of 20 \u03bcl. According to the manufacturer's protocol, in the first step, 10 \u03bcl mixture was incubated for 2 min at 42 \u00b0C, and then 10 \u03bcl of master mix was added and incubated for 15 min at 37 \u00b0C and 5 s at 85 \u00b0C. The cDNA was preserved at \u221280 \u00b0C until further use." ] },{ "paper_id": "e8c2bc95762a2aefd919b02ae90131bc67716140", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mice CBF1 mice (8 weeks of age, female) were purchased from SLC (Shizuoka, Japan). All experiments were approved (No. 208021 and 209082) by an independent animal ethics committee at National Institute of Infectious Diseases, Tokyo, Japan.", "All phospholipids were provided by NOF Co. (Tokyo, Japan). Reagent grades of cholesterol were purchased from Wako Pure Chemical (Osaka, Japan).", "OVA was labeled with fluorescence using an AlexaFluor 488 protein labeling kit (Invitrogen) according to the manufacturer's protocol.", "Vaccines have played an important role in disease prevention and have made a substantial contribution to public health. Upon natural infection, it is known that the host responds by inducing both humoral and cellular immunity against the pathogen. However, most of the currently approved vaccines work by inducing humoral immunity [1] [2] [3] . For protection against viruses that are highly mutable and frequently escape from antibodymediated immunity, such as influenza A viruses, HIV, and HCV, humoral immunity is insufficient [4] [5] [6] [7] . Consequently, the development of vaccines that induce cellular immunity is critical to novel vaccine strategies." ] },{ "paper_id": "e8d7fb48d727d602587af256f10d5b389af1d7a1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Author Contributions: Y.Y., K.K. and D.S. synthesized the compounds; V.K. and S.V.M. compiled the NCI-60 activity; A.J. interpreted the NMR data and drafted the manuscript; J.W., C.L., A.K.P. and V.S.P. planned and designed the whole study and finalized the manuscript.", "Funding: Please add: This research received no external funding; See the \"Acknowledgements Section\" for details." ] },{ "paper_id": "e8d81518d127913ce42b22fbdd96d416c4f82e44", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rosa M Ferraz and Andrea Vera have equally contributed to this review. ", "Although being not a standard insertional approach, the principles governing such engineering processes are similar to those discussed above. In this context, the protein hydrolysis splitting a fluorophore and its quencher has been also a successfully proven biosensing principle [60] .", "Other conformation-linked effects of molecular interactions might also result in detectable activity changes or phenotypes acting as macroscopic signals for a given analyte. Gaining further knowledge about enzyme structure and dynamics would necessarily offer additional possibilities of rational protein engineering [58] for exploitation of such conformational signals." ] },{ "paper_id": "e8dcb73fafb728fc6297e33e0374b7ef8016e1ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using Graph-Pad Prism v7.0 (GraphPad Software, Inc., San Diego, CA). Data are expressed as the mean -standard error for each group. To compare group statistics, Mann-Whitney tests were performed.", "This research was funded by DARPA funding W31P4Q-15-1-0003 awarded to Inovio Pharmaceuticals.", "Supplementary Figure S1 Supplementary Figure S2 Supplementary Figure S3 ", "The DNA plasmid pMERS was designed, as previously described. 2,25 pMERS encodes the light and heavy chains for the full-length anti-MERS envelope glycoprotein monoclonal antibody. The light and heavy chains are expressed as a single mRNA transcript and then cleaved post-translationally at a porcine teschovirus-1 2A (P2A) cleavage site. A furin cleavage site (RGRKRRS) was also included to ensure complete removal of the P2A from the final in vivo produced antibody. pNP encodes the full-length nucleoprotein (NP) from influenza A (H1N1, A/Puerto Rico/8). The MERS and NP transgenes were cloned into a modified mammalian expression vector (pVax1, Genscript) under the control of the human cytomegalovirus promoter. pRFP reporter gene plasmid was purchased from Aldevron (Fargo, ND)." ] },{ "paper_id": "e8e766af194b641ae3a9636379a18515c053ae65", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Differences in antibody levels among plasma from P. falciparumexposed multigravidae, P. falciparum -exposed men, and nonexposed control donors were analysed by one-way anova , or by one-way analysis of ranks for non-normal distributed data. If statistically significant ( P < 0\u00b705) overall differences were detected, significant pair-wise ", "Selection for VSA PAM expression was done essentially as described elsewhere (7) . In brief, monoclonal PAM1\u00b74 or PAM8\u00b71 antibodies were immobilized on Protein A-coated magnetic beads (Dynal) and mixed with 3D7-or HB3-IEs.", "In conclusion, our evidence support current efforts to develop PAM-specific vaccines based on VAR2CSA and highlight the versatility of human monoclonal antibodies generated from clinically immune donors in these investigations." ] },{ "paper_id": "e8f4d22d624e8deec9597ce88e53b1751386cd1d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It has been previously reported that PRRS has an evident seasonal pattern, showing high incidence during fall and winter (October through January), and low during spring and summer [February through September (5)]. Surprisingly, after stratifying the data by geographical region, there was no obvious visual indication of predictable yearly patterns for any of the regions besides Minnesota/Iowa (Figure 2) .", "The concept of near real-time disease surveillance is important in the context of emerging PRRSV strains given that rapid identification of an epidemic (i.e., emergence of novel PRRSV strains) will likely result in a reduction of outbreak duration due to timely implementation of prevention and control measures to decrease virus spread within and across geographical regions.", "Time-dependent reproductive numbers were described separately for the four investigated geographical areas, as well as for each participating production system (20 systems represented by letters A-T). A production system was defined as two or more swine sites with a common owner or management structure. The Kruskal-Wallis test was used to determine whether the median TD-Rs differed across the four areas. Furthermore, the Dunn's test of multiple comparisons (12) was applied, adjusting for multiple comparisons using the Bonferroni correction method. All statistical analyses were performed using STATA/ IC version 14.1.", "Results support the observation that region-level insights cannot be provided by using data that are aggregated from large national projects. Furthermore, regional-level control and prevention strategies should not be made based on the assumption that PRRS transmission dynamics are the same across geographical regions of the same country. Stratification of data would be able to provide a better estimate on which control and prevention measures, if any, would work best and provide the best benefit for specific regions." ] },{ "paper_id": "e8f7192873a7eab54d8f845f5bf5fc450cbe2e37", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PRR sensing of viruses triggers a series of intracellular signaling cascades that converge on two major families of transcription factors -nuclear factor kappa-light-chain-enhancer of activated B cells (NF\u03baB) and interferon regulatory factor (IRF) (Fig. 1) . These transcription factors translocate to the nucleus where they upregulate their respective proinflammatory and antiviral programs [35, 36] . The major signaling pathways involved are illustrated in Fig. 1 .", "Most children with RSV develop mild symptoms such as cough, fever, sore throat and runny nose. Up to 40% of infants develop lower airway symptoms (e.g. shortness of breath, wheeze, bronchiolitis) and 0.5-2% of all infected infants are hospitalized [52] . Risk factors for severe disease include premature birth, low birth weight, young age, male gender, chronic lung disease, congenital heart disease, immune deficiency, low socio-economic status and tobacco exposure [52] . The presence of pathogenic bacteria (Streptococcus, Moraxella, Haemophilus) in the nasopharyngeal microbiome increases the risk of the infection spreading from the upper to the lower airways and inducing more severe symptoms [53] .", "The advent of microarrays enabled the measurement of gene expression patterns on a genome-wide scale [8] . Microarrays comprise a vast array of oligonucleotide probes of 25 bases or more in length, fixed to a solid surface. The probes bind to labelled target molecules (e.g. cDNA derived from mRNA), and the signal intensity is quantified. Despite this major technological advance, cross-hybridization of related sequences limited the signal-to-noise ratio [9] . Microarrays are slowly being phased out and superseded by deep sequencing technologies for gene expression profiling (RNA-Seq). RNA-Seq entails the generation of a library of cDNA fragments from total RNA or mRNA, followed by ligation of adapters, PCR amplification and high throughput sequencing [10] . This generates millions of short sequencing reads (e.g. 50-200 bases) , which are aligned to a reference genome sequence, and summarized as gene-or transcriptlevel counts. Compared with microarrays, advantages of RNA-Seq include single base resolution, superior sensitivity and dynamic range, and the ability to detect novel transcripts. The data from microarray and RNA-Seq experiments is typically submitted to a public repository at the time of publication (e.g. Gene Expression Omnibus; http://www.ncbi.nlm.nih.gov/geo/; Sequence Read Archive; www.ncbi.nlm.nih.gov/sra), allowing other researchers to freely access the data for reanalyses [11] .", "RSV is an enveloped, single strand, negative sense RNA virus of the family Paramyxoviridae. There are two antigenic subtypes (RSV-A, RSV-B). The genome encodes seven structural proteins and four non-structural proteins. The envelope is encoded by three glycoproteins, namely the small hydrophobic protein, the attachment protein G and the fusion protein F. Virus entry is mediated by binding of the F protein to host-cell nucleolin [17] ." ] },{ "paper_id": "e8fa6ff57f5e18b27fa9d70df3d3c90f4633264d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e9011bcb647874593aa8c4c7a3010573f82a1558", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2015, 7, page-page 9 in the membrane fusion process [82] , additional studies are warranted to elucidate its mechanistic contributions to fusion and tie them to its form and composition.", "Viruses 2015, 7, page-page 2", "Viruses 2015, 7, page-page 5", "According to the current model [28] , fusion is initiated when gD binds one of its cellular receptors, nectin-1, a cell adhesion molecule, herpesvirus entry mediator HVEM, a member of the TNFalpha family [29] , or modified heparan sulfate [30] . This engagement releases gD from its autoinhibited dimeric state [31, 32] and enables it to somehow transmit a signal to gH/gL [33] [34] [35] , which, in turn, activates gB [36] [37] [38] (Figure 3 ). This sequential activation process is triggered " ] },{ "paper_id": "e901c7268b77c894b19e9e46a76f53d852f212ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where \u03c3 st is the total number of shortest paths from node s to node t and \u03c3 st (k) is the number of those paths that pass through k.", "PLOS Neglected Tropical Diseases | https://doi." ] },{ "paper_id": "e90d316cde320ab2cecb088c9242a9ef3766718c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Central venous catheter infections were defined by criteria adapted from the Dutch surveillance network of nosocomial infections (PREZIES). [13] Mucositis was diagnosed based on clinical and radiological (typhlitis) criteria. Clinical criteria included pain when swallowing, nausea, vomiting, abdominal pain/cramping and diarrhea, physical examination and the absence of a positive microbiological test.", "[18] BAL seems to be the diagnostic procedure with the highest yield. Despite the low detection rates of a probable pathogen in approximately 50% of cases, it is the most sensitive procedure for detecting IFD.", "The mean interval between CXR and LDCT was 3.1 \u00b1 6.3 hours. The mean radiation dose for LDCT exams was 0.24 \u00b1 0.15 mSv, which is comparable to 2-3 chest radiographs (average ", "The study was approved by the local institutional review board (approval number NL41415.041.12) of the university medical center Utrecht. Written informed consent was obtained from all patients. This prospective study was conducted at the haematology ward of the university medical center Utrecht, a tertiary care oncology center, between March 2013 and December 2014." ] },{ "paper_id": "e911d262fbf4b651d8b2f2acb97c71e157a4d4cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "https://doi.org/10.1371/journal.ppat.1006867.g001", "https://doi.org/10.1371/journal.ppat.1006867.g007", "Human cytomegalovirus (CMV), a member of the human herpesvirus family, is a common opportunistic virus causing severe ailments and deaths in people with immature or compromised immune systems [1] [2] [3] [4] . HCMV ability to evade the host immune system can significantly impact the course of illness. For example, predisposition to bacterial and fungal infections is common for HCMV positive patients undergoing hematopoietic stem cell transplant procedure [5, 6] . HCMV expresses viral proteins to modulate the host immune responses at every step of its life cycle, which play a crucial role in viral pathogenesis [7] [8] [9] ." ] },{ "paper_id": "e9239100c5493ea914dc23c3d7a262f4326022ac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Western blotting. Proteins in sodium dodecyl sulfate (SDS) solubilizer (0.0625 M Tris\u00b7HCl [pH 6.8], 10% glycerol, 0.01% bromophenol blue, 2% [wt/vol] SDS, with 2% 2-mercaptoethanol] were heated at 95\u00b0C for 5 min, electrophoresed through 8% (wt/vol) polyacrylamide-SDS gels, transferred to nitrocellulose membranes (Bio-Rad), and incubated with mouse monoclonal anti-MHV-HR2 10G (obtained from Fumihiro Taguchi, Nippon Veterinary and Life Sciences, Tokyo, Japan), mouse anti-C9 (EMD Millipore), mouse monoclonal anti-MHV HE, clone 5A11, or goat anti-human IgG (sc-2453; Santa Cruz Biotechnologies). After incubation with appropriate horseradish peroxidase (HRP)-tagged secondary antibodies and chemiluminescent substrate (Thermo Fisher), the blots were imaged and processed with a FluorChem E (Protein Simple).", "Microscopy and image acquisition. Live-cell images were captured in a z series on an electronmultiplied charge-coupled-device digital camera (EMCCD Cascade 2; Photometrics) and deconvolved using SoftWoRx. Identical conditions were applied to all acquisitions. Deconvolved images were analyzed by an identical algorithm in Imaris 8.3.1 (Bitplane).", "Supplemental material is available online only. ", "Statistical analysis. Unless stated otherwise, all experiments were repeated independently at least three times. Each data point graphed represents the mean of an independent repeat (N), generated from three or four technical repetitions (n \u03ed 3 or 4). Statistical comparisons were made by unpaired Student's t test. Error bars indicate the standard errors of the data. P values less than 0.05 were considered statistically significant." ] },{ "paper_id": "e92488019ca299d19beabb885c7c71b12b535712", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cytotoxicity tests of all cell lines were carried out in a 96-well format with the CellTiter-Glo Luminescent Cell Viability Assay (Promega, Madison,USA) according to the manufacturer's instructions.", "Five distinct CoVs (SARS-CoV, hCoV-NL63, hCoV-HKU-1, hCoV-OC43, hCoV-229E) cause respiratory tract illness in humans, ranging from mild common cold to deadly virus-associated pneumonia [1] . At least seven different animal CoVs cause economically significant epizootics in livestock, and deadly disease in companion animals [1] . The agent of SARS was a novel CoV introduced into the human population from an animal reservoir, resulting in a highly lethal epidemic in 2002/2003 [1, 2] . A tremendous diversity of CoVs exists in complex mammalian and avian reservoirs [1, 3, 4] . Host switching is a common feature in CoV evolution, and novel epidemic CoV can emerge anytime [1, 3, 5] .", "Because Nsp1 proteins of group I and SARS coronaviruses share structural and functional similarities [22] , it was tested whether the inhibitory effect of CspA could be extended to other pathogenic CoVs. These included members of the genera Alphacoronavirus Figure S3 shows reduction of virus replication in a log scale.", "In all experiments the outcome of the mock-treated cells were set as 100%. Data shown are the mean values of at least three experiments. HIV-1 data show one representative experiment out of three, values are averages of triplicates. DMSO was always added as a control corresponding to the highest inhibitor concentration." ] },{ "paper_id": "e952843f8bdc91e48ca6fa5fa94d53abdfb63ff7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Proteasome inhibitors have been shown to interfere with the replication of major human pathogens such as herpesviruses [15, 16] , poxviruses [17, 18] , hepadnaviruses [19] , adenoviruses [20] , influenzaviruses [21] , retroviruses [22] [23] [24] , coronaviruses [25] , paramyxoviruses [26] , picornaviruses [27] and rotaviruses [28] .", "Finally, Ub plays a role in viral release from infected cells [40] , as it will be discussed in more details later on.", "This rapid overview on the involvement of UPS in crucial steps of the viral life cycle suggests immediately that viruses are connected to Ub in different ways, either by usurping the host's Ub-conjugating system or by evolving their own one." ] },{ "paper_id": "e95f81436f54620002c9fc909ba8ff591006bf27", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DNA and RNA were simultaneously extracted from 200 ml of throat swab specimen using QIAamp MiniElute Virus Spin (QIAGEN, Germany). Reverse transcription of virus RNA was conducted by Superscript III transcriptase and random hexamer primers (Invitrogen, Life Technology, USA), both kits were used according to the manufacturer's instructions.", "Inf-A, -B and -C, PIV -1, -2, -3 and -4, RSV-A and -B, HMPV, HCoV, and AdV were detected by a standard reverse transcription-PCR (RT-PCR) or PCR techniques as previously described using specific primers listed in Table S1 [11, [23] [24] [25] , and amplified products were detected by agarose gel electrophoresis.", "All research involving human participants was approved by the Medical Ethics Review Board of Zhongshan School of Medicine, Sun Yat-sen University, in accordance with the guidelines for the protection of human subjects. Written informed consent was obtained from each participant/guardian." ] },{ "paper_id": "e96b011c26501fc8432fd96787fe0aba49a08e0b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "for each country i. The second scenario is a hypothetical scenario in which no travel restriction takes place." ] },{ "paper_id": "e97ccc39b73b40f090df148361e6326f0a5798b6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cells were fixed in 2% glutaraldehyde (Electron Microscopy Sciences, Washington, PA, USA), washed three times in phosphate buffered saline and serially dehydrated in acetone. The tissue was post-fixed in 1% osmium tetroxide and embedded in an Araldite resin (Polysciences, Inc., Washington, PS, USA). Semi-thin sections (1 \u00b5m) were cut using an ultra-microtome (Reichert Ultracut S, Leica Aktiengesellscharft, Wien, Australia) with a diamond knife and were stained with toluidine blue for light microscopic examination. Ultra-thin sections (80 nm) mounted on copper grids were electron contrasted with uranyl acetate (1.5 hours, 30\u00b0C, Electron Microscopy Sciences) and lead citrate (40 minutes, 20\u00b0C, Electron Microscopy Sciences, Washington, PA, USA), and were examined with a transmission electron microscope (EM 208S, FEI Company, Hillsboro, Oregon, USA)." ] },{ "paper_id": "e97dc3686befac553f8f1a09459ae59b089b4b8b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All turkey procedures were approved by University Committee of Animal Care and Supply (protocol # 19940211) at the University of Saskatchewan, Saskatoon, Canada according to guidelines set by the Canadian Council of Animal Care.", "Day-old Hybrid poults obtained from Chinook belt Hatcheries, Calgary, Canada were housed in isolation rooms throughout the experiments. The avirulent TAdV-3 isolate (pheasant origin) was passaged in sero negative turkeys by oral inoculation and purified from crude spleen extracts, as described earlier [32] .", "Raw files were analysed with Proteome Discoverer 1.4 software suite (Thermo Scientific). Parameters for the spectrum selection to generate peak lists of the collisioninduced \"dissociation (CID) spectra were activation type: CID\"; (s/n cut-off: 1.5; total intensity threshold: 0; minimum peak count: 1; precursor mass: 350-5000 Da). The peak lists were submitted to an in-house Mascot 2.3 server against \"the following databases\": Uniprot_Trembl 20111103 (17 651 715 sequences; 5,747,683, 275 residues) and Uniprot-Swissprot 20110104 (523 151 sequences; 184 678 199 residues) all species taxonomy." ] },{ "paper_id": "e981fac56a2168159157612f40eb0f5fa17a6660", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "e98b7f593cd7bdd1bff632f4770505561768b9c8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We included age and gender as covariates since these factors have been shown to affect the HRQoL [26, 27] .", "None.", "Not applicable.", "The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention." ] },{ "paper_id": "e98c156b8632c84d14cfb03a1614b36563479bed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "One possible direction of vector development may include the merging of genetic elements from two vastly different virus expression systems. This next section describes two such systems.", "PapMV also has immunostimulatory properties, and can act as a nanoparticle. PapMV nanoparticles can elicit an \u03b1-IFN-dependent response, and when administered intra-tumorally can slow down melanoma progression and prolong survival in animal models [58] [59] [60] [61] [62] . PapMV undergoes rapid endocytosis by antigen-presenting cells, resulting in CD8+ T cell proliferation. Mice treated systemically with PapMV nanoparticles followed by B16-OVA cells six hours later exhibited fewer tumor nodules compared to control mice. The fact that this result could not be reproduced with capsid monomers or naked virus RNA indicated that the assembled nanoparticle itself was required for immune protection [60] .", "Plant virus particles can also be a platform technology for developing nations to utilize for growing their own pharmaceutical industries. By equipping poor countries with virus constructs and freedom to operate, a plant-made pharmaceutical industry could become a reality. Improvements in manufacturing infrastructure, financial support, and the maturation of a regulatory framework surrounding plant-derived pharmaceuticals are all essential for their commercialization in the developing world. If these obstacles are overcome, it would seem that many of the examples presented in this review could play a significant role in improving the lives of many. ", "Liu and Kearney have developed a tobamovirus that infects legumes, based on Sun Hemp Mosaic Virus (SHMV) that incorporates some of the attributes of the strategies developed by Icon and TRBO vectors [35] . Their \"SHEC\" vector lacks a CP, and thus cannot form virions, and also replicates very poorly in the absence of the silencing suppressor P19. Such tobamovirus-based systems can further regulate vaccine production under highly inducible and contained conditions." ] },{ "paper_id": "e9904ae72aa384d02a168cbee9347f4af5afda06", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Introduction: Respiratory syncytial virus (RSV) and influenza virus infections are a significant healthcare risk for immunocompromised patients.", "From December 2016 to April 2017, 251 asymptomatic patients were screened. 66 (26%) of these patients were aged 18 or younger and were screened on the pediatric ward. Of the remaining 185 adult patients, 11 (5.9%) received swabs on the emergency ward, whereas 174 patients were screened exclusively on the adult hematooncological ward. Overall, 665 screening samples were obtained, 23% of which (n=152) were from pediatric patients and 77% from adults (n=513). The mean screening sample number per patient was 2.3 for pediatric patients and 2.8 for adults. The majority (98%) of the screening samples were nasopharyngeal swabs (n=654). 11 samples were pharyngeal washes and were exclusively obtained from adult patients.", "Competing interests" ] },{ "paper_id": "e990cc7120ae9e3ef809a225842f9d110f38b042", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The reptile C. difficile isolate (E6) was susceptible to all antimicrobial drugs (MICs range 0.19-2 \u03bcg/ml) tested except to tetracycline, for which a decreased susceptibility was found (MIC 6 \u03bcg/ml).", "Multilocus sequence typing (MLST) technique was used for characterisation of strains which did not belong to a known PCR ribotype. By this technique, seven housekeeping loci are studied by PCR and subsequent sequenced, providing a sequence type (ST) profile and a clade [23] based on these genes alleles [24] . A maximum likelihood tree with 1000 bootstrap replicates was constructed based on the Kimura 2-parameter model [25] . A total of 37 strains were used for this purpose: one from this study (E6), 17 from previous works carried out by our team (Hu, RC and RF isolates; data not published for Hu isolates) [26] , and 19 from the PubMLST database to provide a context for C. difficile population (ST1, ST3, ST5, ST11, ST32, ST37-39, ST41, ST67, ST96, ST122, ST177-181, ST200 and ST206). Initial tree(s) for the heuristic search were obtained by applying the Neighbour-Joining method to a matrix of pairwise distances estimated using the Maximum Composite Likelihood approach. Evolutionary analyses were conducted in MEGA7 [27] ." ] },{ "paper_id": "e99a0adb1aa26558acfc74fa0c7197a8a591b6ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Specific-pathogen-free white leghorn chickens were purchased from the Beijing Merial Vital Laboratory Animal Technology Co., Ltd, China. All the animals used in this study were cared for in accordance with established guidelines, and the experimental protocols (including the possibility of animal death without euthanasia) were approved by the Animal Welfare and Ethical Censor Committee of China Agricultural University (Approval No. SYXK 2013-0013) .", "Control Challenged 3 dpc a 5 dpc 7 dpc 10 dpc 3 dpc 5 dpc 7 dpc 10 dpc Trachea 0/3 b 0/3 0/3 0/3 3/3 3/3 1/3 2/3 Lung 0/3 0/3 0/3 0/3 1/3 2/3 3/3 0/3 Spleen 0/3 0/3 0/3 0/3 1/3 2/3 1/3 0/3 Forestomach 0/3 0/3 0/3 0/3 3/3 2/3 2/3 0/3 Kidney 0/3 0/3 0/3 0/3 2/3 3/3 3/3 2/3", "Conceived and designed the experiments: S-hY, JZ, and G-zZ. Performed the experiments: S-hY, YC, and GX. Analyzed the data: JZ, YZ, and G-zZ. Contributed reagents/materials/analysis tools: G-zZ. Wrote the paper: S-hY, YC, and G-zZ." ] },{ "paper_id": "e9a9765d57cbca2e0c985f6fdcd04de38b0384cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The full-length ORF2 of 38 PCV3-positive samples were amplified as previously described [24] using the PrimeS-TAR Max DNA Polymerase (Takara, China). The PCR products were separated by electrophoresis on 1.0% agarose gels, purified with the Gel Extraction Kit (Omega, China) and cloned into the pEASY-Blunt Zero Cloning Kit (TransGen Biotech, China) for sequencing (Biosune Co. Ltd., Shanghai, China). A total of 162 PCV3 sequences from Brazil, other parts of China, Denmark, Germany, Italy, Russia, South Korea, Spain, Thailand and USA were downloaded from NCBI Gen-Bank (Additional file 1: Table S4 ). The phylogenetic tree was constructed by the neighbor-joining method in MEGA 7.0 software (p-distance model, 1000 bootstraps).", "The present study further extends the evidence that the novel virus PCV3 has been widely distributed in Zhejiang, China several years before the first report in the US in 2016. Co-infection of PCV3 with PEDV in Zhejiang was more pronounced than with other swine viral ", "Of the 203 serum samples randomly selected for comparison of qPCR and ELISA data, qPCR showed more positive samples than ELISA (81.3% vs 56.2%)( Table 6 ). With 89 serum samples negative by ELISA, vast majority (n = 81) were found positive by qPCR. These results " ] },{ "paper_id": "e9b2d0e930a4e8ec960b5e4dc7e627b4d243ac0f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA from transfected or infected cells was purified using TriZol reagent (Invitrogen, USA) and the ", "For infection experiments, HeLa cells grown on a 24well plate (with a growth area of 2 cm 2 per well) to 80% confluence were infected with virus stock at 0.5 PFU/ cell in 200 \u03bcl serum-free IMDM media. Cells were incubated with the virus for 2 h at 37\u00b0C, after which 1 ml of complete IMDM media was added. Cells were incubated for an additional 24 h at 37\u00b0C, collected and lysed, and luciferase activity was then measured using a Luciferase assay system (Promega, Madison, WI, USA).", "Phosphorothioate 2''-OMe RNA oligonucleotides designated as ON705 (5'-CCUCUUACCUCAGUUACA-3'), ON654 (5'-GCUAUUACCUUAACCCAG-3') and ONINV (5'-CCUCUUACACUCGUUACA-3') [42] were obtained from GE Healthcare (Little Chalfont, UK). If not otherwise stated, oligonucleotides were used in transfection mixtures at a final concentration of 100 nM (in cases where two oligonucleotides were used, each were used at a final concentration of 100 nM) and delivered to the cells using Lipofectamine\u2122 2000 (Invitrogen). The same reagent was also used to deliver the plasmid vectors to the cells. When cells where transfected with both oligonucleotide(s) and plasmid vectors, the oligonucleotides were always delivered 24 h before the transfection of the cell with plasmids." ] },{ "paper_id": "e9b30d08d16832b101208cf26d563cfefd8649bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ",", "Following foregoing studies [32, 34] , the generating function F j (s) with an exponentially distributed generation time is known to be given by", "for j = 1, 2. Since \u03b3 j is assumed to be independent of host type j, R i j = \u03b2 i j /\u03b3, (2) simplifies to" ] },{ "paper_id": "e9b3af3ad2b2abfacc4228e0ae590cc645f29718", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "glycyrrhizic acid monoammonium salt and can be considered as a newer modified biopolymer for colonic drug delivery. ", "Eq. 2.", "In order to determine the significance of each factor, analysis of variance was performed.", "The other part of the colon tissue was preserved in formalin buffer solution for histological examination." ] },{ "paper_id": "e9c51ce7b8c15bff3f9cb4de5afc2c862d5544bf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For histopathology investigation, brain tissues were collected from the mice and fixed in 4% paraformaldehyde; the hematoxylin-eosin staining protocol was followed for tissue staining.", "Statistical analysis. Student's t test and log rank tests were used to evaluate the statistical significance of differences. A value of P \u03fd 0.05 was considered statistically significant.", "Supplemental material is available online only. SUPPLEMENTAL FILE 1, XLSX file, 0.1 MB." ] },{ "paper_id": "e9c7ab1074e8ce62dbab3300ed0cb5babd980e69", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Engchanil C, Kosalaraksa P, Lumbiganon P, Lulitanond V, Pongjunyakul P, Thuennadee R, et al. (2006) . Therapeutic potential of chloroquine added to zidovudine plus didanosine for HIV-1 infected children. J Med Assoc Thai 89: 1229-1236.", "The author would like to acknowledge the British Society for Antimicrobial Chemotherapy (BSAC) for inspiration of my previous review paper.", "Ekins S, Freundlich JS, Coffee M (2015). A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus. F1000Res 3: 277.", "The author wish to confirm that there are no known conflicts of interest associated with this publication and there has been no financial support for this work that could have influenced its outcome. The author also declared not to receive any assistance of a professional medical writer or similar service. Thus, it can be stated 'None to declare'. disease in the in vivo guinea pig model. J Gen Virol 96: 3484-3492." ] },{ "paper_id": "e9c899d06f0e31a0d2c58cd4d82edb0086f9ed04", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The shelter had been ongoing for three-and-a-half years.", "Amplification, sequencing and analysis of 3a and 3c gene from the type II FCoV", "Multiple sequence alignments were preformed with ClustalW 2.0 and manually edited in EditSeq (DNASTAR, Madison, USA). Phylogenetic analyses were conducted using MegAlign, version 7.2.1 (DNASTAR, Madison, USA). Bootscan and similarity graphs were prepared with SimPlot 3.5.1 software (SCRoftware, Baltimore, USA). " ] },{ "paper_id": "e9c8c9036e9dd48230c81ff006be5fceba73660f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Postmortem examination confirmed generalized necrotizing pneumonia with diffuse alveolar damage and right middle lobe hemorrhagic infarct. The proximal tubules of both kidneys showed acute tubular necrosis but no microangiopathic thrombosis. Histology of the heart and the brain was unremarkable. Tissue cultures were negative.", "In-house real-time RT-PCRs were performed according to hospital laboratory standard operating procedures for the qualitative detection of human Metapneumovirus (hMPV) RNA and of Mycoplasma pneumoniae (MP). The target of amplification for hMPV was the nucleoprotein gene (N gene) with primer sequences and method as described by Hopkins et al. and 45 cycles were run on real-time PCR (ABI prism 7900 HT FAST) [17] . Positive and negative controls were included, and a Ct value of \u226437 was considered positive. The target of amplification for MP was the ADPribosylating toxin gene encoding the CARDS (communityacquired respiratory distress syndrome) toxin using primer pairs and method as described by Winchell et al. [18] . Both internal DNA control and a positive and negative control were included in the reaction run. A Ct value \u226434 was considered positive.", "History of immunization with the 7-valent vaccine is not a guaranteed prevention against pneumococcal infection in children [1] [2] [3] . Evolving serotypes associated with severe lobar pneumonia, pleural effusion, and PICU admission despite prior immunization have been previously reported locally [4] ." ] },{ "paper_id": "e9c971f80258e83c52a7e490ae2bf8af0e59e232", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Yam (Dioscorea spp.) is a popular vegetatively propagated staple crop cultivated for its starchy tubers in West Africa. Yam mosaic virus (YMV, genus Potyvirus, family Potyviridae) causes \"mosaic disease\", the most economically important viral disease of yams, which can reduce yields by up to 40% [6, 17] . YMV is endemic in the West African \"yam belt\" stretching from western Cameroon to C\u00f4te d'Ivoire, which is known to be the largest edible-yam production region in the world [2] . YMV is most frequently detected in D. rotundata, the dominant yam species cultivated in the yam belt [2, 4, 6] . Since yams are clonally propagated using whole tubers, portions of the tubers (setts), or vine cuttings, the virus perpetuates from season to season and spreads to new areas along with the infected planting material [6] .", "The use of virus-free planting materials remains the most effective method to control the spread of YMV [8] . The development of sensitive, low-cost, field-based diagnostic tools is an important requirement to achieve this goal. Two common methods employed in the detection of yam viruses include enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR), with the latter being the most widely used for YMV diagnosis [10, 13] . However, both ELISA and RT-PCR are lab based and require sophisticated equipment, precluding adoption of diagnostics in poorly equipped laboratories. Isothermal amplification methods, such as recombinase polymerase amplification (RPA) [13] and reverse transcription (RT) loop-mediated isothermal amplification (LAMP) [10] , are relatively simple and rapid to perform, with high specificity and sensitivity, and are suitable for poorly equipped laboratories and on-site diagnosis [1, 9] .", "Yam (D. rotundata) leaf tissues and tubers were sourced from plants maintained in the screenhouse and experimental fields of the International Institute of Tropical Agriculture (IITA, Ibadan, Nigeria). About 100 mg of leaf sample was processed for total RNA extraction using a modified CTAB method [15] . Tuber tissues were excised by inserting a steel cork borer of 1 cm diameter into the tuber surface to a depth of about 1 cm, and total RNA was extracted from the plug of tissue. Extracted RNA was suspended in 50 \u00b5l of RNase-free water and stored at \u221220 \u00b0C until use. The RNA concentration was measured using a NanoDrop 2000 spectrometer (Thermo Scientific, UK) as per the manufacturer's instructions. The total RNA concentration was adjusted to 100 ng/ \u00b5l, and 2 \u00b5l was used as a template for all assays in this study, unless specified otherwise." ] },{ "paper_id": "e9cabdd892daccdddc682fef1749e2475a7e5fa2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The datasets generated and/or analyzed in this study are available from the corresponding author on reasonable request.", "Ethics approval and consent to participate This study was reviewed and approved by the Institutional Ethics Committee of Jiangsu Institute of Parasitic Diseases (JIPD). The written informed consent was obtained from all participants before the interview or evaluation.", "Consent for publication Not applicable. ", "Authors' contributions GSD, GDZ, HYZ and JC conceived and designed the study. GSD, CQC and PM organized the microscopical test. GDZ, GSD, YYC, WWM, YPG, and SQW analyzed the data. GDZ drafted the manuscript, and HYZ and JC revised the manuscript. All of the authors read and approved the final manuscript." ] },{ "paper_id": "e9d01ab9a55093ad1c1277a7845d3254d3ad6fe8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cystic fibrosis (", "In 1999, in a clinical trial for ornithine transcarbamylase (OTC) deficiency, an Ad5 vector carrying the OTC gene was delivered to an 18-year-old male subject named Jesse Gelsinger. He received a dose of 3.8 \u00d7 10 13 viral particles via the femoral artery for delivery to the liver [67] [68] [69] . Four days after administration, he died from multiple organ failure and associated cytokine storm. Although this disease is unrelated to CF, it tragically demonstrated that high systemic doses of Ad can be fatal. In total, 9 CF clinical trials used Ad as the delivery vehicle, the last published in 2001 [70, 71] .", "In 1999, the first AAV serotype 2 vector clinical trial tested single and two dose treatments, reporting safe dose-dependent gene transfer to the maxillary sinus with little to no cytopathic or host immune response [90] . In the midst of designing and testing new vectors, three additional single dose " ] },{ "paper_id": "e9d32ac6db6f898b035aab6d4357342c3ae2442b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Demographic characteristics and possible transmission routes are presented as numbers (percentages). Viral load for RT-PCR are presented as mean 6 SEM values. Differences among groups regarding to occupation, working location and vaccination were determined by using Fisher exact test or univariate logistic regression. Odds ratio (OR) values were calculated with 95% confidence intervals (CI). Student's t-test was used for statistical comparisons between continuous variables. P value of less than 0.05 was statistically significant. All analyses were performed using SPSS 13.0 (SPSS Inc., Chicago, IL, USA).", "(3) Provide 75% alcohol-based solution for hand rub in all inpatient rooms, corridors, and outpatient clinics.", "(3) Analysis of epidemiologic trends of patients and hospital workers reported to suffer influenza-like illness." ] },{ "paper_id": "e9dfffbed92e23efc7241bae7623b4584f50b69e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A new era of global public health is on the horizon.", "Finally, innovations can turn challenges to opportunities. As discussed above, the world faces multiple challenges at the same time, and their solution requires novel approaches through innovations in public health. For example, the Medicine Patent Pool is expected to serve as a one-stop shop to handle complicated intellectual property and patent issues for the manufacture of generic drugs. Another important innovation is the various attempts to introduce different pricing policies for targeted populations based on their affordability. UNITAID is introducing innovative financing 13 to reduce the prices of commodities by collecting an international solidarity levy.", "How do all of these pieces come together to form a big picture? Japan has the unique opportunity in 2016 to host the G7 summit meeting and the Tokyo International Conference on African Development, which offers an international consensus-building forum for the new era of global public health. Already, Prime Minister Abe 14 has published his firm commitment on global health through his contribution to The Lancet." ] },{ "paper_id": "e9f9bb005036503310d511566fbfc6b1a82d8fdd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Resistance of S-pp expressing mutant D1128A S protein to neutralization by mAb 1A9", "To generate plasmids for the expression of mutant S, specific primers were designed for two-round PCR site-directed mutagenesis of wild-type S gene using the Expand High Fidelity PCR System (Roche). The PCR products were then cloned into the pXJ39 expression vector using BamHI and XhoI restriction sites to form pXJ39-S-N1056K, pXJ39-S-D1128A, pXJ39-S-D1128A/ N1056K, pXJ39-S-D1128E and pXJ39-S-D1128N plasmids.", "Ascites were produced by injecting hybridoma cells into the peritoneal cavities of pristine-primed BALB/c mice. The protocol was approved by the Institutional Animal Care and Use Committee (IACUC) of the Biological Resource Centre, A*Star, Singapore (Protocol Number: 110694). All the procedures were carried out in strict accordance with the recommendations of the National Advisory Committee for Laboratory Animal Research (NACLAR) guidelines in Singapore. All efforts were made to minimize suffering and euthanasia was performed using carbon dioxide." ] },{ "paper_id": "ea007e00fc6123e617913bd68cd8b54c4f0b111a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RotaRod 1 performance tests for the quantification of motor coordination was conducted on an accelerating rod (TSE Systems GmbH, Bad Homburg v. d. H\u00f6he, Germany) from five rounds per minute (rpm) to 55 rpm over a maximum period of five minutes. The rpm value was automatically recorded when the mice fell off the rod. Three measurements per animal were performed and obtained values averaged [48] .", "Leukomyelitis was graded in cervical, thoracic and lumbar spinal cord cross sections using a two-part, semiquantitative scoring system (leukomyelitis score) including perivascular infiltrates (PVI, 0 = no changes; 1 = scattered PVI, 2 = two to three layers, 3 = more than three layers of PVI) and hypercellularity (1 = 1-25 cells, 2 = 26-50 cells, 3 = > 50 cells per high power field) as previously described [44, 47, 48, 52] . Arithmetic averages were calculated for each segment and each parameter and a final score was determined by averaging the scores of the three segments from each animal and adding the scores of PVI and hypercellularity.", "During all experiments, weekly clinical scoring and RotaRod 1 performance tests for quantifying motor coordination deficits were performed by two examiners (AU, AB) in a non-blinded manner as previously described [47] [48] [49] [50] . Briefly, each animal was scored once weekly for the following clinical parameters: a) general appearance (0 = normal appearance; 1 = mild change [shaggy and scruffy hair]; 2 = moderate change [scruffy appearance and hunched back]; 3 = severe changes [unkempt appearance, urinary incontinence]), b) behavior and activity (0 = no change, 1 = mild change [mildly reduced spontaneous movement]; 2 = moderate change [moderately reduced spontaneous activity with unchanged induced activity]; 3 = severe change [no spontaneous movement, reduced induced activity]), and c) gait (0 = normal gait; 1 = mild change [mild ataxia with inconsistent waddling gait]; 2 = moderate change [moderate ataxia with consistent waddling gait]; 3 = severe change [severe ataxia with reduced righting response]; 4 = spastic paresis of hind legs). The final score (0 to 10 points) was calculated by summarizing the scores of the aforementioned parameters. Animals reaching the maximum of points in one or multiple parameters were excluded from the experiment and euthanized immediately for animal welfare purposes." ] },{ "paper_id": "ea023fc02c5314abb3e56a827e5eac71de12db9b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All analyzed datasets for this study are included in the manuscript and the Supplementary Files.", "This work was supported by Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado da Bahia (FAPESB; Grant PNX0019/2009 to AB) and Belgian FWO (Grant G0D6817N). KF was supported by a fellowship from Science without Borders (PVE Anne-Mieke Vandamme). TD was supported by the Institute for the Promotion of Innovation through Science and Technology Flanders (IWT-Vlaanderen), project 141614. CN-C, AB, and CO were senior investigators from Conselho Nacional de Pesquisa Cient\u00edfica (CNPq). HN was supported by FAPESP (Grant Nos. 2012/19278-6 and 2017/50137-3) . BA was supported by the National Institutes of Health (U01AI115940).", "KF and JVW designed the experiments. KF performed the experiments and analyses. CN-C, MB, and JO collected the samples. AB, TD, RK, JVW, and HN contributed to analysis. KF, CN-C, JVW, BA, and CO wrote the manuscript. All authors read and approved the final manuscript.", "All legal guardians of pediatric patients and adult participants signed a written term of informed consent. This study complied with the guidelines of the Declaration of Helsinki and was approved by the Institutional Review Board of the Federal University of Bahia (protocol no. 067/2009)." ] },{ "paper_id": "ea1eff3e4dd61110688eb2c07a616443dee8867b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ea23fbae1cee451e0beca6f5b2f6684519f63a67", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Since DNA sequencing has become easier and cheaper, an increasing number of closely related viral genomes have been sequenced. However", "Currently, the client-server nature of GATU relies on the use of our server for searches; high-throughput users can contact the authors for local installation instructions. In addition, we have also modified GATU to run as a simple stand-alone application that does not connect to the viral databases at the VBRC [2] .", "Before implementation of GATU, the following goals were set for the program: 1) provide automated transfer of annotations, but do not take decision-making out of the hands of the annotator; 2) provide a simple platformindependent graphical user interface (GUI); 3) reuse tools familiar to researchers in the field in order to lessen the learning curve; 4) when feasible, pre-calculate alignments to reduce the waiting time during the hands-on checking of annotations." ] },{ "paper_id": "ea2a30291a27a30b944a84050fff8bdf64e94130", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Scientific World Journal May 1980 [2] . The last naturally occurring case was reported in Somalia on 26th October 1977 [3] . It is assumed that about 300 million people died of smallpox in the twentieth century alone. Approximately 30% of those infected with smallpox died around the globe and those who survived lived with ugly scars.", "This inquiry provides an analysis of important issues from public health, clinical, and research aspects. The verdict is quite strong with nearly 60.6% of those who have answered the question, in favour of preserving the two remaining smallpox viral stocks, and, among the various reasons given, utility of specimens for future research is predominantly strong. Some other minor reasons include historical links.", "Among the 60.6% of those participants who answered the questionnaire in favour of the virus stocks not to be destroyed, the major reason quoted ( " ] },{ "paper_id": "ea3edffefb5fa20412b31e223330af336503afaf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Keywords: Epidemiological monitoring, Line list, Infectious disease outbreak, Influenza A virus, H7N9 subtype", "Authors' contributions EHYL, GML, BJC and HY designed the study. EHYL, TKT and PW performed the analyses. JZ, QL, BL, JSB, SS, JYW, SRM, CR, HJ, YL, JY, QZ, ZC, FL, ZP and LF collected data. EHYL wrote the first draft and all authors contributed to review and revision of the report. EHYL and JZ contributed equally to this work. BJC and HY are guarantors. All authors read and approved the final manuscript." ] },{ "paper_id": "ea40bddad18086f300f45b71a07f3e4c14e060eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reagents. All chemicals were purchased from Sangon Co. unless otherwise stated. were expressed in E. coli as truncated GST188 or Stv108 fusion proteins as described earlier [20] . Similarly, four sets of 35 overlapping 6-8mer peptides (P12-P46) corresponding to P4, P6, P9, and P10 sequences were also made, which overlapped each other by 5-7 residues.", "Briefly, the synthesized annealed DNA fragments encoding each P4 to P46 peptides corresponding to the hZP3 cDNA sequence [22] , incorporating BamH I and TAA-Sal I cohesive end on their 5 and 3 ends, were inserted into the BamH I and Sal I sites downstream of the Stv108 or GST188 gene in pXXStv-3 or pXXGST-1 plasmid. The resultant recombinant plasmids expressing each target short peptide fused with Stv108 or GST188 protein were transformed into the BL21(DE3)(pLysS) E. coli strain (Novagen, Inc., Madison, Wis, USA). Each recombinant clone was first grown in 3 mL of Luria Broth (LB) containing 100 \u03bcg mL \u22121 ampicillin at 30 \u2022 C with continuous shaking at 200 rpm overnight. Next day, 60 \u03bcL of cell suspension was inoculated in 3 mL of fresh LB and grown until the cell density reached 0.6-0.8 at OD600, and then further grown for 4 h at 42 \u2022 C to induce expression of the recombinant protein. For screening positive recombinant clones, each cell pellet harvested from induced target clones was first used to run SDS-PAGE gel using the pellet containing Stv108 or GST188 protein expressed by pXXStv-4 or pXXGST-2 plasmid as negative controls, and nucleotide (nt) sequence of all the recombinant clones were subsequently determined (United Gene Holding Ltd., Shanghai). The cell pellets containing each short peptide fusion protein were stored at \u221220 \u2022 C.", "Care and treatment of the animals was based on the standard laboratory animal care Clinical and Developmental Immunology 3 protocols approved by the Institutional Animal Care Committee. Six male New Zealand White rabbits were obtained from SIPPR-BK Lab Animal Co., Ltd. (Shanghai, China). The immunization schedule was as follows: six rabbits (number 073-076) weighing 2.0 \u00b1 0.5 kg were immunized intramuscularly with 0.5 mg of chemically synthesized peptide P1 or P2 conjugated with KLH (Sigma) and emulsified in complete Freund's adjuvant (CFA) (Sigma) at multiple sites on the rabbit's back, respectively. The animals were boosted three times intramuscularly with 0.25 mg of same peptide antigen emulsified in incomplete Freund's adjuvant (Sigma) at 2 week intervals. Serum samples from immunized animals were collected 7 days after the third booster, and the antibody titer was assessed by ELISA. Nonimmune sera from two animals (number 077-078) who only received CFA and P3 as unrelated peptide antigen were used as negative controls in the ELISA, respectively.", "The human zona pellucida (hZP) is an extracellular matrix surrounding eggs, which consists of four sulfated glycoproteins designated as ZP1, ZP2, ZP3, and ZP4 [1, 2] . ZP glycoproteins mediate several critical events during fertilization process such as initial recognition and binding of the spermatozoa to the egg in a species-specific manner, induction of the acrosome reaction in the zona-bound spermatozoon, and prevention of polyspermy [3, 4] . By virtue of their critical role during fertilization, ZP glycoproteins have been proposed as target for developing contraceptive vaccines [5, 6] . Although active immunization with purified or recombinant ZP (r-ZP) proteins induces infertility in various mammalian species, the contraceptive efficacy is invariably associated with either transient alteration or complete loss of ovarian function [7] [8] [9] [10] . The observed ovarian pathology following active immunization with ZP antigens may be due to (i) presence of ZP-specific T-cell epitopes (TCE) within a B-cell epitope (BCE), for example peptide corresponding to mouse ZP3 (mZP3) amino acid (aa) residues 330-342 (peptide 330-342 ) [11] , (ii) autoimmune ovarian disease (AOD) that can be adoptively transferred by the ZP3 peptide-activated CD4 + T-cells to na\u00efve recipients but does not occur when only antipeptide antibodies are administered [12] , and (iii) the minimal and modified BCE peptide 335-342 of mZP3, which had no longer a ZP-specific TCE (phenylalanine, a key residue of the \"oophoritogenic\" TCE, substituted by alanine), induced infertility in mice with eight different haplotypes without any AOD when it was co-linearly synthesized with a foreign \"promiscuous\" TCE [13] ." ] },{ "paper_id": "ea4880d01d03a59bb3de58e8ae226c5487e38e6c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Brucella. Several extremely dangerous pathogens that can infect humans and animals are found in the Brucella biocluster. These bacteria are easily transmitted by ingestion of unsterilized milk or meat from infected animals or close contact with their secretions or by inhalation of aerosols. Brucella species have slightly different preferred host specificities: B. melitensis infects goats and sheep, B. abortus infects cattle, B. suis infects pigs, B. ovis infects sheep, B. canis infects dogs, and B. neotomae infects wood rats.", "Taxonomists have alternated between individual species naming and naming as a single species B. melitensis, containing B. melitensis 16M and five other biovars: abortus, canis, neotomae, ovis, and suis. Recently, four additional species of Brucella have been described, including two that infect marine mammals. The current convention adopted by the International Committee on Systematics of Prokaryotes, subcommittee on Brucella (http://www.the-icsp.org/ subcoms/Brucella.htm) recommends re-approval of the classical Brucella species with their recognized biovars.", "Coxiella burnetii. Q fever is a zoonosis caused by Coxiella burnetii, an obligate Gram-negative intracellular bacterium [35] . C. burnetii infects various hosts, including humans, ruminants, and pets. Because of its highly infectious nature, C. burnetii is recognized as a biothreat agent. The bacterium can exist in a spore-like life cycle and remain viable and virulent for many months. Phylogenetically it occupies a unique niche, with very few near neighbors. The closest known organism based on genomic and 16S rRNA analysis is Legionella pneumophila [36] .", "The V. cholerae biocluster primers were previously field-tested using natural water samples from both freshwater lakes and the Georgian coastal zone of the Black Sea. Of the 278 total water samples screened, nine different Vibrio species were detected, 114 samples were positive for V. cholerae, and five samples were positive for the cholera toxin A gene (ctxA) [14] . The results were confirmed with conventional PCR." ] },{ "paper_id": "ea77ef3c24536b33485875684a34ca6539084c5c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed by two-way analysis of variance using GraphPad Prism version 5.00 (GraphPad Software, San Diego, CA, USA). When a significant effect was observed, pairwise comparisons were performed using the Bonferroni post-hoc test. All data are reported as mean 6 SD. " ] },{ "paper_id": "ea7ae35a6203f68c29d8aa305a9d89ba8c76d284", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The appropriate management of HID cases requires high-level diagnostic capabilities.", "On-site visits were performed by the project coordinator assisted, when feasible, by the project partner of the explored country from February-November 2009.", "The participant selection process led to the inclusion of 48 isolation facilities identified for the referral and management of HIDs in 16 countries Table 1 .", "The data were collected during on-site visits using checklists specifically developed during the first year of the project [7] . The checklists were drafted by the steering committee members (including partners from France, Germany, Greece and the United-Kingdom) and then discussed with and approved by all of the partners. The coordination team (based at the National Institute for Infectious Diseases in Rome, Italy) considered the strength scores of these assessments to be indispensable." ] },{ "paper_id": "ea85420ea72fab3346afc8aaf42b17f571b99a85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This section begins with various approaches to finding the time-dependent probability distribution of gap lengths in a pairwise alignment, under several evolutionary models.", "Models which allow for heterogeneity of indel and substitution rates along the sequence also fall into this category of latent variable models. The usual way of allowing for such spatial variation in substitution models is to assume a latent rate-scaling parameter associated with each site [4, 5] . For indel models, this latent information must be extended to include hidden site boundaries [56] .", "A number of excellent, realistic sequence simulators are available including DAWG [99] , INDELible [100] , and indel-Seq-Gen [101] ." ] },{ "paper_id": "ea97faa57e408d3c7a5b84dbe3da7ae4feb9992e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition to the advantage of speed, the described assays overcome the challenges of detection of these organisms by culture. Although culture is considered a gold standard method (and was so considered in this study), colonial identification is challenging and subjective because it is done using the human eye and a dissecting microscope. Artifacts may be misidentified as colonies, yielding false-positive results, or colonies may be overlooked, yielding false-negative results. Although PCR may be considered more technically complex, in a laboratory where technologists are familiar with PCR, this approach is more user-friendly (and generalizable among assays for various microorganisms) than culture.", "Predicted amplified product, primer, and probe sequences were subjected to BLAST searches using the National Center for Biotechnology Information (NCBI) genomic database (http://www.ncbi.nlm.nih.gov/). Analytical sensitivity was assessed by spiking a series of six tenfold dilutions of quantified genomic DNA from M. hominis ATCC 23114, U. urealyticum ATCC 27816, and U. parvum ATCC 27815D into genitourinary samples. Each dilution was extracted in triplicate and each extract was assayed in duplicate. The limit of detection was the lowest dilution where all six replicates were detected. Inclusivity and cross-reactivity were assessed using a panel organisms (Table 2) , including 16 members of the Mollicutes class.", "Specimens. 283 genitourinary specimens (swabs, urine) submitted to the Mayo Clinic Clinical Microbiology Laboratory in transport medium (e.g., UTM, M5) for M. hominis and Ureaplasma culture were evaluated. No clinical data associated with these specimens was available. This study was approved by the Mayo Clinic Institutional Review Board.", "The two assays were independently optimized on the LightCycler 480 II platform employing LightCycler 480 Software version 1.5 (Roche Applied Science). 15 L of PCR master mix, containing final concentrations of 1X Roche Genotyping Master (Taq DNA polymerase, PCR reaction buffer, deoxyribonucleoside triphosphate with dUTP substituted for dTTP and 1 mM MgCl 2 ), 1 mM (additional) MgCl 2 , and 1X of each of the LightCycler primer-probe sets (Table 1) were added to a 96-well LightCycler 480 plate. Extracted nucleic acid (5 L) was then added to each well. The cycling program was as follows: denaturation at 95 \u2218 C for 10 min; amplification for 45 cycles of 10 s at 95 \u2218 C, 15 s at 55 \u2218 C (single acquisition), and 15 s at 72 \u2218 C; melting curve analysis for 30 s at 95 \u2218 C, 10 s at 59 \u2218 C, 15 s at 45 \u2218 C (ramp rate of 0.1 \u2218 C/s), and 0 s at 80 \u2218 C (ramp rate of 0.14 \u2218 C/s and continuous acquisition); and cooling for 30 s at 40 \u2218 C. Positive and negative controls were included in each run. The positive control consisted of the abovementioned plasmids in S.T.A.R. buffer : sterile water (1 : 1) at a concentration of 1,000 targets/ L. The negative control consisted of 1,000 colony forming units of Escherichia coli ATCC 25922 S.T.A.R. buffer : sterile water (1 : 1) at a concentration of 1,000 targets/ L." ] },{ "paper_id": "eaa5563d3b1791ebb166e18abfaba4e22b965049", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 6:26516 | DOI: 10.1038/srep26516 viruses, this is between 10 5 to 10 6 virus particles/mL 4, 5 . With filtration techniques, both TEM and SEM of viruses can be carried out with as little as 5000 particles per sample 7 .", "Bacterial growth. Salmonella Senftenberg (kindly provided by Dr. George Golding, National Microbiology Laboratory) strains were grown overnight in 3 mL LB broth at 37 \u00b0C with shaking. Fifty \u03bc L of bacteria were then sub cultured into 3 mL LB broth and grown at 37 \u00b0C with shaking for 4 hours to the approximate mid-log phase of growth. The bacteria were fixed at 1:1 v/v in 1% paraformaldehyde and 2% gluteraldehyde for 1 hour at room temperature. Leptospira biflexa serovar Patoc (kindly provided by Dr. Robbin Lindsay, National Microbiology Laboratory) was grown in Ellinghausen and McCullough media modified by Johnson and Harris (EMJH) (Royal Tropical Institute, The Netherlands). The inoculate culture was placed at 30 \u00b0C for 14 days and then stored at room temperature in low light.", "(BHK-21:ATCC) were grown to 80% confluence in high-glucose Dulbecco's Modified Eagle's Medium supplemented with 10% fetal bovine serum and 1X Penicillin-Streptomycin. The BHK-21 cells were infected with 1 mL of Modified vaccinia Ankara (MVA) virus (kindly provided by Dr. Jingxin Cao, National Microbiology Laboratory) and incubated for 48 hours at 37 \u00b0C with 5% CO 2 . The infected cells underwent 3 freeze-thaw cycles in the presence of the growth media, alternating between \u2212 80 \u00b0C and room temperature. MVA was collected in the supernatant after removing cells and debris by centrifugation at 3000 \u00d7 g for 3 min." ] },{ "paper_id": "eaa61130ab5e4b11c8b104c76dfa4b56f496fb49", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "eaaa5939391fb99e06e8d6b8723e6b061632b1c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step 2 -First questionnaire round", "Step 5 -Second consensus meeting", "Step 1 -Literature search and selection of recommendations" ] },{ "paper_id": "eaba1af19b87795dc237a55c0236d89ede3cf46a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "-An adequate storage of viral particles after collection.", "The nucleotide sequences data have been submitted to GenBank under the following accession numbers: KU729665, KU729669, KU729666, KU729670, KU729667, KU729671, KU729668 and KU729672." ] },{ "paper_id": "eabb427018b4decc5d1e04772814238be2a6d9d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The regression coefficients b = (b 0 , b 1 , b 2 , . . ., b 6 ) were then determined from historical ILI data and Wikipedia data. ", "with K being the number of weeks in each season and i = 1, 2, . . ., M.", "and each choice of p yields a discretely sampled solution vector" ] },{ "paper_id": "eabfb15b60476742917f92c6fb60a7bc6ec203aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "eac85c85c3a2ac1d3fe53e1e3b3fee98f52527ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Funding The study was not funded by any organization.", "A cross-sectional survey was conducted for a 3-month period from November 2015-January 2016 at Umm Al Qura University, Makkah, Saudi Arabia.", "The data were coded, entered and analyzed using SPSS. Descriptive statistics, frequencies and percentages were used to summarize data. An ANOVA test was used to determine the association of study disciplines and academic year with the knowledge score on MERS. P < 0.05 was considered statistically significant.", "Undergraduate students studying medicine, dentistry pharmacy and dentistry were approached and recruited through social networking websites (Facebook, Twitter and Whatsapp). Students were eligible to participate if they were in year 4, 5 or 6 of their undergraduate program. The password-protected survey links were posted on various official college social media pages. An introductory paragraph outlining the aims and objectives of the study as well as instructions to complete the questionnaire was posted along with the survey." ] },{ "paper_id": "eacaf861a42b91fc9ed93bfffc97a13685747c40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Spearman's r Rank Order Correlations were conducted using GraphPad Prism release 7.0 (GraphPad Software, San Diego, CA, USA).", "Results", "well as a significant increase in severe fetal abnormalities, including spontaneous abortion, stillbirth, hydrocephaly, microcephaly, hydranencephaly/hydrops fetalis, and placental insufficiency [10] [11] [12] [13] [14] . ZIKV is a small, enveloped positive-strand RNA virus [15] . The genomic RNA of this mosquito-borne flavivirus contains a single open reading frame (ORF) that encodes a polyprotein [16, 17] . This polyprotein undergoes co-and post-translational processing to produce three structural proteins, which are capsid (C), pre-membrane (prM), and envelope (E), in addition to seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) [17, 18] . Of the three structural proteins, E is the major surface glycoprotein, containing three domains (I, II, III) and two transmembrane helices [17] [18] [19] . The majority of flavivirus E proteins upon post-translational modification are modified by N-glycans at amino acid 153/154 within a highly conserved glycosylation motif of N-X-T/S at positions 154-156 (where X is any amino acid except proline) [16] . This is a primary target of neutralizing antibodies and is required for virus entry [20] ." ] },{ "paper_id": "eaccbbd4d93f295b6c22ae217f159c288b29deb6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lungs of UNC and experimentally infected pigs were processed routinely for haematoxylin and eosin (H&E) and immunohistochemistry staining, as described previously [26] .", "Our study had been approved by Animal Care and Use Committee of Guangdong Province, China. All animal procedures were performed according to guidelines developed by the China Council on Animal Care and protocol approved by Animal Care and Use Committee of Guangdong Province, China.", "For RNA library construction and deep sequencing, equal quantities of RNA samples from three UNC individual lungs were pooled, RNA samples from the three infected pig lungs (N96) were pooled, and RNA samples from the three infected individual lungs (N168) were pooled. Approximately 6 mg of RNA representing each group were submitted to Solexa (now Illumina Inc.) for sequencing." ] },{ "paper_id": "ead34dbe8d24c80ca48b9f828aa34be52a65a8a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Figure S2 ", "Sequence data were deposited in to NCBI Bioproject under accession number PRJNA417283." ] },{ "paper_id": "ead6fda7cdb2bb2469ff48365833bd63d0b7dd1a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We employed the likelihood-based method or generation interval-informed method of White and Pagano [23] , using the following formula:", "The transmission dynamics are governed by the following system of equations:", "The authors declare no conflict of interest." ] },{ "paper_id": "eae06fd0ce129fbfb73f70fd0c49df18c40632dd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "eaf46f27d9c28f8b3c818b0d7969d9188a7e9c11", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cloning and expression of full-length and truncated GAV His 6 -tagged N proteins", "The synthetic peptide (MPVRRPLPPQPPRNARLI) was purchased from Shanghai Science Peptide Biological Technology Co. Ltd., China. The lyophilized peptide, reported by the manufacturer to be 99.2% pure as determined by high performance liquid chromatography (HPLC), was dissolved to appropriate concentration in double-distilled water." ] },{ "paper_id": "eafa4d1bd1e62bf88d6d2813002cfe6c33be8b95", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A nation-wide influenza surveillance program in Malaysia was initiated in 2004 under the national influenza pandemic preparedness plan. As a requirement, attending doctors from two respective designated government polyclinics per state were instructed to collect throat swab specimens from patients with influenza-like illnesses. Simultaneously, clinical and epidemiological information of the patients were recorded in a standardized questionnaire and sent together with the clinical specimens to the national public health laboratory for influenza virus isolation and identification.", "Cross neutralization activity of convalescent human sera was tested using a micro-neutralization test against 100 TCID 50 of each of the four viruses using a previously published method [5] .", "Human sera were tested for the presence of virus-specific IgM and IgG antibodies by indirect immunofluorecence assay using the fixed infected cells prepared above. Convalescent human serum samples were serially diluted from 1:20 to 1:2560 with sterile PBS. Twenty microlitres of the diluted sera was used for immuno staining as previously described [15] . The end point titre of positive assay was taken as the highest serum dilution that gave at least five cells with positive immunofluorescence." ] },{ "paper_id": "eb018f450fa6903ccf3c0c151b24a814ee81fd55", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis. Two-way ANOVA analysis were used to analyze data. Experiments were repeated at least three times. Results were considered significant at p < 0.05.", "Innate immunity provides a robust first line of defense against invading pathogens. After detecting invading viruses, host cells initiate several signaling cascades to generate type I interferons (IFNs) such as IFN-\u03b2 and IFN-\u03b1 . Type I IFNs activate the JAK-STAT pathway, resulting in expression of hundreds of interferon-stimulated genes, which can target every stage of the viral life-cycle and protect host cells from invading viruses 1 ." ] },{ "paper_id": "eb02e66bf6c521ac15b2dfa14b2b7966f137c876", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Detecting avian influenza virus has become an important public health strategy for controlling the emerging infectious disease.", "We collected 3401 throat swab or lower respiratory tract samples, among which 2094 were tested positive to influenza or avian influenza virus. Among the positive results, 78 were H3N2, 17 were seasonal H1N1, 1871 were H1N1pdm, 103 were untyped influenza A, 16 were B, 1 was H5N6, and 8 were H7N9 virus. The activity of H7N9 virus and that of seasonal viruses especially H1N1pdm were observed in 2014 (Table 3) ." ] },{ "paper_id": "eb07f3436bd925c0de35ecbe26930536e8bcf200", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ ", respectively." ] },{ "paper_id": "eb0a05f4e7d9d276e308e8f6e80617962b07f9cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Adult mesenchymal stem cells (aMSCs) are stem cells.", "The authors declare no conflict of interest.", "The chemokine (C-X-C motif) ligand 12" ] },{ "paper_id": "eb0d926b1fa6dc7d9f86a001f8ccd69407c5ed86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DNA sequences were manually trimmed to remove indels and aligned using Geneious v6.1.7 (Biomatters Ltd.) using default settings. This alignment and a species trees representing currently accepted primate relationships [68] were used as input files for PAML analysis [44] and additional analyses using HyPhy software on Datamonkey.org [45] .", "(DOCX) S2 Table. OAS gene family evolutionary summary for 11 primate species using PAML. (DOCX) S9 Table. OAS gene family log likelihood scores and parameter estimates for two models of variable \u03c9 among sites assuming the f3x4 model of codon frequencies in PAML. (DOCX) S10 Table. OAS2 gene (20 species) log likelihood scores and parameter estimates for four models of variable \u03c9 among sites assuming the f3x4 model of codon frequencies." ] },{ "paper_id": "eb0fb44015f899d2b00fc41e9e65ea13fc7fcde1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The mortality from cardiovascular disease function takes the form of Equation (1):", "\uf062 is a vector of estimated parameters and j", "(2) 2 \uf063 (0.01,10) = 23.29." ] },{ "paper_id": "eb1b9685e0eaa51bef8c8a20729643d888e0a324", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Besides the considerable diversity in APC specific receptors, also in the approach to target these receptors there appears to be plenty of choice.", "In this section we will discuss the three main targeting approaches while a detailed overview of the performed preclinical and clinical in vivo APC targeting experiments in the framework of antitumor immunotherapy is summarized in Table 2 .", "A final hallmark of their professionalism is represented by their differential anatomical locations, expression of different markers, distinct antigen processing capacities, and variable responses to maturation stimuli or, in other words, their subdivision in specialized subtypes, as discussed in the next section.", "In summary every DC subset has its own functional specialties, which opened up exciting possibilities for targeted manipulation to tune the immune response by harnessing subset specific attributes. Subsequently antitumor vaccination became not only a question of proper DC activation but also of selecting the most appropriate DC subtype [34, 44] ." ] },{ "paper_id": "eb1cc7c78d58eee6f6f81092426a9a5c9aab696c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "eb2843b666bbd106400ec51a67b584e7731c18d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GST pull-down assay. GST, GST-FSCN1 or GST-VIME proteins were expressed in Escherichia coli BL21" ] },{ "paper_id": "eb289af3995ebdf5654f8553444b4dbc6ca30667", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(Drew Scientific). Plasma cytokine levels plasma were quantified using a mouse-specific MILLIPLEX MAP kit (Millipore) as described 35 .", "Systemic infection caused by MDR fungi is a growing global health concern. It is estimated that approximately 1.5 million cases of disseminated mycoses occur annually and are associated with high mortality rates 1-3 . Fungal pathogens are a major cause of hospital-acquired infection 4 , particularly among surgical patients and those with indwelling catheters 5 . Increased risk of systemic fungal infection is also associated with biologic therapies for treatment of inflammatory or autoimmune diseases 6,7 .", "The failure to develop agents that are selective against eukaryotic pathogens has impeded the clinical introduction of new antifungals 14 . Currently, there are but three classes of antifungal drugs that are relied upon for treatment of invasive fungal infections: polyenes, azoles, and echinocandins 20 . Echinocandins, introduced nearly 20 years ago, are the most recently approved class of antifungals. Limitations associated with use of currently available agents include limited activity spectra 17,21,22 , serious adverse side effects 23,24 , and lack of activity against biofilms 25, 26 . The emergence of MDR fungal pathogens underscores the urgent need for development of new approaches for treatment of fungal infections [27] [28] [29] ." ] },{ "paper_id": "eb4451db661165d4d518ea8b812b9d0963e84736", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "eb49cb90e8f1868b1d73beef301de0ebc481f183", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "BmNPV particles were fixed with a mixture of 2% paraformaldehyde and 2% glutaraledehyde in 0.1 M cacodylate buffer, pH 7.4 and postfixed in 1% osmium tetroxide in the same buffer. After further washes with the above buffer, the specimens were collected and embedded in agarose. The agarose blocks were dehydrated in ethanol and embedded in an Epon/Araldite mixture. The ultrathin sections were stained with uranyl acetate and lead citrate, and then examined with a Hitachi H7500 electron microscope at 80 kV.", "Proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) using 12% polyacrylamide and subjected to Western blot. Under the non-reducing condition, samples were mixed with sample buffer lacking \u03b2-mercaptoethanol and boiled. Following it, the proteins were blotted onto a polyvinylidene fluoride (PVDF) membrane using Mini Trans-Blot Electrophoretic Transfer Cell (Bio-Rad, Hercules, CA, USA). After being blocked in 5% skim milk in Tris-buffered saline containing 0.1% Tween 20 (TBST), the membrane was incubated in either 1:10000 diluted mouse anti-FLAG M2 antibody (Sigma-Aldrich, St. Louis, MO, USA) or 1:4000 diluted rabbit anti-Bmgp64 polyclonal antibody for 1 hour. The membrane was washed with TBST, and then incubated in 1:20,000 diluted anti-mouse or anti-rabbit IgG antibody labeled with horseradish peroxidase for 1 hour. Detection was performed using ECL Plus Western blotting reagent (GE Healthcare UK Ltd.). Specific bands were detected using a Fluor-S/MAX multi-imager (Bio-Rad). Bands on SDS-PAGE gels were analyzed by Quantity One 1-D analysis software (Bio-Rad).", "For protein expression in Bm5 cells, recombinant BmNPV was prepared by transfection of recombinant BmNPV bacmid DNA into Bm5 cells. Following transfection, BmNPV is required to be amplified several times in order to obtain sufficient virus titer for protein expression. Moreover, time to amplify BmNPV is required due to slow growth rate of Bm cells compared to Sf-9 cells." ] },{ "paper_id": "eb4b8f43f68db5e493984b7e4e56d9f804d7e885", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "-FC, HY and VK were responsible for conception and design, analysis and interpretation of data, and gave the final approval -JM was responsible for conception and design, revising the manuscript and gave the final approval" ] },{ "paper_id": "eb4e468f68974db552de7a9f4e41d95607b0c461", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Domestic cat Mya-1 na\u00efve feeder cells [55] were prepared for co-culture by cultivation in LBT + IL-2, plated in MEM containing 10% fetal bovine serum, 100 U of penicillin, 100 ug of streptomycin/ml, and 1% glutamax, and dispensed at 2 \u00d7 10^6 cells/ml in appropriate media in a 24 well plate. Reconstituted lion PBMCs were then added to Mya-1 cells at a volume of 400 ul (4-6 \u00d7 10 5 cells)." ] },{ "paper_id": "eb5417b7729ff5548e5b9ddcb837fa52efc586f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Both the mixed and single alkaloids of M. cordata strongly inhibited proliferation and induced apoptosis of cancer cells [6, 70] . The anticancer drug Ukrain \u2122 is an isoquinoline type. The major components of Ukrain \u2122 are chelidonine, sanguinarine, chelerythrine, protopine, and allocryptopine. Ukrain \u2122 exerted cytotoxic effects in cancer cells without negative effects on normal cells [71] , and had radiosensitization effects on cancer cells, while exerting radioprotective effects on normal cells [72] .", "A pharmacophore model represented a series of common features of a set of ligands with a special pharmacological target. The features of a pharmacophore model reflected the target-ligand interaction mode. Pharmacophorebased virtual screening was an alternative to docking. By fitting a compound against a panel of pharmacophore models derived from multiple pharmacological targets, the potential targets of the compound can be outlined." ] },{ "paper_id": "eb5cf729cc61df11fa28230ff5f15bc1ec559bc5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Amplicon Length (bp) ", "PCV3 was first identified in the USA in 2015; from tissues of animals presenting porcine dermatitis and nephropathy syndrome (PNDS) and reproductive disorders, but that had tested negative for PCV2; a metagenomics approach revealed an uncharacterized virus [6] . PCV3 has since been identified in Asia [9] [10] [11] , South America, and Europe [12] [13] [14] [15] [16] in swine with various clinical syndromes [6] . Its comparable prevalence in healthy swine [17] and wild boar [18, 19] however, raises questions about its role in swine pathogenesis.", "The following are available online at http://www.mdpi.com/1999-4915/11/9/786/s1, Table S1 : Reference sequences information used in this study, Table S2 : Sequences information sequenced in this study. " ] },{ "paper_id": "eb5dcf1546dae050e8aa82aecc2d4b2cc472cbc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We obtained ethical approval for this study from the ethics committee of the Hannover Medical School.", "Viral persistence (viral shedding) is defined as the time period from first positive diagnostic test to sustained negativity. Duration of viral persistence was minimally 4 days (case 7) and maximally at least 63 days (case 1)see also Table 1 .", "Therapeutic options for patients in hematopoietic stem cell transplantation and with intensive cancer therapy, who are severely infected by RSV, include the use of systemic or aerosolized ribavirin and polyclonal intravenous immunoglobulins (IVIG) [19, 20] . The RSVspecific monoclonal antibody Palivizumab has been used for treatment and for passive immunization (prophylaxis) in high risk pediatric patient groups [19] [20] [21] ." ] },{ "paper_id": "eb5f4f63cdb4bfd57256d362dbd01063522c9f05", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accurately characterizing evolutionary relationships between organisms and their genomes is the basis of comparative genomic methods for interpreting meaning in sequence data, and for this reason the use of molecular phylogenetics has become widely used (and sometimes indispensable) in a multitude of research fields such as systematics, medical research, drug discovery, epidemiology, and population dynamics [3] . For example, the use of molecular phylogenetics was of considerable assistance in predicting the evolution of human influenza A [4] , understanding the relationships between the virulence and the genetic evolution of HIV [5, 6] , identifying emerging viruses as SARS [7] , recreating and investigating ancestral proteins [8] , designing neuropeptides causing smooth muscle contraction [9] , and relating geographic patterns to macroevolutionary processes [10] .", "Before proceeding, we shall introduce some notation and definitions that will prove useful throughout the article.", "i\u2208V" ] },{ "paper_id": "eb657ff6a2abb31f6e8c6c9ac91814cb8fcda133", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In conclusion, this is the first report of KFD involving testitis and pathologically proven asymmetrical brain regions. ", "Kikuchi-Fujimoto disease (KFD), or histiocytic necrotizing lymphadenitis, is known to be a benign disease that usually resolves spontaneously. It is a rare disease and was first reported in Japan in 1972 [1, 2] . KFD usually affects female patients under the age of 30 years and is characterized by regional lymphadenopathy with tenderness, predominantly in the cervical region, and is usually accompanied by mild fever and night sweats. It is of clinical importance because it is often misdiagnosed as tuberculosis, lymphoma, or systemic lupus erythematosus (SLE); therefore, the diagnosis should be confirmed by biopsy study. Diseases that generally accompany KFD are SLE, arthritis, mixed connective tissue disease, and similar conditions; however, comorbid testitis has not yet been reported. Neurological complications occur in about 11% of cases, as revealed by a review of 244 cases in which a minority of cases evolved to developing encephalitis [3] . Brain magnetic resonance imaging (MRI) includes symmetrical hyperintense T2-weighted and FLAIR (fluidattenuated inversion recovery) signals in the temporal lobes, pons, and periaqueductal gray matter [4] [5] [6] [7] . This is the first report of KFD occurring with testitis and pathologically proven asymmetrical brain regions.", "KFD was first described in Japan in 1972 and has increasingly been recognized worldwide since 1982 Fig. 2 a Axial T1-weighted magnetic resonance image shows that the lesion has an isointense signal. b After administration of gadolinium contrast, material internal enhancement is not observed. c Coronal T2-weighted magnetic resonance image shows that the lesion has low signal intensity (arrow) Fig. 3 Left cervical lymph node biopsy shows conspicuous apoptotic necrosis in paracortical and cortical areas with an abundance of macrophages and large lymphoid cells, which have irregular nuclei [hematoxylin-eosin staining \u00d7 4 (left), \u00d740 (right)] [8] . According to a review [3] that summarized 244 KFD cases, the mean age was 25 (1-64) years, and 70% were younger than 30 years; 33% were men, and 77% were women. Most of the cases were reported from East Asia and the Far East (50%), and the others were from Europe (27%) and America (7%). As in the present case, the most common symptoms were fever (35%), fatigue (7%), and cervical lymphadenomegaly (100%) [3] . Our case did not show any evidence of SLE, lymphoma, tuberculosis, arthritis, or viral disease based on laboratory findings and cervical lymph node biopsy." ] },{ "paper_id": "eb65ef8d3ff24ddb51c4f091a46394f513a9d4d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Delhi and DuPre fellowship, Multiple Sclerosis Society International Federation (MSIF), UK for a fellowship. This work was supported by the Department of Biotechnology BT/PR20922/MED/122/37/2016 to JD. KS thanks Research to Prevent Blindness, NIH grant EY015014, and the F. M. Kirby Foundation. The authors thank IISER Kolkata and University of Pennsylvania, Philadelphia, for support. The funders had no role in the study design, data collection, and interpretation, or the decision to publish the work.", "Serial sections from eye, optic nerve, and brain were stained by the avidin-biotin-immunoperoxidase technique (Vector Laboratories) using 3, 3-diaminobenzidine as substrate, and a 1:100 dilution of anti-Iba1 (Wako, Richmond, VA, USA), and 1:40 dilution of antiviral nucleocapsid antiserum (mouse monoclonal anti-N; Nucleocapsid protein of MHV-JHM, monoclonal clone 1-16-1, Kindly provided by Julian Lebowitz, Texas A&M, College Station, TX) as primary antibodies. Control slides from mock-infected mice were incubated in parallel.", "MS, RK and KD performed the wet lab experiments and wrote their contributions. KS and JD designed the studies and wrote the paper." ] },{ "paper_id": "eb6bcd87e93e2bac6bd7b03367102b0a05e458e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The neighbor-joining phylogenetic tree of Chinese FB rabies virus isolates, using the full length N gene (1353 bp) for reconstruction." ] },{ "paper_id": "eb6e2916b4a94b8c8a3e7d58f70158dc04191503", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethical permission to conduct the survey was obtained from the department of medical research and studies, Jeddah, Kingdom of Saudi Arabia (approval number A00298). This department is registered in Saudi National Committee for Biomedical Ethics (Registration number H-02-J-002).", "We aimed to explore the knowledge, attitudes and behaviours of healthcare workers in the Kingdom, particularly focusing on the recent disease of international significance MERS-coronavirus (MERS-CoV)." ] },{ "paper_id": "eb6e2ba036db0dcd7515f6c8b74938e89201b8ab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ChIP-qPCR assay. Chromatin immunoprecipitation (ChIP) assay was carried out as described earlier. 53 Chromatin obtained was purified using the QIAquick PCR purification kit (Qiagen, Venlo, The Netherlands). The eluted genomic DNA was subjected to SYBR green real-time qPCR with the APAF1 ChIP primers, forward GCC CCG ACT TCT TCC GGC TCT TCA and reverse GGA GCT GGC AGC TGA AAG ACT C. The results were expressed as fold enrichment over control (NT siRNA or pLPC-Flag).", "Flow cytometry. Annexin V and 7AAD staining of cells was done using annexin V PE/FITC apoptosis detection kit (BD Pharmingen, San Jose, CA, USA) according to the manufacturers' instructions. Samples were acquired on BD FACS Calibur (20 000 cells per sample; BD Biosciences, NJ, USA) and analyzed using Flowjo version 9.3.3 software (Tree Star Inc, Ashland, OR, USA).", "Taken together, our findings argue in favor of a critical role of antiapoptotic protein API5 in IAV-induced apoptosis and virus replication. NP-API5 association has a negative bearing on cellular levels of API5, which mitigates API5-induced suppression of E2F1-APAF1-dependent apoptotic signaling thus favoring virus propagation." ] },{ "paper_id": "eb7682d19e11ed030c9541c61514075c2080535a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These results add to the body of evidence that the DFAT does not perform as well as newer diagnostic methods in detecting viruses.", "Supplemental material for this article may be found at https://doi.org/10.1128/JCM .00399-18.", "SUPPLEMENTAL FILE 1, XLS file, 0.1 MB." ] },{ "paper_id": "eb824213356f63dbaabe4c3f454914e24d6e6a71", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DDESC: Dragon Database for Exploration of Sodium Channels in Human; DES: Dragon Exploration System." ] },{ "paper_id": "eb83b27bafc37b40794c2c7cc1b921cbcdb4138c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No untoward effects or additional protection were noted if a third NTHi lysate dose was added on day 3. Observations through day 21 showed no subsequent mortality.", "Summary statistics for virus in lung tissue were compared using Student's t-test. Proportions of mice surviving pathogen challenges were compared using Fisher's exact text, and log-rank comparisons of survival distribution were performed using Kaplan-Meier estimation. All data shown are representative of at least two independent experiments, and were not combined for analysis because of modest differences in virus challenge doses. Analyses were performed using SAS/STAT (SAS Institute)." ] },{ "paper_id": "eb856c32c1a41e6513729e126e84e639ce4f5a68", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Titre frequency distributions for the pathogens detected are depicted in Fig. 2 . Most samples have high antibody titres for CPV (>160) and for CAV (>64), but for CDV most positive samples have relatively lower titres.", "A list of individual and environmental factors associated with previous exposure to viral pathogens is presented, highlighting the need for management actions for the improvement of health of dog populations and the urgent prevention of disease-induced mortality of already threatened Atlantic Forest's wild carnivores.", "Regarding antibody titre frequency and duration of immunity, mostly high levels of antibodies against CPV and CAV were found. The duration of antibodies to the viral agents studied here is longer than two years [38] , and such titres may indicate that the exposure to these agents is mostly recent. However, as said before, it is not possible to accurately determine the timing of exposure from antibody titres, and our cross-sectional serological approach does not permit deeper inferences on temporal-spatial dynamics of exposure neither detects pathogen introduction or seroconversion events.", "Proportionally more CDV and CPV-exposed dogs were found in small areas. Perhaps the reduced perimeter of these areas allows less space between properties and households, and ensures higher host densities, contact rates and exposure (including environmental) to these agents. Therefore, small areas should be prioritized in health improvement efforts for rural dogs aiming also to prevent wildlife disease-associated mortality in the Atlantic Forest, which is currently mostly composed by relatively small remnants [39] ." ] },{ "paper_id": "eb8769154d6a5a4a44f5cea8a1b92082f9c278a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mucus production was confirmed using alcian blue staining. Membrane inserts were stained apically with a 1% alcian blue solution (3% acetic acid, pH 2.5) for 30 sec. The alcian blue solution was removed, and cells were imaged on a Zeiss Axiovert 100 microscope (Oberkochen, Germany) equipped with a Pixera Pro 150ES camera (Santa Clara, CA).", "Results are expressed as a percent change in baseline I sc .", "Statistical comparisons between groups containing multiple donors were performed with SAS/STAT software (v9.2) for Windows, utilizing the Proc Mixed function to carry out a one-way analysis of variance. Statistical comparisons between groups involving cells from a single donor were performed with SigmaPlot 11.0 to carry out a one-way analysis of variance. Differences were considered significant at p < 0.05." ] },{ "paper_id": "eb88125e0384bc94499e00b623b18a7d033d0c1a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We used the databases Web of Science, Natural Sciences Collection and Google Scholar. The dates of last access were 12 October 2015, 12 October 2015, and 8 January 2016, respectively. In retrieved papers we performed a backwards search of the reference list for further relevant studies, and the same was done with these until no further relevant papers could be found.", "Species considered as common human pathogens are Cryptosporidium hominis, C. parvum, C. meleagridis, C. felis, and C. canis. [148] Symptoms in humans include diarrhoea and abdominal pain, and humans are most commonly infected via contaminated water.", "ARTICLE HISTORY" ] },{ "paper_id": "eba0fa2089d19236b36e5b786c1d60e1d083f738", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Exclusion criteria: (i) patients with a demonstrable history of metabolic bone diseases; (ii) those who had a chronic disease history of hypertension, coronary heart disease, and diabetes; and (iii) patients younger than 20 years of age or older than 50 years of age.", "The study was conduct between January 2017 and March 2018 and was approved by the Institutional Review Board of The First Affiliated Hospital of Fujian Medical University. Informed consent was obtained from each patient." ] },{ "paper_id": "ebb05424e38f5e17460ce65e2ccd5a7ad4f73b42", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Approval of protocols and consent forms for ongoing surveillance, where relevant, were obtained by the respective ethical review committees of CDC, KEMRI and Wellcome-Trust, and UVG.", "Background: Knowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention. We present a novel methodology using locally generated data for estimating this burden." ] },{ "paper_id": "ebbad96c3af4aba4be4a1be0d79d535aff8a1551", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consent Written informed consent of this patient's parent has been obtained.", "Her acute symptoms were preceded by a mild cough for one week and two days of bilateral conjunctivitis with clear, mucoid discharge. Review of systems was otherwise negative for diarrhea, bloody stools, abdominal pain, vomiting, gross hematuria, change in urination, or joint swelling or pain.", "Vital signs were notable for a fever of 38.5 \u2218 C and a normal blood pressure of 100/59. Physical exam showed a smiling infant with multiple erythematous and violaceous nonblanching plaques over her face, trunk, feet, and bilateral ears. Nonpitting edema of her hands and feet was also appreciated ( Figure 1 ). Laboratory testing showed white blood cell count 11,6000 per microliter, platelets 437,000 per microliter, blood urea nitrogen 6 mg/dL, creatinine 0.23 mg/dL, prothrombin time 10.6 sec, and activated partial thromboplastin time 33.7 seconds. Urinalysis was also normal. C-reactive protein was mildly elevated at 3.3 mg/dL (reference range 0.0-1.0 mg/dL)." ] },{ "paper_id": "ebbaea6d90c8fe4ccbb6e65a842689b104acba90", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The relative intensities of protein bands were analyzed with ImageJ software. Data were presented as mean \u00b1 standard deviation (SD). Results from different groups were compared by the Student's t test. Values of p < 0.05 were considered statistically significant.", "Data curation: HG. Formal analysis: MH. Investigation: HG QY YW. Methodology: HG MH YW." ] },{ "paper_id": "ebbe2e390320b9cd9399ba2e7d011df6e953971e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additionally, lipid rafts act as signal platforms for the EGFRassociated signaling cascade and correlate with the adhesion of TGEV. In conlusion, these results provide valuable data of the mechanisms which are responsible for the TGEV pathogenesis and may lead to the development of new methods about controlling TGEV.", "For viral labeling, viruses were filtered with 0.22\u03bcm filter, and then clarified by centrifugation at 10,000\u00d7g for 2.5 h, followed by ultra-centrifugation using 20%, 40%, 60% sucrose gradient at 10,000\u00d7g for 2.5 h, viruses were labeled with the fluorescent probe DyLight 594 NHS Ester (Thermo Scientific) according to the manufacturer's instruction. Unincorporated dye was removed by using commercial fluorescent dye removal columns (Thermo Scientific).", "All results are presented as means \u00b1 standard deviation from three independent experiments. Significant differences between control and experimental groups were analyzed using Student's t test. Differences were considered significant at * 0.01 < p < 0.05, ** p < 0.01." ] },{ "paper_id": "ebc2ff4fdabfafc1ceb338e54aa4d11240efeef9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A 4 ml of blood was collected weekly from each goat by jugular venipuncture using a clean sterile disposable syringe and needle into heparinized and plain tubes for hematological, biochemical, and serological analysis.", "The hematological profiles were carried out manually as outlined by Jain [16] . Thin blood smears were made on clean glass slides, fixed in absolute methanol, and stained with Giemsa. The slides were viewed for blood parasites. Packed cell volume (PCV) was done using the Hawksley microhematocrit centrifuge set at 10,000 r.p.m for 5 min. PCV capillary tubes were read using the graphic reader. Plasma protein concentration was determined using the Goldberg refractometer (TS Meter, American Optical Scientific Instrument Division Buffalo, N.Y., U.S.A). Total red blood and white blood cell counts were determined using the improved Hawksley hemocytometer. ) using spectrophotometric methods as previously described [9] .", "Experimental data were subjected to descriptive statistics and analyzed appropriately with parametric statistics at \u03b1=0.05 using GraphPad Prism version 21." ] },{ "paper_id": "ebc8f68d591a7979fcde0afc4cfcae3a9dac58af", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Spheroplasts were lysed in 100 ml lysis buffer (50 mM Tris-Cl pH 8.0, 2.5 mM EDTA, 1 mM PMSF, 5 mg/ml pepstain, 10 mg/ ml leupeptin, 10 mg/ml aprotinin, 10 mM benzamidine) and centrifuged 5 min at 4uC at 20006g to yield pellet and supernatant fractions. For RNase treatment, 1 U of micrococcal nuclease was added to 100 ml of supernatant and pellet fractions, incubated at 30uC for 15 minutes and inactivated by addition of 2 ml of 0.5 M EGTA (pH 8.0). RNA was isolated and prepared by the hot phenol method [38] , and northern blotting was performed as previously described [21] .", "Samples were prepared for electron microscopy as described [13] . In brief, yeast cells were fixed for 1 hr with 2% glutaraldehyde and 4% paraformaldehyde, washed, and post-fixed for 1 hr with 1% OsO 4 and 1% uranyl acetate. Cells then were dehydrated via a series of step-wise increasing ethanol concentrations ranging from 50% to 100%, and infiltrated and embedded with Spurrs resin. Samples were sectioned and placed on nickel grids, washed, incubated in 15 min in 2% glutaraldehyde, poststained with 8% uranyl acetate and Reynold's lead citrate, and viewed with a Philips CM120 microscope.", "Plant inoculation, RNA isolation, and northern blot analyses BMV RNA1 or its mutants, RNA2, and RNA3 were in vitro transcribed and capped (Ambion, Austin, TX) from EcoRIlinearized plasmid pB1TP3 or its derivatives, pB2TP5 and pB3TP8, respectively [39] . Seven-day-old barley leaves were inoculated with the resulting in vitro transcripts [40] and viral RNA was isolated seven to nine days post inoculation using a Qiagen RNeasy Mini kit. Northern blotting was performed as previously described [21] .", "NMR spectra were collected from a solution of 400 mM peptide in 100 mM SDS and 5% 2 H 2 O using a Varian VNMRS 600 MHz spectrometer equipped with a 5 mm cryogenic triple resonance probe. DSA (4,4-dimethyl-4-silapentane-1-ammonium trifluoroacetate) and deuterated SDS were purchased from Aldrich. The 3D data were collected using HIFI, a rapid methodology for collection of multidimensional NMR spectra [42] . Spectra collected for assignments were: 1 H{ 15 N}HSQC, HNCO, CBCA(CO)NH, HNCACB, HNCA, HN(CO)CA, HN(CA)CO, HN(CA)CB. All experiments were standard Varian Biopack pulse sequences modified for the HIFI method [42] .These sequences are available from the National Magnetic Resonance Facility at Madison. Automatically generated peak lists from HIFI were used as input to the automated assignment package suite (PISTACHIO [43] , LACS [44] , and PECAN [45] . 3D 15 N-edited 1 H-1 H NOESY and 3D 13 C-edited 1 H-1 H NOESY spectra were used as input for the ATNOS/CANDID/CYANA suite of programs [46, 47, 48] . The Protein Structure Validation Software suite of programs was used to assess the quality of the computed structure [49] . Images were rendered using PyMOL molecular graphics software (DeLano Scientific LCC http://www.pymol. org). The NMR and structural data described have been deposited in BioMagResBank (http://www.bmrb.wisc.edu) under BMRB accession number 20027.", "Ten OD600 units of yeast cells grown to mid-logarithmic phase were spheroplasted [37] and resuspended in 350 ml buffer TNT (50 mM Tris-HCl [pH 7.4], 150 mM NaCl, 5 mM EDTA, 5 mM benzamidine, 1 mM PMSF, and 10 mg/ml each aprotinin, leupeptin, and pepstatin A). Spheroplasts were lysed via 25 passes through a 22 gauge, 4 cm long needle. Total lysates were centrifuged for 5 minutes at 4uC at 5006g to remove cell debris, and 250 ml of supernatants were mixed with 500 ml of 60% Optiprep (Axis-Shield, Oslo, Norway). Density gradient centrifugation was performed for 5 hours at 55,000 rpm in a Beckman TLS55 rotor using 600 ml of each sample overlaid by 1.4 ml of 30% Optiprep and 100 ml of lysis buffer [21] After centrifugation, 6 fractions were collected from top to bottom of the gradient. For protein detection, samples were boiled in SDS loading buffer prior to SDS-PAGE and western blotting. For RNA analysis, RNA was isolated and prepared by the hot phenol method [38] , and northern blotting was performed as described previously [21] ." ] },{ "paper_id": "ebcbb4241c95ad27eced8844b2efa4e450535931", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After thorough contact tracing and surveillance, no postexposure cases were identified.", "There have been no reports of sustained human-tohuman transmission in the community. Household transmission is limited for unclear reasons, and nosocomial transmission is well known in healthcare settings in most of the reported clusters and outbreaks [9] .", "We still have insufficient knowledge to fully understand the transmission mode and risk factors. Given the limited treatment options, we depend on our policies and guidelines for reducing transmission." ] },{ "paper_id": "ebd781f1bacf68fbaa6efa2aff4390c20a405999", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "showed the least changes in expression compared to other cytokines following FIPV 79-1146 infection." ] },{ "paper_id": "ebda8d8ac0eb08bf9bd1c3bc80610f72572d1a73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulatorsand the relative contributions of each toward viral pathogenicityis not well-understood.", "Tchitchek et al.", "We identified a total of 3 eigentranscripts for which at least 5 transcripts were correlating, and we identified a total of 3 eigenproteins for which at least 5 proteins were correlating.", "Lung tissues were directly submerged in RNA-Later stabilization solution (Life Technologies) following dissection, placed at 4\u00b0C overnight, followed by freezing at \u221280\u00b0C. Lung tissues were thawed, transferred to 1 ml TRIzol (Life Technologies) and homogenized using a TissueLyser or MagnaLyser. RNA was isolated using QiagenRNeasy Mini columns and the manufacturer's recommended protocol (Qiagen Inc., Valencia, CA). Fluorescently labeled probes were generated from each RNA sample using Agilent one-color Low Input Quick Amp Labeling Kit (Agilent Technologies). Individual cRNA samples were hybridized to oligonucleotide microarrays for gene expression profiling using Whole Mouse Genome Microarray Kit (Agilent Technologies). All the microarray experiments passed the quality control criteria of the Agilent Feature Extraction Software." ] },{ "paper_id": "ebdb4e508a69c6de68663ab53a00331abad6a19a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "delimit all the points that fall above/below the third/first quartile plus/minus 1.5 times the interquartile range (IQR). Orange and blue box plots refer to positive and negative strand respectively. https://doi.org/10.1371/journal.pcbi.1006675.g002 ", "LSC G4 is calculated as the average of LSC windows overlapping the PQS. LSC measure is computed within a sliding window of fixed length (length 20, shift 10), averaging the conservation values of each position extracted from the multiple sequence alignments with Jalview [53] . They are formally defined as:", "Author summary G-quadruplexes are nucleic acid non-canonical structures that have been implicated in the regulation of different biological processes of many organisms. Their presence has been demonstrated also in several viral pathogens, providing new insights into viruses' biology and potentially serving as drug targets. Although experimental validation is needed to confirm the actual folding of G-quadruplexes, they can be inferred in silico directly from the nucleotide sequence. Several computational methods exist for this purpose, but they are all limited to the analysis of independent sequences. Since viral genomes can be highly variable, G-quadruplexes with important functional roles are expected to be PLOS Computational Biology | https://doi.", "Loop_conservation: it is the difference between G4_SCI and the local conservation of the viral sequence spanning the PQS (LSC G4 )." ] },{ "paper_id": "ebe8d3845bdfbc11f865667d68399c4862551d30", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The order Nidovirales comprises enveloped single-stranded, positive-sense RNA viruses. The Nidovirales includes the Coronaviridae that contains viruses with the largest known RNA genome, of around 30 Kb [1, 2] . Coronaviruses (CoVs) have been classified into 3 genera, a, b and c {de Groot, 2010 #9759}. They are the causative agents of a variety of human and animal diseases. In humans, CoVs produce respiratory tract infections, causing from the common cold to severe pneumonia and acute respiratory distress syndrome (ARDS) that may result in death [3, 4, 5] . In animals, CoVs also cause life-threatening diseases, such as severe enteric and respiratory tract infections, and are economically important pathogens [6] . Nevertheless, there is limited information about the molecular mechanisms governing CoV virulence and pathogenesis.", "A recombinant TGEV virus was engineered using a TGEV-SPTV genetic background, with respiratory tropism and adapted to tissue cultures [57] . The mutations required to knock down gene 7 expression were introduced by overlapping PCR using as a template the plasmid pSL-3EMN7, comprising nucleotides 20,372 to 28,087 of TGEV genome [128] . Overlapping PCR fragments, with point mutations and deletions, were amplified using oligonucleotides DORF7 VS (59-GCTCGTCTTCCTCCAT-GCTGTATTTAT-39) and DORF7 RS (59-GATAATTGAT-GAGGTAACGAACTGAGCTCGTCTTCGTTACCTATC-39).", "Generation of recombinant TGEV virus (rTGEV) lacking gene 7 TGEV ORF 7 encodes a 78 amino acid hydrophobic protein." ] },{ "paper_id": "ebf25663cfe4314966c86a48ba4ce6a04a435760", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sodium pentobarbitone was obtained from Boehringer Ingelheim, Artarmon, NSW, Australia), DIZE from Sigma-Aldrich Australia.", "Plasma creatinine (Cr) was measured using an autoanalyser (Beckman Instruments, Palo Alta, CA, USA).", "Blood for the measurement of angiotensin peptides were collected and stored as described above. Frozen LV sections were homogenised in 5mM EDTA solution containing a protease inhibitor (P8340, Sigma Aldrich; components: 104 mM AEBSF [4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride], 80\u03bcM aprotinin, 4mM bestatin, 1.4mM E-64, 2mM leupeptin and 1.5mM pepstatin A), frozen at -80\u00b0C to aid in cell disruption, thawed and centrifuged prior to assaying (Prosearch, Australia). Angiotensin peptide content is expressed per mg of protein content of each individual sample.", "Rats were killed by a lethal dose of sodium pentobarbitone, decapitated and trunk blood collected into either lithium heparin tubes or into EDTA tubes containing 20 \u03bcl/ml of blood of an enzyme inhibitor cocktail [50 mM EDTA, 0.2 M N-ethylmaleimide and 1-2 TIU (trypsin inhibitory units)/ml aprotinin made up in saline] [20] . After centrifugation, plasma was separated, snap-frozen and stored at \u221280\u00b0C. The heart was removed, weighed and the LV was transversely dissected into 3 pieces, with one piece fixed in 4% paraformaldehyde and embedded in paraffin for histopathology. The remainder of the LV was snap-frozen in isopentane and stored at -80\u00b0C for mRNA extraction, peptide analysis and activity assays." ] },{ "paper_id": "ebf258ca8bfc0adbd09d0ebe0c5f25688fbc7c34", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Biochemical markers of apoptosis were also detected by Western blotting analysis. The cells were lysed in lysis buffer described elsewhere and the protein concentration of the lysate was determined by the Bradford method [26] . After resolving the protein lysates by SDS-PAGE, the samples were transferred to nitrocellulose membranes and blocked with 5% milk in TBS containing 0.1% Tween 20 (TBST). The membranes were then probed with 1:1000 primary antibody (mouse multiclonal; Sigma) caspase-3, caspase-8, caspase-9 or GAPDH at 4\u00b0C overnight. After washing in TBST, membranes were probed with 1:5000 secondary horse antimouse HRP-linked antibody (Sigma) for 1 h and developed using ECL reagents (Bioman). The blots were photographed using an X-OMAT 2000 (Kodak) film processor.", "The formation of intracellular ROS was visualized by detecting dichlorofluorescein (DCF) derived from the oxidation of dihydrodichlorofluorescein (H 2 DCF) as previously described [12] . At 12 h post-infection, 5 \u03bcM dichlorofluorescein diacetate (H 2 DCFDA; Invitrogen) was added to each well at 37\u00b0C for 20 min and examined under a fluorescence microscope.", "A Student's t-test and non-parametric tests were used to analyze the experimental data and to compare means. Pvalues of less than 0.05 were considered statistically significant." ] },{ "paper_id": "ebf447e0e1957815cb8cf130a84ed2bde14bacda", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ebf5c3f42606a62d8bb4c03fa96623d0e2a56408", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We performed multiplex PCR for human respiratory viruses using the AdvanSure\u2122 RV realtime PCR Kit (LG Life Sciences, Korea; Supplementary Methods). This assay targets 12 types of pathogenic RNA viruses: rhinoviruses A/B/C, influenza viruses A/B, coronaviruses 229E/ NL63/OC43, respiratory syncytial viruses A/B, parainfluenza viruses 1/2/3, and metapneumovirus; and two types of DNA viruses: adenovirus and bocavirus [14] ." ] },{ "paper_id": "ebf7e1110aa56a3066f9590befe475eb12b3eaa1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "High AST** 1", "Fast breathing, n(%) 166 (83) 75 (86) 0.4 (2) 14 (82) 1.0 (2) 14 (78) 0.6 (2) Cyanosis, n(%) 6 (3)", "Chest indrawings, n(%) 193 (96) 81 (94) 0.3 (2) 15 (88) 0.1 (2) 15 (83) 0.01 (2) Stridor, n(%)" ] },{ "paper_id": "ec0528e8df97c81c3e94673e83bf614c09090cf1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To check potential reagent contaminants, 38 negative controls (DNase-free, RNase-free H 2 O) submitted to the whole HTS process were tested by de novo analysis ( Figure 1 ).", ", and 1 min at 55\u00b0C." ] },{ "paper_id": "ec057f679419810619852bd937fdab879a30e1ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "ec09394ffef7660b3a7013dda8e10786bb51e3d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ec0a66b8b227c1a0ced88608d544e3b98120d557", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Strict aseptic procedures were used [14] to collect blood samples from jugular vein of the calves [15] . A volume of 3 ml was collected into BD Vacutainer \u00ae blood collection tubes and transferred immediately to laboratory for analysis.", "A loop of blood sample was streaked on MacConkey agar plate incubated aerobically at 37 \u00b0C. After 24 h, the bacterial colonies were provisionally identified on the basis of morphology and color change due to lactose reaction to the media, medium size (1-3 mm diameter), bright pink to red with flat or elevated surface and white edges was observed, which is an indication of colony growth [16] ." ] },{ "paper_id": "ec0b7ac5c69486b4c914cf362fc49e176f401516", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Despite multiple papers indicating activation of a Th1 response to vaccine none of these therapies has moved past phase III clinical trials or demonstrated cure in patients. Although the possible reasons for clinical failure of vaccines are numerous, overemphasis on CD8 T cell stimulation may be a factor hindering progress in therapeutic efficacy.", "Ipilimumab (Yervoy \u00ae ) is a humanized mAb against cytotoxic T lymphocyte antigen 4 (CTLA-4), a regulatory receptor upregulated on activated T cells, which received FDA approval for the treatment of metastatic melanoma. CTLA-4 competes with CD28 for CD80/86 ligation and effectively blocks IL-2 production and proliferation [36] . By preventing CTLA-4 from binding to CD80/86, ipilimumab allows for sustained signaling through CD28 to occur without inhibition, effectively \"removing the brakes\" from the immune response. In clinical trials many patients saw increased progression-free survival and rarely complete response; however, the majority of patients also development severe autoimmune complications [37] .", "The authors declare no conflict of interest." ] },{ "paper_id": "ec29bbff5e2e2eeb4bdc6651a3fbb49441ab2fa0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ec2b2544b77c203db7fb59fbcb3f2c12733685e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, 100 mg of ileum to colon tissue was weighted into a 1.5-ml microcentrifuge containing 0.5 ml of PBS buffer with trypsin inhibitor. The ileum to colon tissue was cut into pieces and moderately stirred for 30 min, then incubated at 4\u00b0C for 10 h. After centrifugation (13000 g, 4\u00b0C for 15 min), the supernatant (intestinal mucus) was collected and stored at \u221270\u00b0C prior to use.", "General symptoms of C. difficile-infected hamsters" ] },{ "paper_id": "ec2ecade86e6e7660bd8fc929ab0c602cdf16568", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "293T cells (ATCC CRL-11268) are a SV40 large T antigenexpressing and highly transfectable derivative of 293 cells, which are derived from human embryonic kidney cells transformed with human adenovirus type 5, were grown at 37uC, 5% CO 2 , in Dulbecco's Modified Eagle medium containing 10% Hyclone bovine growth serum, 50 U/mL penicillin and 50 mg/mL streptomycin. Sendai Virus (SeV, from SPAFAS) was used at 25 hemagglutinin units (HAU)/mL. Viruses and cell lines were manipulated according to BSL-2 guidelines under a protocol approved by the Institutional Biosafety Committee.", "Distinct Inhibitory Activities of SARS-CoV nsp1 can be Genetically Separated", "The Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV) is an enveloped, positive-stranded RNA viruses that can cause a severe respiratory disease [6] [7] [8] [9] [10] [11] [12] . Its genome consists of a ,30 kb linear, non-segmented, capped, polycistronic, polyadenylated RNA molecule, the first two-third of which is directly translated into two large polyproteins. These two polypeptides are processed into 16 non-structural proteins (nsps), forming the replicase complex, which is active in the cytoplasm in close association with cellular membranes. Transcription and replica-tion of the coronaviral genome leads to the expression of open reading frames located in the remaining third of the genome, which encode structural proteins such as S (spike), E (envelope), M (membrane) and NP (nucleocapsid protein), as well as other open reading frames (ORFs) whose functions remain to be fully characterized [6] [7] [8] [9] ." ] },{ "paper_id": "ec317e9df67d2d7fba6904163bd6f69a79380d73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 Table. Non-targeted metabolome set. ", "Hela cells (obtained from American Tissue Culture Collection) were cultured in Minimum Essential Media (MEM) complemented with 10% Fetal Bovine Serum (FBS), 100 units/ml penicillin, and 100 \u03bcg/ml streptomycin. For western blotting assay, cells grown in 6-well plate were kept in serum free MEM media for 24 hours. Cells were then either kept in serum free medium (control) or stimulated with soy milk alone, soy EGF or commercial recombined human EGF for different time period as indicated. Cells were lysed by directly adding 1\u00d7 SDS sample buffer (50 mM Tris-HCl, pH 6.8, 10% glycerol, 2% SDS and 5% \u03b2-ME) to the cells after washing 3 times with 1X PBS. EGF bio-activity was determined via EGFR phosphorylation and downstream AKT phosphorylation. Total EGFR was also measured since EGFR is known to undergo internalization when stimulated with EGF. Antibodies used in western blot are anti-p-EGFR (Tyr1068) (#2234, cell signaling Technology), anti-total EGFR (#06-847, Millipore), anti-p-AKT (#4060, cell signaling Technology) and anti-Lamin B1 (# 13435, cell signaling technology) [40] . For immunocytochemistry assay, cells were grown on coverslip in 6-well plate and kept in serum free media for 24 hours before stimulation, cells were then either kept in serum free media (control) or stimulated with human or soy EGF for 6 hours. Cells were washed with PBS and fixed with 4% formalin. EGFR was labeled using anti-EGFR antibody (#4267, cell signaling technology) and detected with Alexa Fluor 594 Goat anti-rabbit IgG (#A11012, life technology). The cell nucleus were shown using mounting medium with DAPI (#H-1200, Vectorshield).", "Total soluble proteins were extracted, quantitated and suspended in sample loading buffer as previously described [31, 32] . Approximately 30 \u03bcg of protein extract from dry seeds of 4 homozygous EGF lines were separated on a 4-20% gradient SDS-PAGE gel (BioRad, Hercules CA) along with extract from a nontransgenic seed. The gel was subsequently stained with 0.1% " ] },{ "paper_id": "ec3316b6d33659c1070099a4395a1c25eeacc446", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Oseltamivir carboxylate, the active metabolite of oseltamivir, was obtained from Charnwood Molecular (Loughborough, U.K.) through synthesis via the NBoc-protected acid from oseltamivir phosphate. Amantadine was obtained from Moehs Catalana (Barcelona, Spain). Ribavirin and rimantadine were purchased from Sigma-Aldrich (St. Louis, MO). Peramivir was obtained from Jubilant Chemsys LTD (Uttar Pradesh, India) as free base through NBoc synthesis, and purity was confirmed using NMR and chiral HPLC. Zanamivir was obtained from Haorui Pharma-Chem, Inc. (Edison, NJ). ", "Cells were passaged in minimal essential medium containing 5% fetal bovine serum (Hyclone Laboratories, Logan, UT). During antiviral evaluations, the serum was removed and the medium was supplemented with gentamicin (50 mg/mL), porcine trypsin (10 units/mL) and EDTA (1 mg/mL).", "The extent of viral cytopathology in each well was determined by staining with Neutral Red (NR) as detailed elsewhere [11] . Briefly, the cells were stained with 0.011% NR diluted in MEM to determine cell viability. Two hours later the plates were processed for quantification of NR uptake into viable cells. The amount of NR taken up by cells was determined spectrophotometrically." ] },{ "paper_id": "ec333538173a5359e0cc9a31a9f5675d36e7d5c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ec3ede6e7539f8a035cf5955a65fa0c9bbb8b3b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although astroviruses are considered gastrointestinal pathogens, viral RNA and infectious viral particles have been recovered from extraintestinal organs in both animals and humans (Table 1 ).", "In addition to limiting viral replication, both studies asked if type I IFN influences astrovirus-induced barrier permeability.", "Studies in immunocompetent humans also show that 70% of healthy adults have antibodies against astroviruses [43] , indicating that an adaptive immune response is mounted in humans. In earlier clinical studies using human volunteers, the majority of subjects that had no or only mild clinical signs had developed anti-astrovirus antibodies [5, 44] . Conversely, subjects that exhibited more severe disease did not develop anti-astrovirus antibodies [44] . Other recent studies have found astrovirus antibodies against astroviruses of other animal species in the absence of disease [45, 46] . For example, humans that work closely with turkeys develop antibodies to TAstV [45] ." ] },{ "paper_id": "ec432ab2fea7d620db7138b7c72ceecf03f09785", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "An inhibitor of GNPTAB processing blocks EBOV infection.", "Disclaimer. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "E bolaviruses, such as Ebola virus (EBOV) and Reston virus (RESTV), and marburgviruses, such as Marburg virus (MARV) have single-stranded, negative-sense RNA genomes and are classified in the family Filoviridae. They cause sporadic outbreaks of severe hemorrhagic fever, with case fatality rates of up to 90% 1 . Although experimental vaccines and therapeutics appear promising [2] [3] [4] [5] [6] , none are currently approved to protect from or treat filovirus infection.", "To further understand the relationship between GNPTAB dysfunction and EBOV infection, we tested fibroblasts from six Table 2 Comparison of the CRISPR-Cas9 screen with previously reported screens Carette 12 Cheng 17 Filone 18 Martin 19 ", "Graphing and statistics. For concentration-response plots, GraphPad Prism 7.0 (GraphPad Software, La Jolla, USA) was used to fit a 4-parameter equation to semilog plots of the data and to derive the concentration of compound that inhibited 50% of the measured effect (EC 50 ). All statistical analyses were also performed in GraphPad Prism 7.0. For Student's t-test, a P value of <0.05 was considered statistically significant. In bar graphs, the individual data points are overlaid." ] },{ "paper_id": "ec4a332b863ec8c1bbf94d605b17c67acddf0889", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To confirm our findings we determined whether the post-seroconversion samples also react with whole virus by performing an immunofluorescence assay with HCoV-NL63 infected cells. In all cases with low HCoV-NL63 antibodies we saw no reactivity with the infected cells. Whereas all samples obtained after seroconversion showed clear reactivity with whole virus (shown for animal number 10 in Figure 3 ).", "Cross-sectional and longitudinal serum specimens were collected from Rhesus macaques with an Indian, Burmese or Chinese genetic background. The Rhesus macaques were either imported or born in The Netherlands in one of the breeding colonies. The animals have not been isolated but remained in a breeding colony and were not used for immunization with antigens or adjuvant, or any other study. All serum specimens were stored at -80 o C and heat-inactivated at 56 o C for 30 minutes prior to analysis.", "The animals of our study were clinically examined on a routine yearly basis for colony health surveillance, but subclinical infections with coronaviruses will go unnoticed during this check up and in the periods between the examinations. Thus it can not be determined whether the seroconversion or reconversion to HCoV-NL63 was accompanied with minor clinical signs. Future studies should be designed to investigate viral infection with human viruses and the accompanying clinical signs to further unravel this subject. Here we show that it is not necessary to sacrifice monkeys by experimental infecting. A well-designed follow up through the years with serum and respiratory samples collected on a regular basis would be sufficient to unravel the potential of the human respiratory viruses to infect rhesus macaques. Once a cohort has set up and samples have been collected for a few years, all newly identified respiratory viruses can be screened with the appropriate serological assays, and infection related to clinical symptoms.", "The generation of the plasmid construct was performed as described [9] . For HCoV-NL63 the following primer combination was used 5' NL63_N5_CT (5' -CACCAAACCTAATAAGCCTCT TTCTCAAC -3') and 3' NL63_Nexp (5' -TTAATGCAAAACCTCGTTGAC -3'), whereas for HCoV-229E the primer combination 5' 229E_5N_CT (5' -CACCCCTTCTCGTAATCAGAGTCCT -3') and 3' 229E_Nexp (5' -TTAGTTTACTTCATCAATTAT -3') was used. The generated pET100_NL63_CT and pET100_229E_CT plasmids were sequenced and shown to be 100% identical to the virus reference sequences of HCoV-NL63 (Amsterdam-01) and HCoV-229E (Inf-1), respectively. Subsequent expression and purification of the HCoV-NL63 and HCoV-229E recombinant carboxyl-terminal nucleocapsid proteins was performed as previously described [9] ." ] },{ "paper_id": "ec5eb5ea6033d1a32e46cb874e3b87b9a700cd5a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ec64f7f7ece2c16fb0a4210295b2527714b11ee0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1) Patient has suffered from acute viral pharyngitis or laryngitis, acute herpetic pharyngitis or laryngitis, acute conjunctivitis, as well as acute tonsillitis, and so forth (2) Patient has taken any medication for relief of symptoms prior to study initiation (3) Patient who has fever (>38.5 \u2022 C) (4) Patient who is on analgesic or anti-inflammatory regimen requiring treatment with analgesics, nonsteroidal anti-inflammatory drugs, or steroids (5) Patient is pregnant, nursing, or a woman of childbearing potential not practicing adequate contraception. Women, who are uncertain if they are pregnant, may participate in the study, if they undergo a pregnancy test, which shows a negative result (6) Patient has comorbid condition, uncontrolled metabolic condition or psychiatric condition that might make tolerance or evaluation of the symptoms difficult \u2020 TCM: traditional Chinese medicine.", "2.9. Statistical Analysis. All data were documented with Epidata 3.0 by two independent individuals, and the files were locked. The intent-to-treat (ITT) population included all randomized patients who received study medication and attended at least one study visit after the start of treatment. Per-protocol (PP) analysis included all randomized patients who completed study medication and followedup after the start of treatment. The analysis of efficacy was performed in the ITT and PP populations. All quantitative data were expressed as mean \u00b1 standard deviation (SD), and one-way analysis of variance (ANOVA) was used to compare the data.", "Based on our experience with TCM in treating common cold and on other similar studies in the literature [17, 18] , we assumed the average efficacy \u03c0 = 80%, noninferiority/equivalence boundary value \u03b4 = \u22120.15. The sample size of each group was 88 according to the formula n = 2[\u03c0(1 \u2212 \u03c0)\u03b4 \u22122 ](z 1\u2212\u03b1 + z 1\u2212\u03b2 ) 2 [19] . We allowed for a dropout rate of approximately 10%. Therefore, 360 common cold patients were needed for this study.", "A total of 377 eligible patients were recruited from five centers in China between November 2010 and March 2011. All patients were examined by one of the clinical study respiratory experts and were enrolled into the study according to the inclusion and exclusion criteria described in Table 1 . All patients gave written informed consent prior to participation. A flowchart illustrating the study procedure is provided in Supplementary material 1 (see Supplementary Material available online at doi:10.1155/2012/254571)." ] },{ "paper_id": "ec757128aeed391827b41d94e53b3fdb598d9900", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ec7ab79619e983bb78f09c3b72c0cd36ea2f4924", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Position Mutation Direction Primer sequence analysis of variance was performed on the logged fusion data, using the statistical R package (www.R-project.org, 2012).", "Infectious Salmon Anaemia Virus (ISAV) is an orthomyxovirus which causes disease in farmed Atlantic salmon (Salmo salar L.). Outbreaks have been reported in all the main salmon producing countries where this viral disease has led to high mortality and serious financial losses [1] [2] [3] [4] [5] [6] . The virus is enveloped with a genome consisting of 8 single-stranded RNA segments in negative orientation. Segments 5 and 6 encode two surface glycoproteins: the Fusion (F) protein and Haemagglutinin-esterase (HE), respectively.", "Protein fractionation CHSE-214 cells were cultivated on 25 cm 2 culture flasks and membrane embedded glycoproteins extracted using a Sub cellular protein fractionation kit (Thermo Scientific) as per the manufacturer's protocol. Protein concentrations from each membrane fraction were measured using a ND 1000 nanodrop (NanoDrop Technologies, Thermo Fisher).", "Chinook salmon embryo cells (CHSE-214, ATCC 1681) were cultured, and transfected as described previously [33] using a Neon 10 \u03bcl kit (Invitrogen), and a total of 2 \u03bcg DNA per reaction (0.5 \u03bcg for HE and 1.5 \u03bcg for the F protein). Reactions were subjected to electroporation conditions of two 20 ms pulses of 1300 V and added to 3.3 ml of culture media. The same cell solution was dispensed in different culture plates including 96 and 48 well plates and 8-well chamber slides (BD Falcon). These cell monolayers were incubated for 48 h at 20\u00b0C and used in the following assays." ] },{ "paper_id": "ec7d9f4fbe48d9c257de95f8a18cc111de8c613c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, it is important to remember that the docking search is not biased by the reference structure. Additionally, each new DINC job is completely independent from all previous jobs. All 20 jobs of a given batch are executed in parallel. Our cluster contains 80 dual processor HP SL230s computing nodes, each one equipped with two Intel E5-2650v2 Ivy Bridge EP processors (for a total of 16 cores per node). The typical running time for a DINC job on our cluster is 30 minutes (for a CPU time of about 8 hours).", "Recent reviews indicate that other docking software can outperform AutoDock 4 in scoring predicted binding modes 26 . In fact, scoring is one of the bottlenecks when trying to achieve greater accuracy in docking-based methods 26 . In terms of sampling, our method could certainly provide results with sub-angstrom accuracy, but this would require a scoring function capable of discriminating between conformations with sub-angstrom differences. Therefore, our method could benefit from using consensus scoring 87 , peptide-specific scoring 88 or HLA-specific scoring 89 . Being a meta-docking application, DINC can integrate alternative sampling strategies or scoring methods. We plan to further investigate these issues in a future study, performing cross-docking and benchmarking on a much larger pMHC dataset.", "Finally, a version of DINC with improved scoring could also provide a more general tool for epitope prediction and virtual screening of MHC binders. Gold standard tools for these tasks usually rely on machine learning methods trained on available datasets of previously tested peptide sequences 90 , which are limited or inexistent for less prevalent MHC allotypes 91, 92 . DINC do not require ad-hoc knowledge on the typical binders for a given MHC allotype, or its preferred primary anchors. Therefore, once the aforementioned challenges are addressed, DINC could potentially complement sequence-based methods in epitope prediction projects, by providing structure-based ranking of peptide-ligands for any MHC of interest." ] },{ "paper_id": "ec7e7937ff0f3f8561b73eb8a4d34de49e35e3ff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Citation: Nordstr\u00f6 m I, Eriksson K (2012) HHV-6B Induces IFN-Lambda1 Responses in Cord Plasmacytoid Dendritic Cells through TLR9. PLoS ONE 7(6): e38683.", "Student's t-test and ANOVA with Bonferronis multiple comparison test were performed using GraphPad Prism version 5 for Window (GraphPad Software, San Diego, USA).", "These studies were approved by The Ethics Committee at the Faculty of Medicine, University of Gothenburg, Sweden. All mothers were given oral and written information, and gave oral consent to participate in the study. Written consent was not required by the Ethics Committee for this study as no personal information or identity was recorded, and the cord blood was collected from the umbilical cord after the birth of the child (law 2003: 460, paragraphs 4 and 13)." ] },{ "paper_id": "ec84301b786a7e9bb2745f5a4141a69e484a92f3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Since the mean generation time of smallpox is approximately 15 days (i.e., half a month) [50, 54] , monthly data contains exactly two generations. Let us consider three successive generations, i, i+1, and i+2. Given the reproduction numbers R i and R i+1 , we get", "By minimizing the negative logarithm of (8), the maximum likelihood estimates of the monthly-approximated reproduction numbers, R j were obtained.", "Thus, for the observation of cases (or deaths with a 1 month lag) from month 0 to N, the likelihood of estimating R j is given by", "First, the presence of seasonality was examined for all 7 datasets using spectral density analysis. Spectral analysis is based on the idea of a theoretical power-spectrum, which partitions the total variance of the series among sinusoidal components [47] . In other words, spectral density decomposes a time series function into a sum of sines and cosines. The density plot (i.e., correlogram) was graphically plotted to determine if a sharp peak at a period of 12 months exists, corresponding to an annual cycle (i.e., seasonality)." ] },{ "paper_id": "ec955d5ff9dc3bdb037e561ee890c4c18fdb4272", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses (CoV, family Coronaviridae) are large enveloped viral particles containing a positive sense single stranded RNA genome (26-30 kb), coding for several structural proteins, including polymerase (Pol), nucleocapsid (N), membrane (M), hemagglutinin-esterase (HE), spike (S) proteins and several non-structural proteins (NSPs). Coronaviruses have been associated with respiratory and enteric infections in humans and ruminants [1] .", "Partial nucleotide sequences are available for Polymerase gene (JN204179, JN204180), Spike (KF272908, KF272910, KF272912, KF272914). The complete gene sequence of the spike protein of Irish BCoV strain RVLC7 was registered in Genbank under the accession number-KF272919.", "Enteric Bovine coronavirus (BCoV) replicates in the epithelial cells of the gut, destroying villi, resulting in severe, often bloody diarrhea in calves, which can be life threatening, due to loss of electrolytes and malnutrition [2] . Disease in calves usually occurs within the first month of life, with respiratory and enteric infections being the most common conditions diagnosed. In adult cows, as a result of close confinement during transport or housing, BCoV is associated with winter dysentery and shipping fever [2] . The spike proteins of BCoV play an important role in immune response, eliciting both cellular immune responses and neutralizing antibodies [3] ." ] },{ "paper_id": "ec9755d0db388d8a9066baffc9fd33bdf24f5bac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Radioactive workplace and/or radioisotope storage and transport device shall be equipped, by its operator, with necessary protection equipment and alarm devices, ensuring that workers involving radiation exposure must wear personal dosimeters.", "Regulations on Safety and Protection of Radioisotopes and Rays Installations [6] Article 29", "Articles 11 to 17" ] },{ "paper_id": "ec99df59b1b63a5da4b31c203e8e1eab566fba68", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conceptualization: WMD MK WDS. " ] },{ "paper_id": "ec9ad2ac0be589d617f25f1cfc349f644d1bebf1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The alternate \"circulating high virulent-low virulent\" FCoV hypothesis of viral pathogenesis suggests that both distinctive pathogenic and benign lineages of FECoV might be present in a cat population and that the disease will develop only in those cats infected by the virulent strains already available from other infected cats [5] . The existence of distinct \"high virulent-low virulent FCoVs\" is an alternate and less popular hypothesis for FIP pathogenesis [5, 10] . As FIP occurs sporadically and outbreaks of FIP in domestic cat populations are rather uncommon, there has been little epidemiologic support for this hypothesis [1] .", "Organ samples were also fixed in 10% buffered formalin and routinely embedded in paraffin. Sections (5 m) were stained with hematoxylin and eosin (HE). The HE-stained slides of the organ sections were evaluated for evidence of granulomatous and pyogranulomatous lesions. ", "The Scientific World Journal pathogenesis of the disease based on the M gene phylogeny from FCoV strains detected in naturally infected cats.", "Membrane (M) Gene. All samples were screened for the presence of FCoV M gene mRNA using primers previously described [12] , with modifications (2RNAmA TAATRM-CATARACGADCCAGCT, nt 26440-26461, and 2RNAmS GTGCTAGVTTTGTCTTCGGACAMC, nt 60-83, positions regarding strain FIPV 79-1179).", "Feline coronavirus (FCoV), a widespread pathogen of domestic cat populations worldwide, is an enveloped singlestranded RNA virus of the order Nidovirales, family Coronaviridae, subfamily Coronavirinae, genus Alphacoronavirus, species alphacoronavirus 1. Most infections are either asymptomatic or result in a mild, self-limiting gastrointestinal disease, and, in these cases, the causative agent is the feline enteric coronavirus (FECoV) pathotype. In contrast, feline infectious peritonitis (FIP), a possible complication of FCoV infection in a small proportion of cats, is a lethal, systemic immune-mediated disease caused by a second FCoV pathotype, feline infectious peritonitis virus (FIPV) [1, 2] ." ] },{ "paper_id": "ec9faa32c45199e8fec10c7a0d3bae3dd0275744", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Genetic distances of aligned RXH HA amino sequences when compared to the 2011 H1N1 vaccine strain (A/California/7/2009 (H1N1)-like virus, accession number: KF527477) were determined using BioEdit Version 7.2.5.", "Transmission case definitions identified nine suspected HAI cases and five CAI laboratoryconfirmed H1N1pdm cases within the observed time period (April-July 2011). HAI cases were distributed across physically separated wards E1 (n = 3), E2 (n = 2), ICU (n = 3) and B2 (n = 1) while CAI cases were distributed across E1 (n = 1), ICU (n = 3) and MREG (n = 1).", "This study demonstrated the value of including molecular sequence analysis as a diagnostic tool to identify nosocomial infections and trace the origins of viruses causing these infections. We have shown how such sequence data could enrich more traditional observational epidemiological data to reveal what may appear to be individual transmission chains but may in fact be multiple independent chains.", "Despite the existence of infection control policies and protocols, nosocomial transmission of respiratory viruses is a common problem that can occur in virtually any health-care setting [1] [2] [3] [4] [5] [6] [7] . The close proximity of patients, visitors and healthcare workers (HCWs) to one another, virus shedding during asymptomatic periods, low vaccination compliance (by both HCWs and the general public) as well as virus persistence in respiratory secretions and fomites can all contribute to the spread of the virus and lead to nosocomial outbreaks [2, [8] [9] [10] [11] [12] . Limiting nosocomial transmissions in hospitals is particularly important as besides increasing the duration and costs of hospitalization, they can increase morbidity and mortality, particularly in high-risk elderly, infant, seriously ill, and immunocompromised patients [2, 3, 13] ." ] },{ "paper_id": "ecb3c8e94fb9e56b8ca7f05687f791f3db024a94", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analyses were performed in the R statistical package (R v. 2.15, www.cran.org).", "All study protocols and procedures were approved by the Institutional Review Boards of the Johns Hopkins Bloomberg School of Public Health, Hong Kong University, the University of Liverpool and Guangzhou People's Hospital No. 12. All participants provided written informed consent (for children, this was provided by their parents).", "Participants were recruited from randomly selected households, in 40 communities in a transect spanning a gradient of decreasing population density extending to the northeast of Guangzhou, China. Details on the methods can be found in Lessler et al. [21] . We define a community to be all of those within the jurisdiction of a single street or village committee (SVC), the smallest administrative unit in China. SVCs hold information on all residential households within their jurisdiction. A list of households was obtained from each SVC and then reordered randomly. Recruitment of households was attempted in sequence from this list until at least 20 households had been recruited into the study. The longitude and latitude of participating households were recorded by study researchers using a handheld GPS device." ] },{ "paper_id": "ecbee46a2f987fb95c2b1a5b0e4d789ea654a19e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Anti-anthrax protective antigen mAb M18 Complex [162] 3ETB bind tightly (\u2264nanomolar K D ) to an antigen are usually required to protect against infection, and their efficient production in an immune response will require the use of correctly folded epitope mimetics.", "Recently published crystal structures of protective monoclonal antibody (mAb) fragments bound to their protective epitopes are listed in Table 1 . Most examples represent epitopes on viral proteins, with the largest number being from HIV-1. In many cases, new biological methods were exploited to isolate these neutralizing antibodies from human sources (e.g. by human memory B-cell immortalization [74] ). Viruses typically display only a few proteins on their surface, which facilitates the identification of suitable antigens and their protective epitopes.", "How has structural knowledge of epitopes recognized by protective antibodies been used for vaccine design? One approach involves epitope grafting, using the tools of protein engineering. Here, the epitope of interest is transferred onto a new protein scaffold (perhaps more stable, or easier to produce, or more immunogenic) that can display the epitope in the correctly folded conformation. Several recent examples document how structure-based methods and modeling can allow prediction of proteins that might be useful as scaffolds for the newly grafted epitopes [72, [75] [76] [77] [78] [79] [80] [81] [82] [83] . In some cases, however, it might still be technically difficult to produce the correctly folded protein subunit vaccine. Moreover, other nonprotective epitopes on the surface of a recombinant protein may still dominate the immune response, thereby deflecting attention away from the protective epitope and leading to a poorly effective vaccine. Also, co-administration with an adjuvant will again be required to boost immunogenicity.", "Many CAPs kill bacterial cells in the micromolar range by mechanisms culminating in disruption of the bacterial cell membrane [41] . The cationic peptides are first attracted electrostatically to the outer bacterial cell surface because of the presence of excess negatively charged phospholipids and glycolipids. They then invade and disrupt the membrane bilayer(s), eventually causing cell lysis. This process was captured recently in a series of time-resolved quantitative microscopy images of the human cathelicidin LL-37 attacking Escherichia coli cells [42] . However, CAPs can also lyse (typically at a higher concentration) mammalian cell membranes, which is a potential source of toxicity and one factor that has so far prevented their application for the treatment of systemic human bacterial infections. On the other hand, some CAPs clearly have different mechanisms of action, which do not involve membrane lysis (for recent reviews, see [36] [37] [38] [39] [40] )." ] },{ "paper_id": "eccc33ccb0e981e31f4d18d258274a7dae3ca2bc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell viability measurement of A549 cells was performed 48 h after treatment of compounds or DMSO control in DMEM supplemented with 10% FBS, using the CellTiter-Glo kit (Promega, Madison, WI, USA). The hit compounds were two-fold serially diluted from 100 \u00b5M (total 8 concentrations) for dose-response titration, and the CC 50 s and IC 50 s were calculated with Prism software (7.04 Edition, GraphPad Software, La Jolla, CA, USA). The assays were performed with 2 replicate wells and repeated twice.", "(2) small molecule inhibitors either targeting the viral proteins including RNA polymerase inhibitors (favipiravir and remdesivir) [5, 6] , VP35 protein inhibitor (GA017) [7] , and glycoprotein [8, 9] or host proteins [10] [11] [12] ; and (3) different nucleic acids, such as siRNA [13] and antisense morpholine substituted oligonucleotides [14] , were reported as potential anti-Ebola agents." ] },{ "paper_id": "eccdf56c0564f35ba8e293bfd967e98b822bfef2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "TE, FT, CK, AP, and FS contributed to the text and approved its final version.", "The Mice We Use in Experiments -Who Are They and How Do They Live?", "A Case for Going Wild: Do T. gondii-Induced Behavioral Changes Exist in Natural Habitats?" ] },{ "paper_id": "ecd247bf710a751792bb6ca40d0b8bcacf2d56ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vibratome sections (250 \u03bcm thick) of the floor of the fourth ventricle of the brains of infant Wistar rats (between 9 and 15 days of age) were prepared to allow ependymal cilia to be viewed on an inverted microscope using a \u00d7 40 objective lens. Each section was submerged under 4 ml of media 199 (M199, Gibco, Invitrogen, Paisley, UK), as described previously [16] .", "To determine ciliary beat frequency, both the brain slices and the respiratory cells in culture were placed in an incubation (37\u00b0C) chamber and were observed via an inverted microscope system (Nikon TU1000, Kingstonupon-Thames, UK). Tissue was allowed to equilibrate for 30 minutes before readings. Beating cilia were recorded using a Motion Pro X4 digital high-speed video camera (Lake Image Systems, Henrietta, N.Y. USA) at a rate of 250 to 500 frames per second using an \u00d7 40 objective as previously described [18] . At least 512 or 1,024 frames were captured, respectively.", "Human respiratory epithelium was obtained by brushing the inferior nasal turbinate with a 2-mm cytology brush (Keymed, Southend-on-Sea, UK) as previously described [7] . Cells were dislodged from the brush into M199 medium and grown to a ciliated phenotype at air-liquid interface as previously described [17] . Ethical approval for the collection of nasal epithelial cells was given by the Leicestershire Ethical Review Committee. " ] },{ "paper_id": "ecd6b92d6dd1c0baf31f1c8c86a6ee100d8e0b4d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 \u2264 12 months use 1 ml \u2022 13 months to 35 months use 2 ml \u2022 \u2265 36 months use 3 ml \u2022 expel excess saline 10. Apply water soluble lubricant to tip of catheter.", "12. Instruct patient to hold their breath if possible.", "13. Advance catheter along the floor of the nose to the age-appropriate mark on tube or until resistance is met." ] },{ "paper_id": "ecd8df7900c3c07863a0ed0e1b6c5d5ecae4e651", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The findings achieved herein are solely the responsibility of the authors.", "The data used to support the findings of this study are available from the corresponding author upon request.", "MERS-CoV-specific antibodies are widely found in dromedary camels (Camelus dromedarius) along with viral shedding of similar viruses detected in human. Accordingly, dromedaries are considered the primary source of MERS-CoV transmission to humans, although the original source for the virus is still unknown [2] [3] [4] ." ] },{ "paper_id": "ecdc5c17ed143ffed9542802ce029dd323bb6a28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest. " ] },{ "paper_id": "ecea1d9607209bfcf32da251f53136e7f5c12f3e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Four-to six-week-old female BALB/c mice and New Zealand white rabbits were purchased from the Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, and kept in the animal facility of the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences. All animal work was done in accordance with the guidelines of the Institutional Animal Care and Use Committee of the Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, and all experimental protocols were approved by the Institutional Animal Care and Use Committee.", "Groups of 5 mice were vaccinated on weeks 0, 2, 4 and 6 with 1.7 nmol of E3R4, E12R4, R4, E3 peptide (Lifetin, Beijing) or phosphate-buffered saline (PBS) formulated with complete Freunds adjuvant (CFA) for priming dose and with incomplete Freunds adjuvant (IFA) for booster immunizations. Groups of 2 rabbits were vaccinated subcutaneously on weeks 0, 2, 4 and 6 with 4 nmol of E3R4 alone or with Alum (Sigma-Aldrich) and monophosphoryl lipid A (Sigma-Aldrich) (Alum-MPL) adjuvant. Sera were collected at weeks 6 and 8 and stored at -20uC.", "Pseudoviruses of HPV16, 18, 45, 58, 6, 11 and 5 (PsV16, PsV18, PsV45, PsV58, PsV6, PsV11 and PsV5, respectively) with encapsidated reporter plasmid pLucf which encoding both luciferase and green fluorescence protein (GFP), or plasmid pEGFP-N1 (Clonetech) which encoding GFP were produced in 293TT cells as previously described [38, 40, 41] with minor modifications. For PsV52 preparation, 16 mg DNA (8 mg of shell plasmid and 8 mg of reporter plasmid) was mixed with 56 ml of TurboFect (Thermo Fisher) and 1.6 ml of unsupplemented DMEM, then added to 6.5610 6 293TT cells as suggested by Prof. Reinhard Kirnbauer. The titer of PsV (infectious units per ml, IU/ml) was determined by GFP expression in 293TT cells as described in http://home.ccr.cancer.gov/lco/pseudovirusproduc tion.htm. L1/L2 expression plasmids, pLucf plasmid, were generously provided by John Schiller, Susana Pang, Chris Buck, Martin M\u00fcller and Tadahito Kanda." ] },{ "paper_id": "eceb1667ac6722e9131eb7d0f560a7f76bfb25f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Next-generation sequencing was conducted on cDNA libraries constructed from total RNA of 222 fecal samples. Via a BLAST search, 59 EV-G-like contigs that were longer than 5,000 nt, including the entire VP1-coding sequence with more than threefold coverage of sequence reads, were identified in 35 (15.8%) normal fecal samples, five (2.3%) fecal samples for mild diarrhea, and 10 (4.5%) diarrheic fecal samples (Tables 1 and 2 ). Eight of 50 samples revealed more than two EV-G-like contigs (Table 1) . Apart from three samples (Ishi-Ya3, Ishi-Ka3, and Ishi-Ka7), 47 samples were found to contain other viruses: Rotaviruses A, C, or H; orthoreovirus; kobuvirus; picobirnavirus; astrovirus; porcine epidemic diarrhea virus (PEDV); posavirus; sapelovirus; St-Valerien virus; sapovirus; or teschovirus (Table 1 and S3 Table) .", "Although we did not initially aim to determine EV-G prevalence among pigs in Japan in this study, contigs that were longer than 5,000 nt were found in 22.5% (50/222) of pigs and on 23.4% (18/77) of farms, suggesting that EV-Gs are widespread among Japanese pigs. Fortyfour strains out of 59 (74.6%) were detected in healthy pigs, indicating that EV-Gs seem not to be associated with diarrhea in pigs, in accordance with other reports [13] [14] 38] . Because the detection limit of the method was not tested, a true prevalence study is needed in the future." ] },{ "paper_id": "ecef0f865903d77f2ffbe8cb1db275b7268ff77f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ecf15cf19a780b1f9e58e9a5b35402ca5886adab", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "well as with RBP-J-Kappa, and LacZ conversion occurred within 30 minutes for both interactions.", "To Microcystins are cyclic heptapeptides synthesized by bluegreen algae that covalently couple to the catalytic subunits of protein phosphotases PP1 and PP2a [9] . Although not completely specific to PP1a, taken together, the data indicate that both EBNA3C and Gadd34 reside in protein phosphotase complexes in B cells.", "Anti-human Gadd34(ab9869), anti-XBP1 (ab37152), anti-Laminin B (ab16048), and anti-eIF2\u03b1 (ab5369) antibodies were purchased from Abcam Inc. Anti-phospho-eIF2\u03b1 (Ser51) antibody was obtained from Cell Signaling Technology. Anti-EBNA3C was purchased from Exalpha Biologicals Inc. Anitbody recognizing only the spliced XBP1 isoform was obtained from Biolegend. Anti-ATF6 antibody, recognizing only the 90 KDa isoform, was purched from Imgenex (San-Diego, CA). Anti-\u03b2-actin (A1978) antibody was obtained from Sigma-Aldrich." ] },{ "paper_id": "ecf2675fbb7883ca4a8f98c34eadb55c6b857aaa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 In addition to developing pharmacological inhibitors of USP28, what are other efficient strategies of targeting USP28 that have clinical adaptability and feasibility for treating cancers?", "USP28 is prevalently overexpressed in human colorectal carcinomas. USP28 also enhances intestinal tumorigenesis. 2, 18 Gliomas USP28 stimulates glioma cell proliferation both in vitro and in vivo. USP28-indued c-MYC upregulation may contribute to glioma tumorigenecity." ] },{ "paper_id": "ecf90eb55cfef5b0212b52caf031abb31a1f11cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Synchronized embryogenic cultures at different developmental stages, consisting of friable-embryogenic callus (EC), incomplete compact pro-embryogenic cultures (ICpEC) and globular embryos (GE) were obtained following previously published methods for longan [15, 65] . The plant materials were stored at \u2212 80\u00b0C for later use.", "Longan may require a large amount of lncRNA to initiate GE formation" ] },{ "paper_id": "ecfcf1c18796bfdf5dfd83193448b5c2f9fbdb81", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ed02cdbaaf52f191ad3bebb5a3bc117524718c8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was approved by the ethical committee of Sendai Medical Center (Sendai City, Miyagi Prefecture, Japan), and written informed consent was obtained from all patients.", "Influenza virus A/Aichi/2/68 (H3N2) was propagated in the allantoic cavities of fertilized chicken eggs. The allantoic fluid containing the viruses was harvested and atomized in simulation experiments using an electric compressor nebulizer (NE-C16; Omron, Kyoto, Japan).", "Throat swab samples in MEM transport medium were centrifuged at low-speed (1500 g) for 15 min, and then inoculated onto Madin-Darby canine kidney (MDCK) cells for viral culture [13] . Viral isolation was assessed within a week by identifying the specific cytopathic effect. The dissolved membrane specimens containing viruses of the coughs were the serially diluted 10-fold with MEM and inoculated onto MDCK cells. The diluted specimens were assessed for active viruses using a conventional plaque assay [14] within 1 h after collection.", "To apply the above system in actual clinical setting, we collected particles from coughs of 56 influenza patients, whose diagnosis was confirmed by viral isolation from throat swabs. The average patient age was 25.4 6 10.5 years (range, 5-67 years), 88% of the samples were from 18-38-year-old patients, and the male-tofemale ratio was 3:1. None of the patients had significant health problems. Forty-five (80%) cases were infected with influenza A(H1) virus, 5 (9%) with A(H3), and 6 (11%) with A(H1N1)pdm09 (Table S1) ." ] },{ "paper_id": "ed22ff950ded9997b793e0cc610c7228fb57e7bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral upper respiratory tract infections remain a major cause of morbidity and mortality worldwide, with influenza infections being an important cause [1, 2] . Influenza viruses A and B cause annual epidemics and produce 3-5 million cases of severe disease and 290,000 to 650,000 respiratory deaths annually [3] . Because influenza epidemics lead to increased social concern each season and the appearance of a novel influenza A subtype virus can cause a pandemic, and disease surveillance is crucial from a public health perspective [4] .", "For each individual, the following variables were collected: reported fever >37.8 \u2022 C, cough, malaise, headache, myalgia, sore throat, shortness of breath, sudden onset of symptoms, coryza, age, sex, comorbidities (chronic cardiovascular disease; pulmonary disease, including asthma; liver disease; renal disease; metabolic disorders including diabetes mellitus; obesity, defined as a body mass index >40; and immunodeficiency), and microbiological laboratory results.", "No specific symptom can accurately diagnose influenza and, therefore, laboratory confirmation in representative samples of clinically compatible cases is crucial. This lack of specific influenza symptoms may explain, at least in part, why syndromic surveillance, which is routinely beneficial for the early detection of outbreaks of various infectious diseases, is not adequate for influenza surveillance [30] .", "A retrospective study of the clinical and epidemiological characteristics of the cases detected in a primary healthcare sentinel surveillance network for eleven years (2008 to 2018) in Catalonia, a Spanish region with 7.6 million inhabitants, was conducted.", "The PIDIRAC (Pla d'Informaci\u00f3 de les Infeccions Respirat\u00f2ries Agudes a Catalunya) sentinel surveillance system [15] is constituted of general practitioners and pediatricians from 40-44 primary care centers distributed throughout Catalonia. The mean number of general practitioners involved during the study period was 32 (ranging from 27 to 35) and the mean number of pediatricians was 26 (ranging from 24 to 28). The mean percentage of the population surveyed was 0.97% (ranging from 0.86 to 1.06)." ] },{ "paper_id": "ed3dac12ca72f06c51d7f68ae5fe6aaaa6f3e740", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human metapneumovirus Ev71:", "Enterovirus IL-6:", "Interleukin-6 MCP-1:" ] },{ "paper_id": "ed468ccf95499f1d19c071accb82a8bc64696ace", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ed526e1eb5a7607af2803906e2f6d4e5bb2dff09", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HCoVs affect all age groups [2, 3] but elicit more serious disease in young, elderly and immunocompromised [4, 10, 11] , frequently resulting in hospitalization. Reports on the prevalence of HCoVs and their association with upper and lower respiratory tract disease vary but range between 3.3% and 16% [2, 3, 10, 12] . Over 70% of the general public has seroconverted towards all four non-severe HCoVs with primary infection shown to occur in childhood [13] and reinfection occurring throughout life [10] . Given the high prevalence of respiratory infections, human coronaviruses represent a substantial disease burden, which is exacerbated by the high implications of healthcare workers in coronavirus outbreaks [12] .", "The outbreak of SARS-CoV in 2003 and MERS-CoV less than 10 years later highlights an additional significant threat of coronaviruses to humans and confirms that the SARS outbreak in 2003 was not an isolated incident. With the ever increasing diversity of animal coronavirus species, especially within bats, the likelihood of recombination leading to future outbreaks is high and the threat of potential pandemics is real as highly pathogenic coronaviruses continue to spill over from zoonotic sources into the human population. Misdiagnosis of these outbreaks pose a further substantial threat to healthcare workers with nosocomial spread to other patients putting further pressure on an already strained healthcare system. As there is currently no antiviral strategy to combat infection with human coronaviruses [14] , and supportive care is the primary treatment regime, the importance of identifying broad spectrum lead compounds is increasing.", "Molecular docking algorithms are often calibrated on a training set of experimental ligand-protein complexes and accuracy of these docking programs is often highly dependent on the training set used [52] . This highlights the importance of confirming that the docking software used for virtual screening is capable of replicating the binding mode of a known, experimental inhibitor for the class of enzymes studied [53, 54] ." ] },{ "paper_id": "ed5375ac7d887e311e407121b4c80e8d0ca0afed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1.2.1 Extensions to RNASHAPES It is generally agreed that predicting a single structure of minimal free energy does not adequately capture the subtlety and versatility of RNA structure formation. The RNASHAPES tool introduced the notion of abstract shapes (Giegerich et al., 2004b; ", "The program PALIKISS allows to predict pseudoknots, including kissing hairpins from aligned sequences. Being composed from the grammars and algebras of the other tools, it inherits all the features and options that make sense for it. *To whom correspondence should be addressed. ", "All tools were augmented with utilities to compute folding energy or abstract shape for sequences that are provided with a structure from an outside source, in a way consistent with the tools' energy model. The graphical motif description tool LOCOMOTIF (Reeder et al., 2007) now uses modules from the RNA shapes studio. The KNOTINFRAME (Theis et al., 2008) tool that predicts -1 ribosomal frameshifts has been updated as well." ] },{ "paper_id": "ed5d3f1db5936c2b86eb9ea46eab96a0b67a124e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "). ", "\ubaa9\uc801: \ucc98\uc74c MERS\uc758 \uc720\ud589\uc774 \uc2dc\uc791\ub41c \ud3c9\ud0dd \uc131\ubaa8\ubcd1\uc6d0 \ud655\uc9c4\uc790\ub4e4\uc758 \uc5ed\ud559\uc801 \ud2b9\uc131\uc744 \ud1b5\ud574\uc11c \uae30\uc874\uc5d0 \uc54c\ub824\uc9c4 \uc720\ud589\ub4e4\uacfc\uc758 \ucc28\uc774\uc810\uc744 \ube44\uad50 \ubd84\uc11d\ud558\uc5ec \ud5a5\ud6c4 MERS \uc608\ubc29\uacfc \uad00\ub9ac\uc5d0 \ub3c4\uc6c0\uc744 \uc8fc\uace0\uc790 \ud558\uc600\ub2e4. \ubc29\ubc95: \ud658\uc790\uc758 \uc5ed\ud559\uc801 \ud2b9\uc9d5\uc740 \uc5ed\ud559\uc870\uc0ac\uc11c\ub97c \uae30\ubc18\uc73c\ub85c \ud558\uc600\uace0, \ubcd1\uc6d0 \ubc29\ubb38\uae30\ub85d\uacfc \uae30\uc800\uc9c8\ud658\uc740 \uac74\uac15\ubcf4\ud5d8\uc2ec\uc0ac\ud3c9\uac00\uc6d0\uc758 \uc790\ub8cc\ub97c \ud655\uc778\ud558\uc5ec \ubcf4\ucda9\ud558\uc600\ub2e4. \ud658\uc790\uc758 \uc784\uc0c1\uc801 \uc99d\uc0c1\uacfc \uac80\uc0ac \uacb0\uacfc\ub294 \ubcd1\uc6d0\uc758 \uc758\ubb34\uae30\ub85d\uc744 \ucc38\uace0\ud558\uc600\ub2e4. \ud658\uc790\uc758 \ubcf4\ud638\uc790\uc640 \ubc29\ubb38\uac1d\uc740 \uac01 \ud658\uc790 \ub610\ub294 \ubcf4\ud638\uc790\uc5d0\uac8c \uc804\ud654 \uc870\uc0ac\ud558\uc5ec \ud655\uc778\ud558\uc600\ub2e4. \uacb0\uacfc: 1\ubc88 \ud658\uc790(Patient zero, #1 case)\uac00 \ud3c9\ud0dd\uc131\ubaa8\ubcd1\uc6d0\uc5d0 \uc785\uc6d0(5\uc6d4 15\uc77c\ubd80\ud130 17\uc77c)\ud55c \uc774\ud6c4 5\uc6d4 18\uc77c\ubd80\ud130 6\uc6d4 4\uc77c\uae4c\uc9c0 17\uc77c\ub3d9\uc548 36\uba85\uc758 \ud658\uc790\uac00 \ubc1c\uc0dd\ud558\uc600\uace0 \uc774\uc911\uc5d0 6\uba85\uc774 \uc0ac\ub9dd\ud558\uc600\ub2e4 (\uce58\uba85\ub960 16.7%). \uc804\uccb4 \ud658\uc790 36\uba85 \uc911\uc5d0 1\ucc28 \uac10\uc5fc(1 st generation) \ud658\uc790\ub294 \ucd1d 26\uba85\uc774\uace0, 2\ucc28" ] },{ "paper_id": "ed638b6b8897dfcc7b28ba26c2bb6048da0501e6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We estimated UIs by taking 1000 samples from the posterior distribution of each quantity and using the 25th-and 975th-ordered draws of the uncertainty distribution.", "Human and animal rights statement The study did not involve human participants and/or animals.", "We report 95% uncertainty intervals (UI) for each estimate-such as rates or numbers of deaths or DALYs.", "Clinical Epidemiology Unit, Lund University, Lund, Sweden. Alireza College of Rheumatology's (ACR) Annual Meeting Planning Committee (AMPC); Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee; and a member of the Veterans Affairs Rheumatology Field Advisory Committee. Other authors have no conflict of interest." ] },{ "paper_id": "ed745dd99691994096cdc638c5398cd65a2c9539", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ed8cb0477be53b0ffb5ebf65d4dd46453be053b2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethical approval was obtained from the institutional review boards at the University of California, Los Angeles Fielding School of Public Health and the Kinshasa School of Public Health, DRC.", "Results from the multiple assays were compared to explore the overlap between EBOV seroreactivity. We ran cross-tabulations on all sociodemographic factors and reported occupation to explore descriptive characteristics of the population and compared these factors to their seroprevalence for each assay. We assessed differences in factors using \u03c7 2 or Fisher exact test. Sensitivity analyses were conducted by including mildly reactive antibody titers with the reactive antibody titers. All analyses were completed using R 3.4.2 and SAS version 9.4 (SAS Institute) software.", "The C-terminal domain of EBOV VP40 (base pairs 583-981) was cloned into the pRen2 plasmid and transfected into Cos-1 cells generating Renilla luciferase antigen fusion proteins. Cell lysates were harvested and used in immunoprecipitation assays with protein A/G-conjugated agarose beads and test serum diluted 1:100 as described by Burbelo et al [32] . The testing procedure has been described elsewhere [31] . VP40 reactivity was determined if the relative luciferase signal postimmunoprecipitation was at least 3 standard deviations greater than the background signal, as determined from a mean of 8 previously identified VP40-seronegative samples [31] . " ] },{ "paper_id": "ed8fa7a5f18148527c4280df39446a4102bd5949", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ed919dda9ed5eb8ab60b40ad6eb04bf2d68cc63f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ed91b54f1a51e6cca478909c62a47c7210a41a31", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cryptosporidiosis is a common gastrointestinal disease caused by a pathogenic protozoan, of the genus Cryptosporidium (Apicomplexa: Cryptosporidiidae) [1] , which affects all mammals, birds, reptiles, and possibly fish [2] New Zealand health authorities reported 19.7 cases per 100,000 between 2004 and 2011, although there were significant regional differences that correlated to exposure to livestock [3] The national reported incidence in 2012 was 31.1 per 100,000-a significant increase from previous years [4] . National statistics tend to underestimate the incidence of infectious gastrointestinal disease, as many cases are not notified, so the true incidence will be higher [5] .", "A laboratory-confirmed case was a clinically-confirmed case that tested positive for Cryptosporidium. ", "Diarrhoea 18 (95) Vomiting 9 (4) Stomach cramps 9 (4) Other (nausea, fever, headache) 6 (32) " ] },{ "paper_id": "ed92789659fddd64f955bda40d980398b681bb6b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "6 (1) 32 97 6 (2) 27 81.8", "6 (1) 32 97 6 (1) 29 87.9" ] },{ "paper_id": "edca7aed5e25c0b8888f93a5f78ce0a1b27ed1d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Linking animal ownership and health status to human health outcomes", "More than 75% of emerging infectious diseases are zoonotic in origin and a transdisciplinary, multi-sectoral One Health approach is a key strategy for their effective prevention and control.", "In Kenya, livestock contributes over 5.5% of the National Gross Domestic Product [6] . About 60% of all cattle, sheep and goats is found in arid and semi-arid areas, where approximately 10 million Kenyans derive their livelihood from livestock. Even in non-arid and semi-arid rural regions of Kenya, most farmers practice mixed farming that includes livestock ownership. For example, among 1500 households participating in a study in Western Kenya, within a non-arid and semi-arid area, 93% of households owned at least one type of livestock with 88% keeping chickens, 55% keeping cattle, 41% keeping goats, and 19% keeping sheep [7] .", "None of the 760 persons tested with well-characterized exposure to camels and camel products (milk) showed evidence of previous exposure MERS COV [41] . To test the hypothesis that perhaps a different strain of MERS COV that is less transmissible from camels to humans is circulating in camels in Kenya we have set up a study to detect and isolate MERS virus strain circulating in camels in Kenya for comparison with strains circulating elsewhere and addition expanded an enhanced surveillance of respiratory illness to Marsabit where camel pastoralists reside to detect any cases in humans." ] },{ "paper_id": "edcbcb53bfb68a6600dc092b57cf09b2a77ac86e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A study physician obtained an oral temperature, completed a symptom survey, and performed a respiratory system examination at each illness visit. All cases were classified as clinically moderate using standard criteria.", "(DOCX) S3", "PLOS Pathogens |" ] },{ "paper_id": "edcf92549f64338ff9e1d47d45b150ef4d6177b0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Where n = 4, i.e. the number of different possible nucleotides. This variability measure takes values between 0 and 1, and describes how dispersed the distribution of the alphabet elements is: higher values correspond to more uniform nucleotide usage; lower values correspond to more biased nucleotide, indicating that some nucleotides are preferred/positions are conserved.", "Experiments were conducted in the BSL-2 animal suite at the Utah State University Laboratory Animal Research Center (LARC). All personnel receive continual special training on blood-borne pathogen handling by this university's Environmental Health and Safety Office. Standard operating procedures for BSL-2 were used.", "Minimum Essential Medium Eagle -Earle's (EMEM medium), Fetal Bovine Serum (FBS), Penicillin-Streptomycin-Nystatin Solution, and Dulbecco's Phosphate Buffered Saline (DPBS) were obtained from Biological Industries (Bet-Haemek, IL). Opti-MEM medium was obtained from Gibco-ThermoFisher (Grand Island, NY). TransIT-X2 Mirus reagent was also used (MC-MIR-6003; Madison, WI).", "Male and female AG129 6-7 weeks old mice with an average weight of 20 g were used. Because of the immunocompromised nature of this strain, AG129 mice (produced in house) were housed in pre-sterilized bonneted (HEPA-filtered) cages in a ventilated cage rack during the duration of the experiment. Animals were randomly assigned to cages and individually marked with eartags. All instruments, eartags, gloved hands, or other surfaces that came in contact with the mice were cold-sterilized with a 10% betadine solution and/or 75% EtOH." ] },{ "paper_id": "eddb4ccfc3420d4cdaafabbc081bec8758930e53", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Unique Dimeric Assembly Supports Sialic Acid-Independent Functionality.", "virus-host interaction | viral attachment | paramyxovirus | structure | glycoprotein" ] },{ "paper_id": "eddc547cbba693715e4fd55e6a946e8ec7d96bc2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The site had 3478 hits, and 30 respondents (88.2%) visited the Extranet (Table 3) Thirty participants were asked a forced-choice question about whether they visited the site and why they visited." ] },{ "paper_id": "eddeda2da89b486d01f0afaf67af974b9f214306", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A list of parameter estimates is given in Table 1 . Further information on parameterisation is provided in S1 Appendix).", "See supplementary material S1 Appendix", "Great circle distance (miles) / average speed of transport (mph)." ] },{ "paper_id": "eddf68bf069ab23f6fbe7c7ab16c1c49335f4de9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To confirm virion capturing by CN3080, we conducted western blot analysis toward the VEEV-TC83 capsid protein.", "TEM grids were evaluated on a JEOL 1011 transmission electron microscope at 80 kV and all digital images were acquired using an Advanced Microscopy Techniques (AMT) camera system.", "The animal study was reviewed and approved by George Mason University Institutional Animal Care and Use Committee. " ] },{ "paper_id": "ede3bef01a48a154a93f1286b907cd5a53a086eb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Secondary IgGs. Horseradish-peroxidase-conjugated (HRPconjugated) anti-rabbit and anti-mouse IgGs (Promega), HRPconjugated anti-goat IgGs (Sta. Cruz), Alexa fluor fluorescent-dyelabeled IgG (Dianova and Invitrogen). Others: Protein G sepharose beads (Pharmacia Amersham), [ 32 P]-labeled a-dCTP (Perkin Elmer), [ 32 P]-orthophosphate (MP Biomedicals).", "Gelsolin. FL-Gln Y438A and FL-D565N [20] .", "Site-directed mutagenesis was performed by single or chimeric PCR, cloned into pCR2.1 vectors (Invitrogen) and verified by sequencing [64] ." ] },{ "paper_id": "edea2cda674c33bb251b64e5416f5380f13d5489", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bagpipe is freely available at http://valdarlab.unc.edu/software.html." ] },{ "paper_id": "edee1fd45587a0a71d88a5db58cc81342840e2f6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza A viruses (IAV) have posed a persistent threat to global public health for centuries, through both recurrent seasonal epidemics and sporadic pandemic outbreaks [1] . Approximately 10% of the global population is infected with an influenza virus annually, resulting in an estimated 3-5 million severe infections and 300,000-500,000 deaths [1] [2] [3] . Initial signs and symptoms include", "Further analyses of additional bacterial toxins and virulence factors may provide evidence for bacterial molecules that are related to post-bacterial adhesion/invasion co-infection pathogenesis.", "The authors declare no conflict of interest." ] },{ "paper_id": "edee452881f826fb72c58ee68a982789b12aa99d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "edf2997357501734a93c1b7e16d44e86a7d20853", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Putative conserved domains, trimer interface, and receptor binding sites were determined by performing a standard protein BLAST (blastp algorithm; https://blast.ncbi.nlm.nih.gov). The sequences producing significant alignments were imported into Geneosis software, (Auckland, New Zealand). Multiple alignment was conducted as previously described [31] , with phylogenetic analysis using Geneosis Pro 5.6.7.", "All amplified fragments were sequenced with BigDye Terminator v.3.1 Cycle Sequencing kit (ThermoFisher cat # 4336917). Briefly, samples were amplified in a PTC-200 thermal cycle (MJ Research) with the following program: 26 cycles of 1\u02daC/S to 96\u02daC, 96\u02daC for 10 seconds, 1\u02daC/S to 50\u02daC, 50\u02daC for 5 seconds, 1\u02daC/S to 60\u02daC, 60\u02daC for 4 minutes. The samples were cleaned using DyeEx 2.0 Spin kit (Qiagen cat # 63204) and loaded onto a 3130xl Genetic Analyzer (Applied Biosystems). Raw sequencing data was edited by the instrument's software (ThermoFisher 3130xl Genetic Analyzer Data Collection Software v3.0), and then imported into GeneCodes Sequencher v4.6.1 sequencing analysis software for further editing. The final sequenced contigs are then imported to NCBI BLAST (https://blast.ncbi.nlm.nih.gov/Blast. cgi) to confirm the identity.", "https://doi.org/10.1371/journal.pone.0199067.g005 addition of urea treatment would substantially weaken the interaction between the antibody and crCD40L.", "A number of methods and reagents have been developed for the analysis of immune responses in cotton rats over the last decade. Up to date, more than 200 genes encoding cytokines, chemokines, cell surface markers and regulatory molecules have been cloned, with various related research reagents being commercially available. As a result, the use of cotton rats in pathogenesis studies addressing mechanistic questions has significantly increased. Nevertheless, the gene encoding CD154 and CD40 ligand (CD40L), remains elusive." ] },{ "paper_id": "edfe02a438fa9b667313da8f03614303fc2a4a14", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ee0050c6fb81a4067d134010d0c80d21edb5df0b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Macaques represent the major non-human primate for studying infectious diseases. They are omnivorous and adaptable. The species most commonly used are rhesus macaques (Macaca mulatta) and cynomolgus macaques (Macaca fasciluraris).", "Group A streptococci colonize the mouth and upper respiratory tract in about 2-5% of world's population (Okumura and Nizet, 2014) . The most common, non-invasive and mild infections caused by GAS are tonsillitis and pharyngitis with estimated 600 million cases per year (Carapetis et al., 2005) .", "Listed as number nine in the list of global killers with around 500,000 deaths annually (Carapetis et al., 2005) , it is obvious that this pathogen can cause severe invasive infections, including pneumonia, sepsis, streptococcal toxic shock syndrome, and necrotizing skin infections (Cunningham, 2000; Carapetis et al., 2005) ." ] },{ "paper_id": "ee019cb6808f738c245cc9de12b08a19951ef594", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "It had not escaped our attention that the released or exposed rc/dslDNA in the cytoplasm may activate innate DNA sensors [55] [56] [57] [58] . However, cytokine response was not detected in CpAM-treated cells. Whether this is due to the deficiency of cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in hepatocytes and hepatoma cells [59] [60] [61] or efficient digestion of the released viral DNA by cytoplasmic nucleases [62] is currently under investigation.", "PLOS Pathogens | https://doi.org/10.1371/journal.ppat." ] },{ "paper_id": "ee06cad1229867a6389ed8a7aaffb5148dd5f8ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A Supporting Information Figure 1 A. Design of 9-, 10-, 11-mer peptides derived from the 15-mer antigen. Overlapping 9-, 10-, 11-mer peptides were each tested for their capability to stabilize the corresponding HLA. A total of 18 different peptides were derived from each 15-mer peptide.", "D. Similar to Part B, HLA-stability ELISA results for soluble HLA-B*55:02 molecules that were ligand-exchanged with 9-, 10-, 11-mers truncated peptides from DENV NS3-108 15-mer peptide.", "I. HLA-stability ELISA results for soluble HLA molecules that were ligand-exchanged with 9-, 10-, 11-mers truncated peptides from the indicated15-mer peptide. Non-irradiated HLA with conditional ligand and no peptide added (-UV), irradiated HLA and no peptide added (+UV), or with indicated 9-, 10-, 11-mers peptides." ] },{ "paper_id": "ee0c318d282c0089cca94f0b2ea4d90db2ab9f8a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We confirm the association of obesity with infection burden and present evidence for putative interaction with sports activity and dietary patterns.", "Background: Respiratory tract infections (RTIs) are a major morbidity factor contributing largely to health care costs and individual quality of life. The aim of the study was to test whether obesity (BMI \u2265 30 kg/m 2 ) is one of the risk factors underlying frequent RTIs in the German adult population. Methods: We recruited 1455 individuals between 18 to 70 years from a cross-sectional survey on airway infections in Germany and invited them to self-report in diaries incident RTIs experienced during three consecutive winter/ spring seasons. RTIs reported in these 18 months and summary measures adding-up individual RTIs were the outcomes of interest.", "Results: Compared to individuals with normal weight, obese individuals reported a consistently higher frequency of upper and lower RTIs and predominantly fell in the upper 10% group of a diary sumscore adding-up 10 different RTI symptoms over time. Obesity was associated both with lower RTIs ( adjusted OR = 2.02, 95%CI = 1.36-3.00) and upper RTIs ( adjusted OR = 1.55, 95%CI = 1.22-1.96). Adjusting for demographic and lifestyle variables did only marginally affect ORs. Stratified analyses suggested a stronger association for women and effect modifications by sports activity and dietary habits." ] },{ "paper_id": "ee0d298d09635c5ae72d4584fba105a705d25afb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.", "96-well Maxisorp immunoplates were coated with 0.2 mg antigen per well or control proteins. Testing human sera, Abs or phage-Abs in PBS containing 2% nonfat milk were then added. For competition ELISA, competitive sera or Abs were pre-mixed with testing Abs for 30 mins at RT and then added. Specific bound Abs or phage-Abs were detected by adding HRPconjugated anti-human IgG or HRP-labeled anti-M13, respectively. TMB substrate for HRP was then added, the reaction was stopped 5 mins later, and absorbance at 450 nm was measured.", "Over the last several years, neutralizing human monoclonal antibodies (mAbs) have been developed as potential therapeutics for the prophylaxis and treatment of SARS [15] [16] [17] [18] [19] [20] . NAbsmediated protection can also prevent the escape of mutant viruses from cytotoxic T-lymphocytes that are commonly associated with rapid disease progression and severity [21, 22] . Although there has not been a recent SARS-CoV outbreak, it is desirable to develop effective Ab-based passive immunotherapy for this zoonotic respiratory pathogen that might continue to evolve under immune pressure within the animal kingdom and has the potential to rapidly adapt in humans." ] },{ "paper_id": "ee14de143337eec0e9708f8139bfac2b7b8fdd27", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bat primary or immortalized cells (Rhinolophus sinicus kidney immortalized cells, RsKT; Rhinolophus sinicus Lung primary cells, RsLu4323; Rhinolophus sinicus brain immortalized cells, RsBrT; Rhinolophus affinis kidney primary cells, RaK4324; Rousettus leschenaultii Kidney immortalized cells, RlKT; Hipposideros pratti lung immortalized cells, HpLuT) generated in our laboratory were all cultured in DMEM/F12 with 15% FBS. Pteropus alecto kidney cells (Paki) was maintained in DMEM/F12 supplemented with 10% FBS. Other cells were maintained according to the recommendations of American Type Culture Collection (ATCC, www.atcc.org).", "Members of the Coronaviridae family are enveloped, non-segmented, positive-strand RNA viruses with genome sizes ranging from 26-32 kb [1] . These viruses are classified into two subfamilies: Letovirinae, which contains the only genus: Alphaletovirus; and Orthocoronavirinae (CoV), which consists of alpha, beta, gamma, and deltacoronaviruses (CoVs) [2, 3] . Alpha and betacoronaviruses mainly infect mammals and cause human and animal diseases. Gamma-and delta-CoVs mainly infect birds, but some can also infect mammals [4, 5] . Six human CoVs (HCoVs) are known to cause human diseases. HCoV-HKU1, HCoV-OC43, HCoV-229E, and HCoV-NL63 commonly cause mild respiratory illness or asymptomatic infection; however, severe acute respiratory syndrome coronavirus (SARS-CoV) and", "Bat fecal swab and pellet samples were collected from November 2004 to November 2014 in different seasons in Southern China, as described previously [16] .", "All sampling procedures were performed by veterinarians, with approval from Animal Ethics Committee of the Wuhan Institute of Virology (WIVH5210201). The study was conducted in accordance with the Guide for the Care and Use of Wild Mammals in Research of the People's Republic of China." ] },{ "paper_id": "ee1b5a9618dcc4080ed100486cedd0969e80fa4d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(1/5 (CCS2), 2/11 (vendors study) and 1/3 (sailor friends)) clinically ill cases were hospitalized.", "The author(s) declare that they have no competing interests." ] },{ "paper_id": "ee2fc6a943eac54444f75f0fbaf099178e36a11d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reporting summary. Further information on research design is available in the Nature Research Reporting Summary linked to this article.", "AN7973 selectively inhibits Cryptosporidium development. The structure and purity of AN7973 were determined by 1 H NMR, 13 C NMR, high resolution mass spectral analysis (HRMS), and high performance liquid chromatography (HPLC) (Supplementary Figs. 1 and 2) .", "Compound characterization. The chemical identity of AN7973 was established through 1 H NMR, 13 C NMR, and high-resolution mass spectral (HRMS) analysis. Compound purity was assessed by high performance liquid chromatography (HPLC) (Instrument and column: HPLC-01 Venusil MP C18 5 \u00b5m 4.6 \u00d7 50 mm)." ] },{ "paper_id": "ee3cc22161595e877450737882a52950fd179672", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "OCT angiography images were acquired using the RTVue XR Avanti with AngioVue (Optovue Inc., Fremont, California, USA), with an A-scan-rate of 70 000 scans per second, a light source of 840 nm, and a bandwidth of 45 nm. Macular cubes (3 \u00d7 3 mm) were acquired, each cube consisting of 304 clusters of 2 repeated B-scans containing 304 A-scans each. Split-spectrum amplitude decorrelation technology was employed to improve the signal-to-noise ratio by splitting the spectrum to generate multiple repeat OCT frames from 2 original repeat OCT frames [15] .", "Findings. There were one male and six female patients of mean age 31.5 \u00b1 7.2 years (range 22-41 years). Table 1 summarizes the demographic data. Three patients reported a prodromal virus infection.", "The authors have no conflict of interest to declare." ] },{ "paper_id": "ee3d6fcf2ed5408aef9c152f2e7145d916a1baee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bladder calculi were submitted to a commercial laboratory (Louis C. Herring and Co., Orlando, FL) and analyzed by integrated crystallography.", "The authors declare that they have no competing interests." ] },{ "paper_id": "ee48061797d29eeef5a9e606841bf8ab04b1d75b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus preparations are now available from the Salk GT3 viral core (http://vectorcore.salk.edu/). All plasmids are available from Addgene (http://www.addgene.org/).", "All mouse work was conducted in biosafety containment level 2 conditions and was approved by the Longwood Medical Area Institutional Animal Care and Use Committee.", "Imaging and physiology data were acquired and analyzed as described previously (Carter and Sabatini, 2004) . Resting membrane potential was determined by the average of three 5-s sweeps with no injected current. Passive properties of the cell, membrane (Rm) and series resistance (Rs) and capacitance (Cm), were measured while clamping cells at \u221265 mV and applying voltage steps from \u221255 to \u221275 mV. The current-firing relationship was determined in current clamp with 1-s periods of injected current from 100 to 500 pA." ] },{ "paper_id": "ee55aea26f816403476a7cb71816b8ecb1110329", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where D represents the vector for a drug compound, and d i its i-th (i = 1,2, ,256) component that can be derived by following the \"2D molecular fingerprint procedure\" as elaborated in [10] . The 53 molecular fingerprint vectors thus obtained for the 53 drugs in are, respectively, given in Supplementary Information S2.", "Now we extract the useful information from Equation (8) ", "Moreover, we used the grey system model approach as elaborated in [68] to further define the next 60 components of Equation (4) ( 1, 2, , 20)", "where \uf028 \uf029 " ] },{ "paper_id": "ee5b43d20a640664510cb7a540caaae4a8e19933", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following variables are listed according to their role in disease introduction, transmission and persistence, though some of these factors may have multiple roles.", "\u2022 Poultry trade and market.", "\u2022 Disease introduction and amplification." ] },{ "paper_id": "ee632fa425607e8ff91fc3730bc0782d43ce9c0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(2) careful design of flow cytometry panels to avoid emission spillover into the channel for the antigen of interest; and (3) choosing the brightest fluorochromes, like R-phycoerythrin or allophycocyanin.", "One weakness of the flow cytometric approach is the reliance on antigens that can be readily conjugated to a fluorochrome or biotinylated. In addition to recombinant proteins and synthesized peptides, labeled polysaccharides, lipids, haptens, virus-like particles, and pseudo viruses have also been used to identify antigen-specific cells by flow cytometry (33, [43] [44] [45] [46] [47] [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] . Further, epitope-specific B cells have been identified by screening bacteriophage-displays or microarray peptide libraries with polyclonal antibodies targeting the native antigen to select conformational epitopes that can be fused to fluorescent proteins for use in flow cytometry (47, 60) .", "JB and JT reviewed the literature, generated figures and tables, and wrote the manuscript. ", "Although the term antigen-specific B cell is used throughout this mini-review to denote the analysis of B cells based on binding between the B cell receptor (BCR) and a specific antigen used as bait, it is important to keep in mind that BCRs within the polyclonal B cell repertoire exhibit a spectrum of polyreactivity. On one end of the spectrum, a highly polyreactive BCR is able to bind multiple structurally unrelated antigens with physiologically relevant affinities. The frequency of polyreactivity in the normal adult human B cell repertoire has been estimated to be 4% of na\u00efve B cells, 23% of IgG+ memory B cells, and 26% of intestinal IgA+ and IgG+ plasmablasts (27-29). On the other end of the spectrum, a mono reactive BCR is activated only when it encounters a single cognate antigen. Although there are exceptions, the accumulation of somatic hypermutations within the variable regions of the BCR during the process of affinity maturation is generally thought to lead to increased affinity and specificity for the cognate antigen (30, 31)." ] },{ "paper_id": "ee6789ddf25ea68748fbc998fa9eb2f81b65302b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ee6d70a53e3262cea6f85bd8b226f6b4c8b5f64b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The protocol was conducted in accordance with the Declaration of Helsinki and French law for biomedical research (Nu ID RCB AFSSAPS: 2009-A00689-48) and was approved by the local Ethics Committee (Comit\u00e9 de Protection des Personnes of Bordeaux 2 University). Every eligible person for participation was asked for giving their written informed consent." ] },{ "paper_id": "ee6e4fcb9272a59d35f6ec53be5a8cff4d8c0b21", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The internal use of samples for diagnostic workflow optimisation was agreed under the medical ethical rules of each of the participating partners.", "Laboratories participating in the evaluation used the TaqMan Fast Virus 1-Step Master Mix (Thermo Fisher) with the same oligonucleotide concentrations and cycling conditions. The QIAGEN One-Step RT-PCR Kit was also tested and found to be compatible.", "To exclude non-specific reactivity of oligonucleotides among each other, causing artificial fluorescent signals, all assays were tested 120 times in parallel with water and no other nucleic acid except the provided oligonucleotides. In none of these reactions was any positive signal detected." ] },{ "paper_id": "ee8483f8f2cc5fe38be4e565eae3af9d0bb8220b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Where DH is enthalpy change, R is gas constant, DS is entropy change and T is the absolute temperature. The entropy change was obtained from the equation,", "N http://www.organic-chemistry.org. N http://mobyle.rpbs.univ-paris-diderot.fr/cgi-bin/portal. py? Form = admetox N https://secure.chemsilico.com/pages/submit.php", "(DOC)" ] },{ "paper_id": "ee8dca216514deeed4c9415bc2ad8a78dc3d9670", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Serum immunoglobulins G (IgG) fraction was purified using protein G-Sepharose (GE Healthcare, Orsay, France " ] },{ "paper_id": "ee92720c10a0cb395a8c1fd940dc0d12c44577f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2.5. Cytotoxicity Assay. Cytotoxicity of auranofin was determined by cell count, and cell viability was assessed by trypan blue dye exclusion test.", "Blotting. Cells were detached, washed with cold PBS, and centrifuged at 700 g for 10 min. The pellet was lysed in cold RIPA lysis buffer (20 mM TRIS pH 8, 150 mM NaCl, 1% Triton-X 100, 0.1% SDS, 1% sodium deoxycholate) containing protease and phosphatase inhibitors for 30 min on ice. Lysates were centrifuged at 10 000 g for 30 min at 4\u00b0C to remove debris.", "The authors declare that there is no conflict of interests." ] },{ "paper_id": "eea9d5e3d2244b3ecfb5e909515e00a4a3cabaa7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "eec9198400dee7d7ec27088377bced55c01a126a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data were analyzed using GraphPad Prism software (GraphPad Software, San Diego, CA). Viral titer data were analyzed with the nonparametric Mann-Whitney test. All differences not specifically stated to be significant were insignificant (p.0.05). ", "Spleens were harvested from mice and single cell suspensions were generated [65] . Cells were counted and diluted in RPMI-1640 media (Sigma, Saint Louis, MO) supplemented with 10% fetal calf serum (HyClone, Logan, UT), 100 U penicillin/ml, 100 mg/ml streptomycin, 10 mM HEPES (N-2-hydroxyethylpiperazine-N9-2-ethanesulfonic acid), 1mM sodium pyruvate, 50 mM 2-mercaptoethanol and 2 mM L-glutamine (cRPMI). In all adoptive transfer experiments, 1610 7 cells were injected into persistently infected RAG1-/-mice by intraperitoneal (i.p.) injection in 0.5ml cRPMI.", "ELISA to detect binding of polyclonal anti-serum or fecal extract-derived antibody to purified MNV virions or MNV VLPs was performed as previously described [27, 56] .", "RAW 264.7 cells were maintained as previously described [28] . Monoclonal antibodies (MAbs) specific to CD4 (YTS191.1 [61] ), CD8 (H35 [62] ) and SFR3-DR5 (ATCC HB-151 [63] ) were produced from hybridoma cell lines in INTEGRA Celline CL1000 flasks (Integra Biosciences, Ijamsville, MD) using CD Hybridoma media (Gibco, Carlsbad, CA) as previously described [64] . All mice (or cage sentinel mice for mice deficient in antibody production) were tested by ELISA for the presence of MNV antibody prior to experiments [27] . All mice used in these studies were seronegative at the initiation of experiments.", "For depletions in WT mice, 500 mg of lymphocyte-depleting antibody or an isotype-matched control antibody [SFR3-DR5, IgG2b] was administered i.p. one day prior and one day after infection. For depletions in adoptive transfer experiments, depleting antibodies were administered to RAG1-/-recipients as described above with one dose one day prior to splenocyte transfer and a second dose on the day of trnsfer. The efficacy of lymphocyte depletion in both sets of depletion experiments was monitored by flow cytometric analysis of splenocytes at the end of the experiment." ] },{ "paper_id": "eecb946b106a94f26a79a964f0160e8e16f79f42", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chest radiologic changes have been considered the gold standard for defining a pneumonia event [11] because clinical findings can be subjective and clinical definitions of pneumonia can be nonspecific. In 2005, to aid in defining outcomes of pneumococcal vaccine studies, the World Health Organization's (WHO) standardized chest radiograph description defined a group of children who were considered most likely to have pneumococcal pneumonia [12] . The term \"end-point consolidation\" was described as a dense or fluffy opacity that occupies a portion or whole of a lobe, or the entire lung. \"Other infiltrate\" included linear and patchy densities, peribronchial thickening, minor patchy infiltrates that are not of sufficient magnitude to constitute primary end-point consolidation, and small areas of atelectasis that in children can be difficult to distinguish from consolidation. \"Primary end-point pneumonia\" included either end-point consolidation or a pleural effusion associated with a pulmonary parenchymal infiltrate (including \"other\" infiltrate).", "The single strongest risk factor for pneumonia is HIV infection, which is especially prevalent in children in sub-Saharan Africa. HIV-infected children have 6 times increased odds of developing severe pneumonia or of death compared to HIV-uninfected children [52] . Since the effective prevention of mother-to-child transmission of HIV, there is a growing population of HIV-exposed children who are uninfected; their excess risk of pneumonia, compared to HIV unexposed children, has been described as 1.3-to 3.4-fold higher [53] [54] [55] [56] [57] .", "Several national guidelines from high-income countries, as well as the WHO recommendations for low-and middleincome countries, recommend that chest radiography should not be routinely performed in children with ambulatory pneumonia [31] [32] [33] . Indications for chest radiography include hospitalization, severe hypoxemia or respiratory distress, failed initial antibiotic therapy, or suspicion for other diseases (tuberculosis, inhaled foreign body) or complications. However, point-of-care lung ultrasound is emerging as a promising modality for diagnosing childhood pneumonia [34] ." ] },{ "paper_id": "eed4a68d4e44f9887b3219ad5813eed5f0c4d42b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "eee5a9068ade4c6776f189045115a90a5785e983", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Equine coronavirus (ECoV) is a positive-stranded RNA virus and belongs to the species Betacoronavirus 1 in the genus Betacoronavirus [1, 2] . The clinical signs associated with ECoV infection during outbreaks in the USA [3] and Japan [4] [5] [6] were fever, anorexia, lethargy and diarrhoea. The same clinical signs were also recorded in an experimental challenge study using Japanese draft horses [7] . The main transmission route is considered to be faecal-oral [7] and ECoV is usually detected in faecal samples. However, the molecular detection of ECoV in faeces from horses with diarrhoea, does not prove causation. Coronaviruses can cause both enteric and respiratory disease in many avian and mammalian species but ECoV is less likely to be found in respiratory secretions than in faeces [8, 9] .", "Phylogenetic analysis was performed for the nucleotide sequences of the complete N and partial S genes (Figure 1 ). The analysis for the N gene showed that Irish ECoVs were independently clustered although they were closely related to Japanese viruses identified after 2009. In the phylogenetic tree of the S gene, Irish ECoVs were closely related to all other ECoVs analysed.", "The accession numbers registered in GenBank/EMBL/DDBJ are as follows: the complete sequences of the N gene; 11V11708/IRL (LC149485) and 13V08313/IRL (LC149486), the partial sequences of the S gene; 11V11708/IRL (LC149487) and13V08313/IRL (LC149488) and the complete sequences from the p4.7 to p12.7 genes; 11V11708/IRL (LC149489) and13V08313/IRL (LC149490). One six-week-old foal was the only clinical case on a public Thoroughbred stud farm with approximately 30 mares when it presented with diarrhoea. Recovery took over three weeks during which it received fluid therapy, probiotics, antiulcer medication and antibiotics. The second foal was a 14-day-old filly, which had been hospitalised with diarrhoea two days prior to sample collection. The foal responded well to supportive treatment and at the time of sample collection, the diarrhoea had resolved. The five ECoV positive samples tested negative for equine rotavirus." ] },{ "paper_id": "eef0ecf5b8e7b179dadaef967e65f2ab68f021e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We sequenced the first Bovine coronavirus (BCoV) complete genome sequence from France. This BCoV was directly sequenced from a fecal sample collected from a calf in Normandy in 2014.", "Accession number(s). The complete genome sequence sequence of the BCoV/FRA-EPI/CAEN/2014/13 isolate has been deposited in GenBank under the accession number KX982264.", "B ovine coronavirus (BCoV) belongs to the Nidovirales order, the Coronaviridae family, the Coronavirinae subfamily, and the Betacoronavirus (https://talk.ictvonline.org/ ICTV/proposals/2008.085-122V.v4.Coronaviridae.pdf). Its genome is a single-stranded, linear, and nonsegmented RNA of around 31 kb. BCoV is responsible for respiratory and enteric diseases in cattle, particularly during winter (1, 2) . To date, the 19 complete BCoV genome sequences available in GenBank databases (consulted on 17 January 2017) originated from the United States or Asia. Here, we report the first complete genome sequence of a BCoV detected in France." ] },{ "paper_id": "eef4cc12b84be0a4217da828b75f06529ba5d01b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The ENA accession PRJEB14673 provides access to the following files: ", "Strains carrying specific and well-characterized deletions present unique and powerful tools for interrogating the function of elements in the deleted regions. While we have not pursued the characterization of other structural variants at this time, the potential for deriving functional insights from copy number gains, inversions, and translocations is promising.", "Brain hemispheres were collected from 13 CC055/TauUnc mice (six females and seven males). Samples were genotyped as described above and classified as wt/wt (n = 4), wt/del (n = 5), or del/del (n = 4) at Npnt. Brain hemispheres were pulverized using a BioPulverizer unit (BioSpec Products, Bartlesville, OK). Total RNA was extracted from 25 mg of powdered brain hemisphere tissue using an automated beadbased capture technology (Maxwell 16 Tissue LEV Total RNA Purification Kit, AS1220; Promega). Purified mRNA was evaluated for quality and quantity by Nanodrop Spectrophotometer (Thermo Fisher Scientific, Waltham, MA). For each sample, complementary DNA (cDNA) was synthesized using 200 ng of starting RNA according to the manufacturer's protocol (SuperScript III First-Strand Synthesis System, 18080051; Thermo Fisher Scientific).", "A single C57BL/6J mouse was obtained from The Jackson Laboratory's pedigreed stock and was sequenced at 303 coverage at NYGC as described for the 69 CC strains.", "Finally, diplotypes were constructed by detecting runs of the maximal inferred posterior probabilities along genomes. Adjacent genotype states were phased to minimize the total number of haplotype transitions. These inferred haplotype reconstructions and posterior genotype probabilities for every 5 kb-genomic window are available at www.csbio.unc.edu/ CCstatus/CCGenomes.", "The proportion of indels among all 53.7 million variants is 16.8%. This proportions drops to 12.9% of the HQHom variants. The HQHom variants are distributed among the 19 autosomes in proportion to their physical length at a frequency of 13.9 SNPs and 2.1 indels per kilobase. Variant frequencies on the X chromosome are lower, with 7.1 SNPs and 1.1 indels per kilobase. The SNP substitutions tabulated for HQHom variants (Table 2 ) are symmetric with respect to reference and alternative alleles; the transition-to-transversion ratios are all near to their expected value of 2, and 11.0% of SNPs occur at CpG dinucleotides. Functional analysis predicted several of the SNP and indel variants to have high impact on gene function (Table S5) ." ] },{ "paper_id": "eef61bdfa49b8652fd660b5b8b7e74cf51922505", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The target population of the TB prevalence survey was residents of 15 years old or above who had lived in the selected clusters for more than 6 months. A population based, cross-sectional survey was conducted using multistage random cluster sampling method.", "The authors declare that they have no competing interests." ] },{ "paper_id": "eefddcf51f8426ecaa9e3ace144dadfb34a74cf5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "3-Methyl-2-vinylquinazolin-4(3H)-one (13j). Amorphous solid, m.p. = 122\u02ddC-124\u02ddC (reference [35] m.p. = 123\u02ddC-125\u02ddC). ", "Diethyl trans-(2-methyl-5-(4-oxo-3,4-dihydroquinazolin-2-yl)isoxazolidin-3-yl)phosphonate (trans-11a). Yellowish oil; IR (film, cm\u00b41) \u03bd max : 3085, 2980, 2929, 2782, 1687, 1610, 1469, 1331, 1132, 1098, 1052 , 13 Diethyl trans-(2-methyl-5-(3-(3-nitrobenzyl)-4-oxo-3,4-dihydroquinazolin-2-yl)isoxazolidin-3-yl)-phosphonate (trans-11d). Data noted below correspond to a 92:8 mixture of trans-11d and cis-11d. A yellowish oil; IR (film, cm\u00b41) \u03bd max : 3070, 2982, 2930, 2910, 1620, 1574, 1531, 1497, 1415, 1298, 1103, 1025, 774 ", "Nitrogen-containing heterocycles form the core of natural products (e.g., alkaloids) and they are also present in many pharmacophores as well as in numerous marketed drugs. Among them, quinazolines and quinazolinones have drawn special attention due to the broad spectrum of biological activities of their derivatives, including sedative [1] [2] [3] , anticancer [4] [5] [6] [7] , antiviral [8] [9] [10] [11] [12] , antibacterial [13] [14] [15] , antifungal [15, 16] , anti-inflamatory [15, [17] [18] [19] and antifibrotic [20, 21] activities. Several reviews focused on the synthetic strategies and biological activities of these compounds have been published [22] [23] [24] [25] [26] [27] [28] [29] . The significant impact of various functional groups installed into quinazoline/quinazolinone frameworks on pharmacological properties have been proven.", "A solution of the nitrone 12 (1.0 mmol) and the respective vinyl quinazolinone (1.0 mmol) in toluene (2 mL) was stirred at 70\u02ddC until the disappearance (TLC) of the starting nitrone. All volatiles were removed in vacuo and crude products were subjected to chromatography on silica gel columns with a chloroform/methanol (100:1, 50:1, 20:1, v/v) mixtures as eluents." ] },{ "paper_id": "ef000d8cdab3895e2321286f16cce2b8aea458d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Samples analysed for Cryptosporidium spp., Salmonella, coronavirus and rotavirus were all negative. Bacteriological analyses showed a mixed flora, dominated by coliforms and Enterococcus spp." ] },{ "paper_id": "ef20a0cd67ce018cf061f154bd8be9d0e58d0f23", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting information S1 (DOCX) S1 Dataset. Raw data collected from trial, organized as separate excel sheets for enrollment, daily assessment, serum total protein, birth weight, exit treatment weight, exit trial weight, serum zinc testing, fecal samples, fecal testing, milk testing, and dead calves. (XLSX) " ] },{ "paper_id": "ef2b8f83d5a3ab8ae35e4b51fea6d3ed9eb49122", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Three serum samples were collected from patients with nervous system symptoms and histories of tick bites. The serum samples were treated with penicillin and streptomycin, then inoculated into the allantoic cavities of chicken eggs. 3 days later, the liquid was collected and divided into two portions (one for inactivation and one for RNA extraction). The RNA and inactivated samples were stored at -70\u00b0C before use.", "There are a variety of different methods available for identifying multiple antigens in one sample simultaneously, such as two-dimensional gel electrophoresis , protein chip, mass spectrometry, and suspension array technology [4] [5] [6] . However, the application of these techniques on pathogen detection is still in an early phase, perhaps due to the complicated use and high cost.", "The optimized ELISA array layout is shown in Figure 3 , which was applied in the following experiments. " ] },{ "paper_id": "ef3260e6249c01ae263e65c11e59fe0279f70277", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Veal calf 7 days to slaughter Cumulative incidence risk [21] \u2022 Normal N(p, \u03c3)", "Sector Compartment (production stage at risk)", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "ef35abb710975a602c24e4eff920d99c022e9132", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The experiment lasted for eight weeks. At the end of treatment, mice were sacrificed and blood samples were drawn by cardiac puncture with heparined tubes. The plasma was separated by centrifugation (3000\u00d7 g for 10 min at 4 \u2022 C) and stored at \u221270 \u2022 C until analysis. The liver tissues was immediately excised for experiments or stored at \u221270 \u2022 C for later use.", "Male ICR mice (20-25 g) were purchased from the Branch of National Breeder Center of Rodents (Beijing, China). Mice were maintained in an environmentally controlled room (23 \u00b1 2 \u2022 C, 55 \u00b1 10% humidity) for 1 week for acclimatization. Then, fifty mice were randomly assigned to five groups (10 mice/group)." ] },{ "paper_id": "ef38ed2f4cc96e16ce011623cc5d15d2d8ca58c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusions: These results show that targeted recombination-mediated mutagenesis provides a powerful tool for expediting the construction of novel RNA genomes and should be applicable to the manipulation of other RNA viruses.", "*Nt position 10665 in vR26/P-12 is reverted from A to G as in the parental cDNA." ] },{ "paper_id": "ef39c95cda9c94452dc64147ea7d9c825e03b8bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Members of our research group conducted the survey. In addition, we recruited and trained investigators with a bachelor's degree or higher and at least one year of work experience in a professional market research company, (preferably in a conservation-related area) [15] . To expedite this search, we also employed a polling firm to help us train investigators involved in the study.", "3. Can wild-sourced animals species used as TCM be substituted?" ] },{ "paper_id": "ef3d6cabc804e5eb587b34249b539c1b5efa4cc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In silico miRNA target prediction. MiRNA target genes were retrieved and compiled using TargetScan 38 and microRNA.org resource 39 . The interactions between miRNAs and intracellular pathways were predicted using DIANA-miRPath v2.0 40 ." ] },{ "paper_id": "ef485cbb4af39866ed7fdb5ec0ce66f92e39511f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "https://doi.org/10.1371/journal.pone.0181801.g004", "https://doi.org/10.1371/journal.pone.0181801.g006", "Histology. The Diagnostic Services Unit of the University of Calgary Faculty of Veterinary Medicine processed the tissues kept in 10% formalin and provided with us with stained hematoxylin and eosin (H&E) sections for evaluation." ] },{ "paper_id": "ef4bd0f82e4290dd3d826add75846fee85ff1181", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Symmetry codes:", "Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/20/08/14638/s1." ] },{ "paper_id": "ef586c7c8fe46545e4d236ad74818063b1ac0c10", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Combining Rule of \"Jun-Chen-Zuo-Shi\"", "Oral Bioavailability", "Presently, the GO enrichment analysis was performed to further probe the vital biological process of achieved targets which were mapped to DAVID (the Database for Annotation, Visualization and Integrated Discovery 10 ) for analyzing targets' biological meaning. The GO terms of biological process were utilized to symbolize genic function. Finally, those GO terms with p-value \u2264 0.05 and FDR \u2264 0.05 were selected for further research." ] },{ "paper_id": "ef58c6e2790539f30df14acc260ae2af4b5f3d1f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the context of a virus infection, the pathway leading from both these proteins have the potential to lead to cell death. Notwithstanding the fact that this might be an efficient way of virus clearance, it also portends pathological outcomes for the infected organism. Future research would probably lead to design of drugs targeting these proteins based on the structural homology of their effector domains, regulating the pathological denouement of their activation without compromising their anti-viral or potential anti-viral functions.", "the endogenous 2-5A levels, mammalian genomes encode posttranscriptional and post-translation inhibitors of RNaseL activity in the form of microRNA-29 and the protein ABCE1 (RNaseL inhibitor or RLI), respectively (Bisbal et al., 1995; Lee et al., 2013) . Direct inhibition of RNaseL function is also observed upon infection by Picornaviruses through, either inducing the expression of ABCE1 or exercising a unique inhibitory property of a segment of the viral RNA (Martinand et al., 1998 (Martinand et al., , 1999 Townsend et al., 2008; Sorgeloos et al., 2013) .", "IRE1 and RNaseL, in addition to biochemical similarities in protein kinase domain and structural similarities in their RNase domain, share the functional consequences of their activation in initiating cellular apoptosis through JNK signaling (Table 1 and Figure 2 ; Liu and Lin, 2005; Dhanasekaran and Reddy, 2008) . Though initial discoveries were made in the context of homeostatic and anti-viral role for the former and latter, differences between the pathways are narrowed by further advances in research. In the same vein, while inhibition of IRE1 signaling in virus infected cells indicates a potential anti-viral role, www.frontiersin.org (Tirasophon et al., 1998; Dong and Silverman, 1999; Papa et al., 2003; Lin et al., 2007) Nature of RNase substrates Both 28S rRNA and mRNAs IRE1\u03b2 can cleave both 28S rRNA and mRNA while IRE1\u03b1 substrates include only mRNAs (Iwawaki et al., 2001) Dissimilarities" ] },{ "paper_id": "ef58c6e981a08c85d2c0efb80e5b32b075f660b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data generated or analyzed during this study are included in this published article or the supplementary information file. The raw and processed HiSeq data has been deposited to GEO (GSE119767; https://www.ncbi. nlm.nih.gov/geo/).", "Virus and viral infection. HPAI A/chicken/Vietnam/0008/2004 H5N1 (H5N1) was obtained from AAHL, CSIRO. Viral stocks of A/Puerto Rico/8/1934 H1N1 (PR8) were obtained from the University of Melbourne. Virus stocks were prepared using standard inoculation of 10-day-old embryonated eggs. A single stock of virus was prepared for use in all assays. All H5N1 experiments were performed within biosafety level 3 laboratories (BSL3) at AAHL, CSIRO.", "To use \u03b2-actin as a loading control, the same membrane was stripped in stripping buffer (1.5% (w/v) glycine, 0.1% (w/v) SDS, 1% (v/v) Tween-20, pH 2.2) and re-probed with a HRP-conjugated rabbit anti-\u03b2-actin monoclonal antibody (Cell Signaling). In some cases, two SDS/PAGE were performed simultaneously with equal amounts of protein loaded onto each gel for analysis of CEACAM1 and \u03b2-actin protein expression in each sample, respectively. Protein band density was quantified using Fiji software (version 1.49J10) 64 . CEACAM1 protein band density was normalized against that of \u03b2-actin and expressed as fold changes compared to controls." ] },{ "paper_id": "ef5fe7296ec8baf90d974cf5737af0da3ed403ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical Package for the Social Sciences (SPSS) for Windows version 11.0 (SPSS Inc. Chicago, IL, USA) was used. For comparison of categorical data, chi-square or Fisher's exact test was used. All tests were two-tailed, and a P value below 0\u00c105 was considered statistically significant." ] },{ "paper_id": "ef6361c7bffb9e92f397d7004bfb3a9c804d7c6a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the Institutional Review Board (B-ER-101-031) of the study hospital, and all patients provided informed consent." ] },{ "paper_id": "ef64fa65c77a221698f7cf13acdcf801ed2d554b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SDS-PAGE was done as described [33] . Proteins were separated on a 12% running gel and 5% stacking gel and visualized by Coomassie Brilliant Blue (CBB) staining. For Western blotting, gel was blotted onto nitrocellulose membrane using electroblotting, (100 V for 1h) and probed with primary antibody. Anti-rabbit HRP was used as secondary antibody and colour was developed with DAB as the substrate.", "The purified scFvs were tested for the viral neutralization potential against a panel of pseudoviruses from clades A, B and C HIV-1 viruses (Table 5) " ] },{ "paper_id": "ef6638accc1ef599ad1aafd47b3a86f2b904cc76", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All authors participated in gathering the data, designing the article, and discussing and editing the manuscript.", "Design: Single case study." ] },{ "paper_id": "ef7110a9022bac2e50c995b0f6b826ff071e48f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The RT-LAMP isothermal amplification method used in conjunction with a chemical heating device provides a portable, rapid and robust NAAT platform that has the potential to facilitate HIV-1 testing in resource-limited settings and POC.", "We demonstrate no difference in the temperature stability of the NINA heaters and amplification consistency at an ambient temperature of 37uC as compared to our temperature-controlled laboratory.", "The reaction tubes were evaluated for the presence of amplification, following addition of the quencher probe at a 2:1 ratio of quencher to labeled-primer, as previously described [21] . Amplification was determined visually by observing fluorescence in the reaction tubes, using the UV lamp from a ChemiDoc XRS system (Bio-Rad Laboratories, Hercules, CA). Amplification was confirmed by electrophoresis using a 1.2% agarose gel containing SYBRH Safe gel stain (Invitrogen), which was subsequently visualized using the ChemiDoc XRS system." ] },{ "paper_id": "ef720b08c80cb574e3db1e48be65750ebb4b5104", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ef821e34873d4752ecae41cd9dfc08a5e6db45e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ef872b80cf38917f64c42bfa52a57beb4399897a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following strains were used for the production of pseudotyped viruses: for HA we used A/Thailand/1(KAN- ", "This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose." ] },{ "paper_id": "efa871aeaf22cbd0ce30e8bd1cb3d1afff2a98f9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In parallel, we characterised the magnitude of the related protein abundance changes observed in distinct cellular pathways ( Figure 4) .", "Sub-cellular fractions (10 mg) were resolved by SDS-PAGE and transferred onto BioTrace PVDF membranes (Pall corporation). The following primary antibodies were used: a-Tubulin (Sc 5286), C23 (Sc 6013), and Fibrillarin (Sc 25397) were from Santa Cruz Biotechnology, and PARP (AM30) from Calbiochem, mouse anti-ZAP 70 (05-253, Millipore), rabbit anti-STAT3 (06-596, Millipore), rabbit anti-ILF3 (ab92355, Abcam), rabbit anti-HSP90 beta (ab32568, Abcam), mouse anti-ADAR1 (ab88574, Abcam), rabbit anti-HDAC1 (ab19845, Abcam), rabbit anti-SSRP1 (ab21584, Abcam) rabbit anti-BOP1 (ab86982, Abcam), mouse anti-KpNB1 (ab10303, Abcam), rabbit anti-HIV-1 Tat (ab43014, Abcam), rabbit anti-CK2A (ab10466, Abcam), rabbit anti-DDX3X (ab37160, Abcam), mouse anti-TNPO1 (ab2811, Abcam), mouse anti-HSP90A (CA1023, MERCK), and rabbit-anti RB1 (sc-102, Santa Cruz).The following secondary antibodies were used ECL: Anti-mouse IgG and ECL Anti-rabbit IgG (GE Healthcare), and Donkey anti-goat IgG (Sc 2020) (Santa Cruz Biotechnology).", "(DOCX)" ] },{ "paper_id": "efaa556b484fbcd9cc34832ffac53ef3e834e9c0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are presented as the means 6 standard deviations (S.D.) and are representative of at least three independent experiments. Differences between groups were analyzed by analysis of variance (ANOVA), and means were compared by Student's t-test. P-values less than 0.05 were regarded as significant. Results for percent initial body weight were also compared by using Student's t test.", "Comparison of survival was done by log-rank test using GraphPad Prism 6 version." ] },{ "paper_id": "efad73082938e5a567397ede3fc326988ea72bb8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Exposure of neonates to Mycobacterium avium subsp.", "Johne's disease (paratuberculosis), a chronic enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), can result in profuse diarrhea, malabsorption of nutrients, and severe weight loss in end-stage disease [1] . Since MAP infection is spread primarily through contaminated feces and/or milk and colostrum, efforts to mitigate disease transmission have focused on preventing infection in the neonate with clean maternity pens and feeding pasteurized colostrum and waste milk [2] . In addition to MAP infection, high incidences of morbidity in neonates are attributed to", "Fecal samples (2 gm) were obtained at day 7 and 14 and then processed by a centrifugation and double-decontamination procedure [17] . Decontaminated samples (200 \u00b5L) were dispensed onto Herrold's Egg Yolk medium (HEYM) and incubated at 39 \u2022 C for 12 weeks. Tissues obtained at necropsy were homogenized in 0.9% hexadecylpyridinium chloride solution with a gentleMACS TM Octo Dissociator, using M tubes (Miltenyi Biotec, San Diego, CA, USA). Following overnight incubation, homogenates were pelleted by centrifugation at 900\u00d7 g for 30 min and resuspended in an antibiotic cocktail containing 100 \u00b5g/mL nalidixic acid, 100 \u00b5g/mL vancomycin, and 50 \u00b5g/mL amphotericin B (Sigma-Aldrich, St. Louis, MO, USA). Samples were incubated overnight and then inoculated onto four slants of HEYM. Slants were incubated at 39 \u2022 C for at least 12 weeks and colony counts of viable MAP were recorded and averaged for the four slants. Confirmation of MAP colonies was performed by picking colonies off the HEYM slants, boiling in ultra-pure water TM distilled water (Life Technologies) to release the DNA, followed by IS900 PCR as described below. DNA from fecal samples was extracted by using the Ambion \u00ae Mag Max TM total nucleic acid isolation kit (Life Technologies, Grand Island, NY, USA) according to the manufacturer's recommendations in conjunction with a Mag Max TM Express processor (AM1840 v2, Applied Biosystems, Life Technologies, Beverly, MA, USA)." ] },{ "paper_id": "efb09a669665f5e0e097c2d5e94c499a6e43bd9e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author would like to thank Dr. Ge Li for critical reading and discussion of this manuscript. This work was supported in part by an intramural fund from the University of Maryland Medical Center and NIH grants (R01 GM127212-01A1 and R21 AI129369-01.", "Geminiviruses do not have their own DNA polymerases and associated DNA synthesis machinery. They rely on host cellular DNA synthesis machinery to duplicate themselves via a dsDNA intermediate. During the rolling circle replication, Rep serves as a multitasking protein. It involves in viral DNA cleavage and joining after one round of replication. It also has ATPase and helicase activities [109] . Since some plant cells are terminally differentiated cells, Rep is responsible for reigniting plant cell cycling by pushing cells from cell cycle G1 phase to S phase where cellular DNA synthesis apparatus is reactivated [110] . To achieve this goal, Rep binds to plant homologue of mammalian retinoblastoma protein to promote the G1-S transition [111] . In this way, Rep reactivates host cell S phase gene transcription and provides a favorable environment for geminivirus replication [110, 112, 113] .", "The author declares no conflict of interests. " ] },{ "paper_id": "efba2008a6ccf1ad2614aebd79a6a741ea6538b9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The extract was centrifuged at 3000 g/min for 25 min and concentrated under 80 \u2218 C for 8 h to prepare polysaccharide. The supernatant was then deproteinized using the Sevag method, and dialyzed against water for 48 h. The final liquid was mixed with three-fold volume of 95% ethanol (v/v) and centrifuged at 3000 g/min for 10 min. The precipitates were successively washed with absolute ethanol, ether, and dried under vacuum at 40 \u2218 C to obtained the crude polysaccharide (yield = 1.2%). EAP content was determined by the phenol-H 2 SO 4 method [19] .", "Unfortunately, their benefits have been significantly restricted by drug-resistance and frequent antigenic mutation [5, 6] . Therefore, the development of novel antiinfluenza agents against the H5N1 subtype is very important.", "Relative qPCR was performed for other eight genes: hactin, h IL-6, h IFN-, and hTNF-for A549 cells; mactin, mTLR-2, mTLR-4, mDectin-1, mMR, mIL-6, mIFN-, and mTNF-for Raw264.7 cells. The sequences of primers were shown in Table 1 . The reaction was run with 95 \u2218 C for 10 min, followed by 40 cycles of denaturation at 95 \u2218 C for 15 sec, annealing at 52 \u2218 C for 30 s, and extension at 72 \u2218 C for 40 s. The fold change in gene expression was normalized to controls (naive mice) by 2 \u2212\u0394\u0394CT using -actin as an internal standard [20] ." ] },{ "paper_id": "efbd0dfc426da5dd25ce29411d6fa37571623773", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Endoplasmin HSP90B1 P14625 9 9 9", "Large neutral amino acids transporter small subunit 1 SLC7A5 Q01650 6 12 9", "Keratin, type II cuticular Hb1 KRT81 Q14533 10 8 9" ] },{ "paper_id": "efc1b7d8cc09b229c5cd7cda3a8ff8446e0d8b63", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequencing was conducted with the primers used for amplification, or with M13 primers after cloning in a pCR2 cloning vector (Invitrogen) .", "Complete polyprotein open-reading frame (ORF) sequences, excluding the partial untranslated regions (UTR) regions obtained by this protocol were used for further analyses.", "The phylogeny ( Fig. 1 ) supports previous suggestions [65] that WNV has an African origin, as the African YAOV roots the WNV group." ] },{ "paper_id": "efcd7d171bb51acf2ef0a631901900497957a3be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study was conducted after obtaining approval from the Mehmet Akif Ersoy University Animal Experiments Local Ethics Committee (MAKU-HADYEK-Submission: 2014/77).", "This work was carried out in collaboration between all authors. EEE, HME and AHK: Designed the experimental procedures. EEE, EG and MK: Conducted the research work. EEE, AHK, MO and AK: Helped in laboratory analysis. All authors read and approved the final manuscript." ] },{ "paper_id": "efcfbaace6df1f5383c167fe24ecfd918b77f8b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "efd27ff0ac04dd60838266386aaebb5df80f4fa9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A possible correlation of virus prevalence and age of infection was assessed using univariate analyses. The Fisher's exact test was used where cell counts below 5 were encountered; otherwise, the chi-squared test was performed. The same statistical tests were used to compare the frequency of subjects with single or multiple infections between age groups. In addition, Pearson correlation was used to examine co-infections of different viruses. All statistical analyses were performed using StataSE 12 (StatCorp. 2007. College Station, TX, USA).", "Acute RTIs are classified as upper (UTRIs) and lower RTI (LRTIs), according to the involved anatomic localization. URTIs cause non-severe but widespread epidemics that are responsible for continuous circulation of pathogens in the community. LRTIs have been classified as frank pneumonia and bronchiolitis with clinical, radiological and etiological features that usually overlap [6, 7] . Viruses are again the foremost agents of LRTIs often misdiagnosed as bacterial in origin and hence treated with antibiotics unnecessarily [8] .", "A set of four multiplex Real-Time RT-PCR assays was established and validated for the detection of the 15 most common respiratory viruses as follows: assay 1: influenzaviruses A and B, RSV, assay 2: parainfluenzaviruses 1-4, assay 3: HAdV, enteroviruses, HMPV and HBoV and assay 4: rhinoviruses and the human coronaviruses OC43, NL63 and 229E (Table 1) ." ] },{ "paper_id": "efd94d1135c5ee11c2af624b344881e079a5ce7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Managers' accounts of this period elaborated the complexity of preparedness planning in terms of the involved institutions, actors, procedures and requirement of the plan. One manager concluded:", "You get no discount. You can never go the shorter way. There was always something that surprised you. We thought this was a lot like a three headed monster, so when you chopped off one of its heads, three other emerged, every solution was followed by more problems.", "We learned that we could not rely on volunteers \u2026 when you work in an infectious disease department you cannot choose what infections you want to work with." ] },{ "paper_id": "efdc5d569bff1bbf7b2233e6b3a84a0c61a10d17", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "efdf0a3bdc300ce80392b2b52be33728db54a51f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Microarray data for 13,107 probes were collected for synchronized young adult populations of 209 recombinant lines previously (Rockman et al. 2010) . We performed linkage mapping as described above on these expression data and identified significant peaks for 3298 probes (File S13). For the H19N07.3 probe (A_12_P104350), the full annotated-LOD data frame is provided (File S14).", "Protein sequences for homologs of the C. elegans H19N07.3 protein (File S21) were input to MUSCLE (Edgar 2004a,b) to generate a multiple-sequence alignment. CLUSTALW was then used to generate a neighbor-joining tree and output as a Newick formatted file (File S22).", "The nematode-specific gene H19N07.3 impacts bleomycin variation" ] },{ "paper_id": "efdfec9626b7961580cf4ecea75e8d4fde27980d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ISG20 is a translational controller PLOS Pathogens | https://doi.org/10.", "Overall, these results indicate that ISG20 discriminates mRNAs based on their self/non-self genesis and also underline the fact that certain viruses, as EBV, may have devised mechanisms to resist this inhibition due to their specific modes of replication.", "Antibodies directed against the following proteins were as follows: Tubulin (T0198), Actin (A5441), Flag (F7425 and F3165), GFP (G1544), HA (H3663), VSV-G (C7706), TNRC6A (HAP015305) from Sigma; mSin3A (ab129087); donkey anti-rabbit IgG (Alexa Fluor 594 conjugate, A-21207) and donkey anti-mouse IgG (Alexa Fluor 488 conjugate, A-21202) from Invitrogen; CREB (4820) and Akt (9272) from Cell Technology; DDX6 (BET1300-460A) from Ozyme; ISG20 (22097-1-AP, in our hands this antibody is highly unreliable on human ISG20 but is more efficient on murine ISG20) from Proteintech; sc35 (NB100-1774) from Novus Biologicals; anti BMRF1 (MAB8186, Merck Millipore); anti BMLF1, anti BRLF1 and BZLF1 were described in [56, 57] ; anti-IFIT1 (PA3-848, Life Technologies). The anti-Gag/p24 antibody (clone 183-H5C) was obtained from the AIDS Reagents Program of the NIH." ] },{ "paper_id": "efe13a8d42b60ef9f7387ea539a1b2eeb5f80101", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Certain pathophysiologic characteristics, including thrombocytopenia and shock, of hantavirus diseases of humans, bear substantial similarity to the hemorrhagic fevers induced by other viruses such arenaviruses, filoviruses and flaviviruses, despite sharing essentially no sequence similarities therewith. Such observations raise questions about whether such commonalities in pathogenesis are chance similarities of phenotype, or instead report the presence of common molecular mechanisms among the viruses.", "(3) Pathogenic effects caused by the activities of specific viral macromolecules. We have reviewed some of the activities associated with the Gn, Gc and N, virally-encoded polypeptides in previous sections.", "(1) Innate immune mechanisms. The nature of interactions between hantavirus pathogen-associated molecular patterns (PAMP) with the pattern recognition receptors (PRR) of susceptible endothelial cells are beginning to be clarified. The prototypical HTNV appears to be recognized by TLR-3 [43] . Such an infection has consequences such as increased expression of HLA-DR in dendritic cells [66] and differentiation of monocytes toward dendritic cells [67] .", "Testing models of pathogenesis can be done more effectively when there is an animal model that mimics key aspects of the disease. There is no such model that closely mimics HFRS, but animal models exist for both the asymptomatic carriage of PUUV and SNV by their native carrier rodents, the bank vole Myodes glareolus and the deer mouse P. maniculatus; as well as a Syrian hamster model using ANDV or the related Maporal virus from Venezuela, for which an HCPS-mimetic disease is observed [70] [71] [72] [73] ." ] },{ "paper_id": "eff26d8739498efca2d32fe2e66cdbebf0569c50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The index GC3s means the fraction of the nucleotides G+C at the synonymous third codon position, excluding Met, Trp, and the termination codons." ] },{ "paper_id": "eff3310317521aed7abe06ef1fa9963ca9d6caf3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results are expressed as mean 6 SEM. The data were analyzed using GraphPad version 5.01 for Windows (GraphPad software). Unpaired two-tailed Student's t test or Mann-Whitney test was used to compare means between different groups. One-way ANOVA with Bonferroni post-test was considered appropriate for multiple comparisons. P value less than 0.05 was considered significant.", "One of the major concerns regarding the use of immunostimulatory adjuvants in humans is the possible increased risk of autoimmune diseases due to targeting pattern recognition receptors by such adjuvants. However, the recombinant Ov-ASP-1 adjuvant we studied corresponds to a secreted filarial protein, which is presented as an antigen in the O. volvulus exposed or infected individuals in Africa. There is no evidence to show that this secreted filarial protein could induce autoimmune disease in the infected patients, thus excluding such a concern.", "Animal protocols were approved by the Institutional Animal Care and Use Committee at the New York Blood Center (mice, Protocols #255 and #194) and the Tulane National Primate Research Center (NHPs, Protocol #P0052). The Tulane National Primate Research Center TNPRC is a USDA-inspected and Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC)-approved facility, and has an Animal Welfare Assurance on file with the Office of Laboratory Animal Welfare. All animal studies were carried out in strict accordance with the recommendations of the American Veterinary Medical Association (AVMA) Guidelines and the approved protocols. The animals were handled delicately. Any treatment was done with extreme care and professionalism to avoid any unnecessary discomfort for the animals." ] },{ "paper_id": "eff8bed68ef6109e8f0c51a8b1ec4b6ca5b6329e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Belgian isolates showed genetic moderate to high genetic variability, with nucleotide identities between 90.1 and 97.2%. Furthermore, they clustered diffusely between strains from different countries around the world, indicating that strains are not distinguishable based on their geographical origin.", "It is clear that new technologies will change the way diagnostics are be performed in the near future. Pricing might currently be an aspect hampering high-troughput analysis of samples in swine veterinary medicine, but as the technology evolves fast, this might become very soon less relevant. Complete overviews of all viruses and other pathogens in a sample will be given in a single readout instead of requiring different diagnostic assays. However, care should be given to the interpretation of such results, as they should only be analyzed by trained veterinarians." ] },{ "paper_id": "f00106cad50635bb15409ac6039b93b5af031565", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Bats are a major reservoir of emerging infectious viruses. Many of these viruses are highly pathogenic to humans however bats remain asymptomatic. The mechanism by which bats control viral replication is unknown.", "KLF4 NR4A3 PTGES RELB RELB SLC6A9 SLC6A9 DDIT4 SLC7A11 SLC7A11 ISG20 ISG20 STC1 STC1 CHAC1 LIF SLC2A3 STC2 NR4A1 NR4A1 BBC3 RASAL1 DDIT3 ADAMTS6 ADAMTS6 ATF3 DUSP8 C3 C3 TRAF1 NFKB2 SLC11A2 PTGS2 SLC11A2 SNX10 SNX10 ATP8B1 LIPG LIPG QPCT STX11 IER3 IER3 BDKRB2 DUSP10 DHRS3 KDM6B INSIG1 KDM6B KDM6B STARD4 ABCG1 CDKL2 MKNK2 SESN2 LPIN1 PER1 ARHGEF2 RASSF1 CAMTA1 MSMO1 PER1 PER1 KIF21B ALDH1L2 ASNS AARS HIVEP2 SGMS2 PFKL SCD MVD FABP3 PSPH RDH11 DHCR7 FDFT1 SQLE HEK293T 8hpi HEK293T 24hpi PaKiT03 8hpi PaKiT03 24hpi" ] },{ "paper_id": "f00f183d0bce0091a02349ec1eab44a76dad9bc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "KH and JS conceived and wrote the manuscript. MA-G read the manuscript and commented on the text.", "While the correlates of vaccine-induced immune protection for infectious diseases, where they are known, are almost exclusively serum or mucosal antibodies (Plotkin, 2010) , ", "Frontiers in Microbiology | www.frontiersin.org" ] },{ "paper_id": "f012e9f73359ad9dbd89f041c7b5380301e1610b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This reduces the reliability of environmental assessment reports and hampers our understanding of host and disease associations.", "Zoological Research 39 (5) ", "Diagnosis: Cusp t3 present on M 1 in first transverse loop, but very small; head and body relatively large; tail length usually larger than head plus body length; belly gray-white; transition between darker dorsal and lighter ventral pelage abrupt; dorsum of feet white, not glossy." ] },{ "paper_id": "f01ad3545245b4f884b48aa2b69c9deb942c3e77", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Genotype 1b phylogenetic analyses were concordant for both genomic regions in all 31 sequences, suggesting no recombination events between these regions.", "The authors declare that they have no conflicts of interest.", "Fabi\u00e1n Aldunate and Natalia Echeverr\u00eda contributed equally to this work.", "Each drug or class of DAA is characterized by specific resistance profiles. The likelihood that a DAA will select for and allow outgrowth of viral populations carrying RASs depends on the DAA's genetic barrier to resistance (the number and type of mutations needed to generate an amino acid substitution that confers resistance), the viral fitness (replicative capacity) of the resistant variant, and viral genotypes and subtypes [7, 8] ." ] },{ "paper_id": "f021d8bdb3482a6965a104dddb2516d179bd9c34", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ies with a larger sample size and a more even distribution of group sizes could be carried out in future to examine whether our present findings can be replicated.", "ICC(1) values of predictors at T1 and psychological indicators at T2 were calculated to examine the independence of the data. All ICC(1) values were < 0.25 (range: 0 to 0.24) and met the criteria for independent measurement [40] ." ] },{ "paper_id": "f02529d9be6c7576b60d295c4e04d15a9a432614", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HEK293 cells were seeded onto poly-lysine-coated coverslips and transfected with the indicated IFITM1 DNA constructs. Cells were fixed in 4% paraformaldehyde in phosphate buffered saline for 10 min at room temperature, permeabilized with 0.1% Triton X-100 for 10 min, and incubated with blocking buffer containing 3% BSA and 6% skim milk. Cells were then stained with indicated primary antibodies (1:100 dilution) for 2 hours at room temperature, followed by staining with FITC or TRITC conjugated secondary antibodies (1:100 dilution). The nuclei were stained by DAPI. Dynasore treatment was performed by incubating cells with 160 \u03bcM dynasore for 1 hour at 37\u00b0C prior to fixation. Images were acquired with Leica TCS SP5 laser scanning confocal microscope using 100x objectives with sequential-acquisition setting. All the images were obtained using the laser power and digital gain below saturation at a resolution of 1024 x 1024 pixels (8 bit). ImageJ software was used for post-acquisition measurement of the fluorescent intensity.", "Deleting the C-terminal sequence of IFITM1 leads to inhibition of HIV-1 entry", "Conceived and designed the experiments: CL WQ. Performed the experiments: RJ SD QP. Analyzed the data: RJ SD SLL CL. Contributed reagents/materials/analysis tools: SLL CL. Wrote the paper: SLL WQ CL." ] },{ "paper_id": "f02d0c1e8b0109648e578662dc250abe349a033c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Six-week-old female C57BL/6 mice were purchased from The Jackson Laboratory. All animal experiments were approved by the Animal Committees of the Institute of Medical Science (The University of Tokyo).", "Bone marrow-derived macrophages (BMMs) were prepared as described previously (Ichinohe et al., 2009) . In brief, bone marrow was obtained from the tibia and femur by flushing with Dulbecco's modified Eagle's medium (DMEM; Nacalai Tesque). Bone marrow cells were cultured for 5 days in DMEM supplemented with 30% L929 cell supernatant containing macrophage colony-stimulating factor, 10% heat-inactivated fetal bovine serum (FBS), and L-glutamine (2 mM) at 37 \u2022 C/5% CO 2 . HEK293FT cells (a human embryonic kidney cell line) and HeLa cells (a human epithelial carcinoma cell line) were maintained in DMEM supplemented with 10% FBS, penicillin (100 units/ml), and streptomycin (100 \u00b5g/ml) (Nacalai Tesque). MDCK cells (Madin-Darby canine kidney cells) and HT-1080 cells (a human fibrosarcoma cell line) were grown in Eagle's minimal essential medium (E-MEM; Nacalai Tesque) supplemented with 10% FBS, penicillin (100 units/ml), and streptomycin (100 \u00b5g/ml) (Nacalai Tesque).", "Statistical significance was tested using a two-tailed Student's t-test. P-values < 0.05 were considered statistically significant." ] },{ "paper_id": "f030f518075c344748867210874ab67ffd02259e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Monosaccharide composition. Aliquots of G-50 column eluates were hydrolyzed with 2 M trifluoroacetic acid, converted to alditol acetates, and analyzed using GC-MS performed as described previously (40) .", "\u2425 9 \u2426 2 T", "Statistical analysis. Statistical analyses of experimental data, employing nonparametric tests as indicated below, were performed using Graph-Pad Prism (GraphPad Software, San Diego, CA). For unpaired and paired comparisons, Mann-Whitney U tests and Wilcoxon matched-pairs signed-rank tests were applied, respectively." ] },{ "paper_id": "f0384ad1acd95e489c5d835a494de1cdd3fd365f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Inflammation-induced, STING-dependent autophagy limits Zika virus (ZIKV) infection in Drosophila brains.", "Microglia have been involved in AD for more than 100 years. Nissl and Alzheimer first described amoebalike glial cells in various neurological states in 1904 and 1910. This amoeba-like glial cell was later confirmed to be a microglia. Microglia were activated in amyloid plaque-enriched areas in Alzheimer's disease brains [79] . Some findings reveal that microglia serve as important physiological functions in learning and memory by promoting learning-related synapse formation through brain-derived neurotrophic factor (BDNF) signaling [80] .", "Microglia play a direct antiviral effect by producing IFN-1 after recognition of virus by pattern recognition receptors (PRRs)" ] },{ "paper_id": "f04518627b8397d11241046b09b3925ce3cd31ac", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell-penetrating peptides (CPPs) are short peptides generally carrying a net positive charge that independently mediate internalization of molecules across cell membranes (e.g., HIV TAT (human immunodeficiency virus trans-acting activator of transcription) peptide 24 and penetratin 24, 25 ). However, CPPmediated delivery often results in limited cytosolic distribution due to endosomal sequestration of cargoes [26] [27] [28] [29] . To avoid endosomal entrapment, CPP may be combined with endosomolytic peptides such as endosomal leakage domains, which bind and transiently destabilize endosomal membranes [30] [31] [32] [33] [34] .", "Live cell imaging and image analysis. Live cell GFP fluorescence was visualized on an inverted tissue microscope Olympus IX70 (Olympus Scientific Solutions Americas Corp, Waltham, MA) and the mean fluorescence intensity was obtained using a SpectraMax i3x fluorescence reader (Molecular Devices, San Jose, CA).", "All relevant data supporting the key findings of this study are available within the article and its Supplementary Information files or from the corresponding authors upon reasonable request. The source data underlying Figs. 1b, d, 2b-f, 3e, 4g, 5a, 6g and Supplementary Figs. 1-4, 5a and 6 are provided as a Source Data file. " ] },{ "paper_id": "f046ba37a3a60a90b3dbcc977182efe1672ba300", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In conclusion, our analysis suggests that viruses have exerted a very powerful selective pressure across the breadth of the mammalian proteome, and suggests the possibility that pathogens in general are the key driver of protein adaptation in mammals and likely other lineages and might have driven many pleiotropic effects on diverse biological functions.", "This dataset represents the largest, most up-to-date set of VIPs backed by individual low-throughput publications. Nonetheless, given that many VIPs were discovered only recently, with half of all publications reporting VIPs published in the past 7 years (Figure 2) , it is likely that many additional VIPs remain to be discovered.", "However, PKR and other fast-evolving antiviral defense proteins may not be representative of the hundreds or even thousands of other proteins that interact physically with viruses (virus-interacting proteins or VIPs in the rest of this manuscript). Most VIPs are not specialized in antiviral defense and do not have known roles in immunity. Many of these VIPs play instead key functions in basic cellular processes, some of which might be essential for viral replication.", "We consider proteins as antiviral if they restrict viral replication in any way, for example by directly engaging viruses for recognition and/or degradation of viral molecules, or if they have been shown to be required for the proper unfolding of the antiviral response. Antiviral proteins were annotated at the same time as VIPs and are listed in Supplementary file 1D.", "So far, Enard et al. have only studied old adaptations that occurred millions of years ago in humans and other mammals. Further studies will investigate how much of the recent adaptation in the human genome can also be explained by the arms race against viruses.", "Most of the VIPs (95%) correspond to an interaction between a human protein and a virus infecting humans (Supplementary file 1A). Human Immunodeficiency Virus type 1 (HIV-1) is the best-represented virus with 240 VIPs, with nine other viruses (HPV, HCV, EBV, HBV, HSV, Influenza Virus, ADV, HTLV and KSHV) having at least 50 VIPs (Supplementary file 1A)." ] },{ "paper_id": "f04ae49e396269b6fc64538613ea9a6d53583bd6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "administered alone or co-administered with one of two adjuvants, AddaVax\u2122 (InvivoGen, USA, used at 25 \u03bcl per mouse) and Matrix-M\u2122 (Isconova, Sweden, used at 25 \u03bcg per mouse). All immunizations were intramuscular and were performed under isofluorane anesthesia in a total volume of 50 \u03bcl administered to the right posterior tibialis muscle." ] },{ "paper_id": "f057fa2845067210cbd31e79d8a83cdff0aa96f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dengue virus serotype 2 (Thailand/16681/1984) (DENV-2) used in this study was kindly provided by Dr. Alvaro Aguilar-Setien. DENV-2 was replicated in C6/36 cells and titrated by plaque assay in BHK-21 cells [42] .", "Dengue virus is transmitted by female mosquitoes mainly of the species Aedes aegypti and A. albopictus. The disease is widespread throughout the tropics, with local spatial risk variations influenced strongly by rainfall, temperature and unplanned rapid urbanization [5] .", "Human cervical carcinoma C33-A (ATCC: CRM-HTB-31), African green monkey kidney Vero (ATCC: CCL81, kindly donated by Dr. Judith Gonz\u00e1lez, Universidad Aut\u00f3noma del Estado de Morelos, Mexico) and baby hamster kidney BHK-21 (C-13) (ATCC: CCL-10) cell lines were maintained in Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10 % fetal calf serum, 100 U/mL penicillin and 100 \u03bcg/mL streptomycin at 37\u00b0C with 5 % CO 2 . Aedes albopictus C6/36 cells (kindly donated by Dr. Celso Ramos, Instituto Nacional de Salud P\u00fablica, Cuernavaca, Mexico) were maintained in Minimum Essential Medium (MEM) supplemented with 10 % fetal calf serum, 100 U/ mL penicillin and 100 \u03bcg/mL at 27\u00b0C.", "Quantitative analyses were performed in triplicate in at least two different assays. Two-way ANOVA and Bonferroni test were performed using GraphPad Prism 5 (GraphPad Software, La Jolla, CA, USA). Differences with p < 0.05 were considered statistically significant." ] },{ "paper_id": "f061e6719f37322dba23bdecaaa47e68fb2c04b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Significance and clinical utility of multiple virus detection by multiplex real-time polymerase chain reaction (rtPCR) in respiratory tract infection remain unclear.", "For each patient, changes of antibiotic management, i.e. either starting or stopping antibiotics, were determined. All other situations were defined as no change.", "To identify patients, the database of the Centre for Laboratory Medicine was searched. Medical records were retrospectively analyzed to obtain basic demographic, clinical, laboratory and radiological parameters and data on clinical management. All chest radiographs (CXR) and computed tomographies (CT) for adults and children were reviewed by a pulmonologist and a pediatrician, respectively." ] },{ "paper_id": "f06986bac5a2e4aaba548056be566362badcde9e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GraphPad Prism 7.0 (GraphPad Software Inc., La Jolla, CA, USA) was used for statistical analyses.", "Porcine epidemic diarrhea virus (PEDV) causes severe enteric illness of swine (PED). The infection results in watery diarrhea, vomiting, and anorexia, which can lead to death in up to 100% of neonatal piglets [1, 2] . Since its first appearance in the 1970s, PED outbreaks have caused enormous economic losses to the swine industry. Nowadays, outbreaks of PED are sporadically reported worldwide with emerging novel strains [3, 4] . PEDV is an enveloped, non-segmented, positive-strand RNA virus, which constitutes the genus Alphacoronavirus of the family Coronaviridae. Its RNA genome encodes replicase proteins and structural proteins including spike (S), envelope (E), membrane (M), nucleocapsid (N), and an accessory protein (ORF3). The virus replicates efficiently in the enterocytes lining the villi of the small intestine, leading to cell death and severe villous atrophy [1] .", "Author Contributions: Conceptualization, A.J.; investigation, methodology, and validation, A.W., J.S., C.K., and K.S.; resources, A.J.; writing-original draft preparation, A.J.; writing-review and editing, A.J. All authors read and approved the manuscript." ] },{ "paper_id": "f06b500cbbffe7641b716dbbb90f0d40ed7839d6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Determining the finite-time transition probabilities involves matrix exponentiation, generally accomplished through an eigen-decomposition of L. Here, we restrict ourselves to infinitesimal rate matrices that yield only real eigen-values and eigen-vectors. Any matrix similar to a symmetric matrix ensures a real eigen-decomposition; consequentially, we formulate", "To map BSSVS into the phylogeography setting, we consider selection among the 2", "Dataset S1 KML file for H5N1 diffusion over time as inferred from HA Found at: doi: 10 ", "With the advent of novel computational techniques like Markov chain Monte Carlo (MCMC) sampling, it has become feasible to integrate many of the models involved and simultaneously estimate parameters of interest. Demographic inference is a wellknown example of genealogy-based population genetics that benefited from these advances [24, 25] . Bayesian MCMC methods also enable ancestral state reconstruction while simultaneously accounting for both phylogenetic and mapping uncertainty. Although this adds much needed credibility to ancestral reconstruction [13] , phylogeographic analysis would benefit even more from fully integrating spatial, temporal and demographic inference." ] },{ "paper_id": "f06dde80e1f11939bb7306853ca92a8c9382ede4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Information recorded on the questionnaires was arranged into Microsoft Excels 2007 spread sheet (Microsoft corporation Berkshire UK). Data was inspected and imported into an SPSS version 19.0 for statistical analysis (SPSS Inc. Chicago USA)." ] },{ "paper_id": "f06f323520d1a5233daf8ef62adb0df997675401", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f071dcbf396ad4171f3984d42f08291385ea9cf7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recently, Tian et al. (2016) developed an attomolar ZIKV oligonucleotide detection method based on loopmediated isothermal amplification and susceptometry. It was demonstrated that hydrodynamic volumes of streptavidinmagnetic nanoparticles were dramatically increased after a successful loop-mediated isothermal amplification reaction. The hydrodynamic volumes are probed as Brownian relaxation frequency shifts, which can be employed to quantify the ZIKV oligonucleotide. The proposed detection system can recognize 1 aM synthetic ZIKV oligonucleotide in 20% serum with a total assay time of 27 min. The results suggested that this could be a promising strategy that may give rise to new possibilities for diagnosing and controlling ZIKV infection.", "Under this subtitle, we intended to elucidate the variety of ways in which liposomes have been used as analytical reagents to date. These methods relying on a tagged liposome could provide numerous ways for signaling molecules to be released to provide a signal. Therefore, it can be stated that these liposomes/immunoliposomes show potential for application in various industrial and medical sectors, including for virus detection through liposome immunoassays.", "MK and SS conceived and designed the review theme. S-YH and SHC helped in writing and reviewing the paper." ] },{ "paper_id": "f07550405043e5c3820e2c85a0b8003b64e8e163", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Results are presented as means6SE of the specified number of samples from 2-3 independent experiments. Comparisons between two populations of data were made using the Student's unpaired ttest with a confidence limit for significance set at 0.05 or less." ] },{ "paper_id": "f0766282327201e2f62b12f14326960106083d73", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All infections were performed in 96-well white clear bottom cell culture microplates unless indicated otherwise.", "In addition, viruses have developed counter-adaptation strategies to escape immune defenses by evading, suppressing or manipulating the host's immune response. Consequently, favorable genetic traits in both hosts and viruses have been naturally selected over time [2] .", "We obtained written informed consent from eligible healthy adult volunteers for blood samples according to a protocol approved by the Massachusetts General Hospital Institutional Review Board." ] },{ "paper_id": "f080c95434a5112c5e2da4e3f93131fed6207fe7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA from tissue was isolated using PureLink Micro-Midi kit (Invitrogen) using manufacturer's protocols and guidelines. RNA quantity was measured by Nanodrop (Thermo Fisher Scientific, Waltham, MA, USA) and integrity confirmed by gel electrophoresis. Samples were precipitated and stored under ethanol at -70\u00b0C. cDNA synthesis was performed on 2 \u00b5g DNAse-treated (Turbo DNA-free\u2122, Ambion, Austin, TX, USA) total RNA using TaqMan \u00ae Reverse Transcription reagents (Applied Biosys-tems, Foster City, CA, USA) and random hexamer primers, according to manufacturer's protocol." ] },{ "paper_id": "f093aa0cf1ddef303ec4c049ab0be105587dd92c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f0b1fa4036434b57c8307d43c39a4193f7e8053a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Zanamivir was purchased as powder (Haosun Pharma, China) and the identity and purity was confirmed by NMR analysis. Zanamivir was either dissolved in carrageenan or placebo solutions, followed by sterile filtration through a 0.22 \u03bcm filter (Sarstedt, Germany). For in-vivo studies all Zanamivir containing solutions were freshly prepared.", "The type of compound interaction was characterized by employing isobolograms (Fig 1) . As described in [62] , isobolograms graphically compare the doses of two compounds needed to reach 50% inhibition to the predicted doses calculated based on a model of drug additivity. A curve linearity of~1 is expected for an additive compound interaction whereas a curve progression <1 argue for synergistic and >1 for an antagonistic compound interaction.", "After the immunostaining cells were stained with 0.005% crystal violet solution to assess the condition of the cell layer and the toxicity of the compounds. IC 50 values and standard deviations were calculated for a sigmoidal dose response model using XLfit Excel add-in version 5.3.1.3." ] },{ "paper_id": "f0c2cd2793d71f1ea11a810442a2c06d5013e899", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "HY performed all the described experiments and wrote the manuscript. YL assisted with some experiments, analyzed experimental results, and edited the manuscript. HW analyzed experimental results. XW reviewed and edited the manuscript. JH, WY, DX, XL, GS, and QN provided experimental help and design." ] },{ "paper_id": "f0c4d40e1879dd1a049298f151940ac168b5f5a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We report the nearly complete genome sequence of a human enterovirus, a strain of echovirus 30, obtained from a cerebrospinal fluid specimen from a teenaged patient with aseptic meningitis in September 2017.", "The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "Data availability. The E-30 sequence of USA/2017/CA-RGDS-1005 has been deposited in GenBank under the accession number MK238483. The quality-filtered FASTQ reads have been deposited in the Sequence Read Archive with the run accession number SRR10082176." ] },{ "paper_id": "f0d935a0e0f1360bf4166b9db8e4cddf67aa9cd7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Poliovirus is the only other virus known to induce degradation of PKR [127] . Although poliovirus RNA and proteins are required, cellular rather than the viral proteases seem to be involved in the degradation [128] . However, the precise mechanism has not been determined yet.", "In the following section we summarize the activating RNA molecules of different virus families, in particular the non-canonical activators established in recent studies such as 5'-triphosphate RNAs and vRNPs of influenza virus. We also give an update on the diverse viral strategies that prevent activation of PKR.", "Activation of PKR by different viral and synthetic RNAs. Latent PKR binds to (1) perfect dsRNA of viral or synthetic origin, (2) synthetic structured RNA with single stranded tails and a 5'triphosphate, (3) HIV-1 TAR RNA or (4) (possibly incomplete) influenza virus vRNP. This leads to dimerization and autophosphorylation of PKR. Active PKR then phosphorylates its substrate eIF2\uf061, which results in a block of translation. PKR consists of two dsRNA-binding motifs (dsRBM1 + dsRBM2 in light green) and the N-terminal and C-terminal lobe of the kinase domain (dark green).", "Historically, PKR was identified as the protein kinase responsible for translation inhibition in response to synthetic dsRNA polyinosinic acid: polycytidylic acid (poly(I:C)) or viral dsRNA derived from vaccinia virus or poliovirus infected cells [18] . Actual binding of PKR to dsRNA was first shown by partial purification of PKR using poly(I:C)-Sepharose [22] . Later studies concluded that PKR requires a minimum of 33bp of perfect dsRNA for induction and around 80 bp and longer for optimal activation [23] . Binding of dsRNA shorter than 33 bp did not activate PKR, but rather inhibited activation by long dsRNA [23] . However, experimental data have accumulated indicating that the range of nucleic acids capable to activate PKR is considerably broader than was originally appreciated (Figure 1 ).", "Many RNA and DNA virus families have acquired one or more gene product(s) that reduce the induction of the latent kinase PKR or phosphorylation of its substrate eIF2\uf061 by very diverse mechanisms. Research in the past decade has revealed that the capacity to antagonize this cellular defence is an important aspect of the virulence and/or host specificity of these viral pathogens. There is recent evidence for rapid evolution of PKR genes in primates and positive selection at specific amino acid sites, supporting the view that this kinase evolves under the constant pressure of antagonistic viral gene functions [151, 152] . Although a lot of information has accumulated on PKR, a number of questions remain concerning the biology of this conserved kinase. These include the precise sequence of events leading from the latent, monomeric, form to the fully phosphorylated dimer, whether allelic differences in PKR are associated with different susceptibility to certain viruses, and the precise roles of several of its cellular interaction partners. A particular technical challenge concerns the characterization of structures within natural viral nucleic acids, which trigger PKR activation inside cells. Clearly, research directed to close these gaps in our knowledge will provide valuable insights into the ongoing arms race between viral pathogens and their hosts. ", "Another RNA that has been considered to be a potential PAMP is the 5'triphosphate containing leader RNA that is transcribed from the most promoter-proximal gene of the Paramyxo-, Rhabdo-and Filoviridae genome [87, 88] . The leader RNA is not encapsidated until substantial amounts of nucleoprotein have accumulated and it has been implicated in activating RIG-I mediated IFN induction by measles virus [89] . However, work by Bitko et al., indicated that the leader RNA of the respiratory syncycial virus and Sendai virus is shielded from RIG-I in a complex with the cellular La protein [90] . No studies have been conducted so far to test whether leader RNA might activate PKR." ] },{ "paper_id": "f0db088c90145abdb3d3709fa3beda244c80f100", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data availability. Sequencing data have been deposited in ArrayExpress (http://www.ebi.ac.uk/ arrayexpress) under the accession number E-MTAB-7849. ", "(This article was submitted to an online preprint archive [28] .)" ] },{ "paper_id": "f0dbc87d51c4d8a07ff83c5fc53afac5f973a20a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f0e6cef57dbae030aea2f324e21e00945ac659cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "N H O H N O OH 1 2 R 1 R 3 R 2 Comp. R 1 R 2 R 3 MIC [ g/mL] MBC [ g/mL] 1 2 3 4 1 2 3 4 1a 5-Cl 4-CH 3 (S)-CH 3 >256 >256 >256 >256 >256 >256 >256 >256 1b 5-Cl 4-CH 3 (S)-CH(CH 3 ) 2 >256 >256 32 32 >256 >256 128 >256 1c 5-Cl 4-CH 3 (S)-benzyl >256 >256 >256 >256 >256 >256 >256 >256 1d 5-Cl 4-CH 3 (R)-CH 2 -indolyl >256 >256 >256 >256 >256 >256 >256 >256 1e 5-Cl 4-OCH 3 (S)-CH(CH 3 ) 2 >256 >256 >256 >256 >256 >256 >256 >256 1f 5-Cl 4-CF 3 (S)-CH(CH 3 ) 2 4 2 2 2 4 4 8 4 1g 4-Cl 4-Br (S)-CH(CH 3 ) 2 8 4 4 4 1 6 8 8 8 1h 4-Cl 3,4-Cl (S)-CH(CH 3 ) 2 2 1 1 1 4 1 4 2 1i 4-Cl 3,4-Cl (S)-benzyl 1 1 0.5 0.5 8 1 8 1 AMP - - - >16 >16 >16 0.25 >16 >16 >16 0.25 CPX - - - >16 >16 >16 0.5 >16 >16 >16 0.5 VAN - - - 2 1 1 1 2 1 1 1", "The antibiotic resistance of invasive pathogens has become one of the most challenging and persistent health problems [1] . Methicillin-resistant Staphylococcus aureus (MRSA) has become the most common clinically relevant multiresistant pathogen [2] causing both healthcare-associated and community-acquired bloodstream infections with mortality rates up to 40% [3] .", "Bactericidal activity is defined as a ratio of MBC to MIC of \u22644 [32] . Table 1 bactericidal activity is expressed in bold." ] },{ "paper_id": "f0f627b8e856fdf97cf414ac42f3536ff1a33134", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sixteen female and 16 male, Chinese-origin, purpose-bred rhesus macaques (Macaca mulatta) of approximately 30 months old were housed at CIT in a dedicated primate unit (temperature of 24\u00b0C\u00b1 3\u00b0C; humidity of 50\u00b1 20%; light/dark cycle of 12 h/12 h). Animals were housed in custom-build group-housing cages (L:1.55 m \u00d7 D: 1.55m \u00d7 H: 2.5m; Volume: 6 m 3 ) with grid floors (up to 6 animals/cage). All macaques had free access to tap water and received a daily ration of 180 g of OWM (E) SQC SHORT expanded diet (Dietex France). In addition, fruits and/or vegetables and plastic toys were given daily as enrichment. Mean body weights were 3 kg (range: 2.3 to 4.2 kg) for males and 2.7 kg (range: 2.2 to 3.1 kg) for females.", "The mouse study was carried out in strict accordance with the European regulations (in particular Council directive N\u00b086/609/EEC) regarding the protection of animals used for experimental purposes, in GSK's animal facilities in Rixensart, Belgium (AAALAC-accredited). The GSK institutional ethical committee reviewed the protocol (approval number 07/142/01/A).", "However, the distribution of mucosal cellular responses among anatomical compartments after IM immunization with Ad vector-based SIV vaccines was previously shown to be comparable between these two models [18, 19, 73] ." ] },{ "paper_id": "f0f89b444071b6fa4be64b86e5d70a4cab8cb492", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nunc MaxiSorp plates (Thermo Fisher Scientific, Waltham, MA, USA) were coated with 1 \u00b5g/mL ZIKV E or EDIII protein and incubated overnight at 4\u00b0C. After blocking for 2 h, the plates were incubated with cultured media containing antibodies at a 1:2 dilution or with a serial dilution of purified mAbs with a blocking buffer. The plates were washed six times with phosphate-buffered saline (PBS). The secondary antibody (goat anti-human IgG, Cat. No. ab6858; Abcam, Cambridge, UK) was applied at a 1:5000 dilution in blocking solution. The plates were incubated at 25\u00b0C for 1 h then TMB substrate was added. Absorbance was measured at 450 nm on a BioTek Synergy HTX Multi-Mode Reader (Winooski, VT, USA).", "IgH repertoires showed dramatic dominant clonal expansion at the early stages of infection but recessed to a steady state by six months", "The Zika virus (ZIKV) is a member of the Flaviviridae family mainly transmitted by Aedes mosquitoes [1] ; however, it is also reported that the virus can be transmitted through both sexual contact and blood transfusions [2, 3] . Clinical evidence shows that ZIKV can cross the placental barrier and cause microcephaly in developing foetuses and neurological complications in adults such as Guillain-Barre syndrome [4, 5] . The ZIKV envelope (E) protein mediates viral attachment to the host cell and fusion with cell membranes [6] ." ] },{ "paper_id": "f0fb3bbd96dad4c907c7fd456cd5783ed8fa7bd6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Escherichia coli strains were routinely grown in Luria-Bertani broth or plates, supplemented with appropriate antibiotics. Chloramphenicol was used at a final concentration of 20 mg/mL for agar plates and 10 mg/mL for liquid cultures. Ampicillin was used at a final concentration of 100 mg/mL. Kanamycin was used at a final concentration of 20 mg/mL. Cloning was carried out using E. coli DH5a, overexpression was performed in E. coli Rosetta(DE3) pLysS (Novagen). C. difficile strains were grown in a glucose-free trypton-yeast based medium (TTY; 3% w/v bactotrypton (BD), 2% yeast extract (Fluka), 0.1% w/v thioglycollate (Sigma) pH 7.4), supplemented with 20 mg/mL of lincomycin when appropriate, or on CLO or TSS plates (Biomerieux).", "Plasmid pWKS1245, for the production of full length Spo0A carrying a C-terminal 6xHis-tag, was constructed in a similar manner using chromosomal DNA from C. difficile 630Derm as a template, but using the PCR product of primers oWKS-1122 and oWKS-1123a.", "Statistical significance was evaluated with an independent sample t-test." ] },{ "paper_id": "f10e409ed733f8ca5e49e4ebd0482663328f2267", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "histopathology Samples from nasal turbinates, trachea, and lungs were collected, fixed in 10% buffered formalin and processed for histopathology, i.e., they were dehydrated through graded alcohols and embedded in paraffin. The 3-\u00b5m thick sections were cut, stained with hematoxylin-eosin and examined in a \"blind-fashion\" manner. In particular, we aimed to evaluate bronchiolar epithelial changes and peribronchiolar inflammation in large, medium, and small or terminal bronchioles, as well as inflammatory changes in alveoli. In the lung, bronchointerstitial pneumonia intensity was assessed by means of a semi-quantitative lesion score. The pathological scores for tracheal and pulmonary tissues were as follows: 0: no lesions, 1: mild lesions, 2: moderate lesions, 3: severe lesions.", "Acute phase proteins (APP) of pigs (Haptoglobin and Serum Amyloid A, SAA) were investigated in BALF samples by commercial colorimetric kits (Haptoglobin kit, Tridelta Development, code TP801. Multispecies SAA ELISA Kit, Tridelta Development, code TP802), according to the manufacturers' directions.", "acKnOWleDgMenTs" ] },{ "paper_id": "f11b19a9e1845ff5ab66a42d5409f8caed24faa1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sample collection and sequencing of a cDNA library produced from female Syrian hamster organs", "GS FLX sequencing generated 1,283,840 reads with an average length of 344 bases. Raw reads were trimmed for quality and reads shorter than 40 bases were discarded. The sequencing resulted in 1,212,395 reads of a total length 426,683,712 bases.", "This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.", "The distogram represented in figure 4A was constructed using the ''squash'' package [40] of the R suite [41] . This representation is a color-coded, rotated triangular matrix indicating the distance between every pair of species in term of number of aligned sequences shared." ] },{ "paper_id": "f123d4b1f4b4e7a2f4fab9605258fbe053a2abd1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "The cytoplasmic HBV capsid particles were resolved in native agarose gel by electrophoresis and transferred onto nitrocellulose membrane, followed by capsid enzyme immunoassay assay (EIA) using antibodies against core (DAKO) and in situ HBV DNA hybridization as described previously [60] .", "HBeAg and HBsAg in culture fluid were detected by HBeAg ELISA kit (Autobio Diagnostics) and HBsAg ELISA kit (Abazyme) following the manufacturer's instructions." ] },{ "paper_id": "f1301ca67dfb936ebc49c73777088997c3fc23a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pentamidine analogues with activity better than that of melarsoprol and/or pentamidine", "In the early 1970s Dann O et al [30] [31] [32] Fig. 6 .", "Novel medicines are typically developed using a trial-and-error approach, which is timeconsuming and costly but yet has the potential to yield new drugs. The application of computer-assisted drug design (CADD) methodologies to this problem has the potential to greatly decrease the time and effort required to discover new medicines or improve current ones in term of their efficacy.", "Polyamines are generally involved in growth and differentiation [64] [65] [66] [67] within the cell and their analogs are also used as anticancer agents, antiparasitic agents, antidiarrhoeals, anti-HIV agents, metal chelators, and gene delivery agents. Since the inhibition of the initial polyamine biosynthesis enzyme, ornithine decarboxylase, by DL-\u03b1-difluoromethylornithine (DFMO) is toxic to African trypanosomes cells, [68, 69] polyamines can become a promising anti-trypanosomal compound." ] },{ "paper_id": "f13c88733ea45be9e923a282dfd42f8c277c187c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "These studies have provided a knowledge base to further develop the HRV experimental model and provide a controlled and useful tool to develop new therapies for the disease areas associated with HRV infection. New treatments for asthma and COPD are urgently needed, and small animal models of asthma are poorly predictive of efficacy. Most drugs that are effective in these animal models are not found to be effective in later stages of development in humans. Models that more closely follow clinical features of human asthma and COPD are needed [32, [147] [148] [149] [150] [151] ].", "This review aims to describe the Human Viral Challenge model; its history, its utility and specifically how it has recently been, and can be used, to potentially accelerate the development of novel therapies for the unmet medical needs of respiratory disease." ] },{ "paper_id": "f14e7b5fff3c2ac074e61beacf4fb1bba524e438", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data are expressed as the means \u00b1 SEM. Differences between groups were assessed by Students's t-test. A probability p < 0.05 was considered significantly different. When ANOVA indicated a significant difference, the Bonferroni post hoc test was then used to assess the difference between groups. All analyses were performed using the Statistical Package for the Social Sciences statistical software for Windows, version 16.0 (SPSS Inc., Chicago, IL, USA).", "The human basophilic cell line KU812 cells (American Type Culture Collection, Manassas, VA, USA) were maintained in RPMI-1640 medium supplemented with 10% (v/v) FBS (RPMI-1640 complete medium). Cells were incubated at 37 \u00b0C in atmospheric air enriched with 5% (v/v) CO 2 . At 70-80% cell confluence, cells dispersed in RPMI-1640 complete medium to a final cell concentration of 10 \u00d7 10 5 cells/ml for further treatment." ] },{ "paper_id": "f1541ead6bf6988b4d08b12873806a89a4b7ff1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No permits were required for the described study, which complied with all relevant regulations." ] },{ "paper_id": "f1570e2dfd60e3bc423fede19c89171ac06da885", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using GraphPad Prism for Windows, Version 4.03 (GraphPad software, San Diego, CA, USA). Changes over time (same group, different time points) were tested using the Wilcoxon signed rank test for paired samples (p W ) or the Friedman test for multiple samples (p F ) with Dunn's posttest (p D ). Multiplicity adjusted p-values for each comparison in a family of comparisons were computed. The frequencies were compared using the Fisher's exact test (p Fisher ). The differences between groups A and B were compared using the Mann-Whitney U-test (p MWU ), and the differences between all three groups were tested using the Kruskal-Wallis test (p KW ). A p-value <0.05 was considered to be statistically significant." ] },{ "paper_id": "f161447bea90a1e414e3cb22557efe9156bab8e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rapid detection and identification of infectious pathogens are necessary for proper treatment of infection and outbreak control measures.", "Many promising approaches are being developed enabling rapid identification of various infectious pathogens such as bacteria or viruses including multiplex (RT)-PCR amplification strategies or novel technologies such as high-performance electrospray ionization mass spectrometry [1, 2] ." ] },{ "paper_id": "f16da7cf7a952fb981dfc0d77280aac9c3ab933a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ebolaviruses (EBVs), according to Kuhn et al. classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .", "As the ecology of most Africa bats is unknown, other opportunities exposing bat to potential maintenance hosts may be discovered in the future. For example, some bat species feed on fish [86] and, more recently, using stable isotopes of carbon and nitrogen as dietary tracers, it was demonstrated that a bat species, Nyctalus lasiopterus, was seasonally feeding on migrating Palearctic birds [87] , a feeding behaviour unknown until now. Failed predation on bats could also be a rare opportunity for infectious transmission [52] ." ] },{ "paper_id": "f17288f985aa9c44a23132028973162a800726f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Test compounds. Recombinant gp120 from HIV-1(III B ), produced in CHO cells, and HIV-1(YU2), produced in insect cells, were purchased from Immunodiagnostics (Woburn, MA). \u2423-1,2-Mannobiose and \u2423-1,3mannobiose were purchased from Dextra (United Kingdom). Laminin, from human placenta, and mucin, partially purified from porcine stomach, were purchased from Sigma, while BSA-GlcNAc was purchased from Dextra Laboratories (United Kingdom).", "Citation Ielasi FS, Alioscha-Perez M, Donohue D, Claes S, Sahli H, Schols D, Willaert RG. 2016. Lectin-glycan interaction network-based identification of host receptors of microbial pathogenic adhesins. mBio 7(4):e00584-16." ] },{ "paper_id": "f176cd025d08014cfb69f9d2b28e92b19a1a7522", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dihydrotanshinone, a lipophilic compound, showed a decimal reduction at 0.5 \u00b5g/mL and excellent antiviral effects at \u22652 \u00b5g/mL with a reduction in titer from 6.5 Log to 1.8 Log TCID 50 /mL by using a pseudovirus expressing MERS-CoV spike protein ( Figure 5(8) ) [36] .", "Polyproteins pp1a and pp1b are processed by 3CLpro (11 cleavage sites) and PLpro (3 cleavage sites), resulting in 16 mature nonstructural proteins, including RNA-dependent RNA polymerase (RdRp) and helicase, which play important roles in the transcription and replication of coronaviruses [40, 52] . Therefore, both proteases are essential for viral replication, making them attractive targets for drug development [52] .", "The authors declare no conflict of interest." ] },{ "paper_id": "f18489a27432115deff5b9be2dd2e0af9d8409a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was approved by the Research Ethics Committee at PKUPH and met international biomedical ethics guidelines. Both the Hospital and the Biostatistics Department of Peking University Health Science Center supervised the acquisition of data. The written consent was given by the patients and the next of kin for their information to be stored in the hospital database and used for research." ] },{ "paper_id": "f18afbc0a4621e7f13dcfbc67c85bf8dfe3b30ea", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Plasmids pPol I-LZH, pPol I-MZH, and pPol I-SZH carrying the L, M and S segments of ZH548, respectively, were cloned in the plasmid pRF108, [24, 36] . The plasmid pPol I-SZHDNSs, derived from pPol I-SZH, carries two BbsI cloning sites in place of NSs [24] . The humanized Renilla reniformis luciferase sequence from phRL-SV40 (Promega, Charbonni\u00e8res-les-Bains, France) was inserted in pPol I-SZHDNSs to give pPol I-SZHDNSs-hRLuc. The structure of pPol I-SZHDNSs-hRLuc plasmid was confirmed by sequence analysis. Recombinant rZHDNSs-GFP [24] and rZHDNSs-hRLuc RVFV stocks were produced under BSL3 conditions. Approximately 5610 5 BHK21/T7 cells were seeded in triplicate in 35 mm culture dishes. The following day, they were combined with FuGENEH6 transfection reagent (Roche Applied Science, Indianapolis, IN) and 0.5 mg each of pTM1-L and pTM1-N [25] , and 1 mg each of pPol I-LZH, pPol I-MZH, and either pPol I-SZHDNSs-GFP or pPol I-SZHDNSs-hRLuc in OptiMEM (Gibco, invitrogen, Carslbad, CA). One day later, the medium was renewed. Five days later, the supernatant containing the rescued virus was collected and stored at 280uC. To produce" ] },{ "paper_id": "f18b80a866dfde9b2c219a73f3721237a8da5063", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Complete raw and normalized microarray data and their MIAME compliant metadata from this publication have been submitted to the GEO database (www.ncbi.nlm.nih.gov/geo) and assigned the identifier GSE111947." ] },{ "paper_id": "f19e6df5a006cb83449f1ec0dd16a9aa6703b0dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus infections continue to pose major public health concerns with the possibility of epidemics and pandemics [1] . A recent outbreak of Ebola virus in 2014 and the global circulation of the pandemic influenza of swine origin (pH1N1) in 2009 resulted in numerous deaths and hospitalizations [2, 3] . Middle East respiratory syndrome (MERS) transmitted from camels to humans, and the human to human infections are being amplified in nosocomial setting in addition to direct household or community-wide transmissions [4, 5] . In addition, although probably less deadlier than Ebola virus, a foodborne noroviral infection causes gastroenteritis in humans, claiming millions of illnesses and hospitalizations, with occasional mortalities [6] . Most of emerging viral diseases are zoonotic in nature, posing unmet needs for personal hygiene and disinfectants for both humans and livestock.", "MDCK (Madin-Darby Canine kidney) were obtained from ATCC (American Type Culture Collection) and cultured in MEM (minimal essential medium, HyClone) supplemented with 10% FBS (fetal bovine serum, HyClone), at 37\u00b0C in 5% CO 2 . Influenza virus A/Puerto Rico/8/34 (H1N1) (PR8) viruses were propagated in 11day-old chicken embryos. The allantoic fluids were harvested and filtered by a syringe filter with a pore size of 0.2 \u03bcm and stored at a freezer (\u221280\u00b0C) until use." ] },{ "paper_id": "f19f2b01d3520c10962617e9f078ff9a5a850c88", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "As shown in (Table 3) .", "2. Sanction and punish all parties involved in organ trade and brokering." ] },{ "paper_id": "f1a107788ce585f3f5a7daa6b2eaf55997935192", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Written informed consent was obtained from the owners of the two farms for the publication of this report and any accompanying images.", "According to the gross and histopathological lesions, eight suspected viruses were detected. Total RNA and DNA were extracted from liver, lung, kidney, brain, and spleen specimens using the UltraPure\u2122 RNA Kit and the General AllGen Kit (CWBIO, Beijing, China), according to the manufacturers' instructions. The extracted RNA " ] },{ "paper_id": "f1a9bb377e28527cda63947734bbd74fe64207a5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background 3", "Lines 373\uf02d\uf033\uf038\uf032", "Housing and husbandry 9" ] },{ "paper_id": "f1b81916fac1ca3d50dde774df2e1bb26bf0fb39", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using GraphPad Prism 5.0 (San Diego, USA). One-way ANOVA followed by Tukey's post-hoc test or unpaired t-test was used for the evaluation of a minimum of three independent experiments. The numbers of independently performed experiments (n) are stated in the corresponding figure legends. p 0.05 was considered as statistically significant. Data are expressed as mean \u00b1 standard error of the mean (SEM).", "In the field of cancer research several studies reported on interesting pharmacological effects of archazolid: It reduced the migration of different invasive tumor cells in vitro and cancer cell metastasis in vivo in a breast tumor mouse model [15] . Furthermore, archazolid activated pathways of cellular stress response and apoptosis in highly invasive tumor cells [16] . In classically activated macrophages, archazolid selectively induced the generation of tumor necrosis factor \u03b1 (TNF\u03b1), which may indirectly promote tumor suppression [17] .", "CytoTox 96 Non-Radioactive Cytotoxicity Assay (Promega) was performed according to the manufacturer's instructions for determining the lactate dehydrogenase (LDH) release after treatment with archazolid. Lysis buffer was added to untreated cells 45 min before the end of treatment to induce the release of this enzyme. LDH is a cytosolic enzyme that is released by leaky cells. Released LDH catalyzes the enzymatic conversion of lactate to pyruvate which provides NADH for the conversion of iodonitrotetrazolium violet into a red formazan product in the presence of diaphorase. The absorbance was measured with a Varioskan Flash microplate reader (Thermo Fisher Scientific) at 490 nm." ] },{ "paper_id": "f1d308db379b3c293bcfc8fe251c043fe8842358", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reactivity for rNP from LASV LCMV JUNV anti-LASV NP", "Purified rNPs. The expression and purification efficiency of arenavirus rNP were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) after staining the gels with Coomassie blue. Purified NP antigens with approximate molecular weights of 62 kDa from Luna, LCM, Lassa, Lujo, Junin, Machupo, Guanarito, Sabia, and Chapare viruses and the purified negative control antigen (\u0394P) are shown." ] },{ "paper_id": "f1d456ea268266ff3c21317c4190e4fcb49b5e4f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Previous studies have suggested that viral respiratory infections and norovirus outbreaks are a common cause of hospitalization or death, particularly among elderly individuals [3] [4] [5] .", "Each site was geographically independent and autonomous for social and care management. Units were located within the larger sites and were defined as a place having a dedicated team at one location.", "GE was defined as the sudden onset of vomiting and/or diarrhea over a 24 h period: (i) diarrhea \ufffd3 episodes, (ii) and/or vomiting \ufffd3 episodes, (iii) or diarrhea or vomiting <3 episodes with two or more other symptoms (diarrhea, vomiting, stomach ache, abdominal cramps, nausea, fever, mucus in stools) [1] ." ] },{ "paper_id": "f1d92c740ecb6d711507ed6e483472c8e1ecb3a6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Parasite species 2", "Adamo, S., and J. P. Webster 2013. Neural parasitology: how parasites alter host behaviour. Journal of Experimental Biology 216:1-2." ] },{ "paper_id": "f1e1e2511e051195c8327a56d5c311a2dd4ab6b3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As newly emerging or re-emerged viruses such as SARS-CoV, MERS-CoV, and ZIKV have become a major threat to public health, the need for broad-spectrum antiviral drug has increased. In this regard, nucleoside analogs that directly target viral RNA-dependent RNA polymerase and present a high barrier to the development of resistant viruses have been considered advantageous. Moreover, recent discovery of a new antiviral mode of nucleoside analogs acting through innate immunity strengthens the molecular basis for their therapeutic application as broad-spectrum antiviral drugs.", "Nucleoside analogs have been historically used for anti-cancer chemotherapy because they inhibit cellular DNA/RNA polymerases [1] . More recently, nucleoside analogs have expanded their therapeutic applications and are being used to develop antiviral drugs against a wide range of serious and life-threatening viruses. Some nucleoside analog drugs targeting specific viral polymerases (acyclovir for herpesviruses, zidovudine for human immunodeficiency virus (HIV), and sofosbuvir for hepatitis C virus (HCV)) have been successful in clinical trials [2] [3] [4] [5] and are currently in use for the treatment of virus-infected patients. Another class of nucleoside analog drugs such as ribavirin, more broadly-acting on various viruses, has been used in conjunction with IFN-\u03b1 [6] . Importantly, extensive studies on the antiviral action of ribavirin have established the underlying molecular framework of nucleoside analogs.", "Nucleoside analogs probably induce different subsets of ISGs, at least with a different pattern, leading to various combinations of ISGs and resulting antiviral outcomes. Moreover, according to Schoggins et al., different viruses are affected by distinct subsets of ISGs and some ISGs such as IRF1, MB21D1, HPSE, DDX58, MDA, and IFITM3 act broadly on various viruses [45] . Thus, more systematic analyses on the subsets of ISGs induced by antiviral nucleoside analogs are required for the identification of better antiviral drugs that can be used broadly or specifically. Given the clinical side effects of IFN treatment, nucleotide analogs that differ from IFN in the activation of subsets of ISGs need to be considered as alternatives. Nevertheless, nucleoside analogs interfering with the host nucleotide synthesis pathway suggest possible side effects in their clinical applications. Careful evaluation of clinical safety is required and their application for the urgent measure of patients infected with deadly viruses would be worth being primarily considered." ] },{ "paper_id": "f1f24521928f5d8565a15a17bd7f79239a3d4116", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Scientific World Journal of treatment more complicated [4] . The highly regulated programmed cell death process of apoptosis is a matter of great interest in oncology and cancer therapy and represents a common molecular pathway for drug resistance and carcinogenesis [5] .", "Cancer is a debilitating disease that afflicts a substantial portion of the world population in all generations and is a major health problem of global concern [1] . Among the various types of cancer, colorectal cancer is the second and third most prevalent cancer among males and females in the United States, respectively. In spite of all the considerable progress in protective methods and recent improvements in screening techniques and chemotherapy, the 1-year and 5-year relative survival rates for patients suffering from colorectal cancer are 83.2% and 64.3%, respectively [2] . In addition, due to bitter controversy over optimal methods for early detection, full compliance of patients with screening recommendations remains a major hindrance for diagnosis at the early stages of cancer development. Development of resistance to chemotherapy also represents a critical issue for which simultaneous treatment with various classes of therapeutics to reduce the resistance has yielded some success [3] . Moreover, the numerous side effects of chemotherapeutic drugs on cancer patients, including hair loss, diarrhea, bleeding, and immunosuppression, have made the process 2", "The critical factors for monitoring the cell health, namely, cell loss, changes in cell permeability, cytochrome release, mitochondrial membrane potential changes, nuclear size, and morphological changes, were studied using a Cellomics Multiparameter Cytotoxicity 3 Kit as described in detail previously [20] . Plates with stained cells were analyzed using the ArrayScan HCS system (Cellomics, PA, USA).", "All the experiments were performed at least three times independently. The results were presented as the mean \u00b1 standard deviation (SD) of the number of experiments shown in the legends. An analysis of variance (ANOVA) was carried out using the prism statistical package (GraphPad Software, USA). < 0.05 was considered statistically significant." ] },{ "paper_id": "f217296b50c75def2bfed98fec3db692e9339f70", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "acknowledgments section [29] . Opinions diverge over whether data providers should review results before publication, collaborate on the analysis, approve the analysis plan in advance, or limit conditions of data reuse [30] . Community-wide standards are needed so that the risk of uncredited secondary analysis will not dissuade scientists from sharing.", "Pharmaceutical company leaders acknowledged that \"depending on the circumstances for the emergency, preliminary data could be made available with clear descriptions of the verifications that are ongoing and the remaining risks to data integrity\" [23] . WHO officials noted that research teams generated and exchanged critical data for novel vaccines faster than ever [24] ." ] },{ "paper_id": "f223f427cbdd077ec84931fad74fb3a7a46fbc67", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Drs. Jixin Zhong, Quan Gong, Aditya Goud, and Srividya Srinivasamaharaj declare that there is no conflict of interests. Dr. Sanjay Rajagopalan has received funding from Takeda Pharmaceuticals.", "Altered expression of soluble DPP4 is commonly seen in many disorders such as solid tumors, autoimmune diseases, hepatitis C, type 2 diabetes (T2DM), and obesity [10] [11] [12] .", "In addition to its peptidase activity, DPP4 also possesses noncatalytic function via interactions with a range of ligands including ADA, caveolin-1, fibronectin, coronavirus spike protein, collagen, glypican-3, insulin-like growth factor 2 receptor, fibroblast activation protein, and CXCR4. By interacting with these ligands, DPP4 plays a role in a variety of processes such as enhancing T cell activation and functional modulation of antigen presenting cells (APCs)." ] },{ "paper_id": "f226ecb8f7484ca7943245de562c6f2f08be80a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To create animations of viral dispersion over time, annotated MCC trees were converted into a keyhole markup language (KML) file using SPREAD3 (v0.9.6). The KML file can be visualized with an open-access Earth map downloaded from Natural Earth (http://www. naturalearthdata.com) as a QGIS software base layer.", "Supporting information S1 ", "Conceptualization: Yu-Ching Lan. " ] },{ "paper_id": "f22bc1c655de9adc805c72dcccbb9ca43dc2ee5a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sequence nomenclature on the phylogenetic trees is country of origin (_sample source for Kilifi indicating if sampled from inpatient (IP) or household (HH))/Unique identifier/Date of specimen collection. The unique identifier for household samples includes the household identifier (first two digits) and subject identifier (the last two digits). All new sequences from this study were deposited in GenBank under the accession numbers KX510136-KX510266.", "The potential transmission networks within and between households were inferred in PopART package v1.7.2 (http:// popart.otago.ac.nz/index.shtml). The networks were reconstructed using median joining trees (MJT) method with an epsilon of zero.", "The samples analyzed in this study were collected following an informed written consent from each individual participant if aged !18 years or through a guardian or parent if aged <18 years and all children assented to participate. The study protocol was reviewed and approved by both the Scientific and Ethics Review Unit (SERU) of the Kenya Medical Research Institute (KEMRI), Nairobi, and Coventry Research Ethics Committee, UK (Munywoki et al. 2014 )." ] },{ "paper_id": "f23dfb23efee3476cb3f07e1e2606d2788ef7c02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f243e05a2d51029218e0c313b20fa57c65104a62", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Currently there are no approved drugs with which to treat EBOV patients. Consequently, during the recent outbreak several agents were administered to patients on a compassionate care" ] },{ "paper_id": "f2615e2f1b1e1de90023706bf99405151406bbd8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The " ] },{ "paper_id": "f261de4ce70f551ec9bdc573256bef4a61f43174", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results show that our automatic method is not only time-efficient but also produces consistent prediction results as human observers.", "Multi-tasking refers to the capability of solving many tasks simultaneously. The current advances of artificial intelligence outperform human beings in effortlessly handling multiple tasks without switching costs. There are a couple of mainstream techniques for solving multi-tasking problems.", "To this end, we made the following contributions:", "The model is trained on COCO dataset for 160k iterations, starting from a learning rate of 0.02 and reducing it by 10 at 60k and 80k iterations. In RPN network, we use 5 scales with box area of the square of 32, 64, 128, 256 and 512 pixels for anchors and 3 ratios of 0.5, 1, 2. There are 256 anchors per image to use for training in total. The Faster R-CNN outputs the individual detection results. The average time cost for this task is 0.011 s.", "SG conceived, designed the analysis, and wrote the majority of this manuscript. MJ and XG conceived, designed the analysis, and revised the manuscript. XS conceived the analysis and participated in the writing of the manuscript. JY and HW collected and performed the analysis. FX read and revised the manuscript. " ] },{ "paper_id": "f2659bd84b8347a97b54698fbc1dea43ef10a85e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GFPdgn direct fluorescence of cryosections from paraformaldehyde fixed mouse livers, and the TUNEL or DAPI labeled fluorescence in cryosections were visualized using a Zeiss Axiovert 200M epi-fluorescence microscope (Carl Zeiss MicroImaging GmbH, Germany).", "For co-immunoprecipitation, the proteins (400\u00b5g) solubilized in RIPA lysis buffer were incubated respectively with primary antibody against Bim, Bcl2, or Bax (2\u00b5g/ml) at 4\u00b0C for 3 hours and precipitated with protein-A/G-Sepharose (Santa Cruz) at 4\u00b0C for 2 hours. After centrifugation, the pellets were washed with RIPA buffer for four times. The immunoprecipitates dissolved in SDS-sample buffer were analyzed by western blotting.", "All quantitative data were presented as mean \u00b1 SD unless otherwise indicated and analyzed using Student t-test for unpaired two group comparison. A p-value <0.05 is considered statistically significant." ] },{ "paper_id": "f2775e93528da5c439a57c542b520d873c8d3e4e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "EH, SF, HH, and ME designed the study, EH, SF, DT, HH, and ME collected the data, EH and SF analyzed the data, EH, SF, HH, and ME wrote the manuscript. All authors approved the final version of the manuscript.", "The study was funded by the Leibniz Institute for Zoo and Wildlife Research and the DFG Research Training Group 2046 \"Parasite Infections: From Experimental Models to Natural Systems\" (SF).", "Raw data has been deposited under accession number PRJNA386767 at NCBI Short Read Archive (SRA).", "To alleviate primer bias and handling problems arising from primers targeting mainly food items we used a multiamplicon sequencing approach (Heitlinger, 2017) . To assess to what extent these methods provide a quantitative estimate of the abundance at a particular level of resolution achieved between taxa, we correlated FEC or FOC with sequence reads." ] },{ "paper_id": "f287cdbc6b706443ee5c1a1e50050515d8a613c7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total amount of three mg total RNA per sample was aliquoted and later prepared a small RNA (sRNA) library. For sequencing library generation, NEBNext \u00d2 Multiplex sRNA Library Prep Set for Illumina \u00d2 (New England Biolabs, Ipswich, MA, USA) was used as per manufacturer's directions. The adding of index codes was done to assign sequences for each sample performed. TruSeq SR Cluster Kit v3-cBot-HS (Illumina, San Diego, CA, USA) was used to performing the clustering of index-coded samples. The libraries were sequenced on an IlluminaHiseq 2000 machine to generate the 50 bp single-end reads. The whole process of sequencing was performed at Novogene.", "The seed region, position 2-8 of a mature miRNA, was identified by aligning all sRNA tags to mature miRNA. Only one nucleotide mismatch at the seed region was permitted.", "The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers):", "The 1% agarose gels were run to check the RNA degradation/contamination. RNA purity was verified using the NanoPhotometer \u00d2 spectrophotometer (Implen, Inc., Westlake Village, CA, USA) and performed by Novogene Experimental Department (Novogene Genomics, Singapore). RNA integrity together with quantitation were evaluated with RNA Nano 6000 Assay Kit of the Agilent Bioanalyzer 2100 system (Agilent Technologies, Santa Clara, CA, USA).", "Statistical analyses were performed using the R software version 3.5.1/R studio version 1.1.456. The graphic illustrations were also generated by VennDiagram, calibrate, datasets, ggplot2, viridis R packages. The coefficient of determination (R 2 ) and Z-score were computed by R and the heatmap.2 function of the gplots R package. Differential expression analysis was carried out using DESeq2. Chord diagram pairwise correlations between clusters were visualized as chord diagrams in R using the circlize package. For dimensionality reduction visualizations, we used the t-SNE algorithm (Van der Maaten & Hinton, 2008). FDR was used for p-value correction (Benjamini & Hochberg, 1995) . The p-value of < 0.05 considered to be statistically significant.", "This study was financially supported by an internal research grant from the Faculty of Veterinary Medicine, Chiang Mai University (Grant No. R000017857) to Phongsakorn Chuammitri, and by Center of Excellence in Veterinary Biosciences (CEVB Grant No. R000020850), Chiang Mai University, Chiang Mai, Thailand (to Phongsakorn Chuammitri). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." ] },{ "paper_id": "f28c1e92be3354c2df1cb282177ef962c3b5c9c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The \u03b2 1 -selective \u03b2-adrenoceptor blocker esmolol is a class II antiarrhythmic drug which has been developed to treat supraventricular tachycardia. After intravenous application esmolol has a short half-life of 9 min. It is rapidly hydrolyzed by plasma esterases, which makes this drug well manageable.", "Several other pharmacological additives have been tried in clinical settings to minimize organ dysfunction after CPB.", "AS wrote the manuscript. SD wrote and edited the manuscript.", "Most of the MMP-inhibitors have only been examined in animal models as they are not approved for human medical treatment. Thus, despite extensive pre-clinical research up to date there is no MMP-inhibitor tested in clinical trials which holds promise for effective medication in patients." ] },{ "paper_id": "f29135f51da3a6598b511bad1514be9195bf1624", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All results are presented as means \u00b1 SEM. Statistical analysis was carried out by using Prism 5 software (GraphPad Software). The significance of the comparison between the two groups were assessed by Two-tailed Student's t-test. p < 0.05 was considered as significant statistical difference.", "After a transfection period of 24 h, the cells and lysates were collected. A Dual-Luciferase Reporter Assay System (Promega) was used to quantify luciferase activities following the manufacturer's instructions. Firefly luciferase activity was normalized to Renilla luciferase activity.", "The authors declare no conflict of interest." ] },{ "paper_id": "f291cfbcb64f14deb49a2dcc95079a17e838cf85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Endemic and seasonally recurring respiratory viruses are a", "1.", "Yes" ] },{ "paper_id": "f292a5fa02dc7ce9ea268920cc8657f4e34360f9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conditions that lead to a loss of tolerance in myelin-specific T cells are not known. Viral infection has long been postulated to be an environmental trigger that contributes to the etiology of MS [11] [12] [13] [14] , although no specific virus has been confirmed as being a causative agent.", "Four-week-and eight-week-old virus-free C57BL/6 mice were purchased from the Jackson Laboratory (Bar Harbor, ME, USA). All animal procedures and care were conducted in accordance with ethical guidelines approved by the Institutional Animal Care and Use Committee.", "Mice immunized with MOG displayed classic features of EAE including tail limpness, waddling gait, hind limb paralysis and ascending paralysis. In contrast, MHV-infected mice do not manifest obvious clinical neurologic impairment. Instead, they typically demonstrate ruffled fur, hunched back posturing, and significant weight loss (data not shown)." ] },{ "paper_id": "f293ae4ed7e4a778e7f9cc024d4e4cb33d69cc6e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f294f0df7468a8ac9e27776cc15fa20297a9f040", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Apart from droplet transmission and contact transmission, are there other methods to transmit SARS-CoV-2?", "Can the susceptibility of asymptomatic carriers be judged by detecting the serum reactivity level of N protein?", "The virus was shown to replicate effectively in ACE2-transfected, but not in mock-transfected T cells. Antibodies targeting ACE2 can block viral replication in Vero-E6 cells [105] .", "Author Contributions: Conceptualization, L.X., Y.W. and X.G.; methodology, J.X. and W.Z.; software, S.Z. and W.Z.; validation, J.X., S.Z. and T.T.; formal analysis, J.X. and S.Z.; writing-original draft preparation, J.X. and S.Z.; writing-review and editing, L.X., Y.W., W.Z. and X.G.; visualization, J.X., S.Z., and A.E.A.; funding acquisition, L.X., Y.W. and X.G. All authors have read and agreed to the published version of the manuscript. " ] },{ "paper_id": "f29df5233e688dddd0286374e0993e43459fe04b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cardiac tissue was flash frozen with liquid nitrogen cooled in a biopress, a fraction weighed (~25-30 mg weight), finely ground, and added to fresh 50% acetylnitrile, 50% water, and 0.3% formic acid at a standard concentration of 25 mg/475 mcl buffer, then fully homogenized on ice for 10-25 s and placed on dry ice/ stored at \u221280\u00b0C. Samples were \"crash\" deprotonized by methanol precipitation and spiked with D27-deuterated myristic acid (D27-C14:0) as an internal standard for retention-time locking and dried. The trimethylsilyl (TMS)-D27-C14:0 standard retention time (RT) was set at *16.727 min. Reactive carbonyls were stabilized at 50\u00b0C with methoxyamine hydrochloride in dry pyridine. Metabolites were made volatile with TMS groups using N-methyl-N-(trimethylsilyl) trifluoroacetamide or MSTFA with catalytic trimethylchlorosilane at 50\u00b0C. GC/MS methods generally follow those of Roessner et al. [33] , Fiehn et al. [34] , and Kind et al. [35] , which used a 6,890 N GC connected to a 5,975 Inert single quadrupole MS (Agilent Technologies, Santa Clara, CA, USA). The two wall-coated, open-tubular (WCOT) GC columns connected in series are both from J&W/ Agilent (part 122-5512), DB5-MS, 15 m in length, 0.25 mm in diameter, with an 0.25-lm luminal film. Positive ions generated with conventional electronionization (EI) at 70 eV are scanned broadly from 600 to 50 m/z in the detector throughout the 45 min cycle time. Data were acquired and analyzed as previously described [36, 37] .", "Cos-7 and HEK293 cells were cultured in DMEM containing 10% FBS, 100 unit/ml penicillin and 0.1% mg/ ml streptomycin. HL-1 cardiomyocytes were cultured in supplemented Claycomb medium containing 10% FBS, 100 unit/ml penicillin, 0.1% mg/ml streptomycin, 0.1 mM norepinephrine and 2 mM l-glutamine. All cells were incubated at 37\u00b0C in a 5% CO 2 humidified atmosphere." ] },{ "paper_id": "f2a4078a4441df3a53a2d719375da1c57bd93346", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We obtained fertility (births/female) at a regional scale (North, Central, and South) from the 2008 Malawi Census.", "We estimated the annual number of children born, who will not be vaccinated, Y j , as:", "We assumed a 14-day serial interval for measles infection. G is given by" ] },{ "paper_id": "f2a43da3e565ffb44289385ed3c6a4658dc166c1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Acute modifications of cytokine patterns can also occur. IL-12+ IL-18 enhance the secretion of IFNc by Th1 cells [14, 15] , and IL-2 enhances cytokine production [16, 17] . In contrast, IL-10, TGFb, prostaglandin E2 (PGE2) and adenosine inhibit inflammatory cytokine production [18] [19] [20] .", "Total RNA was extracted using TRIzol (Invitrogen) according to the manufacturer's instructions. cDNA was prepared by reverse transcription from total RNA using MultiScribe TM Reverse Transcriptase (Applied Biosystems, Foster City, CA) with random hexamer primers (Applied Biosystems). Quantitative real-time PCR (RT-PCR) was performed using the Applied Biosystems 7900HT Sequence Detection System. Primers and probes specific for AR, Heparin-binding EGF-like Growth Factor (HB-EGF), IL-2, IFNc, IL-3, IL-4, IL-5, IL-10, IL-13, CD3d, EGF, Neuregulin (NRG) 1-4, epiregulin (EREG), betacellulin (BTC) and TGFa were all obtained from TaqMan Gene Expression Assays (Applied Biosystems). CD3d gene expression was used as an endogenous control for normalizing mRNA amounts. All samples were run in duplicate and data were analyzed using SDS software (Applied Biosystems).", "7-Aminoactinomycin D (7-AAD) and TAPI-1 was obtained from Calbiochem (Gibbstown, NJ). cAMP agonist (8-CPT-cAMP) and cAMP antagonist (Rp-8-Br-cAMP) were purchased from BioLog (Bremen, Germany). Phorbol 12-myristate 13-acetate (PMA), ionomycin, monensin, PGE2, forskolin and 3-Isobutyl-1methylxanthine (IBMX), adenosine were obtained from Sigma (St.Louis, MO)." ] },{ "paper_id": "f2ab1be1bbd80c0f102714fdc90597af2739442c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.", "Since 1997, the highly pathogenic avian influenza A H5N1 viral strain has caused severe disease in poultry and wild birds. Although H5N1 has not spread widely in humans, sporadic infections have been seen throughout countries of eastern Asia, the Middle East and Africa. To date, there have been more than 445 confirmed human cases of H5N1, with 263 deaths (59% mortality rate) reported by the World Health Organization (http://www.who.int/csr/disease/ avian_influenza/country/cases_table_2009_12_11/en/index.html). In almost all cases, those infected with H5N1 had physical contact with infected birds. While the primary mode of transmission may be animal-to-human, the concern remains that this virus may evolve into a strain capable of human-to-human transmission. Vaccination offers a practical and effective measure for controlling the spread of this highly pathogenic virus. The threat posed by emerging strains of influenza is unpredictable and varies among countries, as evidenced by the recent swine origin H1N1 pandemic, highlighting the need for improved vaccines that can confer broad protection against multiple viral strains and various influenza A subtypes." ] },{ "paper_id": "f2af8027b6801850481d09ad0d4c5eb8e31c7d7f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PCR products were amplified from 50 ng of genomic DNA in a 25 mL reaction system containing 1.5 mM MgCl 2 , 1.0 mM dNTPs, 0.25 units of AmpliTaq Gold DNA polymerase (Applied Biosystems), and 16 PCR buffer II; the amplification protocol was: denaturation 10 min at 95uC, a touch-down cycle of 95uC for 30 s, 52uC for 60 s decreased by 1uC in the next cycle for 10 cycles, 72uC for 120 s, then 35 amplification cycles of 95uC for 30 s, 52uC for 60 s, and 72uC for 120 s, followed by an extension of 10 min at 72uC. PCR products were sequenced on an ABI 377. Sequences were aligned and cleaned using SEQUENCHER (Gene Codes).", "Twenty two polymorphic microsatellite loci (20 dinucleotide repeats: FCA006, FCA008, FCA014, FCA069, FCA077, FCA085, FCA091, FCA098, FCA105, FCA126, FCA129, FCA139, FCA205, FCA208, FCA211, FCA224, FCA229, FCA230, FCA247, and FCA281; and two tetranucleotide repeats: FCA391 and FCA441) were amplified [44] . Microsatellites were scored in an ABI 377 and analyzed using GENESCAN 2.1 and GENOTYPER 2.5. These loci are located on 11 of the 19 F. catus chromosomes, occurring in different linkage groups or at least 12 centimorgans apart [44, 45] .", "Second, the occurrence of recent bottlenecks was evaluated for microsatellite data using the method of Cornuet & Luikart [37] in BOTTLENECK [65] and using 10,000 iterations. This approach, which exploits the fact that rare alleles are generally lost first through genetic drift after reduction in population size, employs the standardize differences test, which is the most appropriate and powerful when using 20 or more polymorphic loci [37] . Tests were carried out using the stepwise mutation model (SMM), which is a conservative mutation model for the detection of bottleneck signatures with microsatellites [66] .", "Four, to test the significance of the total mtDNA genetic variance, we conducted hierarchical analyses of molecular variance [40] (AMOVA) using ARLEQUIN 2.0 [77] . Total genetic variation was partitioned to compare the amount of difference among population groups, among populations within each groups, and within populations." ] },{ "paper_id": "f2b40d30efe21fe521d22798d4c0e185e4ad6799", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Financial/Non-financial Disclosures: The authors have no interests to declare." ] },{ "paper_id": "f2ce9e73f368fc128cd28a0246b3ff8aa3079a42", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Here, we present the calculation of vaccine effectiveness (VE) for the Netherlands in 2014-15 and 2015-16 stratified for particular risk groups, namely chronic conditions and older age.", "We considered only the ILI cases in the weeks when there was virological confirmation of influenza by the Dutch Sentinel Practice Network, and of these cases, we used only the number of ILI cases above a seasonal baseline incidence for non-epidemic ILI.", "Influenza-like illness was defined as the acute onset of fever (measured temperature \u226538 \u00b0C), with muscle pain or headache and cough or sore throat (designated as ILI hist case definition in the Text box Case Definitions). The analyses included only the participants that submitted at least 3 symptom surveys throughout the monitoring season, designated as \"active\" participants." ] },{ "paper_id": "f2d560b5f6bd9fcad15c0b5e6e4284cfe9386e3c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Approximately 36.7 million people are living with HIV, with 20.9 million having access to antiretroviral therapy (ART) [1] . ART has been successful in controlling HIV-1 replication, especially in suppressing HIV loads, restoring immune function, as well as improving longevity and quality of life [2] . Yet, steps should be taken to develop more drugs based on the very rapid emergence of drug resistance and the poor pharmacokinetics of drugs [3] [4] [5] .", "The N36 peptide (10 nM) was incubated with an equal molar concentration of C peptide at 37 \u2022 C for 30 min in phosphate-buffered saline (PBS; pH 7.2). CD spectroscopy were acquired on a Jasco spectropolarimeter (Model J-815), using a 1 nm band width with a 1 nm step resolution from 195 to 270 nm at room temperature. The \u03b1-helical content was calculated from the CD signal by dividing the mean residue ellipticity at 222 nm. Thermal denaturation was performed by monitoring the ellipticity change at 222 nm from 20 \u2022 C to 98 \u2022 C at a rate of 1.2 \u2022 C/min [15, 16] .", "Viruses 2019, 11, x FOR PEER REVIEW 5 of 12", "Anti-HIV drugs play an important role in preventing and treating AIDS [27] , a series of ARTs, including nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), integrase inhibitors (IIs), protease inhibitors (PIs), fusion/entry inhibitors (EIs), and pharmacokinetic enhancers, have been developed [28] . ART has successfully transformed HIV-1 infection into a chronic and manageable disease [29] . However, prevalence of drug resistance and treatment is only effective before HIV-1 develops resistance against the administered drugs [30] . HIV fusion inhibitors have received widespread attention as they act extracellularly, prior to invasion of " ] },{ "paper_id": "f2d842780b9928cc70f38a4458553f2431877603", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All results are expressed as mean values \u00b1 standard deviations (SDs) (n = 3). The significance of difference was calculated by one-way analysis of variance, and values p < 0.001 were considered to be significant.", "The influenza strain A/Leningrad/134/17/1957 H2N2) was purchased from National Control Institute of Veterinary Bioproducts and Pharmaceuticals (Beijing, China). Virus was routinely grown on MDCK cells. The stock cultures were prepared from supernatants of infected cells and stored at \u221280 \u00b0C.", "Patchouli alcohol and oseltamivir were obtained from Sigma Chemical Co. (St. Louis, MO, USA, purity > 99%) and was stored in glass vials with Teflon sealed caps at \u221220 \u00b1 0.5 \u00b0C in the absence of light." ] },{ "paper_id": "f2d95ab758e878195eefa64325961667efeb4c14", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Histology. Half of the tissues (brain, lung, uterus/ovary, and spleen) from each experiment were preserved in 4% (vol/vol) phosphate-buffered paraformaldehyde. Fixed tissues were embedded in paraffin, sectioned at 5 \u00b5m, and stained with hematoxylin-eosin (HE) for the examination of histological changes by light microscopy. The pathologist was blinded to each group.", "Data availability. The authors declare that the data supporting the findings of this study are available with the article and its Supplementary Information files, or are available from the corresponding author upon request.", "Transmission electron microscopy. Negative-staining electron microscopy of purified VLPs and ZIKV was performed as described previously. Briefly, 20 \u00b5l of VLP or ZIKV suspension was fixed in copper grids (Electron Microscopy Sciences, Inc.) and negatively stained with 1% ammonium molybdate. Virus particles were visualized by using a FEI Tecnai G2 Spirit transmission electron microscope (TEM) at 80 kV at the Microscopy and Imaging Facility at The Ohio State University. Images were captured on a MegaView III side-mounted charge-coupled-device camera (Soft Imaging System, Lakewood, CO), and figures were processed using Adobe Photoshop software (Adobe Systems, San Jose, CA)." ] },{ "paper_id": "f2df4fc3c60338755fd23da3d7e01c0455e20745", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The complete genome sequence of the SAIBK isolate was submitted to GenBank and assigned the accession no. DQ288927.", "The complete genome of the SAIBK strain is 27,534 nucleotides (nt) in length, including the poly(A) tail. It has a classical IBV genome organization with 10 open reading frames (ORFs):", "Infectious bronchitis virus (IBV) causes tremendous economic losses to the poultry industry. Here, we report the complete genome analysis results for a new natural recombination nephropathogenic IBV strain named SAIBK, which was isolated in the Sichuan province of China in 2005." ] },{ "paper_id": "f2e06c174008ed721d0a244309601c9923548901", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PCA is a multivariate statistical method that is used to explore the relationships between variables and samples." ] },{ "paper_id": "f2e835d2cde5f42054dbd0c20d4060721135c518", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The study was conceived by RC and OK. RC and OK, MO and TD were involved in the design of the study, which was conducted by MO and TD. RC and OK analyzed the data. RC and OK wrote and revised the manuscript. All authors read and approved the final manuscript. ", "Objective: Recognizing increasing interest in community disease surveillance globally, the goal of this study was to investigate whether respiratory viruses circulating in the community may be represented through clinical (hospital) surveillance in Nigeria.", "Reagents were validated in the experimental location using an inbuilt validation protocol to confirm issues of false negative and false positive results were not of concern. Amplification reaction was carried out as described by the manufacturer: reverse transcription 50 \u00b0C-30\u2032, initial activation 94\u00b0-15\u2032, 45 cycles: denaturation 94\u00b0-30\u2033, annealing 60\u00b0-1\u2032 30\u2033, extension 72\u00b0-1, final extension 72\u00b0-10\u2032, hold 4\u00b0. Visualization was performed using electrophoresis on a 2% agarose gel in TBE 1X with EtBr, in presence of RV15 OneStep A/B/C Markers; molecular weight marker. Specimen processing was not blinded as there was no risk of experimental bias. Standardized procedures were used for community and clinic sampling." ] },{ "paper_id": "f2f78c95ab378a31bd35dc1de84e0ec75eb7ce1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were analyzed using Chi-squared test and Fisher's exact test in SPSS 19.0 (SPSS Inc., Chicago, IL, USA). Correlation with climate data was analyzed using multiple linear regression analysis. All tests were two-tailed and a p value < 0.05 was considered as statistically significant.", "Many factors affect the epidemiology of pathogens, such as geographical location and local climate. Guangzhou, a central city and main transport hub in southern China, is located in a subtropical region.", "Some limitations of this study should be noted. First, because our study mainly focused on HBoV1 circulation in hospitalized patients with ARI, HBoV1 in outpatients and the asymptomatic population were not included. Second, many factors can affect virus epidemics, meteorological data analysis alone may not serve as a final conclusive interpretation. Third, the study was only conducted in three hospitals and may not be representative of the overall population." ] },{ "paper_id": "f2f841111913d49cbbd17e0988fc4f49b06c4945", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For aerosol inhalation, MERS-CoV-Hu/Jordan-N3/2012 strain (GenBank accession no. KC776174.1) [9] was grown in Eagle's Minimum Essential Medium (Lonza, MD, USA) on Vero E6 cells.", "Complete blood cell counts were determined on PET-scan days [5] . Body temperature or body weight were monitored once daily or once every other day, respectively." ] },{ "paper_id": "f2f9088055600d4160e36db5cb6ea000916390a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f2fcc16391f946c99717b63ec9a24e5384aac381", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The envelope glycoprotein (Env) of the human immunodeficiency virus type 1 (HIV-1) includes the gp120 surface subunit and the gp41 transmembrane subunit. As a class I transmembrane protein, gp41 plays a significant role in the membrane fusion and virus entry of HIV-1 1,2 . After the binding of the gp120 to the cellular receptors, gp41 undergoes conformation changes after fusion peptide (FP) inserts into the", "Scientific RepoRts | 5:13028 | DOi: 10 .1038/srep13028" ] },{ "paper_id": "f3016563bf2b8e925c63a3c6a9e11e287907863c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study aimed to investigate the factors associated with trust in physicians among the Koreans. Rather than focusing on the physician behaviors, which were the main issue in the previous studies, we attempted to investigate patients' traits which can affect their subjective perceptions, focusing on their health-related conditions, behaviors and attitudes as well as their demographic and socio-economic characteristics.", "The dependent variable in our study is general trust in physician. In most prior studies from the US, trust in physicians is based on the concept of my physician [1] . However, unlike in many western countries, the concept of my physician is rather unusual in Korea due to the practical absence of gate-keeping function [24] . In this study, we assessed general trust in physicians (subsequently referred to as trust in physicians). Subjects were asked, \"How much do you trust physicians in Korea in general?\" Response was categorized as a 5-point scale ranging from not at all (1) to very much (5) . For the analysis, this 5-point scale was re-categorized into 3-point scale (not trust, ambiguous, trust).", "We performed the t-test and analysis of variance (ANOVA) to examine the difference in trust in physicians among the different groups in each variable of patient characteristics. An ordinal logistic regression models was employed to assess the relationship between patient trust and patient characteristics. For data acquisition and analysis, IBM SPSS Statistics (version 22) and Stata (version 13) were used." ] },{ "paper_id": "f3025ff285a3ab111229e38adaa5edb38406d3e1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We analyze all the simulations via MCMC methods and provide posterior summaries. For each simulated outbreak, single chains were run for 20,000 iterations with a 10,000 iteration burn-in. Trace plots, density plots, and autocorrelation plots were examined to explore sampler convergence.", "The following simulation study was designed to assess the validity and utility of our proposed approach and provide guidance in selecting prior distributions. A description of the simulations, including how the data are generated and summarized is included next." ] },{ "paper_id": "f318f02676fa086210640feb3fb488ae9522ba95", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Interfaces between molecules were analyzed with the PISA server (Krissinel & Henrick, 2007) . Interactions between molecules were initially evaluated using the CCP4 program CONTACT with a maximum contact distance of 3.6 \u00c5 .", "Furthermore, localization of the Pro-Pro motif may protect the extended unstructured C-terminus from proteolytic cleavage by host enzymes (Vanhoof et al., 1995) .", "In all three cases the recorded images were processed with XDS (Kabsch, 1988) and the reflection intensities were processed with COMBAT and scaled with SCALA (Evans, 1993) from the CCP4 program suite (Collaborative Computational Project, Number 4, 1994) . Data-collection statistics are shown in Table 1 ." ] },{ "paper_id": "f3284e9c3eef64c4badcedf21d266309a360374a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The RCA template and primers were designed to amplify sequences encoding a zinc finger protein for the expression of an artificial repetitive protein. ", "Comparison of MW-RCA with conventional RCA using four DNA polymerases", "The intensity of SYBR Green I fluorescence emission was measured using a fluorescence plate reader (FluoroCount, Packard) with a 96-well white microwell plate (Thermo Scientific)." ] },{ "paper_id": "f328ee900e91ba6c3bcc9a8f27e8fac7cd8c5eeb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data was exported and analysed using SPSS 17.0.1 (SPSS Inc.). MS prevalence was calculated using the formula:", "Data is available in the manuscript. Further data will be made available upon request.", "In the laboratory, swabs in VTM were immediately stored at \u221280 \u2218 C until needed. Vacutainers containing clotted blood were placed on the laboratory bench for at least 1 h for further separation. Vacutainers were centrifuged at 1500 rpm for 3 mins. Sera were harvested into prelabelled 2 mL centrifuge tubes and stored at \u221220 \u2218 C until needed." ] },{ "paper_id": "f32dc6c0ebf9a1623dc3b3b3eb15cfbaf12755d4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: ", "The primers used in this study were previously described including U1F (5\u2032-CATGCTCCTCGGTGGTCTCA-3\u2032) and U1R (5\u2032-GTCCGGGTCCATCACAGGGT -3\u2032) [ ", "In conclusion, this study is the first to report of canine Kobuvirus in dogs in Thailand. CaKoVs were mostly detected in clinical dogs of young age. However, the viruses " ] },{ "paper_id": "f33491026ec8a7ac58322108f149d5dc9d8dca89", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Normalized protein abundances were exported from Progenesis QI and arcsinh-transformed. Using an in-house written R script (R Foundation for Statistical Computing, Vienna, Austria). Benjamini-Hochberg corrected one-way ANOVA was used for the calculation of the FDR-corrected p-values (29) . For proteins passing a significance level of 0.05, a post hoc test (Tukey's honest significant difference method) was conducted to obtain p-values for pairwise comparisons. immunoblots Immunoblots were performed as described previously (30) .", "Functional annotations were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID, ver. 6.8) (27, 28) .", "The flow cytometric analysis was performed as described previously (31) using herein indicated antibodies." ] },{ "paper_id": "f33e644d058bc8373378c115878be06346298687", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments were approved by the University of Edinburgh's Local Ethical Review Committee and were carried out in accordance with UK Home Office regulations. C57Bl/J6 mice were housed in a 14 h light-10 h dark cycle, with food and beverage provided ad libitum.", "All data were analysed using GraphPad Prism software. Normal distribution was assessed using a non-parametric test of distribution; the Kolmogorov-Smirnov test. To determine statistical significance between the control group and more than one treatment group, one-way ANOVA followed by Bonferroni post hoc tests were applied to normally distributed data, while Kruskal -Wallis followed by Dunn post hoc tests were applied to data that were not normally distributed. Where controls were compared with a single treatment, a paired t-test was used. All results are presented as mean + SEM. Statistical significance was set at values of P , 0.05.", "At the end of the culture, ovaries were fixed in 10% neutral buffered formalin (Sigma-Aldrich Ltd, UK) overnight at 48C, wax embedded and serial sectioned at 5 mm. IHC for cleaved caspase 3 (CC3) and mouse vasa homologue Ovarian toxicity of docetaxel in neonatal mice (MVH) used fluorescent secondary antibodies, while IHC for cleaved caspase 8 (CC8) used an avidin-biotin visualization system." ] },{ "paper_id": "f34cdf2bec51c797567dedf6f00954351ebe5320", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide ", "This study was funded by Newport Laboratories.", "Further work is necessary to determine the pathogenic potential of this novel reassortant bovine MRV." ] },{ "paper_id": "f37275235174f60a5028e7d86859fecd6550f737", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Spinal cords were isolated at defined time points and fixed overnight with 4 % paraformaldehyde at 4\u00b0C.", "Sections were subsequently cryoprotected in 30 % sucrose for 5-7 days, separated into 12 coronal sections, and embedded in optimum cutting temperature (OCT) formulation (VWR, Radnor, PA, USA) [48] . Coronal sections (8 \u03bcm thick) were cut, and sections were stained with luxol fast blue (LFB) in combination with hematoxylin and eosin (H & E). Areas of total white matter and demyelinated white matter were determined with Image J Software. The percent demyelination was calculated by dividing the area of demyelinated white matter by the total white matter area using established methods previously described [47, 49] .", "MicroRNAs (miRNAs) are a new class of evolutionarily conserved gene-regulatory molecules that function to repress key target genes, primarily at the post-transcriptional level through specific mRNA 3\u2032 untranslated region (3\u2032 UTR) interactions [1] . Because miRNAs commonly target critical signaling proteins and transcription factors with potent regulatory impacts on the immune system [2, 3] , it is accepted that miRNAs have an important effect on immune system activation and cellular differentiation. Recent work by our group and others has determined that miR-155 is an important regulator of immune cell development and function. Following its original identification as an oncogene in chicken lymphomas [4] , miR-155 was discovered to be overexpressed in mammalian hematopoietic cancers and shortly thereafter established as an immunomodulatory noncoding RNA in macrophages and B lymphocytes [5] [6] [7] [8] [9] . It is now clear that miR-155 is expressed by and functions within a variety of activated immune cell types that include various T cell populations, NK cells, and dendritic cells [6, 7, [10] [11] [12] . In addition, miR-155 represses a variety of immunoregulatory proteins that include signaling molecules such as Ship1 [13] and Socs1 [14] , as well as transcriptional regulators such as Jarid2 [15] , Ets1 [16, 17] , PU.1 [18] , and Fosl2 [19] ." ] },{ "paper_id": "f3869eb49905ee75dbd6acd2964cb74f69154b2a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 We accept pre-submission inquiries \u2022 Our selector tool helps you to find the most relevant journal ", "Data were analysed with the GraphPad Prism 6.01 software. Significant differences between groups were assessed by multiple t tests. P < 0.05 was considered significant.", "The development of vaccines against PRRSV has been only partially successful so far and remains a challenging task (for comprehensive reviews, see [32] [33] [34] ). There are currently two types of PRRSV vaccines on the market: modified live-virus vaccines (MLV) and inactivated vaccines [35] [36] [37] . MLV are typically more efficacious than inactivated vaccines [38, 39] . Numerous alternative PRRSV vaccine approaches have been explored with limited success so far (reviewed in [32, 40] ). These efforts include for instance DNA vaccines, subunit and peptide vaccines, viral vector vaccines and plant-derived vaccines [30, [41] [42] [43] [44] [45] [46] .", "The experiments in pigs were performed in compliance with the Swiss animal protection law and approved by the animal welfare committee of the canton of Berne, Switzerland (Authorization Number BE89/11)." ] },{ "paper_id": "f38ba8043876aa7abbefa69c26edc2aa3aaa4e94", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ILTV Serological testing for ILTV was not performed. No ILTV detected in any of the samples when examined by PCR.", "Intensification of agriculture in Africa is accelerating, thanks to novel technologies, financial initiatives, changing social infrastructure and private sector engagement (Pretty et al. 2011) , and policies promoting increases in consumption and productivity for a range of livestock species (Sumberg and Thompson 2013) . Ethiopian entrepreneurs are setting up large, intensively managed flocks of exotic breeds, particularly in areas close to Addis Ababa (Mammo 2012) . Government-owned poultry multiplication centres throughout the country (Pagani and Wossene 2008) , non-governmental organisations and private individuals also distribute intensively reared chickens to smallholders (Pagani and Wossene 2008; Anon 2014) . As a result, more urban and suburban households now keep flocks of 50 to 1000 birds under semi-intensive management (FAO 2008) . The close links between intensive and smallholder farms facilitate disease spread, exacerbated by low biosecurity, and poor access to veterinary inputs and expertise among smaller producers (Sambo et al. 2014) .", "aMPV Serum samples were considered to be positive for aMPV if titres \u22651656, as per the manufacturer's guidelines. Sixteen (21.9%) samples tested positive (Fig. 1a) . All the OP swabs were negative for aMPV by RT-PCR. A turbinate from a necropsied bird from group 3 was positive for aMPV subtype B.", "Sampling was conducted over a 2-week period in May 2012. At the time of study, the farm consisted of 11 sheds, nine of which were populated. Three sheds which housed grandparent birds were situated separately to the main body of the poultry production premises. The main premises consisted of a hatching house; incubator and brooder sheds (both disused); one large new breeder shed; two multi-age multi-breed sheds containing parent birds and multiplier flocks and two sheds containing indigenous chicken ecotypes. These last two were not sampled due to local concern over biosecurity, as any losses incurred in this flock would interrupt an experimental breeding programme. All birds on the farm were vaccinated against NDV, but unfortunately records of vaccination schedules for the birds sampled were not available." ] },{ "paper_id": "f38f3b112e4b702b60ba56be806d418bbb2b83c3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f39671c6a9f5a19d6db58094f4a8f07f6e036085", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Type I IFNs (IFN-\u03b1 and IFN-\u03b2)", "Type III IFNs (IL-28A/IFN-\u03bb1, IL-28B/IFN-\u03bb2, and IL-29/IFN-\u03bb3)" ] },{ "paper_id": "f3a378151096d647f4982841888e944c7aa031b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments were performed at least in triplicate. The measured values are represented as mean \u00b1 SD from three independent experiments. The statistical significance analyses were performed using the Student's t-test. Data considered significant when * P < 0.05, and highly significant when * * P < 0.01.", "For Western blotting, the cells were collected at the indicated time points and. The lysed cell extracts were resolved by 10% SDS-PAGE and transferred onto a nitrocellulose membrane (Pall). The nitrocellulose membrane was then blocked with 10% skim milk powder in TBST (20 mM Tris, 55 mM NaCl, 0.1% Tween 20) overnight at 4 \u2022 C. The membrane was incubated with primary and secondary antibodies as described previously (Zhu et al., 2013) . The membrane was washed 3 \u00d7 5 min, before being protein abundance analysis. The antibody-antigen complexes were visualized using enhanced chemiluminescence detection reagents (Thermo).", "The full-length porcine EGR1 cDNA fragment was cloned into a pcDNA TM 3.1/myc-His(-)A vector (Invitrogen) to construct a Myc-tagged EGR1 eukaryotic expressing plasmid (Myc-EGR1, including a C-terminal Myc tag). The constructed plasmid was analyzed and verified by DNA sequencing. A series of plasmids expressing HA-tagged type I IFN pathway-related proteins [including MDA5, RIG-I(CARD), VISA, TBK1, IRF3 and IRF7], and the IFN-\u03b2 promoter luciferase reporter plasmids and control plasmid Renilla luciferase pRL-TK were kindly provided by Hongbing Shu's Laboratory (Zhou et al., 2014; . The plasmids were transfected into cells using OPTI-MEM medium and the Lipofectamine 2000 (Invitrogen) reagent according to the manufacture's protocol." ] },{ "paper_id": "f3a5b128f4800dbbb0f49ee409acb2c0216e24dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Population or system level sensitivity estimates that include the effects of sample quality are limited. Grijalva and colleagues [39] estimated the diagnostic sensitivity in a capture recapture study of children hospitalized for respiratory complications at 69% for a RT-PCR based system and 39% for a clinical-laboratory based system (passive surveillance of tests performed during clinical practice, and using a variety of commercially available tests)." ] },{ "paper_id": "f3b46e7e8f58799207cc44515f859c1daf5e4dfc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral DNA and RNA were isolated with the QIAamp MinElute Virus kit (Qiagen, Westburg, The Netherlands) according to the instruction manual. EBC extracts were eluted in 60 \u03bcl elution buffer and NS extracts in 110 \u03bcl elution buffer.", "Although an inventive, new and promising method, EBC collected by the RTube\u2122 does not appear to be appropriate for diagnosis of respiratory infections. Nonetheless, this method may provide an alternative for current sample procurement for epidemiological studies of circulating viruses. This technique also confirms the observation that viruses are able to disseminate through normal breathing, particularly RV." ] },{ "paper_id": "f3b7f4469ac01f1ce916d24172570c43c537627e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For flow cytometric analysis, the same antibodies were used.", "Total RNA was isolated from cell cultures using TRI reagent (Sigma-Aldrich, Munich, Germany). Real time PCR for H5 was performed using described methods [35] . The following primers were used: sense 59 acg tat gac tac ccg cag tat tca g 39; antisense 59 aga cca gcy acc atg att gc 39; probe 6-FAM-tca aca gtg gcg agt tcc cta gca-TAMRA.", "Two groups were compared by t-test. More groups were compared by ANOVA with subsequent Student-Newman-Keuls test." ] },{ "paper_id": "f3b9fc0f8e0a431366196d3e835e1ec368b379d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f3bc1d07fd0e855faa2e2eb98d9b97852eb88c03", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Comparisons of the restrictiveness of different interventions become less straightforward when they differ on more than one dimension; for example, where one intervention violates right M but not right N, and the other violates right N but not right M. Similarly, comparisons become less straightforward when one intervention violates the rights of more people, and the other violates the rights more extensively.", "Having outlined the five desiderata that we take to constitute the standard approach to the assessment of nonconsensual IDC interventions, we", "See 39 It is merely an indicator, rather than a determinant, because the intervention may also cause or prevent other harms that would need to be included in the consequentialist calculus, and because deontological side constraints may rule the intervention out even if it satisfies this desideratum.", "On this interpretation, the least restrictive alternative desideratum may be regarded as reflecting a deontological constraint on either the pursuit of the good (on constrained consequentialism), or self-protection (on a self-defense-based justification)." ] },{ "paper_id": "f3c309c596c20f48f493b77e714ce957d877bdcb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Soil use classes were obtained from the TerraClass data mosaic from 2004 to 2016, because the study sites were in an area with a high cloud presence, which prevented observation (the area was not observed).", "The analyzes were considered positive when presenting the cycle threshold (CT) \ufffd 40. In order to guarantee a reliable test result, the measurements of contamination control were performed with the use of positive animal control (SA11 prototype) and a negative control (ultrapure water).", "Emerging and reemerging infectious diseases are increasing each year in several countries, with an impact both on human populations and on domestic and wild animals living in areas with considerable forest remnants [1] . Most of these diseases are of viral origin, suggesting the emergence and reemergence of viruses that are triggered by human activities that modify the environment [2] .", "A total of 80 stool samples were selected, reextracted and analyzed using PCR for the VP4 gene. Eight strains (10%) were positive for VP4 gene, being 2 strains bellowed to P [6] genotype and 6 to P[4]-type, according to ", "The qualitative real-time polymerase chain reaction (qRT-PCR) used the NSP3 gene and the TaqMan probe from a highly conserved region of the rotavirus non-structural protein 3 (NSP3), which was previously used in samples from human origin and with low viral loads ", "Acute gastroenteritis is one of the main causes of mortality in humans and young animals. Domestic and mainly wild animals such as bats, small rodents and birds are highly diversified animals in relation to their habitats and ecological niches and are widely distributed geo-", "The satellite image was generated using the sensor Sentinel 2 of the European Space Agency (ESA) (https://sentinel.esa.int/ web/sentinel/user-guides/sentinel-2-msi) with Open Access CC-BY License (http://open.esa.int/) from the years of 2017 and 2018." ] },{ "paper_id": "f3cbc0503581249a834895fc94cd3bae24714a0d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "data, which should use hierarchical models, may result in biased estimation of the variation and also lead to incorrect conclusions." ] },{ "paper_id": "f3d150545162ff3cc253c235011a02a91ee676cb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All tests were two-sided, and p-values below 0.05 were considered to denote statistical significance. All statistical analyses were performed using SPSS statistical software version 21.0 (SPSS Inc., Chicago, IL, USA).", "Consecutive adults ( [19] ." ] },{ "paper_id": "f3de553d9173bab4ad066e7d00994c165a7d9a41", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "iii) Promiscuous restriction where some TCRs will use a series of different restriction elements to bind to and, therefore, interact with a wider variety of different peptides.", "Gastrointestinal infections and in more extreme cases myocarditis (inflammation of the heart) and pericarditis (inflammation of the sack surrounding the heart) T1D [92] [93] [94] [95] Hepatitis B Hepadnaviridae Liver inflammation SLE [96, 97] Hepatitis C Hepadnaviridae Liver inflammation MG [98, 99] , GD [100, 101] , T1D [102, 103] ", "Latent infection that in healthy individuals causes limited symptoms but can be more detrimental in immuno-compromised individuals SLE [112, 113] , MS [114] Herpes simplex virus 6 Herpesviridae Infects almost all children causing a rash before becoming latent MS [105, 115, 116] Human Coronavirus (HCoV) Coronaviridae Upper respiratory and gastrointestinal tract infection MS [117] Human Foamy Virus Retroviridae Asymptomatic GD [118, 119] , RA [120] , SLE [120] , MG [121] ", "Asymptomatic unless in immuno-compromised patients where is can cause progressive multifocal leukoencephalopathy and other diseases MS [127] [128] [129] Parvovirus B19 Paroviridae Causes childhood exanthema (a widespread rash)" ] },{ "paper_id": "f3e85a35ab89c9a55eeb83c6e17f881d5c497d82", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Serine peptidase inhibitor, Kazal type 5 or chicken ovomucoid \u2022 Lymph-epithelial Kazal-type-related inhibitor (LEKTI)." ] },{ "paper_id": "f3f471d10a36a7a28e9050c10bd4dfd680cba17b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author(s) declare that they have no competing interests.", "where 1 sch (t) is a function which indicates when schools and day care centres are opened or closed: ", ",..., While day care centres and schools are closed, children (age a i ) need adult supervision at home. Their contact with susceptible adults (age a s ) increases by the \"child care factor\" F CC :" ] },{ "paper_id": "f3f9545f7a7fee9a2b6d72c0cd36ca66687809be", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chromatographic conditions. Columns: Cosmosil 5C18-MS-II (4.6 ID \u00d7 250 mm) Manf. No. K63663. Mobile phase: Acetonitrile (A)-0.1% H 3 PO 4 (B); Flow rate: 1.0 mL/min; column temperature: 30 \u00b0C; detection wavelength: 280 nm; injection volume: 10 \u03bcL, the gradient elution program is shown in Table 1 [11] .", "3 mg of chlorogenic acid, forsythia, thymol, and magnolol were transferred to a brown volumetric flask and methanol was added to prepare a 0.5 mg/mL standard solution." ] },{ "paper_id": "f4016789973bc61cdb84c457c95e15426e2143b3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analysis was performed using Prism 4 software (Graph Pad, La Jolla, CA)." ] },{ "paper_id": "f401da36e7206731f86a12c49781c3d1b36347f9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "[52] tvc s Line H6 Wild type Tvc receptor conferring susceptibility to ASLV(C) infection.", "[58]", "[54]" ] },{ "paper_id": "f407fa076e02563e41223d43873e7fd604bdd637", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusions/Significance: Our data strongly suggest that 4-aminoquinoline drugs and their metabolites exacerbate B19Vassociated anemia by promoting B19V replication. Consideration should be given for choosing a non-4-aminoquinoline drug to partner artemisinin compounds in combination antimalarial therapy.", "All patients were participants in a prospective observational and genetic study of severe pediatric infections (http://www.malariagen. net/home/). Written informed consent was obtained from each parent/guardian. Ethical approval for the study was obtained from both the PNG Institute of Medical Research Institutional Review Board and the Medical Research Advisory Committee of the PNG Department of Health. The study was conducted in accordance with the Helsinki Declaration." ] },{ "paper_id": "f40d65d9dcb0b71bd266e62f77bc51d4c449eed1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f4117ab009596bf0f4ab6391615d5124125b1006", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell lines and reagents. HeLa R19 cells were maintained in Dulbecco's modified Eagle's medium (Gibco) supplemented with 10% fetal calf serum, penicillin, and streptomycin and grown at 37\u00b0C in 5% CO 2 . The PI4KA inhibitor A1 (50) was kindly provided by T. Balla (National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD) and used at a concentration of 10 nM.", "Quantitative PCR. A NucleoSpin RNA kit (Macherey-Nagel) was used to isolate RNA from lysed cells. Random hexamer primers were used with a TaqMan reverse transcription reagent kit (Roche) to synthesize cDNA. Quantitative PCR was carried out using the LightCycler 480 SYBR green I master kit (Roche) for 45 cycles (5 s at 95\u00b0C, 10 s at 60\u00b0C, and 20 s at 72\u00b0C) on a LightCycler 480 (Roche). Resulting threshold cycle (C T ) values were expressed as fold increase with the value at t \u03ed 2 h set as 1.", "Viral titer determination. Total virus titers (of intra-and extracellular particles) were determined by freeze-thaw lysis of infected cells and endpoint titration." ] },{ "paper_id": "f415c477bac80d18eec2b6775efd8d660a7688ba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f42073cb33dc2aa926898dd2ab05da828f8e7790", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No competing interests were disclosed. Competing Interests:", "This article is included in the Zika & Arbovirus ", "I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard." ] },{ "paper_id": "f421ab87adfb959664409ada2f3849ec1a977320", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Continuous variables reported in medians, 25-75% interquartile ranges unless otherwise specified. The Bonferroni correction was applied to correct for multiple testing when analyzing families that included different parameters such as signs/symptoms at presentation or medications used.", "(2) Other includes Asian, Native Hawaiian and unknown.", "CXR: chest-x-ray; BWT: bronchial wall thickening; CBC: complete blood count." ] },{ "paper_id": "f4237ea9635b4330639d7f678c719a05f7c9d8a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The " ] },{ "paper_id": "f426954f62f73eccb16b672e9e93dfb6d48af618", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(DOC) ", "Table S1 Relative risk of adverse outcomes by cohort.", "Only patients without a diagnosis of infection present on admission were included in the study. The inclusion criteria included immunocompetent ICU patients greater than or equal to eighteen years of age admitted to the hospital between the third quarter, 2006, and second quarter, 2009. Patients with a primary or secondary ICD 9 code signifying a history of organ transplantation, human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), autoimmune disease, leukemia, pancytopenia, or lymphoma were excluded. Immunocompetency was defined as the absence of the aforementioned diagnoses. A total 209,695 patients met the study criteria." ] },{ "paper_id": "f435af9f4c369a6738a5c079f5f9b486cf9e63e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ethics statement. All animal experimental protocols were carried out in strict accordance with the UK Home Office guidelines and under license granted for experiments involving regulated procedures on animals protected under the UK Animals (Scientific Procedures) Act 1986. The experiments were performed in The Pirbright Institute (TPI) Home Office licensed (X24684464) experimental animal house facilities and were approved by TPI's animal welfare and ethical review committee under the terms of reference HO-ERP-01-1. Trial 1 used SPF RIR chickens obtained from TPI Poultry Production Unit in Compton. Trial 2 used the same chicken breed but obtained from The National Avian Research Facility in Edinburgh." ] },{ "paper_id": "f437e7708a092a65e1bf20065dfdfb2e17546825", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In Central Africa, data on influenza-like illnesses (ILIs) are recent. HBoV has only been described in Cameroon in data showing a 10.6% prevalence [9] .", "Statistical analysis was performed using Statview V5.0 software. Pearson's Chi squared test and Fisher's exact test were used to analyze the results. A two-tailed critical alpha value of 0.05 was used. A p-value below 0.05 was considered to indicate statistical significance." ] },{ "paper_id": "f43e2e8087f69f1fd27714d2f600d66321d8f0e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All research protocols and survey instruments were reviewed and approved by the institutional review boards at the U.S. and foreign institutions participating.", "It also raises questions about what accounts for the remaining 80% of the variance. Further research with more comprehensive instrumentation is necessary to begin to answer these questions." ] },{ "paper_id": "f442fd7cf9f7ab6a2939acae3d1eea548dafac20", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The human lungs are a large organ and span a relatively long anatomical distance. As a result, pulmonary histology differs substantially depending on anatomical location and specific tissue function.", "Third-generation lentiviral packaging plasmids (pMDL (gagPol), pRev, pVSV-g) were generously provided by Prof. Dr. B. Berkhout and Dr. J. Eekels along with the green fluorescent protein (GFP)-modified pLKO backbone containing a non-mammalian short-hairpin (sh)RNA control (pLKO_GFP; Mission\u2122 SHC202) that should not target any known mammalian gene, but will engage with RISC [26] . The isopropyl \u03b2-D-1-thiogalactopyranoside (IPTG)-inducible lentiviral backbone pLKO-puro-IPTG_3xLacO harboring the non-mammalian shRNA control was purchased (Mission\u2122SHC332; Sigma Aldrich, Buchs, Switzerland). The puromycin resistance gene was replaced via restriction digestion cloning using a polymerase chain reaction (PCR)-amplified fluorescent mCherry marker containing overhangs with compatible restriction sites to generate the pLKO-mCherry_IPTG_3xLacO lentiviral backbone.", "Data was plotted using GraphPad Prism 7 and figures were assembled in Adobe Illustrator CC 2018 software package." ] },{ "paper_id": "f44786ccd9fbd63530866db7c60cac06fb9b0fb9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "L is the pathlength of the cuvette used, the A terms are the absorbance at the excitation and emission wavelengths, and F values are the corrected and observed fluorescence intensities." ] },{ "paper_id": "f456aeb3d2dd8f321a23068ec9ed25c611b819e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "User data online resources. Although the education was mainly face to face, online supportive resources were available to increase the educational impact. The graph in S1 shows the use of the website and social media in time. 27 ", "Note: Supplemental tables and figure appear at www.ajtmh.org." ] },{ "paper_id": "f45c3a707e3c465ca99703e6ea202702841a5b97", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f46d2803581226a9a94026693e95db88e7c70641", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Protective efficacy of PAV3-HA following lethal challenge", "suggesting that a replication-competent PAV3 vector which would be easy to produce at high titres could also be a promising vaccine candidate. Nevertheless, performance of this new vaccine vector will need to be addressed in other animal species, including nonhuman primates, before its real utility as a human vaccine can be predicted more accurately. Overall, this study supports a complementary role for cellular immunity during early H5N1 infection and the further development of porcine adenoviruses as human vaccine candidates.", "The increased neutralizing antibody response following PAV3-HA vaccination was statistically significant at day 21 (p = 0.045) relative to AdHu5-HA." ] },{ "paper_id": "f46dfc953ba5eba42f02a55f53fdafab33736135", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Currently, there is no cure for severe liver disease and the only management option is liver transplantation when liver failure is life-threatening. New therapies that target the misfolded a1AT or attempt to correct the underlying genetic mutation are currently under development.", "Anti-trypsin \u03b11-Antitrypsin (\u03b11AT) is a member of the serine proteinase inhibitor (serpin) superfamily. The primary role of \u03b11AT is to inhibit the proteolytic enzyme elastase secreted by activated neutrophils (NE), which degrade elastin within connective tissues. Thus, \u03b11AT maintains the structural integrity of lung elastin [73, 74] .", "Considering the protein maturation checkpoints in the early secretory pathway (ER, ERES, ERGIC), we can distinguish three different situations that could cause a disease linked to trafficking ( Figure 1 ):", "Cystic fibrosis (CF) is the most common lethal monogenic autosomal recessive disease among the Caucasian population, and it is caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) glycoprotein, which normally functions as a chloride/bicarbonate channel at the apical membrane of epithelia [53] [54] [55] . Thus, its function is to maintain ion and fluid homeostasis. The human CFTR belongs to the ATP-binding cassette (ABC) transporter superfamily, and consists of 12-transmembrane domains (TMDs) that form the translocation pathway, two cytoplasmic nucleotide-binding domains (NBDs) that hydrolyze ATP, and a regulatory (R) domain that must be phosphorylated to allow the channel to open [55, 56] ." ] },{ "paper_id": "f4714dd09f8ab317ec688ba087e67239b2b93367", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "not evolve in therians until separation of the monotreme lineage.", "C18ps ", "Zn finger genes" ] },{ "paper_id": "f472fa905ba1adcbb2fb5ebc78ce1efdae91eaa8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations GDP: gross domestic product; FDI: foreign direct investment; PRD: Pearl River Delta Region; SARS: severe acute respiratory syndrome.", "Challenges that must be faced PRD faces a stupendous challenge with regard to public health and access to basic health services because these issues are dealt with separately by each city prefecture.", "Even in assembly-line production, enforcement of occupational health and safety standards are lax and hours of work are dangerous to human health. One survey, for example, reports that 63.8% of migrants work seven days a week without rest, and that the average work week (for 63.9% of them) is 56 hours [10] . This situation reflects the exceedingly low salary structure for migrant labor. Before the strikes of 2010, the basic wage was around 900 Yuan (less than $140) a month thus forcing laborers to work overtime to earn enough to live and save a small margin. The spate of last year's suicides at the Foxconn electronics plant in Shenzhen [11] (the biggest factory in the world with 300,000 employees) are directly linked to these conditions.", "The PRD's growth was fueled from two sources: 1) massive amounts of external capital, originally from Hong Kong and later from the rest of the world; and 2) a massive inflow of 20 million unskilled migrant laborers from rural villages, which allowed China to maintain its competitive advantage in labor-intensive activities. Over the period between 1978 to 2007, PRD's GDP grew at an annual rate of 21.2%, more than twice the national average [5] . It is now the wealthiest city-region of China (outside of Beijing and Shanghai), and a strategic hub for China's national economic development plans." ] },{ "paper_id": "f475c055c4630c81ab519125a20ba96cd3e17e4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Adegoke AO and Grant MD (2015) Enhancing human immunodeficiency virus-specific CD8 + T cell responses with heteroclitic peptides.", "Enhancing CD8 + T cell responses Frontiers in Immunology | www.frontiersin.org conservative and semi-conservative aa substitutions at positions 3, 5, and 7 of native peptide epitopes (23) .", "The finding that T cells from mice immunized with pigeon cytochrome c made stronger proliferative responses in vitro against tobacco hornworm moth cytochrome c than against pigeon cytochrome c itself was the first documented example of a heteroclitic peptide stimulating an enhanced immune response (6) . Subsequent findings in various other experimental systems reiterated these seminal findings of Solinger et al. that certain peptide variants can restimulate more potent immune responses than the native, WT, reference or index peptide epitopes the immune system was actually exposed to (4, (7) (8) (9) (10) (11) (12) (13) (14) . In this review, we will focus on the possible utility of heteroclitic peptides for immunotherapy of human immunodeficiency virus (HIV) infection." ] },{ "paper_id": "f481624491ae43193cf1229d54d99e8ddcef9479", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although not covered here, the endogenous microbiome is likely to play an important role as a mediator of pulmonary immune responses during infection. The crosstalk at the interface of microbial pathogens and human host epithelium presents multiple opportunities for the development of clinically relevant therapies. Targeting host mechanisms may provide less opportunities for the emergence of pathogen resistance, and if used in combination with direct antimicrobial medications may prove superior to monotherapy.", "S. pneumoniae is typically susceptible to many commonly used \u03b2-lactam antibiotics like penicillin. However, their resistance to multiple antibiotic classes is growing (216) . Current vaccines for pneumococcal disease include 13-valent pneumococcal conjugate and 23-valent polysaccharide vaccines (217) . Despite broad immunization practices however, invasive pneumococcal disease remains common with high morbidity and mortality. Similar to influenza, targeting the microbe-host interaction could provide novel treatment strategies for pneumococcal disease. One example is S-carboxymethylcysteine (S-CMC) which is a mucolytic agent used in COPD which has been shown to inhibit adherence to both pharyngeal and alveolar epithelia (218, 219).", "All authors participated in writing and editing the paper and approved the final submission. Figures were drawn by AS (Figure 1 ) and MT (Figures 2, 3) . " ] },{ "paper_id": "f4819ac40713b21c42a2cad54d3db7626fdf0956", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 50% inhibition concentration (IC50) was calculated using the Reed-Muench analysis [26] [27] [28] .", "Data was presented as mean \u00b1 standard deviation (SD). Comparisons for all pairs were performed by the Student t test using SPSS version 17.0 (SPSS, IL, USA). A P value of <0.05 was considered to be significant. The IC 50 and CC 50 values were calculated using GraphPad Prism (GraphPad Software Inc., San Diego, CA, USA).", "Influenza viruses are responsible for seasonal epidemics and occasional pandemics, which cause significant morbidity and mortality. The vaccines need to be reformulated almost every year owing to antigenic drift, and the timely production of pandemic vaccines remains problematic because of the limitations of current technology [1] [2] [3] [4] . Antiviral drugs play a significant role in controlling the spread of the disease, but the emergence of drug-resistant viral strains has been reported occasionally [5, 6] , which has become a serious public health concern globally. Therefore, safe and effective new antiviral drugs need to be developed urgently to combat viral infections for either therapeutic or prophylactic purposes." ] },{ "paper_id": "f488237187c7b67ffdf93185574e610b8c7cc999", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(v) Homogenize the tissue by centrifuging 3-4 times at full speed for 20 s each at FastPrep centrifuge. Wait 1 min between the centrifuge steps to avoid overheating of the samples.", "Supplementary file 1: Metagenomics sample processing protocols consisting of reagents, equipment, reagent setup, and the procedure (steps 1-120, with options for RNA extractions from ticks or mosquitoes) with timing specifications. In addition, a troubleshooting table is given for selected steps as well as some examples for anticipated results with Figures A1, A2, and A3.", "(iii) Rinse the mosquitoes with nuclease-free water. Discard carefully the water." ] },{ "paper_id": "f48a26496eec9f955c65e9d89305c4bc5df2718a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sendai virus (SeV, Cantell strain) was prepared in chicken embryos as described previously [29] . Pulau virus (PulV) was prepared and titered as described previously [33] . For infection of cells, virus was incubated with cells for one hour at 37uC, then replaced with normal cell culture medium for the indicated time.", "All animal experiments were approved by the Australian Animal Health Laboratory (AAHL) animal ethics committee (protocol number 1389). Immortalized and cloned P. alecto kidney (PaKiT03) and lung (PaLuT02) cells established previously [35] were cultured in DMEM/F12-Hams (Sigma), supplemented with 10% foetal calf serum (FCS, Hyclone), 100 units/ml penicillin, 100 mg/ml streptomycin and 50 mg/ml gentamycin (Sigma). Human embryonic kidney HEK293T cells were cultured in DMEM supplemented with 10% FCS (Hyclone), 15 mM Lglutamine, 100 mg/ml penicillin, NEAA/Na-py/fungizone. All cells were maintained in a humidified atmosphere of 5% CO 2 at 37uC.", "Sequence alignment was performed using ClustalX and visualized using GeneDoc (http://www.nrbsc.org/gfx/genedoc/ index.html). Alignment files were visualized using EMBOSS Plotcon to determine the conservation of IRF7 proteins among different species. Genomic intron-exon maps of the genes were drawn using Fancy Gene v1.4 by comparing individual IRF7 ORFs of P. alecto, horse and human (http://host13.bioinfo3.ifomieocampus.it/fancygene/). Phylogenetic trees were constructed using the neighbour joining method and MEGA4.1 program with 1000 bootstrap replicates [36] ." ] },{ "paper_id": "f4a7339511490ed2b84a8b9189b5f2f05ff57082", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Other newly discovered viruses are related more closely to known viruses but can provide a broader phylogenetic baseline for computational comparative analyses that can be used to detect undiscovered elements in economically and medically important species.", "One of the earliest examples described is found in segment S1 of mammalian orthoreovirus (Ernst & Shatkin, 1985) .", "Internal ribosome entry" ] },{ "paper_id": "f4a82ad66962355ffb09e4d1b57fde3e94f0ec53", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Spleens from 14 day-immunized mice were initially fixed with paraformaldehyde and embedded in 4% low-gelling-temperature agarose (type VII-A; Sigma-Aldrich) prepared in PBS. 150\u03bcm slices were cut with a vibratome (VT 1000S; Leica) in a bath of ice-cold PBS. For immunolabeling, samples were saturated with PBS supplemented with 10% of fetal calf serum, then were labeled with primary antibodies anti-B220-APC (clone RA3-6B2) and anti-IgD-PE (clone 11-26c.2a) and analyzed with a spinning disk confocal microscope equipped with a CoolSnap HQ2 camera (Photometrics) and a 20x objective. Images were acquired and analyzed with MetaMorph 7 imaging software Molecular Devices).", "The quantification of IgG or IgM secreting cells was assayed by ELISpot technique. Briefly, plates were coated with HEL. After saturating, the cells were distributed into the micro wells in RPMI1640-2%FCS. The plates were incubated for 12 h at 37\u02daC, 5% CO2 atmosphere. After extensive wash, plates were incubated with goat anti-mouse IgM or anti-IgG labeled with alkaline phosphatase. After washing, the revealing substrate was added (2,3 mM 5-bromo-4-chloro-3-indolyl phosphate diluted in 2-amino-2-methyl-1-proprenolol buffer).", "Sample means were compared using the Student's t test. Sample means were considered significantly different at p < 0.05." ] },{ "paper_id": "f4aa788ab898b28b00ee103e4d4ab24a2c684caf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession numbers. The raw sequencing data for all RNA-Seq runs included in this work are publically available in the NCBI BioProject database under accession number PRJNA300864 (http: //www.ncbi.nlm.nih.gov/bioproject/PRJNA300864).", "IMPORTANCE" ] },{ "paper_id": "f4ac2b1e9b9523671d7c38c27a19f1eec2e15d75", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f4c1afe385e9e31eb5678e15a3c280ba97326554", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data from our study are summarized as frequencies and percentages for categorical variables. Quantitative variables are presented as medians, 25th and 75th percentiles. To compare those variables according to the viral infection status, Fisher tests " ] },{ "paper_id": "f4c43e4ae49ca69dbac32620bd0a73ecbb683b91", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Populations. Blood and tissue samples were homogenised to provide single cell suspensions [12] . Red blood cells were lysed, and the mixed leucocyte population was washed and stained with various combinations of the following fluorescent antibody stains: CD3 (SP34-2), CD8 (LT8), CD11c (SHCL3), CD14 (M5E2), CD16 (3G8), CD20 (Bly1), CD45RA (5H9), CD54 (HCD54), CD56 (B159), CD69 (FN50), CD163 (GHI/61), and MCHII (L243) (BD Bioscience, Insight Bioscience, AbD serotec). Samples were fixed in 4% paraformaldehyde for 48 hrs at 4 \u2218 C and analysed by flow cytometry (FACScanto II BD) within 72 hours of staining.", "Marmosets have been used to model the infection syndrome caused by a number of public health pathogens including Lassa virus [3] , Hepatitis C virus [4] , Dengue virus [5] , Herpesvirus [6] , Junin virus [7] Rift Valley Fever [8] , and SARS [9] . Marmosets have also been used to model a number of biodefense pathogens including Eastern Equine Encephalitis virus [10] , Bacillus anthracis [11] , Francisella tularensis [12, 13] , Burkholderia pseudomallei [14] , Marburg haemorrhagic fever virus [15, 16] , Ebola haemorrhagic fever virus [16] , and Variola virus [17] . The utility of marmosets to assess medical countermeasures has also been demonstrated; a vaccine has been tested for Lassa fever [18] and the efficacy of ciprofloxacin and levofloxacin has been tested as postexposure therapies for anthrax and tularemia, respectively [19, 20] .", "Identification markers Marmoset (present data)", "This, in conjunction with the small size of marmosets, their immune response to infection that is comparable to humans, and the ability to house more statistically relevant numbers within high containment, makes the marmoset an appropriate animal model for biodefense-related pathogens." ] },{ "paper_id": "f4cd52975e6aa33e8c947082eda9b261952b0f8f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Conclusions: Two E. coli W mutants were engineered that could effectively produce the bio-active flavonol glycosides hyperoside and quercitrin starting from the cheap substrates sucrose and quercetin. This novel fermentationbased glycosylation strategy will allow the economically viable production of various glycosides.", "Background: Flavonoids are bio-active specialized plant metabolites which mainly occur as different glycosides. Due to the increasing market demand, various biotechnological approaches have been developed which use Escherichia coli as a microbial catalyst for the stereospecific glycosylation of flavonoids. Despite these efforts, most processes still display low production rates and titers, which render them unsuitable for large-scale applications.", "Culture samples were primarily analyzed by TLC on Silica gel 60 F 254 precoated plates (Merck, Germany). All plates were run in a closed TLC chamber and developed using standard visualization techniques and agents: UV fluorescence (254 nm) or by staining with 10 % (v/v) H 2 SO 4 and subsequent charring. The mobile phase for detecting the various flavonols and corresponding glycosides consisted of an ethyl acetate:acetic acid:formic acid:water (100:11:11:27 v/v) mixture [63] . Product spot intensities of other flavonol glycosides were processed and quantified using ImageJ [64] . HPLC quantification of sucrose, fructose and glucose was performed using an X-bridge Amide column (35 \u03bcm, Waters, USA) as described previously [45] . Quercetin, hyperoside, quercitrin and isoquercitrin were detected with the method described by Pandey et al. [41] using a Varian HPLC system (Agilent technologies, California). Mass spectrometry for determination of the various flavonol glycosides was performed with a Micromass Quattro LC (McKinley Scientific, USA). Detection was performed in negative mode ESI-224 MS with a capillary voltage of 2.53 kV, a cone voltage of 20 V, cone and desolvation gas flows of 93 and 420 L/h, and source and cone temperatures of 150 and 350 \u00b0C, respectively." ] },{ "paper_id": "f4cebabd74b16e710fb41a737d8ef84b7d565d8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest.", "Additional and more detailed methods can be found in supplementary information.", "Open field behaviour. Mice were placed into a walled arena (grey polyvinyl chloride; 45 \u00d7 45 cm) and allowed to explore for 20 min. Animals were monitored by EthoVision XT analysis software (Noldus, Wageningen, Netherlands)." ] },{ "paper_id": "f4f0d1b957340175fd951c8fa9c27815dd589f26", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DMGF (98% purity by high performance liquid chromatography) isolated from the dried needles of Taxus media var. Hicksii was kindly provided by Yung-Shin Pharmaceutical Industry Co., Ltd. (Taichung, Taiwan) [7] . Briefly, the dried needles of Taxus media var. Hicksii (10 kg) were extracted with methanol (MeOH) at a preferred ratio of 1:1 (w/v) at room temperature to yield a methanol extract. The crude methanol extract was partitioned with water/ethyl acetate (EtOAc) (1:1), mixed with 350 g silical gel 60 N (Timely, Japan) for packing in an open column, and eluted with different ratios of hexane/EtOAc to afford 5 fractions (4:1, 3:1, 7:3, 13:7, 3:2, A-E). Fraction E was further purified by recrystallization from hexane/acetone (3:1) then re-chromatographed with the same elution condition to give 4.2 g (98.5 %) of DMGF sample.", "The docking of DMGF into CREB was explored using iGEMDOCK software [30] [31] [32] [33] , which have been shown to be powerful tools for molecular recognition and screening [34] . CREB1 (PDB code: 2LXT) was selected from Protein Data Bank (PDB) and DMGF was docked with it. The parameters of iGEMDOCK were setting such as population was set to 300, generation was set to 70 and solution was set to 100 [32] .", "Total cellular RNA was extracted with TriZol reagent (Life Technologies, Glasgow, UK) according to the manufacturer's instructions. Total RNA was reverse-transcribed using the Superscript\u2122-III kit (Invitrogen, Carlsbad, CA). PCR analysis was performed on aliquots of the cDNA preparations to detect gene expression. The amplified products were visualized on 2% agarose gels. The PCR conditions were 4 min at 94\u00b0C followed by 30 cycles of 30 seconds at 95\u00b0C, 30 seconds at 55\u00b0C, and 1 min at 72\u00b0C. The following primers were used for the amplification reaction: 5\u02b9-GTG CCT GAG ATA ACT CAC CAC-3\u02b9 as the forward primer and 5\u02b9-TTC TGC ACT TAC ACA GAA AGG-3\u02b9 as the reverse primer for Cdc42; 5\u02b9-AAG ACA TCC AAC AGC CAG AA-3\u02b9 as the forward primer and 5\u02b9-TGT AGC CAC GTC CCG AGT-3\u02b9 as the reverse primer for PAK1; 5\u02b9-CCC TAT CCT ATC CGC AAA CA-3\u02b9 as the forward primer and 5\u02b9-CGC ACC TCA GGA TAC CAC TT-3\u02b9 as the reverse primer for Rac1; 5\u02b9-CCC CCA AAT GGT CCT AAT CT-3\u02b9 as the forward primer and 5\u02b9-ACA TGT CCA ATG TCT GGA A-3\u02b9 as the reverse primer for N-WASP1; 5\u02b9-GGG GCA TCA TCA AGA GCA-3\u02b9 as the forward primer and 5\u02b9-GAG GAC TAG GGT GGT TCAG-3\u02b9 as the reverse primer for LIMK; and 5\u02b9-CCA GCC GAG CCA CAT CGC TC-3\u02b9 as the forward primer and 5\u02b9-ATG AGC CCC AGC CTT CTC CAT-3\u02b9 as the reverse primer for GAPDH. The amplification was performed in 30 cycles of 50-60\u00b0C for 30 s, 72\u00b0C for 1 min, and 94\u00b0C for 30 s." ] },{ "paper_id": "f4f36a8e9fee64d59ccf22b724c7dab345102658", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following the successful cloning of receptor for SARS coronavirus a few years ago, Dr. Wenhui Li and colleagues raised attention again by publishing a possible receptor for hepatitis B virus in eLife. We will briefly review the significance of this finding and the future prospects of hepatitis B research.", "The molecules on the cell membrane needed for HBV infection can be divided into two classes: low affinity and high affinity molecules. Among others, the heparan sulfates in the membrane proteins mediate the broad, but less specific, virus-cell interaction. However, the high affinity membrane partners for HBV remain elusive (the carboxypeptidase D found for duck hepatitis B virus may be the only serious contender [2] ).", "NTCP is a transmembrane protein, usually located in the lateral surface (canalicular) of hepatocytes, which mediates bile acid transport [7] . Geographically, it is a good candidate for an HBV receptor. Moreover, the authors could convert the cell lines previously non-permissible to HBV infection to permissible by over-expression of NTCP, again supporting its possible role in the HBV infection process. This can be a critical and long-awaited discovery toward understanding HBV receptors and establishing an experimental HBV infection system." ] },{ "paper_id": "f4f75af02b7226c5b2363de1a75821a4b9b20412", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vaccine strategies aiming at blocking/limiting infection by SARS-CoV mainly focus on targeting the SARS-S viral glycoprotein [100] . Nonetheless, such a strategy poses a singular dilemma for CoVs, as previous vaccination protocols have highlighted the possibility of immune-mediated enhancement of the disease [104] .", "The basic genome organization and replicative cycle is similar for all CoVs. Gene 1 encodes all predicted replicase/transcriptase proteins, which are translated from input genomic RNA, while genes 2-9 encode structural and accessory proteins, including the envelope spike (S) protein, which are translated from separate subgenomic mRNAs. CoVs use a unique discontinuous mechanism to transcribe a series of progressively larger subgenomic mRNAs, and each contains a leader RNA sequence that is derived from the 5' end of the genome [99] .", "The [94] . More than 8,000 cases, including almost 800 deaths, were reported during the outbreak period and increasing age and comorbidity were risk factors for severe disease and death [95] . Since 2003, only sporadic cases have been reported; however, the possibility that SARS outbreaks could reemerge naturally or be deliberately released is a public health concern. Like influenza viruses, SARS-CoV circulates in animal reservoirs, with bats that are thought to transmit the virus to small mammals with exposure to these small animals as the source of human infections [96] . The clinical disease is similar to other severe acute respiratory infections, including influenza, and the SARS case definition includes clinical, epidemiologic, and laboratory criteria [97, 98] .", "Hepatitis C virus (HCV) is a positive-sense single stranded RNA enveloped virus causing chronic hepatitis in most untreated patients (about 80%), with the consequent risk of developing cirrhosis and hepatocellular carcinoma. More than 170 million people (2%-3% of the world population) are infected worldwide, and a protective vaccine is not yet available, whereas therapeutic options are still limited and not completely effective [19] . For these reasons chronic HCV infection represents the major indication for liver transplantation in Europe and United States. Moreover, transplanted recipients are subject to high risk of graft re-infection and to a more severe and rapid progression of the liver disease [20] ." ] },{ "paper_id": "f4f804bac7b32c84ad6572776df684df2a2e5fda", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Other contaminants potentially affecting eggs and embryos were determined in liver, including heavy metals (Cd, Zn, Pb and Hg), following Blanco et al. [23] , dithiocarbamate thiram, disulfuram, polybrominated diphenyl ethers, organochlorines and brominated flame retardants, following Lemus et al. [12] and carbamate and organophosphate pesticides (carbofuran, aldicarb and fenthion) following Elliot et al. [24] . We measured brain cholinesterase activity to assess early exposure to anticholinesterase pesticides [25] . Potential contamination was assessed by comparison with levels from apparently normal wild birds of other species [26] in the absence of basal levels for bearded vultures.", "Table S1", "Found at: doi:10.1371/journal.pone.0014163.s001 (0.05 MB DOC)" ] },{ "paper_id": "f4f9ea9e0aeb74d3601ee316b84292638c59cc53", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Co-expression data from COXPRESdb 40 . Three preprocessed co-expression datasets (Hsa.c4-1, Hsa2.c2-0 and Hsa3.c1-0) including pre-calculated pairwise Pearson's correlation coefficients for human were collected from COXPRESdb. The correlations are calculated as follows:" ] },{ "paper_id": "f4ff5cb594614337119fc4d7e39600c41119f80b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f501b5ccc17158a3018dc5688b253e31ba0380d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Other centralities used to globally evaluate the structure of a network include:", "Graph theory is a powerful abstracting machinery that allows to model several types of system, both natural and human-made, ranging from biology to sociology science [28] . A graph, also called network, provides a system representation in terms of relationships among the elements that make it up; a set of nodes V, stands for the elements of the system, while a set of edges E, stands for their relations. Mathematically, we refer to a graph as G = (V , E) (Fig. 1a) .", "Formally, betweenness can be defined as" ] },{ "paper_id": "f50562c5a5e9f206dba3c559e6b4f5b65aadf7f4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The range of viruses that commonly infects the respiratory tract is notoriously wide (rhinovirus, coronavirus, respiratory syncytial virus [RSV] , adenovirus, parainfluenza virus, coxsackievirus, cytomegalovirus). However, no specific cytomorphologic alteration been found to date that could represent a turning point in epidemiology, despite viral infections accounting for the bulk of human infectious diseases, or in prognosis and therapy. Some have strongly linked with the carcinogenesis of several tumor types, particularly Burkitt's lymphoma and nasopharyngeal carcinoma (NPC), or Epstein-Barr virus (EBV) [10] [11] [12] .", "Oropharyngeal, laryngoscopic and otoscopic evaluations were normal.", "The Prick test ruled out allergy toward common trophic and aeroallergens." ] },{ "paper_id": "f5080088701ed43effa979603627b2a3ad53d5aa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At time of harvest, media was removed, cells were rinsed once with 1\u00d7 PBS and lysed with 1\u00d7 RIPA (150 mM sodium chloride, 1.0% Triton X-100, 0.5% sodium deoxycholate, 0.1% sodium dodecyl sulfate (SDS), 50 mM Tris, pH 8.0 with phosphatase, and protease inhibitors (Sigma-Aldrich)) for 5 min at room temperature (RT). Lysates were collected and equal protein amounts were separated by SDS-PAGE and blotted onto a PVDF membrane by wet-blotting (Bio-Rad). Membranes were blocked with 5% milk or 5% BSA in TBS containing 0.1% Tween 20 (TBS-T) for 1 h at RT. Primary antibodies were diluted in blocking buffer and incubated overnight at 4\u00b0C. Membranes were washed 3\u00d7 in TBS-T for 5 min at RT. Secondary antibodies were diluted in blocking buffer and incubated at RT for 1 h with rocking. Membranes were washed 3\u00d7 in TBS-T for 5 min at RT. HRP detection reagent (GE Healthcare) was mixed 1:1 and added to the membrane, which was then incubated at RT for 5 min. Membranes were exposed to film and developed.", "To evaluate whether type I and/or III IFN protect primary human IECs from viral infection, organoid cultures were treated and the viral antigen levels within these organoids ( Figure 3D) .", "Human colon tissue was received from colon resection (52) (53) (54) from the University Hospital Heidelberg under the approved study protocol S-024/2003 and human ileum and jejunum were purchased from Baylor University and transferred by signed MTA. Stem cells containing crypts were isolated following 2 mM EDTA dissociation of tissue sample for 1 h at 4\u00b0C. Crypts were spun and washed in ice-cold PBS. Fractions enriched in crypts were resuspended in Matrigel and maintained in basal culture media (53) Advanced DMEM/F12, supplemented with 1% penicillin/ streptomycin, 10 mM HEPES, 50% v/v Wnt3A conditioned media, 1\u00d7 B-27 (Life technology), 1\u00d7 N-2 (Life technology), 2 mM GlutaMax (Gibco), 50 ng/mL EGF (Invitrogen), 1 \u00b5g/mL Spondin (Peprotech), 100 ng/mL Noggin (Peprotech), 10 nM Gastrin (Sigma), 1 mM N-acetyl-cysteine (Sigma), 10 mM nicotinamide (Sigma), and 500 nM A-83-01 (Tocris). Differentiation media is the same as above except without Wnt3A, nicotinamide and 50% reduced levels of R-Spondin and Noggin. Organoids were stained after cryo-sectioning of embedded organoids in Tissuetek." ] },{ "paper_id": "f50b6632623eb4fe2193588b4f2c217c7125872d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Although to date no virus has been recognized as a causative factor of MS, the possibility that both autoimmunity and neurodegeneration in MS may coexist and commonly be explained following a viral infection is reviewed here.", "Autoimmune responses to myelin antigens are observed following infection with TMEV. Despite the fact that this autoimmunity to myelin components may not play a major role in the initiation of demyelination, it may probably contribute to lesion progression in chronically diseased animals [29] .", "It was suggested that virus infection may initiate or exacerbate organ-specific autoimmune diseases [77] . There is growing evidence about possible mechanisms by which virus infection can trigger autoimmunity. Among them are: (a) molecular mimicry, (b) bystander activation, and (c) epitope spreading (figure 1)." ] },{ "paper_id": "f50bc0f52caca340de8ba25900681253da739f2f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f5133d66a71eb5add9881ec5f254fc0757a7ee06", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "By applying several steps of Bayes' rules, the probability P i (c) is given by:" ] },{ "paper_id": "f51b986600acc015fa48820a1ec11c90ea871d6d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using Graphpad Prism 6 software. Time-course studies were analyzed by two-way ANOVA with Bonferroni's or Tukey's multiple comparison post-test for two group and three group comparisons, respectively. Comparisons between three groups at a single time point were made using one-way ANOVA with Tukey's multiple comparisons post-test. A p value of <0.05 was considered significant for all analyses." ] },{ "paper_id": "f533213ea544502d4d5aee4e6fabea7b1f0ceabc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For confocal microscopy analysis, replication inhibition assay was performed on cells seeded on coverslips in 6-well plates (TPP, Switzerland ", "To ensure broad specificity of NSPAH towards different hMPV strains, the study was performed also using different hMPV strain (clade A1). Similar antiviral effect was observed (Fig 4; S8 Fig) .", "Virus yield was determined by reverse transcription (RT) quantitative real-time PCR (qPCR).", "Human metapneumovirus (hMPV) is associated with acute infections of the respiratory tract, with increased severity in children, infants, elderly, and immunocompromised patients [1] [2] [3] [4] . hMPV was identified in 2001 in the Netherlands [5] and sorted to the Pneumoviridae family. Its prevalence in children and infants requiring hospitalization worldwide reaches 4-25% [6, 7] . Moreover, serological studies showed that~70% of children are seropositive at the age of five [8] . Symptoms associated with the infection are usually mild (e.g., cough, subfebrile temperature), but more severe disease also occurs (e.g., bronchitis, pneumonia) [9, 10] ." ] },{ "paper_id": "f53604d28e212733384d7ec28e84d4a62e506254", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No ethical approval was required for this study as all clinical samples collected were either animal waste products, surplus to diagnostic requirements, or derived from a previously published and ethically approved study [17] .", "Stools were diluted 10% w/v in phosphate-buffered saline, pH 7.2, and solids were removed by centrifugation at 80006g for 5 min. Viral nucleic acid was extracted from 140 ml of each clarified stool suspension by the GenElute TM Mammalian Total RNA Miniprep Kit (Sigma Aldrich) according to the manufacturers' instructions.", "A 1-step qRT-PCR protocol was used to improve ease and efficiency of sample handling. 2 ml of extracted RNA was added to 26 Precision OneStep qRT-PCR MasterMix (PrimerDesign Ltd), 6 pMol/ml primers, and 3 pMol/ml probe. The thermal cycle protocol used with a ViiA7 qPCR machine (AB Applied Biosystems), was as follows: 55uC for 30 mins, inactivation of reverse transcriptase at 95uC for 5 mins, and then 40 cycles consisting of denaturation at 95uC for 15 s, then annealing and elongation at 60uC for 1 min." ] },{ "paper_id": "f54b1d2032db8537d80fc36e29bc6fcdfb878435", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments and procedures involving animals were approved by the Animal Welfare and Ethical Censor Committee at Harbin Veterinary Research Institute (HVRI). All animal experiments in this study were approved by the Animal Ethics Committee of the HVRI of the Chinese Academy of Agricultural Sciences with license SYXK (Heilongjiang) 2011022.", "Viruses 2017, 9, 209 4 of 10 with PBS, peroxidase activity was revealed by incubation with 0.03% Nitro blue tetrazolium chloride(NBT)/5-bromo-4-chloro-3-indolyl phosphate (BCIP), 0.006% H2O2 in PBS for 5 min.", "Viruses 2017, 9, 209 5 of 10", "A monolayer of MDCK cells in 96-well plates were inoculated with serial dilutions of the virus strains (each dilution with five replicates). The cytopathic effect (CPE) was observed daily and the number of wells showing more than 50% pathological changes were recorded. TCID50 titers were calculated as described previously [32] . Each dilution was done in five repetitions." ] },{ "paper_id": "f54e577394738498bde347596b1dd5b1156d235d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The well-recognized 2012 pertussis outbreak in Washington State overlapped a respiratory viral season characterized by wide-spread circulation of influenza, respiratory syncytial virus (RSV), and other respiratory", "The protocol for this retrospective cohort study was approved by Seattle Children's Institutional Review Board. All authors declare no competing interests that could potentially influence data analysis and conclusions.", "Proportions were compared using Chi square, McNemar's exact Chi square, two-sample test of proportions, and one-way ANOVA as appropriate. Statistical analyses were performed using Stata 12.1 (Statacorp, College Station, TX)." ] },{ "paper_id": "f55b841ff2d5939a229e9a7053d26e48b5139610", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A standardized questionnaire was administrated by clinical personnel, to record patients' demographic characteristics and medical history. The questions included information on date of enrollment and symptom onset, sex, age and clinical symptoms. Nasopharyngeal (NP) swabs were collected from all enrolled cases and placed in cryovials containing virus transport medium (Copan kit, Italy). The specimens were kept refrigerated at 4\u00b0C at the sentinel site and then transported twice weekly to CERMES for testing. Samples were aliquoted, screened for influenza A and B viruses by real-time reverse transcription polymerase chain reaction (rRT-PCR), and then stored at \u221280\u00b0C.", "Among the selected children, 56 % (90/160) were <1 year of age (median age among children age <5 years: 9 months), 46 % (73/160) were female and 78 % (125/ 160) had a duration of symptoms \u22643 days. Most patients presented with a recorded temperature >38\u00b0C (58 %; 93/160), cough (96 %; 155/160), dyspnea (69 %; 111/160) and chest indrawing (76 %; 122/160). Few patients presented with tachypnea or had difficulty in breastfeeding (15 %; 25/160).", "The authors declare that they have no competing interests. Submit your manuscript at www.biomedcentral.com/submit", "Nucleic acid was extracted using the QIAamp mini kit (Qiagen, Germany) in accordance with the manufacturer's protocol. An internal control (IC) was added to each extraction tube in order to assess the quality of the extraction at the end of the amplification. " ] },{ "paper_id": "f55d236f93a8d11a6265a8c3fdfaa2c32b3af19b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mean \u00b1 SD 10.71 \u00b1 4.39 (Average adherence rate: 53.5%)", "Step 1", "Step 2 \u03b2 t (p) 95% CI \u03b2 t (p) 95% CI ", "On the other hand, high-quality equipment and adequate communication systems can increase the \"wearing rate\" [4, 31] . Thus, supportive training programs to raise nurses' positive perceptions and attitudes are needed to improve their wearing of personal protective equipment. Particularly, nurse educators with organizational support should develop and provide specialized guidelines and interventions that identify the characteristics and problems unique to each department rather than a standardized approach for the entire nursing staff in a hospital." ] },{ "paper_id": "f56a6e854737649264b48f3709c54551d3660edd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thus, a continuing search for new therapeutic agents to target novel viral life cycle stages is needed.", "To examine HIV-1 DNA integration, semiquantitative nested Alu-HIV-1 integration PCR was done as described previously [44, 76] , but with slight modifications. The following primers were used for the first round of amplification:", "where DU~densitometric units:" ] },{ "paper_id": "f56c5a350cc09b29ab51068039bfb27523945e09", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "File S1 Supplementary materials.", "\u00f06a \u00c0 \u00c0c\u00de", "Author Contributions" ] },{ "paper_id": "f580401828d99aa0874fc10a731aa34a8cfb69b3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The iterative 2L-PCA technique described in Method section is used for the binding affinity study of peptides based on the sequences and experimental data listed in Table 2 ", "and F A W", "and H W S" ] },{ "paper_id": "f582baa8aa4a5f3af8356e86df3d5c29ff426c85", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "4. The English grammar needs some brush up, such as \"the placenta barrier\" (line 177), \"such as fever, rash, and but \" (line 193), etc.", "The order of panels in Figure 4 was adjusted accordingly.", "7. In line 326, both reference 31 and 53 are related with pseudotyped MERS-CoV, but no reference was provided about the preparation of pseudotyped VSV." ] },{ "paper_id": "f58cfab11be3906401550ffe0ba6e444d1056853", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The amount of viral RNA was quantified by using One Step PrimeScript RT-PCR Kit (Takara, Dalian) according to the manufacturer's protocol as previous described [64] with EV71 specific premiers (Fwd, 5 0 -GGCCATTTATGTGGGTAACTTTAGA-3 0 ; Rev, 5 0 -CGGGCAATCGTGT CACAAC-3 0 ) and probe (5 0 FAM-AAGACAGCTCTCGCGACTTGCTCGTG-BQH1 3 0 ).", "RD cells at 90% confluence on glass slides were transfected with indicated EV71 transcript. The cells were fixed at 24 h post-transfection with pre-cooled acetone at -20\u00b0C for 30min, followed by washing in PBS for 3 times and incubation with mouse anti-EV71 VP1 monoclonal antibody (Chemicon International, Madison, WI) for 60 min at 37\u00b0C. The cells were then washed in PBS and incubated with Alexa Fluor 488-labeled goat anti-mouse IgG (Invitrogen) for another 45 min. Cells were incubated with DAPI at room temperature for 5 min to stain the nuclei. Finally, the cells were rinsed again with PBS and visualized under a fluorescent microscope (Olympus, Tokyo, Japan). ", "NTPase activities were determined via measuring the released inorganic phosphate during NTP hydrolysis using a direct colorimetric assay as previously described [30] . All of the results given with this quantitative assay were averages of three repeated experiments." ] },{ "paper_id": "f592542c73a8294125b53d9eeef9a61cfcd9b1a3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Alanine 231 is conserved as well, in that the position is valine or glycine among the enteroviruses) [14] and hydrophobic or small residues (alanine, glycine, valine or serine) among DNA polymerases [15] .", "T G gaa gag aag ctg ttt tgt ttt gcc tac aca ggg D used as a positive control for mutagenesis. DNA from resulting colonies was sequenced at the LSUHSC sequencing core and proper mutant sequence confirmed. Appropriate plasmids were grown and isolated using qiagen kits.", "Wild type Renilla A231C DOUBLE D233A MOCK sample was taken for \"time zero\" and the remaining cells were split into dishes." ] },{ "paper_id": "f595066c0454a407001920c8baf1edb260e9bb9d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Step 1. Set an initial kernelK 1 at the first layer. Here the initial kernel is defined as:", "Step 2. Let f = ( f 1 , . . . , f n ), Denote by | f | the length of f , so here | f | = n. Then define the second layer neural response of f at t :", "where T 1 is the template set at the first layer, here we consider all possible substrings of length k making up the template set T 1 , so here T 1 = A k . H 1 is the transformation set at the first layer.", "where x, y \u2208 A k . x = {x 1 , . . . , x k } and y = {y 1 , . . . , y k } are substrings of the same length k. x = y if and only if x i = y i for i = 1, . . . , k." ] },{ "paper_id": "f5ad2323eb387f6e271e2842bb2cc4a33504fde3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ORF1a/1b and 530-541", "ORF1a/1b and 7399-7411", "ORF1a/1b and 14048-14061" ] },{ "paper_id": "f5ae3f66face323615df39d838e056ab5fcc98df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Amplification was performed in two reactions. To avoid generating small products from adjacent forward and reverse primers, amplicons were assigned to alternate Table 3 ).", "Bioanalyzer (Agilent). Adapter trimming, quality filtering, kmer normalization of sequencing reads, de novo assembly, calculation of mean genome coverage was as previously described [31] ." ] },{ "paper_id": "f5b706d0529bfcf7e2d1dfc037df5b6f95fc5ec0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Continuous variables were summarized as mean \u00b1 standard deviation (SD) or median (interquartile range)." ] },{ "paper_id": "f5bdf18567bb3760e1ce05008135f0270badbd5c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f5dc4bad737644cb25aeb8e23ba999402b0df872", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 Routine use of oral or injectable antibiotics cannot be recommended in calves without systemic illness.", "\u2022 Susceptibility tests of bacteria cultured from faecal samples do not reliably predict treatment outcomes in diarrhoeic calves [37] .", "The reluctance of veterinarians and farmers to adopt the principle of continued feeding of the diarrhoeic calf led to diverging developments in osmolality of ORS for calves and humans. Commercially available ORS for calves range from isotonic to highly hypertonic, whereas WHO recently changed their recommendation towards a hypotonic formula [13] . Higher osmolality ORS for calves is a reflection of a higher concentration of glucose which is added to provide additional nutritional support. Nonetheless, the provision of high-energy ORS cannot prevent negative energy balance in calves [35] and hypertonic solutions are known to slow abomasal emptying rates compared with isotonic solutions, thereby delaying plasma volume expansion [31] .", "\u2022 In calves with diarrhoea and systemic involvement (marked depression, anorexia, fever), the risk of bacteraemia or septicaemia as well as bacterial overgrowth of the small intestine is increased. In such circumstances, administration of broad-spectrum beta-lactam antimicrobials (ceftiofur, amoxicillin or ampicillin), potentiated sulphonamides, or fluoroquinolones (where permitted) is recommended." ] },{ "paper_id": "f5dd178e6cfe607d118df9d16716cd68605dbee4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Appendix S1 Appendix with additional references. " ] },{ "paper_id": "f5df82125769765004c7dd11f066688e6dc3cc76", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f5e8e27a130f3239cafe592f4174b290849b0f2f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We have shown that the T cell chemoattractant chemokine interferon-inducible protein 10 kDa (IP-10)/CXCL10 is rapidly expressed in response to JHMV infection and is strictly colocalized with viral RNA within the CNS [31] . Among the cell types responsible for CXCL10 expression, astrocytes were the primary cellular source as demonstrated through both in vitro and in vivo experiments [31] .", "Available evidence indicates that the cause of MS is multifactorial and includes the genetic background of the individual as well as potential environmental influences [4, [14] [15] [16] . Although viruses such as herpes simplex virus type-1 (HSV-1), measles, human T cell leukemia virus type-1 (HTLV-1), human coronaviruses, human herpesvirus-6 (HHV-6), human endogenous retroviruses (HERV), and Epstein Bar Virus (EBV) have been suggested to be associated etiologically with MS, no clear causal relationship between MS and viral infection has been firmly established [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] . The development of animal models in which the clinical and histopathology is similar to that observed in the majority of patients is imperative in order to better understand the underlying pathological mechanisms contributing to MS.", "The response of the innate immune system to viral-induced demyelination has been appreciated for a number of years, however new questions have arisen as to how neutrophils contribute to demyelination. Although the observance of neutrophils in MS patients has been elusive, likely due to their transient nature, patient samples indicate substantial evidence of neutrophil attractants and markers during disease. This is supported through evidence from several animal models of demyelination from our lab and others that have shown neutrophil recruitment into the CNS enhances demyelination. While the exact mechanisms of neutrophil contribution to demyelination remain obscure, recent studies employing autoimmune models of neuroinflammation/demyelination argue for a role for NETs and other neutrophil host defenses as possible instigators of damage. This information has emphasized the potential for targeting these cells as a therapeutic strategy to limit white matter damage. " ] },{ "paper_id": "f5e971f5c6854bcf76a7963effbbd79e62becab0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 Dataset. Spreadsheet containing the data used in this study. (CSV) S1 ", "Complement, the primary mediator of serum bacterial killing capacity (BKC), is a first-line immune defense that is continually produced at low levels in the absence of pathogenic challenge, and functions to prevent infection [36, 37] . Complement levels can increase quickly following infection, but the duration of the complement pulse is generally short compared to the rise in antibody levels following infection (Fig 1) [38] .", "We used commercially available in vitro diagnostic ANA kits (Hemagen # 6659 96, Columbia, MD, USA) to assess aIgG and aIgM concentrations [51] . Sera were diluted 1:1,600 and 1:400 for IgG and IgM, respectively. We again used HRP-conjugated anti-IgG or anti-IgM detection antibodies added to the plates at concentrations of 0.2 \u03bcg/ml and 0.25 \u03bcg/ml, respectively. See the manufacturer's product data sheet for a full description of the test kit.", "Surprisingly, nIgM and aIgM were negatively correlated with age in females, and there was no association between any measure of IgG and age. Several studies have found that nIgG and aIgG increase with age [48, 73, 74] . It is possible that isotype switching from IgM to IgG may account for the decreased nIgM and aIgM observed in older hyenas." ] },{ "paper_id": "f5e974ef3a8c983ae63ac4f4aa2b6ec0e3678032", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The pathogenicity of these viruses is typically species-dependent, as is the severity of infection; they infect mainly their natural hosts and/or species that are closely related. Certain virus infections, however, can cross the species barrier, with the prime example being the zoonotic SARS-CoV, a novel coronavirus that is thought to have originated from bats before it adapted to its intermediate host, civet cats, and finally to humans [13] . Bat colonies, which are scattered worldwide, are widely known to play host to a variety of coronaviral and adenoviral pathogens while acting as natural wildlife reservoirs of these viruses [14] [15] [16] .", "A number of stimuli can precipitate apoptotic events, including cell homeostatic imbalance such as cell stress, and the binding of ligands to cell surface \"death\" receptors; these in turn trigger the onset of major apoptotic pathways: the extrinsic or intrinsic pathway [24] .", "The dephosphorylation of eIF2alpha is established by cellular protein phosphatase-1 (PP1), which functions to regular various cellular processes through the physical interaction of its catalytic subunit (PP1c) with regulatory proteins such as GADD34/CHOP that is induced by DNA damage signals [159, 160] .", "For arteriviruses, the common leader sequence of EAV sub-genomic viral RNAs, too, possesses the ability to interact several cellular proteins from the cytoplasmic fractions of Vero cells, likely for the modulation of EAV RNA synthesis [172] .", "To ascertain the involvement of cellular factors in TGEV RNA synthesis, TGEV 3' and 5' genome ends were used as baits for RNA affinity protein purification [171] . Of the ten cellular proteins pulled down with either genome end, poly(A)-binding protein (PABP), hnRNP Q, and glutamyl-prolyl-tRNA synthetase (EPRS) were confirmed to enhance TGEV infection through their respective interactions with the TGEV 3' end, while glyceraldehyde 3-phosphate dehydrogenase (GAPDH)-originally employed as a control-was discovered, surprisingly, to have a diminishing effect on TGEV infection instead [171] .", "Moreover, host endosomal membranes are forced to undergo conformational changes for the fusion of virus and host cell membranes during virus uncoating; membrane integrity is also antagonized during the process of virus disassembly. As such, these drastic alterations to membranes may elicit downstream pro-death signals that prompt infected cells to commit suicide [36] ." ] },{ "paper_id": "f5edded3536428635cad1f78fe6dc38002690a43", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In addition, indirubin extracted from indigo naturals in Danggui Long Hui Wan (Pill of Angelica sinensis, Gentian and Aloe) could treat leukemia. Diterpenonid versicolaction extracted from Tripterygium Wilfordii Hook can be used as immunosuppressive agents for treating rheumatoid arthritis (RA). Biphenyl dimethyl dicarboxylate (DDB) extracted from Schisandra chinensis could decrease the ALT and AST activity. Tetramethylpyrazine extracted from Ligusticum Chuanxiong Hort has showed a good effect for ischemic cerebrovascular disease. Cantharidin extracted from Mylabris could treat liver cancer. Moreover, other active components such as ginsenoside, total puerarin flavonoids, polyporus umbellate polysaccharides, ganoderma lucidum polysaccharide, anisodamine, tanshinone, trichosanthin, tetrahydropalmatine, tetrandrine, rubidate, ilexonin A, and ferulic acid sodium.", "It is meaningful to promote the original innovation in integrative medicine researches through further understanding the connotation of syndrome diagnosis, therapeutic principle, and classical prescription by modern science and technology. Among these studies, three researches below are honored.", "Compared with TCM theory, Chinese herbs are much easier to be modernized and recognized. Therefore, it is of great significance in promoting modernization, industrialization, and industrialization of the Chinese herbs, by ways of combining modern technology with fully understanding of classical prescriptions and herbs." ] },{ "paper_id": "f5f1cd43740b5b6eca8b3cf2714fc0854a746519", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Quality control, mapping of RNA sequencing reads and counting mapped reads Initial control quality was assessed by the FastQC software version 0.11.3 [52] . Raw reads were than trimmed for low quality bases using the Trimmomatic tool version 0.32 [53] applying minimum Phred quality score >10 averaged across the sliding window of five bases. Furthermore, all reads with the length below 40 bp were removed.", "Tissue samples were homogenized on a TissueLyzer LT (Qiagen, Hilden, Germany). Total RNA was extracted with the Qiagen RNAeasy Kit (Catalog ID 74104, Qiagen, Venlo, Netherlands) according to the manufacturer's instructions. The quality of the 64 total RNA samples was verified using a 2200 TapeStation RNA Screen Tape device (Agilent, Santa Clara, CA, USA) and the concentration ascertained using an ND-1000 spectrophotometer (Nano-Drop, Wilmington, DE).", "Libraries were prepared with the Illumina TruseqRNA sample prep kit (Catalog ID FC-122-1001, Illumina, San Diego, USA) following the manufacturer's protocol and evaluated with the Agilent Tape Station 2200. Libraries were quantified by Picogreen and then normalized to 10 nM as recommended by Illumina for cluster generation on the Hiseq2000. Equimolar amounts of each library were mixed before NaOH denaturation.", "The trimmed reads were mapped to the Gallus gallus reference genome (Gallus_gallus-4.0, release 80 [54] ) using a spliced aligner TopHat2 version 2.014 [55] . The Gallus gallus gene annotation used for mapping was retrieved from Ensembl database version 80 (www.ensembl.org). The mapping quality was assessed using a set of Python scripts within the RSeQC toolkit [56] . The quality control assessment included inspection of the read coverage over the full gene body in order to assess if reads coverage was uniform and if there was any 5' or 3' bias as well as how the mapped reads were distributed over genome features." ] },{ "paper_id": "f5f2eb53666c84eb688a501f5042f1147440a7ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell pellets were collected and lysed in lysis buffer with protease inhibitor cocktail (Sigma-Aldrich). The particulate fraction was removed by centrifugation. Proteins (20-40 \u03bcg) were separated on 10% SDS-PAGE and subjected to immunoblotting analysis ). Primary antibodies used were rabbit anti-actin (1:1,000; Sigma-Aldrich), rabbit anti-GAPDH (1:2,000; ExCell Bio), mouse anti-SMN (1:1,000; Abnova), mouse anti-Myc (1:2,000; Cell Signaling Technology), rabbit anti-ubiquitin (1:1,000; Cell Signaling Technology), mouse anti-FLAG (1:1,000; Sigma-Aldrich), rabbit anti-HA (1: 1,000; Cell Signaling Technology), and mouse anti-rhodopsin (Huang et al, 2006) (1:1,000; Santa Cruz). Horseradish peroxidaseconjugated secondary antibodies were detected with Western Lighting Chemiluminescence Reagent Plus (Pierce). For quantifying SMN proteins, SMN band intensities were normalized with actin or GAPDH and compared between different groups using ImageJ software.", "Inhibiting cysteine proteases for SMA Wang et al.", "To determine the splicing pattern of SMN2-GFP, 1 \u03bcg total RNA of each positive clone was reverse-transcribed into cDNA and removed by RNase H (Invitrogen) in 37\u00b0C for 20 min. SMN2-GFP cDNA was amplified by the primers: SMN-exon4-F, 59-AATCAGATAA-CATCAAGCCCAAATC-39, GFP-R, 59-CTTCAGGGTCAGCTTGCCGTA-39, and subsequently ligated into the pMD19 T-vector (Takara). TA Clones in Escherichia coli were assessed by PCR analysis. Different SMN isoforms could be separated on a 2% agarose gel." ] },{ "paper_id": "f5f53c6d9a31095c447315d0c2ebc42cbcebcfd2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Discussed in text. participated in discussions. PM designed this study and edited the manuscript. All authors read and approved the final manuscript.", "Abbreviations: Armstrong 53b (Arm53b); baculovirus Autographa californica GP64 (GP64); charge-coupled device (CCD); dystroglycan (DG); feline immunodeficiency virus (FIV); glycoprotein precursor (GP-C); firefly luciferase (Luc); lymphocytic choriomeningitis virus (LCMV); nuclear targeted \u03b2-galactosidase (ntLacZ); optical density (OD); PBS/ 0.1% (w/v) Tween-20 (PBST); relative light units (RLU); Rous sarcoma virus (RSV); transducing units per milliliter (TU/ ml); vesicular stomatitis virus (VSV-G); wheat germ agglutinin (WGA); 50% reduction in binding (C 50 )." ] },{ "paper_id": "f5fb2153b992cdc2d4bdb3678e667126c9a27689", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bartonellosis should be regarded as one of the major potential emerging infections of man. Most is known about 'cat scratch disease' caused primarily by Bartonella henselae acquired directly from an infected cat and mostly likely transmitted between cats by the cat flea Ctenocephalides felis [21] [22] [23] . This infection becomes particularly significant in immunocompromised individuals (e.g.", "programme [28] . The committee is chaired by the author and includes academic experts on small animal zoonotic infection (including rabies, leishmaniosis and vector-borne diseases), first opinion veterinary practitioner representation and delegates from the OIE and Centers for Disease Control and Prevention (CDC) in the USA. The committee is funded by the WSAVA Foundation through sponsorship by a consortium of the pet food and small animal pharmaceutical industry and commenced a three year programme of work in January 2011.", "The 'One Health' concept states simply that there should be a seamless interaction between veterinary and human medicine with clinicians, researchers, agencies and governments working together for the benefit of domestic and wild animal and human health and the global environment. Such interactions may take place at many levels -from management of zoonotic infectious disease outbreaks in the field, to joint research programmes to integrated policy making and funding decisions." ] },{ "paper_id": "f5fb59693963a0b96d112341f8f2a9f2b1d7a34c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GTT and ITT performed upon intraperitoneal injection of 2 mg/g BW of D-glucose or 0.75 mU/g BW of insulin, respectively, as previously described (22) . Tail vein blood was collected for measurements.", "For immunostaining, islets were handpicked under a stereomicroscope and fixed in a 10% formaldehyde solution. Islets were stained with primary antibodies against insulin followed by Alexa Fluor 488 secondary antibody staining and DAPI was used to visualize nuclei. Sections or islets were visualized with an AxioImager.", "MitoSOX, MitoTracker green and red, and DCFDA staining were done according to manufacturer's instructions (Invitrogen). Data were acquired with a FACS Calibur flow cytometer (BD Biosciences)." ] },{ "paper_id": "f5fd6b1f388f2244e5631dacb82c774638d30797", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, since a historical sketch can be informativeparticularly considering a cellular component as enigmatic as the IC-we start by recalling the developments that lead to the placement of this compartment on the map of the cell.", "Regarding other transport factors, the two IC-associated Rab proteins, Rab1, Rab2, and their effector proteins, many of which function in membrane tethering, have been discussed elsewhere (Saraste 2016) . Generally, the IC localization of the latter-for example, GM130 ( Fig. 1 ; see also Marra et al. 2007 )-opens up for their participation in homotypic fusion events within the permanent IC network, or in transport between central IC elements and the Golgi stacks (Model C).", "Since this model presents the pre-Golgi elements as cargo carriers themselves, they have also been referred to as transport complexes (TCs; Bannykh and Balch 1997; Stephens and Pepperkok 2001) . Indeed, the well-documented size and shape heterogeneity of the vacuolar, tubular and vesicular IC elements (Fig. 3 ; Ying et al. 2000) opens up for their function as different types of carriers-\"cars and trucks\" (Fan et al. 2003 )-with the ability to accommodate different types of large or small cargo, such as procollagen fibers, lipoprotein particles, soluble or membrane-bound proteins or lipids. Interestingly, carrier formation at ERES for largesized cargo turns out to involve a highly complex interplay between the COPII machinery, IC membranes, and novel organizers, such as TGF and TANGO (Hanna et al. 2018) ." ] },{ "paper_id": "f5fe14c66ff48ce3cff7c81201c1800cb725b097", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Aliquots of blood (20 \u03bcL) obtained from the abdominal artery were diluted 1:10 in Turk's solution (0.1% crystal violet in 3% acetic acid) for cell quantification. After semi-excision of the trachea, a plastic cannula was inserted and airspaces were washed with 0.5 mL of 0.9% sodium chloride containing 2.6 mM EDTA with a 1 mL syringe. This operation was repeated twice. BAL was centrifuged (600 g for 10 min, 4\u00b0C) and the cell-free supernatants were frozen at -80\u00b0C for subsequent cytokine analysis. Cell pellets were re-suspended and an aliquot (190 \u03bcL) was diluted 20:1 in Turk's solution (3% crystal violet in 20% acetic acid) for cell quantification.", "In both cases, total and differential counting was obtained with a Neubauer chamber using a \u00d740 objective in the light microscope Axioskop II mot plus (Zeiss, GR). BAL cells were distinguished in polymorphonuclear (PMN), mononuclear phagocytic cells (monocyte/macrophages -MPC) and lymphocytes (LY), whereas blood cells were divided into PMN, peripheral blood monocytes (PBMC) and LY.", "Aliquots of blood and BAL fluids were centrifuged at 4000 and 600 g for 10 min, respectively. Concentrations of tumor necrosis factor (TNF)-\u03b1, transforming growing factor (TGF)-\u03b2 and interferon (IFN)-\u03b3 were measured using specific enzyme-linked immunosorbent assay kits purchased from R&D System (Abingdon, UK).", "Total lung hydroxyproline contents were determined using a well-accepted assay [27] . Briefly, samples of lung homogenate (500 \u03bcL) were added to 1 mL of 6 N hydrochloric acid for 8 h at 120\u00b0C. To a 5 \u03bcL sample of the digested lung, 5 \u03bcl of citrate/acetate buffer (5% citric acid, 7.2% sodium acetate, 3.4% sodium hydroxide, and 1.2% glacial acetic acid, pH 6.0) and 100 \u03bcL of chloramine-T solution (282 mg of chloramine-T, 2 ml of Npropanol, 2 ml of distilled water, and 16 mL of citrate/ acetate buffer) were added. The resulting samples were then incubated at room temperature for 20 min before addition of 100 \u03bcl of Ehrlich's solution (Aldrich, Milwaukee, WI), 9.3 mL of N-propanol, and 3.9 mL of 70% perchloric acid. After a further incubation at 65\u00b0C samples for 15 min, samples were read at 550 nm in a DU640 spectrophotometer (Beckman, Fullerton, CA); hydroxyproline concentrations were then calculated from standard curve (0-100 \u03bcg/mL hydroxyproline)." ] },{ "paper_id": "f5ff89ebfdd0375d034c112c6c1c7e163fa69a0c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data and swabs result from a surveillance system that received regulatory approvals, including the CNIL (National Commission for Information Technology and Civil Liberties Number 1592205) approval in July 2012. All the patients have received oral information and gave their consent for swab and data collection. Data were collected for surveillance purpose and are totally anonymous.", "Patients' sex-ratio was 0.63 (86 men and 136 women) and mean age was 28.4 years [min 0; max 81]. Ten percent had less than 5 years, 24% 5-15 years, 63% 15-65 years and only 3% were 65 and older.", "Regarding co-infections, nine swabs revealed the presence of two viruses, among which6 involved influenza viruses (Table 2) .", "During the study period, a minority of the weeks (21 i.e. 20%) did not include any sampled swab, mainly outside flu season." ] },{ "paper_id": "f601b810174ec3f6056d0806959c06a2b211f3ca", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "IFN\u03b2 does not restore acquired responses nor reduce MUC5B.", "Follow-up: Subjects had repeat visits at three monthly intervals when clinically stable and were followed up for a minimum of 6 months. Subjects reported to the study team when they developed symptoms of an acute exacerbation defined using the East London cohort criteria 60 and were seen within 48 h of symptom onset. Sputum samples were collected at the onset of exacerbation and at 2 weeks during exacerbation." ] },{ "paper_id": "f60263668f8bb59ae4bd30498e2f04c18157773e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Hemagglutination inhibition (HI) was performed according to [39] adapted to microtiter plates.", "Graphs were generated using KaleidaGraph v.3.6 graphing software (Synergy Software, Reading, PA). Statistical analyses were performed using the GraphPad Prism 4.0 software package (GraphPad Software, San Diego, CA). P values less than 0.05 were considered significant.", "Alternative Language Abstract S1 Translation of the abstract into Thai by Ekachai Jenwitheesuk. Author Contributions", "This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose." ] },{ "paper_id": "f6069d299d3a03300b5ce41868efc5f2391a7544", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f60eb9280104d1ff7ca8ade5a7ccdeca43afce2f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by the NHLBI (grant no. R01HL083254) to E.D.", "Nucleotide sequence accession number. The complete genome sequence of HPV-Fin864 is available in GenBank under the accession no. KC311731.", "A divergent human gammapapillomavirus (\u2425-HPV) genome in a nasal swab from an elderly Finnish patient with respiratory symptoms was genetically characterized. The L1 gene of HPV-Fin864 shared <70% nucleotide identity to other reported \u2425-HPV genomes, provisionally qualifying it as a new species in the Gammapapillomavirus genus." ] },{ "paper_id": "f61c2dbfa5417548e87ffd4da8286b37f9479b09", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The aim of this pilot study was to evaluate the therapeutic and safety performance of an intramuscular treatment protocol of multidose of allogeneic adipose stem cells (ASCs) isolated, characterized, and expanded ex vivo from a healthy canine donor.", "Considering the efficiency in obtaining high cell counts and minimal induced morbidity during cell collection [34] , it was decided to use the omentum adipose tissue as a source of ASCs.", "ASCs display a spindle-shaped morphology and a strong attachment to the surface of the culture vessel ( Figure-2a) . Population doubling time was 32 h, which persisted during the whole expansion procedure." ] },{ "paper_id": "f625d4a9a3a6e1dad4c03e5e79e04b3e6b098997", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f62a6a8b129d2104c5db1535b07e090ddf5ca7d3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We intend to apply this optimized method for the detection of airborne viruses in indoor and outdoor environments.", "Background: Airborne viruses remain one of the major public health issues worldwide. Detection and quantification of airborne viruses is essential in order to provide information regarding public health risk assessment." ] },{ "paper_id": "f62e14e75bd446217bb09ec6824559f88116c366", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lungs were prepared from infected mice and immersionfixed for 24 h in 4 % buffered formaldehyde solution (pH 7.4), dehydrated in a series of graded ethanol and embedded in paraffin. Sections were cut from five evenly distributed levels and stained with haematoxylin and eosin. For each group (KO and WT, virus), three mice were studied and five sections per mouse were analysed for inflammation using a semi-quantitative scoring system from 0=none, 1=mildly, 2=moderately, 3=severely increased cellular infiltration. In addition, bronchiolar structures with and without epithelial cell necrosis were counted on one section to calculate percentages of affected bronchi.", "In conclusion, these results demonstrate that both the loop and distant amino acids are necessary for causing severe symptoms upon infection in Tmprss2 \u00c0/\u00c0 mice.", "This work was supported by intra-mural grants from the Helmholtz-Association (Program Infection and Immunity), a start-up grant from the University of Memphis Tennessee Health Science Center, and a research grant FluResearchNet (No. 01KI1006F) from the German Ministry of Education and Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. I S. 1206, 1313 and BGBl. I S. 1934). The protocol used in these experiments has been reviewed by an ethics committee and approved by the relevant authority, the 'Nieders\u20ac achsisches Landesamt f\u00fcr Verbraucherschutz und Lebensmittelsicherheit, Oldenburg, Germany' (Permit Numbers: 33.9.42502-04-051/09 and 3392 42502-04-13/1234).", "However, it should be noted that the above changes were still not sufficient to completely restore the high virulence of a virus with a complete H3-HA [PR8_HA(HK)], suggesting that further distant amino acids might be important as well.", "Recombinant viruses were generated by DNA transfection as described earlier [34] . All pHW-2000 plasmids containing eight segments of PR8 (A/Puerto/Rico/8/34, H1N1) were kindly provided by Robert Webster (St. Jude, Memphis, USA). HEK 293T and MDCK cells were co-cultured in a six-well plate and grown 24 h at 37 C in 5 % CO 2 until cells reached confluency. Cells were washed and 800 \u00b5l OptiMEM (Gibco) were added. Transfection was performed using Lipofectamine 2000 (Invitrogen) or TransIT-LT1 (Mirus Bio LLC) according to the manufacturer's instructions using 1 \u00b5g of each plasmid and 15 \u00b5l Lipofectamine or 16 \u00b5l TransIT-LT1, respectively. Within 24 h post transfection medium was exchanged with 2 ml MEM containing 1 % P/S and 1 \u00b5g TPCK-trypsin (tosyl phenylalanyl chloromethyl ketone treated trypsin) (Sigma). Cells were monitored every day until a cytopathic effect appeared and virus was harvested. After amplification of virus, RNA was extracted and whole virus genome was confirmed using next generation sequencing by Illumina (see Cells and viruses)." ] },{ "paper_id": "f63338a20d7b3df2c60068dddfb9086ece7ba5fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Engine; http://www.sbg.bio.ic.ac.uk/phyre2/). In addition, the sample was heated from 25\u00b0C to 85\u00b0C for a denaturation profile analysis.", "b Calculated using a conversion factor of 1.33 (Supplementary Table S1 ).", "Severe acute respiratory syndrome (SARS) is a respiratory disease caused by SARS coronavirus (SARS-CoV), a category C pathogen as defined by the U.S. National Institute of Allergy and Infectious Diseases of the U.S. National Institutes of Health. The original outbreak in Guangdong Province, China became a pandemic between 2002 and 2003 and caused approximately 800 deaths and more than 8000 infections. Although the overall mortality rate was about 10 percent, the mortality exceeded 50 percent among older adults. 1 In preparation for future pandemics and in light of concerns about the use of SARS-CoV in acts of terrorism, scientists have spent intensive efforts to develop vaccines against SARS. Such vaccines would ideally be stockpiled for future use in the event of an outbreak." ] },{ "paper_id": "f635dd0f13ee3859c7e4b653398c9b9dba9895d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "After 72 h, the viral titers were determined as described above.", "All normalized data were plotted and fitted to a nonlinear regression curve in GraphPad Prism (GraphPad Software) to generate the IC 50 .", "As shown in Fig. 1 , HPLC analysis of the B. licheniformis extract showed a single peak (Fig. 1b) at the retention time of 16-17 min, which is identical to the standard substance surfactin derived from Bacillus subtilis (Fig. 1a) . (Fig. 1) ." ] },{ "paper_id": "f6453a0485975f0892250dc5821c218633339584", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f64d07df542245c19781c36476a6cde273627f87", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Despite all these techniques, if a molecule is identified, it must then go through the steps of its clinical evaluation.", "Finally, in order to anticipate the emergence of resistance in bacteria, some molecules have the significant advantage of not being used alone, of focusing on multiple targets and thus eradicating the infection as quickly as possible.", "LP, SB, and J-MR drafted and revised the manuscript. All authors read and approved the final manuscript." ] },{ "paper_id": "f659c70f5c28f2b2694bc76b0a57b47d8d6362d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each reaction contained 400 ng of purified protein mixed with 1 pmol Cy5-labeled SL26 or S4 dsRNA radiolabled by a polynucleotide kinase reaction in a buffer containing 50 mM Tris-HCl (pH 7.5), 4 mM MgCl 2 , 50 mM NaCl, and 1 mM dithiothreitol. The reaction was irradiated with UV at 1200 mJ for 3 min. and then subjected to SDS-PAGE. The signals were detected and quantified with a phosphorimager. The gel was then stained with Coomassie blue to visualize the locations of proteins.", "Toll-like Receptor 3 (TLR3), the focus of this study, is composed of a large ligand-binding ectodomain, a transmembrane helix, and a signaling Toll/IL-1 receptor homology (TIR) domain [11, 12] . The ectodomain contains 23 leucine-rich repeats flanked with cysteine-rich caps and a bipartite motif, both of which are critical for ligand binding [13, 14] . TLR3 localizes to either the plasma membrane or acidic endosomes, the latter was presumed to be the site of high affinity binding to dsRNA [15, 16] . Ligand binding induces the TLR3 dimer to orient the two TIR domains to recruit adaptor proteins and activate signal transduction [6, 14] .", "The HCV 1b polymerase can enhance dsRNA-induced signaling by TLR3", "Viral nucleic acids are agonists for innate receptors that can activate anti-viral responses [1, 2, 3, 4] . The receptors include the RIG-I-like receptors that are localized to the cell cytoplasm and several membrane-associated Toll-like receptors [5, 6] . Mutations in these receptors have been correlated with pathologies in viral infections in humans [7, 8, 9, 10] . Understanding how the innate immune receptors can interact with agonists will be important for the detection and response to viral infections.", "RdRp assays were performed as 20 mL reactions containing 20 mM sodium glutamate (pH 8.2), 12.5 mM DTT, 4 mM MgCl 2 , 1 mM MnCl 2 , 0.5% Triton X-100, 0.2 mM GTP, 0.1 mM ATP and UTP, 250 nM [a-32 P] CTP (MP Biomedicals), 2 pmol PE46 and 1 pmol LE19p as templates [26] . The reaction mixture was incubated at 30uC for 1 h and terminated by phenolchloroform extraction, followed by precipitation of the RNA in the presence of two volumes of ethanol, 5 mg glycogen and 0.3 M NaOAc (pH 5.2). RNA products were separated by 20%-7.5 M urea polyacrylamide gels. The signals were detected and quantified by using a PhosphorImager." ] },{ "paper_id": "f65cdf4a48c1ad11e613449dad480736e9d26945", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Depending on age and immunological status, the infection of young domestic carnivores and a few species of large felids can be sub-clinical, acute (characterized by leukopenia, fever, depression, dehydration, and diarrhoea), or cause sudden death [2, 15] . However, in mustelids (otters, badgers, ferrets, martens and fishers) and viverrids (genets and civets), the pathogenicity of the disease caused by feline-like parvoviruses is still unclear. Reports refer mainly to serological or virological evidences rather than to clinical or anatomo-histological data (reviewed by [2] ). MEV infection of minks is an exception, since most infected animals, in particular the young ones, develop acute hemorrhagic enteritis, frequently associated with leukopenia [16] .", "Shortly after death, or shortly after being found dead on the road, animal carcasses were preserved in sealed plastic bags, taken refrigerated into a collection center and kept frozen at 220uC until necropsy. Animal Corpse transportation was done under the license from the Institute for Nature Conservation and Biodiversity (ICNB -Licence no. 222/2010/TRANS).", "The mongoose isolate clustered with two FPLV strains from a tiger and a lion obtained during an outbreak that occurred in 2006 at the Lisbon Zoo, Portugal [25] (Fig. 5 ).", "Our data revealed a non-significant spatial autocorrelation of the collected samples (Moran' I = 0.09; p = 0.206). Two of the morphometric variables were highly correlated (body total length versus tail length: r = 0.773; body mass versus body condition: r = 0.749), and thus tail length and body mass were excluded from further analysis." ] },{ "paper_id": "f6610246f9b5c9535a4ad4e96fa4bee87624cbc1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f6686ac18c05ec72b33fbed5485fc922531d2529", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f66963a9155d44a7f734c0f1d30cab3371cd99fa", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ELISA. ELISA assays using a microtiter plate assay were performed individually on the samples in each group chosen randomly and matched across the groups. Primary and secondary antibodies were obtained from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA, USA). A standard curve was generated by four-parameter curve-fitting using SoftmaxPro V 1.11 software, (Molecular Devices Corp., Sunnyvale, CA, USA).", "Statistical analysis. The data analyses were performed by SPSS 15.0 (SPSS, Inc., Chicago, IL, USA). Statistical significance of the differences was determined using the Student's t-test, and the Tukey method was performed to correct multiple comparisons. All the values were reported as the mean \u00b1 standard deviation, and P<0.05 was considered to indicate a statistically significant difference.", "In conclusion, A2MG is involved in multiple mechanisms underlying SONFH, including blood coagulation, hyperlipidemia, free radicals and MMP degradation. This underscores the critical role of A2GM in the development of SONFH. Therefore, A2GM may become a novel potential biomarker and a novel therapeutic target for SONFH." ] },{ "paper_id": "f670f4bb6f79e54d7603f8520853b1f0d105b588", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f678c06b6289cc9940ffc9f2007bb58c58773563", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f6a6f1fcc991eaf6e733d88adb25a3a7a8e65546", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Potential route of horizontal gene transfer of hemagglutinin-esterase (HE) from Orthomyxoviridae to Coronaviridae. Structural similarity is reported as TM-score.", "An interesting pattern of genetic exchange arises in bacteriophages. Bacteria have already been observed to donate their genes to phages [78] , which leads to accelerated evolutionary rates in the latter. It is also noted that massive HGT between bacteria and their phages is likely to be a common phenomenon [78] . Here, we observe that phages co-infecting the same or related hosts can exchange genetic information (e.g., phage integrase family).", "Unlike cellular organisms, viruses do not constitute a monophyletic group, in which the phylogenetic history can be traced back to a common ancestor. The origin and relatedness of different virus families is currently a subject of active discussion. It is unclear whether viruses have evolved by reduction of genes from cellular species, whether they descended from mobile elements of other organisms or whether they precede cellular life and are ancient self-replicating units. Possibly, all of these hypotheses are true, for a subset of viral families [1] . The recent discovery of giant viruses [2, 3] revived this discussion with suggestions that a certain clade of giant viruses may represent a fourth domain of life [4] ." ] },{ "paper_id": "f6a9c8aafc0ead13250df25ee0f5882f9aeedd76", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(3) 5-Helix", "(1) PIE12-trimer (1) Tat", "(2) Cyclin T1 [107]" ] },{ "paper_id": "f6b79474869aa89ef3a3cab01f39abac279c5132", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "shRNA vectors targeting p115 (TRCN0000065070, TRCN0000065071, TRCN0000065072) and Sec16A (TRCN0000246015, TRCN0000246016) and non-Targeting control shRNA were purchased form Sigma (St. Louis, MO). Lentiviral vector production and transduction was conducted as described previously [85] .", "Sec16A and p115 influence the type I IFN antiviral response at the transcriptional level", "HeLa cells were transfected with 40 nM siRNA using Lipofectamine2000 (Invitrogen). siRNA p115, Sec16A and the non-targeting pool siRNA duplexes were purchased from Dharmacon (Lafayette, CO). Sequences are as follow: Sec16A (#3: 59-ggagagcuuucgcgcugua-39; #4: 59-ccucaguccucuagcgugu-39) and p115 (#3: 59-guuauuauguggagguuug-39; #4: 59-ugauggagguauaguaguu-39)." ] },{ "paper_id": "f6c3322832e870befdabba94767a6422dfd67d2b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virus infections possess persistent health challenges in swine industry leading to severe economic losses worldwide.", "Porcine parvovirus (PPV) is the common cause of reproductive failure in swine herds. This single-stranded DNA virus of Parvoviridae family is transmitted through oral-nasal routes. Stillbirths, mummification, embryonic death, and infertility (SMEDI syndrome) are linked to PPV infection. Conventionally, PPV was considered genetically conserved but recent evidences suggest that several virulent strains have emerged due to its high mutation rate [17] .", "Vaccine is not available so far against ASFV, and the control measures depend entirely on early identification and culling of infected herds and adoption of strict sanitary measures [35] . Vaccine development is hindered by the antigenic diversity and multitude of immune-evasion strategies used by the virus. An effective vaccine will definitely help in control and eradication of ASFV from endemic countries and prevent its geographical expansion [20] . [5, 28] Porcine epidemic diarrhea (PED) RNA particle, inactivated and live-attenuated virus (in Asia)" ] },{ "paper_id": "f6c72b0d5522ce852bc2aeb711ab57fb75b3489a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f6d1e68561dad02f11de4b9882893826bb6321a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\"This practice makes prosecutors more than the people in power that deal with [criminal] cases. They may care for many things and open their minds. They will pay attention to how to tidy up their communities\u2026.Harm reduction is something similar that we do.\"", "\"When WHO becomes a political organization, it becomes relatively unfair to Taiwanese people. Why should we be treated like this? Somewhat like a colonized land but worse than the status of a colony. A colonized land at least has a ruling master, but we have nothing. We simply lack an identity to participate\u2026to gain a vision for Taiwan and connect with the international community. Our director hopes our [harm reduction] program can achieve that goal. Anti-TB or anti-AIDS, it does not matter.\"", "In my study, many-if not all-prosecutors and parole officers shifted among the roles of punishment, surveillance, and education. However informal, unrecognized, and non-certified, they are indeed health educators in a pragmatic sense [11] ." ] },{ "paper_id": "f6d2afb2ec44d8656972ea79f8a833143bbeb42b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Early work with intact vaccinia virus vectors raised safety concerns, as there was substantial reactogenicity that hindered recombinant vaccine development [108] . Two vaccinia vectors were developed to address these safety concerns. The modified vaccinia virus Ankara (MVA) strain was attenuated by passage 530 times in chick embryo fibroblasts cultures. The second, New York vaccinia virus (NYVAC) was a plaque-purified clone of the Copenhagen vaccine strain rationally attenuated by deletion of 18 open reading frames [109] [110] [111] .", "The structural proteins are provided in cell culture production systems. One important feature of the replicon systems is the self-replicating nature of the RNA. Despite the partial viral genome, the RNAs are self-replicating and can express transgenes at very high levels [67] .", "Adeno-associated viruses (AAV) were first explored as gene therapy vectors. Like rAd vectors, rAAV have broad tropism infecting a variety of hosts, tissues, and proliferating and non-proliferating cell types [58] . AAVs had been generally not considered as vaccine vectors because they were widely considered to be poorly immunogenic. A seminal study using AAV-2 to express a HSV-2 glycoprotein showed this virus vaccine vector effectively induced potent CD8 + T cell and serum antibody responses, thereby opening the door to other rAAV vaccine-associated studies [59, 60] .", "AAV vector systems have a number of engaging properties. The wild type viruses are non-pathogenic and replication incompetent in humans and the recombinant AAV vector systems are even further attenuated [61] . As members of the parvovirus family, AAVs are small non-enveloped viruses that are stable and amenable to long-term storage without a cold chain. While there is limited preexisting immunity, availability of non-human strains as vaccine candidates eliminates these concerns. Modifications to the vector have increased immunogenicity, as well [60] ." ] },{ "paper_id": "f6d409a4fff5c3c4d7d84cee872e80615e2027a4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "where P ji denotes the conditional probability that an individual that left i moves to j.", "where k is a constant. Using the hazard function, the abovementioned density function is modeled as", "where a 0 is an intercept, x ji is the dichotomous variable that describes the presence of Aedes mosquitoes (for i = 1), CHIKV (for i = 2) and DENV (for i = 3) in country j, and \u03b2 i represents the coefficient for corresponding variable i.", "Modeling f j (t ) in this way, the mean arrival time of the ZIKV to a country j would be proportional to the effective distance from the origin of spread (i.e., Brazil in our case study)." ] },{ "paper_id": "f6d6d7efc1686a7d219ecfc55f9a48ce72d4fb00", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession numbers. The whole-genome sequences of the NPL-PEDV/2013 and NPL-PEDV/2013/P10 strains have been deposited at DDBJ/EMBL/GenBank under accession no. KJ778615 and KJ778616.", "PEDV is a member of the Coronavirinae subfamily and belongs to the Alphacoronavirus genus. Its genomic size ranges from approximately 26 to 32 kb, which is relatively large for an RNA virus. Although vaccines for PEDV exist in China, Japan, and South Korea, there is no approved vaccine in the United States or Europe (3) . Furthermore, PEDV is still evolving within the U.S. swine population.", "highly contagious swine disease. While older pigs have a chance of survival, 80 to 100 percent of PEDV-infected piglets die within 24 h of being infected. PEDV spreads primarily through fecal-oral contact (1, 2) . Once the virus is internalized, it destroys the lining of piglets' intestines, making them incapable of digesting and deriving nutrition from milk and feed (1) . The virus causes diarrhea, vomiting, and death from dehydration and starvation (2) ." ] },{ "paper_id": "f6d97909fada387260787c6961eb1c4c36dac9d1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f6df4efd2fd556e59aae0df8de281f84bf762dff", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This study successfully showed viral infection-induced dysbiosis in the GI tract. Our results substantiate the potential link between the balance of microorganisms in the GI and swine health and development. Future studies are needed in order to determine the functional relationship between diarrheacausing agents including PEDV and dysbiosis/recovery of the gut microbiota.", "The gastrointestinal tract of mammals is a complex ecosystem with distinct environments and comprises hundreds of different types of bacterial cells. The gut microbiota may play a critical role in the gut health of the host. We herein attempted to identify a microbiota shift that may be affected by porcine epidemic diarrhea (PED). We observed significant differences in microbiota between the control and PED virus (PEDV)-infected groups at both the phylum and genus level. Most commensal bacteria (i.e. Psychrobacter, Prevotella, and Faecalibacterium) in the healthy gastrointestinal tract were decreased due to dysbiosis induced by PEDV infection.", "Porcine epidemic diarrhea (PED) is an enteric disease in swine caused by PED virus (PEDV), which is a member of the family Coronaviridae (21) . PEDV was first identified in England in 1971 (17) , and outbreaks of the virus have since been reported and recently in Europe, Asia, and the USA (4, 20, 25, 27) . The first case of a virus outbreak occurred in South Korea in 1992, and has since been followed by yearly outbreaks (11, 24) . PED poses the most serious threat to infant piglets, with morbidity and mortality rates previously reported to be between 80 and 100% (19) , thereby engendering economics losses in the pork industry." ] },{ "paper_id": "f6e29e95c1b0aa88f0ebebc39c62fb3bd461be2f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data has been deposited in Gene Expression Omnibus (GEO) number GSE103119.", "Portions of this work were presented at the Pediatric Academic Societies Meeting, Washington, DC, May 4-7, 2013." ] },{ "paper_id": "f6e4ddea2e155bf319fedff2b6111ba9ee863f1e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "subretinal fibrosis, and proliferative vitreoretinopathy (PVR) continue to be significant causes of reduced visual outcomes [3, 4] .", "The authors alone are responsible for the content and writing of the paper." ] },{ "paper_id": "f6e6534cb423c1823ad38d7d5c0a98c303f2efdb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viruses 2014, 6 5048 against HIV-1. This article reviews the applications of IAVs in vaccine development, with particular emphasis on the design of inoviral-based vaccines against HIV-1.", "Our knowledge of HIV-1 neutralization epitopes initiated from the isolation of several neutralizing monoclonal antibodies (2F5, 4E10, b12 and 2G12) that were described between 1993 and 1994 [102] [103] [104] . Thus far, neutralizing monoclonal antibodies have been found to target four major epitopes on the HIV-1 envelope gp41 and gp120 glycoproteins [105] [106] [107] . These monoclonal antibodies target the MPER epitope of gp41 (monoclonal antibodies 2F5, 4E10, M66.6, CAP206-CH12 and 10e8) [107] [108] [109] [110] [111] [112] [113] [114] [115] ; the V1V2-glycan of gp120 (PG9, PG16, CH01-04 and PGT 141-145) [116] [117] [118] [119] ; the glycan dependent site of the gp120 V3 loop (PGT121-123, PGT125-131 and PGT135-137) [119] ; and the CD4-binding site (b12, HJ16, CH103-106, VRC01-03, VRC-PG04, VRC-PG04b, VRC-CH30-34, 3BNC117, 3BNC60, NIH45-46, 12A12, 12A21, 8ANC131, 8ANC134, INC9 and IB2530 [102, 114, [120] [121] [122] [123] [124] [125] [126] [127] [128] . Monoclonal antibody 2G12 targets the surface glycans on the outer domain of gp120 that is distinct from the four major epitope target sites described above [102, 104, 129] ." ] },{ "paper_id": "f6e7d1aaef6479469705a2ae0ea9a5e5a5e18abf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Palivizumab, a humanized mAb against respiratory syncytial virus (RSV) derived from animal cell culture, has a heterogeneous glycosylation pattern. The same antibody derived from plant cells (Nicotiana benthamiana) that had their xylosyl-and fucosyltransferase activities deleted produced G0-dominated glycans, palivizumab-N. This form of glycosylation showed enhanced FccRIII binding and better protection against RSV challenge (Hiatt et al, 2014) .", "To summarize the discussion on the immune regulatory functions of IC engagement of FccRs, Fig 1 categorizes ", "The involvement of ICs in cross-presentation was initially noted in an assay to study the in vivo tumor killing by antibodies. EG7 tumor was inhibited or eradicated with an antibody against CD4 Glossary Self-tolerance breaking While immune tolerance refers to the lack of immune response to an antigen as a result of central (thymic selections) or peripheral (lack of co-stimulation) tolerance education, an extrinsic trigger, such as the same antigen presented to the host in an immune complex, can initiate specific immune recognition against the tolerized antigen. The end results can be detrimental in cases of autoimmunity, or beneficial, as in the immune attack on tumor antigens.", "Immune complex, as a form of autoimmune disorder and a tool in clinical therapy, has been an important topic of modern immunology. Binding of antigen by antibody, an immunologically simple event, changes properties of the original ligand, resulting in modulated antigen processing, presentation, receptor signaling, and inflammatory responses. On a larger scheme, antibody immune therapy has become one of the successfully implemented biomedical technologies in modern health care. Immunoglobulin-based new drugs such as rituximab, ipilimumab, and alemtuzumab are among the highly effective in cancer treatments (Sondak et al, 2011; Scott et al, 2012) . Intravenous immunoglobulin, IVIG, is also a choice treatment of autoimmunity, pediatric infections, and antibody deficiencies (Schwab & Nimmerjahn, 2013) . In contrast, use of classically defined IC represents an old subcategory among the list of options. ICs in vaccine development and clinical interventions are becoming increasingly sophisticated, largely attributable to the newly gained understanding of Fcc receptors (FccR; Ravetch, 2010) . However, IC-mediated functions are not solely controlled via those receptor engagements. For instance, its ability to transport antigen is also a consideration of anatomic location; its roles at different stages of immune induction and memory formation are modulated by additional spatiotemporal factors." ] },{ "paper_id": "f6ed1f1e9999e57793addb1c9c54f61c7861a995", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total cellular proteins were extracted by lysing cells in lysis buffer containing 1% Triton X-100, 0.5% NP-40, 150 mM NaCl, 10 mM Tris-HCl (pH 7.4), 1 mM EDTA, 1 mM EGTA (pH 8.0), 1% SDS, 0.2 mg/ml PMSF, 1 \u03bcg/ml aprotinin, 1 mM sodium orthovanadate, 2 \u03bcg/ml pepstatin, 2 \u03bcg/ml leupeptin, and 50 mM sodium fluoride for 5 minutes. The homogenate was then boiled for 10 minutes and stored at -70\u00b0C until use. The concentrations of total protein in cell extracts were determined by BCA\u2122 Protein Assay Kit (Pierce, IL, USA).", "Statistical analysis was performed by Student's t test. Differences were considered statistically significant when p values were less than 0.05." ] },{ "paper_id": "f6f9df0c4bf4a1d1b2a045660350523c0300f3e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Authors' contributions CO, NK and RH designed the study and co-wrote the manuscript. AR, JH, GW, RH obtained the data and did the TEM and light microscopy analysis. All authors read and approved the final manuscript.", "Additional file 1: Video S1. The first epithelial edge in the video is taken from a patient with PCD due to absent inner dynein arms and Availability of data and materials Data in this manuscript are freely available to any scientist or clinician who needs access by emailing a request to Dr. R. A Hirst (rah9@le.ac.uk).", "Ethics approval and consent to participate Ethical approval was granted from Leicestershire Ethics Committee (UHL 1061) and permission obtained from the University Hospitals of Leicester to publish anonymised patient data collected as part of the standard clinical care of the PCD patient group." ] },{ "paper_id": "f6fa68c5038374d5ae1b2c1e5a0929e6c1e8ea44", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The samples were desalted by C18-ZipTips (Millipore), spotted onto a 400/384 AnchorChip-Target (Bruker Daltonics) and mixed with 0.8 \u03bcl of matrix solution (HCCA, \u03b1-Cyano-4-hydroxycinnamic acid) on target. The spots were dried thoroughly and re-crystallized with methanol.", "Data collection was performed automatically on Bruker Reflex III MALDI mass spectrometer. The range of measurement was set to 0 -4 kDa. Main instrument parameters were: reflector positive mode, 25 kV and matrix deflection 0 -600 Da.", "Additional file 1: Supplemental Data. Protein identification data and Supplemental Figure S1 ." ] },{ "paper_id": "f6fad98294179598664366ea99a8caa991b74340", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The binding of poliovirus to bacteria enhances coinfection by promoting the delivery of multiple virions to a single cell [3] . Coinfection results in enhanced rates of recombination, which can increase fitness of the viral progeny. These data indicate that poliovirus not only gains higher thermostability during transmission from its interaction with bacteria but also raises its effective multiplicity of infection by more efficiently binding PVR and increasing the rates of superinfection. The resulting rates of genetic recombination from superinfected cells results in enhanced viral fitness.", "Commensal bacteria are essential for the development of a mature innate and adaptive immune system [39, 40] . Not surprisingly, viruses can use the microbiota and microbial components to modulate the innate immune response to infection. Mouse mammary tumor virus (MMTV) incorporates LPS-binding molecules, including the innate immune Toll-like receptor 4 (TLR-4), into its envelope to bind bacterial LPS [41] . MMTV-bound LPS stimulates TLR-4 signaling in the host and creates an IL-10-dependent immunosuppressive environment that allows viral persistence [42] . Another key component of the innate immune response, Type III interferon (IFN), plays a crucial role in regulating MNoV infection. Enteric bacteria counteract the Type III IFN response, enabling the establishment of persistent infection [29] . Interestingly, the induction of Type III IFN by murine astrovirus can provide protection against MNoV [43] , indicating that the interplay between viruses and microbiota extends beyond bacteria.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111" ] },{ "paper_id": "f6fcf1a99cbd073c5821d1c4ffa3f2c6daf8ae29", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In the only study to examine the effect of sample type on molecular analysis, 64 nasopharyngeal aspirates (NPA; an URT sample), 30 tracheal aspirates, 13 sputa and three BAL were examined. The tracheal aspirates and BAL returned the highest viral load values followed by NPA and sputum. Unsurprisingly, higher viral loads generally paralleled whole genome sequencing and culture success and, in NPA testing, were significantly correlated with severe disease and death [49, 94, 103] . This study demonstrated the importance of LRT sampling for whole genome sequencing.", "In the region of Ar Riyad, including the capital city of Riyadh, a hospital based cluster began, within a single hospital, from late June 2015 [205] . By mid-September there had been approximately170 cases reported but the outbreak appeared to been brought under control in November.", "Additional file 1: Figure S1 . The " ] },{ "paper_id": "f6fdeab5faa3141b4d0ba262210e6662a7aa261a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The importance of the UPS in antiviral restriction will be discussed here using HIV as an example.", "[2-5]." ] },{ "paper_id": "f703b510de361a759c9fe3419fa3aeb092c95512", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f715f94955504e6dbe3963ec0ccebb0a431e7c4e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Astroviruses (AstVs) are non-enveloped, positive-sense, single-stranded RNA viruses belonging to the Astroviridae family. Currently, two genera: namely Mamastrovirus and Avastrovirus are distinguished within this family. The genus Mamastrovirus includes astrovirus species isolated from humans and a number of mammals. Isolates originated from avian species, such as turkey, chickens, ducks, and other birds are classified into the genus Avastrovirus 1, 2 . AstVs have been detected in humans and a variety of animal species, including nonhuman primates, other mammals and avian species [3] [4] [5] . Their genomes are 6.8-7.9 kb in length, consisting of a 5\u2032untranslated region (UTR), three open reading frames (ORFs), a 3\u2032-UTR and a poly (A) tail 6 . The high degree of genetic diversity among AstVs and their recombination potential signify their capacity to cause a broad spectrum of diseases in multiple host species 3, 7, 8 . Human classical AstVs are a frequent cause of acute gastroenteritis in young children and the elderly, occasionally with encephalitis 8 .", "One-day-old goslings (Anser anser domesticus) were obtained from a local hatchery. Birds were raised in negative pressured isolators with ad libitum access to feed and water. Three experiments were conducted to investigate the pathogenicity of the isolate. Animal infection experiments were approved by the China Agricultural University Animal Ethics Committee. Gosling experiment 1", "To determine the infectious titers of the 4 th and 9 th passage, the virus suspension was 10-fold serially diluted with PBS and inoculated into 9-day-old goose embryos via the chorioallantoic membrane route. The embryos were incubated for 7 days at 37\u00b0C and the mean embryo lethal dose (ELD 50 ) of infectious virus was calculated using the Reed-Muench method 32 . " ] },{ "paper_id": "f7185938312bfa794681998fe0bff4e2697c053d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Adjuvants composed of emulsions include oil in water (o/w) and water in oil (w/o) systems. There are two formulations approved for human use in Europe, MF59 and AS03. There is also another compound, Montanide, under phase III stage trials.", "Several vaccines based on VLPs are currently approved for human use (Gardasil and Cervarix), demonstrating that VLP provide an appropriate immunity against papillomavirus [27, 29, 108] . Moreover, other VLP-based vaccines are under development, including vaccines against influenza [109, 110] , HIV [111] , or Norwalk virus [112] , and in clinical trials [113] .", "Regarding to safety concerns, Anderson et al. have pooled and analyzed the safety data obtained from a number of vaccine development programs comprising ISCOMATRIX. Overall, the ISCOMATRIX vaccines were found to be safe and well tolerated, with no vaccine-related deaths or serious adverse events. Reactogenicity at the injection site was found to be the most frequent adverse event compared with subjects who received placebo or active comparator; however, this reactogenicity was generally mild, self-limiting, and of short duration. Until the end of the study, ISCOMATRIX vaccines have not been associated with events suggestive of autoimmune or allergic disorders nor events of anaphylaxis [138] ." ] },{ "paper_id": "f719d2ff295ade18c5946296cd7c2436727d2822", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Recombinant MERS-CoV PL pro preparation" ] },{ "paper_id": "f7204b21080d07e2bb6ffc6fedaa1bf60ba5d67c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Then Var(PC i )~e 0 i Se i~li i~1,2,:::,p \u00f02\u00de", "Var(X 1 )z:::zVar(X p )~l 1 zl 2 z:::zl p~V ar(PC 1 )", "Wip\u00c3ZScore p i~1,2,:::,p", "Another property of the principal components is:" ] },{ "paper_id": "f72764a9a0f911eb892cf04752566d6ef4ee54c4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Working stocks of HSV-1 SC16 were grown on HaCaT cells and assayed on Vero cells [17] . Mutant viruses lacking functional genes for gH (SCgHZ) [14] , gB (HFEMdUL27-lacZ) [18] or gD (SC16gDdelZ) [18] were grown and assayed on helper cell lines expressing the corresponding glycoprotein: CR1 cells, expressing gH [19] ; D6 cells expressing gB [13] ; and VD60 cells expressing gD [18] . All stocks were grown using an MOI of 0.1.", "All cells other than Human Foreskin Fibroblasts (HFF) (ATCC cell line CRL-2522) were grown in Glasgow Modified Eagles Medium supplemented with 10% foetal bovine serum, 4 mM glutamine, 100 units/ml penicillin and 100 ug/ml streptomycin. HFF cells were grown in Dulbecco modified Eagles medium supplemented as described above but with the addition of 1x MEM non-essential amino acids.", "Western Blotting gD and the major tegument protein, VP16, were detected by immunoblotting using the monoclonal antibodies LP2 and LP1, respectively [25] [26] . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting were performed as described previously [27] ." ] },{ "paper_id": "f72f4443be3e73ec7e6e37ae426caaf5a4924abe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronavirus. Until the recent outbreaks of severe acute respiratory syndrome (SARS) (2003) and Middle East respiratory syndrome (MERS) (2014/2015), coronavirus (CoV) morbidity and mortality were generally worse for domesticated animals rather than for humans, particularly within porcine and poultry farms. Coronaviruses usually secretion), levels of anti-S1 and anti-N antibodies were significantly increased, even in atypically studied secretions such as ophthalmic and nasal secretions (44) . Interestingly, they observed a synergy against the spike protein, but not against the nucleocapsid, in mice vaccinated against both proteins.", "Rotavirus. Diarrheal disease is the second leading cause of death in children under the age of 5 worldwide, with rotavirus responsible for 40% of hospitalizations due to diarrheal illness (50) . It is estimated that rotavirus killed approximately 215,000 children in 2013. The World Health Organization recommends inclusion of a rotavirus vaccine in all global vaccination protocols, and there are currently two modified live vaccines licensed worldwide (51) . The global implementation is ongoing, but in countries where data are available, vaccination has resulted in a 33% reduction in hospitalization due to rotavirus morbidities. Unfortunately, both vaccines have limited (50% to 60%) efficacy in developing countries and are associated with a low-level risk of intussusception (52) . A recombinant Lactobacillus-based vaccine could address the need for a subunit rotavirus vaccine that provides the benefits of a probiotic and the appropriate safety profile for use in neonates and infants. Two main avenues of lactobacillus-based rotavirus protection have been attempted in mice. The first avenue used typical oral vaccination with L. casei, inducing mucosal IgA and neutralizing serum IgG against porcine Rotavirus major protective antigen (PA) VP4 in mice (53) . The second used antibody fragments to confer protection. \u00c1lvarez et al. expressed a protective antirotavirus llama antibody fragment on the surface of L. rhamnosus, protecting against diarrhea in a mouse pup model (54) . Another group adapted the use of anti-rotavirus hyperimmune bovine colostrum (HBC) in the same model system, expressing an anti-HBC protein from Streptococcus, which binds HBC antibodies, thus conferring protection when orally dosed (55) .", "Fish-related viruses. Aquaculture is an important food supply paradigm, and with it comes the typical pathogen problems that large-scale animal farms encounter. Vaccination against fish pathogens can be performed by intraperitoneal administration (which can be cost-prohibitive), by immersion, or orally via feed, with the latter two options suffering from a lack of vaccine persistence in water and from the particularly strong mucosal tolerance observed in fish. For a comprehensive summary of vaccination attempts in fish, see the excellent review by Embregts and Forlenza (56) . Lactobacillus vaccine vectors can provide an effective and easily administered system for pisciculture. The first set of studies targeted infectious pancreatic necrosis virus (IPNV), a birnavirus that afflicts rainbow trout. Direct oral administration with L. casei expressing portions of viral capsid generated significant serum IgM and afforded challenge protection in two studies by the same group (57, 58) . Two viruses that primarily affect carp, Cyprinid herpesvirus 3 (Koi herpesvirus [KHV]) and Rhabdovirus carpio (spring viremia of carp virus [SVCV]), have also been studied. The two antigens (KHV ORF81 and SVCV glycoprotein) were expressed together in L. plantarum and dosed orally in carp and koi. The resulting serum IgM and challenge survival data were promising, particularly for a vaccine that offers dual protection (59) . Further Lactobacillus studies must be conducted, looking in particular at cellular mucosal immunity in fish, as well as at the potential for multiple pathogens to be addressed with a single modified Lactobacillus vaccine.", "Bacillus anthracis. Though infections are relatively rare, the prevalence of natural Bacillus anthracis in soil and its potential as a bioterrorist agent gives antianthrax vaccines some priority. Protective antigen (PA), the only antigen used in Lactobacillus vaccinations, is well studied and has been tested in other vaccine systems with various degrees of success (67) . One of the earliest proof-of-concept Lactobacillus experiments involved dosing BALB/c mice with L. casei either orally or intranasally. That early study showed that the antibody responses against heterologous protein exceeded the antibody responses against the bacteria itself (68). Ten years later, Mohamadzadeh et al. combined an L. acidophilus or L. gasseri strain with DC-pep, resulting in neutralizing antibodies and challenge survival in A/J mice (69, 70) . That same group later observed colonic DC activation, Th17 and regulatory T cell (Treg) upregulation, and upregulation of pattern recognition receptor genes with a single vaccine dose (71) ." ] },{ "paper_id": "f73808579d362b40e0f9c8ef0d87868a0e3e3481", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Definition 2 (stem):", "Definition 3 (hairpin Loop): There must be at least MinLoop (MinLoop \u2265 3) unpaired bases in any hairpin loop structure.", "Parameters i, j and k need to satisfy the following three constraints:" ] },{ "paper_id": "f7417991beaa7bd0483f9dbdd549c12eeee26508", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations Poly(I:C): polyinosinic:polycytidylic acid; LPS: lipopolysaccharide; MS: multiple sclerosis; OLs: oligodendrocytes; preOLs: oligodendrocyte precursors; TLR: Toll-like receptor; TNF\u03b1: tumor necrosis factor alpha; TNFR1: TNF\u03b1 receptor 1.", "All data are expressed as means \u00b1 SEM. Data were analyzed using two-tailed student's t-tests for comparisons between two groups or multiple level analysis of variance (ANOVA) followed by Bonferroni's post-hoc test where appropriate to distinguish differences between multiple groups. All statistics were calculated using GraphPad Prism 4 (GraphPad Software, San Diego, CA). Differences were considered significant when p < 0.05." ] },{ "paper_id": "f7453f0f1f131d4f8603bf708f8c08d9b9e8806f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "SKI-1 inhibitors LCMV, LASV [89, 90] Peptides and peptidomimetics CHIKV, SFV WNV, DENV H5 and H7 influenza [52, 134] ", "Funding: This research received no external funding.", "The author declares no conflict of interest." ] },{ "paper_id": "f74ee87b0db54450d2684da633a56b6f159a6c0b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f763d5c729b3a02773062e212f3f2632d2ebb574", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The development of effective cold preventives is hampered by the multiplicity of viruses and the complex interplay between host and virus [7, 8] . For decades, intense research has focused on applications of broad-spectrum antivirals like interferons (\u03b1, \u03b2, or \u03b3), capsid binding proteins, or soluble receptors directed against rhinoviral infection and/or replication. Some therapies showed efficacy in clinically induced infections but failed to significantly prevent colds in larger field studies that included multiple types of respiratory viruses. Nasal applications of interferons showed good preventative efficacy but were typically accompanied by adverse reactions like nasal bleeding [9] .", "Vaccination presents an effective method for managing seasonal influenza and respiratory, syncytial virus (RSV) in children. However, the efficacy of vaccination depends on the immunological fitness of the recipient and primarily in 2 Evidence-Based Complementary and Alternative Medicine older individuals or those with chronic heart disease only insufficient immunity can be built up, resulting in a reduced immunity in this vulnerable population [10, 11] .", "Colds comprise a syndrome of symptoms, typically with nasal complaints, cough, sore throat, and sometimes constitutional complaints, like headache, malaise, and fever [5] . The symptoms are typically self-limiting, and they represent a reaction to infection by Rhino-, Corona-, Adeno-, Respiratory Syncytial and (Para-) influenza virus [6] ." ] },{ "paper_id": "f7658f780f7b559a2ddb1649957efda8a94f534b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA from suspended diarrheic stool samples was isolated using Qiazol reagent (Qiagen GmbH, Hilden, Germany) following the manufacturer's protocol and quantified on a Nanodrop spectrometer [49] . Extracted RNA (500 ng) was used to prepare a pool of first-strand cDNA by random-priming reverse transcription (RT) using recombinant MMLV-RT (Promega Corporation, Madison, WI, USA) and random hexamer (Qiagen GmbH, Hilden, Germany) at 37 \u2022 C. Enzymatic activity of the MMLV-RT was stopped by keeping the cDNA reaction mixture at 80 \u2022 C for 3 min.", "GeneJET plasmid Miniprep kit (Thermo Fisher Scientific, Waltham, MA, Vilnius, Lithuania). Positive recombinant clones were sequenced by the Bigdye terminator Sanger sequencing method in an ABI 3730 x l sequencer (Eurofins Genomic India Ltd., Bangalore, India). The sequences were deposited in GenBank with Accession Numbers MG553198 (NSP4 gene), MG553199 (VP4 gene) and MG553200 (VP6 gene). ", "Supplementary Materials: The following are available online at http://www.mdpi.com/2076-0817/7/1/23/s1." ] },{ "paper_id": "f76b1d637fdb9e5d6a32d1a6d3804a2acb9f0f23", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f76f29653d5c53667e4a9615ca50f8b94c753d36", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "Murine L929 fibroblasts (Sigma), 17Cl1 cells (gift from S.G. Sawicki) were cultured in MEM10%. Murine embryonic fibroblasts (C57BL/6 MEFs) were maintained at low passage in DMEM10% (Dulbecco's Modified Eagle Medium-GlutaMAX). Huh-7 cells (gift from V. Lohnmann) were cultured in DMEM5% and 0.5mM sodium pyruvate. MRC-5 cells (human lung fibroblast-like cells; Sigma) were maintained at low passage in MEM10%, supplemented with 1% non-essential amino acids (NEAA). HEK293-Mx1-Luc cells (gift from G. Kochs) were maintained in DMEM10%, supplemented with G418 (200 \u03bcl/ml) [60] ." ] },{ "paper_id": "f7735a5236aeba514810bd4538357cb4f4e09fce", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "upregulation suggests an enhanced effect on the proteasomal pathways by nsp11. SUMO1 (small ubiquitin-like modifier 1) has multiple functions by attaching itself to substrates referred to as sumoylation. After sumoylation, protein may undergo degradation through the proteasome [33, 34] .", "system. C1R is autoactivated and then cleaves C1S for activation. Activated C1S cleaves C4 and C2, resulting in the activation of C3-convertase complex [28] . C3 is a central molecule in the complement system whose activation is essential for all the important functions performed by this system [29] . The downregulation of C1S, C1R, and C3 suggests the possible suppression of the complement system by nsp11.", "Primer sequence" ] },{ "paper_id": "f7740a58d95fb643e40af517b3da5a3d925edb50", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza is considered the most prevalent infectious disease in humans. Over the past century, this virus has accounted for three major pandemics, which cumulatively killed tens of millions of individuals [182] . In particular, H1N1 influenza, also known as Spanish flu, killed more than 20 million people around the globe [183] . Recently, the emergence of H7N9 and H5N1 in China has raised concerns [184, 185] . Fortunately, no sustained person-to-person spread of these viruses has been confirmed to date.", "HIV-1 RT is a key, multifunctional enzyme during the retroviral life cycle. It has a DNA polymerase activity on both RNA and DNA templates and a ribonuclease H activity on RNA-DNA hybrid template [60] . HIV-1 RT catalyzes conversion of the single stranded genomic viral RNA into double stranded proviral DNA, which in turn is integrated into the host genome.", "In summary, aptamer technology is well-suited for treating viral infections, and there are now many examples, illustrating that a wide range of viruses can be inhibited by aptamers and have potential for clinical applications.", "Rabies is a viral disease that causes nerve damage and death in many mammals. The causative agent of rabies is the rabies virus (RABV), which can be transmitted between species, often through saliva transferred during a bite from a rabid animal. Currently, there is no effective treatment for rabies once symptoms develop, and death occurs within weeks. Although post-exposure rabies treatments are available to treat RABV-infected patents before the virus invades the central nervous system, the virus still causes about ~60,000 deaths annually worldwide [192] .", "All HPV nucleic acid aptamers reported to date targeted the E7 proteins for the therapeutic treatment of the high-risk HPV16 subtype. The HPV E7 gene is oncogenic and can cause malignant transformation of cervical cell lines, while downregulation of this gene induces programmed cell death (apoptosis) [201] . Hence, inhibiting this protein represents a rational way to kill HPV + cervical carcinoma cells." ] },{ "paper_id": "f781ae4966ab37b3cc7cf282c732db401856870b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Paramyxoviruses constitute a large family of single stranded, negative-sense, enveloped RNA viruses that can lead to important diseases in humans and animals [1] . Historically, Paramyxoviridae have been subdivided into seven genera based on biochemical properties and SDS-PAGE patterns of viral structural proteins: Rubulavirus, Avulavirus, Respirovirus, Henipavirus, Morbillivirus, Ferlavirus and Aquaparamyxovirus. Taking genome sequences and protein data into account many currently described paramyxoviruses are assigned as unclassified, e.g. rodent-borne Tailam Virus [2] , Nariva Virus [3] and Bank Vole Virus [4] , as well as paramyxoviruses detected in bats [5] .", "The organ material used in this work was provided by the Institute of Pathology, Faculty of Veterinary Medicine, Leipzig University and derived from dead animals euthanized for medical reasons unrelated to this study.", "Urine samples from cats were collected as part of the routine physical examination at the Department of Small Animals, Leipzig University. The material was stored at \u221220 \u2022 C (for not more than 4 weeks) before RNA isolation was conducted.", "Part of the work reported in this manuscript resulted in the patent entitled \"New Paramyxovirus and uses thereof\" with the international application no.: PCT/EP2017/071392." ] },{ "paper_id": "f787f681d002077ccf52bcea98f4e708d71fd41d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Despite the elimination of endemic measles transmission in the United States [1] [2] [3] , measles cases continue to occur from time to time, mostly due to importation. In 2014-2015, there was a large measles outbreak that was linked to one or more Disney theme parks [4, 5] . The outbreak consisted of 131 cases involving 14 local health jurisdictions in California as well as other U.S. states and countries.", "Measles cases continue to occur despite its elimination status in the United States. To control transmission, public health officials confirm the measles diagnosis, identify close contacts of infectious cases, deliver public health interventions (i.e., post-exposure prophylaxis) among those who are eligible, and follow-up with the close contacts to determine overall health outcomes. A stochastic network simulation of measles contact tracing was conducted using existing agent-based modeling software and a synthetic population with high levels of immunity in order to estimate the impact of different interventions in controlling measles transmission." ] },{ "paper_id": "f78956e70c8bd1756ffb24ae47c35c3217bed384", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This work was supported by Midwestern University Faculty Start-up Fund and NIH Grants 1R03AI088342 and 1R15AI101920, and American Heart Association Midwest Affiliate Grant 13SDG17310011 to AKM.", "The authors declare no conflict of interest.", "Weidang Li contributed to writing section 3, editing all sections, and formatting of the manuscript. Medha Joshi contributed to writing section 4. Smita Singhania contributed to writing section 2. Kyle H. Ramsey contributed to sections 1 and 5, and to editing the entire manuscript. Ashlesh K. Murthy contributed to conceptualization of this review article, writing of all sections, and editing the entire manuscript." ] },{ "paper_id": "f793bcacac81ad9341709c9351c6c40c49f4c52e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequences ( ", "Viruses 2015, 7 4564 Keywords: classical swine fever virus; virus-host interactions; NS5A; eukaryotic elongation factor 1A; internal ribosome entry site" ] },{ "paper_id": "f7a1f8ff3552ac192d882ad7ef31d46c21ca1e32", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f7b0a4b72da3b040ec9904ad1137e7c5c0eab777", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In silico data set assembly", "BBAP de novo assembly of full and partial data sets", "Background: The accuracy of metagenomic assembly is usually compromised by high levels of polymorphism due to divergent reads from the same genomic region recognized as different loci when sequenced and assembled together. A viral quasispecies is a group of abundant and diversified genetically related viruses found in a single carrier. Current mainstream assembly methods, such as Velvet and SOAPdenovo, were not originally intended for the assembly of such metagenomics data, and therefore demands for new methods to provide accurate and informative assembly results for metagenomic data.", "Contigs with identical terminal sequences longer than the given threshold are merged together into extendedcontigs. Identical terminal sequences were identified by self-BLAST of contigs. This step is optional and dependent on the nature of the data set." ] },{ "paper_id": "f7b30ee89775bc82607cc6bc87feb5934b47625f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The list of recently discovered gastrointestinal viruses is expanding rapidly. Whether these agents are actually involved in a disease such as diarrhea is the essential question, yet difficult to answer. In this review a summary of all viruses found in diarrhea is presented, together with the current knowledge about their connection to disease.", "The gastrointestinal tract is a vulnerable organ for infections as there is constant contact with the outside, mainly via the oral route. Inflammation of the stomach and the intestines (gastroenteritis) can cause nausea, vomiting and diarrhea. Gastroenteritis is responsible for two to three million deaths each year, making it one of the most common causes of mortality [1] . Mainly children in developing countries, but also immuno-compromised individuals in developed countries, suffer from diarrhea. While bacterial and parasitic gastrointestinal infections are declining as a result of proper disposal of sewage and safe drinking water, viral gastroenteritis is not declining in developing countries [2] . In the developed world, viruses are already the most common pathogens causing diarrhea [3] .", "In conclusion, the long list of viruses identified in the gastrointestinal tract is most probably not final yet. It is to be expected that several novel viruses will be described in the near future, since detection of these agents using the current next-generation sequence technologies is no longer a difficulty. Therefore, adding relevance to the discovery of novel viruses should be the main goal for future studies." ] },{ "paper_id": "f7bb1f005066cb4930f83cde4cdc1ff3fe411def", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In a RCT of lung transplant recipients with RSV infection, the incidence of new or progressive bronchiolitis obliterans syndrome at day 90 was significantly reduced in 16 patients who received a small interfering RNA against the RSV Ngene (ALN-RSV01) compared with placebo (n = 8) (6\u00c13% versus 50%, P = 0\u00c1027). 109 In a larger follow-up multicentre phase IIb study, treatment with ALN-RSV01 showed a greater than eightfold reduced risk in developing bronchiolitis obliterans syndrome at day 180. 110", "In recent years, an increasing number of cases of novel animal influenza A viruses infecting humans have been reported. These include multiple avian influenza A virus subtypes, in particular H5N1 and H7N9, and swine-origin H3N2v. Reasons for this increase include both social factors, for example, increased human populations living in close proximity to animals and increased surveillance and diagnostic testing. Risk assessment tools have been developed by many authorities around the world (e.g. the European CDC, US CDC, USAID and WHO) to assist in predicting the likelihood that a particular virus will emerge and its associated impact, as well as prioritising the development of candidate human vaccine viruses. 2 These tools allow continual reassessment as new data become available and provide an objective, transparent process with which to make resource allocation and pandemic planning decisions.", "This review highlights the main points which emerged from the presentations and discussions at the 3rd isirv-Antiviral Group Conference -advances in clinical management. The conference covered emerging and potentially pandemic influenza viruses and discussed novel/pre-licensure therapeutics and currently approved antivirals and vaccines for the control of influenza. Current data on approved and novel treatments for non-influenza respiratory viruses such as MERS-CoV, respiratory syncytial virus (RSV) and rhinoviruses and the challenges of treating immunocompromised patients with respiratory infections was highlighted.", "Palivizumab prophylaxis of premature infants of <6 months of age has been shown to reduce hospitalisation due to RSV by 55%. 76 Preventing RSV during infancy has been associated with reduction of wheezing later in life. 77 Trials of other monoclonal antibodies have typically shown that they do not achieve superiority compared to palivizumab and therefore do achieve licensure. Furthermore, treatment with neutralising monoclonal antibodies does not appear to reduce virus load or disease severity in hospitalised infants. 78 Alternative options for RSV therapy to be assessed in future clinical trials include inhaled nanobodies, aerosolised peptides, nucleoside analogues and RNA-interference molecules." ] },{ "paper_id": "f7c3160bef4169d29e2a8bdd79dd6e9056d4774c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Accordingly, this review elaborately details the epidemiology and global expansion of CHIKV, describes its clinical features and pathogenesis and its symptoms and complications, and finally nominates a possible vaccine approach against CHIKV infection.", "More than 50% of patients who suffer from severe CHIKF are over 65 y old, and more than 33% of them die. Most adults who suffer from severe CHIKF have underlying medical conditions [6, 24, 27] . The other group that is disproportionately affected by severe CHIKV is children. Other complications associated with CHIKV, from most common to least common, include respiratory failure, cardiovascular decompensation, meningoencephalitis, severe acute hepatitis, severe cutaneous effects, other central nervous system problems, and kidney failure [6, 18, 20, 23, 24, 26, 27] .", "Clinical and epidemiological similarities with dengue fever make CHIKV diagnosis difficult, which may lead physicians to misdiagnose CHIKV as dengue fever; therefore, the incidence of CHIKV may actually be higher than currently believed (Table 1 ) [6, 12, 35] ." ] },{ "paper_id": "f7d4270a51caf2ea8758476bad0e0537f2d47075", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f7ddd78bba691e9200cece8a05b3486fab895885", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "found it to be required for efficient recruitment of eIF3 and the ribosome [12] .", "Some of the well-characterized ITAFs are human antigen R (HuR), La autoantigen, programed cell death 4 (PDCD4), polypyrimidine tract binding (PTB) protein, heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), hnRNAC1/C2 upstream of NRAS (UnR), nuclear factor 45 (NF45), insulinlike growth factor 2-binding protein 1 (IGF2BP1), Y-box protein 1 (YB1), and poly(C) binding protein (PCBP) [20, 49, 50] . The levels, activity, and localization of these ITAFs are regulated by various signaling pathways, which in turn regulate the IRES-mediated translation. Hence many of these ITAFs are implicated in tumor cell survival and cancer progression.", "Many cellular mRNAs are known to comprise IRES elements, but they do not share structural or sequence similarities, unlike their viral counterparts [20, 31] . However, similar to viral IRESes, cellular IRESes participate in multiple interactions with the canonical initiation factors and ITAFs to recruit the ribosome [1, 20] . In fact, despite sequence and structural dissimilarities, cellular IRESes are reported to share critical ITAFs [20] . IRES elements have been identified in mRNAs encoding stress response proteins (proand antiapoptotic), such as X-linked inhibitor of apoptosis (XIAP), cellular inhibitor of apoptosis 1 (cIAP1), B cell lymphoma extralarge (Bcl-xL), Bcl-2, Bag-1, apoptotic proteaseactivating factor 1 (Apaf-1), p53, L-myc, N-myc, c-myc, and death-associated protein 5 (DAP5) [1, 8, [32] [33] [34] ].", "The ITAFs are protein factors that interact specifically with the IRES based on the sequence and structure of the mRNA and modulate IRES-mediated translation. ITAFs can act as a molecular chaperone or modify the structure of RNA to facilitate direct recruitment of the eukaryotic initiation factors and the ribosome to form 48S initiation complex." ] },{ "paper_id": "f7de41208aece195ba22060365f3e3eb91e43d88", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, there is lack of commercially available dromedary antibodies against immune cell markers, making T cell immunity in camels difficult to assess appropriately.", "All data are available in this manuscript, no data in an archive. " ] },{ "paper_id": "f7f482ba4aaa3ef0d620d9aad8c9635f88806d8e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 7:40351 | DOI: 10.1038/srep40351" ] },{ "paper_id": "f7ff81d2d3ae773aa28836cc485617983d7499ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GraphPad Prism software (version 7) was used for the statistical analyses. Quantitative results were compared using nonparametric Mann-Whitney U-test and a p-value of <0.05 was considered evidence of statistically significant difference and visualized by a * .", "Cell samples were analyzed using a FACS LSR IIor Fortessa cytometer (BD Biosciences) and the data were analyzed using FlowJo software version 10 (TreeStar); see Supplementary Figure 1 for gating strategy.", "The following fluorochrome-conjugated monoclonal Abs were used for flow cytometry. Surface staining: \u03b1-CD8, \u03b1-CD11b, \u03b1-CD45.2, \u03b1-CD44, \u03b1-CD103, \u03b1-CD69, \u03b1-CD49a, \u03b1-CD127, \u03b1-KLRG1, \u03b1-CD4, and \u03b1-CD107a. For intracellular cytokine staining we used: \u03b1-IFN-\u03b3, \u03b1-IL-2, and \u03b1-TNF. Staining for intracellular molecular markers involved: \u03b1-Granzyme B, \u03b1-Bcl-2, and \u03b1-Ki-67. All antibodies were purchased from Biolegend, eBioscience or BD Bioscience as anti-mouse antibodies." ] },{ "paper_id": "f80a73f77c3831a921a232122099f8aa5798dfd2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To investigate the roles of monocytes in the healthy EEHV-positive calves, blood samples were collected from the persistent EEHV4-infected and EEHV-negative calves, with infection status determined by conventional polymerase chain reaction (PCR) test during the prior six months. The details of each animal's history and the tests performed are shown in Table 1 .", "Analysis of the blood obtained within the three days prior to an elephant's death from either EEHV1A-HD or EEHV4-HD indicated marked neutrophilia in all EEHV-infected calves. Monocytopenia and thrombocytopenia were observed in some animals, especially those infected with EEHV1A (Table 2 ). In contrast, blood leukograms taken 2-3 weeks before death in the EEHV1A-and EEHV4-infected calves did not differ significantly from the reference values (data not shown).", "https://doi.org/10.1371/journal.pone.0222158.g004" ] },{ "paper_id": "f81a3ef89c4144309cf86374440e2a3a8a0e095c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Overt respiratory disease associated with simian adenoviruses has also been observed [9] . Although adenoviruses are significant pathogens, genetically modified strains are being actively explored as potential vectors for vaccines and gene therapy [10] .", "Virochip analysis was performed as previously described [21, 23] . Briefly, samples were labeled with Cy3 or Cy5 fluorescent dye, normalized to 10 pmol of incorporated dye, and hybridized overnight using the Agilent Gene Expression Hybridization kit (Agilent Technologies, Santa Clara, California). Slides were scanned at 3 mm resolution using an Agilent DNA Microarray Scanner. Virochip microarrays were analyzed with Z-score analysis [18] , hierarchical cluster analysis [50] , and E-Predict, an automated computational algorithm for viral species prediction from microarrays [51] . Only Z-score analysis, a method for assessing the statistical significance of individual Virochip probes, yielded a credible viral signature on the microarray.", "Total nucleic acid was extracted from body fluid or swab samples using commercially available kits (Qiagen, Valencia, CA). 200 mL of sample were passed through a 0.22 mm filter (Millipore, Temecula, CA) to remove bacteria and cellular debris and then treated with Turbo DNase (Ambion, Culver City, CA) to degrade host genomic DNA prior to extraction. For tissue samples, lung or liver tissue was homogenized in a 15 mL Eppendorf tube using a disposable microtube pestle (Eppendorf, San Diego, CA) and scalpel, and RNA extraction was then performed using TRIzol LS (Invitrogen, Carlsbad, CA), followed by isopropanol precipitation and two washes in 70% ethanol. Extracted nucleic acid was amplified using a random PCR method to generate cDNA libraries for Virochip and deep sequencing analyses as previously described [18, 21] .", "Sera from random blood donors were obtained from the Blood Systems Research Institute (San Francisco, CA); sera were derived from affiliated donor banks in California (Blood Centers of the Pacific, San Francisco, CA), Nevada (United Blood Service, Reno, NV), and Wyoming (United Blood Services, Cheyenne, Wyoming) and de-identified prior to analysis." ] },{ "paper_id": "f81a5f06d5cbc6998bddce29a3eb508d8ceb83f7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Unpaired two-tailed t tests or analysis of variance (ANOVA) with Bonferroni's post hoc analysis was used for comparisons between groups, and Pearson's test was used to assess linear correlation with SPSS version 16 (SPSS, Chicago, IL, USA) and GraphPad Prism version 6 (GraphPad Software, La Jolla, CA, USA) software. P values <0.05 were considered statistically significant.", "TMB substrate (R&D Systems) was added after a further wash and left to develop in the dark for 20 minutes. Absorbance at 450 nm was read following the addition of 2 N sulphuric acid ('stop' solution) using a FLUOstar OPTIMA plate reader. Ang (1-7) concentration was interpolated from a standard curve generated by serially diluting recombinant human Ang (1-7) (5000-78.125 pg/ml). The assay showed minimal cross-reactivity with a number of closely related peptides, including Ang I, Ang II and Ang III.", "Previous measurements of ACE-1 activity, measured by fluorogenic activity assay, were available for all cases [4, 41] . Total soluble (Nonidet P-40-extracted) and insoluble (6 M guanidine hydrochloride-extracted) A\u03b2 levels were measured previously by sandwich enzyme-linked immunosorbent assay (ELISA) [42] , and cerebral amyloid angiopathy (CAA) severity, which was graded semi-quantitatively on a 4-point scale by a method adapted from that of Olichney et al. [43] , had previously been reported [44] . Phosphorylated tau (p-tau) load (area fraction of cerebral cortex immunopositive for p-tau) had been measured for all cases, as previously reported [45, 46] . ACE1 genotype data for the Alu 237-bp insertion(I)/deletion(D) (indel) polymorphism (rs1799752) in intron 16 of the ACE1 gene were previously reported [5, 41] . Last, all cases had previously been apolipoprotein E (APOE)-genotyped [44, 47] by a polymerase chain reaction method [48] ." ] },{ "paper_id": "f81ae57f3c989bf53683a523da0a1799ebd19862", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The genomic viral RNA was extracted from 200 ml of samples by using a High Pure viral RNA kit (Roche Diagnostics, Manheim, Germany) according to the manufacturer's instructions. The RNA was eluted in a final volume of 100 ml of elution buffer and kept at 280uC until further analysis.", "Written informed consent for the use of the clinical specimens was obtained from all patients involved in this study. This study was approved by the Ethics Committee of the Jiangsu Provincial Center for Disease Prevention and Control.", "Real-time RT-PCR for detection of H7N9 virus was carried out using the primers and probes recommended by the WHO Collaborating Centre in Beijing [5] and the SuperScript III Platinum One-Step qRT-PCR Kit (Invitrogen) according to the instructions. The cycling conditions were composed of 20 min at 50uC, 2 min at 95uC, followed by 40 cycles with 94uC for 15 s and 60uC for 1 min, and a final extension cycle of 72uC for 10 min." ] },{ "paper_id": "f81e9eb1b488b5a21f7bfbe5ece67dbd80425f86", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Throat Swab Cloacal Swab 1 dpi 3 dpi 5 dpi 1 dpi 3 dpi 5 dpi", "The care and use of experimental animals were approved by the Institute Animal Care and Use Committee, National Taiwan University (approval no. NTU-103-EL-3 issued on 1 March 2014). All animal experiments were conducted in accordance with approved guidelines.", "Two-week-old SPF chickens (JD SPF Biotech, Miaoli, Taiwan) were intranasally infected with IBV 2992/02 [5] at a dose of 10 6 EID 50 per chicken. Throat and cloacal swabs were collected in tryptose phosphate broth (Difco Labs, Detroit, MI) at one, three and five dpi. The swabs were clarified by centrifuging at 3000\u00d7 g for 20 min and stored at \u221280 \u2022 C until further testing with ICS and RT-PCR." ] },{ "paper_id": "f8207b55dbdf90c353bda7975f849d94bd704653", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total viral nucleic acid (DNA and RNA) was extracted from 140 \u03bcl of each clinical specimen using the PureLink\u2122 Viral RNA/DNA Mini Kit (Invitrogen, Carlsbad CA, USA) according to the manufacturer's recommendation. DNA/RNA are eluted with 60 \u03bcl nuclease-free water and stored at \u221280\u02daC until use.", "A two-step multiplex real-time RT-PCR was performed with a Bio-Rad CFX-96 thermocycler (Bio-Rad Laboratories) and the Anyplex\u2122 II RV16 Detection kit (Seegene) for a simultaneous testing of Influenza viruses (fluA and fluB), Human respiratory syncytial virus (RSVA and RSVB), Human adenoviruses (HAdV), Human metapneumovirus (HMPV), Human coronavirus (229E, NL63, OC43), Human parainfluenza virus (PIV1, -2, -3 and -4), Human rhinovirus (HRV), Human enterovirus (HEV) and Human bocavirus (HBoV), as previously described [12] .", "The data obtained daily were entered into an Epi Info database (Centers for Disease Control and Prevention, Atlanta, GA) and analyzed using Epi Info." ] },{ "paper_id": "f8243fd9214e2e45a222a43aad977d882f17e1e9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To visualize the protein structural residues and their chemical environment we had used the crystallographic structure from PDB database submitted by Russell et al. [55] and the molecular visualization tool PyMOL [56] .", "Here this technique is used to compute the protein descriptors to determine similarity/dissimilarity between different protein sequences including short protein stretches. To avoid error of false similarity when analysing short sequences, we have added a stretch of 20 aa peptides at the beginning of each sequence for filling up all the initial coordinates with the value 1 before starting the calculation of protein descriptors, a technique that is useful for comparative studies.", "To analyze solvent accessibility we have used SABLE secondary structure prediction server [54] . Body regions of twenty proteins were submitted to calculate relative solvent accessibility.", "To make quantitative comparisons between different sequences plotted in this system, we follow the method given in Raychaudhry and Nandy [41] . The weighted centre of mass of each graph is calculated by summing the co-ordinate values of each point and then a graph radius, g R , is computed. The g R represents the Base Distribution index or numerical descriptor for nucleic acids. The g R is a very sensitive measure of the sequence composition and distribution [41, 49] , the values depending on the type of mutations and where in the sequence they occur. g R is especially useful in comparing equal length sequences [50] ." ] },{ "paper_id": "f8290fc7f4fb355f1da52f816acfb2113691acb3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\ue062e authors contributed equally in the writing of the paper. ", "Pseudotyping with measles virus H/F ENV envelope glycoproteins confers transduction capacity to resting human B and T cells, with the possibility of targeting these immune cell types for the induction of tolerance [30, 158] .", "Our organisms are constantly in direct contact with an extensive variety of substances, particles, and living organisms of diverse origins. While many of these comprise a potential list of pathogens, the vast majority of them, including commensal bacteria, pollen, yeast, mites, and many types of chemicals are largely innocuous. \ue062erefore, in the \ufffdrst instance the default immunological response to these antigens is tolerance and unresponsiveness. In addition to this, if an immune response is triggered by a potential pathogen/threat, autoprotective mechanisms exist to minimise collateral damage and loss of tolerance towards the organisms' own components (autoantigens)." ] },{ "paper_id": "f82bb9d2d37888e87a1f8f42c7f898a809c3bc94", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Husbandry and experiments were in accordance with the German Animal Welfare Legislation (Tierschutzgesetz: http:// foundation.aalas.org/). All experiments were also approved by the local Institutional Animal Care and Research Advisory Commitee and by the local government, namely the Lower Saxony State Office for Consumer Protection and Food Safety (approval ID: 509c-42502-03/651).", "The primer design application within LIMSTILL is Primer3based and parameters are set to design primers with an optimal melting temperature of 58uC.", "PCR was performed using a touchdown thermocycling program (92uC for 60 sec; 12 cycles of 92uC for 20 sec, 65uC for 20 sec with a decrement of 0.4uC per cycle, 72uC for 30 sec; followed by 20 cycles of 92uC for 20 sec, 58uC for 20 sec and 72uC for 30 sec; 72uC for 180 sec; GeneAmp9700, Applied Biosystems). PCR reaction mixes contained 5 ml genomic DNA, 0.2 mM forward primer and 0.2 mM reverse primer, 200 mM of each dNTP, 25 mM Tricine, 7.0% Glycerol (w/v), 1.6% DMSO (w/v), 2 mM MgCl 2 , 85 mM Ammonium acetate pH 8.7 and 0.2 U Taq Polymerase in a total volume of 10 ml." ] },{ "paper_id": "f837cfe73ee695265382ec9873726fcd7b24d9b1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This review details the airway disease phenotypes of existing CF animal models, and examines their strengths and weaknesses for basic and pre-clinical research.", "Rats have intrinsic advantages for routine use as a model of CF including low cost and maintenance, rapid reproduction rate, and large litter sizes. The CFTR knockout rat demonstrates many pulmonary phenotypes including airway surface defects, a CF-like electrical profile in nasal and tracheal tissues, abnormal mucus production, and tracheal malformations. Although promising, further in-depth characterisation of the airway disease that is present, or readily inducible, would aid investigators in using this model for research applications.", "Abbreviations ASL: Airway surface layer; BAL: Bronchoalveolar lavage; CACC: Calcium-activated chloride channel; CF: Cystic fibrosis; CFTR: Cystic fibrosis transmembrane conductance regulator; cAMP: Cyclic adenosine monophosphate; ENaC: Epithelial sodium channel; FABP: Fatty acid binding protein; I sc : Short circuit current; MCC: Mucociliary clearance; MCT: Mucociliary transport; NPD: Nasal potential difference; PCL: Periciliary liquid; siRNAs: Short-interfering RNAs; SPF: Specific pathogen free" ] },{ "paper_id": "f849d3e71f4d2eae8a1e39802195bc9c06fc30ae", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In a previous study, CoVOC43 was the most commonly detected coronavirus [25] , followed by CoV (NL63 HKU1), with similarly moderate detection frequencies.", "This observational study has several limitations: 1) The small subgroup numbers may lead to differences in detection rates, making it worthwhile to consider a multicenter study with greater numbers of surgical cases to further examine the impact of VRI on postoperative outcomes; 2) The possible bacterial pathogens in the PSP were not considered; 3) no information was available about the vaccination and immunological status of eligible patients.", "Respiratory virus is well known to cause significant morbidity and mortality in pediatric populations [1] [2] [3] ; especially in neonates or very young infants; in patients with chronic heart or lung disease; and in the immunosuppressed [4] . Numerous studies have described viral respiratory infection (VRI) as a leading cause of illness and death in people of all ages [5] . The most frequent community-acquired respiratory viruses are respiratory syncytial virus (RSV), parainfluenza virus (PIV), human influenza virus (IV), human metapneumovirus (HMPV), and human rhinovirus (HRV) in the respiratory infection patients, hematopoietic cell transplant recipients, and hematologic malignancy patients with an immunocompromised status [3, [6] [7] [8] [9] ." ] },{ "paper_id": "f84decc775e81850bbfcbf71972377db10e4863c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f85f1c88d5f92b9177f3c652fe643d7f13df947e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The fresh or stored wheat samples were ground in a Retsch MM400 mixer mill (Retsch, Haan, Germany) for 1 min at 30 Hz, the sample powder was homogenized with 600 \u03bcl extraction buffer (0.1 M Tris-HCl, pH 7.4, 2.5 mM NaCl, and EDTA) and 600 \u03bcl supercritical water-phenol, then centrifuged at 12,000 rpm for 15 min. The aqueous phase was precipitated with 4 M LiCl. After incubation at -20\u00b0C for 2 h or overnight, the precipitate was collected by centrifugation (12,000 rpm) at 4\u00b0C for 15 min. The resultant pellet was washed twice with 70% ethanol, dried at 37\u00b0C for about 5 min, and dissolved in 60 \u03bcl deionized distilled water. The RNA extract was stored at -20\u00b0C.", "Novel nucleic acid amplification methods, loopmediated isothermal amplification (LAMP) for DNA and RT-LAMP for RNA, have been developed [18] . The high specificity and sensitivity, rapid execution, performance under isothermal condition, time-saving, easy observation of by-products [19] , and low cost make RT-LAMP unrivaled among diagnostic techniques. It is easy and simple to perform only with four appropriate primers, a reverse transcriptase for RNA template, a DNA polymerase and a water bath or heat block for reaction. Therefore, in recent years, many pathogenic viruses have been detected by these methods, including human [20] [21] [22] [23] [24] , animal [25] and plant [26] [27] [28] [29] [30] [31] [32] viruses.", "In the present study, the RT-LAMP method was used successfully for detection of WYMV for the first time. This method could result in more accurate diagnosis for monitoring WYMV." ] },{ "paper_id": "f869e0515c1a31c8d4c1770a053ce1d933c30241", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Acyclovir is the most commonly used HSV antiviral. Though resistance to acyclovir is clinically insignificant in otherwise healthy individuals (0.1-0.7%) [5] , immunosuppressed individuals have much higher incidences (4-10%). The prevalence of resistance is very strongly linked to the degree of immunosuppression and duration of acyclovir exposure [45] . These issues highlight the important role that host-targeted or broadly-acting antivirals could play in treatment of drug-resistant HSV infections." ] },{ "paper_id": "f86ac2580002e6b374ec325717eeee73e84af1c5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The research ethics committee of Shenzhen Second Peoples' Hospital reviewed and approved the experimental protocols [Licence No. 2009-001] (Appendix S1). Both the Guide for the Care and Use of Laboratory Animal (1996) [31] and the ARRIVE (Animals in Research: Reporting In Vivo Experiments) guidelines [32] were followed.", "After micro-CT scanning, femoral heads were sawed in half longitudinally along the coronal plane. Halves were decalcified and embedded in paraffin; and halves were embedded in Methyl methacrylate (MMA) without decalcification.", "2. Undecalcified sections. The MMA embedded femoral heads were sectioned along the sawed plane using a diamond saw (Isomet, Buehler). The cut surface was polished on a soft cloth rotating wheel [39] . The surfaces were acid-etched with 37% phosphoric acid for 2-10 seconds, followed by 5% sodium hypochlorite for 20 minutes. The samples were then sputtercoated with gold and palladium, as described previously [40, 41] and examined for bone matrix and features of osteocytes in the scanning electron microscope (SEM) (JSM-6300, JEOL, Japan)." ] },{ "paper_id": "f8710043513b5790e20921e8a36d1cc94b402701", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Virology Journal 2009, 6:166 http://www.virologyj.com/content/6/1/166" ] },{ "paper_id": "f879891cd4353fbb6baa973c04bc1cf2dc3a3fd6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Genotyping pathogens and their hosts using RNA-seq of field-collected infected leaves", "were dispersed among 4,633 genes that displayed clusterspecific unique amino acid substitutions, of which 177 had detectable secretion signals (Figure 5a ). Using the most highly ranked PST effector candidates from our previous study [20] , we identified 42 genes that encoded cluster-specific polymorphic proteins that displayed features typical of characterized effector proteins ( Figure 5a ).", "Background: Emerging and re-emerging pathogens imperil public health and global food security. Responding to these threats requires improved surveillance and diagnostic systems. Despite their potential, genomic tools have not been readily applied to emerging or re-emerging plant pathogens such as the wheat yellow (stripe) rust pathogen Puccinia striiformis f. sp. tritici (PST). This is due largely to the obligate parasitic nature of PST, as culturing PST isolates for DNA extraction remains slow and tedious." ] },{ "paper_id": "f87c8bfc787731a80acd6bf082c748c41afb8a4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All phages and bacteria were propagated in lysogeny broth (LB: 10 g NaCl, 10 g Bacto tryptone, and 5 g Bacto yeast extract per liter of water) at pH 7. Bacterial cultures were initiated by transferring a single colony from a streak plate into 10 mL LB in a sterile 50 mL flask capped with a 20 mL beaker. Culture flasks were incubated with shaking (120 rpm) at 25uC for 18 hours, allowing bacteria to attain stationary-phase density (,6610 9 cells mL 21 ).", "Cystovirus 6 used in these experiments is a descendant of the strain originally isolated from bean straw in 1973 [16] . 6's host of isolation was the Gram-negative bacterium, P. syringae pathovar phaseolicola (ATCC # 21781; hereafter PP) [16] . In our study, we used a nonpermissive host, P. pseudoalcaligenes East River isolate A (hereafter ERA), to isolate 6 host range mutants (HRMs). The ERA receptor to which 6 binds has not been determined, but is likely the ERA pili. Two other nonpermissive hosts, P. syringae pv. tomato (hereafter TOM) and P. syringae pv. atrofaciens (hereafter ATRO), were used in some assays. All bacteria and virus stocks were obtained from Paul Turner, Yale University, New Haven, CT.", "Plaque sizes for 13 HRM genotypes were estimated from digital photographs of plaques formed on ERA. All LB plates used for plaque assays were poured at the same time and were weighed to maintain consistency. Each mutant's lysate was diluted and plated such that between 20 to 100 plaques formed on the ERA lawn after 48 hrs growth. Digital photographs were taken using a Kodak Gel Logic 440 digital imaging system. ImageJ software (NIH, Bethesda, MD; http://rsb.info.nih.gov/ij/) was used to estimate the total area of the plaque. For each genotype, at least 35 plaque size estimates were made across 3 plates." ] },{ "paper_id": "f87ca9ce6ad3323737c273a36a56a08d050b2d26", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rhinolophus ferrumequinum Hungary PCR [15] Myotis myotis Germany PCR [16] Astroviridae", "Myotis myotis Germany PCR [16] Mamastrovirus ", "Italy PCR [22, 28] " ] },{ "paper_id": "f87fb7ecfabe0bae476e587f8c5eb01b15b24db0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GI, KS, and GY designed the simulation models. GI conducted the finite element analysis, and wrote the main paper. All authors discussed the results and implications, and commented on the manuscript at all stages.", "where V B is the bridge voltage, and R i is the change in the resistance of R i . A fixed constraint was applied on the end of each beam.", "Analytical solutions of nanomechanical sensing are available for a simple cantilever model. For example, the deflection of the freeend of a cantilever ( z) induced by isotropic internal strain in a receptor layer (\u03b5 f ) is given by the following equation (Yoshikawa, 2011) :" ] },{ "paper_id": "f880418303ca5f21c858eca97f076216919bb4b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MMP7-null mice are more susceptible to oral infection by MAdV-1", "Mature HD5 and Crp23 were obtained by oxidative refolding of partially purified linear peptides and purifying the correctly folded species by reverse-phase high-pressure liquid chromatography (RP-HPLC) [21] . ProHD5 and HD5Abu were chemically synthesized and purified as described [61, 62] . Crp2 was synthesized, refolded, and purified using the same method as for HD5 [61] . Purified Crp4 was produced in E. coli and purified by RP-HPLC [63] .", "All mouse experiments were performed in strict accordance with the Guide for the Care and " ] },{ "paper_id": "f889617cc2152ead5c5070ee3ee24dcf86248bad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "MNGCs were defined as cells containing a minimum of three nuclei and quantified per field using the formula: (number of nuclei within MNGCs/total number of nuclei) \u00d7 100. MNGC formation efficiency was compared to an internal negative control treatment for each experiment.", "Results" ] },{ "paper_id": "f89c1c613071fcb7fdb5d956e91a807b83456ea3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tumour necrosis factor-\u03b1 (TNF\u03b1) is an important proinflammatory cytokine of the immune system. Dysregu-lated TNF\u03b1 responses are implicated in several inflammatory diseases including rheumatoid arthritis. In this condition, TNF\u03b1 antagonism, either with recombinant soluble receptors or neutralising antibodies, improves disease activity scores [1] .", "Analysis \u03b1 2 -Macroglobulin was measured using a RIA sensitive to 7.8 ng/ml. Rabbit anti-human \u03b1 2 -macroglobulin (Dako, Copenhagen, Denmark) was used as anti-serum and human serum (Behringwerke, Marburg, Germany) as standard. Human \u03b1 2 -macroglobulin (Capell-Organon, Turnhout, Belgium) was iodinated. Tracer and standard or sample was mixed with antiserum before adding goat anti-rabbit anti-serum (AstraZeneca, Lund, Sweden). The bound fraction was measured using a gamma counter. The intra-and inter-assay coefficients of variation are between 3.8-6.0% and 3.1-7.2%, respectively. IL-8 was measured using a commercially available enzyme-linked immunosorbent assay (R&D Systems, Abingdon, UK). ECP and MPO were also measured using commercially available assays (Phadia, Uppsala, Sweden and Calbiochem, Darmstadt, Germany, repectively). The limits of detection for IL-8, ECP and MPO were 31.2 pg/ml, 2.0 and 1.6 ng/ml, respectively.", "Topical TNF\u03b1 produces a nasal inflammatory response in humans that potentially is mediated through increased neutrophil activity." ] },{ "paper_id": "f8abd9e10df6beeffec38bc7dd7083318e0d69ed", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Some physical delivery technologies for improving gene-based immunization have been listed in number 1 to 5 as following:", "Generally, the methods of delivering a DNA plasmid are divided into:", "Further work will be required to determine the mode of action of this prime-boost approach." ] },{ "paper_id": "f8b28dc077a4d62178940c43350079dd6b0b91bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For ultrastructural analysis in ultrathin sections infected cells were fixed for at least 1 hr in a mixture of 2.5% formaldehyde prepared from paraformaldehyde powder, and 0.1% glutaraldehyde in 0.05 M cacodylate buffer pH 7.3 to which 0.03% picric acid and 0.03% CaCl 2 were added. The monolayers were washed in 0.1 M cacodylate buffer, cells were scraped off and processed further as a pellet. The pellets were post-fixed in 1% OsO 4 in 0.1 M cacodylate buffer pH 7.3 for 1 h, washed with distilled water and en bloc stained with 2% aqueous uranyl acetate for 20 min at 60\u00b0C. The pellets were dehydrated in ethanol, processed through propylene oxide and embedded in Poly/Bed 812 (Polysciences, Warrington, PA). Ultrathin sections were cut on Leica EM UC7 ultramicrotome (Leica Microsystems, Buffalo Grove, IL), stained with lead citrate and examined in a Philips 201 transmission electron microscope at 60 kV.", "Before sequencing, all virus stocks were grown in cultures of the C6/36 clone of Ae. albopictus cells [16] , obtained from the American Type Culture Collection (ATCC), Manassas, VA. Infection was characterized by detachment of cells and cell lysis. " ] },{ "paper_id": "f8bd14ffe1272be4d4c25d0d6f23f2479c0d1475", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Total RNA was extracted 40 hrs after electroporation, followed by agarose gel analysis and Northern blotting using radiolabeled TBSV probe as described [17] . The template for the TMV RNA probe was generated by PCR using the full-length cDNA for TMV and primers #2890 (59-TCTGGTTTGGTTTGGACCTC-39) and #2889 (59-GTAATACGACTCACTATAGGGATTC-GAACCC-39). The normalization of samples was done based on quantified ribosomal RNA levels in total RNA samples visualized by ethidium-bromide staining of gels." ] },{ "paper_id": "f8c2f1a1903f8370c15b5be2e4d32e91f2641b03", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chamaemelum nobile herb + ---", "Perilla frutescens herb + ---", "Agastache foeniculum herb + ---" ] },{ "paper_id": "f8de6043ca1a372d6ea60880034cfb6abbc4b147", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Viral RNA was extracted from the cultures using a QIAamp Viral RNA Mini Kit (Qiagen, Hilden, Germany). The RNA was eluted in 60 \u03bcL of Buffer AVE and was used as the template for RT-PCR.", "The nucleotide sequences of the ten dromedary MERS-CoV genomes sequenced in this study have been submitted to the GenBank sequence database under accession nos. KX108937-KX108946.", "In addition to the bootscan analysis, possible recombination breakpoints were also detected using RDP, GENECONV, BOOT-SCAN, MAXIMUM CHI SQUARE, CHIMAERA, SISCAN and 3Seq implemented in Recombination Detection Program Version 4 (RDP4). Automasking was used for optimal recombination detection. The RDP analysis was run without a reference and with a window size of 60, the BOOTSCAN window size was increased to 500, the MAXCHI and CHIMAERA number of variable sites per window was increased to 120, and the window size and step size for SISCAN were increased to 500 and 20, respectively. Potential recombination events detected by four or more of the seven independent recombination detection methods in the ten genomes in this study were further analyzed with phylogenetic trees constructed using sequences upstream and downstream of the potential recombination breakpoint." ] },{ "paper_id": "f8e6c1da1ba9b222863bb9369bfc92a7a908b6e0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The proposed model was selected and considered extremely favorable for several reasons:", "The significance level was set to p-value < 0.1 (i.e. method's default) for the SLAC, FEL, FUBAR, FEEDS and MEDS methods, while the posterior probability threshold for the FUBAR method was set to 0.9.", "All considered field strains formed a monophyletic group including only Italian strains (Additional file 1).", "The actual reasons behind the strength of selective pressures imposed by vaccination, especially in veterinary medicine, are still not fully understood." ] },{ "paper_id": "f8efe7295a7cf875c8a695df3e87a42e651ce60d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We organized a day's training for our research assistants on how to use Personal Digital Assistant device (PDAs) Samsung Galaxy note 8 GT-N5100 (Samsung Electronics Co. Ltd., Seoul, Korea) in capturing data.", "Any healthcare worker attending directly to patients in emergency situation was therefore eligible for inclusion in the study. Our sampling frame consisted of a list of a total of 200. From this list, we then took a systematic random sample of all eligible health workers to represent the sample size. After obtaining written informed consent indicated by signature and or thumbprint of participants, we then administered the questionnaires within the two facilities.", "Data were collected electronically using tablets for cloud storage through CommCare ODK version 2.27.2, aggregated into Microsoft Excel file, exported into STATA version 14 and analyzed. Descriptive statistics was used to summarize the distribution of various variables into tables and figures. Categorical variables were analyzed using chisquare tests and logistic regression for associations." ] },{ "paper_id": "f8f2a61fb217ad9fb00b93b7ec2bbb016bcbb881", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Understanding the clinical management of common veterinary problems and patterns of AMU may provide the necessary exposure information to help interpret AMR trends, identify potential problem areas in prescribing practices and provide evidence-based practice guidelines for practitioners [12] [13] [14] [15] [16] .", "The objectives of this study were to: ", "Collecting clinical management and AMU data at the veterinary patient level has not been legislated in Canada and remains a challenge in veterinary medicine in Canada [11, 17, 18] ." ] },{ "paper_id": "f8f49888663fdad58dabb5d7f9f8556b36d34587", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Veronika I. Zarnitsyna thanks the organizers of the Multi-Scale Physics of Lymphocyte Development Summer Seminar 2012 that sparked her interest in the problem of T cell cross-reactivity. Brian D. Evavold was supported by NIH R01 NS071518 and R01 AI096879, Joseph N. Blattman was supported by a Virginia G. Piper Personalized Medicine Bridging Award, and Veronika I. Zarnitsyna and Rustom Antia were supported by an NIH MIDAS grant U01 GM070749. We also thank the Reviewers for their comments and suggestions.", "Another reason for why humans need a more diverse repertoire than mice pertains to the number of pathogens to which they are exposed. As humans live longer than mice, other factors being equal, they will be exposed to more pathogens and require a lower P E .", "www.frontiersin.org which gives" ] },{ "paper_id": "f8f5d842db3bc80e5c22011583b8e965abfe624c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This current Ebola outbreak started in Gu\u00e9ck\u00e9dou and Macenta districts of Guinea during December 2013 [35] , and WHO proclaimed the EVD outbreak on 23 March 2014. As the situation deteriorated, from all of the available evidence, Director-General Margaret Chan of WHO defined the epidemic to be a Public Health Emergency of International Concern. Figure 1 ", "The Ebola epidemic of West Africa had been viewed as a public health emergency of international concern by the World Health Organization (WHO) on 8 August 2014, attributed to its explosive course and high fatality [1] . Ebola virus disease (EVD), also known as Ebola hemorrhagic fever, was first identified in Yambuku and the surrounding areas in Zaire and South Sudan in 1976 [2, 3] . The largest public reaction, which might provide clues for government and health authorities to reform existing modes of health education.", "To understand the public reaction in China to the outbreak of EVD in West Africa, we carried out an innovative network digital epidemiologic study based on the online data retrieved from 20 July to 4 September in 2014, in which the epidemics had aroused significant attention and reaction in China." ] },{ "paper_id": "f8f601687c9a9a4debc34112cec0165ad81fb15d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All data is represented as mean 6 standard deviation. Statistical analyses were performed using Student's t-test. p,0.05 are considered statistically significant." ] },{ "paper_id": "f9075b3b2fcb919dd92b981ac6161302c5f904cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal experiments were performed according to institutional guidelines and Swiss federal and cantonal laws on animal protection. Animal experiments were approved by the following ethical committee: Service de la consommation et des affaires v\u00e9t\u00e9rinaires, Affaires v\u00e9t\u00e9rinaires, Canton de Vaud, Switzerland (permit numbers 2283 and 2216).", "Lungs were inflated with 1 ml 10% formalin, embedded into paraffin and stained with hematoxylin and eosin. Stained slides were analyzed by light microscopy. Pulmonary emphysema was quantified using Image J software by measuring the mean linear intercept for airspace enlargement and destruction index for alveolar wall destruction. 10 fields of view at 20X magnification per section of lung were used for quantification as described previously [31, 32] .", "Airway cells were recovered by bronchoalveolar lavage and either analyzed by flow cytometry as described below or spun onto slides for differential cell counts. Slides were stained with Diff-Quik (Dade) and counts were performed according to standard criteria.", "Statistical significant differences were assessed using the Student's t test (two tailed, unpaired). P-values below 0.05 were considered significant and were depicted with p#0.05 (*), p# 0.005 (**), p#0.0005 (***). Standard error of the mean was applied." ] },{ "paper_id": "f909ff3d201ad4ddc44488137db54eb2a4be076e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Consumers in wealthier economies might be receptive to microbicides costing $1-2 or even more per dose; however, consumers in lesser-developed economies might find $1-2/dose to be prohibitive. Hence, absent subsidies, there exists a continuing need to lower COGS for APIs such as Griffithsin.", "For model building, batch schedules were calculated under the initial assumption of 24/7 operation for 330 days per year. Plant uptake of nutrients and growth were assumed to be linear reaching 15 g FW per plant at viral inoculation and then increasing in mass to reach 40 g FW per plant at harvest. A 5% failure rate of TMV inoculation was assumed (Pogue et al., 2002) . The Griffithsin expression rate was fixed at 0.52 g/kg FW ", "The scheduling of 3 batches is summarized in the equipment occupancy chart in Figure 2 . As shown, seeding, germination, transplant, pre-inoculation, inoculation, and post-inoculation occur sequentially, and the batches are staggered by 3.44 days.", "The results generated by the software for the upstream operations are shown in Figure 1 , with scheduling shown in the equipment occupancy chart in Figure 2 . The following descriptions elaborate on the schema presented in each figure.", "The 10 L of eluant process fluid is sent through a viral clearance filter and transferred into a pool/storage tank. Subsequently, the extract is sent through an ultrafiltration/diafiltration cycle to remove salts introduced in the chromatography column. After ultrafiltration, the product is transferred into a storage tank to be mixed with the final formulation components. The concentrated Griffithsin is diluted to give a concentration of 10 g/L Griffithsin in 10 mM Na 2 HPO 4 , 2.0 mM KH 2 PO 4 , 2.7 mM KCl and 137 mM NaCl at pH 7.4. The final volume of the DS is 21 L per batch.", "The environmental assessment of the plant-based production of Griffithsin indicates low impact, particularly if the plant nutrient solutions are recycled in a hydroponic system and if waste streams containing TMV are treated in a biowaste heat or chemical treatment process. The assessment method used, although semi-quantitative, utilizes mass input and output stream data generated by SuperPro, along with independent assessment of compound toxicity and/or environmental impact (for example using Material Safety Data Sheet information), and allows comparison between alternative production strategies, process configurations or chemical components used in the manufacturing process." ] },{ "paper_id": "f9162c1be900c7bab2cc52de3e8cdef666c4824c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Previous analyses [10] suggested that exposure to microbial peptide sequences can modulate immune responses to similar pathogen and allergen derived peptide epitopes. Specifically, those studies suggested that such microbiome-derived peptides might be perceived as self by the immune system and thereby be tolerogenic, resulting in the elimination or functional silencing of potentially reactive T cell clones.", "https://doi.org/10.1371/journal.pone.0196551.t002 ", "Supporting information S1 ", "We recruited 10 healthy adults from San Diego, USA. All participants provided written informed consent for participation in the study. This study was performed with approvals from the Institutional Review Board at La Jolla Institute for Allergy and Immunology (protocols VD-101 and VD-071). No detailed clinical history including vaccination records is available for the participants. PBMC (peripheral blood mononuclear cells) were isolated from collected blood or leukapheresis by density gradient centrifugation, according to manufacturer's instructions. Cells were cryopreserved in liquid nitrogen suspended in FBS containing 10% (vol/vol) DMSO." ] },{ "paper_id": "f9187e3a34dfe7e63989291c32b4f8254de5e6a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Here, we used a variety of sequence-derived features to generate various different modes of general PseAAC that have proven useful in our previous studies. These include:", "Sp", "Acc" ] },{ "paper_id": "f91df0d67f4d6fc329815c233f76b5ef0dd3876a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "f93195034f642c748faae11cb58300881eb7b2bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are expressed as the mean \u00b1 standard deviation (SD) of three independent experiments. Student's t-tests were performed. Values of p < 0.05 were considered statistically significant and p < 0.01 were considered statistically highly significant.", "Porcine deltacoronavirus (PDCoV), a newly detected porcine coronavirus, as well as porcine transmissible gastroenteritis virus (TGEV), porcine rotavirus (PRV), and porcine epidemic diarrhea virus (PEDV) are the major pathogens of the porcine epidemic diarrhea disease. They cause microscopic intestinal lesions leading to serious diarrhea and often dehydration to death (1, 2) .", "Quantitative RT-PCR (qRT-PCR) was performed using SYBR green Supermix (ABI-7500, Life, USA). The primer sequences are shown in Supplementary Table 1 . The relative gene expression levels were calculated using the 2 \u2212 CT method." ] },{ "paper_id": "f93269b90d3654488b158876258d42402d64afb3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To study the host response elicited by SARS-CoV, it is essential to use cell lines, such as Vero E6, MA-104, CaCo-2, Huh7,", "Cell lysates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Proteins were transferred to a nitrocellulose membrane with a Bio-Rad mini protean II electroblotting apparatus at 150 mA for 2 h in 25 mM Tris-192 mM glycine buffer, pH 8.3, containing 20% methanol.", "Membranes were blocked for 1 h with 5% dried skim milk in TBS (20 mM Tris-HCl, pH 7.5, 150 mM NaCl) and incubated with antibodies specific for hsp60 (Cell Signaling, Ref. RT-PCR analysis of XBP-1 mRNA" ] },{ "paper_id": "f93f20813c626fb775bbb73b1c14c906cd61e899", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "PEDV is a single-stranded RNA virus, approximately 28 kb in size, which belongs to the genus Alphacoronavirus 8 . The PEDV genome comprises of seven open reading frames (ORFs) that encode for non-structural proteins responsible for viral genome replication and transcription, as well as four structural proteins, namely spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins 8,9 . Among the structural proteins, the S glycoprotein plays a critical role in host affinity, virus-cell recognition, membrane fusion and entry 1,10,11 . Moreover, it contains multiple neutralizing epitopes that make it a suitable target for vaccines designed to neutralize PEDVs 12-14 .", "Porcine epidemic diarrhoea virus (PEDV) causes porcine epidemic diarrhoea (PED), a highly contagious disease characterized by acute watery diarrhoea, vomiting, and dehydration, and with a high mortality rate particularly in suckling piglets 1,2 . The first outbreak of PED was recorded in the European and Asian swine industries in the early 1970s and then spread to many countries 3,4 . In 2010, novel and highly virulent PEDV strains were identified in China, which later spread to several countries 1,5,6 . These new variants of PEDV have caused high morbidity and mortality in neonatal piglets, resulting in serious economic loss to the swine industry 1,7 . Thus, there is an urgent need for in-depth and comprehensive studies on the antigenicity and immunogenicity of PEDVs in order to facilitate disease control and eradication.", "To understand the antigenicity of PEDV, we generated a panel of neutralizing mAbs (NmAbs) by immunizing BALB/c mice with inactivated PEDV viral particles. The neutralizing epitopes of the PEDV-PT S protein, recognized by two of the NmAbs, were characterized using a series of C-terminal truncated recombinant PEDV-PT S proteins under native and denaturing conditions. This approach allows us to identify conformational epitopes of PEDV-PT strain and helps in understanding the antigenicity and pathogenesis of the G2b PEDV." ] },{ "paper_id": "f9410459142b63fb34eac0375dda7d9b6460b3fe", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Antemortem sampling consisted of collection of sputum samples using a probang cup as described in the OIE Terrestrial Manual 2012, Chapter 2.1.5, section B [2] . Briefly, approximately 10 ml of OPF was collected with probang cups and transferred to ice-cooled conical tubes containing 10 ml of MEM with 25mM Hepes. OPF samples were frozen in 1-2 hours to -70\u00b0C until further processing (see below).", "Randomizations and bootstrapping methods to compute statistical significance and confidence intervals were calculated using REST 2009\u00a9 software [40] , generating 6000 random pairs of carriers and control, and using assay efficiency previously determined for each assay in our laboratory.", "Cytokine gene expressions of caudal DSP tissue samples, collected from 12 FMDV-carrier and 3 control (uninfected) animals were analyzed. Relative gene expression between FMDV-carriers and controls was normalized using the GAPDH housekeeping gene. The statistical comparison between the carrier and control groups was carried out by randomizing data points from each group and calculating the relative expression [39] :" ] },{ "paper_id": "f9426bdcd204747d493857d5a88efaf70c2cbee5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at http://www.mdpi.com/2073-4425/9/9/442/s1, Table S1 : 51 runs of sRNA-seq data for invertebrate virus detection, Table S2 : Homologous sequences of ORF3b. ", "In Vivo experiments revealed that the biogenesis pathway that was responsible for svRNA-N's synthesis was not dependent on Dicer or Drosha as the canonical biogenesis of miRNAs and svRNA-N were able to silence mRNA expression by targeting its 3' UTR. However, the mechanisms underlying infection or pathogenesis of both SARS-CoV-cpsR-19 and svRNA-N are still unknown.", "Forward Primer Reverse Primer" ] },{ "paper_id": "f9572dc31ce0512cc966d43fbe693656af18a03c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Blood collected in 10 mL tubes with no anti-coagulant was centrifuged at 3200 g for 15 min at 4uC. The serum was collected and stored at 220uC until use. Plasma was collected from blood sampled in heparinised tubes and stored at 220uC before use." ] },{ "paper_id": "f9700deed61ea92d41891cf29eccddac0ee0ca15", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ured by using a 2\u2032,7\u2032-dichlorofluorescin diacetate (DCF-DA)-Cellular Reactive Oxygen Species Detection Assay Kit (Beyotime Institute of Biotechnology, Shanghai, China). Cells were incubated with 10 \u03bcM DCF-DA for 30 min at 37 \u00b0C and washed three times with PBS. The fluorescence was observed by a fluorescent microscope (Eclipse Ti, Nikon, Melville, NY, USA) from five random fields and measured by ImageJ software (National Institutes of Health, Bethesda, MD, USA). Cellular apoptosis analysis. Cellular apoptosis was analyzed by performing a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay using an in situ cell death detection kit (Beyotime Institute of Biotechnology, Shanghai, China) following the manufacturer's instructions. After 4% paraformaldehyde fixation and 0.1% Triton X-100 permeabilization, cells were incubated with 50 \u03bcl TUNEL reaction mixture for 60 min at 37 \u00b0C in the dark and then rinsed with PBS three times. Then after a 10 min DAPI (5 mg/ml) counterstain at room temperature, cells were photographed with a fluorescent microscope (Eclipse Ti, Nikon, Melville, NY, USA) from five random fields. The apoptotic index = (positively stained apoptotic cells)/(total number of cells) \u00d7 100%.", "As the incidence of chronic renal failure (CRF) increases at an alarming rate, CRF has been considered a major public health problem worldwide 1 . CRF is a syndrome characterized by progressive and irreversible deterioration of renal function 2 . In humans, CRF is mainly caused by hypertension, glomerulonephritis, and diabetes mellitus 3, 4 . This condition is made worse by a deterioration in nutrition level caused by accumulation of uremic toxins and reduced food intake, which could be attributed to many factors, such as gastrointestinal congestion, loss of appetite, and reduced glomerular filtration rate 4-6 . Compared to patients with other chronic diseases, patients with CRF tend to require longer and more frequent hospitalizations which are associated with higher morbidity and mortality 7 . Therefore, it is urgent to develop alternative medicines and novel therapies for the treatment of CRF.", "In conclusion, our results demonstrate that H 2 S is able to ameliorate CRF in rats by inhibiting apoptosis and inflammation through the ROS/MAPK and NF-\u03baB signaling pathways (Fig. 11) . Therefore, H 2 S or its releasing compounds may serve as a potential therapeutic molecule for CRF.", "Western blot analysis. Renal tissues were homogenized in RIPA lysis buffer (Sigma, St. Louis, MO, USA). Protein concentrations of the homogenates were measured by the BCA protein assay kit (Beyotime Institute of Biotechnology, Shanghai, China). The extracted proteins (50 \u03bcg) were separated on SDS-PAGE gel and transferred to a PVDF-nitrocellulose membrane. After blocking, the membranes were incubated with primary antibodies to detect the target proteins. Anti-extracellular signal-regulated protein kinase 1/2 (ERK1/2), anti-phospho (p)-ERK1/2 (Thr202/Tyr204), anti-c-Jun N-terminal kinase (JNK), anti-p-JNK (Thr183/Tyr185), anti-p38, anti-p-p38 (Thr180/Tyr182), anti-p50, anti-p65, and anti-p-p65 (Ser536) antibodies were purchased from Cell Signaling Technology (Danvers, MA, USA). Anti-Bax, anti-Bcl-2, anti-Caspase-3, anti-Cleaved Caspase-3, and anti-\u03b2-actin antibodies were purchased from ProteinTech (Chicago, IL, USA). The horseradish peroxidase-conjugated secondary antibody was purchased from Cell Signaling Technology. The reaction was visualized using an enhanced chemiluminescence system (Thermo Fisher Scientific, Rockford, IL, USA). The bands were quantified by densitometry using ImageJ software." ] },{ "paper_id": "f98d0564028d3963a79b75d9bd46fe5a1a5b8541", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Serum samples were tested at a 1:20 dilution for presence of IgG antibodies reacting with MERS-CoV (residues 1-747), severe acute respiratory syndrome (SARS)-CoV (residues 1-676) and human coronavirus (HCoV)-OC43 (residues 1-760) spike domain S1 antigens using extensively validated protein-microarray technology [7] , [17] . HCoV-OC43 S1 was used as proxy for bovine CoV (BCoV), which is known to circulate commonly in dromedary camels [7] .", "One limitation to this study is the convenience sampling scheme which may have led to bias associated with owners allowing samples to be collected from more tractable individuals (e.g., older). However, we sampled across a range of ages and sexes in each herd.", "Blood was stored on ice for transport to the Mpala Research Centre, where it was centrifuged and serum separated and frozen at -20\u00b0C. Samples were shipped on dry ice for testing at Erasmus University, Netherlands. All sera were transported in agreement with Dutch import regulations regarding animal disease legislation. Basic demographic and management data relating to each herd and each camel were collected. Herds were categorized by management type (e.g., commercial, commercial/pastoralist, nomadic) and the degree of isolation from any new camels that enter the herd. Isolation categories included: low isolation (6 or more camels enter herd in 1 yr or camels move around consistently with high probability of interacting with other camels); intermediate isolation (3-5 camels enter herd in 1 yr); and high isolation (1-2 camels enter herd in 1 yr). Ages were assigned as: young ( 6 months), juvenile (6 months-2 years), and adult (> 2 years) based on dental wear and herder/owner knowledge.", "Understanding the epidemiology of MERS-CoV in dromedary camel populations is critical in assessing and managing the risk to humans posed by the circulation of the virus." ] },{ "paper_id": "f996c22e999ecc9ff3b5cce74bae47fa8b323f23", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ADE modifies DENV entry into target cells through Fc\u03b3 R. However, activation of various receptor-mediated pathways, such as downregulation of intracellular innate and adaptive antiviral mechanisms, could also contribute to enhanced dengue pathogenesis 3 . Activating Fc\u03b3 Rs are known to signal through phosphorylation of immunoreceptor tyrosine-based activation motif (ITAM) and spleen tyrosine kinase (Syk) 4 . Activated Syk controls a number of pathways, including actin remodelling necessary for phagocytosis 5 and STAT-1-dependent interferon-stimulated gene (ISG) induction independent of interferon receptor signaling 4 . Induction of ISGs would create an intracellular environment unfavorable for enhanced DENV replication. To counter this early activating Fc\u03b3 R-triggered antiviral response, DENV co-ligates the inhibitory leukocyte immunoglobulin-like receptor B1 (LILRB1) during ADE 6 . LILRB1 recruits SH2 domain-containing phosphatase-1 (SHP-1) to dephosphorylate Syk and downregulate STAT-1 induction of ISG response 6,7 .", "Over the last decade alone, the global burden of dengue has doubled, with an estimated 50 to 100 million symptomatic cases annually 1 . The risk of severe disease is augmented when dengue virus (DENV) is opsonized with non-or sub-neutralizing levels of antibodies that ligate Fc-gamma receptors (Fc\u03b3 Rs) for enhanced entry and replication in monocytes, macrophages and dendritic cells. This phenomenon, termed antibody-dependent enhancement (ADE), engenders the elevated viraemia and vascular leakage that is characteristic of severe dengue. Indeed, we have recently demonstrated ADE clinically and identified how this process could be exploited to enhance live attenuated viral vaccination 2 .", "In both professional and non-professional phagocytes, cellular compartmentalization is utilized as a means of self-defence against human pathogens. Compartment borders restrict pathogen access to the cytosol, and the expression of pattern recognition receptors and danger receptors aid pathogen detection and elimination 8 . Determining how DENV is compartmentalized, depending on the mode of entry, is thus a hitherto unexplored investigation that could provide unique insights into the pathogenesis of dengue." ] },{ "paper_id": "f997749a5fc2672a931ecc329c5f3e1c4c6cae9b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bears live in all the continents except Africa, Antarctica, and Australia, and they are classified into eight species including giant panda (Ailuropoda melanoleuca). The largest among all is polar bear (Thalarctos maritimus), followed by brown bear (Ursus arctos), American black bear (Ursus americanus), Asiatic black bear (Selenarctos thibeta-nus), spectacled bear (Tremarctos ornatus), sloth bear (Melursus ursinus), and sun bear (Helarctos malayanus). All of these species are endangered -five are listed in Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) Appendix I, whilst the remaining three are listed in Appendix II [1] .", "Over the years, extensive research has been done in establishing methods to analyze and quantify the total and individual bile acids and their glycine and taurine conjugates in serum [11, 12] , pharmaceuticals [13, 14] , and bile [15] [16] [17] , including bear gall drainage [18] . These methods mainly consisted of thin layer chromatography [13, 18, 19] and high-performance liquid chromatography [11, 12, [14] [15] [16] [17] 20, 21] .", "(2) The medium-term goal was to expand this program across China and continually reduce the number of bears on farms; and" ] },{ "paper_id": "f9a61ae749c3d53492b38119c9fbe5f0e448b52a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Approval for the study was granted by the University of Southampton Ethics Committee (study ID: 491) and", "Cough hygiene:", "When you are infected: Cover your nose or mouth with a tissue every time you cough or sneeze Throw the tissue away at once in a disposable container (e.g. plastic bag)" ] },{ "paper_id": "f9a7674c9052c8a2db502ec640a9e9cd1d6cef34", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The results of AAPC were presented in Tables 3, 4 , 5 and 6 in Appendix. No significant difference was detected." ] },{ "paper_id": "f9c39fa24056184c67ec47da4da93ba583c36e84", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ST cells were cultured in high-glucose Dulbecco's modified Eagle's medium (DMEM; GIBCO, UK) containing 10% heat-inactivated fetal calf serum (HyClone, China) and antibiotics (100 \u03bcg/ml streptomycin and 100 U/ml penicillin); the culture medium was replaced every 3 days. TGEV H16 strain was obtained from the National Control Institute of Veterinary Bioproducts and Pharmaceuticals (Beijing, China) and propagated in ST cells.", "To study the protective effect of shRNAs against TGEV destruction, the MTS cell proliferation assay was performed on ST cells stably expressing shRNA plasmids." ] },{ "paper_id": "f9d015b725d247948462394085053cff02c94791", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A total of 20 \u03bcg of total RNA was electrophoresed on a 10% NovexTM TBE-Urea Gel (Invitrogen) and transferred to a Hybond-N+ membrane using a semi-dry electroblotter at 400 mA for 30 min, followed by UV crosslinking. Oligo DNA probes (10 ng each) were labeled with gamma [32P]-ATP using a MEGALABEL Kit (Invitrogen). Hybridization was performed in hybridization buffer (10% SDS, 10% dextran sulfate, 1 M NaCl, 0.5 mg/mL sonicated salmon sperm DNA) at 65\u00b0C overnight. The membranes were washed twice in 2x SSC and 0.5% SDS at room temperature for 30 min and in 0.2x SSC and 0.5% SDS at 65\u00b0C for 30 min. Next, the signals were visualized with a BAS-3000 image-analyzer (GE Healthcare, Little Chalfont, UK).", "Tissue samples were stained to identify and measure Ki67 levels. The tumors were detected with primary monoclonal probes for Ki67 overnight at 4\u00b0C. After incubation with a suitable second antibody, the tissue microarrays were treated with diaminobenzidine and counterstained with hematoxylin. All tissues were observed and photographed (10X) with a microscope (Carl Zeiss, Oberkochen, Germany)." ] },{ "paper_id": "f9d40df8555bd7f3d0269178141f9e5ce11c6e2e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Potential conflicts of interest. All authors: No potential conflicts." ] },{ "paper_id": "f9e8af068e552f4327e0e7cdd359674967d9d422", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "\u2022 On page 8 it is stated that \"Traditional risk assessment methods estimate these [mortality and morbidity] separately as numbers of cases\". I don't really agree with this statement. There are many health impact assessment methods which can consider both together and which are not incidence-based.", "The section would benefit from additional references to supporting literature.", "The MS is generally well written and certainly merits publication." ] },{ "paper_id": "f9f0d3495e6f8f04b60c9e1cf9a3cf1423d51cc7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thailand is a middle to high income country with the estimated population of 69 million in 2016. The population density was 135 people per square kilometer and varies from 100 to 250 people per square kilometer in each region [10] . Surveillance was conducted in 17 provinces in all five regions of Thailand (Fig. 1) . The 30 participating hospitals in these provinces were selected based on having an intensive care unit and hospital staff willing to participate in the SevPn activities.", "Lung tissue from fatal cases were sent to the regional pathology network for histopathological testing where they were embedded in paraffin, cut into 3 \u03bcm-thick sections, deparaffinized in xylene, and rehydrated in graded alcohol. Each section was stained with hematoxylin and eosin. Additional specialized testing was performed if there was clinical suspicion for a particular disease, such as silver staining for Pneumocystis jirovecii. Acute serum and/or convalescent serum were sent for serological testing and storage for further diagnostic testing if required by the clinical committees.", "Respiratory, blood, and serum specimens were shipped to NIH in Bangkok where they were stored and tested or sent to other academic centers that had laboratory capacity for further testing based on clinician request. For the tracheal aspirates, viral and bacterial testing were performed on different samples. Tracheal aspirates in viral transport media (VTM) were tested by multiplex real-time reverse transcription polymerase chain reaction (rRT-PCR) [13] for a panel of six viruses including influenza A and B, parainfluenza virus, adenovirus, respiratory syncytial virus (RSV), and human metapneumovirus. Singleplex rRT-PCR was performed for subtyping of influenza A-positive specimens and for MERS Co-V starting in September 2012 [14] . For bacterial testing, tracheal aspirates in sterile tubes (without VTM) were tested by conventional multiplex PCR for 11 bacterial pathogens: Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, Escherichia coli, Staphylococcus aureus, Burkholderia pseudomallei and Acinetobacter species. A separate multiplex real-time PCR was used to detect atypical bacteria including Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella species. All multiplex PCRs used for testing were developed by the NIH [15] .", "The laboratory network provided laboratory testing and consultation to the clinicians of the surveillance hospitals and transferred specimens to other laboratories as needed. The focal point was a staff member at the specimen receiving and distributing center of NIH.", "This report describes the methodology of the SevPn surveillance system and provides preliminary results on each of its objectives from December 2010 through December 2015." ] },{ "paper_id": "f9faf42edda00faefb4ea08c2c4234b027990579", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data were expressed as mean\u00b1SD. All statistical analyses were carried out using the SPSS software (Version 13.0). Comparison of variables between groups was performed by One-Way ANOVA followed by LSD post-hoc test. P values of <0.05 were statistically considered significant.", "Whole cell extracts were prepared from cells by lysis in 1 mL lysis buffer containing 50 mmol/L Tris (pH7.4), 0.5% NP-40 and 0.01% SDS and a cocktail of protease inhibitors. Total protein (30 \u03bcg) was boiled for 5 min in 1\u00d7 loading buffer, chilled on ice and then separated on 10% sodium dodecyl sulfate (SDS)-polyacrylamide gels. Subsequent to transfer onto PVDF membranes (Millipore, USA), non-specific protein interactions were blocked by incubation in 5% nonfat dry milk in TBST buffer containing 50 mmol/L Tris-HCl, 150 mmol/L NaCl, and 0.05% Tween 20 (pH7.6) at 4\u00b0C for 1 h. Membranes were then incubated at 4\u00b0C overnight with anti-PARP or anti-\u03b2-actin monoclonal antibody (Cell Signaling, USA), anti-Bcl-2 or anti-Bax (Bioworld, USA) in fresh blocking buffer. Unbound antibody was removed by three 10-min washes in TBST buffer. Membranes were then incubated with horseradish peroxide-conjugated secondary antibody (Santa Cruz Biotechnology, USA) for 1 h at room temperature followed by three 10-min washes with TBST buffer. The blot was developed with ECL reagent (Applygen Technologies, USA).", "In summary, we demonstrated that HHV-6A induces cell apoptosis in cultured T lymphocyte cells through the mitochondria-mediated apoptosis pathway, as evidenced by (1) " ] },{ "paper_id": "fa0630536ffb3bc1d387a3bfea810be65fd6f950", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Soon after its discovery, RNAi was considered a novel option to treat viral infections. Successful RNAi applications have been reported for most classes of medically relevant viruses including HIV-1, HBV, HCV, SARS-coronavirus, influenza virus und poliovirus [111, 112] . Some of these approaches have already reached the stage of clinical testing. While RNAi-mediated therapies against HIV-1 and HBV are based on shRNA expression systems [113] , the most advanced clinical phase II trial makes use of chemically synthesized siRNAs against RSV, which are administered by a nasal spray [114] .", "Interferons (IFNs) belong to the group of the cytokines and have antiviral and immunomodulating activities. Suspected from early investigations demonstrating the release of cytokines from CVB3 infected human monocytes [98] , the role of IFNs in CVB3 infections became obvious when IFN-\u03b2 knockout mice proved to be highly susceptible to CVB3 infections and developed a breakdown and disruption of cardiomyocytes [99] .", "Several studies demonstrated naturally occurring mutants resistant to pleconaril and, moreover, pleconaril treatment seems to result in rapid emergence of resistant CVB3 mutants [68, 69] . Such mutants predominantly contain a single amino acid substitution, Ile-1092 Leu/Met in the hydrophobic pocket of the canyon which prevents efficient binding of the compound, while it does not impair binding of the virus to cellular receptors [69] . In order to overcome virus resistance, new pleconaril derivatives have recently been synthesized and successfully tested against pleconaril-resistant mutants [70] ." ] },{ "paper_id": "fa07cb83c9ec268f4be524c374659bc3584fca6f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Lungs and tracheas of euthanized tree shrews were preserved in 10% phosphate-buffered formalin. Tissues were then processed for paraffin embedding and cut into 4-\u03bcm-thick sections. One section from each tissue sample was subjected to standard hematoxylin and eosin staining, while another was processed for lectinhistochemistry.", "Furthermore, tree shrews used in the present study were determined to be seronegative for influenza A viruses (H1N1), using the hemagglutination inhibition (HI) test. Some animals in each group after inoculation with the two viruses possessed recognizable HI antibody titers range from 80 to 640 Hemagglutinating Units (HAU) ( Table 1) ." ] },{ "paper_id": "fa0a24c1abcfc2964ea0a8f4c4c3df322713eca7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Amaryllidaceae" ] },{ "paper_id": "fa0ea39aff2c19a92de12d6f0323721a9bfa38a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Specific pathogen-free (SPF) cats were obtained from the breeding colony of the Feline Nutrition and Pet Care Center, School of Veterinary Medicine, University of California, Davis, CA. Animals were housed and maintained according to regulations and guidelines of the University of California Davis Institutional Animal Care and Use Committee (UC Davis IACUC approval numbers 15,309 and 16,637).", "Virus detection or virus loads in blood did not correlate with development of FIP based on viral RNA concentrations " ] },{ "paper_id": "fa137f1562d599f03605b83bc68f91e5105110d9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fa16032841f11e0924b539d21444915e3bcc9a0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Blood collected from STG90 and wild-type mice was centrifuged at 3,000 rpm for 10 min, and plasma was stored at 220uC until analysis. Plasma levels of total albumin, aspartate aminotransferase, alanine transaminase, and other total proteins were analyzed using an automatic blood chemistry analyzer (Selectra II, Merck, Germany).", "3D8 scFv exhibits resistance to HSV type1 and PRV in stably transfected cell lines", "(TIF)" ] },{ "paper_id": "fa1d2145aa1af1e5232d8d425f36f4e9bb20f392", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each of the two genetically and antigenically distinct groups of hMPV (A and B) can be further divided into genetic subgroups 1 and 2 (Boivin et al., 2002) .", "(+) and (-) denote sense and anti-sense strand, respectively. glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene served as an internal control. Fluorescence signals cycle threshold (Ct) was based on optimization and values \u226438 were considered positive.", "Purified PCR products were subjected to Sanger sequencing." ] },{ "paper_id": "fa2c978f246035c7e524e301c1ed8f9a5178dfde", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, the results demonstrate that small, but statistically significant, changes can be detected with our protocols under the conditions described for Figure 5 .", "(2) Reduction of noise and false positives" ] },{ "paper_id": "fa47af75688fa3fab2afde5ed3f1a7fdd9624746", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Authors declare that they have no significant competing financial, professional or personal interests that might have influenced the performance or presentation of the work described in this manuscript." ] },{ "paper_id": "fa4d272c79931c9d40575defb54ac24b37869bc9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Current MultiBacTAG applications include artificial amino acid cross-linking to map interactions in protein complexes, fluorescence labeling of specific targets to measure structure and dynamics in proteins and glycolengineering proteins compatible with human tissue studies. We anticipate that the platform will also be adopted for custom-design proteins for therapeutic biotechnology and pharmaceutical applications. As an example, we used MultiBacTAG to engineer trastuzumab (also known as Herceptin), an antibody that associates with cancer cells, to recognize breast cancer cells in human tissue [58, 59] .", "Following the same logic, further SVNs were developed for improved manufacturing of selected classes of protein biologics of pharmacological interest. Kinases are cornerstones of signal transduction in cells, and many disease states, notably cancer, are caused by malfunction of kinases and their interactions. Smallmolecule drugs acting as kinase inhibitors are prolifically used in cancer chemotherapy, and the discovery of new and better kinase inhibitors is a major driving force in oncology research and development. A vital prerequisite to sustain these efforts is the supply of high-quality recombinant kinases for screening and structure-based design approaches. Kinases are often inherently fragile proteins that require helper molecules, such as chaperones, for proper folding during expression. To enhance recombinant production of properly folded and soluble kinases, we designed SVNs that contain up to seven chaperones in the viral LoxP site (Fig. 4) . To balance the quantities of individual chaperones produced, we again applied our polyprotein strategy. The resulting \"kinase factory\" produced previously unobtainable kinases at high levels, in soluble and functional form.", "The MultiBac system was shown in its first configuration in 2004 [11] , which had been developed to address the challenge of efficient multiprotein complex production for structural biology applications. Subsequently, we received requests from laboratories in both academia and industry exemplifying the need for such a tool-kit, a trend that has not since subsided. The numerous important structures elucidated using MultiBac-produced samples evidenced how useful the system is. We, and others, invested considerable effort over the years to streamline MultiBac, rendering it more user-friendly and accessible, with improvements such as alternative methods for inserting genes of interest.", "The original AcMNPV genome from which the MultiBac is derived contains all the information required for the virus to sustain its life cycle in nature, starting from uptake by the host (the fall armyworm), the infection of midgut cells, followed by massive amplification and release of occluded viral particles when the worm lyses. Many of these functions are dispensable, or even detrimental, in laboratory cell culture. The advent of powerful DNA synthesis and assembly technologies has now made it feasible to \"rewire\" entire genomes. Genome improvement by eliminating undesired functionalities is a major ambition in current synthetic biology. The baculoviral genome is around 140 kb, which is the size of an average BAC, and within the size that is capable of complete de novo synthesis, as recently shown [64] ." ] },{ "paper_id": "fa5d4e0d5a2afc924b07e8835aa0ac3cf0646089", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fmicb. 2017.00672/full#supplementary-material", "The Italic underlined nucleotides are restriction enzyme sites.", "Frontiers in Microbiology | www.frontiersin.org", "SLC performed most of the experiments, collected and analyzed data and wrote the manuscript. LW, LZ, WS, YN, and ZY participated in preliminary data acquisition. JYC contributed to plasmids construction. XZ helped with data analysis. SW and XC contributed to shRNA design and revised the manuscript. JLC and MG revised the manuscript. SYC and JLC conceived of the study, participated in study design and coordination. All authors read and approved the final manuscript. " ] },{ "paper_id": "fa5e90f78c7365ea9ad6b8b9cf9b6e43a1ca727c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "As shown in a series of recent publications [38] [39] [40] [41] [42] [43] [44] [45] in response to the call in a comprehensive review [46] , user-friendly and publicly accessible web-servers represent the future direction for developing practically more useful prediction and modeling methods or demonstrating new and novel findings, we shall make efforts in our future work to provide a web-server for the approach and finding presented in this paper.", "Pharmacophore modeling can provide valuable insight into ligand-receptor interactions. Pharmacophore searches are the best option to find a range of chemical structures with viable features. A pharmacophore model can be considered as the ensemble of steric and electrostatic features of different compounds, which are necessary to ensure optimal supramolecular interactions with a specific biological target structure and to trigger or to block its biological response. Thus, pharmacophore modeling is the method of choice for the first round of compound selection. This ability of a pharmacophore model is used to find new classes of inhibitors when one class is known. This is known as \"scaffold hopping\" [19] [20] [21] .", "The pharmacophore hypothesis was generated using GALAHAD module of SYBYL, which operates in two main stages: The ligands are aligned to each other in internal coordinate space, and then the conformations produced are aligned in Cartesian space. The feature considered in developing the pharmacophore model includes HBD atoms, HBA atoms, hydrophobic and charged centers [35] [36] [37] . In our study, eight compounds shown in Table 1 were selected to carry out the pharmacophore hypothesis and the genetic algorithm was used to create conformers for all molecules. The compounds selected to generate the pharmacophore hypothesis are highly active and structurally diverse." ] },{ "paper_id": "fa6b3fafeedf308826d58db91499b7c09f172310", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "High levels increased PWD [112, 115] Stimulated growth rate Soil heavy metal contamination", "Modulated immune functions Co-resistance", "Reduced the markers of intestinal inflammation Potential source of pathogens?" ] },{ "paper_id": "fa84d62d8e80e07fdcd1f5543bec8c3f2cb46b74", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The author(s) declare that they have no competing interests.", "BK carried out bacteriological examination of samples, isolation and cloning of mycoplasmas and drafted the manuscript.", "All authors read and approved the final manuscript." ] },{ "paper_id": "fa8f28950eb66ca369acb51e3cbb5b3ee178f82f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "plasmid DNA, though optimization for target cell types can also help improve translation efficiency (Yamamoto et al., 2009) .", "There are over a dozen clinical trials using mRNA for vaccines, adjuvants, or to express antigens either in dendritic cells ex vivo or by direct injection. However, gene replacement therapy is still in pre-clinical development (Kaczmarek et al., 2017) .", "Several classes of non-coding RNAs have been identified including piwi-interacting RNAs, endogenous siRNAs, long-noncoding RNAs, and circular RNAs. The function of these species and their role in disease biology are being actively investigated (Esteller, 2011) . As the role of non-coding RNAs in cancer biology continues to unfold, therapeutic approaches to modulate them will be of increasing interest (Gutschner and Diederichs, 2012) . Therapeutic delivery of non-coding RNAs will face similar challenges to other types of RNA, such as stability and uptake into appropriate cells and intracellular compartments." ] },{ "paper_id": "fa93cc1d684bce742748b879031332537855f5ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There is no conflict of interests to declare, and all authors certify that they have no commercial associations that might pose a conflict of interests in connection with this paper.", "All surgeries were performed by the corresponding author using previously reported methods [12] . During surgery, histological examination of subchondral bone was performed to confirm the diagnosis of ONFH.", "The Scientific World Journal 3 All patients in the two groups fully complied with rehabilitation instructions." ] },{ "paper_id": "faa8c6b399eff710bae62ce297e56c19fe212e74", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations ADCC: antibody-dependent cellular cytotoxicity; ADCs: antibody-drug conjugates; AEG-1: astrocyte elevated gene-1; AIV: avian influenza viruses; CDC: complement-dependent cytotoxicity; CMC: chemistry, manufacturing, and control; CMV: cytomegalovirus; DHF: hemorrhagic fever; DSS: dengue shock syndrome; DTSSP: 3,3\u2032-dithiobis[sulfosuccinimidyl propionate]; EpoR: erythropoietin receptor; hCXCL8: human CXC ligand 8; hnRNP: heterogenous ribonucleoproteins; HPV: human papillomavirus; IFP: interstitial fluid pressure; mAbs: monoclonal antibodies; MMPs: matrix metalloproteinases; MPS: mononuclear phagocyte system; PAK: p21-activated kinase; PDCs: peptide-drug conjugates; RES: reticuloendothelial system; SARS: severe acute respiratory syndrome; SH: Src homology; TIMP-2: metalloproteinases-2; TpoR: thrombopoietin receptor; VEGF: vascular endothelial growth factor.", "Authors' contributions H-CW, C-HW, I-JL, and R-ML contributed to the literature review, writing, and figure design. H-CW and C-HW compiled the manuscript and revised it critically to meet publication standards. All authors read and approved the final manuscript.", "The authors declare that they have no competing interests." ] },{ "paper_id": "faac6cddc8f0126d5f93e948689eead41f54ad1f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Complete autopsy, ancillary investigations and histological examination of the tissues did not reveal any other possible cause of death.", "Byard et al. [5] emphasizes the need to examine the upper aerodigestive tract at autopsy in all age groups, not only early childhood, as such lesions may not produce marked symptoms and signs prior to lethal airway occlusion.", "We suggest that particular attention should be paid to the epiglottisboth macro and microscopically, as concomitant epiglottal edema may very well offer an explanation for the sudden and unexpected collapse and death of children with tonsillitis and associated tonsillar hypertrophy. " ] },{ "paper_id": "faad09d0c4532ac11d673b84f539be583e897df9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The relative size or extent of a region.", "doi:10.1371/journal.pcbi.1003561.t001", "and" ] },{ "paper_id": "faada181a26e163dce05aa155b1516a66bb6154b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The implications for airport screening as an epidemic control policy and the importance of reinforcing public hygiene education", "For the comprehensive and effective surveillance of dengue infection, both active surveillance and passive surveillance were performed. The active surveillance includes fever screening at the airport, health statements from the inbound passengers, screening for contact with confirmed cases and school-based reporting. The passive surveillance refers to the hospital-based reporting system for the notification of either imported or domestic dengue cases. All relevant data and diagnostic results were reported via the web-based National Surveillance System for subsequent tracking and management." ] },{ "paper_id": "fac028a97db9169282fd01c3ca41d4eb7afb3f5c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Oral infection of laboratory mice with S. Typhimurium causes typhoid-like symptoms without clinical signs of gastroenteritis and can be used to study genetic determinants of systemic infections. IFN-\u03b2 \u2212/\u2212 mice show increased resistance to S. Typhimurium in lethality and bacterial spread in this model (67, 68) .", "Upon colonization of germ-free mice with a two-component bacterial community, IFN-responsive genes are strongly upregulated in cecal epithelia (100) .", "JP and SST wrote the manuscript.", "Salmonella enterica serovar Typhimurium causes gastroenteritis and is one of the most frequent causes of bacterial foodborne disease in Western countries, representing a major economic problem (86) ." ] },{ "paper_id": "fac2afdb0450de6c766a24baf26e3ce6e03e09e2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Human embryonic kidney cells (HEK293) were obtained from and cultured in the medium recommended by the American Type Culture Collection (Manassas, VA). All cell lines were incubated at 37uC and 5% CO 2 under humidified conditions.", "The data are presented as the mean 6 the standard error. Statistical analyses were performed with the nonpaired two-tailed Student t -test, assuming equal variance. Statistical significance was defined as P,0.03.", "HIV antigens, incorporated within HVR2, are exposed on the virion surface" ] },{ "paper_id": "fac9ef6ba1ca4bdb16baad83f0146e6a5c3b906f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A Supporting Information Figure 1 A. Design of 9-, 10-, 11-mer peptides derived from the 15-mer antigen. Overlapping 9-, 10-, 11-mer peptides were each tested for their capability to stabilize the corresponding HLA. A total of 18 different peptides were derived from each 15-mer peptide.", "D. Similar to Part B, HLA-stability ELISA results for soluble HLA-B*55:02 molecules that were ligand-exchanged with 9-, 10-, 11-mers truncated peptides from DENV NS3-108 15-mer peptide.", "I. HLA-stability ELISA results for soluble HLA molecules that were ligand-exchanged with 9-, 10-, 11-mers truncated peptides from the indicated15-mer peptide. Non-irradiated HLA with conditional ligand and no peptide added (-UV), irradiated HLA and no peptide added (+UV), or with indicated 9-, 10-, 11-mers peptides." ] },{ "paper_id": "facba90187f6bee3be651d71fc54a715055eaa1d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Within one year, 40 (4.2%) and ten (1%) patients had received influenza and streptococcus pneumonia vaccine.", "Categorical variables were described with counts and percentages. Data for continuous variables were presented as mean (SD) or median (IQR) where appropriate. The proportions of individuals in each age and PSI groups diagnosed with each pathogen of interest were compared using \u03c7 2 tests (SPSS for Windows 13.0)." ] },{ "paper_id": "facbfdfa7189ca9ff83dc30e5d241ab22e962dbf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "faced14dbb3af799525a67f97bd6d5b904a365e3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Interspecies transmission of pathogens may", "Most of the well-known human viruses persist in the population for a relatively long time, and coevolution of the virus and its human host has resulted in an equilibrium characterized by coexistence, often in the absence of a measurable disease burden.", "Coronaviruses (CoVs) primarily infect the upper respiratory and gastrointestinal tract of mammals and birds. Five different currently known CoVs infect humans and are believed to cause a significant percentage of all common colds in human adults. Surprisingly, recent studies revealed that approximately 6% of bats sampled in China were positive for CoVs [21] . Subsequent phylogenetic studies revealed that bat CoVs that resembled human SARS-CoV clustered in a putative group comprising one subgroup of bat CoVs and another of SARS-CoVs from humans and other mammalian hosts. According to the current hypothesis SARS-CoV has arisen by recombination between two bat viruses. Phylogenetic analysis of SARS-CoV isolates from animals indicate that the resulting bat virus was transmitted first to palm civets (Paguma larvata), a wild cat-like animal hunted for its meat, and subsequently to humans at live animal markets in southern China [22] ." ] },{ "paper_id": "fad068abaa998641db5de8113fced6b3ef3d613f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "periodontal tissue injury [11] [12] [13] . Thus, methods to control the inflammatory response and to eliminate periodontal bacteria are considered to be important for the inhibition of periodontal disease.", "Real-time reverse transcription-polymerase chain reaction (RT-PCR) for quantitative detection of mRnA expression. Ca9-22 cells were incubated in DMEM with 10% fetal bovine serum until confluent.", "(2020) 10:3113 | https://doi.org/10.1038/s41598-020-59730-9" ] },{ "paper_id": "fad38d4f310922f5af4326b319cfaf1eb8f70282", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Our study suggests that junior healthcare workers should also be focused and educational program must be designed to target this group to increase their knowledge about JE." ] },{ "paper_id": "fadd90c71b61efc6c47a0117d160ca9c77a914ec", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For a summary of functionally defined lncRNAs see Supplementary Tables S2 and S3 where web references are linked to easily retrieve the available information about the lncRNA of interest.", "Author Contributions: E.A., R.S.B., L.B., writing-original draft preparation; S.C., F.C., writing-review and editing; S.C., supervision. All authors have read and agreed to the published version of the manuscript. " ] },{ "paper_id": "fadf1a77d8e94ac8611eb79cf4d0da59872d72bb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are generally presented as average 6 sem with n being the number of animals. Data acquired in paired experiments using littermates were evaluated by paired t-test. Significance was assumed when p,0.05.", "Otocysts, altered or intact, were maintained in organ culture for two days. Otocysts were placed into 12-well plates (Cat# 353503, Fisher, St. Louis, MO), submersed in DMEM/F-12 media (Cat# 12500-062, Invitrogen, Carlsbad, CA) supplemented with 10% fetal bovine serum (Cat# 30-2020, ATCC, Waldorf, MD) and 1% penicillin-streptomycin (Cat# 15140-122, Invitrogen) and incubated at 37uC in a humidified atmosphere enriched with 5% CO 2 (HeraCell 240, Heraeus, Germany). Media was changed every 24 hrs.", "Freshly isolated or cultured otocysts were fixed at 4uC for 2 hrs in a solution containing (in mM) 150 NaCl, 3.6 KCl, 5 HEPES, 1 CaCl 2 , 1 MgCl 2 and 5 glucose, pH 7.4 and 4% paraformaldehyde. Fixed otocysts were processed through a sucrose gradient (10% and 20%, each 20 min, followed by 30% overnight, all at 4uC), infiltrated with polyethylene glycol (Cat# 72592-B, Electron Microscopy Sciences, Hatfield, PA) and cryo-sectioned (12 mm, CM3050S, Leica, Germany). Serial sections throughout the entire cochlea were obtained from embryos between ages E11.5 and E14.5 and mid-modiolar sections of the cochlea were obtained from embryos between ages E15.5 and E18.5 and from neonates aged P3." ] },{ "paper_id": "fae708f3b0a6023fccad707c4417b521f84fc328", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Global distribution data for bioclimatic variables, mammalian and avian diversity and anthropogenic variables were collected from multiple sources [61] [62] [63] . For each of the global raster datasets, we calculated zonal statistics for all species using their geographical habitat distributions. A complete list of variables, their explanations, sources, and calculated statistics can be found in Supplementary Table 3 and Supplementary Table 4 .", "Maintenance of these viruses in non-vertebrate hosts pose a great hurdle for disease control efforts, where public health measures such as vaccines could control disease transmission in urban settings, but sylvatic cycles could continue to be a source of spillover to populations in rural areas 26 . Moreover, sylvatic circulation of flaviviruses could alter primate population dynamics and contribute to extinction risks in vulnerable primate populations as has been evident for YFV-related primate declines in South America with outbreaks that have decimated populations of howler monkeys (Alouatta spp.) 27 .", "Following the first discovery of ZIKV in 1947 in a sentinel rhesus macaque in Uganda 29 , efforts to recognize potential natural wildlife reservoirs for ZIKV have been limited. As of 2017, the World Health Organization categorizes Southeast Asia as a region with active human transmission of ZIKV. However, evidence of ZIKV in Southeast Asian primates to date is limited to detection of exposure in Bornean orangutans (Pongo pygmaeus) from Eastern Sabah, Malaysia in 1996-1998 30, 31 . Our model results predict additional host candidates, Macaca fascicularis, and Macaca nemestrina, which should be evaluated further for their potential to maintain ZIKV and their ability to pose ongoing spillover risk to humans.", "Surveillance programs which aim to identify sylvatic hosts of viral diseases face many logistical hurdles, including accessing wild species that often reside in remote habitats and procuring large numbers of high-quality samples for virus detection. However, recognition of wildlife hosts for zoonotic pathogens is important for evaluating pathogen evolution within wildlife reservoir populations, advancing early detection of outbreaks through identification of sentinel species, mitigating risk at animal-human interfaces, and monitoring threats that zoonotic pathogens might pose to wildlife 6 . When compared to viruses with a limited host range, zoonotic viruses with high host plasticity are more likely to spread after spillover by secondary human-to-human transmission and are known to have greater geographic spread 7 . While vector-borne viruses have greater host plasticity in general 7 , members of the flavivirus genus demonstrate a varying propensity towards host range; some infect species within a narrow range of taxonomic relatedness while others infect a wide range of vertebrate taxa 4 ." ] },{ "paper_id": "fae8f01ff5ef7b1737b60dfba0e183bdf482aaba", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "No [8] SIVmus mustached monkey", "No [8] SIVgsn greater spot-nosed monkey", "Yes [8] SIVmnd mandrill" ] },{ "paper_id": "faf7a4e9db24c30637224f708ad868ecfc1d9da6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Individuals are divided into children (c, age less than 19y) and adults (a, otherwise). Population size and age structure per municipality as of January 1, 2008 are obtained from Belgian Statistics [54] .", "where the element ij (i = a, c, j = a, c) is given by:", "The force of infection for a susceptible individual of age class i (i = a, c) in a given patch p is given by:", "Given the central role of mixing patterns largely supported by evidence [7, 8, 20, 48] , the heterogeneous country-specific contact variations measured in Europe [4, 32] , and the marked difference expected in individual behavior during a seasonal flu epidemic vs. a pandemic, here we extend prior approaches to introduce a data-driven spatially explicit model fully parameterized on Belgium. The aim is to reduce assumptions in favor of input data, and to exclusively focus on seasonal influenza and associated parameterization." ] },{ "paper_id": "fafa45b4080e37b2d37450168738d991a0399343", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data are presented as the means \u00b1 standard error of the means (sem). Data from IFN-treated groups were compared to vehicle-treated groups and significant differences were determined by one-way analysis of variance (ANOVA) followed by Turkey's post hoc t test (GraphPad Prism \u00a9 Home, San Diego, CA)." ] },{ "paper_id": "fb0191a305e3289b1be275259659e20b096247b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Read-overlap graph generation. To evaluate evidence for putative SV and large INDEL calls generated by assembly methods, we can employ a read-overlap graph generated by exhaustive pairwise alignment of a set of reads which co- " ] },{ "paper_id": "fb077b4ea64b29cf81d88b9160f6ebb1d4a3d776", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The traditional RNA annotation database RefSeq and Ensembl do not contain circRNA information currently. Instead, seven independent circRNA databases are available (Table 3 ) [82] [83] [84] [85] [86] [87] [88] .", "The common consensus of the functions of ncRNA is that they regulate gene expression at both transcriptional and epigenetic levels. The exact mechanism of this regulation varies by ncRNA categories; and some may be yet to be discovered. As HTS technology and sequencing library construction methods advance, we come closer to elucidating the entire human RNA spectrum and uncovering the secrets of ncRNAs.", "The number of definable lncRNAs varies by study. In 2005, a study claimed to have identified over 35,000 lncRNAs [11] . Another study in 2007 estimated that there are four times more lncRNA compared to protein-coding RNA [48] . In the ENCODE lncRNA release (Version 26), 15,787 lncRNAs were identified, further categorizing them into four sub-classes: antisense, large intergenic non-coding RNAs (lincRNA), sense intronic, and processed transcripts. In the latest study in 2017 by Hon et al., 27,919 human lncRNAs with high confidence 5' end were described [49] .", "Novel bioinformatic tools have contributed greatly to the identification of the new circRNAs from RNA-seq data. Notable circRNA identification tools are find_circ [71] , MapSplice2 [72] , Segemehl [73] , circExplorer [74] , circRNA_finder [75] , CIRI [76] , ACFS [69] , KNIFE [77] , NCLscan [78] , DCC [79] and UROBORUS [80] . Information regarding these tools is listed in Table 2 . In addition, CircView, a platform visualization tool, is specifically developed to visualize circRNAs detected from these tools [81] . Furthermore, unlike other types of ncRNAs, circRNAs are not well-annotated." ] },{ "paper_id": "fb0a470971165da64de3314623977282563c7a04", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The rabbit polyclonal antisera K114 [33] and K135 [34] to VSV and MHV-A59, respectively, have been described before as is the mouse monoclonal antiserum 10G, which is directed against the MHV-A59 S2 domain [35] .", "Stocks of 700 mM cycloheximide (CHX, Sigma), 125 mM bafilomycin A1 (BafA1, Enzo Life Sciences), 120 mM dynasore (Dyn, Enzo Life Sciences), 1 mM nocodazole (Noc, Sigma), 1 mM latrunculin A (LatA, Sigma), 2 mM jasplakinolide (Jasp, Sigma), 1 mM brefeldin A (BrefA, Sigma) were prepared in DMSO and used at 1:1000 final concentration.", "Stocks of 5-bromo-4-chloro-3-indolyl-b-D-galactopyranoside (X-Gal, Sigma) were prepared at 40 mg/ml in dimethyl sulfoxide (DMSO). Stocks of 500 mM potassium ferrocyanide (K 4 [Fe(CN) 6 ), 500 mM potassium ferricyanide (K 3 [Fe(CN) 6 ), and 200 mM magnesium chloride (MgCl, all Sigma) were prepared in water (H 2 O).", "The a-peptide cDNA was isolated from an E. coli field isolate by DNA extraction and PCR. The cDNA was subcloned into a pCAGGS vector by restriction/ligation (BamHI/SbfI) and used from there. The DM15 gene was isolated from a DH5a E. coli lab strain by DNA extraction and PCR. The gene was cloned into a pCAGGS vector for (transient) expression and into a MLV-based pQCXIP transfer vector (Clontech) for the generation of stable cell lines, by restriction/ligation (XmaI/NotI in pCAGGS, SmaI/PacI in pQCXIP)." ] },{ "paper_id": "fb113c8235675412d874b092faf5b997ac410434", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Other blood proteins showed variable results summarized in Fig. 4 . The total protein concentration in blood sera of calves dropped significantly 2 days after", "Statgraphics Centurion XVI (Version 16.1.18, Statistical Graphics Corporation) and R [37] were used for statistical analyses. Due to the small sample sizes, data were assumed not to be normally distributed and nonparametrical tests were chosen for statistical evaluation of all data.", "Spearman Rank Correlations and multiple regression analyses were used to identify significant correlations between the severity of clinical signs and APPs assessed in BALF or blood, respectively." ] },{ "paper_id": "fb24be7627ebce76ab2862e689432a8a0de11343", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Ornithine decarboxylase, RT -HIV-1 reverse transcriptase, CRT -Ca 2+ -binding protein calreticulin, HVP-16 -human papilloma virus 16, LAMP-1 -lysosome-associated protein 1, sarsN -nucleocapsid SARS coronavirus protein, LCMV -lymphocytic choriomeningitis virus, MHC I -major histocompatibility complex class I, MHC II -major histocompatibility complex class II", "To be degraded by the proteasome, proteins must bear a specific signal -a chain of ubiquitin molecules (Ub), small polypeptides consisting of 76 amino acid residues. The eukaryotic cell has a specialized group of enzymes that recognize protein substrates and covalently attach polyubiquitin to these substrates. This enzymatic group is called the ubiquitinconjugating system [20] ." ] },{ "paper_id": "fb2c5faf4ed6df2563f6f1830de5b7fbad0ead87", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Influenza typically results in mild-to-moderate illness in healthy individuals. However, disease severity tends to increase in children, the elderly, and individuals with chronic medical conditions (pulmonary, cardiovascular, liver, renal, and neurological diseases or immunosuppression).", "One death was reported in a FLUA patient affected by quadriplegia and chronic respiratory failure. It is possible that FLUA could have been responsible for further impeding the patient's ability to breathe.", "Viral DNA and RNA was extracted from 400 \u03bcL of specimen using the EZ1 Virus Mini Kit v. 2.0 on the EZ1 Advanced XL platform (Qiagen, GmbH, Hilden, Germany) and eluted into 60 \u03bcL of elution buffer." ] },{ "paper_id": "fb3b1aad0a6c7504ba963a48906f6cbac748de77", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fb3c146b1766b4aa33df1637742bf93159967289", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses. Statistical analyses were performed in Microsoft Excel 5.0 (Microsoft Corporation, http://www.microsoft.com/) using Student's two-tailed t tests. Mean 6 standard deviation (SD) was calculated for each graph. If visually absent, error bars are too small to be depicted based on the scale of the y-axis. ", "Mice. BALB/c mice (Charles River Laboratories, http://www.criver. com/) were purchased for use in these studies. C.B6-Klra8 Cmv1-r /UwaJ, referred to as Klra8, (Jackson Laboratory, http://www.jax.org/), B10.D2, and B10.D2-DAP12-deficient (DAP128) animals were bred in pathogen-free breeding facilities at the Centre d'Immunologie de Marseille-Luminy (Marseille, France). Experiments were conducted in accordance with institutional guidelines for animal care and use. Protocols have been approved by the French Provence ethical committee (number 04/2005) and the US Office of Laboratory Animal Welfare (assurance A5665-01).", "Quantification of viral titers and serum cytokine levels. Spleens were homogenized [14] , and viral titers were determined by plaque assay using mouse embryonic fibroblasts with centrifugal enhancement or NIH-3T3 cells [73] . Serum was collected at the indicated time points and cytokine levels were determined by ELISA for IFN-a (PBL Biomedical Laboratories, http://www.interferonsource.com/) and IL-12p70 (R&D Systems, http://www.rndsystems.com/) per the manufacturer's instructions.", "CD8 T cell stimulation for IFN-c production. For intracellular IFNc detection, splenic lymphocytes were isolated and then incubated with IE-1 ( 168 YPHFMPTNL 176 ) or m164 peptide ( 257 AGPPRYSRI 265 ) (10 \u00c07 M) pulsed P815.B7 cells at a 10:1 ratio for 6 h with brefeldin A (Sigma-Aldrich, http://www.sigmaaldrich.com/) added for the last 3 h of culture. Cells were then harvested and analyzed for CD8a, CD43, and intracellular IFN-c protein by three-color staining followed by flow cytometry." ] },{ "paper_id": "fb4ca5437ec6856a1f57ece571120c64f17b13ad", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "**The prevalence ratio could not be computed due to all the tweets in Cycle 42 containing a photo.", "TwitterScrapper, a Python library. 3 Given the date we can retrieve all tweet IDs with that hashtag from that date until present or any interval specified by the user." ] },{ "paper_id": "fb4cdfdd952f7140a732d294b97f611c456aa6f0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The first human trial using the VIP approach started in January 2014 and is a phase 1, randomized, blinded, doseescalation study of an rAAV1 vector coding for PG9, a potent broadly neutralizing antibody, in high risk, healthy adult males (ClinicalTrials.gov number, NCT01937455). Another study evaluating using VIP in HIV-positive subjects is scheduled to get underway soon [6] .", "In addition to disease prevention as noted above, studies have also demonstrated an application for VIP in the effective treatment of previously-infected animals. Using HIV-1-infected humanized mice, Horwitz, et al., demonstrated that following initial treatment with anti-retroviral therapy (ART), a single injection of adeno-associated virus directing expression of broadly neutralizing antibody 10-1074, produced durable viremic control after the ART was stopped [26] .", "Many options exist for vectoring the transgene into the host tissue, each with distinct advantages and limitations. Naked plasmid DNA is relatively easy to use, does not elicit significant immunogenicity, and has the potential for inexpensive large-scale production [20, 27] . Recent advances in both the mechanism of delivery [28] and optimization of plasmid and electroporation conditions [29] have improved the concentration and duration of antibody production, but it has yet to prove as potent as viral vectoring.", "VIP has been demonstrated to be effective in a host of animal models for the prevention of infection with several pathogens, especially those commonly afflicting travelers (see Table 1 ), including influenza A virus [13, 14] , malaria (Plasmodium falciparum) [15] , hepatitis C virus [16] , respiratory syncitial virus [17] , Bacillus anthracis [18] , dengue virus [19] , and chickungunya virus [20] . In addition to the protection conferred by systemic neutralizing antibodies, protection against infection with influenza A virus has also been demonstrated following intranasal administration of vectored local antibody production [21] .", "From the early practice of scarification to prevent smallpox through the creation of targeted, recombinant vaccines, the development of effective vaccines has been one of the great achievements in public health and medicine, resulting in millions of lives saved. Modern vaccines typically protect by eliciting immunity following exposure to an inactivated or attenuated whole pathogen or recombinant components of a pathogen [1] . This approach works well for diseases in which natural infection leads to immunity and protection against re-infection and has resulted in the eradication of smallpox and dramatic declines in such diseases as diphtheria, measles, and polio [2] . However, it has been more challenging to develop effective vaccines against diseases for which prior infection does not offer full future protection, such as HIV, malaria, hepatitis C virus, and influenza A [1] ." ] },{ "paper_id": "fb515d76fcd0dcf243425b037693e00c9a1afd34", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fb6b4f00d820aad697369de4f7f29b709541e973", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In July of 2013, fecal samples from diarrheal sows, collected in a pig farm in Jiangsu province of east China, were submitted to our lab for routine laboratory diagnostics. PEDV positivity was confirmed by reverse transcription PCR (RT-PCR) according to the method reported previously [2] . One of the PEDV-positive samples, from a sow with very mild clinical sign, was used to inoculate into Vero cells to isolate the virus, as described previously [2] . This PEDV strain, designated FL2013 strain, was successfully passaged and propagated, as characterized by typical PEDV-induced cytopathic effects (CPE), such as cell fusion and syncytia formation (data not shown), which was similar to what we observed for the CHGD-01 strains [2] . The other field PEDV samples collected from pigs with severe clinical sign could not adapt to Vero cells. The complete genomic cDNA of the FL2013 strain was further determined using the 3rd cell culture passaging virus by amplification of twelve regions covering the PEDV genome as described previously [2] . The sequences were assembled and analyzed using DNASTAR program and MEGA6.0 program [9] .", "Background: Since 2010, a variant Porcine epidemic diarrhea virus (PEDV), which causes an acute, highly contagious, and devastating viral enteric disease with a high mortality rate in suckling pigs, broke out in China and spread rapidly to neighboring countries, even to the North America. This virus gradually became the main subtype of PEDV worldwide. However, there were no reports of mild pathogenicity of a variant porcine epidemic diarrhea virus in China. Findings: In 2013, a PEDV-positive sample from a sow with very mild clinical sign was used to inoculate in Vero cells to isolate the virus. This PEDV field strain, designated FL2013 strain, was successfully propagated and genetically characterized. The phylogenetic trees based upon either the complete genome or S gene showed that the FL2013 strain belongs to the genogroup G2b. The S gene of FL2013 has a 7-aa deletion (FEKVHVQ) in the C-terminus comparison with the other G2 PEDV sequences. Further comparative pathology study indicated that the FL2013 strain had reduced virulence to newborn piglets. Conclusions: A novel variant PEDV strain FL2013 with reduced virulence, as determined by the pathological study, was identified from east China. This strain is closely related to the genogroup-2 PEDV strains prevalent in the U.S. and China currently, but had a short deletion at the 3\u2032-end of the spike gene.", "Porcine epidemic diarrhea virus (PEDV) is an enveloped, single-stranded, positive-sense RNA virus in the genus Alphacoronavirinae of the family Coronaviridae. PED, which is caused by PEDV, is characterized by severe diarrhea, dehydration, and high mortality rates in the affected swine [1] . PEDV variants belonging to genogroup 2 (G2) have been emerging in China in a large-scale outbreak characterized by approximately 80-100 % morbidity rates and high mortality rates among suckling piglets since late 2010 [2] . Highly virulent PEDV strains, phylogenetically related to the G2 Chinese PEDV variants (shared \u226599.5 % nt identity), suddenly emerged in the United States in May 2013 and rapidly spread throughout the country, causing severe economic losses [3, 4] . The second PEDV variant in the US, designated S INDEL PEDV, with insertions and deletions in the N terminal region (S1 subunit) of the spike (S) protein same as the G1 PEDV, was identified subsequently [5] . The S INDEL strains caused reportedly milder disease in the field, indicating that the S gene contains major virulent determinants [6] . The other large S-deletion PEDV strains were also identified, including one Korean field strain with a 204-aa deletion [7] , and a US cell-adapted strain with a 197-aa deletion [8] . Whether these S-deletion PEDV strains have distinct pathogenic characteristics, have not been described." ] },{ "paper_id": "fb6c8bb97e2115a2551f7a278889f3dd54c538fb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We missed the fact that this technology raises major issues for people-issues of ethics, of choice, of trust, even of democracy and globalization. As we tried to understand what had happened, we realized that we needed to hear directly from people about what they thought, what their concerns were and what they thought we ought to do. If we are to close the gap between those who believe in the benefits and those who have concerns, then something has to change (Ivinson and Bach 2002, 43; Bach and Ivinson 2002, 131) .", "Products made out of cattle brain, it's medieval. I find it distressing that there are still products like this that Dr Shapiro would use in his protocols without even knowing about it. The diabetes program at U of A is world-renowned. To find out at this stage that the enzyme is grown in bacteria that are exposed to cow brain is really distressing (Sinnema 2007) .", "We thought we were doing some great things. A lot of other people thought we were making some mistakes. We were blinded by our own enthusiasm.", "What we are collectively doing now and planning to do in the future with xenograft transplants creates the ideal conditions for animal viruses or infections to cross the species barrier into humans and proliferate \u2026 Xenotransplants thus represent one of the best experiments we could devise to 'create' new infectious agents. It would be somewhat paradoxical if the main legacy of modern medicine's involvement in transplantation were another infection such as HIV (Collignon 1998, 519) .", "Sobbrio and Jorqui observed that public engagement on xenotransplantation in Canada and Australia represented significant developments in 'experimental democracy' (Sobbrio and Jorqui 2014, 523) . They wrote, democratic social contract between institutions and citizens; they aimed at engaging citizens in more direct decision-making; they explored and inquired into relevant issues about technological innovation and social change; and they attempted to introduce a new concept of scientific citizenship through the identity of the citizen scientist (Sobbrio and Jorqui 2014: 528) .", "As discussed in Part I, islet allograft is generally restricted to patients with brittle or severe diabetes. Patients seeking such treatment need to demonstrate poor quality of life and that they are at risk of health complications exceeding the dangers associated with islet transplantation.", "The Publics in/and Xenotransplantation: initial responses to the risk of retroviral contagion" ] },{ "paper_id": "fb6da430431e830785d08a54b099e711fabe252e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fb773634dcd17957e12be78e5c33ba753d82d3f5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The authors declare no conflict of interest.", "The final section of this review is dedicated to a brief analysis of glutathionylation in inflammation, focusing on nuclear factor kappa \u03b2 transcription factor (NF\u03baB)'s glutathionylation.", "Overall, a deeper knowledge of the chemical and regulatory processes through which glutathionylation occurs could pave the way for the identification of novel targets to control microbial infections and related host responses. " ] },{ "paper_id": "fb775c4af00b99294d4e8812a3f23ba6aca32774", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Zoonosis is the leading cause of emerging infectious diseases. In a recent article, R. S. Shabman et al. (mSphere 1[1]:e00070-15, 2016, 10.1128 report the identification of a novel gammaherpesvirus in a cell line derived from the microbat Myotis velifer incautus. This is the first report on a replicating, infectious gammaherpesvirus from bats. The new virus is named bat gammaherpesvirus 8 (BGHV8), also known as Myotis gammaherpesvirus 8, and is able to infect multiple cell lines, including those of human origin. Using nextgeneration sequencing technology, the authors constructed a full-length annotated genomic map of BGHV8. Phylogenetic analysis of several genes from BGHV8 revealed similarity to several mammalian gammaherpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV). Citation Host KM, Damania B. 2016. Discovery of a novel bat gammaherpesvirus. mSphere 1(1):e00016-16.", "Previous reports have shown that multiple gammaherpesviruses can be found in the bat reservoir (27) (28) (29) ; however, this was the first report to identify and characterize a replicating, infectious gammaherpesvirus. Further, betaherpesvirus sequences have been identified within the bat reservoir (27) , as well as a replicating betaherpesvirus, suggesting that bats are a suitable host for a range of different herpesviruses (30) . As BGHV8 displays some similarity to human herpesviruses, including KSHV, it is somewhat plausible that the human population may have some cross protection against BGHV8. However, there also exists a potential for the transmission of this bat gammaherpesvirus into humans. In summary, the article by Shabman et al. (19) represents an exciting new step in understanding the bat viral reservoir. ", "BGHV8 clusters with the Rhadinovirus genus, which contains the human pathogen KSHV (22) . BGHV8 shares homology with KSHV immunomodulatory genes as depicted in Table 1 . The homology between the proteins encoded by BGHV8 and those encoded by KSHV is not very high, and yet it is likely that certain functions are conserved between these proteins, as has been shown previously for KSHV and other herpesviruses (23, 24) . Some of the BGHV8 homologues in KSHV play roles in the prevention of apoptosis, immune evasion, and viral replication (Table 1) . Additionally, the KSHV v-FLIP protein may also contribute to tumorigenesis (25, 26) . Indeed, the MVI-it cell line used in the study was isolated from a bat tumor, suggesting that in concordance with other gammaherpesviruses, BGHV8 may likely also possess oncogenic potential." ] },{ "paper_id": "fb77f295f754abf6a7e99a90dad5626180c5b177", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fb833d8df33cd6cc025d22afa9b7831725ea0afb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine epidemic diarrhea (PED) is a highly contagious swine enteritis caused by porcine epidemic diarrhea virus (PEDV), which belongs to the order Nidovirales and family Coronaviridae. The typical symptoms of PED are diarrhea, vomiting, and dehydration, which can be especially dangerous to suckling piglets [1, 2] . The mortality of neonatal piglets younger than 5 days old can approach 100% [3] [4] [5] . PED first appeared in Britain in 1971, followed by an outbreak of diarrhea in several pig farms in Belgium in 1977 [6] . These outbreaks led to identification of a coronavirus-like particle named CV777, which is now recognized as the classic PEDV strain. In recent years, PED epidemics have become prevalent in swine-raising countries in Asia, including South Korea, China, Japan, and Vietnam, and can cause enormous economic loss [7, 8] .", "Conclusions: This established S1 indirect ELISA is capable of detecting serum antibodies against PEDV, and due to its high sensitivity and specificity, it could be applied for serological evaluation and indirect diagnosis of PEDV infection.", "Of the numerous pathogens which can cause swine viral diarrhea, PEDV, TGEV, and PoRV account for the largest proportion [26] . In the present study, 16/149 anti-PoRV antibody positive sample and 27/195 anti-TGEV antibody positive samples were tested PEDV antibody positive, which indicated there may be co-infection of PEDV and other virus." ] },{ "paper_id": "fb8dfa6988a6f08b4b64a0d5c7843c854a8328d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The transmembrane domains TMD1 and TMD2 were generated as ideal helices using the MOE software package (Molecular operating environment, www.chemcomp.com).", "The simulations were run on a DELL i7-930 workstation and a 28 core Opteron based computer cluster with Infiniband interconnects.", "Plots and pictures were made with VMD-1.8.7 and MOE-2008.10 and 2010.10." ] },{ "paper_id": "fb8e2e76092de55f4b7f22bd0106f6c3853ca3bd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Healthy A. anguilla elvers with an average weight of 20 g were purchased from an eel farm in Fujian (China). The elvers were monitored in freshwater at room temperature (25-28\u00b0C) for 2 weeks in order to confirm their vital status. Prior to the dissection, the fishes were sacrificed by anesthesia using 80 mg/L of MS-222 (Cantin), and then disinfected by 2% iodine tincture and 75% alcohol three times, respectively, in turn. Sterilized Ca ++ /Mg ++ -free Dulbecco's Hanks balanced salt solution (D-Hanks) containing 200 IU/mL of penicillin and 200 \u03bcg/mL of streptomycin (Sangon) was prepared and stored at 0\u00b0C. ", "Each experiment was repeated at least three times. The data were shown as mean \u00b1 standard error (SE) and the statistical significance was determined by one-way analysis of variance (Turkey's HSD test) (Davis, 2001) using IBM SPSS (www.ibm.com/analytics/).", "Forward sequence (5\u2032-3\u2032) Reverse sequence (5\u2032-3\u2032)", "The viability of the virus infected cells was determined the Tryphan blue staining method." ] },{ "paper_id": "fb9b75c5e290a5ff3b49c2f0f93e05a1dcff78df", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Thirty-six sequences of Tollip protein were downloaded from KEGG ( Table 1 ). The phylogenetic reference used was the Tree of Life Web Project, ToL (http://tolweb.org/tree/), which were used in topological comparisons with Tollip generated data.", "The effect of reticulate evolutionary events was analyzed through a neighbor-net analysis [30] and converted into a splits graph using the drawing algorithms implemented in SplitsTree4 software -version 4.10 [31] . The neighbor-net method was based on the pairwise distance matrices of Tollip complete sequences alignment with deletion of gaps and non-informative parsimony sites; the matrices were calculated and corrected with the Poisson distribution model [32] .", "To check if selection affected the patterns of genetic diversity, we tested if the protein was under positive selection. Tajima's D statistic [37] was calculated by testing the mutation neutrality hypothesis [38] , as previously described by Coscoll\u00e1 and colleagues [39] . In order to investigate the presence of positively selected codons, the estimation of both positive and purifying selection at each amino acid sites was calculated from the ratio of non-synonymous to synonymous substitutions, v, as previously described [40] . Analyses were conducted using the Selecton version 2.1 software [41, 42] . The significance of scores was obtained by using a Likelihood Ratio Test that compares two nested models: a null model that assumes no selection (M8a) [43] and an alternative model that does (M8) [44] .", "Tollip polymorphisms were correlated with several human diseases like atopic dermatitis [69] , inflammatory bowel disease [70] , tuberculosis [71] and other. In atopic dermatitis (AD), Singlestrand conformation polymorphism (SSCP) of the tollip sequence is correlated to AD. We could infer that amino acid exchanges of A (Ala) to S (Ser) occur at residue 222. Ser222 has a higher correlation to healthier controls (5.4%) when compared with Ala222 (2.7%) [69] . Residue 222 is occupied by A in 52.78% of sequences and is largely distributed in vertebrate sequences (subgroups 1-10), excluding oaa sequences. We found that it suffers a strong positive selection, through Selecton analysis (Fig. 6) , shown as residue 245. In this case, seems that residue is conservated through vertebrata, subgroups 1 to 10, and we are inclined to believe that this is a trait which has became from an ancestor at amphibian level, and this mutation could be benefic to them too." ] },{ "paper_id": "fb9e05516efdae3600796552393fd3e3c26cb3d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Baseline characteristics of the whole cohort were obtained from the hospital's electronic database. Demographic and clinical data were recorded at the initiation of PD, and included age, sex, status before PD (pre-dialysis CKD, hemodialysis, and failed renal transplantation), body mass index (BMI), medications, comorbidities, and smoking status. The comorbidities included diabetes mellitus (DM), hypertension, CVD and Charlson Comorbidity Index, which is one of the most commonly used scoring systems to predict the risk of mortality. Blood tests, consisting of white blood cell (WBC) counts, hemoglobin, total cholesterol, triglyceride, calcium, phosphate, alkaline phosphate (ALP), uric acid, glutamic-pyruvic transaminase (GPT), intact parathyroid hormone (iPTH), ferritin, transferrin saturation, serum albumin, blood urea nitrogen (BUN), and creatinine were checked at the laboratory of Changhua Christian Hospital. The use of medications was recorded based on prescriptions, and included angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor blocker (ARB), hypouricemic agent (allopurinol), erythropoiesis stimulating agents (ESA), loop diuretic (furosemide), calcium channel blocker (CCB), vitamin D, and statins. Information on PD-related parameters included daily ultrafiltration, total Kt/V urea, residual renal function (RRF), daily urine volume, normalized protein nitrogen appearance (nPNA) and dialysate-to-plasma creatinine ratio (D/P creatinine) at 4 h. RRF, in milliliters per minute per 1.73 m 2 , was derived from averaging the values of creatinine and urea clearance and standardized for body surface area.", "Multivariate linear regression analysis with backward elimination procedure and removal criterion for probability of F-distribution \u22650.100 was used to evaluate associations between clinical parameters at baseline and UA, and to estimate the expected change in serum UA level in relation to changes in significant clinical parameters. Associations between UA and the outcomes of interest were evaluated using Cox proportional hazard models, which were constructed using five levels of adjustments: model 1, adjusted for sex, age, the status before PD, smoking status, and BMI; model 2, adjusted for model 1 covariates plus medications; model 3, adjusted for model 2 covariates plus comorbidities; model 4, adjusted for model 3 covariates plus PD-related parameters; model 5, adjusted for model 4 covariates plus laboratory data. The results are shown as hazard ratios (HRs) and 95% confidence intervals (CIs).", "Crude analysis of cardiovascular mortality rate between the sex-specific tertiles of serum uric acid levels (p = 0.002)." ] },{ "paper_id": "fba08f3ce8a1335d06623126e44863cf1e73a509", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Possible combinations are one mutagen and a conventional antiviral drug or using several RNA mutagens in combination or sequence as proposed by Perales and Domingo [109] [110] [111] .", "As a consequence of the emergence of RBV-resistant mutations and subsequent treatment failure, clinicians could draw back on combination therapies to overcome or avoid this phenomenon." ] },{ "paper_id": "fbaaee7a5ac9ab3324e82bc7b8706edc5bd1524e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(This article was submitted to an online preprint archive [32] .)", "Chemical reagents. Mifepristone was obtained from Sigma-Aldrich, and ulipristal acetate was from D-Innovation Pharmaceutical Inc., Chengdu, Sichuan, People's Republic of China. Both compounds were USP grade.", "complete and more potent immune responses to autologous or heterologous antigens than the corresponding nonreplicating viruses." ] },{ "paper_id": "fbad56e66ee9453d193dfbbd775248044e0af261", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GraphDNA allows plots to be saved as PNG formatted files (save as, under File menu), the best resolution is obtained if the application window is stretched to its maximum size before saving; alternatively, screen images can be captured." ] },{ "paper_id": "fbaf6a3ac63158b74ca6b50f01c98d56936a844d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "pCDEF3 muSOX (Adgene 131695) and vhs (Addgene 131696) and SOX have been previously published [25] . pCDEF3-GFP was used as a control.", "RNA was reverse transcribed using AMV RT (Promega) with random 9-mer primers. Total RNA was DNase treated with TURBO DNase (ThermoFisher) or DNase treated on column with Zymo Direct-zol RNA MiniPrep Plus DNase. cDNA was quantified using iTaq Universal SYBR Mastermix (BioRad) and transcript-specific primers. All qPCR results are normalized to 18S levels and WT or vector control set to 1." ] },{ "paper_id": "fbb13d5bcfe0597fc854533fa1637fd4c415bb5a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All animal experimental protocols were carried out in strict accordance with the UK Home Office guidelines and under licence granted for experiments involving regulated procedures on animals protected under the UK Animals (Scientific Procedures) Act 1986. The experiments were performed in the IAH Home Office licensed (PCD30/4301) experimental animal house facilities and were approved by the IAH ethical review committee under the terms of reference HO-ERP-01-1, using chickens obtained from the IAH Poultry Production Unit.", "Avian infectious bronchitis virus (IBV) is a gammacoronavirus, subfamily Coronavirinae, family Coronaviridae, Order Nidovirales [2] and is the aetiological agent of the acute highly contagious poultry disease infectious bronchitis (IB) [3] [4] [5] [6] . IBV is a highly infectious pathogen of domestic fowl that replicates primarily in epithelial cells of the respiratory tract [7, 8] causing IB characterised by nasal discharge, snicking, tracheal ciliostasis and rales in chickens [1] . Although IBV is primarily associated with respiratory tract infections, it is also responsible for major economic losses to poultry industries worldwide as a result of poor weight gain and decreased egg production [9] . In addition, some isolates have been found to be associated with renal disease and can be highly nephropathogenic [10] [11] [12] .", "Coronaviruses are enveloped viruses that replicate in the cell cytoplasm and contain an unsegmented, single-stranded, positivesense RNA genome of 28 to 32 kb [13] [14] [15] . IBV, like all coronaviruses, contains the four structural proteins; spike glycoprotein (S), small membrane protein (E), integral membrane protein (M) and nucleocapsid protein (N), which interacts with the genomic RNA. The coronavirus S glycoprotein is a type I glycoprotein that oligomerises in the endoplasmic reticulum [16] to form trimers [17] , which constitute the coronavirus virion spikes observable by electron microscopy. The S protein is assembled into virion membranes, through non-covalent interactions with the M protein [18] , and is responsible for binding to the target cell receptor and fusion of the viral and cellular membranes, fulfilling a major role in the infection of susceptible cells [19] ." ] },{ "paper_id": "fbb1af3990778d2061c8466c3a5156fececf146b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fbc5981e0920859187fee6c4243de58c9906f2ee", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Nucleotide sequence accession number. The genome sequence of PEDV strain JS2008 was deposited in GenBank under accession number KC109141.", "This work was supported by the Special Fund for Independent Innovation of Agricultural Science and Technology in Jiangsu Province [CX (12) 3076].", "A field porcine epidemic diarrhea virus (PEDV) strain, JS2008, was isolated from stool samples of a piglet with acute diarrhea on a vaccinated farm in eastern China. We sequenced and analyzed the complete genome of strain JS2008, which will help increase our understanding of the molecular characteristics of the epidemic PEDV in China." ] },{ "paper_id": "fbcfed5be85b5356dd0d103c8b6ab37296035cf5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There is a light at the end of the tunnel. The WHO recently announced plans to stockpile H5 influenza vaccine and create a policy framework for vaccine allocation and recommendations for its use [22] . Several recent developments in H5 vaccines have made this stockpile feasible: the development of H5N1 vaccines with adjuvants that reduce the required dose as much as fourfold [23] and the finding that adjuvant-enhanced vaccines may provide cross-protection against strains that have undergone up to seven years of genetic drift [24] . Furthermore, the manufacturing capacity of 500 million doses is calculated on a requirement for three strains of flu virus for standard vaccinations; in crisis mode, three times as much monovalent pandemic flu vaccine could be produced.", "Recently, the Bill & Melinda Gates Foundation, the Pasteur Institute and the Wellcome Trust, began planning, with major medical-research funders and other stakeholders, several projects to enhance the research effort and reduce the risks from the threat of pandemic influenza over coming decades [22] . In the next few years, they plan to develop, maintain and disseminate a central inventory of funded research activities that are relevant to human influenza to ensure that stakeholders are well-informed. They will also coordinate road-mapping exercises to identify knowledge gaps to assist funders and researchers in establishing research-funding priorities, with specific focus on vaccines, drug therapies and epidemiology/population science (for example, diagnostics, surveillance, transmission and modelling), in the hope of developing a cohesive health-research agenda for pandemic influenza.", "Every country's healthcare system would be stretched to the limit in the event of a global pandemic of bird flu. The ability of healthcare facilities to maintain strict infection control measures would be challenged. The sudden surge in health manpower and facility need would be acutely felt among healthcare workers, epidemiologists and laboratory technicians. Countries must set up AI pandemic contingency plans and high-level coordinating committees comprising of representatives from multiple ministries and agencies." ] },{ "paper_id": "fbd7cb291782d73cc8b480cddd13f2b664f25cdb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Monkeypox virus (MPV), an orthopoxvirus similar to variola virus, is the causative agent of monkeypox in many species of non-human primates, but it is also a human pathogen with a clinical presentation similar to that of smallpox. MPV is considered a big threat to human life and therefore research is being carried out to develop drugs and therapeutic agents against this virus [74] .", "TCRV is not a human pathogen, but exhibits a close antigenic relationship with Junin and Guanarito viruses [76] , therefore could serve well as a model virus for arenavirus derived diseases without human pathogenic potential and adequate safety for laboratory manipulation.", "The authors declare no conflict of interest.", "While these results suggest the versatility of the idea of effective viral inhibitions using functionalized nanoparticles, it also indicates that other core materials could also be efficient as long as they are not toxic to the host cells." ] },{ "paper_id": "fbf1ce71db9a70babb5b4902d23438c1956125c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Highly pathogenic respiratory viruses, like the H5N1 influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV), represent significant threats to public health and global economic stability. They cause acute lung injury (ALI) that rapidly progresses to acute respiratory distress syndrome (ARDS), the former most notably in the elderly [1, 2, 3] . Moreover, after viral clearance many SARS and H5N1 patients develop diffuse alveolar damage (DAD) that often progresses to pulmonary fibrosis, another devastating end stage lung disease, characterized by dysregulated cell proliferation during wound repair [4, 5, 6] .", "To explore the mechanism of NSC158362's antiviral activity we performed cell culture assays to determine if any of the known the enzymatic activities of PLP were inhibited.", "Human nasal and tracheobronchial epithelial cells were obtained from airway specimens resected from patients undergoing elective surgery under UNC Institutional Review Boardapproved protocols by the UNC Cystic Fibrosis Center Tissue Culture Core. Briefly, primary cells were expanded on plastic to generate passage 1 cells and plated at a density of 250,000 cells per well on permeable Transwell-Col (12-mm-diameter) supports. HAE cultures were generated by provision of an air-liquid interface for 4 to 6 weeks to form well-differentiated, polarized cultures that resemble in vivo pseudostratified mucociliary epithelium.", "We found that NSC158362 is able to block SARS-CoV replication by more than 500 fold in culture. We also showed that NSC158362 has a strong anti-SARS-CoV effect using HAE cells, a physiological model of lung architecture containing ciliated cells that are the in vivo target of the virus." ] },{ "paper_id": "fbf214b2ff7bf5dc3d5dab6096d53cb086f0dea4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fbf232152712b5e379797c6b0008bb7926001bb7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Flow cytometric analysis. Single-cell suspensions were prepared from spleens or from cell cultures.", "Serum titers of anti-CII or anti-SRBC IgG were determined as previously described 51, 54 . Briefly, 96-well ELISA plate were coated with bovine CII (50 \u03bc g/ml) or extracted SRBC membranes (20 \u03bc g/ml) (prepared as described previously 55 ) overnight at 4 \u00b0C. Each diluted serum sample was added and incubated. Horse-radish peroxidase (HRP) conjugated goat anti-mouse IgG (H + L), IgG1and IgG2a Abs (Invitrogen, San Diego, CA, USA) were used. The optical density is measured spectrophotometrically at 450 nm.", "Comparisons between 2 groups were performed using an unpaired 2-tailed t-test. For experiment involving multiple groups, one-way analysis of variance (ANOVA) followed by Turkey's multiple comparison test was used, except for analysis of clinical scores which used two-way ANOVA followed by Dunnett's multiple comparison test. P values less than 0.05 were considered significant." ] },{ "paper_id": "fbf7143172cc18e911174a7ce32856a0a63afc1c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The active antigen of Pandemrix \u00ae derived from the A/ California/7/2009 (H1N1). Pandemrix \u00ae also contains an immunologic adjuvant AS03 which consists of DL-\u03b1tocopherol (vitamin E), squalene and polysorbate 80. Thiomersal (thimerosal) is added as a preservative. Other components are formaldehyde, sodium deoxycholate, and sucrose [20] . The vaccine is generated in hen's eggs and therefore also contains traces of egg proteins. A single dose of the vaccine was injected by occupational physicians with the recommended dosage and vaccination procedure.", "The mean duration of symptoms lasted 3.5 days, the maximal duration of symptoms was reported with 40 days.", "Various infectious diseases play a major role in occupational health. Next to classical diseases such as tuberculosis [1] , new diseases including SARS [2] [3] [4] or the novel influenza A H1N1/2009 virus [5, 6] are endangering occupational health in the last years. The novel influenza A H1N1/2009 virus was first identified in Mexico and led to pandemic warning of the WHO in June 2009 [7] .", "Personal protective equipment is important to prevent transmission of novel A/H1N1 as stated earlier by Shine et al [21] . However, vaccination is the most effective means of preventing influenza transmission and associated morbidity and mortality. It is most important to realize that an effective measure against a pandemic is to have vaccinated and well-informed health care workers." ] },{ "paper_id": "fc151568de57c0456578757131c3b49b86286b3c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In ssRNA + viruses, the RNA helicases are implicated in several functions including RNA genome replication, ribosome biogenesis, messengers RNA transcription, pre-mRNA splicing, RNA maturation, RNA export and degradation, as well as RNA translation [19, 20] .", "Basing on certain signature motifs in the amino acid sequence, Gorbalenya and Koonin have shown that all helicases can be classified in several genetic families [21] . All but two of the helicase families can be grouped into one of three larger \"superfamilies,\" designed as superfamily 1 (SF1), superfamily 2 (SF2) [22] , and superfamily 3 (SF3) [23] ." ] },{ "paper_id": "fc1c7fe95eca6c5aba24577043ad02c15bfce43a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following information was extracted in each study included: the first author, year of publication, country, WHO criteria for dengue case classification, ethnicity, matching criteria of controls, genotype method, sample size, the numbers of the severe dengue and uncomplicated clinical dengue case (indicated as DF in this paper) with different genotypes.", "The quality of each study was assessed independently by two researchers according to the Newcastle-Ottawa Scale (NOS) for case-control study. This criteria include three sectors: selection (a maximum score of four), comparability (a maximum score of two) and exposure (a maximum score of three). The third researcher was asked to conduct the quality assessment if inconsistent existed. ", "The authors declare no conflict of interest." ] },{ "paper_id": "fc212dc72c96fcedc6e724394fe67ff77087a5d5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Positive-Sense Single Stranded RNA ((+) ssRNA) Viruses", "Orthomyxoviridae and Bunyaviridae", "Single Strand RNA Retroviruses (ssRNA-RTs)" ] },{ "paper_id": "fc221d8af0a962a17778721217b1f9f914f353b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All experiments were performed at least three times. All data were analyzed using SPSS (IBM, New York, NY, USA) and Graphpad Prism 5 (Graphpad Software Inc., La Jolla, CA, USA). Pearson's correlation coefficients between different assays were calculated, and significance was defined as Po0.05.", "In conclusion, an RBD ELISA may be an alternative to an S1 ELISA for determining infection at an early stage and in patients with poor serological responses to MERS-CoV. In addition, an S ELISA may be an useful alternative to the MERS S ppNT, which was shown to be a reliable surrogate of neutralization activity, and may be useful for large-scale seroepidemiological studies of MERS-CoV infection.", "The recombinant His-tagged extracellular domain (amino acids 1-1297) of MERS-CoV (HCoV-EMC/2012) spike (S) expressed in Baculovirus-Insect cells was purchased from Sino Biological Inc. (Beijing, China). Construction of expression plasmids for the RBD (amino acids 367-606) of MERS-CoV and the method used for subsequent expression in Baculovirus-Insect cells were described previously. 8 The NTD (amino acids 18-353) of S was expressed in Baculovirus-Insect cells and was provided by the Institute of Microbiology, Chinese Academy of Sciences. Expression and purification of NP in a prokaryotic system were performed as described previously. 9 Purified NTD, RBD and NP were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and WB." ] },{ "paper_id": "fc26cafc8843bb3223e9e9af13a91df3b9274ea6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fc29089acf4b70c64a5a5e4ea64a318e8d52edbb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Polyclonal anti-Actin, anti-CLTC and anti-ADFP (anti PLIN2) antibodies were purchased from Abcam W (Cambridge).", "Disclosures: Simon C and Aguilar-Gallardo C are co-inventors of the International Patent Application No. PCT/EP2011/004941 entitled \"Methods for tumor treatment and adipogenesis differentiation\".", "The clarification of the roles played by the differentially expressed genes and proteins in the process of adipogenic transdifferentiation in HCCL cultures should provide the basic foundation to develop novel molecules for cancer therapy." ] },{ "paper_id": "fc3262c27f701261cfc1b27bc0495f6bd8b3e3fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Methods Protoc. 2018, 1, x FOR PEER REVIEW 9 of 12 breast cancer resistance protein known as P-glycoprotein [51] . This is a big breakthrough to the future of therapeutic tools against cancer using Q\u03b2 phage and nanobodies. ", "The mechanisms of viral infection and prevention are the most difficult investigations in virology research. Virus tropism and neutralizing antibodies are the major crucial steps in virus life cycles and vaccine development respectively. To better understand the molecular pathways of infection and prevention, we must utilize synthetic biology. Synthetic biologists would simplify and engineer complex artificial biological systems that investigate natural biological phenomena [7, 8] .", "The desire of the molecular biologist to engineer natural biological entities that address future evolution are growing significantly. This includes the use of Darwin's postulates as they relate to in vitro molecular evolution." ] },{ "paper_id": "fc524fbd93be3db421c75c589e2299524a75fa26", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chloroquine diphosphate was kindly supplied by FarManguinhos (Fiocruz, Rio de Janeiro, Brazil). The lyophilized powder was diluted in double distilled water to 20 mM. The chloroquine solution was filtered through a 0.22 \u00b5m membrane and stored at \u221280 \u2022 C.", "Mean and standard deviation (SD) were calculated for each assay. One way analysis of variance (ANOVA) was conducted using the non-parametric test (Kruskal-Wallis) followed by Dunn's multiple comparisons test. A p-value of <0.05 was considered significant. All analyses were performed on GraphPad Prism v.7 (GraphPad Software, San Diego, CA, USA). The sample size is provided in the respective figure legends.", "Our results suggest that the chloroquine concentrations inhibiting ZIKV replication in vitro may overlap the highest drug concentrations detected in humans [56] . We therefore suggest that the therapeutic potential of chloroquine for Zika be subjected to further study." ] },{ "paper_id": "fc58f48d9ac1d492c691a36eb76e377442dc149a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: Autophagy is an essential process in eukaryotic cells in which autophagosomes form to deliver cellular organelles and long-lived proteins to lysosomes for degradation. Many studies have recently identified the regulatory mechanisms involved in the interaction between viral infection and autophagy.", "Cells were collected, and total RNA was extracted using TRIzol (Invitrogen). Two micrograms of RNA was obtained with the Reverse Transcription Kit as described above. The synthesized cDNAs were amplified with specific primers (Additional file 1: Table S1 ). The final products were visualized on a 1.5% agarose gel that was electrophoresed at 110 V for 45 min.", "Cells of the African green monkey kidney epithelial cell line Marc-145 purchased from ATCC were cultivated in Dulbecco's Modified Eagle's Medium (DMEM, Invitrogen) supplemented with 10% fetal bovine serum (FCS) at 37\u00b0C in a 5% CO 2 atmosphere. HBSS (Hank's Balanced Salt Solution) was purchased from Sigma and can induce autophagy. The PRRSV strain CH-1a (the first PRRSV2 strain isolated from China) was provided by Dr. Guihong Zhang at the South China Agricultural University, China." ] },{ "paper_id": "fc5a448b2c227817cd29625972acb40e853cac89", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Three examples to illustrate the conceptual framework", "-Surveillance design: Describes activities and methods used for implementing, analysing and communicating surveillance system components, e.g. populations, sampling, diagnostics, case definition, and statistics.", "-Intervention: The process of implementing measures directed at mitigation." ] },{ "paper_id": "fc5cc0fedf50af659b515f25de57a6c7d841d342", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Statistical analyses were performed using one-way ANOVA followed by the Student's t test. Statistically significant changes were classed as [*] for p,0.05, [**] for p,0.01, and [***] for p, 0.001. Protein concentrations were determined in 96-well microtiter plates by following the instructions of Bradford's method and using a kit from Bio-Rad Laboratories (Hercules, CA). Typically, one part of concentrated dye reagent was diluted with 4 parts of double-distilled water and mixed thoroughly before use; 6 dilutions of BSA standard (0.05-0.5 mg/mL) were used in the tests and samples were assayed in triplicate. The concentrations of proteins were determined from the standard curve.", "LPS, dexamethasone, Bay 11-7082, and p-nitrophenyl phosphate (pNPP) were purchased from Sigma (St. Louis, MO); all chemicals were .98% pure. Various culture media and supplements were obtained from Invitrogen Technologies (Carlsbad, CA). Fetal calf serum was from Hyclone (Thermo Fisher Scientific, Waltham, MA). Antibodies against iNOS and COX-2 were purchased from Abcam (Cambridge, UK) and Cayman (Ann Arbor, MI) respectively. The antibody against glyceraldehyde 3phosphate dehydrogenase (GAPDH) was obtained from Abcam Ltd. The enhanced chemiluminescence (ECL) reagent was purchased from Amersham Biosciences (Piscataway, NJ). Penicillin, streptomycin, and horseradish peroxidase (HRP)-conjugated anti-mouse secondary antibodies were purchased from Invitrogen Technologies.", "Caco-2 cells (50,000/well) cultured in 12-well plates were treated with reagents every day starting 24 hours after plating, and cells were harvested on days 1, 6, 11, 16, and 21. Cultures were collected using a lysis buffer containing 100 mM potassium phosphate buffer, 0.2% Triton X-100, and 1 mM dithiothreitol (pH 10.4). IALP activity in Caco-2 cells was measured by mixing the samples with 5 mM pNPP in an IALP buffer (pH 10.4) containing 0.1 M glycine, 1 mM MgCl 2 , and 1 mM ZnCl 2 . After incubating the samples at 37uC for specified times, absorbance was measured at 405 nm to determine enzyme activity, which was expressed as mmol cleaved substrate/mg protein." ] },{ "paper_id": "fc5e4a2de7d202adad95ea3fe26625bdebe817cf", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Cell culture and RNA aptamer transfection. All cells in this study were cultured in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. USP14 aptamer transfection was performed in 6-well plates using Lipofectamine 2000 (Invitrogen). Cells were transfected for 6 h and whole cell extracts were collected 24 h after the media was changed." ] },{ "paper_id": "fc7e5ad5354977c8df7a4dfa7ffe37eed76a975f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The emerging viruses exert a significant public health threat [2, 3] and include ebolaviruses, henipaviruses, lyssaviruses and coronaviruses [4] [5] [6] [7] [8] [9] . These are all viruses that can cause infections through inhalation routes of exposure, and viruses such as Hendra, Nipah, and SARS viruses cause severe respiratory infections in humans.", "Bats (order Chiroptera, suborders Megachiroptera and Microchiroptera) are a widely distributed group of mammals that comprise~20% of all known mammalian species [1] . They are reservoirs of many emerging and reemerging zoonotic viruses, some of which are highly pathogenic in humans.", "Coronaviruses, order Nidovirales, family Coronaviridae, subfamily Coronavirinae, are enveloped positive-sense single-stranded RNA viruses. There are four CoV genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus [10] . After it was found that SARS-CoV probably originated in bats [11, 12] , a flurry of investigations uncovered many more novel bat CoVs [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] . The recent description of a bat CoV related to MERS-CoV in Mexican bats [27] emphasized the relevance of investigating neotropical bats for CoVs." ] },{ "paper_id": "fc83785220bddefb3ae13e33fc3a49f9290cdc84", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1. Health questionnaire. " ] },{ "paper_id": "fc89cc67ce1d4e381a17de2c92a9b882f264197d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Serum dilutions were incubated for one hour in a moist, dark box at 37\u00b0C. Antibody binding was detected using an unconjugated goat-anti-bat whole immunoglobulin G (IgG) (Bethyl Laboratories Inc., Montgomery, TX, USA) at a dilution of 1:800, in combination with a Fcfragment specific AlexaFluor647-labelled rabbit-anti-goat IgG (Jackson ImmunoResearch Laboratories Inc, West Grove, PA, USA) at 1:1100. Both conjugates were titrated to determine the optimal working concentration prior to sample analysis. Each incubation period followed three washing steps using wash buffer (Maine Manufacturing, Maine, USA).", "Prior to analysis, we inactivated all bat sera in a water bath at 56\u00b0C for one hour. Four-fold sample dilutions were prepared in Blotto Blocking Buffer (Thermo Fisher Scientific Inc., Rockford, MA, USA) containing 0.1% Surfactant-Amps (Thermo Fisher Scientific Inc.). We used five microliters of serum for a starting concentration of 1:40.", "As described previously [7] , all animals used in this study were captured and sampled with permission from the Wildlife Division, Forestry Commission, Accra, Ghana. Geographic coordinates of the sampling site in Kumasi/Ghana were N06\u00b042\u00b402.0\u00b4\u00b4W001\u00b037\u00b429.9\u00b4\u00b4. Capturing was conducted under the auspices of Ghana authorities. Following anesthesia using a Ketamine/Xylazine mixture, skilled staff exsanguinated all bats (permit no. CHRPE49/09; A04957). Samples were exported under a state contract between the Republic of Ghana and the Federal Republic of Germany. An additional export permission was obtained from the Veterinary Services of the Ghana Ministry of Food and Agriculture (permit no. CHRPE49/09; A04957). Materials of all sacrificed animals were used for various studies [8] [9] [10] [11] ." ] },{ "paper_id": "fc8c37b262255f1af7df6aa9bbbce30f5d5aa20a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "3.5 \u00d7 10 6 3.2 \u00d7 10 6 HRV-76 1.9 \u00d7 10 4 HRV-2 3.2 \u00d7 10 4 HRV-9 5.6 \u00d7 10 5 ", "Supplementary Table 1 . HRV types and titer in 1-, 3-, 5-, 7-, and 10-valent vaccine. Inactivated-TCID50 per 100 \u03bcl i.m. dose used in 1-valent, 3-valent, 5-valent, 7-valent, and 10valent inactivated HRV vaccines depicted in Figure 1 .", ". Original antigenic sin in 10-valent inactivated HRV-vaccinated mice. Mice (20 per group) were vaccinated i.m. with either PBS + alum or 2-valent (HRV-16 and HRV-76) inactivated HRV + alum in order to establish pre-existing immunity to types 16 and 76 in one group. (a) Sera were collected 18 days later and tested for nAb against HRV-16 and HRV-76. All mice were vaccinated i.m at day 28 and boosted at day 56 with 10-valent inactivated HRV that included types 16 and 76 (10-valent composition listed in Supplementary Table 2) . Sera were collected at days 46 (b) and 74 (c) and pooled for each group for nAb against the 10 types in the vacccine. Error bars show 95% confidence interval. The dashed line represents LOD. Undetectable nAb were assigned LOD/2." ] },{ "paper_id": "fc923e6d8eafe27c1056242b741ed1dcc6e574a7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fc9a6a00498ee4dfeaf7c201c3341aca6ad21409", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "DNS4 BTV mutants are pathogenic in mice models of disease Next, we assessed the virulence of DNS4 BTV mutants in two murine models of bluetongue infection [46, 47] . 129sv IFNAR (2/2) mice, which are deficient in the type I IFN receptor, are susceptible to infection and disease induced by BTV inoculated by various routes [46, 48] . Newborn NIH-Swiss mice inoculated intracerebrally are also susceptible to BTV infection [47] . These models have been previously used to assess BTV virulence [47, 49] .", "All experimental procedures carried out in this study are included in protocol number 5182/2011 of the Istituto G. Caporale ", "Interestingly, BFAE cells infected with BTV-1 revealed that NS4 expression was evident as early as 2 hours post infection, similar to that observed for other BTV structural and nonstructural proteins (Figure 3 )." ] },{ "paper_id": "fca0580d965f2ac6c66e345eab40c436d6468c66", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fcb1ba715b2516823fee057cbb0f8276c76d19d7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "RT-PCR was performed with SuperScript III One-Step RT-PCR System with Platinum Taq (Invitrogen\u2122). PCR conditions used were: 45\u02daC for 60 min and 95\u02daC for 5 min, 35 cycle of 94\u02daC for 40 sec, 55\u02daC for 1min and 72\u02daC for 5 min, and a final elongation step of 72\u02daC for 5 min, followed by final hold at 4\u02daC. PCR products were run on a 1.2% agarose TBE gel stained with RedSafe\u2122 nucleic acid staining solution (iNtRON Biotechnology). All PCR products were excised and cleaned up with WIZARD SV Gel and PCR clean-up system (Promega) following manufacturer's protocol and sequenced using Sanger sequencing at the AGRF.", "The amplified PCR products were cleaned up using WIZARD SV Gel and PCR clean-up system (Promega) following manufacturer's recommendations and two libraries with dual indexing for each sample were generated (DNA and cDNA) with Illumina Nextera XT DNA Sample Preparation kit, according to manufacturer indications. After visualise it with Agilent 2200 Tape Station System (Agilent Technologies), the libraries were submitted to the Australian Genome Research Facility (AGRF) for a 250 bases paired-end sequencing on the MiSeq Illumina platform.", "To enrich for viral DNA and RNA, a DNase/RNase step was incorporated using a modified protocol described previously [6, 12] . Each sample was treated with a cocktail of DNases (Turbo DNase, from Ambion, Baseline-ZERO from Epicentre, Benzonase from Novagen and DNase I from Roche) and RNase A (QIAGEN). This mixture was incubated in a water bath at 37\u02daC for 3 hours. To stop the enzymatic activity, EDTA (AMRESCO) was added in a final concentration of 15 mM to each sample and incubated at 75\u02daC for 10 min." ] },{ "paper_id": "fcb1c4ac23381ffb7dbeaad05aa5307cf4386912", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "By setting \uf0f2 r of the PBS at 8.2 GHz as 67.13 25 , q = . \u00d7 e 1 16 10 7 can be obtained by comparing equation (13) and equation (14) .", "To investigate the resonant effect, we first measured the residual viral infectivity of influenza A virus after illuminating microwave of different frequencies.", "We describe the forced displacement as", "Therefore the decay rate of the oscillation equals to the imaginary part of the frequency (b/2m*), which corresponds to \u03c9 0 /2Q 19 :" ] },{ "paper_id": "fcc20c80be8954f1682993217bbd2a78659a16f1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The emergence and re-emergence of infectious diseases represent a significant threat to global public health and socioeconomic stability as witnessed by numerous outbreaks over the past few decades [1] . The Middle East respiratory syndrome-coronavirus (MERS-CoV), first identified in Saudi Arabia in 2012, was the second zoonotic introduction of a highly pathogenic coronavirus into the human population within a decade [2] . Since its emergence, MERS-CoV continues to spread to countries outside of the Arabian Peninsula and has caused epidemics with high fatality rates [1, 3] ." ] },{ "paper_id": "fcc66c2bb245f7ddfeccc64ffc5a10013af74a60", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mosquitoes are vectors that can transmit an array of pathogens that often cause devastating human diseases [1] . Traditionally considered a problem for tropical regions, mosquitoes are increasingly becoming a global public health challenge [2, 3] due to a changing global environment, urbanization, increases in the global movement of populations, and the emergence of insecticide resistance [4] . Estimates suggest nearly half the world's population is at risk for mosquito-borne diseases [5, 6] , and as such, there is an urgent need for novel approaches to reduce the burden of disease.", "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "New England Biolabs (NEB, Ipswich, MA) unless otherwise indicated. All oligonucleotides and gene blocks (summarized in S1 Table) were obtained from Integrated DNA Technologies (IDT, Coralville, IA, U.S.A.)." ] },{ "paper_id": "fccc2cff358d6c08f512003b88bab9934e4ffa7a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Reagents 3-Hydroxyphthalic anhydride (HP), 2,4,6-trinitrobenzenesulfonic acid (TNBS), human serum albumin (HSA), \u03b2-lactoglobulin (\u03b2-LG), chicken ovalbumin (OVA), and bovine serum albumin (BSA) were purchased from Sigma. Horseradish peroxidase (HRP)-conjugated goat anti-human IgA and IgE antibodies were purchased from Abcam (UK). HRP-conjugated rabbit anti-mouse IgG antibody was purchased from Dako (Denmark). The HPV16-and HPV-58-L1/L2-expressing plasmids and Luciferase pCLucf plasmid were kindly provided by Dr. John Schiller at the Laboratory of Cellular Oncology, National Cancer Institute, NIH, MD, USA.", "The animal study was reviewed and approved by Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College (approval number: ILAS-VL-2015-001).", "This work was supported by an intramural fund of Fudan-Jinbo Functional Protein Joint Research Center, Fudan University." ] },{ "paper_id": "fcce653525bba82ca40e8934a2e37ee4de6e2c23", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Analyses were conducted using Stata 11 (StataCorp, College Station, TX) and R 3.2.2.", "Note: Supplemental figure appears at www.ajtmh.org." ] },{ "paper_id": "fcd0b20d3b55d4c5029f98c3612ff577394ebf3d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Clinicopathologic findings (procyte Idexx, catalyst Idexx), CBC and restricted serum biochemical analysis were within reference intervals except for leukocytes (22. 14 K/ul, reference interval, 2.87-17.02 K/ul), absolute segmented neutrophils (18.2 K/ul, reference intervals 1.48-10.29 K/ul), absolute monocytes (0.72 K/ul reference intervals 0.05-0.67 K/ul); ALT (132 U//l, reference interval, < 130 U/l), AST (57 U/l, reference intervals <48 U/l) and GGT (4 U/l, reference intervals 0-1 U/l).", "The data supporting our findings are contained within the manuscript.", "Authors' contributions FG, AS and SP coordinated the case report and reviewed the literature; JM conducted the cases; all authors contributed to writing the manuscript and read and approved the final manuscript." ] },{ "paper_id": "fcd821f2f9391938a54442ec69f64e2370597be5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The following figure supplement is available for figure 2: ", "The following source data and figure supplement are available for figure 5:", "UI R R V W a R R V W a UI R R V E T D R R V E" ] },{ "paper_id": "fcd9e38e06549c39625f00187d5b8f4a769b584f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The values are presented as the means with standard error (SE). Statistical significance among the different groups was calculated by Student's two-tailed t-test using GraphPad Prism Statistical Software. *, **, and *** indicate P < 0.05, P < 0.01, and P < 0.001, respectively.", "Although ZIKV E protein is a key target for developing ZIKV vaccines, studies have found that antibodies targeting ZIKV EDI/II are generally cross-reactive and poorly neutralizing, potently enhancing ZIKV and DENV infection, whereas those targeting ZIKV EDIII have the most potent neutralizing activity against ZIKV infection 28 . In addition, antibodies targeting DENV and/or WNV E proteins, including the fusion loop region, may bind and cross-react with ZIKV EDI/II region, but they do not neutralize ZIKV infectivity, thus promoting antibodydependent enhancement (ADE) [29] [30] [31] .", "ZIKV RNA copies in the sera and tissues of challenged mice were detected by qRT-PCR as previously described 38 . Briefly, ZIKV RNA was extracted using the QIAamp MinElute Virus Spin Kit (for sera) (Qiagen) and the RNeasy Mini Kit (for tissues) (Qiagen). The extracted ZIKV RNA was quantified using one-step qRT-PCR with Power SYBR Green PCR Master Mix, MultiScribe Reverse Transcriptase, and Ambion RNase Inhibitor (Thermo Fisher Scientific, Waltham, MA, USA) in the ViiA 7 Master Cycler PCR System (Thermo Fisher Scientific) according to the manufacturers' instructions. The forward and reverse primers used for the amplification were 5\u2032-TTGGTCATGATACTGCTGATTGC-3\u2032 and 5\u2032-CCTT CCACAAAGTCCCTATTGC-3\u2032, respectively." ] },{ "paper_id": "fcededebc295dbf0fa5130e94002b7fe0a921f51", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In order to identify a wave of infections during an infectious disease outbreak, we make use of the analytic solution of the Richards growth model (Richards, 1959) of the form", "Here we choose to use the confirmed case data only. More recently updated data from some PAHO countries/territories are also accessed from the PAHO website (Pan American Health Organization, 2016c) . Data used in this study with model fit are provided in Table S1 .", "Previous estimates of R 0 employing vastly different modeling methodologies tend to result in varying estimated values for various affected regions, and in some cases with wide 95% ranges (see Table 3 ). However, we note that in the only other study that also makes use of the same methodology to estimate R 0 in both land-based and island regions, namely that of Rojas et al. (2016) , the resulting estimates are respectively 1.41 (1.15-1.74) for Girardot, a land region in Colombia, for San Andres Island, Colombia. The significantly higher R 0 range for island region when compared to land region is consistent with our own findings of geographical heterogeneity in transmissibility of Zika virus." ] },{ "paper_id": "fcf41a33dfcb8326a794806dc8bd7585c7e9e591", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Finally, the zoonotic transmission assessment of C. parvum in France would require a comparative investigation of variable genetic loci both in human and animal samples.", "Consequently, in our work based on the utilization of Cryptosporidium generic primers, the amplification of a single fragment with a single sequence is not conclusive evidence that the sample contains only a single species.", "Prevalence of C. parvum, C. ryanae, and C. bovis in relation to calf age", "However, based on our results, it is possible to confirm the predominance of different species of Cryptosporidium by group of age among the calves." ] },{ "paper_id": "fcf74132e357aaadf7be22016a76d437664db797", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In any case, and although a long way has yet to be completed before the implementation of these antiviral strategies in clinical practice, the current scenario and their potential benefits support future research efforts aimed to repositioning of lipid metabolism modulators as antiviral compounds. ", "The authors declare no conflict of interest." ] },{ "paper_id": "fd0802a5e13561915fb90cbfe5bb12a751197e28", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) represents the prototypical ligand for aromatic hydrocarbon environmental contaminants which elicit a wide range of toxicity through activation of the aryl hydrocarbon receptor (AhR) 1 . AhR is a basic helix-loop-helix/PAS transcription factor localized in the cytoplasm. Because AhR is expressed in a variety of tissues, it mediates species-and tissue-dependent toxicities, including chloracne, wasting, teratogenicity, immunotoxicity, liver tumor promotion and carcinogenicity 2-6 . More recent studies have shown that AhR activation can not only cause toxicity but also regulate the immune response, specifically the regulation of T cell differentiation 7-9 .", "Also, in addition to TCDD, other innocuous ligands for AhR have also been identified such as dietary indoles, indole-3-Carbinol (IC3) that are found in high concentrations in cruciferous vegetables 10-13 . Natural flavonoids present in fruits and vegetables, including apigenin, quercetin, and resveratrol are also known to act as AhR ligands 10,13-15 . There are also known endogenous ligands of AhR that are derived from tryptophan metabolism 16 . The precise mechanisms through which AhR ligands mediate such a wide range of effects following activation of AhR, remain unclear.", "In order to test the ability of TCDD to bind VEGFR1, we used tritiated TCDD ([3H]-TCDD) (American Radiolabelled Chemicals Inc., St. Louis, MA) along with a modified ELISA-based assay system as reported elsewhere 21, 24 . In these studies, recombinant hVEGFR1 full-length protein (Biolegend, San Diego, CA) that contained the predicted TCDD binding site (Fig. S4) [3 H ]-TCDD from non-coated wells (nonspecific binding) were subtracted from CPM readings from respective VEGFR1-coated wells. For blocking assays, the previous steps were repeated until blocking with 2% BSA. After this blocking and subsequent wash step, wells were incubated for 1 hour with either a well-known ligand for VEGFR1, a splice variant of VEGF-A known as VEGF-165 (Biolegend, San Diego, CA) 25 or anti-VEGFR1 antibody [AP-MAB0702] (Abcam, Cambridge, MA) at a concentration of 1000 ng/ml. After a wash step, [3 H]-TCDD was added to the wells at 500 ng/ml and incubated for 1 hour before detection of CPM as explained above. A schematic of the binding and blocking assays is depicted in the Fig. S4 ." ] },{ "paper_id": "fd1910cd1f9847cf0b72bbcf0d94447807c9de66", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "ELM is freely accessible at http://bioinformatics.czc.hokudai. ac.jp/ELM/. The web interface has been tested in the following web browsers: Google Chrome (version 36), Microsoft Internet Explorer (version 11) and Mozilla Firefox (version 31).", "We use MEGAN software version 4.62.5 for the LCA analysis [8] . MEGAN assigns sequence reads into taxa at different hierarchical levels such as family, genus, and species in the taxonomic ordering relation.", "The taxonomic classification of metagenomic sequences is an important task in NGS data analyses [8] . It has been widely applied to investigate the relationship between human health and the microbiome [9] . Recently, a metagenomic analysis of the virome in a monkey infected with simian immunodeficiency virus was conducted, suggesting that the virome was associated with enteropathy caused by HIV [10] . Through the first screening with NGS, the novel influenza virus H17N10 was identified in bats from metagenomic samples [11] .", "To prepare for the risk of emerging infectious diseases, we need to identify pathogenic viruses through surveillance of livestock and wild animals. Although universal PCR primers against 16S ribosomal RNA are available for the identification of bacteria, we needed specific PCR primers to identify viruses. In recent years, NGS technologies have become available for identifying novel viruses that cannot be found by Sanger sequencing due to the difficulty of isolation and passage culture [7] .", "Most emerging infectious diseases are zoonoses, the pathogens of which are transmitted between humans and animals. The 2009 pandemic H1N1 influenza virus spread worldwide through reassortment that exchanged a gene segment between pigs and humans [1] . Recently, cases of influenza A virus H7N9 transmitted from birds to humans have been reported [2] . The 2003 severe acute respiratory syndrome (SARS) outbreak originated from the transmission of a novel bat coronavirus [3] . For the sporadically endemic Ebola virus, bats are suspected to be the natural reservoir, but this is still controversial [4] . Vector-borne zoonoses caused by transmission of viruses through mosquitoes and ticks have also become a public health concern. The 1999 outbreak of West Nile virus (WNV) that occurred in New York was caused by the transmission of the WNV among birds, horses and humans via mosquitoes [5] . Similarly, severe fever with thrombocytopenia syndrome (SFTS) was found to be due to a virus transmitted by ticks [6] ." ] },{ "paper_id": "fd19cfef82dc2fd1ee48be9b10563d681610c000", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Effect of urea on the size-and-shape changes of \u03b4-crystallin variants", "doi:10.1371/journal.pone.0145957.g008 was unfolded by stepwise dissociation or directly unfolded with 5 M GdmCl could be different. The consequence of this might be that protein folding occurs via different pathways leading to the refolded monomers with different conformations to associate into native structure or alternative structures without function.", "responsible for the conversion of argininosuccinate into arginine and fumarate in the urea cycle. \u03b4-Crystallin and ASL share about 70% amino acid sequence identity and function as homotetramers, with four identical multi-subunit active sites [1-6].", "Electrophoresis was performed using a PhastSystem (GE Healthcare). The samples were subjected a PhastGel 4-15% gradient gel which contains the Native Buffer Strip (0.88 M L-alanine, 0.25 M Tris/HCl pH 8.8) attached to the surface of the gel and both electrodes. The electrophoresis was carried out at 10 mA and 15\u00b0C for 400 Vh. After electrophoresis, the gel was fixed in 20% (w/v) trichloroacetic acid and stained with Coomassie Brilliant Blue R250." ] },{ "paper_id": "fd1b26543d016107178798ed466d39ecfe4572cc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Culture based methods are the gold standard for diagnosing invasive pneumococcal disease (IPD). However culture based methods typically require at least several hours to a day or more incubation before an organism is detected. Furthermore, these methods often demonstrate limited diagnostic sensitivity, particularly post antibiotic treatment or in cases with low sample volume, as is often the case with children [10, 11] . Molecular amplification methods such as PCR and Loop-mediated isothermal amplification (LAMP) have been used to diagnose IPD [12, 13] . These methods are reported as sensitive, are not reliant on having viable organisms and have the potential to deliver more rapid results.", "In order to determine the limit of background human DNA tolerated by the RPA and PCR reactions, varying quantities of human genomic DNA (100, 200 and 400 ng) were added to reactions containing 50, 20 or 4 S. pneumoniae (DSM 20566) GE.", "Bacterial strains and growth conditions S. pneumoniae bacterial reference strains (n = 8), non-S. pneumoniae reference strains (n = 54) and invasive S. pneumoniae clinical isolates (n = 19) were evaluated in this study (Table 1 ). All strains were cultured overnight in brain heart infusion (BHI) medium (Oxoid, UK) at 37\u00b0C. For enumeration, 100 \u03bcL of serially diluted bacterial suspensions were spread plated on Columbia blood agar and incubated for 24 hrs.", "LepA sequences were obtained from GenBank (http:// www.ncbi.nlm.nih.gov/genbank), and the Functional Gene Pipeline and Repository (FunGene; http://fungene.cme. msu.edu) website. Sequences were aligned using the multiple sequence alignment tool ClustalW [38] . Following alignment, S. pneumoniae specific PCR and RPA primers and probes were manually designed ( Table 2 ). The sequences were finally screened for homology using the BLASTn algorithm (http://blast.ncbi.nlm.nih.gov/Blast.cgi) to confirm their specificity. All oligonucleotide primers and probes were purchased from Integrated DNA Technologies (Leuven, Belgium), with the exception of the RPA probe, " ] },{ "paper_id": "fd1e95e046ac945ddbd0a1a515dcabf031f31244", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The lysates from tissues were separated by SDS-PAGE then transferred onto nitrocellulose membranes. Membranes were blocked with 5% non-fat milk in Trisbuffered saline containing 0.1% Tween 20. Then membranes were incubated with following primary antibodies: anti-BLVRA (1:1000, Santa Cruz), eNOS (1:1000, Santa Cruz), phospho-eNOS (S1177) (1:1000, Santa Cruz), TLR4 (1:1000, Abcam), Actin (1:3000, Abcam), 3-Nitrotyrosine (3-NT, 1:1000, Abcam), 4-Hydroxynonenal (HNE, 1:1000, Abcam), dinitrophenol (DNP, 1:1000, Abcam), IL-1\u03b2 (1:1000, Abcam), IL-6 (1:2000, Abcam), TNF-\u03b1 (1:1000, Abcam), Lamin B (1:1000, Abcam) at 4\u00b0C overnight followed by appropriated secondary antibodies (1: 5000, Santa Cruz) for 2 h. Immunocomplexes were visualized by ECL ECL plus Kit (GE Healthcare and Life Science). Relative density of immunoblots was analyzed by ImageJ software as described [23] ." ] },{ "paper_id": "fd23dc1e8db2de0724d76fdadf0fd2f675be960e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fd28c322b33337c09ccb3d0785d8c2494efa0946", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Anterior nasal specimens were obtained using BBL Culture Swab Plus double applicators (Becton Dickinson, Sparks, MD) from 200 patients. Swabs were inserted into both left and right nostril of each study subject. One study coordinator collected all specimens." ] },{ "paper_id": "fd28e6d03eef27b0454f13ca539dc1498242a4c2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fd31ade73c720f893a5ddb2370df90a84511ec4a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fd4ab143e7dd8db7255b11177505986e87b50943", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supplementary Materials: The following are available online at http://www.mdpi.com/1660-4601/17/2/564/s1. Table S1 : Primers and PCR assays for multiplex PCR. Table S2 ", "Student's t-test and chi-square test were used to analyze and compare the categorical demographic characteristics including clinical manifestations and laboratory tests. Kappa statistic was used to evaluate the consistency between PCR and original tests (categorical variables) and Cohen's kappa coefficient (\u03ba) was regarded as poor to fair consistency if \u03ba \u2264 0.4; moderate consistency if 0.41 \u2264 \u03ba \u2264 0.60; and good consistency if 0.61 < \u03ba. A two-sided p < 0.05 was considered statistically significant. Statistical analyses were performed using the SPSS software version 23.0 (SPSS Inc., Chicago, IL, USA).", "This study was approved by the Institutional Review Board of the MacKay Memorial Hospital, Taipei, Taiwan (approval no. 14MMHIS030). For children with respiratory symptoms and with a clinical suspicion of virus infection, a test for RSV antigen test, human parainfluenza virus (PIV) type 3 antigen test, viral PCR for enterovirus, or viral cultures was prescribed by the judgment of pediatricians. A nasopharyngeal swab or aspiration was performed by pediatricians using a small swab that was inserted into the nostril. The cotton swab was then inserted and mixed in a 2.5 mL viral transport medium. After testing original tests, the residual specimens were stored at \u221220 \u2022 The viral nucleic acids were extracted from 200-\u00b5L of each sample using the High Pure Viral Nucleic Acid Kit (Roche Applied Science, Castle Hill, Germany) following the manufacturer's instructions. Extracted nucleic acids were eluted in 100 \u00b5L elution buffer and stored at \u221270 \u2022 C. Reverse transcription (RT) was carried out using High-Capacity Complementary DNA (cDNA) Reverse Transcription Kit (Applied Biosystems Part Number: 4375575 Rev.C). The total volume of RT mix was 40 \u00b5L per reaction, containing 4 \u00b5L RT buffer (10\u00d7), 1.6 \u00b5L dNTP mixture (25 mM of each dNTP), 4 \u00b5L random primers (10\u00d7), 2 \u00b5L RNase inhibitor (20 U/\u00b5L), 2 \u00b5L MultiScribe Reverse Transcriptase (50 U/\u00b5L), and 26.4 \u00b5L template, whereby the RT reagent mix was prepared on ice. The thermal profile of the RT program consisted of 10 min incubation at 25 \u2022 C, 120 min RT at 37 \u2022 C, 5 min RT inactivation at 85 \u2022 C, and cooling down to 4 \u2022 C and was performed in a 96-well GeneAmp PCR System 9700. The resulting cDNA was stored at \u221220 \u2022 C." ] },{ "paper_id": "fd4b79d3d28a8c01c635987b474443590c240f4c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Primarily and persistently infected tissuemonocytes/M\u03a6s and fibroblasts in multiple tissues Massive M1 polarization served as a modulator of the viral pathogenesis including pulmonary edema, hemorrhage, and lymphoid depletion that characterize the disease [55, 56] PCV2 (ssDNA, Cirvoviridae) Monocyte/M\u03a6 lineage cells, including alveolar M\u03a6s, are the major target cells Acute infection reduced alveolar M\u03a6s phagocytosis and microbicidal capability; and persistence increased inflammatory and pro-apoptotic responses, which led to lymphopenia and immunosuppression [57, 58] FMDV ((+)ssRNA, picornaviridae)", "Early infection of porcine T and B cells caused viremia; immunocomplex promoted productive infection and killing of mDCs Increase IL-10 production in infected DCs, loss of pDC cell function coincides with lymphopenia in FMDV-infected pigs; macrophage depletion in vaccinated mice severely decreased vaccine protection [59] [60] [61] [62] [63] ", "Human respiratory epithelial cells, and antibody-enhanced infection of macrophages and immune cells Depletion of alveolar M\u03a6s 1-2 day before infection, (but not at 2 dpi), prevented lethal disease, and enhanced viral clearance [44, 45] IAV (Segmented (-)RNA, Orthomyxoviridae)" ] },{ "paper_id": "fd4f419edc4e7a9ee255ea3bdc5b458a86ae4ab3", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sequence of euthanasia of the EG and SG calves was random, determined by drawing of lots.", "To mimic standard managerial conditions, direct contact was chosen as challenge procedure for both EG and SG. The commingling was done by moving EG into the other two groups' pens for 24 h.", "Samples from SG were also tested for antibodies to bovine respiratory syncytial virus (BRSV) by Svanovir BRSV-Ab (Boehringer Ingelheim). The optical density (OD) at 450 nm was measured and corrected by subtracting the OD for the negative control. Percent positivity (PP) was calculated as (sample OD/positive control OD) \u00d7 100, and a PP-value of <10 was regarded as negative.", "The standard curve covered the range from 10.8 to 1.08 \u00d7 10 10 plasmid copies, and showed a strong linear relationship with a high coefficient of determination (R 2 = 0.996) and a high amplification efficiency (96.5 %). The limit of quantification (LOQ) for the plasmid was 10.8 copies which represented 3.6 log 10 BCoV VRC per nasal swab and ml plasma, 4.6 log 10 VRC/g feces and 4.2 log 10 VRC/g tissue." ] },{ "paper_id": "fd521d37325a60e6ed92aa9bcf4541b9a68ee90e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The sequences of M were screened for potential H2-K d / H2-D d /H2-L d 9-mer epitopes using the algorithms from the SYFPEITHI website [13] , the HLA peptide binding prediction website (BIMAS) [14] and PRED BALB/c [15] . The 27 peptides (Table 2) , with highest binding score (BS) as predicted by each algorithm, were synthesized by Scilight Biotechnology LLC (Beijing, China) and purified to a purity > 95% using high performance liquid chromatography (HPLC).", "Isolated splenocytes were added to U-bottomed 96-well plates (Corning Inc) at 10 6 cells/well in 100 \u03bcL complete RPMI-1640 medium supplemented with 10% FCS. The cells were then mixed with 100 \u03bcl media containing Note: The 27 peptides with highest binding score (BS) as predicted by each algorithm are shown, starting with the peptide giving the highest score at the top for each protein. Sequences of 9 mers are given from BIMAS, SYFPEITHI and PRED BALB/c predictions, respectively. The N-terminal amino acid position is indicated for epitopes predicted from the whole M protein.", "The iELISA results, the percentage of IFN-\u03b3 positive CD3 + CD8 + T lymphocytes and the number of spots per 2 \u00d7 10 5 splenocytes were analyzed using the analysis of variance (ANOVA), and a probability value below 0.05 was considered significant." ] },{ "paper_id": "fd5e3020671499cde830bd25de618009ece0af13", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All Vivo-Morpholino (MO) oligos were commercially procured from Gene Tools LLC, (Philomath, OR, USA). MOs were", "All animal experiments were approved by the institutional animal ethical review board named ''Institutional Animal and Ethics Committee of National Brain Research Centre''. The animal experiment protocol approval no. is NBRC/IAEC/2007/ 36. Animals were handled in strict accordance with good animal practice as defined by Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Ministry of Environment and Forestry, Government of India." ] },{ "paper_id": "fd6a5e41d7c2ffcd1079e540927707456897b6a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fd70fe1475a302013f71a976dd9270cf5ecbe12e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fd71de909bf3d6539246e78e650a76f6eb90b23b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Porcine reproductive and respiratory syndrome virus (PRRSV) is a single-stranded, positive-sense RNA virus with a genome size of approximately 15 kb. PRRSV belongs to the Arteriviridae in the order of Nidovirale. PRRSV causes acute respiratory disease in neonatal and young piglets and reproductive failure in pregnant sows. PRRSV primarily infects and destroys alveolar macrophages during acute infection of swine. In addition to macrophages, PRRSV has also been identified by immunohistochemistry in dendritic-like cells in tonsils and lymph nodes [1] , suggesting that dendritic cells may either be susceptible to PRRSV or capture PRRSV by taking up apoptotic infected cells.", "PRRSV activates the transcription of type I interferon in porcine alveolar macrophages, peripheral blood mononuclear cells, and monocyte-derived dendritic cells. However, PRRSV interferes with the translation of type I interferon in these cells partly through cytopathogenicity since UV and heat-inactivated viruses lose their ability to interfere with the induction of type I interferon by porcine transmissible gastroenteritis virus or Poly I:C. Further studies are needed to delineate the exact mechanisms by which PRRSV interferes with the translation of type I interferon in its natural host cells.", "Porcine reproductive and respiratory syndrome virus (PRRSV) is not only a poor inducer of type I interferon but also inhibits the efficient induction of type I interferon by porcine transmissible gastroenteritis virus (TGEV) and synthetic dsRNA molecules, Poly I:C. However, the mechanistic basis by which PRRSV interferes with the induction of type I interferon in its natural host cells remains less well defined. The purposes of this review are to summarize the key findings in supporting the post-transcriptional control of type I interferon in its natural host cells and to propose the possible role of translational control in the regulation of type I interferon induction by PRRSV." ] },{ "paper_id": "fd738b997979c4b38c3a9aaa1b148a090fe94613", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "65 -72-74", "[M + 1] + C25H26F3N3O2 (457.49)3j 73" ] },{ "paper_id": "fd80a87a02d130989492acfc82db606ee470ab53", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Japanese encephalitis virus (JEV) belongs to the family Flaviviridae and is a mosquito-borne zoonotic pathogen that causes human encephalitis and meningitis. The 10,976 nucleotides (nts) genome contains a single open reading frame (ORF) encoding a polyprotein which is subsequently processed into three viral structural proteins and seven nonstructural proteins [1] . The ORF is flanked by 5' and 3' untranslated regions (UTRs) which contain many important cis-acting elements involved in the regulation of viral translation, replication, and pathogenesis [2] [3] [4] [5] .", "The titration of infectious virus was performed as previously described [32] . Briefly, serial 10-fold dilutions of virus were made in serum-free alpha-MEM medium, and 0.1 ml of each dilution was added per well to a monolayer of BHK-21 cells in a 12-well plate. After 1 hour of absorption at 37\u02daC, the cells were washed with PBS and overlaid with growth medium containing 0.3% LE agarose (Lonza), and the plaque was visualized with naphthol blue-black solution (0.1% naphthol blue-black, 1.36% sodium acetate and 6% glacial acetic acid) at 4 days postinfection. Viral titers were determined as plaque forming units per milliliter.", "Supporting information S1 ", "Detailed methods for the construction of clones are described in the Supporting Information S1 Text. The majority of plasmids used for this study were constructed by RT-PCR using synthetic oligonucleotides, as listed in S1 Table. The cDNA encoded RdRp domain from amino acids at position 274 to 905 of the JEV NS5 protein was amplified by RT-PCR and cloned into pET28a (Novagen)." ] },{ "paper_id": "fd80f38e8161b81dc184779877ca0bd283ac2d2d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.", "This work was funded by National Institutes of Health grants EY013124, EY021558, and EY014104, a Senior Scientific Investigator Award grant (to JC) from Research to Prevent Blindness, Inc., New York, NY, The Falk Foundation, and the Massachusetts Lions Eye Research Fund.", "FIGURE 6 | Transcription map for HAdV-D37. Genes are divided by early (shaded) or late expression. Red brackets denote large areas of \"noncoding\" DNA, but many additional, smaller, potential coding regions exist between and within known genes. Adapted from Robinson et al. (2008) with permission." ] },{ "paper_id": "fd8ee38a505cf79732f5ba487e15f11619b84150", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fd9051e7bcf001955cb7625a5b2c51ddf58218dc", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Bat cells used for this study were previously generated from P. alecto as described in Crameri et al [42] . Cells used include PaLuT02 (clonal P. alecto lung cells immortalized with SV40T), PaFe (primary P. alecto foetus cells), PaFeT (SV40 T immortalized P. alecto foetus cells) and PaKi (primary P. alecto kidney cells). All bat cells were maintained in Dulbecco's Modified Eagle's Medium Nutrient Mixture F-12 HAM (Sigma), which also contains 15 mM HEPES, NaHCO3, pyridoxine and L-glutamine, with 10% bovine calf serum (BCS, Hyclone), 100 U/ml penicillin, 100 mg/ mL streptomycin and 1.25 ug/ml of amphotericin B (Invitrogen). All cells were maintained at 37uC with 5% CO 2 . Human epidermoid carcinoma cells (HEp-2) were maintained in modified Eagle's Minimal Essential Medium (EMEM) supplemented with 10% BCS (Hyclone), 100 U/ml penicillin, 100 mg/mL streptomycin and 1.25 ug/ml of amphotericin B (Invitrogen).", "The henipavirus stocks used in this study were derived from the following isolates: Hendra virus/Australia/Horse/1994/Hendra (HeV), Nipah virus/Malaysia/Human/1999/PKL (NiV-M) and Nipah virus/Bangladesh/Human/2004/Rajbari R1 (NiV-B). All work with live Hendra and Nipah viruses was carried under BSL-4 conditions at the Australian Animal Health Laboratory (AAHL), Geelong, Australia.", "The bat cells (PaLuT02, PaFe, PaFeT, PaKi, PaLuT02) were infected with either HeV, NiV-M or NiV-B at an MOI of 10 for 24 h. Immunofluorescence was undertaken as previously described [58] ." ] },{ "paper_id": "fd955af6faa247ced61613abf842cf3affac6bb2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Mucosal surfaces serve as the entry sites for the majority of infectious pathogens, including influenza viruses, and provide the first line of defence against infection [9] . During the early stages of infection, the immune response is non-antigen specific, involving natural killer (NK) and natural killer T cells (NKT cells) which, through the activation of antigen presenting cells (APCs), indirectly respond to danger signals derived from invading pathogens. Macrophages and dendritic cells (DCs) express numerous Toll-like receptors (TLRs) [10] and respond to microbial pathogens by producing type I interferons (IFN) and cytokines. There are ten different TLRs, each binding specific classes of compounds. Unmethylated CpG dinucleotides present in bacterial DNA are recognized by TLR9 [11] [12] [13] , single-stranded (ss)RNA viruses, such as vesicular stomatitis virus and influenza virus are recognized by TLR7 [14] , and dsRNA longer than 30 base pairs, produced during the viral replicative cycle, is recognized by TLR3 [11, 13, 15, 16] .", "In addition to influenza and hepatitis B, CpG ODNs have also been evaluated for their adjuvant potential with protein vaccines targeting hepatitis C virus [117] , herpes simplex virus -1 (HSV-1) [132] , SARS-CoV [133, 134] , bovine herpesvirus [135] , simian immunodeficiency virus [136] , Plasmodium yoelii [137] and melanoma antigen [129] and antibody therapy [127, 138] . In contrast to mice, protocols for immunizing humans and livestock require higher doses of CpG ODN to exert adjuvant activity [132] .", "TLR7 is an intracellular TLR, located on endosomal membranes, which recognizes ssRNA in a sequence-independent manner as long as the RNA contains several uridine residues in close proximity to each other [158, 159] . Nucleosides and nucleotides from intracellular pathogens, guanine nucleoside analogues, stabilized immunoregulatory RNA, short dsRNA oligonucleotides containing several uridine residues in close proximity (i.e. short interfering RNA (siRNA)) [160] and imidoazoquinolinebased compounds such as 852A and imiquimod (IMQ) [161] are also recognized by TLR7. As with TLR9, pDC are the primary IFN-\u03b1 producing cells following exposure to a TLR7 agonist and stimulation of TLR7 results in induction of IL-6, IL-12, MIP-1\u03b1, MIP-1\u03b2, TNF-\u03b1 and IFN-\u03b2 among others [161] [162] [163] [164] [165] . Single-stranded RNA induction of TLR7 also stimulates autophagy, a cellautonomous innate defence mechanism for elimination of intracellular pathogens, in macrophages. This induction of autophagy appears to be effective in eliminating intracellular microbes, even when the target pathogen is normally not associated with TLR7 signalling [166] .", "Development of antivirals has focused primarily on vaccines and on treatments for specific viral agents. Although effective, these approaches may be limited in situations where the etiologic agent is unknown or when the target virus has undergone mutation, recombination or reassortment. Augmentation of the innate immune response may be an effective alternative for disease amelioration. Nonspecific, broad-spectrum immune responses can be induced by double-stranded (ds)RNAs such as poly (ICLC), or oligonucleotides (ODNs) containing unmethylated deocycytidyl-deoxyguanosinyl (CpG) motifs. These may offer protection against various bacterial and viral pathogens regardless of their genetic makeup, zoonotic origin or drug resistance." ] },{ "paper_id": "fd990c95b7300a2e18a8be156f159943246e06b5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Location of strain-specific codon diversification given, per ORF.", "Complete genome sequences were aligned using Muscle 3.8 (Edgar, 2004a,b) and manipulated in BioEdit 5.0.9 (Hall, 1999) . Annotations were applied using CTV reference isolates T36 , T30 , and T318A (Ruiz-Ruiz et al., 2006) as references.", "A total of 2 g of young green bark tissue from samples obtained either from field or glasshouse collections were ground to a fine powder in liquid nitrogen, and total RNA extracted using Trizol reagent (Invitrogen, Carlsbad, CA, USA), with modifications to the protocol to account for scale. Briefly, the powdered tissue was homogenized in 10 mL of Trizol reagent and 2 mL of chloroform and incubated on ice for 10 min. Samples were then separated by centrifugation at 12000 \u00d7 g for 20 min, and the upper aqueous phase mixed with an equal volume of isopropanol before precipitation at \u221220\u02daC for at least 2 h. Total RNA was pelleted by a further round of centrifugation, and washed with 70% ethanol before airdrying at room temperature. The pellets were re-suspended in 100 \u00b5L of dH 2 O, and the small RNA fraction, fragments of less than 200 bp, recovered by processing through an Ambion mirVana miRNA isolation kit (Ambion, Austin, TX, USA) as per the manufacturer's protocol. Small RNA presence and quality was checked on an Agilent 2100 Bioanalyzer platform (Agilent Technologies, Palo Alto, CA, USA).", "In summary, the adaptive landscape over which CTV strains have evolved and diversified is comprised of host factors, including species, resistance genes, and active host defenses such as RNAi. Vector species also exert significant selection on specific strains, and are important for the persistence and spread of novel variation." ] },{ "paper_id": "fd9c2af38cd8dd7a06b25e2cd2233a74a48a37cd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The 1572 bp RT-PCR product, which covers the nucleocapsid protein gene of CDV, was generated from viral genomic RNA template extracted from CDV-FOX-TA strain using N-forward and N-Reverse primers (Table 1) " ] },{ "paper_id": "fdc201b99c8f08d1e81622ac71114605c5980a8d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Supporting Information S1 File. Supporting Information File 1.", "Kenya Ethics Review Committee (KEMRI/RES/7/3/1) and the Biomedical and Social Ethics Review Committee of the University of Warwick (134-07-2011) approved the study. Written informed consent was sought from participants aged !18 years and from parents or guardians of those aged <18 years. The data was analyzed anonymously to generate a Who Acquires Infection From Whom (WAIFW) matrix.", "(DOCX)", "We argue that RSV vaccine in 5-10m old children would result in significant herd immunity and lead to marked reduction in disease in those <6 months old. There are a group of vaccines that have already been subject to extensive trials and have relatively few obstacles remaining to develop an effective licensed product. We therefore propose that promotion of these candidates could have clear global public health benefit." ] },{ "paper_id": "fdd06eeb020a963754fee36852a5918a93f7856d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "This definition is similar to previous studies [18, 29] except that a longer time (180 days) has been used instead of 90 days, taking into account the practice of prescribing antihypertensive drugs for a period of more than 90 days (range 14 to 168 days; median 56 days) among a significant proportion of physicians as found in our database." ] },{ "paper_id": "fdd420ba12ea83c4db57fccfe77d5aad622db3c6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Taiep rats of different ages (one and six months old) were obtained from the vivarium of the Institute of Physiology, BUAP. Sprague-Dawley (SD) rats (negative controls) were supplied by CINVESTAV vivarium. Institutional Animal Care and Use Committee (IACUC) approved our animal use procedures with the protocol number 410-08. Animals were maintained in rooms with controlled conditions of temperature (22 \u00b1 1 \u2218 C) and lightdark cycle (12 : 12 h light : dark; light onset at 07:00). Food and water were provided ad libitum. All procedures were in accordance with the Mexican current legislation, the NOM-062-ZOO-1999 (SAGARPA), based on the Guide for the Care and Use of Laboratory Animals, NRC. All efforts were made to minimize animal suffering.", "Immunofluorescence. CCR2, CCR5, CXCR2, and CXCR4 were detected in brain sagittal slices of 6-monthold SD and taiep rats ( = 3 per each group). Rats were deeply anesthetized with chloral hydrate and perfused through the ascending aorta with 100 mL of PBS 1x and then by 150 mL of 4% paraformaldehyde in PBS. Their brains were removed and maintained in the fixative for 48 h at 4 \u2218 C. Each brain was included in paraffin and was cut into 3 m slices on the sagittal plane using a Leica RM 2135 microtome (Leica Microsystems, Nussloch, Germany). Slices were individually collected on a glass slide. Tissue slices (previously deparaffinized) were rehydrated and incubated with 0.5% IgG-free bovine serum albumin in PBS-Tween 20 (0.1%) for 20 min at RT. Slices were incubated with rabbit monoclonal antibodies to CCR2, CCR5, CXCR2, or CXCR4 (1 : 500 dilution, Abcam Inc., Cambridge, MA, USA) at 4 \u2218 C overnight. The secondary antibody was a goat anti-rabbit IgG conjugated with fluorescein isothiocyanate (FITC). The counterstaining was made using DAPI or propidium iodide (2 g/mL). Tissue slices were mounted on glass slides using VECTASHIELD (Vector Laboratories, Burlington, Ontario, Canada). The fluorescence within the cells was analyzed with 5x and 40x objectives of a Leica DMIRE2 microscope using the filters A for DAPI, K3 for FITC, and TX2 for propidium iodide (Leica Microsystems, Wetzlar, Germany). The images were digitalized with a Leica DC300F camera (Leica Microsystems, Nu\u00dfloch, Germany) and processed with a workstation Leica FW4000, version V1.2.1 (Leica Microsystems Vertrieb GmbH, Bensheim, Germany). Samples incubated with only the secondary antibodies were used as negative controls.", "The authors have no financial, personal, or other relationships with other people or organizations within five years of beginning the submitted work. The authors declare that they have no conflict of interests.", "All values are provided as the mean \u00b1 standard error of the mean (SEM). The difference between the groups with respect to age in all the assays was analyzed using a one-way ANOVA test. The differences between SD and taiep rats were determined with unpaired Student'stest. All statistical analyses were performed using the Graph-Pad Prism software (GraphPad Software Inc., San Diego, CA, USA). values < 0.05 were considered significant. Analysis of qPCR data was performed based on a webbased PCR Array Data Analysis protocol (http://pcrdataanalysis.sabiosciences.com/pcr/arrayanalysis.php) provided by SABiosciences (Qiagen) and the results are expressed as a fold change." ] },{ "paper_id": "fdf021cfe745daed338cce7eaa5e548581477ff4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For the ZTP, the first two moments (mean and variance), for values y i . 0, are given by:", "The density for the ZTP, for every count x 2 1; 2; :::, is given by:", "Let y i be the number of pups born to litter i, where y i is a positive integer (zeros are not observed). For any categorical variable x, let the notation x\u00bdi indicate the value of x relevant to i: in particular, let h\u00bdi denote litter i's batch h \u00bc 1; . . . ; 48; let r\u00bdi denote its parity order r \u00bc 1; . . . ; 12; and let \u00f0j; k\u00de\u00bdi denote its parentage, defined by maternal strain j and paternal strain k, where \u00f0j; k\u00de 2 f1; . . . ; 8g 2 . The effect of parental strains on y i was modeled using an overdispersed zero-truncated Poisson (ZTP) regression (data scales of the model in brackets):", "KEYWORDS" ] },{ "paper_id": "fdf03dcd427aa029a6b213288a7e862519decafb", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Use of glycyrrhizin and its derivatives as MCP-1 production inhibitors US2004138171(A1)", "Ultrasonic extracting method for changing glycyrrhizic acid leaching phase balance CN101486750 A Use of glycyrrhetic acid and/or glycyrrhizin for producing cosmetic preparations for tanning the skin US2009280074(A1)", "Use of iso-glycyrrhizic acid and salt thereof in treating allergic rhinitis CN101396368 B", "Use of glycyrrhizin for the treatment of standard therapy-resistant hepatitis C patients WO2004056374 A1" ] },{ "paper_id": "fdf25867c1135bdc7fe68249c3a7f79fa05b9619", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Immunofluorescence assay for localization of non-structural protein B1. In whole viral infection.", "The 336-nt RGNNV B1 gene was cloned from the RGNNV genome as previously described 8 . PCR products were sequenced by dye termination method using an ABI PRISM 477 DNA sequencer (PE Biosystems, Foster City, CA, USA). The sequences were scanned against the GenBank database BLAST (www.genome.jp/tools/clustalw/) and the SBASE domain prediction system (www.icgeb.trieste.it/sbase/) programs 8 .", "RNA viruses belonging to the Nodaviridae family are classified as Alphanoviruses, which primarily infect insects and Betanoviruses, which predominantly infect fish 1-3 . Betanodaviruses belong to the Betanovirus class and cause virus nervous necrosis (VNN) disease, which is characterized by necrosis of the central nervous system (including the brain and retina), abnormal swimming behavior, darkening of the skin and weight loss 4,5 . Mass mortality caused by VNN in larval and juvenile populations of several teleost species has a significant global economic impact 5 . Betanodaviruses are thought to modulate innate/acquired immunity and may be a useful model for understanding the pathogenesis of RNA virus-mediated diseases." ] },{ "paper_id": "fe13f9eaf3edd3aaa5e8cb92a882eec76caa3c9e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fe14106f9f3d2b3b6d8ea619cfcc4363148dc84b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Throughout the experimental period the animals were monitored daily for clinical observations." ] },{ "paper_id": "fe1dea09375e7ab4f239b5c57cd522fc05ff3e37", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The risk of colibacillosis can be reduced through simple precautions.", "i. By thorough cleaning of poultry houses.", "iii. By washing hands carefully before and after food preparation and after toileting. iv. By avoiding eating raw or undercooked poultry. v. By wrapping fresh meats in plastic bags at the market to prevent fluids from dripping on other foods. vi. By ensuring the correct internal cooking temperature especially when using a microwave.", "ii. By ensuring proper ventilation of the poultry houses and chlorination of drinking water.", "E. coli of the O2:K1 serotype isolated from human urinary tract infections and from septicemic chickens are phenotypically highly related. A distinction between both groups was only possible by examining their plasmid contents [43] . Cherifi et al.", "i. By washing hands carefully before and after food preparation and after toileting or changing diapers. ii. By avoiding eating raw or undercooked eggs (or foods made with raw eggs) and poultry. iii. By wrapping fresh meats in plastic bags at the market to prevent fluids from dripping on other foods. vi. By ensuring the correct internal cooking temperature especially when using a microwave. v. By avoiding chicks and ducklings as pets for small children." ] },{ "paper_id": "fe2000f280297c40bc53ce95d703a9ca6aac19fd", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Both the N-and C-terminal domains of hPIV3-C are required for its activity", "hPIV3-C has opposite effects on IFN-a/b and EGF signaling pathways", "Purified complexes and protein extracts were resolved by SDSpolyacrylamide gel electrophoresis (SDS-PAGE) on 4-12% NuPAGE Bis-Tris gels with MOPS running buffer (Invitrogen), and transferred to a nitrocellulose membrane. Proteins were detected using standard immunoblotting techniques. 36FLAGand GST-tagged proteins were detected with a mouse monoclonal HRP-conjugated anti-36FLAG antibody (M2; Sigma-Aldrich) and a rabbit polyclonal anti-GST antibody (Sigma-Aldrich), respectively. Specific antibodies were used to detect endogenous STAT1 (clone-1; BD Biosciences), GRB2 (clone-81; BD Biosciences), phospho-ERK1/2 (clone-12D4; Upstate), ERK1/2 (CT; Upstate), phospho-eIF4E (Ser209; Cell Signaling), eIF4E (Cell Signaling), phospho-S6 235-236 (Ser235/236; Cell Signaling), S6 (clone-54D2; Cell Signaling) and hPIV3-HN (M02122321; Abcam). Secondary anti-mouse and anti-rabbit HRP-conjugated antibodies were from GE-Healthcare. Densitometric analysis of the gels was performed using a specific module of Photoshop CS3 Extended (Adobe Systems Inc.)." ] },{ "paper_id": "fe21f4cd051907ab122c5583ca3d95ccaacba508", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Dendritic cells (DCs) detect viral infection through Toll-like receptors (TLRs), key components of the innate immune system [10] .", "IL-9 in culture supernatants was measured by IL-9 ELISA (Life Technologies) according to the manufacturer's instructions. ", "For pair-wise comparisons of different conditions from the same donors or different donors, we used a non-parametric two-tailed paired or unpaired t-test, respectively. Data were presented as the mean \u00b1 standard error (SEM). The p values (p) of 0.05 or less were considered statistically significant.", "As controls, we used blood from age-and gender-matched individuals without inflammatory or degenerative diseases of the central or peripheral nervous system. These subjects were volunteers that underwent blood drawing." ] },{ "paper_id": "fe2c4dd2b0a96acbdcd6566d94bf227c497995ef", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The findings imply that a procedure for mass detection of fever such as self-reported questionnaires and thermal camera scanning may serve as an effective tool for detecting febrile arrivals at quarantine stations. Future research can benefit from looking at the sensitivity, specificity, positive predictive value, and negative predictive value of the entry screening system.", "The purpose of this research was to measure fever prevalence and the effectiveness of a fever screening procedure in detecting febrile arrivals at an international airport in Korea.", ": Fever prevalence at an international airport in Korea was 0.002%. Self-reported fever was significantly positively associated with tympanic temperature (p< 0.001). The difference between the thermal camera temperature (36.83\u00b0C) and tympanic (or ear) temperature (38.14\u00b0C) was not statistically significant." ] },{ "paper_id": "fe4829233859c2471b9aa99a1027a1fab44b153c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Figures for RNAscope and IHC are representative of sections obtained from three animals. Data for Figure 4 , expressed as the mean \u00b1 SEM (sections obtained from five animals), were analyzed using one-way analysis of variance (ANOVA) with Bonferroni's multiple comparison post hoc test using GraphPad Prism software v.5.0 (Graphpad). A p-value < 0.05 was considered statistically significant.", "MFL, IM and SV designed the experiments and wrote the manuscript. MFL and SV performed the in situ hybridization and immunofluorescence experiments and analyzed the data. IM, SV and MPB revised the manuscript. All authors reviewed the results and approved the final version of the manuscript.", "This work was supported by the Dean of Biomedical Research (Toulmin pilot project) provided by the Georgetown University Medical Center (IM), NIH grants R03 NS095038 (SV), R01 NS082308 (MPB) and R21 NS089446 (IM) from the National Institute for Neurological Disorders and Stroke." ] },{ "paper_id": "fe53e5ca071be4ba98a8366548192fc00d35333b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The VODKA algorithm is open-source and available at: https://github.com/itmat/VODKA." ] },{ "paper_id": "fe58b17bca43d017cf1af9b5748147b25f067b7d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Pools were constituted as reported by Strillacci et al. [66] . Five GK and two NK pools were made of 21 \u2212 31 Holstein male calves each ( Table 7) .", "During the years, various strategies have been implemented to prevent or minimize the prevalence of BRD. Among others, these include antibiotic treatment on a preventative or metaphylactic basis, non-antibiotic alternatives and vaccination [4] . Unfortunately, these strategies have collectively failed to reduce the prevalence of BRD (see citations in [14] ). To date, methods for detecting morbid cattle involve subjective visual appraisal and depend on the stage and extent of the disease. However, clinical signs of BRD may often go undetected in feedlot calves [15] , emphasizing the need of an objective and reliable early risk predictor [5] . Genomic-based approaches may thus serve as additional methods for control of BRD.", "and", "Kosher slaughtering, a routine procedure in Israel and other countries [34] , offers particular advantages for genetic analysis of BRD. Kosher slaughtering involves two steps: The actual slaughter, and then a close and detailed examination of the lungs of the slaughtered animals for adhesions. Cattle presenting lungs completely clear of adhesions, indicative of their having been BRD free, are classed as \"Glatt\" kosher. Cattle presenting severe pulmonary adhesions, indicative of one or more severe bouts of BRD, are classed as \"non-kosher\" or \"treif\". Animals presenting light adhesions are classed as standard-kosher [35] ." ] },{ "paper_id": "fe5d9afd46890e2338d8d0febf8eaa8bd2166d60", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "fe60210f629f9953405917869332d549f39e5a1b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Fold of the s2m RNA, the Pentaloop, and a Nucleotide Quartet", "Coordinates, native and derivative amplitudes, and experimental phases have been deposited in the RCSB Protein Data Bank (http:// www.rcsb.org/pdb/) under accession number 1XJR and are also available with other supplementary materials at http://www.chemistry. ucsc.edu/%7Ewgscott/sars." ] },{ "paper_id": "fe6515a4d40bf3c4c53be769971d38fada210810", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1: Figure S1 . ", "Monthly aggregated data on average temperature and total precipitation from January 2012 through December 2016 in Rhode Island was retrieved from the National Centers for Environmental Information [12] .", "Rhode Island Hospital infection control software system (TheraDoc; Premier, Charlotte, NC) was queried to find positive microbiology laboratory identification of respiratory viruses identified by the respiratory viral panel ( . Only the first encounter with one of the above-noted pathogens was included if a patient had multiple episodes of positive laboratory testing for that pathogen within 30 days. We excluded MRSA identified only from nares screening. Incidence reflected counts with no denominator based on the assumption that there was no significant year-to-year variability between practices in obtaining respiratory specimens (Additional file 1: Figure S1 )." ] },{ "paper_id": "fe768cfead153c07c019ac6d722021f035738dc4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "GraphPad Prism 5.0 (GraphPad Software, La Jolla, CA, USA) was used for statistical analyses. The differences in mean values of virus titer between groups were analyzed by two-way ANOVA. All results were represented as means \u00b1 standard error of means; p-values of <0.05 were considered statistically significant.", "Human embryonic kidney (HEK) 293T and African green monkey (VeroE6) cells stably expressing porcine aminopeptidase N (VeroE6-APN) were grown and maintained in Opti-MEM medium supplemented with 10% heat-inactivated fetal bovine serum (FBS). Cells were cultured in humidified air containing 5% CO 2 at 37 \u2022 C.", "The ORF3-myc in positive clones, designated pPEDV AV12 _ORF3-FL and-Trnc, were verified by direct nucleotide sequencing." ] },{ "paper_id": "fe7d921c5fbcd19fd95d17f31eb4149a5dfe2ae6", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Vitamins and LL-37 vs. allergy, virus infection and tonsillar immune response", "Human tonsil samples were obtained from 110 elective tonsillectomy patients (Table 1) from Satakunta Central Hospital, Pori, Finland, from April 2008 to March 2009 and biobanked. Tonsillectomy was done according to clinical indications. Written informed consent was obtained from the study patients and/or their guardians. The ethics committee of Turku University Hospital approved the study. All patients filled a standard questionnaire to obtain information of their allergic diseases and respiratory symptoms. Atopy was defined as positive immunoglobulin E (IgE) antibody (>0.35 kU/L) to any of the following allergens: codfish, cow's milk, egg, peanut, soybean, wheat, cat, dog, horse, birch, mugwort, timothy, Cladosporium herbarum or Dermatophagoides pteronyssinus (Phadiatop Combi 1 , Phadia, Uppsala, Sweden). Animal sensitization was defined as positive IgE antibodies to cat, dog, horse or Dermatophagoides pteronyssinus. Birch, mugwort, timothy and Cladosporium herbarum were considered as pollen aeroallergens. The eczema was defined as atopic eczema, if a child was atopic and had typical symptoms that included pruritus, typical morphology and chronicity of atopic eczema (Hanifin and Rajka Diagnostic Criteria for Atopic Dermatitis)." ] },{ "paper_id": "fe83b78b82d15a20c4c1b07f472785d851b5f982", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Twenty three patients (68%) had severe or very severe COPD. During the previous 30-day period, antibiotic or oral steroid therapy for exacerbations of COPD was reported by 7 and 8 patients, respectively. Eleven patients had received antibiotics within the 24 hours preceding ICU admission. With the exception of 4 patients, all had a " ] },{ "paper_id": "fe8673fd11cb2de090872b54b123acd6610ebfd1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "A = 1, C = \u22121, G = 2, T = \u22122, N = 0 Real number A = \u22121.5, C = 0.5, G = \u22120.5, T = 1.5, N = 0.0 EIIP A = 0.1260, C = 0.1340, G = 0.0806, T = 0.1335, N = 0 Atomic A = 70, C = 58, G = 78, T = 66, N = 0 Pair A or T = 1, C or G = \u22121, N = 0 Complex number A = 1 + 1i, C = \u22121 + 1i, G = \u22121 \u2212 1i, T = 1 \u2212 1i, N = 0 + 0i DNA Walk A = [1, 0], C = [0, 1], G = [0, \u22121], T = [\u22121, 0], N = [0, 0] Tetrahedron A = [0, 0, 1], C = \u2212 \u221a 2 3 , \u2212 \u221a 6 3 , 1 3 , G = \u2212 \u221a 2 3 , \u2212 \u221a 6 3 , \u2212 1 3 , T = 2 \u00d7 \u221a 2 3 , 0, \u2212 1 3 , N = [0, 0, 0]", "A = [0, 0, 1, 0], C = [1, 0, 0, 0], G = [0, 1, 0, 0], T = [0, 0, 0, 1], N = [0, 0, 0, 0]" ] },{ "paper_id": "fe8ae98f3112f0ecf862177dd5745232b9d1f966", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Abbreviations: AEGIS, Automated Epidemiological Geotemporal Integrated Surveillance; CUSUM, cumulative sum; EWMA, exponential weighted moving average; SARS, severe acute respiratory syndrome * To whom correspondence should be addressed. E-mail: ben_reis@ harvard.edu", "or" ] },{ "paper_id": "fe90da34ca7b4f7fd6711bd870cb2163b8fd4ef4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "i.e. Streptococcus pneumoniae (375), Enterococcus faecalis (240), Staphylococcus aureus (647) which may cause streptococcal pneumonia, meningitis, bacteremia, infectious lesions, neonatal infections and septicemia [64] [65] [66] .", "Relatively fewer Gram-positive bacteria were obtained from guano. The main genus among these is Staphylococcus. It included Staphylococcus aureus (a RG-2 organism), Staphylococcus nepalensis (13) and Staphylococcus lentus (49) , which are well-known to cause various infections in humans as well as in other animals 57, 58 . Therefore, it may pose a threat to the herds of sheep and goats grazing nearby bats' roosting sites.", "Both Citrobacter koseri (41) and Citrobacter freundii (29) are the opportunistic pathogens causing neonatal infections but the neonatal meningitis caused due to C. koseri have a high mortality rate 54 . Similarly, Serratia marcescens (24) is a common cause of nosocomial, urinary tract and wound infections 55, 56 ." ] },{ "paper_id": "fe954b75ed45c02d47090ee70d25c726b24b081c", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At the end of March 2009, an outbreak of novel influenza A (H1N1) (here after called A/H1N1) infection occurred in Mexico, followed by ongoing spread to all over the world in a short period [1] . On June 11 2009, the World Health Organization raised its pandemic alert level to the highest level, phase 6 [2] , meaning that the A/H1N1 flu had spread in more than two continents and reached pandemic proportions. As of June 13, 2010, it had caused over 18,172 deaths in more than 214 countries and overseas territories or communities [3] . Most illness, especially the severe illness and deaths, had occurred among healthy young adults, which was markedly different from the disease pattern seen during epidemics of seasonal influenza [4, 5] .", "This study was approved by the institutional review board of the Tongji Medical College of Huazhong University of Science and Technology. All respondents were informed consent. We respected their wishes whether to accept our survey and promised to protect their secrets." ] },{ "paper_id": "fe9776ca32f2901c58c1df81f6d9767803909869", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Each mosquito pool was subsequently homogenized in an appropriate amount (300-700 \u03bcl, depending on the number of individuals) of cooled minimal essential medium (MEM, Gibco by Life Technologies, Grand Island, USA) supplemented with Earle's salts, non-essential amino acids (NEAA, 1%, Gibco by Life Technologies), and antibiotics. Homogenization was performed using an automatic TissueLyser II (Qiagen, Redwood City, USA) and Tungsten Carbide Beads 3 mm (Qiagen) followed by centrifugation at 10,000 x g for 5 min. All mosquito suspensions were stored at -80\u00b0C until processed.", "The RT-PCR assays were carried out using One", "A total of 603 mosquitoes (when one egg raft was counted as one individual mosquito) were trapped in Vienna between 28 August and 10 September 2014, and assigned to 45 pools (Table 1) .", "The WNV positive samples were subjected to virus isolation attempts by intracerebral inoculation into suckling mouse brain (SMB), as described earlier [11] . The bacteriologically sterile SMB suspension (designated SMB 1 ) was subsequently used for differential inoculation of adult (5-6 week old) ICR female specific-pathogen-free (SPF) mice. They were injected with 1% infectious SMB 1 suspension intracerebrally (i.c., 0.04 ml, under anesthesia), 0.2 ml intraperitoneally (i.p.) and 0.2 ml subcutaneously (s.c.), respectively. Each of the three groups consisted of 4 mice." ] },{ "paper_id": "feaab7f92856f7b66f9e069f2686bc90660e9029", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Palmatine:", "Coptisine:", "Jatrorrhizine:" ] },{ "paper_id": "feb72aaab347ff388a21fc4d96575c5cbf29c020", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There were a higher proportion of cases with co-infections than controls, consistent with other reported results [17] .", "Clinical and demographic variables are presented as medians and interquartile ranges or percentages, Mann-Whitney U or chi-square tests were used for comparisons, as appropriate. Odds ratios and 95% confidence intervals (95% CI) were calculated to evaluate factors associated with death.", "Analyses were performed using SPSS (IBM, Armonk, NY, USA), version 17.0. P values of <0.05 were considered significant." ] },{ "paper_id": "feb7c5090a73fadeb2bde113221095746da8f12b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "(a) An improved paradigm: new models for supporting research and development of new therapeutics", "Three clinical trials have published their results. The Ebola Tx convalescent plasma trial demonstrated no overall survival benefit, although data on neutralizing antibody titres in this cohort are needed to determine if more targeted approach holds promise in the future [34] . A trial of TKM-130803 conducted in Sierra Leone found no survival benefit compared with historical controls [35] . Investigation of favipiravir determined that it was unlikely to be of benefit to patients with high viral load, but that further investigation is warranted in patients with less pronounced viraemia [36] . In addition, interim reporting of the ZMapp trial indicates no conclusion to date, but some promise [37] .", "Cite this article: Rojek AM, Horby PW. 2017 Offering patients more: how the West Africa Ebola outbreak can shape innovation in therapeutic research for emerging and epidemic infections. Phil. Trans. R. Soc. B 372: 20160294. http://dx.", "The lack of an available treatment for EVD, or at least a drug that was ready to go straight into patients enrolled in a clinical trial, at the beginning of the epidemic was a significant failure." ] },{ "paper_id": "fec3f745a9b28ad09219b8a5a83433af27cc5b01", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Additional file 1. Additional figures.", "GraphPad Prism 6.0 (GraphPad Software, Inc., La Jolla, CA, USA) was used for all univariate statistical analyses. The date of neutralization activity was presented as the mean value \u00b1 SEMs and analyzed by Student's t-test. *P values < 0.05 were considered to be significant.", "Input (clones) Output (clones) Enriching factor a 1 5 \u00d7 10 9 1 \u00d7 10 6 2 \u00d7 10 \u22124 2 5 \u00d7 10 9 6 \u00d7 10 7 1.2 \u00d7 10 \u22122 3 5 \u00d7 10 9 3 \u00d7 10 7 6 \u00d7 10 \u22123" ] },{ "paper_id": "fec800677847384e7ac7f2bc3164762e729360f2", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All of the analyses were conducted in R software version 2.5.1. The significance level was set to 0.05 for all analyses.", "Subset analysis with peaks seasons only, or vaccine matched years only, generally derived larger RR estimates ( Table 3 ). The estimates for CRD became significantly higher than one, and the Brisbane estimates were much greater than the Hong Kong ones. Many outcomes could not be estimated due to negative values of excess rates.", "We also conducted a subset analysis by using the data of influenza peak seasons only. The influenza season was defined as January to July in Hong Kong, and May to November in Brisbane. We conducted another subset analysis by excluding the data for the mismatched years (2003, 2004, and 2008 in this study)." ] },{ "paper_id": "feccc27dc3c4100c8080abda883969ec979956c9", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "To validate CRCM4.2.3 temperature output used in modelling R 0 , and to compare with an ensemble of climate models (Table S3) , we compared DD > 0\u00b0C output from the models with observed (ANUSPLIN)", "Daily maximum temperature (\u00b0C) Figure S4 . Daily normal of ANUSPLIN daily maximum temperatures for each cluster for the period 1971 to 2010.", "Local sensitivity analysis was used to quantify the impact of variation of individual parameters on estimated R 0 (Benton and Grant 1999) . Local sensitivity analyses were performed for data from one site of each of the five Canadian clusters: Point Pelee, London, Wiarton, Hemmingford and Timmins. All parameters were varied one at a time by 5% (above and below baseline values, with all other parameter values set at baseline values) and 3-year mean R 0 values for each site for each year from 1972 to 2069 7 were obtained. A comparative index S i was used to assess the sensitivity of the change in R 0 , from one time slice to another, to a 5% change in the i th parameter:" ] },{ "paper_id": "fed1fd6ad6a0fff6d3532a8b13f12f25347928b7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Despite the limitations, the findings of this study provide a recommendation for policymakers to promote bonding social capital and linking social capital as crucial for resolving health emergencies and other situations that place the citizenry at risk. The study results indicate the critical role that local, interpersonal networks play in enhancing communication platforms and in augmenting government credibility if a country is to mount a viable defense against a future influenza pandemic.", "Since the outbreak of severe acute respiratory syndrome (SARS) in 2003, the World Health Organization (WHO) has urged countries to prepare for a possible, future influenza pandemic [1] . In June 2009, the WHO declared the first influenza pandemic, influenza A/H1N1, of the past 40 years [2] . By August of 2010, an estimated 18,449 deaths in 214 countries were due to this disease [3] . Scientists are concerned that the number of viral outbreaks will increase in the future as worldwide populations become more dense and mobile. Furthermore, habitat loss due to deforestation may cause pathogen-carrying animals to migrate closer to human settlements, which could lead to virus mutation and outbreaks of influenza pandemic [4] .", "This study examined construct validity through an exploratory factor analysis on all of the social-capital variables. This analysis showed that each variable fits well under presumed dimensions and that there are significant relationships existing between the variables and the concepts. Many variables were also found to have significant relationships with the theoretical concepts of previous studies and, thus, to have construct validity. The variables on membership of organizations were positively correlated with self-rated health [26] . The variables regarding contacts with neighbors and government trust were positively related to individual health and status-based sociable resources (i.e., income) [27, 28] ." ] },{ "paper_id": "fed39ba33ece570bf3f7e8879cf448bf93cd069e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "1. Lagos, Nigeria on 20 July 2014 (t 1 ); 2. Dallas, USA on 19 September 2014 (t 2 ).", "; m :", "Solving these differential equations gives In summary, we infer (\u03bb,i 0 ,\u03b8 before ,\u03b8 after ) using the likelihood L \u03bb; i 0 ; \u03b8 before ; \u03b8 after \u00f0 \u00de \u00bc L inc \u03bb; i 0 ; \u03b8 before ; \u03b8 after \u00f0 \u00de L export \u03bb; i 0 \u00f0 \u00de:", "The WAN model: We combine our OAG data with the GPWv4 data to calculate the population size of the catchment area of each airport as follows:", "which is congruent with the EAT statistic in Gautreau et al. 18 for estimating the order of epidemic arrival across different populations. The expected time of the nth exportation is given by" ] },{ "paper_id": "fee63d10e8db56b72c9385149a4e57afa8500981", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "However, the FIP cats were identified with a higher frequency as carrying more than one FIP-susceptible SNP (50.7%) than the control cats (29.0%), showing a significant association with disease susceptibility (P = 0.0059, OR = 2.51) ( Table 4 ).", "Samples were collected from 71 FIP cats and 93 FCoVinfected asymptomatic cats from 2005 to 2014 at the National Taiwan University Animal Hospital for an association analysis. This study required no specific ethical approval, as the analysis was performed retrospectively from samples of diseased animals routinely submitted to our diagnostic laboratory.", "Several pedigreed cats, including Abyssinians, Himalayans, Birmans, Bengals, Ragdolls, and Rexes, were reported to have a higher incidence of FIP than other breed cats [2] . Recently, a genome-wide association study of Danish and American Birman cats populations identified five SNPs involved in FIP susceptibility [20] . However, none of these SNPs showed a similar correlation in the present study, concordant with the postulation by the authors that these associations might only be relevant to Birman breed or other breeds with similar genetic traits [24] ." ] },{ "paper_id": "feeef400771697981198a218da58c34ebb7963a0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Sequence data for P. cristatus has been deposited in Short Read Archive under project number SRP083005 (BioProject accession: PRJNA040135, Biosample accession: SAMN05660020) and accession codes: SRR4068853 and SRR4068854. We have provided the draft genome assembly, assembly statistics, gene-set and their annotations, alignments, and individual gene tress at our web server 1 . This data is publicly available for download with proper citation as mentioned on the web page.", "total, there are three tree topologies possible with respect to the three taxa:", "(t1) ((Ficedula,Taeniopygia), Anas, (Meleagris, (Gallus, Pavo))); (t2) ((Ficedula,Taeniopygia), Anas, (Gallus, (Meleagris, Pavo))); (t3) ((Ficedula,Taeniopygia), Anas, (Pavo, (Gallus, Meleagris)))." ] },{ "paper_id": "fef1b7df61f24d4ef20baa830f7b89ad75495e40", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Data was entered in Microsoft Excel 2013\u00ae (Microsoft Corp., Redmond, WA, USA), and analyses were conducted in R 3.2.5 [29] .", "Network terminology and metrics are defined in Table 1 ." ] },{ "paper_id": "ff026fb53971d5bfa70c0b9b017d011cc7deee0e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Chemicals and materials. 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) was purchased from Chembridge (ID: 5570320, San Diego, CA, USA). Ricin for screening, animal experiments and for in vitro validations was supplied by Bruno Beaumelle 14 . Toxin B (TcdB) was produced from Clostridium difficile VPI10463, lethal toxin (TcsL) was produced from Clostridium sordellii IP82 49 and anthrax toxin were produced and purified as described previously 50 .", "The following products were purchased from the indicated commercial sources: [ 14 C]-leucine (Perkin-Elmer); Stx-2 (List Lab, USA); DMSO (D4540), diphtheria toxin DT (D0564), bafilomycin A1 (B1793), Hoechst 33342 (14533), filipin III (F4767), Acridine Orange (A6014), gelatin (G7765) were purchased from Sigma. The following commercial antibodies were used in this study: rabbit anti-Rab7 (ab137029) were from Abcam; Rabbit anti-Rab7 (D95F2) (#9367), rabbit anti-EEA1 (#3288) were from Cell Signaling, Rabbit anti-Lamp1 (L1418) and mouse anti-beta-actin (A2228) from Sigma-Aldrich; rabbit anti-MEK2 (N-20, sc-524), mouse anti-chlamydial SCIENTIFIC REPORTS | 7: 15567 | DOI:10.1038/s41598-017-15466-7 trachomatis HSP60 protein (clone A57-B9, sc-57840) from Santa Cruz Technologies; mouse anti-SNAP-25 (SMI-81, 836304) from Biolegend; mouse anti-RNP (ribonucleoprotein) conjugated with FITC from Fujirebio; Alexa 488-donkey anti-rabbit (A10042), Alexa 546-donkey anti-mouse (A10036) and LysoTracker Deep Red (L12492) were from ThermoFisher Scientific." ] },{ "paper_id": "ff03bab2cb87384f817f827dd9331ac2d3cea67d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "LLC porcine kidney cells (LLC-PK) were maintained in DMEM supplemented with 10% fetal bovine serum (FBS) (PAN, Germany) and 1% antibiotic-antimycotic at 37 \u2022 C in a humidified atmosphere of 5% CO 2 . The rabbit anti-PDCoV N monoclonal antibody was prepared in our laboratory. FITC-conjugated goat anti-rabbit IgG was purchased from Bioss.", "The experiments were performed in triplicate. Data are shown as the mean \u00b1 standard deviation (SD). A one-way ANOVA test was used to measure significant differences between groups. p values < 0.05 were considered statistically significant." ] },{ "paper_id": "ff09007b2973bf3dc9a0435228a1b220587763da", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "At least two members of the selection committee reviewed each article identified, writing a summary and providing a score on a scale of 30. There were no a priori guidelines on how to score. Reviewers sought to identify those reports that demonstrated readability for a broad audience, and were both innovative and relevant with the potential to make a significant impact on health. The process resulted in three articles rising above the rest. These \"finalists\" were then ranked in order by each committee member, the synthesis of which resulted in selection of the article which would receive the honors, 3 which were presented at the 2018 Annual Meeting. 4 ", "Finally, the importance of assessing cost-effectiveness and opportunity cost was apparent from the selected literature. Just because we can do something does not mean that we should-perhaps greater impact may be found elsewhere. One of the articles nicely described why diverting resources to extend the current 80% coverage of the intervention to 90% would not meaningfully decrease overall prevalence of the targeted disease. Instead, the resources could potentially make more significant health improvements if allocated to other areas. 9 ", "* Ultimate selection. \u2020 Three finalists." ] },{ "paper_id": "ff218f343fbca258501ba42368ecbb57660e5a8f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The teicoplanin analogue LCTA-949 ( Figure 1 ) was synthesized as reported elsewhere [9] . Ribavirin [1-(b-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide (Virazole; RBV)] was purchased from ICN Pharmaceuticals (Costa Mesa, CA).", "Thus, LCTA-949 interferes with the earliest stages of the viral replication cycle.", "The lipophilic fluorescent probe 1,19-dioctadecyl-3,3,39,39tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate salt (DiD) (Molecular Probes, Eugene, OR) was used to label the viral membrane of DENV-2 virus particles, as previously described [29] . In brief, DENV-2 16681 wild type virus was propagated in C6/36 cells and harvested at 3 days p.i. Subsequently, the virus was purified on a potassium-tartrate density gradient (10 to 35%, wt/vol) by ultracentrifugation (Beckman type SW41 rotor, 2 h, 125,0006 g, 4uC) and stored at 280uC. Virus preparations were analyzed with respect to the infectious titer (PFUs) and the number of genome-containing particles (GCPs), as described before [29] . Before labeling, tartrate was cleared by using a 100 kDa filter device (Millipore, The Netherlands). While vortexing, approximately 10 10 GCPs of virus (equivalent to ,10 8 PFUs) was mixed with 2 nmol DiD dissolved in dimethyl sulfoxide (DMSO) with an end concentration of DMSO of ,2.0%. To remove unbound dye, the DiD-labeled virus was filtered with a Sephadex G-50 Fine (Pharmacia, Uppsala, Sweden) column prepared in a glass pasteur pipette. Different fractions were collected, stored at 4uC and used within 2 days.", "Glycopeptide antibiotics (i.e. teicoplanin, eremomycin and vancomycin) are used for the treatment of gram-positive bacterial infections. Synthetically modified glycopeptide antibiotics (SGPAs) have been reported to be endowed with in vitro antiviral activity against retro-and corona viruses [7, 8] . For human immunodeficiency virus (HIV) it was shown that semisynthetic glycopeptide aglycons potentially interfere with the viral entry process [9] . The mechanism by which deglycosylated SGPAs exert antiviral activity against other viruses remains unclear.", "The genus flavivirus (family Flaviviridae) comprises several pathogens, including dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), tick-borne encephalitis virus (TBEV) and Japanese encephalitis virus (JEV). Flaviviruses that are pathogenic to man are transmitted to humans by bites of mosquitoes or ticks [1] . The incidence and geographical distribution of the four distinct DENV serotypes and its vector are increasing dramatically. DENV causes more than 50 million infections annually (mainly in South-East Asia and Latin America) and infections with this virus may develop into dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) [2] [3] [4] . Increased disease severity has been associated with pre-existing heterologous DENV antibodies, a phenomenon described as antibody-dependent enhancement (ADE) of infection. Antibodies have been found to enhance viral entry into Fc-c-receptor-bearing cells and to alter the antiviral immune response, leading to increased virus particle production and subsequent immune activation. During homologous re-infection, antibodies are believed to neutralize the infecting virus and provide life-long protection against disease development. Intriguingly, however, during heterologous re-infection, cross-reactive antibodies have been implicated to enhance viral replication leading to a higher infected cell mass and increased viral burden. There is neither a vaccine nor a specific antiviral therapy available [3] . This is also the case for YFV that, together with DENV, is a leading cause of hemorrhagic fever worldwide, although a highly efficacious vaccine is available [5] . Furthermore, vector-control strategies that were once successful in eliminating YFV have faltered, thereby leading to a re-emergence of the disease [5] . The World Health Organization currently estimates that there are 200,000 cases of yellow fever annually of which over 90% occur in Africa, resulting in about 30,000 deaths per year [6] . There is, as is the case for most of the other flaviviruses, no antiviral drug available for the treatment of YFV infections." ] },{ "paper_id": "ff220214e91fabc8d302d1605cd9bac44fac507f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Two independent investigators (YNN and BML) reviewed all titles and abstracts to discard duplicated and non-controlled studies. Then, the full texts of the remaining studies were screened in accordance with previously designed study inclusion criteria to determine eligibility. Disagreements were resolved by a third investigator (ZAL).", "To ascertain quality, a maximum of nine points was assigned to each study: four for selection, two for comparability, and three for outcomes. A composite score > 6 was regarded as indicative of high quality. Two studies were rated a total score of 9, four studies had a score of 7, and four studies had a score of 6 ( Table 3 ). The funnel plots showed no evidence of publication bias.", "Trial registration: PROSPERO (ID: CRD42018112384).", "If any of the abovementioned information was not included in a publication, we contacted the corresponding authors by email to obtain the data needed to quantify the measures of association. When the opinions of the two collectors differed, a decision was reached by consensus or consultation with a third investigator." ] },{ "paper_id": "ff2a6501716b8ff2b5e96ef3034f15309ce90c43", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "2. An elementary adapted SIR indirectly transmitted iteration", "From this perspective, one can observe how a characteristic feature of the epidemic is modified by indirect transmission.", "(3:8)" ] },{ "paper_id": "ff2b36ea32d849a577ae66637bbe359f108f35d8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "a1111111111 a1111111111 a1111111111 a1111111111 a1111111111", "DF is an important public health problem, especially in urban areas [3] , where it usually presents in large outbreak. The costs of treatment and management during a DF outbreak are a serious burden for health systems, especially when there is a risk for saturation of health facilities [4] .", "ArcGIS ArcINFO 10 was used for processing and analyzing spatial data, SQL server was used to create a Geodatabase, Arc SDE 10 was used as interpreter between entre SQL and ARCGIS. Statistical analyses were performed using STATA 12.", "The protocol of the project was reviewed and approved by the Comit\u00e9 de Etica y de Prevenci\u00f3n de Conflictos de Interes (Institutional Review Board) CI 1046 No 1160 and Departamento de Investigaci\u00f3n (External Review) Servicios de Salud de Morelos, Mexico DEI/CEI/0281/2012." ] },{ "paper_id": "ff449311692ce29ca9d598747ab871602adb297f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Scientific RepoRts | 7:45922 | DOI: 10.1038/srep45922", "Results" ] },{ "paper_id": "ff4fffe02138b0b232334d997965d11fd936916b", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The Kathmandu Valley is situated at an altitude of 1,300 to 1,350 meters above sea level and has a sub-tropical, temperate climate. There are four distinct seasons; premonsoon/spring (March to May), monsoon/summer (June to September), post-monsoon/autumn (October to November) and winter (December to February) [18] . Temperatures may rise to 35\u00b0C in summer, while minimum temperatures can fall to 0\u00b0C in winter.", "Three hundred and twenty-four NPA aliquots were stored beyond 3 months at 2 to 8\u00b0C before analysis in Nepal. Of these, we re-analyzed the 133 that yielded a negative result, now using the aliquot that had been frozen at -70\u00b0C and transported on dry ice to Norway. This was done at the Department of Microbiology and Infection Control, University Hospital of North Norway, Troms\u00f8, Norway, using the Hexaplex Plus assay and an automated extraction platform (NucliSens \u00ae easyMAG, bioM\u00e9rieux, Durham, NC, USA). Nucleic acids were extracted from 400 \u03bcl of sample, negative and positive processing controls and amplification control using the extraction principle with magnetic particles of this platform." ] },{ "paper_id": "ff59f8566e5916d6f252eee6835b820a799642e7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The peripheral blood IgM + /IgD + /CD27 + Bmem correspond to circulating splenic marginal zone B cells and contribute to protection against blood-borne T-independent pathogens (15, 21) . Pneumococcal polysaccharide-specific IgM + /IgD + /CD27 + Bmem displayed somatic mutations when isolated post immunization with a T-independent vaccine (Pneumovax) (22) . A vesicular stomatitis virus-Ebola vaccine generated a neutralizing IgM response that persisted despite administration of a booster vaccine (23) . These studies point to a previously under-appreciated contribution of hyper-mutated IgM + Bmem to protection against pathogens.", "HS, KS, JW, CW, JB, RB, JJ, and ML contributed to the writing and editing of this review article.", "Considering the knowledge and tools available to us, the goal of developing precise and personalized therapeutics is coming closer to fruition." ] },{ "paper_id": "ff6b55c00278cf8081dec1ad430940165b23d91e", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Background: We describe human rhinovirus (HRV) detections in SaKaeo province, Thailand.", "All participants were informed of the study objectives and written consent was obtained. This study protocol was reviewed and approved by the Centers for Disease Control and Prevention (CDC) Internal Review Board and the Thailand Ministry of Public Health Internal Review Board." ] },{ "paper_id": "ff6ee9512267f847d91a0185e794ac98f15fe5d0", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Knock-in of pPL2 derivative plasmids was performed by standard methods [41] . Briefly, constructed pPL2 plasmids were transformed into chemically competent SM10 E. coli, selecting on chloramphenicol. Donor SM10 and recipient L. monocytogenes were mixed at a 1:1 ratio on a non-selective BHI plate at 37\u00b0C for 4-24 hours, then trans-conjugation was selected for by plating bacteria on BHI containing streptomycin plus either chloramphenicol (pPL2), erythromycin (pPL2e), or tetracycline (pPL2t). Single colonies were re-streaked for purifying selection onto BHI containing the same antibiotics as used after trans-conjugation.", "YjbH, Spx, OhrA, and GshF have defined roles in maintaining redox homeostasis in the presence of disulfide and organic peroxide stresses in Firmicutes. In B. subtilis OhrA is a peroxiredoxin required during organic hydroperoxide stress [32] . In S. aureus and B. subtilis YjbH interacts with Spx to regulate the abundance and activity of Spx [28, 31] . Specifically, YjbHbound Spx is recognized by the ClpXP protease and is degraded so that Spx concentrations are low under steady-state conditions [42, 43] . During disulfide stress the YjbH:Spx interaction is disrupted by intramolecular disulfide bonds in both proteins that result in reduced proteolysis of Spx. B. subtilis Spx represses transcription of 176 genes and activates transcription of 106 genes [44] , the majority of which are required to adapt to redox stress, including genes for production of the low-molecular weight (LMW) thiol utilized by B. subtilis, bacillithiol [45] . L. monocytogenes spxA1 cannot be deleted and its regulon has not yet been characterized [23] . Similarly, in Streptococcus pneumoniae simultaneous deletion of both spxA1 and spxA2 paralogues is lethal [46] , supporting the notion that the Spx regulon(s) may contain essential genes in some Firmicutes." ] },{ "paper_id": "ff6f7ec41fcfb1353aea25253c33ae25469f6a07", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "In information provided to donors, NHS Blood and Transplant explains how plasma is used but does not make it clear either that no plasma from UK donors is used in fractionation or that its 'male preference policy' operates in a way where women's plasma is seldom used at all:", "While many national blood services are founded on voluntary unremunerated donation, closer analysis of the literature reveals how, within transfusion science and blood policies, categories of donor and recipient bodies construct moral hierarchies and scales of exchange and use value which have excluded MSM and migrants as donors, and segregated blood along racial lines in some countries (Bekker and Wood, 2006; Martucci, 2010; Starr, 1998; Valentine, 2005) . Polonsky et al. say:", "Transfusion science is a discourse or truth regime which creates and translates rules into clinical practices and industry standards in blood services. It underpins not only the organisation and delivery of such services but also the global plasma products industry. Gendered bodies are both naturalised and made invisible in a discourse which draws heavily on universalising myths that seek to value blood and plasma donation as a social and public good, and ties donation to citizenship and social solidarity. It also assumes that bioavailability (Cohen, 2005) has equalising effects whereby all donations are equally valued, despite evidence to the contrary which we will discuss in more detail later.", "Transfusion science draws on a set of rationalities about the immune system which have emerged within a specifically gendered historical context (Haraway, 1995) . The biomedical body was conventionally seen to represent the nation-state and invading organisms as foreigners. More recently, scientific and cultural understandings see the immune system as a complex networked system (Martin, 1994) . Within this framework, maternal bodies, in particular, are often represented as paradoxical and explanations about why the genetically distinct fetus is not rejected by the mother have provoked considerable debate and stimulated a long history of investigation. In pregnancy the fetal and maternal circulations have increasingly been understood as closely interconnected. Maternal fetal microchimerism refers to the mixing of cells from the maternal and fetal body (Kelly, 2012; Martin, 2010) and placental 'border crossings' which may provoke an immunological response. Kelly's (2012) account of the emergence of gestational cell transfer science and understandings of maternal-fetal microchimerism reveals the extent of scientific uncertainty about the significance and meaning of these exchanges. While previously thought to be pathological, fetal cells entering the maternal circulation have more recently been considered normal." ] },{ "paper_id": "ff76f00bf68006acc97c8720dd4f11e69d17c272", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ff77d5ebc39274bb7729f2b5261bca574bdfd6a8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Coronaviruses are ubiquitous in the environment, and they infect various animal species causing lesions of varying severity in different organs [1, 2] . The virions of coronaviruses are enveloped, roughly spherical particles that possess a linear, nonsegmented, positive-sense RNA genome of up to 32 kb [2, 3] , which is the largest genome among all known RNA viruses.", "Specimens positive for HCoV-OC43 were tested for coinfection with other respiratory viruses, including HCoV-229E, HCoV-NL63, HCoV-HKU1, Flu A and B (influenza A and B viruses, respectively), PIV 1, 2, 3 (parainfluenza virus types 1, 2 and 3, respectively), RSV (respiratory syncytial virus), hMPV (human metapneumovirus), adenovirus and picornaviruses (including enterovirus and rhinovirus), as described previously [30, 35] .", "Amino acid alignments of partial S and N protein sequences were performed using the BioEdit Sequence Alignment Editor and GeneDoc software (http://www.nrbsc.org/gfx/genedoc)." ] },{ "paper_id": "ff78beee1e6b1052a3578f330c8f820c60411340", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Tissues were fixed in 10% neutral phosphate buffered formalin, routinely processed, sectioned at 5 \u00b5m and stained with hematoxylin and eosin (HE) for histopathologic examination. For immunohistochemistry (IHC), paraffin tissue sections were quenched for 10 minutes in aqueous 3% hydrogen peroxide. Epitopes were retrieved using Dako Target Retrieval solution (Dako, USA) in a Biocare Medical Decloaking Chamber. The primary antibody applied to the sections was a mouse monoclonal anti-Ebola Sudan (F344G5). It was used at a 1:800 dilution for thirty minutes. They were then visualized using a horse radish peroxidase labelled polymer, Envision\u00ae + system (anti-mouse) (Dako, USA) and reacted with the chromogen diaminobenzidine (DAB). The sections were then counter stained with Gill's hematoxylin. ", "CV-1 cells were grown to 95% confluence and infected with 10-fold serial dilutions of whole blood for 1 h at 37\u00b0C. The inoculum was then removed, and cells were overlaid with fresh MEM plus 2% FBS. At 14 days postinfection, the plates were assessed for the lowest dilution at which 50% of the wells exhibited cytopathology. TCID 50 per milliliter was calculated according to the Reed-Muench method.", "However, a better strategy would be to screen candidate drugs in immunocompetent small animals using wild-type SUDV to avoid the need to develop rodentadapted models, before progression to studies in NHPs. Ferrets and pigs initially emerged as excellent models of human respiratory diseases as their lung physiology closely mimics that of humans. Interestingly, among characterization of many respiratory virus infections such as various influenza strains [8] , respiratory syncytial virus [9] , Nipah virus [10] , and coronaviruses [11] , other viruses have also recently been tested in ferrets including hepatitis E [12] , and three species of ebolavirus [13] [14] .", "Nonhuman primates (NHP) most closely mimic clinical manifestations of filovirus infections in humans and have provided invaluable insight into the pathogenesis and course of filovirus disease. Yet due to ethical, cost and space restraints that accompany NHP studies, smaller animal models such as mice or guinea pigs are typically the first choice for initial filovirus drug, vaccine and pathogenesis studies. Although wild-type filoviruses do not cause significant disease in adult, immunocompetent rodents, these viruses have been adapted to rodents so that virulence and lethality are observed [3] [4] [5] . Even though these rodent models do not reproduce all hallmark clinical signs of filovirus disease, their relative ease-ofuse and low cost make them attractive first options for evaluating anti-viral prophylactics and therapeutics." ] },{ "paper_id": "ff7bf5c8a285587c9e39f4acacd57aee0aa77981", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The gating strategy for immune cell populations is described in Supplementary Figures S1, S2.", "All values are expressed as the mean of each cohort, and the error bar indicates the standard deviation (SD). Student's t-test was used when comparing two groups. One-way analysis of variance (ANOVA) with Dunnett's correction was performed for comparing more than two groups. A P < 0.05 was considered statistically significant.", "This work was supported by grants from the Ministry of Health and Welfare (HI13C0826) and the Ministry of Agriculture, Food and Rural Affairs (MAFRA; 716002-7) of the Korean Government.", "YL, JL, and BS designed the study, analyzed the data, and wrote the manuscript; YL and JL conducted the research study; YJ and S-US provided technical assistance about CAIV and KO mice, respectively; JC provided the scientific advice about RSV infection and protection; BS supervised all the experiments as well as the preparation of the manuscript." ] },{ "paper_id": "ff7d7dea55e89908b0a3935c6e5ce52cd8a165b4", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Exosome concentrations were indirectly measured by protein quantification in a Bradford assay. To quantify protein concentration, 20 \u00b5L of exosomes sample were incubated with 180 \u00b5L of Bradford reagent (Bio Rad Laboratories, Hercules, CA) at RT. Absorbance was read 5 min after at 595 nm, and protein concentration was extrapolated from a standard concentration curve of Bovine Serum Albumin.", "We thank Debjani Roy (TiGenix NV) for review of the manuscript. Ramon Menta, Borja del Rio and Cristina Ramirez (TiGenix S.A.U.) for technical assistance. Raquel Tarazona is a member of Inmunopatolog\u00eda Tumoral research group (CCV005). This work was supported in part by a grant to Rebeca Blazquez (TE12066), Javier G. Casado (TA13042), and a project to Javier G. Casado (IB13123) from GobEx cofinanced by FSE.", "Supporting this idea, previous reports have demonstrated that the immunomodulatory capacity of MSCs against NK cells (19, 20) , cytotoxic T lymphocytes (21) , \u03b3\u03b4 T cells (22) , dendritic cells (23, 24) , or invariant NKT cells (25) is mediated by a paracrine mechanism.", "Data were statistically analyzed using the Student's t -test for variables with parametric distribution. For the proliferation assay, an ANOVA with post hoc Bonferroni test was performed. The p-values \u22640.10 or \u22640.05 were considered statistically significant. All the statistical determinations were made using SPSS-21 software (SPSS, Chicago, IL, USA)." ] },{ "paper_id": "ff81f65bce47ed0a1a6e586dc196c6543e97d861", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Michael acceptors are present in other classes of drugs. Examples of such drugs are entacapone (antiparkinsonic) [7] , dimethyl fumarate (antipsoriatic; since 2013 used in treatment of multiple sclerosis) [5] , rupintivir (experimental antiviral drug against human rhinoviruses) [8] , exemestane (cytostatic) [9] , and ethacrynic acid (diuretic) [10] .", "Carboxylic acids 3a,b were prepared by hydrolysis of esters 2a,b with lithium hydroxide following the previously described procedure [29] .", "Michael acceptors have been explored in a prodrug strategy for cancer cell-specific targeting. In the review published by Zhang et al., two doxorubicin prodrugs with maleimide moieties have been described [6] . The maleimide component is responsible for the binding to human serum albumin. Once the drug carrier arrives at the targeted cancer tissue, doxorubicin is released from the carrier by the cleavage of hydrazone or glycosidic bond in the acidic environment of cancer cells. The prodrugs demonstrate superior anticancer efficacy than the parent drug." ] },{ "paper_id": "ff983b21fe80f1f3bf064a3cbc564b63111cadf5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Following the global influenza pandemic caused by the novel influenza A virus in 2009 (H1N1-2009), the world continues to be threatened by emerging respiratory diseases such as the Middle East Respiratory Syndrome (MERS) in 2012 and Avian Influenza A (H7N9) in 2013 [1, 2] . The onset of MERS and H7N9 infections in humans are typically characterized by high fever (\u2265 38\u00b0C) and cough, and can lead to progressive pneumonia, respiratory failure and death, contributing to case fatality rates of 35% and 19% respectively at the time when this study was performed [2] [3] [4] .", "As the study population was partially recruited through opportunistic sampling of members in the same households, all logistic and linear regression analysis used a multilevel mixed-effects model with a random intercept to adjust for effects observed due to potential household clustering. Statistical significance was considered at P < 0.05 for all analyses.", "Moving forward, the study proposes that a concerted effort be orchestrated between the media and health authorities, to seamlessly communicate information through news articles about specific preventive measures the public can take to protect themselves during outbreaks. Future surveys should try to understand how local communities network and communicate and the barriers and facilitators for individuals to take action in the event of an outbreak. More studies should also be done to analyse the effectiveness of tailored messages. Qualitative studies in the form of focus groups may be useful to pre-test and assess the responses of multi-cultural audiences regarding uptake of information. This will benefit the design of health communications during early stages of development. Additionally, in-depth interviews can also be employed to elicit personal responses and concerns of the messages, for individuals who may be difficult to reach, particularly vulnerable groups who have limited writing and reading skills. " ] },{ "paper_id": "ff986fb85af07d524411d6eb829e38be349df839", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Generously allowed region 5.2" ] },{ "paper_id": "ff9d9713206da30022af4f9095058368eeb1f3f8", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ffaa82089f00d6e0b4710f59b4016c59c5879ea7", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Other laboratory parameters (e.g., liver enzymes, bilirubin, urea, and creatinine) can be variably increased, depending on the degree and localization of organ damage, but they are not helpful in making an aetiological diagnosis [15, 27, 38] .", "The virus can be detected in various tissues and ascitic fluid [50, 56, 60, 61] . Liver (48%) and spleen (42.3%) samples appear more likely to contain detectable FCoV than the kidneys (21.1%). In addition, the amounts of RNA extracted from fresh tissues were significantly higher than from tissue fixed in formalin, ethanol or Bouin's solution [61] .", "The order of the genes encoding the viral polymerase (Pol) and the four structural proteins (the spike, envelope, membrane, and nucleocapsid proteins) is 5 -Pol-S-E-M-N-3 . These genes are present in all coronaviruses. The feline coronavirus genome also includes additional genes (3a, 3b, 3c, 7a, and 7b) that encode nonstructural proteins. The functions of these gene products are not fully understood [2] .", "Veterinary Medicine International 5 Figure 6 : Kidney of a cat with FIP. Severe degenerative and advanced necrotic changes within the lining endothelium of the convoluted tubules (mostly cytoplasmolysis). Frank patchy interstitial nephritis, as indicated by the heavy infiltration of lymphocytes, plasma cells and some dead neutrophils, together with dilatation and congestion of the interstitial blood vessels. The photograph was kindly provided by Dr. Diane Addie." ] },{ "paper_id": "ffb147f62b6570ee48fa765305c24ebcc8e4912f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We have isolated a novel lectin, named HRL40 from the green alga Halimeda renschii.", "In recent decades, the molecular structures, oligosaccharide-binding specificity, and biological activities of hemagglutinins from marine algae (Rhodophyta and Chlorophyta) have extensively been", "Protein content was determined by A 280 , presuming that a protein concentration of 1 mg/mL gives A 280 of 1.0, or by the Pierce BCA Protein Assay Kit (Thermo Fisher Scientific, Rockford, IL, USA) using bovine serum albumin as a standard." ] },{ "paper_id": "ffba0e28de0ad62150f452c30641548e56503bb1", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Observed risk index Reporting bias", "Code availability. All data and code used to generate the models are available on GitHub (doi: 10.5281/zenodo.400978) 65 , as is the code used to generate the reporting effort layer (doi: 10.5281/zenodo.400977) 66 .", "Received: 1 June 2016 Accepted: 7 August 2017" ] },{ "paper_id": "ffbe34e6cdad2e0807c420ddee33b842e38e219d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ffcc037270daaf7a3c1869c957f412948e45de17", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ffd640ccc48cf505cf385e2a7ab7d2720e3ec427", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Rickettsia rickettsii causes Rocky Mountain spotted fever and spreads to humans by ticks. The signs of this disease are fever, headache, muscle pain, and spots with very dark rash. Hiking in an area with many infested ticks is a great risk factor. A tick bite of <20 h is usually not enough to transfer these bacteria to a person (77) .", "Ehrlichiosis (Anaplasma phagocytophilum) and Lyme disease (Borrelia burgdorferi) have emerged as an important vector-borne zoonotic disease since 1980s (78, 79) . Hard ticks are principal vectors, whereas small rodents are known as their natural vertebrate reservoir. A wide variety of signs including rash, joint pains, fever, enlarged lymph nodes, and some neurological signs may www.frontiersin.org develop. The trend of house buildings in woodlots where humans share the same ecology with reservoirs and vectors was found to be correlated with the increased frequency of such diseases in humans (79) .", "Companion animals are increasingly treated as family members, and pets have many bacteria that may infect their owners. The human population of the European Union (EU) was approximately 500 million 1 in 2012. The number of pet owning households was estimated at around 70 million in 2010 2 ." ] },{ "paper_id": "ffd791c34aa1431d8571663c1fa722086d0ad90f", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ffe04775867d268ef18a29f13138e407b6aa8ea5", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "All statistical analyses were performed using Stata V9.0 (Stata Corp, Tex) for Windows, with the level of significance set at 5%." ] },{ "paper_id": "ffe3b2ad5b565d38aebab45629d4329fe8bf4e02", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "For visualization of viral particles cells grown in a 25 cm 2 flask were fixed with glutaraldehyde (final concentration 2.5%) over night at 4\u00b0C as soon as a CPE became visible. Photographic documentation of samples was performed on a FEI Tecnai G2 transmission electron microscope (TEM).", "The study shows the presence of a coltivirus-related virus in bats from Sub-Sahara Africa. Serological studies could help to assess its impact on humans or wildlife health." ] },{ "paper_id": "ffe663e4ef5018da41f057533520b9d85ec86e18", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "references of all retrieved studies and reviews to identify any additional studies. We considered full text articles published in any language. We did not consider abstracts or other material presented at medical conferences or unpublished data. The research and ethics committee of our institution waived the need for patient-level consent for this study as only aggregate and previously published data was collected.", "Data Sources" ] },{ "paper_id": "ffe7169e14eea9af001ae388632123d43eeb9697", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "Experiments were performed in triplicate and results were expressed as mean \u00b1 standard deviation (SD). After verification of the normal distribution of data, 2-way ANOVA was used. Tukey's test (for pairwise comparisons of the means) was used to test for differences between the groups. Differences were considered significant at p<0.05.", "Acute lower respiratory tract infections are a persistent public health problem. Despite the remarkable advances in antibiotic therapies, diagnostic tools, prevention campaigns and intensive care, respiratory infections are still among the primary causes of death worldwide, and there have been no significant changes in mortality in the last decades [1] . Childhood acute community-acquired pneumonia is one of the leading causes of morbidity and mortality in developing countries. In children who have not received prior antibiotic therapy, the main bacterial causes of clinical pneumonia in developing countries are Streptococcus pneumoniae and Haemophilus influenzae type b, and the main viral cause is the respiratory syncytial virus [2] ." ] },{ "paper_id": "ffee1423c1320d7070fe9a871224a468768a4c10", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [] },{ "paper_id": "ffef8194e52de95fe345db7dd12fe3185d786978", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "We ran the GABranch analysis on the sequence alignments of predicted binding regions from each HLA allele.", "may have caused positive selection on only a few sites. Such selection is hard to detect because \u03c9 is averaged over all sites of the sequence. Selection may also have been weak due to the fact that this is a rare HLA allele (1%) [42] ." ] },{ "paper_id": "fff1e7b356f0d6cf7b28b019974833200e38f843", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "There are several limitations in the present study. The case numbers are not large enough to represent general population. Furthermore, we conduct a retrospective study;", "While comparing with laboratory results, patients who were <1 year old had higher white blood cell (WBC) count.", "Continuous data were analyzed statistically by one-way ANOVA test followed by post-hoc Holm-Sidak test for pairwise comparison. Categorical data were compared with each other statistically by Chi-square analysis with Yates correction for continuity or Fisher's exact test while the sample size was small. Statistical significant was defined as P < 0.05." ] },{ "paper_id": "fff3678cfe3ce7a9ccae1e7becf17d5d71d1b54a", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "The nucleus of a cell is the main store house of tumor protein p53 where it binds to DNA. When any damage occurs in the DNA of a cell by some external agents like toxic chemicals, radiation, exposure to sun light or ultra violet rays, p53 plays the crucial role in activating other genes and inhibits cell cycle to repair the damage [4] . In case of failure of DNA repair, the tumor protein p53 prevents the cell from dividing and provokes signals to a wide variety of genes that contribute to TP53 mediated cell death i.e., apoptosis [5] .", "logw RCB c \u00de \u00c0 1 [47] Where, O tot is the total number of codons", "The advent of whole genome sequencing in different organisms and the easily accessible nucleotide database from NCBI (GenBank) have attracted much attention of the scientific community to study CUB in gaining clues for understanding the molecular evolution of genes and genome characterization." ] },{ "paper_id": "fffaed7e9353b7df6c4ca8f66b62e117013cb86d", "task": 0, "abstract": "WHAT IS KNOWN ABOUT TRANSMISSION, INCUBATION, AND ENVIRONMENTAL STABILITY?", "body_text": [ "N-glycosylation on both E and NS1 proteins has been shown to play important roles throughout the DENV infection cycle from virion attachment, entry, maturation, assembly to secretion.", "SY, TN-K, and SA wrote the manuscript. PR provided suggestions and edited the manuscript." ] }]